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PMC5482912_01

Female

A 26-year-old black woman, born in Cape Verde and living in Portugal since the age of 3 years, presented with anal and vaginal suppuration. She had a known history of two deliveries, including a cesarean section in 2005 and a vaginal delivery in 2011 without episiotomy. During the second trimester of her second pregnancy, she had a bartholinitis requiring surgical drainage. She was using oral contraceptives and denied previous use of intrauterine devices. She was a smoker (6-7 cigarettes/day) and did not drink alcohol. She denied recent travels to Africa. The patient was first admitted in 2013 for complaints of anal and vaginal suppuration lasting 2 weeks, without fever or other accompanying symptoms. Perianal inspection revealed the presence of an external fistulous orifice in the posterior perineum, close to the left labium majus. On rectal examination, there was a palpable induration of the left anterior rectal wall. Her gynecological examination was unremarkable. A pelvic computed tomography excluded the presence of abscesses or other pelvic masses. The patient was put on antibiotics and underwent rectal examination under anesthesia, where no abscess was found. Two fistulous tracts were identified and treated with seton placement, including one tract involving the vagina. Biopsies of the indurated rectal wall were taken, and pus was collected for analysis. Pelvic magnetic resonance imaging 1 month after hospital discharge revealed multiple fistulous tracts, including trans-sphincteric and suprasphincteric tracts and a rectovaginal fistula (Figure 1). An extensive work-up to exclude inflammatory bowel disease (IBD) was done, including an upper endoscopy, colonoscopy with ileoscopy, small bowel capsule endoscopy and computed tomography enterography, which were unremarkable. Endoscopic biopsies of the colon, terminal ileum, and stomach did not show any significant findings. Anti-Saccharomyces cerevisiae antibodies titer was also negative. Cytology and cultural exams of both rectal and vaginal exudates and biopsy of the rectum were negative for neoplastic cells and microorganisms, including Mycobacterium tuberculosis. Serologies of Chlamydia trachomatis and human immunodeficiency virus were also negative, as was a VDRL test for syphilis. In the following 3 years, the patient underwent multiple abscess drainages, fistulae treatment by seton placement, and empiric antibiotic courses, with no overall improvement (Figure 2). This situation had a high impact on the patient's quality of life, eventually leading to clinical depression. Despite high suspicion of inflammatory bowel disease, a complete endoscopic investigation again was negative. In 2016, repeated anal cytology revealed the presence of bacterial colonies compatible with Actinomyces spp. (Figure 3). The patient was then hospitalized and completed a 6-week course of intravenous (IV) penicillin G, after which she was started on oral amoxicillin, which is to be maintained for 12 months. This resulted in a remarkable clinical improvement, allowing for the removal of setons (Figure 4). The reevaluation magnetic resonance imaging, performed after only 5 weeks of antibiotic therapy, showed almost complete resolution of the fistulous tracts (Figure 5). Currently, after 6 months of oral amoxicillin, the patient is clinically well, with no perianal suppuration, and reports a significant improvement in her quality of life. Although notably reduced, the vaginal fistula is still patent and will possibly require surgical correction.

PMC3015282_01

Male

A 52-year-old Native American male presented to the neurosurgical service with a precipitous decline in mental status. The patient's medical history included hypertension with a previous cerebrovascular accident, metabolic encephalopathy related to chronic alcoholic liver disease, intravenous drug use, and aseptic meningitis for which he had been treated four months earlier. On arrival, he was afebrile and his vital signs were stable. His Glasgow Coma Scale (GCS) score was 4 with extensor posturing noted. A comprehensive emergency room evaluation included a serum toxicology screen positive for cocaine and a basic head computed tomogram (CT) that demonstrated communicating hydrocephalus. There was no evidence of intracranial hemorrhage. The patient was admitted to the intensive care unit (ICU), and a right frontal external ventricular drain (EVD) was placed after normal coagulation parameters were confirmed. Both lumbar and ventricular CSF cultures were negative for infectious pathogens, including bacteria, fungus, and tuberculosis. A follow-up head CT demonstrated good position of the EVD with ipsilateral ventricular decompression. However, the left ventricular system remained distended. The placement of a contralateral EVD was associated with radiographic improvement of the hydrocephalus. Thereafter, the patient's GCS score improved to 14, and he became alert and purposeful but remained confused. Symptomatic elevations in intracranial pressure (ICP) accompanied efforts to wean the EVDs. The patient was scheduled for placement of a VP shunt, but the procedure was delayed because of infectious complications (blood, urine) and electrolyte abnormalities encountered during the patient's ICU course. His GCS score declined in conjunction with these metabolic issues, fluctuating between 6 and 10 in the midst of stable serial head CT and electroencephalographic (EEG) evaluations. Following medical clearance, the patient was taken to the operating room. Bifrontal ventricular catheters were inserted given the demonstrated isolation of the lateral ventricles on the patient's first postventriculostomy head CT. These catheters converged through a "Y" connector onto a single medium-pressure valve. The distal aspect of the shunt system was tunneled subcutaneously to a minilaparotomy wound and was placed within the peritoneum. There were no apparent intraoperative complications, and the patient was extubated and returned to the ICU with his neurological examination unchanged. Given the patient's persistent obtundation, a feeding jejunostomy was placed by a general surgeon five days later through a standard laparoscopic approach without intraoperative difficulty. Insufflation pressures within the peritoneum were maintained at approximately 15 mm Hg for the duration of the procedure (1.5 hours). Postoperatively, the patient tolerated extubation but was markedly more lethargic than his baseline condition. Within the recovery room, he failed to improve from a GCS of 4 (E 1, V 1, M 2) and developed intermittent periods of apnea. He was reintubated and the neurosurgery service was notified. An emergent head CT demonstrated ventriculomegaly with no evidence of intracranial hemorrhage or pneumocephalus. The patient was returned to the operating room for an anticipated shunt revision, with efforts at bilateral shunt taps technically unsuccessful. Intraoperatively, the shunt valve was disconnected from the distal system tubing. Brisk CSF outflow was observed from the valve. When the two ventricular catheters were disconnected from the proximal aspect of the shunt valve, CSF drained well from both. A manometer connected to the proximal aspect of the distal shunt tubing measured a static fluid column at 35 cm H2O. Irrigation through the distal tubing with sterile saline initially met with resistance but was overcome with approximately 5 ml of fluid. Subsequent manometric testing repeatedly demonstrated distal fluid run off to less than 3 cm H2O. With the individual shunt components verified as functional, the system was reconnected and the single incision reapproximated in a layered fashion. Postoperatively, the patient improved to a GCS of 7 (E 2, M 4, V I) consistent with his prelaparoscopic neurological examination. A follow-up basic head CT obtained the next morning demonstrated a return of the patient's base-line ventricular size. The patient remained neurologically stable throughout the remainder of his acute hospitalization, and no further shunt difficulties were observed.

PMC6260552_01

Male

A 53-year-old man was admitted for mobility of tooth. The dentist suggested the presence of a mass located at the tooth root by physical examination. Computed tomography revealed a well-demarcated radicular cyst of 4 cm in diameter at the tooth base. Carcinomatous infiltration of squamous cell carcinoma was observed in the excisional biopsy of the lesion. In microscopic evaluation, tumoral infiltration revealed features of moderately differentiated squamous cell carcinoma. Malignant cells infiltrated the underlying connective tissue stroma in solid groups and sheets. Numerous neutrophils were present within the cytoplasm of the malignant cells as well as in the surrounding stroma. The internalized neutrophils were intact (Figure 1). Desmosomal connections were observed between the tumor cells in some areas. The tumor cells showed moderate cellular pleomorphism. The diffuse immunoreactivities of P63 and CK5/6 were determined in the malignant cells by immunohistochemical staining. Additionally, perineural invasion was found, whereas vascular invasion was not observed. Because surgical margin was positive for tumor cells, partial maxillectomy and bilateral neck dissection was performed. Bone infiltration was present. Furthermore, diffuse neutrophilic emperipolesis was observed in cancer cells by microscopic evaluation. Some of the neutrophils in the tumor cells revealed degenerative changes by high-power field (x1000) microscopic evaluation (Figures 2-4), while some neutrophils included apoptotic bodies. Nearly one year later, local relapse developed and additional therapeutic manipulations including surgery, radiotherapy, and chemotherapy (cisplatin) were done. Tumor recurrence occurred in the periparotid and right neck lymph nodes after six months (Figure 5). Chemotherapy (cisplatin) and radiotherapy were performed for the recurrence. Two more relapses developed in the right neck, left submandibular lymph nodes and in the superficial and deep soft tissues of the neck three months apart. Tumor showed continuity along the surgical margin in the excised biopsy sample and a pericapsular invasion at the submandibular lymph node. Chemotherapy was continued. The endmost tumor recurrence was in the palatine tonsil and posterior parotideal region. Following unresponsive chemotherapy, pembrolizumab treatment was started eight months prior to this study (Figure 6). A complete response occurred following the sixth dose of pembrolizumab. Secondary adrenal insufficiency and pulmonary reactivation tuberculosis developed as the side effects of treatment. Tuberculosis was identified by PCR and compatible chest CT findings. Pembrolizumab was interrupted and antituberculous treatment was started. Pembrolizumab was commenced when the tumor progressed to a 15 cm mass (Figure 7). Following the fourth dose of pembrolizumab, the tumor regressed to 4 cm (Figure 8) and the patient is currently alive for four years.

PMC6044139_01

Female

The patient is a 57-year-old female who presented with 5 months of progressively worsening visual acuity and diabetes insipidus. Magnetic resonance imaging (MRI) showed a heterogeneous rim-enhancing 17 x 13 x 25 mm suprasellar lesion. The patient has no significant medical comorbidities. An endoscopic endonasal resection of the lesion was performed. DURAFOAM dural graft implant was used to close the dura and a nasoseptal flap was placed over the defect. The lesion was confirmed on pathology to be an adamantinomatous craniopharyngioma. Day 1 postoperative computed tomography of the brain (CTB) showed a small bifrontal pneumocephalus [Figure 1a]. Two days postoperatively, the patient developed rhinorrhoea and lower limb diplegia. CTB demonstrated an expanding pneumocephalus with mass effect [Figure 1b]. This was decompressed via bilateral frontal burr holes and CTB showed a slight reduction in the volume of the pneumocephalus [Figure 1c]. Four days after the operation, her Glasgow Coma Scale (GCS) again deteriorated to 10 (M6V1E3) with lower limb diplegia. Percutaneous aspiration of the pneumocephalus via bilateral frontal burr holes was performed. The aspiration continued until the patient started to verbalize and move her lower limbs. A transnasal transphenoidal repair of the dural defect was performed. Dural substitute was removed and a fascia lata graft inlay was used to repair the defect. However, the negative intracranial pressure drew the fascia lata graft intradurally. A fascia lata onlay graft with autologous blood patch was then used and the nasoseptal flap was replaced and secured with a TISSEEL fibrin sealant. Ten hours after the operation, the patient's GCS dropped to 11 (M6V1E4) and CTB again showed re-accumulation of the pneumocephalus. Percutaneous aspiration was performed and the patient returned to her neurological baseline. Three days after the last percutaneous aspiration, rhinorrhoea was again observed. This was followed 2 days later by another episode of GCS reduction to 13 (M6V3E4) with diplegia. CTB showed an expanding anterior pneumocephalus with mass effect. Percutaneous aspiration was performed with GCS recovery. The following day, GCS dropped to 9 (M6V2E1), and percutaneous aspiration was again performed for improvement in GCS. An endoscopic repair of the CSF leak was performed. During the operation, a leak was found between the leaflets of the previous fascia lata repair. A fat bath plug was placed over the defect with a large single piece of fascia overlaid. The repair was then tested with Valsalva three times. The nasoseptal flap was overlaid and augmented with a left inferior turbinate free mucosal graft. Postoperative CTB showed a significant reduction in the size of the pneumocephalus [Figure 1d]. The patient made an uneventful recovery and discharged GCS 15 with no neurological deficit.

dural repair, skull base surgery, tension pneumocephalus

PMC6993058_01

Female

A 33-year-old pregnant woman of 9-week gestation was referred to our reproductive genetics clinic for counseling (Figure 1A). The 5-year-old proband (II-1) was born at full term with low birth weight (2,162 g). She was presented with jaundice in skin and sclera shortly after birth to the present (Figure 1B). Echocardiography showed an atrial septal defect. Other features include hepatosplenomegaly and curly hair (Figure 1B). Laboratory testing done at that time revealed raised cholestasis makers, including total bilirubin (TBIL) 231.1 mumol/L (normal range 5.1-17.1 mumol/L), direct bilirubin (DBIL) 187.6 mumol/L (normal range 0-6 mumol/L), total bile acid (TBA) 99.7 mumol/L (normal range 0-10 mumol/L), gamma-glutamyl transpeptidase (GGT) 174 IU/L (normal range 7-50 IU/L), aspartate aminotransferase (AST) 81 IU/L (normal range 0-40 IU/L), and alkaline phosphatase (ALP) 876 IU/L (normal range 42-383 IU/L). Further tests showed normal values of vitamin D, vitamin E, and prothrombin time (PT). The clinical features of the patient suggested a diagnosis of Alagille syndrome.

alagille syndrome, jag1, rna assay, prenatal diagnosis, targeted sequencing

PMC9902497_01

Male

A 51-year-old male was found to have a large HCC (13.5 cm x 12.5 cm x 13.8 cm) in liver segments 5-8 during a routine check-up. The patient had no clinical symptoms at the time of the diagnosis. The patient was infected with hepatitis B years ago and had stage 3 hypertension and hyperlipidemia, but not diabetes. The body weight, height, and BMI of the patient were 83 kg, 1.71 m, and 28.38 kg/m2, respectively. Laboratory tests indicated that the patient's levels of alanine transaminase (ALT; 325 U/L), alkaline phosphatase (ALP; 186 U/L), total bilirubin (TBIL; 40.0 mumol/L), direct bilirubin (DBIL; 10.3 mumol/L), creatinine (155 mumol/L), and blood ammonia (66 mumol/L) were abnormal. The alpha-fetoprotein (AFP) level was significantly increased (>800 ng/ml). The patient's liver function was grade A, with a Child-Pugh score of 6. The preoperative retention rate of ICG at 15 min was not available due to a lack of equipment in our hospital at that time. The HCC had not invaded the left lobe of the liver or adjacent/distant organs in preoperative assessment. The tumor stage was Barcelona Clinic Liver Cancer (BCLC) stage B and China liver cancer stage Ib. The estimated preoperative standard liver volume (SLV) was 1386.16 ml, and the evaluated FLR was 300 ml based on CT assessment (Figure 1). The 22% FLR/SLV was insufficient to permit the removal of the tumor in one operation with major hepatectomy; the risk of posthepatectomy liver failure (PHLF) would be too high. After a multidisciplinary team (MDT) discussion, ALPPS-based multidisciplinary treatment was planned, and the patient agreed to receive such treatment. The surgery was performed laparoscopically. First, the gallbladder was resected. The right portal vein was separated from the hilar plate and clipped with a Hem-o-Lok (Johnson & Johnson, United States). Then, the parenchymal transection was performed via an anterior approach, following the ischemia line on the liver. Notably, intraoperative bleeding was difficult to control due to fibrosis and edema. To control the damage, the liver parenchymal tissue was only partially transected (to a point approximately 5 cm from the liver surface). Thus, it would be more appropriate to call our procedure "Mini-ALPPS." The right hepatic pedicle was sutured with black suture silk (Johnson & Johnson:Ethicon, United States). Finally, a surgical drain (Guangdong Sunlight Medical Ltd., China) was routinely placed in the hepatorenal fossa and the foramen of Winslow. The surgery required approximately 255 min and resulted in the loss of 800 ml of blood. On postoperative day (POD) 18 after stage I Mini-ALPPS, a CT was performed to re-estimate the degree of FLR hypertrophy. After evaluation, the FLR/SLV was only 34.63%; this was still not sufficient for stage II right hepatectomy. Based on this finding, we and the patient considered further interventions to facilitate FLR hypertrophy and prevent potential tumor progression during the waiting period. After stage I surgery, a CT scan still revealed a rich arterial blood supply to the tumor. After an MDT discussion, we decided to administer TACE to the patient. On POD 22 after stage I Mini-ALPPS, TACE was performed. Hepatic angiography showed that the main arterial supply of the tumor originated from the right hepatic artery. Arterial derangement of the large tumor could also be observed. The right hepatic artery was blocked with 10 ml lipiodol mixed with 20 mg epirubicin and 20 mg lobaplatin. After chemoembolization, the arterial flow to the large tumor almost completely disappeared (Figure 2). After stage I Mini-ALPPS, CT on POD 37 revealed that the FLR/SLV had increased to 46.89%. Theoretically, the FLR/SLV now meets the requirements of stage II hepatectomy; however, due to the patient's moderate fever after TACE, stage II surgery was not performed until POD 56 after stage I surgery. Considering the intraoperative bleeding that occurred at stage I, an open operation was planned at stage II to better control possible bleeding. Before the stage II surgery, the AFP level decreased to 126.81 ng/ml. During the surgery, we found significant hypertrophy of the left lobe of the liver. The parenchymal transection was still performed with anterior approaches. The right hepatic artery, right hepatic duct, and right portal vein were successively separated and cut after ligation with Hem-o-Lok (Johnson & Johnson, United States). The remaining liver parenchyma was then gradually dissected using an ultrasonic scalpel (Johnson & Johnson, United States) and bipolar coagulation (KANGJI Medical, China). The major vein of the right liver was separated, cut, and continuously sutured with 5-0 Prolene suture (Johnson & Johnson, United States). The right hemihepatectomy was completed after the removal of all related ligaments of the right liver. Finally, as is routine, a silicone drainage tube (Guangdong Sunlight Medical Ltd., China) was placed into the right subphrenic space. The surgery required approximately 260 min and resulted in the blood loss of 450 ml. One unit of packed red blood cells was administered, and the patient recovered without eventful complications. Histopathology confirmed a 12 cm x 9 cm x 14 cm HCC in the resected liver (Figure 3). The paracancerous liver tissues were graded as G1S1 according to the biopsy criteria of the Chinese Program of Prevention and Cure for Viral Hepatitis and graded as F1 fibrosis according to the METAVIR classification. The patient was discharged 15 days after stage II Mini-ALPPS. The patient received adjuvant transarterial chemotherapy 30 days after stage II Mini-ALPPS. 3 months later, his TBIL (40.0 mumol/L), DBIL (10.7 mumol/L), and creatinine (138 mumol/L) were still moderately elevated, but his AFP (3.94 ng/ml) was normal, and the CT scan showed no sign of residual tumor or recurrence. The patient was followed up regularly, every 3 months. After 586 days, stage II Mini-ALPPS, the patient was diagnosed with tumor recurrence (his AFP was 20.18 ng/ml, and his CT scan revealed the presence of two novel subcapsular nodules in the residual left liver and multiple metastatic nodules in the lung). The patient then received sorafenib and PD-1 inhibitor therapy. The patient has survived for 1,920 days since ALPPS surgery so far.

hcc, tace, long-term survival, mini-alpps, salvage

PMC9929662_01

Male

This 60-year-old asymptomatic male patient presented in our outpatient department because of a suspicion of primary lung cancer as discovered on a chest X-ray performed by his general practitioner. He was an active smoker and had signs of an old myocardial infarction on electrocardiography (EKG) but no other relevant medical history. His physical examination did not show any abnormalities. The screening X-ray showed a shadow in the right upper lobe (RUL) for which the patient was referred to a pulmonologist. A subsequent CT-thorax showed two nodules: one in the right lower lobe with a long axis diameter of 30 mm and one in the RUL with a long axis diameter of 17 mm. Both nodules were deemed of sufficient high risk of lung cancer to warrant further analysis. A positron emission tomography (PET)-scan was therefore performed which showed both identified nodules to be fluorodeoxyglucose (FDG)-avid, without mediastinal involvement or other signs of metastatic disease (see Figure 1). Patient was subsequently referred for minimal invasive biopsy of these nodules. A navigation bronchoscopy was considered most optimal, because both nodules could then be sampled in one procedure. After induction of general anesthesia, an inspection bronchoscopy was performed following the workflow as described above. While it was expected that only the right side was affected, inspection bronchoscopy revealed a third adverse finding. During the routine inspection, a submucosal lesion with dotted vessels of approximately 5 mm was observed in the left upper lobe (LUL). Based on its appearance, sampling for further analysis was believed indicated. Repeated sampling using a forceps biopsy instrument was performed (see Figure 2). Subsequently, the navigation bronchoscopy procedure ensued. An EWC (Medtronic) with a 180 degrees angulated distal tip was inserted in the target segment of the RUL and a first CBCT spin was performed. The target nodule and route were segmented for further image guided navigation which in this case required several CBCT scans for repositioning of the catheter in order to access this RUL nodule. Lesion access was confirmed with rEBUS and CBCT (Figure 3). Subsequently, this lesion was sampled with transbronchial needle aspiration and (new) forceps biopsy providing both cytological and histological samples. As ROSE was not able to provide a certain diagnosis, the lesion was sampled extensively for histology. Next, for the second nodule, the EWC was inserted in the target segment of the right lower lobe (RLL) using augmented fluoroscopy for the second nodule and its planned route which were segmented on the initial high dose CBCT. Navigation towards this lesion resulted in immediate access of the nodule and position confirmation was obtained by rEBUS and a new CBCT spin (Figure 3). Both a new TBNA needle and biopsy forceps were used to prevent cross-contamination for sampling of this third target. ROSE did provide a preliminary diagnosis suspicious for malignancy in the second nodule. At the end of the procedure, an X-ray was obtained using the CBCT system to check for signs of a pneumothorax, which were not found. Although there was no imaging based suspicion of lymphadenopathy, a systematic linear EBUS examination of the mediastinal and hilar lymph nodes was performed to check for signs of nodal disease. All lymph node regions showed small lymph nodes (<5 mm) with benign B-mode characteristics, which is why no fine needle aspiration was performed. After observation in day care setting, the patient was discharged the same day without complications. Pathological analysis of tissue samples revealed the endobronchial lesion in the LUL as a squamous cell carcinoma of the lung based on immunohistochemistry, tropomyosin receptor kinase (TRK) positive, tumor protein 53 (TP53) positive, programmed death ligand-1 (PD-L1) <1%. The RUL nodule was diagnosed as a non-small cell carcinoma of the lung not otherwise specified (NOS), with no further differentiation possible due to a low malignant cell count which precluded further molecular and clonal analysis. The lesion in the RLL was diagnosed as an adenocarcinoma of the lung, thyroid transcription factor 1 (TTF1) positive with PD-L1 <1%. There was insufficient material to perform clonal analysis on the two parenchymal lesions. Based on the pathology findings, and the radiological and clinical presentation of the lesion, the multidisciplinary tumor board including the pathologist concluded that it was most likely that this patient suffered from three separate primary pulmonary malignancies. They were respectively staged as: RUL cT1bN0M0, RLL cT1cN0M0 and endobronchial: cT1aN0M0. Although pathological examination was not able to fully differentiate if the non-small cell lung cancer (NSCLC) NOS of the RUL was a third primary or an ipsilateral metastasis of the RLL lesion, it was decided to not perform repeat biopsy of the RUL nodule to prevent further diagnostic delay. Due to the uncommon presentation, a cerebral magnetic resonance imaging (MRI) was performed which ruled out cerebral metastases. Subsequently, an additional mediastinoscopy showed no lymph node metastases. Because the patient did not have the pulmonary reserve to safely undergo a right sided pneumonectomy, a video assisted thoracoscopic surgical lobectomy was performed to resect the RLL. Stereotactic ablative radiotherapy was used to treat the lesion in the RUL, and the endoluminal squamous cell carcinoma was treated with endobronchial cryoablation. Unfortunately, the lymph node dissection performed during surgery of the RLL lesion revealed nodal metastases in levels 10 right and 11 right resulting in a final staging of pT1cN1 PL0 R0. Due to this upstaging, the patient received adjuvant chemotherapy in the form of carboplatin and pemetrexed for four cycles. No severe adverse events took place during the diagnostic process and following treatment. Patient is currently more than 12 months post-treatment and has no signs of recurrence, both on imaging and repeated bronchoscopy and re-biopsy of the endoluminally treated squamous cell carcinoma. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

case report, cone beam ct navigation bronchoscopy, multi-modality treatment, synchronous tumors

PMC2836177_01

Male

A gentleman born in 1979 had an asymptomatic murmur during childhood. Investigations confirmed hemianomalous pulmonary venous drainage to the right atrium without an atrial septal defect. The parents were Jehovah's witnesses and refused cardiac surgery with use of blood products. When aged 15 years, an adult cardiologist advised surgery and the patient was operated on by a general cardiac surgeon unused to congenital heart disease but willing not to use blood. The atrial septum was confirmed to be intact at operation and the oval fossa was enlarged to allow redirection of blood from the right pulmonary veins using a baffle of autologous pericardium to the left atrium. Recovery was uncomplicated. Seven months later he complained of increasing dyspnoea on effort and chest infections. He was reviewed once by a respiratory physician without further investigations or referral to cardiology. He trained and worked as a stonemason. He presented again aged 28 years, with a three-week history of right-sided pleuritic chest pain, high fever and a dry cough. On examination there was reduced air entry, coarse crepitations and a pleural rub at the right base. Chest radiography showed a dense patchy consolidation of the right lower lobe, probably also involving the middle lobe (Figure 1). He was treated with intravenous cefuroxime and oral clarythromycin but failed to respond as symptoms continued over several weeks with febrile exacerbations. An infectious disease specialist was involved and several alterations in the antibiotic regime were made. Tuberculosis was excluded on serial sputum cultures and infective endocarditis was considered possible but a transthoracic echocardiogram was reported as normal. Contrast computerised tomography scan of the thorax reported extensive consolidation within the right lung and probable chronic posterior pleural effusion. Bronchoscopy showed hyperaemic right main bronchial mucosa with inflammation especially around the right upper lobe bronchus. No lesions or pus were found to explain the situation. Despite the "normality" of the heart but because of past cardiac surgery, he was referred to the monthly Grown Up Congenital Heart (GUCH) clinic. A diagnosis of obstructed right pulmonary venous drainage was made from the chest X-ray (Figure 1). This stimulated review of his previous investigations. Computerised tomography scan cuts at the level of the heart and pulmonary vessels showed completely obstructed right pulmonary veins (Figure 2). No pericardial baffle was identified upon review of cross-sectional transthoracic echocardiographic images. There was also no flow to be seen across the atrial septum at the level of the created "atrial septal defect" on colour Doppler. A repeat transthoracic echocardiogram with spectral Doppler interrogation of the pulmonary arteries showed normal antegrade flow from the main pulmonary artery into the left pulmonary artery but none into the right pulmonary artery.

PMC3201101_01

Male

A 59-year-old man was admitted to our hospital because he was experiencing severe respiratory distress. He had been diagnosed with intestinal catarrh when he was 1 year old, nephritic syndrome when he was 13 years old, and pleuritis when he was 57 years old. He was an HBV carrier, but not immunocompromised. He did not have a history of tuberculosis. He lived in a rural district composed mainly of paddy fields and worked as an engineer in an office. He was an ex-smoker, having quit smoking at the age of 30 years. Six months before hospital admission, he presented with edema of the left leg and low-grade fever. At the time of presentation, he tested positive for anti-Chlamydia pneumoniae immunoglobulin antibodies and was treated with clarithromycin. He experienced symptom relief with this treatment within a few weeks. However, 4 months before hospital admission, soon after the treatment was discontinued, he developed low-grade fever, a skin eruption resembling folliculitis in the left upper arm, and adenopathy of multiple lymph nodes. Two weeks before hospital admission, he presented with bilateral swelling of the fingers and feet (Fig. 1A). Further, the skin eruption had progressed to ulceration (Fig. 1B). Isolates from the ulcer exudate were cultured and revealed cutaneous infection with mycobacterial species. He was therefore referred to our department. Chest X-ray (CXR) findings were normal, but computed tomography (CT) revealed the presence of tiny miliary nodules in both lung fields (Fig. 2A). Five days before admission, the patient developed a fever (temperature >38 C). He was urged to admit himself to our hospital because of severe respiratory distress. Physical examination revealed tachypnea and 80% oxygen saturation in room air. Prominent inspiratory crackles were heard over both lower lung fields. CXR showed diffuse bilateral infiltration (Fig. 3), and CT revealed the presence of multiple nodules and infiltrates in both lung fields (Fig. 2B). Blood gas analysis in room air revealed a partial pressure of oxygen in arterial blood (PaO2) of 46 mmHg and a pH of 7.46. The other blood parameters were as follows: hemoglobin level, 11.3 g/dL, was within normal limits; leukocyte count, 14.4 x 103 cells/L, was high; and C-reactive protein level, 20.8 mg/L, was high. The brain natriuretic peptide level was 30.0 pg/mL, which was within the normal limits. We initiated treatment with a broad-spectrum panel of antimicrobial agents, namely, meropenem and ciproxacin, along with methylprednisolone pulse therapy. However, over the next 24 hours, the patient developed severe respiratory failure (PaO2/fraction of inspired oxygen [PF ratio] <200) and required intubation and mechanical ventilation with positive end-expiratory pressure. Intubation was followed by bronchoscopy with bronchoalveolar lavage (BAL). Positive results were obtained in Ziehl-Neelsen staining of a sputum smear and BAL fluid, but negative results were obtained for Gram staining. We therefore strongly suspected mycobacterial infection. Although M. tuberculosis and the MAC were not detected in polymerase chain reaction analysis of the patient's samples, we continued to suspect a miliary mycobacterial infection. Therefore, we initiated treatment with a 4-drug regimen comprising rifampicin 450 mg/day, isoniazid 300 mg/day, pyrazinamide 1500 mg/day, and streptomycin 1 g/day. Meropenem and ciproxacin were discontinued 17 days after hospital admission because the patient's condition improved. Skin biopsy which was done at 1 weak after admission revealed diffuse infiltration of mixed inflammatory cells in the dermis, which was consistent with the diagnosis of cutaneous NTM infection (Fig. 4). CXR and CT revealed a gradual improvement in the patient's condition, and the patient was weaned off mechanical ventilation 23 days after admission. About 1 month after admission, we identified M. szulgai in cultures of the sputum, skin ulcer exudate, and BAL fluid using the colorimetric microdilution plate hybridization method. About 2 months after admission, the bilateral infiltrates had almost completely disappeared from the lungs (Fig. 2C), and the patient was discharged.

mycobacterium szulgai, acute respiratory distress syndrome, cutaneous infection

(B) CT scan obtained upon admission, showing shadows and nodules on both lung fields.

PMC4735080_01

Female

A 48 year old woman presented to her ophthalmologist with complaints of headache and double vision. She first noticed diplopia two months prior to evaluation, which waxed and waned in intensity. One month later, she had recurrent severe diplopia, most prominent on rightward gaze, accompanied by nausea, headache, and photophobia. Her symptoms persisted and progressed to include and right-sided eyelid heaviness. The patient was previously healthy, born in New York City, and had worked in maintenance. Neurologic exam revealed right ptosis, sluggish pupil, lateral gaze palsy, and diminished medial as well as downward gaze. She also had hypoesthesia in the V2 distribution. The patient was afebrile and had no meningeal signs. She had no pulmonary symptoms. Results of complete blood count, routine chemistry, complement testing, and serum ACE were normal. Sedimentation rate was elevated at 49. MRI of the brain was performed, showing an enhancing lesion in the right cavernous sinus (Fig. 1). A Quantiferon -GOLD test was performed as part of the initial work-up, and returned positive (Nil 0.046, TB Ag > 10, Mitogen > 10, TB-Nil > 10). Result of chest X-ray and HIV testing were negative. 18-FDG PET-CT was performed to assess for additional disease sites that would be more amenable to biopsy. PET-CT cuts in the chest revealed a subcarinal mass with intense uptake (SUV of 11). Biopsy of the subcarinal lymph node was performed using a robotic VATS procedure. Lymph node pathology revealed both necrotizing and non-necrotizing granulomas, and cultures subsequently grew M. tuberculosis, susceptible to all first-line drugs. The patient was started on therapy with INH 300 mg daily, rifampin 600 mg daily, pyrazinamide 1500 mg daily, and levofloxacin 750 mg daily. Ethambutol was not given because of concern for potential ocular toxicity, given her cranial nerve deficits and diplopia. She was also treated with daily prednisone. Pyrazinamide was discontinued in 3 months, and levofloxacin in four months. She was treated with INH and rifampin to complete a 12 month course. The patient's gaze palsies improved while on therapy, though her facial hypoesthesia persisted. Repeat MRI 3 months into treatment showed improvement of cavernous sinus lesion. MRI after treatment showed near-complete resolution of the lesion (Fig. 2).

cns tuberculosis, cavernous sinus syndrome, extrapulmonary tuberculosis, fdg-pet, tuberculoma, tuberculosis

PMC3336240_02

Male

Social history obtained upon admission revealed her current partner, and father of the baby, was a 50-year-old man with a history of incarceration, residence in shelters for the homeless, and prior hospitalizations for respiratory infection that was suspicious for tuberculosis. Initial workup of the mother in the ED at hospital no. 1 revealed elevated liver enzymes in the range of 400-500's, leukopenia, and maternal fever. HIV Elisa was negative and HIV RNA viral load was ordered. The patient was admitted to the hospital. To evaluate the patients' headache, neurology and infectious disease consults were requested and a lumbar puncture was performed. VDRL and Cryptosporidium test were ordered and were negative. The working diagnosis at this time was disseminated infection with Herpes simplex virus (HSV). The infectious disease physician recommended intravenous acyclovir for 10 days. On antiviral therapy day number five, the patient requested transfer to another private hospital (henceforth identified as hospital no. 2) where her obstetrician had admitting privileges. Of note, HIV viral load was still pending at time of transfer. Upon arrival at hospital no. 2, a Maternal-Fetal medicine specialist from our teaching institution was consulted to evaluate the presumed disseminated HSV infection. Social history in the transferring note received from hospital no. 1 stated that the patient's partner was currently hospitalized with renal failure and end-stage AIDS. The plan at this time was to continue intravenous Acyclovir for the presumed disseminated HSV infection while HIV workup was in progress. Repeating HIV rapid screen test, HIV RNA viral load, and CD4 and CD8 counts were done, a PPD test was placed, and workup was ordered for elevated liver enzymes. Consultations with infectious disease and hepatology were requested. WBC on admission to hospital no. 2 was 4.3; Hepatitis A, B, C serologies, Human Granulocytic Ehrlichiosis IgG and IgM, and Toxoplasmosis IgG and IGM were negative. A right upper quadrant ultrasound was performed and ruled out any pathology. The PPD was read as negative. Blood cultures were negative. Rapid screen HIV test was again negative. Several days after admission to hospital no. 2, laboratory results were received from hospital no. 1, which were significant for HIV viral load being greater than 500,000 copies/mL and CD4 count of 227 cell/mm3. Thus the patient received the new diagnosis of acute HIV infection. She was started on an antiretroviral regimen of Combivir 150 mg/300 mg 1 tablet twice daily and Viracept 625 mg 2 tablets twice daily. On hospital day 6, her liver function tests decreased to an AST of 191, ALT of 365, and an alkaline phosphatase of 111. HIV RNA viral load that was obtained on admission to hospital no. 2 returned as 434,000 copies/mL. CD4 count was 323.9 cell/mm3. Her symptoms of fever and headache resolved and she was later discharged home without further complications or findings. Of note, laboratory studies as an outpatient at approximately 3 weeks later demonstrated a CD4 count of 447 cell/mm3 and a viral load of 869,000 copies/mL. Antiretroviral therapy was continued as outpatient. At 33 weeks and 5 days gestational age, her CD4 count was 177 cell/mm3 and viral load was 128 copies/mL. The patient presented to hospital no. 2 at 37 weeks and 2 days in early labor complicated by chronic hypertension with superimposed preeclampsia. She was admitted for delivery. Based on the last viral load being less than 1,000 copies/mL, she was allowed a trial of vaginal delivery. She received a loading dose of zidovudine at 2 mg/kg followed by maintenance dosage of 1 mg/kg throughout labor. She also received magnesium sulfate for seizure prophylaxis. The viral load during this admission was 74 copies/mL. She underwent a low transverse cesarean section secondary to arrest of dilation and gave birth to a 4 pound 11 ounce infant girl with Apgar scores of 8 and 9 at one and five minutes, respectively. The patient was discharged on postoperative day number three without complications. The infant was negative for HIV infection at four months of life.

PMC4901173_01

Male

35 year-old hispanic male with history of Diabetes Mellitus and inguinal hernia presented with two-week history of productive cough and weight loss. He denied hemoptysis, fevers, chills, recent travel or sick contacts. Initial physical exam was significant for left-sided rhonchi. Chest radiograph revealed a lingular opacity with associated effusion. He was started on broad-spectrum antibiotics, and subsequent chest CT (Fig. 1) showed a left upper lobe consolidation with a large multi-locular cavitation and air-fluid levels. On our evaluation patient appeared older than stated age, with noted temporal wasting, poor dentition and gynecomastia. Additionally, subtle signs of atrophy were seen in the upper extremities with abdominal obesity and a left inguinal hernia. He answered questions appropriately but with slowed mentation and mini-mental exam was 25. Bilateral ptosis was evident with normal pupillary reflexes. Cranial nerves were intact. Motor strength was grossly 4/5 without fasciculations. When shaking his hand, a delay in relaxation of the thumb was seen, and percussion of the thenar eminence elicited a contraction of the thumb. Furthermore a delayed grip release was evident. Laboratory investigations resulted negative for HIV and Tuberculosis, however respiratory cultures grew gram-negative bacilli and gram-positive cocci in pairs. Later, a barium swallow (Fig. 2) showed laryngotracheal aspiration. Based on the described findings a clinical diagnosis of DM (Steinert's disease) was made. He was started on an eight-week course of antibiotics, improved significantly and was discharged with Neurology and Pulmonology follow-up.

differential diagnosis, lung abscess, myotonic dystrophy

CT Chest: Left upper lobe consolidation with multilocular cavitation.

PMC150380_01

Male

A 17 years old male patient referring to a private medical clinic with an arthritis at his left knee was given non steroidal anti-inflammatory therapy. As his arthritis continued, he was admitted to our hospital. In 1988, he had a craniotomy and a cerebral mass was excised but he had no further pathology reports concerning the excised material and he was continuing to take antiepileptic medications. In 1994 for pulmonary tbc, he had been given antituberculosis therapy for one year. He had no trauma or surgical intervention to his left knee. In his physical examination, his body temperature was 39.2 C, multiple lymphadenopathy with different sizes at the axillar region, hepatosplenomegaly and arthritis at his left knee was detected. Laboratory examination revealed erythrocyte sedimentation rate (ESR) 86 mm/h, hemoglobin 9.5 gr/dl, leukocyte 5900 /mm3, thrombocyte 473 000/m3, CRP 221 mg/dl (normal < 5 mg/dl), Ig G 20.9 g/l (normal 7-16 g/l), Ig A 5.5 g/l (normal 0.7-4 g/l), Ig M 2.8 g/l (normal 0.4-2.3 g/l), albumin 24 mg/dl (normal > 35 mg/dl), PPD 20 mm diameter and HIV, rheumatoid factor and brucella agglutination tests were all negative. All the other biochemical tests were normal. X rays and magnetic resonance imaging (MRI) of the left joint showed septic arthritis (Figure 1) and patellar osteomyelitis (Figure 2). As the synovial fluid analysis displayed 80 % polymorphonuclear leukocytes, ceftriaxone 2 g/day and teicoplanin 400 mg/day were intitiated with the diagnosis of septic arthritis. His cranial MRI was normal except secondary findings due to his previous cranial operation. In the computerized tomography (CT) of the thoracal region, there were multiple lymph nodes at the axillary region and multiple calcified lymph nodes at the hilar region but bilateral pulmonary paranchimal regions were normal. The results of the blood cultures were negative. At the examination of synovial fluid, AARB was negative. Aspergillus fumigatus was isolated from the synovial fluid. Excisionel biopsies were taken from the left knee synovium and axillary lymph node. Histopathological examination of the left knee specimen expressed granulomatous lesion due to Aspergillus (Figure 3) and the lymph node biopsy from the axillary region showed changes compatible with the granulomatous disease. The patellar osteomyelitic tissue was surgically excised and another synovial fluid sample was taken from the left knee at the same session. From the tissue samples cultures Aspergillus fumigatus were yielded. Antibiotic treatment switched to Amphotericin B deoxicolate 0.7 mg/kg/day. G6PD level were normal. As the nitroblue tetrazolium test (NBT) was positive, the patient was diagnosed as chronic granulomatous disease. Surgical debridement was performed. On the 37 th day at the total dosage of 820 mg of amphotericin B nephrotoxicity developed and the therapy switched to itraconazole 400 mg/day. The infection was treated with surgical debridement and antifungal treatment. At the 37th day, ESR decreased to 25 mm/h and CRP was <5 mg/dl. The surgical wound healing was very slow and we could not introduce IFN-gamma because the licensed use of this preparation is not available in our country. The patient was given co-trimoxazole for prophylaxis and itraconazole therapy. As the surgical wound healed, the co-trimoxazole prophylaxis and itraconazole therapy were discontinued at the 6th month. The limitation of the range of motion of the knee joint excellently responded to physical therapy and rehabilitation program that lasted three weeks and a knee joint flexion of 90 degrees was achieved. The patient can perform all the activities of daily living including the school activities and he is not receiving any prophylactic medicine.

PMC7024080_01

Male

A 31-year-old G2P1A0L1 presented to our clinic for follow up at 20 weeks of gestation with the diagnosis of ICP. The patient reported that her symptoms started as early as 10 weeks of gestation of her spontaneously conceived pregnancy. Initially the patient used topical steroids in an attempt to relieve her symptoms to no avail. She later sought medical attention from several dermatologists who prescribed creams for eczema and dermatitis that included lotions, antihistamines and oral steroids reaching 40 mg daily also to no avail. Despite two weeks of treatment the pruritis increased in severity and at this point ICP was suspected for which total bile acid salts TBAS as well as liver function tests were ordered. The patient discontinued her previous medications and was started prophylactically on ursodeoxycholic acid (UDCA) at a dose of 250 mg TID. At 18 weeks of gestation the results of her laboratory tests showed an increase in TBAS of 9.1. At this point the patient was referred to a maternal fetal medicine specialist at our center. At our clinic, the patient was followed every 3 weeks with out-patient clinic visits until 33 weeks of gestation and then weekly afterwards. Nonstress tests were performed twice weekly as of 28 WG and follow up growth scans at 2-3 week intervals. The estimated fetal weight was within 50th percentile range at all times. The levels of TBAS were measured every 3 weeks. Her UDCA doses were modified depending on her serum bile salt values. The patients' TBAS values are presented in Figure 1. By the end of her pregnancy she was receiving 2000 mg daily of UDCA with mild tolerable symptoms. Her liver function tests were within the normal limits at all times during pregnancy. SGOT values ranged between 13 and 20 U/L, SGPT values ranged between 8 and 14 U/L, while bilirubin was less than 0.1 mg/dl. The patient was induced at 37+1 weeks of gestation using misoprostol and then followed by oxytocin for labor augmentation. The patient progressed smoothly to full dilation within 12 hours of induction. She delivered a live born male of weight 3340 grams and Apagr score of 8 and 9 at 1 and 5 minutes respectively. The patient and her child were discharged home on the day 1 post vaginal delivery in a stable condition. Follow up TBAS 1-week post-partum revealed a value of 5.9 micro-mol/L, with complete resolution of symptoms. The patient provided an informed consent with which we were given permission to access her medical chart.

