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Tuberculosis_Dataset

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PMC4992389_01

Female

This is a 57 year old female with hypothyroidism history for 20 years who consulted for fever, arthralgia and erythema nodosum. She presented with a 10 day history of subcutaneous nodules in lower limbs, fever, and arthritis. On physical examination, there was hepatosplenomegaly, and no lymphadenopathy. On the skin examination there was hot nodules on the front and sides of the legs. On ophtalmological examination, there wa keratitis. Biological findings showed an elevated erythrocyte sedimentation rate (123 mm during the first hour), a normocytic normochromic non-regenerative anemia (9 g / dl), a positive polyclonal hyper gamma globulin rate (16 g / L), an elevated C-reactive protein rate (190 mg / L), renal failure (creatinine 200 umol / l, Urea 16 mmol / l, Renal clearance: 28 ml / min), anti-nuclear and anti-native DNA antibodies were positive. There was also significant proteinuria (1g/day). Calcium and phosphate balance over a 3 day periods was normal. Chest X-ray showed Mediastinal enlargement suggestive of mediastinal adenomegaly with calcifications (Figure 1). On chest CT there was mediastinal lymph nodes in Barety space and bilateral hilar lymphadenopathy which were partially calcified. There were changes in the lung parenchyma described as ground glass infiltrates with pleural nodules, pleural and pericardial effusions (Figure 2). Tuberculin intradermal test was negative, mycobacteruim tuberculosis wasn't present in gastric fluid. On functional respiratory tests there was distal obstructive deficit with a normal DLCO. Bronchoscopy showed macroscopically normal bronchi. Bronchial biopsies suggested non specific inflammation lesions. Renal Ultrasound revealed poorly differentiated kidneys with a small left kidney, which didn't allow the renal biopsy. Skin biopsy was performed on healthy skin and showed no lupus band. Renal biopsy was contrindicated by the findings of the renal ultrasound. Biopsy of the salivary glands showed chronic sialadenitis the special Congo Redstain revealed amyloid deposits around the vessels and interlobular ducts (Figure 3) which are birefringent amyloid deposits under polarized light (Figure 4). Accordingly, the retained diagnosis was the association of SLE, sarcoidosis (Lofgren syndrome) and amyloidosis. Our patient has already been treated. There was a complete regression of the erythema nodosum lesions under analgesics and potassium iodide after 4 weeks. There were no indications for corticosteroid therapy because kidneys were already affected, CKD stage (Chronic kidney disease) with small dedifferentiated kidneys and there were no signs of activity of sarcoidosis. The patient was prescribed Colchicine 1mg per day and Nivaquine 200mg per day. The patient monitoring included a chest CT, a transthoracic echocardiography (which showed regression of the pericardial effusion), creatininemia and Proteinuria. A rectal biopsy was scheduled.

amyloïdosis, lupus erythematosus, sarcoïdosis

Mediastinal lymph nodes in Barety space and bilateral hilar lymphadenopathy on chest CT.

PMC6046143_02

Male

A 76-year-old man was referred to our service for progressive redness and pain in the right eye. Six months earlier, his disease had been diagnosed as conjunctivitis, episcleritis, and senile furrow degeneration and he had been unsuccessfully treated with topical tobramycin/dexamethasone. His ocular and medical history and review of systems were unremarkable. BCVA in the right eye was 20/25 and slit-lamp examination revealed limbal injection, fine inferior keratic precipitates, and temporal corneal thinning with an overlying epithelial defect that measured 5 mm vertically and 2 mm horizontally and stained with fluorescein. The presumptive diagnosis of PUK was made and the patient was started on moxifloxacin q.i.d., doxycycline 100 mg bid, vitamin C 1 g bid, and topical lubricants. Lab workup was notable for positive purified protein derivative (PPD) and QuantiFERON gold. Cyclic citrullinated peptide antibody test, a marker for rheumatoid arthritis, was also positive. All other laboratory assays were unremarkable and chest x-ray was normal. An infectious disease specialist was consulted at this time who recommended isoniazid, pyridoxine, and rifampin for the treatment of latent tuberculosis. We also consulted the rheumatology service that recommended we proceed with immunosuppression using prednisone 1 mg/kg and mycophenolic acid. His condition improved after one month and a prednisone taper was initiated. However, PUK recurred, at which point oral prednisone was restarted at the original moderate dose and amniotic membrane was placed via a PROKERA lens (Bio-Tissue, Doral, FL) to promote epithelial corneal healing. He returned two weeks later with worsening keratitis at which point the lens was removed and topical prednisolone acetate t.i.d. was initiated. Symptoms stably improved for three months, after which he was very slowly tapered off topical and systemic prednisone. At his last visit, 16 months after presentation, he remains asymptomatic with a BCVA of 20/30. Figure 2 demonstrates a slit-lamp photograph taken at presentation and AS-OCT images taken before and after treatment. The etiology for this patient's PUK was deemed related to his autoimmune disorder with possible rheumatoid arthritis. Given the need for immunosuppression, antituberculosis medications were initiated under the care of an infectious disease specialist.

PMC3228391_01

Male

A 13-month-old Haitian boy presented to Project Medishare field hospital in Port-au-Prince, with a 4-day history of traumatic brain injury (TBI). A cement block fell through the roof of his "sheet" tent, striking him on the right side of the head. He initially lost consciousness, and once he was more alert, was noted to be hemiplegic. The family did not seek immediate medical attention, but when he became increasingly sleepy and irritable, they brought him to the hospital. On examination, the child exhibited left hemiplegia, prominent scalp veins, a bulging fontanelle, irritability, and a depressed level of consciousness. Computed tomography (CT) scanning was unavailable at the field hospital, and a decision for urgent surgical intervention was made based on the patient's history of neurological deterioration and observed signs of increased ICP. General anesthesia was induced, and then the patient positioned supine for a typical trauma flap craniotomy/craniectomy procedure. A reverse question mark scalp incision was utilized and a myocutaneous flap elevated, revealing a large frontoparietotemporal linear depressed skull fracture with active herniation of cortical tissue from the fracture line [Figure 2]. Multiple burr holes were placed with a Hudson Brace, and then a Gigli saw was used to perform a craniectomy in three large pieces, roughly corresponding to the frontal bone, parietal bone, and squamous temporal bone. A large dural rent was extended to create a stellate dural opening. Epidural hemostasis was achieved using bipolar cautery and Surgicel (Ethicon, Cincinnati, OH, USA). Evacuation of a small intraparenchymal hematoma and brain elevation out of the large craniectomy defect resulted in significant brain relaxation. After hemostasis was ensured, the stellate dural flaps were laid on the brain surface and the entire defect was covered with a thin layer of Fibrillar hemostatic agent (Ethicon) [Figure 3a]. The three bone flaps were then placed on the surface of the dura/fibrillar cushion in approximate anatomic position [Figure 3b]. Because of the expansion of the brain out of the craniectomy and the requisite increase in surface area, there were gaps of 5-10 mm between each of the flaps. The bone flaps were not affixed in any way to the skull or to each other, but were fairly adherent in their positions. The scalp was then reapproximated under mild tension in a standard fashion. After surgery, the patient remained intubated, but was extubated on postoperative day 1. He was transferred out of the pediatric ICU after several days. He was alert and feeding well immediately, and was noted to have movement of the left hand and lower extremity by postoperative day 6. The incision site remained intact without swelling or defect. The patient had excellent cosmetic outcomes and neurological recovery, and was discharged on postoperative day 10 [Figure 4]. Due to the unique nature of this case and the post-disaster condition in Haiti, long-term clinical or radiographic follow-up was not available.

craniectomy, free-floating craniectomy, intracranial pressure, traumatic brain injury

PMC5012722_01

Female

A 33-year-old woman came to Department of Fertility, Endocrinology and Reproduction at Saiful Anwar public Hospital and consulted that she has not menstruated since 5 years ago (28 years old). Her initial menarche was at the age of 14 years and it is in accordance with the normal growth of a child at her age. The patient had a regular menstrual period of 5-7 days, she replaced the pads for 2-3 times / day, and had no menstrual pain. The patient has a history of injective contraceptive that was done every once a month in 2010, and after the injection, she menstruated for two months and then it stopped. Based on clinical examination and a physical examination, the patient was diagnosed with secondary amenorrhea. Investigations that were used are ultrasonography, thorax X-ray and CT Scan Head. Ultrasonography and thorax X-Ray showed that patient is suspected to have right pleural effusion. CT-Scan examination showed that bilateral ethmoidal sinusitis and pituitary gland was within normal limits. The treatment plan in this patient is P test therapy with Prothyra 1x10 mg for 7 days, with control on 2 weeks after the use. P test showed a negative result, because after 14 days of progesterone consumption the prothyra is not bleeding. The treatment is followed by a E+P test (Estrogen+Progesterone) with Estrogen 1x0.625 mg for 21 days and an addition of Progesterone 1x10 mg on 12th-21st days, while the control was performed one week after the drug runs out. Based on the E+P test, the obtained results were FSH: 8.71 MIU/mL, LH: 3.1 IU/L, Prolactin: 319.4 ng/mL. The E+P test showed a negative result, so it was necessary to do hysteroscopy and curettage for the uterus evaluation. Hysteroscopy results showed that there were grade 4 adhesions in the uterine cavum, with a pale colored connective tissue in the uterine cavum, which refers to the diagnosis of secondary amenorrhea suspect tuberculosis endometritis, while the result of tissue curettage was examined on the Anatomical Pathology department. Results of anatomical pathology hysteroscopy showed endometrial tissue with stromal looks granulomas with lymphocytes, histiocytes, epithelioid and Langhans multinucleated giant cells and no malignancy was found in this preparation, which showed that patient's diagnosis is secondary amenorrhea suspected tuberculosis endometritis (Figure 1). Based on the Anatomical Pathology hysteroscopy result, treatment was done by using anti-tuberculosis drug category I (FDC 1X3 tab) for 6 months. Anatomical pathology result through macroscopic observation showed visible network of approximately 0.3 cm and 0.4 cm in diameter with a grayish-white color, while the microscopic observations showed fibromuscular tissue at high cylindrical epithelium with polyps shaped vacuolar, and inflammatory granulomatic and aplastic cells were not found (Figure 2).

tuberculosis, anti-tuberculosis drug, secondary amenorrhea

PMC4793953_01

Male

A white, sixty-six-year-old man born and residing in Miracema,Rio de Janeiro, was admitted in August 2014 for having had cough for three months, weight loss of six kg in a month, and febrile episodes over the 10 previous days. The patient underwent renal transplantation in January 2013 and he was using prednisone, 5 mg/day; mesalazine, 1,080 mg/day; and tacrolimus, 8 mg/day. He had systemic arterial hypertension, diabetes mellitus and gout, controlled with oral medications. He used to visit a farm and perform soil management frequently. Physical examination showed good general conditions, there was no palpable lymphadenopathy; dermatological examination revealed shallow ulcerated lesions on the palate surrounded by erythema, measuring about 8 mm; multiple mulberry-like erythematous eroded papules giving to the lesion a cobblestone appearance (Aguiar-Pupo stomatitis); erythematous papule with a central umbilication of about 3 mm located at the left nasal wing (Fig. 1); and an infiltrated erythematous plaque with irregular borders and indistinct boundaries, of approximately 1 cm in diameter, located on the left flank (Fig. 2). Chest x-rays showed bilateral nodular infiltrate, so it was started empirical treatment for tuberculosis and bacterial pneumonia. AFB bronchial lavage was negative however, the direct mycological examination found fungal structures compatible with paracoccidioidomycosis. Biopsies in the described mucocutaneous lesions were performed, including oral ulcers, which were consistent with this diagnosis (Fig. 3). All materials were subjected to culture and there was growth of P. brasiliensis. Itraconazole, 400 mg daily, was started, but after five days of treatment the patient had clinical worsening and liposomal amphotericin B was introduced. The basal serum cortisol was normal and abdominal CT scan showed no specific changes; however, in lung CT (Fig. 4) an extensive involvement with bilateral nodular infiltrates, an excavated area suggestive of necrosis in the middle third of the right lung, and bilateral pleural effusion, largest in the right lung, were seen. Despite the prescribed therapies, the patient died.

PMC6454994_01

Male

The 56-year old Chinese patient underwent radical resection and was diagnosed with renal clear cell carcinoma (stage II) in 2015. Diagnosis of the disease was based on magnetic resonance (MR) imaging and pathological findings of kidney cancer (6x4 cm, no lymphovascular invasion, sarcomatoid features, or necrosis), and there was no significant increase in tumor markers. After surgery, IL-2 and IFN-alpha-2b were administered for 2 months each. Lung metastasis was confirmed in April 2016 (Figure 1), and a tyrosine kinase inhibitor (Sunitinib) was administered for 3 months. The drug was discontinued after progression of lung metastasis was found. After cryosurgery for lung metastasis, an immune checkpoint inhibitor (nivolumab) was used for 2 months. Gross hematuria occurred in January 2017. Ultrasonography revealed space-occupying lesions in the bladder, and transurethral cystectomy was performed under general anesthesia. Postoperative pathology showed metastatic clear cell carcinoma. Later, imaging revealed metastases to the right pleura, right kidney, liver, left ribs, and right tonsil. The patient showed systemic fatigue, back and lower limb pain, difficulty walking, recurrent daily fever (around 38.5 C), poor appetite, and emaciation. Peripheral blood erythrocyte count dropped below 3x1012/L and hemoglobin below 100 g/L; the Karnofsky score was 30. After hospital admission, the patient received parenteral nutrition, blood transfusion, analgesics, and other symptomatic treatments. MBV treatment was started on April 12, 2017, after consultation with the patient and his family. This case report was approved by the ethics committee of Fuda Cancer Hospital, Jinan University and was in accordance with the Declaration of Helsinki; the patient's written informed consent including the images for publication was received for this study. The MBV includes 6 kinds of heat-inactivated bacteria, namely 1) Pertussis bacillus (concentration 9 billion/mL), 2) Diphtheria bacillus endotoxin (concentration 20 Lf/mL), 3) Tetanus bacillus endotoxin (concentration 5 Lf/mL), 4) Typhoid bacillus (concentration of 300 million/mL), 5) Bacillus paratyphoid A/B (concentration 150 million/mL each), and 6) 10% Staphylococcus aureus solution (concentration 1 billion/mL). Strains were purchased from National Institutes for Food and Drug Control. Zhejiang Weixin Biological Pharmaceutical Co., Ltd., was entrusted with technical service and culture of bacterial media. Additional additive included 0.1% Poly I:C (tlrl-pic; InvivoGen, San Diego, CA, USA) and 30% fat emulsion for injection, blended in a certain proportion. The most common adverse reactions recorded included local (injection site swelling and blisters) and systemic (chills, fatigue, and fever) reactions. Liver function was evaluated based on the levels of alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (T.BIL), and gamma-glutamyl transpeptidase (GGT) multiple times during MBV treatment. Bone marrow hematopoietic function was evaluated based on the levels of peripheral blood erythrocytes and hemoglobin. Peripheral blood (2 mL) was collected before and multiple times during MBV treatment for the detection of immune function. Flow cytometry (Facscanto II; BD, Franklin Lakes, NJ, USA) was used for analysis. The analyzed indexes included the number and function of lymphocytes in the peripheral blood. The BD Multitest 6-color TBNK reagent (no 644611; BD) was used to detect the number of CD3+CD4+ cells (95% range: 441-2,156 cells/mL), CD3+CD8+ cells (95% range: 125-1,312 cells/mL), total CD3+ cells (95% range: 603-2,990 cells/mL), and CD3-CD16+CD56+ cells (95% range: 95-640 cells/mL). The BD Cytometric Bead Array (CBA) Human Th1/Th2 Cytokine Kit II (no 551809; BD) was used to detect the expression of IL-2 (95% range: 8-12.5 pg/mL), IL-4 (95% range: 3.5-6 pg/mL), IL-6 (95% range: 2.7-8.5 pg/mL), IL-10 (95% range: 1.8-4 pg/mL), TNF (95% range: 1.7-2.5 pg/mL), and IFN-gamma (95% range: 1.5-4 pg/mL). The tests were performed according to the protocols given in the instruction manuals. Results above or within the reference range were considered to indicate normal immune function. One or more values below the reference range was considered to indicate immune dysfunction. Since no tumor markers can be used to evaluate tumor activity, CTCs were measured as a biomarker for the identification of patients at high risk of relapse and to monitor immune responses to therapy. According to our previously published reports, CD45-CK+CD326+ cells were defined as CTCs. In normal conditions, the reference number of CTCs is 0-1 cells/7.5 mL blood. CTCs >5 indicate poor prognosis and high risk of recurrence or metastasis. CTCs <5 indicate low risk of recurrence or metastasis. The detection procedure included collection of 7.5 mL blood from the patient and isolation of mononuclear cells using human peripheral blood lymphocyte separation solution (Haoyang Biological Manufacture Co., Ltd., Tianjin, China). Isolated cells were enriched by binding to magnetic CD326 (Ep-CAM) MicroBeads (Miltenyi Biotec Ltd., Bergisch Gladbach, Germany) using magnetic-activated cell sorting. Enriched cells were labeled with monoclonal antibodies targeting CD45, CD326, and CK (Miltenyi Biotec Ltd.) and counted by flow cytometry. Changes in MR tumor imaging were monitored to evaluate the curative effect of MBV. According to the RECIST 1.1 guideline, therapeutic effect is categorized as a CR, disappearance of tumor detection of all target lesions; partial response (PR), total reduction in the diameter of the target lesions >=30%; stable disease (SD), tumor regression fails to reach PR or progressive disease (PD); or PD, total progression of the tumor diameter >=20%.

metastatic renal clear cell carcinoma, mixed bacterial vaccine

PMC7406913_01

Male

An 84-year-old gentleman presented with a 3-day history of fevers, non-productive cough, mild headache and delirium. His previous medical history included hypertension, hypercholesterolemia, atrial fibrillation and hearing impairment. He was living at home in a semi-rural area of New South Wales with his partner and was fully independent in his activities of daily living. He was an ex-smoker having ceased smoking in his thirties. He had worked as a plumber with minor asbestos exposure. On presentation, he was febrile to 39.6 and his pulse oximetry was 94% on room air with a respiratory rate of 18. Physical examination revealed inspiratory crackles in the left upper zone. He was cardiovascularly stable. Ten days prior to developing symptoms, the patient was working in his outdoor backyard garden shovelling approximately 500 kg of topsoil and home compost. The patient was also exposed to two 25 kg bags of commercial potting mix that were stored in his garden shed. In the process of preparing and working with soil and compost materials, the patient did not practice strict infection control measures, including wearing of masks, frequent handwashing and opening bags of commercial potting mix in well ventilated areas. The patient also had no recent sick contacts, no overseas travel, no contact with air-conditioning units or cooling towers and no exposure to birds. His white blood cell count was 14.6 x 109/L (neutrophil count 12.3 x 109/L, lymphocyte count 1.0 x 109/L) and his C-reactive protein level was 210 mg/L. He also suffered from acute on chronic kidney injury with a creatinine level of 131 micromol/L (Table 1). His liver function tests were unremarkable. A chest radiograph showed consolidation in the left upper lobe (Fig. 1). His initial diagnosis was lobar community-acquired pneumonia, and as per local antimicrobial guidelines he was empirically treated with intravenous benzylpenicillin and oral doxycycline. The patient tested positive for L. pneumophilia 1 antigen in his urine sample with urinary antigen enzyme immunoassay, and his antibiotic regimen was changed to dual therapy with azithromycin 500mg once daily and ciprofloxacin 500mg twice daily for 48 hours, followed by monotherapy with azithromycin 500mg once daily. Nasopharyngeal swabs for polymerase chain reaction (PCR) testing confirmed L. pneumophilia infection. Both acute and follow-up convalescent serologies were negative for L. pneumophilia and L. longbeachae. Sampling and analysis of suspected contaminated home soil was not feasible as this was a single isolated case and no home soil was available for sampling. The patient denied having any exposure to ponds, fountains and other sources of stagnant water at home. A notification was made to the local public health unit and because this was an isolated case, no further investigation or contact tracing was necessary as there were no other outbreaks of Legionnaires' disease at the time of presentation. Thorough review of the clinical presentation strongly suggests that there were no other sources that the patient could have acquired the infection except for his recent exposure to home soil and potting mix.

atypical pneumonia, community acquired pneumonia, legionella, legionnaires' disease

PMC5339407_01

Male

A 45-year-old non-smoker male patient presented to the emergency department of a territorial hospital complaining for hemoptysis. On the day of admission, he reported that he had expectorated approximately 50ml of bright red blood. He denied any other symptoms, including fever, cough, dyspnea or chest pain. On his medical history he reported a similar episode of hemoptysis 5 years ago the cause of which remained unknown despite clinical investigation which included computed tomography (CT) of the chest, immunologic examinations and fiberoptic bronchoscopy. The patient denied any other medical problem and was not receiving any medication. On physical examination, he was a pleasant apparently healthy man with body temperature 36,8 C, pulse rate 110 beats/min, blood pressure 130/80 mmHg, respiratory rate 21 breaths/min and oxygen saturation 95% on room air. Auscultation disclosed mild crackles in the right lower lobe. No other abnormal findings were found in the rest of the physical examination. In the laboratory tests, the patient's hemoglobin was 13.1g/dL, hematocrit: 40.7%, white blood cell count was 7410 cells/muL (77.6% neutrophils and 15.1% lymphocytes), and platelet count was 161 000/muL, D-Dimers: 436mug/L (normal values up to 500mug/L) while the values for urea nitrogen, creatinine and electrolytes were within the normal range. Immunologic tests revealed only slightly increased Antinuclear Antibodies (ANA) (1:160). Sputum Gram stain, cultures for common bacteria and examination for M Tuberculosis were negative. ECG was normal. The patient's chest x-ray on admission, revealed an area of consolidation in the middle lobe. Computed tomography of the chest revealed some bronchiectasis along with an area of consolidation in the middle lobe. The patient was admitted and received oxygen therapy, intravenous amoxycilline-clavulanic acid and intravenous tranexamic acid at a dose of 1 g four times daily. During the following days, the patient continued to experience streaks of blood in his sputum on a daily basis sometimes accompanied by dyspnea and tachypnea, and 2 days later, a new episode of massive hemoptysis occurred, and the patient was transmitted to our hospital for further evaluation and treatment. On admission to our hospital the patient underwent a CT angiography of the thoracic aorta and its branches (including bronchial arteries) which revealed some mild anatomical abnormalities in the bronchial arteries suppling the right lower lobe and ground glass opacities in the middle and right lower lobe, without showing a specific bleeding origin (Fig. 1). Although the examination was not sensitive enough, it also gave the impression of a thrombus in the left main artery. Thus, a CT pulmonary angiography was performed which revealed a large thrombus on the left main artery involving the pulmonary arteries for the left upper, the lingual, and the left lower lobe (Fig. 2). An ultrasonography was performed and the presence of a thrombus in the lower extremities and the pelvis was excluded. Echocardiography did not reveal any cardiac abnormalities. Although the leg and pelvis ultrasonography was negative, an inferior vena cava temporary filter (ALN Optional Vena Cava Filter, ALN, France) was placed via femoral approach since anticoangulant treatment was contraindicated. Tranexamic acid was discontinued. A few hours later the patient experienced a new episode of massive hemoptysis and became severely dyspneic. On clinical examination he was found to be tachypneic, tachycardic and hypotensive. Oxygen saturation had dropped to 78% on room air. An emergency angiography was performed with the aim of embolizing any potential sources of bleeding from the bronchial circulation. Selective angiography from the right bronchial artery revealed extravasation of contrast from three different branches of the middle lobe and embolization was performed using a micro-catheter (Progreat , Terumo, Japan) and N-butyl-2-cyanoacrylate (NBCA; Histoacryl ) diluted in a 1:3 ratio, with oily X-ray contrast agent Lipiodol . Final angiogram demonstrated complete occlusion of the target vessels without any sign of bleeding (Fig. 3). Following this procedure, the patient was stabilized and returned to the ward. Hemoptysis has been ceased. However, the patient became febrile and developed chest pain in the right hemithorax together with cough and expectoration of dark bloody sputum. Post-procedural chest CT revealed a consolidation of the right lower lobe suggestive of a pneumonia (Fig. 4). High-flow oxygen was administered to achieve target saturation of 94-98%. Blood cultures were collected (their result was available a few days later and they were negative) and antimicrobial therapy was changed to meropenem and linezolide. 3 days after bronchial embolization, the patient's symptoms improved and hemoptysis was completely settled down. The patient received treatment with subcutaneous fondaparinux (in a dose of 7.5mg administered subcutaneous once daily) and underwent monitoring of anti-Xa activity twice a week. The patient was discharged a few days later with the advice to continue treatment with fondaparinux and to return 3 months later for the removal of the inferior vena cava filter. By that time his symptoms had disappeared and he had remained free of hemoptysis. Follow up chest CT demonstrated complete resolution of the consolidation and no other signs of parenchyma disease.

computed tomography, embolization, fondaparinux, hemoptysis, pulmonary embolism

Chest CT revealing multiple foci of ground glass opacity in the middle and right lower lobe.

PMC5339407_01

Male

A 45-year-old non-smoker male patient presented to the emergency department of a territorial hospital complaining for hemoptysis. On the day of admission, he reported that he had expectorated approximately 50ml of bright red blood. He denied any other symptoms, including fever, cough, dyspnea or chest pain. On his medical history he reported a similar episode of hemoptysis 5 years ago the cause of which remained unknown despite clinical investigation which included computed tomography (CT) of the chest, immunologic examinations and fiberoptic bronchoscopy. The patient denied any other medical problem and was not receiving any medication. On physical examination, he was a pleasant apparently healthy man with body temperature 36,8 C, pulse rate 110 beats/min, blood pressure 130/80 mmHg, respiratory rate 21 breaths/min and oxygen saturation 95% on room air. Auscultation disclosed mild crackles in the right lower lobe. No other abnormal findings were found in the rest of the physical examination. In the laboratory tests, the patient's hemoglobin was 13.1g/dL, hematocrit: 40.7%, white blood cell count was 7410 cells/muL (77.6% neutrophils and 15.1% lymphocytes), and platelet count was 161 000/muL, D-Dimers: 436mug/L (normal values up to 500mug/L) while the values for urea nitrogen, creatinine and electrolytes were within the normal range. Immunologic tests revealed only slightly increased Antinuclear Antibodies (ANA) (1:160). Sputum Gram stain, cultures for common bacteria and examination for M Tuberculosis were negative. ECG was normal. The patient's chest x-ray on admission, revealed an area of consolidation in the middle lobe. Computed tomography of the chest revealed some bronchiectasis along with an area of consolidation in the middle lobe. The patient was admitted and received oxygen therapy, intravenous amoxycilline-clavulanic acid and intravenous tranexamic acid at a dose of 1 g four times daily. During the following days, the patient continued to experience streaks of blood in his sputum on a daily basis sometimes accompanied by dyspnea and tachypnea, and 2 days later, a new episode of massive hemoptysis occurred, and the patient was transmitted to our hospital for further evaluation and treatment. On admission to our hospital the patient underwent a CT angiography of the thoracic aorta and its branches (including bronchial arteries) which revealed some mild anatomical abnormalities in the bronchial arteries suppling the right lower lobe and ground glass opacities in the middle and right lower lobe, without showing a specific bleeding origin (Fig. 1). Although the examination was not sensitive enough, it also gave the impression of a thrombus in the left main artery. Thus, a CT pulmonary angiography was performed which revealed a large thrombus on the left main artery involving the pulmonary arteries for the left upper, the lingual, and the left lower lobe (Fig. 2). An ultrasonography was performed and the presence of a thrombus in the lower extremities and the pelvis was excluded. Echocardiography did not reveal any cardiac abnormalities. Although the leg and pelvis ultrasonography was negative, an inferior vena cava temporary filter (ALN Optional Vena Cava Filter, ALN, France) was placed via femoral approach since anticoangulant treatment was contraindicated. Tranexamic acid was discontinued. A few hours later the patient experienced a new episode of massive hemoptysis and became severely dyspneic. On clinical examination he was found to be tachypneic, tachycardic and hypotensive. Oxygen saturation had dropped to 78% on room air. An emergency angiography was performed with the aim of embolizing any potential sources of bleeding from the bronchial circulation. Selective angiography from the right bronchial artery revealed extravasation of contrast from three different branches of the middle lobe and embolization was performed using a micro-catheter (Progreat , Terumo, Japan) and N-butyl-2-cyanoacrylate (NBCA; Histoacryl ) diluted in a 1:3 ratio, with oily X-ray contrast agent Lipiodol . Final angiogram demonstrated complete occlusion of the target vessels without any sign of bleeding (Fig. 3). Following this procedure, the patient was stabilized and returned to the ward. Hemoptysis has been ceased. However, the patient became febrile and developed chest pain in the right hemithorax together with cough and expectoration of dark bloody sputum. Post-procedural chest CT revealed a consolidation of the right lower lobe suggestive of a pneumonia (Fig. 4). High-flow oxygen was administered to achieve target saturation of 94-98%. Blood cultures were collected (their result was available a few days later and they were negative) and antimicrobial therapy was changed to meropenem and linezolide. 3 days after bronchial embolization, the patient's symptoms improved and hemoptysis was completely settled down. The patient received treatment with subcutaneous fondaparinux (in a dose of 7.5mg administered subcutaneous once daily) and underwent monitoring of anti-Xa activity twice a week. The patient was discharged a few days later with the advice to continue treatment with fondaparinux and to return 3 months later for the removal of the inferior vena cava filter. By that time his symptoms had disappeared and he had remained free of hemoptysis. Follow up chest CT demonstrated complete resolution of the consolidation and no other signs of parenchyma disease.

computed tomography, embolization, fondaparinux, hemoptysis, pulmonary embolism

CT pulmonary artery angiography detected thrombus within segmental branches of the left pulmonary artery (circles).

PMC5339407_01

Male

A 45-year-old non-smoker male patient presented to the emergency department of a territorial hospital complaining for hemoptysis. On the day of admission, he reported that he had expectorated approximately 50ml of bright red blood. He denied any other symptoms, including fever, cough, dyspnea or chest pain. On his medical history he reported a similar episode of hemoptysis 5 years ago the cause of which remained unknown despite clinical investigation which included computed tomography (CT) of the chest, immunologic examinations and fiberoptic bronchoscopy. The patient denied any other medical problem and was not receiving any medication. On physical examination, he was a pleasant apparently healthy man with body temperature 36,8 C, pulse rate 110 beats/min, blood pressure 130/80 mmHg, respiratory rate 21 breaths/min and oxygen saturation 95% on room air. Auscultation disclosed mild crackles in the right lower lobe. No other abnormal findings were found in the rest of the physical examination. In the laboratory tests, the patient's hemoglobin was 13.1g/dL, hematocrit: 40.7%, white blood cell count was 7410 cells/muL (77.6% neutrophils and 15.1% lymphocytes), and platelet count was 161 000/muL, D-Dimers: 436mug/L (normal values up to 500mug/L) while the values for urea nitrogen, creatinine and electrolytes were within the normal range. Immunologic tests revealed only slightly increased Antinuclear Antibodies (ANA) (1:160). Sputum Gram stain, cultures for common bacteria and examination for M Tuberculosis were negative. ECG was normal. The patient's chest x-ray on admission, revealed an area of consolidation in the middle lobe. Computed tomography of the chest revealed some bronchiectasis along with an area of consolidation in the middle lobe. The patient was admitted and received oxygen therapy, intravenous amoxycilline-clavulanic acid and intravenous tranexamic acid at a dose of 1 g four times daily. During the following days, the patient continued to experience streaks of blood in his sputum on a daily basis sometimes accompanied by dyspnea and tachypnea, and 2 days later, a new episode of massive hemoptysis occurred, and the patient was transmitted to our hospital for further evaluation and treatment. On admission to our hospital the patient underwent a CT angiography of the thoracic aorta and its branches (including bronchial arteries) which revealed some mild anatomical abnormalities in the bronchial arteries suppling the right lower lobe and ground glass opacities in the middle and right lower lobe, without showing a specific bleeding origin (Fig. 1). Although the examination was not sensitive enough, it also gave the impression of a thrombus in the left main artery. Thus, a CT pulmonary angiography was performed which revealed a large thrombus on the left main artery involving the pulmonary arteries for the left upper, the lingual, and the left lower lobe (Fig. 2). An ultrasonography was performed and the presence of a thrombus in the lower extremities and the pelvis was excluded. Echocardiography did not reveal any cardiac abnormalities. Although the leg and pelvis ultrasonography was negative, an inferior vena cava temporary filter (ALN Optional Vena Cava Filter, ALN, France) was placed via femoral approach since anticoangulant treatment was contraindicated. Tranexamic acid was discontinued. A few hours later the patient experienced a new episode of massive hemoptysis and became severely dyspneic. On clinical examination he was found to be tachypneic, tachycardic and hypotensive. Oxygen saturation had dropped to 78% on room air. An emergency angiography was performed with the aim of embolizing any potential sources of bleeding from the bronchial circulation. Selective angiography from the right bronchial artery revealed extravasation of contrast from three different branches of the middle lobe and embolization was performed using a micro-catheter (Progreat , Terumo, Japan) and N-butyl-2-cyanoacrylate (NBCA; Histoacryl ) diluted in a 1:3 ratio, with oily X-ray contrast agent Lipiodol . Final angiogram demonstrated complete occlusion of the target vessels without any sign of bleeding (Fig. 3). Following this procedure, the patient was stabilized and returned to the ward. Hemoptysis has been ceased. However, the patient became febrile and developed chest pain in the right hemithorax together with cough and expectoration of dark bloody sputum. Post-procedural chest CT revealed a consolidation of the right lower lobe suggestive of a pneumonia (Fig. 4). High-flow oxygen was administered to achieve target saturation of 94-98%. Blood cultures were collected (their result was available a few days later and they were negative) and antimicrobial therapy was changed to meropenem and linezolide. 3 days after bronchial embolization, the patient's symptoms improved and hemoptysis was completely settled down. The patient received treatment with subcutaneous fondaparinux (in a dose of 7.5mg administered subcutaneous once daily) and underwent monitoring of anti-Xa activity twice a week. The patient was discharged a few days later with the advice to continue treatment with fondaparinux and to return 3 months later for the removal of the inferior vena cava filter. By that time his symptoms had disappeared and he had remained free of hemoptysis. Follow up chest CT demonstrated complete resolution of the consolidation and no other signs of parenchyma disease.

computed tomography, embolization, fondaparinux, hemoptysis, pulmonary embolism

Post-procedural chest CT demonstrating consolidation of the right lower lobe at the area of embolization. Note the embolic material (glue) within the consolidation (white arrows).

PMC3976875_01

Female

Two sisters of Malaysian-Chinese origin were diagnosed with CH during infancy. The proband, III-2, was detected to have CH by neonatal screening and the diagnosis was confirmed at 10 days after birth with serum TSH of 120.0 muIU/mL (Normal range: 0.3-5.0 muIU/mL) and free T4 of 5.0 pmol/L (Normal range: 20-68 pmol/L). Her elder sister, III-1, was also detected to have CH (but not by neonatal TSH screening as it was not available), at 3 weeks of life with serum TSH of 96.5 muIU/mL and free T4 of 2.0 pmol/L when she presented with prolonged jaundice. Both sisters received thyroid replacement with L-thyroxine. Technetium-99m thyroid scintigraphy was performed when they were 3 years old when L-thyroxine was temporarily stopped for 6 weeks and the thyroid function test was repeated. The thyroid scan revealed the presence of thyroid glands despite having a rise in TSH and low free T4. In their late teenage years, they developed goiter. Thyroid ultrasonography revealed that both of them had multinodular goiter (MNG). Both sisters had elevated levels of thyroglobulin as the goiters progressed. III-2's thyroglobulin (hTG) level measured when she was 20 years old was 193 ng/mL (reference range 0-55 ng/mL), whilst her elder sister's was much higher at 2288 ng/mL. The proband and her sister (III-1) subsequently underwent total thyroidectomy at the age of 20 years and 24.5 years, respectively. Histology of their thyroid glands revealed the presence of multiple macro- and microfollicular adenomata arising in a background of dyshormonogenetic goiter. The elder sister had a small ventricular septal defect, while the proband had no other congenital anomalies and both of them had normal growth and development. Their parents (II-1 and II-2) who are biologically unrelated were all healthy and euthyroid with no congenital anomalies. However, their maternal grandmother (I-4) was reported to have goiter and had subsequently undergone thyroidectomy with the histology results unknown. Written informed consent was obtained from the parents for their blood and their children's (III-1 and III-2) blood and thyroid tissues for TPO gene analysis. This study was approved by the University of Malaya Medical Centre (UMMC) Ethical Committee (Institutional Review Board) in accordance with the ICH-GCP guideline and the Declaration of Helsinki (Reference number, 654.16). Genomic DNA was extracted from peripheral venous blood from the proband, the affected sister, and their healthy family members using QIAamp DNA Blood Mini Kit (Qiagen, Germany) according to the manufacturer's protocol. The TPO gene was PCR-amplified with flanking intronic primers covering all the 17 exons. A PCR reaction mixture (50 muL) containing 100-250 ng was prepared in the presence of a final concentration of 1X Taq buffer with KCl, 2.5 mM of MgCl, 200 muM of dNTP, 8% dimethyl sulfoxide (DMSO), 1 unit of Taq DNA polymerase (Fermentas, USA), and 20 pmol of each forward and reverse primers. Thirty-five cycles of amplification were carried out with standard PCR protocol at annealing temperature of 55 C for all coding exons for 30 seconds. The PCR products were purified using QIAquick PCR purification kit (Qiagen, Germany) and then sequenced using ABI Prism Gene Sequencer, Model 3100, Version 3.7 (Research Biolabs, Singapore). The Human Splicing Finder (http://www.umd.be/HSF/) was used to analyze the existence of alternative splice sites in exon 13 of the TPO gene as a consequence of the c.2268dup mutation. The analysis was done on the whole of exon 13 (171 bp), 50 nucleotides upstream of exon 13 (3' end of intron 12), and 50 nucleotides downstream of exon 13 (5' end of intron 13). Following thyroidectomy, tissue samples were immediately kept frozen in dry ice and then stored at -80 C. A piece of the pathologically normal tissue was taken near the colloid nodules and the abnormal tissue was taken from the thyroid lesion. Tumors were diagnosed histopathologically and no evidence of malignancy was detected. Each piece of tissue sample of about 30 mg was homogenized and total cellular RNA (tcRNA) was then extracted from the normal and lesionic areas of the thyroid tissues using RNeasy Mini (Qiagen, Germany) according to the manufacturer's instruction. The extracted tcRNA was treated with DNase (Ambion, UK) and then reverse transcribed to complimentary DNA (cDNA) using the High Capacity RNA-to-cDNA Kit (Applied Biosystems, USA). The cDNA was then used as a template to PCR-amplify the coding exons (exons 2-17) using overlapping primers that cover the exon-exon junctions (see Supplementary Table 1 (S1) in the Supplementary Material available online at http://dx.doi.org/10.1155/2014/370538). PCR amplification and the subsequent PCR product purification and sequencing were performed as described earlier except that cDNA was used as a template instead of genomic DNA. Complementary DNA samples prepared from thyroid tissue taken from three individuals without the c.2268dup mutation were used as positive controls. Quantitative real time PCR (qRT-PCR) was used to analyze TPO gene expression in the normal and lesion areas of the thyroid tissues of the proband and her sister. Comparison of the TPO gene expression in thyroid tissues of the proband and her sister was also made. The expression of the TPO gene was normalized to that of a housekeeping gene, the TATA box-binding protein (TBP). In addition, the ratio of TPO mRNA variants in c.2268dup mutation-free individuals was also calculated and compared to the two sisters. Total TPO mRNA transcripts were analyzed using E4F and E5R primer pair covering a region from exons 4 to 5. Primer pairs spanning exons 12 to 13 (E12/13F and E13R) were designed to target normally spliced transcripts, (TPO1, TPO2, TPO3, TPO4, TPO5, TPO2/3, and TPO2/4). Meanwhile, the E12/I12F and E13R primer pair was used to target alternatively spliced-derived transcripts with an insertion of 34 bp between exon 12 and exon 13. TPO6 that does not contain exon 12 and exon 13 was amplified using E11 and E11/15 primers. All qRT-PCR oligonucleotide sequences are listed in Supplementary Table 2 (S2). The qRT-PCR experiments were performed on a StepOnePlus system (Perkin-Elmer/Applied Biosystems). The amplification reaction was carried out using 1X SYBR Green PCR Mastermix (Applied Biosystems, USA), containing 10 ng of cDNA and 200 nM of each primer. The sample was initially denatured at 95 C for 5 min followed by 40 cycles of denaturation at 95 C for 15 sec and subsequent annealing and elongation step at 59 C for 1 min. Melting curves were performed to check the specificity of the amplicons. Each experiment was carried out in triplicate. Comparison of total or target gene mRNA expression was done by calculating the differences in the threshold cycles. The fold change in expression between tissue samples was calculated by where DeltaDeltaCt = (Ct targeted TPO mRNA - Ct TBP) lesionic area - (Ct targeted TPO mRNA - Ct TBP) normal area. The fold change in expression between patients was calculated by where DeltaDeltaCt = (Ct targeted TPO mRNA - Ct TBP) proband - (Ct targeted TPO mRNA - Ct TBP) proband's sister. Total 10 ng of cDNA sample from normal and lesionic areas of thyroid tissue (5 ng template from each area) of each patient was used as the template. Meanwhile, the ratio of TPO mRNA variants to total TPO mRNA in each tissue types was determined by the following calculation. For normal area of thyroid tissue, For lesionic area of thyroid tissue, Microsomal protein was isolated from the frozen thyroid tissue specimens. Thirty milligram of tissue was homogenized in ice-cold phosphate buffered saline (PBS) containing Pierce Protease Inhibitors Cocktail (Thermo Scientific, USA) and subsequently centrifuged for 15 min at 3,000 xg at 4 C to remove nuclei and cytoskeletal components. The supernatant was then ultracentrifuged in the Optima L-100k (Beckman Coulter, USA) at 100,000 xg for 2 h at 4 C. The pellet was collected and then dissolved in lysis buffer (50 mM Tris-HCl, pH 7.3; 150 mM NaCl; 5 mM EDTA; 10% glycerol (w/v); 1% Triton X-100 (w/v), protease inhibitors). The mixture was ultrasonicated using Power Sonic 405 (Hwashin Technology, Korea) to improve the yield of the extracted protein. Immunodetection analysis was performed using mouse monoclonal MoAb47 primary antibody (Abcam, UK) and WesternDot 625 Western blot kits (Invitrogen, USA) to detect the presence of TPO protein in the tissue specimens from both patients. Twenty mug of microsomal fraction extract for each sample and 300 ng of a positive control (recombinant fragment of human thyroid peroxidase from Abcam, product code: ab73765, UK) were used in this analysis. The expression of TPO in normal and lesion areas of thyroid tissue from both patients were quantitated by densitometry scanning using Image-J software (http://rsbweb.nih.gov/ij/). The expression of TPO in normal and lesionic areas of the thyroid tissues was normalized to the expression of beta actin. The total expression of TPO protein in the proband was also compared to that of her sister. Microsomal fraction extracts prepared from patients' thyroid gland tissues were immediately used for enzymatic assay. Microsomes prepared from thyroid tissues from rats were extracted using the same method and were then used as a positive control. Twenty mug of each microsomal fraction were added to 1 mL of reaction mixture containing 40 mM guaiacol (Sigma-Aldrich, USA) and 67 mM sodium phosphate buffer, pH 7.5. The enzymatic reaction was initiated by adding final concentration of 0.25 mM H2O2. The absorbance was measured at 470 nm (OD470) at every second for 3 min at room temperature.

