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moukaii

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Tuberculosis_Dataset

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PMC4501471_03

Male

45-year-old male patient was admitted to hospital with the productive cough and occasional white sputum for 5 years. The male patient had a past history of pulmonary tuberculosis (21 years ago; unavailable medical records). There was no such history as hemoptysis, loss of appetite, weight loss nor fever. He worked on the highland for long term. The remainder of history was unremarkable. Physical examination was unremarkable. Chest CT scan showed anterior wall of the trachea mucosa was less smooth as well as partial visible flat elevation. Bronchoscopy showed left and front wall surface of tracheal with multiple nodular eminences, hard texture and nodules spread to the carina. Spirometric test showed residual volume to total lung capacity percentage increased slightly. Histopathologic examination showed chronic inflammation of bronchial mucosa with interstitial ossification. The diagnosis was TPO. What is more, during the hospitalization, the patient once appeared sudden abdominal pain, hematochezia. Snap multiple liquid gases flat was found in abdominal plain film. Diagnosis was intestinal obstruction. One colonoscopy check in the mirror at 65 cm showed that a cauliflower like uplift surface hyperemia, erosion pollution moss covered margin irregularly. Histopathologic examination of biopsy sample was reported as a moderately differentiated adenocarcinoma. The patient received surgical operation treatment.

ossification, tracheal disease, tracheal stenosis, tracheobronchopathia osteochondroplastica

PMC3420557_01

Female

An eighteen-year-old unmarried young girl was admitted with fever for fifteen days. She had mild cough and mucoid expectoration with no haemoptysis. The fever was continuous, high grade (varying between 103 to 105 F), with mild chills and rigors off and on (nonspecific). No sore throat, urinary, or bowel problem was reported. Anorexia and weight loss was insignificant. There was no history of tuberculosis or treatment for any major illness in past. History of poisoning was absent. Menstrual history was normal. She was none responding to broad spectrum antibiotics like clarithromycin and amoxicillin-clavulanic acid combination. On examination she was mildly anemic but no cyanosis, lymphadenopathy, jaundice, or any organomegaly could be found. Chest examination revealed only occasional crepts bilaterally. In chest X-ray PA view, low-density peripheral infiltrates were seen bilaterally (Figure 1). On routine investigation, hemoglobin was 10.5 gm%, total leucocytes count was 8000 per cubic mm & differential count was P-59, L-36, M-1, and E-4. Urine routine examination was normal. Widal and PBF for malarial parasite were negative. Sputum for AFB was negative thrice and pyogenic was sterile. Serum HIV was negative. Ultrasonography for abdomen and thorax was normal. On fibro-optic bronchoscopy no lesion could be seen. CT scan sections show peripherally placed bronchiectatic patches (Figure 2). The bronchoalveolar lavage sample on culture revealed unusual fungus Cunninghamella bertholletiae (Figure 3). Patient was put on fluconazole empirically at the dose of 150 mg twice a day with a prompt response and was discharged in three days.

PMC4778188_01

Male

A 37-year-old male with complaints of loose stools (3-4 episodes per days) was hospitalized. Physical examination of the patient revealed anorexia, fever, mild abdominal pains for 1 week, and he admitted to be chronic alcoholic. The patient was suffering from hypertension for the past 6 months and had a previous history of pulmonary tuberculosis diagnosed a year back, for which he was under antituberculous treatment for 6 months. Due to this, he developed leukopenia along with liver dysfunction related to his treatment. A patient on antitubercular chemotherapy was said to have leukopenia if he has any of the following: (1) White blood cell (WBC) became <3000/mm3 during chemotherapy for patients with pretreatment WBC more than 4000/mm3 or (2) WBC decreased more than 1000/mm3 in patients with pretreatment WBC between 3000 and 4000/mm3. His total leukocyte count was <3000/cc3 during antituberculous chemotherapy with pretreatment. The ultrasonography report also showed parenchymal liver dysfunction, which was further confirmed by liver function test, where the level of gamma globulin was increased and albumin levels were found to be lower than the normal. The patient's aspartate aminotransferase level was higher than 31 IU/l and alanine aminotransferase higher than 34 IU/l. Freshly passed loose stool sample from the patient was received in the parasitology section, Department of Microbiology, JIPMER. The stool specimen was watery and contained blood and mucus. Routine stool microscopy was performed immediately after receiving the sample, which showed the presence of motile trophozoites about 65 mum in length and 30 mum in width and cysts of varying sizes ranging from 15 to 30 mum in diameter. The active ciliated trophozoites were identified as B. coli [Figure 1 and Video 1] and the cysts were identified as cysts of Entamoeba coli [Figure 2]. Trichrome staining (Wheatley modification for the fecal specimen) was performed after wet mount examination for the confirmation of the wet mount findings and better visualization of the internal structures [Figure 3]. The treating team was immediately informed of the condition and was advised to start the treatment and review his antitubercular therapy as it was the factor responsible for the patient being relatively immunocompromised along with his alcoholic state. Further work up on the patient showed no extraintestinal manifestations such as peritoneal spread or other necrotizing lung infections, or any genitourinary lesions. The patient was treated with metronidazole 750 mg three times daily for 5 days and the patient improved gradually. The patient slowly improved with therapy after 1 week and his antitubercular therapy was also reviewed. He was discharged after 5 days with advice to change his life style and for follow-up after 1 month.

balantidiasis, balantidium coli, ciliate protozoa, dysentery

PMC6791407_01

Female

The patient was a 62-year-old Chinese woman with no previous disease history. She was admitted to our hospital in August 2016 due to intermittent fever with cough for 2 years, left chest wall redness, and swelling for 3 months. She presented with a fever and cough repeatedly from September 2014. Laboratory tests showed increased white cells and chest computed tomography (CT) suggested patchy infiltration in the left lower lobe, with mediastinal lymph node enlargement (Figure 1A-D). Empirical treatment with cephalosporin was partially effective, but the symptoms were recurrent. In May 2016, she developed redness and a swelling in the left front chest wall with pain and high fever. She was admitted to our hospital for incision and drainage of the disease site and antibiotic administration. At the time of admission, laboratory tests showed white blood cells counts of 20.61x109/L (3.5-9.5x109/L); neutral cell percentages of 0.744 (0.4-0.75); hemoglobin: 79 g/L (130-175g/L), platelets: 384x109/L (125-350x109/L), blood C-reactive protein (CRP): 43.6 mg/L (0-8 mg/L), high levels of Immunoglobin G (IgG): 50.5 g/L (7.51-15.6 g/L); blood (1, 3)-D glucan (G tests): 146.20 pg/mL (<100.5 pg/mL); and blood galactomannan test (GM) positivity (0.64) (<0.5). HIV serology tests were negative, and normal CD4+ T cell counts and serum globulins levels (including IgA, IgM, and total IgE) were within normal reference ranges. Serum cryptococcal capsular antigen tests and blood tuberculosis infection T cell spot tests (T-SPOT.TB) were negative. Chest CT (2016-8-27) showed alveolar consolidation in the anterior segment of the left upper lobe, and an anterior chest wall with rib destruction and multiple lymphadenopathies in the left axillary and mediastinum (Figure 1E-H). Fungal spores were detected in pus from the left chest wall and microbial cultures showed T. marneffei growth. Disseminated T. marneffei (lung, skin, and bone) were established and the patient was administered amphotericin B followed by itraconazole therapy. After 8 months of regular treatment, her condition improved and antifungal drugs were ceased. The patient was followed up regularly in the clinic (Figure 1I-L). In July 2017, she again developed a high fever. Laboratory examinations after hospital admission showed white blood cells counts of 11.66x109/L; neutral cell percentages of 0.647; hemoglobin: 80 g/L; platelets: 308x109/L; blood CRP: 53.9 mg/L; IgG: 30.2 g/L; erythrocyte sedimentation rates of 66 mm/h (0-20 mm/h); and CD4+ T lymphocyte ratios of 32.6% (34-52%). G-tests, GM, and pro-calcitonin were within the normal range. Repeat chest CT scans showed consolidation in the left and right upper lobes. Bronchoscopy examinations were pathogen negative. After 2 weeks of treatment with beta-lactam antibiotics combined with oral antifungal drugs, no improvement in symptoms was observed and abnormal lung infiltration was observed in CT scans. CT-guided percutaneous right lung biopsy was performed. Pathological examinations demonstrated lung inflammation in the absence of granuloma formation. Mycobacterium avium (M. avium) was cultured and identified from mass spectrometry. Anti-NTM treatment included azithromycin, ethambutol, moxifloxacin, and rifabutin which were prescribed from August 2017. Due to adverse gastrointestinal and allergic reactions of the skin after 1 month of anti-NTM combination therapy, the patient refused treatment and was followed up in the clinic. No recurrence of the fever was observed. In May 2018, the fever recurred with hand rashes, and the patient was admitted to the hospital a third time. Her body temperature peaked at 40 C with increased pulmonary infiltration accompanied by left sternoclavicular joint destruction (Figure 2A-C). Physical examinations revealed multiple palpable lymph nodes in the left neck, erythematous plaques, and nodules in both hands (Figure 3A). Blood tests were similar to previous examinations in which increased numbers of white blood cells, CRP, and high levels of serum IgG were observed. Immune electrophoresis revealed polyclonal gammopathy, and blood/bone marrow cultures were negative. After biopsy from the left cervical lymph node and left sternoclavicular joint, M. avium was cultured from both sites. Histopathology demonstrated inflammation from the lymph nodes, and small amounts of elastic fibers with small blood vessels. Histopathology of the hand skin showed neutrophil infiltration (Figure 3B and C). Microorganism cultures were negative. The patient was finally confirmed as disseminated NTM secondary to disseminated T. marneffei. In view of the negative microbial cultures in skin biopsy tissues, and the rapid resolution of hand rashes with steroid ointments, Sweet's syndrome was diagnosed. Combination anti-NTM therapy was re-prescribed from June 2018. After 1 year of treatment, the patient's symptoms and pulmonary consolidation improved. Bone destruction and lymphadenopathy, however, remained obvious (Figure 2D-F). Laboratory tests were in the normal range except for IgG (Figure 4). The patient presented multiple intracellular pathogen infections without HIV or immunodeficiency. Serum cytokines including IL-2, IL-4, IL-6, IL-10, TNF-alpha, and IFN-gamma were within the normal range. Serum samples from both patients and controls (blood donors) including anti-IFN-gamma autoantibodies, anti-IL-12 autoantibodies, anti-TNF-alpha, and IL-12 were assessed using ELISA kits (Cloud-Clone Corp). Patient serum was tested as four independent samples and statistical analysis were performed using unpaired t-tests (GraphPad Prism Software). The mean concentration of anti-IFN-gamma antibodies in the serum samples of the patient (range: 33.13-47.06 ng/mL) was 2.85-fold higher than healthy subjects (range: 8.41-20.02 ng/mL) (P<0.01) (Figure 5). No statistically significant differences between patients and controls for TNF-alpha, IL-12, and anti- TNF-alpha were observed (data not shown).

mycobacterium avium, sweet’s syndrome, talaromyces marneffei, autoantibodies, interferon-gamma

2018-5-8 chest CT showed right upper lobe consolidation, and ,destruction of the left sternoclavicular joint (arrows).