PMC9189518_01

Male

A 68-year-old male patient with a background history of hypertension presented with abdominal pain in the right upper quadrant associated with anorexia for 1-month duration. However, he did not report any fever, chills, altered bowel habits, melena, or per rectal bleeding. He had no previous abdominal surgeries. The general examination was unremarkable, devoid of any fever or tachycardia but the abdominal examination revealed a palpable liver extending beyond the costal margin. His basic blood biochemistry revealed an elevated leucocyte count of 16.8 x 103/microL with a C-reactive protein level of 9.4 mg/L and an elevated erythrocyte sedimentation rate of 119 mm/h. His liver and renal profiles were normal. Ultrasound abdomen revealed a hypoechoic lesion in the liver measuring 8.9 x 6.4 cm involving liver segments V, VI, and VII without internal vascularity suggestive of a liver abscess. Further imaging with triphasic CT of the chest, abdomen, and pelvis revealed a large irregular shaped loculated peripheral enhancing, centrally hypo-attenuated fluid density lesion measuring 8.3 x 10.8 x 6.1 cm in size involving segment IVA and IVB of the liver suggestive of a liver abscess with mass effect on the common hepatic artery branches (Figure 1). The CT did not show any features of intrahepatic or extrahepatic biliary obstruction. The collection was drained under ultrasound guidance with a pigtail catheter. Aspirated purulent fluid investigations confirmed a liver abscess. The full report revealed 17,600 mm3 of pus cells and protein of 9000 mg/dL with a significant growth of Escherichia coli, suggestive of the diagnosis of a liver abscess with cytology report confirming the diagnosis. The mycobacterial investigations for tuberculosis, amoebiasis, and Burkholderia pseudomallei, three important causes for liver abscess in South Asian region were negative. Upon further investigations, an elevated HbA1c of 6.4% in the pre-diabetic range was found although FBS was normal. Echocardiography was normal without any features to suggest endocarditis. The investigation for a cause continued with upper GI endoscopy, which was normal. However, interestingly, the colonoscopy revealed a denture impacted at the sigmoid colon adjacent to multiple diverticula. There was no endoscopic feature of diverticulitis. The patient was unaware of having swallowed a denture. The denture was removed carefully using a snare and foreign body forceps. There was superficial ulceration at the site of impaction but no obvious perforation seen on careful examination. It was thought that a microperforation would have spontaneously healed during the delayed personation. The patient was treated with intravenous cefotaxime for 2 weeks according to the sensitivity reports. The patients had an uneventful recovery. He discharged following 2-week hospital stay. Serial follow-up ultrasound scans revealed a resolving abscess. As the denture had only plastic attachments, it was difficult to identify on the previous CT scans; however, there was evidence of colonic perforation from a foreign body depicted in the CECT images retrospectively (Figure 2).

hepatic abscess, colonic perforation, foreign body

PMC5356201_01

Male

As a teenager in 1982, our patient, now 52 years old, presented with intermittent colicky pain, constipation, and abdominal distension. He also had intermittent bouts of melena, during which his hemoglobin dropped to ~6 g/dL, requiring multiple blood transfusions. There was no history of any nonsteroidal anti-inflammatory drug (NSAID) intake. Multiple gastroduodenoscopies revealed duodenal ulcers, for which proton pump inhibitors were prescribed on regular basis. These symptoms persisted for 7 years, but during an episode of small bowel obstruction and GIB he underwent a laparotomy at a local hospital where jejunal ulcerations were identified and resection anastomosis was done. Biopsy of the resected specimen showed nonspecific ulcers. After surgery, however, there was no symptomatic relief. He was extensively evaluated during this period. Gastroduodenoscopy, colonoscopy, abdominal computed tomography, and Meckel's scans were all normal. For the next 10 years, the patient underwent several abdominal surgeries with no clinical improvement. He consulted several gastroenterologists. Barium studies revealed small bowel strictures and ulcerations. Small bowel tuberculosis (TB) was suspected, and antitubercular drugs were given empirically. As the patient didn't respond, Crohn's disease became the leading diagnosis. He received corticosteroids, mesalamine, and azathioprine for a prolonged period. His small bowel symptoms didn't improve, but he developed complications of steroids such as cataracts and uncontrolled diabetes. He also developed features of chronic diarrhea and hypoproteinemia. Capsule endoscopy showed a stricture along with superficial ulceration of the mucosa in the mid-jejunal area (Figure 1). The capsule became lodged in the stricture and was retrieved using an enteroscope. Diagnostic laparotomy, adhesiolysis, on-table enteroscopy, and resection anastomosis of distal ileal segment were performed in 2005.The resected ileal segment showed multiple, superficial, circular and linear ulcers and sharply demarcated ulcers with normal surrounding mucosa. The microscopy showed nonspecific ulcerations and a few angioectasia (Figure 2). The ectasias on pathology did not show any evidence of obliteration or hypertrophy, which is inconsistent with diagnoses of Crohn's disease or TB. Thus, from the clinical features, endoscopic pictures, and biopsy evaluation, a diagnosis of CMUSE was made. The patient was kept on a nonresidual diet, medium chain triglycerides, high protein, and dietary supplementations. His obstructive symptoms improved and hypoproteinemia was corrected. Periodic GIBs persisted, however, for which he received blood transfusions as before. Five years later, hormonal therapy consisting of ethinyl estradiol and norethisterone successfully addressed his angioectasias stopped his GIBs. For the past 7 years he has been on hormonal therapy and a nonresidual diet, and he is symptom-free. As a complication of hormonal therapy, however, he developed gynecomastia and loss in libido, so the therapy was stopped. The melena reappeared, and the hormonal therapy resumed.

PMC3088116_01

Male

The study was approved by the Institutional Review Board of Children's Hospital and Research Center at Oakland in accordance with the Declaration of Helsinki. The clinical sample was obtained from the rectal mucosa of a male who had a history of sex with men and presented with severe hemorrhagic proctitis. Briefly, a 26-year-old male presented to a San Francisco Bay area clinic with a complaint of severe rectal pain with blood on defecation. He described a series of encounters with homosexual men and unprotected anal receptive intercourse during the prior month until the onset of rectal pain 5 days prior to the clinic visit. The rectal bleeding had commenced 1 day earlier. The man had a history of gonorrhea in the past but no other known STDs, no known exposure to men with known STDs, and no history of illicit drug use. He was reported to be HIV negative and had no other medical conditions, was not on any over-the-counter or prescription medications, and appeared to be in excellent health. On the physical exam, he was a well-appearing male, afebrile, and normotensive, with no evidence for an ulcerative lesion on the glans or shaft of the penis and no inguinal adenopathy. The anus was inflamed, and on proctoscopy, there was extensive bleeding of the mucosa, with evidence of a purulent discharge. Four swabs from each quadrant of the rectum were obtained and placed in transport medium. Three swabs were sent to the clinical laboratory for standard detection of Neisseria gonorrhoeae by commercial PCR and culture and of C. trachomatis by commercial PCR. The fourth swab was sent to the Chlamydia Research Laboratory at CHORI for in-house C. trachomatis culture. Reference strains D/UW3, L1/440, L2/434, L2a/TW-396, and L3/404, a clinical L2b strain from Amsterdam (a kind gift from Servaas Morre), and the clinical sample, referred to as L2c, from the above-described case, were analyzed. Each strain was propagated in the human cervical adenocarcinoma cell line HeLa229 using our previously described protocols. The clinical sample was diluted and directly plaque purified using sequential plaque purifications per our referenced protocols. To verify the clonal purity of the plaques, ompA and MLST genes were amplified by PCR and cloned separately using a TOPO TA cloning kit (Invitrogen); 10 clones of each were randomly selected for Sanger sequencing using techniques we have described previously. The confirmed clonal plaques were then individually propagated in tissue culture. A total of two passages were performed for L2c to generate sufficient gDNA for genome sequencing. The EBs for each C. trachomatis isolate were purified from contaminating human cells using DNase treatment followed by gradient ultracentrifugation, and genomic DNA was purified from each isolate using a High Pure PCR template preparation kit (Roche Diagnostics, Indianapolis, IN) as we previously described. For determination of MOI based on IFUs, duplicate serial 10-fold dilutions of purified EBs were used to infect HeLa cells in 24-well plates. After 24 to 48 h, the cells were fixed in methanol, washed with phosphate-buffered saline (PBS), and stained using the Pathfinder Chlamydia culture confirmation monoclonal antibody (MAb) (Kallestad Diagnostics, Chaska, MN) in accordance with the manufacturer's directions. The number of IFUs per well was divided by the number of cells per well; an average was taken for duplicate wells to arrive at the MOI per strain. HeLa cell monolayers grown in minimal essential medium (MEM) containing 10% fetal bovine serum (UCSF Cell Culture Facility, San Francisco, CA) and 1 microg/ml gentamicin (MP Biomedicals, Solon, OH) at a confluence of 80% on 12-mm coverslips (Fisher Scientific, Pittsburgh, PA) in 24-well plates were infected with either reference strains L1/440, L2/434, L2a/TW-396, L3/404, and D/UW3, clinical strain L2b from Amsterdam, or the clinical strain L2c from this study in sucrose-phosphate-glutamine (219 mmol/liter sucrose, 3.82 mmol/liter KH2PO4, 8.59 mmol/liter Na2HPO4, 4.26 mmol/liter glutamic acid, 10 microg/ml gentamicin [MP Biomedicals], 100 microg/ml vancomycin [Acros Organics, Morris Plains, NJ], and 25 U/ml nystatin [MP Biomedicals] in distilled water, pH 7.4) at an MOI of 1, unless indicated, for 2 h on an orbital shaker at room temperature. The inocula were aspirated, and the infected monolayers were cultured in a humidified incubator at 37 C with 5% CO2 in Dulbecco's modified MEM (Cellgro, Manassas, VA) with GlutaMAX-1 (Life Technologies, Rockville, MD) supplemented with 10% fetal bovine serum (UCSF Cell Culture Facility), 0.45% glucose solution (Cellgro), 20 mM HEPES (UCSF Cell Culture Facility), 0.08% NaHCO3, and 1 microg/ml cycloheximide. At 12, 18, 24, 36, and 48 h (48 h for D/UW3 only) postinfection, the coverslips were fixed with methanol for 10 min, rinsed in PBS, and incubated for 30 min with anti-C. trachomatis specific lipopolysaccharide (LPS) MAb (Virostat, Portland, ME) and anti-IncA MAb 3H7 (gift from Daniel D. Rockey) or polyclonal anti-IncA (gift from Ted Hackstadt). The secondary antibodies were Cy-3 conjugated IgG (Jackson ImmunoResearch, West Grove, PA) for LPS and fluorescein isothiocyanate (FITC)-labeled IgG (Jackson ImmunoResearch) or Alexa 488 (Invitrogen) for IncA and chlamydial heat shock protein 60. DAPI (4',6-diamidino-2-phenylindole dihydrochloride) (Vector Laboratories, Burlingame, CA) was used to stain DNA. The inclusions formed by the reference LGV and D/UW3 strains and the clinical L2c strain were visualized on a Zeiss 510 confocal microscope. Light microscopy was used to examine the D/UW3, LGV, and clinical L2c strains at 36 h, but no inclusions were observed for any LGV strains at this time point. We examined incA expression using our previously described techniques, with slight modifications. HeLa cells were infected at 0, 2, 12, 24, and 48 h with D/UW3, L2/434, and L2c at an MOI of 5. Total RNA was extracted using an RNeasy minikit (Qiagen, Valencia, CA) per the manufacturer's instructions; on-column DNase (Qiagen) treatment was performed to remove contaminating DNA. cDNA was generated from 2 microg of total RNA using TaqMan reverse transcriptase (RT) reagents and random hexamers (Applied Biosystems, Foster City, CA). Quantitative real-time PCR was performed in replicate using SYBR green chemistry, reagents, primers (see Table S1 in the supplemental material), thermocycling, and standard curves as we previously described. 16S rRNA was used for normalization. Negative controls and the standard curves for each gene were used as previously described. Analysis of the dissociation curves was used to verify the specificity of the amplified products. The conversion of the mean threshold cycle values determined the relative amounts of target and control gene from the respective standard curve. Three independent experiments were performed. Growth curves for strains D/UW3, L2/434, and L2c were generated using quantitative PCR as we previously described. Briefly, each strain at an MOI of 1 was grown in HeLa cells and harvested at 0, 12, 18, 24, 36, and 48 h, and total RNA was extracted and reverse transcribed as described above. Each quantitative PCR consisted of 1x SYBR green master mix (Applied Biosystems), 1 microl of cDNA, and 5 pmol of each primer (16S rRNA and glyceraldehyde-3-phosphate dehydrogenase [GAPDH] as described in reference 56) in a total reaction volume of 25 microl run on an ABI 7900 (Applied Biosystems) using our thermocycling profile as previously described; standard curves were generated, and negative controls for each primer pair were included in each run as we previously described. GAPDH was used for normalization. Melting curves were used to verify the specificity of the reactions and the absence of primer dimmers. Samples were amplified in triplicate where the mean was used for analysis. Three independent experiments were performed. Reference strains D/UW3 and L2/434 and the clinical L2c strain from this study were analyzed in a cytotoxicity assay adapted from the method of Belland et al. (42). HeLa cells were grown to 80% confluence as described above in 24-well plates. The monolayers were treated with 1 ml DEAE-dextran (45 microg/ml) in Hanks' balanced salt solution (HBSS) for 15 min at 37 C. The cells were infected at an MOI of 100 (~5 x 107 IFU) with each strain and mock infected in duplicate at room temperature for 4 h on an orbital shaker. The inocula were removed, and the cells were washed with HBSS and incubated for an additional 4 h in growth medium as described above except for the addition of 10 microg/ml gentamicin (MP Biomedicals), 25 microg/ml vancomycin (Fisher) to prevent any nonchlamydial bacterial growth. The monolayers were visualized under light microscopy at x400 magnification. The cells were scored for rounding, detachment, and lysis compared to the levels for uninfected control cells by the following metric: (-), same as cell control; 3+, 100% of cells affected; 2+, 75% of cells affected; and 1+, 25% of cells affected. The above-described experiments were repeated using 1 microg/ml of doxycycline to pretreat cells before infection. In addition, the assay was repeated using L2/434 and a higher passage number (passage no. 20) for L2c. A total of two independent experiments were performed for each of these studies. To detect the toxin protein, a Western blot analysis was performed as we have previously described, with modifications. Briefly, L2/434, D/UW3, and L2c were independently grown in HeLa cells as described above at an MOI of 100. Purified EBs from each isolate were solubilized in Laemmli buffer, run on NuPAGE Novex 4 to 12% bis-Tris precast gels (Invitrogen) with a BenchMark prestained protein ladder (Invitrogen), and electrophoretically transferred onto a BioTrace polyvinylidene difluoride (PVDF) membrane (Pall Life Science, Port Washington, NY) at 120 V for 2 h in 1x NuPAGE transfer buffer (Invitrogen) with 10% methanol. The membrane was incubated with 5% skim milk in 1x Tris-buffered saline (TBS) and 0.1% Tween 20, washed with 1x TBS-0.1% Tween 20, and reacted overnight with a polyclonal antiserum against recombinant CT166 (gift from Harlan Caldwell) at a 1:500 dilution. The membrane was washed, and secondary antibody (goat anti-rabbit IgG conjugated to horseradish peroxidase [HRP]; Bio-Rad, Hercules, CA) was applied at a 1:1,000 dilution, incubated at room temperature, and washed in 1x TBS prior to detection using the SuperSignal West Pico chemiluminescent substrate (enhanced chemiluminescence [ECL] detection system; Thermo Scientific, Rockford, IL) and CL-XPosure Film (Thermo Scientific). The purified genomic DNA from the clinical case was shotgun sequenced using a combination of the 454/Roche GS-FLX Titanium and GS Junior instruments (454 Life Sciences, Branford, CT). The 809,874 reads were generated with an average read length of 404 nt. Preliminary analysis suggested an unusually high proportion of contamination of DNA from the HeLa cell culture. Therefore, 618,844 reads of human origin were removed (identified by mapping to the hs19 golden path release of the genome []) using Newbler gsMapper 2.5 software. We assembled a random subset of 50,000 of the remaining reads de novo using the 454 gsAssembler software program, version 2.0.01.14, with default parameters. The order of the contigs in the final genome sequence was determined using a combination of the possible connections between contigs suggested by overlapping reads and information from mapping contigs against the L2/434 reference genome. After determination of the correct path through the contig graph, the contigs were assembled to form the final sequence. To accomplish this, the ends of adjoining contigs were matched using BLAST against the database of reads. Reads found in both contigs were assembled into a consensus sequence that bridged the two contigs to form a single, larger contig. The majority of gaps were small enough to be spanned by a single read. The plasmid was a single contig with reads overlapping the beginning and end, indicating the expected circular redundancy. For verification of the sequences, we aligned the original reads to the consensus chromosomal and plasmid templates using gsMapper 2.3; 91.6% of the 191,030 human screened reads (average length, 436 nt) mapped to the chromosome, and 6.8% mapped to the plasmid. The remaining unmapped reads were found not to assemble de novo into any contigs consisting of more than 2 reads, suggesting that these were mostly contamination that had not matched the human reference sequence. The mapped assemblies were inspected to remove a small number of errors. The final assembly, with an average redundancy of coverage of approximately 75-fold, was used for annotation. The identity of each base in the final consensus sequence was determined by majority vote. The gsMapper software revealed two possible structural variants in a minority of sequence reads. The first was a deletion between coordinates 133542 and 155549 present in 4 sequence reads. The second was a deletion between bases 849581 and 849942 present in 19 sequence reads. The L2c consensus chromosome and plasmid sequences were annotated automatically using the Integrative Services for Genomics Analysis pipeline. Promoter 2.0 prediction (), Bacterial PROMoter prediction (), and the Berkeley Drosophila Genome Project neural network () were used to identify the ftsK putative promoter region, including the initiation site, -10 and -35 promoter elements, and ribosome binding sites. The default parameters were used for prediction scores for significance. To verify the regions of diversity (L2-D hybrids), single amplicons of these regions (the tarp gene, incA, hctB, and toxin locus genes; the IGR upstream of ftsK) that were identified by the SAS program Q-plotGenome (see below) and genomic analyses (see below) as divergent from L2/434 were amplified, cloned using a TOPO TA cloning kit (Invitrogen), and Sanger sequenced using primers (see Table S1 in the supplemental material) designed to amplify and sequence the full length of each as previously described. Ten clones were sequenced for each. The sequences were compared with those of the following available reference strains (GenBank accession numbers are given in parentheses): A/2497 (EU121607), B/HAR36 (EU121608), C/TW3 (EU121609), D/UW3 (AE001273), L2/434/Bu (AM884176), and L2b/UCH-1/proctitis (AM884177) for the tarp gene; A/HAR13 (CP000051), B/Jali20/0T (FM872308), C/TW3 (EU121596), D/UW3 (AE001273), L2/434/Bu (AM884176), and L2b/UCH-1/proctitis (AM884177) for hctB; A/HAR13 (CP000051), B/TW5 (DQ064209), B/TZ1A828/OT (FM872307), Ba/Apache-2 (DQ064210), C/TW3 (DQ064211), D/UW3, E/Bour (DQ064214), F/IC-CAL3 (DQ064215), G/UW57 (EU247624), H/UW4 (EU247625), i/UW12 (DQ064218), Ia/870 (DQ064219), J/UW36 (DQ064220), K/UW31 (DQ064221), L1/440 (DQ064222), L2/434/Bu, L2b/UCH-1/proctitis, and L3/404 (DQ064224) for incA; C/TW3 (AY647994), D/UW3, H/UW4 (AY647999), and L2/434 for the cytotoxin locus; and A/HAR13, B/Jali20/0T, D/UW3, L2/434, and L2b/UCH-1/proctitis for the IGR upstream of ftsK. To detect recombination, we developed a program called Q-plotGenome that was written as a set of macros in the SAS software 9.2 language (SAS Institute, Inc., Cary, NC) to compare the genome sequences of L2c with those of reference strains L2/434 and D/UW3. The core of the program is similar to that of SimPlot except that it covers the entire 1-Mb genome instead of a discrete sliding window of limited size; it samples a series of fixed-length subsequences (windows) from one genome and then compares them to windows from the other genome. Q-plotGenome is, thus, a tool for comparing DNA sequences in the range of 1 Mb plus and for displaying results graphically. The description of Q-plotGenome is detailed in Text S1 in the supplemental material. To identify statistically significant recombination breakpoints or regions, SimPlot software 3.5.1 () was utilized as we have previously described. The parameters included a window size of 200 base pairs (bp), a step of 20 bp, neighbor-joining trees calculated using the Kimura-2-parameter distance model (60), and 1,000 bootstrap replicates to determine confidence for each branch (Fig. 7). For a global analysis, we used a version of the BLAST score ratio approach to identify recombinants. We aligned the databases of both (i) raw L2c sequences and (ii) 100-nt windows along the L2c chromosome sequence separated by 50 nt against the L2/434 genome as a reference and the other complete genomes listed in the previous section. Matches with a BLAST score ratio of <0.95 were plotted using Circos software (Fig. 5). For analysis of specific regions, nucleotide sequences were aligned by ClustalW 1.8, MUSCLE, or MAUVE. Gaps were removed using GBLOCKS with default parameters. Phylogenic inference and tree plotting were performed using the MEGA 3.1 package described previously or PHYLIP programs DNApars, Seqboot, and Consensus. Neighbor-joining trees were calculated using the Kimura 2-parameter model that assumes constant nucleotide frequencies and their rates of substitution among sites (60) and 1,000 bootstrap replicates. For detection of strain D-specific SNPs within the L2c data, we first identified SNPs between the D/UW3 and L2/434 genomes using the show-snps tool of the MUMmer package. We then mapped L2c against L2/434 using gsMapper 2.3 and extracted the number of "D"-like and "L2"-like nucleotides at each variant position from the 454AllDiffs.txt output using a custom script. Similar analyses were performed for D(s)/2923. The complete chromosome and plasmid sequences were submitted to the NCBI GenBank database (accession no. CP002024). The NCBI genome project identification number is 47581. The raw data from the 191,030 human screened L2c reads were deposited in the NCBI short read archive (sra; accession no. SRP002231). The sequence of the L2c toxin gene from the initial plaque purification was submitted to GenBank (accession no. 2981755).

PMC5694584_01

Female

An 82-year-old woman presented with a recent history of dysphagia and heartburn. She underwent upper endoscopy which demonstrated a fungating mass extending 10 cm in length and protruding into and filling the lumen. The edges were necrotic and biopsies were obtained from the base of the lesion. Histology showed discohesive, small to medium sized cells, arranged primarily in solid nests, with focal necrosis (Figure 1). Cytologically, the cells showed scant to moderate amounts of cytoplasm and eccentric, irregular nuclei with prominent nucleoli. There was focal pagetoid involvement of the overlying squamous mucosa (Figure 2). Immunohistochemical stains were performed and the neoplastic cells were negative for cytokeratin AE1/AE3, cytokeratin cocktail, synaptophysin, chromogranin, p63, thyroid transcription factor 1 (TTF-1), leukocyte common antigen, and other lymphoid markers while they were diffusely positive for CD56. This immunophenotype excluded the possibility of squamous cell carcinoma. Then, stains for malignant melanoma were performed and demonstrated that the neoplastic cells were focally positive for S-100 protein while other MM markers including Melan-A and SOX10 were diffusely positive (Figure 3). Based on the morphology and immunohistochemical phenotype, and the absence of a primary tumor elsewhere, a diagnosis of primary esophageal melanoma with aberrant expression of CD56 was rendered. Molecular testing did not reveal a V600E or V600K mutation in the BRAF oncogene or in the C-kit oncogene. A positron emission tomography (PET) scan was performed and highlighted the mass in the distal esophagus. It also revealed a 2 cm hypermetabolic liver lesion and hypermetabolic gastroesophageal lymph node (Figure 4). This PET scan also incidentally revealed bilateral hypermetabolic thyroid lesions. Fine needle aspiration of the thyroid nodules revealed papillary thyroid carcinoma. Chemotherapy was initiated with pembrolizumab, a monoclonal antibody that is given for metastatic or unresectable melanoma, but the patient's disease progressed with more extensive hepatic involvement by metastatic disease, and she died shortly thereafter.

PMC10019966_01

Male

A 73-year-old wheelchair-bound male, with a history of chronic right frontal lobe infarct with residual left-sided weakness, atypical parkinsonian syndrome, three-vessel coronary artery disease, non-ST segment elevation myocardial infarction, hypertension, hyperlipidemia, and neurogenic bladder, presented with weakness, imbalance, and gait disequilibrium beginning in 2008. Brain magnetic resonance imaging in January 2008 was remarkable for leptomeningeal and nodular enhancement in both cerebral hemispheres involving the frontal and parietal lobes, suggestive of frontoparietal pachymeningitis. He was also found to have midcervical myelopathy and underwent cervical spine laminectomy in 2009. There was some question of a dural fistula of the superior sagittal sinus, but a cerebral angiogram was negative for vascular malformation. An outside lumbar puncture in 2008 was reportedly normal. In 2010, the patient had an extensive workup including a lumbar puncture and serology, which was negative. Cerebrospinal fluid studies included Gram stain, fungal culture, acid-fast stain, tuberculosis culture, malignant cell cytology, serum protein electrophoresis, immunoglobulin G index, oligoclonal bands, myelin basic protein, cryptococcal antigen, and viral panel (herpes simplex virus, arbovirus, California encephalitis virus, Saint Louis encephalitis virus, western equine encephalitis virus, eastern equine encephalitis virus, and West Nile virus). Serology studies included the complete blood count with differential, angiotensin-converting enzymes, immunoglobulin G typing, erythrocyte sedimentation rates, C-reactive protein, antinuclear antibodies, cytoplasmic antineutrophil cytoplasmic antibodies, perinuclear antineutrophil cytoplasmic antibodies, atypical anti-neutrophil cytoplasmic antibodies, Lyme titers, rheumatoid factor, rapid plasma reagin, venereal disease research laboratory tests, viral cultures, and Sjogren's syndrome antibody testing. 24-hour urinary copper was also normal. Electromyography showed the right carpal tunnel and fifth lumbar radiculopathy. The patient declined a meningeal biopsy at that time and was given the presumptive diagnosis of idiopathic pachymeningitis. Following this workup in 2010, the patient had interval brain magnetic resonance imaging which was relatively stable but with some fluctuations in the leptomeningeal enhancements which, according to his daughter, appeared to correlate with clinical fluctuations in weakness and mobility. The patient's functional status gradually worsened from 2010 to 2012, as he was no longer able to drive or work in 2010. In 2011, he began having difficulty walking without a handrail and had intermittent falls once per year. He was treated at an outside hospital for a right frontal lobe stroke with residual left-sided weakness in 2012. Magnetic resonance imaging on presentation to our hospital in 2020 showed chronic deep white matter infarct in the right frontal lobe. The patient was also diagnosed with an atypical parkinsonian syndrome in 2013 and had follow-up at our Parkinson's and Movement Disorders Center through 2020, due to his neurologic examination showing flat affect, fluent but dysarthric speech, ideomotor apraxia, moderate hypomimia, mildly diminished downward ocular saccades, neck rigidity, asymmetric left-predominant bradykinesia, and postural instability. The patient was trialed on multiple treatments, including pramipexole, carbidopa-levodopa, and ropinirole without much improvement in his parkinsonian symptoms. He ultimately became wheelchair-bound in 2019. During hospitalization for sepsis and cardiogenic shock in January 2020, repeat brain magnetic resonance imaging showed further interval increase in the size and number of multiple heterogeneously enhancing dural base and leptomeningeal lesions compared to brain magnetic resonance imaging performed in October 2019 at an outside hospital (Figure 1). Of note, outside October 2019 imaging also showed an interval increase in leptomeningeal nodular enhancement compared to prior imaging in 2017. The lumbar puncture was unremarkable. Magnetic resonance imaging of the cervical and thoracic spine showed only some age-related changes. Chest computerized tomography did not show any abnormalities related to possible sarcoidosis. The patient subsequently underwent a brain biopsy in September 2020, which showed granulomatous pachymeningitis without necrosis, suggestive of neurosarcoidosis. He then received treatment with 3 months of prednisone 60 mg daily from October 2020 to January 2021, discontinued after lack of symptomatic improvement in his weakness and mobility in addition to development of leg swelling. Further treatment with dexamethasone and disease-modifying therapy was offered. However, after discussion, the patient, his family, and the care team ultimately agreed not to proceed given his comorbidities and age.

PMC6198577_01

Male

86-year-old man with a history of hypertension and type 2 diabetes mellitus had been treated for end stage kidney disease with continuous cycling peritoneal dialysis since February 2017. He presented to the home dialysis unit complaining of difficulties with initial drain alarms on his cycler for the last 2 nights and "whitish" dialysate. He denied abdominal pain or constitutional symptoms aside from weight loss associated with resolution of peripheral edema. He did not have any previous episodes of peritonitis or history of TB contact. His examination was unremarkable including normal vital signs and lack of abdominal tenderness. As per out unit peritonitis protocol, 1L of 2.5% Dianeal was allowed to dwell for 2 hours and the effluent was sent for analysis including cell count, differential, bacterial, and mycobacterial cultures. Given the "milky" appearance of the fluid, triglycerides were also ordered. He received empiric intraperitoneal antibiotics including ceftazidime and vancomycin. Total nucleated cell count was 354 * 106/L with 87% lymphocytes, 8% monocytes, and 3% neutrophils. Cultures were negative. Triglyceride (TG) concentration was 6.3 mmol/L (557 mg/dl). Based on the elevated TG concentration he underwent a CT scan with contrast of the abdomen and a second dialysate sample was sent for cell count, TG, cytology, and flow cytometry (the dialysate was no longer cloudy). He was found to have a mildly enlarged spleen and multiple enlarged lymph nodes in the mesentery, retroperitoneum, and inguinal regions including a cluster of enlarged nodes forming a conglomerate retroperitoneal mass suggestive of lymphoma. There was a moderate increase in density of the mesentery, possibly on the basis of lymphatic obstruction. His total nucleated cell count remained elevated at 420 with 96% lymphocytes; TG concentration was only 0.21 mmol/L. Cytology was negative for malignant cells. Flow cytometry of the dialysate showed predominately monotypic B cells with lambda light chain restriction that coexpressed CD20 and CD19 but lacked CD5 and CD10 suggestive of a monoclonal lymphoid process. An inguinal lymph node biopsy revealed predominant diffuse to nodular pattern of small monotonous lymphocytes, suggestive of B cell lymphoma. Immunohistochemical stain was positive for CD20 (diffuse), BCL2 (diffuse), and few remaining CD21 (FDC). It was negative for CD3, CD5, CD10, CD23, and C43. Kappa and lambda stains were nonspecific. Ki67 proliferation index was less than 5%. Final diagnosis was monoclonal B cell lymphoproliferative disorder, likely of low grade. He is being followed by the malignant hematology team, with no active treatment. From a PD perspective, the patient had no further episodes of chylous ascites and remains on CCPD.

PMC4078420_01

Female

A 34-year-old woman presented with 1-month history of intermittent right flank pain and occasional fever. Two-months earlier she had one episode of gross hematuria. Clinically, a ballotable and bimanually palpable vague lump was appreciated in right hypochondrium. She did not have any history of pulmonary TB in the past. A marginally elevated erythrocyte sedimentation rate was noted. Although urine culture was sterile, 10-12 pus cells were seen on microscopic urine examination. Chest X-ray was normal. Contrast-enhanced computed tomography (CECT) showed a heterogeneously enhancing lesion 8 x 7 cm in dimension with areas of necrosis, involving the right kidney with enlarged aortocaval and paraaortic lymph nodes [Figure 1a and b]. Right renal vein and inferior venacava were normal. She then underwent right radical nephrectomy [Figure 2]. Histopathology showed presence of acid-fast bacilli with multiple granulomas consistent with GUTB [Figure 3a and b]. Postoperatively we started oral antitubercular therapy. Patient recovered well, completed her antitubercular therapy, and after 1 year of follow-up she is free of TB.

extrapulmonary tuberculosis, genitourinary tuberculosis, pseudotumor, renal cell carcinoma

PMC6057280_01

Male

A 50-year-old male with no past medical history presented to the hospital with one week of painless blurry vision of the right eye. He had also been having intermittent fevers, headache, body aches, and a nonpruritic maculopapular rash on the bilateral lower extremities for 6 months. On further review of systems, the patient noted one isolated episode of left knee swelling as well as testicular swelling in the past. The patient otherwise denied any neck stiffness, nausea, vomiting, Raynaud's phenomenon, oral ulcerations, chest pain, shortness of breath, abdominal pain, or photosensitivity. He worked as a flooring installer, and he did not have any toxic habits such as smoking, drinking, or illicit drug use. The patient's vital signs were normal. On physical exam, the patient was found to have bilateral papilledema and optic nerve erythema, right greater than left, right inferior nasal quadrant visual field defect, and a right afferent pupillary defect. Muscle strength was 5/5 throughout, and reflexes were 2+ throughout. Sensation to light touch, pinprick, vibration, and proprioception was intact. The bilateral lower extremities demonstrated a maculopapular rash (Figure 1). The admitting labs were notable for a microcytic anemia (Hb 11.6 gm/dL (ref 13.6-17.3); Hct 35.3% (ref 39.8-50.7); MCV 76.9 fL (ref 80.3-98.1)), hyponatremia (133 mmol/L (ref 136-144)), elevated ESR (33 mm/hr (ref 0-15)), and elevated CRP (13.3 mg/L (ref 0.0-7.0)). Urinalysis did not show protein or blood. Lumbar puncture was colorless/clear with 2/cumm RBC (ref 0), 56/cumm WBC (ref 0-9), 39% segmented neutrophils (ref 0-2), 53% lymphocytes (ref 40-80%), 30 glucose (ref 40-70), 69 protein (ref 15-45), with presence of oligoclonal bands, an elevated IgG index (+19.8 mg/24 hr (ref -9.9 to +3.3)), and normal opening pressure (16 cm H20 (ref 10-25 cm H20)). The initial CT scan of brain and orbits demonstrated no acute intracranial process, and the MRI of the orbits was also unremarkable. Given the patient's history of fever, myalgia, rash, and joint pain with CSF studies showing both a neutrophilic and lymphocytic pleocytosis, there was concern for infectious etiologies, including both bacterial and viral infections, as well as autoimmune etiologies. The differential diagnoses included neuromyelitis optica, multiple sclerosis, neuropsychiatric SLE, HIV, syphilis, tuberculosis, coccidioidomycosis, cryptococcus, Lyme, and West Nile virus. Further investigation was pursued to work up the aforementioned etiologies, and the patient was found to have a positive double-stranded DNA (>1 : 640), low C4 (10 mg/dL (ref 16-47)), low CH50 (13 U/mL (ref 31-60)), normal C3, negative ANA by immunofluorescence assay (repeated twice) and negative anti-Sm/RNP, anti-SSA/B, Coombs antibody, anti-beta2 glycoprotein, anticardiolipin, and lupus anticoagulant. ANCA, ACE, and cryoglobulin were negative. Rheumatoid factor was positive (38 IU/mL (ref < 14)). The infectious disease service was consulted, and the infectious workup including HIV, hepatitis antibodies, cocci antibodies, RPR, cryptococcus antibodies, Lyme antibodies, West Nile virus antibodies, and Quantiferon Gold were all negative. CSF cultures showed no growth. Skin biopsy of the lower extremity rash was done, pending results. The presence of a high-titer positive double-stranded DNA antibody raised concern for an autoimmune etiology, although in the setting of a negative ANA the validity of the dsDNA titer was questioned with a high concern for a false-positive test. Given the lack of other findings to suggest autoimmune disease, the rheumatology service requested additional studies. Given the negative infectious workup to date, the neurology service recommended initiation of pulse corticosteroids with methylprednisolone 1,000 mg intravenous daily for which the patient received 2 doses, with improvement in his symptoms, which was then followed by oral prednisone taper. Approximately one week later, the patient returned to the hospital with acute onset right arm weakness and numbness. On physical exam, the patient was found to have 4/5 muscle strength in the right upper extremity with decreased sensation to light touch over the fourth and fifth digits of the right hand. MRI of the brain showed multiple subacute infarcts in the left parietal lobe (Figure 2). CT angiogram of the brain was negative. Furthermore, the results of skin biopsy had returned demonstrating leukocytoclastic vasculitis (Figure 3). With these new clinical, radiographic, and pathologic findings, there was concern for a CNS small vessel vasculitis possibly secondary to SLE given satisfaction of SLICC criteria which included low C4 and low CH50, high-titer double-stranded DNA, maculopapular rash of the lower extremities, and bilateral papilledema and erythema resulting from cranial neuropathy of the optic nerves. SLICC criteria require that there be greater than or equal to 4 criteria met including at least 1 clinical and 1 laboratory criteria. The patient's history of knee swelling also raised concern for synovitis, although this did not meet the SLICC criteria explanation for synovitis as our patient demonstrated swelling in only one joint, and SLICC criteria require synovitis in two or more joints. Other etiologies such as embolic phenomenon from endocarditis or paraneoplastic syndrome were considered; as a result, blood cultures were sent, and ECHO was done showing no valvular vegetations. Blood cultures had shown no growth x 5 days. As a result of the above workup, the patient was given a working diagnosis of neuropsychiatric SLE (NPSLE) with new onset neurologic changes, and he was treated with pulse dose methylprednisolone 1 gram for a total of five days with prednisone taper as well as one induction dose of intravenous cyclophosphamide 1,000 mg. After the patient was discharged, the blood cultures that had been initially reported as no growth, were later found to have 2/4 bottles positive for Gram-variable bacteria. The cultures were sent to Public Health for confirmation, and the organism was speciated as Brucella melitensis by PCR. Subsequently, the patient was readmitted to the hospital and confirmed to have positive Brucella serologies including total antibody titer (1 : 320 (ref < 1 : 80)), IgG (6.99 (ref < 0.80)), and IgM (1.42 (ref < 0.80)). Brucella bacteremia, positive Brucella serum serologies, and clinical presentation with subacute stroke were all consistent with a diagnosis of neurobrucellosis. On further history, the patient noted to have eaten unpasteurized cheese in Mexico 6 months prior which was thought to be the source of infection. The corticosteroids were tapered off, no further doses of cyclophosphamide were given, and the patient was given four weeks of intravenous ceftriaxone as well as three months of oral doxycycline and rifampin. On follow-up, the patient's serum Brucella IgM became negative, repeat blood cultures showed no growth, and repeat lumbar puncture demonstrated resolution of pleocytosis. The patient's symptoms of weakness, blurry vision, headaches, intermittent fevers, and body aches resolved. The patient's visual acuity returned to normal, and the papilledema resolved, but the patient was noted to have some residual optic nerve atrophy.

PMC9744598_01

Female

A 10-year-old Native American girl from northern New Mexico presented with a 5-month history of intermittent neck, right arm, and shoulder pain with progressive right arm weakness. Approximately one month prior to admission, she developed left leg weakness causing multiple falls weekly, progressive visual changes, and aphasia. The girl was afebrile and well appearing. She demonstrated weakness in her right deltoid, bicep, and hand. Right-sided pronator drift, Hoffmann's reflex and Babinski's reflex, and narrow-based gait were noted. No skin nodules were seen. Her peripheral white blood cell count was 14.8 cells x 103/muL, with 88% polymorphonuclear cells, 9% lymphocytes, and 3% monocytes. Contrasted magnetic resonance imaging (MRI) of the brain was unremarkable. A contrasted MRI scan of the cervical spine revealed a 2.8 cm anterior intradural, extramedullary enhancing mass without restricted diffusion. A dural tail, centered at the level of the fifth cervical vertebra, was present, with enhancement and cord compression (Figure 1). Angiography demonstrated patent major cervical arteries. Testing for tuberculosis, Coccidioides immitis, Bartonella henselae, Histoplasma spp., and Cryptococcus spp. was negative. A chest X-ray scan was unremarkable. C-reactive protein, erythrocyte sedimentation rate, and lumbar puncture were not obtained at admission. The patient underwent resection of the mass, with resultant anterior C5 and C6 corpectomies, C4-C5 and C6-C7 discectomies, and C4-C7 arthrodesis. The lesion was extremely adherent to the dura, requiring dissection and mobilization from the nerve root and spinal cord. Histopathology demonstrated fibrous tissue with caseating granulomas, with negative Fite's, Grocott-Gomori methenamine silver (GMS), and Gram stains. On postoperative day nine, a large pseudomeningocele developed in the neck, which improved following insertion of a lumbar drain. The patient resided in an area likely endemic for O. lupi. Black flies of the Simulium genus reside in the state along the Rio Grande river, with increased numbers noted during warm weather months. However, our patient denied exposure to putative risk factors for this infection (no exposure to bodies of freshwater, to areas where there are dogs with ocular disease, or to black fly bites). Initially, no helminth was seen, but a tissue specimen was sent to the Centers for Disease Control and Prevention. Fragments of inflamed, dense fibrous connective tissue contained abundant granulomas with irregular borders and areas of central necrosis. Intervening stroma contained strands of inflammatory infiltrates comprising plasma cells and macrophages, admixed with hemorrhage and occasional eosinophils. Within a few fragments of tissue were remnants of foreign material compatible with the cuticular wall of a degenerating nematode (Figure 2), for which morphological details could be emphasized using a trichrome stain. The outer cuticular ridges were dome-shaped and consistent with filariae in the genus Onchocerca. Other features typical of Onchocerca spp. that were evident included a thick hypodermis, weakly developed muscle cells rather vacuolated in appearance, and broad lateral chords. Longitudinal sections of the cuticular wall revealed two inner striae per ridge, morphologically compatible with O. lupi, likely damaged by host immune response (Figure 3). No microfilariae were identified. The polymerase chain reaction test of these anatomic specimens definitively confirmed the species' identity as O. lupi. The patient was treated with a single dose of ivermectin (12 mg), followed one week later by a six-week course of doxycycline (200 mg once daily). After completing a 26-day hospital stay (with 21 days postoperatively in the pediatric intensive care unit), she was discharged with slightly decreased strength in her right arm. She returned to a normal neurological examination at a two-month follow-up visit in the infectious disease clinic. A contrasted MRI scan and plain films of the cervical spine five months after discharge revealed only postsurgical changes.