PMC10006502_01

Male

A 74-year-old man visited our hospital with dyspnea and a low-grade fever that had persisted for two weeks. He had no medical history of tuberculosis or use of anti-tuberculosis drugs. Chest radiography revealed a right pleural effusion (Fig. 1), and thoracentesis was performed. The pleural fluid was yellow, and laboratory findings were as follows: total cell count, >100 cells per high power field; lymphocytes, 79.2%; lactate dehydrogenase, 500 U/L; total protein, 4.9 g/dL; adenosine deaminase, 92.9 U/L. Furthermore, the interferon-gamma release assay results were positive. Thus, the patient was diagnosed with tuberculous pleurisy, and treatment with RFP (450 mg/day), isoniazid (INH, 300 mg/day), ethambutol (EB, 500 mg/day), and pyrazinamide (PZA, 1.2 g/day) was initiated. Seven days after treatment initiation, the patient visited our hospital because of oral bleeding. Physical examination revealed mild oral bleeding and multiple purpuric lesions in his legs. The platelet count had decreased from 217 x 103/muL at baseline to 1 x 103/muL. Other laboratory findings were as follows: white blood cell count, 5300 cells/muL; hemoglobin, 11.4 g/dL; prothrombin time, 10.9 s; fibrinogen, 513 mg/dL; D-dimer, 10.7 mug/mL; C-reactive protein, 3.51 mg/dL; and platelet-associated immunoglobulin G (PAIgG), 286 ng/107 cells (normal value, less than 46 ng/107 cells). Liver and renal functions were normal. Markers for hepatitis B and C virus and cytomegalovirus were negative. Thrombocytopenia due to the effect of anti-tuberculosis drugs was suspected, and the four drugs were discontinued. Although platelet transfusion of 20 units was done on days one and two after treatment discontinuation, platelet count increased only up to 16 x 103/muL (Fig. 2). Since the bleeding subsided after the platelet transfusion and the platelet count gradually improved, we followed up until the side effects disappeared. The results of the drug-induced lymphocyte stimulation test were negative for the four drugs. On day 12 after discontinuation, levofloxacin was introduced, and EB, PZA, and INH (in this order) were reintroduced gradually. Since thrombocytopenia did not occur after restarting these drugs, he was diagnosed with rifampicin-induced thrombocytopenia. The patient was able to continue treatment since then, and the right pleural effusion disappeared.

rifampicin, thrombocytopenia, tuberculosis

PMC8696818_01

Male

A 20-year-old man presented to the emergency department after sustaining a major laceration to his right forefoot when he jumped off a boat into a saltwater river and cut his foot on the boat's spinning propeller. He had no relevant medical history. His surgical history was notable for open reduction and internal fixation of his right lateral malleolus during adolescence. On initial presentation, he was in severe pain. He had a 15- to 20-cm laceration extending from the base of the fifth metatarsal across the dorsum of the foot to the great toe with exposed subcutaneous tissue and apparent tendon lacerations (Figure 1). He had no dorsal sensation to light touch distal to the laceration and decreased strength in the flexor hallucis longus and tibialis anterior, with no appreciable function of the dorsal foot extensors. His dorsalis pedis and posterior tibial pulses were palpable but weak, his capillary refill was less than 3 seconds, and his toes were warm and well perfused. Radiographs of the right foot showed fractures at the head of the first metatarsal, the great toe proximal phalanx, and the distal diaphysis of the second, third, and fourth metatarsals. There was also subluxation of the fourth and fifth tarsometatarsal joints with the distal cuboid visualized in the wound. There was also a corticated fragment proximal to the base of the fifth metatarsal (Figure 2a-c). Immediately on arrival to the emergency department, the patient was given intravenous cefazolin (2 g), gentamicin (300 mg; 4 mg/kg/dose), and doxycycline (100 mg), as well as a tetanus booster. His wounds were irrigated with 2 L of normal saline mixed with betadine and covered with betadine-soaked gauze. A temporary posterior slab splint was applied. He was then taken promptly to the operating room, where the wound was carefully debrided and thoroughly irrigated with 12 L of antibiotic solution (consisting of 40 mg of neomycin and 200,000 units of polymyxin B) using cystoscopy tubing. Attention was then turned to reduction of the open fractures. Starting with the great toe, the proximal phalanx was reduced with a point-to-point reduction clamp. Two Kirschner wires (K-wires) were used to hold the reduction. For the second metatarsal, a K-wire was first placed antegrade out of the metatarsal at the open fracture site and then sent retrograde into the proximal portion of the second metatarsal after reduction was performed. The same procedure was used to achieve and maintain reduction of the third metatarsal. The fourth toe was found to be subluxated at the fourth metatarsophalangeal joint. As described above, a K-wire was first sent antegrade from the base of the proximal phalanx to the tip of the toe, reduction was performed, and the K-wire was then passed retrograde into the fourth metatarsal base to stabilize the reduction. This K-wire in the fourth metatarsal base stabilized the patient's fourth tarsometatarsal joint dislocation by sending it retrograde into the cuboid with the cuboid-metatarsal articulation held reduced. Further stabilization of the cuboid-fifth metatarsal was achieved with a K-wire that was passed retrograde from the lateral aspect of the fifth metatarsal base into the cuboid. The patient's great toe metatarsophalangeal joint was also grossly unstable, and a K-wire was passed antegrade from the proximal phalanx out of the medial cortex and then retrograde into the first metatarsal. Intraoperatively, it was noted that there was significant bone loss from the first metatarsal head. Intraoperative fluoroscopy was used to confirm adequate positioning for all of the reductions described above (Figure 3a-c). After open reduction and pinning of the fractures, the patient's second, third, fourth, and fifth extensor digitorum longus and extensor digitorum brevis tendons were repaired with 4-0 Prolene sutures (Ethicon, Somerville, NJ). A Bunnell-type suture augmented with a running epitendinous suture was used, and the ankle was held in dorsiflexion while the extensor tendons were repaired. Intraoperatively, the patient was given prophylactic cefazolin, gentamicin, and doxycycline. The wound was first grossly reapproximated with 2-0 Nylon vertical mattress sutures to relieve tension. The edges were then slowly reapproximated, first with 2-0 Monocryl and then with 3-0 Nylon sutures. The wound was completely closed at the conclusion of the case, and no skin tension was noted. After wound closure, the patient was given a right ankle block for postoperative pain control. His wound was then dressed with Xeroform petrolatum wound dressing (DeRoyal Industries, Powell, TN), 4-in gauze pads, and sterile soft-roll gauze. A posterior slab splint with a stirrup was then applied with the ankle held in neutral dorsiflexion. The patient recovered well after surgery and continued treatment with cefazolin and gentamicin for 24 hours for his open fractures and doxycycline for 96 hours for Vibrio prophylaxis. On postoperative day 1, he reported substantial pain that was not alleviated by multiple breakthrough doses of intravenous hydromorphone hydrochloride. A popliteal nerve catheter was placed by the anesthesia team. The popliteal nerve catheter, in combination with oral hydromorphone hydrochloride, provided symptom relief, and his pain was well controlled by postoperative day 4. He was discharged on postoperative day 4 with the popliteal nerve catheter in place and was advised to remain nonweightbearing for 6 to 8 weeks. The popliteal nerve catheter was discontinued on postoperative day 7, at which time the patient's pain level had decreased considerably. At his 2-week postoperative visit, darkened eschar was visible over the great toe wound, although no sign of infection was noted. He was insensate to the dorsal foot distal to the laceration at that time. His splint was changed to a cast at that time, and he was advised to remain nonweightbearing. He was followed in clinic every 2 weeks, and at 8 weeks after the initial procedure, he returned to the operating room for removal of the pins and debridement of the great toe eschar. He was again placed in a posterior slab splint with a stirrup and advised to remain nonweightbearing for an additional 2 weeks, which was determined in consultation with the plastic surgery service for optimal healing of the great toe wound. He recovered without complication. Two weeks after pin removal (10 weeks after the initial procedure), his splint was changed to a boot and he began bearing weight. He also began physical therapy twice weekly for 8 weeks. Physical therapy sessions included an evaluation of ankle range of motion/sensation/strength, manual therapy (massage), electrical stimulation, gait training, and stretching/strengthening exercises. Active plantarflexion of the toes was encouraged, as well as active dorsiflexion, actively assisted dorsiflexion, and passive dorsiflexion. Passive plantarflexion was permitted at 3 months after surgery. His great toe wound ultimately healed with local wound care. Three months after the initial procedure, he was transitioned from a boot to a postoperative shoe. At the 5-month postoperative visit, his wounds were healed (Figure 4) and he had good strength with ankle dorsiflexion and plantarflexion, although he had limited range of motion and weakness of his toes in dorsiflexion (extensor hallucis longus/extensor digitorum longus strength of 2/5, with a score of 5 indicating maximum strength). He continued to remain insensate to the dorsal foot distal to the laceration. Radiographs at the 9-month postoperative visit showed progression of healing of the fractures (Figure 5a-c). At this visit, he was cleared to return to his regular activities, including competitive weightlifting. At his 1-year postoperative visit, he reported continued stiffness and pain in his great toe. Although the pain did not prohibit him from participating in his regular activities, he had extremely limited active and passive range of motion at the first metatarsophalangeal joint. Otherwise, he had full strength in ankle dorsiflexion and plantarflexion, and the sensation of his dorsal foot distal to the laceration had returned. His toe extensors had 20 degrees less extension than those of the contralateral side, but he reported no functional deficits in his activities of daily living. Radiographs showed complete healing of the metatarsal shaft fractures with arthritis of the first metatarsophalangeal joint (Figure 6a-c). Given his persistent pain and stiffness, he was interested in potential surgical treatment. On the basis of imaging findings and his limited range of motion, a metatarsophalangeal joint arthrodesis was presented to him as an excellent option for pain relief. He plans to undergo surgery in the near future.

amputation, forefoot, high-energy injury, motorboat propeller

PMC7536454_02

Female

Her parents were healthy first-cousin adults with O+ blood-group. The father had a neonatal history of jaundice and blood-exchange-transfusion. Her sibling was a normal 4-year-old female, who also had a history of neonatal jaundice that recovered with home phototherapy. The parents denied having any liver/hemolytic or other disorders in the family. She was discharged after 36-hr in a good condition without icterus from the nursery. She was first icteric on the 4th day with total (T) bilirubin (Bil): 18 mg/dL and direct (D) Bil: 0.6 mg/dL. The parents chose home phototherapy although they were advised for hospital admission. They rechecked bilirubin on the 7th day of life because they felt the jaundice was getting worse. The mother mentioned some poor feeding in her baby. She was hospitalized with TBil: 34 mg/dL and DBil: 2.7 mg/dL, so intensive phototherapy, sepsis tests, and antibiotic therapy were performed. She was prepared for exchange transfusion. The infant responded very well to intensive phototherapy; therefore, the exchange transfusion was withheld. The mother was satisfied with her breastfeeding soon after. Six-hours of intensive phototherapy resulted in TBil: 22 mg/dL and DBil: 1.2 mg/dL. The baby had bronze skin and dark urine, but her stool had a greenish color. In laboratory tests, white blood cells (WBC) were 12,700, hemoglobin (Hb): 16.9 mg/dL, platelet (Plt): 223,000, glucose (Glu): 122 mg/dl, erythrocyte sedimentation rate (ESR): 1 mm/h, C-reactive protein (CRP): 5.3 mg/L, sodium (Na): 147 mmol/L, potassium (K): 5.5 mmol/L, creatinine (Cr): 0.4 mg/dl, reticulocytes (retic): 0.3%, blood group and Rh: O+, glucose-6-phosphate dehydrogenase (G6PD): normal. Urinalysis first showed blood (+1), protein (2+), and bilirubin (2+). The second urine sample was normal. Blood/urine cultures were negative, alanine aminotransferase (ALT) as 91 IU/L, aspartate aminotransferase (AST): 100 IU/L, and thyroid-stimulating hormone (TSH): 1.8 mIU/L. Abdominal ultrasonography was normal, showing normal sized liver/spleen. Cardiac consultation and echocardiography showed normal results. The infant's yellowish and bronze-skin color improved significantly, with normalization of urine color. Stool color was still normal. T/Dbilirubin and hemoglobin levels gradually decreased. She was discharged after 7 days of antibiotic-therapy and advised to be followed as an outpatient with ALT: 61 IU/L, AST: 69 IU/L, gamma-glutamyl transpeptidase (GGT): 25 IU/L, TBil: 9.2 mg/dl, DBil: 1.2 md/dl, Hb: 10.3 mg/dL. The baby still looked icteric and mildly bronzed a week later; she had an acceptable weight gain while on breastfeeding with normal urine/stool color, and neither hepatosplenomegaly nor abdominal distension. At the second outpatient visit, laboratory values were TBil: 5.2 mg/dl and DBil: 2.4 mg/dl, Hb: 9.7 mg/dL, WBC: 7600/mm3, Glu: 169 mg/dl, retic: 0.4%, ALT: 61IU/L, AST: 69 IU/L, and she was still icteric and producing greasy stool. Metabolic screen tests were ordered. A week later, abdominal distension with dark urine and acholic stool developed. She was readmitted. Her feeding was good and she was lively. Hepatosplenomegaly could not be detected because of severe ascites, but abdominal ultrasonography revealed enlarged liver/spleen with a large amount of fluid in the abdominal cavity. Blood tests revealed the following: WBC: 6500/mm3, Plt: 266,000/mm3, Hb: 8.7 mg/dL, mean corpuscular volume (MCV): 110 fl, and retic: 16.7%. A blood-smear showed a large amount of acanthocytes (spur cells). Glu: 169 mg/dl, TBil: 6.3 mg/dl, DBil: 4 mg/dl, ALT: 84 IU/L, AST: 304 IU/L, albumin (Alb): 2.8 mg/dl, ESR: 6 mm/hr, CRP: 5 mg/L, prothrombin time (PT): 21 sec, partial thromboplastin time (PTT): 65 sec, Na: 134 mmol/L, K: 5 mmol/L, ferritin: 2827 ng/ml. Ascitic fluid had Glu: 95 mg/dl, protein: 0.8 mg/dl, WBC: 0-1 mm3, and RBC: 3200 mm3 and a negative culture. Urinalysis showed 12-15 leukocytes unit. Broad-spectrum antibiotics, vitamin K, packed-cell, and albumin were administrated. In this hospital admission, the mother informed us that three of the paternal second cousins had icterus and abdominal distension requiring exchange-transfusion and one with kernicterus; one of which is still alive. She added no more information. As the patients' records were reviewed, we noticed that their living relative had known galactosemia. The infant's soy-based formula was substituted thereafter. All fluid cultures were negative except for urine culture which revealed Klebsiella (25,000 colony count). The infant's condition, icterus, and abdominal distention gradually improved. Urine sugar chromatography then also showed a dense galactose band. All tests significantly improved after the lactose-free formula substitution. The baby did well and had normal growth and feeding without icterus in subsequent follow-up visits. Galactose-1-phosphate-urydiltransferase deficiency (<5%) also confirmed the diagnosis. An ophthalmic examination was also normal. Written informed consent was obtained from the patient's family.

cholestasis, galactosemia, indirect hyperbilirubinemia, neonatal jaundice

PMC1310521_01

Male

A 46 year-old man with HIV/AIDS (CD4 T-cell 115 x 106/l) presented with two weeks of left 5th digit pain and swelling. He denied any history of recent trauma to the hand, fever, weight loss, or other systemic symptoms, but did note an occasional dry cough. He had traveled repeatedly between his native country Ivory Coast, West Africa and the United States. He was not taking antiretroviral medications at the time of presentation. On physical exam his fifth digit was swollen and erythematous at the proximal intraphalangeal joint [figure 1]. His laboratory values on admission were as follows: white blood cell count 5000 cells/mm3, hemoglobin 11.6 grams/dl, hematocrit 33.9%, platelets 280,000 platelets/mm3, eosinophils 9.0%, and erythrocyte sedimentation rate (ESR) of 60 mm/hour. Left hand radiography was significant for soft tissue swelling over the left finger with joint space narrowing and cortical lucencies with cystic degenerative changes in the proximal phalanx [figure 2]. Admission chest radiography demonstrated right hilar lymph node enlargement with multiple scattered nodules and a resolving right lower lobe infiltrate. Computed tomography scan of the chest revealed multiple pulmonary nodules [figure 3], necrotic lymph nodes, and splenomegaly. The patient underwent incision, drainage, and biopsy of the affected finger. Operative findings were significant for purulent, mottled, soft, yellow bone. Rare acid-fast bacilli were demonstrated on biopsy of the both phalanx and synovial fluid samples [figure 4]. We used the Gen-PROBE Amplified Mycobacterium tuberculosis Direct Test which employs a transcription-mediated amplification and hybridization protection assay to qualitatively detect Mycobacterium tuberculosis complex ribosomal RNA (rRNA). Several weeks later cultures of all surgical material grew Mycobacterium tuberculosis [figure 5]. Multiple Ziehl-Neelsen stains of induced sputum samples were negative for acid-fast bacilli, but all specimens sent for sputum culture grew Mycobacterium tuberculosis. Antituberculous treatment was initiated with rifampin, isoniazid, pyrizinamide, and ethambutol prior to culture results. After 12 weeks of treatment, marked improvement in the finger lesion was noted [figure 6].

Computed Tomography Scan of the chest showed mediastinal lymphadenopathy and multiple bilateral pulmonary nodules.

PMC3420776_01

Male

A 54-year-old Japanese man who had been diagnosed with RA for 8 years according to the 1987 American Rheumatism Association classification criteria for RA was admitted with polyarthritis. He complained of pain and swelling in the wrists, fingers, and knees and had difficulty walking without assistance. He claimed to have morning stiffness lasting about 3 hours. Past medical history included a left total knee arthroplasty complicated by a traumatic fracture of the left distal femur postoperatively and a cerebral infarction with residual right hemiparesis. His medication regimen included sulfasalazine (1000 mg/day), bucillamine (300 mg/day), mizoribine (150 mg/day), and prednisolone (10 mg/day). The Steinbrocker stage was IV and functional class was 4. He was unable to stand unassisted due to bilateral knee pain. Swelling and tenderness were present in the proximal interphalangeal and metacarpophalangeal joints of both hands and fingers, as well as in the wrists and knees. Right-sided muscle weakness was observed. Laboratory findings were as follows: white blood cell count 8800/mm3 (75.6% neutrophils, 19.5% lymphocytes, 2.9% monocytes, 0.3% eosinophils, 0.2% basophils), hemoglobin 10.7 mg/dL, platelets 48.7 x 104/muL, erythrocyte sedimentation rate (ESR) 75 mm/h, C-reactive protein (CRP) 3.58 mg/dL, rheumatoid factor (RF) 219.6 IU/mL, and anticyclic citrullinated peptide antibody (ACPA) 189 IU/mL. Serum beta-D-glucan was negative. The purified protein derivative skin test for tuberculosis was negative. Treatment was initiated with subcutaneous injections of etanercept 25 mg twice a week. Blood samples were collected before the first dose (at baseline), 24 hours after the first injection (day 1), daily until day 8, and weekly thereafter. Specimens were centrifuged at 3000 rpm and the sera stored at -80 C until the assay was performed. TNF-alpha, TNFR-I and -II, IL-6, and IL-1 beta concentrations were measured using commercial ELISA kits. After initiating etanercept, the patient's clinical condition improved markedly, with swelling and tenderness of the wrists and finger joints significantly better. He was able to stand with the aid of crutches despite residual hemiparesis. The duration of morning stiffness dropped to below 30 minutes. The 28-joint count Disease Activity Score (DAS28) dropped significantly within the first 4 weeks and continued to decrease (DAS28 = 8.09, 5.37, 4.73, and 4.60, at baseline, 4 weeks, 8 weeks, and 12 weeks, resp.), achieving the European League Against Rheumatism (EULAR) moderate response criteria. The CRP dropped to below 0.30 mg/mL within the first 2 weeks of therapy. Subsequently, the oral immunosuppressive regimen of sulfasalazine, bucillamine, and mizoribine was discontinued after initiation of treatment. Prednisolone was reduced to 5 mg/day. After 12 weeks of treatment with etanercept, the patient developed a nonproductive cough along with a fever of 38 C. Serum beta-D-glucan was found to be positive, and sputum polymerase chain reaction (PCR) was positive for pneumocystis (Figure 1). Etanercept was discontinued, and an antifungal regimen initiated. Preceding etanercept therapy, the serum IL-6 levels were found to be elevated, correlating with the high CRP value and high clinical disease activity. Conversely, the serum level of TNF-alpha was nondetectable (<0.2 pg/mL); the sTNFR-I, -II, and IL-1 beta values were not found to be significantly elevated (Figure 2). After initiation of etanercept, there was a rapid decline in the IL-6 and CRP levels, whereas the levels of TNF-alpha and sTNFR-II increased significantly within 24 hours after administration of the first dose to a plateau after 2 weeks (range: 100 pg/mL to 170 pg/mL) and 6-7 weeks (range: 300 ng/mL to 700 ng/mL), respectively. The sTNFR-I and IL-1-beta levels remained relatively unchanged (sTNFR-I levels at baseline, 3.56 ng/mL; 4 weeks, 3.36 ng/mL; 8 weeks, 2.93 ng/mL; 12 weeks, 3.58 ng/mL). At week 12, concurrent to the patient developing clinical symptoms of PCP, the levels of IL-6, CRP, and TNF-alpha showed an acute peak, which tapered downward over the following 3 weeks with the institution of an appropriate antifungal regimen (Figures 3 and 4).

PMC5403801_01

Female

A 60-year-old female came to our hospital with complaints of dysphagia for 4 months (primarily for solids), with loss of weight and appetite. No history of cough with expectoration. No history of fever. Patient was apparently normal prior to these 4 months. Blood investigations revealed leucocytosis with lymphocytosis, with an elevated Erythrocyte Sedimentation Rate. Patient tested negative for Human immunodeficiency virus (HIV). Patient underwent Upper Gastrointestinal Endoscopy by an experienced gastroenterologist which revealed a hemi circumferential ulcerative growth from 30 cm to 34 cm in the distal esophagus from which biopsy was taken (Fig. 1). Contrast enhanced computed tomography of the thorax showed circumferential thickening involving the distal esophagus, no evidence of invasion of adjacent structures seen, enlarged aortopulmonary lymph node with necrosis (Fig. 2). Histopathology revealed ill defined epithelioid granulomas with giant cells and caseating necrosis, no evidence of malignancy, no acid-fast bacilli seen. Tuberculosis-polymerase chain reaction (TB-PCR) was positive. Patient was started on ATT and was asked to review after 2 months of intensive phase of ATT with isoniazid, rifampicin, pyrazinamide, and ethambutol. On follow up patient had symptomatically improved and repeat UGI scopy showed complete resolution of the lesion (Fig. 1). Patient was advised to continue ATT as per the protocol. Patient was completely relieved of the symptoms after 6 months of treatment.

anti-tuberculous treatment (att), dysphagia, esophageal tuberculosis, tb-pcr, upper gastrointestinal endoscopy

PMC8536460_01

Female

A 77-year-old Asian woman presented with a right occipitotemporal headache for 1 week (day 1) but reported no other aural or nasal symptoms. Her medical history included diabetes mellitus, hypertension, rectal cancer, colon cancer, liver cirrhosis, and hepatocellular carcinoma. On physical examination, the right nasopharyngoscopic view revealed an ulcerative mass covered with a thick yellowish discharge that could not be easily removed by suction in the roof and posterior walls of the nasopharynx. However, both otoscopy of the right ear and laryngoscopy showed no abnormalities. No other abnormalities, such as cervical lymphadenopathy, were observed in other head and neck areas. Both the acid-fast Bacillus culture test and polymerase chain reaction test of the sputum and nasopharyngeal smear were negative, but the T-SPOT.TB test was positive (both panels A and B > 50 spots). Cervical computed tomography (CT) revealed neither a mass shadow in the nasopharynx nor cervical lymphadenopathy (Figure 1(a)). No evidence of bony destruction or intracranial extension was observed (Figure 1(b)). Furthermore, chest and abdominal CT revealed no abnormalities. Histopathological examination showed caseous necrosis in granulomas and epithelioid cell granulomas with Langhans giant cells. Furthermore, Ziehl-Neelsen staining revealed the existence of acid-fast bacilli. Although the differential diagnosis of TB and NTM was a notable challenge, we began using antituberculosis medication for the treatment, consisting of a combination of rifampicin (R, 600 mg), isoniazid (H, 300 mg), ethambutol (E, 750 mg), and levofloxacin (LVFX, 250 mg) (HER LVFX for 2 months plus HR for 10 months), considering her medical history of liver cirrhosis and diabetes mellitus, because of the possibility of primary nasopharyngeal TB. Although the posterior walls of the nasopharynx were still covered with a yellowish discharge after starting treatment, right vocal cord paralysis and right dysphagia developed on day 101. CT revealed a diffuse enhancing mucosal irregularity in the right nasopharynx (Figure 1(c)) and bony erosion of the external skull base (Figure 1(d)). Nasopharyngeal carcinoma was the most important differential diagnosis owing to the neurological findings and the bony erosion. We performed a deep tissue biopsy using a rigid nasal endoscope and cupped forceps under local anesthesia and confirmed a pus discharge from the right nasopharynx. Histopathological examination showed no malignant findings, and the bacteriological examination of the pus was negative. On day 127, the patient's headache and neurological findings disappeared, and the yellowish discharge of the right nasopharynx had decreased. After that, we performed the same tissue biopsy and drainage again. On day 217, improvement of the bony erosion of the external skull base was confirmed (Figures 1(e) and 1(f)). On day 233, the yellowish discharge disappeared completely.

PMC3937486_01

Female

A 20-year-old woman, mother of a 1.5-year-old child, presented with a swelling in the genitalia of 6 months duration. Cutaneous examination revealed a single, non-tender, pedunculated, polypoid growth, about 6 x 7 cm, hanging from the left labium minus [Figure 1]. She had minimal swelling of the left labium majus. There was a tiny ulcer near the superior commissure of the labia majora. However, many scars were seen on the medial aspect of both the thighs, which were attributed to pruritic ulcers in childhood, details of which were unavailable. Her vagina, cervix, and uterus were normal. Systemic examination, including the eyes and oral mucosa, did not reveal any abnormality. Filariasis being endemic in Cuddalore district of Tamil Nadu, elephantiasis of external genitalia due to filariasis, besides, lymphogranuloma venereum and granuloma inguinale were also considered. A clinical diagnosis of soft fibroma was entertained and an excision biopsy of the nodule was undertaken. Histolopathological examintion (HPE) revealed multiple non-caseating granulomas, edema, and dense lymphocytic infiltration in the dermis. Ziehl-Neelsen staining for Mycobacterium tuberculosis was negative [Figure 2]. Special stains for fungal organisms were not performed. A week later, at the time of suture removal, the patient presented with multiple typical "knife-cut" ulcers on the external genitalia, in the inguino-crural fold, interlabial creases, and natal cleft, leaving no doubt in the diagnosis of CCD [Figure 3]. Biopsy from knife cut ulcers could not be carried out since the patient was not willing to undergo the procedure. She did not have any intestinal symptoms or pain abdomen at any time in the past or present. On investigation, she was found to have hypochromic microcytic anemia (Hb: 10.5 gm/dl) and mild neutrophilic leucocytosis. Other relevant investigations including Mantoux test, ultrasonogram of the abdomen, and chest radiograph were not contributory. Both Enzyme-Linked ImmunoAssay (ELISA) test for HIV and VDRL test were negative. The patient was referred to a gastroenterologist for further work up, and no gastrointestinal involvement was reported. With this background, a diagnosis of CCD was made. The patient was managed with metronidazole 400 mg t.i.d. for 1 week and ciprofloxacin 500 mg bid. for 10 days in addition to oral prednisolone at 30 mg/day, which was gradually tapered over a period of 6 weeks. She reported after 2 weeks with ulcers showing signs of healing, and by 6 weeks, they resolved. Later, the patient was lost on follow-up. However, she reappeared 2 years later with massive swellings of both the labia majora, more marked on the left labium majus. She gave a history of having had a full-term normal child, 3 months earlier, delivered by an elective lower segment caesarean section (LSCS) in view of the edema of the labia majora [Figure 4].

cutaneous crohn's disease, metastatic crohn's disease, non caseating granulomas

PMC9092591_01

Female

A 7-month-old female neutered Bengal cat was referred to the Queen Mother Hospital for Animals following unknown trauma that had occurred the same day. Clinical examination revealed non-weightbearing left pelvic limb lameness secondary to two grade IIIB open fractures. A left, comminuted, mid-diaphyseal tibial fracture was present, with a 35 x 23 mm soft tissue defect on the medial aspect of the crus, resulting in exposure and contamination of the fracture site. Ipsilateral mid-diaphyseal fractures of metatarsals II-V were also present, with a 60 x 30 mm wound on the dorsolateral pes. Nociception and vascularity were intact. The remainder of the examination was unremarkable. The cat was initially treated with methadone (0.2 mg/kg IV q4h [Synthadon; Animalcare]), amoxicillin-clavulanate (20 mg/kg IV q8h [Augmentin; GlaxoSmithKline]) and intravenous fluid therapy (2 ml/kg/h [Hartmanns; Dechra]). The wounds were lavaged using 6 l sterile saline (Hartmanns; Dechra). Bacteriology samples were then taken to identify residual contamination, and sterile dressings (Primapore; Smith & Nephew) were applied. Venous blood gas analysis was unremarkable aside from mild respiratory acidosis, hyperkalaemia (potassium 5.0 mmol/l, reference interval [RI] 3.6-4.6), hypercalcaemia (calcium 1.41 mmol/l; RI 1.13-1.33) and hyperglycaemia (glucose 11.9 mmol/l; RI 4.7-7.3). Thoracic radiographs revealed a small-volume pneumothorax, which was treated conservatively. Pelvic limb radiographs confirmed left tibial and metatarsal fractures as previously described and a mid-diaphyseal fibular fracture (Figure 1a,b; Figure 2a,b). Abdominal and thoracic-focused assessment with ultrasonography for trauma was performed and was unremarkable. Fracture repair was pursued under general anaesthesia (GA) 36 h after presentation. Anaesthetic protocol included methadone (0.2 mg/kg IV [Synthadon; Animalcare]) and medetomidine (0.005 mg/kg IV [Sedator; Dechra]), ketamine (0.5 mg/kg IV [Anesketin; Dechra]) and alfaxalone (1.8 mg/kg IV [Alfaxan; Jurox]) coinduction. A bupivacaine (2 mg/kg, up to a total volume of 0.8 ml per site [Marcain 0.5%; Aspen]) femoral and sciatic nerve block was performed to achieve circumferential locoregional anaesthesia of the crus and pes. The tibial fracture was stabilised with a modified bilateral uniplanar (modified type 2) ESF (Figure 1c,d; Figure 3a,c,e,g,i). The metatarsal fractures were stabilised with a modified type 2 freeform ESF (Figure 2c,d; Figure 3b,d,f,h,j). The wounds were surgically debrided and lavaged, bacteriology samples were taken and wet-to-dry dressings were placed. Microbial culture following surgical debridement and lavage isolated Bacillus species, Acinetobacter species and a third, unidentified isolate; a course of amoxicillin-clavulanate (20 mg/kg q12h [Kesium; Ceva]) and pradofloxacin (5.5 mg/kg q24h [Veraflox; Bayer]) was required to ensure susceptibility of all isolates. Antibiotics were discontinued when all wounds were covered with granulation tissue. Ongoing open wound management consisted of daily surgical layered debridement and replacement of wet-to-dry dressings, which were changed to a foam dressing (Allevyn; Smith&Nephew) with hydrocolloid gel (Intrasite; Smith&Nephew) when no devitalised tissue remained. After 10 days of wound management, both wounds had a small amount of healthy granulation tissue circumferentially in the periphery of the wound, but there was minimal evidence of wound contracture or epithelialisation and large areas of tibial and metatarsal bone remained exposed (Figure 3e,f). Ten days postoperatively, forage of the exposed tibial diaphysis, partial apposition of the cranial and caudal musculature within the tibial wound, and placement of NPWT was performed under GA using the same aforementioned protocol. Under aseptic conditions the ESF bars and pins were padded with cohesive bandage (VetWrap; 3M). Black polyurethane foam (400-600 mum pore size) was applied to the cranial and caudal aspect of the limb, including the wounds and incorporating both ESFs, from the pes to the level of the proximal tibia. The construct was sealed with adhesive polyurethane film (Opsite; Smith&Nephew). Continuous negative pressure (-125 mmHg) was applied. The dressing was replaced at 48-84 h intervals (Figure 4), totalling 8 days of NPWT. At cessation of NPWT, the tibial wound was completely covered by healthy granulation tissue (35 x 15 mm; Figure 3i). This wound was left open to heal by second intention. Healthy granulation tissue was present throughout the pes wound (55 x 30 mm), although a small portion of metatarsals III and V remained exposed (2 x 8 mm and 3 x 16 mm, respectively; Figure 3j). Hydrogel (Intrasite gel; Smith&Nephew) and foam (Allevyn; Smith&Nephew) dressing was applied over this wound, and was replaced twice within 11 days. At that stage, granulation tissue covered the entirety of the wound, while the size of the wound remained unchanged. A free meshed skin graft from the left flank was used for closure. The graft was covered with paraffin gauze (Jelonet; Smith&Nephew) and polyurethane foam (Allevyn; Smith&Nephew). The dressing was changed three times in 14 days. Six weeks after admission, a weightbearing left pelvic limb lameness was present (4/10), with reduced tarsal range of motion, attributed to prolonged immobilisation. The graft donor site wound and the tibial wound were fully healed and there was 100% graft take (Figure 5). The cat was discharged with instructions to continue crate rest, with short periods of controlled exercise (5 mins, 3-5 times daily, increasing by 5 mins each fortnight), as well as continued monitoring of the skin graft site and ESFs. The cat was re-examined 16 weeks after the initial surgery. A 4/10 left pelvic limb lameness remained. Radiographs revealed delayed union of the tibial fracture (Figure 1e,f), functional malunions of metatarsals II-IV and an atrophic non-union of metatarsal V. After the cat was anaesthetised with the same protocol as previously described, the metatarsal ESF was removed (Figure 2g,h) and two loose pins from the tibial ESF were removed. A Jamshidi needle biopsy sample from the distal tibial fragment and a pin tip from the metatarsal ESF were submitted for microbial culture, which were both negative. Twenty weeks postoperatively, repeat radiographs of the tibia confirmed non-union of the tibia; thus, revision surgery was performed (Figure 1g,h). The tibial ESF was removed. Autologous bone graft was harvested from the left ilial wing. Following transverse ostectomies of the tibial and fibular fracture margins to reopen the medullary canals and allow a transverse surface for compression, the graft was applied to the fracture site and the tibia was stabilised with a medially positioned 2.7 mm locking compression plate (LCP; Synthes) placed in load (Figure 6a,b). Histopathology (for completeness) of the ostectomised fracture margins revealed immature callus and bone remodelling, and culture was negative. The cat was discharged 5 days postoperatively with meloxicam (0.05 mg/kg q24h PO [Metacam; Boehringer Ingelheim]), restricted exercise and a physiotherapy plan. Re-examination of the cat 10 weeks after internal fixation (30 weeks after trauma) showed a 3/10 left pelvic limb lameness. Both tarsus and stifle had full range of motion. Radiographs revealed radiographic union of the tibial fracture; the radiographic appearance of the pes was unchanged from the previous description (Figure 6c,d; Figure 2i,j). Gradual return to normal exercise was recommended.

npwt, external skeletal fixation, open fracture, trauma, vacuum-assisted closure, wound healing

PMC2841811_01

Female

A 21-year-old female presented with left-sided chest pain and low grade fever for one month. The clinical examination and X-ray chest were suggestive of moderate pleural effusion. She underwent thoracocentesis and about one liters of straw colored fluid was drained. The fluid was exudate (protein 4 gm %), lymphocytes predominant (cells 6800/mm3, 90% lymphocytes) with adenosine deaminase (ADA) level of 120 units. Her routine investigations including blood count, fasting blood sugar, liver function tests, renal function tests, urine examination, etc., were normal but erythrocyte sedimentation rate (ESR) was 110 mm in the first hour. Mantoux test revealed an induration of 15 mm. She was HIV sero negative and ultrasound abdomen was normal. Pleural biopsy revealed features of tubercular granulomas. Pleural fluid culture by Bactec method revealed mycobacterium tuberculosis sensitive to first line antituberculosis drugs. She was initiated on intermittent, directly observed, thrice weekly antituberculosis chemotherapy with isoniazid (600 mg), rifampicin (450 mg), and pyrazinamide (1,500 mg), under category III revised national tuberculosis control program of India. She responded with above treatment and became asymptomatic with regression of pleural effusion that disappeared completely after four weeks of therapy. She remained asymptomatic till six weeks when she noticed dull aching pain abdomen at epigastrium and left hypochondrium. The pain gradually increased and did not subside with the addition of omeprazole and antacids. There was no associated vomiting and diarrhea. On examination, there was tenderness at left hypochondrium. Ultrasound abdomen this time revealed mild splenomegaly with multiple hypoechoic areas (the largest one measuring 19 x 15 x 10 mm3, at lower part) [Figure 1]. CT scan abdomen also confirmed enlarged spleen with multiple miliary size abscesses. There were no other intraabdominal abnormalities. Ultrasound-guided fine needle aspiration cytology (FNAC) of splenic lesion revealed the collection of inflammatory cells including epitheloid cells, lymphocytes, multinucleated giant cells with extensive caseous necrosis; but no acid-fast bacilli [Figure 2]. A possibility of paradoxical response to antituberculosis therapy was strongly considered. She was given a course of oral prednisolone starting at 40 mg/day that was rapidly tapered off in four weeks, while she was maintained on the same antituberculosis regimen. There was marked clinical response on steroid therapy and repeat ultrasound abdomen, following a course of systemic corticosteroid showed near complete resolution of the splenic lesions; which completely disappeared at the end of antituberculosis treatment that patient received for six months.

paradoxical response, splenic abscess, tuberculosis

PMC10325872_01

Male

A 11-year-old boy of Congolese descent, born in Belgium and without significant medical history, presented with nonbloody diarrhoea for several weeks and unintentional weight loss. He reported a recent history of rhinitis and coughing with spontaneous improvement. He received all of his recommended vaccines (BCG vaccine not included) and he never left Belgium. The family history indicated no documented cases of TB or recent visits to a country with a high burden of TB. Physical examination was normal. Laboratory investigations showed a mild microcytic anaemia and slightly elevated inflammatory markers; sedimentation 29 mm/hr (normal range 0-13 mm/hr), and C-reactive protein level 16 mg/L (normal range <3 mg/L). Chest X-ray demonstrated minimally reduced lung translucence with possible ground-glass opacity, but an additional CT-thorax was unremarkable. The tuberculin skin test (TST) and the interferon-gamma release assay (IGRA), executed with T.SPOT.TB, were also negative. Abdominal ultrasound demonstrated discrete wall thickening of the terminal ileum with accompanying mesenteric lymphadenitis (four enlarged lymph nodes noted, the largest 27 x 16 mm). One week after presentation, he was referred for a colonoscopy because of markedly elevated faecal calprotectin of 4735 mg/kg (normal range <50 mg/kg) which is indicative of bowel inflammation.

PMC10325872_02

Male

Eight days after referral, a colonoscopy was performed and ileocecal inflammation was confirmed, a hallmark sign of Crohn's disease. After the procedure, he developed high fever with respiratory symptoms (dyspnea and crackles) and a reduced oxygen saturation of 80%. His chest X-ray (Figure 1(a)) demonstrated bilateral alveolar consolidations and a reticular enhanced lung parenchyma in the lower lobes. Amoxicillin/clavulanate was initiated in assumption of the diagnosis of aspiration pneumonia and respiratory support with low-flow oxygen therapy was started. In the absence of clinical and biochemical improvement, treatment was switched to ceftriaxone and metronidazole on day 5. Further respiratory deterioration was noted on day 7, and respiratory support was switched to high-flow oxygen therapy. A chest X-ray and computed tomography (CT) scan (Figures 1(b) and 1(c)) of the thorax revealed increased asymmetric bilateral (right more than left) patchy alveolar consolidations with adjective ground-glass opacity, suggestive for a superinfection above the initial aspiration pneumonia. One day later, the treatment was switched to meropenem. Eventually, gradual respiratory and biochemical improvement was noted. Respiratory support with high-flow oxygen therapy was tapered and switched to low-flow oxygen therapy on day 14, which could be stopped on day 17. Biopsies of the gastric corpus, the terminal ileum and the ileocecal valve revealed chronic inflammation with granulomas. The pathologist noted that these appeared larger and more abundant than normally encounters in Crohn's disease and TB was in the differential diagnosis. Microscopic examination of the biopsy material was not supplemented by mycobacterial culture (not possible because fixed in formaldehyde) nor PCR analysis. Furthermore, work-up for TB included radiological imaging with a brain MRI and abdominal CT scan. TST and IGRA (QuantiFERON) were repeated. Blood, CSF, gastric lavage (three times), and bronchoalveolar lavage fluid were inoculated for mycobacterial cultures (after fluorescence microscopy). Mycobacterial PCR was performed on CSF and faeces (GeneXpert MTB/RIF in accordance with the KNCV protocol). Because of persistent gastrointestinal symptoms, despite dietary treatment with Modulen , corticosteroids were associated together with precautionary TB treatment on day 15. Beside abnormalities revealed on the abdominal CT scan (discrete ileocecal bowel wall thickening, two lymph nodes with calcification and ascites fluid), investigations for TB came back negative. Bacterial cultures and multiplex polymerase chain reaction-test for viral infections and Pneumocystis jirovecii on bronchoalveolar lavage fluid were also negative. Faeces were negative for parasites. Meropenem was continued till day 19, and the patient was discharged on day 22. A positive evolution was noted on a new chest CT scan on day 50 (Figure 1(f)), with minor residual abnormalities suggestive of a previous infection. Two months after presentation, the family was screened which demonstrated a positive TST (induration of 15 mm) in his 9-month-old sibling, indicating recent exposure of the family to an infectious TB case. Corticosteroids were tapered to stop, and TB treatment was continued for 9 months. Complete clinical recovery was observed and currently, 12 months after finishing the TB treatment, no symptoms recurred.

PMC3760210_01

Male

A 4-year-old male patient presented with a superficial lump on left side of the abdominal wall since 1 month. The differential diagnosis of a lipoma, an abscess, or a tuberculous abscess was considered by the clinicians. The patient was sent to the pathology department for FNAC, it being the primary investigation in such cases. On examination, the lump measured 3.5 x 3 cm in size, slightly tender and soft to firm in consistency. Fine needle aspiration was done using 22G needle and 10 mL syringe without aspiration technique and yielded straw colored slightly turbid fluid. The smears were air dried and stained with May Grunwald Giemsa, haematoxylin, and eosin stains. Modified Ziehl Neelson stain was performed on one smear to rule out tuberculosis. On microscopic examination, fair number of neutrophils, lymphocytes, palisading histiocytes, eosinophils, and degenerated cells were noted. No granuloma or atypical cells were seen. Presence of eosinophils warranted closer look and on careful examination of five smears made from the aspirate, a solitary detached hooklet of cysticercus (Figure 1) was noted along with the inflammatory background. A diagnosis of cysticercosis cellulosae infection was made. The cytological diagnosis was further confirmed on serological examination for cysticercus. A final diagnosis of subcutaneous cysticercosis was given. The patient was advised antihelminthic therapy and antibiotics and is responding well. The patient also underwent imaging techniques, and lesions at other sites were ruled out.