PMC6791407_01

Female

The patient was a 62-year-old Chinese woman with no previous disease history. She was admitted to our hospital in August 2016 due to intermittent fever with cough for 2 years, left chest wall redness, and swelling for 3 months. She presented with a fever and cough repeatedly from September 2014. Laboratory tests showed increased white cells and chest computed tomography (CT) suggested patchy infiltration in the left lower lobe, with mediastinal lymph node enlargement (Figure 1A-D). Empirical treatment with cephalosporin was partially effective, but the symptoms were recurrent. In May 2016, she developed redness and a swelling in the left front chest wall with pain and high fever. She was admitted to our hospital for incision and drainage of the disease site and antibiotic administration. At the time of admission, laboratory tests showed white blood cells counts of 20.61x109/L (3.5-9.5x109/L); neutral cell percentages of 0.744 (0.4-0.75); hemoglobin: 79 g/L (130-175g/L), platelets: 384x109/L (125-350x109/L), blood C-reactive protein (CRP): 43.6 mg/L (0-8 mg/L), high levels of Immunoglobin G (IgG): 50.5 g/L (7.51-15.6 g/L); blood (1, 3)-D glucan (G tests): 146.20 pg/mL (<100.5 pg/mL); and blood galactomannan test (GM) positivity (0.64) (<0.5). HIV serology tests were negative, and normal CD4+ T cell counts and serum globulins levels (including IgA, IgM, and total IgE) were within normal reference ranges. Serum cryptococcal capsular antigen tests and blood tuberculosis infection T cell spot tests (T-SPOT.TB) were negative. Chest CT (2016-8-27) showed alveolar consolidation in the anterior segment of the left upper lobe, and an anterior chest wall with rib destruction and multiple lymphadenopathies in the left axillary and mediastinum (Figure 1E-H). Fungal spores were detected in pus from the left chest wall and microbial cultures showed T. marneffei growth. Disseminated T. marneffei (lung, skin, and bone) were established and the patient was administered amphotericin B followed by itraconazole therapy. After 8 months of regular treatment, her condition improved and antifungal drugs were ceased. The patient was followed up regularly in the clinic (Figure 1I-L). In July 2017, she again developed a high fever. Laboratory examinations after hospital admission showed white blood cells counts of 11.66x109/L; neutral cell percentages of 0.647; hemoglobin: 80 g/L; platelets: 308x109/L; blood CRP: 53.9 mg/L; IgG: 30.2 g/L; erythrocyte sedimentation rates of 66 mm/h (0-20 mm/h); and CD4+ T lymphocyte ratios of 32.6% (34-52%). G-tests, GM, and pro-calcitonin were within the normal range. Repeat chest CT scans showed consolidation in the left and right upper lobes. Bronchoscopy examinations were pathogen negative. After 2 weeks of treatment with beta-lactam antibiotics combined with oral antifungal drugs, no improvement in symptoms was observed and abnormal lung infiltration was observed in CT scans. CT-guided percutaneous right lung biopsy was performed. Pathological examinations demonstrated lung inflammation in the absence of granuloma formation. Mycobacterium avium (M. avium) was cultured and identified from mass spectrometry. Anti-NTM treatment included azithromycin, ethambutol, moxifloxacin, and rifabutin which were prescribed from August 2017. Due to adverse gastrointestinal and allergic reactions of the skin after 1 month of anti-NTM combination therapy, the patient refused treatment and was followed up in the clinic. No recurrence of the fever was observed. In May 2018, the fever recurred with hand rashes, and the patient was admitted to the hospital a third time. Her body temperature peaked at 40 C with increased pulmonary infiltration accompanied by left sternoclavicular joint destruction (Figure 2A-C). Physical examinations revealed multiple palpable lymph nodes in the left neck, erythematous plaques, and nodules in both hands (Figure 3A). Blood tests were similar to previous examinations in which increased numbers of white blood cells, CRP, and high levels of serum IgG were observed. Immune electrophoresis revealed polyclonal gammopathy, and blood/bone marrow cultures were negative. After biopsy from the left cervical lymph node and left sternoclavicular joint, M. avium was cultured from both sites. Histopathology demonstrated inflammation from the lymph nodes, and small amounts of elastic fibers with small blood vessels. Histopathology of the hand skin showed neutrophil infiltration (Figure 3B and C). Microorganism cultures were negative. The patient was finally confirmed as disseminated NTM secondary to disseminated T. marneffei. In view of the negative microbial cultures in skin biopsy tissues, and the rapid resolution of hand rashes with steroid ointments, Sweet's syndrome was diagnosed. Combination anti-NTM therapy was re-prescribed from June 2018. After 1 year of treatment, the patient's symptoms and pulmonary consolidation improved. Bone destruction and lymphadenopathy, however, remained obvious (Figure 2D-F). Laboratory tests were in the normal range except for IgG (Figure 4). The patient presented multiple intracellular pathogen infections without HIV or immunodeficiency. Serum cytokines including IL-2, IL-4, IL-6, IL-10, TNF-alpha, and IFN-gamma were within the normal range. Serum samples from both patients and controls (blood donors) including anti-IFN-gamma autoantibodies, anti-IL-12 autoantibodies, anti-TNF-alpha, and IL-12 were assessed using ELISA kits (Cloud-Clone Corp). Patient serum was tested as four independent samples and statistical analysis were performed using unpaired t-tests (GraphPad Prism Software). The mean concentration of anti-IFN-gamma antibodies in the serum samples of the patient (range: 33.13-47.06 ng/mL) was 2.85-fold higher than healthy subjects (range: 8.41-20.02 ng/mL) (P<0.01) (Figure 5). No statistically significant differences between patients and controls for TNF-alpha, IL-12, and anti- TNF-alpha were observed (data not shown).

mycobacterium avium, sweet’s syndrome, talaromyces marneffei, autoantibodies, interferon-gamma

2018-5-8 chest CT showed right upper lobe consolidation, and ,destruction of the left sternoclavicular joint (arrows).

PMC6791407_01

Female

The patient was a 62-year-old Chinese woman with no previous disease history. She was admitted to our hospital in August 2016 due to intermittent fever with cough for 2 years, left chest wall redness, and swelling for 3 months. She presented with a fever and cough repeatedly from September 2014. Laboratory tests showed increased white cells and chest computed tomography (CT) suggested patchy infiltration in the left lower lobe, with mediastinal lymph node enlargement (Figure 1A-D). Empirical treatment with cephalosporin was partially effective, but the symptoms were recurrent. In May 2016, she developed redness and a swelling in the left front chest wall with pain and high fever. She was admitted to our hospital for incision and drainage of the disease site and antibiotic administration. At the time of admission, laboratory tests showed white blood cells counts of 20.61x109/L (3.5-9.5x109/L); neutral cell percentages of 0.744 (0.4-0.75); hemoglobin: 79 g/L (130-175g/L), platelets: 384x109/L (125-350x109/L), blood C-reactive protein (CRP): 43.6 mg/L (0-8 mg/L), high levels of Immunoglobin G (IgG): 50.5 g/L (7.51-15.6 g/L); blood (1, 3)-D glucan (G tests): 146.20 pg/mL (<100.5 pg/mL); and blood galactomannan test (GM) positivity (0.64) (<0.5). HIV serology tests were negative, and normal CD4+ T cell counts and serum globulins levels (including IgA, IgM, and total IgE) were within normal reference ranges. Serum cryptococcal capsular antigen tests and blood tuberculosis infection T cell spot tests (T-SPOT.TB) were negative. Chest CT (2016-8-27) showed alveolar consolidation in the anterior segment of the left upper lobe, and an anterior chest wall with rib destruction and multiple lymphadenopathies in the left axillary and mediastinum (Figure 1E-H). Fungal spores were detected in pus from the left chest wall and microbial cultures showed T. marneffei growth. Disseminated T. marneffei (lung, skin, and bone) were established and the patient was administered amphotericin B followed by itraconazole therapy. After 8 months of regular treatment, her condition improved and antifungal drugs were ceased. The patient was followed up regularly in the clinic (Figure 1I-L). In July 2017, she again developed a high fever. Laboratory examinations after hospital admission showed white blood cells counts of 11.66x109/L; neutral cell percentages of 0.647; hemoglobin: 80 g/L; platelets: 308x109/L; blood CRP: 53.9 mg/L; IgG: 30.2 g/L; erythrocyte sedimentation rates of 66 mm/h (0-20 mm/h); and CD4+ T lymphocyte ratios of 32.6% (34-52%). G-tests, GM, and pro-calcitonin were within the normal range. Repeat chest CT scans showed consolidation in the left and right upper lobes. Bronchoscopy examinations were pathogen negative. After 2 weeks of treatment with beta-lactam antibiotics combined with oral antifungal drugs, no improvement in symptoms was observed and abnormal lung infiltration was observed in CT scans. CT-guided percutaneous right lung biopsy was performed. Pathological examinations demonstrated lung inflammation in the absence of granuloma formation. Mycobacterium avium (M. avium) was cultured and identified from mass spectrometry. Anti-NTM treatment included azithromycin, ethambutol, moxifloxacin, and rifabutin which were prescribed from August 2017. Due to adverse gastrointestinal and allergic reactions of the skin after 1 month of anti-NTM combination therapy, the patient refused treatment and was followed up in the clinic. No recurrence of the fever was observed. In May 2018, the fever recurred with hand rashes, and the patient was admitted to the hospital a third time. Her body temperature peaked at 40 C with increased pulmonary infiltration accompanied by left sternoclavicular joint destruction (Figure 2A-C). Physical examinations revealed multiple palpable lymph nodes in the left neck, erythematous plaques, and nodules in both hands (Figure 3A). Blood tests were similar to previous examinations in which increased numbers of white blood cells, CRP, and high levels of serum IgG were observed. Immune electrophoresis revealed polyclonal gammopathy, and blood/bone marrow cultures were negative. After biopsy from the left cervical lymph node and left sternoclavicular joint, M. avium was cultured from both sites. Histopathology demonstrated inflammation from the lymph nodes, and small amounts of elastic fibers with small blood vessels. Histopathology of the hand skin showed neutrophil infiltration (Figure 3B and C). Microorganism cultures were negative. The patient was finally confirmed as disseminated NTM secondary to disseminated T. marneffei. In view of the negative microbial cultures in skin biopsy tissues, and the rapid resolution of hand rashes with steroid ointments, Sweet's syndrome was diagnosed. Combination anti-NTM therapy was re-prescribed from June 2018. After 1 year of treatment, the patient's symptoms and pulmonary consolidation improved. Bone destruction and lymphadenopathy, however, remained obvious (Figure 2D-F). Laboratory tests were in the normal range except for IgG (Figure 4). The patient presented multiple intracellular pathogen infections without HIV or immunodeficiency. Serum cytokines including IL-2, IL-4, IL-6, IL-10, TNF-alpha, and IFN-gamma were within the normal range. Serum samples from both patients and controls (blood donors) including anti-IFN-gamma autoantibodies, anti-IL-12 autoantibodies, anti-TNF-alpha, and IL-12 were assessed using ELISA kits (Cloud-Clone Corp). Patient serum was tested as four independent samples and statistical analysis were performed using unpaired t-tests (GraphPad Prism Software). The mean concentration of anti-IFN-gamma antibodies in the serum samples of the patient (range: 33.13-47.06 ng/mL) was 2.85-fold higher than healthy subjects (range: 8.41-20.02 ng/mL) (P<0.01) (Figure 5). No statistically significant differences between patients and controls for TNF-alpha, IL-12, and anti- TNF-alpha were observed (data not shown).