PMC4427073_01

Male

We present a case of a 32-year-old immunocompetent Iranian male who presented to the emergency room with a generalized tonic-clonic seizure lasting for 3 minutes. He denied any history of trauma, fever, or previous seizures. Furthermore, he did not have any genitourinary symptoms, including dysuria, hematuria, or penile discharge. A computerized tomography (CT) scan of the head failed to show any acute central nervous system insult. After that, the patient was admitted to the hospital. Prior to this admission, he gave history of an admission 12 months ago to a hospital outside the country, where he complained of fatigue, weight loss, and fever. Reports from the hospital showed that he also had chronic moderate ascites and a left pleural effusion. However, several laboratory and imaging tests were done and it was concluded that there was no evidence of infectious disease, chronic liver disease, or malignancy. It was recommended that he may need more investigations or a laparoscopy with peritoneal tissue biopsy, which was not done. Upon the latest admission, the respiratory rate was 12 breaths per minute, the body temperature was 36.9 C, and the blood pressure was 112/70 mmHg. The patient had mild tachycardia of 109 beats per minute. Physical examination was unremarkable including the respiratory system examination. Digital rectal examination was not performed since the patient did not have any genitourinary or gastrointestinal symptoms. During this hospitalization, the patient received anti-epileptic treatments and multiple investigations were done. The laboratory investigations, urine routine and microscopy, cultures, virology screen, including human immunodeficiency virus, as well as the autoimmune markers did not show any significant issues. Also, three sets of sputum acid-fast bacilli smears were done, which were all negative. Further invasive tests were performed including endoscopy and colonoscopy which were unremarkable. A lumber puncture was also performed with a normal initial pressure, 0 mm3cell count, glucose of 4.1 mm per liters, and protein of 764 mg per liter. At the same time the serum glucose was 6 mmol per liter. A magnetic resonance image of the brain was done concluding multifocal enhancing foci suggestive of an infective process (Figure 1). Due to his previous history, CT-chest, abdomen, and pelvis were also done. The chest-CT was unremarkable. The abdominal CT showed mild peritoneal ascites with evidence of mild splenomegaly. The ascetic fluid taken was translucent and yellow in color and the serum-ascites albumin gradient 5 gram per liter (0.5 gram per deciliter). Furthermore, the analysis was negative for Ziehl-Neelsen, gram stain, and culture. The pelvis CT also showed an enlargement of the prostate and a right prostate lesion extending to the seminal vesicles (faint ring enhancing lesion measuring 3x2.7x3 cm) (Figure 2). The case was discussed with the patient and he agreed to start anti-tuberculosis treatment and to have a trans-rectal biopsy of the prostate. The biopsy showed multiple slides of necrotizing granulomata suggestive of tuberculosis (Figure 3). Ziehl-Neelsen stain was also performed, and the diagnosis of miliary tuberculosis was confirmed (Figure 4). He was started on anti-tuberculosis therapy with isoniazid, rifampicin, ethambutol, pyrazinamide, and pyridoxine for 12 months. At follow-up the prostate biopsy tubercle bacilli culture result came back positive. The patient was asymptomatic with a normal physical examination and laboratory tests with no drug side effects.

complication, disseminated, miliary, prostate, tuberculosis

PMC4719901_01

Male

A 41 year old male, with a past medical history of HIV with no recent CD4 count, was admitted with a several month history of fatigue, night sweats, anorexia, painful swallowing with ulcers over the upper lip, and painful draining ulcers in inter-gluteal fold. On physical exam, these ulcers were noted to have a purulent discharge, with erythema of the surrounding skin. He was also found to have painful pretibial nodules and oral thrush. Chest examination included normal breath sounds and regular heart sounds. The abdominal examination was non-tender and soft with normal bowel sounds. The initial impression was cutaneous herpes involving perianal skin and lips, with a bacterial superinfection. Odynophagia was attributed to possible candidal esophagitis versus herpes esophagitis. Accordingly, treatment with acyclovir, fluconazole, vancomycin and piperacillin/tazobactam was initiated. Serologies for FTA-ABS for syphilis were found to be positive, with an RPR titer of 1:4, and weekly treatment for latent syphilis with benzathine penicillin was started for duration of three weeks. Empiric treatment for Lymphogranuloma venereum (LGV) was begun with doxycycline. CD4 count was 78, and therefore, prophylaxis for PCP was initiated with atovaquone, as the patient had an allergy to trimethoprim/sulfamethoxazole. At this time HAART therapy was initiated as well. Eventually serologies for Chlamydia trachomatis, Neisseria gonorrhoeae, LGV serology, and acid fast smear for TB were negative. Our patient's condition improved with antibiotics and the patient was discharged with antiretroviral therapy and scheduled for a follow up as outpatient. Two months later the patient was readmitted with perianal ulcers, and multiple painful oral ulcers. The largest ulcer was measured at 10 mm x 7 mm in diameter; at this time a differential diagnosis of ulcers secondary to an HSV infection and oral thrush was considered. The patient was noncompliant with the antiretroviral medications since discharge from the hospital. His CD4 count at this time was less than 20, HAART medications were resumed during at admission. The patient was started on fluconazole for possible candidal esophagitis, acyclovir for cutaneous herpes, and primary antimicrobial prophylaxis for pneumocystosis and toxoplasmosis. Upper endoscopy was done, and showed a large 5 cm deep ulcer in the lower esophagus. The patient went for colonoscopy that showed active GI bleed from the descending colon. Patient had technetium-labeled red blood cell bleeding scan which was negative. Angiography was performed which did not reveal any actively bleeding vessel but during the procedure the patient developed massive lower gastrointestinal bleeding, requiring 20 units of transfused blood. He underwent subtotal colectomy with ileostomy and a PEG tube was placed for feeding. Biopsy of esophagus showed mild acute and chronic inflammation. Biopsy from duodenum, stomach and esophagus was negative for fungal elements, HSV1, HSV2, and CMV PCR. Colon biopsy showed punched out ulcers, associated with monocytic inflammation, vasculitis with thrombi, mural necrosis with histiocytes and lymphocytes in the vascular wall. A diagnosis of Behcet's disease, along with Behcet's colitis was made based on the histopathology findings and the correlating clinical history. Subsequently treatment with colchicine twice a day was initiated for mucocutaneous manifestations of Behcet's disease until resolution of symptoms.

aids, behcets, hiv

PMC9958272_01

Male

Here, we present a 69-year-old male patient who resides in southern Saudi Arabia and works as a farmer. His past medical history includes uncontrolled type II diabetes and laparoscopic cholecystectomy one year prior to presentation. He presents to the emergency department on (day 0), with a two-week history of left lower abdomen pain, a one-year history of intermittent fever, and weight loss. Initially, abdominal examination revealed paraumbilical and left lower quadrant tenderness with distension but no organomegaly and other systems where unremarkable. Laboratory investigations showed leucocytosis 22.95 * 10^9/L with a differential of neutrophilia and eosinophilia (21.7 %), Haemoglobin of 126 g/L,Platelets of 518 * 10^9/L,C-reactive protein 262.48 mg/L (rest of labs were normal). Abdominal x-ray showed faecal impaction, nonspecific distribution of bowel gases, no air under diaphragm and no signs of bowel obstruction. CT abdomen and pelvis with contrast showed multifocal segmental wall thickening in the distal ascending, proximal transverse, and distal descending colon, with fluid collections suggesting concealed perforations (day 0). The patient was admitted to the general surgery unit with a diagnosis of severe diverticulitis, and he was started on Piperacillin/Tazobactam and maintained nothing by mouth. The patient's symptoms worsened, and he had blood-stained stool. As a result, CT abdomen and pelvis with contrast was repeated, demonstrating recurrence of multifocal segmental wall thickening involving the hepatic flexure, proximal transverse, and distal descending colon, as well as evidence of concealed perforation and interval increase in size of surrounding collections (day 4). Overall findings were suggestive of severe diverticulitis versus aggressive infections like basidiobolomycosis and actinomycetes (Fig. 1, Fig. 2, Fig. 3). Infectious diseases team was involved after release of the second abdominal CT result and recommended for surgical intervention, obtaining biopsy for bacterial, TB, fungal cultures, and histopathology in addition to an empiric start of liposomal amphotericin B, Amoxicillin/Clavulanic acid and tigecycline. Although kept on broad spectrum antimicrobial agents, patient condition worsened, and he was persistently febrile. His white blood cells increased to 31.7 * 10^9/L with absolute eosinophils count increased to 3.58 * 10^9/L. His haemoglobin dropped to 10 g/dL therefore, a third abdominal CT with contrast was arranged that revealed redemonstration of circumferential wall thickening of the colon but interval increase in size of fluid collection measuring approximately 7.9 x 9 cm, compared to 7.7 x 9.1 cm as well as interval increase in abdominopelvic ascites with surrounding inflammatory changes (day 8). The patient was taken to operation room and found to have faecal peritonitis due to multiple colon perforation at sigmoid, transverse, and descending colon with small bowel adhesion and adhesions between small bowel and transverse colon. Adhesolysis was done in addition to total colectomy and end ileostomy was created with placement of two drains (day 9). After the operation, the patient was transferred to intensive care unit (ICU) for close monitoring and observation. Interestingly, his absolute eosinophils count dropped immediately after surgery and reached down to 0.08 * 10^9/L. While being in ICU, the patient's haemoglobin dropped to 69.0 g/L, and he was started to inotropic support and transfused several units of packed red blood cells. He maintained minimal ventilator settings with minimal respiratory secretions. Abdominal and pelvic CT was repeated two days after surgery and showed no collection found. Bacterial tissue culture showed heavy growth of Pseudomonas aeruginosa and carbapenem resistant Klebsiella variicola. Blood culture from the central line, showed Bacteroides fragilis. Fungal tissue culture showed Candida glabrata. Histopathology showed extensive inflammation involving the full thickness of the colon tissue and extended to the serosal surface. The inflammation consists of mixed inflammatory cells along with sheets of eosinophils and multiple foci of fungal microorganism. The fungal microorganisms are hyphae that are irregularly branched, thin walled, occasionally septated and surrounded by thick eosinophilic cuff splendore-Hoeppli phenomenon (Fig. 4, Fig. 5, Fig. 6). Despite surgical intervention, continuing liposomal amphotericin B 5 mg/kg IV once per day, Itraconazole 200 mg orally twice per day and modifying antibacterial agents; patient's condition deteriorated and passed away due to refractory septic shock.

basidiobolomycosis, eosinophilic colitis, gastrointestinal basidiobolomycosis, splendore–hoeppli phenomenon

PMC4026146_01

Female

An 11-year-old Caucasian girl was evaluated in an outside emergency department after a 4-day history of tachycardia, shortness of breath, wheezing, and tachypnea. She was treated for presumed pneumonia and started on antibiotics. After 24 hours of persistent tachycardia (160-190 beats per minute) she was transferred to our academic institution for further treatment and evaluation. Review of systems revealed no heat intolerance, diaphoresis, tremor, weight loss, difficulty sleeping, or fatigue, but she did report recent onset of diarrhea and decreased oral intake. Notably, the patient felt that her tachycardia had begun only 4 days prior to admission. Upon her arrival, thyroid function tests were performed and revealed a markedly elevated free T4 (>6 ng/dL), elevated T3 (>500 ng/dL), and suppressed TSH (<0.01 mIU/L). Review of her records revealed that a TSH measured by her primary care doctor 3 months before admission was suppressed (TSH <0.08 mIU/L). Pertinent findings on her initial physical exam included blood pressure (BP) 136/67, heart rate (HR) 132, temperature 36.6 C, height 144 cm (20th percentile), and weight 36 kg (20th percentile). There was no proptosis or exophthalmos. She had mild flattening of the face and micrognathia. Her thyroid was diffusely enlarged, smooth, and firm with no palpable nodules. A thyroid bruit was not appreciated. She had slight tremor of her hands at rest. Given her thyroid function studies and physical exam findings, she was presumptively diagnosed with Graves disease and was prescribed propranolol 10 mg 4 times daily (1.25 mg/kg/day) and propylthiouracil (PTU) 50 mg 3 times daily (4.7 mg/kg/day). Notably, this case occurred prior to the Food and Drug Administration's (FDA) release of a black box warning for PTU secondary to liver toxicity. Thyroid autoantibody assays were ordered and she was discharged from the hospital the following day with instructions to follow up with Pediatric Endocrinology. Thyroid autoantibody testing confirmed the diagnosis of Graves disease. Thyroid binding inhibiting immunoglobulin assay (TBII) was markedly elevated at 51% (16% or less), thyroid-stimulating immunoglobulin (TSI) assay was normal at 98% (0-129%), thyroid peroxidase antibodies were elevated at 835.1 IU/mL (<3.9), and thyroglobulin antibodies were negative (<1:100). A thyroid uptake scan was not performed given the unequivocal laboratory values. The patient returned to the Pediatric Endocrinology clinic 4 days after hospital discharge. The family noted increasing difficulty administering 2 different medications multiple times per day. As such, the relative risks and benefits of continued anti-thyroid medication versus surgery versus RAI were discussed. Because the patient and her mother eagerly sought more definitive therapy, she was referred to our radiation oncology colleagues and scheduled for RAI ablation. She remained on propranolol for treatment of her symptoms, but PTU was discontinued. Eight days later, the patient received 10 mCi of I-131 as an oral tablet for thyroid ablation. Vital signs measured prior to ablation revealed temperature of 36.2 C, HR 101, and BP 129/55. The following morning she reported being unusually sleepy and became increasingly unresponsive over the next 2-3 hours. She was transported to the closest emergency department and was intubated upon arrival due to hypopnea. Shortly after intubation, she had a tonic-clonic seizure and was given 1 mg intravenous lorazepam. Blood samples drawn just prior to her seizure demonstrated serum glucose 38 mg/dL (treated with intravenous dextrose) and potassium 6.5 mmol/L (treated with sodium polystyrene sulfonate and furosemide). A computed tomography scan of her head was performed and was normal. She was transferred to the Pediatric Intensive Care Unit at our institution for additional evaluation and treatment. Pediatric Endocrinology was again consulted for management of her Graves disease and evaluation for possible thyroid storm. Pertinent findings on physical exam included temperature 37.2 C, HR 158, BP 96/57, and endotracheal tube in place. She was not sedated, but was not fully coherent. Her thyroid remained diffusely enlarged and firm without bruit. She had tachycardia with no murmur, and was noted to have mild upper right extremity weakness. Repeat thyroid function tests revealed persistently elevated free T4 (>6 ng/dL), elevated T3 (>500 ng/dL), and suppressed TSH (<0.01 mIU/L). Serum cortisol and ACTH levels were measured to assess for adrenal insufficiency and stress-dose hydrocortisone was provided given the history of hypoglycemia and hypotension and the known association of relative adrenal insufficiency with thyrotoxicosis. Given the combination of her Graves disease, I-131 therapy, and seizure, a presumptive diagnosis of thyroid storm was considered, although she was afebrile, somewhat hypotensive, and had only mild tachycardia. Low-dose intravenous propranolol was initiated with plans to titrate as needed to control her heart rate. MRI was obtained to evaluate her right extremity weakness and revealed diffuse, abnormally increased FLAIR signal with associated cerebral edema throughout the left and right cerebral cortex and subcortical gray matter, as well as patchy areas of involvement in the left parietal lobe, left parafalcine occipital lobe, left and right temporal lobe, and right uncus and parahippocampal gyrus. The following day the patient became febrile and had a second seizure. Hydrocortisone (100 mg intravenous every 6 hours), propranolol (150 mg every 8 hours), PTU (150 mg every 6 hours), and supersaturated Potassium Iodide (SSKI) (6 drops orally every 6 hours) were given for the treatment of thyroid storm. Ten days after her admission, she developed elevated liver enzyme concentrations and was transitioned from PTU to methimazole. Her clinical status improved rapidly and she was extubated 48 hours after admission. She continued to have right-sided weakness and aphasia that improved throughout the remainder of her admission. She was discharged home approximately 1 month after her I-131 ablation with free T4 2.77 ng/dL (0.93-1.7) and T3 245 ng/dL (80-200). Notably, she developed additional elevations of her liver enzyme concentrations while taking methimazole and eventually had to discontinue use of both PTU and methimazole. Her T4 and T3 concentrations remained markedly elevated for nearly 2 months before demonstrating a trend towards normalization. She finally achieved elevation of her TSH at 8 months after ablation. Additional review of her imaging confirmed that the stroke affected the middle cerebral artery distribution of her left cerebral hemisphere. During the first year after her thyroid storm she required therapy for a seizure disorder as well as occupational, speech, and physical therapy. Five years after her thyroid storm, she continued to have some difficulty with memory and data integration but continues to make progress academically, socially, and developmentally.

graves disease, hyperthyroidism, iodine radioisotopes, pediatrics, thyroid storm

PMC3338235_01

Female

A 21-year-old college student presented to a tertiary care hospital with history of on and off low-grade fever for 3 months and abdominal pain for 1 week. She had no history of cough with weight loss or facial rashes. On admission, she was conscious but anxious and pale. She had blood pressure on the lower side of normal with distended abdomen. Both tuberculosis and vasculitis like systemic lupus erythematosus (anti-dsDNA, anti-sm-RNA) were ruled out in view of low-grade fever with abdominal pain. Erect X-ray and abdomen ultrasonography were normal. On the third day of hospital admission, she developed septic shock (mean blood pressure <65 mmHg) with altered sensorium for which she was intubated and transferred to the intensive care unit (ICU). Magnetic resonance imaging of head, cerebrospinal fluid study and serum sodium level (137 mmol/L) were all within normal limits. She had leukocytosis (21,000/cmm), anemia (5 gm/dL), thrombocytopenia (20,000/cmm) and deranged liver function tests (prothrombin time 6 s prolonged). Echocardiography showed mild diastolic dysfunction with ejection fraction >60%. She was managed conservatively with fluids, sedation, noradrenaline (0.5-3 mug/kg/min), vasopressin (0.01 U/min) infusion, broad-spectrum antibiotics and platelet and packed cell transfusion. Several blood and endotracheal tube aspirate cultures were sterile. On the fifth day, repeat ultrasonography of the abdomen revealed thickened and dilated nonobstructed bowel loops with coarse hepatic echo-texture. The gastro surgeon refused active management fathoming patient's prolonged shock. Since ICU admission, she had high nasogastric aspirates with feed intolerance despite the use of prokinetics; however, she started accepting nasogastric feeds on day 6. But, after a few hours of enteral feed, she developed rapidly rising intraabdominal pressure (>18 mmHg) with sudden deterioration in hemodynamics and increasing metabolic academia and hyponatremia (serum sodium 124 mmol/L). She passed large amounts of fresh blood-mixed loose stools, which was later found to be negative for Clostridium dificile. Bedside abdominal ultrasonography suspected presence of air shadows within the hepatic portal vein. Urgent computed tomography (CT) scan abdomen revealed pneumatosis intestinalis of the small bowel with dilated bowel loops [Figure 1] and gas in portal venous system [Figure 2]. In a setting of prolonged septic shock, vasopressor support and metabolic acidosis, the clinical and radiological picture was that of mesenteric ischemia. Exploratory laparotomy, done immediately, showed multiple areas of gangrenous patches and dusky discoloration of the jejunum with air bubbles in the subserosa. The major mesenteric vessels were pulsating and there was no evidence of thrombus, atherosclerosis or visible occlusion. No bowel perforation was detected. In view of extensive distribution of gangrenous patches, the surgical team released the intrabowel pressure by surgical incisions in the wall of the jejunum so as to reduce the increasing distension. She succumbed within 4 h of operation. Postmortem examination could not be conducted as consent was not available.

enteral feeding, nonocclusive mesenteric ischemia, vasopressin

PMC3280479_01

Male

The patient was an 82-year-old man with a past medical history of tuberculosis of the spine, treated 50 years earlier. He had an episode of acute gallstone pancreatitis in 2004 that was treated conservatively, and subsequently refused surgical intervention for his gallstone disease. He had no other significant medical history and did not consume alcohol or smoke. He presented with an acute onset of severe bilateral lower limb pain associated with paresthesia for one day's duration. He also complained of mild epigastric pain, abdominal distension and nausea for two days prior to the onset of lower limb pain. There was no previous history of claudication or cardiovascular risk factors such as family history, hyperlipidemia, or diabetes mellitus. Physical examination revealed pale and cold lower limbs up to the level of mid thigh bilaterally with pulses absent in the posterior tibia, dorsalis pedis and the popliteal arteries bilaterally. Capillary refill was delayed to 5 s bilaterally. There was tenderness on deep palpation and mild guarding over his epigastrium associated with some abdominal distension with sluggish bowel sounds. Laboratory investigation revealed leukocytosis (23.6 x 109/l), markedly elevated serum amylase levels (2,450 U/l) and lipase levels (5,265 U/l), high creatine kinase levels (8,556 U/l), and the arterial blood gas picture showed metabolic acidosis. Liver function revealed mild transaminitis and raised alkaline phosphatase (229 U/l) and a bilirubin level of 38 U/l. C-reactive protein was also elevated (45.6 mg/l). Ranson score was 5 on admission. In view of his findings, the diagnosis of acute pancreatitis and bilateral lower limb ischemia complicated by rhabdomyolysis was made. Computed tomography of the abdomen revealed findings consistent with acute severe pancreatitis associated with choledocholithiasis and cholelithiasis. Computed tomographic angiography revealed occlusion of the left superficial femoral artery as well as the bilateral popliteal, tibial and peroneal arteries (fig. 1). He was admitted to the surgical intensive care unit for management and started on intravenous fluids, antibiotics, and heparin, and was kept on a nil-by-mouth regime. The patient was offered bilateral above-knee amputations, which he initially refused. He improved clinically with these supportive measures, and the ileus resolved. Laboratory indicators also improved with normalization of liver enzymes, amylase levels, creatine kinase levels and blood gases (fig. 2). Ranson score at 48 h was 7. However, the ischemia of his lower limbs worsened and necessitated bilateral above-knee amputation during the same hospital admission. He recovered uneventfully post-operatively and was discharged well.

acute limb ischemia, acute pancreatitis, arterio-pancreatic syndrome

PMC5207469_01

Female

Very briefly, we would like to introduce our case report as follows. Mrs A, a 28-year-old woman, was admitted to the Department of Psychiatry in our hospital because of recurrent depressive episodes and aggravating compulsive behaviors. Two years prior to admission, this patient developed her first depressive episode after breaking up with her ex-boyfriend. Thereafter, this patient became depressed and had insomnia, loss of appetite, and loss of interest. Meanwhile, she began to repetitively tidy up her belongings and check whether the windows and doors were closed. There was no suicidal ideation reported at that moment and she could still adhere to the work as a bank staff. However, pressure at work made her situation worse. Her obsessive behaviors gradually aggravated, with repetition rate remarkably increasing from several times per day to dozens of times per day. The obsessive behaviors always worsen when her mood became labile. This patient became easily upset and agitated when being persuaded by her family members. About half a year prior to admission, this patient reported the first suicidal attempt after fighting with her parents. She went into emotional outburst, stood at the window, and claimed to end her own life. Her parents even kneeled on the floor to take her out of committing suicide. Since then, she had reported repetitive suicidal attempts. She would rush to the balcony or windows and would attempt to commit suicide by jumping down from the building, while she was also reported with dangerous driving behaviors. Consequently, her daily life and job were seriously disrupted. The patient was then sent to our hospital by her parents. A primary diagnosis of OCD was made, and paroxetine was prescribed at a daily dose of 40 mg. About a week later, the patient became extremely excited, talkative, and vigorous. Although paroxetine was discontinued soon afterward and quetiapine was initiated, her manic state lasted for nearly 3 weeks. Therefore, hospitalization was suggested by her doctor. After admission, a comprehensive physical and laboratory examinations were performed to exclude unknown underlying physical diseases. Besides, cranial magnetic resonance imaging scan was also normal. According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, this patient was dually diagnosed with bipolar I disorder and OCD. Quetiapine was gradually titrated up to 700 mg per day with concomitant valproate at 1,000 mg per day. Although her emotion became stable with these mood stabilizers, the patient reported an inadequate response in symptoms of OCD. A small dose of atypical antipsychotics was considered to enhance the treatment efficacy. Fascinatingly, an add-on therapy of aripiprazole 10 mg per day promoted accelerating alleviation of her obsessive behaviors. Meanwhile, no severe adverse events were observed. Her remission in emotional and OCD symptoms was well maintained in the follow-up visits. No suicidal attempt was reported after hospital discharge. A detailed rating of clinical scales is recorded in Figure 1. This work was approved by the Institute Ethical Committee of the First Affiliated Hospital, Zhejiang University School of Medicine, and written informed consent was obtained from the patient and her guardians.

aripiprazole, bipolar disorder, obsessive–compulsive disorder, suicide

PMC7276592_01

Male

A 13-year-old right-handdominant boy presented with pain and locking while moving the right shoulder during basketball activity and recurrent swelling around his right shoulder. There was no history of trauma, major illness, or surgery. His pain did not improve with conservative treatment, which included nonsteroidal anti-inflammatory drugs and physical therapy. On physical examination, he had a swollen right shoulder, but there were no signs of erythema, warmth, or muscle atrophy in his right shoulder. Active forward elevation of the right shoulder was 160 , external rotation was 70 , and internal rotation was at level T8. Plain radiographs of the right shoulder showed no abnormal findings (Fig. 1), but computed tomography (CT) and magnetic resonance imaging (MRI) showed several loose bodies in the axillary pouch and a large calcified mass lesion in the subscapular bursa (Fig. 2 and 3). Arthroscopy under general anesthesia in the beach chair position was performed through standard posterior and anterior portals. Arthroscopic examination showed several loose bodies in the glenohumeral joint (Fig. 4a). However, intrasynovial chondroid nodules were not seen in the glenohumeral joint. A sublabral foramen was found at the anterosuperior portion of the glenoid that communicated with the subscapular bursa (Fig. 4b). Multiple large calcified mass lesions and intrasynovial chondroid nodules were seen in the subscapular bursa, suggesting Milgram Stage 2 (transitional phase) (Fig. 4c). Loose bodies both in the glenohumeral joint and in the subscapular bursa were removed through a standard anterior portal, and proliferative thickened synovium of the subscapular bursa was also resected using a motorized shaver through the sublabral foramen. The histological examination of the loose bodies confirmed cartilaginous synovial metaplasia consistent with primary synovial chondromatosis (Fig. 5). The range of motion exercise was initiated from the day after surgery. Three weeks after the operation, he was symptom free with full range of motion and was able to return to sports. At follow-up after 5 years, he remained asymptomatic, and there was no clinical and radiographic evidence of recurrence.

shoulder, arthroscopy, subscapular bursa, synovial chondromatosis

PMC3189475_01

Male

The patient is a 51-year-old man who arrived at our facility complaining of fever, chills, myalgia, and generalized weakness that had begun 5 days before coming to the hospital. His fever was continuous, and he reported that his eyes have been yellow for the previous 3 days; he also complained of a headache in the frontal area. He is a fishery officer and works in the rice paddies as well. He reported severe vomiting 4 to 5 times per day and a decreased appetite and a change in urine color during the previous few days. The patient had no significant familial history of any disease. Except for one capsule of Omeprazole (20 mg) each day for heartburn; he reported no other current medications and no history of drug abuse history. The patient's physical examination showed the following vital signs: blood pressure 120/80 mmHG, pulse of 80, respiratory rate of 18, and temperature of 38 C. His conjunctiva was congested. No neck stiffness was detected. On both arms multiple petechia and, purpura were observed, but there was no sign of ecchymosis. The heart beat was normal. No organomegaly was detected in an abdominal examination. The lower limbs had normal appearance and function. The laboratory data are shown in Table 1. After a brain CT scan the radiologist reported "multiple hemorrhagic lesions in the temporal and parietal lobes, especially in the left side" (see Figure 1). The patient's chest X-ray was normal, and he tested negative for HBs Ag and HBs AB. His diagnosis was reviewed, and in view of the deranged hepatorenal functions and seasonal prevalence (recent floods in the area where the patient resided), leptospirosis was clinically suspected, which was further confirmed by the positive serum IgM-ELISA (IgG value of 100 and an IgM value of 20). Epidemics of leptospirosis in our region and unavailability of Microscopic agglutination test (MAT) made us to consider IgM-ELISA for confirmation of leptospirosis. In an abdominal sonography, 70 cc of fluid were found in Morison's pouch, and the liver exhibited hepatitis-like changes. An MRI showed intracranial hemorrhage, especially in the left lobe. With intracranial hemorrhage care and Ceftriaxone (1 mg/day) and Dexamethasone (8 mg two times daily) for 1 week and 15 unit platelets, his condition improved. After 26 days of hospital care with a normal platelet count and normal renal function the patient was discharged from hospital.

PMC6375111_01

Male

A 10-year-old boy presented to our outpatient clinic with abdominal pain. He reported recurrent epigastrial pain for the past 3-4 months, which has increased in severity and frequency, thus prompting the parents to seek medical help. The patient also developed diarrhea during the last month prior to presentation. On closer questioning, he described awakening at night with pain, accompanied by sweating and extreme paleness during the painful episodes. The description of the symptoms was alarming, prompting further investigation. On clinical examination he did not have specific findings: he was pale and his lower abdomen was tender and full. Routine full blood count and biochemistry revealed normal values apart from a slight normocytic anemia, the patient was found to have normal immunoglobulin levels. A subsequent abdominal ultrasound (US) showed an ~20-22 mm-wide band-like cystic mass stretching in front of the right psoas muscle and above the bladder. A follow-up US 10 days later, by the same radiologist identified a gross increase in the size of the abdominal mass, now dislocating the bowels and causing an obstruction (Figure 1). In order to specify the exact location, origin and nature of the mass, an abdominal MRI scan was performed. Based on the imaging, we had a strong suspicion of dealing with a solid tumor originating from the retroperitoneal space or the mesenteries (Figure 2). Pediatric surgeons performed a laparotomy. They located the mass to be in the middle part of the ileum and the attaching mesentery containing numerous cysts with localized infiltration of the bowel wall. A 30 cm long, macroscopically abnormal part of the ileum was resected. Pathologic examination was consistent with intestinal lymphangiectasia based on the dilated lymphatic system/vessels in the submucosa, subserosa and even in lamina propria (Figure 3). The edges of the resection line revealed normal histologic features. Secondary causes of intestinal lymphangiectasia (IL) (eg, cardiac conditions, lymphoma, mesenteric tuberculosis, etc) or associated conditions described in the literature (Noonan, Turner, Klippel-Trenaunay, Hennekam, von Recklinghausen syndrome) were not identified. Family history was negative for PIL and also free of inherited disorders. The early postoperative period was uneventful, and there were no complications. The patient's symptoms subsided, with no further signs of PIL during follow-ups for the next 4 years; he had only occasional abdominal symptoms for which he was started on proton pump inhibitor (PPI). Albumin and immunoglobulin levels stayed within normal range for his age. Serial abdominal USs have not revealed any signs of recurrence up to date.

abdominal mass, abdominal pain, children, follow-up, surgery

PMC5624136_01

Female

23-year-old female presented to the Emergency Room with carpopedal spasms and tingling numbness in hands. Patient endorsed tingling sensation in hand since a month which was intermittent and unrelated to wrist movement. She denied history of preceding trauma and swelling in hands. There was no history of similar complaints in the past or any prior surgery. She denied complaints like nausea, vomiting, and diarrhea. Tingling in hands was not associated with paresthesia in other extremities and sensory or motor deficits. Patient was a known case of multidrug resistant tuberculosis and was being treated with the following drugs for two months: amoxicillin-clavulanate, ethionamide, intramuscular capreomycin, linezolid, and para-aminosalicylate (PAS) granules. Patient was afebrile and her initial vital signs were normal with a pulse of 78/min and blood pressure of 110/76 mm of Hg. On examination, flattening of chest wall on the left side was noted. Trail's sign was positive with a deviation of the trachea to the left side. On auscultation of lung fields, breath sounds were diminished on the left. These findings suggested presence of tuberculous fibrosis in the left lung. No other stigmata of TB were noted and rest of the physical examination was unremarkable. Initial blood-work at the time of presentation revealed a low serum calcium level of 6.98 mg/dL. Patient was hospitalized and detailed investigations were done. Coexisting with hypocalcemia, other electrolyte abnormalities noted were as follows: serum sodium of 130 mEq/L, potassium of 1.8 mEq/L, chloride of 95 mEq/L, calcium of 6.98 mg/dL, and magnesium of 0.5 mg/dL. Serum albumin was 4 g/dL. Serum creatinine was normal and remained so throughout the course of hospitalization. The arterial blood gas evaluation showed metabolic alkalosis without respiratory compensation with pH of 7.5, HCO3 of 30 mEq/L, and PaCO2 of 30 mmHg. Routine urine examination revealed a 2-4 pus cells, 1-2 RBCs, and 1-2 epithelial cells, in the absence of proteinuria and glycosuria. Urine calcium/creatinine ratio was 0.49 (>0.2), which confirmed hypercalciuria. Urinary prostaglandin-E level was not performed as this assay is not readily available in our institute. Vitamin D and serum parathyroid levels were found to be in the normal range, thus ruling out hypovitaminosis D and secondary hyperparathyroidism, respectively. Patient was treated symptomatically; injectable calcium, magnesium, and potassium were administered to correct electrolyte abnormalities. Due to the association of aminoglycoside antibiotics with alterations in electrolyte levels, capreomycin was discontinued. Subsequently, the electrolytes started to rise after two days of stopping capreomycin (Table 1). Patient was discharged once her symptoms resolved and the serum electrolytes were normalized. On follow-up, there were no complains of tingling sensations or carpopedal spasms and electrolytes remained to be in the normal range.

PMC7292157_01

Female

A 15-year-old girl presented with severe pain upon terminal micturition, a pain that persisted for approximately 2 hours. When pain occurred, she was unable to move. The pain had been present for more than 1 month. She was treated with multiple antimicrobials, but no improvement was observed. Although urinalysis revealed a high white blood cell count, urine culture, cytology, polymerase chain reaction for tuberculosis, and adenovirus infection were all negative. The blood interferon-gamma assay for tuberculosis infection was also negative. She underwent cystoscopy, hydro-distention, and bladder biopsy under general anesthesia. Cystoscopy demonstrated severe erosion throughout the trigone (Fig. 1). Post-distension capillary hemorrhage was observed in only a small part of the posterior wall. Her bladder capacity was 700 mL at 80 cm H2O. Electric fulguration was performed for the trigonal ulcer. Severe inflammation with granulation and lymphocyte infiltration were found on histological assessment of the bladder biopsy from the trigone (Fig. 2). Postoperatively, her symptom improved temporarily, but gradually returned to the preoperative status 1 month later. Although several medications were tried in combination, including suplatast tosilate at 100 mg TID, tranexamic acid at 250 mg TID, potassium citrate/sodium citrate hydrate at 1 g TID, and loxoprofen sodium hydrate at 60 mg TID, her symptoms did not improve. Two months after the first operation, she underwent the second surgery. The trigonal ulcer had recurred and electric fulguration was performed again. The symptom was relieved temporarily, similar to that after the first surgery. Weekly bladder injections of 50 mL of 50% dimethyl sulfoxide were continued for 10 weeks. However, her symptoms did not improve and she was unable to attend school. Thus, the third surgery was scheduled 7 months after the second procedure. During the third surgery, complete electric resection was performed for the recurrent trigonal ulcer (Fig. 3). After the third procedure, pain on urination disappeared (Table 1). She has had no pain without medication for 15 months postoperatively.

adolescent, complete transurethral resection, ulcerative interstitial cystitis

PMC4320933_01

Female

An 80-year-old Japanese female was hospitalized due to swollen cervical lymph nodes. She had no previous history of TB treatment. Her cervical Computed Tomography scan (Figure 1) findings showed multiple swollen lymph nodes, mainly in the left neck. Furthermore, laboratory studies revealed a serum C-reactive protein level of 0.26 mg/dL and lactate dehydrogenase level of 233 IU/mL (Table 1). We present an outline of the microbiological findings in Table 2. The patient was suspected of having tumors of the lymph nodes. Three weeks after the first examination, an incision biopsy of a cervical lymph node was performed for diagnostic purposes. The histopathological findings from the biopsy tissue (Sample A) revealed necrotizing granulomas. Therefore, the patient was suspected of having an infection of acid-fast bacteria in the lymph nodes. Laboratory studies revealed a positive enzyme-linked immunospot assay for tuberculosis (ELISPOT) and were negative for immunoglobulin A antibodies against Mycobacterium avium complex-specific glycopeptidolipid core antigen (Capilia MAC) (Table 1). Five weeks after the first examination, an incision rebiopsy of a cervical lymph node (Sample B) was performed for culture and PCR analysis of the tissue. The histopathological findings from the rebiopsy tissue (Sample B) revealed necrotizing granulomas, too. PCR analysis of a biopsy sample using the Cobas TaqMan revealed a positive result for Mycobacterium avium and a negative result for Mycobacterium tuberculosis. The patient was thus diagnosed as having Mycobacterium avium lymphadenitis. Seven weeks after the first examination, clarithromycin 800 mg, rifampicin 450 mg, and ethambutol 500 mg were started for daily administration. Nine weeks after the first examination, a culture of acid-fast bacteria from rebiopsy tissue (Sample B) was positive in liquid culture medium. A culture of rebiopsy tissue was done at medical laboratory in Toyama Prefectural Central Hospital. PCR analysis of a cultured colony using the Cobas TaqMan revealed a negative result for Mycobacterium avium and a positive result for Mycobacterium tuberculosis. These findings suggested that the patient not had only Mycobacterium avium lymphadenitis but also tuberculous lymphadenitis, and thus isoniazid 300 mg daily was added to her regimen. Questioning the paradoxical PCR results, we analyzed a remaining frozen specimen from sample A by PCR using the Cobas TaqMan. This analysis revealed a positive result for Mycobacterium avium and a negative result for Mycobacterium tuberculosis. All PCR analyses were carried out at the same private clinical laboratory testing facility in Japan. Next, an alternative original PCR method on a frozen specimen of sample A was conducted by the Research Institute of Tuberculosis. This PCR analysis of sample A revealed a negative result for Mycobacterium avium (negative of IS1311 and DT1) and a positive result for Mycobacterium tuberculosis (positive of IS6110). Finally, a separation of viable bacteria in cultured colonies revealed no Mycobacterium avium colonies and all Mycobacterium tuberculosis colonies by PCR using the Cobas TaqMan. Thus, it was suggested that the patient did not have Mycobacterium avium lymphadenitis but tuberculous lymphadenitis, and clarithromycin was discontinued from her regimen. The patient continued treatment for tuberculous lymphadenitis with antitubercular drugs and experienced a reduction in cervical lymph node swelling.

PMC6348535_01

Female

A previously healthy, immunized, 15-month-old girl was admitted with 2 weeks of daily intermittent fevers and 3 days of decreased intake, irritability, and an intermittent cough. Systems review was otherwise unremarkable, including no history of torticollis, neck swelling, neck pain, or drooling. She was not on any home medications except acetaminophen as needed. There was a sick contact at daycare with Streptococcal tonsillopharyngitis, and her mother had a mild cough and congestion. There was no travel history. Examination demonstrated fever (up to 40.5 C) with otherwise normal vital signs and no distress. She had small, nontender bilateral cervical lymphadenopathy, a clear oropharynx, no conjunctivitis, and no oral or extremity changes. Cardiovascular, respiratory, abdominal, and joint examinations were normal. A faint erythematous maculopapular rash was noted on her legs. A multidisciplinary approach to fever of unknown origin (FUO) in a toddler was taken, which included Infectious Disease, Oncology, and Rheumatology specialist consultation. An extensive infectious workup was negative. This included blood, urine, and throat cultures, as well as testing for tuberculosis, Epstein-Barr virus, human immunodeficiency virus, parvovirus, adenovirus, cytomegalovirus, and hepatitis A, B, and C. Chest radiograph, abdominal ultrasound, and blood smear demonstrated no evidence of any malignant processes. Further investigations revealed elevated inflammatory markers, including a white blood cell count (16 x 109/L; reference range = 6.5-13 x 109/L), C-reactive protein (290 mg/L; 0.1-1 mg/L), erythrocyte sedimentation rate (76 mm/h; 2-34 mm/h), and ferritin (523 microg/L; 5-100 microg/L), with an associated normocytic anemia (hemoglobin 87 g/L; 102-127 g/L). Liver enzymes, platelets, albumin, and an echocardiogram were unremarkable. With no identifiable infectious or oncologic etiology, the patient was managed with supportive care. Despite no direct evidence apart from prolonged fever and elevated inflammatory markers (including anemia, an indirect sign of inflammation), she was treated with intravenous immunoglobulin on day 18 of fever for concern of atypical Kawasaki disease. Although this resulted in some clinical improvement, her fevers persisted. Subsequently, indomethacin was trialed for suspicion of an undeclared systemic juvenile idiopathic arthritis. Given that her oral intake and fevers were improving, and no new symptoms had developed, she was discharged home on day 20 of fever with close follow-up arranged. The patient re-presented to the emergency department 4 days later with persistent fevers, intermittent stridor, drooling, and coughing when drinking. Further imaging revealed the diagnosis.

fever, fever of unknown origin, retropharyngeal abscess

PMC8075668_01

Male

A 45-year-old male received a simultaneous pancreas kidney (SPK) transplant due to diabetes and end-stage renal disease (ESRD) . After transplantation, he had no major clinical complications and was discharged on postoperative day 30. His previous tuberculin skin test (TST) was negative, and he denied known TB exposure. The immunosuppressive regimen included basiliximab, prednisone, tacrolimus, and mycofenolate mofetil. During the second month posttransplant, he returned to the hospital complaining of fever, night sweats, and chills. Abdominal ultrasonography revealed perigraft collections (renal and pancreatic abscesses), whereas the chest radiograph was normal. He received broad-spectrum antibacterial treatment and underwent percutaneous drainage of the abscesses, with transient resolution of fever. Laboratorial analysis revealed acid-fast bacilli (AFB) on Ziehl-Neelsen stain. Antituberculous therapy was started with standard drugs: rifampin, isoniazid, pyrazinamide, and ethambutol Concurrently, considering that the recipient's TB abscesses were located near the grafts, suggesting donor involvement, the transplant harvesting center was contacted for additional information regarding the donor and the other organ recipients. At that time, two recipients had already died, and a look-back investigation was carried out (Figure 1). The patient subsequently presented with anti-TB drug toxicities: haemolytic anaemia (related to rifampicin) and blurred vision (due to ethambutol), both in the 2nd month of treatment resulting in a change of therapy. At this time, the patient presented disseminated disease involving grafts, lungs, CNS, and thyroid.The clinical deterioration of the patient imposed immunosuppressive cessation, leading to acute cellular rejection of the grafts, and dual graft loss with return to hemodialysis and insulin therapy. The patient underwent exploratory laparotomy with a surgical finding of caseating necrosis all over the mesenterium and around pancreatic graft, but affecting the renal graft. The removal of the renal graft was the only viable treatment encountered (Figure 2). After several ultrasound guided punctures to drain intra-abdominal TB abscesses and 18 months of anti-TB therapy, the patient was considered cured. However, he died from complications related to ESRD and dialysis, two years after transplantation.

PMC10475506_01

Female

A 60-year-old female with a medical history of essential hypertension, type 2 diabetes mellitus, epilepsy, and normocytic anemia was brought to our emergency department (ED) due to four weeks of progressive dyspnea. One-month prior, she had presented to an urgent care facility with a productive cough of one-month duration. A chest x-ray (CXR) (Fig. 1) demonstrated a significant right upper lobe consolidation concerning for community-acquired pneumonia and she was prescribed levofloxacin for seven days. She had a follow-up appointment with her primary care provider two weeks later without improvement of symptoms and was prescribed another course of antibiotics with amoxicillin-clavulanate and azithromycin. Two weeks later, she was brought to our ED for persistent cough, dyspnea, and hypoxia on a portable pulse oximeter noticed by a family member. On presentation, vitals were the following: temperature 97.2 F, tachycardia to 104 beats per minute, blood pressure 124/63 mmHg, respiratory rate 20 per minute, and oxygen saturation of 87% on room air. Due to a moderately elevated Well's score of 4.5 (high suspicion for PE and heart rate >100) and markedly elevated d-dimer 5672 ng/mL (normal <500 ng/mL), a computed tomography (CT) pulmonary angiogram was performed which revealed a saddle PE with a large proximal clot burden (modified miller score 16) (Fig. 2). Right ventricle (RV) ischemia and pressure overload were also evident from elevated cardiac biomarkers (troponin I 0.29 ng/mL (normal <0.03 ng/mL) and brain-natriuretic peptide 888 pg/mL (normal <100 pg/mL)) confirming a diagnosis of sub-massive intermediate-high risk PE. A 2D-transthoracic echocardiogram revealed a left ventricle (LV) ejection fraction of 65%, an increase in the RV to LV ratio at 1.4 (normal 0.8), and normal RV systolic function (tricuspid annular plane systolic excursion 21 mm (normal >=17 mm) (Fig. 3). Venous duplex ultrasound of the lower extremities found no evidence of deep venous thrombosis. The patient was started on supplemental oxygen and therapeutic enoxaparin. Interestingly, in addition to PE, there were innumerable nodular and patchy tiny areas of consolidations bilaterally concerning for multifocal infection (Fig. 4). Differential diagnosis included COVID-19 pneumonia, community acquired pneumonia, fungal infection, and miliary TB. On further interviewing, she reported a remote exposure to a homeless population and current excavating construction near her job. She also endorsed a thirty-pound unintentional weight loss over the last five months. She was immediately placed into airborne isolation. Infectious workup was remarkable for positive tuberculin purified protein derivative test at 15 mm induration, positive sputum acid-fast bacilli (AFB) culture, and positive sputum polymerase chain reaction (PCR) for mycobacterium tuberculosis. The rest of the infectious workup was negative including fungal culture and COVID-19 PCR. She was started on an anti-tuberculosis regimen of rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE). After two weeks of treatment and three negative AFB sputum cultures, she was deemed non-contagious and was discharged home on enoxaparin and RIPE therapy. Enoxaparin was selected for anticoagulation to avoid the interaction of direct-oral anticoagulants and warfarin with rifampin. She had frequent telehealth follow up over the next two months with a resolution of her dyspnea and cough. The local authority was informed within 24 h of TB diagnosis and contact tracing was initiated as well.

hypercoagulable state, miliary tuberculosis, pulmonary embolism, tuberculosis, venous thromboembolism

CT Pulmonary Angiogram: Saddle pulmonary embolism seen on CT pulmonary angiogram demarcated by the red arrow. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article. ).