PMC7276625_01

Female

A 19-year-old healthy female presented to the musculoskeletal oncology clinic with a chief complaint of the right-sided groin pain for 3 weeks. The pain was progressive in nature and atraumatic in origin. The patient noted significant pain with functional activity in addition to nighttime pain. Oral anti-inflammatory medications did not relieve the pain completely. Radiographs were obtained by her primary care provider, which demonstrated a large, aggressive lesion with some mixed lytic and blastic features about the proximal femur (Fig. 1). On careful examination, there appeared to be a thin cortical rim over the margin of the lesion medially. Magnetic resonance imaging was obtained and demonstrated an aggressive appearing lesion centered near the inferomedial femoral neck as well as the lesser trochanter (Fig. 2). The lesion demonstrated a lytic appearance with some extension through the cortex. A soft tissue mass of approximately 6cm in size was present which abutted the iliopsoas and vastus musculature causing adjacent mass effect. The patient underwent an open biopsy of the lesion through a posterolateral approach to the proximal femur. Sections from the curettage specimen showed a proliferation of relatively uniform large polygonal cells with eccentric round nuclei and abundant eosinophilic cytoplasm (Fig. 3). These cells were associated with the formation of new woven bone and seen growing in large sheets. By immunohistochemistry, the cells showed diffuse positive staining for SATB2, consistent with osteoblastic differentiation. Tumor necrosis was not present and mitotic activity was low (1-3 mitotic figures per 10 high-power fields). Overall, the morphologic features were consistent with an epithelioid osteoblastoma. After a diagnosis of epithelioid osteoblastoma was established, the patient returned to the operating room for extensive curettage of the lesion through a posterolateral approach followed by insertion of a short cephalomedullary intramedullary nail. Before insertion of the nail, an argon beam was used to ablate the curettage bony and soft tissue margin. Following insertion of the nail, the defect was then filled with allograft cancellous bone as well as demineralized bone matrix and the wound was then closed. The patient was made partial weight-bearing for a period of 6 weeks followed by full weight-bearing. Her pain was reported to be significantly relieved at the 6-week post-operative visit and she was ambulating with a mildly antalgic gait. One year post-operative imaging did not reveal any hardware complications or lesion recurrence (Fig. 4). In addition, on examination at the 1-year post-operative follow-up,the patient was not limited in gait or function. We will continue to follow the patient with serial radiographs and physical examinations for years to evaluate for recurrence.

epithelioidosteoblastoma, benign bone tumor, proximal femoral nail

PMC6612668_02

Male

A 40-year-old male presented with a trans-axial thoraco-abdominal gunshot wound. He was hemodynamically unstable, and a damage control laparotomy was performed. Gastric and diaphragmatic injuries were repaired and a grade IV liver injury was packed. The packs were removed after 24 h and a closed suction drain was left in the subhepatic space. Six days after laparotomy, CT abdomen showed non-perfusion of liver segments 2 and 3, a large central intrahepatic hematoma and a subhepatic collection. A percutaneous ultrasound-guided puncture of the collection returned bile and an 8 Fr pigtail drain was placed. He subsequently developed a persistent bile leak and rising serum bilirubin (13-38 mmol/L). ERC demonstrated extravasation of contrast into the subhepatic space and no filling of the proximal bile ducts. MRCP showed complete disruption of the extrahepatic bile duct but an intact confluence. A PTC was performed noting a porto-biliary fistula and an 8 Fr PTBC was positioned into the subhepatic space. At extraluminal PTC/ERC rendezvous a 10 x 80 mm fully covered SEMS was placed, bridging the defect (Fig. 2). The patient developed haemobilia 48 h later. Angiography showed a bleeding right hepatic artery false aneurism successfully managed with an endovascular stent.

bile duct injury, endoscopic percutaneous rendezvous, minimally invasive, self expanding metal stent

PMC8060088_01

Male

A previously healthy 12-year-old male patient was presented to our clinic with right knee pain and functional instability, 1.5 years after a football injury. On physical examination, the knee was unstable with a highly positive Lachman test (Figure 1) and anterior drawer test (Figure 2), there was a mild effusion, collateral ligaments appeared stable, and meniscus signs were negative. MRI revealed a complete tear of the ACL. In addition, an osteochondral lesion of the lateral femoral condyle with a diameter of 1.5 cm was seen. He had been treated nonoperatively with physiotherapy in another facility and was referred due to ongoing pain and giving-way episodes. For his age, the patient was very early in his development (Tanner stage 1) with wide open physes of femur and tibia. After discussing several options with the patient and his parents, we decided to proceed with an all-epiphyseal ACL reconstruction using a quadricep tendon autograft. Under general anesthesia and nerve block, the patient was positioned in supine position on the normal table (Figure 3). A perioperative single-shot antibiotic coverage was given, and a tourniquet was applied. First, a 5 cm x 10 mm x 5 mm quadricep tendon autograft was harvested through a minimally invasive technique (Figure 4) and prepared for an all-inside ACL reconstruction. Here, 15 mm of both ends of the graft was augmented with a fiber loop with fiber tag (FiberLoop w FiberTag Braided Polyblend Blue Suture Loop 20") (Arthrex) and connected to an ACL tight rope (ACL TIGHTROPE) (Arthrex) . Then arthroscopic examination of the knee was performed, which revealed a total tear of the ACL. The remnants were debrided, and the femoral and tibial footprints were identified (Figure 5), leaving some tibial fibers in place. Both menisci appeared normal, and the cartilage was unremarkable. Even on the lateral femoral condyle, which demonstrated an osteochondral lesion on MRI, the cartilage appeared stable and did not require any further surgical attention. Under fluoroscopy (Figure 6) in true lateral position as well as under direct arthroscopic vision, a guidewire was placed into the exact femoral footprint of the ACL from outside-in. This was over drilled with a 7 mm FlipCutter (FlipCutter II S. A.-N.-1.-7.) (Arthrex) to create the final 1.5 to 2 cm long femoral tunnel. Guiding sutures were pulled through the femoral condyle for later graft placement. During the entire process, it was made sure that the drilling was done strictly epiphyseal. On the tibial side, a guidewire was inserted from the anteriomedial aspect of the proximal tibia into the posterior part of the tibial ACL footprint. It was over drilled with a 6 mm FlipCutter (FlipCutter II S. A.-N.-1.-6.) (Arthrex) in retrograde fashion to create a 1.5 cm tibial tunnel. The drilling again was done under fluroscopic control for a strict epiphyseal position. Guiding sutures were placed in the tibial tunnel and consequently retrieved together with the femoral sutures through the anteriomedial arthroscopic portal. Then, the femoral end of the graft was inserted through the arthroscopic portal, the button flipped on the outside of the lateral femoral condyle, and the graft pulled into the femoral tunnel. The tibial end of the graft was inserted in the similar way, followed by 10 ranges of motion cycles of the knee. Finally, the graft was tensioned in about 20 degrees of flexion. A distal ABS button (TightRope ABS (Attachable Button System)) (Arthrex) was inserted under direct vision to ensure its direct sit on the bone (Figure 7). A final arthroscopic check of the graft and washout of all debris was performed, wounds were closed, and a brace was put on the leg. The postoperative protocol included early mobilization with weightbearing as tolerated. The child was allowed to remove or wear the brace as wished. Closed chain exercises were initiated early postoperative with special precautions for the weakened quadricep tendon. Physiotherapy continued routinely for 6 weeks postoperatively followed by a guided exercise program. A return to high pivoting activities and competitive sports was only allowed after 9 months.

PMC3366760_01

Male

Melioidosis was confirmed for the first time in New Caledonia in February 1999 in a 46-year-old male nurse who worked at the health center of Ouegoa, a village in the Northern Province. He was admitted to the hospital with fever, acute renal insufficiency, pneumonia, and septic shock. Blood culture grew an oxidase-positive, gram-negative rod, which was initially identified as a Pseudomonas sp. by the local laboratory but later confirmed as B. pseudomallei by the Pasteur Institute when the patient was transferred to the hospital in the capital city, Noumea. He had been treated for tuberculosis 20 years earlier. He required intubation and ventilation, and treatment was begun with a combination of ceftazidime and amikacin. Ten days after admission, when B. pseudomallei infection was confirmed, treatment was changed to the combination of imipenem and trimethoprim/sulfamethoxazole. Numerous cutaneous abscesses cultured B. pseudomallei, and he slowly recovered. The second case came from the same location of Ouegoa but not from the same tribe. The patient was a 43-year-old man with diabetes mellitus and chronic renal failure who required a kidney transplant in 2001. He was taking the immunosuppressant medication tacrolimus when "B. gladioli" septicemia was diagnosed in April 2002. Two months later, he was admitted to the hospital with pneumonia, and blood cultures grew B. pseudomallei. He made a full recovery after therapy with a combination of ceftazidime and trimethoprim/sulfamethoxazole. In July 2003, a 58-year-old man, living in Poum, 50 km from Ouegoa, was admitted with fever, pneumonia, and renal impairment. This man had tuberculosis in 1993 and was a smoker and alcoholic. Treatment was with amoxicillin/clavulanate for 24 hours followed by a combination of cefotaxime, ofloxacin, and metronidazole for 48 hours. He was transferred to Noumea with severe hypoxemia from bilateral pneumonia and hepatocellular insufficiency. A gram-negative bacillus was isolated from bronchial secretions. Therapy was changed to a combination of ceftazidime and ciprofloxacin, and he slowly improved. The organism was identified as B. pseudomallei 7 days after the patient's transfer to Noumea. A lung lobectomy was performed after 2 months for persisting pulmonary infection, and B. pseudomallei was cultured from the surgical specimen. The patient continued to receive trimethoprim/sulfamethoxazole on a long-term basis. In June 2004, a 67-year-old woman with a history of diabetes mellitus came to the hospital with abscesses on her thigh, from which B. pseudomallei was cultured. She was otherwise healthy and recovered fully after receiving therapy for melioidosis. She lives in Poindimie, about 200 km southeast of Ouegoa. The bacterium, also called Whitmore bacillus, is an oxidase-positive, gram-negative rod. It is commonly misidentified, sometimes as various species of the Pseudomonas genus. The bacterium grows aerobically on most agar media and usually produces clearly visible colonies within 24 hours at 37 C. In our cases, B. pseudomallei was identified with API 20NE and API 32GN (API system SA, Lyon, France). Two of the isolates were sent to the Centre d'Identification Moleculaire des Bacteries of Pasteur Institute in Paris, where the identity was confirmed by amplifying and sequencing the 16S rRNA gene. These strains were also defined by multilocus sequence typing (MLST) at Imperial College, London, and compared with isolates from Australia and Thailand. Both strains were new sequence types. When a minimum evolution analysis was performed on the concatenated sequences of the 2 strains and compared with Australian and Thai strains on the MLST website (http://bpseudomallei.mlst.net/), the New Caledonian strains clustered well within groups of Australian sequence types (Figure). Furthermore, 1 of the strains was a single-locus variant (i.e., 6 of 7 alleles identical) of a strain from the east coast of Australia. This comparison suggests that New Caledonian B. pseudomallei strains are linked to Australian strains. New Caledonia is a fragment of the ancient continent of Gondwana and subsequently separated from Australia and New Zealand. The diverse but distinct phylogeny of strains of B. pseudomallei in Southeast Asia and Australia may reflect geographic isolation over long periods.

PMC9472478_01

Unknown

A total of 49 patients had a positive COVID-19 test during this period. In the outbreak described here which occurred in a non-urban area at the height of the Omicron surge, no additional acute care capacity was available in the vicinity after the first two patients were transferred, which necessitated management of the additional patients on site. At the time, the Japanese government had just included short-course remdesivir as a treatment option in its COVID-19 management guideline. Since remdesivir was the only COVID-19 agent that was readily available without restrictions, patients were treated with this agent as soon as they developed symptoms consistent with COVID-19 and the diagnosis was confirmed by a positive test. Thirty-four of them were on the rehabilitation ward, and 15 of them were on the palliative care/internal medicine ward. Three of them did not receive remdesivir and were excluded from the analysis. The reasons for not receiving remdesivir were immediate transfer to an acute care hospital (2 patients) and impaired renal function (1 patient). The remaining 46 patients who received at least one dose of remdesivir constituted the cohort for this study. The demographics and remdesivir therapy administered are described in Table 1 . The median age was 75, and 41 had received at least one dose of mRNA vaccine. While the timing of vaccination was unknown, most of them likely received the doses more than six months earlier, since the age group (60 years old and greater) was largely vaccinated by the end of July 2022 in Japan. However, none had received the third dose. The median Charlson comorbidity index was 6, which corresponds to an estimated background 10-year survival of 2%. Documented COVID-19-related symptoms included fever (39 patients), sore throat (17 patients), cough (17 patients), headache (5 patients) and fatigue (2 patients). Based on the COVID-19 severity classification system adopted in Japan, 34 patients had mild disease (i.e. not requiring supplemental oxygen), 12 patients had moderate disease (i.e. requiring supplemental oxygen), and none had severe disease (i.e. requiring mechanical ventilation). Only one patient was asymptomatic. In all except one patient, remdesivir was started within 2 days from the symptom onset (positive test in the case of the one asymptomatic patient) and administered for a median of 3 days. The median time from onset to resolution of symptoms was 4 days (IQR, 2-7). Two patients were discharged prior to 14 days, and an additional 3 patients were discharged prior to 28 days. Of the patients followed up to 14 and 28 days from onset, 41/44 (95.3%) and 35/41(85.4%) were alive, respectively. All 6 deaths occurred among patients on the palliative care/internal medicine ward who had advanced malignancy (lung cancer [2], pancreatic cancer [2], colon cancer [1], renal cancer [1]). Additionally, two and one patients had history of diabetes and stroke, respectively. They all developed moderate disease, with SpO2 at room air ranging between 86 and 94%. Two of these deaths were possibly related to COVID-19, where one patient had cardiac arrest of undetermined cause and the other patient expired from respiratory failure. The remaining 4 deaths were deemed to have been due to underlying illnesses and unrelated to COVID-19. Specifically, all patients who died were both age 70 or greater and had malignancy (Fig. 1 ). While information is limited in the literature, COVID-19 in inpatient palliative care settings has been associated with extremely high mortality. In contrast, all patients on the rehabilitation ward were alive at 28 days. Even when these vulnerable patients survive COVID-19, cognitive and functional decline is commonly observed. In this cohort, the median performance status score was 3 at onset, 14 days and 28 days (Table 2 ). Most patients maintained the same performance score over the course of 28 days, and none of the surviving patients had a decline in the performance status score of greater than one. This suggests that the negative impact on the functional levels of those who survived the infection was minimal. In terms of safety, short-course remdesivir was generally well tolerated. Three patients developed transient liver function test abnormalities, one patient developed transient renal function abnormality, and one patient had itching at the infusion site. Institutional outbreaks in non-acute care settings have accounted for a significant portion of morbidity and mortality over the course of the COVID-19 pandemic thus far, including in Japan. Vaccination has dramatically reduced the risk of severe disease and deaths across age groups, but waning protection over time has been recognized as a major concern especially among the elderly, and the advent of the Omicron variant has further compromised the efficacy conferred by two doses of vaccines. In this context, uncertainties remain over the risk of severe disease and death for vulnerable patients hospitalized in non-acute care settings. We acknowledge that a major limitation of our study is the lack of untreated patients as this was not a controlled clinical study, and we were not able to find such data in the literature, either. Though not directly comparable, a study from the U.K. in the Omicron period reported a 28-day mortality rate of 5.48% among long-term care facility residents with COVID-19, the majority of whom were either previously infected or received a booster vaccination, down from 10.75% in the pre-Omicron era. During surges of infection, transferring patients from non-acute care settings to acute care hospitals can be challenging when the latter are also overwhelmed with excessive demand. The approach described here, where high-risk COVID-19 patients are identified and treated expeditiously, may represent the most effective and realistic COVID-19 care in non-acute care settings during such periods especially among those who have not received a booster vaccination. While remdesivir is available only as an intravenous infusion, future advent of safe and potent oral antiviral agents may make this approach more generalizable.

covid-19, drug therapy, p, r, remdesivir, alliative care, ehabilitation

PMC6636569_01

Male

A 44-year-old male patient was hospitalized because of progressive dyspnea, cough, and fever during one month. His past medical history was unremarkable. He appeared initially with mild fever, dry cough, and night sweating but untreated. After two weeks, he felt shortness of breath and coughed up yellow sputum. He had been admitted in the general hospital where he had undertaken the first bronchoscopy which revealed the negative results of bronchoalveolar lavage (BAL) for both acid-fast bacillus (AFB) smear and M. tuberculosis polymerase chain reaction (PCR). He had been diagnosed with community-acquired pneumonia but not improvement after a 10-day course of antibiotic therapy and was transferred to our tertiary hospital. On admission, he was alert, with body temperature 37 C, pulse rate of 84 beats/min, respiratory rate of 28 breaths/min, and blood pressure of 120/80 mmHg. He was supplied with oxygen via bag-valve mask at 10 L/min, and the result of arterial blood gas showed pH 7.38, PaO2 70 mmHg, PaCO2 32.7 mmHg, and HCO3- 19.4 mmol/L. Physical examination revealed dullness on percussion, fine crackles, and decreasing breath sound at the right lower lung field. Cell blood count with white blood cells 8.84 G/L (77.5% neutrophil and 13.3% lymphocyte) and hematocrit 38.2%, C-reactive protein level 78.4 mg/L, and mildly elevated liver transaminase level were recorded. The rapid testing for human immunodeficiency virus was negative. Chest X-ray showed consolidation in the right lower hemithorax, and the first contrast-enhanced chest computed tomography (CT) revealed small necrotizing cavities in this consolidation area (Figure 1(a)). With aforementioned information, we suspected differential diagnoses as follows: necrotizing pneumonia with particular pathogens (high-virulence bacteria, tuberculosis, or fungal infection) or noninfectious diseases (autoimmune disease, malignancy, or vascular disease). The antinuclear antibodies test was negative and the histopathological result of transthoracic lung biopsy showed an inflammatory process. He was treated with the combination of broad-spectrum antibiotics (meropenem, ciprofloxacin, and vancomycin) during four days but he still had fever. The adjunctive therapy with corticosteroid (40 mg methylprednisolone intravenous once daily) was commenced, and his condition improved spectacularly (defervescence, breath normally without oxygen) but the fever reoccurred on the fourteenth day after hospitalization. The second chest CT undertaken showed a significant regression of the consolidation (Figure 1(b)). The second bronchoscopy showed the positive BAL results for AFB smear and M. tuberculosis PCR. The treatment with a six-month antituberculosis regimen resolved his condition completely on follow-up.

PMC7582097_01

Male

A 44-year-old artisanal digger of coltan (Niobium + Tantalum) was transferred to hospital for multi-drug-resistant tuberculosis or rifampicin-resistant tuberculosis (MDR/RR-TB) treatment. As per the national guidelines, he has completed the first-line drug regimen, including 2 months of rifampicin (R), isoniazid (H), pyrazinamide (Z), and ethambutol (E), followed by 4 months of R and H (2RHZE/4RH). Due to persistence of symptomatology, he was retreated for failure by an 8-month regimen, including streptomycin (S) for the first 2 months (2SRHZE/1RHZE/5RHE). MDR/RR-TB was suspected as the patient persisted having fever, cough with bloodstained mucopurulent sputum a month after his second rifampicin-susceptible TB (RS-TB) treatment. The patient's history noted that, for four months since the first occurrence of respiratory manifestations to the first RS-TB, the patient self-medicated with cotrimoxazole and sought traditional/religious leaders help without success. On clinical examination, he presented with pyrexia, was dyspneic with reduced chest compliance, dullness on percussion with absence of tactile fremitus and majorly diminished breath sounds on the left side of the chest. Laboratory investigations showed a leukocytosis (21 7 x 109 per L) with marked eosinophilia. Sputum culture showed gram-negative bacteria (non-identified). Ziehl-Neelsen test for acid-fast bacilli on different sputum samples and HIV-infection serology were negative. Xpert-MTB/RIF on sputum sample was positive. Chest x-ray showed a mosaic of lesions suggestive of a complicated PTB (Fig. 1). CT-Scan was not available in the province. Audiometry confirmed a bilateral sensorineural hearing loss (103 and 105 dB on the right and left respectively) post streptomycin ototoxicity. In addition to MDR-TB and respiratory failure, we treated possible colonization (bacterial subsequently developed into an abscess and chronic pulmonary aspergillosis). We combined moxifloxacin (Mfx), clofazimine (Cfz), E, and Z throughout, supplemented by kanamycin (Km), prothionamide (Pto), and high dose isoniazid (Hh) during a 4-month intensive phase (4KmMfxPtoCfzZHhE/5MfxCfzZE) for MDR-TB short regimen. Cochlear implant, line probe assays to detect isoniazid resistance as well as mycobacterial culture were unfortunately not available for logistical reasons. Evolution was characterized by onset of severe septic status requiring "hygienic thoracic surgery" that could have not been performed in our setting. The patient passed away at the third month of hospitalization.

complication, democratic republic of congo, mycobacterium tuberculosis, thoracic surgery

PMC5863343_01

Female

The patient is a 56-year-old female with a past medical history of hypertension, hyperlipidemia, and ulcerative colitis who presented with complaints of joint pains for over 30 years. Her symptoms started with pain in the back radiating down the leg which later progressed to involve her shoulders, arms, wrists, and legs. She also described occasional swelling in her ankles, nonrefreshing sleep, and joint stiffness. Eight years before presenting to our clinic, she was given a diagnosis of chronic Lyme disease based on non-CDC-approved testing and received IV ceftriaxone. However, repeat Lyme testing with IgG and IgM antibody by our facility was negative. MRI of her tibia and fibula two years prior to presenting in our clinic had revealed marrow edema, but a biopsy of her bone marrow was normal. Upon initial presentation to our clinic, she was felt to have inflammatory arthritis and was treated with prednisone taper starting at 40 mg daily and weaned off slowly over several months. This helped her joint pain but did not resolve her symptoms completely. She was then trialed on treatment with hydroxychloroquine, methotrexate, and pregabalin without significant improvement. At the time of diagnosis, exam revealed raised erythematous papules and plaques consistent with urticaria. They were distributed over the neck, upper back, and some on the arms. There were no signs of palpable purpura or necrosis. On joint exam, she had tenderness and swelling on palpation of bilateral 3rd PIPs. There was also tenderness in both shoulders, elbows, forearms, pretibial regions, and ankles without any swelling, erythema, or warmth. There was no evidence of synovitis or dactylitis in the feet. A detailed workup was performed (including ANA, ENA panel, RF, ANCA, serum protein electrophoresis and immunofixation, Lyme serology, muscle enzymes, ESR, CRP, ferritin, and cryoglobulins). She was found to have elevated inflammatory markers, with ESR 48 mm/hr, CRP 4.3 mg/dL, and ferritin 320.2 ng/mL. The electrophoresis and immunofixation revealed an IgM kappa monoclonal gammopathy. The rest of the blood work was negative. A bone survey of all long bones and a bone scan were also performed which showed diffuse osteitis and remodeling of long bones. Based on the urticarial rash, IgM kappa monoclonal gammopathy, abnormal bone remodeling, and elevated acute phase reactants, she fulfilled the Strasbourg criteria for diagnosis of Schnitzler syndrome. She was started on anakinra 100 mg subcutaneous daily. The patient also tested quantiferon positive and was started on isoniazid and vitamin B-6 simultaneously for treatment of latent tuberculosis. The patient noticed significant improvement in her urticarial rash within days after initiating the anakinra. Shortly after that, she also had progressive decline in her musculoskeletal pain and gradually became symptom free. The improvement was also reflected in her inflammatory markers. Her CRP dropped from 4.3 mg/dL to 0.7 mg/dL, and ESR dropped from 48 mm/hr to 4 mm/hr.

PMC10393732_01

Female

A 38-year-old Jordanian lady, with no known chronic illness, presented the 3rd time to emergency department with worsening symptoms of high grade fever, productive cough, exertional shortness of breath and dizziness for 10 days. Patient had positive sick contact with her kids whom suffered from upper respiratory tract infection symptoms. On her previous two visits to the emergency departments, she was vitally stable and treated as a case of community acquired pneumonia with oral antibiotics - Amoxicillin / clavulanic acid on the first visit and azithromycin on the 2nd visit, however, she was unable to complete the treatment due to multiple vomiting episodes, thus, she presented for the 3rd time in 10 days to the emergency department with worsening symptoms. She looked septic with oral temperature of 38.5 degree celsius, blood pressure of 86/51 mmhg, heart rate of 108 beats/minute, tachypenic with respiratory rate of 26 breaths / minutes, peripheral oxygen saturation of 93% on room air. Chest auscultation was remarkable for bilateral diffuse crackles on middle and lower lobes with scattered wheezes, other systematic examination was unremarkable. Lab test results showed markedly elevated C-reactive protein of 295 mg/L with negative procalcitonin of 0.47 ng/ml (Table 1). X-ray of the chest - PA view (Fig. 1) showed worsening bilateral lower zones infiltrates more pronounced on the right lower zones as compared to her 1st ED visit. Patient was treated as a case of sepsis secondary to community acquired pneumonia with intolerance to oral therapy. Her blood pressure improved with fluid resuscitation and she was commenced initially on IV ampicillin/ sulbactum plus azithomycn with symptomatic treatment. Patient continued to spike high grade fever with no clinical improvement for which antibiotics escalated to IV piperacillin/tazobactam on day 4 of admission and further work up was requested. High resolution CT scan was done and revealed bilateral basal air space opacities with peri bronchovascular distribution and centrilobular nodules with branching pattern suggestive of tree in bud predominantly in lower lobes (Fig. 2). Tests for tuberculosis from the sputum and autoimmune disorders did not yield any positive results. Bronchoscopy (Fig. 3) was done on day 9 of admission and showed inflamed looking airways, especially right upper lobe secondary carina with inflamed submucosal and mucosal changes. Broncho-alveolar lavage (BAL) was positive for candida albicans but negative for TB work up. Her BAL cell count differential revealed 36% Neutrophils and 64% Macrophages with no eosinophil or Lymphocytes present. The endobronchial biopsies revealed a rare non-necrotizing granuloma. She had negative sputum and blood cultures apart from persistently positive candida albicans isolated from the sputum. She had no clinical response to 6 days of IV piperacillin/tazobactam on day 10 of admission, she was therefore started on anidulafungin to treat a probable case of candida pneumonia infection after a thorough discussion with the infectious disease team in the hospital. She fortunately improved dramatically, this was reflected in both her clinical and biochemical status within the first 24hrs of starting anidulafungin (Fig. 4) which she continued intravenously for 4 days then discharged on oral fluconazole for another 20 days based on the susceptibility results. She showed complete recovery upon her post discharge follow up both clinically and radiologically (Fig. 5). Notably, our patient has been previously healthy with no preceded history of acute infection or visits to healthcare facilities prior to her acute illness, she has 5 kids and all delivered via normal vaginal delivery and her last child is 10 months old. She has naive surgical history and had not been on any acute or chronic medications besides no prior history of candida infections.

broncho-alveloar lavage, candida albicans, granuloma, immune-competent, pneumonia

PMC5713644_01

Male

A 33-year-old male was brought to the emergency department by ambulance having been exposed to an explosive flash burn from a nitrous compressor while welding. The patient sustained burns to the face, neck, hands, and arms. His immediate first aid was to jump into a swimming pool of cold water. His burns were clinically assessed as 5% TBSA and mainly of superficial partial thickness. The epidermal layer had blistered and been removed, but the underlying dermis remained sensate and with a brisk capillary refill. The patient was known to the VABS as he had sustained a 40% TBSA burn 12 years previously, following a fire while cooking with hot oil. Remarkably, all of the flash burns from the welding accident had affected previously grafted or scarred skin. The patient was admitted for 48 h for analgesia and to establish a dressing plan and face care protocol on the ward. Once comfortable, he was discharged home to have dressings in the community and for clinic follow-up; within an expectation, his wounds would heal within the 3-week target. Five days later, the patient re-presented to the emergency department feeling feverish and complaining of general malaise. On examination, he had sloughy, infected burn wounds on the face, neck, hands, and arms. He was swabbed for microbiology, then commenced on intravenous antibiotics. Despite the wounds having been previously assessed as superficial partial thickness, it was apparent that the burns had failed to improve and would not heal without surgical intervention (see Figs. 1a, b and 2a, b). The burns were subsequently debrided in theatre with the Versajet II (hydrosurgery system), before being autografted. Split thickness thigh skin was used to sheet graft the dorsum of the hands with Artiss (fibrin sealant) to improve adhesion. Scalp skin was harvested to better match the skin of the face and neck. In addition due to the large amount of skin previously harvested from the patient's thighs in his previous burn surgery, it was thought that further use of these areas for grafting of the face would give suboptimal results. Scalp skin was inset on the face as sheet grafting with Artiss. Thigh skin meshed 2:1 was used to reconstruct the less cosmetically sensitive areas on the arms. Grafts were checked at 3 days and found to be intact and adhering well (see Figs. 1c, d and 2c, d). The patient was discharged home satisfied that his new grafts had improved the cosmesis of his previously scarred facial burns. Seven months following surgery, the patient continues to attend clinic for long-term follow-up of his wounds. As is the usual practice in our department, he is undergoing treatment with pressure garments and silicone in order to keep scarring to a minimum and prevent contractures (see Fig. 3).

burn scar, non-healing, previous burns

PMC5361631_01

Male

A 28-year-old man presented with fever, pharyngitis and cervical lymphadenopathy after returning from the Solomon Islands 2 days prior to his presentation. His past medical history was notable for CGD, which was diagnosed as a child following presentations with recurrent pneumonia and sinusitis. He was treated for pulmonary tuberculosis at age 4 years, but subsequently presented 2 years prior to his current admission with left upper lobe cavitary lung lesions and was retreated for culture-negative tuberculosis with rifampicin, isoniazid, pyrazinamide and ethambutol. One month prior to his current admission, the patient travelled to rural areas of the Solomon Islands. The patient was not taking his antibiotic prophylaxis at the time. He described both fresh and salt-water contact with a number of lacerations on his feet, although none of these became inflamed or infected. One week prior to return to Australia, he became unwell with a prominent sore throat, fever and subsequent neck pain. After arrival in Australia, he presented to our institution. On examination the patient was febrile (39 C), had significant hypotension [systolic blood pressure 70 mmHg (9.3 kPa)], a pulse rate of 160 beats min-1, a respiratory rate of 24 breaths min-1 and an oxygen saturation of 93 % on room air. His neck was asymmetrically swollen on the left, without any fluctuance. The oropharynx was erythematous and oedematous without a visible collection or any evidence of airway compromise. The lacerations on his feet were all well healed, with no evidence of inflammation. Initial tests revealed an elevated total white cell count (17x109 cells l-1) and neutrophils (10.2x109 cells l-1), C-reactive protein of 286 mg l-1 and a lactate level of 3.2 mmol l-1. A chest X-ray demonstrated a new opacity in his left lower lobe. Arterial blood gases demonstrated pH 7.44, pO265 mmHg (8.7 kPa) and pCO232 mmHg (4.3 kPa). Ultrasonography of his neck revealed an occlusive thrombus of the left mid to upper internal jugular vein. This was subsequently confirmed with computed tomography (CT), which demonstrated thrombosis of the left internal jugular vein at the level of the thyroid cartilage, extending superiorly to the base of skull (Fig. 1). The CT imaging also demonstrated centrally necrotic consolidation in the anterior left lower lobe and multiple ill-defined pulmonary nodules. These clinical and imaging findings were consistent with Lemierre's syndrome, that is, internal jugular vein thrombophlebitis.

chromobacterium violaceum, lemierre's syndrome, meropenem, trimethoprim/sulfamethoxazole

PMC7732962_01

Female

Patient is a 51-year-old female with a past medical history of hypothyroidism and pulmonary tuberculosis. Three years before seeking medical attention, she experienced mild episodes of upper abdominal pain associated with dark black, tarry feces. During the past year, these episodes became more frequent; thus, a gastroenterologist consultation was required. Anemia (Hb; 11 mg/dl) and fecal occult blood test was positive at that time. Due to this, an upper endoscopy was requested. A 103 x 46.6 mm submucosal mass in the lesser curvature 5 cm away from the cardias covered with normal mucosa was detected (Fig. 1A). To further investigate the submucosal tumor, endoscopic ultrasound (EUS) was done, revealing that the low-echo lesion had a regular and clear margin and was inside the submucosal layer. A color doppler image showed a vascular signal extending into the center of the low-echo lesion from the periphery. EUS fine-needle aspiration was achieved for pathological evaluation and was completed safely without any complications (Fig. 1B). Immunostaining was performed, revealing positivity for CD34 and CD 117, and was negative for S100 and anti-alpha-Sm-1. Gastric GIST was diagnosed. A contrast-enhanced abdominal computed tomography (CT) unveiled the 102 x 56.3 x 46.6 mm gastric mass. It also didn't reveal any masses or lymph nodes; thus, surgery was decided, and a preoperative check-up was scheduled. Nonetheless, as the Covid-19 pandemic started to unfold in Ecuador, most surgeries were delayed or canceled. The outpatient clinic was closed, and the quarantine combined with the fear of Covid-19 caused anxiety in the general population and affected all our patients. In our case, the patient missed her appointments and remained untreated for five months. Since then, the patient endured the same symptoms; nonetheless, they became more severe as time passed. Suddenly, the patient underwent severe hematochezia, followed by fatigue and syncope; thus, she was brought immediately to the emergency room. On clinical evaluation, a hypotensive and diaphoretic patient was encountered. After reanimation, mild abdominal pain was detected in her upper abdomen. Complementary exams revealed severe anemia (Hb: 5.5 mg/dl), and a contrast-enhanced computed tomography revealed the previous 102 x 56.3 x 46.6 mm gastric tumor; however, contrast extravasation was seen from the tumor vessels into the gastric cavity (Fig. 2A & B). Two red cell concentrates were transfused, and surgery was decided. A laparoscopic and endoscopic cooperative approach was chosen. On laparoscopy, no masses, lymph nodes, or free liquid was seen. After this, three (10 mm, 10 mm, and 5 mm) gastrostomies were done using an ultrasound device (Harmonic, Ethicon, Johnson & Johnson), the trocars were placed through them, and the inner gastric surface was seen. The bleeding gastric GIST was detected; it measured about 60 x 46 mm and had a 2 x 3 mm bleeding ulcer; the tumor was identified and grasped with the endoscope. After gaining adequate traction and using two consecutive 2.5 mm endo staplers (30 mm), the tumor was completely resected. After this, the tumor was extracted, the trocars were removed from the stomach, and the gastrostomies were closed using a 3-0 sterile synthetic absorbable monofilament. (PDS, Johnson & Johnson Medical) The rest of the procedure was completed without complications (Fig. 3A-C). Pathology reported a total tumor excision; the tumors were composed of spindle cells with eosinophilic cytoplasm and low mitosis. Gastric GIST was the final diagnosis. The postoperative course was uneventful; after blood transfusion and surgery, she remained stable, and liquids were initiated on the first postoperative day. She was discharged on postoperative day five without any complications. On follow-ups, two months later, the patient is doing well without any difficulties.

cooperative approach, covid-19, gastric gist, gastrointestinal stromal tumors, upper gastrointestinal bleeding

PMC4762790_01

Female

A 60 year old woman was admitted in the Department of Internal Medicine because of a 15 day history of intermittent fever of 38 C, aching pain over the forehead and fatigue. She reported no rigors, arthralgias, nausea, vomiting rash, postnasal drip, cough, diarrhea, urinary symptoms and any other pain or weight loss. At the onset of fever, she had been referred to another clinic where she was thought to suffer from some infection. White blood cell count was 11,500/mul, ESR 50 mm/h and CRP 7 mg/dl (normal value <0.5 mg/dl). However, blood and urine cultures were sterile, CT imaging of the brain, sinus, chest and abdomen-pelvis showed no sites of infection and transthoracic echocardiography was normal. Her fever resolved without antibiotics, and after her discharge on the fifth hospital day she stayed afebrile for a further 5 days before her symptoms recurred. The patient had no other medical history. She mentioned trekking as a hobby and had been on vacation to Cyprus 2 months earlier. She had no known allergies, had never smoked and had no recent exposure to ill persons. When she presented to our Department, clinical examination confirmed temperature of 38.2 C while all other vital signs were normal. There was no neck stiffness and the remainder of the neurologic examination was normal. Chest was clear on auscultation but she had a 2/6 systolic murmur at the mitral area which was not present at her previous hospitalization. There were no hepatosplenomegaly, lymphadenopathy, abdominal tenderness or masses. She had no skin lesions and temporal arteries were clinically normal bilaterally. Laboratory analysis revealed raised ESR (100 mm/h) and CRP (17 mg/dl - normal value <0.5). White cell count was 10,000 mm3 with 72% neutrophils and 21% lymphocytes. Hemoglobin was 12 g/dl and platelet count 200,000/mm3. Electrolytes, total protein, albumin, globulin, uric acid and LDH were normal, as were tests of coagulation, renal and liver function. Six sets of blood cultures were obtained from different sites at the peak of fever and when she was afebrile, and trans-esophageal echocardiography (TEE) was performed on suspicion of infective endocarditis. Blood cultures were all sterile, however TEE showed a small mitral lesion which resembled vegetation. No abnormality or serious regurgitation of the valve was noticed. These findings were considered indicative of blood culture negative infective endocarditis. Treatment with intravenous ceftriaxone 2 g was administered focusing on the HACEK group of bacteria. Further diagnostic tests were pursued for fastidious organisms including brucella agglutinin tests (Wright, Wright Coombs), serologic tests for C. burnetii, Bartonella, Chlamydia, Mycoplasma, as well PCR for Tropheryma whippelii. Prolonged incubation of the blood cultures was requested to address the possibilities of HACEK pathogens, and nutritionally deficient streptococci (Abiotrophia defective, Granulicatella). The LightCycler SeptiFast test was also performed to detect, as a multiplex real-time PCR assay, possible bacteria or fungi causing bloodstream infection. All tests were negative except for the screening test for C. burnetii. An IgG anti-phase II antibody titer of 1/1024 and an IgM anti-phase II antibody titer of 1/64 were detected. Anti-phase I antibodies were IgG 1/256 whereas IgM as well as PCR were found negative (National Reference Center of Parasitology Zoonoses and Geographical Medicine in Heraklion-Crete). These results were strongly indicative of acute Q fever. It is established in the literature that endocarditis is the major clinical manifestation of chronic Q fever. As a result, our first estimation of endocarditis based on the TEE findings and the diagnosis of acute Q fever were contradictory. Considering the febrile course and positive serology, treatment was changed from ceftriaxone to doxycycline 100 mg bid plus hydroxychloroquine 600 mg daily, in case of evolution to chronic Q fever. After 7 days of treatment, the fever persisted. Even more, the patient presented with more frequent and higher peaks of fever up to 38.5 C which did not respond to regular non-steroidal anti-inflammatory drugs. The patient appeared unwell and laboratory analysis revealed a further rise of inflammatory markers (ESR: 120 mm/h and CRP: 22 mg/ml) and worsening anemia of chronic disease. Renal and liver function remained normal. A second TEE showed the same mitral valve lesion. Therefore, further work-up was performed. Serum ferritin level was 400 ng/ml (normal range 10-291 ng/ml), not markedly raised to suggest adult-onset Still's disease. PCR assay for CMV was negative as was the serologic test for HIV and the quantiferon test as evidence of latent tuberculosis. The AgK39 for leishmaniasis was also negative. Temporal artery biopsy was normal and bone marrow analysis revealed a reactive marrow with no signs of infiltration or granuloma. Endoscopy of the gastrointestinal tract and biopsies did not suggest inflammatory bowel disease. Investigations for the possibility of a systemic autoimmune disease were requested: serum complement levels were normal; antinuclear antibodies were borderline weak positive at 1/80, anti-dsDNA, ANCA, RF Factor and all other autoantibodies were negative, with the exception of IgM anticardiolipin antibodies and the anti beta2 GPI IgM antibodies, which were twice the normal values. The patient's constitutional symptoms, valvular involvement, raised inflammatory markers and some positive autoantibodies suggested the possibility of a non infectious systemic inflammatory process. FDG-PET/CT scan was requested, which revealed increased uptake of FDG (indicating any kind of inflammation) in the ascending aorta, aortic arch and thoracic descending aorta, strongly suggestive of the presence of a large vessel vasculitis/aortitis (Fig. 1). We concluded that our patient was suffering from acute Q fever, complicated by aortitis. Treatment with intravenous methylprednisolone, 1 g daily for 3 days was initiated. The patient became afebrile within 24 h, inflammatory markers returned to normal and her general status improved markedly and rapidly. Serological follow up, 21 days after the first screening, confirmed the diagnosis of acute Q fever. An IgG anti-phase II antibody titer of 1/512 and an IgM anti-phase II antibody titer of 1/128 were detected, whereas an IgG anti-phase I antibody was only 1/256 (Table 1). The patient recovered and she was discharged from hospital on 15 mg of methotrexate once a week, 32 mg of methylprednisolone per day to be tapered, 200 mg of doxycycline and 600 mg of hydroxychloroquine daily, for at least 1 year.

coxiella burnetii infection, fdg-pet scan, q fever, vasculitis

PMC6925563_01

Female

A 14-year-old girl with NBS presented with a typical phenotype and genotype (homozygotic NBN gene mutation 657del5) has suffered since early childhood from acute and chronic infections of the respiratory tract, paranasal sinuses, cryptococcal meningoencephalitis, chronic bronchitis, chronic pneumonia, symptomatic Epstein-Barr virus (EBV) reactivation, hepatitis of unknown etiology with cholestasis, and skin infections including disseminated actinomycosis and non-tuberculosis granulomas. She has also been diagnosed and treated for secondary hemophagocytic lymphohistiocytosis (HLH), complicated with facial vasculitis, hypertension and cardiomyopathy. Additionally, she had a tri-lineage hematological insufficiency and hypogammaglobulinemia (IgA < 10 mg/dl, IgG 85 mg/dl). Absolute numbers of lymphocytes showed combined B- and T-cell immunodeficiency: 0.266 G/l for CD3; 0.084 G/l for CD4; 0.140 G/l for CD8 and 0.077 G/l for CD19. Due to an increasing number of life-threatening infectious complications, confirmed progressing immunodeficiency and marrow hypocellularity, she was referred for HSCT from a matched unrelated donor. On admission, she was in overall poor clinical condition, with Lansky performance score of 80, infection of the skin, symptoms of chronic pulmonary disease with various pulmonary rhonchi, oxygen saturation of 94%, and abnormal liver function tests. The preparative RIC regimen included fludarabine (30 mg/m2/day; days from -9 to -5), cyclophosphamide (5 mg/kg bw/day; days from -5 to -2) and antithymocyte globulin (total 8 mg/kg bw divided between three consecutive days from -3 to -1). Due to previous infections, she was on continuous therapy with antibiotics. Other anti-infective prophylaxis included posaconazole and acyclovir. She received also prophylaxis against veno-occlusive disease with defibrotide. The graft included peripheral blood stem cells from HLA-matched, AB0/Rh-matched woman (11.6 x 108 NMC/kg bw; 7.8 x 106 CD34+ cells/kg bw). Prophylaxis against graft-versus-host disease (GVHD) included cyclosporine A and mycophenolate mofetil, however due to deterioration of parameters of the renal function, cyclosporine was converted to sirolimus, which in turn was converted to methylprednisolone, due to facial vasculitis (Fig. 1). Additionally, at day +5 rituximab was administered prophylactically against EBV reactivation and development of post-transplant lymphoproliferative disorder (EBV-PTLD). During an early post-transplant period she was in otherwise good condition, however she suffered from severe mucositis, fever episodes, and necessity of total parenteral nutrition (TPN). Hematological and platelet recovery occurred at days +12 and +25, respectively. She was discharged from the transplant ward at day +28 with 49% donor chimerism, normal hematopoiesis in bone marrow, and no CMV or EBV viremia. At day +35 she complained of acute abdominal pain accompanied by significant elevation of gamma glutamyl transpeptidase (3673 U/l), alkaline phosphatase activity (643 U/l) and a total and conjugated bilirubin level (5.17 mg/dl and 4.15 mg/dl, respectively). On magnetic resonance (MRI) cholangiopancreatography, the common bile duct (CBD) was widened with a diameter of 6 mm and in the distal part of CBD there were bile deposits of 5 x 3 mm size. She was qualified to urgent endoscopic retrograde cholangiopancreatography (ERCP). After sphincterotomy, removal of bile deposits was carried on with endoscopic basket. Additionally a 5 cm 7F prosthesis was inserted into the distal CBD (Fig. 2). She was initially planned for early (within 7 days) CBD prosthesis removal, however this approach was postponed because of post-ERCP pancreatitis development with elevation of serum and urine amylase activity (2701 U/l and 3803 U/l, respectively). In the subsequent MRI examination, signs of pancreatic edema and irregularity of pancreatic borders were noted. Despite the presence of peripancreatic fluid collections, stranding fat densities and temporary signs of paralytic ileus she was successfully treated with TPN, fluid resuscitation and broad-spectrum antibiotics. She was qualified to elective laparoscopic cholecystectomy, which was performed 6 weeks after ERCP. On laparoscopy a thickened, callous wall of the gall bladder was revealed. Liver surface appeared to be nodular with increased consistency. Due to the problems with clear delineation of gall bladder bed, the lack of possibility of proper identification of hepatic hilum structures and bleeding, the procedure was converted to the open cholecystectomy. After gallbladder and biliary stent removal, a careful hemostasis of gallbladder fossa was performed using argon beam coagulation and 4DryField starch powder. In the early postoperative course an increased amount of drained fluid was observed but drainage was removed on the third postoperative day and spontaneous biliary flow without any complications was obtained. Due to subsequent transient elevation of serum amylase and poor wound healing she was successfully managed conservatively with vancomycin and ceftriaxone. Further postoperative course was uneventful. Two weeks later she was admitted to hospital with mild acute lower gastrointestinal bleeding. Stool samples were tested negative for rotavirus, adenovirus and norovirus, but positive for Campylobacter jejuni and Clostridium difficile. Blood CMV and EBV reactivation were also ruled out. The ileocolonoscopy revealed a 3-4 cm crater-like ulcer located 2-3 cm from the anal margin, which was covered by yellowish slough surrounded by reactive mucosa. Another ulcer was found at the recto-sigmoid junction (Fig. 3). Microscopically, lymphocytic and neutrophilic mucosa infiltrate that focally infiltrated crypt epithelium with mild crypt distortion and signs of regeneration were present in the entire colon. Based on histopathology, CMV infection and GVHD in the colon were excluded. The girl was treated with intravenous azithromycin and orally budesonide and mesalamine. A clinical and endoscopic improvement was noted at the second endoscopy performed four weeks later. Three month later no complaints were reported (Table 1). There were symptoms of immunological recovery, and the girl presented an increasing donor chimerism (63%).

cholecystitis, choledocholithiasis, cholelithiasis, gut ulcer, hematopoietic cell transplantation, pancreatitis

PMC3949340_01

Female

A 38-year-old, house keeper woman was admitted in Alzahra hospital because of chills, fever, and generalized malaise. She also complained about exertional dyspnea and nonproductive cough of 2 years duration and had a history of Raynaud's phenomenon that started 8 months prior to admission. She was a nonsmoker with no documented lung disease and denied any other symptom. Physical examination revealed Velcro-like rales at the bases of both the lungs, but no sign of skin nail involvement or heart failure. Tuberculosis and other infections were ruled out. Laboratory tests showed a high positive titer of anti-nuclear antibody, erythrocyte sedimentation rate of 73, and C-reactive protein of 3 + and a normocytic normochromic anemia, whereas test for anti-Scl70 antibody and anti-centromere antibody was negative [Table 1]. Computed tomography scan showed bilateral ground-glass pattern suggestive of ILD [Figure 1]. Spirometry was done, which showed a moderate restrictive pattern. She was treated with prednisolone (1 mg/kg) and pulse of cyclophosphamide (1 g/month) for 6 months, and then put on Cellcept for another 6 months, but ILD did not improve. Thus, the patient was treated with rituximab 2 g (1 gram every 14 days) and showed gradual improvement, then she was subsequently treated with 100 mg of azathioprine daily, prednisolone 5 mg bid, and calcium plus vitamin-D. She has been followed up for 2 years and has not shown any other manifestation.

interstitial lung disease, rituximab, systemic sclerosis sine scleroderma

High-resolution CT scan showing lung fibrosis.