mycobacterium avium, sweet’s syndrome, talaromyces marneffei, autoantibodies, interferon-gamma

2018-5-8 chest CT showed right upper lobe consolidation, and ,destruction of the left sternoclavicular joint (arrows).

PMC6791407_01

Female

The patient was a 62-year-old Chinese woman with no previous disease history. She was admitted to our hospital in August 2016 due to intermittent fever with cough for 2 years, left chest wall redness, and swelling for 3 months. She presented with a fever and cough repeatedly from September 2014. Laboratory tests showed increased white cells and chest computed tomography (CT) suggested patchy infiltration in the left lower lobe, with mediastinal lymph node enlargement (Figure 1A-D). Empirical treatment with cephalosporin was partially effective, but the symptoms were recurrent. In May 2016, she developed redness and a swelling in the left front chest wall with pain and high fever. She was admitted to our hospital for incision and drainage of the disease site and antibiotic administration. At the time of admission, laboratory tests showed white blood cells counts of 20.61x109/L (3.5-9.5x109/L); neutral cell percentages of 0.744 (0.4-0.75); hemoglobin: 79 g/L (130-175g/L), platelets: 384x109/L (125-350x109/L), blood C-reactive protein (CRP): 43.6 mg/L (0-8 mg/L), high levels of Immunoglobin G (IgG): 50.5 g/L (7.51-15.6 g/L); blood (1, 3)-D glucan (G tests): 146.20 pg/mL (<100.5 pg/mL); and blood galactomannan test (GM) positivity (0.64) (<0.5). HIV serology tests were negative, and normal CD4+ T cell counts and serum globulins levels (including IgA, IgM, and total IgE) were within normal reference ranges. Serum cryptococcal capsular antigen tests and blood tuberculosis infection T cell spot tests (T-SPOT.TB) were negative. Chest CT (2016-8-27) showed alveolar consolidation in the anterior segment of the left upper lobe, and an anterior chest wall with rib destruction and multiple lymphadenopathies in the left axillary and mediastinum (Figure 1E-H). Fungal spores were detected in pus from the left chest wall and microbial cultures showed T. marneffei growth. Disseminated T. marneffei (lung, skin, and bone) were established and the patient was administered amphotericin B followed by itraconazole therapy. After 8 months of regular treatment, her condition improved and antifungal drugs were ceased. The patient was followed up regularly in the clinic (Figure 1I-L). In July 2017, she again developed a high fever. Laboratory examinations after hospital admission showed white blood cells counts of 11.66x109/L; neutral cell percentages of 0.647; hemoglobin: 80 g/L; platelets: 308x109/L; blood CRP: 53.9 mg/L; IgG: 30.2 g/L; erythrocyte sedimentation rates of 66 mm/h (0-20 mm/h); and CD4+ T lymphocyte ratios of 32.6% (34-52%). G-tests, GM, and pro-calcitonin were within the normal range. Repeat chest CT scans showed consolidation in the left and right upper lobes. Bronchoscopy examinations were pathogen negative. After 2 weeks of treatment with beta-lactam antibiotics combined with oral antifungal drugs, no improvement in symptoms was observed and abnormal lung infiltration was observed in CT scans. CT-guided percutaneous right lung biopsy was performed. Pathological examinations demonstrated lung inflammation in the absence of granuloma formation. Mycobacterium avium (M. avium) was cultured and identified from mass spectrometry. Anti-NTM treatment included azithromycin, ethambutol, moxifloxacin, and rifabutin which were prescribed from August 2017. Due to adverse gastrointestinal and allergic reactions of the skin after 1 month of anti-NTM combination therapy, the patient refused treatment and was followed up in the clinic. No recurrence of the fever was observed. In May 2018, the fever recurred with hand rashes, and the patient was admitted to the hospital a third time. Her body temperature peaked at 40 C with increased pulmonary infiltration accompanied by left sternoclavicular joint destruction (Figure 2A-C). Physical examinations revealed multiple palpable lymph nodes in the left neck, erythematous plaques, and nodules in both hands (Figure 3A). Blood tests were similar to previous examinations in which increased numbers of white blood cells, CRP, and high levels of serum IgG were observed. Immune electrophoresis revealed polyclonal gammopathy, and blood/bone marrow cultures were negative. After biopsy from the left cervical lymph node and left sternoclavicular joint, M. avium was cultured from both sites. Histopathology demonstrated inflammation from the lymph nodes, and small amounts of elastic fibers with small blood vessels. Histopathology of the hand skin showed neutrophil infiltration (Figure 3B and C). Microorganism cultures were negative. The patient was finally confirmed as disseminated NTM secondary to disseminated T. marneffei. In view of the negative microbial cultures in skin biopsy tissues, and the rapid resolution of hand rashes with steroid ointments, Sweet's syndrome was diagnosed. Combination anti-NTM therapy was re-prescribed from June 2018. After 1 year of treatment, the patient's symptoms and pulmonary consolidation improved. Bone destruction and lymphadenopathy, however, remained obvious (Figure 2D-F). Laboratory tests were in the normal range except for IgG (Figure 4). The patient presented multiple intracellular pathogen infections without HIV or immunodeficiency. Serum cytokines including IL-2, IL-4, IL-6, IL-10, TNF-alpha, and IFN-gamma were within the normal range. Serum samples from both patients and controls (blood donors) including anti-IFN-gamma autoantibodies, anti-IL-12 autoantibodies, anti-TNF-alpha, and IL-12 were assessed using ELISA kits (Cloud-Clone Corp). Patient serum was tested as four independent samples and statistical analysis were performed using unpaired t-tests (GraphPad Prism Software). The mean concentration of anti-IFN-gamma antibodies in the serum samples of the patient (range: 33.13-47.06 ng/mL) was 2.85-fold higher than healthy subjects (range: 8.41-20.02 ng/mL) (P<0.01) (Figure 5). No statistically significant differences between patients and controls for TNF-alpha, IL-12, and anti- TNF-alpha were observed (data not shown).

mycobacterium avium, sweet’s syndrome, talaromyces marneffei, autoantibodies, interferon-gamma

2019-06-04 chest CT showed gradually absorption of pulmonary consolidation but remains of bone destruction and lymphadenopathy after treatment (arrows).