PMC9720557_01

Female

A 59-year-old female Noida resident presented to us in the surgery OPD of Sharda Hospital with complaints of chronic right sided hypochondriac region pain and heaviness which was insidious in in onset, episodic in nature, mild in intensity, dull aching type of pain., with associated occasional nausea and vomiting more after heavy meals. No other significant positive history was obtained. Patient was taking regular medication for hypertension from outside for last 15 years since she was diagnosed to be hypertensive. She has had blood pressure within normal limits on examination. Patient has had no history of any chronic illnesses like tuberculosis diabetes, jaundice in the past. Patient has undergone lower segment caesarean section twice in the past with 2 alive children. Also, patient has undergone laparoscopic tubal ligation done more than 20 years back outside. There was no pallor, icterus, clubbing or any lymphadenopathy. On abdominal examination, there was old well healed surgical scars with soft protuberant abdomen, but no palpable lump, no organomegaly. Patient was admitted and investigated. Whole abdomen Ultrasound revealed multiple Gall bladder calculi largest ~12.5 mm, thickened gall bladder wall, with normal Common Bile Duct diameter and multiple small renal calculi ~4 mm. Rest scan was unremarkable. Blood investigations done were essentially unremarkable except for the renal functions which were impaired with levels of Serum Creatinine-2 mg % and Blood Urea- 76 mg%. So, in view of left renal calculus and deranged renal parameters along with a history of long-standing hypertension, patient was advised to undergo Diethyl Triamine Pentacetic Acid (DTPA) scan for assessment of renal functions. DTPA revealed bilateral kidneys having mildly reduced function with non-obstructed disease. With the given history, clinical presentation, ultrasonography and DTPA findings, the diagnosis of chronic calculous cholecystitis with poor pre-existing renal functions (chronic kidney disease CKD) with hypertension was made. She was suggested for stenting surgery for renal problem to which the patient was unwilling as poor renal functions were well tolerated by the patient and therefore only gall bladder problem was addressed on patient request. After thorough workup and informed consent, patient was posted for elective laparoscopic cholecystectomy (Fig. 1). Per op. -Gall bladder distended, thick walled, dense Calot's adhesions, between omentum and Gall bladder body. Multiple small discrete white patches seen on bowel surfaces. Dilated Hartmann pouch with impacted stones seen (Fig. 2a). Laparoscopic cholecystectomy was therefore converted to open cholecystectomy due to adhesions and to prevent any iatrogenic injury to the biliary tree. Post-operative period was uneventful. Patient was allowed liquids orally, the evening following surgery. Patient tolerated the surgery well and has had satisfactory progression in improvement. Drain was removed on 2rd post-operative day. Patient was discharged on 3rd post-operative day with sutures in situ and alternate day dressing with antibiotics and symptomatic treatment was advised. Biopsy revealed apart from chronic calculus cholecystitis, a chronic schistosomal infestation of gall bladder. Gall bladder shows atrophic mucosa with dense chronic inflammation with wall showing calcific deposits and numerous basophilic ova entrapped in the fibrous tissue. Few of the ova were calcified (Fig. 2b). Patient fared well with Anti helminthic (Tablet Praziquental) treatment and related symptomatic medication in the follow-up. At 12 months post-operative period patient has no new symptoms or any evidence suggestive of urinary bladder or digestive tract involvement.

bilharziasis, cholecystectomy, gall bladder, schistosomiasis

PMC7261438_01

Female

On February of 2020, a 76-year-old woman was referred to our hospital in Matsumoto, Japan, from another hospital in Japan, where she was admitted for sore throat, dry cough, and fever that started on February 7, 2020 (symptom onset day 1; SOD#1). (The term "symptom onset day" is used to illustrate the patient's clinical course, and the term "hospital day" is used to describe treatment measures.) Past medical history was significant for diabetes mellitus, hypertension, and glaucoma, but she was otherwise healthy and did not smoke. The patient, an American living in the United States, was visiting Japan and arrived at Yokohama Harbor aboard the Diamond Princess cruise ship. Due to a COVID-19 outbreak inside the cruise ship, she was kept in the cruise ship and underwent viral testing as part of quarantine inspection. A reverse transcription polymerase chain reaction (RT-PCR) test, performed by the Japan Ministry of Health, Labour and Welfare, produced a positive result for SARS-CoV-2. One day before admission to our hospital, the patient was started on lopinavir-ritonavir (400 mg/100 mg twice daily orally) and moxifloxacin (400 mg once a daily orally). She was transferred to our hospital on SOD#12 (hospital day 1; HD#1). On admission, her body temperature was 38.3 C, and her oxygen saturation (SpO2) by pulse oximetry was 93% on 8 L/min of supplemental oxygen via mask. Physical examination revealed coarse crackles in the upper chest on the right. Laboratory examination revealed peripheral blood lymphopenia (350/muL) and elevated levels of blood urea nitrogen (BUN, 28.9 mg/dL), creatinine (1.62 mg/dL), C-reactive protein (CRP, 12.90 mg/dL), and lactate dehydrogenase (LDH, 325 U/L) (Table 1). Chest computed tomography (CT) images showed ground-glass opacities (GGOs) and consolidation (Fig. 1A and B). Due to possible community-acquired pneumonia caused by bacteria and influenza virus, the patient was treated with piperacillin-tazobactam and peramivir (at a loading dosage of 300 mg, reduced to 150 mg every 24 hours due to renal failure). Her respiratory failure progressed, leading to endotracheal intubation. An endotracheal aspirate obtained through the intubation tube was positive for SARS-CoV-2 on RT-PCR. Laboratory examination revealed a low gamma-globulin level on HD#3 (SOD#14); intravenous immune globulin (IVIG) (at a dosage of 5000 mg every 24 hours intravenously) was administered from HD#3 (SOD#14) to HD#8 (SOD#19). On HD#8 (SOD#19), the patient's respiratory status progressively deteriorated; she exhibited dyspnea despite fever alleviation. The respirator setting at the time was assist/control (volume-controlled ventilation), tidal volume was 300 ml, positive end-expiratory pressure (PEEP) was 14 cmH2O, and respiratory frequency was 13 per minute. Her hypoxemia was not improved even if we regulated PEEP. We considered whether this deterioration might be due to increased airway dead space caused by pulmonary embolism or acute pulmonary edema; however, these diagnoses could not be confirmed with evidence on chest CT scans, which were unobtainable because there was concern about the risk of infecting other patients in the radiology unit. We conducted a compression ultrasound, but were not able to point out deep vein thrombosis. The patient's respiratory status continued to worsen and, despite optimal ventilator settings, we were unable to maintain her PaO2/FiO2 above 70 torr. Therefore, we decided to proceed to venous-venous extracorporeal membrane oxygenation (V-V ECMO) on HD#8 (SOD#19). For V-V ECMO, venous catheters were placed in the right common femoral vein (for drainage) and right internal jugular vein (for infusion). Her hemodynamics were maintained using vasoactive agents; we were able to normalize her body water with diuretics and stabilize her oxygenation by ECMO. On HD#16 (SOD#27), to prevent bacterial infection related to catheterization, the previous antibiotics were replaced with vancomycin. Her respiratory status gradually improved. On HD#16 (SOD#27), viral testing of an endotracheal aspirate sample showed that SARS-CoV-2 was undetectable using RT-PCR. A tracheotomy was performed on HD#18 (SOD#29); ECMO was discontinued on HD#19 (SOD#30). Intravenous meropenem was administered for ventilator-associated pneumonia (VAP) prophylaxis. Chest CT scans obtained on HD#22 (SOD#33) showed enlarged abnormal shadows, GGOs, and consolidation in the upper lobe of the right lung, suggesting organizing pneumonia (Fig. 1C and D), which could result in chronic respiratory failure after ECMO cessation. On HD#25 (SOD#36), the patient was started on methylprednisolone 250 mg daily for three days with improvement of her organizing pneumonia on chest x-ray (Fig. 2E and F). On HD#40 (SOD#51), the patient was taken off the respirator, and her condition was stable.

ards, acute respiratory distress syndrome, acute respiratory distress syndrome, covid-19, coronavirus disease, coronavirus, ecmo, extracorporeal membrane oxygenation, gamma-globulin, ivig, intravenous immune globulin, organizing pneumonia, rt-pcr, reverse transcription polymerase chain reaction, sars-cov-2, severe acute respiratory syndrome coronavirus 2

Chest computed tomography (CT) images. (A-B) Images taken on SOD#9. (A) Ground-glass opacities (GGOs) in the anterior segment of the right upper lobe.

PMC7261438_01

Female

On February of 2020, a 76-year-old woman was referred to our hospital in Matsumoto, Japan, from another hospital in Japan, where she was admitted for sore throat, dry cough, and fever that started on February 7, 2020 (symptom onset day 1; SOD#1). (The term "symptom onset day" is used to illustrate the patient's clinical course, and the term "hospital day" is used to describe treatment measures.) Past medical history was significant for diabetes mellitus, hypertension, and glaucoma, but she was otherwise healthy and did not smoke. The patient, an American living in the United States, was visiting Japan and arrived at Yokohama Harbor aboard the Diamond Princess cruise ship. Due to a COVID-19 outbreak inside the cruise ship, she was kept in the cruise ship and underwent viral testing as part of quarantine inspection. A reverse transcription polymerase chain reaction (RT-PCR) test, performed by the Japan Ministry of Health, Labour and Welfare, produced a positive result for SARS-CoV-2. One day before admission to our hospital, the patient was started on lopinavir-ritonavir (400 mg/100 mg twice daily orally) and moxifloxacin (400 mg once a daily orally). She was transferred to our hospital on SOD#12 (hospital day 1; HD#1). On admission, her body temperature was 38.3 C, and her oxygen saturation (SpO2) by pulse oximetry was 93% on 8 L/min of supplemental oxygen via mask. Physical examination revealed coarse crackles in the upper chest on the right. Laboratory examination revealed peripheral blood lymphopenia (350/muL) and elevated levels of blood urea nitrogen (BUN, 28.9 mg/dL), creatinine (1.62 mg/dL), C-reactive protein (CRP, 12.90 mg/dL), and lactate dehydrogenase (LDH, 325 U/L) (Table 1). Chest computed tomography (CT) images showed ground-glass opacities (GGOs) and consolidation (Fig. 1A and B). Due to possible community-acquired pneumonia caused by bacteria and influenza virus, the patient was treated with piperacillin-tazobactam and peramivir (at a loading dosage of 300 mg, reduced to 150 mg every 24 hours due to renal failure). Her respiratory failure progressed, leading to endotracheal intubation. An endotracheal aspirate obtained through the intubation tube was positive for SARS-CoV-2 on RT-PCR. Laboratory examination revealed a low gamma-globulin level on HD#3 (SOD#14); intravenous immune globulin (IVIG) (at a dosage of 5000 mg every 24 hours intravenously) was administered from HD#3 (SOD#14) to HD#8 (SOD#19). On HD#8 (SOD#19), the patient's respiratory status progressively deteriorated; she exhibited dyspnea despite fever alleviation. The respirator setting at the time was assist/control (volume-controlled ventilation), tidal volume was 300 ml, positive end-expiratory pressure (PEEP) was 14 cmH2O, and respiratory frequency was 13 per minute. Her hypoxemia was not improved even if we regulated PEEP. We considered whether this deterioration might be due to increased airway dead space caused by pulmonary embolism or acute pulmonary edema; however, these diagnoses could not be confirmed with evidence on chest CT scans, which were unobtainable because there was concern about the risk of infecting other patients in the radiology unit. We conducted a compression ultrasound, but were not able to point out deep vein thrombosis. The patient's respiratory status continued to worsen and, despite optimal ventilator settings, we were unable to maintain her PaO2/FiO2 above 70 torr. Therefore, we decided to proceed to venous-venous extracorporeal membrane oxygenation (V-V ECMO) on HD#8 (SOD#19). For V-V ECMO, venous catheters were placed in the right common femoral vein (for drainage) and right internal jugular vein (for infusion). Her hemodynamics were maintained using vasoactive agents; we were able to normalize her body water with diuretics and stabilize her oxygenation by ECMO. On HD#16 (SOD#27), to prevent bacterial infection related to catheterization, the previous antibiotics were replaced with vancomycin. Her respiratory status gradually improved. On HD#16 (SOD#27), viral testing of an endotracheal aspirate sample showed that SARS-CoV-2 was undetectable using RT-PCR. A tracheotomy was performed on HD#18 (SOD#29); ECMO was discontinued on HD#19 (SOD#30). Intravenous meropenem was administered for ventilator-associated pneumonia (VAP) prophylaxis. Chest CT scans obtained on HD#22 (SOD#33) showed enlarged abnormal shadows, GGOs, and consolidation in the upper lobe of the right lung, suggesting organizing pneumonia (Fig. 1C and D), which could result in chronic respiratory failure after ECMO cessation. On HD#25 (SOD#36), the patient was started on methylprednisolone 250 mg daily for three days with improvement of her organizing pneumonia on chest x-ray (Fig. 2E and F). On HD#40 (SOD#51), the patient was taken off the respirator, and her condition was stable.

ards, acute respiratory distress syndrome, acute respiratory distress syndrome, covid-19, coronavirus disease, coronavirus, ecmo, extracorporeal membrane oxygenation, gamma-globulin, ivig, intravenous immune globulin, organizing pneumonia, rt-pcr, reverse transcription polymerase chain reaction, sars-cov-2, severe acute respiratory syndrome coronavirus 2

Chest computed tomography (CT) images. (A-B) Images taken on SOD#9. (B) Partial consolidation and GGOs in the right middle and lower lobes and distribution of lesions in the subpleural area and periphery of the lung, showing "crazy-paving" pattern.

PMC7261438_01

Female

On February of 2020, a 76-year-old woman was referred to our hospital in Matsumoto, Japan, from another hospital in Japan, where she was admitted for sore throat, dry cough, and fever that started on February 7, 2020 (symptom onset day 1; SOD#1). (The term "symptom onset day" is used to illustrate the patient's clinical course, and the term "hospital day" is used to describe treatment measures.) Past medical history was significant for diabetes mellitus, hypertension, and glaucoma, but she was otherwise healthy and did not smoke. The patient, an American living in the United States, was visiting Japan and arrived at Yokohama Harbor aboard the Diamond Princess cruise ship. Due to a COVID-19 outbreak inside the cruise ship, she was kept in the cruise ship and underwent viral testing as part of quarantine inspection. A reverse transcription polymerase chain reaction (RT-PCR) test, performed by the Japan Ministry of Health, Labour and Welfare, produced a positive result for SARS-CoV-2. One day before admission to our hospital, the patient was started on lopinavir-ritonavir (400 mg/100 mg twice daily orally) and moxifloxacin (400 mg once a daily orally). She was transferred to our hospital on SOD#12 (hospital day 1; HD#1). On admission, her body temperature was 38.3 C, and her oxygen saturation (SpO2) by pulse oximetry was 93% on 8 L/min of supplemental oxygen via mask. Physical examination revealed coarse crackles in the upper chest on the right. Laboratory examination revealed peripheral blood lymphopenia (350/muL) and elevated levels of blood urea nitrogen (BUN, 28.9 mg/dL), creatinine (1.62 mg/dL), C-reactive protein (CRP, 12.90 mg/dL), and lactate dehydrogenase (LDH, 325 U/L) (Table 1). Chest computed tomography (CT) images showed ground-glass opacities (GGOs) and consolidation (Fig. 1A and B). Due to possible community-acquired pneumonia caused by bacteria and influenza virus, the patient was treated with piperacillin-tazobactam and peramivir (at a loading dosage of 300 mg, reduced to 150 mg every 24 hours due to renal failure). Her respiratory failure progressed, leading to endotracheal intubation. An endotracheal aspirate obtained through the intubation tube was positive for SARS-CoV-2 on RT-PCR. Laboratory examination revealed a low gamma-globulin level on HD#3 (SOD#14); intravenous immune globulin (IVIG) (at a dosage of 5000 mg every 24 hours intravenously) was administered from HD#3 (SOD#14) to HD#8 (SOD#19). On HD#8 (SOD#19), the patient's respiratory status progressively deteriorated; she exhibited dyspnea despite fever alleviation. The respirator setting at the time was assist/control (volume-controlled ventilation), tidal volume was 300 ml, positive end-expiratory pressure (PEEP) was 14 cmH2O, and respiratory frequency was 13 per minute. Her hypoxemia was not improved even if we regulated PEEP. We considered whether this deterioration might be due to increased airway dead space caused by pulmonary embolism or acute pulmonary edema; however, these diagnoses could not be confirmed with evidence on chest CT scans, which were unobtainable because there was concern about the risk of infecting other patients in the radiology unit. We conducted a compression ultrasound, but were not able to point out deep vein thrombosis. The patient's respiratory status continued to worsen and, despite optimal ventilator settings, we were unable to maintain her PaO2/FiO2 above 70 torr. Therefore, we decided to proceed to venous-venous extracorporeal membrane oxygenation (V-V ECMO) on HD#8 (SOD#19). For V-V ECMO, venous catheters were placed in the right common femoral vein (for drainage) and right internal jugular vein (for infusion). Her hemodynamics were maintained using vasoactive agents; we were able to normalize her body water with diuretics and stabilize her oxygenation by ECMO. On HD#16 (SOD#27), to prevent bacterial infection related to catheterization, the previous antibiotics were replaced with vancomycin. Her respiratory status gradually improved. On HD#16 (SOD#27), viral testing of an endotracheal aspirate sample showed that SARS-CoV-2 was undetectable using RT-PCR. A tracheotomy was performed on HD#18 (SOD#29); ECMO was discontinued on HD#19 (SOD#30). Intravenous meropenem was administered for ventilator-associated pneumonia (VAP) prophylaxis. Chest CT scans obtained on HD#22 (SOD#33) showed enlarged abnormal shadows, GGOs, and consolidation in the upper lobe of the right lung, suggesting organizing pneumonia (Fig. 1C and D), which could result in chronic respiratory failure after ECMO cessation. On HD#25 (SOD#36), the patient was started on methylprednisolone 250 mg daily for three days with improvement of her organizing pneumonia on chest x-ray (Fig. 2E and F). On HD#40 (SOD#51), the patient was taken off the respirator, and her condition was stable.

ards, acute respiratory distress syndrome, acute respiratory distress syndrome, covid-19, coronavirus disease, coronavirus, ecmo, extracorporeal membrane oxygenation, gamma-globulin, ivig, intravenous immune globulin, organizing pneumonia, rt-pcr, reverse transcription polymerase chain reaction, sars-cov-2, severe acute respiratory syndrome coronavirus 2

Chest computed tomography (CT) images. (C-D) Images taken on SOD#33. (C) Subpleural consolidation in the right lung.

PMC7261438_01

Female

On February of 2020, a 76-year-old woman was referred to our hospital in Matsumoto, Japan, from another hospital in Japan, where she was admitted for sore throat, dry cough, and fever that started on February 7, 2020 (symptom onset day 1; SOD#1). (The term "symptom onset day" is used to illustrate the patient's clinical course, and the term "hospital day" is used to describe treatment measures.) Past medical history was significant for diabetes mellitus, hypertension, and glaucoma, but she was otherwise healthy and did not smoke. The patient, an American living in the United States, was visiting Japan and arrived at Yokohama Harbor aboard the Diamond Princess cruise ship. Due to a COVID-19 outbreak inside the cruise ship, she was kept in the cruise ship and underwent viral testing as part of quarantine inspection. A reverse transcription polymerase chain reaction (RT-PCR) test, performed by the Japan Ministry of Health, Labour and Welfare, produced a positive result for SARS-CoV-2. One day before admission to our hospital, the patient was started on lopinavir-ritonavir (400 mg/100 mg twice daily orally) and moxifloxacin (400 mg once a daily orally). She was transferred to our hospital on SOD#12 (hospital day 1; HD#1). On admission, her body temperature was 38.3 C, and her oxygen saturation (SpO2) by pulse oximetry was 93% on 8 L/min of supplemental oxygen via mask. Physical examination revealed coarse crackles in the upper chest on the right. Laboratory examination revealed peripheral blood lymphopenia (350/muL) and elevated levels of blood urea nitrogen (BUN, 28.9 mg/dL), creatinine (1.62 mg/dL), C-reactive protein (CRP, 12.90 mg/dL), and lactate dehydrogenase (LDH, 325 U/L) (Table 1). Chest computed tomography (CT) images showed ground-glass opacities (GGOs) and consolidation (Fig. 1A and B). Due to possible community-acquired pneumonia caused by bacteria and influenza virus, the patient was treated with piperacillin-tazobactam and peramivir (at a loading dosage of 300 mg, reduced to 150 mg every 24 hours due to renal failure). Her respiratory failure progressed, leading to endotracheal intubation. An endotracheal aspirate obtained through the intubation tube was positive for SARS-CoV-2 on RT-PCR. Laboratory examination revealed a low gamma-globulin level on HD#3 (SOD#14); intravenous immune globulin (IVIG) (at a dosage of 5000 mg every 24 hours intravenously) was administered from HD#3 (SOD#14) to HD#8 (SOD#19). On HD#8 (SOD#19), the patient's respiratory status progressively deteriorated; she exhibited dyspnea despite fever alleviation. The respirator setting at the time was assist/control (volume-controlled ventilation), tidal volume was 300 ml, positive end-expiratory pressure (PEEP) was 14 cmH2O, and respiratory frequency was 13 per minute. Her hypoxemia was not improved even if we regulated PEEP. We considered whether this deterioration might be due to increased airway dead space caused by pulmonary embolism or acute pulmonary edema; however, these diagnoses could not be confirmed with evidence on chest CT scans, which were unobtainable because there was concern about the risk of infecting other patients in the radiology unit. We conducted a compression ultrasound, but were not able to point out deep vein thrombosis. The patient's respiratory status continued to worsen and, despite optimal ventilator settings, we were unable to maintain her PaO2/FiO2 above 70 torr. Therefore, we decided to proceed to venous-venous extracorporeal membrane oxygenation (V-V ECMO) on HD#8 (SOD#19). For V-V ECMO, venous catheters were placed in the right common femoral vein (for drainage) and right internal jugular vein (for infusion). Her hemodynamics were maintained using vasoactive agents; we were able to normalize her body water with diuretics and stabilize her oxygenation by ECMO. On HD#16 (SOD#27), to prevent bacterial infection related to catheterization, the previous antibiotics were replaced with vancomycin. Her respiratory status gradually improved. On HD#16 (SOD#27), viral testing of an endotracheal aspirate sample showed that SARS-CoV-2 was undetectable using RT-PCR. A tracheotomy was performed on HD#18 (SOD#29); ECMO was discontinued on HD#19 (SOD#30). Intravenous meropenem was administered for ventilator-associated pneumonia (VAP) prophylaxis. Chest CT scans obtained on HD#22 (SOD#33) showed enlarged abnormal shadows, GGOs, and consolidation in the upper lobe of the right lung, suggesting organizing pneumonia (Fig. 1C and D), which could result in chronic respiratory failure after ECMO cessation. On HD#25 (SOD#36), the patient was started on methylprednisolone 250 mg daily for three days with improvement of her organizing pneumonia on chest x-ray (Fig. 2E and F). On HD#40 (SOD#51), the patient was taken off the respirator, and her condition was stable.

ards, acute respiratory distress syndrome, acute respiratory distress syndrome, covid-19, coronavirus disease, coronavirus, ecmo, extracorporeal membrane oxygenation, gamma-globulin, ivig, intravenous immune globulin, organizing pneumonia, rt-pcr, reverse transcription polymerase chain reaction, sars-cov-2, severe acute respiratory syndrome coronavirus 2

Chest computed tomography (CT) images. (C-D) Images taken on SOD#33. (D) Posterior consolidation with air bronchogram in the posterior segments of the lower lobes of both lungs.

PMC7139628_01

Female

E.L. is an 18-year-old Caucasian male, who is accused of having severely wounded another student in a scuffle after school two years earlier. Due to the physical conflict, E.L.'s schoolmate reported an injury of his left eyeball, and E.L. was charged with causing serious personal injuries. E.L. has a complex clinical history. Born at term of natural childbirth, he was artificially fed, and his development followed regular phases until the age of 2. In the course of subsequent months, first symptoms of a delay in language development emerged, and, at the age of 4, E.L. was diagnosed with an Autism Spectrum Disorder (ASD). While attending the first years of primary school, he showed good interactions with peers, though experiencing significant learning difficulties. According to his parents' accounts and consistent with school reports, sometimes E.L. appeared restless and hyperactive. Clinical assessment identified mild cognitive disability associated with language disorder, subsequently revised as learning disability associated with affective immaturity and scarce tolerance to frustrations. At the age of 8, E.L. was hospitalized for re-assessment of his diagnosis, which was indeed revised as a developmental mixed disorder with a major impairment of linguistic capacity. In the same period, E.L. experienced epileptiform seizures. At the age of 9, following a MRI, he was diagnosed with Grey Matter Heterotopia, while first problems of socialization appeared alongside: E.L. became a target of his peer social pressure and bullying to the extent that he decided to move school the year after. E.L. has a mild and submissive temperament, particularly wishful to establish meaningful friendship relationships, a trait of his personality that has paradoxically backfired with him becoming the object of bad jokes and mistreatments by his classmates and acquaintances. He has a very supportive family, with parents thoughtfully caring for his health and social concerns. Over the years, E.L. has undergone further diagnostic refinements, which progressively evidenced depressive tendencies and social withdrawal along with linguistic and cognitive disabilities and developmental emotional disorder. In medical records, the condition of E.L. is described as characterized by attention and memory lability especially in the school context, motor instability, affective immaturity, and difficulty in emotion regulation and inhibition (F80.8, F81.9, F93 ICD10). Within the overall picture, however, the clinical implications of GMH are left almost completely unconsidered except for their role in the emergence of epileptic seizures. The troubles in adaptation and socialization led E.L. to experience severe episodes of social rejection and bullying, which made him feel profoundly sad and worthless. As an aggravation of this psychological condition, at the age of 16, seven months before the dispute with his schoolmate, he engaged in a suicidal attempt by ingesting an overdose of sleeping pills. He was hospitalized with the diagnosis of depression in a passive-dependent personality and thought disorders, started on antipsychotic treatment (aripiprazole, 10 ml per day). The therapeutic program increased his behavioral control, but negatively affected personal interests, energy, and socialization, so that the antipsychotic dosage was progressively reduced until complete discontinuation, which was reached a couple of months before the criminal conduct he was later charged with. On the day of the alleged offence, E.L. had a verbal dispute with one of his classmates for a trivial reason, and received verbal abuse in return. On leaving the school, E.L. found that girl along with her boyfriend and other schoolmates, waiting for him beyond the school gate threateningly staring at him. Frightened by the scene, E.L. tried to escape running as fast as he could, but he was intercepted and stopped by the boyfriend of his classmate who roughly blamed him for the dispute he had had with the girl few hours before. A scuffle ensued, and the two boys fell to the ground, with E.L. punching blindly a break through and free himself from people around him. Following the fight, E.L. reported small facial and knee injuries while his antagonist was diagnosed with an outbreak of his left eyeball. Shocked by the unpredictable evolution of the events, E.L. became progressively more aware of the severity of the injuries he had inflicted. Very soon, he started to feel guilty and became regretful. He repeatedly declared he had never intended to harm his mate so severely and explained his exclusive aim had been to escape the frightened situation he had found himself in. Rather interestingly, he also displayed an almost complete amnesia for the event and his running off. E.L. is submitted to expert examination following a Court order to establish his criminal liability at the time of the facts and the actual risk of recidivism. The psycho-forensic assessment included clinical interviews and test administration, the results of which are displayed in Table 1. Furthermore, E.L. underwent a structural Magnetic Resonance Imaging (sMRI) scan to ascertain the presence of a previously reported area of heterotopic grey matter in E.L.'s brain. MRI was performed on a GE Signa 3T scanner (GE Healthcare). As Table 2 shows, E.L. appears to have a normal level of intelligence with mild impairment in processing speed and receptive linguistic capacities. He appears suspicious, with persistent persecutory thought contents, phobic ideas, and obsessive worries regarding the future. E.L. preferably adopts a defensive modality of coping with anger expression, with a dominance of repressive and avoidant tendencies. His affective state is dysphoric and characterized by high levels of anxiety. The neuropsychological assessment reveals a poor executive capacity of inhibiting dominant responses, set shifting, planning, and strategic control. However, E.L. appears able to choose and manage effective problem solving strategies, which do not imply space or time constraints. Finally, a low risk propensity is observed. The psychometric conclusions are consistent with evidence obtained through the clinical interviews. The outcome of sMRI scanning confirms previous evidence of a sub-ependymal GMH in E.L.'s brain, excluding the presence of other morphological and/or structural abnormalities (Figure 1).

grey matter heterotopia, epilepsy, impulsivity, inhibitory control, neurodevelopmental disorder

PMC9412100_01

Male

A 67-year-old male was admitted to our hospital due to unconsciousness and fever. The patient had fever symptoms 3 days before admission, the highest temperature was 39.6 C, and no special treatment was given. The patient had a history of drunkenness and aspiration 1 week before admission. One day before admission, the patient suddenly lost consciousness with quadriplegia. Physical examination: the patient was in a deep coma; the diameter of the bilateral pupils was 2 mm; the Glasgow score was E1V1M3; and the muscle strength of the limbs was grade 2. Blood analyses revealed evidence of leukocytosis (33.6 x 109/L) and elevated C-reactive protein (CRP) levels (199.80 mg/L), neutrophils percentage (93.80%), and procalcitonin range (1.58 ng/ml). Head computed tomography (CT) showed multiple intracranial space-occupying edema, and chest CT showed a right upper lobe space occupying the cavity. Brain magnetic resonance imaging (MRI) showed multiple divergent intracranial abscesses, which were low signal on the T1 weighted image and high signal on the T2 weighted image and were significantly enhanced. On the day of admission, the patient had difficulty breathing and was given mechanical ventilation with tracheal intubation (Figure 1). On day 3, a tracheotomy was performed. The patient had no history of tuberculosis, sputum tuberculosis and tuberculosis infection T cell detection was negative. To determine the patient's intracranial infection, we performed a lumbar puncture on the third day after admission. Cerebrospinal fluid (CSF) analyses revealed leukocytosis (10,300 x 106/L), elevated protein levels (140.39 mg/dL), decreased glucose levels (0.27 mmol/L), and normal chloride concentration level (120.2 mmol/L). However, pathogens were not detected in the cultures, and Gram staining assays were prepared from CSF, sputum, and blood samples. We used vancomycin (2 g every 12 h, ivgtt) combined with meropenem (1 g every 8 h, ivgtt) and ornidazole (0.5 g every 12 h, ivgtt) as an empirical anti-infection treatment. We used mNGS to identify pathogens in CSF and alveolar lavage fluid on 5th day after admission (Table 1). We stopped vancomycin and meropenem, then switched to ceftriaxone (2 g every 24 h, ivgtt) combined with amikacin (0.4 g every 12 h, ivgtt) for anti-infection treatment. The patient's consciousness and limb muscle strength gradually improved during the subsequent treatment. Two weeks after admission, the patient's body temperature was normal, and no more than 39 C. Celsius Routine blood leukocyte count, neutrophil ratio, and procalcitonin levels decreased gradually to normal levels. We performed lumbar puncture during hospitalization at the third week after admission, which showed that the patient's intracranial pressure was 180 mmH2O and the color of the CSF was light blood and clear; CSF analyses showed normal leukocyte count (15 x 106/L), elevated protein levels (72.3 mg/dL), and normal glucose levels (4.37 mmol/L) and chloride concentration level (119 mmol/L). We then sequenced the CSF again at 4 weeks after admission, suggesting that S. intermedia could still be detected, but its relative abundance decreased from 39.34 to 5.62% (Table 2). We continued to use ceftriaxone in the treatment of intracranial infection until the patient's body temperature was normal for 2 weeks, we stopped all antibiotics at 6 weeks after admission (Table 3). After 8 weeks, the patient's consciousness became clear, and the muscle strength of the limbs recovered to grade 4. CT showed that the size of the lesion and the degree of edema improved significantly, the patient's upper right pneumonia was better than before, and the patient was discharged at the 10 weeks after admission (Table 3). The 3-month follow-up head MRI showed that the brain abscess had basically disappeared (Figure 2).

streptococcus intermedia, case report, cerebrospinal fluid, meta-genomic next-generation sequencing, multiple brain abscesses

PMC7649852_01

Male

A 75-year-old male had a history of hypertension, diabetes mellitus, and smoking 20 cigarettes per day for 50 years. He had no history of atrial fibrillation. He underwent a medical checkup, and upper gastrointestinal endoscopy revealed middle thoracic esophageal squamous cell carcinoma. Since submucosal invasion by the cancer was suspected, surgery was planned after chemotherapy, and one course of FP therapy (5-fluorouracil, 800 mg/m2/day, continuously for 5 days, and cisplatin, 80 mg/m2, on day 1) was administered. Eleven days after the end of the first course of FP therapy, the patient underwent CECT to evaluate the effects and possible complications of the treatment. He was asymptomatic at that time, and his vital signs were unremarkable. Tests of the patient's coagulation status revealed a shortened activated partial thromboplastin time (21.2 s) and a high D-dimer level (1.6 mug/mL). CECT images obtained about 1 month earlier had not shown any abnormalities in the aorta (Figure 1); however, the new CT images incidentally revealed a floating mass in the ascending aorta (Figure 2). The mass exhibited uniform low density, but did not display enhancement. On the same day, 4D-CT was performed for further examination. The patient received 100 mL of 300 mg/mL iodinated contrast medium for the CECT and 65 mL of 370 mg/mL iodinated contrast medium for the 4D-CT; however, his renal function did not deteriorate. 4D-CT images showed that the mass was attached to the anterior wall of the ascending aorta along a region measuring about 18 mm in length. A 36-mm-long part of the mass was moving up and down, and the movement was synchronized with the patient's heartbeat (Figure 3(a), (b) and Video 1, 2). Since the appearance of the floating mass suggested that it was soft, we suspected a thrombus or benign tumor. Moreover, it seemed that the mass could become dislodged at any moment, which could have resulted in serious embolic complications. Therefore, the patient underwent emergency surgery the next day. Since malignancy could not be completely ruled out, replacement of the ascending aorta was performed. During the operation, the mobile mass was found to be attached to the anterior wall of the ascending aorta. A microscopic examination revealed that the mass was a fibrin thrombus, which was attached to the aortic wall. The aortic wall exhibited evidence of atherosclerosis; however, no continuity was found between the thrombus and tunica intima (Figure 4). The patient received heparin (5000 units) for 11 days postoperatively. His postoperative course was uneventful, and he was given an ambulatory discharge at 15 postoperative days. About 2 months after the discharge, he underwent surgery for esophageal cancer. He took 30 mg edoxaban as an oral anticoagulant for 188 days until his D-dimer level normalized, and the thrombus had not recurred after about a year.

four-dimensional computed tomography, ascending aorta, fibrin thrombus, floating thrombus

PMC2634970_01

Unknown

The search engine does not log any information on the users submitting the queries, not even the IP-address which theoretically could pin-point the user geographically. The data are therefore aggregated on a national level, meaning that only national outbreaks and trends can be discovered. In February 2008, Vardguiden performed a survey directed to the visitors of the web site. In total 1,224 persons were questioned, out of which 1,000 replied. According to this survey, 85.1 per cent of the visitors were women. The majority of all visitors were between 21 and 35 years old, and 63.4 per cent lived in the Stockholm County. Of the respondents, 74.3 per cent used the search engine on the web site to look for the information they require. As timeliness may be crucial in the case of an outbreak, sources conveying as early outbreak indicators as possible should be identified. Zeng & Wagner have constructed a model : based on health psychology literature : on people's behaviour when falling ill. The model consists of four phases: recognition of symptoms, interpretation of symptoms, cognitive representation of illness, and seeking treatment. The model implies that outbreak indicators are found in different sources depending on which phase the infected persons are in. For the first phase, one potential source are records of absenteeism. During the second and third phases, the social surrounding plays an important role. Also, ill people may seek advice on medical help lines and web sites during these two phases. The model shows the natural delay between noting of symptoms and seeking treatment by, for example, visiting a pharmacy or a health centre, which is done only during the fourth phase. According to Zeng & Wagner the queries will reflect a person's symptoms when in the second phase (interpretation of symptoms), while during the third phase (cognitive representation of illness) the search terms are more disease oriented. Consequently, the queries reflecting symptoms should be an even earlier indicator than queries reflecting diagnosis. In theory, this model probably has great bearing, but the acuteness of an influenza illness means that it is difficult to discern the phases with the time resolution used in this study. However, if the queries could be analysed momentaneously, such an approach would probably allow for a more accurate representation of the epidemic pattern. Andersson et al. have shown that the sentinel reports cannot be used to predict the number of laboratory verified cases in the Swedish data set. This fact is a strong argument for complementing the influenza surveillance with analyses based on other data sources. By : as in this study : using web query data, it is also possible to obtain a baseline for the time of the year when no conventional influenza surveillance is performed. In addition, public holidays such as Christmas, when seeing a GP is more difficult, are covered with this source. Assumingly, different strata of the population are covered by the web queries, compared to those covered by the reporting from the health care. The use of the internet is increasing, and we can therefore expect to get more and more data points, and consequently more reliable results. With time, the internet will be an integrated part of most citizens' life and for this reason we will also get a much more diverse group of users. Thus, the web queries have the potential to reflect the population as a whole. This is opposed to the sentinel system as well as the laboratory testing, which probably over-report groups that are more vulnerable to the disease. With the presented study we show that web queries can indeed be a reliable and cost-effective source for identification and estimation of the development of the aggregated influenza activity in a society. We feel that this first, scientific evaluation of its usefulness is an important proof of concept that could stimulate further investigations, and also an important foundation for reliable exploitation of similar systems for various kinds of surveillance. Web query logs are obtained at a low cost, and give a unique access to ill individuals who may yet not be seeking care. This paper shows the potential of web queries as an accurate and labour extensive source for syndromic surveillance. In future work, we will explore how to best utilize the web queries for other diseases, with characteristics different from influenza, such as norovirus infections.

PMC3350267_01

Female

A 22-Year-old female Gravida II, Para I Live I with 6 months of pregnancy came to hospital with decreased foetal movements for 2 days. There was no history of bleeding or draining per vagina, and no history of hypertension, diabetes, tuberculosis, bronchial asthma, and epilepsy. Also there was no history of consanguinity. Her first pregnancy was full term, normal delivery. Per abdominal examination showed 34 wks of gestation with breech presentation. Foetal heart sounds present. Ultrsonography were revealed a single viable foetus with breech presentation. Foetal head deformed. There was a well-circumscribed cystic mass in the foetal abdomen measuring 15.4 x 15.4 cm. Other investigations were within normal limits. Patient delivered a single dead foetus weighing 2.4 kg by breech presentation after aspiration of 700 mL of fluid from foetal abdomen on induction by prostaglandins. Placenta expelled out in toto. Dead foetus was subjected to pathological examination.

PMC9079228_01

Female

A 69-year-old Japanese woman was referred from a local hospital for left pleural effusion noted on a chest radiograph during a routine hospital visit. The patient had mild dyspnea and normal oxygenation without any other symptoms. She had smoked 10 cigarettes per day for 29 years but denied any occupational exposure to dust. She reported no history of allergy, tuberculous infection, or pancreatic or autoimmune disease. On physical examination, she exhibited normal vital signs and peripheral oxygen saturation at room air. However, the left lung had decreased lung sounds on auscultation. Laboratory testing (Table 1) revealed a white blood cell count of 3800/muL with 65.5% polymorphonuclear leukocytes and 5.0% eosinophils. Chest radiography revealed moderate left pleural effusion (Fig. 1). The pleural fluid was drained via thoracentesis. It exhibited findings consistent with lymphocyte-dominant exudative pleural effusion, and the ADA level was elevated to 69.7 U/L (Table 2). Tuberculous pleurisy was suspected; however, the pleural fluid bacterial cultures and polymerase chain reaction (PCR) tests for tuberculosis and nontuberculous mycobacteria, and the interferon-gamma release test yielded negative findings. In addition, the rheumatoid factor, anti-cyclic citrullinated peptide antibodies, antinuclear antibody, and the analysis for tumor markers were negative. We excluded rheumatoid pleuritis, systemic lupus erythematosus, and carcinomatous pleurisy based on the clinical findings. Fluorodeoxyglucose (FDG) positron emission tomography imaging revealed FDG accumulation in the mediastinal and cervical lymph nodes (Fig. 2). Neither lymphadenopathy nor pleural thickening was detected on contrast-enhanced computed tomography of the neck to the pelvis (Fig. 3). The culture positivity rate of the pleural fluid in tuberculous pleurisy is low. Based on the clinical findings, IgG4-RD and tuberculous pleurisy were suspected. However, distinguishing between IgG4-RD and tuberculous pleurisy is challenging since both the diseases are characterized by pleural effusion and high ADA levels. We ascertained that tissue diagnosis for definitive diagnosis was warranted for both tuberculous pleurisy and IgG4-related pleurisy; thus, thoracoscopy was conducted. The histological analysis revealed dense lymphocytic infiltrates and mild eosinophilic infiltrates with no malignancy or granuloma (Fig. 4A). Additional blood tests revealed a serum immunoglobulin G (IgG) level of 3065 mg/dL, IgG4 of 724 mg/dL, and serum immunoglobulin E level of 5309 mg/dL. Immunohistochemical staining revealed 286 IgG4-positive plasma cells/high-power field in the pleural membranes (Fig. 4B); the ratio of IgG4-to IgG-positive plasma cells (IgG4/IgG) was 46% (Fig. 4B and C), which met the diagnostic criteria for IgG4-RD. Hence, the patient was diagnosed with IgG4-related pleural effusion. She was treated with prednisolone (PSL) at 40 mg/day (0.6 mg/kg/day), which achieved complete resolution of the pleural effusion. The responsiveness to PSL further supported the diagnosis of pleurisy secondary to IgG4-RD.

adenosine deaminase, immunoglobulin g4-related pleurisy, tuberculosis

PMC7193652_01

Male

A 52-year-old Caucasian male sustained a TBI due to a motor vehicle accident. He had a Glasgow Coma Scale (GCS) of 13; his mean arterial pressure of 60 mmHg was maintained by a norepinephrine drip. When he developed a dilated left pupil with decerebrate posturing (GCS 5), he required intubation. The computed tomography (CT) showed a large left epidural hematoma (EDH) with a 2 cm midline shift warranting a craniotomy [Figures 1 and 2]. During the surgery, no intracranial pressure (ICP) monitor was placed. Postoperatively, in the neurocritical invasive care unit, standard ASA monitoring included oxygen saturation (pulse oximeter), end-tidal CO2 monitoring, standard electrocardiographic, arterial line monitoring of blood pressure (BP), and serial arterial blood gas assessments were performed. The postoperative CT scans showed continued resolution of the EDH and improvement of the edema and midline shift (GCS of 6-7). However, at the end of the 2nd week, the patient expired due to complications of TBI (e.g., multiorgan failure). The main question is whether the use of an ICP monitor would have changed this patient's course and outcome.

brain trauma foundation, decline invasive monitoring, intracranial pressure, neurocritical monitoring, traumatic brain injury

PMC4009261_01

Male

Our patient is a 59-year-old Southeast Asian male with past medical history significant for gastroesophageal reflux disease, hiatal hernia, and hyperlipidemia. He initially presented with low-grade fevers, generalized weakness associated with decreased appetite and weight loss. Subsequently, he noticed dark discoloration of the urine. He did not take any medications. He was a lifetime nonalcoholic and used to smoke occasionally (1-2 cigarettes/week). Family history was significant for diabetes mellitus, hypertension, myocardial infarction, and stroke. Initial laboratory work showed elevated liver enzymes and raised amylase, lipase (Table 1). Ultrasound and computerized tomography (CT) of the abdomen showed dilated common bile duct, dilated pancreatic duct, and enlarged lymph nodes in the porta hepatis, peripancreatic and perigastric regions. A hypoechoic mass measuring 3 by 4 cm was seen in the pancreatic head. There was a strong suspicion of pancreatic carcinoma (Figure 1). Endoscopic ultrasound- (EUS-) guided fine needle aspiration (FNA) of the pancreatic mass showed reactive atypia with no evidence of malignancy and celiac lymph node FNA cytology showed atypical cells with granuloma (Figures 2(a) and 2(b)). Quantiferon gold came back positive and mycobacterium tuberculosis (MTB) DNA was detected via polymerase chain reaction (PCR) from the biopsy specimen. Tumor markers including CA19-9 (carbohydrate antigen 19-9), AFP (alpha-fetoprotein), CA 125 (cancer antigen 125), and CEA (carcinoembryonic antigen) were normal. Angiotensin converting enzyme level was also within normal limits. Subsequently, the patient developed jaundice associated with fever. Endoscopic retrograde cholangiopancreatography (ERCP) was done and a biliary stent was placed in the common bile duct. Biopsy from the distal common bile duct also showed granulomatous inflammation. Patient was started on antituberculosis treatment (ATT) with rifampin 600 mg, ethambutol 1200 mg, isoniazid 300 mg, and pyrazinamide 1500 mg, which he tolerated well. IgG4 came back positive at 0.5 g/L (0.25 g/L-0.318 g/L) leading to suspicion of autoimmune pancreatitis. He was also started on prednisolone 40 mg orally every day. One month after the initiation of treatment, a repeat CT scan of the abdomen did not show any changes in the size of the pancreatic head mass or lymph nodes. Six months after initial presentation, he developed an episode of acute pancreatitis. By this time he was on ATT for five months and prednisolone for four months. CT scan showed increase in the size of lymph nodes and persistent common bile duct and pancreatic duct dilatation (Figure 3). Another ERCP was performed with stent exchange and retrieval of few gallstones. Pancreatic mass and the pancreatic duct could not be reached. EUS-guided biopsy of the lymph node showed reactive hyperplasia and was negative for malignancy or granuloma. MTB DNA was negative. Ampullary tissue biopsy also showed inflammatory changes. Magnetic resonance cholangiopancreatography (MRCP) was also performed which showed persistent enlarged lymph nodes and enlarged pancreatic duct but some regression of pancreatic mass. Patient completed a total of eighteen months of ATT and was tapered off steroids as well. Follow-up laboratory tests showed normal liver function test, amylase and lipase level (Table 1). IgG4 levels also decreased to a normal range (Table 1). He had a few episodes of self-resolving nausea and abdominal pain. Imaging studies including CT, ultrasound, and MRCP repeated after completing ATT and steroids continued to show enlarged lymph nodes in the porta hepatis, peripancreatic regions, dilated CBD, and pancreatic duct with atrophic looking pancreas (Figures 4(a) and 4(b)). At present, patient is doing well with minimal symptoms and is able to maintain weight.