PMC5259939_01

Female

A 68-year-old lady presented to surgery outpatient department with swelling and pain in the right submandibular region for the last 2 months. Local examination showed a soft and fluctuant swelling of 4 x 3 cm over right submandibular region. It was warm and tender on palpation. Clinical examination of the orofacial region did not revealed any odontogenic or nonodontogenic foci of infection. All the hematological parameters were normal except for mild peripheral eosinophilia (12%) and a low hemoglobin level. A clinical diagnosis of submandibular pyogenic abscess was made and to exclude tuberculosis, FNAC was advised. FNAC from the swelling yielded purulent material along with a creamy white thread. Smears showed adult gravid female filarial worm having an intact outer cuticle layer and body cavity filled with different stages of developing ova and microfilariae [Figure 1]. In addition, numerous embryos and coiled larvae and fully straightened larvae of W. bancrofti that were sheathed and had no nuclei in the tail end were also visualized. The background was composed of inflammatory cells including neutrophils, lymphocytes, macrophages, and eosinophils. Hence, a final diagnosis of filarial abscess was made.

adult female worm, filarial abscess, submadibular region

PMC10122477_01

Male

The patient was a 63-year-old male with chronic hepatitis B for 40 years, cirrhosis for 10 years, duodenal varicose vein sclerosis, type 2 diabetes for 5 years, and thrombocytopenia for 5 years. In June 2018, the patient was diagnosed with hepatocellular carcinoma and undergone right lobe hepatectomy. Sorafenib 400mg bid was taken orally for 6 months after operation. On November 1, 2018, the electronic colonoscope showed multiple telangiectasia of the colon. In June 2019, percutaneous transhepatic portal vein and duodenal vein embolization was performed once. In August 2020, pulmonary metastasis and mediastinal lymph node metastasis were observed. Bronchial artery infusion (BAI) and splenic artery infusion chemotherapy were performed three times on September 29 and November 13, 2020, with regimen consisted of pirarubicin 60mg, fluorouracil 750mg, oxaliplatin 50mg and interleukin 2 million IU, and on December 18, 2020, with regimen consisted of gemcitabine 1g and cisplatin 40mg. The patient was also treated with 200mg of camrelizumab for four courses from September 14, 2020, to March 29, 2021. After 21 days of the last dose of camrelizumab, diarrhea appeared and gradually worsened with 5 to 6 episodes of thin mucus and bloody stools from April 19, 2021, but without abdominal pain. The blood cell analysis showed: white blood cell count (WBC) 2.93x109/L, platelet count (PLT) was 72x109/L, hemoglobin (HB) was 138g/L and C-reactive protein was 4.42 mg/L. Afterwards, patient was admitted to hospital. His lab profile revealed alanine aminotransferase (ALT): 28U/L, serum total bilirubin (Tbil): 32.43 umol/L, serum creatinine (Cr): 45.8 umol/L, hepatitis B surface antigen (HBsAg): 0.6IU/mL. Hepatitis C antibody was negative indicated that Hepatitis C infection was excluded. Routine stool on April 21 showed brown loose stool with OB+ and red blood cell (RBC) 2/HP. No pathogenic bacterium grew in a stool culture, so we excluded infection. Abdominal CT showed there were no morphologic abnormalities of colon and rectum. Immunotherapy was interrupted. On April 23, 2021, colonoscopy showed multiple flake congestion and edema in the terminal ileum and colon mucosa. Histopathological evaluation showed chronic inflammation of colonic mucosa (Figure 1). On April 24, loperamide 5mg bid as a symptomatic treatment was given. The patient has shown improvement, with a decrease in mucus and non-bloody diarrhea to once a day. After oral administration of enteric-coated sulfasalazine capsule, 0.25g bid was given for 6 weeks, diarrhea and bloody stool disappeared. On June 8, 2021, colonoscopy showed congestion and edema of colonic mucosa, and scattered patchy erythema mainly in descending colon and sigmoid colon. The biopsy specimens were taken from the erythematous mucosa of transverse colon (Figure 1). Pathological evaluation showed chronic inflammation of colonic mucosa and hyperplastic polyp. BAI chemotherapy consisting of gemcitabine 1g, cisplatin 40mg, and interleukin-2200 IU was administered on September 7, 2021. On September 30, immune therapy was resumed. Two hundred milligrams of camrelizumab was given. No obvious discomfort occurred during follow-up. Colonoscopy was performed again in January 2022, and no colonic disease was found.

anti-programmed cell death blockade, camrelizumab, colitis, immune checkpoint inhibitor, immune-related colitis

PMC5394822_01

Male

An 88-year-old man presented with a 2-week history of gradually progressive breathlessness and dry cough. There was no associated fever, loss of weight, or appetite. He denied any edema of the feet and orthopnea. His history was remarkable for hypertension and coronary artery bypass grafting done 8 years ago. He was diagnosed with GIST 4 months ago when he presented with gastric discomfort and a computed tomography (CT) scan of the abdomen showed a 12 cm x 11 cm x 8.5 cm posterior mediastinal mass. A subsequent endoscopic ultrasound-guided biopsy showed tumor cells positive for C-Kit and DOG-1. He was commenced on tablet imatinib 400 mg/day for his GIST, but after 1 month of the treatment, he began to complain of breathlessness on exertion. He was a lifelong nonsmoker. There was no history of tuberculosis or tuberculosis contact. On examination, he was mildly tachycardic with a pulse rate of 90/min. His blood pressure was normal and jugular venous pressure was not raised. He had no pallor, icterus, cyanosis, clubbing, lymphadenopathy, or pedal edema. His respiratory system examination revealed diminished breath sounds in the right infrascapular and infraaxillary area. His abdomen was soft on palpation and no organomegaly was felt. His complete blood count, renal function tests, and liver function tests were all normal. His transthoracic two-dimensional echocardiogram showed normal left ventricular (LV) ejection fraction of 55%. A chest radiograph [Figure 1] showed a right pleural effusion and high-resolution CT chest [Figure 2] showed a large right-sided pleural effusion and unchanged posterior mediastinal mass with no consolidation or lymphadenopathy. He underwent a thoracentesis of the pleural fluid; 1100 ml was aspirated. Results of pleural fluid aspiration were: protein: 3.3 g/dl (total serum protein: 5.4 g/dl); lactate dehydrogenase (LDH): 223 IU/L (serum LDH: 280 IU/L); white blood cell count: 1040/mm3 (50% lymphocytic); adenosine deaminase (ADA): 4.1 (normal: 0-40 U/L). His pleural fluid cytology showed lymphocyte predominance and no malignant cells. Pleural fluid aerobic and tuberculosis cultures and GeneXpert were all negative. He was diagnosed to have an exudative effusion with a low ADA. An oncologist's opinion was sought who ruled out metastasis as a cause of the effusion. In the absence of other causes of pleural effusion, a diagnosis of imatinib-induced pleural effusion was made. Imatinib was withdrawn; the patient gradually improved and a repeat chest X-ray at 3 months poststoppage of drug showed complete resolution and no refilling of the fluid [Figure 3]. The patient declined any further treatment for his GIST and was not put on any other medication. He remains under regular chest radiograph and sonography follow-up over 1 year and has no recurrence of his effusion.

PMC10239888_01

Male

A 14-year-old adolescent presented to our hospital with a complaint of syncope during exercise (playing basketball). He reported feelings of dizziness, sweating, and blackness before fainting. He denied having chest pain or abnormalities in limb movement before and after the occurrence of the episodes. He suffered from two similar episodes in the preceding 2 years while playing basketball and while running. He denied having a family history of coronary artery disease, cardiomyopathy, hypertension, and diabetes. He was diagnosed as experiencing a vagal syncope because of a positive tilt test result a year ago in a local hospital. However, a review of his previous medical records did not reveal any abnormalities. A physical examination on admission revealed normal levels of blood pressure (120/60 mmHg), heart rate (78 beats/min), respiratory rate (18/min), and oxygen saturation of 99% (room air). Cardiac and pulmonary examinations showed normal heart sounds without murmurs and with clear lungs. Laboratory test results indicated normal levels of blood glucose, high-sensitivity troponin, CK-MB, N-terminal B-type natriuretic peptide (NT-proBNP), D-dimer, CBC w/diff, and CMP. The renal and hepatic functions were within normal limits. The baseline ECG displayed sinus rhythm (HR = 78 bpm) without significant abnormalities (Figure 1A). Transthoracic echocardiography (TTE) showed normal cardiac structure and function (Figure 1B). To further investigate the possible reason for syncope, coronary CTA was performed, which revealed an anomalous origin of the LCA originating from the left side of the right sinus of Valsalva and ran between the aorta and the pulmonary artery with an intra-arterial wall course of approximately 20 mm in length (Figure 2A). To clarify whether the anomalous origin of the LCA was the real reason for syncope, we performed CT-FFR on all coronary branches at rest, which revealed an abnormal FFR of the left anterior descending artery (LAD, 0.79) but a roughly normal FFR of the left circumflex artery (LCX, 0.84) and the right coronary artery (RCA, 0.90) (Figure 2B). CT-FFR is a physiologic simulation technique that models coronary flow from routine coronary CTA. To evaluate lesion-specific ischemia, CT-FFR is measured 2 cm distal to a stenotic lesion. A CT-FFR value >0.8 is considered normal, values between 0.76 and 0.8 denote a borderline condition, and a value of 0.75 or less represents an abnormal condition. Since CT-FFR of the LAD was lower than normal at rest, we reasoned that it should be even lower during physical exercise. The cardiac team concluded that the AAOCA was the reason behind the patient's syncope, following which a surgical correction with a modified unroofing procedure was performed. One week after surgery, repeat CT-FFR was performed to evaluate the effectiveness of the corrective surgery, and the result showed a successful revascularization of the LCA (Figure 3A) and a significantly improved LAD flow with CT-FFR 0.91 (Figure 3B). CT-FFR of the LCX (0.91) and RCA (0.88) remained within normal limits. The patient was discharged 10 days after surgery and followed up on an outpatient basis. He soon resumed his normal activities and had no recurrence of syncope.

anomalous aortic origin of a coronary artery, computed tomography angiography, fractional flow reserve, sudden cardiac death, unroofing procedure

PMC7529156_01

Male

Our patient, a 35-year-old right-handed male, a soldier by occupation and a resident of Greater Noida, Uttar Pradesh, India, presented with the complaints of fever for the past 2 weeks and altered sensorium for the past 4 days following an episode of generalized tonic-clonic seizure. There was no associated upper or lower respiratory tract symptoms, no burning micturation, ear discharge, rashes, or other skin lesions or head trauma. His investigations showed that he was HIV-1 reactive. He had a history of prolonged fever for 1 month a year back and had been diagnosed with tubercular lymphadenitis by the fine-needle aspiration study. He was prescribed rifampicin, isoniazid, pyrazinamide, and ethambutol for the same, and he was continuing to take all of them till date. There was no history of addictions. He was married for 7 years and had two children. Examination revealed normal vitals in a conscious but disoriented patient with a staring look and a Glasgow Coma Scale score of 11/15. General examination revealed pallor and oral thrush. Neurological examination revealed a Folstein's Mini-Mental State Examination (MMSE) score of 12/30 with no signs of meningismus. Due to the condition of the patient, whatever restricted examination of motor system, sensory system, and cranial nerves was possible was normal. Examination of cardiovascular, respiratory, abdominal, and musculoskeletal system was within normal limits. Investigations revealed an erythrocyte sedimentation rate of 33 mm (1st h) and a mild normocytic normochromic anemia (hemoglobin - 10.4 g%). Other biochemical parameters (liver function, kidney function, and blood sugar) were normal. Urine examination was also normal. A repeat testing of HIV by the ELISA confirmed the presence of antibodies against HIV-1. The CD4 count was 156/mm3, with a CD4 percentage of 14%. The differential diagnosis includes HIV with the likelihood of CNS opportunistic infections or HIV encephalopathy. Cerebrospinal fluid (CSF) examination reveals 10 cells, all mononuclear, with a sugar of 56 mg%, and a protein of 46 mg%. The adenosine deaminase levels were found to be 10 IU/L (within normal limits), and the CSF did not show any organism on Gram stain or Ziehl-Neelsen stain. The India ink staining for Cryptococcus was also negative. The polymerase chain reaction (PCR) in CSF was negative for Mycobacterium tuberculosis, human herpesvirus-6/herpes simpex virus, Toxoplasma gondii, and Cytomegalovirus. The PCR for JC virus could not be carried out due to financial constraints. Serum Widal, venereal disease research laboratory, hepatitis B surface antigen, Hepatitis C RNA, and IgG antibodies against toxoplasma were all negative. Imaging of the brain revealed bilaterally symmetrical, T2/FLAIR hyperintensities noted in the white matter, involving the bilateral centrum semiovale, periventricular, posterior limb of the internal capsule, and midbrain (cerebral peduncle) suggestive of encephalitis on magnetic resonance imaging [Figure 1]. The patient's attendant did not give consent for a brain biopsy. The final diagnosis was made to be HIVE in a treatment-naive patients with a CD4 count of 156/mm3 with oral candidiasis. He was started on antiretroviral therapy with triple-drug regimens of tenofovir, lamivudine, and efavirenz along with antieplieptics and fluconazole. After 3 months of follow-up, he was seizure free, and his MMSE revealed marked improvement (from 12/30 to 20/30). The CD4 count also showed improvement from 156/cumm to 325/cumm.

human immunodeficiency virus, and encephalitis, human immunodeficiency virus encephalitis, low cd4

PMC7719304_01

Female

The patient was a 38-year-old woman. Her main complaint was "deep abdominal pain and discomfort for nearly a month", accompanied by nausea and vomiting. After anti-infection treatment, abdominal CT revealed space-occupying lesions on the anterior edge of the inferior vena cava, which were diagnosed as a pancreatic tumor or enlarged lymph node. Ten days later, abdominal MRI showed abnormal signals at the hepatic hilum and near the celiac trunk, which led to the diagnosis of enlarged lymph nodes. The overall initial diagnosis was proposed as "pancreatic space-occupying lesions". The patient's clinical signs, blood routine, biochemical examinations, and duodenoscopy were all normal, and no abnormalities were observed in serum tumor markers AFP, CEA, CYFRA21-1, SCC, NSE, HE4, CA125, CA19-9, CA15-3, CA50, CA242, or CA72-4. Since the patient refused a biopsy of the tumor, 18F-FDG PET-CT was performed in order to understand the nature of the tumor and the condition of the systemic lymph nodes. As shown on 18F-FDG PET-CT (Figure 1), a soft-tissue mass about 2.8 cm in diameter was present in the hilar area, with punctate high-density shadows, unclear borders, and abnormal concentration of imaging agent. The maximum standardized uptake value (SUVmax) was 9.4 on initial imaging, but had became 12 2 hours later ony delayed imaging. Enhanced CT (Figure 2) revealed no vascular envelopment in the mass. Based on these results, the patient was diagnosed with tuberculosis of celiac lymph nodes. This diagnosis was confirmed by the strong positive result from the tuberculin test. Five months after antituberculosis treatment, the patient's clinical symptoms had disappeared. Follow-up checking using 18F-FDG PET-CT imaging (Figure 3) showed that the mass had become smaller with a diameter of about 1.5 cm, along with increased internal punctate high-density shadow and SUVmax reduced to 8.1. These follow-up findings demonstrated effective antituberculosis treatment and led to continued treatment for the patient.

18f-fdg pet/ct imaging, differential diagnosis, lymph-node tuberculosis

PMC5253515_02

Female

A 29-year-old woman diagnosed with Arnold Chiari malformations had an occipitocervical decompression surgery, due to progressive headache, in 2013. Two years later, a second decompression surgery was done due to progressive ataxia and paraesthesia in her right arm. During the surgery, a titanium plate was attached to the remains of C1, and a synthetic dural substitute was inserted. Postoperatively two MRI scans within a month revealed accumulation of CSF superficial to the dural repair site. A dural repair with a synthetic mesh was repeated twice. When the patient for the third time leaked CSF from the wound, the leakage was sealed with porcine ADM (StratticeTM pliable). A suitable piece of StratticeTM pliable was placed over the leak site and sutured, see Figure 1. Before closing, the ADM was covered with TachoSil and TissellTM. After insertion, no CSF leakage was observed. However, the inserted ADM pulsated. The soft tissue was closed in layers. No drains were inserted. Eight months postoperatively, the patient had not experienced further setbacks. The healing process is ongoing.

acellular dermal matrix, dural repair, dural substitute, porcine acellular dermal matrix, strattice

PMC5152955_01

Female

A two years old girl was admitted to our division because of fever, cough and dyspnea. The girl had arrived in Italy from Romania just seven days before when she reached his family living in a nomad camp. The first chest x-ray showed right pleural effusion and right middle and lower lobes consolidation. Antibiotic therapy was started without any clinical benefit. Therefore, a tuberculin skin test (TST) was performed with a markedly positive result after 72 hours. Because of sudden worsening dyspnea, emergency chest computed tomography (CT) was carried out and the presence of relevant pleural effusion all around the right lung, with parenchymal lung consolidation and paratracheal, subcarinal and hilar lymphadenopathy was highlighted (Figure 1). Interferon-gamma releasing assay (IGRA) tests firstly gave an indeterminate result but, repeated a week later, it gave a positive result. An evacuative thoracentesis was made and polymerase-chain-reaction (PCR) resulted positive for Mycobacterium tuberculosis (Mtb). An anti-TB therapy with isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZD) was begun with rapid improvement of the girl's clinical conditions. All the microscopic, nucleic acid amplification techniques and cultural exams carried out on gastric lavages and urine gave negative results for Mtb. The last chest x-ray, carried out after one month of therapy, showed an almost complete resolution of the pleural effusion, of the parenchymal disventilation areas and of the lymphadenopathy. About 75% of childhood TB disease is pulmonary and up to a third of all pediatric pulmonary TB cases may be complicated by pleural effusion, which may also be found without any significant concomitant parenchymal disease. Pulmonary TB commonly presents with a persistent (>21 days) and unremitting cough, with or without fever, not improving despite appropriate first line antibiotic treatment. The diagnosis of TB is not usually considered in a febrile child unless the fever is persistent (> 7 days) or other clinical features suggestive of TB are present. Positive family history for travelling or origins from TB endemic countries and overcrowded living environments should induce the diagnostic suspicion of TB. The examination of pleural fluid is important to establish the diagnosis of TB pleuropneumonia. Nevertheless, cultures of the fluid are positive only in a low number of cases and it takes them a long time to get the result. Nowadays PCR is an helpful diagnostic tool for early diagnosis and it has good sensitivity and specificity. During the last years, IGRA was introduced into clinical practice as a diagnostic tool with high specificity for the diagnosis of Mtb infection, even though it is not able (as TST) to discriminate between active TB disease and latent TB infection. During childhood, due to the lymphocytic anergy secondary to infections, IGRA tests may initially give indeterminate results. As a consequence, in case of strong suspicion of TB, IGRA should be repeated even in case of undeterminate results.

case-report, children, management, therapy, tuberculosis

Chest computed tomography revealed the presence of relevant pleural effusion all around the right lung, with parenchymal lung consolidation and paratracheal, subcranial and hilar lymphadenopathy.

PMC5152955_02

Female

A five year old girl, born in Romania and affected by neonatal hypoxic-ischemic encephalopathy, was admitted to our division because of fever and lymphadenopathy. The lymph-node was a latero-cervical, unilateral, painful, swelling lymph node fixed but soft in the middle, with the overlying skin appearing thin, shiny and erythematous. Lymph node characteristics did not change despite amoxicillin -clavulanate and anti-inflammatory therapy. The neck ultrasonography (US) highlighted hypoecoic, bunched, necrotic lymph nodes measuring 4.5 cm as a whole. TST showed a positive reaction (>15 mm induration) and the IGRA was positive. Ziehl Nielsen staining of the smears, cultures and nucleic acid amplification, collected by three early morning gastric washings and performed for up to three consecutive days, gave negative results for Mtb. Urine tests (Ziehl Neelsen staining, cultures and nucleic acid amplification) were negative too. Chest x-ray and abdominal US evaluation were negative. Surgical evaluation was performed and lymph nodes drainage was carried out by fine needle aspiration. The analyses carried out on the drained material showed a positivity of nucleic acid amplification (PCR) for Mtb. An anti-TB therapy with INH, RMP and PZD was begun. After the beginning of the therapy, girl's clinical conditions improved, fever disappeared and lymph nodes size progressively diminished. TB lymphadenitis in superficial nodes is the most common form of extrapulmonary TB in children. The laterocervical nodes become involved secondary to the extension of a primary pulmonary lesion. Lymph nodes localization develops 6-9 months after an initial TB infection. In developed countries more than two-thirds of pediatric lymphadenopathy have infectious causes other than TB, therefore cases of lymphadenitis are commonly treated with a high-spectrum antibiotic; nevertheless, it would be mandatory to give the instruction to return for reevaluation in case of no clinical improvement in order to perform other investigations to reach a final diagnosis. In our case, patient's medical history, familiar origins from a TB endemic country, and the particular lymph node characteristics (unilateral, involving multiple nodes, fixed to underlying tissues, initially non-tender, solid, covered by erythematous skin and successively tending to colliquation and fluctuation), should give the suspect of TB etiology and allow the beginning of the diagnostic procedures described in our clinical case. Systemic signs and symptoms other than low grade fever are usually absent. Primary medical treatment, aimed to reduction of the high-grade inflammation, could be also followed by surgical removal in order to prevent fistulae development. Since cross-reactivity between PPD-Mantoux test and non tubercular micobacteria (NTM) antigens, and less likely between IGRA tests and NTM antigens exists, microbiological tests performed on the infected lymph nodes should be the basis of differentiating between NTM and tuberculous lymphadenopathy.

case-report, children, management, therapy, tuberculosis

PMC5152955_03

Female

A two years old child of Rumanian origins, born in Italy to a TB-affected mother, was admitted to our division because of persistent fever (39 C). Chest radiography revealed a typical miliary reticulo-nodular pattern (Figure 2). IGRA tests, as well as Ziehl Neelsen staining of the smears, cultures and nucleic acid amplification (collected by undertaking three early morning gastric aspirate for up to three consecutives days), gave positive results for Mtb. Anti-TB therapy with INH, RMP, PZD and Etambutol (ETM) was begun. Nevertheless, only few hours after the beginning of therapy, the patient presented drowsiness and a diminished level of consciousness, horizontal nystagmus, trismus, frontal release signs (suck), miosis with loss of reaction to light. Cerebrospinal fluid examination was performed and revealed the presence of Mtb nucleic acid. A non-contrast head CT scan showed two hypodense space-occupying lesions in the subcortical white matter and in the knee of the right internal capsule. TB meningitis was therefore diagnosed and corticosteroid therapy was begun with a rapid improvement of his clinical conditions. However, a left hemiparesis appeared. Contrast-enhanced brain magnetic resonance imaging (MRI), performed one week after, showed meningeal enhancement, a reduced measures of the space-occupying lesion in the subcortical white matter, abnormal enhancement of basal cisterns and decreased diameter of the focalised lesion of the right internal capsule knee (Figure 3). A few weeks later, the child presented vomiting, apathy and drowsiness. The non-contrast head CT scan highlighted the presence of obstructive hydrocephalus and signs of intracranial hypertension (enlarged ventricles and peri-ventricular hypodensities). The child underwent ventricular-peritoneal derivation and symptoms resolution was achieved. The last contrast-enhanced MRI showed enlarged ventricles with no signs of intracranial hypertension and the presence of a focal lesion at the knee of the right internal capsule. An angio-RMI study showed no vascular abnormalities. To date, the patient shows good clinical conditions, although the left hemiparesis, requiring long term physiotherapy, is still present. An erosion of a parenchymal focus of TB into a blood or lymphatic vessel may result in dissemination of the bacilli and in a miliary pattern, with small nodules on the chest x-ray. The TB meningitis is the most severe extra-pulmonary TB-related complication, that results from hematogenous spread of primary or postprimary pulmonary disease or from the rupture of a subependymal tubercle into the subarachnoid space in a time of 3-6 months generally. A lot of cases show old pulmonary lesions or miliary pattern on chest radiograph. In fact, it's accepted a close concordance between TB meningitis and miliary TB in young children. Because of the haematogenous spread of bacilli during a lung miliary pattern, it is important to considerate the possibility of an extra-pulmonary involvement. In clinical practice two different types of Central Nervous System involvement may develop: tuberculoma and meningitis. Tuberculoma usually shows a good response to treatment, with resolution of acute signs and symptoms, even if with the possibility of sequelae depending on the first focal lesion. In contrast, the treatment of a meningeal involvement is still a clinical challenge. In fact, in our case, the anti-tubercular therapy was effective against lung and brain lesions, but the meningeal involvement showed a progression, up to meningeal thickening and hydrocephalus. The accelerating clinical illness usually correlates with the development of hydrocephalus, as in the present case. Even the use of high-dose corticosteroids may not stop meningeal inflammation. However, clinical trials demonstrated that corticosteroids should be routinely used in HIV-negative patients with TB meningitis to reduce death and disabling residual neurological deficits among survivors, although sometimes more aggressive anti-inflammatory drugs may be needed. Sometimes profound abnormalities in electrolyte metabolism may be observed, due to salt wasting syndrome or development of syndrome of inappropriate antidiuretic hormone secretion. We concluded the management of our patient with an angio-RMI study. TB can be considered as a vasculitis, and a significant percentage of children with TB generally presents ischemic brainstem lesions. Moreover, studies are necessary to show the exact meaning of these lesions, their implication for the patient's management and the possible use of anti-inflammatory and of anti-platelets agents to prevent neurological lesions and sequelae. The present case deals with a premature female infant, born in Italy from a Nigerian mother with HIV infection and pulmonary TB during pregnancy. The infant came to our attention, after having been in another hospital, because of pulmonary TB and HIV infection. At birth, she had an episode of asphyxia and was transferred to a Neonatal Intensive Care Unit (NICU). Two months after discharge from NICU, the child presented with weight loss, diarrhea, dehydration and acute severe dyspnea. Admitted to the Pediatric Intensive Care Unit, she was intubated and ventilated. Here the diagnosis of congenital HIV and TB was achieved on the bases of positive bacterioscopic analysis and PCR on the bronchoalveolar lavage, positive IGRA, positive bacterioscopic and cultures analysis on urine, positive cultures on the gastric aspirates and the presence of typical lesions in pulmonary CT scan. Abdominal US revealed two hypoechoic hepatic lesions and a hypoechoic spleen area. A case of congenital TB was then suspected because of urine positivity for Mtb and both liver and spleen hypoecoic lesions. She was admitted to our division in order to continue the anti-TB (INH, PZD, and ETM), corticosteroid and highly-active anti-retroviral therapy (HAART). An antibiotic prophylaxis with cotrimoxazole was also begun. The 6 months follow up shows a child in good clinical conditions. Congenital TB is a rare manifestation of TB. Clinical manifestations of congenital and neonatal TB are non-specific, they usually present like neonatal sepsis and diagnosis is often delayed. Low birth weight and prematurity are common features of HIV and TB infected neonates born to HIV-infected mothers with TB. Cantwell et al proposed diagnostic criteria for congenital TB. Among them we mention the onset of TB clinical manifestations in the first two weeks of life, the presence of a primary focus or granulomas in the liver and the demonstration of placenta and genital area contamination. These criteria increase diagnostic sensitivity, but the diagnosis remains difficult since confirmation of the primary complex or detection of granulomas in the liver has to be carried out by biopsy, which is not always available. In our case a liver biopsy was never performed. The co-infection between TBC and HIV really represents a clinical challenge for physicians, especially in childhood. Impressively, HIV-infected children demonstrate an increased risk of rapid disease progression, unsatisfactory treatment response and TB recurrence; moreover, TB mortality is six times higher among HIV-infected children than among uninfected ones. It has been showed that a close link exists between clinical developments of these two infectious diseases. On one hand TB is able to induce a quicker progression of HIV disease by increasing viral replication and reducing CD4+ T-cells counts. On the other hand, since protective immunity to TB infection depends on the CD4+ T-cell subset, HIV infected children with decreased CD4+ T-cells count are at greater risk of TB disease progression. TB treatment of HIV-infected children is a challenge, too. The lack of clinical trials in children creates concerns regarding common toxicities, drug interactions, side effects and the best time for the introduction of HAART following TB diagnosis. In fact, the management of TB in HIV-infected children usually deviates from standard protocols. Despite local and international guidelines, therapy often has to be individualized. Regarding the best time to introduce HAART, WHO recommends to begin the treatment at different time points, starting earlier in the more immunocompromised children or where response to TB treatment is poor. The management of TB-HIV co-infected children is of special difficulty due to the peculiar immunologic background and the extensive drug-drug interaction, and so requires a broader and specific discussion, which is above the purpose of this manuscript. The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance the tenets of the Helsinki Declaration, and has been approved by the authors' institutional review board or equivalent committee. Informed consent has been obtained from all individuals included in this study.

case-report, children, management, therapy, tuberculosis

PMC9484660_01

Male

A 54-year-old male, HIV-infected, undergoing antiretroviral therapy, with a history of pulmonary TB, was admitted to the infectious diseases department for dyspnoea, fever and asthenia. Two months previously, he had completed a 6-month course of anti-TB drugs with poor compliance. Clinical symptoms date back to these 2 months: persistent cough, low-grade fever, night sweats, fatigability and weight loss of 5 kg. On admission, the physical examination revealed mucocutaneous pallor, dyspnoea with decreased breath sounds in both lungs, fever (38.5-39 C) and a weight of 47 kg. Laboratory investigations showed anaemia (haemoglobin: 10.5 g dl-1), leucopenia (1.38 109 l-1), neutropenia (0.96 109 l-1) and lymphopenia (0.32 109 l-1). The CD4+ T-cell and CD8+ T-cell counts were 140 cells microl-1 and 180 cells microl-1 respectively, and the CD4+/CD8+ cell ratio was 0.78. The CRP level was high (171 mg l-1). A chest CT scan with maximal intensity projection showed scattered nodular consolidation with a tree-in-bud pattern predominantly in the upper lobe (Fig. 1). Testing for mycobacteria (Ziehl-Neelsen stain and GeneXpert), routine bacterial cultures and screening for respiratory viruses using the FilmArray respiratory panel with multiplex PCR were negative. The RT-PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and blood cultures were also negative. The patient was treated as a likely miliary TB and placed on empirical anti-TB drugs. He also received a combination of third-generation cephalosporin with aminoglycoside without significant clinical improvement. On day 15 of admission, a chest CT scan showed the appearance of a pleural effusion and worsening of consolidation (Fig. 1). A bronchoscopy with bronchoalveolar lavage (BAL) was performed. At this time, the patient had a fever of 40 C, respiratory distress and an increased CRP level of 243 mg l-1. Antibiotic therapy was changed to a combination of imipinem and aminoglycoside, together with trimethoprim/sulfamethoxazole and fluconazole (FLC) (200 mg/day). Direct examination of BAL fluid showed septate hyphae and annelloconidia (Fig. 2). The smears obtained by cytocentrifugation of BAL fluid were stained using the May-Grunwald-Giemsa method and examined under a light microscope with x40 and x100 objectives, ruling out Pneumocystis pneumonia. Culture on Sabouraud media showed the growth of cream-coloured, dry, cottony and circular colonies after 48 h of incubation at 35 C (Fig. 3). Lactophenol cotton blue preparation showed true hyphae with rectangular arthroconidia without blastoconidia (Fig. 4). Identification was done by the VITEK-2 System (bioMerieux, France) using a YST card with a probable value of 99 %. Species confirmation was carried out using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) (Bruker Daltonik, Bremen, Germany). The FLC treatment was continued. The susceptibility testing was performed using Fungitest (BioRad, France). The strain was sensitive to amphotericin B (AMB) and 5-flucytosine (5-FC) with a minimum inhibitory concentration (MIC) <2 mug ml-1 each, with intermediate susceptibility to FLC (8 mug ml-1 <MIC<64 mug ml-1). A second BAL was performed 1 day later and revealed similar results. Galactomannan antigenemia and blood cultures were negative. On day 20 of hospitalization, day 4 of FLC therapy, the patient was switched to AMB. However, the patient's clinical condition deteriorated rapidly, and he died due to septic shock. The patient was neutropenic with an absolute neutrophil count of 0.93 109 l-1 upon admission and 0.86 109 l-1 on the day of death. No autopsy was conducted.

hiv, saprochaete capitata, geotrichosis, lung, tuberculosis

PMC6243367_01

Male

A 26-year-old male patient of Indian origin who had previously defaulted on his treatment for tuberculous peritonitis (Figure 1), without other known comorbidities, presented with ptosis and down and outward deviation of the left eye. Clinical examination was positive for meningeal signs and complete left oculomotor nerve palsy. A lumbar puncture was performed, which yielded clear fluid with lymphocytic pleocytosis with very low cerebrospinal fluid (CSF) glucose level of 18 mg dl-1 (normal 45-80 mg dl-1). CSF adenosine deaminase level was 23.3 (normal 1-9 IU l-1). CSF polymerase chain reaction detected M. tuberculosis and M. tuberculosis complex consisting of M. bovis, M. microti and M. africanum. Serology was negative for human immunodeficiency virus infection. Cysticercosis immunoglobulin G level was found to be 0.9 ( >1.1 ng dl-1 is considered positive). MRI of the brain with contrast performed at this time showed multiple parenchymal nodular enhancing lesions in all the lobes of the bilateral cerebral hemispheres with mild surrounding oedema. (Figure 2) A diagnosis of multiple parenchymal tuberculomas with TBM was made. The patient was restarted on antitubercular therapy (ATT) with the addition of steroids. The left oculomotor nerve palsy clinically resolved with treatment. Repeat MRI performed 1 month later showed persisting basal meningeal enhancement with disappearance of most of the tuberculomas. However, the patient continued to have recurrent headaches. He completed the 9-month treatment course for the tuberculomas, but at follow-up 4 months after the conclusion of treatment, he presented with incontinence of urine for the past 2 months and one episode of generalized tonic-clonic seizures. A repeat MRI showed evidence of multiple rounded lesions that were mildly T1 hyperintense compared with the cortex and isointense compared with the white matter, and T2 hypointense compared with the cortex. There was perilesional oedema and ring enhancement of the lesions in a racemose pattern in bilateral insular cortices and sylvian fissures, with ring-enhancing lesions in the cavernous sinus, the pituitary and suprasellar cisterns, floor of the third ventricle, perimesencephalic cistern abutting the cerebral peduncles on both sides and the quadrigeminal cistern. Meningeal enhancement was present in the parasellar regions (Figure 3). This led us to suspect the possibility of recurrence of the tuberculomas, and the patient was started on antitubercular chemotherapy. A differential diagnosis of paradoxical response was considered. At this time, a chronic lacunar infarct in the left gangliocapsular region was noted (Figure 4). Despite extensive history taking and examination, no symptoms were attributable to this lacunar infarct. A clinical decision to continue the antitubercular chemotherapy with corticosteroids was taken. Following this, the patient adhered strictly to the treatment regimen, which started with isoniazid, rifampicin, pyrazinamide, ethambutol and streptomycin for 6 months with corticosteroids, followed by maintenance therapy with isoniazid, rifamicin and ethambultol. Two further contrast-enhanced MRI studies of the brain were performed over the next year, 6 months apart (Figure 5). There was an increase in the size of one of the lesions, while the other lesions remained of similar size. There were no new lesions, no development of hydrocephalus or meningeal enhancement. MR spectroscopy (MRS) was performed owing to the lack of response to ATT. MRS showed evidence of reduced choline and N-acetyl-aspartate, with a lipid/lactate peak (Figure 6). The patient is currently asymptomatic on maintenance treatment with isoniazid, rifampicin and ethambutol with corticosteroids, with the ring-enhancing lesions showing minimal change over 12 months (three 6-monthly MRIs). A current lumbar puncture shows normal CSF cytology and biochemistry with normal adenosine deaminase levels (1.75 IU l-1).