PMC6791407_01

Female

The patient was a 62-year-old Chinese woman with no previous disease history. She was admitted to our hospital in August 2016 due to intermittent fever with cough for 2 years, left chest wall redness, and swelling for 3 months. She presented with a fever and cough repeatedly from September 2014. Laboratory tests showed increased white cells and chest computed tomography (CT) suggested patchy infiltration in the left lower lobe, with mediastinal lymph node enlargement (Figure 1A-D). Empirical treatment with cephalosporin was partially effective, but the symptoms were recurrent. In May 2016, she developed redness and a swelling in the left front chest wall with pain and high fever. She was admitted to our hospital for incision and drainage of the disease site and antibiotic administration. At the time of admission, laboratory tests showed white blood cells counts of 20.61x109/L (3.5-9.5x109/L); neutral cell percentages of 0.744 (0.4-0.75); hemoglobin: 79 g/L (130-175g/L), platelets: 384x109/L (125-350x109/L), blood C-reactive protein (CRP): 43.6 mg/L (0-8 mg/L), high levels of Immunoglobin G (IgG): 50.5 g/L (7.51-15.6 g/L); blood (1, 3)-D glucan (G tests): 146.20 pg/mL (<100.5 pg/mL); and blood galactomannan test (GM) positivity (0.64) (<0.5). HIV serology tests were negative, and normal CD4+ T cell counts and serum globulins levels (including IgA, IgM, and total IgE) were within normal reference ranges. Serum cryptococcal capsular antigen tests and blood tuberculosis infection T cell spot tests (T-SPOT.TB) were negative. Chest CT (2016-8-27) showed alveolar consolidation in the anterior segment of the left upper lobe, and an anterior chest wall with rib destruction and multiple lymphadenopathies in the left axillary and mediastinum (Figure 1E-H). Fungal spores were detected in pus from the left chest wall and microbial cultures showed T. marneffei growth. Disseminated T. marneffei (lung, skin, and bone) were established and the patient was administered amphotericin B followed by itraconazole therapy. After 8 months of regular treatment, her condition improved and antifungal drugs were ceased. The patient was followed up regularly in the clinic (Figure 1I-L). In July 2017, she again developed a high fever. Laboratory examinations after hospital admission showed white blood cells counts of 11.66x109/L; neutral cell percentages of 0.647; hemoglobin: 80 g/L; platelets: 308x109/L; blood CRP: 53.9 mg/L; IgG: 30.2 g/L; erythrocyte sedimentation rates of 66 mm/h (0-20 mm/h); and CD4+ T lymphocyte ratios of 32.6% (34-52%). G-tests, GM, and pro-calcitonin were within the normal range. Repeat chest CT scans showed consolidation in the left and right upper lobes. Bronchoscopy examinations were pathogen negative. After 2 weeks of treatment with beta-lactam antibiotics combined with oral antifungal drugs, no improvement in symptoms was observed and abnormal lung infiltration was observed in CT scans. CT-guided percutaneous right lung biopsy was performed. Pathological examinations demonstrated lung inflammation in the absence of granuloma formation. Mycobacterium avium (M. avium) was cultured and identified from mass spectrometry. Anti-NTM treatment included azithromycin, ethambutol, moxifloxacin, and rifabutin which were prescribed from August 2017. Due to adverse gastrointestinal and allergic reactions of the skin after 1 month of anti-NTM combination therapy, the patient refused treatment and was followed up in the clinic. No recurrence of the fever was observed. In May 2018, the fever recurred with hand rashes, and the patient was admitted to the hospital a third time. Her body temperature peaked at 40 C with increased pulmonary infiltration accompanied by left sternoclavicular joint destruction (Figure 2A-C). Physical examinations revealed multiple palpable lymph nodes in the left neck, erythematous plaques, and nodules in both hands (Figure 3A). Blood tests were similar to previous examinations in which increased numbers of white blood cells, CRP, and high levels of serum IgG were observed. Immune electrophoresis revealed polyclonal gammopathy, and blood/bone marrow cultures were negative. After biopsy from the left cervical lymph node and left sternoclavicular joint, M. avium was cultured from both sites. Histopathology demonstrated inflammation from the lymph nodes, and small amounts of elastic fibers with small blood vessels. Histopathology of the hand skin showed neutrophil infiltration (Figure 3B and C). Microorganism cultures were negative. The patient was finally confirmed as disseminated NTM secondary to disseminated T. marneffei. In view of the negative microbial cultures in skin biopsy tissues, and the rapid resolution of hand rashes with steroid ointments, Sweet's syndrome was diagnosed. Combination anti-NTM therapy was re-prescribed from June 2018. After 1 year of treatment, the patient's symptoms and pulmonary consolidation improved. Bone destruction and lymphadenopathy, however, remained obvious (Figure 2D-F). Laboratory tests were in the normal range except for IgG (Figure 4). The patient presented multiple intracellular pathogen infections without HIV or immunodeficiency. Serum cytokines including IL-2, IL-4, IL-6, IL-10, TNF-alpha, and IFN-gamma were within the normal range. Serum samples from both patients and controls (blood donors) including anti-IFN-gamma autoantibodies, anti-IL-12 autoantibodies, anti-TNF-alpha, and IL-12 were assessed using ELISA kits (Cloud-Clone Corp). Patient serum was tested as four independent samples and statistical analysis were performed using unpaired t-tests (GraphPad Prism Software). The mean concentration of anti-IFN-gamma antibodies in the serum samples of the patient (range: 33.13-47.06 ng/mL) was 2.85-fold higher than healthy subjects (range: 8.41-20.02 ng/mL) (P<0.01) (Figure 5). No statistically significant differences between patients and controls for TNF-alpha, IL-12, and anti- TNF-alpha were observed (data not shown).

mycobacterium avium, sweet’s syndrome, talaromyces marneffei, autoantibodies, interferon-gamma

2019-06-04 chest CT showed gradually absorption of pulmonary consolidation but remains of bone destruction and lymphadenopathy after treatment (arrows).

PMC6791407_01

Female

The patient was a 62-year-old Chinese woman with no previous disease history. She was admitted to our hospital in August 2016 due to intermittent fever with cough for 2 years, left chest wall redness, and swelling for 3 months. She presented with a fever and cough repeatedly from September 2014. Laboratory tests showed increased white cells and chest computed tomography (CT) suggested patchy infiltration in the left lower lobe, with mediastinal lymph node enlargement (Figure 1A-D). Empirical treatment with cephalosporin was partially effective, but the symptoms were recurrent. In May 2016, she developed redness and a swelling in the left front chest wall with pain and high fever. She was admitted to our hospital for incision and drainage of the disease site and antibiotic administration. At the time of admission, laboratory tests showed white blood cells counts of 20.61x109/L (3.5-9.5x109/L); neutral cell percentages of 0.744 (0.4-0.75); hemoglobin: 79 g/L (130-175g/L), platelets: 384x109/L (125-350x109/L), blood C-reactive protein (CRP): 43.6 mg/L (0-8 mg/L), high levels of Immunoglobin G (IgG): 50.5 g/L (7.51-15.6 g/L); blood (1, 3)-D glucan (G tests): 146.20 pg/mL (<100.5 pg/mL); and blood galactomannan test (GM) positivity (0.64) (<0.5). HIV serology tests were negative, and normal CD4+ T cell counts and serum globulins levels (including IgA, IgM, and total IgE) were within normal reference ranges. Serum cryptococcal capsular antigen tests and blood tuberculosis infection T cell spot tests (T-SPOT.TB) were negative. Chest CT (2016-8-27) showed alveolar consolidation in the anterior segment of the left upper lobe, and an anterior chest wall with rib destruction and multiple lymphadenopathies in the left axillary and mediastinum (Figure 1E-H). Fungal spores were detected in pus from the left chest wall and microbial cultures showed T. marneffei growth. Disseminated T. marneffei (lung, skin, and bone) were established and the patient was administered amphotericin B followed by itraconazole therapy. After 8 months of regular treatment, her condition improved and antifungal drugs were ceased. The patient was followed up regularly in the clinic (Figure 1I-L). In July 2017, she again developed a high fever. Laboratory examinations after hospital admission showed white blood cells counts of 11.66x109/L; neutral cell percentages of 0.647; hemoglobin: 80 g/L; platelets: 308x109/L; blood CRP: 53.9 mg/L; IgG: 30.2 g/L; erythrocyte sedimentation rates of 66 mm/h (0-20 mm/h); and CD4+ T lymphocyte ratios of 32.6% (34-52%). G-tests, GM, and pro-calcitonin were within the normal range. Repeat chest CT scans showed consolidation in the left and right upper lobes. Bronchoscopy examinations were pathogen negative. After 2 weeks of treatment with beta-lactam antibiotics combined with oral antifungal drugs, no improvement in symptoms was observed and abnormal lung infiltration was observed in CT scans. CT-guided percutaneous right lung biopsy was performed. Pathological examinations demonstrated lung inflammation in the absence of granuloma formation. Mycobacterium avium (M. avium) was cultured and identified from mass spectrometry. Anti-NTM treatment included azithromycin, ethambutol, moxifloxacin, and rifabutin which were prescribed from August 2017. Due to adverse gastrointestinal and allergic reactions of the skin after 1 month of anti-NTM combination therapy, the patient refused treatment and was followed up in the clinic. No recurrence of the fever was observed. In May 2018, the fever recurred with hand rashes, and the patient was admitted to the hospital a third time. Her body temperature peaked at 40 C with increased pulmonary infiltration accompanied by left sternoclavicular joint destruction (Figure 2A-C). Physical examinations revealed multiple palpable lymph nodes in the left neck, erythematous plaques, and nodules in both hands (Figure 3A). Blood tests were similar to previous examinations in which increased numbers of white blood cells, CRP, and high levels of serum IgG were observed. Immune electrophoresis revealed polyclonal gammopathy, and blood/bone marrow cultures were negative. After biopsy from the left cervical lymph node and left sternoclavicular joint, M. avium was cultured from both sites. Histopathology demonstrated inflammation from the lymph nodes, and small amounts of elastic fibers with small blood vessels. Histopathology of the hand skin showed neutrophil infiltration (Figure 3B and C). Microorganism cultures were negative. The patient was finally confirmed as disseminated NTM secondary to disseminated T. marneffei. In view of the negative microbial cultures in skin biopsy tissues, and the rapid resolution of hand rashes with steroid ointments, Sweet's syndrome was diagnosed. Combination anti-NTM therapy was re-prescribed from June 2018. After 1 year of treatment, the patient's symptoms and pulmonary consolidation improved. Bone destruction and lymphadenopathy, however, remained obvious (Figure 2D-F). Laboratory tests were in the normal range except for IgG (Figure 4). The patient presented multiple intracellular pathogen infections without HIV or immunodeficiency. Serum cytokines including IL-2, IL-4, IL-6, IL-10, TNF-alpha, and IFN-gamma were within the normal range. Serum samples from both patients and controls (blood donors) including anti-IFN-gamma autoantibodies, anti-IL-12 autoantibodies, anti-TNF-alpha, and IL-12 were assessed using ELISA kits (Cloud-Clone Corp). Patient serum was tested as four independent samples and statistical analysis were performed using unpaired t-tests (GraphPad Prism Software). The mean concentration of anti-IFN-gamma antibodies in the serum samples of the patient (range: 33.13-47.06 ng/mL) was 2.85-fold higher than healthy subjects (range: 8.41-20.02 ng/mL) (P<0.01) (Figure 5). No statistically significant differences between patients and controls for TNF-alpha, IL-12, and anti- TNF-alpha were observed (data not shown).

mycobacterium avium, sweet’s syndrome, talaromyces marneffei, autoantibodies, interferon-gamma

2019-06-04 chest CT showed gradually absorption of pulmonary consolidation but remains of bone destruction and lymphadenopathy after treatment (arrows).