PMC2718127_01

Male

A 65-year-old man with intermittent, colicky periumbilical pain which first occurred two months earlier was admitted to hospital. He had an eight-year history of congestive heart failure caused by mitral valvular regurgitation and atrial fibrillation. He was nonalcoholic, and there was no history of diarrhea, hematochezia, or melena. Physical examination showed an increased bowel sound. Vital signs at admission were stable, and laboratory findings including white blood cell count, a liver function test and electrolytic balance were within the normal ranges. Electrocardiography revealed atrial fibrillation, and chest radiography demonstrated cardiomegaly (not shown). To exclude acute appendicitis, initial ultrasonography (US) was performed, and this demonstrated diffuse, segmental, concentric wall thickening of the terminal ileum just proximal to the ileocecal valve. The mucosal folds were blunted and there was low level echogenicity (Fig. 1A). Nonspecific ileitis, Crohn's disease, intestinal tuberculosis or ischemic enteritis were suggested as possible causes of the bowel wall thickening, and in order to evaluate the terminal ileum, colonoscopic examination was performed. The ascending colon was found to be completely obstructed by a circumferential mass lesion, and the colonoscopic fiber could not be advanced further. Subsequent CT scanning showed a markedly dilated small bowel and ascending colon, with concentric, hyperattenuating, focal wall thickening in the hepatic flexure of the ascending colon (Fig. 1B). In addition, the terminal ileum was dilated and showed diffuse, concentric wall thickening of its long segments with heterogeneous contrast enhancement. In the thickened wall, focal areas of poor contrast enhancement were also noted (Fig. 1C). There appeared to be several possible diagnoses, including ischemic enterocolitis caused by thromboembolism of mesenteric vessels arising from atrial fibrillation, inflammatory bowel disease involving the ascending colon and terminal ileum, and ischemic or infectious enteritis associated with colon cancer. Although surgery was recommended, the patient refused. Stool culture yielded lactose-fermenting Gram-negative bacillus, urine culture yielded Citrobacter freundii, and Gram staining of urine revealed the presence of Gram-negative rods; no organisms were isolated from blood cultures. In addition to conservative management of congestive heart failure, the patient underwent antibiotic therapy with amoxacillin, tobramycin or aztreonam for two weeks and ciprofloxacin for several days. Symptoms such as abdominal pain ameliorated, the level of bowel sound decreased, and laboratory findings continued to be within normal ranges. Vital signs were stable, except for intermittent fever of up to 38.2C until 30 days after admission. At this time, the patient complained of sudden abdominal pain and his clinical condition deteriorated. Emergency right hemicolectomy was performed, with resection of the distal ileum. At surgery, the hepatic flexure of the ascending colon was found to be completely obstructed by a hard concentric mass, and about 15 cm of the terminal ileum, just proximal to the ileocecal valve, was markedly dilated and diffusely thickened. About 500 ml of clear, yellowish ascites was also present. A cut section of the thickened terminal ileum revealed marked submucosal edema to a depth of approximately 10 mm, though there was no evidence of mucosal lesion. The colonic mass was confirmed microscopically as a poorly differentiated adenocarcinoma. Microscopic examination also showed that the mucosal folds of thickened ileal loop were blunted by submucosal edema and there was extensive inflammatory reaction, with infiltrations of neutrophils. In some areas of the thickened bowel wall, there was extensive destruction of underlying tissue by irregular-shaped abscesses. Neutrophil infiltration extended into the subjacent muscular layer and even to the serosa (Fig. 1D). The inflammatory reactions provided no evidence of granuloma formation, and the histologic findings were consistent with phlegmonous enteritis.

PMC2892652_01

Male

A 30-year-old male patient was electively admitted to our general surgery clinic in June 2009 with a diagnosis of fistula in ano. His past medical history revealed a serious fall during a football game which resulted in a left acetabular fracture in 1993. Open reposition and internal fixation procedures had been performed two months after this accident. Postoperatively, he had developed abscesses on the upper medial aspect of his left thigh in the second month and on the lateral aspect of the left gluteal region in the third month. All these abscesses had been treated by surgical drainage and with antibiotics. Three years after the hip operation, he had developed a perianal abscess which was also drained. However, the intermittent spontaneous purulent discharge in the perianal region continued for 13 years since the patient did not seek any medical care during this period. His past medical history was not conclusive for any inflammatory bowel disease. Pelvic magnetic resonance imaging (MRI) performed in a different medical center eight months prior to his admission demonstrated an abscess cavity, measuring 2 cm in diameter, located superior to the levator ani muscle and its tract of 10 cm coursing from its internal opening in the rectum down to the perianal region (Figure 1). The laboratory analysis including complete blood count, blood biochemistry, and erythrocyte sedimentation rate were within normal limits. Physical examination revealed the presence of two external openings 7 cm and 3 cm from the anal verge at the 3 o'clock and 2 o'clock positions, respectively. The results of digital rectal examination and colonoscopy were normal and the internal opening of the tract was not visualized. Based on these clinical findings, surgical intervention for the complex fistula in ano was planned. After bowel preparation, the patient was taken to the operation room. Under general anesthesia, the patient was placed in a jack-knife position and the buttocks were taped apart. The fistula tracts were laid open to the level of the anal sphincters. At this level, digital examination was performed towards the upper part of the tract and a foreign body located above the levator ani muscle was felt. A nonabsorbable braided thread of 5 cm in length and 6 mm in thickness was extracted (Figure 2). After partial excision and curretage of the tract, a penrose drain was placed and the wound was closed with interrupted simple absorbable sutures (Figure 3). Following the discovery of this object, a plain pelvic radiography was performed, this demonstrated advanced left acetabular degeneration with no other foreign body visible. Following an uneventful postoperative recovery, the patient was discharged home on the third postoperative day. On follow-up visits, complete resolution of the perianal fistula was observed after a month. The patient remained symptom-free during the 7-month follow-up period.

PMC5315210_01

Female

We report the case of a 20-year-old woman who lost her driver's license after sustaining a moderate TBI in May 2013 after a car crash involving a deer. When transferred to intensive care, she presented a score of 10/15 on the Glasgow Coma Scale (GCS). Following the accident, she presented a posttraumatic amnesia, diffuse axonal injury with several bilateral petechiae, hemorrhagic contusions mostly located in the right frontal lobe, an infringement of the third right cranial nerve, mild right optic neuropathy, left hemiparesis, balance impairment (43/56 on Berg Balance Scale (BBS), difficulty in performing ADL and cognitive impairments, including memory impairment, decline in audioverbal and visual attention, decline in the ability of abstraction, reduced organizational capacity, decreased visuospatial abilities, cognitive fatigability and apathy. At the time of the accident, the participant held a Learner's License - Passenger Vehicle (Class 5) and had very little driving experience. Having failed her first attempt to the Probationary License - Passenger Vehicle (Class 5), she was planning to perform her second attempt to the Societe de l'Assurance Automobile du Quebec (SAAQ) on-road test as required by Quebec's provincial legislation. In order to regain her Learner's License - Passenger Vehicle (Class 5), she had to obtain an evaluation certifying her functional capacity for driving. She underwent an in-clinic assessment, which revealed mild posttraumatic cognitive impairments (i.e., cognitive fatigability that interferes with the sustained attention span and vigilance weakness that generates a slow reaction time when stimuli appear slowly); sufficient muscle strength, range of motion and coordination; proper reaction time; sufficient overall perceptual-cognitive functions for driving and sufficient behavior. Following this assessment, she received a 10-hour on-road driving training with a driving instructor and a 3-hour in-simulator-specific road rules learning with a driving instructor. Driving ability of the posttrauma subject was assessed during an on-road evaluation conducted by an occupational therapist in May 2014 at the Quebec City Rehabilitation Institute (IRDPQ). During this test, the participant did not demonstrate the operational and tactical skills required to drive safely. The difficulties observed during the road test were consistent with cognitive sequelae observed in clinical settings. These seemed to cause functional impairments interfering with her driving performance. Considering the deficiencies observed during the on-road assessment, the lack of improvement during training sessions and the integration difficulties of the basics of driving, the improvement potential was estimated as low. Therefore, no other subsequent road test was envisaged by the IRDPQ. In-simulator driving rehabilitation presents a promising method to improve driving skills after TBI. The aim of this study is to evaluate the effectiveness of an in-simulator training program with automated feedback on driving performance in a TBI individual.

assessment, driving, rehabilitation, simulator, traumatic brain injury

PMC9047745_02

Unknown

A small Chinese study including 70 JSLE and adult SLE patients (all >16-years old, mean age of the study population not specified) has compared maintenance tacrolimus and azathioprine treatment, showing similar, low LN relapse rates in both treatment arms, with tacrolimus demonstrating a more favorable safety profile than azathioprine. In another small study from China, 26 patients with LN and persistent proteinuria of >1.5g/24-h despite treatment with cyclophosphamide (>8 g in <6-months), were commenced on 2-3mg of tacrolimus daily. 23/26 patients demonstrated an overall renal response (10 complete and 16 partial renal response). Most patients had biopsy confirmed LN (class III=5, class IV=2, class V=5, class III+V=7, class IV+V=4 and unknown n = 3), with patients with class V LN demonstrating higher rates of remission (Table 4). Further research is required in JSLE to evaluate the role of tacrolimus in studies that are sufficiently powered. In a small randomized controlled trial including 18 JSLE and SLE patients (mean age 29-years) with WHO class III/IV LN, no additional effect was seen in those treated with human umbilical cord-derived mesenchymal stem cells over and above standard immunosuppression (intravenous methylprednisolone and cyclophosphamide followed by maintenance oral prednisolone and MMF, Table 4). The trial was stopped early when it became clear that it would not demonstrate a positive treatment effect. New evidence relating specifically to each of the SHARE LN recommendations is very limited. Where new evidence could be identified from pediatric, young adult or adult SLE studies it is summarized below. SHARE recommends that "Immunosuppressive treatment should be guided by a diagnostic renal biopsy". No new original research studies could be identified that relate to this. However, very similar statements have also been endorsed by the Joint EULAR and European Renal Association European Dialysis and Transplant Association (ERA-EDTA) recommendations for the Management of Adult and Pediatric Lupus Nephritis, and the American College of Rheumatology (ACR) Guidelines for Screening, Treatment, and Management of Lupus Nephritis. When assessing response to initial LN induction treatment, SHARE recommends that "Partial renal response should be achieved preferably by 6 months but no later than 12 months following initiation of treatment" and that "Treatment should aim for complete renal response with urine protein:creatine ratio<50 mg/mmol and normal or near-normal renal function (within 10% of normal GFR)". Again, there is no new pediatric evidence relating to this recommendation. An adult SLE study has since suggested that partial renal response should be achieved sooner (by 12-weeks after commencement of induction therapy for class III or IV LN), with lack of a partial renal response by 12-weeks ultimately predicting poor renal response, and damage accrual. These authors have also shown that early achievement of a complete renal response (by 12-weeks) is significantly associated with maintaining a complete response at 3-years (p = 0.012), less frequent SLE flares (p = 0.026) and damage (p = 0.029) during the subsequent 10-years of follow-up, highlighting the need for assessment for and importance of timely achievement of partial and complete renal response. Further studies are needed to investigate the achievability and impact of such renal outcomes in JSLE. The SHARE recommendations advocate that "In case of LN with proteinuria, ACE-inhibitors or ARBs should be considered as additional treatment. Combined use of ACE inhibitors and ARBs should be guided by pediatric nephrologists". No new original evidence relating to this recommendation could be found. However, the Brazilian Society of Rheumatology consensus guidelines for the diagnosis, management and treatment of LN in adult SLE have also concluded that "ARBs and ACE inhibitors should be used as antiproteinuric agents unless contraindicated". In relation to the treatment of class I LN, SHARE recommended that "Low-dose prednisone (<0.5 mg/kg/day) could be considered in class I LN, although treatment choice should be guided mainly by other clinical features" and that "For the treatment of class I LN alone, adding a DMARD is not necessary". This is echoed by the pediatric Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group clinical practice guideline for glomerulonephritis that were published in 2012 (subsequent to the original SHARE literature review), suggesting that patients with class I LN should be treated according to their extrarenal JSLE manifestations. For the treatment of class II LN, SHARE made the following recommendations: "First line treatment of class II LN should be prednisolone (with a starting dose of 0.25-0.5 mg/kg/day, with a maximum of 30 mg/day) tapering over a total duration of 3-6 months" and "For the treatment of active class II LN, a DMARD is necessary in persistent proteinuria and/or when failing to taper corticosteroids after 3-months of low dose prednisolone". Unfortunately, no new evidence could be found in relation to these recommendations. For induction treatment for class III/IV LN, with or without class V, SHARE recommended "MMF or intravenous CYC, in combination with corticosteroids". This is supported by the recent observational study from the UK JSLE Cohort Study (discussed above) which showed comparability between MMF and cyclophosphamide as induction treatments in JSLE. From the adult SLE literature, a large randomized trial (n = 362, mean age 31.9-years) has demonstrated improved rates of complete and partial renal remission at 24-weeks in patients treated with low-dose MMF, tacrolimus, and steroids compared to monthly intravenous cyclophosphamide and steroids for proliferative LN induction treatment. The SHARE recommendations also advised that "maintenance treatment for class III or IV LN should consist of MMF or Azathioprine, for at least 3-years". No new pediatric evidence could be found relating to maintenance therapy. However, the American College of Rheumatology also recommends MMF or Azathioprine for maintenance treatment (in addition to low-dose prednisolone), and the pediatric KDIGO guidelines suggest a calcineurin inhibitor can be used for maintenance therapy if a patient is intolerant to MMF or Azathioprine. There was no new evidence guiding the length of maintenance treatment for proliferative LN, or on the treatments that should be used for pure class V LN. Adequately powered randomized controlled trials looking at conventional LN induction and maintenance therapies, investigating of the role of calcineurin inhibitors, and looking at treatment of class V LN in isolation are therefore warranted. Five of the SHARE recommendations relate to treatment of LN flares and refractory disease. No new evidence could be found relating to these recommendations. All the new evidence relating to LN SHARE treatment recommendations is summarized in Supplemental Table 1. Despite this extensive literature search, no papers met the inclusion criteria for this section of the review. It is recognized that management of pediatric APS remains challenging due to a lack of large-scale prospective studies, with most treatment recommendations based on adult studies. Hydroxychloroquine is thought to have anti-thrombotic properties. In asymptomatic patients with persistently positive antiphospholipid antibodies, the use of low dose aspirin is controversial, with one small placebo-controlled trial showed no benefit after 2-years. For those who have already suffered from a thrombosis, the main goal of treatment is to prevent further thrombosis through treatment with long term anti-coagulation therapy such as warfarin. The role of immunosuppressive treatment remains uncertain. A further literature search was performed specifically reviewing for new evidence relating to each SHARE management recommendation for pediatric APS and CAPS. No new evidence could be found relating to the specific management for pediatric APS. A case series of 21 patients with pediatric CAPS (from 1990 to 2013) was found, which suggested that immunosuppression with corticosteroids or rituximab may confer survival benefit. In this study, none of the patients who received rituximab died, however, the odds ratio for survival crossed 1 and was not statistically significant, potentially likely relating to the small sample size. Case reports have also suggested ecluzimab may be beneficial in treatment of CAPS in adults however this has not yet been assessed in children. This review highlights that treatment paradigms in JSLE are often needing to be extrapolated from adult SLE, whilst RCTs in JSLE are particularly scarce, especially any that are sufficiently powered to demonstrated statistical significance. Most available treatment options are not targeted (conventional DMARDs), and known to cause significant associated adverse events and toxicity, particularly in vulnerable children and young people. Although biologic therapies are used extensively for many autoimmune conditions, there have been several notable setbacks in developing a robust evidence base for SLE, with only belimumab so far licensed for use in SLE in the past 50-years. Difficulties with definitions and use of outcome measures in SLE clinical trials have contributed to these setbacks. The Belimumab in JSLE (PLUTO trial) summarized above raises important questions about the applicability of adult SLE outcome measures in JSLE. In this trial, the adult SLE primary outcome measure (SRI4) was not met in the pediatric age group, but the pediatric-derived major secondary outcome measure (PRINTO/ACR 30, 50) was achieved. Given the known differences in disease activity, severity and damage demonstrated between pediatric, adolescent, and adult SLE, it is important that lessons are learnt from such studies. Most of the more recent published evidence relate to treatment of LN, with a marked dearth of studies on NP-JSLE and APS. T2T approaches are hoped to offer an opportunity to improve further the clinical management of JSLE patients by using existing treatments in a structured way with the aim of more aggressively controlling disease activity at an early stage, preventing organ damage and improving HRQOL. Such approaches are already part of routine clinical care in many areas of adult medicine (e.g., rheumatoid arthritis, hypertension, diabetes), with growing international evidence for the potential role of T2T in JIA in recent years. Development and testing of such an approach as part of the TARGET LUPUS research programme is eagerly awaited.

antiphospholipid syndrome, biologics, childhood-onset systemic lupus erythematous, juvenile-onset systemic lupus erythematous, lupus nephritis, pediatric rheumatology, treatment

PMC5827882_01

Male

The patient, a 38-year-old active-duty Marine, presented to our clinic with a history of persistent right knee pain that occurred while going up and down stairs and was most prominent along the anterior knee. His medical history was significant for a diagnostic arthroscopy done elsewhere for a "clean up" of the right knee, which provided minimal pain relief. The operative report and images demonstrated Outerbridge grade IV changes involving the lateral patellar facet, grade III and IV changes along the medial patellar facet, and grade IV changes along the entire trochlea down to the intercondylar notch. Magnetic resonance imaging (MRI) of his right knee was obtained, which demonstrated ongoing patellofemoral osteoarthritis with a kissing lesion involving the trochlea and lateral facet of the patella with subchondral cyst formation. No evidence of new pathology was present elsewhere in the knee. After exhausting all conservative treatment options, he underwent an uncomplicated patellofemoral arthroplasty for isolated right knee patellofemoral degenerative joint disease. Four months after surgery, the patient had regained full range of motion (ROM) of his right knee and returned to his previous activity level, including running and playing basketball. Furthermore, he was able to pass the required endurance tests for military active-duty reinstatement. Approximately ten months after surgery, he returned with moderate, sharp right knee pain, which he attributed to prolonged physical activity and playing sports. His knee pain was predominantly over the lateral joint line and was associated with catching and clicking. Clinical examination was significant for tenderness over the lateral joint line with positive Thessaly and McMurray tests. A mild effusion was present, and the ROM of the right knee was 0-125 . A stability examination revealed moderate (2B) laxity with Lachman and anterior drawer tests. No varus or valgus instability was present, and results of the dial and reverse pivot shift tests were normal. Based on his clinical examination and concern for lateral meniscus and anterior cruciate ligament (ACL) pathology, a metal reduction MRI was acquired. The images revealed an intact patellofemoral arthroplasty; however, evaluation of the ACL and menisci was nondiagnostic due to metallic susceptibility artifacts (Figures 1-3). The findings and treatment options were discussed with the patient, and due to his persistent pain and mechanical symptoms, he was scheduled for a diagnostic arthroscopy. Prior to his surgery, we were afforded the opportunity to use a new diagnostic needle arthroscopy (mi-eye 2 ; Trice Medical, King of Prussia, PA) to evaluate his knee joint. After written consent was obtained, the patient's right knee was prepped in a standard sterile fashion, the subcutaneous tissue was infiltrated with 5 cc of 1% lidocaine, and mi-eye 2 was inserted into the lateral joint space. The mi-eye 2 quickly confirmed the presence of a complex, degenerative tear of the lateral meniscus. Upon further examination, we discovered an ACL tear, an intra-articular loose body, and a grade IV chondral lesion on the medial femoral condyle measuring approximately 20 mm x 20 mm (Figure 4). The mi-eye 2 provided direct visualization of the knee joint without requiring a formal operating room procedure and yielded an immediate diagnosis of the patient's intra-articular pathology, which was either equivocal or not evident on MRI. As a result of the findings, the surgical plan was changed, and the patient subsequently underwent an arthroscopic partial lateral meniscectomy, allograft ACL reconstruction, and osteochondral allograft transplantation. The patient had an uncomplicated postoperative course and was discharged on the day of surgery. Knee ROM exercises were started immediately. He was managed with non-weight-bearing restrictions for 3 weeks, followed by progressive weight bearing from weeks 3 to 6, and then full weight bearing beginning 6 weeks after surgery.

PMC6400852_01

Male

A 74-year-old man was admitted to our institution for investigation of progressive neurological symptoms. The patient was diagnosed with seropositive RA in 2015, which was quiescent on maintenance methotrexate, hydroxychloroquine and low-dose prednisone (10 mg daily). Titers of both rheumatoid factor and antibodies to cyclic citrullinated peptide were elevated. One week prior to admission, the patient developed fluctuating confusion, apathy, word-finding difficulty, right-sided weakness and gait imbalance. He had also experienced several other similar self-limited episodes within the 3 preceding months. The initial neurological examination was remarkable for decreased attention span, severe expressive aphasia, bilateral postural tremor, right hemiparesis and hypoesthesia, as well as a shuffling and wide-based gait. Clinical evaluation by rheumatology confirmed absence of synovitis and no evidence of extra-articular RA involvement. Gadolinium-enhanced head magnetic resonance imaging (MRI) showed finite areas of scattered restricted diffusion and enhancement within the cortex and leptomeninges of the left hemisphere near the vertex, suspicious for meningoencephalitis (Figures 1A,B). Cerebrospinal fluid (CSF) analysis showed 6 white blood cells (WBCs), 85% lymphocytes and 15% monocytes, a protein concentration of 0.86 g/L (normal 0.15-0.45 g/L) and a normal glucose content. CSF bacterial and fungal cultures were negative, as were cryptococcal antigen, herpes simplex virus, and syphilis testing. Serum C-reactive protein was markedly elevated at 135 mg/L (normal 0-5 mg/L). Antinuclear antibodies and anti-neutrophil cytoplasmic antibodies were negative. Serologies for human immunodeficiency virus and anti-onconeural antibodies were negative. Methotrexate blood levels were within nontoxic range and immunoglobin G4-subclass titers were normal. Additionally, QuantiFERON-TB testing for Mycobacterium tuberculosis was negative. Serum angiotensin-converting enzyme (ACE) level was mildly elevated (66 U/L), as was beta 2-microglobulin (4.6 mg/L). High-resolution computed tomography (CT) scan of the chest was not suggestive of sarcoidosis. Shortly after admission, the patient experienced two brief generalized tonic-clonic seizures. Following treatment with phenytoin, the patient's mental status and neurological examinations normalized completely. Electroencephalography (EEG) revealed nonspecific diffuse cortical slowing without interictal epileptiform activity. Two weeks later, the patient developed recurrence of his presenting neurological symptoms, in addition to new asymmetrical acute parkinsonism of the right hemibody (rigidity, bradykinesia, and resting tremor). Titration of his antiepileptic medication and addition of levetiracetam, lacosamide, and clobazam allowed for control of the symptoms, except for parkinsonism. The patient subsequently developed marked fluctuations of his mental status, ranging from an apathetic state to a confused and combative state. Repeat EEG and CSF analysis were essentially unchanged from previous. CSF cytology showed occasional atypical lymphocytes negative for CD3 and CD20. Additional analyses on CSF, including Mycobacterium tuberculosis culture, PCRs for Epstein-Barr virus and cytomegalovirus, ACE level and anti-neuronal cell surface antibodies, all proved negative. A follow-up MRI, 4 weeks after admission, showed progression of the left-sided cortical and leptomeningeal areas of restricted diffusion and enhancement, as well as new right frontoparietal cortical diffusion restriction and leptomeningeal enhancement (Figures 1C,D). A whole-body positron emission tomography scan did not reveal evidence of an underlying malignancy. Further work-up with a bone marrow biopsy showed no evidence of lymphoid neoplasm. An open meningeal biopsy was performed and gross examination revealed thickening and opacification of the meninges. Hematoxylin and eosin (H&E) stained sections demonstrated meningothelial hyperplasia (Figure 2A) with acute and chronic inflammation associated with fibrosis and entrapment of the underlying brain parenchyma, which showed evidence of chronic gliosis. The most striking feature was the presence of classical zones of palisading necrobiosis (Figure 2B). The chronic inflammatory aggregates consisted in reactive CD3 positive T cells with fewer number of CD20 positive B lymphocytes, as well as CD68 positive macrophages and CD138 plasma cells with no evidence of light chain restriction (Figures 2C,D). Despite the presence of perivascular leptomeningeal inflammation, no significant vasculitis was present. All the special stains for microorganisms, mycobacteria, and fungal elements were negative. The histopathological findings were consistent with leptomeningeal involvement by nodular rheumatoid meningitis. Following histopathological confirmation of the diagnosis, immunosuppressive therapy with monthly cyclophosphamide (500-750 mg/m2 for 6 months) and high-dose corticosteroids was initiated. Corticosteroid regimen consisted of methylprednisolone 1,000 mg IV daily for 5 days, then prednisone 80 mg daily (1 mg/kg) tapered by 10 mg every 2 weeks up to a dose of 40 mg daily, at which point the dose was tapered by 5 mg every 2 weeks for 2 months then by 5 mg every 4 weeks for 4 months. Methotrexate was discontinued due to its failure to prevent disease progression, while hydroxychloroquine was continued. One month following treatment initiation, the patient's neurological examination improved, although confusion and bilateral postural tremor persisted. Furthermore, most parkinsonian features, except for mild leg rigidity, largely resolved following immunosuppressive therapy. Residual parkinsonism was not felt to be severe enough to warrant dopamine-replacement therapy, especially as it was felt that the parkinsonism was most likely secondary to the underlying RM and not due to a primary neurodegenerative process. Additionally, dopamine-replacement therapy was withheld as it was previously reported to be ineffective in a case of rheumatoid meningitis-induced parkinsonism. All antiepileptic drugs, aside from lacosamide, were eventually tapered without clinical or electrographic seizure recurrence. Repeat MRI 3 months after treatment initiation showed complete resolution of previous findings (Figures 1E,F), correlating with normalization of CRP levels. Despite this radiographic improvement, the patient suffered from persistent behavioral and cognitive deficits with intermittent periods of agitation. The neuropsychiatric sequelae remained disabling enough for the patient to eventually be transitioned to a long-term care facility.

corticosteroids, immunosuppressant, parkinsonism, rheumatoid arthritis, rheumatoid granuloma, rheumatoid meningitis, seizure, vasculitis

PMC10422985_01

Male

A 1-year-old boy was admitted to our hospital for "abdominal distension for 1 week and anus blockage, and no flatulence and defecation for 3 days". One week prior to being admitted, the child developed abdominal distension without obvious inducement, no fever, no nausea and vomiting, no diarrhea, and he received no special treatment. His symptom of abdominal distension persisted, and there was no flatulence or defecation for 3 days ago. So the child was admitted to our emergency department. Manifestations of the child at admission: shock; low blood pressure (55/30 mmHg); rapid heart rate (200 beats/min); significantly prolonged capillary refilling time (4 s); elevated lactic acid (3.4 mmol/L); lack of consciousness; dyspnea; severe abdominal distension. Indirect intra-abdominal pressure was 15 mmHg at this time. Arterial blood gas analysis showed metabolic acidosis and low levels of sodium and potassium. A blood routine test showed leukocytosis and mild anemia. Biochemistry showed a significant decrease in albumin. Conservative fluid resuscitation, ventilator support, and anti-infective therapy were used to maintain a stable internal environment. The General Pediatric Surgery Department was promptly consulted on the diagnosis and treatment of this child while we actively corrected his shock status as his abdominal distension was very severe. Poor response; rhonchi in both lungs when breathing; no evident rales; distended and soft abdomen; no palpable abnormal mass. Anal examination: smooth finger entry; a mass (about 6 * 5 cm in size, poorly circumscribed, poor mobility) was palpable in the sacrococcygeal area; no blood staining after finger stall withdrawal. Body temperature 38.2 C, heart rate 200 beats/min, respiratory rate 50 breaths/min, blood pressure 55/30 mg. Auxiliary examination: blood routine and biochemistry are shown in Table 1; tuberculosis antibody (-); fecal routine: occult blood (+), fecal culture (-); negative PPD test results (PPD is an intradermal test to diagnose tuberculobacter infection by injecting a small amount of tuberculin into the skin at the injection site.). Erect abdominal radiograph (Figure 1) indicated the intestine was pneumatic, dilated, rigid, and stiff, with a tendency to straighten, spaces between the intestine walls were thickened, and gas distribution was uneven. Intestinal obstruction was likely based on the erect abdominal radiograph. Abdominal B-mode ultrasound imaging: No evident causes of acute abdominal disease were detected, abundant gas accumulated in partial intestine, effusion was dilated in partial intestine, a hypoechoic area, about 5.1 * 4.9 * 4.8 cm in size was observed in the sacrococcygeal area, with a uniform echo, clear boundary, and regular shape. Color Doppler flow imaging (CDFI): punctate blood flow signal was observed, PSV: 25.6 cm/s, RI: 0.6. Whole blood was collected from the child before surgery. Serological tests revealed positive perinuclear antineutrophil antibody (P-ANCA) and elevated vasoactive intestinal peptide concentrations, both of which are markers that are currently highly distinctive in determining ulcerative colitis. Prompt exploratory laparotomy and decompression were performed as the abdominal pressure of the child continued to rise to the ACS level (abdominal compartment syndrome). It was found that small intestinal blood circulation was good, and the entire colon was dilated with a diameter of more than 6.1 cm and there was no blood circulation disturbance. TM was determined to be likely based on the above data and the patient's significant clinical manifestations of septic shock. Colonoscopy (Figure 2) revealed numerous purulent masses and ulcers on the surface of the colon. The pathology after colon biopsy (Figure 3) showed that the crypt structure had changed, and crypt abscess had formed. Mucosal and muscular layer eosinophils < 5 / HP, and ganglion cells can be seen in the muscular layer (Figure 4). After other diseases were ruled out and the clinical manifestations were combined with auxiliary examination results, the patient was diagnosed with UC. We conducted sacrococcygeal magnetic resonance imaging (MRI) (Figure 5) and surgically removed the sacrococcygeal mass, then sent it for pathological examination after surgery. The pathological change was diagnosed as yolk sac tumor based on imaging, pathomorphology, and immunohistochemical results (Figure 6). The patient underwent an emergency exploratory laparotomy as his intra-abdominal pressure kept increasing after having been administered anti-shock medication, gastrointestinal decompression, an indwelling anal canal to lower intra-abdominal pressure, and other treatments. The entire colon was found to be highly dilated during the surgery. Appendectomy + colonic irrigation via appendiceal catheterization + intestinal exteriorization + colonic biopsy was performed after the colonoscopy showed ulcers and numerous purulent masses in the colon. Intestinal exteriorization + abdominal wall suspension was performed due to an unachievable primary abdominal closure caused by intra-abdominal hypertension. The child underwent enteroscopy + return of exteriorized intestine + terminal ileostomy when the abdominal distension was relieved on the 7th day after surgery. Colonoscopy + sacrococcygeal mass resection was performed after excluding surgical contraindications. Colonoscopy indicated that intestinal inflammation continued to exist without significant improvement. Postoperative pathology of the sacrococcygeal mass indicated yolk sac tumor. The child was given 6 courses of JEB chemotherapy (etoposide: 120 mg/m2, vgtt, d1-3; carboplatin: 600 mg/m2, vgtt, d2; bleomycin: 15 mg/m2, vgtt, d3). Enteroscopy was performed for the fourth time after these 6 courses and showed that intestinal inflammation disappeared completely. Stoma closure after terminal ileostomy was then performed. The child was treated for about 1 year, was hospitalized 9 times, underwent 4 surgeries, and received 6 courses of chemotherapy. Gastrointestinal symptoms of UC and TM in this patient completely disappeared after the sacrococcygeal YST resection, which was aided by postoperative chemotherapy. The child's body grew and developed well during the 7-year follow-up with no recurrence of the tumor, and no recurrence of ulcerative colitis. The follow-up is still ongoing.

children, paraneoplastic syndrome, toxic megacolon, ulcerative colitis, yolk sac tumor

PMC9342706_02

Male

The second patient, a 31-year-old male, came to the orthopedic clinic with left ankle pain following a twisting injury while playing basketball. He had twisted his ankle several times however this time his ankle was really painful. On physical examination, retromalleolar pain was present in addition to ankle instability. Positive anterior drawer test was noted and talar tilt test showed no end point. MRI result showed peroneal sheath filled with fluid collection in addition to peroneal brevis split tear. Over the lateral ligament complex, the anterior talofibular ligament (ATFL) was redundant and heavily fibrotic. Calcaneofibular ligament (CFL) was fibrotic and redundant as well. Intraarticular pathological findings showed the presence of anterior bony impingement over the distal tibia. We concluded that the source of ankle pain was due to concomitant peroneal tear in lateral ankle instability. We planned to address all symptomatic findings surgically.

ankle injury, peroneal tendon injury, peroneal tendon surgery

PMC3589207_01

Male

A 34-year-old, recently diagnosed HIV-positive male presented to us with complaints of sudden painless decrease in vision in both eyes, 1 week before. On ocular examination, patient denied perception of light with indirect ophthalmoscope in dark room. Pupils were equal in size, and direct and consensual reflexes were normal. Ocular movements were full. Anterior segment slit lamp biomicroscopy and fundus examination with indirect ophthalmoscope were clinically within the normal limits. Systemic evaluation revealed no definite focal neurological deficits. A clinical diagnosis of cortical blindness was made. The patient underwent visual evoked potential (VEP) and magnetic resonance imaging (MRI). VEP showed non-recordable response (Figure 1). Axial T2-Flair MRI of the brain and orbit (Figure 2a) showed hyperintense signal intensity lesions bilaterally in the parieto-occipital white matter. Axial T2-Flair diffuse-weighted image (Figure 2b) showed hyperintense lesions bilaterally in the parieto-occipital white matter. MR spectroscopy showed elevated lactate and choline peak and reduction in the N-acetyl aspartate (NAA). These features were suggestive of demyelination. Optic nerve course, caliber, and signals were within the normal limits. Patient was evaluated systemically by the AIDS care physician and neurologist. Clinically, no cognitive or neurological deficits or other manifestations related to parieto-occipital and frontal disease were found. Patient CD4 count was 104 cells/mm3. Blood and CSF analyses to rule out other neurological illness commonly seen in patients with HIV such as cerebral tuberculosis, toxoplasmosis, Cryptococcus infection, or lymphoma were negative. The patient was initiated on highly active antiretroviral therapy (HAART) but refused inpatient treatment. Patient was brought to us few weeks later in an unresponsive state with terminal neurological illness and died within few hours.

PMC2660713_01

Male

The first patient was a 49-year-old man with cough and weight loss. His sputum contained acid-fast bacilli, and he simultaneously received a diagnosis of HIV infection with a CD4-positive T-lymphocyte count (CD4 count) of 9 cells/mm3. Tuberculosis therapy was begun and comprised isoniazid, rifampin, pyrazinamide, and ethambutol; he was also started on a fixed-dose combination of zidovudine, lamivudine, and abacavir. DNA was extracted from the initial sputum smear taken at the time of presumptive tuberculosis diagnosis according to previously published methods. The GenoType CM/AS reverse line blot assay (Hain Lifesciences, Nehren, Germany) was weakly positive for M. tuberculosis complex. The patient's cough resolved, and he completed a 9-month course of tuberculosis therapy. When fever subsequently developed, he was admitted to the hospital; CD4 count was 13 cells/mm3. Mycobacterial blood culture grew acid-fast bacilli after 12 days of incubation; results of AccuProbe MTB and MAC tests were negative. Heat-killed cells from the positive blood culture were identified as M. simiae by the INNO-LiPA reverse-line blot. Sequencing of the full 16S rDNA gene, ITS, and hsp65 gene identified the isolate as "M. sherrisii." The 16S rDNA and hsp65 sequences were identical to the M. sherrisii American Type Culture Collection (ATCC; Manassas, VA, USA) BAA-832 strain sequences deposited in the GenBank sequence database under accession nos. AY353699 (16S rDNA) and AY365190 (hsp65). The ITS sequence was identical to that of M. sherrisii strain FI-95229 (accession no. DQ185132), isolated from sputum of a patient in Italy. The Tanzania patient was treated with azithromycin, 500 mg/day, and ethambutol, 800 mg/day. His fever abated and he remained well, with 109 CD4 cells/mm3 as of last follow-up in 2008.

PMC2660713_02

Male

The second patient was a 36-year-old HIV-infected man with a 3-month history of fever and weight loss and 31 CD4 cells/mm3. He had been taking fixed-dose combination stavudine, lamivudine, and nevirapine for 5 months, but his adherence to therapy was poor. A mycobacterial blood culture grew acid-fast bacilli after 15 days of incubation; AccuProbe MTB and MAC test results were negative. Heat-killed cells from the positive blood culture were identified as M. simiae by the INNO-LiPA reverse-line blot and again as M. sherrisii by sequencing of the full 16S rDNA gene, ITS, and the hsp65 gene. The 16S rDNA gene had a single base-pair difference when compared with the M. sherrisii ATCC BAA-832 strain sequence in GenBank. We deposited the new 16S rDNA sequence in GenBank under accession no. EU883389. The hsp65 sequence was identical to the M. sherrisii ATCC BAA-832 strain sequence (accession no. AY365190); the ITS sequence was identical to the M. sherrisii strain FI-95229 (accession no. DQ185132) sequence. The patient was treated with azithromycin, 500 mg/day, and ethambutol, 800 mg/day; fever abated. At follow-up in 2008, the patient was continuing treatment with azithromycin and ethambutol but had abdominal pain and hepatosplenomegaly. Abdominal ultrasonography showed retroperitoneal lymphadenopathy. Follow-up mycobacterial blood cultures have been negative.

PMC2660713_03

Female

The third patient was a 36-year-old HIV-infected woman with a 4-month history of bilateral skin lesions affecting the lower extremities (Figure) and 206 CD4 cells/mm3. HIV infection had been diagnosed 18 months earlier; baseline CD4 count was 6 cells/mm3. She began fixed-dose combination stavudine, lamivudine, and nevirapine soon after her HIV diagnosis. An incisional biopsy from the active margin of a leg lesion showed several foci of dermal necrosis with dense lymphocytic infiltrate and Langhans-type giant cells consistent with granulomatous inflammation of tuberculosis (Figure). Culture of biopsy material was positive for M. avium complex. The isolate reacted only with the M. avium-intracellulare-scrofulaceum complex probe of the INNO-LiPA reverse-line blot. The 16S rDNA gene and ITS sequences were identical to the M. avium complex ATCC 35770 (Melnick) strain sequences published by Boddinghaus et al. and available in the Ribosomal Differentiation of Microorganisms database (http://rdna.ridom.de). The ITS sequence was also identical to the MAC ATCC 35770 strain sequence available in GenBank (ITS sequevar MAC-D, accession no. L07851). The hsp65 sequence was identical to the ATCC 35770 sequence (accession no. U85637). Because the full 16S rDNA gene sequence of this strain was not available in GenBank and only a small fragment of hsp65 was available, we deposited our sequences under accession nos. EU815938 (16S rDNA) and EU935586 (hsp65). This patient was treated with azithromycin, 500 mg/day, ethambutol, 800 mg/day, and rifampin, 600 mg/day. Her lesions abated over the subsequent weeks, and she remained well as of follow-up in 2008.

PMC3702071_01

Female

A 50-year-old patient presented in August 2010 with heavy and irregular bleeding per vaginum for last 10 months. She had undergone dilatation and curettage (D and C) and cervical biopsy in December 2009 for menorrhagia. Histopathology showed a disordered proliferative phase with chronic cervicitis. Patient received medical management with temporary relief. She had a second episode of menometrorrhagia in March 2010 followed by a repeat D and C. The endometrial curettings was reported as simple hyperplasia without atypia. Her general, local examination and routine investigations were normal. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed and the patient was discharged in satisfactory condition on eighth post-operative day. Histology revealed endometrium in proliferative phase and myometrium showed multiple non-necrotizing epithelioid cell granulomas. Stain for AFB, fungal organisms were negative [Figure 1]. No cytomegalovirus inclusion bodies were seen and there was no evidence of vasculitis. Uterine cervix showed chronic cervicitis and bilateral adnexa were unremarkable. Workup for systemic disorders i.e., tuberculosis, vasculitis and sarcoidosis was negative. Patient was asymptomatic at 6 weeks and one year follow-up.

granulomatous inflammation, myometrium, uterus

PMC3702071_02

Female

A 40-year-old presented with pain and mass lower abdomen of five months duration with no menstrual irregularity. General physical examination was normal, local examination was suggestive of fibroid corresponding to size of 18 weeks pregnant uterus. Her routine investigations were normal. Ultrasonography revealed a large single intramural fibroid 10 x 9.7cm with thin endometrium and normal ovaries. Ultrasound guided FNAC was consistent with findings of leiomyoma. Patient underwent a total abdominal hysterectomy. Histopathological examination revealed endometrium in secretory phase, uterine tumor as leiomyoma and in addition myometrium showed caseating epithelioid granulomas along with Langerhans and foreign body giant cells [Figure 2]. Stain for AFB was positive. Screening for tuberculosis elsewhere in the body was negative. Patient was started on ATT despite hysterectomy and absence of tuberculosis elsewhere because the adnexa was left behind where the possibility of a tubercular focus could not be ruled out. Currently patient has completed Category I DOTS therapy and asymptomatic on follow-up.

granulomatous inflammation, myometrium, uterus

PMC3869947_01

Female

Marissa was a 17-year-old with bipolar I disorder and comorbid attention deficit hyperactivity disorder, who lived with her mother, father, grandmother, and two brothers, one 19 and one 16. She was being treated with lithium 1200 mg and quetiapine 200 mg. She had had several instances of self-injurious behaviors (e.g., cutting). Her parents described the household as a "war zone" due to her frequent outbursts of rage. All family members agreed that Marissa's rages created huge problems for the family, but they disagreed on the causes of these episodes. Her mother described them as being "manic-like," with rapid speech, excessive movements, and flight of ideas. She was particularly worried about how Marissa would cope when she went off to college the following year; would she curse at her professors and alienate her roommates? Marissa claimed that her "attacks" were largely triggered by the highly critical, hostile, and insulting interactions she had with her brothers, who, she said, regularly called her "fat and stupid." When asked, her brothers used more colorful words to describe her behavior. In the early sessions of FFT, the clinician encouraged Marissa, her parents, and her brothers to identify the triggers, early warning signs, and potential preventative strategies for her rage reactions. Her reactions were often precipitated by family arguments (e.g., certain looks from her brothers) or multiple requests from her parents that confused her. The clinician assisted her in developing a stress thermometer, which clarified the stages of her angry escalations. Marissa and her family members were then encouraged to use a set of emotional self-regulation techniques when her mood escalations began, including: disclosing to one another that "something isn't feeling right"; using calming self-talk "when we feel the heat rising"; mindful breathing; exiting the situation (e.g., going outside to cool down), or attempting to separate the warring members of the family. With repeated practice, Marissa found that she could better control her outbursts with her parents, but was still repeatedly provoked by her brothers. When their interactions degenerated into back and forth yelling matches, she was especially likely to start self-cutting. The communication enhancement module focused on her relationships with her brothers and encouraging each of them to practice active listening (paraphrasing, asking clarifying questions, nodding one's head to show acknowledgment). The use of these skills was helpful to Marissa and her brothers in slowing down their volatile interactions. Being able to limit negative interchanges to a maximum of three "volleys" also helped to reverse these predictable sequences. In the final segment of FFT, Marissa and her parents worked on problem solving to maximize her chances of making a successful adjustment to college. The sessions included how to manage her medications (i.e., filling her medication prescriptions and taking her pills without reminders), getting herself out of bed in the morning without continual intervention by her parents, and completing household tasks. They also involved emotional self-regulation techniques to use when she felt herself becoming angry with others (e.g., deep breathing, distraction). By the end of treatment, Marissa still had impulsive, angry reactions brought on by negative interactions with her brothers. However, both Marissa and her parents reported that these episodes were becoming fewer and further between, did not last as long, and were not as destructive. She reported fewer suicidal thoughts and better overall mood states. Her brothers, although still angry with her, acknowledged that they had not understood the nature of her mood disorder, had on many occasions deliberately provoked her. She acknowledged, in turn, that they were becoming more patient with her. At termination, she continued with her ongoing pharmacotherapy appointments but did not seek additional therapy.