PMC9702973_01

Male

A 71-year-old man with a history of hypertension and type 2 diabetes was admitted to our hospital with a diagnosis of COVID-19 pneumonia from a private care facility. The patient was transferred to our hospital after a 48-hour admission to the emergency department of another hospital, where tocilizumab (maximum dose 800 mg) and corticosteroid (4 mg every 6 hours) were administered. An initial COVID-19 real-time polymerase chain reaction (RT-PCR) test for SARS-CoV-2 was performed using a throat swab, which showed a positive result for SARS-CoV-2. The patient had received no COVID-19 vaccine because it was not available in our country at the time of presentation of this case. On arrival, he presented with signs of hypoxemic respiratory insufficiency and showed pulmonary involvement by COVID-19 based on typical computed tomography (CT) findings (COVID-19 Reporting and Data System [CO-RADS] 5-6). Therefore, the patient was intubated, with an arterial oxygen partial pressure (PaO2)/fractional inspired oxygen (FIO2) ratio of 120 prior to intubation, and mechanical ventilation was initiated. Serum tests revealed leukocytosis: 29.000 k/uL, lymphopenia: 0.40 K/uL, C-reactive protein: 44 mg/L, interleukin-6 (IL-6): 4365 pg/mL, ferritin: >2000 ng/mL, D-dimer: 6520 ng/mL, lactate dehydrogenase (LDH): 785 U/L, and creatinine: 2.1 mg/dL. Culture samples were taken and empiric antibiotic therapy was started with imipenem and levofloxacin. After a few days of hospitalization, the patient's renal function deteriorated and, therefore, four hemofiltration sessions were prescribed. Chest radiography (CXR) revealed the presence of a cavitary image in the right upper lobe. On day 7, the hemoculture and urine culture results showed no bacterial growth; however, the patient's clinical condition did not improve. Broad-spectrum antibiotics, meropenem, vancomycin, and the antifungal fluconazole, were prescribed. In addition, a bronchoscopy procedure was performed, which revealed erythematous lesions in the bronchial tree, abundant purulent secretions, and a cavitary lesion mainly in the right bronchial tree (Picture 1). Bronchoalveolar lavage (BAL) revealed erythematous lesions in the bronchial tree, abundant purulent secretions, and a cavitary lesion, mainly in the right bronchial tree. The BAL samples isolated Klebsiella pneumoniae and Pseudomonas aeruginosa carbapenemase class A. Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) Biotyper mass spectrometry, molecular biology methods, multiplex PCR, and molecular identification were performed. The right BAL fungal culture isolated Trichosporon asahii (Picture 2A and B). The BAL sample was negative for both Ziehl Neelsen (ZN) stain and GeneXpert mycobacterium tuberculosis (MTB)/rifampicin (RIF; Xpert), and the Lowenstein-Jensen culture for tuberculosis was also negative. Ceftazidime/avibactam, colistin, and voriconazole were administered. Despite all the efforts, the patient presented with disease progression, septic shock, and multi-organ failure, and died after 15 days of hospitalization. (See the time lines in Table 1). Unfortunately, the evolutionary chest CT was not performed in this patient because the equipment was under technical maintenance due to excessive demand during the pandemic. However, disseminated opacities were observed in all lung quadrants, indicative of severe CARDS (Picture 3).

sars-cov-2, bronchoalveolar lavage, fungi, intensive care units, spike protein

PMC5777553_01

Female

A 37-year-old female professional dancer sustained an ACL injury to her right knee in a motorcycle accident in 2011. She underwent subsequent ACLR. At the time of surgery, examination revealed 3+ Lachman and 3+ pivot-shift tests, with no concomitant injuries. The reconstruction was performed with 8-mm-diameter quadrupled hamstring tendons, normally the first choice for women at this age in our country. The femoral tunnel was drilled close to the anteromedial bundle position with an outside-in technique. The fixation was performed with metal interference screws at 30 of knee flexion. Postoperatively, the patient participated in standard rehabilitation for ACLR and underwent an uncomplicated recovery. Even though an improvement in instability was noted in activities of daily living, the patient still complained of episodes of giving way with rotational movements, mainly during dance-related jumping and landing exercises. As a result, further rehabilitation was prescribed focusing on quadriceps and gluteal muscle strengthening and proprioception. One year following ACLR, the patient had good core stability and negative Lachman (KT-1000 of 4 mm) and anterior drawer test results but had a residual pivot glide. Despite continued participation in rehabilitation, the patient was unable to perform professional dance activity owing to persistent rotatory instability. Given the failure of this additional nonoperative treatment at 2 years following ACLR, a surgical procedure was considered. It was noted that the first reconstruction was technically adequate, with an intact graft (Figure 1) and appropriate tunnel positioning (Figure 2). There was no clinical or magnetic resonance imaging evidence of concomitant intra-articular pathology (eg, altered bony morphology, tibial slope, or meniscal/chondral lesions). The surgical options initially proposed were ACL revision or an augmentation of the posterolateral bundle. The patient was counseled regarding the surgical morbidity and possible complications of a revision procedure. In addition, the possibility of performing an isolated reconstruction of the ALL was discussed. It was specifically stated that isolated ALL reconstruction had not previously been reported as a treatment for persistent instability after a technically adequate ACLR but that we had experience of good results of combined ACL and ALL reconstructions for the treatment of patients with high-grade pivot shift. The patient was completely aware and accepted the risks of ALL reconstruction in preference to a revision ACL procedure. Initially, knee arthroscopy was performed to assess the integrity of the ACL graft and any associated lesions. The ACL graft, though with an imperfect vascularized appearance and minimal laxity, was intact and functional, and no associated lesions were found. For the ALL reconstruction, a lateral incision was made in line with the iliotibial band, and a femoral tunnel on the posterior border of the lateral epicondyle and a tibial tunnel between the Gerdy tubercle and the fibular head (7 mm distal to the lateral tibial plateau) were created with a 7-mm drill. An allograft semitendinosus tendon from our institution's tissue bank was used as a graft, and fixation was performed at 30 of flexion and neutral rotation with absorbable 7 x 25-mm interference screws (Smith & Nephew) (Figures 3 and 4). The allograft was chosen because, despite being a low-morbidity solution, we did not want to harvest either the iliotibial band or the contralateral side. After the ALL reconstruction was performed, repeat clinical examination revealed that the preoperative pivot glide had been abolished (see the Video Supplement). Postoperative rehabilitation comprised immediate range of motion exercises and full weightbearing with a brace worn while walking for 3 weeks. At 6 weeks postoperatively, the patient stated that the knee was more stable, and at 3 months, she returned to her dance activities without restriction and without subjective complaints of rotational instability. At 4 months after the ALL reconstruction, she was back to her preinjury level of dance participation. At 2 years after reconstruction of the ALL, the patient experienced no further instability and had negative pivot-shift and Lachman test results. The IKDC score increased from 87.4 at 4 years after ACLR to 96.6 at final follow-up after ALL reconstruction. Informed consent was obtained from the patient for publication, including photographs and video material.

anterior cruciate ligament, anterolateral ligament, pivot shift, rotatory instability

PMC7287400_01

Female

A 44 year old Caucasian woman complained of very intense low back and pelvic pain episodes. She had two previous pregnancies with vaginal deliveries and a family history of acute myocardial infarction, stroke, and hypertension. A previous laparoscopy (Fig. 1A, B) revealed substantial pelvic and abdominal vascularisation on the left in the infundibulum and inferior vena cava, excluding the diagnosis of endometriosis. On physical examination, the patient was 47 kg and her body mass index was below 18.5 kg/cm2. Two imaging tests (Fig. 1C, D) demonstrated compression of the LRV between the SMA and the aorta, suggesting reflux to the left ovarian vein, which was significantly dilated, and explaining the pelvic varices secondary to renal vein compression visible on laparoscopy. Because the diagnostic hypothesis was pelvic congestion secondary to NCS, the chosen approach was intravascular stent placement (Zilver Vena stent, 16 mm x 60 mm, Cook Medical, US) and balloon angioplasty (ATB Advance, 14 mm x 40 mm, Cook Medical, US) (Fig. 2A, B). Doppler ultrasound (Fig. 3B) and post-operative computed tomography (CT) angiography confirmed that the device was properly placed and the LRV compression was resolved (Fig. 3A, C). The patient reported improvement of symptoms. Nevertheless, one month later, she returned because of intense pain episodes, similar to the previous ones. Doppler ultrasound and magnetic resonance angiography (Fig. 4A) confirmed that the stent was correctly placed, and a patent LRV suggested that the NCS was resolved. Because the patient continued to complain of pain, a new ultrasound was performed, this time by a different operator, to examine the various painful sites. This examination revealed extrinsic compression of the LRV proximal to the vena cava, now by the portal vein (Fig. 4B). The patient underwent a second surgical procedure for diagnostic purposes to confirm the potential compression. The procedure was performed under local anaesthesia and, as the catheter and guide wire passed through the renal vein, the patient reported low back pain. Following sedation, an intravascular ultrasound (Fig. 5A) was performed, and measurement of intravascular LRV pressure before and after stent placement (Fig. 5B) showed pressure differences and extrinsic vein compression, suggestive of significant stenosis. Then, a second intravascular stent was placed (Zilver Vena stent, 16 mm x 60 mm, Cook Medical, US) using a telescoping technique. The patient remained without pain for two weeks and was discharged from the hospital. Then, the pain returned. Doppler ultrasound (Fig. 6A), magnetic resonance imaging, and excretion urography revealed nephroptosis of the right kidney (Fig. 6B) that had been previously undetected (Fig. 3A). As the case was reassessed, the patient reported extreme joint mobility for the first time which, in association with the new image demonstrating nephroptosis, opened a new line of investigation. The patient scored 9 (maximum score) on the Beighton scale and met the criteria for EDS and hypermobility. She was referred to a team specializing in pain management with nerve block and to the genetics department, where the diagnosis of EDS was confirmed.

diagnosis, low back pain, nutcracker syndrome, pelvic pain, treatment

PMC8712700_01

Male

Patient 1 (male) presented with hyperopia and astigmatism at age 6. Shortly after, bilateral neurosensorial hearing loss was diagnosed and required the use of bilateral hearing aids. IDDM was diagnosed at age 6.7 years and treatment with multiple daily insulin injections (MDI) was initiated consisting of insulin aspart and glargine. Double heterozygous missense WFS1 gene variants (c.409_424dup16; p.Val142fs*251 and c.1628 T>G; p.Leu543Arg) were confirmed at age 7.8 years with Sanger sequencing. One year later, patient 1 developed diabetes insipidus (see Table 1). At baseline, aged 11.3 years, with a standardized body mass index (sBMI) of 0.82, insulin requirements of 1 U/kg/day, patient 1 had a C-AUC of 122 ng*min/mL, HbA1c of 8% (64 mmol/mol), and a TIR of 53% and TAR of 40%. Liraglutide was initiated at 0.6 mg/day and the maximum dose of 1.8 mg/day was progressively achieved. As shown in Figure 1, at the latest 27-month follow-up C-AUC decreased to 102 ng*min/mL. Insulin requirements decreased to 0.47 U/kg/day, HbA1c improved to 7.5% (58 mmol/mol). Glucometrics via CGM showed improvements in TIR and TAR at 71% and 21%, respectively while TBR remained stable. The total daily insulin dose (TDD) was reduced by 53%. No adverse events occurred. Patient 2 (female) had an unremarkable medical history except for transient mild speech delay. IDDM was diagnosed at age 5.2 years and insulin therapy was started with MDI consisting of insulin aspart and glargine. At age 8.2 years, two previously unreported likely pathogenetic variants (c.316-1G>A; c.757A>T and p.Lys253Ter), a splice site disruption and premature stop codon respectively, were identified by Next Generation Sequencing (NGS), and a WS diagnosis was confirmed. At baseline, aged 10.7 years, patient 2 presented with a sBMI of -2.08, insulin requirements of 0.28 U/kg/day, C-AUC of 28 ng*min/mL, HbA1c of 6.7% (50 mmol/mol), and a TIR of 69% recorded via CGM. Liraglutide was started at a dose of 0.3 mg/day and gradually increased to 1.8 mg/day. At 20 months, C-AUC increased to 48 ng*min/mL, TDD, TIR, TAR, TBR, and HbA1c remained stable. No severe adverse events were recorded. Patient 3 (male) was diagnosed with IDDM at age 9 years and began insulin therapy with MDI consisting of insulin lispro and glargine. Prior to being diagnosed with IDDM, the patient had been complaining of visual impairment. Past medical history was unremarkable except for a transient mild motor delay. Family history was positive for bilateral congenital hypoacusia in his biological father and sister. WS diagnosis was established by NGS which confirmed a double heterozygous missense variant (c.605A>G; p.Glu202Gly and c.1289C>T; p.Ser430Leu) at age 11.4 years. At baseline, aged 12.3 years, patient 3 had a sBMI of 1.59, C-AUC of 111 ng*min/mL, HbA1c of 7.5% (58 mmol/mol) and insulin requirements of 0.5 U/kg/day. TIR, TAR, and TBR were 70, 20, and 10% respectively. Liraglutide was started at a dose of 0.3 mg/day and progressively increased to 1.8 mg/day as tolerated. At the 16-month follow-up the patient showed sBMI of 1.92, C-AUC of 90 ng*min/mL, HbA1c of 9.4% (79 mmol/mol), insulin requirements of 0.78 U/kg/day, and a TIR of 29%. TDD remained stable. No adverse events occurred. Patient 4 (male) was diagnosed with IDDM at age 12.3 years and started insulin therapy with MDI consisting of insulin aspart and glargine. Prior to his diabetes diagnosis, the patient had an unremarkable past medical history. At age 13.4 years the patient complained of worsening vision and heterozygous WFS1 variants revealed a premature stop condon and missense variants (c.387G>A; p.Trp129 and c.1675G>C; p.Ala559Pr respectively) was confirmed with Sanger sequencing which revealed a double heterozygous variant. At baseline, age 14, patient 4 had a C-AUC of 296 ng*min/mL, HbA1c of 8.5% (69 mmol/mol), sBMI of -0.77 and insulin requirements of 0.4 U/kg/day. Glucometrics recorded TIR, TAR and TBR were 73%, 26%, and 1% respectively. Liraglutide was started at a dose of 0.6 mg/day and progressively increased to 1.8 mg/day as tolerated. At the latest 8-month follow-up, patient 4 had a sBMI of -1.17, C-AUC measuring 313 ng*min/mL, HbA1c improved to 7.1% (54 mmol/mol) and insulin requirements decreased to 0.08 U/kg/day. Glucometrics recorded TIR and TAR at 62% and 38%. TDD was reduced by 80%. No adverse events occurred.

glp1 receptor agonists, wolfram syndrome, wolfram syndrome 1 (wfs1), liraglutide, monogenic diabetes, neurodegeneration

PMC7522523_01

Female

The challenges of HdI in case of COVID-19 are: (i) less effectiveness, periodic outbreaks can still occur, (ii) unevenly distributed within a population, clusters of susceptible hosts that frequently contact one another may remain, (iii) the proportion of immunized individuals surpasses the HdI threshold, susceptible individuals will be found in the risk zone for local outbreaks, (iv) nonrelevant infection fatality rate (IFR) and case fatality rate (CFR). Still there is no straightforward, ethical path to reach the goal with HdI in case of COVID-19, due to the societal consequences of achieving it are devastating. A nonuniform COVID-19 case fatality rate (CFR) has been reported across age groups, with the vast majority of deaths occurring among individuals 60 years old or greater. Sex- and ethnicity-specific CFRs suggest that genetic, environmental, and social determinants may affect in susceptibility to COVID-19 and the severity of SARS-CoV-19 infections. Sodium chloride (NaCl) also called 'table salt' as coating material on the fiber surface of the filtration unit of surgical mask effectively deactivated a number influenza virus species, suggesting a new strategy in the protective measures to avoid primary/secondary infection and transmission of many viruses, including SARS-CoV-19. On the other hand, the natural adsorbents, including clay, charcoal, and clay minerals showed 99.99% adsorption of CoVs. Some minerals that may act against CoVs are selenium, copper, iron, chromium, potassium, zinc, and so on. Moreover, medicinal plants or their derivatives are also evident to act against hCoVs. The main limiting aspects of this comprehensive review emerge from the studies that have been performed on these drugs that are still only experimental. Many of the studies analyzed included a relatively small number of patients and as a result data that are not statistically significant. That is why many old drugs with a well-known mechanism of action are re-proposed for the treatment of COVID-19. As no vaccine against COVID_19 has been approved yet, vaccine types have not been included in this paper. In addition, this review did not consider the cases of special patients such as the pediatric population and pregnant women, as they are excluded from clinical trials for ethical reasons. The strength of this review is providing of the recent data with regard to the management of the COVID-19, within the environment in which information is rapidly changing and being made available; and it will be beneficial to health professionals.

covid-19 proposed therapy, severe acute respiratory syndrome coronavirus 2 (sars-cov-2), convalescent plasma, pandemic, therapeutic challenges

PMC6311819_01

Male

Our patient is a 38-year-old male who presented with right chest wall and shoulder pain after a weight lifting injury. The patient was performing a one-rep max bench press when he felt a pop in his right upper arm, accompanied by severe pain. There was no history of anabolic steroid use. He was initially treated with ice and a sling by a trainer and presented to the emergency department for further evaluation. Plain films were negative for fracture or dislocation and the patient was neurovascularly intact, so he was discharged home by ER staff in the sling. He presented to the orthopedic clinic the following day with moderate pain in the chest and arm. He denied numbness and paresthesia. On physical examination, there was a large amount of swelling and ecchymoses throughout the right upper arm extending into the pectoralis major muscle belly. Additionally, there was a large bulge in the anterior chest with loss of contour of the axillary fold (Figure 1). The patient had full active range of motion of the elbow, wrist, and digits. He was sensory intact throughout the right upper extremity with a 2+ radial pulse. An MRI was scheduled to determine the extent of the injury and to aid in surgical planning. The patient was given oxycodone and valium to alleviate the pain and muscle spasms until surgery, which was scheduled after his MRI. The MRI demonstrated avulsion of the pectoralis major tendon from its insertion on the humerus with retraction as well as strain of the anterior deltoid (Figures 2 and 3). He was scheduled for surgery in five days. Two days later, the patient returned to our facility with severe worsening pain in the right upper arm. Intracompartmental pressure readings in the anterior compartment of the arm taken about the midpoint of the biceps at the point of maximal swelling were 37, 39, and 42 mmHg with a diastolic blood pressure of 71 mmHg (Figure 4). Thus, with a diagnosis of compartment syndrome confirmed, we proceeded to the operating room for an emergency fasciotomy with repair of the pectoralis major tendon rupture. An extended deltopectoral approach was used, and the deltopectoral and biceps fascia were released. Immediately, a large amount of hematoma was expelled and the muscle bellies visibly bulged from the incision sites (Figures 5 and 6). All muscles still appeared viable. No apparent vascular damage was noted. Upon further dissection, both heads of the pectoralis major were found to be avulsed from the proximal humerus (Figure 7). After preparation of the footprint with curette and rongeur, three double-loaded 4.5 mm Mitek suture anchors (DePuy Synthes, Raynham, MA) were placed lateral to the bicipital groove for the repair of the tendon. The proximal and distal suture anchors were used such that one suture of each was run in a Krakow fashion along the superior and inferior aspects of the tendon, respectively. The remaining suture from each of those anchors was passed in a horizontal mattress fashion medial to the Krakow stitches. The middle suture anchor was used to place a horizontal mattress stitch with a medial ripstop stitch (Figure 8). The wound was irrigated, and a negative pressure dressing was applied. The patient was made nonweightbearing and placed in a sling with a circumferential strap to ensure adduction of the arm. The patient returned to the operating room four days later to undergo irrigation and debridement with a tension-free primary wound closure. He was again placed into his sling and given strict instructions to avoid abduction and external rotation of the arm. The patient did well postoperatively and was discharged home in a stable condition that same day with a one-week follow-up appointment. He continued to do well and was instructed to remain nonweightbearing in his sling for a total of 6 weeks before beginning formal therapy. Gentle stretching and passive range of motion were then begun, followed by strengthening exercises at the 12th week mark. At his four-month follow-up, the patient had active forward flexion of the shoulder to 150 , abduction to 150 , and external rotation of 50 . His rotator cuff, biceps, triceps, wrist extensors, wrist flexors, and interossei all demonstrated 5/5 strength. There were no sensory deficits on examination. He continues to attend therapy for motion and strengthening and has a lifting restriction of <5 pounds at work.

PMC6370127_01

Male

A 66-year-old male patient who suffered recurrent pleural effusion for more than 6 months and coughed for 2 months was admitted to hospital for clear diagnosis and treatment. He was previously engaged in a job which exposed him to dust and talcum powder for a long time. He underwent right thoracentesis and anti-infective treatment before admission. The patient's cough and shortness of breath were slightly relieved. He still experienced pleural effusion and had symptoms of cough and shortness of breath. On physical examination, the patients' blood pressure was 110/80mm Hg and SaO2 was 96%. Respiratory rate was 18 times per minute. Heart rate was 87 times per minute. Temperature was 36.8 C. There was decreased breath sound at right lung base. There was no edema in lower limbs. Laboratory examinations revealed that complete blood count and serological data, including the C-reactive protein level and procalcitonin level, was within the normal range. Laboratory tests related to the immune system were also negative. The comprehensive metabolic panel, including total protein, liver function tests, showed pro-BNP of 1211pg/mL, D-dimer of 4.85ug/mL, total protein of 47.1 g/L, albumin of 31.9 g/L, globulin of 15.2 g/L, serum troponin I of 0.002ng/mL. Echocardiography indicated diastolic dysfunction. Chest X-ray taken at the time of admission demonstrated bilateral pleural effusion. There was much pleural effusion on the right side. During the hospitalization, the patient underwent thoracentesis 3 times on right side while 1 time on left side. The 1st thoracentesis which is performed on day 1 of admission drainaged egg-yellow effusion (Fig. 1). The biochemical examination showed lymphocyte count of 98%, monocyte count of 2%, glucose of 6.88 mmol/L, total protein 37.8 g/L, lactate dehydrogenase (LDH) of 96mmol/L, adenosine deaminase of 5.1U/L. The subsequent 2 thoracentesis also presented as egg-yellow effusion. The biochemical result were suggestive of exudative effusions for both of them. Cultures were also negative. Cytological examination of all pleural effusion samples revealed mesothelial cells and numerous lymphocytes without cancer cells. For this patient with repeated pleural effusions, we considered the possibility of pneumonia effusion, or tuberculosis, or tumor? Initial treatment was mainly based on anti-infective therapy in the early hospital stay. Levofloxacin was selected as antibiotics. However, we found that pleural effusion did not decrease but increased after a dynamic observation of pleural fluid using doppler ultrasound examination. As a result, we suspended the use of levofloxacin on day 14 of admission. Other diagnosis was suggested. In order to find the diagnosis, thoracoscope (day 5), GeneXpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) test on pleural effusion (day 13) and chest CT angiography (day 15) were all performed during early hospitalization. GeneXpert MTB/RIF test on pleural effusion was negative. Chest CT angiography demonstrated left lower pulmonary embolism (Fig. 2). The thorascopy showed hyperaemia and black tissue of the parietal pleura, that were biopsied. The specimen was submitted for cytopathologic valuation. Paraffin electron microscopy of pleural biopsy was consistent with pleural amyloidosis (Fig. 3). The lesion was mainly comprised of amyloid deposition. Congo red stain was positive in the pleural tissue (Fig. 4). When viewed under polarized light, the affected tissue typically shows apple-green birefringence after staining with Congo red (Fig. 5). The stainability of Congo red stain was not lost by potassium permanganate treatment, the lesion was pathologically confirmed to be amyloidosis, excluding the amyloid protein A (AA) type (Fig. 6). The patient refused bone marrow biopsy. We could not further distinguish whether the disease was primary or secondary, despite there were no significant clinical symptom of multiple myeloma. As a result, immunoglobulin light chain (AL) type amyloidosis of pleura was suggested. The final diagnosis of this patient was AL pleural amyloidosis and left lower pulmonary embolism. In aspect of pulmonary embolism, Nadroparin calcium combined Warfarin were performed as anticoagulative therapy. Thirteen days later, chest CT angiography did not see previous pulmonary embolism lesion (Fig. 7). And the patient's heart was functioning normally. In aspect of pleural amyloidosis, the patient was repeatedly advised to undergo bone marrow biopsy and pleurodesis. The patient refused and requested for discharge after serious consideration. The patient's shortness of breath was relieved at the time of discharge, and the pleural effusion was less than before. After discharge, the patient's phone could not be connected during our follow-up.

PMC7210920_01

Male

A 16-year-old previously healthy young man presented to the Pediatric Infectious Disease Clinic in September of 20151week after arriving in the United States from a refugee camp in Mozambique with a 3-month history of pain and swelling in the upper leg just below the knee. He had no fever noted, no erythema over the knee, and his symptoms had not changed appreciably since arrival in the United States. He had not received any antimicrobial therapy for this condition. His erythrocyte sedimentation rate (ESR) at presentation was 40 mm/h with a C-reactive protein (CRP) level of 0.9 g/dL and a leukocyte count of 6,900 cells/microL (50% polymorphonuclear cells, 37% lymphocytes, 11% monocytes, 1% eosinophils, and 1% basophils). On examination, his affected knee was slightly swollen with mild tenderness over the medial aspect. No discharge or erythema was noted. His range of motion for his knee was slightly decreased for flexion and extension, and an antalgic gait was present. At that time, a plain radiograph demonstrated concerns of chronic osteomyelitis of the right proximal tibia although tumor or subacute fracture was also considered (Fig. 1). Contrasted magnetic resonance imaging (MRI)demonstrated findings consistent with chronic osteomyelitis along the medial aspect of the proximal tibial epiphysis and metaphysis, however, with a cloaca extending from a cortical disruption of the posteromedial tibial metaphyseal cortex (Fig. 2). Given a desire to pursue potential debridement and obtain cultures simultaneously, he underwent surgical debridement of the area the following day, cultures from which were sterile. Given his recent exposure to a refugee camp in Africa, the resulting potential for infection with an unusual organism was also felt to justify the need for an open biopsy with cultures. A cortical window was not created although extensive debridement of the area was performed. The joint space was not entered during the surgery. No orthopedic hardware or antimicrobial-impregnated beads were placed. Post-operatively, his wound healed well, with resolution of a serous drainage after several days. Given a non-reactive QuantiFERON gold assay for Mycobacterium tuberculosis and the frequency with which Staphylococcus aureus is implicated in osteoarticular infections in otherwise healthy children, we pursued empiric therapy for methicillin-susceptible S. aureus with nafcillin (chosed for its potent activity against this pathogen and ability to administer as a continuous infusion at home).He demonstrated marked improvement after completing 6 weeks of parenteral therapy, and his ESR and CRP normalized approximately 8 weeks into treatment. Per our local practice guidelines, he completed 6 months of total therapy with cephalexin in April of 2016. Given involvement of the growth plate with his infection, follow-up imaging was obtained 10 months post-operatively, which revealed a 1.3 cm leg length discrepancy (right leg shorter than his left). He was seen again in the infectious disease clinic 3 months after antibiotic completion and was back to his normal baseline, with plain radiographs demonstrating no concerns of recrudescent disease. A follow-up MRI was not obtained. He played a season of varsity soccer for his local high school that fall without incident. In April of 2017, approximately 1 year after completing therapy, he was seen in the infectious disease clinic again. At that time, the patient reported a 7-day history of pain, redness, and swelling along the inner aspect of the right upper leg below his knee overlying his prior surgical site. However, his father reported that he had complained of these findings for several months. A firm, tender erythematous mass over the medial aspect of the proximal tibia was noted on examination, underlying his surgical scar, although no drainage was present and the range of motion of his knee was normal. He had been a febrile and denied any recent trauma to the area. His ESR and CRP were normal at this time, as was his total leukocyte count and his differential leukocyte count. Plain radiographs demonstrated concern of recrudescent chronic osteomyelitis in the proximal tibia, with worsening sclerotic changes compared with his most recent radiograph (Fig. 3). A contrasted MRI demonstrated abnormal signal intensity in the proximal tibial metaphysis and epiphysis, with an abscess connected to a nidus of presumed chronic osteomyelitis througha fistula tract running inferior to the physis (Fig. 4 and 5). He was taken to the operating room shortly after this, where an abscess eroding through to the posterior aspect of the proximal tibia was noted. The superficial portion of the abscess was drained, with drilling through the affected bone into the posterior aspect of the tibia followed by curettage of the entire area. A cortical window was not created nor was periosteal elevation noted. His post-operative wound healing was uneventful. Operative cultures produced monomicrobial growth of P.aeruginosa, which, given the heavy growth in the primary streaks on the agar plate, was not felt to be a contaminant. This isolate demonstrated intermediate resistance to piperacillin-tazobactam (minimum inhibitory concentration (MIC)=32/4 mg/L), resistance to gentamicin (MIC>2 mg/L), aztreonam (MIC>16 mg/L), and ciprofloxacin (MIC>2 mg/L).The isolate was susceptible to meropenem (MIC of 1 mg/L), cefepime (MIC of 8 mg/L), ceftolozane and tazobactam (MIC=1.5 mg/L), and ceftazidime (MIC of 4 mg/L).Cefepime and ceftazidime MICs were confirmed with E-testing.Noimprovement was seen after 72 h of empiric cefazolin, but he did improve following transition to meropenem. Immunological evaluation revealed normal levels of natural killer cells, immunoglobulins (IgG, IgA, IgM, and IgE), tetanus, and pneumococcal antibodies. A lymphocyte subset panel was normal. He also demonstrated a normal lymphocyte proliferation response to phytohemagglutinin and pokeweed mitogen and a non-reactive serology to human immunodeficiency virus.Given the absence of an oral treatment option, he was treated initially with several days of cefepime, followed by 49 days of meropenem. He was then transitioned back to cefepime for 14 days followed by 56 days of ceftazidime. A contrasted MRI performed 7 weeks and plain radiographs performed 3 months into treatment demonstrated no recrudescence of disease (Fig. 6). He maintained normal inflammatory markers during treatment. At the end of 4 months of therapy, his physical examination was normal and his antibiotic therapy was discontinued. He denied any persistent symptomatology and was participating in soccer again without difficulty.

chronic osteomyelitis, pseudomonas, nosocomial

PMC5479967_01

Male

A 39-year-old African American man presented to the Emergency Department (ED) with a one-week history of epigastric pain. He had a seven-year history of chronic arthritis in his hands, feet, and back but was otherwise healthy. He reported experiencing epigastric pain after dining out for his birthday a week prior to presentation. The pain was gnawing, non-radiating, non-positional, and constant, but there were no fevers, chills, nausea, vomiting, or diarrhea. All other individuals dining with him were asymptomatic. He medicated himself with naproxen but the pain worsened, prompting his visit to the ED. The patient had emigrated from Cape Verde to the United States 20 years previously. He was a bodybuilder, had noticed recent weight loss as well as a poor appetite and had lost 30lbs in the three months before presentation. He lived with his wife and worked for a printing company, did not smoke tobacco or use illicit drugs, rarely drank alcohol and had no allergies. There was no family history of note. His only outpatient medication was naproxen as needed for arthritis. On examination he was in extreme pain with a blood pressure of 112/70, pulse 111, respiratory rate 18, and oxygen saturation was 100% breathing room air. Abdominal examination revealed a flat abdomen, normoactive bowel sounds, no bruits, a soft and tender epigastrium, and no rebound tenderness, rigidity, or guarding. Carnett's and Murphy's signs were negative. There were no palpable masses, no hepatosplenomegaly, and no hernias. Rectal examination was normal. There was no palpable lymphadenopathy. There was no active synovitis, palpable swelling, or joint line tenderness on peripheral joint examination. Neurological examination was non-focal. Laboratory results revealed microcytic anemia (Hb 11.9 g/dL; normal 13.5-18 g/dL) and mild leukocytosis (Table 1). Contrast-enhanced computed tomography (CT) of the abdomen and pelvis showed extensive mesenteric lymphadenopathy (Fig. 1). He was admitted to the general medical floor due to his intractable abdominal pain and for further workup. At that point, the differential diagnosis for this relatively young man with chronic joint pain, chronic weight loss, recent onset epigastric pain, and microcytic anemia included primary GI lymphoma, gastroduodenal tuberculosis (TB), and peptic ulcer disease. He was treated with morphine, pantoprazole, intravenous fluids, and kept nothing by mouth for an esophagogastroduodenoscopy (EGD) the following day. The EGD performed on admission day two was macroscopically normal; gastric and duodenal biopsies were taken. He resumed eating and the abdominal pain was controlled with acetaminophen. On admission day three, he underwent ultrasound-guided mesenteric lymph node biopsy. The same day, histopathological examination of the duodenal biopsy revealed Periodic Acid-Schiff (PAS)-positive macrophages. Whipple's disease was diagnosed, and the mesenteric lymph node biopsy was subsequently found to be congruent with a diagnosis of Whipple's disease, revealing PAS-positive macrophages (Fig. 2). The patient received ceftriaxone (2 g i.v.) for two weeks and was prescribed trimethoprim-sulfamethoxazole (160 mg trimethoprim/800 mg sulfamethoxazole) for one year. At six months follow-up, abdominal pain and arthralgia had resolved.

mesenteric lymphadenitis, trimethoprim-sulfamethoxazole, whipple’s disease

PMC5463149_02

Male

The diagnosis of autism was made at the age of 3 years based on communication and social interaction impairments and restricted, repetitive patterns of behaviour and interests. Behavioural problems were reported early, before the age of 2 years, with intense and repeated mutilations of cheekbones and eyes, culminating in a bilateral blindness at the age of 4 years by intumescent white cataract after numerous surgical complications. Behavioural problems and self-injurious behaviours (SIB) compromised his school attendance. The parents separated when he was five years old. The patient was hospitalized three times in a child psychiatry unit thereafter with inconclusive antipsychotic treatments. He remained without specialized care. He only received the occasional intervention of associative home help. A major developmental regression was reported at home after the loss of sight: increasingly important attachment to adults and grasping behaviour, loss of walking, increase in SIB, and a diet almost exclusively made up of dairy products. At the age of 7 years and 7 months, he was admitted in a dedicated neurodevelopmental child psychiatric unit. He was initially prescribed tiapride hydrochloride 40 mg/d, cyamemazine 40 mg/d, paracetamol 600 mg/d, melatonin 6 mg in the evening, hydroxyzine dihydrochloride 25 mg/d when needed, and two ophthalmic eye drops. SIB were prominent and nearly permanent, preventing any interaction: knee blows on his face, punches against his cheekbones, and banging his head against the walls. He did not react to the sound of his name or to simple instructions. He had lost the ability to walk and moved on his back by jerking on the ground or requested to be carried, constantly clinging to adults. Eating at a table was unthinkable. He was spoon-fed, immobilized. Several episodes of regurgitation and vomiting, followed by rhinorrhoea, were observed. These episodes were marked by a refusal of solid oral intake (solid food, medicine), a marked resurgence of crying, irritability, grabbing, and SIB. His intestinal transit was altered, with episodes of diarrhoea (false constipation), encopresis, and coprophagia. He also showed mood fluctuation, alternating between emotional outbursts with bursts of self-stimulatory behaviours (stereotypies) and significant irritability, intolerance to frustration, opposition behaviours, tantrums, and sleeping troubles. The psychiatric evaluation found a severe autistic syndrome (Children Autism Rating Scale (CARS) = 38) and severe ID (Vineland-II development age equivalent to 12 months in areas of communication and social skills and 15 months in autonomy).

PMC6536806_01

Male

A 55-year-old immunocompetent male was involved in a motor vehicle collision 2 years prior to presenting to our institution. He sustained an open ankle fracture after being ejected from the driver's seat into a pasture ditch, sustaining lacerations from barbed wire and resulting in a grossly contaminated open fracture. He was initially managed with irrigation and debridement (I&D) and placement of an external fixator. He subsequently underwent definitive fixation but during the next two years, experienced episodic drainage from incisions that was managed symptomatically with oral antibiotics. He had persistent pain which led him to seek evaluation at our institution. Upon presentation to our clinic, he was noted to have a severe planovalgus alignment, two draining sinuses, radiographic hardware failure (Figure 1), and elevated inflammatory markers including a white blood cell (WBC) count of 11 K/mm3, C-reactive protein (CRP) of 18.7 mg/L, and Erythrocyte Sedimentation Rate (ESR) of 18 mm/hr. He was diagnosed with an infected nonunion with underlying chronic septic arthritis of the tibiotalar joint and osteomyelitis of the distal tibia and fibula and scheduled for a staged ankle fusion following eradication of his infection. At our index surgery, the patient underwent a complete hardware removal with the exception of a broken screw tip from the most proximal fibular screw, extensive debridement of the ankle including excision of 11 centimeters (cm) of diseased distal fibula, 1.5cm of tibial plafond, and 0.5cm of talar dome, placement of an antibiotic spacer to the residual tibiotalar joint (impregnated with 2 grams of vancomycin and 2.4 grams of tobramycin per 40 grams of cement), and application of a ringed (Ilizarov) external fixator (Figure 2). Intraoperatively, multiple tissue cultures were obtained and found to be positive for Enterococcus faecalis, Enterobacter cloacae, and Mycobacterium senegalense, which grew from regular bacterial cultures. Postoperatively, the patient was started on a 4-week regimen of piperacillin-tazobactam for the E. faecalis and E. cloacae osteomyelitis followed by a 6-week regimen of imipenem, ciprofloxacin, and minocycline for his M. senegalense based on the in vitro antibiotic susceptibilities from the culture (Table 1). Three months after his index surgery, he continued to have drainage from 2 sites and the decision was made to undergo a repeat I&D with placement of a new antibiotic spacer (impregnated with vancomycin and tobramycin). Intraoperatively, the distal tibia had the appearance of persistent infection including purulence and caseous material which was cultured and noted to be positive for Bacillus species (not anthracis) and persistent M. senegalense growth, again from regular bacterial cultures (Table 1). At this point, based on the recurrent isolation of M. senegalense, the decision was made to continue imipenem and change the oral antibiotics to linezolid and azithromycin for another three months. Finally, after finishing 3 more months of imipenem, it was replaced with doxycycline to complete another 3 months of an all oral regimen. Four months later, he had closure of all wounds, demonstrated downtrending inflammatory markers (WBC, ESR, CRP), and was felt to be ready for fusion. During the procedure, no purulence was encountered, iliac crest autograft was utilized to augment the tibiotalar fusion and compression through the joint was achieved through the ringed external fixator (Figure 3). Multiple tissue cultures were taken intraoperatively with no growth noted and postoperatively he was continued on his regimen of linezolid, azithromycin, and doxycycline. Six months postoperatively, he had a successful fusion with no sinus tracts or drainage (Figure 4). He was able to have his ringed external fixator removed and one year postoperatively the patient continues to do well, fully weightbearing through the extremity and has not shown any signs of recurrence (Figure 5).

ilizarov external fixator, mycobacterium senegalense, nontuberculous mycobacterium, osteomyelitis

PMC3514062_02

Male

A 70-year-old man presented with a 10-month history of deep erythemas, subcutaneous nodules, and skin ulcers on the right upper limb and a 2-month history of ache and tumidness. These lesions had initially appeared 1 month prior as an isolated indolent nodule on the right wrist after a minor laceration to the second digit of his right hand, which was his dominant hand. As the disease progressed, the primary nodule enlarged and multiple nodules developed in an ascending fashion along the path of lymphatic drainage. A skin biopsy of a nodule performed at a local hospital showed infectious granuloma formation with acid-fast bacilli (AFB) identified within the tissue. Routine histopathology examination was repeated 1 month later, and this also produced an infectious granuloma reaction. Tissue cultures indicated that Sporotrichum schenckii could be growing in diseased tissues. The patient was diagnosed with sporotrichosis and prescribed orally administered potassium iodide and itraconazole. After 3 months of treatment, the lesions improved but had not completely healed. At this point, the patient topically applied a nonprescription Chinese herbal preparation, which exacerbated the skin lesions; these became swollen, red, and intensely painful on the whole right upper limb with ulceration of even the partial lesions. The patient was advised to continue antifungal treatment with terbinafine, itraconazole, and potassium iodide for several months. Fresh nodules and erosive papules developed on the dorsum of the right hand during the treatment, followed by diffuse tumidness with deep ulceration. In April 2011 after 8 months of no significant therapeutic effects with antifungal treatment, the patient was transferred to our hospital. Another two biopsies were re-examined before admission, and consistent results were obtained that exhibited granulomatous changes. All special stains, including AFB stains, and tissue cultures were negative for infectious organisms. Since the onset of the disease, the patient did not complain of systemic discomfort. He was in good general condition and did not have a history of hepatitis or tuberculosis. He had not travelled abroad but reported having a fish tank at home. Dermatological examination revealed a large area of deep erythema and edema with nodules, ulcerations, and crusts on the right upper limb that was abnormally sensitive to the touch. He had a nummular deep ulcer with severe tenderness on the dorsum of the second digit, which limited movement (Figure 1A and B). No axillary lymph node was palpable. Routine laboratory analysis demonstrated mild anemia and hypoproteinemia. Human immunodeficiency virus antibody test indicated negative results, and no active pulmonary disease was detected by chest radiography. A skin biopsy of a nodule on the patient's right forearm displayed a neutrophilic and histiocytic granuloma, with no caseous necrosis. Multinucleated giant cells were also observed (Figure 2). All special stains, including AFB and periodic acid-Schiff (PAS) stains, were negative for infectious organisms. Tissue cultures showed that the colonies grew on Lowenstein-Jensen (LJ) medium at 32 C for 10 days (Figure 3). Fungal and other standard bacterial cultures were negative. After identifying a nontuberculous mycobacteria (NTM) infection based upon the positive tissue cultures, certain species of NTM were suspected. M. marinum, a relatively common cause of mycobacterial skin infection that can spread in a sporotrichoid manner, was the first to be considered. The patient was then treated with orally administered rifampicin (450 mg, once daily), clarithromycin (500 mg, twice daily), and moxifloxacin (400 mg, once daily) for 4 weeks. However, the right upper limb became swollen again, with purulent secretions draining from the ulcer, and new lesions appeared during the treatment. Because the aggressive infection progressed so rapidly that multiple ulcers resistant to the combined therapy presented one after another, M. ulcerans infection was also suspected. The therapeutic regimen was then altered with the addition of intravenous amikacin (400 mg, once daily) to the antimicrobial regimen and suspension of moxifloxacin. Surprisingly, the skin nodules rapidly decreased in size, and ulcer cavities had fresh tissue within several weeks (Figure 1C and D). The organism was subsequently identified as M. marinum, sensitive to clarithromycin, rifampin, moxifloxacin, and amikacin, and all the four drugs were consistent with the prescribed regimen. With close surveillance of liver and kidney function and other side effects of amikacin, the combined antibiotics were used consistently for 6 months. After this period, the lesions had significantly subsided, leaving hyperplastic and atrophic scars, and new nodules did not recur (Figure 1E and F). A skin biopsy and culture taken at this stage were negative for AFB.

mycobacterium marinum, amikacin, clarithromycin, nontuberculous mycobacteria, skin infection

PMC7152536_01

Male

A 76-year-old male was admitted to our hospital for treatment of cerebral infarction in January 2018. The patient had a history of bladder cancer that was successfully treated by transurethral resection, and had also been treated for hypertension and dyslipidemia for several years. In addition, the patient had subclinical nonspecific interstitial pneumonia (NSIP). At admission, a complete blood count revealed the presence of polycythemia with an elevation of hematocrit to 64.7% (normal range: 40-50%) and hemoglobin to 20.9 g/dL (normal range: 13.7-16.8 g/dL). The peripheral leukocyte cell count and platelet count were 12.3x109/L (normal range: 3.3-8.6x109/L) and 274.0x109/L (158.0-348.0x109/L), respectively. A routine polycythemia work-up, including cytologic, histologic and chromosomal analyses of bone marrow hematopoietic cells and genetic analysis of peripheral blood mononuclear cells, showed that the patient fulfilled the diagnostic criteria for JAK2V617F mutation-positive PV. Ruxolitinib treatment at 20 mg/day was initiated in March 2018, while hydroxyurea was avoided as the first-line treatment due to NSIP. Three months later, a solitary tumor at the ascending colon and several peritoneal nodules were identified by colonoscopy and 18F-fluorodeoxyglucose-positron emission tomography combined with computed tomography (Figure 1A and B). Laparoscopic surgical resection of the colon tumor and peritoneal nodules resulted in a histologic diagnosis of adenocarcinoma for the ascending colon tumor and epithelioid cell granulomas with partial necrosis for the peritoneal nodules (Figure 1C). The peritoneal nodules were suspected to involve mycobacterial infection, but histologic examination with Ziehl-Neelsen staining, mycobacteria culture, and polymerase chain reactions (PCRs) for MTB and AMI of these nodules were all negative. During this period, ruxolitinib was continued for the treatment of PV. However, in September 2018, the patient presented with pyrexia, fatigue, and abdominal distension. Blood tests revealed elevation of the peripheral leukocyte count to 10.2x109/L, including 83% neutrophils, 8% lymphocytes, 7% monocytes, 1% basophils and 1% eosinophils, thrombocytosis of 789.0x109/L, and modest anemia with a hemoglobin level of 11.5 g/dL. Further laboratory tests showed slight elevation of serum lactate dehydrogenase to 296 U/L (124-222 U/L) and elevation of C-reactive protein to 15.0 mg/dL (0.00-0.14 mg/dL). An interferon-gamma (IFN-gamma) release assay (IGRA) was negative. A CT scan showed the emergence of an abnormally thickened peritoneum and massive ascites (Figure 1D). Abdominal paracentesis revealed the presence of exudative ascites containing 1.21x109 cells/L of mononuclear cells and 0.71x109 cells/L of lobulated neutrophils without neoplastic cells. Further work-up of ascites disclosed an elevated level of adenosine deaminase (ADA) to 57.5 U/L (-36.0 U/L), while PCR for MTB or atypical mycobacteria was negative. The patient reported no past MTB infection or history of exposure to MTB, but we tentatively diagnosed peritoneal MTB based on the high ADA level in ascites and the histologic finding of epithelioid cell granuloma in peritoneal nodules resected in surgery. Treatment for PV was changed from ruxolitinib to hydroxyurea, and four-drug anti-MTB therapy of isoniazid, pyrazinamide, rifampicin, and streptomycin was initiated. Finally, a mycobacterial culture of ascites yielded MTB colonies after 50 days of culture, which led to the definitive diagnosis of tuberculosis peritonitis. The four-drug anti-MTB treatment successfully resolved the symptoms and was terminated after 6 months of treatment. The patient has continued hydroxyurea treatment with no signs of recurrence of tuberculosis peritonitis or worsening of NSIP.

polycythemia vera, ruxolitinib, tuberculosis peritonitis

PMC2997500_01

Female

In June 2004, a 21-year-old white woman presented with spiking fevers, bruising, shortness of breath, and malaise. Laboratory findings revealed a white blood cell count of 21,700/muL with 47% circulating blasts. Subsequent bone marrow evaluation demonstrated AML with del(9q). Lumbar puncture was negative for cerebral spinal fluid (CSF) involvement. The patient underwent prompt treatment with cytarabine (Ara-C) 200 mg/m2 continuous infusion for seven days and idarubicin 12 mg/m2 daily for three days. Bone marrow evaluation at day 14 revealed residual leukemia, and repeat bone marrow evaluation three weeks later was negative. The patient subsequently received consolidative treatment with four cycles of high dose Ara-C. While receiving the chemotherapy, the patient developed pain in her left shoulder which radiated down the left arm from the elbow into the ulnar two fingers with numbness in those digits. The pain progressed, and further work-up was pursued including electromyography (EMG), which was consistent with an ulnar neuropathy. The patient underwent transposition of the ulnar nerve and carpal tunnel release because of new slight thumb numbness. The patient's symptoms progressed despite the procedure to include impaired dorsiflexion of the left great toe, numbness of her right calf, and numbness and weakness of the right thumb and index finger. Ten months after her initial diagnosis, associated fatigue prompted a repeat bone marrow evaluation, which was consistent with relapsed AML. Magnetic resonance imaging (MRI) of the brachial plexus and lumbar spine revealed bilateral brachial plexus involvement by a presumed chloroma and leukemic infiltration of the left and right lumbosacral plexus. The patient initiated treatment with mitoxantrone and etoposide. Repeat bone marrow evaluation was negative and repeat MRIs of the brachial plexus and lumbar spine demonstrated resolution of the leukemic involvement. While post-treatment biopsy of the chloroma sites was not performed, it was felt that based on the available imaging, clinical improvement, and bone marrow aspiration results, that the patient had attained a complete response to treatment. The patient underwent an unrelated donor-matched allogeneic bone marrow transplant. The conditioning regimen included total body irradiation (TBI) to 1375 cGy in 11 fractions administered three times daily with a consolidative boost to the left brachial plexus to 600 cGy in four daily fractions. The boost was added because residual microscopic disease could not be ruled out. Graft versus host disease (GVHD) prophylaxis included tacrolimus plus methotrexate. Repeat bone marrow aspiration posttransplant demonstrated cytogenetic remission with full donor chimerism and normal karyotype. The patient completed five monthly doses of intrathecal Ara-C (70 mg) as central nervous system (CNS) prophylaxis. Cytopathology on all the CSF samples was negative for malignancy. The patient's posttransplant course was complicated by hepatic fungal infections, GVHD, involving the upper gastrointestinal tract and liver, and renal insufficiency resulting in a very slow but physically remarkable recovery to eventually include triathlon training. While on immune suppression including tacrolimus and prednisone, the patient developed leukemia cutis of the right chest that resolved completely with the tapering of immunosuppressive medications. A bone marrow evaluation at the time of the skin biopsy revealed a normal karyotype, all donor by diagnostic molecular pathology. Approximately one year posttransplant, the patient developed progressive left intrinsic hand weakness with an associated palpable mass in her left upper extremity. An MRI study was consistent with a chloroma of the biceps brachi along the course of the musculocutaneous nerve. Fine needle aspiration of the mass was consistent with leukemic infiltration; CSF analysis and bone marrow aspiration at the time of the peripheral nerve biopsy were negative for leukemic involvement, and polymorphism analysis with DNA primers demonstrated complete donor engraftment. The patient received a course of radiation therapy to 3000 cGy in 15 fractions to the mass, with complete clinical resolution of the lesion by treatment completion. Seven months after completion of the patient's last course of radiation, she developed new right arm and leg pain. Work-up including MRIs demonstrated three presumed chloromas near the right elbow (ulnar nerve), right upper deltoid (axillary nerve), and right psoas region (lumbar plexus). Biopsy of the right psoas lesion was consistent with chloroma (Figure 1); CSF analysis and bone marrow biopsy were negative and polymorphism analysis did not detect any host cells. The patient underwent her third course of radiation to the right elbow, right deltoid region, and right paraspinal psoas mass, each to 2400 cGy in 12 fractions. All sites demonstrated a clinical and radiographic response (Figure 1) on followup. Three months after completion of treatment, the patient developed new pain in her left first and second toes. Imaging was consistent with a left peroneal nerve chloroma for which she received 2400 cGy in 12 fractions. The patient had been completely tapered off immunosuppression and was doing well on no further therapy until 14 months later, when she palpated a new mass in her left forearm, which was biopsied and consistent with a leukemic infiltrate. Further work-up did not reveal any systemic disease with bone marrow evaluation showing full donor chimerism and no CSF involvement. The patient was neurologically asymptomatic; however, neurological examination was consistent with median nerve involvement. A course of 2400 cGy in 12 fractions to the left forearm was initiated with clinical resolution. Despite the patients multiple recurrences and courses of radiation, she remained in excellent physical condition with continued participation in triathlons and road races. Despite receiving a low dose donor lymphocyte infusion of 1 x 105 CD3+ cells/kg several months before, the patient developed right lower extremity weakness along the femoral distribution approximately one year after her last radiation treatment. MRI, computerized tomography (CT), and positron emission tomography (PET) were consistent with a right femoral nerve chloroma extending into the right inguinal canal (Figure 2). The patient received another course of 2400 cGy in 12 fractions with a cone down to avoid overlap with the prior radiation field (right psoas chloroma). Clinical improvement was observed during the course of treatment without any associated treatment toxicities. Repeat MRI one month after treatment demonstrated complete resolution. Since completion of her last course of radiation therapy, she has received no further therapy and has not shown any evidence of recurrence of chloroma or leukemia; the patient plans to resume her triathlon training.