PMC5812064_01

Female

Patient A, a 40-year-old female, suffered from episodes of upper abdominal and back pain accompanied by vomiting since a year before presentation. Initially, complaints presented predominantly postprandial but eventually even in the absence of any provocative factors. She had lost 9 kg (15% total body weight). Her medical history mentioned fibromyalgia. Furthermore, she had been smoking cigarettes for 20 years (ten pack years) but quitted 8 months before presentation. Her medication consisted of oral contraceptives and isosorbide mononitrate 50 mg daily on trial during 3 months which appeared to have a positive effect on her complaints. The diagnosis of chronic splanchnic ischemia was by the exclusion of several other diseases and after numerous other investigations. Computed tomography angiography (CTA) revealed a high-grade stenosis at the ostia of the superior mesenteric artery (SMA), the celiac trunk, and the inferior mesenteric artery [Figure 1]. The patient was presented for splanchnic revascularization. After retrograde duplex-guided puncture of the right femoral artery, a diagnostic angiography confirmed a pinpoint stenosis of the celiac trunk and SMA. Subsequently, the right brachial artery was punctured. The stenosis in the celiac trunk was passed easily, and a 5 mm x 19 mm self-expandable stent was placed. Subsequently, a 5 mm x 15 mm self-expandable stent was placed in the SMA. Postballooning was performed after the stent placements. The procedure was uncomplicated resulting in a technical successful revascularization [Figure 2]. During the procedure, the patient experienced an increased abdominal tension, pain, and nausea. Angiography, however, showed a patent SMA and celiac trunk, without evidence of distal embolization, dissection, or thrombosis of the target vessels. Approximately 7 h after the procedure, a CTA was performed because of persisting significant abdominal complaints in the epigastric region despite administration of substantial amounts of analgesics. CTA revealed patent stents in the SMA and celiac trunk and adequate peripheral blood flow. No laboratory abnormalities were detected (serum lipase level 16 U/l, C-reactive protein 2 mg/l). The day after the procedure pain persisted in the epigastric region. No hepatosplenomegaly was observed. A gastroscopy showed no abnormalities. Serum lipase levels as well as liver function tests and infection parameters remained low. Serum lactic acid level was 1.0 mmol/l. Even more than 50 h after the initial procedure, complaints did not diminish. Once again CTA was repeated, showing patent splanchnic arteries [Figure 3a]. However, an impressive hyperperfusion state of liver and spleen was visualized, accompanied by ascites (Figure 3b). Symptoms were considered to be due to splanchnic reperfusion and diminished spontaneously after a few days

complication, intestine, reperfusion syndrome, revascularization

PMC6748175_01

Male

A 19-year-old male who played as a football goalkeeper visited our hospital with complaints of sustained pain from the right wrist to the hand after punching a ball. In the emergency department, the patient exhibited swelling at the right wrist and tenderness at the anatomical snuffbox of the right wrist and second metacarpal base area. Plain radiographs of the right wrist showed a displaced scaphoid body fracture (type 2B according to the Herbert classification). No other fractures could be identified on plain radiographs (Figure 1). Computed tomography (CT) scan was performed for the right wrist to obtain details on the fractured scaphoid. In addition to the displaced scaphoid body fracture, the CT scan revealed a displaced trapezoid fracture that was not clearly observed on plain radiographs. The fracture pattern of the trapezoid was vertical (Figure 2). Surgery was performed at 11 days after the patient's initial hospital visit. Open reduction and internal fixation of the fractures was performed with two 1 cm minimal incisions over the scaphoid and trapezoid using a cannulated headless compression screw (double-threaded screw; MEIRA Corporation, Nagoya, Japan) for each fracture (Figure 3). After surgery, the patient's right wrist was placed in a short-arm thumb spica cast for 2 weeks. Range of motion exercise was initiated at 2 weeks after surgery. The fracture line was still visible in the scaphoid, but most part of the fracture site was united at 5 months after surgery (Figure 4). The patient returned to play as a football goalkeeper and is currently free of symptoms.

PMC9663657_01

Male

A 31-year-old man came to our hospital with left hip pain and intermittent fever for 1 month. For nearly a year, the patient occasionally has abdominal distention which alleviated after defecation. The frequency of defecation was about once every two days. The mass was seen as a reddish skin color around the anterior superior iliac spine which was painful and palpated. The laboratory examination revealed white blood cell 13.25 x 109/L (3.5-9.5), neutrophil percentage 85% (40-75), platelet 420 x 109/L (125-350), C-reactive protein 82.6 mg/L (0-10) and erythrocyte sedimentation rate 48 mm/h (0-20). The tumor-related biomarkers (AFP, CEA, PSA, CA19-9, ferritin), serum tuberculosis antibodies and T-cell spot test for tuberculosis infection (T-TB.Spot) were within normal limits. The whole abdomen CT and pelvic contrast-enhanced MRI were performed. The imaging revealed a left PA (Figures 1A,B) Colonoscopy revealed mucosal stiffness and multiple polyps on the ascending colon (Figure 1C). Then, the mucosal biopsy of ascending colon was performed. To sum up, we think that it may be the PA secondary to inflammatory bowel disease. But pathology was not in line with the typical manifestations of inflammatory bowel disease.

case report, constiption, inflammatory bowel disease, intestinal neuronal dysplasia, psoas abscess

PMC4085885_01

Unknown

A 24-year-oldathlete presented following a fall onto an outstretched hand during a football match, total functional impotence of both upper limbs with swollen elbows, pain, without skin opening or motor deficit (A). Radiography of both elbows was objectified a fracture of the both olecranon (B). The patient was treated by tension-band wiring fixation with precocious postoperative rehabilitation (C). Two months after surgery, we note a consolidation of the fracture with satisfactory mobility of both elbows. Olecranon fractures may be caused by direct injury to the posterior part of the elbow joint or indirectly by forces generated within the triceps muscle during a fall on a partially flexed elbow. The clinical picture is obvious and conventional radiographs are usually sufficient to depict the lesion and the potential associated injuries. The bilateral form is very rarely described in the literature. The goals of treating olecranon fractures are anatomic restoration of the articular surface, repair of the elbow extensor mechanism, restoration of joint stability and motion, and prevention of stiffness and other complications. Treatment options include immobilization, surgical reduction and fixation with tension-band wiring or plate osteosynthesis. The active mobilization after surgery will restore the patient to normal functions as early as possible.

fracture, footballer, olecranon

PMC9989549_02

Unknown

Progress. The interprogrammatic group consisted of delegates from the Ministry of Public Health and Social Welfare, the LCSP, the Expanded Program on Immunization, the child and adolescent health programs, and the indigenous health program, as well as delegates from the health regions where the survey was conducted. Field implementation of a school-based serosurvey concluded in February 2020, laboratory analysis of samples was completed in 2021, and the preliminary analysis of the survey results was completed in 2022. The study population included 1 200 children (6-15 years old) from schools in the Chaco region. Fourteen antigens were analyzed for the study to obtain data on ten diseases (Table 2). Challenges. Fieldwork was prolonged due to flooding and difficulties in accessing the study areas. A total of 1 104 samples were collected. Regarding laboratory analysis of specimens at the LCSP, there were two issues identified. In the beginning, a buffer prepared at LCSP did not pass quality control, and the CDC sent the reagent from Atlanta to help overcome the problem, causing delays in the analysis of specimens. Then, when the LCSP completed the analysis of all specimens, the inter-laboratory comparison of results for the measles antigen showed significant differences between LCSP and CDC. Since LCSP ran out of reagents to repeat standard curves to establish new cutoffs, the decision was to retest the specimens at the CDC. The analysis of specimens took longer due to the impact of the COVID-19 pandemic limiting laboratory access for CDC staff, but it was completed by the end of 2021. The results of the survey are expected to be available in 2023. Progress. The first interprogrammatic group was established in 2018 with delegates from programs for neglected infectious diseases (NIDs), vaccine-preventable diseases (VPDs), malaria, the national laboratories directorate of the Ministry of Health, and the IBMP. The group proposed to carry out an integrated serosurvey using specimens from a sera bank of a national dengue study to obtain serology data for selected communicable diseases of interest in rural populations of the country's northern region. Due to the limited ability to respond to the research questions using the proposed sera bank, the group decided in 2021 to develop a new protocol. This revised protocol will use specimens collected regularly for the epidemiological surveillance of communicable diseases in hard-to-reach populations to carry out a retrospective integrated serosurvey. This effort involves additional partners such as the Institute of Scientific and Technological Communication and Information in Health at Fiocruz, the Evandro Chagas Institute, the Tropical Medicine Foundation, and the University of Sao Paulo, among others. The protocol is expected to be completed and implemented in 2023, as well as laboratory training on the Multiplex platform. In addition to the three countries participating in the initiative, integrated serosurveillance has been expanded to countries that have implemented surveys to assess the epidemiological status of NIDs. Guatemala conducted a national survey to estimate the prevalence of soil-transmitted helminth infections in school-age children and 20 antigens related to ten diseases were tested on the Multiplex platform (Table 2). Guyana conducted a survey of school-age children in six regions of the country to determine the level of transmission of lymphatic filariasis, and tested serology for 18 antigens related to ten diseases. In these two countries, samples were analyzed at the CDC (Table 2). Mexico was the only country in the initiative to complete the analysis of the integrated serosurvey results by the end of 2021. The laboratory group organized, cleaned, and validated the survey database. The laboratory team initially carried out a preliminary analysis of the raw laboratory results. Then, a database combining laboratory and survey results, including demographic data and risk factors of surveyed participants was compiled. This process took longer than expected since data entry from the paper-based questionnaires did not have adequate staff and time devoted to this task. A statistician from CDC assisted in the analysis process for Mexico, including an in-person visit when the database was compiled. In 2019, the CDC and InDRE team worked together for several months to produce the first set of results. In February 2020, PAHO had an in-person visit to support the interpretation of results and to discuss them with the interprogrammatic team. Simple univariate and bivariate analysis of seroprevalence data, accounting for the cluster survey design, was produced for each group of diseases included in the survey. Serosurvey results were triangulated with program data to understand the results in the context of the surveyed populations. For instance, vaccine coverage by age cohorts and historic reports of cases and outbreaks of VPDs in the studied population were used to interpret seroprevalence for measles, rubella, and diphtheria. Because of the survey design and nature of the survey as a pilot, the results were not robust enough to be used for programmatic decisions. However, the interprogrammatic team in Mexico understood the utility of serosurveillance as a complementary tool to characterize the transmission of communicable diseases and monitor the impact of interventions. The experience with the first integrated serosurvey in Mexico was used in 2021 to start developing a second serosurvey protocol. In the meeting held in Mexico on March 2020 with delegates of countries and institutions participating in the Multiplex initiative, the need to reinforce country capacities to analyze and interpret integrated serosurveillance data was highlighted. In April 2021, PAHO and CDC conducted a five half-day virtual workshop with delegates from interprogrammatic groups of Brazil, Guatemala, Guyana, Mexico, and Paraguay focused on reinforcing skills to effectively use integrated serosurvey data. Theory and practical sessions were completed to review the rationale, concepts, approach, laboratory aspects, survey data preparation, data analysis, and data triangulation and interpretation. PAHO and CDC published a toolkit to help countries to plan, implement, analyze, and use the results of integrated serosurveillance to improve programmatic decisions. This toolkit was developed based on the experience of the initiative. Paraguay, Guatemala, and Guyana will complete and publish the analysis of results in 2023. The following are the most important lessons learned from integrated serosurveillance in the Americas: The country coordinating team should be clearly defined from the beginning and include those responsible for the programs, experts in the subject matter and diseases under study, statisticians, experts with experience in survey design, epidemiologists, laboratory technicians, and professionals with other profiles according to the proposed protocol and the expected use of results. When monitoring several diseases at once, it is challenging to define the optimal age range and sample size to ensure the objectives of the study are met. Considering that, a household survey might be the best option, instead of a school-based survey. This would fulfill the needs of programs for diseases having significant transmission, or that require monitoring of routine immunization activities, in children below school age. Proper training, supervision, and monitoring of field teams are crucial to ensure adherence to the methods and procedures established in the protocol. Logistical situations and contingencies that could affect fieldwork should be, when possible, identified in advance to adjust the timeline, resource, and financing requirements. Disaggregated epidemiological data (e.g., cases and outbreaks) and historical data on interventions implemented (e.g., vaccination coverage, mass drug administration, etc.) are needed during the survey design phase to help define the research questions, and to interpret results using triangulation techniques. While the MBA is more complex than single target assays for serology, the assay is robust, the technique is easy to train, and data are generated for multiple antigens in a single sample. Technology transfer is an ongoing process; close and continuous communication and support are critical among participating laboratories to maintain and revalidate laboratory capacities in countries. In addition to improving laboratory capacities, it is crucial to ensure appropriate skills in survey design, statistical methods, data analysis, and interpretation to generate valid, reliable, and generalizable results to support actionable programmatic decisions. This process takes time and must integrate different disciplines, the programs' responsible, and the support of partners such as academies and research groups. Table 3 presents some of the key aspects in the planning, implementation, data analysis, and decision-making to consider when implementing integrated serosurveys.