PMC3621155_01

Female

A 30-year-old housewife presented with a one-week history of progressive painless bilateral ptosis. Initially the ptosis affected the left eye and was followed five days later by ptosis of the right eye. She also noticed gradual-onset malaise and fatigability upon doing her regular activities progressing to decreasing dexterity in both upper limbs and fatigability on walking. She denied any preceding history of flu-like symptoms or gastrointestinal infection and no diurnal fluctuation in her symptoms were present. Her medical history was otherwise unremarkable. Neurological examination revealed normal mental status. There was bilateral ptosis (Figure 1) with inability to open the lids volitionally. Upward gaze produced mild lid elevation. The pupils were equal and reactive to light, and there was no restriction in horizontal and vertical eye movement, and Bell's phenomenon was preserved. Neurological examination of the cranial nerves was otherwise normal. Sensory examination was normal. Muscle strength, tone, coordination, and gait were normal. Deep tendon reflexes were absent. Complete blood cell count and biochemical laboratory screening (renal, liver and thyroid function, electrolyte, and glucose) were normal. Since ocular myasthenia gravis needed to be ruled out, an edrophonium test was performed but was negative, and repetitive supramaximal stimulation (SRS) testing on day 9 of the illness with recording from the right abductor digiti minimi (ADM) and the both biceps did not show a decremental response. Cerebrospinal fluid (CSF) analysis yielded albuminocytological dissociation with a protein of 0.6 gm/L (normal 0.15-0.45 gm/L) and less than 5 white blood cells/uL (normal < 5/ul). CSF glucose was normal. CSF viral serology and gram stain and culture as well as tuberculosis smear and culture were negative. Serum anti-GQ1B, antiganglioside and antiacetylcholine receptor antibodies sent on day 12 of the illness (before initiating treatment) were negative. Magnetic resonance imaging (MRI) of the brain was normal. Nerve conduction study (NCS) (Tables 1 and 2) performed on day 10 of the illness revealed significant reduction in the compound motor action potentials (CMAP) with conduction blocks in the median and ulnar nerves and reduced motor conduction velocity (MCV) in the lower limbs with reduced CMAP amplitudes. The F wave was preserved but dispersed in the upper limbs and absent in the lower limbs. Electromyography (EMG) showed diffuse signs of denervation in all myotomes of the face, upper limbs, and lower limbs. In addition, significant polyphasia was noted in the muscles of the face. These findings were consistent with acute predominantly axonal inflammatory polyradiculoneuropathy. By that time (day 10 of the illness), the patient started developing a gradual increase in lower limb weakness and had increasing difficulty in walking. The patient was started on intravenous immunoglobulin (IVIG) therapy (0.4 g/kg/day IV for 5 days) with rapid and complete resolution of her neurological findings (Figure 2).

PMC9494791_01

Female

A 79-year-old woman with hypertension, ischemic heart disease, and Hashimoto's disease sustained a closed fracture of the left distal radius due to a fall from patient's height. The patient underwent closed reduction and immobilization in a plaster cast. Because of secondary displacement, eight weeks later, patient received open reduction and stabilization with a volar titanium locking plate and screws. After surgery, the patient suffered from severe pain and edema, but ultrasound showed no pathology related to the performed operation, and the symptoms relieved spontaneously. After a 2.5-year asymptomatic period, the patient reported pain and edema of patient's left wrist. The radiograph showed the loosening of one screw, causing conflict with soft tissues. We removed the implant, but we also found serous masses penetrating the surrounding tendon sheaths. Microbiological cultures revealed no pathogens; tuberculosis was excluded as well. Due to suspected infection, the patient empirically received clindamycin and ciprofloxacin. One month after the implant removal, the surgical wound presented as ulceration with fistulae and purulent discharge (Fig. 1); radiographs revealed osteolysis within the styloid process of the radius. Despite many negative microbiological cultures, we still suspected infection as the most probable cause. We performed debridement of the lesion with application of local antibiotic carrier gentamicin beads and collagen gentamicin sponge with the addition of 1 g of cefazolin and 1 g of vancomycin. Negative pressure wound therapy (NPWT) to improve wound healing followed the surgery. After two weeks, wound healing was satisfactory. After another month, radiographs showed a pathologic fracture in the site of the previously treated osteolytic bone defect and screw canals. We performed external fixation with wrist canal decompression and local administration of gentamicin beads again. The wound healing was slow and microbiological cultures revealed Enterococcus faecalis. Targeted antimicrobial therapy with levofloxacin resulted in only partial improvement. As new purulent skin lesions appeared, we took skin and bone biopsies (Fig. 2). Histopathology of the bone was unspecific, but excessive numbers of neutrophils and plasmacytes were found in the skin. Radiographs showed a progressing deformation of the wrist and osteomyelitis (Fig. 3 A, B). After exclusion of plasmacytoma and other hematologic conditions, PG was diagnosed. The introduction of immunosuppressive treatment with prednisone and CsA gave excellent clinical effects. Unfortunately, every attempt to reduce the prednisone dose below 20 mg/day led to the lesion's recurrence despite concurrent CsA treatment with an adequate trough level of 100-130 ng/ml. Given the poor patient tolerance of the treatment and two episodes of superinfection, the immunologic treatment was not continuous, leading to a massive PG relapse (Fig. 4 A, B). Severe pain, deformation of the extremity, and function alteration were the reasons for amputation of the proximal 1/3 of the forearm. The immunosuppressive treatment was discontinued after surgery because of the risk of infection. The wound healing was primarily good, but PG lesions relapsed in the stump after several weeks. Magnetic resonance showed fistulae and edema in soft tissues and osteomyelitis in forearm bones, but the culture from the wound was negative. Immunosuppressive treatment was started again, with an initially good response. Unfortunately, a massive relapse of ulcers occurred after decreasing the prednisone dose below 10 mg/day. The next half of a year of local and systemic treatment did not succeed, which ultimately led to exarticulation in the scapulohumeral joint. At this point in time, 6 years had already passed since the primary fracture. The wound healing was good, but immediately after the surgery, the patient was diagnosed with COVID-19. High-resolution computed tomography scans showed that the viral inflammation affected 90% of both lungs. The patient was in a severe condition and required 6 mg/day of dexamethasone and high-flow oxygen therapy (40 l/min 100% O2). Five days later, when patient's condition improved, oxygen supplementation was limited and ultimately ended after 10 days. After two weeks, the patient was discharged home on prednisone 30 mg/day. The prednisone dose was gradually reduced and withdrawn after 8 months. There was a relapse of PG one year after disarticulation - a purulent ulcer with morphology typical for PG in the postoperative scar. After a return to prednisone therapy, the ulcer healed completely. Now, every attempt to reduce prednisone dose below 30 mg/day results in a relapse of PG lesions, making the patient GC-dependent. Currently, the 85-year-old patient is suffering from iatrogenic Cushing syndrome, with kidney failure and fatigue as the most prominent symptoms. We are applying local GCs to avoid increasing the dose of systemic GCs. Ethical standards: The written consent of the patient for publishing the case report was obtained.

internal fixation of fracture, nonhealing wound, osteomyelitis, pyoderma gangrenosum

PMC7204963_01

Male

A 57-year-old previously homeless male with a history of trauma from a bicycle crash originally presented to our level 1 trauma center for the evaluation of back and flank pain and a "click" in his chest. He was found to have an acute fracture of the left seventh rib and chronic nonunion of left eighth through twelfth ribs [Figure 1 and Table 1]. He underwent elective rib plating for symptom management in addition to evacuation of hemothorax and pulmonary decortication for fibrothorax and trapped lung. The seventh through tenth ribs were plated with a bicortical locking rib fixation system, and a 28 Blake chest tube was placed [Figure 2]. At least three bicortical locking screws were placed proximal and distal to the fracture locations. He tolerated the procedure well and had significant improvement in his symptoms on follow-up. He denied any residual pain or clicking of the ribs and could finally get a good night's sleep. An improvement in his symptoms greatly improved his quality of life so that he was able to obtain a job, was able to rent an apartment, and was no longer homeless. Three months later, he was riding his bicycle when he was again hit by a motor vehicle. In addition to numerous devastating injuries including a significant traumatic brain injury (TBI) prompting admission to our ICU, he was found to have flail chest with lateral and posterolateral rib fractures of the first through tenth ribs and periprosthetic fractures of the seventh through tenth ribs [Figure 3 and Table 1]. The rib plating hardware was completely intact, except for a single displaced screw from the seventh rib plate [Figure 4]. He was also found to have a hemothorax, for which a chest tube was placed. Notably, there was increased difficulty of the chest tube placement due to the prior pulmonary decortication and rib plating. His new rib fractures were treated nonoperatively due to his poor clinical status from his TBI. Unfortunately, he expired from his injuries.

flail chest, periprosthetic fracture, rib fracture, surgical rib fixation

PMC7500831_01

Female

A 49-year-old female patient came to our clinic with increasing pain and swelling in her left wrist for two months. She was a housewife and had no known disease other than hypertension and RA. The patient was treated with a diagnosis of seronegative RA in another clinic, and she has been using methotrexate (MTX) 10 mg/week and prednisolone 5 mg/day along with RTX for two years (4 cures of RTX in total). The last infusion of RTX was administered approximately 5 months before the date she applied to our hospital. There were no signs of inflammation in her joints except the left wrist. In laboratory tests, hemogram, liver transaminases, urea, creatinine, uric acid levels and urine analysis were within normal limits. The erythrocyte sedimentation rate (ESR) was 46 mm/h and the C-reactive protein (CRP) level was 18 mg/L. Rheumatoid factor (RF), anti-cyclic citrullinated peptide antibodies (ant-CCP) and antinuclear antibodies (ANA) were negative. Chest radiography and sacroiliac joint radiography were within normal limits. Thereupon, the dose of methotrexate was increased to 15 mg/week and the dose of prednisolone to 10 mg/day. At the control two months later, there was no decrease in the patient's complaints. Moreover, redness and cutaneous fistulization developed on the radial side of the left wrist (Figure 1). The patient complained of intermittent fever and loss of appetite. Her temperature was 37.0 C, blood pressure 135/80 mmHg, and heart rate 72/minutes. Chest and abdominal examinations were normal. There was no lymphadenopathy in head and neck examination. Laboratory evaluation showed an increase in ESR (62 mm/h) and CRP (53 mg/L). There was no infiltrative lesion or pleural effusion on chest radiography. The patient was hospitalized. Blood and urine cultures were found negative. The lesion on the left wrist was debritted. Histopathologic evaluation revealed the presence of acid-fast bacilli. Polymerase chain reaction test and culture confirmed mycobacterium tuberculosis. Quadruple anti-TB treatment (ethambutol, rifampicin, pyrazinamide and isoniazid) was started. Prednisolone was terminated by reducing 2.5 mg per week. MTX and RTX were withdrawn. She was treated with 12-months course of antituberculous treatment and responded well (Figure 2). After antituberculous treatment, the patient who did not suffer pain or swelling in her other joints was not given any medication for RA. The absence of joint complaints despite not receiving immunosuppressive therapy for over a year, negative serological tests for RF, anti-CCP and ANA, and the absence of typical erosions for RA in the joints suggest that the initial diagnosis of RA may not be correct. The patient may have had viral arthritis or reactive arthritis. Less likely, the patient may be in prolonged remission.

infection, rheumatoid arthritis, rituximab, tuberculosis

PMC7596336_01

Female

53 years old female, with 15 pack year (half pack a day for 30 years) smoking history, presented to urgent care with dry cough and dyspnea on exertion. Two weeks prior to the presentation, she started to have dry cough associated with mild sore throat and rhinorrhea. Two days prior to the presentation, the patient developed mild gradual onset dyspnea on exertion, which prompted her to go to urgent care. A Chest X ray was done and showed diffuse pulmonary micronodules (Fig. 1). Subsequently, the patient was transferred to our institute for further evaluation for possible TB. She denied fever, night sweats, anorexia or weight loss, and her vital signs were in normal range. She did not require any oxygen supplementation. Patient was well appearing and breathing comfortably in ambient air. Chest auscultation revealed minimal bilateral expiratory wheezing. No rash, lymphadenopathy or abdominal organomegaly was appreciated. The patient does not have chronic medical conditions and takes no daily medications. She reported that she moved into an old house 2 months ago and did not notice any molds in her house. She lives with two cats. She smokes half a pack per day for 30 years and denies alcohol or illicit substance use. She works in a pastry store. She lives in New England area and denied any recent domestic or international travel. Last long-distance travel was more than 20 years ago. She went to England and Barbados. On further inquiry, the patient had varicella in her 30s when she was postpartum, which she contracted from her elementary-school-aged daughter. Neither of them were hospitalized. CT pulmonary angiogram showed numerous, diffuse, subcentimeter, pulmonary nodules throughout the lungs, many of which demonstrate calcification with an associated calcified mediastinal lymph node (Fig. 2). Patient's CBC with differential, basic chemistry profile, liver functional test, inflammation markers including ESR and CRP were all within normal limits. Respiratory pathogen panel was negative. Urine and serum histoplasma antigens were negative. Coccidoides antibody was negative. Patient was not able to produce sputum even with induction, hence AFB culture with smear was not performed. TB QuantiFERON was negative. VZV IgM was negative, but IgG was positive. HIV was non-reactive. CT of abdomen and pelvis showed no intraabdominal abnormalities. A multidisciplinary discussion was held between internal medicine, pulmonary medicine, infectious disease as well as radiology. Given patient was overall well appearing, no B symptoms, fever or hypoxia, no travel history to endemic mycoses area or occupation exposure history, as well as pan-negative lab data including non-reactive fungal, TB and HIV serology. Pt was presumptively diagnosed with healed chronic granulomatous lung infection. Given she had history of varicella 20 years ago and her VZV IgG was positive, we believe her lung lesions are most likely secondary to healed VZV lung infection. After careful weighing risk and benefit, no further invasive testing such as bronchoscopy or lung biopsy was recommended. We believe patient's respiratory symptoms, including cough and shortness of breath, were related to obstructive lung disease rather than pulmonary nodules. She was treated empirically with prednisone and albuterol/ipratropium nebulizer with significant improvement and discharged with a 5-day course of prednisone. The patient followed up with primary care physician one month after discharge and was feeling well. Her lung nodules do not require further follow-up imaging. One year after discharge, patient self-reported feeling well in a follow up phone call by one of the authors.

diagnosis of exclusion, diffuse pulmonary nodules, granuloma, varicella-zoster virus

CT chest showed numerous, diffuse, subcentimeter, pulmonary nodules throughout the lungs (indicated by arrows), many of which demonstrate calcification.

PMC8558794_01

Male

A 12-year-old boy presented with intermittent, foul-smelling, occasionally blood-stained left ear discharge for 3 years which did not improve with conventional antibiotic therapy. He had no other features suggestive of TB such as cervical lymphadenopathy, weight loss, and night sweats. Otoendoscopic examination revealed a fleshy polyp at the posterior superior and attic area associated with thick yellowish discharge. The pars tensa of the tympanic membrane was intact (Figure 1). Computed tomography (CT) temporal bone revealed soft tissue opacity in the middle ear with the ossicular erosions and destructions. There was also soft tissue density in the mastoid region with loss of septation and dehiscence of tegmen and sigmoid plate. However, the facial nerve canal, internal acoustic meatus, cochlea, and vestibule were intact (Figure 2). The audiometric examination revealed severe mixed hearing loss. The patient underwent modified radical mastoidectomy under general anesthesia, via a postaural approach using the out-to-in technique (Figure 3(a)). Upon drilling the mastoid, a cystic lesion was encountered (Figure 3(b)). The drilling was done around the cyst; however, it got punctured during the procedure and yielded dirty turbid whitish fluid. The remaining cyst and tissues were removed and sent for histopathological evaluation. There was a sequestrum as well which was also removed. The granulation tissues at the attic were removed. Posterior bony canal wall was drilled out and canal wall down mastoidectomy was performed. The lenticular and long process of incus was necrosed and removed. The malleus head was removed to evaluate the anterior epitympanum (attic). Stapes suprastructure was partially necrosed (Figure 3(c)). Temporalis fascia graft was placed after clearing the disease. There were no postoperative issues. The cyst wall along with granulations tissues were sent for histopathological examinations (Figure 3(d)). The histopathological report showed epithelioid cell granulomas, Langerhan's type giant cell, chronic inflammatory cells, and granulation tissue, consistent with TB. The cyst wall lining epithelium was attenuated with chronic inflammatory cells infiltration and giant cell reaction (Figure 3(e)). The antitubercular medications were started for the patient, and finally, the patient recovered after completion of chemotherapy (Figure 3(f)). The patient was followed up for 1 year, the cavity healed however, the hearing did not improve.

tuberculosis, mastoid cyst, otitis media

PMC6180882_01

Male

The patient is a 44-year-old immigrant male who presented to our institution with multiple masses in bilateral parotid glands, left greater than right. He had a history of neurocysticercosis, presumably owing to ingestion of uncooked pork in Mexico and had undergone a previous craniotomy with removal of the brain mass in Mexico. The patient had been vaccinated against tuberculosis, and subsequent work-up for systemic tuberculosis was negative. This new onset of bilateral parotid masses since his emigration to USA was presumed to represent cysticercosis lesions. A CT scan of the neck with i.v. contrast demonstrated bilateral parotid masses with a dominant, ring-enhancing, hypodense lesion in the left superficial parotid gland, which measured 3.0 x 2.9 cm (Figure 1). A left superficial parotidectomy was performed, and upon pathological analysis, the peripherally enhancing lesion grossly appeared as a large yellowish fluid-filled cyst (Figure 2). Micropathology revealed a squamous epithelium-lined cyst with lymphoepithelial complexes (brown islands) consistent with a lymphoepithelial cyst (Figure 3). This raised the concern of HIV infection, which was confirmed with serological studies.

PMC6037825_01

Female

A 70-year-old female patient was admitted with complaints of lower abdominal pain of 5 months duration. Pain was initially intermittent but steadily worsened to require management with narcotics. The patient reported constipation but denied rectal bleeding. At the time of presentation, she had urinary retention that led to the placement of an indwelling Foley catheter which revealed hematuria in the bag. She reported anorexia, nausea, abdominal bloating, and worsening of bilateral leg edema, but did not have any vomiting, hematemesis, chest pain, melena, jaundice, fever, chills, night sweats, or weight loss. Her CT scan showed a large heterogeneous but predominantly fatty pelvic mass compressing the bowel and bladder (Figure 1). Two needle core biopsies were done which revealed only benign adipose tissue. Patient was sent for upper and lower gastrointestinal endoscopies and MRI. She further complained of persistent lower abdominal and pelvic pain, and difficulty urinating. An MRI showed a 13 cm x 10 cm x 10 cm pelvic mass that appeared well encapsulated and nested between the rectosigmoid and sacrum. There was no suspicious lymphadenopathy (Figure 2). The patient was admitted for the resection of the mass with possible colostomy. She had no history of heart disease, rheumatic fever, neurological disorder, diabetes, ulcers, asthma, tuberculosis, or kidney, liver, or thyroid disease, and had no suspicious lesions on the skin. The patient underwent bilateral ureteral stent placement followed by resection of a large 18 cm sacrococcygeal tumor with en-bloc low anterior rectosigmoid resection and Hartmann's stump. On gross examination, the tumor was an unencapsulated, tan-yellow solid mass, measuring 13 cm x 13 cm x 7 cm. The cut surface was tan-yellow, with minute foci of hemorrhage. The tumor was approximately 0.3 cm away from the adjacent colon and did not involve the same. Histopathologically, the tumor consisted predominantly of mature adipose tissue with no atypia. Few thin and moderately thick collagen bands were noted. Foci of hemorrhage and minute areas of extramedullary hematopoiesis were identified. Fresh tumor tissue was analyzed for chromosomal abnormalities. Routine karyotyping was done. An abnormal female karyotype was observed after examination of 20 metaphase cells. There was a clonal abnormality: all metaphases had trisomy of chromosome 5. No other abnormality was found. Fluorescence in situ hybridization (FISH) analysis of fresh tissue was done, FISH analysis summary is shown in Table 1. LSI DDIT3 and LSI FOXO1 dual color break-apart DNA probes (Vysis Inc.) were used to detect the rearrangements associated with the DDIT3 (CHOP) gene in the 12q13 region and FOXO1 (FKHR) gene in the 13q14 region, respectively. Two hundred interphase cells were examined for each probe. Within the limitations of the procedure, the hybridization produced a normal pattern for both probes, consistent with no translocations, deletions, or rearrangements of the DDIT3 (CHOP)/12q13 or FOXO1 (FKHR)/13q14 genes. Fluorescence in situ hybridization analysis of formalin-fixed paraffin-embedded tissue was performed using the Vysis MDM2 DNA probe (Abbott Molecular Inc.), which contains two probes. The LSI MDM2 DNA probe labeled spectrum Orange, specific for the MDM2 gene locus on 12q15; while the CEP 12 DNA control probe labeled spectrum Green which is specific for DNA sequence at the centromeric region of chromosome 12p11.1-q11.2. At least 50 non-overlapping cells were scored. The results of hybridization produced an MDM2:CEP12 ratio of 1.0 (Table 2). This was consistent with no amplification of the MDM2 gene, ruling out the possibility of a well-differentiated (WD) liposarcoma. Further immunostaining with HMB-45 and MART-1 was also negative. Based on these findings a final diagnosis of adrenal myelolipoma was rendered. Upon recent follow-up (status post-resection 3.5 years), the patient was asymptomatic with no tumor recurrence.

adrenal myelolipoma, chromosomal abnormalities, extra-adrenal myelolipoma, in situ hybridization, presacral region

PMC4967656_01

Male

We observed a 22-year-old male patient with marked darkening of the skin, especially on the palms and areolae, jaundice on the skin and sclera, astheno-adynamia, hypotension (80/50 mm Hg), pain in the right hypochondrium. The physical examination revealed asthenic constitution, height 180 cm, body weight 55 kg, reduced facial and body hairs, reduced subcutaneous fat tissue, jaundice on the skin and visible linings, heart rate 105 bpm, enlarged liver, brownish spots on the gums and on the hands. The patient reported that several years ago he was treated with local antimycotic agents for alopecia areata and subsequently received local antimycotics for perioral rash and oral lesions. The clinical-laboratory investigations revealed increased serum levels of total and indirect bilirubin, AST, ALT, GGT and LDH, low serum sodium and chlorides, but normal potassium, a mild increase in FT4 with increased TSH, very high morning ACTH levels with serum morning cortisol below the normal ranges, and normal testosterone. Whole blood count, biochemical studies, coagulation, glucose, iron, copper, iron-binding capacity, urine sediment, were normal at baseline and during the follow-up. The patient was HBsAg, anti-HBc IgM, anti-HCV and anti-HAV IgM negative. The immunological investigations showed very low serum IgA levels (0.16 g/l) with normal IgG and IgM, negative ANA, ANCA, AMA, LKM-1 antibodies, antiGAD-60, anti-IA-2, anti-thyroglobulin antibodies, a mild increase in anti-TPO antibodies titer, a marked increase in IgG anti-tissue transglutaminase antibodies - 200 U/ml (Table 1), with no changes in cellular immunity (Th, Ts, B and NK cells with normal CD4/CD8 ratio), negative T-SPOT-TB test; HLA type - A*01; B*08; DRB1*03; DQB1*02; karyotype - 46, XY. The thyroid ultrasound examination revealed normal homogenic glandular parenchyma, thyroid volume 7.8 ml. The abdominal ultrasound failed to visualize the adrenal glands. The liver biopsy showed no inflammation, no fibrosis. The computed tomography (CT) of the brain revealed normal position and symmetrical narrowing of the ventricular system, narrowing of the subarachnoid spaces, normal hypothalamus and pituitary gland. The patient was diagnosed with partial serum IgA deficiency together with primary hypocorticism (Addison's disease) based on typical skin darkening, astheno-adynamia, hypotension, very high ACTH levels with low morning serum cortisol, no CT changes in the hypothalamus and pituitary gland. He was treated with saline and glucose infusions, Mannitol, Famotidine, intravenous glucocorticosteroids (methylprednisolone 60-80 mg per day), Fludrocortisone 0.1 mg. The patient was discharged with improvement and remained on the following treatment: Dehydrocortisone 5 mg 1 + 1/4 tablet, Fludrocortisone 0.1 mg 1/2 tablet every morning (1/4 tablet in winter months).

addison‘s disease, partial iga deficiency, thyreoiditis, tissue transglutaminase antibodie

PMC4531569_01

Female

A 38-year-old, gravida 4, para 2, female Korean patient presenting with indigestion and vague abdominal discomfort of several months' duration was referred from a private clinic for a large retroperitoneal mass that was discovered on abdomen computer tomography. She had suffered from cervical tuberculosis 7 years ago, and this had been confirmed by excisional biopsy at a private clinic, and it was eradicated after a 1 year treatment with anti-tuberculosis medications. The large cystic abdominal mass was palpated on her right flank and in the RLQ abdomen on the physical examination. It was mobile, non-tender and estimated to be about 8 cm in diameter. The rest of her pelvic examination was unremarkable. The laboratory findings including colonoscopy and serum tumor markers (CEA, CA 125, and CA 19-9) were within the normal limits. Imaging studies on abdomen and pelvis computer tomography showed an unilocular cystic mass, 10x8x6 cm3 in dimensions, was located at the inferior aspect of the liver and posterior along the right colon, and the right retroperitoneal mass had displaced the right colon ventromedially. It was an encapsulated cystic mass that contained fluids, and there was no lesion in the pelvic organs (Figure 1). A celiotomy was performed; there was a large cystic retroperitoneal mass adhered to the right colon and its mesocolon, right kidney and duodenum, but it had not invaded to the adjacent organs. Macroscopically there was no lesion observed in the ovaries and fallopian tubes, appendix, right colon, kidneys and pancreas. The retroperitoneal tumor was completely removed with no spillage of its contents, and no combined resection with the associated organs was performed. Upon gross examination, the specimen was a thin-walled, multilocular cyst with a dominant loculus that measured 10.0x7.5x5.5 cm3. The external surface is smooth and pinkish. Upon opening it, it contained mucinous fluids and inner surface is smooth. The wall of the cyst contained smaller cysts; the largest of these measured 0.8 cm in diameter. The thickness of the walls was less than 0.1 cm. There are no solid areas or papillary projections. On the histologic examination, the cyst was lined by a single layer of tall columnar epithelium with clear cytoplasm and small nuclei that were basely located in the cells (Figure 2). There was no papillary growth or stromal invasion of epithelium. The cyst wall consisted of fibrocollagenous tissue of varying cellularity and vascularity. No pancreatic or ovarian components were found (Figure 3). Immunohistochemical staining showed that the lining cells were positive for cytokeratin, cytokeratin 7, CAM 5.2, and carcinoembryogenic antigen, but the cells were negative for cytokeratin 19, epithelial membrane antigen, estrogen and progesterone (Figure 4). The final diagnosis was primary mucinous cystadenoma arising from the retroperitoneum. The patient had an uneventful postoperative recovery, and there was no lesion or recurrence on the follow-up abdomen and pelvis computer tomography at postoperative one year.

PMC6838894_01

Female

A 42-year-old former smoker woman (30 pack-years) presented to the Emergency Department with acute onset of dyspnea, cough and fever. The patient had no comorbidities and the physical exam was within normal limits. In order to exclude a pulmonary thromboembolism, a computed tomography angiography was performed, revealing bilateral hilar and mediastinal lymphadenopathy and various areas of ground glass of both the inferior lobes. Several blood tests were done in order to exclude an infectious disease; the tests were negative, including QuantiFERON-TB Gold test. Bronchoscopy showed a marked thickening of the tracheal carina extending for a few millimeters to the medial aspect of both mainstem bronchi (Fig. 1). Histopathology examination of the bronchial biopsies performed in this area revealed sheets of epithelioid cells with eosinophilic granular cytoplasm, positive for S100 and NSE and negative for CAM5.2 (Fig. 2; Fig. 3), consistent with a diagnosis of GCT. An endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) of the lymph node stations #4R, #7 and #11Rs was performed and the cytopathological examination suggested their "reactive" nature by showing a predominance of lymphocytes. Culture of bronchoalveolar lavage (BAL) for common bacteria, fungi and mycobacteria proved negative. The tumor was ablated with Nd:YAG laser (Fig. 4) during rigid bronchoscopy under general anesthesia and the patient is currently free of disease 12 months after treatment.

airway tumors, s-100, trachea, tracheal granular cell tumor, tracheal malignancies

PMC7328498_01

Female

A 3-month-old entire female British Shorthair cat was referred to the Queen Mother Hospital for Animals for further management of thermal burns. The kitten had fallen into a bath of scalding water for approximately 30 s before she was removed, and first aid was administered by placing her in cold water for approximately 10 mins. In the UK, hot water is stored at 60 C to kill Legionella species. Although the temperature of the scalding bath water is not known, given that the bath was being filled exclusively with hot water the temperature was likely to have been between 45oC and 55oC. The kitten presented to the primary care practice obtunded, vocalising and shivering. The haircoat was wet, with erythematous skin and sloughing from the digital pads and anal mucosa. The respiratory rate was 20 breaths per min, heart rate was 170 beats per min and mucous membranes were pink and moist, with a capillary refill time <2 s. Thoracic auscultation was unremarkable. The kitten was assessed as euhydrated. The rectal temperature was 37.9oC. Severe pain limited further examination. Methadone was administered intramuscularly (IM) at 0.3 mg/kg (Synthadon; Animalcare). The kitten was sedated with medetomidine at 25 microg/kg IM (Domitor; Vetoquinol) to facilitate intravenous (IV) catheter placement. The level of sedation was insufficient after 15 mins and a second dose of medetomidine at 20 microg/kg IM was administered, which provided suitable sedation for IV catheter placement. Following IV placement, cefuroxime 15 mg/kg IV (Zinacef; GlaxoSmithKline) was administered. IV isotonic crystalloid therapy was initiated at 6 ml/kg/h (compound sodium lactate; Aquapharm) for approximately 2 h prior to referral. The kitten presented to the referral hospital approximately 6 h after sustaining the burn trauma. On arrival, the kitten was obtunded, overtly painful, vocalising and resistant to handling. An IV fentanyl bolus (Fentadon; Dechra) of 2 microg/kg was administered and continued as a constant rate infusion (CRI) at 4 microg/kg/h. Limited physical examination confirmed respiratory and cardiovascular stability. Measurement of blood pressure and rectal temperature were not tolerated owing to pain and distress. The kitten was euhydrated and weighed 1.53 kg with a body condition score (BCS) of 4/9 and muscle condition score of 2/3. Initial point-of-care venous blood gas and metabolite analysis identified mild hyperglycaemia attributed to stress (8.5 mmol/l; reference interval [RI] 4.7-7.3 mmol/l [156.6 mg/dl; RI 84.6-131.4 mg/dl]); all other results were within the RIs (Table 1). IV isotonic crystalloid therapy (compound sodium lactate) was restarted at 6 ml/kg/h. Throughout hospitalisation, IV potassium chloride (Hameln) was supplemented as required by adding it into the crystalloid fluid bag. A modified Colorado State University Medical Center Feline Acute Pain Scale score of 9/12 prompted escalation of analgesia. IV ketamine (Anaestamine; Animalcare) 0.5 mg/kg followed by 0.2 mg/kg/h CRI and IV medetomidine (Medetor; Virbac) 0.1 microg/kg followed by 0.5-1 microg/kg/h CRI were introduced sequentially to achieve a pain score of 2-4/12. This multimodal analgesia protocol was continued for 3 days and then gradually weaned as guided by serial pain scoring. General anaesthesia was performed following initial stabilisation within 2 h of admission. The kitten was premedicated with midazolam 0.2 mg/kg IV (Hyponovel; Roche) and anaesthesia was induced with propofol (PropoFlo; Abbot) administered incrementally to effect (total dose 2.5 mg/kg). Anaesthesia was maintained with isoflurane delivered in 100% oxygen. The haircoat was clipped, revealing scalding and erythema of the ventral thorax, abdomen, thoracic and pelvic limbs, and perineum, with areas of ulceration (Figure 1). The head, neck, oral cavity and corneas were unaffected. The extent of thermal injury was approximated to be 80% of the total body surface area (TBSA) based on the 'rule of nines'. The burn injury was classified as deep partial thickness (second degree). Ulcerated areas were cleaned with dilute iodine; antimicrobial cream was not applied as the lesions were small and superficial. The patient was instrumented with a central venous catheter, urinary catheter and oesophagostomy feeding tube (O-tube); correct placement was confirmed with thoracic radiography. The O-tube was placed as described by Mazzaferro, and the insertion stoma was covered with a sterile dressing and checked twice daily for signs of infection. Pyrexia of 39.7oC was documented after the kitten had recovered from general anaesthesia. Prior to sustaining the thermal burn injury, the kitten was being fed a mixture of complete and balanced wet/dry kitten foods appropriate for growth. Daily resting energy requirement (RER) was calculated to be 96 kcal/day using the formula RER = 70 x body weight (kg)0.75. The most recent daily weight was used to calculate the daily RER during hospitalisation. A veterinary liquid diet (Gastrointestinal High Energy; Royal Canin) was fed as a CRI within 12 h of admission at 50% of the kitten's calculated RER (48 kcal). The kitten initially showed no interest in voluntary intake of food and provision of enteral nutrition via the O-tube was incrementally increased to 100% (96 kcal/day) within the first 48 h (Figure 2). The therapeutic liquid diet (Gastrointestinal High Energy; Royal Canin) was chosen for ease of administration and high calorie content. It was used for all O-tube feeds and administered as a CRI. Although marketed for dogs, this liquid diet met the minimum nutritional content recommended for growing kittens for the majority of nutrients (Table 2). The protein, calcium and phosphorus levels of this diet were slightly below the minimum content recommended for growing kittens. In order to mitigate this deficiency, the kitten was also offered a canned wet food diet specifically formulated to support growth in cats (Hill's Science Plan Kitten) at six intervals throughout the day. Prior to planned anaesthesia and surgical procedures, the kitten received a final feed the night before at 2 am, after which food was withheld and the O-tube CRI stopped. Feeding was restarted once the kitten had recovered from anaesthesia and the frequency of feeds and CRI volume adjusted to ensure the daily calorie target was met. The kitten remained euhydrated based on clinical examination throughout hospitalisation; therefore, fluctuations in body weight were not attributed to changes in fluid balance. Haematology and biochemistry panels sampled on admission revealed a non-regenerative mild anaemia, neutropenia, hypoalbuminaemia, hypocholesterolaemia and increased alanine aminotransferase (ALT) activity (Table 1). On day 2, the kitten remained pyrexic at 39.9oC. The urinary catheter was removed and the central venous catheter was replaced as it had been removed by the patient. Pyrexia persisted despite new vascular access. No erythema or discharge of the O-tube site was detected on daily assessment. Urinalysis indicated no evidence of urinary tract infection and urine culture demonstrated no microbial growth. IV potentiated amoxicillin 20 mg/kg q8h (Augmentin; GlaxoSmithKline) was initiated on day 3. On day 3, the kitten started to eat small quantities of kitten food (Hill's Science Plan Kitten) when offered by hand. The calories ingested voluntarily were minimal and O-tube feeding continued at 100% of the calculated RER. Neutropenia resolved on day 4 (Table 1); however, the pyrexia persisted, with the rectal temperature fluctuating between 39.3oC and 40.5 C. In the absence of documented infection, the pyrexia was attributed to severe systemic inflammation. Antibiotics were continued due to the severity of the skin lesions (Figure 3). Biochemistry revealed static hypoproteinaemia, hypomagnesaemia, improved ALT and increased creatine kinase activities (Table 1). Magnesium was not supplemented or reassessed in the absence of clinical signs or associated electrolyte derangements consistent with hypomagnesaemia. Blood glucose remained mildly increased throughout hospitalisation (Table 1). Between admission and day 4, the kitten lost 80 g (5.2% body weight loss), decreasing to 1.45 kg. On day 4, the kitten received a total of 120 kcal (130% of its calculated RER for the most recent daily body weight), of which 36 kcal (30%) was voluntary intake of kitten food. By day 6, the kitten's calorie intake increased to 240 kcal/day (260% of the calculated RER for the most recent daily body weight), 120 kcal (50%) of which was achieved via voluntary intake. The kitten's appetite continued to improve and by day 7 it was eating 96 kcal/day (104% of its calculated RER), and also tolerating 144 kcal/day (157% of calculated RER) via the O-tube. Between days 4 and 8 of hospitalisation, the kitten's body weight decreased further to 1.40 kg (3.5% body weight loss). On day 8 of hospitalisation, general anaesthesia was planned to facilitate wound debridement (Figure 4); thereafter, silver sulfadiazine cream (Flamazine; Smith&Nephew) was applied daily. On day 9, voluntary food intake had increased to 120 kcal/day (133% of calculated RER using the most recent daily body weight), which was matched by O-tube feeding to bring the total daily calorie intake to 240 kcal/day (266% of the calculated RER). On day 11, general anaesthesia was performed to facilitate extensive debridement of the more severely affected left inguinal area and hindlimb, and to perform an epidural consisting of 0.1 mg/kg morphine (Morphine Sulfate; Macarthys Laboratories) and 1.5 mg/kg ropivacaine 0.25% (Naropin; AstraZeneca) to provide regional anaesthesia postoperatively. This enabled de-escalation of systemic analgesia from fentanyl 1-5 microg/kg/h CRI to methadone 0.1-0.2 mg/kg IV q4h (Comfortan; Dechra). On day 13, buprenorphine (Buprecare; Animalcare) 0.01-0.02 mg/kg IV q6h, gabapentin (Gabapentin; Milpharm) 8 mg/kg PO q12h and meloxicam (Metacam; Boehringer Ingelheim) 0.05 mg/kg IV q24h were introduced. Throughout days 9-12 of hospitalisation, the kitten's total calorie intake was gradually increased. However, voluntary intake did not exceed 120 kcal/day (133% of the calculated RER), despite the kitten being offered in excess of this amount. As such, in order to increase voluntary intake further, 4 g of veterinary therapeutic instant diet powder (Convalescence Support; Royal Canin) was added to all meals offered. This increased voluntary calorie intake to approximately 145 kcal/day (161% of the calculated RER), with a minimal increase in the volume of food ingested. In addition, 225 kcal/day (250% of the calculated RER) was provided via the O-tube CRI. This resulted in the kitten receiving a total of 315 kcal/day (350% RER) by day 12. Despite increased nutritional provision, between days 8 and 12 of hospitalisation the kitten lost a further 50 g of body weight (3.6% body weight), decreasing to 1.35 kg. On day 14 of hospitalisation, a new heart murmur was documented. Echocardiography did not reveal underlying structural disease or changes consistent with endocarditis. The murmur was deemed to be haemic secondary to anaemia (Table 1). Cardiac troponin I was mildly increased (0.4 ng/ml; RI <0.04). The mild increase in cardiac troponin I concentration was attributed to myocardial injury related to systemic inflammation. While hospitalised, the kitten received IV fluid therapy (IVFT) at 5-6 ml/kg/h based on regular assessment of hydration status, fluid intake and losses. On day 13, IVFT was decreased from 5 ml/kg/h to 3 ml/kg/h. The following day, IVFT was reduced further to 1 ml/kg/h before being discontinued on day 15. Fluid therapy was discontinued as clinical assessment indicated that enteral fluid intake was sufficient to meet the kitten's needs and significant losses were not occurring. Dyspnoea developed on day 15 of hospitalisation and the kitten was placed in an oxygen kennel set at 60% fraction of inspired O2. Thoracic radiographs identified cardiomegaly without infiltrative pulmonary disease. Point-of-care ultrasound identified diffuse pulmonary B lines on day 16 of hospitalisation. Pulmonary B lines are associated with peripheral interstitial-alveolar disease of varying aetiology. Acute respiratory distress syndrome was suspected, although thromboembolism or aspiration pneumonia could not be excluded. The respiratory signs resolved within 7 days of occurring and oxygen therapy was de-escalated. The kitten remained persistently pyrexic since admission. On day 16, septicaemia was diagnosed when repeat haematology documented phagocytosis of bacterial cocci. Blood cultures were obtained prior to escalation of antibiosis. The kitten had been receiving potentiated amoxicillin (Augmentin; GlaxoSmithKline) 20 mg/kg q8h since day 3 of hospitalisation. IV imipenem (Primaxin; Merck Sharp & Dohme) 10 mg/kg q8h was introduced concurrently pending blood culture results. Growth of multidrug-resistant Escherichia coli and Pseudomonas aeruginosa (resistant to potentiated amoxicillin) was reported after 48 h incubation from enrichment culture. Both isolates were susceptible to imipenem, which was continued for a total of 5 days. Potentiated amoxicillin was discontinued once the culture results had been received. The kitten's pyrexia resolved within 24 h of initiating imipenem (Primaxin; Merck Sharp & Dohme). Throughout days 12-17 of hospitalisation, the kitten's total calorie intake was increased to 385 kcal/day (438% of the calculated RER) by increasing the calories fed via the O-tube. Calorie consumption is reported in relation to the kitten's RER for ease of comparisons throughout this paper as the RER calculation is only dependent on body weight. On day 17, the O-tube was prematurely removed by the patient. The kitten was able to maintain a voluntary calorie intake of 289 kcal/day (328% of the calculated RER) and its weight remained static. Between days 12 and 24, the kitten's body weight gradually increased by 50 g to 1.4 kg (3.6% of its current body weight). Cessation of weight loss indicated that its apparent energy requirements were being met. The kitten was discharged from the hospital on day 24. Dietary recommendations at discharge were to feed a minimum of 289 kcal/day (328% of the calculated RER) of a complete and balanced growth diet (Hill's Science Plan Kitten) and increase the amount of food offered if there was a decrease in body weight. Body weight was 1.4 kg vs 1.53 kg on admission. BCS was 3/9 vs 4/9 on admission and the muscle condition score had decreased from 2/3 to 1/3. There was incomplete healing of the thermal burns at discharge. Medication dispensed included sublingual buprenorphine 0.02 mg/kg q8h (Buprecare; Animalcare), oral meloxicam (Metacam; Boehringer Ingelheim) 0.05 mg/kg q24h and gabapentin (Gabapentin; Milpharm) 8 mg/kg q12h, to be discontinued at the discretion of the primary care veterinary surgeon. Clinical reassessment was performed at the primary care practice 5 days after discharge (Figure 5). At follow-up 18 months post-injury the kitten weighed 3.97 kg with a BCS of 4/9 and muscle condition score of 2/3. In addition, there had been complete healing of the deep partial-thickness burns and full regrowth of hair.