PMC6348891_01

Female

A 63-year-old female presented with epigastric pain, loss of appetite, abdominal bloating, regurgitation, and episodic projectile vomiting of five-year duration. These symptoms were aggravated particularly after meals. Her bowel opening was normal. The patient had lost 20 kilograms over five years. The patient had a background history of hypothyroidism for which she was on thyroxine replacement therapy. She was clinically euthyroid. She had undergone a vaginal hysterectomy for uterovaginal prolapse at the age of 39 years. There was no significant family history for bowel disorders. On physical examination, she had a body mass index of 13. She was pale. There were peripheral stigmata of chronic malnutrition and vitamin B12 deficiency. She had a distended abdomen, visible peristalsis, and hyperacute bowel sounds. There was no clinically demonstrable free fluid in the abdomen. She had anaemia (haemoglobin-8.9 g/dl, haematocrit-27.3%, mean corpuscular volume-97.4 fl, mean corpuscular haemoglobin-31.6 pg, mean corpuscular haemoglobin concentration-325 g/l, and red cell distribution width-58.4 fl), with normal platelet (402 x 103/mul) and leucocyte (8.07 x 103/mul) counts. Blood picture showed macrocytic red cells and hypersegmented neutrophils. Abnormal chemical pathological investigations comprised of elevated C-reactive protein (20.1 mg/l), hypoproteinaemia (59 g/dl), hypoalbuminaemia (25.3 g/l), hypovitaminosis B12 (160 pg/ml), and hypocholesterolaemia (total cholesterol-125.5 mg/dl, HDL-32 mg/dl, LDL-66.3 mg/dl, and triglycerides-136.4% with normal VLDL-27.2 mg/dl). Serum ionized calcium was 2.41 mmol/l. Serum iron studies favoured anaemia of chronic disease (serum iron-95 mug/dl, total iron binding capacity-138 mug/dl, iron saturation-40.8%, and ferritin-238 mug/l). She was biochemically euthyroid (TSH-4.65 mIU/l). Ultrasonography was suggestive of subacute small intestinal obstruction with distended first part of the duodenum filled with fluid. Multiple tortuous small bowel loops were noted around the pancreas with increased peristalsis. Large bowel was distended with gas. There was no bowel wall thickening, mass lesions, or free fluid in the abdomen. Computed tomography (CT) of dual slice contiguous axial sections of the abdomen obtained after intravenous, oral, and rectal contrast administrations demonstrated mild dilatation of the first and second parts of the duodenum with no evidence of significant obstruction to distal passage of oral contrast. The stomach was not distended. A focal calcification of the segment VII of the liver was noted, which was likely to be an incidental finding. There was no CT evidence of an annular pancreas or superior mesenteric artery syndrome. A spiral CT was repeated after one week. It showed markedly distended proximal bowel loops involving the duodenum and the proximal jejunum. No definite transition point was identified. There was a whirl appearance seen in the mesentery and superior mesenteric venous branches around the superior mesenteric artery raising the suspicion of a possible midgut volvulus. Mild mesenteric engorgement was also seen. No definite CT evidence of diverticuli was seen. Upper gastrointestinal (UGI) endoscopy revealed multiple duodenal diverticuli with a small hiatus hernia. Barium meal and follow-through study revealed a slightly distended duodenum without evidence of obstruction or persistent narrowing. Magnetic resonance enterography revealed multiple dilated small bowel loops with loss of valvulae in the right side of the abdomen (Figure 1). There were numerous outpouchings arising from the small bowel. However, with unexplained weight loss, we wanted to exclude a gastrointestinal malignancy and intestinal tuberculosis. We opted for laparotomy out of diagnostic laparoscopy and laparotomy. Multiple large diverticuli were noted extending from the first part of the duodenum to the proximal ileum (Figure 2). Diverticuli were measuring from 0.5-12.0 cm. There was macroscopic evidence of diverticulitis. There was gross gastric dilatation. Proximal small bowel was dilated without a definitive transition point. The rest of the terminal ileum and colon were normal macroscopically. Small bowel was not surgically resected because she was not a suitable candidate for a primary anastomosis as she had nutritional deprivation and the risk of short gut syndrome. We closed the abdomen without any surgical interventions. Because of macroscopic evidence of diverticulitis, intravenous cefuroxime 750 mg 8 hourly and intravenous metronidazole 500 mg 8 hourly were administered for 7 days and were converted to oral cefuroxime 500 mg 12 hourly and oral metronidazole 400 mg 8 hourly for another 21 days. She had an uneventful postoperative period. She received complementary parenteral nutrition with amino acids, electrolytes, dextrose, and lipid injectable emulsions followed by standard polymeric formulae containing whole proteins. Soluble fibres were gradually introduced to her diet. She received a high-calorie diet, initially 125% of the daily calorie requirement followed by 150% of the daily calorie requirement after one month. Thousand international units of vitamin B12 was administered intramuscularly every other day for five days, and oral vitamin B complex 1 mg three times a day was continued for six months, with folate and micronutrient replacement. Iron-rich food and standard formulae were used to supplement micronutrients such as selenium and zinc for six months. She had a remarkable recovery with no recurrence of symptoms following 10 months follow-up.

PMC6850519_01

Unknown

A 48-match sample of in-game footage of Nike Academy (16-20-year-olds) matches for the 2017 season was used during the study and identified examples of players performing in a number of number of outfield positions (i.e. central defender, full-back, central midfield, left/right midfield and central wide/attacking player). The Nike Academy was an English football academy funded and administrated by Nike, Inc. until 2017. The academy had a revolving squad of unsigned under-20 players and was run with the intention of helping players find a professional football club. The academy was based at St Georges Park National Football Centre (UK) and the squad was made up of players scouted worldwide and drafted to the squad through the Nike Most Wanted football trials. Full ethical approval was provided by Liverpool John Moores University Ethics Committee (15/EHC/044), and verbal and written informed consent was obtained from the participants and the Nike Academy to use match recordings. In this study, we used a reliable and valid procedure to generate video clips of the required attributes for all six outfield playing positions (central defender, fullback, central midfielder, wide midfielder, centre-forward and wide attacker). The standardization process followed the systematic review of 4320 minutes of match footage in order to find video clips that were representative of various outfield positions. All the agreed player film sequences were incorporated into SportsCode Gamebreaker 10.3.1. for editing and reviewing purposes by members of the research team. Training in the use of SportsCode Gamebreaker 10.3.1. was provided by one of the authors (AM) (~3 hours training) who has extensive experience of performance analysis education. In total (n = 15) film sequences were produced for each of the outfield positions (i.e. central defender, fullbacks, central midfielder, wide midfielder, centre-forward and wide attacker). Each positional sequence contained (n = 10) clips that lasted for approximately 90 seconds each (15.00 minutes total). To test for attribute acceptance for each position, we asked the participants to watch the video clips and to concurrently verbalise their cognitions from when the video clip started until it ended. Before the beginning of each clip, a black screen presented the name of the playing position and a numbered countdown (3-2-1) was provided, to aid participant visualisation. In addition, a still image with a circle around the player under observation was shown. To achieve acceptable content validity, the observations were recorded and consensus as to whether the attributes were efficiently shown in the player position-specific videos was determined. This approach demonstrated the presence of these attributes and provided the likely language a scout would adopt when thinking about the attribute. In order to confirm the existence of the definitions within each category two members of the research team independently reviewed the recordings and used the following equation to determine inter-observer agreement (IOA): [(Agreements) / (Agreements + Disagreements)] x 100. For example, if there was eight agreements and two disagreements then the equation would be [(8) / (8 + 2)] x 100 = (8/10) x 100 = 80%]. In order to check for observer consistency, the intra-observer reliability (IOR), was established by performing the same test, two weeks after the initial data collection sufficient time for complete memory lapse. The results of this study found that the IOA for central defender was 0.87 (87%); full back 0.80 (80%); central midfielder 0.84 (84%); left/right midfielder 0.80 (80%) and central/wide attacking player 0.86 (86%). The results of the IOR for central defender were 0.83 (83%); full back 0.81 (81%); central midfielder 0.83 (83%); left/right midfielder 0.82 (82%) and central/wide attacking player 0.84 (84%). Following full ethical approval, provided by Liverpool John Moores University Ethics Committee (15/EHC/044), two full-time talent scouts (i.e. Adam and Ben [pseudonyms]) were purposively sampled from a category one English Premier League academy (see, for an overview of academy category status). Adam (44 years) had worked as a talent scout for (17 years) and Ben (26 years) had worked as a talent scout for (3 years). Purposive sampling methods are commonly regarded as suitable for studies where the research team are interested in capturing the best knowledge concerning the research topic and studies which employ content analysis procedures. Prior to commencing the study both Adam and Ben provided written informed consent and were notified that they could withdraw from the study at any time. Gatekeeper consent to undertake video recording was obtained from the club's academy director as well as the gatekeeper for the opposing team, subsequent informed consent was also obtained from each individual player. If we are to fully understand the role of the talent scout and their decision-making processes it is important the complexities of the identification process are captured in situ before attempting to recreate similar conditions in more controlled, simulated environments. The study was, therefore, conducted at the club's academy site as the research team were granted permission by the club's academy director, to observe and record a competitive game between the clubs under 15 team and another junior-elite under 15 team. The game was played mid-week, kick off 1900 hours, on a regulation size (100.5m x 64.0m) artificial 4G pitch, under floodlights with clear weather conditions. Adam and Ben were trained in concurrent verbal reporting using an adapted version of the instructions outlined by Ericsson and Kirk. This included assigning warm-up exercises such as mental calculations to shape their verbal behaviour. For example, "So that you understand what I mean by think-aloud, let me give you an example. Assume I asked you 'How much is 127 plus 35?'. Now think-aloud so I can hear how you solve this problem. The participants practised providing verbal reports with feedback provided by members of the research team until level I or II verbal reports was established. Training in concurrent verbal reporting techniques was provided by a member of the research team who has published previously using this procedure in both sport and simulated medical domains. All concurrent verbal report training was conducted on the day of the game to ensure complete understanding of the task requirements. Prior to the game commencing, a Lavalier microphone and radio transmitter (Sennheiser ew 122-p G3), was connected to a Dictaphone (Olympus WS-853) which was fitted to both participants. Adam and Ben also wore GoPro camera's (GoPro Hero 5) which were attached to their chest in order to determine whether the team they were scouting were in possession of the football or not. Adam and Ben were instructed to verbalise their thought processes in real-time without self-censoring, or attempting to justify or explain their thoughts, as per the verbal reporting protocol. Each participant took up a position at pitch level on opposite sides of the pitch on the half way line (Fig 1) and engaged in a full 90-minute football game, with the typical 15-minute half-time interval. During the game, Adam and Ben were allocated a research assistant who stood behind them listening for verbal reporting occurring. If either participant stayed quiet for longer than 30-seconds, following verbal reporting protocols, they were prompted by the research assistant to "think aloud". For the first half of the game, Adam and Ben were asked to focus on the game as a whole. This was intended to represent a scouting assignment where no particular individual had been chosen for observation, and so the scout was responsible for identifying those individuals who they believed to be talented. For the second half, the research team selected two individuals from one team (the team with whom the scouts were not associated) to focus their attention and provide verbal report data. Following the game Adam and Ben engaged in a debrief and informal semi-structured interview with members of the research team to discuss their thoughts on the verbal reporting protocol, including any difficulties or concerns that they had. This was recorded using a Dictaphone and transcribed away from the academy environment. Verbal reports for both participants were transcribed verbatim, generating 15 single-spaced pages of text from 189 minutes and 20 seconds of total recorded audio. Ericsson and Simon outlined analysis procedures for verbal reporting protocols, where they highlighted relevance, consistency, and patterns of verbalisation streams as important. However, due to the exploratory nature of this study, and the broad range of factors likely to be covered by scouts in a dynamic game environment, it was deemed appropriate to conduct line-by-line deductive content analysis (see). Deductive content analysis is often exemplified by cases where researchers wish to code data based on an existing categorisation matrix. Any categorization matrix can be regarded as valid if the categories adequately and accurately captures what was intended. Following transcription, verbal report data were converted to a Notepad text file and imported into Microsoft Excel (2016). Each verbatim statement was then coded using the coding criteria outlined in the codebook generated in Study 1. Each verbal report was then simultaneously and independently coded by a second trained member of the research team using the attribute definitions contained in the codebook. Each concurrent statement was coded using a colour system which was aligned to the attribute presented in Table 1. IOA estimates were conducted using the same method noted above, and suggested that two coders had equivalently coded (70.3%) of the verbalisations. The remaining verbalisations (29.7%) were re-coded by the two raters following a line-by-line debrief and discussion. Following line-by-line deductive content analysis, frequency counts of the individual phrases were imported into the statistical package for the social sciences (SPSS V25) where descriptive statistical analysis procedures were conducted (i.e. means and standard deviations). The informal debrief data were transcribed line-by-line and content analysis with inductive reasoning was conducted to develop themes and a process of continual examination and comparison was performed. Following hermeneutic procedures provided by Thomas and Pollio, information-rich verbalisations were identified as meaning units, which were subsequently grouped into sub-themes. Verbalisations were pieces of coded text that related to an attribute and ranged in the number of words they contained. This process was initially completed by two (MJR & SR) of the research team before being shared with the remaining two team members (AM & CL) to consider trustworthiness surrounding interpretation of data.

PMC10246367_01

Unknown

A 16-year-old patient with no relevant history presented a TBI without loss of consciousness. The patient reported headaches, nausea, and dizziness. On physical examination, the patient was alert, oriented in all spheres, with reactive intermediate isochoric pupils, mobilizing 4 extremities on command, without sensory-motor deficits or gait disturbances. A brain computed tomography (CT) without contrast was performed, displaying a "ping-pong" fracture with a diameter of 30.5 mm and depression of 9.2 mm. No intraparenchymal lesions were identified. Brain CT bone window and 3D reconstruction showed the fracture in the left parietal bone [Figures 1 and 2]. Laboratory tests were performed and showed low values of ionic and total serum calcium (4.8 mg/dL and 7.8 mg/dL, respectively). With this result, the serum parathyroid hormone (PTH) levels were analyzed, which showed a low value as well (6 mg/dL), diagnosing hypocalcemia and hypoparathyroidism. Consultation with the endocrinology service was made and the patient started on calcium carbonate and vitamin D supplements, remaining under observation in the general ward for 48 h with a favorable evolution. Due to the absence of neurological deficits, intraparenchymal lesions, large cosmetic defects, and/or symptomatic progression, conservative management was performed. Hospital discharge was granted with follow-up instructions and TBI warning signs. The patient did not attend the last control (6 months after the trauma), so the evolution of the depressed "ping pong" fracture is unknown. In the previous control (1 month after the trauma), there were no complications.

age, bone mineralization, depressed, fracture, “ping-pong”

PMC5152954_01

Female

A 17- year- old woman was regularly treated for years with TNF- a- blocker adalimumab based on her refractory SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome. TB- Screening with IGRA (Interferon Gamma Release Assay) before the therapy with TNF- a-blocker tested negative. Due to increasing dyspnea, somnolence and septic shock, she was treated in the emergency room of a community hospital. Through sputum, blood culture and cerebrospinal puncture, the diagnosis of severe tuberculosis with meningitis and pulmonary infiltrates was rendered. After the diagnosis of tuberculosis, her regular therapy with adalimumab was discontinued. The standard treatment of four antibiotics (INH isonicotinic acid hydracide 300 mg daily, RIFA rifampicin 600 mg daily, PZA pyrazinamide 2000 mg daily and SM streptomycin 1000 mg daily) was initiated. Five months after the discontinuation of the adalimumab therapy, we observed cerebral lesions in the basal meningeal region and in the follow- up cerebral MRI- Scan (Fig.1 and Fig 2). Due to cerebral progression and consequential tonic- clonic convulsive seizure, the initiation of antiepileptic drugs with levetiracetam has been initiated. Because of the raising intracranial pressure and ventricular distension, a ventriculo- peritoneal shunt was also installed after the first tonic-clonic convulsive seizure. A neurosurgical intervention was not considered based on location of those cerebral lesions. The oral steroid prednisolone dose was elevated to 80 mg per day. Under the oral steroid therapy clinical conditions improved in patient. Steroid therapy was continued for overall 6 months with stepwise reduction of the dose until the maintenance dose of 7.5 mg per day. The patient still has a slightly vertigo distraction, but she stays employable at a limited level.

adalimumab, igra (interferon gamma release assay), iris (immune reconstitution inflammatory syndrome), paradoxical reaction, sapho (synovitis, tnf (tumor necrosis factor), tuberculosis (tb), acne, hyperostosis, latent tuberculosis infection (ltbi), osteitis) syndrome, pustulosis

PMC5152954_02

Male

A 37- year- old Indian man with diagnosed Psoriasis arthritis was treated with adalimumab on a regular basis. TB-Screening with IGRA (Interferon Gamma Release Assay) before the therapy with TNF- a- blocker tested negative. He was diagnosed with severe disseminated miliary tuberculosis with extensive acute respiratory distress syndrome under treatment with adalimumab. Laboratory examination revealed initial CRP 10.3 mg/dl, LDH 489 U/L and Leukocyte with 14.0 GIGA/L. The initial contrast enhanced CT- Scan revealed severe progressive bilateral pulmonary infiltrates (Fig.3a). During that period, intensive care was required. After the first treatment course of two weeks antituberculosis treatment with four antibiotics (INH isonicotinic acid hydracide 300 mg daily, RIFA rifampicin 600 mg daily, PZA pyrazinamide 2000 mg daily and SM streptomycin 1000 mg daily), the contrast enhanced CT scan showed regressive bilateral pulmonary infiltrates (Fig.3b). Under the tuberculosis therapy, the laboratory parameters were also improved after 2 weeks of treatment; CRP 2.8 mg/dl, LDH 203 U/L and Leukocyte was 12.1 GIGA/L. During the treatment of tuberculosis therapy, therapy with TNF- alpha- blocker adalimumab was discontinued. Six weeks after the discontinuation of the adalimumab therapy, he developed a prolonged paradoxical reaction with reverse episodes of fever, elevation of CRP 7.1 mg/dl; Leukocyte of 16.0 GIGA/L and LDH of 276 U/L. and progressive bilateral pulmonary infiltration which were revealed in both contrast enhanced CT-scan and chest x- ray (Fig. 4, 5). Multiple blood cultures rendered no clear evidence of pathogen agents. HIV- test was again tested negative. Not until the initiation of steroid prednisolone therapy with a daily dose of 1.5 mg/kg could we improve his general condition. After two weeks of prednisolone therapy, his laboratory findings were also improved; CRP 4.2 mg/dl, Leukocyte of 10.0 GIGA/L and LDH of 252 U/L. We continued the steroid therapy for overall 6 months with stepwise reduction of the dose until the maintenance dose of 7.5 mg per day. The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance the tenets of the Helsinki Declaration, and has been approved by the authors' institutional review board or equivalent committee. Informed consent has been obtained from all individuals included in this study.

adalimumab, igra (interferon gamma release assay), iris (immune reconstitution inflammatory syndrome), paradoxical reaction, sapho (synovitis, tnf (tumor necrosis factor), tuberculosis (tb), acne, hyperostosis, latent tuberculosis infection (ltbi), osteitis) syndrome, pustulosis

PMC10161436_02

Male

A 23-year-old male Indian medical student was referred to physical therapy after tearing his right anterior cruciate ligament (ACL) while playing flag football and undergoing subsequent ACL reconstruction surgery. Clinical examination was consistent with status post ACL reconstruction. The patient was treated with standard of care after an ACL reconstruction, including weight bearing as tolerated, gait training, interventions to decrease pain and effusion, cryotherapy, electrostimulation for muscle reeducation, quadriceps and lower extremity strengthening, and neuromuscular training. Patient was seen for 8 visits over 3.5 weeks. Patient initiated physical therapy in his hometown while on his winter break from medical school. After 8 visits of physical therapy, patient returned to medical school and transferred to a physical therapy clinic more convenient to his medical school campus. Social swearing, as opposed to annoyance swearing, serves interpersonal functions, such as group bonding and impression management and is seen as positively charged. The PT utilized social swearing during treatment sessions with the goal of motivating the patients and enhancing the social connection with the patients, to improve therapeutic alliance. It is important to note that the social swearing implemented by the PT did not include weaponized use of taboo language to inflict or subject the patients to demeaning emotional insult or harassment. The PT began to swear during the 3rd physical therapy visit for both patient cases and swore 2-3 times each visit thereafter. Swearing was initiated on the 3rd visit to ensure rapport between the patient, and PT was established, with swearing being utilized to further improve their relationship and therapeutic alliance. Each episode of swearing by the PTs was attempted to be well-timed for the purpose of motivation and solidarity. For example, during case 1, the PT said, "Hell yes bro, that is good s***! Keep up the f***ing good work!", while the patient was performing a challenging exercise. The patient smiled and proceeded to say, "F*** yeah dude, let's f***ing go!" and then continued performing his exercises. An example during case 2, the PTs said, "Dude, if you continue to work your f***ing a** off like this, you will become a f***ing animal!" during a treatment session. The patient started laughing immediately and said, "You're damn right." and continued to work through his exercises. The Helping Alliance Questionnaire (HAQ), a self-reported outcome measure that is completed by both the patient and the PT, was used to monitor the therapeutic alliance at 2 points during the episodes of care of these patients to help show the evolution of the therapeutic alliance and swearing over time. An additional swearing survey was developed by the researchers, based on the works of Giffin and Stephens et al., to better understand the context in which swearing occurred. The swearing survey was completed at discharge and included questions about the patients' general opinions of swearing, thoughts on the professionalism and acceptability of swearing in physical therapy, and how swearing effected the patient-PT relationship, and also included questions based on the possible psychological mechanisms by which swearing fulfills positive functions. This swearing survey is presented in Fig. 1. Summaries of the therapeutic alliance and swearing survey outcomes are presented in Tables I and II, respectively. During the 4th visit, the patient and PT completed the HAQ. At discharge, the patient and PT completed the HAQ again (7th visit). At the 4th visit, the patient scored 94/114 on the HAQ and the PT scored 92/114 (19 = poor therapeutic alliance and 114 = strong therapeutic alliance). At discharge, the patient scored 89/114 on the HAQ, and the PT scored 98/114. These results suggest that the patient's self-reported therapeutic alliance score decreased (94/114 to 89/114) as the PT swore during treatment sessions, while the PT's self-reported therapeutic alliance increased (92/114 to 98/114). The patient completed the researcher-developed swearing survey at discharge. The patient disagreed with the following statements: "I find swearing offensive," "I only swear around my friends and family," and "PT swearing is unprofessional." The patient agreed with the following statements: "I change or monitor my use of swearing based on the people I am talking to or the people around me" and "PTs should be able to swear around their patients." The patient swears more than 4 times per day and believed that the PT swearing did not affect their relationship or his motivation. When asked "How did you feel the first time a swear word was used in your therapy?" the patient responded, "It didn't bother me at all. I am used to it." Based on the possible psychological mechanisms by which swearing fulfils positive functions, the most noted effect on this patient was that the PT swearing was funny or humorous. All other mechanisms were scored at 50% or less agreement from the patient. Specific swearing survey results are listing in Table II. Similar to case 1, the patient and PT completed the HAQ during the 4th visit and again at discharge (8th visit). At the 4th visit, the patient scored 110/114 on the HAQ, and the PT scored 100/114 (19 = poor therapeutic alliance and 114 = strong therapeutic alliance). At discharge, the patient scored 113/114 on the HAQ, and the PT scored 110/114, suggesting that both the patient's and PT's self-reported therapeutic alliance scores increased (patient 110/114 to 113/114; PT 100/114 to 110/114) as the PT swore during treatment sessions. At discharge, the patient strongly disagreed with "I find swearing offensive" and "PT swearing is unprofessional" and agreed with "I only swear around my friends and family" and "PTs should be able to swear around their patient." Patient neither agreed nor disagreed with "I change or monitor my use of swearing based on the people I am talking to or the people around me." The patient reported swearing more than 4 times per day and believed that the PT swearing helped their relationship and increased his motivation. When asked "How did you feel the first time a swear word was used in your therapy?" the patient responded, "Increased the mood in they gym." The patient fully agreed that the PT swearing made him feel a positive emotion, was funny or humorous, distracted him from thinking about other things, felt like a new or different experience, and made him feel more confident. The patient did not agree at all that the PT swearing made him feel a negative emotion.

communication, physical therapy, professionalism, swearing, therapeutic alliance

PMC6546850_01

Male

A 68-year-old male patient was transferred to our neurological department after he had been admitted to another hospital twice before. The first admission had taken place 3 months before in July 2018 due to visual impairments (hemianopsia to the right) and uncommon behavior. The MRI had shown a T2-weighted (T2w)-FLAIR hyperintensity in the left temporooccipital lobe that had been interpreted as an ischemic stroke. The results of cardiovascular investigations had been normal and the patient had been discharged. In August 2018 he had been admitted again with a progression of symptoms consisting of severe sensory aphasia, psychomotoric deficits and progressive visual impairments. The MRI had displayed a massive enlargement of parietooccipital lesions in both hemispheres predominantly affecting the left white matter (Figure 1). The polymerase chain reaction (PCR) for JCV in the cerebrospinal fluid (CSF) had been positive whereas routine analysis of the CSF had shown normal results (cell count and distribution, lactate, protein). PCR for Varizella zoster virus had been negative. Serologic tests for Borrelia burgdorferi, Treponema pallidum, Herpes simplex virus, measles, Varizella zoster virus, HIV and hepatitis B and C had also been negative. The patient was then transferred to our department for further diagnostics. His general physician and relatives revealed that the medical history contained no record of frequent or severe infections. He had never received any kind of immunosuppressive treatment. In 1999 the patient had suffered from a myocardial infarction. The medical history was unremarkable apart from arterial hypertension and a helicobacter-positive gastritis. In 2017 he had got a viral infection with mild influenza-like-symptoms. Neither the patient nor his family knew of any recent vaccinations. Upon admission to our neurologic department he had developed a right sided homonymous hemianopsia, severe sensory aphasia and disorientation. Our CSF analysis showed a pleocytosis (22 cells/mul) and an elevated protein concentration (0.72 g/l). The cell-distribution was mostly lymphocytic, but monocytes and granulocytes were found as well. CSF specific oligoclonal bands (type 2) were present and there was an intrathecal production of IgG and IgM. The JCV-PCR (1E3 c/ml) from CSF and the JCV-antibody-index (24.000 AU/ml serum) were positive. All additional tests were negative (HSV, VZV, and Ebstein-barr-virus (EBV) in the CSF by PCR, as well as tickborn encephalitis (TBE), enterovirus, and cytomegalovirus serologically; CSF-antibody-indices for HSV, EBV, VZV and CMV). All investigated autoimmune encephalitis antibodies (anti-NMDAR, -AMPAR1/2, -CASPR2, -LGI1, -GABAR-b1/b2, -Yu, -Hu, -Ri, -Amphiphysin, -CV2/CRMP-5, -Ma1/2, -GAD, -SOX1, -Tr(DNER), -Zic4) were negative in serum and CSF. Further investigations concerning an immunodeficiency were inconspicuous. An HIV-test was negative. The blood tests including peripheral blood cell count and inflammatory parameters showed mild eosinophilia (10,3%), elevated rheumatoid factor (60.5 IU/ml), Cardiolipin-IgM-antibodies (14 MPL-U/ml), and antinuclear antibodies (ANA, 1:320) of unspecific speckled pattern in the immunofluorescence and without specificity against ds-DNA or extractable nuclear antigens. An abdominal sonography showed a splenomegaly and prominent lymph nodes but no sign of neoplasia. We performed a whole-body PET/CT (including the brain) with 296 MBq 18F-Fluorodeoxyglucose (18F-FDG) 60 min p.i. to search for a malignancy or an inflammatory disease. The PET scan showed prominent mediastinal lymph nodes with moderately high metabolism, however, it did not reveal any profound hypermetabolic lesions. 18F-FDG uptake in the brain was further evaluated using statistical parametric mapping (SPM) for comparison with a reference group. The cerebral glucose metabolism was lowered bilaterally in parietotemporal and occipital areas with a clear predominance on the left side. The metabolism in the frontal cortex, basal ganglia, and cerebellar regions appeared to be normal (Figure 2). A biopsy of the prominent mediastinal lymph nodes identified in the PET investigation showed no signs of malignancy or granuloma. Additionally ACE and the soluble IL-2-receptor in the blood were normal, so sarcoidosis seemed unlikely. The HLA-DR-expression and phenotyping of lymphocytes showed normal results [amount and distribution of CD3+, CD4+, CD8+, B-cells (CD20+), and natural killer cells (CD16+)]. In addition to extensive phenotyping of peripheral blood mononuclear cells (PBMC) even the functional analyses by proliferation assays of PBMC by plant lectins (PHA, Con A, PWM), tuberculin (PPD) and anti-CD3, spontaneous and antibody-dependent NK-cell activity (ADCC) were within normal range. During inpatient treatment the patient developed a cough and had impaired breathing. The tracheal exudate was positive for HSV using PCR so we started a therapy with intravenous aciclovir which improved the respiratory symptoms markedly. In September 2018 a progression of the patient's symptoms with focal and generalized seizures occurred. We started a medication with levetiracetam and had to add valproate and lacosamide to the antiepileptic treatment due to recurring seizures. The MRI showed a further expansion of the lesions with a new peripheral contrast enhancement (Figure 3) as a sign of a PML-related immune reconstitution inflammatory syndrome (PML-IRIS). We treated the patient with a high dose of corticosteroids (1 g/d methylprednisolone for 5 days intravenously). After this therapy the seizures decreased and the anticonvulsive treatment could be reduced to levetiracetam and valproate. Finally, we applied a treatment with mirtazapine to our patient, which is able to block the specific serotonin-receptors used by JCV, since this was beneficial in a previous report of a PML in an immunocompetent patient. Mefloquine, another drug with potentially antiviral effects against JCV, was not included to the treatment as seizures are a strict contraindication. After nearly 2 months the patient was transferred to a rehabilitation facility. Visual impairments, disorientation and a sensory aphasia were still persistent. During the following weeks the patient developed severe dysphagia until oral intake of food and fluids was no longer possible. The patient died 2 months after the transfer to a nursery home due to a respiratory infection and pulmonary insufficiency.

jc-virus, corticosteroid, immunocompetence, progressive multifocal leukoencephalopathy (pml), spontaneous immune reconstitution inflammatory syndrome (iris)

PMC6787162_01

Male

The proband, a 20-year-old male, was referred to the Neurometabolic Clinic at McMaster University for investigation in the context of gross developmental delay, emotional outbursts, speech and swallowing difficulties, hypotonia, and ataxia since childhood. He was born at term following an uncomplicated pregnancy (birth weight 3,200 g) and developed appropriately until 8 months of age, where he had developmental regression following a mild traumatic brain injury. Axial hypotonia was noted at 1 year of age. He had delays in his walking, started to cruise at 3 years of age and was non-verbal. During his early adulthood, his symptoms progressed, with severe generalized slowing of movements, muscular fatigue, and swallowing difficulties. Currently, he spends most of his time in his wheelchair but walks on occasion with one person assistance. There were no ocular, dental, auricular, or skeletal anomalies identified by clinical examination and targeted X-ray evaluation. His parents are double first cousins from Pakistan with an unremarkable medical or family history. The other family members do not report a history of developmental delay or neurological features. The proband's physical examination was abnormal. He appeared short and cachectic; he was 50.5 kg, 161.5 cm tall and used a wheelchair for ambulation. He was unable to sit independently. There was evidence of cognitive impairment and non-verbal vocalization, including screams. He would occasionally swat at the examiner. Cranial nerve examination demonstrated horizontal and rotatory nystagmus without ptosis, cataracts, or retinopathy. He had a right eye esotropia. Cerebellar examination demonstrated ataxia and bilateral coarse hand tremors. Lower cranial nerves and hearing were normal. Motor examination demonstrated generally reduced muscle bulk, paratonia, with grade 3-4-/5 muscle weakness. He had normal muscle stretch reflexes in the upper extremities and absent in the lower extremities with downgoing toes. His serial brain MRI's demonstrated progressive cerebellar and vermian atrophy with increased FLAIR signal in cerebellum and periventricular white matter. His echocardiogram, nerve conduction study, POLG sequencing, serum lactate, and karyotype were normal.

lonp1, electron microscopy, granular bodies, mitochondrial cytopathy, whole exome sequencing

PMC4150339_01

Male

A 32-year-old male presented to the surgical clinic with multiple left axillary lymph nodes. His complaints had been persistent for the previous eight months and had been preceded by development of furuncles in the axilla. Although he had infrequently taken treatment from several practitioners, there was no relief to his complaints. He subsequently developed fever ranging from 100-101 F. There was no family or past history of tuberculosis or loss of weight or appetite. Jaundice was not present. The patient had a negative Montoux test. Hematological evaluation revealed a raised erythrocyte sedimentation rate (ESR) of 28 mm in the first hour by the Wintrobes method. Other hematological parameters, including a coagulation profile, were normal. The chest radiograph did not reveal any abnormality. Liver function tests showed the total bilirubin level to be 0.7 mg/dL, serum alkaline phosphatase was 52 U/L, and serum alanine and aspartate aminotransferases were 21 U/L and 28U/L, respectively. The patient was referred to the Department of Pathology for FNAC, with a provisional diagnosis of tuberculosis, a disease rampant in rural as well as urban India. On palpation, three lymph nodes were discernible in the left central axilla which were discrete, firm, and mobile, ranging in size from 0.8 to 2.0 cm, with pain in the largest one. FNA was performed on the largest lymph node. A blood-tinged caseous aspirate was obtained and several fixed and dry smears were prepared, which were stained with hematoxylin and eosin, Giemsa, and Ziehl Neelson (ZN) stains. Smears were cellular showing intact and degenerated neutrophils, histiocytes, and eosinophils, along with several loose epithelioid cell granulomas, giant cells, and a variable number of lymphoid cells [Figure 1a]. The background showed extensive caseous necrosis. When the ZN stained smears were being screened for the presence of acid fast bacilli, classical hooklets of Echinococcus were noticed [Figure 2a]. The hooklets were semi-translucent, retractile, and sickle-shaped, with an inner semi-translucent core of a similar shape. Alerted by this discovery, a further search revealed scolices of Echinococcus, which were large ovoid structures [Figure 2b]. However, no lamellated membrane was identified. In addition, classic granular, beaded, acid fast bacilli of Mycobacterium tuberculosis were seen [Figure 1b]. This enabled us to render a diagnosis of tuberculous lymphadenitis with coexistent echinococcal infection. An ultrasound of the abdomen was unremarkable. Contrast-enhanced computed tomography was advised for the chest as well as liver, which the patient could not afford. The echinococcal indirect hemagglutination test was negative. Retrospectively, the patient gave a history of contact with a dog. Polymerase chain reaction as well as culture for Mycobacterium tuberculosis was positive. Antihelminthic as well as anti-tuberculous therapy was started. However, the excision could not be performed as the patient was lost to follow-up.

axilla, coexistent, hydatid, tuberculosis

PMC5619536_01

Male

A 74 year-old man, a retired bank clerk, presented with hand tremors that had started five years earlier and worsened over the last year. The tremors were more severe when the patient had to hold objects with his hands or when he was worried. He also complained of gait disturbance attributed to previous traumatic lesions of the ankle and knee joints that occurred during his lifetime as a football (soccer) player. Recently, he had manifested several episodes of urinary incontinence and a few incidents of fecal incontinence. His wife reported that he had become progressively more forgetful over the last five years, with difficulties in remembering appointments, messages or where he had kept his things. In the last month he had presented episodes of misinterpretations of TV programs as real events and of not recognizing his house as his own. No other physical illness was reported. His mother had a similar tremor when she was very old. She died at the age of 94, but after 89 years she began to show cognitive decline. One of his sisters also has hand tremors but no memory complains, whereas his other sister and brother were apparently unaffected. He had two daughters and the only offspring of one of the daughters was a 7-year-old mentally deficient boy. His two sons were clinically normal. On examination his blood pressure was 140 x 80 mm Hg, and there were signs of arthrosis in both ankle and knee joints. His gait was slightly ataxic and action (postural and kinetic) tremors in upper extremities, left greater than right, were evident. Rest tremor as well as bradykinesia and rigidity were absent. The hand tremors made it difficult to evaluate the coordination of the upper extremities, whereas no coordination problems were present in his legs. The subject also had voice tremor. He scored 20 on the Mini-mental State Examination (MMSE), a low score given his 16 years of schooling, in spite of his incapacity for drawing or writing because of the tremor (Figure 1). He was easily distracted and was unable to accurately repeat sentences from the MMSE or to obey the simple commands involved in the test. In the memorization of drawings from the Brief Cognitive Battery, he showed more severe learning than delayed recall impairment demonstrated by his score of 5 out of the 10 items in the learning test, while in the delayed recall test he was able to recall 4 of the 5 items. In the Dementia Rating Scale he scored 88, with low performance across all subtests (drawing and writing incapacities further reduced his score). He scored 3 on the Digit span in both direct and reverse order. In the Logical Memory of the Wechsler Memory Scale he attained the 6th percentile on immediate recall, but was able to reach the 10th percentile after 30 minutes. Semantic verbal fluency was low for animals in one minute (5 animals) as well as for supermarket items (6 items). Phonemic verbal fluency was also very low, with a total score of 4 for the letters F, A and S together, and 2 for the letter P. His score on the Stroop Color Test was poor with 22 errors (1.8 standard deviations below the mean for his age). His score on the Questionnaire of Functional Activities was 7 (scores higher than 5 are indicative of impairment in instrumental activities of daily living, often observed in dementias). Routine laboratory tests were normal except for a high serum level of triglycerides. EKG was normal. Brain MRI images were acquired on a 1.5T MR system (Signa Excite - GE - Milwaukee - USA) using an 8 Ch head coil. Axial T2-weighted FSE (TR: 2200 ms / TEef: 90 ms / NEX: 1), axial FLAIR (TR: 11000 ms / TEef: 104 ms / TI: 2200 ms / NEX: 1); pre and post Gadolinium axial MTC T1-weighted (TR: 500 ms / TE: 19 ms / TI: ms / NEX: 1 / MT offset: 1200 Hz) images were collected as per routine investigation. There was marked ventricle enlargement, with slight augmentation of the remaining CSF spaces. Diffuse T2 and FLAIR white matter hyperintensities were found in both superior and infratentorial compartments, with a distinct distribution, being symmetrical in the middle cerebellar peduncles (MCP), splenium of the corpus callosum, middle pontine region and periaqueductal grey matter - and most of the bi-hemispheric white matter and periventricular regions (Figure 2). These lesions did not exhibit contrast enhancement and had no corresponding MR signal alterations on the Magnetization Transfer Contrast images. Additionally, an area of tissue loss located in the anterior vermis (at the culmen and declive lobules) was detected indicating a possible earlier infarct. Analysis of the FMR1 gene showed a premutation with (CGG)90. The presence of the premutation in this patient prompted the genetic counseling of his two daughters, obligate permutation carriers. The examination of his mentally retarded grandson revealed the FMR1 full mutation, thus establishing the diagnosis of fragile X syndrome. He was treated with primidone 100 mg/day associated with propranolol 40 mg/day with partial improvement in the tremor, making eating and shaving easier for him. An informed consent form was signed by the patient's son authorizing the publication of the case for medical and scientific purposes.