americas, serology, communicable diseases, surveillance

PMC5617086_01

Female

A 39-year-old woman was admitted to our clinic for the first time in a traumatic VS, whose duration at that time was 5 months. The cause of initial brain damage was severe TBI with skull fracture, DAI II with contusion in the polar parts of the left temporal and frontal lobes, and subarachnoid hemorrhage. Fractures of the ribs and left shank were detected in the acute period of trauma. In-life monitoring and treatment lasted for 13 months and included 2 hospitalizations at the clinic (lasting 1 month each), with an interval of 7 months between them. During both hospitalizations to treat spasticity, botulinum toxin (BT) A (incobotulinumtoxinA; Merz Pharma GmbH & Co. KGaA, Frankfurt, Germany) was injected into all spastic muscles; the total dose was 800 U (20 U/kg of body mass) at the first hospitalization and 300 U at the second. In addition, after the first hospitalization, the patient began to receive an N-methyl-d-aspartate receptor (NMDA) receptor antagonist (memantine) and a carbonic anhydrase inhibitor (acetazolamide). Because of repeated infection (pneumonia), the patient received courses of antibacterial therapy 3 times. At both hospitalizations, clinical neurologic examinations (the level of consciousness was assessed with the Coma Recovery Scale-Revised [CRS-R], and assessment of muscle tone was performed according to the modified Ashworth Scale [MAS]) and PET were performed prior to and 3 weeks after treatment. All examinations (including electroencephalography [EEG], MRI and PET) and treatments were conducted according to the medical board's decisions and the protocol approved by the Institutional Academic Council of the N.P. Bechtereva Institute of the Human Brain of the Russian Academy of Sciences (IHB RAS) and the local ethical committee. Written informed consent was obtained from the patient's mother. When not hospitalized, the patient remained at home. In the months after the second hospitalization, against a background of continuous positive dynamics, the patient (40 years old at that point) died due to sudden cardiac failure. Along with a standard autopsy, a neuropathologic brain analysis was also performed.

adult human neurogenesis, axonal growth, botulinum toxin therapy of spasticity, functional state of the brain, improvement of consciousness, vegetative state

PMC5730425_01

Female

A 58-year-old female was admitted to the department of surgery through the ED with a chief complaint of severe abdominal pain and discomfort as well as a syncopal episode thought to be related to patient's hypotensive state. She had a history of chronic pain syndrome treated with long-term sublingual 8 mg-2 mg Suboxone film therapy, current infection of hepatitis C, chronic untreated constipation, reported history of irregular heartbeat and possible history of coronary artery disease treated as outpatient with Plavix. The patient was unable to provide any family history. She currently lives with her husband and is unemployed. She stated that her only positive drug history was the suboxone. Her past surgical history revealed a partial hysterectomy, a cholecystectomy as well as an appendectomy. On initial physical exam, the patient was found to have a diffusely tender and distended abdomen and hematochezia. She was afebrile and hypotensive with a systolic blood pressure in the 80s-90s. Her white blood count on admission was 6.5 x 109/L. Abdominopelvic CT scan revealed a bowel perforation most likely in the distal colon, ascites and fecal impaction of the large bowel (Fig. 1, Fig. 2). The initial diagnosis was perforated ischemic bowel. Emergency surgery was performed by Dr. Sylvanus Oyogoa. Intraoperatively, she was found to have extensive stool in the peritoneal cavity as well as hemoperitoneum. There was a large fecal mass located in the sigmoid colon causing pressure necrosis on surrounding tissues that had progressed to bowel perforation. Fecal material was protruding through the perforation site into the peritoneal cavity. Hartmann's procedure was used to resect the affected bowel. A splenic rupture was also noted and a splenectomy was performed (Fig. 3). The colostomy was created in the full quadrant bisecting with simple fashion and a wound VAC was placed following closure. The patient was given antibodies initially and was given Zosyn, Flagyl and Vancomycin. Post-op diagnosis was perforated bowel, fecal peritonitis, hemoperitoneum and splenic rupture. Postoperatively, she continued to show signs of sepsis as well as continual complaints of worsening abdominal pain. On POD six, a second abdominopelvic CT scan was performed and revealed increased free fluid within the abdominal cavity, increased attenuation more dependently, extraluminal oral contrast is seen in the fluid within the abdominal cavity consistent with bile leak. High-density fluid present in the left upper quadrant was suggestive of a contrast leak at the location of splenectomy (Fig. 4). This raised concern for possible venous leak and a second exploratory laparotomy with washout was performed on POD seven. Preoperative diagnosis was perforated gut with fecal peritonitis, intraabdominal abscess, and sepsis. Upon exploration of the cavity, the patient had lots of murky dusky looking fluid in the abdomen. There was no evidence of compromised bowel, she had multiple loculated abscesses within the small bowel and other areas, which were opened and washed out very gently with antibiotic solution and sterile solution. The patient tolerated the procedure well and was brought to the recovery room in stable condition. Post-op diagnosis was intraabdominal abscesses and sepsis. After re-operation, she showed steady recovery with conservative treatment.