hypermetabolic state, enteral nutrition, resting energy requirement, sepsis

PMC7438891_01

Female

A 33 year old woman who at the end of 2002 went to the emergency department complaining of insomnia and fatigue. She was diagnosed with anxiety disorder and was discharged. Six weeks later she was readmitted to the hospital with weakness, generalized myalgia, and a tingling sensation in her extremities. Given the early recurrence, the neurology department was consulted. In the neurological exam her mental state was normal, her pupils were normal symmetrical, and reactive to light. There was no facial asymmetry and the other cranial nerves were normal. Muscle tone was increased in bilateral lower extremities. Grade II-III spasticity was diagnosed, as well as decreased vibratory sensitivity and bilateral Hoffman sign (involuntary flexion movement of the index finger when the examiner flicks the fingernail of the middle finger down), bilateral Babinski sign (plantar flexor response) and positive Romberg sign, with a tendency to fall to the right. Routine blood test was normal, except for cholesterol level (268 mg/dL). Magnetic resonance imaging (MRI) detected seven of demyelinating lesions of various sizes, especially periventricular and supratentorial and some infratentorial, as well as cortico-subcortical atrophy. No signs of progressive multifocal leukoencephalopathy were visualized. In mid- 2003 she had an optical neuritis (left retrobulbar type) visual outbreak, with a complete recovery, and 4 years later a spinal outbreak that presented itself as a paraparesis. The patient began treatment with beta-1a interferonin 2008 and because of her lack of response to the treatment due to some outbreaks and an increase in EDSS of up to a score of 5.0, in 2009 it was considered convenient to change to Natalizumab as a high activity treatment. She continued that treatment for 7 years but the persistence of attacks, although spread over the time, and the progression of associated disability (EDSS score 5.5), indicated a further change to another high efficiency therapy, i.e., Alemtuzumab, with which she completed the two cycles indicated on the data sheet. During her neurological examination the prominent features were: a visual optical neuritis-type aftermath, a minimal oculomotor alteration, invalidating spastic paraparesis, right hemiparesis, and sphincter disorders which currently would be defined by a score of 6.0 on the EDSS scale. Standing out as comorbidities were: depression as a reaction to her illness, notable spasticity, fatigue and joint pain, all of them being treated pharmacologically for the past 5 years. Three years ago, given her disability and lack of response to the symptomatic treatment prescribed, rTMS treatment was proposed, which she accepted. Based on the results obtained with TMS in previous clinical studies carried out in patients with MS, as well as in its equivalent experimental model in rats (experimental autoimmune encephalomyelitis, EAE) and in other neurodegenerative diseases, the main objective was to improve the degree of disability in this patient. We also wanted to examine her evolution at the neuropsychological level and her biomarkers of oxidative damage in blood, in order to look for links between these aspects. Cycles of a daily session of rTMS were prescribed. These were grouped into 5 consecutive days, followed by 3 weeks resting, until 14 cycles (70 sessions in all) were completed, spread over 14 months. The stimulation was applied at 3 cm in front of the Cz point in the craniocaudal axis. The stimulation power was established as a function of the motor threshold of the patient, representing 90% of its total value. It was administered as a continuous stimulation with a frequency of 1 Hz during a span of 600 s in each session. In each session, we follow this protocol in two steps: First step: Obtaining the Motor Evoked Threshold at Rest: the patient had her threshold evoked motor calculated at rest, by stimulation of the motor cortex in the left hemisphere, evoking electromyographic responses (EMG) in the contralateral muscles, called motor evoked potentials (MEP). The threshold of motor excitability at rest (TM) is defined as the minimum intensity (expressed as the percentage of the maximum output power of the stimulator) capable of producing a reproducible MEP in a resting muscle in 50% of 10 shots. Second step: Administration of the Transcranial Magnetic Stimulation: A Rapid 2 Magstim device (Magstim Co. , Whitland, Carmarthenshire, Wales) equipped and connected to a figure-of-eight coil of 70 mm was used. This equipment is used to calculate the TM and the percentage of it to which the treatment will have to be applied. The selection of the specific point of stimulation in the Supplementary Motor Area (SMA) was sufficiently anterior to prevent the propagation of the impulse from triggering the muscular contraction of the shoulders, trunk, and lower limbs. The position of the coil was marked on the scalp to ensure consistent placement of the coil throughout the experiments; the patient was fitted with a lycra cap on which to indicate and also mark the exact stimulation point, as well as on which to place and hold the coil during the therapeutic session. The coil was oriented toward the posterior area in order to trigger a postero-anterior current. The TM was calculated in relation to the evoked potential and according to international standards. Based on it, TM was defined as the lowest stimulus intensity that elicited a minimum MEP amplitude of 50 mV in the completely relaxed FDI muscle in at least 5 out of 10 consecutive trials. During this treatment time, periodic physical and neurocognitive evaluations were made, as well as blood analyses (Table 1). The neuropsychological tests were generally orientated toward assessing the patient's cerebellar and motor functions (as in the 9 HolePeg Test and the Timed 25-Foot Walk) and her short and medium term mnesic capacity (as is the case of the Selective Reminding Test, 10/36 Spatial Recall Test, Symbol DigitModalities Test, Paced Auditory Serial AdditionTask and Word List Generation Test). Generally speaking, the results of the tests showed an improvement in the patient's motor and neurocognitive abilities (displaying an increase in the scoring scales), as well as a lower degree of disability (falling from 6 to 5 points in the EDSS scale as from the second month of treatment with rTMS) (Figure 1) and a better perception of her health in relation to the impact of the disease on it (showing a drop in the EQ-5D-5L and MSIS-29 scales scoring) (Figure 2). This improvement, according to the evaluation scales, was produced practically starting from a short time after the beginning of the treatment (at between 4 and 8 months), and was maintained the whole time. Only a small increase in Timed 25-Foot Walk was observed; in the first four evaluations it lasted 12 s and in the last one 15, which could correspond to a slight slowing down of her ambulation. The laboratory study took into consideration routine biochemical magnitudes and oxidative stress parameters (Table 2). It was carried out at two moments: half-way through and at the end of the treatment period. In both laboratory studies a very slight, or clinically irrelevant variation was generally observed, although the oxidative stress parameters displayed a notable change, with a tendency toward an antioxidant status.

case report, compassionate use trial, disability, multiple sclerosis, neuroplasticity, oxidative stress, psychometry, transcranial magnetic stimulation

PMC9842888_01

Male

A 42-year-old man was diagnosed with rectal cancer (cT2N2bMx [UICC 8th edition]) with a solid nodule measuring 21 x 20 mm in diameter at the superior segment (S6) of the left lower lobe on the chest computed tomography (Fig. 1). The lung nodule was considered to be either primary lung cancer or metastatic lung tumor originating from the rectal cancer. Firstly, the patient underwent laparoscopic ultralow anterior resection with lateral lymph node dissection for the rectal cancer (moderately differentiated tubular adenocarcinoma, pT4aN2bMx). Six weeks after rectal surgery, we performed robotic-assisted thoracoscopic S6 segmentectomy to both diagnose and treat the tumor. As the intraoperative pathological diagnosis of the lung nodule was metastatic tubular adenocarcinoma resembling rectal adenocarcinoma, we did not perform further resection. The patient had an uneventful postoperative course and was discharged on the 4th postoperative day. We conducted detailed pathological examinations of the obtained tumor samples, including IHC analysis of markers for differentiating metastatic and primary lung adenocarcinoma. Hematoxylin-eosin staining of the lung tumor demonstrated columnar epithelial cancer cells consisting of tubular structures (Fig. 2a); these morphologies resembled rectal adenocarcinoma (Fig. 2i). However, contrary to our expectations, TTF-1 (clone: SPT24, Novocastra, San Ramon, CA, USA) was positive in the lung tumor sample (Fig. 2b), prompting us to retrospectively review the rectal adenocarcinoma specimen. Surprisingly, TTF-1 was also positive in the rectal adenocarcinoma specimen (Fig. 2j). Further results of IHC were as follows: the lung tumor sample was napsin A (-) (clone: IP64, Novocastra, San Ramon, CA, USA), cytokeratin 7 (CK7) (-) (clone: SP52, Ventana, Tucson, AZ, USA), cytokeratin 20 (CK20) (+) (clone: SP33, Ventana, Tucson, AZ, USA), Caudal-related homeobox transcription factor 2 (CDX2) (weakly +) (clone: CDX2-88, Biocare Medical, Pacheco, CA, USA), special AT-rich sequence binding protein 2 (SATB2) (+) (clone: EPNCIR130A, abcam, Cambridge, UK), and beta-catenin (+) (clone: 17C2, Leica Biosystems Newcastle Ltd, Newcastle, UK) (Fig. 2c-h); the rectal adenocarcinoma sample was napsin A (-), CK7 (-), CK20 (partly +), CDX2 (weakly +), SATB2 (+), and beta-catenin (+) (Fig. 2k-p). Hence, we diagnosed the lung tumor as metastatic rectal adenocarcinoma based on the histological findings and the IHC results. We applied MEBGEN RASKET -B kit (RASKET-B) (Medical & Biological Laboratories Co., Tokyo, Japan) for the pulmonary lesion and confirmed BRAF wild and KRAS mutation (G12R). The pathological stage of the rectal cancer was confirmed as pT4aN2bM1 stage IV (UICC 8th edition), and the patient initiated systemic chemotherapy based on the results of RASKET-B.

colorectal adenocarcinoma, metastatic lung tumor, thyroid transcription factor-1

PMC5687147_01

Female

A 25-year-old female with uncomplicated ventricular septal defect presented to our casualty medical ward with the complaint of intermittent low-grade fever of 3-month duration. She had generalized malaise, loss of appetite, and weight loss over the same period. There was no history suggestive of chronic respiratory illnesses, tuberculosis, or connective tissue disorders. She was diagnosed to have small ventricular septal defect (VSD) since childhood and was on regular echocardiographic evaluation. She did not have history or peripheral evidence of intravenous drug abuse. On examination, she was thin built, pale, and febrile. There was no lymphadenopathy or features of autoimmune connective tissue disorders. She did not have finger clubbing. Her pulse rate was 90 beats per minute and blood pressure was 110/70 mmHg. There was no cardiomegaly. She had a left parasternal thrill and a harsh pan systolic murmur over the left lower sternal edge. There were no features of heart failure. Other systems' examination was unremarkable. Her investigations revealed white blood cell count 14 x 103/microl, neutrophils 75%, lymphocytes 18%, hemoglobin 8.8 g/dl, platelets 224 x 103/microl, erythrocyte sedimentation rate (ESR) 40 mm in 1st hour, C-reactive protein (CRP) 75 mg/l, alanine transaminase (ALT) 26 IU/l, and aspartate transaminase (AST) 30 IU/l. Anti-nuclear antibodies (ANA) were negative. The electrocardiogram (ECG) showed sinus tachycardia. Chest radiograph was normal. The 2D echocardiogram (2DE) revealed a perimembranous VSD, left to right shunt with a maximum pressure gradient of 105 mmHg. There was moderate tricuspid regurgitation with a maximum tricuspid pressure gradient of 36 mmHg. There was 7 mm x 4 mm-sized vegetation attached to the posterior leaflet of the tricuspid valve. The pulmonary valve was free of vegetations. There was moderate pulmonary hypertension. Her transoesophageal echocardiogram (TOE) confirmed the tricuspid valve vegetation (Figures 1 and 2). There were no abnormalities seen in other cardiac valves. Her blood culture was positive for Streptococcus bovis in two samples. She was diagnosed to have infective endocarditis based on fulfilling modified Duke's criteria and empirically started on intravenous ceftriaxone and gentamicin. Subsequent culture confirmed that the organism was sensitive to empirical antibiotics, hence continued. She also underwent detailed colonoscopy and upper gastrointestinal endoscopy, and both were normal. Her ultrasound scan of the abdomen did not reveal any abnormality. She was given intravenous gentamicin for 2 weeks and ceftriaxone for 6 weeks and made an uneventful recovery. The patient was referred to the cardiology department for further assessment for closure of VSD.

PMC3287964_01

Female

In August, 2008, a 36 year-old woman with no prior history of liver disease presented to her primary care physician complaining of abdominal pain of five days duration. The pain was constant, sharp, localized to the right upper quadrant, non-radiating, and associated with nausea but no vomiting. Review of systems was positive for fatigue. Initial laboratory testing revealed only a mildly elevated alanine aminotransferase (ALT) of 42 IU/L. A right upper quadrant ultrasound demonstrated hepatomegaly and steatosis. Two weeks later, the patient presented to an outside hospital with worsening right upper quadrant pain, low-grade fevers, nausea and vomiting. An MRI of the abdomen revealed a two cm enhancing lesions of the right hepatic lobe. Fine needle biopsy of the lesion demonstrated a nonspecific, mixed inflammatory cellular infiltrate and steatohepatitis. There was no evidence of malignancy. Fungal and mycobacterial cultures were negative. The patient was discharged without a specific diagnosis, and no treatment was instituted. Two months later, the patient presented to Loyola University Medical Center with worsening right upper quadrant pain and fever. An abdominal CT scan revealed a 4.8 x 4.7 cm mass lesion involving the right hepatic lobe that was suspicious for malignancy (Figure 1). The patient underwent a partial right hepatectomy with excision of the mass. Histopathological studies of the resection specimen showed florid necrotizing granulomatous inflammation with pseudotumor formation (Figure 2, 3). Immuno-histochemical stains for mycobacteria, fungal organisms, and cytomegalovirus were negative. The patient's presenting symptoms resolved, and she was discharged home after an uneventful postoperative recovery. In April of 2009, the right upper quadrant pain and low-grade fevers recurred. The patient presented to an outside hospital where an extensive evaluation was initiated (Table 1). Serologies for acute viral hepatitis were negative. Qualitative antibodies for toxoplasmosis, human immunodeficiency virus, and Entamoeba histolytica were negative. An EIA for Borrelia burgdorferi antibodies was negative. IFA assays for Bartonella henselae and Bartonella quintana were negative. Testing for urinary histoplasmosis and blastomycosis antigens and cryptococcus serum antigens were negative. Skin testing for tuberculosis and quantiferon gold were negative. A random liver biopsy showed mild macro- and micro-vesicular steatosis and non-specific chronic inflammation. Repeat special stains, fungal and mycobacterial cultures were negative. The patient's symptoms improved, and she was discharged home on analgesics. In July of 2009, the patient once again presented to an outside hospital with right upper quadrant pain, nausea, and fevers of up to 102.4 F. An abdominal CT revealed several low attenuation lesions involving both segments of the liver, with the largest one measuring 4.1 x 2.9 cm (Figure 4). The patient was transferred to Loyola University Medical Center for further evaluation. A detailed travel and exposure history to ticks, rodents or other vectors of unusual infectious etiologies was unrevealing. On physical examination, the patient was afebrile. There was no lymphadenopathy or hepato-splenomegaly. Her right upper quadrant was tender to palpation without rebound tenderness or guarding. Laboratory analysis revealed an aspartate aminotransferase (AST) of 93 IU/L UNITS, alanine aminotransferase (ALT) of 74 IU/L, alkaline phosphatase of 193 IU/L, and total bilirubin of 0.6 mg/dL. The hemoglobin was 13.4 gm/dL, and the WBC count was 4.9 K/UL with a normal differential. Bacterial blood cultures, urinalysis, stool cultures, and stool tests for Clostridium difficile were negative. A chest radiograph showed no infiltrates or lymphadenopathy. The antinuclear antibody was 1:40, and anti-mitochondrial antibody testing was negative. On the third day of her hospitalization, the patient developed a temperature of 101.1 F. A comprehensive investigation for fever of unknown origin was initiated (see Table 1). Antibody titers for Bartonella quintana, and Brucella sp. were negative. An RPR was negative. Repeat HIV antibody testing was negative. A peripheral smear for malaria was negative. A transesophageal echocardiogram did not reveal any valvular vegetations. The patient refused a lumbar puncture. A percutaneous liver biopsy was performed and revealed extensive granulomatous hepatitis with occasional fibrin rings, with a background of mixed, micro- and macro-vesicular steatosis. Based on the presence of fibrin rings, the possibility of Q fever was entertained. However, ELISA testing for Coxiella burnetti antibodies was negative. Repeat special stains and cultures for AFB, fungal organisms, and cytomegalovirus were negative. Steiner silver stains for spirochetes and bacteria - including Bartonella sp.- were negative. The patient was empirically treated with a seven-day course of piperacillin and tazobactam. She remained afebrile for the remainder of her hospitalization. Based on the diagnosis of granulomatous hepatitis and the unrevealing workup for infectious organisms, the patient was started on empiric prednisone. Her liver enzymes, which had already been down-trending at the start of prednisone treatment, normalized over the next several weeks. Her symptoms resolved, and she was discharged home on a tapering dose of prednisone. Based on the striking features of her hepatic granulomas, the possibility of hepatic Bartonella infection was raised, despite the negative Bartonella antibody titers. A sample of formalin-fixed liver tissue from the initial liver resection was sent to the University of Arkansas for PCR testing. Using previously validated assay conditions, a 153 bp fragment of the B. henselae 16S rRNA gene was amplified, and confirmed by Southern blot hybridization. Upon further questioning, the patient reported that she had intermittently come in contact with a cat while visiting her mother's house, although she did not recall any cat scratches or bites. Based on the presumptive diagnosis of hepatic bartonellosis, the patient was started on azithromycin 250 mg daily, and her prednisone was discontinued. Two weeks later, the patient developed diarrhea and abdominal cramping that were attributed to her antibiotic. Azithromycin was discontinued, and the patient was started on a nine-week course of clarithromycin at a dose of 500 mg twice daily. Her symptoms completely resolved. In May of 2010, the patient presented to our emergency room with recurrent right upper quadrant pain. On examination, she was afebrile and her vital signs were stable. There was no jaundice. Right upper quadrant tenderness was present in the area of the excisional scar. There was no palpable hepato-splenomegaly. No skin rashes were present. AST and ALT levels were elevated to 109 IU/L and 75 IU/L, respectively. The total bilirubin, alkaline phosphatase, and INR were normal. A liver-protocol CT revealed a 2.4 cm, low-density lesion at the previous surgical site, which was thought to be nonspecific. However, given her recurrent symptoms, she was empirically treated with a six-week course of ciprofloxacin 500 mg twice daily. At a subsequent clinic visit in September of 2010, she reported improvement in her abdominal pain. However, the AST and ALT activities had risen to 139 IU/L and 195 IU/L, respectively. A transjugular liver biopsy demonstrated small, scattered, non-caseating granulomas with a background of micro- and macrovesicular steatosis. A sample from the biopsy was sent to the University of Washington for PCR analysis. Using conventional PCR conditions and primers targeting the ribC gene (5'-GATATCGGTTGTGTTGAAGA-3', 5'-AATAAAAGGTATAAAACGCT-3'), a 393 bp PCR product specific for B. henselae was amplified from the biopsy material. In order to determine whether the patient was bacteremic, venous blood samples were sent to the Intracellular Pathogens Research Laboratory (IPRL), Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University. Using a previous described diagnostic platform, conventional PCR targeting the 16S-23S intergenic spacer (ITS) region was performed on DNA extracted from blood, serum, and Bartonella alpha Proteobacteria growth medium (BAPGM)enrichment blood cultures. No amplification products were obtained from pre-enrichment blood and serum samples obtained on three sequential days. In contrast, a target band was obtained from one of three post-enrichment blood cultures. DNA sequencing of the amplicon was diagnostic for the ITS region of the SA2 strain of B. henselae, thereby establishing B. henselae bacteremia. The patient's serum tested negative for antibodies against B. henselae, B. koehlerae, or Bartonella vinsonii subsp. berkhoffii genotypes I, II or III antigens. Subsequently, using 16S-23S ITS primers, B. henselae DNA (SA2 strain by DNA sequencing) was amplified and sequenced from paraffin blocks containing material from the initial liver resection (January 2009) and from the follow-up biopsy obtained in September of 2010 (Figure 5). These data demonstrated the presence of the SA2 B. henselae strain in the patient's liver throughout her course. Immunohistochemical staining for B. henselae using a recently described B. henselae monoclonal antibody assay showed rare coccobacilli with positive staining and appropriate morphology for B. henselae, however, clusters of organisms were not visualized (data not shown).

PMC9768602_04

Male

In 2019, a 69-year-old man was referred due to incremental neutrophilic leukocytosis and fatigue since several months. Medical history included diabetes mellitus type 2. Medical therapy comprised sitagliptin/metformin (50 mg/1000 mg BID), rosuvastatin (10 mg QD), and allopurinol (100 mg QD). Biochemical analysis showed normocytic anemia with concurrent neutrophilic leukocytosis and 2.7% blasts. Electrophoresis and immunofixation indicated MGUS (IgG lambda type). Bone marrow biopsy showed hypercellularity with blast excess (20%). Cytogenetic analysis identified a complex karyotype with monosomy of chromosome 7, trisomy of chromosome 14, and deletion of p12 ( Table 2 ). CSF3R (44%), SETBP1 (45%), and U2AF1 (42%) appeared mutated. The diagnosis of AML secondary to CNL was made. Complete morphologic and cytogenetic remission was obtained after eight cycles of decitabine. Planned allogeneic HSCT was postponed due to flu and the SARS-CoV-2 pandemic. The patient relapsed several months later. Cytogenetic analysis detected the reoccurrence of previous described mutations in combination with a new translocation t(17;22) ( Table 2 ). Despite that no CR was obtained after remission-reinduction, allogeneic HSCT was performed. Bone marrow analysis 2 and 4 months afterwards showed no blast excess; mutated CSF3R was absent. The patient recovered and is currently, more than 2 years after HSCT, in CR. Paraproteinemia and neutrophilic leukocytosis did not reoccur.

chronic neutrophilic leukemia, monoclonal gammopathy, multiple myeloma, myeloid malignancy, myeloproliferative disorders, myeloproliferative neoplasm

PMC7652712_01

Male

A 22-years-old Male presented with chief complaint of weakness on both lower limbs for 6 months prior to admission. The weakness also came along with back pain. There was no previous history of trauma or fever. There was history of night sweat and decrease of body height. Patient then went to nearest hospital, underwent x-ray examination, and was told that there was a spondylitis TB. Patient got anti TB drugs for 2 months, and after that the weakness improved. Patient was able to walk, but the back pain persisted. Patient was then referred to our hospital for further treatment. There was no disturbance in micturition and defecation. There were no other families with the same condition as the patient. From physical examination we could not find any abnormality. Muscle power for both lower limbs were +4. The timeline of patient's clinical course is shown in Table 1. The results of X-ray examination were loss of lumbar lordosis, decrease of body height at L5, burst fracture of L5, end plate sclerosis at level L4-L5 and L5-S1, decrease intervertebral body height at L4-L5 and L5-S1, and fusiform soft tissue opacity around vertebrae L4-S1 (Fig. 1). The findings of MRI examination of the lower vertebrae were loss of lumbar lordosis, decrease of body height at L5, decrease intervertebral body height at L4-L5 and L5-S1, protrusion of L4-L5 intervertebral disc into the spinal cord, and paraspinal abscess (Figs. 2 and 3). The local kyphotic angle is 21.1 and regional kyphotic angle is 15.7 . The patient was diagnosed by paraparesis due to spondylitis Tb of L4-S1 with paravertebral abscess at L4-S1 Frankle D then underwent anterior debridement and fusion (Fig. 4). Patient was given two months of intensive four-drug therapy, including isoniazid (H), rifampicin (R), ethambutol (E), and pyrazinamide (Z), followed by two drugs (RH) therapy for a continuation phase of 4 months. Patient was followed up physically and radiographically at one, three, six months, and one year after the surgery. Postoperative radiograph showed restoration of vertebral height and visible expendable mesh (Fig. 5). Three months and six months and one year post operative follow up showed good functional outcome and sign of fusion from x ray (Fig. 6) and CT (Fig. 7). This kind of procedure is currently rare procedure without clear comparison between conventional pedicle screw and rod system for corpus destruction of lumbal spondylitis tuberculosis with anterior debridement and fusion using expendable mesh cage. However, we hope this case report will provide further evaluation and long-term larger follow up study (cohort study) for another kind of spondylitis tb procedure as an alternative treatment despite better or worse for selective patient.

anterior debridement, case report, expendable cage, fusion, spondylitis tuberculosis

PMC5562676_01

Female

A 56-year-old woman with a history of atrial fibrillation, hypertension, congestive heart failure, and mechanical mitral valve repair following rheumatic heart disease on warfarin was transferred to our hospital after being found unresponsive. On arrival, her blood pressure was 141/66. She was awake and able to move all four extremities to command; however, she had no verbal output, and her Glasgow Coma Scale (GCS) was 10 (E = eye opening 3, V = verbal response 1, and M = motor response 6). A head CT (Figure 1A) demonstrated a small ICH in the left periventricular white matter with significant intraventricular blood. CT angiogram of the head (Figure 1B) was suggestive of Moyamoya-like vasculopathy involving the left internal carotid artery (ICA) summit. Laboratory testing showed an INR of 3.6. She received intravenous vitamin K and prothrombin complex concentrate for INR reversal. Following intubation for airway protection due to declining mental status, an EVD was placed; however, drainage ceased within 1 h of placement due to obstruction of the catheter with blood. On repeat clinical exam off sedation, the patient was not following commands with a GCS of 4T. She had fixed, non-reactive pupils at 3 mm; absent corneal, oculocephalic, cough, and gag reflexes; no spontaneous breaths; and slight flexion to painful stimuli in the upper extremities. Repeat head CT showed worsened IVH (Figure 1C) with hydrocephalus and apparent compression of the midbrain (Figure 1D). The patient's husband was immediately informed that these developments were concerning for a devastating functional outcome, if she were to survive. Consequently, no further attempt was made to adjust the EVD for improved drainage or place a second EVD. Her code status was changed to "do not resuscitate" in the evening of admission. Her husband requested time to consider full comfort measures as goals of care, while continued routine ICU care would be pursued. Given the non-functioning EVD, obtained ICP readings were deemed inaccurate and thus not further acted upon through EVD manipulation or osmotherapy. However, the patient's clinical exam spontaneously improved over the following 48 h, while supportive ICU care was continued. She began overbreathing the ventilator and regained reactive pupils, cough, and gag reflexes, with absent, but eventual return of corneal and oculocephalic reflexes. On motor exam, she extended in the right arm and leg, but moved the left arm spontaneously and withdrew in both left arm and leg. Shortly after these observations, her EVD then started to drain spontaneously, without intervention, again approximately 48 h after initial placement. Based on this clinical improvement, the patient's husband requested that her code status be changed back to "full resuscitation." Repeat head CT on postbleed day 4 (Figure 1E) showed improved hydrocephalus, although still with ventricles "casted" from IVH. A more aggressive care approach was pursued at that time, and a left-sided EVD was placed. A diagnostic cerebral angiogram confirmed a Moyamoya syndrome characterized by (1) chronic occlusion of the left supraclinoid ICA above the origin of the anterior choroidal artery, (2) a meshwork of small vessels replacing the ICA summit, proximal ACA, and proximal MCA, and (3) robust collaterals supplying the L MCA vascular territory via a widely patent anterior communicating artery and leptomeningeal collaterals derived from the distal L PCA (Figures 1F,G). No definite, angiographically demonstrable culprit lesion was demonstrated. However, in light of these findings, empiric administration of intraventricular tissue plasminogen activator was deferred, given an unknown further risk of intracranial hemorrhage in the setting of the patient's unique cerebrovascular anatomy. The patient was extubated safely 1 week after admission. At the time of discharge to inpatient rehabilitation, 3 weeks posthemorrhage, the patient was able to follow commands intermittently and could move the right arm in the plane, the right leg with flicker movement, and the left arm and leg antigravity. Figure 1H shows a surveillance head CT at 3 weeks without residual intraventricular blood. At the time of outpatient follow-up at 12 weeks, the patient was alert, communicated well, was able to eat by herself, and required two-person assist for walking. Neurologic examination showed her to be partly oriented, with full ability to follow commands and no evidence of aphasia. On cranial nerve testing, she could count fingers in central visual fields only. Gaze was dysconjugate with a right third nerve palsy and bilateral restricted upgaze. The remaining cranial nerves were intact. Motor exam showed near full strength in the upper extremities and strength of 4 of 5 in the lower extremities. Sensory and cerebellar functions were intact. Her mobility had further improved, and at 9 months, she is able to ambulate with a rolling walker and requires one-person assist at times.

intracerebral hemorrhage, intraventricular hemorrhage, outcome, prognosis, self-fulfilling prophesy

PMC8339249_01

Female

A 73-year-old woman visited a local doctor complaining of persistent dry cough for three months. Chest computed tomography (CT) showed consolidation in the right lower lobe. She was considered to have bacterial pneumonia and received treatment with garenoxacin for one week, but her symptoms did not improve. Then, she was referred to our institution where she was diagnosed as having diabetes mellitus at 73 years old and received treatment with sitagliptin 50 mg/day. She had no history of smoking or dust exposure. Her vital signs on the first visit included a heart rate of 73 beats/min, blood pressure of 110/63 mmHg, and body temperature of 35.9 C. Chest auscultation revealed fine crackles. She had no signs or symptoms of edema, arthritis, skin lesions characteristic of DM, myalgia, muscle tenderness, or muscle weakness. Arterial blood gas analysis under ambient air showed a pH of 7.423, partial pressure of carbon dioxide of 39.7 mmHg, and partial pressure of oxygen (PaO2) of 74.3 mmHg. Laboratory findings were as follows: white blood cell count, 6300/mm3; neutrophils, 4300/mm3; eosinophils, 200/mm3; basophils, 0/mm3; monocytes, 400/mm3; lymphocytes, 1300/mm3; hemoglobin, 11.9 g/dL; platelet count, 26.3 x 104/mm3; serum total protein, 7.3 g/dL; albumin, 4.0 g/dL; normal liver transaminase; lactate dehydrogenase, 207 IU/L; creatine kinase, 72 U/L; creatinine, 0.68 mg/dL; C-reactive protein, 0.26 mg/dL; ferritin, 471 ng/mL; Krebs von den Lungen-6 (KL-6), 609 U/mL; surfactant protein-D, 42.0 ng/mL; and brain natriuretic peptide, 7.9 pg/mL. Her anti-nuclear antibody titer was x 40 with a homogeneous pattern. Rheumatoid factor, anti-cyclic citrullinated peptide antibody, anti-aminoacyl tRNA synthetase antibody, anti-Sjogren's-syndrome-related antigen A antibody, proteinase 3-anti-neutrophil cytoplasmic autoantibody (ANCA), and myeloperoxidase ANCA were all negative, as were beta-D glucan, Cryptococcus antigen, and interferon gamma release assay (QuantiFERON ). Pulmonary function testing showed obstructive respiratory dysfunction (Table 1). Chest radiography showed consolidation in the right lower lung field (Fig. 1). Chest high-resolution CT (HRCT) showed subpleural consolidation with volume reduction in the right lower lobe and localized ground-glass opacity in the left lower lobe (Fig. 2A). Bronchoalveolar lavage (BAL) obtained from the right B8b had a total cell count of 1.7 x 105 cells/mL (macrophages, 45.0%; lymphocytes, 48.1%; neutrophils, 2.3%; and eosinophils, 4.6%). The CD4/CD8 lymphocyte ratio was 2.2. No significant pathogens were cultured from the BAL. Transbronchial lung biopsy (TBLB) of the right B8a was performed, but no alveoli were present in the specimens. We suspected that she might have cryptogenic organizing pneumonia, invasive mucinous adenocarcinoma, or malignant lymphoma. We treated her with prednisolone (PSL) 40 mg per day and observed the response to the treatment. Although she received PSL for two weeks, her pulmonary lesions did not improve (Fig. 2B). We discontinued the PSL and performed TBLB of the right B10, but only a few atypical cells were present in the specimens. Two months after discontinuation of the PSL, chest HRCT showed slight worsening of the left lower lobe consolidation (Fig. 2C). A SLB of the right upper lobe was performed to obtain a definitive diagnosis. The specimen showed subpleural perilobular airspace organization and fibrosis, subpleural fibroelastosis, and inflammation in the respiratory bronchioles (Fig. 3). We considered that she had ILD, but we could not specifically diagnose ILD based on these pathological findings. Therefore, we determined that she had unclassifiable idiopathic interstitial pneumonia. One month after SLB (6 months after the first visit), cracking and hyperkeratosis of the tips and margins of her fingers (mechanic's hand) and erythematous papules on the dorsum of the right proximal interphalangeal joints and distal interphalangeal joints (Gottron's papules) appeared (Fig. 4). Manual muscle testing revealed no weakness of the muscles, and electromyography showed no myogenic changes. Arterial blood gas analysis under ambient air showed a PaO2 of 78.1 mmHg. Her levels of lactate dehydrogenase of 270 U/L, KL-6 of 789 U/mL, surfactant protein-D of 130 ng/mL, ferritin of 477 ng/mL, and C-reactive protein of 1.62 mg/dL were all elevated. The anti-MDA5 antibody index was 665 (normal: <32). Her levels of creatine kinase of 51 U/L, myoglobin of <21 ng/dL, and aldolase of 5.2 IU/L were not elevated. Chest HRCT showed worsening of the bilateral subpleural consolidation and ground-glass opacity (Fig. 5A). On the basis of these findings, we held a multidisciplinary discussion and made a diagnosis of anti-MDA5 antibody-positive CADM associated with ILD. She was then treated with PSL, tacrolimus, and intravenous (IV) cyclophosphamide, and she was administered trimethoprim/sulfamethoxazole as prophylaxis for pneumocystis pneumonia. IV cyclophosphamide was discontinued after two cycles because cytomegalovirus (CMV) infection and invasive pulmonary aspergillosis developed. After the treatment was initiated, her clinical symptoms improved, and her KL-6 and ferritin levels decreased (Fig. 6). Six months after starting the treatment, chest HRCT showed improvement of the consolidation and ground-glass opacity (Fig. 5B and C). Subsequently, the anti-MDA5 antibody index was measured in cryopreserved serum obtained on her first admission, and it proved to be 740.

anca, cytoplasmic autoantibody, anti-melanoma differentiation-associated gene 5, bal, bronchoalveolar lavage, cadm, clinically amyopathic dermatomyositis, cmv, cytomegalovirus, ct, computed tomography, clinically amyopathic dermatomyositis, dm, dermatomyositis, hrct, high-resolution computed tomography, ild, interstitial lung disease, ivcy, intravenous cyclophosphamide, interstitial lung disease, kl-6, krebs von den lungen-6, mda5, anti-melanoma differentiation-associated gene 5, psl, prednisolone, pao2, partial pressure of oxygen, rp-ild, rapidly progressive interstitial lung disease, slb, surgical lung biopsy, slowly progressive, surgical lung biopsy, tblb, transbronchial lung biopsy

Pulmonary findings of chest high-resolution computed tomography. (A) At the initial visit, subpleural consolidation with volume reduction in the right lower lobe and localized ground-glass opacity in the left lower lobe were present.

PMC8339249_01

Female

A 73-year-old woman visited a local doctor complaining of persistent dry cough for three months. Chest computed tomography (CT) showed consolidation in the right lower lobe. She was considered to have bacterial pneumonia and received treatment with garenoxacin for one week, but her symptoms did not improve. Then, she was referred to our institution where she was diagnosed as having diabetes mellitus at 73 years old and received treatment with sitagliptin 50 mg/day. She had no history of smoking or dust exposure. Her vital signs on the first visit included a heart rate of 73 beats/min, blood pressure of 110/63 mmHg, and body temperature of 35.9 C. Chest auscultation revealed fine crackles. She had no signs or symptoms of edema, arthritis, skin lesions characteristic of DM, myalgia, muscle tenderness, or muscle weakness. Arterial blood gas analysis under ambient air showed a pH of 7.423, partial pressure of carbon dioxide of 39.7 mmHg, and partial pressure of oxygen (PaO2) of 74.3 mmHg. Laboratory findings were as follows: white blood cell count, 6300/mm3; neutrophils, 4300/mm3; eosinophils, 200/mm3; basophils, 0/mm3; monocytes, 400/mm3; lymphocytes, 1300/mm3; hemoglobin, 11.9 g/dL; platelet count, 26.3 x 104/mm3; serum total protein, 7.3 g/dL; albumin, 4.0 g/dL; normal liver transaminase; lactate dehydrogenase, 207 IU/L; creatine kinase, 72 U/L; creatinine, 0.68 mg/dL; C-reactive protein, 0.26 mg/dL; ferritin, 471 ng/mL; Krebs von den Lungen-6 (KL-6), 609 U/mL; surfactant protein-D, 42.0 ng/mL; and brain natriuretic peptide, 7.9 pg/mL. Her anti-nuclear antibody titer was x 40 with a homogeneous pattern. Rheumatoid factor, anti-cyclic citrullinated peptide antibody, anti-aminoacyl tRNA synthetase antibody, anti-Sjogren's-syndrome-related antigen A antibody, proteinase 3-anti-neutrophil cytoplasmic autoantibody (ANCA), and myeloperoxidase ANCA were all negative, as were beta-D glucan, Cryptococcus antigen, and interferon gamma release assay (QuantiFERON ). Pulmonary function testing showed obstructive respiratory dysfunction (Table 1). Chest radiography showed consolidation in the right lower lung field (Fig. 1). Chest high-resolution CT (HRCT) showed subpleural consolidation with volume reduction in the right lower lobe and localized ground-glass opacity in the left lower lobe (Fig. 2A). Bronchoalveolar lavage (BAL) obtained from the right B8b had a total cell count of 1.7 x 105 cells/mL (macrophages, 45.0%; lymphocytes, 48.1%; neutrophils, 2.3%; and eosinophils, 4.6%). The CD4/CD8 lymphocyte ratio was 2.2. No significant pathogens were cultured from the BAL. Transbronchial lung biopsy (TBLB) of the right B8a was performed, but no alveoli were present in the specimens. We suspected that she might have cryptogenic organizing pneumonia, invasive mucinous adenocarcinoma, or malignant lymphoma. We treated her with prednisolone (PSL) 40 mg per day and observed the response to the treatment. Although she received PSL for two weeks, her pulmonary lesions did not improve (Fig. 2B). We discontinued the PSL and performed TBLB of the right B10, but only a few atypical cells were present in the specimens. Two months after discontinuation of the PSL, chest HRCT showed slight worsening of the left lower lobe consolidation (Fig. 2C). A SLB of the right upper lobe was performed to obtain a definitive diagnosis. The specimen showed subpleural perilobular airspace organization and fibrosis, subpleural fibroelastosis, and inflammation in the respiratory bronchioles (Fig. 3). We considered that she had ILD, but we could not specifically diagnose ILD based on these pathological findings. Therefore, we determined that she had unclassifiable idiopathic interstitial pneumonia. One month after SLB (6 months after the first visit), cracking and hyperkeratosis of the tips and margins of her fingers (mechanic's hand) and erythematous papules on the dorsum of the right proximal interphalangeal joints and distal interphalangeal joints (Gottron's papules) appeared (Fig. 4). Manual muscle testing revealed no weakness of the muscles, and electromyography showed no myogenic changes. Arterial blood gas analysis under ambient air showed a PaO2 of 78.1 mmHg. Her levels of lactate dehydrogenase of 270 U/L, KL-6 of 789 U/mL, surfactant protein-D of 130 ng/mL, ferritin of 477 ng/mL, and C-reactive protein of 1.62 mg/dL were all elevated. The anti-MDA5 antibody index was 665 (normal: <32). Her levels of creatine kinase of 51 U/L, myoglobin of <21 ng/dL, and aldolase of 5.2 IU/L were not elevated. Chest HRCT showed worsening of the bilateral subpleural consolidation and ground-glass opacity (Fig. 5A). On the basis of these findings, we held a multidisciplinary discussion and made a diagnosis of anti-MDA5 antibody-positive CADM associated with ILD. She was then treated with PSL, tacrolimus, and intravenous (IV) cyclophosphamide, and she was administered trimethoprim/sulfamethoxazole as prophylaxis for pneumocystis pneumonia. IV cyclophosphamide was discontinued after two cycles because cytomegalovirus (CMV) infection and invasive pulmonary aspergillosis developed. After the treatment was initiated, her clinical symptoms improved, and her KL-6 and ferritin levels decreased (Fig. 6). Six months after starting the treatment, chest HRCT showed improvement of the consolidation and ground-glass opacity (Fig. 5B and C). Subsequently, the anti-MDA5 antibody index was measured in cryopreserved serum obtained on her first admission, and it proved to be 740.

anca, cytoplasmic autoantibody, anti-melanoma differentiation-associated gene 5, bal, bronchoalveolar lavage, cadm, clinically amyopathic dermatomyositis, cmv, cytomegalovirus, ct, computed tomography, clinically amyopathic dermatomyositis, dm, dermatomyositis, hrct, high-resolution computed tomography, ild, interstitial lung disease, ivcy, intravenous cyclophosphamide, interstitial lung disease, kl-6, krebs von den lungen-6, mda5, anti-melanoma differentiation-associated gene 5, psl, prednisolone, pao2, partial pressure of oxygen, rp-ild, rapidly progressive interstitial lung disease, slb, surgical lung biopsy, slowly progressive, surgical lung biopsy, tblb, transbronchial lung biopsy

Pulmonary findings of chest high-resolution computed tomography. (B) Two weeks after she began receiving prednisolone (PSL), consolidation had not improved.

PMC8339249_01

Female

A 73-year-old woman visited a local doctor complaining of persistent dry cough for three months. Chest computed tomography (CT) showed consolidation in the right lower lobe. She was considered to have bacterial pneumonia and received treatment with garenoxacin for one week, but her symptoms did not improve. Then, she was referred to our institution where she was diagnosed as having diabetes mellitus at 73 years old and received treatment with sitagliptin 50 mg/day. She had no history of smoking or dust exposure. Her vital signs on the first visit included a heart rate of 73 beats/min, blood pressure of 110/63 mmHg, and body temperature of 35.9 C. Chest auscultation revealed fine crackles. She had no signs or symptoms of edema, arthritis, skin lesions characteristic of DM, myalgia, muscle tenderness, or muscle weakness. Arterial blood gas analysis under ambient air showed a pH of 7.423, partial pressure of carbon dioxide of 39.7 mmHg, and partial pressure of oxygen (PaO2) of 74.3 mmHg. Laboratory findings were as follows: white blood cell count, 6300/mm3; neutrophils, 4300/mm3; eosinophils, 200/mm3; basophils, 0/mm3; monocytes, 400/mm3; lymphocytes, 1300/mm3; hemoglobin, 11.9 g/dL; platelet count, 26.3 x 104/mm3; serum total protein, 7.3 g/dL; albumin, 4.0 g/dL; normal liver transaminase; lactate dehydrogenase, 207 IU/L; creatine kinase, 72 U/L; creatinine, 0.68 mg/dL; C-reactive protein, 0.26 mg/dL; ferritin, 471 ng/mL; Krebs von den Lungen-6 (KL-6), 609 U/mL; surfactant protein-D, 42.0 ng/mL; and brain natriuretic peptide, 7.9 pg/mL. Her anti-nuclear antibody titer was x 40 with a homogeneous pattern. Rheumatoid factor, anti-cyclic citrullinated peptide antibody, anti-aminoacyl tRNA synthetase antibody, anti-Sjogren's-syndrome-related antigen A antibody, proteinase 3-anti-neutrophil cytoplasmic autoantibody (ANCA), and myeloperoxidase ANCA were all negative, as were beta-D glucan, Cryptococcus antigen, and interferon gamma release assay (QuantiFERON ). Pulmonary function testing showed obstructive respiratory dysfunction (Table 1). Chest radiography showed consolidation in the right lower lung field (Fig. 1). Chest high-resolution CT (HRCT) showed subpleural consolidation with volume reduction in the right lower lobe and localized ground-glass opacity in the left lower lobe (Fig. 2A). Bronchoalveolar lavage (BAL) obtained from the right B8b had a total cell count of 1.7 x 105 cells/mL (macrophages, 45.0%; lymphocytes, 48.1%; neutrophils, 2.3%; and eosinophils, 4.6%). The CD4/CD8 lymphocyte ratio was 2.2. No significant pathogens were cultured from the BAL. Transbronchial lung biopsy (TBLB) of the right B8a was performed, but no alveoli were present in the specimens. We suspected that she might have cryptogenic organizing pneumonia, invasive mucinous adenocarcinoma, or malignant lymphoma. We treated her with prednisolone (PSL) 40 mg per day and observed the response to the treatment. Although she received PSL for two weeks, her pulmonary lesions did not improve (Fig. 2B). We discontinued the PSL and performed TBLB of the right B10, but only a few atypical cells were present in the specimens. Two months after discontinuation of the PSL, chest HRCT showed slight worsening of the left lower lobe consolidation (Fig. 2C). A SLB of the right upper lobe was performed to obtain a definitive diagnosis. The specimen showed subpleural perilobular airspace organization and fibrosis, subpleural fibroelastosis, and inflammation in the respiratory bronchioles (Fig. 3). We considered that she had ILD, but we could not specifically diagnose ILD based on these pathological findings. Therefore, we determined that she had unclassifiable idiopathic interstitial pneumonia. One month after SLB (6 months after the first visit), cracking and hyperkeratosis of the tips and margins of her fingers (mechanic's hand) and erythematous papules on the dorsum of the right proximal interphalangeal joints and distal interphalangeal joints (Gottron's papules) appeared (Fig. 4). Manual muscle testing revealed no weakness of the muscles, and electromyography showed no myogenic changes. Arterial blood gas analysis under ambient air showed a PaO2 of 78.1 mmHg. Her levels of lactate dehydrogenase of 270 U/L, KL-6 of 789 U/mL, surfactant protein-D of 130 ng/mL, ferritin of 477 ng/mL, and C-reactive protein of 1.62 mg/dL were all elevated. The anti-MDA5 antibody index was 665 (normal: <32). Her levels of creatine kinase of 51 U/L, myoglobin of <21 ng/dL, and aldolase of 5.2 IU/L were not elevated. Chest HRCT showed worsening of the bilateral subpleural consolidation and ground-glass opacity (Fig. 5A). On the basis of these findings, we held a multidisciplinary discussion and made a diagnosis of anti-MDA5 antibody-positive CADM associated with ILD. She was then treated with PSL, tacrolimus, and intravenous (IV) cyclophosphamide, and she was administered trimethoprim/sulfamethoxazole as prophylaxis for pneumocystis pneumonia. IV cyclophosphamide was discontinued after two cycles because cytomegalovirus (CMV) infection and invasive pulmonary aspergillosis developed. After the treatment was initiated, her clinical symptoms improved, and her KL-6 and ferritin levels decreased (Fig. 6). Six months after starting the treatment, chest HRCT showed improvement of the consolidation and ground-glass opacity (Fig. 5B and C). Subsequently, the anti-MDA5 antibody index was measured in cryopreserved serum obtained on her first admission, and it proved to be 740.

anca, cytoplasmic autoantibody, anti-melanoma differentiation-associated gene 5, bal, bronchoalveolar lavage, cadm, clinically amyopathic dermatomyositis, cmv, cytomegalovirus, ct, computed tomography, clinically amyopathic dermatomyositis, dm, dermatomyositis, hrct, high-resolution computed tomography, ild, interstitial lung disease, ivcy, intravenous cyclophosphamide, interstitial lung disease, kl-6, krebs von den lungen-6, mda5, anti-melanoma differentiation-associated gene 5, psl, prednisolone, pao2, partial pressure of oxygen, rp-ild, rapidly progressive interstitial lung disease, slb, surgical lung biopsy, slowly progressive, surgical lung biopsy, tblb, transbronchial lung biopsy

Pulmonary findings of chest high-resolution computed tomography. (C) Two months after discontinuation of PSL, bilateral consolidation developed. Then, a surgical lung biopsy (SLB) of the right upper lobe was performed (arrow).