ataxia, dementia, essencial tremor, fragile x, premutation, tremor

PMC9937636_01

Female

A 43-year-old female presented to the emergency department for a first episode of sudden onset shortness of breath and several episodes of hemoptysis. The patient did not have any chest pain, cough, fever, weight loss, hematemesis, hematochezia, or hematuria. The patient did not have any history of exposure to toxic substances, smoking, or alcohol. Her past medical history was remarkable for hypertension diagnosed five years back. The patient was on medical treatment (Valsartan/Amlodipine 160mg/10mg tablet), but she had discontinued her medication for the last two months. In addition, she had a history of uncontrolled diabetes mellitus type 2. On physical examination, the patient was tachypneic (respiratory rate 30 per minute) with low oxygen saturation SPO2 90% on room air that improved with oxygen supplementation by 3 L/min nasal cannula to 99%, hypertensive (blood pressure=224/143, tachycardiac (heart rate 105 per minute) and normal temperature. On auscultation, chest is clear, no wheezes or crackles, and normal s1 and s2 without any added sounds or murmurs. Laboratory blood tests were all within the normal range. Notably, her hemoglobin dropped from 14.7 to 13.6 g/dL and her hematocrit dropped from 43.1% to 40.6%. White blood cells WBC= 8x103/microliter. Procalcitonin=0.05 ng/mL. Normal coagulation studies (INR=0.9, Aptt=26.4 seconds). Renal function tests were within the normal range (urea 5.8 mmol/L, creatinine 83 mumol/L), Na 138 mmol/L, K=4 mmol/L. Chest x-ray (Figure 1) showed prominent broncho-vascular markings with focal infiltrates in the right middle zone and cardiomegaly. CT chest with contrast (Figure 2) (pulmonary angiography protocol) showed diffuse fluffy ground glass opacities bilaterally involving the right upper and middle lobes, which suggest alveolar hemorrhage or edema with no evidence of pulmonary embolism. Echocardiography showed mildly reduced left ventricular systolic function with a calculated ejection fraction of 47%, grade 1 diastolic dysfunction, and normal left atrial pressure. There was mild concentric left ventricular hypertrophy. COVID-19 PCR, acid-fast bacilli smear, tuberculosis PCR and immunology workup were all negative. During bronchoscopy, mucosa was looking normal without active bleeding; however, sequential lavage taken from the right upper lobe was hemorrhagic, worsening and not clearing. Bronchial wash and bronchial alveolar lavage consisted of reddish and turbid fluid. Microscopy was negative for malignancy and granuloma. Bronchoscopy showed 26% lymphocytes with positive hemosiderin-laden macrophages. Within a few hours, blood pressure was controlled with three boluses of intravenous labetalol 20mg and Valsartan/Amlodipine 160mg/10mg tablet. Hemoptysis stopped. Shortness of breath improved, and oxygen requirements gradually decreased (blood oxygen saturation 98% on room air). No other drugs were needed. The patient was discharged home after 48 hours on Valsartan/Amlodipine 160mg/10mg tablet. Based on the clinical presentation, imaging, bronchoscopy findings and laboratory blood tests, the patient was diagnosed with DAH as a complication of severe hypertension.

diffuse alveolar hemorrhage, hemoptysis, severe hypertension, sob - shortness of breath, sudden-onset, uncontrolled hypertension

PMC9981548_01

Female

A 25-year-old Caucasian female presented to the emergency department with intermittent joint pains for four weeks and hemoptysis. She reported first symptoms of difficulty making a fist, first with the right hand and then progressing to the left hand. She reported migratory joint pain that affected her bilateral elbows and shoulders. Each joint pain episode lasted approximately 36 hours before migrating to different joints. Three days before admission while she was traveling in the Midwest United States, she had three bouts of small-volume hemoptysis, approximately one teaspoon each time, which prompted her to come to the hospital. A review of systems was notable for an unexplained 15-pound weight loss in one year. She has a past medical history of migraine and a history of Achilles tendon infection in 2019. She took sarecycline daily for acne for two months before admission. She works with chimpanzees in the laboratory. Her physical examination was significant for non-blanchable purpuric rash on the left elbow and toes and swelling and erythema of the left knee (Figure 1 and Figure 2). Her nasal and otoscopic examination was unremarkable. Her presenting blood investigation was notable for normocytic anemia, low iron levels, and hypereosinophilia (eosinophils 9%) (normal range: 0%-5%). She had mildly elevated total bilirubin and C-reactive protein (CRP). Her urine analysis was positive for ketones and red blood cells (RBCs). Initial chest X-ray showed confluent airspace disease, prominent in the lower lobe, and right greater than left (Figure 3). In summary, the patient presented with migratory joint pain, purpuric rash, weight loss, anemia, low iron levels, indirect hyperbilirubinemia, hypereosinophilia, microscopic hematuria, and mild hemoptysis. Due to the subacute course and systemic involvement, an autoimmune process such as systemic vasculitis was highly suspected. Within the differential, infectious and paraneoplastic processes were also considered. Infectious workup, including human immunodeficiency virus (HIV), hepatitis B and C panels, Histoplasma, parvovirus, Mycoplasma pneumoniae, tuberculosis, Pneumocystis jirovecii, Cytomegalovirus, herpes simplex virus (HSV)-1, and HSV-2, were all negative. Transthoracic echocardiogram did not show evidence of endocarditis or atrial myxoma. Vasculitis diseases such as ANCA-associated vasculitis and immune complex vasculitis were highly suspected. We sent autoimmune laboratory results for ANCA and other autoimmune diseases that could be related to immune complex vasculitis such as cryoglobulins vasculitis, lupus, and rheumatoid arthritis. Goodpasture's syndrome and sarcoidosis were also in the differential diagnosis, which could be obtained by bronchoscopy. Anti-glomerular basement membrane (GBM) antibody was sent for possible Goodpasture's syndrome. The sarecycline that the patient used before admission has never been reported to be associated with ANCA-associated vasculitis before. Finally, a skin biopsy was suggested and did not show vasculitis. However, it revealed dermal blood vessels with intravascular thrombi without evidence of vasculitis. Because of the increased risk of hypercoagulable states from intravascular thrombi and concern for hemolytic anemia, hematology was consulted. The patient underwent multiple hematology workups, including prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, beta-2 glycoprotein, cardiolipin antibody, cryoglobulins, lupus anticoagulant, protein C, protein S, antithrombin III, and factor V Leiden, which were all negative. She had mildly elevated D-dimer (592 ng/mL) (normal range: <281 ng/mL), which did not support any specific diagnosis. Her direct and indirect Coombs tests were negative, suggesting that this was less likely to be autoimmune hemolytic anemia. Her peripheral blood smear did not show evidence of schistocytes, and her lactic dehydrogenase (LDH), haptoglobin, was negative, which helped rule out microangiopathic hemolytic anemia. Pulmonology was consulted due to an unclear diagnosis, and bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy was performed. The bronchoscopy revealed erythematous lesions on the tracheal mucosa (Figure 4). Cytology from BAL was negative for malignancy. Biopsy showed airway wall fibrosis, chronic inflammation, and scattered eosinophils with no definitive evidence of vasculitis. Fragments of lung parenchyma with hemosiderin-laden macrophages and focal intra-alveolar fibrin were seen. The findings were consistent with diffuse alveolar hemorrhage. Hypersensitivity pneumonitis was less likely due to a negative test. Acute eosinophilic pneumonia was less likely due to low numbers of eosinophils from BAL. Later in her hospitalization, the autoimmune laboratory results came back. Antinuclear antibody (ANA), anti-GBM antibody, and cyclic citrullinated peptide (CCP) were negative. Rheumatoid factor was 19.5 IU/mL (normal range: <12 IU/mL). Her anti-PR3 antibody and cytoplasmic ANCA (c-ANCA) titer were positive at 1:320. Given the positive anti-PR3 antibody and c-ANCA, ANCA-associated vasculitis, especially GPA, microscopic polyangiitis (MPA), was the most likely diagnosis. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) is more associated with anti-myeloperoxidase (MPO) antibody than PR-3 antibody and thus less likely to be the cause. The patient was treated with 1 g methylprednisolone for three days before transitioning to prednisone 60 mg daily for presumptive vasculitis. Nephrology was consulted for microscopic hematuria. Her urine sediment showed multiple white blood cells, dysmorphic RBC, and RBC casts raising concerns of renal involvement from systemic disease. Since the diagnosis remained unclear even after a skin biopsy and a bronchoscopy, a kidney biopsy was performed. Finally, a kidney biopsy showed pauci-immune necrotizing and crescentic glomerulonephritis involving about 20% of intact glomeruli and minimal (1% of glomeruli) chronic changes of the parenchyma (focal global glomerulosclerosis). A diagnosis of granulomatosis with polyangiitis with articular, pulmonary, renal, and skin involvement was made. Due to her fertile age, rituximab was chosen instead of cyclophosphamide to avoid side effects as it was not an inferior option. The patient eventually received one dose of IV rituximab at 375 mg/m2 and was discharged with outpatient rheumatology follow-up.

anca vasculitis, gpa, granulomatosis with polyangiitis, hemoptysis, thrombotic vasculopathy, wegener’s granulomatosis

PMC6742882_01

Male

A healthy 18-year-old right-hand dominant male presented to clinic 5 days after injuring his left shoulder during a high school football game. The patient reported landing directly on his left shoulder after being tackled. He noted immediate pain and inability to move his left shoulder. On-site athletic training staff removed him from play and placed him into a sling. This was an injury to his non-throwing arm. At his initial evaluation 5 days after his injury, he continued to have severe pain and limited motion. He denied any previous shoulder injury. Examination was limited due to guarding. Clinically, he had significant ecchymosis about the upper arm and tenderness to palpation throughout the proximal shoulder. Active forward elevation was limited to 60 . He had weakness with posterior rotator cuff testing. There were no appreciable signs of instability on examination. Plain radiographs including anteroposterior, axillary lateral, and outlet views of the shoulder were obtained in office and demonstrated no evidence of acute fracture or dislocation. There was no evidence of Hill-Sachs deformity. The patient was sent for magnetic resonance arthrogram (MRA) to further evaluate his injury. MRA (Figs. 1A and B) demonstrated a full-thickness tear of the infraspinatus with minimal retraction. The supraspinatus and subscapularis were intact. No biceps or labral pathology was identified. After discussing options with the patient and his family, the decision was made to proceed with arthroscopic rotator cuff repair. Ten days after sustaining his injury, the patient was taken to the operating room. Preoperatively, the patient received an interscalene block and general endotracheal anesthesia was administered. The patient was then placed in the lateral decubitus position with 10 pounds of traction applied to the shoulder. A standard posterior portal was created and a 30 arthroscope was inserted into the glenohumeral joint. Copious hemarthrosis was evacuated from the joint. The anterior labrum, superior labrum, biceps, and subscapularis showed no evidence of injury. A full-thickness tear of the infraspinatus was confirmed while viewing from the articular side. Visualization from the lateral portal confirmed the massive midsubstance "L"-shaped tear of the entire infraspinatus tendon (Fig. 2). A knotless, speed bridge double-row construct was performed to repair the tendons after debridement of the free tendon edges and tendon footprint. Two 4.75 mm SwiveLock anchors loaded with FiberTape (Arthrex, Naples, Florida [FL]) were placed just lateral to the articular margin, one anterior and one posterior on the footprint. The tape-type sutures were passed in a horizontal mattress fashion through the tendon. An additional FiberLink (Arthrex, Naples, FL) was passed through the most posterior aspect of the infraspinatus tendon. The lateral row was then created with two additional 4.75 mm SwiveLock anchors (Arthrex, Naples, FL). Visualization from the lateral portal confirmed an excellent restoration of the tendon to the footprint following repair (Fig. 3). Skin closure was performed in a normal fashion, and the patient was then placed in an abduction sling following the arthroscopic repair. Routine care was provided postoperatively. Physical therapy was initiated at 1 week postoperatively. The sling was discontinued 6 weeks after surgery. At 5 months following his repair, his range of motion was normalized. He demonstrated forward elevation of 180 , lateral abduction of 180 , and external rotation at neutral of 70 . Strength assessment with Jobe's testing and external rotation testing at neutral revealed no clinical difference compared to the uninjured shoulder. At the final 18-month follow-up, clinical strength and motion testing were equal to his uninjured shoulder. While the patient had no intentions of playing college football, he was able to return to weight training and playing recreational ice hockey.

arthroscopy, infraspinatus, rotator cuff, shoulder

PMC4304892_01

Male

A 60-year-old man underwent arthroscopic repair for a supraspinatus tear of his left shoulder. A single 5.5-mm poly-L-lactic acid anchor (Spiralok , DePuy Mitek) was threaded with two strands of #2 (Orthocord ) suture. His medical history does not include rheumatoid arthritis, tuberculosis or previous allergies. At three-month follow-up, the patient reported a constant low-grade dull left shoulder ache. At nine months, the pain had worsened. He described 'crunching sensation' with shoulder movement. Physical examination revealed a swelling over the anterior aspect of the left shoulder. His range of movements was as follows: external rotation to 50 , elevation to 140 , abduction to 95 and internal rotation to the third lumbar vertebra. Movement was painful and produced crepitus. The visual analogue pain score was 8/10. C-reactive protein, leukocyte and erythrocyte sedimentation levels were normal. Plain radiographs of the shoulder showed no abnormality. A magnetic resonance imaging showed fluid distended subacromial and subdeltoid bursae, containing numerous small bodies of intermediate density on proton density sequences (Figures 1 and 2). The patient underwent a left shoulder arthroscopic debridement, evacuation of loose bodies, poly-L-lactic acid anchor and suture removal. Intra-operatively, hundreds of grain-like loose bodies filled the subacromial and subdeltoid bursae. The supraspinatus repair was partially disrupted. No macroscopic evidence of infection could be seen. The poly-L-lactic acid anchor showed no fragmentation. No organisms were grown from operative specimens (early and late cultures). Microscopically, the loose bodies were found to be inflammatory rice bodies, with an inner amorphous core of acidophilic material, surrounded by a plasma and lymphocytic cell infiltrate, with an outer rim of fibrin-like material. No foreign body granulomas or polymer debris were seen microscopically. Allergen testing using the British Contact Dermatitis Society standard extensive series, as well as patch testing to both anchor and suture material were negative. Post-operatively, the patient's pain improved almost immediately. Two months later, a magnetic resonance imaging scan showed complete resolution of the rice bodies, with mild residual subacromial and subdeltoid bursitis. The patient regained a full range of shoulder movement but continued to complain of pain and weakness with overhead activity. Six months post-arthroscopic debridement, a revision arthroscopic rotator cuff repair was performed using a 5.5-mm Titanium anchor loaded with suture (Orthocord ). At 12-month follow-up, the patient was pain-free. He remained asymptomatic at two years' post-operation.

PMC5805845_01

Male

Tracheobronchomalacia (TBM) is characterized by weakness of cartilaginous supporting structures of tracheal and bronchial walls, resulting in central airway obstruction. Here, we report a patient of 26-year-old, morbidly obese man presents with worsening upper airway obstruction (UAO) for two weeks. Previously, he was admitted to ICU with metabolic encephalopathy and multiple organ dysfunction syndromes. Initially, he had a brief episode of generalized tonic-clonic seizure due to alcohol withdrawal syndrome, and was intubated with a styletted 8.5 mm cuffed endotracheal tube (ETT) by an anesthesiologist with one attempt. At ICU, his blood culture was positive for Staphylococus Aureus. His hospital course was complicated by severe ARDS (PaO2/FiO2 40.1, Oxygen index 32.4), severe alcoholic hepatitis (requiring prolonged course of prednisone), fulminant hepatic failure (Albumin 2.9 g/dL, PT 18.5 secs, and INR 1.66, Hepatic encephalopathy grade 4), and acute kidney injury stage 1 (urine output 870 ml/24 hours, serum creatinine 1.5 mg/dL). He was on pressure-regulated volume controlled with lung protective strategies. His peak pressure was in the range of 23-37 cmH2O. Then, he was extubated successfully on ICU day 15 without any signs of upper airway obstruction. A 14-day course of antibiotics was completed and he was discharged on day 23 of hospitalization. Two weeks later, he was re-admitted because of UAO. Biphasic stridor, hoarseness, productive cough and shortness of breath were appreciated. Physical exam showed stable hemodynamics but hypoxemia (SpO2 86%, on room air) and increase work of breathing. Chest X-ray showed no infiltration. Contrast-enhanced spiral CT of neck reveals mild subglottic wall thickening with patent airway. ENT performed direct laryngoscopy. It showed proximal tracheal stenosis of 6 cm, involving tissue just below cricoid. This stenosis is inclusive of the segment with dynamic airway collapse. Proximal trachea and subglottic area was subsequently dilated up to 8 French of endotracheal tube size. He was discharged with beclomethasone, proton pump inhibitor and ciprofloxacin. The second bronchoscopy was performed at day 8 after discharge because of persistent shortness of breath. Tracheal stenosis was found with a diameter of 5 mm. Subsequently, narrowed airway was dilated by balloon, cauterized by Argon plasma coagulation and injected with mitomycin C. The third bronchoscopy was repeated at day 14 after discharge because of recurrent UAO. It showed subglottic stenosis of approximately 1.5 cm below the vocal cords. Trachea was stenotic (90% occlusion) from 1.5 cm below the vocal cords to roughly 6 cm above the carina with near total collapse during expiration. Balloon dilation was performed in the trachea using a 6 cm (length) and 15 mm (diameter) CRE balloon with 50% dilatation of lumen size for management of tracheal stenosis. Cryotherapy was performed in the trachea for destruction of abnormal tissue. Mitomycin C was then injected into the granulation tissue. He was discharged with extended period of steroid taper and amoxicillin/clavulanic acid. The plan is to follow as outpatient for evaluation for possible stent placement and/or tracheostomy.

PMC3350127_01

Male

The patient was a 3-month-old male with cyanotic congenital heart disease consisting of double outlet right ventricle, near absent intraventricular septum, and aortic arch hypoplasia, who had previously undergone a Norwood stage I palliation with 3.5 mm modified Blalock-Taussig shunt (see Figure 1). He presented at 3 months of age for the next stage of palliation, a cavopulmonary anastomosis (bidirectional Glenn). His weight was 5.8 kg (31% percentile) and height was 58 cm (18% percentile). Pulse oximetry demonstrated O2 saturations of 70 to 80%, which was appropriate for his lesion. Cardiac catheterization findings included a widely patent arch with estimated normal pulmonary artery (PA) pressures (mean of 12 mmHg in the RPA) by reverse pulmonary vein wedge, a BT shunt widely patent and arising from the innominate artery with flow to the branch pulmonary arteries. The preoperative CXR was unremarkable except for prior sternotomy. A preoperative echocardiogram demonstrated the above described anatomy, insignificant atrioventricular valve insufficiency, a patent modified Blalock-Taussig shunt, and patent proximal branch PA's. Anesthesia was induced with fentanyl 50 mcg and pancuronium 1 mg, after premedication with intravenous midazolam 1 mg. After endotracheal intubation, anesthesia was maintained with a balanced anesthetic consisting of end tidal isoflurane concentrations of 0.4% and high-dose fentanyl (~100 mcg/kg) in air/oxygen mixture. A left subclavian central venous catheter was placed after induction. A right femoral arterial line was in place from earlier heart catheterization. The patient tolerated anesthetic induction, placement of invasive lines and monitors and the pre-incision period with stable hemodynamics. In addition to standard ASA monitors, bilateral cerebral and somatic oximetry (Somanetics INVOS) was monitored throughout the case. Transesophageal echocardiography (TEE) was not used. It is not our practice to use TEE for cavopulmonary anastomosis procedures or procedures in which the cardiac chambers are not opened. Cardiopulmonary bypass (CPB) commenced with bicaval venous cannulation at the inferior vena cava-right atrial (IVC-RA) junction and the innominate vein. The modified Blalock-Taussig shunt was ligated and divided at the initiation of cardiopulmonary bypass. The azygous vein was divided and the superior vena cava was separated from the right atrium. The bidirectional cavopulmonary anastomosis was constructed. The patient was weaned from CPB on dopamine (initially at 5 mcg/kg/min, range 0-5 mcg/kg/min) and milrinone (0.5 mcg/kg/min). Nitroprusside 0.5 mcg/kg/min, titrated to effect, was used briefly for a period of hypertension. Dexmedetomidine (0.7 mcg/kg/hr) was started during rewarming for post-op sedation. After successfully separating from cardiopulmonary bypass, O2 saturations were near 100% and the transpulmonary gradient (CVP-LAP) was 8 to 9 mmHg. The left subclavian venous line tip was visible in the superior vena cava, near the innominate vein-superior vena cava (SVC) junction. Modified ultrafiltration was performed, protamine administered, and routine decannulation and sternotomy closure were performed. The cardiopulmonary bypass time was 36 minutes. During the postbypass period the patient had stable vital signs with invasive blood pressures (IBPs) of ~90/40, heart rates (HRs) of ~150, oxygen saturations of 80-90% on 100% FiO2, central venous pressures (CVPs) of 12, and transpulmonary gradient (CVP-LAP) of 7-9 mmHg. Cerebral and somatic saturations were unchanged from baseline and the prebypass period. Preparations were being made to transport the patient to the ICU when a sudden drop in SpO2 to the 60's, a sudden rise in CVP to the mid 20's, ST segment elevation, and an acute change in the patient's color (head and face became profoundly plethoric) were noted. EtCO2 was also markedly decreased although there was no change in ventilation. Bradycardia soon followed as oxygen saturations continued to decline. Cardiopulmonary resuscitation (CPR) was immediately started with chest compressions and administration of resuscitative drugs. Preparations for reopening the chest and initiating cardiopulmonary bypass (CPB) were made while CPR continued. Profound hypoxemia persisted despite good quality CPR, confirmed with an arterial pulse with compressions and adequate ventilation. The chest was reopened during the administration of CPR with no evidence of tamponade. On examination of the superior vena cava, an abundant collection of air bubbles was visible through the wall of the vein, appearing to fill the entire superior vena cava from the pulmonary anastomosis to the innominate vein (see Figure 2). A needle was placed in the superior vena cava and a large amount of air escaped through the needle hole. Myocardial function had begun to decline despite some improvement in oxygenation, so the patient was placed emergently on cardiopulmonary bypass. Sixteen minutes had elapsed since hemodynamic collapse and initiation of full CPB. No air bubbles in the systemic circulation were observed at aortic cannulation, offering some assurance that the emboli were confined to the cavopulmonary circuit. Approximately 3 mL of air was aspirated from the SVC while the patient was on CPB. The patient was separated from cardiopulmonary bypass after 36 minutes, with hemodynamics nearly identical to those before arrest, the exception being slightly lower oxygen saturations, 80-85%. During the bypass period, efforts were made to determine the source of the emboli and prevent further expansion, but no definitive source was ever discovered. Unfortunately, echocardiography was not used during the initial procedure, so it was not available at the time of the arrest. The patient remained stable after the second bypass period and tolerated chest closure. Systemic hypothermia was initiated Intra-op and continued for 24 hours post-op with a target temperature of 34-35 C. He was taken to the PICU in stable condition. The patient did well over the remainder of his hospital course with no discernible neurological or cardiovascular sequelae of the arrest and was discharged to home on POD 10.

PMC9852623_01

Male

A 50-years-old retired man came to our institution with a 1-year history of neck stiffness and muscle weakness. He reported the feeling on the cotton while walking and the patient's bilateral tendon hyperreflexia and Hoffmann's sign were positive. His family and medical history were not significant. Laboratory results showed a normal erythrocyte sedimentation rate (5 mm) and C-reactive protein (1.2 mg/L). The cervical spine Magnetic resonance imaging (MRI) demonstrated that the cervical disc at the level of C3/4 was herniated to the left from the median, and the spinal cord was obviously compressed (Figures 1A, 2A,C). Chest CT showed an old foci of pulmonary TB in the upper lobe of the left lung (Figure 1B). A preoperative enhanced MRI ruled out the possibility of a tumour in the patient's cervical spine (Figures 3A-D). Thus, the patients were considered to be cervical spondylotic myelopathy (Figure 4A). The patient then underwent an anterior cervical discectomy and fusion (ACDF) at the C3/4 segment in hope of a cure. The patient's herniated cervical disc was carefully removed and the bleeding was stopped. The implant was allogeneic bone-filled polyetheretherketone (PEEK). On the second day postoperatively, an x-ray examination (Figure 4B) confirmed the decompression of the spinal cord, and the implant structure was stable and the position was correct. Postoperative MR of the patient's C3/4 and C4/5 segments showed good postoperative decompression and no vertebral body infection (Figures 2B,D). Postoperative laboratory results showed normal erythrocyte sedimentation rate (5 mm) and C-reactive protein (4.1 mg/L). The preoperative CT showed no infection in the cervical vertebrae (Figures 5A,B). The postoperative cervical spine CT showed successful surgical decompression, stable endophytes and no signs of infection in the vertebral body (Figures 5C,D). One week postoperatively, the patients didn't show any complaints and can walk independently when leaving the hospital. However, 2 weeks postoperatively, the patient developed neck pain, which was worsened when lying down and turning to the left. He came to our department again on 2021.8.16. Since the onset of the disease, The patients did not show any symptoms of TB infection such as low-grade fever, night sweats, occasional fatigue, insomnia, and no obvious abnormality in limb movement and sensation. The cervical spine MRI imaging 2 months after surgery (Figures 1C,D, 4C) showed bone erosion at the C4/5 vertebral body edge with swelling of the paravertebral soft tissue, and inflammatory manifestations of the C4/5 intervertebral disc and vertebral body. The patient's pain was not relieved after 48 h of empiric antibiotic (ceftriaxone) treatment. Although vancomycin was used to upgrade the antibiotics, after 48 h, there was still no obvious improvement. The elective surgery was arranged for the patient immediately. Six hours before the operation, the patient reported insomnia and night sweats for the past 2 days. After follow-up, the patient was found to have a low fever. New assay results showed neutrophil percentage 52.10%; lymphocyte percentage 41.1%; tuberculosis -infected T cell culture (TBA: 13sfc/2.5*10e5; TBB: 6 sfc/2.5*10e5) was positive and IFN release was detected -gamma-specific lymphocytes. After out-of-hospital consultation, the patient was diagnosed with cervical spine TB, and received anti-tuberculosis drug treatment: isoniazid (INH) 0.3 g QD, rifampicin (RMP) 0.45 g QD, ethambutol (EMB) 0.75 g QD, levofloxacin 0.5 g QD. One-week post-treatment, the patient's neck pain was relieved, and he requested to be discharged home for treatment after informed consent. The patient was instructed to continue the course of anti-tuberculosis treatment, with cervical collar fixation to avoid activities involving neck movement and weight-bearing for 3 months. The patient was kept regular follow-ups. On June 16, 2022, the patient underwent a cervical spine x-ray examination and the results showed (Figure 4D) that the C3/4 and C4/5 segments were fused, and the paravertebral soft tissue swelling disappeared. The patient's neck pain improved significantly, and it is recommended to continue anti-tuberculosis treatment.

adjacent segment infection, anterior cervical discectomy and fusion, cervical spine, cervical spondylotic myelopathy, tuberculosis

PMC7419425_01

Female

A 2-month-old female Pug was presented with a history of the vestibular episodes especially during or after eating. The owners first noticed the episodes when the puppy started to eat dry food. General physical examination was unremarkable. Neurological examination showed very mild vestibular ataxia while the puppy was walking. However, after the postural head testing, playing and eating, the vestibular deficits became transiently pronounced, showing moderate head tilt to the left, moderate vestibular ataxia with drifting to the left and a broad-based stance. After several seconds to a minute, the deficits mostly disappeared. Neuroanatomic localization was consistent with vestbulo-cerebellum. Differential diagnoses included congenital and degenerative causes, nevertheless, inflammatory and infectious conditions were considered as well. The complete blood count (IDEXX Lasercyte) and serum biochemistry results (IDEXX Catalyst, Clip 10) were normal for a puppy. Brain MRI was performed on the initial presentation day, and multiplanar T2W, T2W-FLAIR, T1W, and T1W post intravenous administration of a gadolinium based contrast agent (Omniscan, GE Healthcare AS, NO, 0.1 mmol/kg) images were acquired. The T1W and T2W sagittal images showed a reduced size of the nodulus and uvula of the caudal cerebellum with hypoplasia of the caudal cranial fossa (Figure 4A), without contrast enhancement. The patient also had a midline fusion defect of the dorsal arch of C1, however, did not demonstrate any associated cervical instability. The cerebrospinal fluid (CSF) analysis [cisternal tap, TNCC and cytology (Statspin Cytofuge 12)] was within normal limits. Both infectious disease PCR assays (Ehrlichia canis, canine herpes virus, canine parvovirus, canine distemper virus, Neospora caninum, Toxoplasma gondii, and Anaplasma phagocytophilum) and tick encephalitis antibody testing from CSF were negative. Caudal cerebellar hypoplasia was suspected and no treatment was administered. The owners report a stable status after 4 months, and the puppy has learnt to compensate for the deficits. The episodes continue to occur; mostly after playing with sticks and toys and now are rarely noted during eating.

mri, cerebellum, postural, transient, vestibular

PMC6462797_01

Female

A 35 year old healthy lady presented to our department on sixth postoperative day [POD] with an external biliary fistula and intra-abdominal sepsis. She had undergone laparoscopic converted to open cholecystectomy for acute calculous cholecystitis. She had a biliary injury that was identified intra-operatively, managed by Roux-en-y hepaticojejunostomy[RYHJ]. The anastomosis leaked. An interno-external percutaneous transhepatic biliary drainage[PTBD] extending across the leak was performed at our hospital on POD 7 for both right and left hepatic ducts. On POD nine, she had an upper gastrointestinal bleed. Esophagogastroduodenoscopy and Contrast enhanced computed tomography [CECT] abdomen did not reveal the source of bleeding. On conventional hepatic arteriogram, a leaking cystic artery pseudoaneurysm was identified (Fig. 1). During angioembolisation, due to a short stump of cystic artery, coils were placed in right hepatic artery [RHA]. However, one of the coils accidentally migrated into the left hepatic artery [LHA] and could not be retrieved. LHA stenting was performed, with good flow of contrast across the stent (Fig. 2). However, LHA developed spasm in its distal part, resulting in complete block of LHA and RHA. On first day after coiling, there was significant elevation of liver enzymes with features of ischemic hepatitis. CECT abdomen with arteriography revealed poor enhancement of hepatic arterial tree in the segmental branches with partial revascularization from inferior phrenic and retroperitoneal arteries. The patient's relatives were explained the possibility of a need for an emergency liver transplant. The patient improved over the next 48 h, was transferred out of intensive care unit and oral feeds were started. Abdominal drain was removed after it stopped draining bile. She was discharged on POD 28 with PTBD catheters in situ. On POD 33, her liver function tests were within normal limits, percutaneous transhepatic cholangiogram showed trickle of contrast across the RYHJ, and the PTBD catheters were clamped. PTBD catheters were kept longer than 6 months and intervening periodic cholangiograms revealed anastomotic narrowing. Balloon dilatation of the stenosed anastomosis was performed on multiple occasions. Liver function was normal all along. Fourteen months after surgery, cholangiogram revealed a worsening of RYHJ stricture (Fig. 3). A CECT abdomen and conventional angiogram performed at 18 months showed a blocked RHA and LHA. Multiple collaterals were seen arising from the right inferior phrenic artery, retroperitoneum and along the hepatoduodenal ligament (Fig. 4). In view of the collateral formation and persistent tight stricture with failed multiple dilatations, a surgical revision of the anastomosis was planned. Prior to surgery, right PTBD catheter was maneuvered from right to left duct across the hilum, draining externally. During surgery, utmost care was taken not to release any adhesions in the hepatoduodenal ligament and not to mobilize liver from the diaphragmatic attachments to preserve all collaterals. Hilar dissection was kept to a minimum and the PTBD catheters guided the identification of biliary hilar confluence. A minor segement IV hepatotomy was done to expose the left hepatic duct and the roof of biliary confluence. Previous anastomosis was resected, and a Roux loop was prepared. A 2 cm single layer, interrupted 5-0 polydioxanone RYHJ was fashioned to the anterior wall of the biliary confluence with an extension onto the left duct. Her postoperative recovery was uneventful. Cholangiogram on POD 10 showed a good flow across the anastomosis with no sign of a leak, and she was discharged with a clamped PTBD catheter. The PTBD catheter was removed 6 weeks after the surgery. The patient is doing well at 1 year follow up. Liver function is normal. She is being followed up to evaluate for secondary patency.

case report, complete hepatic arterial ischemia, complex biliary injury, revision hepaticojejunostomy

PMC2810472_01

Male

26-year-old African American male presented with shortness of breath of over two months. He was previously healthy and had a normal CBC and differential eighteen months prior to admission. CT scan showed bilateral pleural effusions, generalized lymphadenopathy, ascites, and splenomegaly (Figure 1). Pleural fluid analysis and cytology showed an inflammatory infiltrate, reactive mesothelial cells, and 25%-30% eosinophils. No neoplastic cells were identified. Glucose, LDH, lipase, and amylase were normal. The pH was alkaline (7.53) and protein was consistent with an exudative effusion. CBC revealed a leukocytosis of 44.6 x 109/L; absolute eosinophil count (AEC) was 35.6 x 109/L. Peripheral blood smear, lymph node biopsy, and bone marrow aspiration showed eosinophilia with normal morphology, lymphoid hyperplasia, and hypercellular marrow with eosinophilia, respectively. Other studies for parasitic infection, HIV, and TB were negative. Bone marrow flow cytometry showed polytypic B cells. FISH analysis and PCR assay for FIP1L1-PDGFRA fusion transcript did not detect an abnormality. A trans-thoracic echocardiography showed left ventricular ejection fraction 55%-60% with no diastolic dysfunction. A diagnosis of hypereosinophilic syndrome was made by exclusion. As initial treatment of hydroxycarbamide provided no clinical benefit or reduction in the eosinophilia, prednisone was added with prompt reduction of the eosinophilia. A trial of imatinib was given despite negative FIP1L1-PDGFRA without benefit. He had recurrent pleural effusions requiring repeated thoracentesis which continued to demonstrate persistent elevated eosinophil counts (Table 1). A permanent catheter was placed in the right pleural space and accessed for thoracentesis of about two liters every three to five days along with repeated large volume paracentesis for persistent ascites.Figure 2 shows that despite normalization of the patient's peripheral eosinophilia, his pleural effusions remained refractory to therapy. Four months after his initial presentation, he developed bilateral empyemas with methicillin resistant staphyloccus aureus as a complication of multiple thoracentesis, rapidly deteriorated in spite of aggressive management and died from multiple organ dysfunction.

PMC9527843_01

Male

A 23-year-old male was referred to the outpatient unit of the surgery department, with a left side neck swelling of 1-month duration [Figure 1]. There was no history of trauma, tuberculosis, pain, discharge, and no limitation in mouth opening. Examination revealed a soft, partially mobile, nontender swelling, 5.5 cm x 4.5 cm in size, on the left side of submandibular area with normal overlying skin. No cervical lymphadenopathy was found. Fine-needle aspiration cytology (FNAC) revealed pus-like fluid mixed with blood showed numerous anucleated squamous cells along with scattered giant cells and few inflammatory cells indicating a benign cystic lesion. Computed tomography (CT) scan showed a well-circumscribed rounded cystic lesion, measuring about 3.2 cm x 2.6 cm x 3.1 cm with peripherally enhancing thin wall in the left submandibular region posterior to the submandibular gland and anterior to the sternocleidomastoid muscle. There was no sign of infiltration into the nearby structures. Both lobes of thyroid gland, carotid, and jugular vessels appeared normal. There was no significant enlarged cervical lymph node and no obvious mass lesions in the oral cavity, oropharynx, and larynx. Differential diagnosis included branchial cleft cyst, tuberculosis, salivary gland neoplasm, neurogenic neoplasm, and metastatic lymph node enlargement. The imaging features and location were suggestive of 2nd branchial cleft cyst [Figure 2]. Complete surgical excision was done under general anaesthesia using the left transverse cervical approach. Incision was followed by exposure of platysma with careful dissection and the lesion was found separate from the left submandibular gland and removed in toto [Figure 3]. The lesion was sent for histopathological examination. Macroscopically, specimen was a round unilocular cyst measuring about 4.8 cm x 4.2 cm x 3.0 cm. The cut surface showed a cystic mass filled with purulent material and multiple grayish-yellow nodules were present. Microscopy showed cyst wall with a stroma of lymphoid type, having germinal center in a few areas, covered by stratified squamous epithelium with reactive changes. Cystic lining revealed granulomatous features with foamy histiocytes, giant cells (Touton type) and lymphocytic infiltrate [Figure 4]. Our diagnosis was consistent with a branchial cleft cyst with XGI. Postoperative course was uneventful and the patient was discharged from the hospital on 4th postoperative day and has been in regular follow-up for 9 months and doing well.

branchial cleft cyst, neck mass, xanthogranulomatous inflammation

PMC4812510_01

Male

A 19-year-old male patient was admitted to Subei People's Hospital of Jiangsu (Yangzhou, China) on 5th September 2011 with a 2 month history of recurrent fever and intermittent thoracic back pain. The recurrent fever did not occur at specific times and the temperature did not exceed 38.0 C. The patient also reported limited mobility, decreased appetite and weight loss, but did not experience chills or night sweats. There was no history of exposure to TB or of a chronic cough. The patient presented a normal general physical condition, with a body temperature of 37.3 C. A physical examination revealed slight tenderness over the mid-thoracic spine, lumbar spine and left sacroiliac joint. No paraspinal swelling or spasms were observed, while the sensation, muscle strength and muscle tone of the lower extremities were normal. Laboratory examinations showed a normal white blood cell count [6.6x109/l; normal range (NR), 3.5-9.5x109/l] and normal levels of hemoglobin (120 g/l; NR, 110-160 g/l), human leukocyte antigen-B27 (78; NR, 0-145) and rheumatoid factor (5.0 IU/ml; NR, 0-14 IU/ml). In addition, tests for autoantibodies, immunoglobulin, TB antibodies and tumor-associated antigens were negative. The erythrocyte sedimentation rate (ESR) was 75 mm/h, which was higher than the normal range (0-15 mm/h), and the C-reactive protein level was normal (10 mg/l; NR, 0-10 mg/l). Human immunodeficiency virus (HIV) and purified protein derivative (PPD) tests were negative. Further imaging analysis showed normal abdominal ultrasound findings and X-rays of the chest, thorax, lumbosacral region and pelvis. CT reconstruction of the sacroiliac joint indicated multiple round hypodense lesions with a hyperdense center, as well as some cortical destruction and soft tissue swelling in the lumbar and sacral vertebrae, and the left ilium regions (Fig. 1). A contrast-enhanced CT scan of the chest, with Omnipaque (1.5 ml/kg; GE Healthcare Life Sciences, Shanghai, China) as the contrast enhancement agent, demonstrated an irregular patchy hypodense signal in the left lung lobe with a patchy translucent shadow inside, which was enhanced heterogeneously (Fig. 2). A chest CT scan showed multiple round hypodense lesions with higher central density in the thoracic vertebrae, ribs and sternum (Fig. 3). Furthermore, a CT reconstruction of the thoracic spine indicated bone destruction with partial cortical perforation (Fig. 4). MRI scans revealed multiple round ring signal shadows with a continuous finishing border from Th12 to S4 in the anterior, central and posterior elements, but not in the end plate. In addition, sagittal T1-weighted and T2-weighted images revealed a hypodense signal in the internal of the lesions and a slightly hypodense signal in the peripheral region, which was accompanied by soft tissue swelling, with visible ring enhancement and soft tissue enhancement following intravenous administration of gadolinium (GE Healthcare Life Sciences) (Fig. 5). Based on the symptoms and all the aforementioned examinations, lymphoma, metastatic disease or bone TB were suspected. Since the CT and MRI findings did not allow for a final diagnosis, a CT-guided biopsy from the lesions in the Th7 vertebral, left iliac and adjacent left lung using an 8-gauge needle (Yangzhou City Jiangzhou Medical Instrument Co., Ltd., Yangzhou, China) was performed to confirm the diagnosis. However, no evidence of granulomata, necrosis, lymphoma or other malignancies was observed. Subsequently, an open biopsy was performed in order to establish a pathological diagnosis, during which fish-shaped soft tissue adhesion with surrounding tissues under the lamina of Th7 and local sequestrum formation were observed. Part of the surrounding soft tissues and bone lesions were removed for pathological examination and culturing. Upon hematoxylin and eosin staining of the tissue and visualization under the Olympus BX43 microscope (Olympus Corporation, Tokyo, Japan), a large amount of necrosis, epithelioid cells, Langerhans giant cells and dead bone were observed (Fig. 6), which are characteristics of TB. The results of Acid-Fast Bacilli culturing (Sinobest Biotech Co., Ltd., Shanghai, China) were negative; however, a polymerase chain reaction performed by Shanghai Genechem Co., Ltd. (Shanghai, China) was positive for TB. Based on these observations, a diagnosis of multifocal skeletal TB was established. The patient was discharged from the hospital on 27th September 2011. Postoperatively, the patient was administered a common quartet anti-TB chemotherapy regimen, including isoniazid (300 mg/day), rifampicin (600 mg/day), pyrazinamide (750 mg/day) and ethambutol (750 mg/day; all Shanghai Sine Pharmaceutical Co., Ltd., Shanghai, China) for 12 months. The patient's symptoms greatly improved after 1 month of anti-TB treatment and the ESR decreased to 65 mm/h. At the final follow-up on 11th March 2013, the patient was free of symptoms and the ESR had decreased to the normal value. MRI scans obtained following 20 months of anti-TB therapy showed that the range of the extensive abnormal signal intensity had become smaller, as compared with that before anti-TB treatment was initiated (Fig. 7). Informed consent was obtained from the patient's family prior to the publication of the present case.

multifocal, skeletal tuberculosis, vertebral

Contrast-enhanced chest computed tomography scans showing irregular patchy hypodense change in the left lung lobe with patchy translucent shadow inside.