buprenorphine, constipation, opioids, stercoral perforation, suboxone

PMC7315312_01

Female

Ossifying tracheobronchial disease is a rare benign lesion occurring in trachea and bronchus. Its clinical manifestations are not specific. In the past, ossifying tracheobronchial disease was often missed and misdiagnosed by clinician. With the development of electronic bronchoscopy, reports on ossifying tracheobronchial disease are increasing at home and abroad. Previous studies reported that the duration of TO was long, the onset age of TO was normally more than 50 years old, and there were occasional cases among adolescents and children. Reports from overseas showed that there was no significant difference in the prevalence of TO between males and females. It was also reported that the prevalence of TO between males and females was about 3 : 1. In China, there was no significant difference regarding the prevalence of TO between males and females in most studies. In this report, six patients were male, all aged over 40 years old, which indicated that men are more susceptible to this disease. The pathogenesis of TO is still unclear. There are several possible reasons, including congenital tracheobronchial dysplasia, long-term physical, chemical, or mechanical stimulation (fumes and irritating gases), chronic inflammation of tracheobronchial mucosa, metabolic disorders (endocrine hormone level or abnormal calcium and phosphorus metabolism), amyloidosis and degeneration, and selective IgA deficiency. The possible cause may also be the result of interaction between several reasons. In this report, two of five patients had a history of smoking. Studies in the past showed women had no history of smoking, but had a history of exposure to soot and dust. Thus, a long-term chronic inflammatory stimulation was also associated with TO. Long-term exposure to soot could stimulate airway mucosa, which may be one risk factor for the formation of TO. Jinyun et al. reported that patients with TO had chronic rhinitis and chronic sinusitis at the same time, while Shipeng et al. found that patients with TO accompanied with tuberculosis. Our study also showed that one patient had tuberculosis history in the past, and one patient had chronic sinusitis and nasal polyposis history, suggesting that chronic infection may be related to the pathogenesis of TO. In the past, some researchers have proposed that the formation of new bone and cartilage may be related to the transforming growth factor beta 1, a synergistic transformation of bone morphogenetic protein 2, endocrine hormone level, or abnormal calcium and phosphorus metabolism in vivo. It is generally believed that TO develops slowly and has no specific clinical manifestations. The severity of the disease is related to the extent of the lesion and the degree of lumen obstruction. Common symptoms include cough, expectoration, chest congestion, and shortness of breath; rare symptoms include breathlessness, laboured breathing, hoarseness, foreign body sensation in the pharynx, and dysphagia. Six patients in this report had no special clinical symptoms. It is reported that a patient has many years of asthma history. He was misdiagnosed as bronchial asthma in adolescence and was diagnosed as TO by bronchoscopy in adulthood. In addition to pulmonary tuberculosis, chronic rhinitis, and chronic sinusitis, TO could also be accompanied by lung cancer, allergic bronchopulmonary aspergillosis, carbon sequestration, chronic atrophic gastritis, and other diseases. In this report, two patients with TO were accompanied with chronic atrophic gastritis and Helicobacter pylori infection history. Jinyun et al. reported that one patient with TO was complicated with Helicobacter pylori infection. Therefore, whether Helicobacter pylori infection is related to the morbidity of TO needs further study. Yun et al. reported that a patient's alveolar lavage fluid showed mild nonspecific cell clusters, which were easily confused with malignant tumors, but there was no follow-up results in the study. There was no specific manifestation of pulmonary function in patients with TO. Some patients had normal pulmonary function, and some can also show restrictive or obstructive pulmonary ventilation dysfunction. Of the six cases reported in this paper, two cases had normal pulmonary function as their pulmonary function was not affected due to the early stage of the lesion. Three patients indicated obstructive pulmonary ventilation dysfunction, and one reason maybe the proliferation of intrabronchial nodules, which results in narrow lumen and airflow limitation; another reason might be the combination of chronic obstructive pulmonary disease. One patient indicated restrictive pulmonary ventilation dysfunction, which may be caused by severe lesions and long duration, resulting in decreased compliance of lung tissue. This is similar to the results of lung function reported in previous studies. Because the lesions of patients with TO are mostly located in the trachea and bronchus and do not involve lung parenchyma and alveolar wall tissue, the diffusion function of patients is usually normal. Chest X-ray examination is not sensitive to the diagnosis of TO. CT examination is meaningful for the diagnosis of TO. CT can show multiple small nodules with or without calcification, which protrude from the trachea and main bronchial submucosa to the lumen. Nodules vary in size, and most lesions are located in the anterior and lateral walls of the trachea, which narrowed the lumen. When the lesion is serious, it can cause lumen collapse and atelectasis. It was reported that the tracheal membranes may also be involved in some patients with severe fusion, but it is also believed that the disease can be excluded if the membranous part is involved. All six patients had right bronchial lesions with different manifestations, but it may suggest that TO is more likely to invade the right bronchi. However, there is no previous report on this issue, so more cases are needed for further confirmation. Thoracic MRI T1- and T2-weighted images can also be beneficial to the diagnosis of TO. Diffuse trachea and diffuse irregular thickening of the main bronchial tube wall could be represented by moderate intensity signal; punctate calcification could be represented by low intensity signal; and coronal position could show the extent of wall thickening. The manifestations of TO under bronchoscope are characteristic, which can determine the diagnosis and lesion range. Biopsy under bronchoscope is helpful for further diagnosis. Therefore, bronchoscopy is considered as the "gold standard" for clinical diagnosis of TO. In recent years, the number of TO cases has increased gradually, which is closely related to the development and popularization of bronchoscopy technology. The typical manifestations are small nodules of different sizes and uneven distribution under the bronchoscope, which protrude from the trachea and bronchial submucosa to the lumen. The surface of the nodules is often covered with yellow or white secretions, which can be disseminated and fused into pieces when the lesions are serious. This may result in narrowing or beaded changes of the lumen. Typical lesions have a pebble-like appearance and nodular nature, which is difficult to get using biopsy forceps. Most of the lesions are located in the anterior and lateral walls of trachea and bronchus, and the lesions less likely invade glottis, supraglottic tissues, and tracheal membranes (posterior wall of the trachea). When the nodules are concentrated together, they can fuse into larger nodules, making the lumen narrow or even obstructed. Some patients may have multiple bronchial polyps, which makes the stenosis of the lumen more obvious. The texture of TO lesion is hard. According to the literature, only 55% of patients can be diagnosed by the first histopathological biopsy, and crocodile forceps can be used for bronchoscopic biopsy to improve the positive rate of biopsy. Typical pathological manifestations of TO were bone tissue or focal ossification under tracheobronchial mucosa, which served as the evidence for diagnosis of TO. Inflammatory cells such as lymphocytes and neutrophils infiltrated under mucosa, squamous epithelial metaplasia, and nonspecific hyperplasia could be also seen in some mucosa. Pathological findings in some patients with TO suggested keratinization of tracheal mucosal epithelium, which is the manifestation of different stages of the same disease, or suggesting the combination of other diseases, are not yet confirmed. Ihara et al. found that fluorescent bronchoscopy can show squamous metaplasia of tracheal mucosal epithelium, which is helpful to improve the diagnostic rate. There is no special treatment for TO at present. Patients with TO are prone to recurrent pulmonary infection and/or atelectasis. Treatment principles are anti-infection, drainage of airway secretions, inhalation of bronchodilators, inhalation of glucocorticoid spasmolysis, and anti-inflammation, which can alleviate the symptoms of patients. For some advanced lesions, the endoscopic interventional therapy or surgery can be used to relieve clinical symptoms. Tracheal intubation is more difficult in patients with progressive TO. TO is a benign disease, and among which male adults, particularly the middle-aged males, are more likely to suffer from it. There is a lack of specificity in clinical manifestations so far, and the right bronchus is more likely to be invaded. The causes may be related to chronic infection, including Helicobacter pylori infection. Chest CT can be used for the preliminary diagnosis of TO, and bronchoscopy and histopathological examination can be used for the final diagnosis. There is no well-recognized treatment guideline for TO worldwide at present, and symptomatic treatment is mostly adopted. However, there is still a lack of large-scale cases and multicenter, prospective studies to provide the evidence for the standardized diagnosis and treatment of TO.

PMC6245346_01

Female

An 8 days old exclusively breastfed female infant was referred to our hospital because of an infection of the umbilicus without fever. She was the second child of nonconsanguineous parents, both of Arab-Berber descent, born after 39 weeks of pregnancy, complicated by intrauterine growth restriction. Birth weight 2.570 kg (SD -1.6), length 48 cm (SD -0.8), and head circumference 32 cm (SD -1.7). The mother was known to have Crohn's disease, treated with oral methylprednisolone, in a gradually reducing dose with a maximum of 32 mg daily, and adalimumab, 40 mg subcutaneously every 2 weeks for up to 3 months before delivery. Additional investigations revealed a latent tuberculosis (positive interferon gamma release assay), for which she used INH 300 mg once a day, in combination with pyridoxine 125 mg, which both were started immediately after delivery. Family history is negative for hematologic diseases, syndromes, or early unexplained death. Physical examination of the neonate was, besides a local infection of the umbilicus, normal for her age. No (skeletal) malformations, cutaneous, or nail abnormalities; hepato-splenomegaly; or hypotonia were noted. However, complete blood count showed a picture of severe isolated neutropenia (hemoglobin 18.2 g/dL, mean corpuscular volume 97, plate-lets 254x109/L, leukocytes 7.56x109/L, and absolute neutrophil count [ANC] 0.04x109/L; C-reactive protein 73.1 mg/L). The child was admitted and broad-spectrum intravenous antibiotic treatment (ampicillin and cefotaxime) was started. Cultures of the umbilicus revealed the growth of Staphylococcus aureus. Urine and blood cultures remained negative. The infection improved; however, the isolated neutropenia persisted. No viral etiology (TORCH, which includes Toxoplasmosis, Other [syphilis, varicella-zoster, parvovirus B19], Rubella, cytomegalovirus, and herpes infections, [para] influenza, respiratory syncytial virus, adenovirus) could be demonstrated. Testing for antineutrophil antibodies was not done, as the tests often show false-positive and false-negative results. Bone marrow aspiration revealed a severe dysgranulopoiesis, characterized by a maturation stop after meta-/myelocyte stage (Figure 1), indicating severe congenital neutropenia. Maternal usage of adalimumab during pregnancy can cause neutropenia because it can cross the placenta from the maternal circulation into the fetal circula tion. Also, agranulocytosis due to INH, used by the mother while breast-feeding, could not be excluded. Tuberculosis was excluded in the child, and the complete blood count of the mother did not show neutropenia. As a probability scale, we use the Naranjo algorithm, and this case was scored for both medications separately. INH was scored "3," while adalimumab was scored "4," both as a "possible" likelihood to be responsible for the neutropenia (Naranjo scores: 9 or 10 indicate "definitely"; 5-8 rate the likelihood as "probable"; 1-4 "possible"; <1 "doubtful"). Breast-feeding was terminated, and filgrastim (Neupogen , Amgen Inc., Thousand Oaks, CA, USA) 5 microg/kg subcutaneously was started. A very slow increase of ANC was seen, and so filgrastim dose was increased to 10 microg/kg subcutaneously, with good improvement. ANC increased to a maximum of 35.85x109/L. Two months after birth, filgrastim was terminated which, initially, led to a decrease of ANC, before it stabilized in the normal range (Figure 2). Two weeks after terminating, the filgrastim a new bone marrow aspiration (Figure 1) and a complete blood count was repeated. Both were normal, which excluded severe congenital neutropenia.