PMC8339249_01

Female

A 73-year-old woman visited a local doctor complaining of persistent dry cough for three months. Chest computed tomography (CT) showed consolidation in the right lower lobe. She was considered to have bacterial pneumonia and received treatment with garenoxacin for one week, but her symptoms did not improve. Then, she was referred to our institution where she was diagnosed as having diabetes mellitus at 73 years old and received treatment with sitagliptin 50 mg/day. She had no history of smoking or dust exposure. Her vital signs on the first visit included a heart rate of 73 beats/min, blood pressure of 110/63 mmHg, and body temperature of 35.9 C. Chest auscultation revealed fine crackles. She had no signs or symptoms of edema, arthritis, skin lesions characteristic of DM, myalgia, muscle tenderness, or muscle weakness. Arterial blood gas analysis under ambient air showed a pH of 7.423, partial pressure of carbon dioxide of 39.7 mmHg, and partial pressure of oxygen (PaO2) of 74.3 mmHg. Laboratory findings were as follows: white blood cell count, 6300/mm3; neutrophils, 4300/mm3; eosinophils, 200/mm3; basophils, 0/mm3; monocytes, 400/mm3; lymphocytes, 1300/mm3; hemoglobin, 11.9 g/dL; platelet count, 26.3 x 104/mm3; serum total protein, 7.3 g/dL; albumin, 4.0 g/dL; normal liver transaminase; lactate dehydrogenase, 207 IU/L; creatine kinase, 72 U/L; creatinine, 0.68 mg/dL; C-reactive protein, 0.26 mg/dL; ferritin, 471 ng/mL; Krebs von den Lungen-6 (KL-6), 609 U/mL; surfactant protein-D, 42.0 ng/mL; and brain natriuretic peptide, 7.9 pg/mL. Her anti-nuclear antibody titer was x 40 with a homogeneous pattern. Rheumatoid factor, anti-cyclic citrullinated peptide antibody, anti-aminoacyl tRNA synthetase antibody, anti-Sjogren's-syndrome-related antigen A antibody, proteinase 3-anti-neutrophil cytoplasmic autoantibody (ANCA), and myeloperoxidase ANCA were all negative, as were beta-D glucan, Cryptococcus antigen, and interferon gamma release assay (QuantiFERON ). Pulmonary function testing showed obstructive respiratory dysfunction (Table 1). Chest radiography showed consolidation in the right lower lung field (Fig. 1). Chest high-resolution CT (HRCT) showed subpleural consolidation with volume reduction in the right lower lobe and localized ground-glass opacity in the left lower lobe (Fig. 2A). Bronchoalveolar lavage (BAL) obtained from the right B8b had a total cell count of 1.7 x 105 cells/mL (macrophages, 45.0%; lymphocytes, 48.1%; neutrophils, 2.3%; and eosinophils, 4.6%). The CD4/CD8 lymphocyte ratio was 2.2. No significant pathogens were cultured from the BAL. Transbronchial lung biopsy (TBLB) of the right B8a was performed, but no alveoli were present in the specimens. We suspected that she might have cryptogenic organizing pneumonia, invasive mucinous adenocarcinoma, or malignant lymphoma. We treated her with prednisolone (PSL) 40 mg per day and observed the response to the treatment. Although she received PSL for two weeks, her pulmonary lesions did not improve (Fig. 2B). We discontinued the PSL and performed TBLB of the right B10, but only a few atypical cells were present in the specimens. Two months after discontinuation of the PSL, chest HRCT showed slight worsening of the left lower lobe consolidation (Fig. 2C). A SLB of the right upper lobe was performed to obtain a definitive diagnosis. The specimen showed subpleural perilobular airspace organization and fibrosis, subpleural fibroelastosis, and inflammation in the respiratory bronchioles (Fig. 3). We considered that she had ILD, but we could not specifically diagnose ILD based on these pathological findings. Therefore, we determined that she had unclassifiable idiopathic interstitial pneumonia. One month after SLB (6 months after the first visit), cracking and hyperkeratosis of the tips and margins of her fingers (mechanic's hand) and erythematous papules on the dorsum of the right proximal interphalangeal joints and distal interphalangeal joints (Gottron's papules) appeared (Fig. 4). Manual muscle testing revealed no weakness of the muscles, and electromyography showed no myogenic changes. Arterial blood gas analysis under ambient air showed a PaO2 of 78.1 mmHg. Her levels of lactate dehydrogenase of 270 U/L, KL-6 of 789 U/mL, surfactant protein-D of 130 ng/mL, ferritin of 477 ng/mL, and C-reactive protein of 1.62 mg/dL were all elevated. The anti-MDA5 antibody index was 665 (normal: <32). Her levels of creatine kinase of 51 U/L, myoglobin of <21 ng/dL, and aldolase of 5.2 IU/L were not elevated. Chest HRCT showed worsening of the bilateral subpleural consolidation and ground-glass opacity (Fig. 5A). On the basis of these findings, we held a multidisciplinary discussion and made a diagnosis of anti-MDA5 antibody-positive CADM associated with ILD. She was then treated with PSL, tacrolimus, and intravenous (IV) cyclophosphamide, and she was administered trimethoprim/sulfamethoxazole as prophylaxis for pneumocystis pneumonia. IV cyclophosphamide was discontinued after two cycles because cytomegalovirus (CMV) infection and invasive pulmonary aspergillosis developed. After the treatment was initiated, her clinical symptoms improved, and her KL-6 and ferritin levels decreased (Fig. 6). Six months after starting the treatment, chest HRCT showed improvement of the consolidation and ground-glass opacity (Fig. 5B and C). Subsequently, the anti-MDA5 antibody index was measured in cryopreserved serum obtained on her first admission, and it proved to be 740.

anca, cytoplasmic autoantibody, anti-melanoma differentiation-associated gene 5, bal, bronchoalveolar lavage, cadm, clinically amyopathic dermatomyositis, cmv, cytomegalovirus, ct, computed tomography, clinically amyopathic dermatomyositis, dm, dermatomyositis, hrct, high-resolution computed tomography, ild, interstitial lung disease, ivcy, intravenous cyclophosphamide, interstitial lung disease, kl-6, krebs von den lungen-6, mda5, anti-melanoma differentiation-associated gene 5, psl, prednisolone, pao2, partial pressure of oxygen, rp-ild, rapidly progressive interstitial lung disease, slb, surgical lung biopsy, slowly progressive, surgical lung biopsy, tblb, transbronchial lung biopsy

Pulmonary findings of chest high-resolution computed tomography. (A) One month after the surgical lung biopsy, bilateral subpleural consolidation and ground-glass opacity had worsened.

PMC8339249_01

Female

A 73-year-old woman visited a local doctor complaining of persistent dry cough for three months. Chest computed tomography (CT) showed consolidation in the right lower lobe. She was considered to have bacterial pneumonia and received treatment with garenoxacin for one week, but her symptoms did not improve. Then, she was referred to our institution where she was diagnosed as having diabetes mellitus at 73 years old and received treatment with sitagliptin 50 mg/day. She had no history of smoking or dust exposure. Her vital signs on the first visit included a heart rate of 73 beats/min, blood pressure of 110/63 mmHg, and body temperature of 35.9 C. Chest auscultation revealed fine crackles. She had no signs or symptoms of edema, arthritis, skin lesions characteristic of DM, myalgia, muscle tenderness, or muscle weakness. Arterial blood gas analysis under ambient air showed a pH of 7.423, partial pressure of carbon dioxide of 39.7 mmHg, and partial pressure of oxygen (PaO2) of 74.3 mmHg. Laboratory findings were as follows: white blood cell count, 6300/mm3; neutrophils, 4300/mm3; eosinophils, 200/mm3; basophils, 0/mm3; monocytes, 400/mm3; lymphocytes, 1300/mm3; hemoglobin, 11.9 g/dL; platelet count, 26.3 x 104/mm3; serum total protein, 7.3 g/dL; albumin, 4.0 g/dL; normal liver transaminase; lactate dehydrogenase, 207 IU/L; creatine kinase, 72 U/L; creatinine, 0.68 mg/dL; C-reactive protein, 0.26 mg/dL; ferritin, 471 ng/mL; Krebs von den Lungen-6 (KL-6), 609 U/mL; surfactant protein-D, 42.0 ng/mL; and brain natriuretic peptide, 7.9 pg/mL. Her anti-nuclear antibody titer was x 40 with a homogeneous pattern. Rheumatoid factor, anti-cyclic citrullinated peptide antibody, anti-aminoacyl tRNA synthetase antibody, anti-Sjogren's-syndrome-related antigen A antibody, proteinase 3-anti-neutrophil cytoplasmic autoantibody (ANCA), and myeloperoxidase ANCA were all negative, as were beta-D glucan, Cryptococcus antigen, and interferon gamma release assay (QuantiFERON ). Pulmonary function testing showed obstructive respiratory dysfunction (Table 1). Chest radiography showed consolidation in the right lower lung field (Fig. 1). Chest high-resolution CT (HRCT) showed subpleural consolidation with volume reduction in the right lower lobe and localized ground-glass opacity in the left lower lobe (Fig. 2A). Bronchoalveolar lavage (BAL) obtained from the right B8b had a total cell count of 1.7 x 105 cells/mL (macrophages, 45.0%; lymphocytes, 48.1%; neutrophils, 2.3%; and eosinophils, 4.6%). The CD4/CD8 lymphocyte ratio was 2.2. No significant pathogens were cultured from the BAL. Transbronchial lung biopsy (TBLB) of the right B8a was performed, but no alveoli were present in the specimens. We suspected that she might have cryptogenic organizing pneumonia, invasive mucinous adenocarcinoma, or malignant lymphoma. We treated her with prednisolone (PSL) 40 mg per day and observed the response to the treatment. Although she received PSL for two weeks, her pulmonary lesions did not improve (Fig. 2B). We discontinued the PSL and performed TBLB of the right B10, but only a few atypical cells were present in the specimens. Two months after discontinuation of the PSL, chest HRCT showed slight worsening of the left lower lobe consolidation (Fig. 2C). A SLB of the right upper lobe was performed to obtain a definitive diagnosis. The specimen showed subpleural perilobular airspace organization and fibrosis, subpleural fibroelastosis, and inflammation in the respiratory bronchioles (Fig. 3). We considered that she had ILD, but we could not specifically diagnose ILD based on these pathological findings. Therefore, we determined that she had unclassifiable idiopathic interstitial pneumonia. One month after SLB (6 months after the first visit), cracking and hyperkeratosis of the tips and margins of her fingers (mechanic's hand) and erythematous papules on the dorsum of the right proximal interphalangeal joints and distal interphalangeal joints (Gottron's papules) appeared (Fig. 4). Manual muscle testing revealed no weakness of the muscles, and electromyography showed no myogenic changes. Arterial blood gas analysis under ambient air showed a PaO2 of 78.1 mmHg. Her levels of lactate dehydrogenase of 270 U/L, KL-6 of 789 U/mL, surfactant protein-D of 130 ng/mL, ferritin of 477 ng/mL, and C-reactive protein of 1.62 mg/dL were all elevated. The anti-MDA5 antibody index was 665 (normal: <32). Her levels of creatine kinase of 51 U/L, myoglobin of <21 ng/dL, and aldolase of 5.2 IU/L were not elevated. Chest HRCT showed worsening of the bilateral subpleural consolidation and ground-glass opacity (Fig. 5A). On the basis of these findings, we held a multidisciplinary discussion and made a diagnosis of anti-MDA5 antibody-positive CADM associated with ILD. She was then treated with PSL, tacrolimus, and intravenous (IV) cyclophosphamide, and she was administered trimethoprim/sulfamethoxazole as prophylaxis for pneumocystis pneumonia. IV cyclophosphamide was discontinued after two cycles because cytomegalovirus (CMV) infection and invasive pulmonary aspergillosis developed. After the treatment was initiated, her clinical symptoms improved, and her KL-6 and ferritin levels decreased (Fig. 6). Six months after starting the treatment, chest HRCT showed improvement of the consolidation and ground-glass opacity (Fig. 5B and C). Subsequently, the anti-MDA5 antibody index was measured in cryopreserved serum obtained on her first admission, and it proved to be 740.

anca, cytoplasmic autoantibody, anti-melanoma differentiation-associated gene 5, bal, bronchoalveolar lavage, cadm, clinically amyopathic dermatomyositis, cmv, cytomegalovirus, ct, computed tomography, clinically amyopathic dermatomyositis, dm, dermatomyositis, hrct, high-resolution computed tomography, ild, interstitial lung disease, ivcy, intravenous cyclophosphamide, interstitial lung disease, kl-6, krebs von den lungen-6, mda5, anti-melanoma differentiation-associated gene 5, psl, prednisolone, pao2, partial pressure of oxygen, rp-ild, rapidly progressive interstitial lung disease, slb, surgical lung biopsy, slowly progressive, surgical lung biopsy, tblb, transbronchial lung biopsy

Pulmonary findings of chest high-resolution computed tomography. One month, and.

PMC8339249_01

Female

A 73-year-old woman visited a local doctor complaining of persistent dry cough for three months. Chest computed tomography (CT) showed consolidation in the right lower lobe. She was considered to have bacterial pneumonia and received treatment with garenoxacin for one week, but her symptoms did not improve. Then, she was referred to our institution where she was diagnosed as having diabetes mellitus at 73 years old and received treatment with sitagliptin 50 mg/day. She had no history of smoking or dust exposure. Her vital signs on the first visit included a heart rate of 73 beats/min, blood pressure of 110/63 mmHg, and body temperature of 35.9 C. Chest auscultation revealed fine crackles. She had no signs or symptoms of edema, arthritis, skin lesions characteristic of DM, myalgia, muscle tenderness, or muscle weakness. Arterial blood gas analysis under ambient air showed a pH of 7.423, partial pressure of carbon dioxide of 39.7 mmHg, and partial pressure of oxygen (PaO2) of 74.3 mmHg. Laboratory findings were as follows: white blood cell count, 6300/mm3; neutrophils, 4300/mm3; eosinophils, 200/mm3; basophils, 0/mm3; monocytes, 400/mm3; lymphocytes, 1300/mm3; hemoglobin, 11.9 g/dL; platelet count, 26.3 x 104/mm3; serum total protein, 7.3 g/dL; albumin, 4.0 g/dL; normal liver transaminase; lactate dehydrogenase, 207 IU/L; creatine kinase, 72 U/L; creatinine, 0.68 mg/dL; C-reactive protein, 0.26 mg/dL; ferritin, 471 ng/mL; Krebs von den Lungen-6 (KL-6), 609 U/mL; surfactant protein-D, 42.0 ng/mL; and brain natriuretic peptide, 7.9 pg/mL. Her anti-nuclear antibody titer was x 40 with a homogeneous pattern. Rheumatoid factor, anti-cyclic citrullinated peptide antibody, anti-aminoacyl tRNA synthetase antibody, anti-Sjogren's-syndrome-related antigen A antibody, proteinase 3-anti-neutrophil cytoplasmic autoantibody (ANCA), and myeloperoxidase ANCA were all negative, as were beta-D glucan, Cryptococcus antigen, and interferon gamma release assay (QuantiFERON ). Pulmonary function testing showed obstructive respiratory dysfunction (Table 1). Chest radiography showed consolidation in the right lower lung field (Fig. 1). Chest high-resolution CT (HRCT) showed subpleural consolidation with volume reduction in the right lower lobe and localized ground-glass opacity in the left lower lobe (Fig. 2A). Bronchoalveolar lavage (BAL) obtained from the right B8b had a total cell count of 1.7 x 105 cells/mL (macrophages, 45.0%; lymphocytes, 48.1%; neutrophils, 2.3%; and eosinophils, 4.6%). The CD4/CD8 lymphocyte ratio was 2.2. No significant pathogens were cultured from the BAL. Transbronchial lung biopsy (TBLB) of the right B8a was performed, but no alveoli were present in the specimens. We suspected that she might have cryptogenic organizing pneumonia, invasive mucinous adenocarcinoma, or malignant lymphoma. We treated her with prednisolone (PSL) 40 mg per day and observed the response to the treatment. Although she received PSL for two weeks, her pulmonary lesions did not improve (Fig. 2B). We discontinued the PSL and performed TBLB of the right B10, but only a few atypical cells were present in the specimens. Two months after discontinuation of the PSL, chest HRCT showed slight worsening of the left lower lobe consolidation (Fig. 2C). A SLB of the right upper lobe was performed to obtain a definitive diagnosis. The specimen showed subpleural perilobular airspace organization and fibrosis, subpleural fibroelastosis, and inflammation in the respiratory bronchioles (Fig. 3). We considered that she had ILD, but we could not specifically diagnose ILD based on these pathological findings. Therefore, we determined that she had unclassifiable idiopathic interstitial pneumonia. One month after SLB (6 months after the first visit), cracking and hyperkeratosis of the tips and margins of her fingers (mechanic's hand) and erythematous papules on the dorsum of the right proximal interphalangeal joints and distal interphalangeal joints (Gottron's papules) appeared (Fig. 4). Manual muscle testing revealed no weakness of the muscles, and electromyography showed no myogenic changes. Arterial blood gas analysis under ambient air showed a PaO2 of 78.1 mmHg. Her levels of lactate dehydrogenase of 270 U/L, KL-6 of 789 U/mL, surfactant protein-D of 130 ng/mL, ferritin of 477 ng/mL, and C-reactive protein of 1.62 mg/dL were all elevated. The anti-MDA5 antibody index was 665 (normal: <32). Her levels of creatine kinase of 51 U/L, myoglobin of <21 ng/dL, and aldolase of 5.2 IU/L were not elevated. Chest HRCT showed worsening of the bilateral subpleural consolidation and ground-glass opacity (Fig. 5A). On the basis of these findings, we held a multidisciplinary discussion and made a diagnosis of anti-MDA5 antibody-positive CADM associated with ILD. She was then treated with PSL, tacrolimus, and intravenous (IV) cyclophosphamide, and she was administered trimethoprim/sulfamethoxazole as prophylaxis for pneumocystis pneumonia. IV cyclophosphamide was discontinued after two cycles because cytomegalovirus (CMV) infection and invasive pulmonary aspergillosis developed. After the treatment was initiated, her clinical symptoms improved, and her KL-6 and ferritin levels decreased (Fig. 6). Six months after starting the treatment, chest HRCT showed improvement of the consolidation and ground-glass opacity (Fig. 5B and C). Subsequently, the anti-MDA5 antibody index was measured in cryopreserved serum obtained on her first admission, and it proved to be 740.

anca, cytoplasmic autoantibody, anti-melanoma differentiation-associated gene 5, bal, bronchoalveolar lavage, cadm, clinically amyopathic dermatomyositis, cmv, cytomegalovirus, ct, computed tomography, clinically amyopathic dermatomyositis, dm, dermatomyositis, hrct, high-resolution computed tomography, ild, interstitial lung disease, ivcy, intravenous cyclophosphamide, interstitial lung disease, kl-6, krebs von den lungen-6, mda5, anti-melanoma differentiation-associated gene 5, psl, prednisolone, pao2, partial pressure of oxygen, rp-ild, rapidly progressive interstitial lung disease, slb, surgical lung biopsy, slowly progressive, surgical lung biopsy, tblb, transbronchial lung biopsy

Pulmonary findings of chest high-resolution computed tomography. six months after starting the treatment, these findings had improved.

PMC3020613_01

Male

A 33-year-old man with acute myeloid leukemia was admitted to a hospital in Seattle, Washington, with neutropenic fever; he was initially treated with ceftazidime. His therapy was changed to acyclovir and imipenem because of unremitting fevers and oral lesions positive for herpes simplex virus type 1, whereupon his fever defervesced immediately. The fever recurred 2 weeks after treatment was begun, and imipenem-resistant E. cloacae was isolated from the blood. After the results of susceptibility testing were obtained, his therapy was changed to levofloxacin, and he exhibited a good clinical response. The E. cloacae isolate was susceptible to piperacillin, piperacillin-tazobactam, ceftazidime, ceftriaxone, cefepime, ciprofloxacin, gentamicin, aztreonam, and trimethoprim-sulfamethoxazole and was resistant to ampicillin, amoxicillin-clavulanic acid, cefazolin, and cefoxitin. By both disk diffusion and E-test methods (AB Biodisk, Solna, Sweden), the zones of inhibition around the imipenem, meropenem, and ertapenem disks were indistinct, with inner colonies extending up to the disk or the highest concentration on the E-test strip (MIC >32 mug/mL) and were interpreted as resistant (Figure 1). Addition of 10 muL of 1,000 mug/mL clavulanic acid to the imipenem, meropenem, and ertapenem disks resulted in clearly defined and enlarged zones of inhibition and loss of the inner colonies (Figure 2). Using either cefoxitin or imipenem as inducers by the disk induction method resulted in the formation of blunted or D-shaped zones of inhibition to meropenem and ertapenem. We performed a carbapenem bioassay by incubating 100 muL of a 50 mug/mL solution of each carbapenem (imipenem, meropenem, or ertapenem) with 100 muL of either crude beta-lactamase extract or phosphate-buffered saline for 90 min at room temperature. The inactivating capacity of the enzyme was then tested by a disk diffusion assay that demonstrated hydrolysis of imipenem, meropenem, and ertapenem. Isoelectric focusing (IEF) to determine isoelectric points (pIs) and general inhibitor characteristics with an ampholine polyacrylamide gel (pH range 3.5-9.5) on a flatbed apparatus (Multiphor LKB, Bromma, Stockholm, Sweden) indicated that this organism produced a beta-lactamase enzyme with a pI of 6.9 that was inhibited by clavulanic acid and not by cloxacillin. This enzyme hydrolyzed 1 mug/mL imipenem on the IEF gel overlay. Inducibility of the enzyme by imipenem (4 mg/L) and cefoxitin (8 mg/L) was confirmed by the broth induction method and IEF. After the broth induction procedure, the uninduced and induced preparations were serially diluted in 0.1 M potassium phosphate buffer, pH 7.0, permitting both qualitative and semiquantitative assessment of enzyme activity among the various beta-lactamases in the isolate, as determined by IEF. The broth induction enzyme preparation from a 100-mL, 3.5-h Mueller-Hinton broth produced a visible but light AmpC band, pI >9.0. The induction with cefoxitin and imipenem increased the levels of both the AmpC and the pI 6.9 carbapenem-hydrolyzing enzyme, as visualized in Figure 3. A cefoxitin-induced preparation of E. cloacae NOR-1 (that produces NmcA) was included as a control strain for IEF. Chromosomal DNA was extracted from overnight cultures with the Qiagen DNeasy Tissue kit (QIAGEN Inc., Valencia, CA). Polymerase chain reaction (PCR)-amplification with a thermal cycler (MJ Research PTC - 200-DNA Engine, San Francisco, CA) was used to obtain a 2,122 base pair gene fragment consisting of the carbapenemase structural gene nmcA and its regulatory gene nmcR. The nucleotide sequences of the primers were 5'- TGC CAG CTT AAT TAT TTT CAG ATT AG -3' (nmcR positions 32-56) and 5'- ATT TTT TTC ATG ATG AAG TTA AGC C -3' (nmcA positions 2,129-2,154). PCR amplification of the nmcR/nmcA genes showed positive results with both NOR-1 and the strain under study, suggesting that the latter strain harbored a carbapenem-hydrolyzing enzyme similar to that of NOR-1. Subsequent sequence analysis of the amplified DNA-region showed a similarity of 100% (2,122 base pairs) between the sequence of our strain and the carbapenemase genes, regulatory (nmcR) and structural (nmcA) genes of the E. cloacae strain NOR-1.

PMC4783553_01

Female

A 24-year-old primigravida at 35-week period of gestation (POG) with MDR-TB was admitted in view of severe growth restriction and oligohydramnios. She had past history of pulmonary tuberculosis at the age of 14 years for which she received treatment for 6 months. She had relapse of pulmonary tuberculosis 1 year back and was suspected to have MDR-TB in view of worsening symptoms along with sputum positivity after 6 months of first line treatment. Sputum testing revealed drug resistance for isoniazid and rifampicin. The patient was started on second line antitubercular drugs, that is, ethionamide, cycloserine, levofloxacin, ethambutol, and pyrazinamide, along with injection of kanamycin for six months till sputum conversion. In continuation phase, injection of kanamycin was omitted and the patient continued to use the rest of the drugs. She conceived while on same treatment and was continued on the same drugs after consultation with pulmonologist. Her general physical examination did not reveal any abnormality and HIV and the rest of the routine antenatal investigations were normal. Fetal evaluation revealed severe growth restriction and oligohydramnios at 28 weeks of gestation. Fetal surveillance was continued with biweekly biophysical profile; she was given antenatal steroids and caesarean was performed at 35 weeks in view of breech with growth restriction with severe oligohydramnios. She delivered healthy baby with birth weight of 1.2 kg (standard deviation of less than 2) with Apgar score of 8 and 9 and there were no obvious congenital malformations. Neonatal work-up for tuberculosis revealed normal chest X-ray and Mantoux and gastric aspirate, cerebrospinal fluid analysis, and urine tested for acid fast bacilli were also negative. Placental membrane tested for acid fast bacilli was also negative. Baby was started on breast-feeding and given isoniazid prophylaxis. Infant's evaluations at 3 months were negative for tuberculosis and the baby continued on the same prophylaxis for 6 months.

PMC4308030_02

Male

Patient 1 is male, firstborn of healthy parents; pregnancy and delivery were uneventful. Neonatal period was complicated by a group B meningococcal sepsis. Seizures occurred from the age of fourteen months, and he developed an epileptic encephalopathy. He suffers from myoclonic seizures of the left arm, atonic seizures, and tonic seizures. The latter were provoked by sudden sounds or unexpected visual stimuli. Neurological examination revealed no focal abnormalities; there is a psychomotor developmental delay with severe learning disabilities. Extended diagnostic work-up, including magnetic resonance (MR) imaging and MR spectography, and neurometabolic and genetic evaluation were all normal. Three seizure types have coexisted since the onset of epilepsy. He was not a suitable candidate for epilepsy surgery. At the age of 5 years, a vagal nerve stimulator was implanted, and a revision took place after two years because of dysfunction and increase in seizure frequency. Ketogenic diet had no effect. At age 10, his epilepsy was still refractory, with seizure frequency varying from several seizures a day to 30 seizures a day, depending on triggering factors. He used lamotrigine and clorazepam at the time of referral to the audiological team. Treatment alternative with sound generators was initiated after counseling both the boy and his parents. During a follow-up period of a year at the child neurology outpatient clinic, his parents reported that he continuously removed his retrainers. As there was no change in seizure frequency, they stopped the sound generator therapy. Patient 2 is the third son of healthy parents, born after an uneventful pregnancy and delivery. At age three months, he suffered from pneumococcal meningitis. He developed a spastic right-sided hemiplegia and localization-related complex partial seizures over a period of two years. He became seizure-free and did not use antiepileptic drugs for several years until he developed startle seizures at age 10. A sudden sound resulted in a tonic seizure, sometimes accompanied by urinary or fecal incontinence. Seizure frequency was variable, depending on triggering factors such as a pencil falling in the classroom or a school bell ringing. He had at least 2-3 seizures a day; they did not respond to antiepileptic drugs. He attends a normal school. His MR imaging showed an encephalomalacia of the left hemisphere. Epilepsy surgery was considered, but his parents preferred the noninvasive treatment alternative with sound generators. He and his parents were counseled by our audiological team, and therapy with sound generators was initiated with considerable success. Over a period of a few years, seizure frequency was reduced to one per month. He was even able to watch fireworks and to set one off himself when wearing his sound generators.

asr, acoustic startle reflex, behavioral therapy, intractable epilepsy, mr, magnetic resonance, retrainers, spes, startle-provoked epileptic seizures, sound generators, startle-provoked seizures

PMC7294351_01

Male

A 28-year-old male patient admitted to the emergency department presented a tonic-clonic seizure, left arm paresis, paraparesis, two months of gait disturbance, and fever (38 C). The patient was diagnosed with HIV-1 three months ago. His CD4+ T-cell count was 669 cells/muL, with a viral load of 23,800 c/mL, CDC stage A1, and naive to antiretroviral therapy (ART). The patient presented a confusional state, somnolence, hypoprosexia, and complex visual hallucinations. The left arm's strength was diminished (3/5), and the lower limbs had symmetric paresis (2/5) and symmetrically augmented myotatic reflexes. Babinski's plantar reflex was absent. The rest of the neurological examination: cranial nerves, optic fundus, and papilla did not have alterations, sensory examination was normal, and there were no meningeal signs, abnormal movements, or ataxia. The CSF was clear and had the following findings: proteins 27 mg/dl, glucose 74 mg/dl (serum glucose 90 mg/dl), and a white blood cell count of 20 cells/mm3 (54% lymphocytes) with no evidence of malignant cells nor oligoclonal bands. The cryptococcus antigen test, polymerase chain reaction (PCR) for M. tuberculosis, VDRL, bacterial cultures, and Gram and Ziehl Neelsen stains in CSF were negative. Serum IgG serology for Toxoplasma Gondii was negative. MRI reported white matter demyelinating lesions, mainly affecting the centrum semiovale, the frontal lobe, and the left parietal lobe; hypointense on T1-weighted images, hyperintense on T2-weighted images and fluid-attenuated inversion recovery (FLAIR) weighted images, DWI with restricted diffusion, and a parietal ring-enhancing lesion after IV gadolinium administration (Figure 1). After meningeal cryptococcal and meningeal tuberculosis infection was discarded, we started ART with abacavir/lamivudine/dolutegravir. Since, ART initiated after symptoms onset, immune reconstitution inflammatory syndrome (IRIS) criteria are not met, we started ART with Abacavir/Lamivudine/Dolutegravir. By exclusion of other diagnoses, ADEM was diagnosed, and the patient received high doses of IV methylprednisolone (1 g/day) for five consecutive days; subsequently, he showed neurological function improvement. After three years of follow-up, the patient showed complete neurological remission with no relapses. He continued on ART with good adherence and undetectable.

PMC9135568_01

Unknown

Bladder cancer is a malignant tumor of the bladder mucosa. It is considered to be one of the ten most common malignant tumors, and its incidence is second only to prostate cancer, ranking second. The disease can occur at any age, even in children. Its incidence increases with age. The highest incidence is between 50 and 70 years old. There are more men than women. The clinical manifestations include bladder irritation sign and macroscopic or microscopic hematuria. The main treatment is surgery, and the 5-year survival rate after surgery is 60%. However, the postoperative recurrence rate is high, up to 50% to 70%, which seriously endangers the life of sufferers. It is of great significance to watch an effective means to appraise the postoperative recurrence of bladder carcinoma for early clinical prevention and treatment and to improve the prognosis of sufferers. Nuclear matrix protein 22 (NMP22) is an internal structural component of the nucleus, involved in DNA replication, transcription, and RNA synthesis, and also plays an important regulatory role in gene conveying. Under normal circumstances, NMP22 is expressed in a small amount in healthy people, but NMP22 can be released in large amounts outside the cell during apoptosis of knub cells. Studies have shown that NMP22 is released into the urine in the form of soluble complexes or fragments in bladder carcinoma, and the concentration can be as high as 25 times that of normal cells. It is a urothelial-specific knub-interrelated marker. Cystatin B (CSTB) is a member of the cysteine protease inhibitor superfamily, which can inhibit the activity of various proteolytic enzymes including cysteine proteases. Previous studies have shown that CSTB is abnormally expressed in various knubs such as breast carcinoma, esophageal carcinoma, and lung carcinoma, and it is widely involved in the occurrence and development of various harmful knubs. In the context of the above research, this study retrospectively analyzed the preoperative expression of NMP22 and CSTB in evaluating the postoperative recurrence of bladder cancer and creatively discovered a new method for assessing postoperative recurrence of bladder cancer, which is a useful tool for clinical evaluation of postoperative recurrence of bladder cancer. It provides a certain theoretical basis and is helpful for clinicians to formulate more timely and reasonable diagnosis and treatment plans for bladder cancer patients.

PMC4362180_01

Female

This was a prospective, randomized, single-center study. All surgeries were performed by one surgeon. Approval from the Institutional Review Board of Medipol University was obtained for the study. Twenty-eight patients (56 eyes) participated in this study conducted at Medipol University of Medicine Eye Clinic, Istanbul, Turkey between March 2014 and May 2014. Patients were included if they were at least 18 years old, and had spherical equivalent manifest refraction between -1.00 and -5.00 diopters (D), and astigmatism less than -2.00 D, stable refraction at least 12 months before surgery, and a minimum follow-up of 3 months. No one had signs of keratoconus, uncontrolled glaucoma, untreated retinal abnormalities, or previous intraocular or corneal surgery. The exclusion criteria were; older than 40 years, diabetes, and history of herpetic keratitis, and previous intraocular, or corneal surgery, pregnancy, nursing, collagen vascular diseases, or dry eye. Pre-operative assessments included uncorrected and best corrected visual acuity, cycloplegic refraction, pachymetry with AS-OCT, examination of cornea with Orbscan and slitlamp biomicroscopic examination of both anterior and posterior segments. Tear function was assessed using a Schirmer I test and the tear film breakup time (TBUT) was determined. Soft contact lens was discontinued for a minimum of 7 days before examination and treatment. Contralateral eyes in each patient were subject to random allocation through which, PRK surgery was carried out on one eye, and LASEK was carried out for the other eye of same patient by the same surgeon. All patients agreed to participate and gave their informed consent forms after the nature of the procedure had been explained. This study was conducted according to the declaration of Helsinki and relevant laws/regulations. All procedures were performed with the VISX Star S4 excimer laser using a standard protocol by the same surgeon. The aim of the surgery was emmetropia. Preoperatively 10% povidone-iodine was used to clean the eyelids and periocular area for 1 minute, and then the eye was washed out with 20 ml of a balanced salt solution. All treatments were performed using topical anesthesia with one drop of 0.5% proparacaine (Alcaine, S.A. Alcon-Couvreur, Puurs, Belgium). A closed-loop lid speculum is used to retract the lids of the eye to be treated, and the other eye was occluded. A 7.0-mm optical zone marker was applied to the cornea, centered over the entrance pupil. The epithelial cell layer of the cornea was debrided with a crescent knife and then photoablation was performed on the corneal stroma. The corneal surface and entire conjunctiva were irrigated with a balanced salt solution and the excess fluid was removed with another cellulose sponge. An alcohol solution cone (J2908, Janach, Como, Italy) with a 10 mm diameter was applied to the corneal surface, and a 20% ethyl alcohol solution diluted with distilled water was filled inside the cone and was left for approximately 40 seconds. At the end of the time a merocel sponge (Medtronic Ophthalmics Inc, Jacksonville, FL) was used to soak up the alcohol in the cone and the entire ocular surface was carefully washed off with a balanced salt solution. An epithelial microhoe (Janach J2916A) was used to detach the flap edge and then the flap was shifted as one intact sheet toward the 12:00 position using an epithelial flap peeler (Janach J2930A). After the denuded corneal surface was ablated, the epithelial flap was washed with balanced salt solution and gently repositioned with using a spatula (Janach J2920A). For all treatment groups, at the end of surgery a therapeutic contact lens (TCL) (Purevision; base curve of 8.3 mm, 0 diopter (D), diameter of 14 mm; Bausch Lomb, Rochester, NY) was fitted to the treated eye with contact lens applanator (Janach J2935) after one drop of both 0.3% ciprofloxacin and 0.1% diclofenac were instilled on the surgical site. Postoperative Medication: All patients were examined daily during 5 days follow up. Postoperative treatment included topical diclofenac and tobramycin drops 4 times daily during the reepithelization period. A preservative-free sodium hyaluronate 0.1% drops were applied every hour during first 48 hours postoperatively and 4 times in a day for 1 month. After re-epithelialization, 0.3% tobramycin (Tobrex, Alcon-Couvreur, Puurs, Belgium) and 0.1% deksametazon (Maxidex ,Alcon-Couvreur, Puurs, Belgium) were administered four times daily for 10 days and twice in a day for 15 days. All patients were examined every day for 5 days, then at the 10th day, and 1, and 3 months. During first 5 days, specifically epithelial healing was followed up. Epithelial wound healing was assessed using Visante OCT Anterior Segment Imaging (Carl Zeiss Meditec, Inc, Berlin, Germany) by imaging the cornea with TCL in-situ. OCT images taken immediately after surgery and then every 24 hours until complete epithelial healing had occurred. Horizontal and vertical radial images through the central cornea were obtained for each eye on central fixation position to show sections of migrating epithelial tissue. The TCLs were removed when complete epithelialization was determined. All patients were interviewed in standardized conditions with prior information to ensure valid reliable responses. Pain, photophobia, and lacrimation were each given a score from 1 to 5. Patients were asked for each complaint separately during 5 days thereafter surgery until complete healing had occurred. At the 10th day, 1 and 3 months after surgery, uncorrected and best spectacle-corrected visual acuity, manifest refraction, slit-lamp microscopy, corneal topography with Orbscan were performed by one investigator. Subepithelial stromal haze was evaluated with the slit lamp microscope using broad tangential illumination, and graded as 0 to 4+ by 2 authors at different times, and different examination rooms. In our study, each patient served as him or her own control subject. The Statistical Package for Social Sciences software version 17 (SPSS Inc, Chicago, IL, USA) was used for statistical analysis. The normality of the distribution of each of the parameters was checked using the normal Kolmogorov-Smirnov test. Visual acuity data were converted from Snellen chart values to LogMAR notation for statistical analysis. The Mann-Whitney U test was used to compare discomfort scores and reepithelization, and chi-squared test was used postoperative uncorrected distance vision. The significance level was set to alpha = 0.95 and p<0.05 was considered significant.

PMC4821250_01

Female

A 63-year-old woman was admitted in our department for evaluation of chronic back pain and neuralgia. She had an abnormal shadow on the chest radiograph followed up since 1999. She has a history of arterial hypertension for 5 years treated by association of diuretics and inhibitor of the conversion enzyme. The patient had not had BCG vaccination. In 1977, she was treated for pulmonary tuberculosis, which was diagnosed for fever, cough, weight loss and night sweats. Chest radiograph showed opacity in the right lower lobe. Tuberculosis skin test was positive, but sputum smear and culture for tuberculosis were negative. She was treated using streptomycine, isoniazid, pyrazinamide and rifampicine for 2 months and then isoniazid and rifampicine for 4 months. The response was good with disappearance of symptoms but the radiological aspect showed persistence of the lower lobe opacity. The patient was lost until its consultation for pain and the persistent opacity was not explored. The chest radiograph at admission (Fig. 1A) showed a round well defined opacity in the right lower lobe and a paravertebral opacity, chest-CT scan showed a round well defined soft tissue mass measuring 38.5/31.3 mm localized on the right lower lobe and a 40 mm (in the greatest diameter) right paravertebral cystic mass (Fig. 1 B and C). The hydatid serology, research of myobacterium tuberculosis in sputum and the histological finding of bronchial biopsy were negative. Preoperative assessments were without anomaly and have included: blood cells account, electrolytes, glycemia, renal and hepatic tests, electrocardiography and transthoracic cardiac echography. Under general anesthesia, and selective tracheal tube intubation, the patient was placed in the lateral position. A right postero-lateral thoracotomy was performed in the sixth intercostal space. Exploration showed a round mass, covered by parenchyma, in the center of the lower lobe. In addition, there was a paraoesophageal cystic mass that was adherent to the vertebral body, oesophagus and lung. A lower lobectomy was performed, in addition to the complete excision of the paraoesophageal cyst (Fig. 2 A,B,C). Gross examination of the lung mass found a cyst with a thin wall and chocolate content, surrounded with 2.5 cm normal parenchyma margins. The paraoesophageal cyst was whitish, cartilaginous in consistency and measuring 4.5/3 cm for both lesions, histology concluded to a bronchogenic cyst (Fig. 3). These cysts were lined by a coating of respiratory type ciliated and pseudostratified, based on a fibrous shell, with a few mucus-secreting bronchial glands. The postero-inferior drain was removed the 3rd postoperative day and the antero-apical drain was removed 6th postoperative day. No perioperative complication was noted. The patient had an uneventful discharge the 7th postoperative day. At 3 weeks, the patient reported a subjective resolution of the symptoms she suffered preoperatively. However, she presented post-thoracotomy pain that was managed successfully using analgesic oral paracetamol therapy. Chest radiograph was normal with 4 years and 7 months of follow-up and the patient is actually asymptomatic (Fig. 4).

bronchogenic cyst, diagnosis, infection, locations, surgery

PMC5457926_01

Male

A 51-year-old man suffering from diabetes mellitus with insulin therapy and diabetic nephropathy was referred to our institution for the investigation of abnormal findings on a chest radiograph. He was a current smoker (30 packs/year). An apical segment right upper lobe cavitary nodule was detected on thoracic computed tomography (CT). We could not detect any large vessels, including the pulmonary veins that penetrated the nodule (Fig. 1). Although the patient was suspected of having pulmonary tuberculosis, a sputum smear for acid-fast bacilli was negative on three examinations. Therefore, we performed flexible bronchoscopy in a supine position without intravenous sedation. No endobronchial abnormalities were detected, and curettage was performed twice and transbronchial lung biopsy (TBLB) four times under fluoroscopic guidance. During bronchoscopy, he had no coughing or major bleeding events, and no pneumothorax on a radiography fluoroscopic examination immediately after bronchoscopy. Rapid on-site evaluation of cytology revealed many inflammatory cells and no malignant cells. The total duration of bronchoscopy was about 30 minutes. During bronchoscopy, the patient remained in the supine position. Immediately after completion of bronchoscopy, his blood pressure decreased to 60/40 mmHg, heart rate decreased to 30 bpm, and oxygen saturation dropped to 70%. A neurological examination revealed a Glasgow Coma Scale (GCS) score of 3/15 points. Hypotension and bradycardia quickly recovered after fluid resuscitation. His level of consciousness improved to GCS 9/15 points; however, left hemiplegia appeared. We suspected an intracranial lesion, and indeed, head CT taken 15 minutes after TBLB showed cerebral air embolism (Fig. 2). Fifteen minutes after head CT, brain magnetic resonance imaging (MRI) on sequences of diffusion-weighted images (DWI) showed hyperintense lesions predominantly located around the air density on CT, which was compatible with air embolism. The patient's level of consciousness improved to GCS 15/15, and the left hemiplegia completely recovered within 1 hour after bronchoscopy. He had no other symptoms. After bronchoscopy, chest radiography revealed that the target lesion had enlarged. The following day, lower left quadrant pain developed. Abdominal CT revealed pneumatosis intestinalis of the descending colon (Fig. 3). In addition, serum creatine kinase and troponin T levels were elevated. Electrocardiogram demonstrated inverted T waves (Fig. 4). Echocardiography revealed no abnormal cardiac wall motion. We considered air embolism in the inferior mesenteric artery and the right coronary artery. The next day, his abdominal pain and laboratory abnormalities improved with maintenance transfusion and fasting. A few days later, Mycobacterium tuberculosis was cultured on bronchoscopy specimens. He was therefore administered anti-tuberculosis drugs, and thereafter the nodule shrank.

Chest CT from a previous institution. A cavitary nodule was detected in the right upper lobe.