PMC7166280_01

Male

In this study, we describe the successful treatment of a patient with TBIR. A 68-year-old Japanese man developed marked hyperglycemia and was hospitalized and diagnosed with TBIR. He had been diagnosed with type 2 diabetes at the age of 47 years and was treated with an oral hypoglycemic drug. The administration of sitagliptin (50 mg/day) was initiated at 6 months prior to hospitalization. The patient developed a cold (symptoms included chills and a runny nose) 1 week prior to hospitalization. Self-monitored blood glucose levels on the day before hospitalization were very high; thus, he visited our hospital. The patient's medical history included meningioma, splenic infarction, colon cancer, and chronic renal failure. However, he had no history of mental illness. His family history was as follows: his father had diabetes, his mother had high blood pressure and chronic renal failure, and his sister had colon cancer. The oral medications included sitagliptin (50 mg/day), glimepiride (0.5 mg/day), irbesartan (50 mg/day), nifedipine (40 mg/day), furosemide (40 mg/day), spironolactone (25 mg/day), aspirin (100 mg/day), famotidine (20 mg/day), allopurinol (50 mg/day), and rosuvastatin (5 mg/day). He had not used insulin injection. His lifestyle history was as follows: he used to smoke 100 cigarettes per day from the age of 20 to 68 years but quit smoking after that. He consumed 750 mL of beer per day from the age of 20 to 65 years. He was unemployed. Physical examination revealed a waist circumference of 107.0 cm and paralyzed left upper and lower limbs (due to sequela of meningioma surgery). The results of the examination showed a random blood glucose level of 587 mg/dL (32.6 mmol/L), immunoreactive insulin (IRI) level of 1340 muU/mL, and C-peptide (CPR) level of 15.7 ng/mL (5.20 nmol/L) (Because the blood glucose level was very high, IRI and CPR were tested using the same specimen.) (Table 1). The patient was hospitalized the next day to investigate and treat hyperglycemia and hyperinsulinemia. On the day of hospitalization, the blood tests showed hemoglobin A1c (HbA1c) of 7.2% (55.2 mmol/mol) and glycoalbumin of 28.1% (Table 1). There was divergence between HbA1c and glycoalbumin values, suggesting a sharp increase in blood glucose levels. On the second day of hospitalization, the fasting blood glucose (FBG) levels were 538 mg/dL (29.9 mmol/L), and the fasting CPR levels were 10.3 ng/mL (3.4 nmol/L). It was impossible to measure the fasting IRI because it was of extremely high value and was affected by the influence of insulin antibody (Table 2). Despite gradually increasing the use of insulin from 10 units/day to 170 units/day in 20 days after hospitalization, blood glucose levels did not decrease sufficiently. Differential diagnosis exhibiting marked insulin resistance is diverse. As a result, the possibility of obesity, chronic kidney disease, and insulin receptor abnormality remained positive in this case; the various physical findings and tests for other conditions were negative. Given that the patient was anti-insulin receptor antibody positive with a binding rate of 71.3%, he was diagnosed with TBIR. We investigated the presence of comorbid disorders such as collagen diseases, including SLE. Physical findings did not indicate collagen diseases, and various autoantibodies were negative. Considering that antinuclear antibodies were positive only for cytoplasmic type, this did not enable the diagnosis of a specific disease. We also considered the possibility of malignant tumors. There were no significant findings in the chest X-ray examination, abdominal ultrasonography, whole-trunk computed tomography examination, and upper and lower gastrointestinal endoscopy. Endocrine disorders were also negative. H. pylori infection was negative. Figure 2 summarizes the clinical course. The administration of insulin-like growth factor-1 (IGF-1; 0.1 mg/kg = 8 mg/day) was initiated at the hospital on day 37. From the first day of administration, total blood glucose (taken four times per day) decreased by 163 mg/dL (9.06 mmol/L) (Table 3). IGF-1 was gradually increased to 0.125 mg/kg (10 mg/day) on hospital day 40. However, despite this decrease in blood glucose levels in response to IGF-1, blood glucose levels increased transiently following prednisolone administration 4 days after initiating IGF-1 administration. The administration of prednisolone (30 mg/day) was started at hospital day 41, and blood glucose, IRI, and CPR levels decreased sharply within 10 days. Given that prednisolone treatment was effective, IGF-1 administration was terminated on hospital day 59. The insulin receptor antibody was negative in the examination on day 23 after the initiation of prednisolone administration. The dose of prednisolone was gradually decreased, and a maintenance dose of 15 mg/day was set on hospital day 83. On hospital day 64, pioglitazone administration was started; however, FBG levels were sometimes as low as 60-70 mg/dL (3.33-3.89 mmol/L). Thus, pioglitazone was discontinued on hospital day 74. On hospital day 71, mitiglinide (10 mg) was administered prior to breakfast and lunch. Blood glucose levels improved with mitiglinide (20 mg/day) and prednisolone (15 mg/day) treatment, and the patient was discharged. Then, the dose of prednisolone was reduced to 10 mg/day and blood glucose control was good. Regarding changes in body weight, during the first 40 days, body weight should have been reduced due to an energy-restricted diet, but the weight loss was moderate. The reason was considered to be an anabolic effect by administration of a large amount of insulin. Over the next 25 days, body weight was thought to have increased gradually because of increased body fluid volume due to the mineralocorticoid action of prednisolone. The rapid weight loss of about 10 kg in the last 25 days coincided with the gradual decline in the dosage of prednisolone. This was thought to be due to a decrease in mineralocorticoid action as well as due to the discontinuation of insulin. There were no serious adverse or unanticipated events observed as well as no change in diet and exercise therapy from start to finish. Food energy intake was restricted to 1600 kcal/day after hospitalization. In summary, the presence of autoimmune diseases at the time of diagnosis was not obvious in the present case. Acanthosis nigricans was not observed, and extreme or prolonged hypoglycemia was not found. The anti-insulin receptor antibody was positive, and the inhibition rate was 71.3%. Treatment with prednisolone and IGF-1 was effective. We identified a case of TBIR that developed 6 months after sitagliptin administration, and the patient caught a cold immediately after this development. Examples of relapsed cases of this disease have also been reported, and it is necessary to continue the survey. The possibility of an association between DPP-4 inhibitor and autoimmune disease was reported, and it is not possible to rule out the involvement of sitagliptin in the onset of this disease. In addition, we considered that the effect of a viral infection ("cold") on immunity might have affected TBIR development. Therefore, further investigations are required.

PMC6348543_01

Male

A 12-year-old boy presented to the Kilimanjaro Christian Medical Centre (KCMC) referral hospital in Moshi, Tanzania, with complaints of 8 days of headache associated with photophobia, neck pain, and vomiting (Figure 1). Eleven weeks earlier, he was admitted at the regional government hospital for similar complaints when he was diagnosed with HIV and treated presumptively (cerebral spinal fluid [CSF] evaluation negative; Table 1) for cryptococcal meningitis (CM) initially with 800 mg intravenous (IV) fluconazole (induction therapy) then transitioned to oral 400 mg (consolidation therapy) according to Tanzanian National Guidelines. Cryp-tococcal antigen (CrAg) lateral flow assay (LFA) was unavailable. He also received trimethoprim/sulfamethoxazole prophylaxis and IV ceftriaxone for possible bacterial meningitis. Three weeks after CM treatment, his clinical status improved and he began antiretroviral therapy (ART) with abacavir, lamivudine, and efavirenz. One month after starting ART and receiving fluconazole consolidation therapy, this patient reported no vomiting, resolution of his headache, and weight gain. Seven weeks after starting ART, he had a relapse of his original presenting symptoms (headache and vomiting) leading to presentation at KCMC. At KCMC, he was slightly tachypneic (respiratory rate = 28 breaths/min), normocardic (heart rate = 87 beats/min), afebrile (temperature = 36.2 C), with an oxygen saturation of 99%. He was severely malnourished (weight = 23 kg; height = 136 cm; body mass index = 12.4 kg/m2; Z = -3) and had a deduced Glasgow Coma Score of 14. He had a positive Kerning's and Brudzinski's sign, papilledema, and mild ataxia. CSF analysis demonstrated a white blood cell count of 6 x 106 cells/L, no organisms on gram stain, and India Ink and CSF CrAg were positive. Urea and creatinine measurements remained unremarkable throughout admission. He received IV fluconazole (240 mg) daily until discharge, prophylactic trimethoprim/sulfamethoxazole, and continuation of his ART. Therapeutic lumbar punctures removing 15 to 25 cc of fluid were performed weekly. Opening pressure was not documented, but was noted to be "high" in one of the procedure notes. The therapeutic lumbar punctures offered relief for a few days, but symptoms of severe headache quickly returned. Acetazolamide was started to reduce intracranial pressure and daily prednisone was initiated for presumed immune reconstitution inflammatory syndrome (IRIS). His CD4 level was not available at the time of KCMC admission, but prior to initiating ART he had a CD4 count of 65 cells/microL. At this admission, his viral load was fully suppressed (HIV RNA <20 copies/mL). Once stabilized, he was discharged home with CM consolidation therapy (fluconazole 400 mg daily), ART, and an oral prednisone taper. One week after discharge, he was readmitted to KCMC with similar complaints of headache and vomiting. Fundoscopy showed papilledema. CSF was CrAg-positive and Gene Xpert was negative for tuberculosis. After 2 weeks, his clinical condition still had not improved, so IV amphotericin B was added to his fluconazole regimen while his steroids were tapered. Despite escalation in management, his condition continued to deteriorate and he died soon after.

PMC3015582_01

Female

In August 2000, a 30-year-old woman presented with fatty food intolerance, gas belch symptoms, abdominal discomfort, and a sour taste in her mouth. She underwent an uncomplicated laparoscopic cholecystectomy; pathology confirmed cholelithiasis and chronic cholecystitis. Her symptoms resolved postoperatively. Four months later, she returned complaining of halitosis, sour taste, bloating, and right-sided abdominal pain of 3-months' duration. She denied having any heartburn. Her family physician had treated her with omeprazole, which initially alleviated the symptoms. Her repeat abdominal examination was normal. An esophogastroduodenoscopy disclosed small fundic polyps and a gastric diverticulum near the fundus that contained old food particles (Figure 1). Minor changes were noted at the gastroesophageal junction that were consistent with mild reflux disease. Pathology revealed benign fundic polyps; biopsies were negative for evidence of Helicobacter pylori. An upper gastrointestinal series revealed a diverticulum in the posterior cardia of the stomach (Figure 2). Seven months after her initial presentation, the patient underwent a laparoscopic resection of the diverticulum. A pneumoperitonieum was obtained with an open Hassan technique. A right-sided port was used to elevate the liver and 2 left-sided ports were used to take down the short gastric vessels with the AutoSonix ULTRASHEARS (US Surgical, Tyco Health Care, Norwalk CT). The posterior cardia of the stomach was then mobilized and inspected. The gastric diverticulum was isolated, dissected free of retroperitoneal attachments to the base of the diverticulum, and transected with an ENDO GIA Universal (US Surgical, Tyco Health Care, Norwalk, CT) (Figure 3). Pathology revealed a 3.0 x 2.5 x 2.0-cm pouch with layers of mucosa, muscularis mucosa, submucosa, and serosa, but not the muscular propria. Postoperatively, the patient did well; at 28-month follow-up, no further symptoms were reported.

PMC10124569_01

Female

A 60-year-old woman was referred to the dry eye clinic at JEC Eye Hospital Kedoya for chronic recurrent redness of her left eye (LE) in the past 6 months prior to her visit. Her past medical history was negative for autoimmune disease and thyroid dysfunction. She had been using spectacles since her early adulthood period and was also diagnosed with anisometropia of the LE. She did not have any history of ocular surgery in either of her eyes. At the time of the referral, she had been using cyclosporine 0.1% eye drop once per day and fluorometholone eye drop four times per day for 1 month and tear substitute every three hours. However, she did not feel any improvement under these medications. The history of her right eye (RE) was unremarkable. On examinations, the best corrected visual acuity (BCVA) was 20/20 in the RE with S3.25 correction and 20/40 in the LE with S-18.00 correction. Intraocular pressure (IOP) of both eyes was within normal limits. At slit lamp examination, the LE showed significant conjunctival hyperemia and redundancy in the superior bulbar area (Figure 1). Positive fluorescein staining was observed on the superior bulbar conjunctiva and superior limbus. The lens of LE showed grade 2 nuclear sclerosis. There was plugging of meibomian gland orifices consistent with MGD in both eyes. The tear break-up time (TBUT) was shortened to 4 seconds in RE and 2 seconds in LE. Schirmer's test without anesthesia was 5 mm on the RE and 2 mm on the LE at 5 minutes. Meibography (Oculus Keratograph 5M, Oculus, Wetzlar, Germany) was performed to evaluate the degree and severity of MGD in both eyes (Figure 2) which revealed grade 1 meibomian gland loss. Her final diagnosis at initial presentation was SLK, mixed type of dry eye disease related to aqueous deficiency and MGD, and senile cataract of the LE. Several treatment alternatives were discussed, including the option to continue cyclosporine 0.1% eye drop which she refused due to intolerable stinging sensations. She was also not keen on punctal occlusion. Accordingly, she opted for treatment combination of auto-SED 50% concentration and silicone hydrogel contact lens (Air Optix Aqua, Alcon, 33% water content) which acted as therapeutic BCL and myopia correction, together with non-preserved lubricants every 1 to 2 hours. She agreed to wear the contact lens during her working hours (6 to 8 hours per day) and administer auto-SED at home (at least 6 times per day), since it was bothersome for her to use the auto-SED at work. In terms of MGD, we decided to perform intense pulsed light (IPL) therapy using the E-Eye device (E-Swin, Houdan, France), which was done in 3 sessions with 4-weeks interval. We also discussed the possibility of cataract surgery for her LE once the ocular surface condition has improved, to prevent worsening of symptoms after the surgery. On review 3 months after her initial visit, the patient had symptomatic relief in her LE. Slit lamp examination revealed significant reduction of inflammation on the superior bulbar conjunctiva of the LE (Figure 3A), and no fluorescein staining was visible. Treatment regimens with auto-SED, contact lens wear, and non-preserved lubricants were continued. Two years following her presentation, the patient remained asymptomatic. Mild superior conjunctival hyperemia without fluorescein staining was found on examination of the LE (Figure 3B). TBUT of both eyes were more than 5 seconds. Schirmer test was done, and the results were 6 and 5 mm of RE and LE, respectively. Meibography was suggested in order to evaluate the extent of meibomian gland loss after treatment. Unfortunately, she refused to do the examination. As for the treatment, she did not mind continuing to wear contact lens and administer auto-SED, especially now that she only needed to use the auto-SED 3 to 4 times per day.

autologous serum, bandage contact lens, cornea, dry eye, superior limbic keratoconjunctivitis

PMC10125731_01

Female

An 86-year-old woman was referred by her optometrist after several months of worsening vision. Ocular history was significant for cataract surgery two years prior and a 25-year history of open-angle glaucoma with a seven-year history of treatment using brimonidine tartrate 0.1% BID OU and artificial tears (ATs). She had no history of contact lens use or eyelid disorders (i.e., styes, blepharitis, and meibomian gland disease) and no history of corneal disorders including recurrent corneal erosion, meibomian gland disease, rosacea blepharitis, blepharokeratoconjunctivitis, or ulcers. The patient reported worsening of her vision since her cataract surgery, most noticeably in the three months prior to her referral, requiring her to use a magnifying glass to read. The referring eyecare provider reported no identifiable corneal lesions prior to 2016, with slow development and progression of bilateral peripheral corneal opacities since that time. The patient also noted photosensitivity in both eyes. She had no pertinent medical history, including hyperlipidemia. On examination, best-corrected distance visual acuity (BCDVA) was 20/60 OD and 20/70 OS. Manifest refraction was +0.75-1.00 x 160 OD and +0.50-1.25 x 165 OS, and IOP was within normal limits in both eyes. Slit lamp examination was remarkable for bilateral dermatochalasis, superficial punctate keratitis (SPK), and peripheral corneal scarring from 4 o'clock to 5 o'clock position and 7 o'clock to 8 o'clock position with superior corneal neovascularization consistent with sectoral interstitial keratitis and lipid keratopathy OU. There was no guttata or corneal lattice, but crocodile shagreen was noted in both eyes. Dilated fundus examination revealed blunted macular reflex OU and C/D ratio of 0.65 OD and 0.75 OS. Findings were consistent with bilateral lipid keratopathy secondary to interstitial keratitis. Infectious and autoimmune workup was ordered in coordination with the patient's primary care physician (PCP), including complete blood count with differential, erythrocyte sedimentation rate, C-reactive protein, auto-antibody titers (ANA, C-ANCA, and P-ANCA), rheumatoid factor, anti-SSA/Ro and anti-SSB/La, purified protein derivative (PPD) skin test and interferon-gamma release assay (IGRA) for tuberculosis, chest X-ray, ACE and lysozyme levels for sarcoidosis, throat and nasal swabs for methicillin-resistant Staphylococcus aureus, stool for ova and cysts, dental and tonsillar exam, Lyme disease titers, and syphilis testing. All tests resulted as negative or within normal limits. The patient's PCP reported no findings in the review of systems or on physical exam consistent with rheumatoid arthritis, systemic lupus erythematosus, Sjogren syndrome, or other similar systemic diseases. The patient was continued on BT and artificial tears (ATs) and then started on difluprednate drops TID OU. Slit lamp photographs taken three weeks later (shown in Figure 1) demonstrated no tangible change in the areas of lipid keratopathy. After excluding all other possibilities, we have concluded that the BT is the most likely cause of this patient's lipid keratopathy. As such, we are planning to discontinue BT in this patient; however, an appropriate alternative glaucoma treatment must be found, and we are in discussion with our glaucoma specialist to determine this.

PMC8440108_01

Female

A 79-year-old woman with RA was referred to our hospital. She was diagnosed with RA because of polyarthritis and positive C-reactive protein (CRP) and anticyclic citrullinated peptide antibody. She had been receiving treatment with MTX and glucocorticoid for 1 year, although her disease activity could not be controlled with these drugs. Consequently, we initiated 40 mg of adalimumab (ADA) for every 2 weeks. However, her disease activity did not improve despite ADA treatment with 7 weeks, and 162 mg of TCZ every two weeks was initiated in combination with 12 mg of MTX every week and 12 mg of methylprednisolone per day. Before the initiation of TCZ, she did not have a history of TB or come in contact with any patient with TB. Blood tests showed a leukocyte count of 12820/muL, lymphocyte count of 1615/muL, CRP of 5.4 mg/dL, and immunoglobulin G (IgG) level of 686 mg/dL (Table 1). The T-SPOT-TB test is a type of T cells recognizing antigens specific to Mycobacterium tuberculosis, and serum beta-D glucan was negative. She had no family history of TB. Chest computed tomography (CT) showed thickening of the pleura and a nodule at the apex of the left lobe (Figure 1). We did not administer anti-TB drugs because the T-SPOT-TB test and sputum test for TB were negative. Since we suspected her to have sulfamethoxazole/trimethoprim (SMX/TMP) allergy, 300 mg of inhaled pentamidine was administered every 4 weeks, as prophylaxis for PCP. However, her disease activity did not improve and TCZ was shortened every week. After every week TCZ treatment, her serum CRP level was 0.01 mg/dL within 1 month. However, the serum IgG levels gradually decreased, and lymphocyte count decreased on day 44 (Table 1). Two months after switching to TCZ, the patient was admitted to our hospital due to sudden high fever with a two-week history of generalized fatigue and cough. She was not in contact with anyone with an infection or coronavirus disease 2019, and she did not go to any infected areas. She was under treatment with 8 mg of methylprednisolone per day, 12 mg of MTX every week, and 162 mg of TCZ every week for RA before admission. On admission, her temperature was 39.1 C, blood pressure was 70/53 mmHg, and respiration rate was 28 with a pulse rate of 136 beats per minute. Her blood oxygen saturation level using pulse oximetry was 96% under an oxygen flow of 10 L/min via nonrebreathing oxygen mask with a reservoir bag. Her Glasgow Coma Scale score was 14: eye opening, 4; verbal response, 5; and motor response, 5. Her height was 149 cm, and her body weight was 33.4 kg. Her body mass index (BMI) was 15.0. Physical examination revealed mild and coarse crackles in the right and left sides of the chest. Blood tests showed a leukocyte count: 1600/muL, neutrophil count: 1208/muL, lymphocyte count: 221/muL, hemoglobin: 10.7 g/dL, platelet count: 154000/muL, total bilirubin: 1.5 mg/dL, CRP: 0.59 mg/L, lactate dehydrogenase: 509 U/L, creatinine: 0.29 mg/dL, prothrombin time: 12.5 sec, activated partial thromboplastin time: 26.5 sec, fibrinogen: 85 mg/dL, D-dimer: 2.4 mug/mL, Krebs von den Lungen-6 (KL-6): 423.3 U/mL, pulmonary surfactant protein-D: 199 ng/mL, and brain natriuretic peptide (BNP): 42.8 pg/mL. The arterial blood gas analysis, while under an oxygen flow of 10 L/min via nonrebreathing oxygen mask with a reservoir bag, showed pH: 7.504, partial pressure of arterial oxygen (PaO2): 159.0 mmHg, partial pressure of arterial carbon dioxide (PaCO2): 33.4 mmHg, base excess: 3.2 mEq/L, HCO3: 26.3 mEq/L, and arterial oxygen saturation: 100%. Calculated fraction of inspiratory oxygen (FiO2) under an oxygen flow of 10 L/min via nonrebreathing oxygen mask with a reservoir bag was 0.76 based on the previous report. The sequential organ failure assessment score was 5. Cytomegalovirus pp65 antigenemia was negative. Serum beta-D glucan level was 286 pg/mL, and the T-SPOT-TB test was positive. Antigen tests for the presence of species of Aspergillus, Candida, and Cryptococcus neoformans were all negative. The PCR-based sputum test for Pneumocystis jirovecii DNA was positive. The antigen test for coronavirus disease 2019 was negative. Streptococcus pneumoniae and Legionella pneumoniae urinary antigen tests were negative. CT scan showed grand glass opacity in all fields with consolidation within the right and left lungs (Figure 2) and mildly swollen kidneys without hydronephrosis. The echocardiography was normal. Her PaO2/FiO2 was 209.2 mmHg. She was diagnosed as having septic shock and also diagnosed as acute respiratory distress syndrome (ARDS) based on the Berlin definition. The clinical course is shown in Figure 3. She was treated with 3 g of meropenem per day. Because of worsening respiratory condition, the dose of methylprednisolone was increased to 80 mg per day for her ARDS based on previous studies. These treatments made her afebrile; however, the respiratory condition gradually worsened, and she required high-flow nasal oxygen on day 3. On the same day, the blood and urinary culture were positive for extended-spectrum beta-lactamase-producing Escherichia coli. Since the result of the sputum test for TB was positive on day 6, daily administration of antitubercular agents including, 200 mg of isoniazid, 500 mg of levofloxacin, and 500 mg of streptomycin was initiated. However, the hypoxemia gradually worsened, and she died of respiratory failure on day 7. With written permission from her family, an autopsy was performed. Bilateral lungs showed gross necrotic and cystic lesions of a maximum size of 30 mm. Histologically, the necrotic lesions consisted infiltration of neutrophils, macrophages, and giant cells with severe inflammatory exudate. However, granulomatous formations were not observed. Ziehl-Neelsen staining aided the detection of acid-fast bacilli (Figure 4(a)-4(c)). These lesions seemed to be of primary TB. A few numbers of pneumocystis organisms were identified in the lungs using Grocott's methenamine silver nitrate staining (Figure 4(d)). Numerous granulomas were present as extrapulmonary lesions in the liver, spleen, kidneys, pancreas, and adrenal glands (Figures 4(e)-4(i)). Some of them contained caseous necrosis and/or Langhans giant cells. Mild lymphocyte infiltration was observed around the renal pelvis.

PMC5896665_01

Male

In this study, we report a 27-year-old single man with no history of psychiatric disorder or drug abuse. His illness initiated with some pure psychiatric symptoms; for 3 years, the case had a fear with the feeling of being followed by others, without any external stressor. His symptoms were then exacerbated to hesitation and muttering, irritability, anger outbursts, bad tempering, and antisocial behavior. He thought his colleagues at work are likely to harm him due to his good skills at his job. His symptoms gradually tended toward depression, severe fatigue and loss of energy, loss of appetite, and weight loss and were followed by joint stiffness and loss of movement control at upper and lower limbs. After 6 months from the appearance of symptoms, he was brought to a psychiatric office being uncertain of hallucinogenic drug abuse. The psychiatrist prescribed citalopram 20 mg daily, risperidone 2 mg three times a day, and biperiden 2 mg three times a day; however, no improvements in the symptoms were observed. Although there was no history of psychiatric disorders and drug abuse, due to some motor neuron involvement, the patient was referred to carry out a brain imaging (magnetic resonance imaging [MRI] without contrast) to rule out organic disorders in a month. He was referred to psychiatrist after 6 months from the appearance of symptoms. The psychiatrist also asked the patient to carry out brain MRI following the medical treatment. The T2-weighted MRI demonstrated periventricular and white matter multiple sclerotic plugs with lesions (Figure 1A and B). Because of the presence of paresthesia, upper and lower limb muscle weakness, ataxia, and urinary incontinency, he was referred to a neurologist. MS diagnosis was made based on the patient's signs, symptoms, and imaging findings. He took methylprednisolone (5 mg three times a day/until remission) and interferon therapy, which resulted in improvements in sensory and motor neuron involvement and socio-occupational behavior and disappearance of hallucination in 40 days (by the time the treatment began). Written informed consent was given by the patient for the publication of this case report.

ms, case report, episode, multiple sclerosis, psychotic disorders, signs, symptoms

PMC6537023_03

Male

A patient of 11 years old was referred to the service for acute urinary retention, following repetitive failure to insert urethral catheter two weeks after trauma to the genitalia during a football match. He complained of difficult and painful micturition and eventually urinary retention. A cystostomy was placed in the emergency room. He was circumcised at age 3 and was treated for recurrent UTI in the past. On physical examination, the urethra meatus was normal; there was a hard, round, palpable mass in a tender penile urethra (Figure 11). A scout film of the pelvis showed an image of a urethral stone (Figure 12(a)). Opacification of lower tract during VCUG confirmed the obstruction from the stone but no reflux (Figure 12(b)). There was marked leukocyturia at 17000/mm3. Citrobacter koseri was isolated from the urine. We removed the calculus via urethrotomy (Figures 13 and 14). The two urinary catheters were kept on the abdomen after dressing (Figure 15). Postoperative follow-up was normal.

PMC5337770_01

Male

A 9-year-old boy presented with a 6-month history of pain and swelling over the medial aspect of the left foot with unknown etiology. The patient was not able to bear weight on the affected foot. There was no history of fever, loss of appetite and other constitutional symptoms. Mild swelling and tenderness were present over the talonavicular joint. The range of motion of the affected foot was painfully restricted. The plain radiographs of foot AP and oblique views showed diffuse osteopenia with marginal erosion of the articular surface of talus and navicular and narrowing of the talonavicular joint with prominent soft tissue medial to the talonavicular joint (figure 1). Hematological investigations were within normal limits except for the raised erythrocyte sedimentation rate (ESR) (30 mm 1st hour) and positive C-reactive protein (CRP-10). We could not get MRI done because of the financial constraint of the patient. We performed needle biopsy from the talonavicular joint under image intensifier and aspirated thick grayish-white material, which was sent for histopathology, culture, and acid-fast bacillus (AFB) staining. There were no acid-fast bacilli seen on AFB staining. On histopathological examination, epitheloid granulomas with caseating necrosis were seen which was suggestive of tuberculosis (figure 2). The growth of Koch's bacillus on culture further confirmed our diagnosis. Anti-tuberculosis therapy (ATT) was started with the first-line of 4 drugs, including rifampicin, isoniazid, ethambutol, and pyrazinamide. After three months, ethambutol was stopped and the remaining 3 drugs continued for the next 3 months, followed by rifampicin and isoniazid for one year. We gave ATT for a longer duration because of the high prevalence of osteoarticular tuberculosis in our country. The patient responded satisfactorily with ATT. At the end of week 8, pain and swelling started to disappear. The patient had no pain on walking, the range of motion of the affected foot was pain-free, and there was no secondary deformity seen in the foot at the end of treatment. After 18 months, the ESR and CRP were within normal limits. The plain radiological findings showed remineralization of bones with sclerosis of joint margins and reformation of the joint space (figure 3). The patient was able to walk pain-free and is presently doing all of his routine activities in the last 3-year follow-up. Written informed consent was obtained from the patient's legal guardian (father) for the publication of this paper and any accompanying images.

antitubercular drugs, child, foot, talonavicular coalition, tuberculosis

PMC9800091_01

Female

A 10-year-old girl was diagnosed with AML (M4); chromosome: chromosome:46, XX; negative fusion gene; Izkf1 negative; full exon sequencing: a frameshift mutation was detected in WT1 gene; RNA SEQ detected after the fusion gene: PRDM16/SKI positive. The patient received induction chemotherapy with daunorubicin, cytarabine, cytarabine, and etoposide (DAE) scheme in June 2020 and achieved a partial response (PR). Then, the patient received consolidation chemotherapy with idarubicin, cytarabine (IA) scheme, and 2 cycles of dicitabine, homoharringtonine, cytarabine, and recombinant human granulocyte colony-stimulating factor (G-CSF) (DEC + HAG) scheme and achieved a PR. After receiving dicitabine, cladribine, cytarabine, and G-CSF (DEC + CLAG) scheme, the patient achieved a complete response (CR); at this stage, the patient was positive for minimal residual disease (MRD), confirmed through flow cytometry (FCM). The patient underwent allo-HSCT from a HLA-mismatched related donor (5/10), after preconditioning with semustine, CLAG, cyclophosphamide, busulfan (CCNU + CLAG + BuCy), followed by cyclosporine A, mycophenolate mofetil, and short-term methotrexate for prophylaxis of GVHD. The patient achieved CR with MRD negativity (CRMRD-) 1 month after allo-HSCT and no GVHD. In May 2021, 4 months after HSCT, the disease progressed to relapse, and the evaluation of bone marrow (BM) showed that 16.5% of blasts, 84.6% of donor chimeric; 32.29% of FCM-MRD; and 7.57% of WT1. We performed the HLA-loss test, but no HLA gene loss was detected. So the patient was treated with azacytidine chemotherapy and DLI, but it was still not achieved CR. The second transplantation was performed 5 months after HSCT1. The patient underwent allo-HSCT from a HLA-mismatched unrelated donor (cord blood) (7/10), after preconditioning with total body irradiation (TBI), CLAG, mefallen, followed by cyclosporine A, mycophenolate mofetil, and short-term methotrexate for prophylaxis of GVHD. The patient achieved CR MRD 1-month after allo-HSCT and no GVHD. The patient was treated with azacytidine and interferon for preemptive therapy, but after that, the patient achieved CR MRD, but the copy number of WT1 in the patient increased gradually. Three months after the HSCT2, the patient was treated with azacytidine and camrelizumab (3 mg/kg/d) injection. On that day, the child felt general pain and discomfort, low fever, gradually developed a skin rash, even blisters, diarrhea, dark green watery stool, jaundice, abnormal liver function, 4-degree GVHD, accompanied by repeated fever hyperferrinemia, hypofibrinogenemia, hypertriglyceridemia, cytopenias, and sIL-2R > 2500 pg/ml (Table 1), which was consistent with sHLH. The children were combined with four degrees of GVHD and sHLH and were gradually reduced and treated with methotrexate (MTX) and MP (5 mg/kg/d), and basiliximab. GVHD and sHLH were gradually controlled. The evaluation of bone marrow (BM) showed CR, no hemophagocyte was found, and the copy number of WT1 decreased.

PMC6344191_01

Female

A 44-year-old woman was admitted to the neurosurgery department of our hospital on December 8, 2014, due to epilepsy, accompanied by headache and decreased muscle strength of both lower limbs for 1 month. Enhanced cranial MRI showed a solid lesion in the left frontal lobe. Intracranial tumor resection was performed on December 17, 2014. The pathological diagnosis was grade II astrocytoma. The prescription dose of head postoperative radiation was: PGTVtb64.4Gy/28fractions; PTVtb50.4Gy/28fractions; TMZ was concurrently administrated with postoperative radiotherapy. The dose of TMZ was 75 mg/m2 daily concurrent with radiotherapy, then 150 mg/m2 postirradiation on a 5-day schedule every 4 weeks. The patient was followed up regularly after radiotherapy. The brain MRI on March 9, 2018, showed irregular ring enhancement in the left frontal lobe, with a range of about 2.9 x 3.4 x 3.5 cm (Fig. 1 A-C). The patient underwent intracranial tumor resection on March 23, 2018, and postoperative pathology was glioblastoma (GBM), WHO grade IV. Immunohistochemistry results: vimentin (+++), glial fibrillary acidic protein (+++), isocitrate dehydrogenase (+++), Olig2 (+++), P53 (+80%), S-100 (+++), neuron-specific enolase (-), Syno (+), NeuN (-), NF (-), ChrA (-), epithelial membrane antigen (-), Ki-67 (+30%). She rejected gene mutation detection of the status of 1p/19q. The brain MRI re-examination on May 11, 2018 showed abnormal enhancement around the local operative area after resection of the left frontal lobe tumor, and there was residual tumor present (Fig. 2 A-C). After the reoperation of recurrence, the patient received conventionally fractionated stereotactic radiotherapy (CFRT) plus TMZ concurrent chemotherapy. The TMZ dose applied was 150 mg/m2 day 1 to day 7, every 2 weeks, concurrent with radiotherapy, then 150 mg/m2 postirradiation on a 7-day schedule every 2 weeks. Epilepsy did not appear again so far. Evaluation of cranial enhanced MRI (Fig. 3 A-C) after chemoradiotherapy showed complete remission of remaining intracranial lesions at the end of radiotherapy and 1 month after radiotherapy. Informed consent of the patient has been obtained.

PMC9940169_01

Male

The patient was a 33-year-old man admitted to the rheumatology ward with severe low back pain commencing in the past 3 months. The pain was mainly in the lumbar and sacroiliac vertebra and sternum, and movement and rotation exacerbated it and woke him up at night. He mentioned 12 kg weight loss. He had a history of non-pasteurized dairy consumption in the past 3 months and no history of trauma, nausea, blurred vision, or fever. Also, no smoking history was mentioned, and he had no family history of hematologic diseases. Different types of NSAIDs were prescribed for back pain, which over time proved ineffective. In physical examination, tenderness was evident in the sternum, right lower ribs, lumbar, and right sacroiliac joint. Also, a decrease in flexion and lateral bending was detected, deep tendon reflexes and muscle forces were normal, and the Babinski test was negative in both limbs. His young age and chief complaints led to the diagnosis of brucellosis, the endemic disease of the region. Other differential diagnoses were propounded, such as tuberculosis, ankylosing spondylitis, and malignancy. The list of laboratory results is shown in the Table 1. Abdominopelvic ultrasonography showed mild spleen enlargement (splenic span of 136 mm). Cranial radiography showed several lytic lesions of different sizes, accompanied by a slight increase in the cranial bone thickness. Thoracolumbar magnetic resonance imaging (MRI) study showed multiple abnormal lesions in vertebral bodies of the thoracolumbar spinal column. In addition, in the pelvis and thoracolumbar MRI, diffused abnormal bone marrow signal intensity was noted in favor of MM (Figure 1). Serum protein electrophoresis (SPEP) showed a peak in beta-1. The urinary protein electrophoresis (UPEP) showed a significant increase in free light chains, IgG/IgA, mixed tubular and glomerular, and Bence Jones proteinuria. Bone marrow aspiration and biopsy (BMA and BMB) were performed for him. Histopathologic examination showed that more than 80% of all nucleated cells were plasma cells or plasmablasts (Figure 2). Immunophenotyping of BMA by flow cytometry shows a predominantly abnormal plasma cell population that is positive for CD38, CD138, and CD56 and negative for CD19. In the cytogenetic study, 44,X,-Y,der(1)del(1)(p13,3p22)del(1)(p31,3p33),del(2)(q13),der(3)t(1;3)(q12;q27),del(6)(q13 q27),-8,del(12)(p11,2),-13,-18,+mar x 2[8]/45,sl,+mar[10]/44,sl,del(1)(q12q25), add(16)(q13)[2] was present. In Fluorescence in situ Hybridization (FISH) report, he had 74% amplification of 1q21, 89% deletion of 6q21, 97% deletion of 13q14.3, 81% positive IGH break, and 81% t(4;14) (p16;q32) FGFR3/IGH. Therefore, the final diagnosis of high-risk MM was made based on the available findings. Treatment started with a VRD regimen which includes bortezomib 1.3 mg/m2 (days 1, 4, 8, 11, 22, 25, 29, 32), lenalidomide 25 mg, and dexamethasone 40 mg. His back pain decreased after the fourth session of treatment. In the BMA and BMB that were taken on the last session of the fourth cycle, plasma cell counts decreased to 3%, contributing to complete remission. Regarding the adequate response, he was selected as a candidate for autologous bone marrow transplantation. 2 days after the first session of the fifth cycle, he was admitted to the emergency department with an abrupt fever of 40 C, anosmia, anorexia, weakness, Mild dyspnea, and reduction in oxygen saturation (91% without oxygen). Laboratory studies and spiral chest computed tomography (CT) were requested. Multiple peripheral patchy ground-glass opacities were unveiled in the CT scan (Figure 3). The coexistence of positive reverse transcription-polymerase chain reaction (RT-PCR) made a definite diagnosis of COVID-19 infection. He was admitted to the infectious disease ward for isolation and treatment, and his chemotherapy session was postponed. After 2 days, the fever subsided. During treatment, he showed no sign of dyspnea or respiratory distress, and oxygen saturation was above 94%. He was discharged from the hospital without any complications. Approximately 20 days after discharge, a vague pain started in his feet and back. The pain intensity increased, and on the day of negative RT-PCR, he was admitted with excruciating pain in the lower limbs and his back, which was resistant to regular analgesic drugs. SPEP, which became normal before COVID-19, showed a peak in beta-1, and MM relapse diagnosis was confirmed. Afterward, he received different treatments such as a repeat VRD regimen, Bortezomib/Cyclophosphamide/Dexamethasone (VCD), Pegylated liposomal Doxorubicin/Bortezomib and Bendamustin containing regimen but non showed any acceptable results.

covid-19, multiple myeloma, poor prognostic, young

PMC4778777_01

Female

Mrs X, a 60-year-old Chinese woman, was admitted to the Department of Infectious Diseases, First Affiliated Hospital of Zhejiang University School of Medicine, because of the feeling of skin infestation. Since her travel to a rural area 4 months ago, she had been persistently feeling insects crawling and breeding under her skin. She complained that these insects bit her skin, causing intolerable pain and itch. She insisted that her living room was full of insects of different sizes, and numerous insect eggs could have washed off when washing her hair. Before admission, she was diagnosed with "pediculosis, allergic dermatitis", and prescribed desloratadine and metronidazole by a dermatologist. Not surprisingly, these agents did not help relieve her sufferings. Since the onset of the aforementioned symptoms, her body weight consequently went down by 8 kg. In her past medical history, she suffered from hypertension for 9 years, which is well controlled by amlodipine 5 mg daily. She denied any personal history of other physical or mental illnesses, illicit drug abuse, or intoxication, as well as a family history of psychiatric conditions. No irritant or traumatic events happened before her current presentation. Besides, she was allergic to sulfonamides and levofloxacin. She had an open appendectomy 40 years before admission and gave birth to her son by cesarean delivery 30 years before admission. A full-body skin examination revealed scattered excoriations with pigmentation caused by self-inflicted scratching. Further laboratory screenings, including profiles of routine blood, urine, stool tests, serum biochemistry, coagulation function, thyroid function, myocardial enzymes, troponin-I, C-reactive protein, rheumatoid factor, erythrocyte sedimentation rate, serum tumor markers, antinuclear antibodies, prolactin, serum VitB12, folate level, hepatitis B and C, human immunodeficiency virus, syphilis, cytomegalovirus, and Epstein-Barr virus, were all within normal limits except that fecal occult blood test was positive. Besides, electrocardiogram and chest computed tomography (CT) were normal. Color Doppler ultrasonography detected a diffusely enlarged thyroid with multiple nodules, and a small hepatic cyst. Cranial magnetic resonance imaging (MRI) (3.0 T) indicated a cystic lesion in the posterior pituitary (Figure 1A). Meanwhile, the patient complained about archorrhagia and insect eggs washing off when cleaning her anus. Therefore, an anorectal consultation was immediately requested. Digital rectal examination was negative, and colonoscopy was suggested. Unexpectedly, when preparing for a bowel cleansing before colonoscopy, this patient ingested five thermos jugs of water (appropriately 12 L) in a few hours. Consequently, she began to feel short of breath, although bedside heart and lung auscultation was normal. Blood pressure was 143/76 mmHg. About 20 minutes later, she became irritated and could not stop scratching her face and head. Rapid blood glucose was 7.7 mmol/L. After another half an hour, in a sitting position, the patient vomited appropriately 50 mL of water, with eyes tightly closed and hands involuntarily trembling. Direct and consensual reactions on both pupils were sensitive. Her neck was soft, but bilateral Babinski's sign became positive. Another 15 minutes later, the patient experienced a seizure, characterized by loss of consciousness, turning up of the eyes, biting of the tongue, clenching of the teeth, frothing of the mouth, and urinary incontinence. After about 5 minutes, seizure gradually alleviated, but the patient remained irritated and her hands repetitively grasped in an involuntary pattern. Immediately, 10 mg of diazepam was intramuscularly injected. A neurological consult considered the aforementioned symptoms to be an epileptic attack and suggested the use of sodium valproate. A quick check on serum electrolytes indicated hyponatremia (120 mmol/L, reference interval: 136-145 mmol/L), hypochloremia (82 mmol/L, reference interval: 96-108 mmol/L), and hypokalemia (3.27 mmol/L, reference interval: 3.50-5.20 mmol/L), which possibly linked to the overintake of water and accounted for the epilepticus insultus. Cranial CT acquisitions were generally normal, although data were not that clear because of noncooperation of the patient. The results of lumbar puncture excluded intracranial infections and revealed a low level of cerebrospinal fluid chlorine. The arterial blood gas analysis indicated uncompensated alkalosis (pH value 7.52, reference interval: 7.35-7.45). As the situation was urgent, the patient was transferred to the Department of Intensive Care Unit (ICU) for further examinations and treatments. In the ICU, vital signs and urine volume of this patient were closely monitored. She was treated with meticulous supportive and nursing care (eg, oxygen uptake, catheter care, and perineal cleaning), intravenous sodium valproate pumping, nasal levetiracetam feeding, and intravenous potassium and sodium supplement at a well-controlled speed. The patient has experienced fever when she was in a mild coma about 1 day after the epileptic attack, and her body temperature increased to a maximum of 39 C. The auscultation of lungs revealed bilateral crackles, and the routine blood test revealed increased count of white blood cells and neutrophils over normal limits. Lung infection was therefore indicated, and antibiotics were prescribed. Meanwhile, hematological tests documented elevated hepatic enzymes and cardiac enzymes. In addition, urine sodium and osmolality, and serum adrenocorticotropic hormone and cortisol levels were screened to exclude diabetes insipidus and syndrome of inappropriate antidiuretic hormone (SIADH). About 45 hours after the epileptic attack, her deteriorated consciousness completely cleared, whereas her cutaneous concerns remained the same as before. After 4 days in the ICU, laboratory examinations basically returned to normal, and the patient was transferred back to the Department of Infectious Diseases. Psychiatric consulting was asked to deal with her persistent psychotic symptoms. Because the patient had abnormal skin sensations without any trace of infection, confirmedly convincing herself of being infected with insects, she met the criteria proposed in 2009 and was thereof diagnosed with DI. Accordingly, she was administered risperidone, titrated to 4 mg/day (1.5 mg at noon and 2.5 mg at night). However, laboratory monitoring revealed an elevated serum level of prolactin (highest at 189.6 ng/mL, reference interval: 2.8-29.2 mmol/L). Furthermore, 3.0 T MRI scanning of the pituitary reported a similar result as earlier (Figure 1B and C). Considering risperidone to be the culprit for prolactin disturbance, its dose was gradually decreased to 2.5 mg/d (night only), and 5 mg aripiprazole (night only) was added together with bromocriptine. Consequently, serum prolactin gradually declined to the normal level. After a 2-month inpatient treatment with atypical antipsychotics, her tactile hallucinations and somatic delusions significantly improved, and continuous medication was suggested after discharge. During outpatient follow-ups, symptomatological remission of DI was maintained. However, the patient developed symptoms of depressed mood and loss of appetite and interest nearly 3 months after hospital discharge. In a psychiatric visit, her Hamilton Depression Rating Scale (17 items) reached a score of 27. She was diagnosed with depressive syndrome after comprehensive psychiatric assessments. Accordingly, citalopram was prescribed and gradually titrated to 40 mg/day. Meanwhile, she was advised to continue her antipsychotics for DI. However, her depressed mood did not significantly improve after a 2-week treatment with citalopram. Nearly 1 month after citalopram was initiated, this woman was reported to have attempted suicide in her own house. She was found trying to jump from the balcony and was stopped after much persuasion. She was then inevitably lost to follow-up, although repeated phone calls were made.

delusional infestation, depressive syndrome, suicide, water intoxication