adalimumab, breast-feeding, congenital neutropenia, isoniazid, neonate

PMC7970232_01

Female

A 7-year-old female with no history of neurological or behavioral disease presented to the emergency department for 2 days of transient vertiginous episodes that affected her ability to walk and resulted in vomiting. These episodes lasted only minutes at a time and occurred predominantly in the morning, shortly after waking up. This acute presentation followed a 2-week course of waxing and waning fever with headaches. Prior to presentation at our emergency department, the patient was seen by an outpatient provider for her fever, where a SARS-nCoV-2 nasopharyngeal PCR test was negative. History was significant for multiple exposures, including multiple tick bites over the past month (with at least 1 that lasted >48 hours), freshwater swimming, and both parents with a recent history of fever and headache preceding the onset of the patient's febrile symptoms. This occurred amidst the SARS-nCoV-2 outbreak in the United States. Initial examination in the evening revealed an afebrile patient without lymphadenopathy or rash. Neurological examination was normal, including intact extraocular movements without inducible vertigo or nystagmus, no ataxia or dysmetria, and negative Romberg sign. Both Kernig and Brudzinski maneuvers were normal. Fundoscopic exam did not show swelling of the optic discs. Intake labs demonstrated elevated transaminases with an AST of 141 and ALT of 268, elevated absolute reactive lymphocyte count to 0.1 k/microL, and white blood cell count 8.37 k/microL. Repeat SARS-nCoV-2 PCR testing was negative. Non-contrast CT of the head did not show acute intracranial pathology. The patient was admitted for observation given her history and lab abnormalities. The next morning on repeat neurologic examination, during assessment of gait the patient abruptly sat on the floor with complaints of "dizziness" and described a tumbling rotation of her surroundings. During the episode, fixed gaze elicited conjugate downbeat nystagmus. She then had an episode of emesis, and her symptoms spontaneously resolved over the next half hour. Our differential for new onset episodic downbeat nystagmus included central processes affecting the cerebellum and brainstem including structural disturbances (such as space occupying lesions, cervicomedullary malformations, cerebellar degeneration, and episodic ataxias), infectious and/or toxic encephalitides, and cerebellar stroke. The history of outdoor activities and prolonged tick exposure raised suspicion for locally endemic arthropod-borne encephalitis. Subsequent work-up included magnetic resonance imaging with and without contrast, magnetic resonance angiography, and cerebrospinal fluid analysis with cytopathology and infectious work-up. Contrast-enhanced magnetic resonance imaging of the brain revealed diffuse leptomeningeal enhancement and parenchymal enhancement affecting the inferior cerebellar folia (Figure 1). Same-day cerebrospinal fluid studies (collected following imaging) demonstrated elevated protein, but otherwise had a negative PCR panel for common causes of meningoencephalitis (not including Epstein-Barr virus) (Table 1). As the patient was afebrile and clinically improving without further episodes, she was discharged on an empiric short course of doxycycline with cerebrospinal and serum antibodies pending (Table 1). Cerebrospinal fluid cytopathology showed lymphocytic pleocytosis and results of infectious work-up found serum Epstein-Barr virus IgM and IgG positivity (Table 1), confirming the diagnosis of Epstein-Barr virus meningitis. The doxycycline was discontinued, and the patient had resolution of her symptoms without other treatments.

mri, cerebellum, children, encephalitis, meningitis, neuroimaging, pediatric

PMC5335783_01

Female

A 20-year-old woman presented to the medicine outpatient department with complaints of chronic cough with sputum of a two-month duration and with a history of significant weight loss of 6 kilogram over 6 months. She also had low grade fever of the same duration. Pain in the left hypochondrium was present for 15 days which was also accompanied by abdominal distension. There was a positive family history of pulmonary tuberculosis in the mother who had been adequately treated 4 years earlier. On physical examination the patient appeared pale and her weight was below the 3rd percentile on the CDC growth chart. A chest examination revealed dullness on percussion and decreased vocal fremitus over the infra-scapular region on both sides and lower lateral chest wall with a diminished air entry on the left side. The abdomen was tender on palpation in the left hypochondrium with mild splenomegaly. The routine blood investigations revealed anaemia, haemoglobin of 8.5 gm/dl (normal range 13-18 gm/dl). The total white blood cell (WBC) counts were within normal limits with a relative lymphocytosis (WBC-5800/mm3 with 52% neutrophils and 48% lymphocytes). The platelet count was 250x103/micro-litre (150x103 to 450x103 per micro-litre of blood) and ESR was elevated to 86 mm in the first hour (normal range is 0-22 mm/hr for men and 0-29 mm/hr for women). The liver function tests were mildly elevated. The total bilirubin was 2 mumol/L (normal level 0.2-0.8 mumol/L) with indirect bilirubin of 1.2 mumol/L and direct bilirubin of 0.8 mumol/L. The serum aspartate amino transferase (AST) was 150 units/L and the alanine amino transferase (ALT) level was 84 units/litre (normal range of AST is 10-40 units/L and of ALT is 10-55units/L). Her chest radiograph demonstrated miliary opacities with a left pleural effusion. The sputum examination was positive for acid fast bacilli confirming pulmonary tuberculosis. The patient was started on anti-tubercular (ATT) treatment. The drugs that were given during the intensive phase of 2 months were isoniazid, rifampicin, ethambutol and pyrazinamide in a standard dose regimen, with a possible subsequent continuation of ATT depending on the patient's response. An abdominal ultrasound (USG) was performed because of the abdominal complaints and it revealed hepato-splenomegaly with multiple small hypoechoic nodules that were scattered throughout the liver and spleen as well as a left-sided pleural effusion. Ascites was noticed in the Morison's pouch, pelvis and the inter-bowel region. The splenic vein had an increased calibre of 1.2cm with a vague hyperechogenicity within it, and demonstrated turbulent flow suggestive of splenic vein thrombosis. The portal vein was normal in calibre (1.2 cm) and showed a monophasic hepatopetal flow. CECT of the thorax and the abdomen was performed to assess the burden of the disease in the chest and also to evaluate the splenic vein. Eighty ml of 350 mg% Omnipaque was used to perform the CECT examination after a delay of 35 seconds, from the root of the neck down to the iliac crest. CECT revealed a left pleural effusion with miliary nodules scattered throughout both lungs along with necrotic mediastinal lymph nodes (Figure 1A, 1B) CT confirmed hepato-splenomegaly with multiple non-enhancing hypodense lesions suggestive of granulomas, as shown in Figure 2. In addition, a 1x1 cm wedge-shaped area was seen with the base abutting the lateral border of the spleen, suggestive of a small infarct, as shown in Figure 3. A partial linear filling defect was seen in the splenic vein which confirmed the presence of a partial thrombus, as shown in Figure 4A, 4B. There was no thrombus in the portal vein or in any of the porto-systemic collaterals. There were sub-centimetre lymph nodes in the omentum, porto-caval region and mesentery. The presence of partial splenic vein thrombosis warranted a work-up for a hypercoagulable state in the patient. The fibrinogen level was elevated to 17.64 mumol/L (normal 4.41-13.23 mumol/L). Prothrombin time was prolonged to 20 seconds (normal range 11-13.5 seconds), the INR was 1.7 (normal range is 0.8-1.1in people who are not on anticoagulant therapy). The levels of protein C, protein S, anti-phospholipid antibodies, anti-thrombin III, factor V Leiden mutation were all normal. Low Molecular Weight Heparin (LMWH) was instituted and the patient was kept under close ultrasound and Doppler follow-up. The thrombus was seen to resolve in 5 weeks.

splenic vein, tuberculosis, venous thrombosis

PMC5269417_01

Female

A 35-year-old woman competing in Tricycle Class T2 (e.g. UCI Para-cycling Classification Guide) with hemiplegia of the left limb induced by transversal myelitis treated with fludrocortisone, pregabalin and codeine consulted our services because of a history of exercise-induced headache, dizziness and syncope subsequent to a concussion caused by a bicycle fall in 2012. While still symptomatic from this first concussion suffered in 2012, the patient experienced worsening of symptoms consecutive to a subsequent fall caused by a loss of consciousness at the end of a strenuous bout of exercise in a competition in August 2014. At the time of the consultation, she reported headaches, neck pain, dizziness, tonic-clonic movements post-high intensity exercise, balance problems, difficulties concentrating and memory problems for more than 1 month following mTBI, which is consistent with the World Health Organisation (ICD-10) definition of PCS. Rest and gradual return to activity was therefore recommended as proposed by major guidelines of sport-related concussion management, and was treated by an interdisciplinary team specialized in the management of patients with mTBI (Giza et al. 2013; Harmon et al. 2013; Mccrory et al. 2013; Ontario Neurotrauma Fondation, 2013, Marshall et al. 2015). Five months later, after being asymptomatic at rest and returned to normal activities and function (work/submaximal exercise training), she attempted an incremental exercise protocol at the Institut Universitaire de Cardiologie et de Pneumologie de Quebec (IUCPQ), aiming at identifying the cause of effort-related syncope. The patient was requested to be well rested, be fasting, well hydrated, abstain from caffeinated beverages or stimulants and alcohol for 2 h prior to the assessment as well as refrained from strenuous exercise for 24 h. The patient performed a stepwise incremental upright cycling protocol carried out on a LeMond Revolution training device equipped with the WattBox system. Intensity was gradually increased every 2 min for the first 4 levels (from 30 to 56 W) and then every minute (from 65 to 220 W) up to exhaustion. Breath-by-breath pulmonary gas exchange was monitored using an automated gaz analyzer (Ultima , CardiO2 gas exchange analysis system; MGC Diagnostics , MN, USA) with the athlete breathing through a mouthpiece attached to a pneumotachometer, for determination of oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange ratio (RER: VCO2/VO2), ventilation and end-tidal partial pressure of carbon dioxide (PETCO2). Maximal exercise values were defined as the highest 60-s averaged values. Middle cerebral artery mean blood flow velocity (MCAvmean) was monitored by transcranial Doppler ultrasound (TCD) (Doppler Box; Compumedics DWL USA, Inc. San Juan Capistrano, CA), through the left temporal window as described by Willie et al. (2011a). Near-infrared spectroscopy (NIRS) was used to measure left frontal cerebral oxygenation (ScO2) (Oxiplex TS; ISS, Champlain, IL, USA). ScO2 was calculated by the ratio of oxygenated hemoglobin (HbO2) on total hemoglobin [HbO2 + deoxygenated hemoglobin (HHb)]: HbO2/(HbO2 + HHb) x 100. Heart rate (HR) was continuously monitored by a 12-lead electrocardiogram (ECG) and blood pressure taken manually every 2 min using a sphygmomanometer. Steady-state baseline data were monitored at rest in test position for 3 min. Data (MCAvmean and ScO2) were sampled at 1 kHz using an analog-to-digital converter (Powerlab 16/35; ADInstruments), and time-aligned with breath-by-breath measurements, for offline analyses. Data were then averaged over 60 sec up to maximal exercise. MCAvmean increased by 20% and did not return to baseline values notwithstanding the presence of hyperventilation-induced hypocapnia at higher exercise intensities (Fig. 1). Despite this increase in cerebral perfusion, ScO2 lowered by 18% during the last 5 min of the exercise protocol (>10% decrease in the last 2 min). The athlete reported headache during the last stages of the exercise protocol. Cardiorespiratory variables reached at maximal voluntary exercise are presented in Table 1. At test cessation, the patient lost consciousness and experienced a succession of convulsion-awakening periods with tonic-clonic movements. She was therefore transferred to the emergency room of the IUCPQ, where she was monitored on electroencephalogram, which remained normal. Thereafter, she was transferred to a specialized affiliate hospital in the field of neurology. A thorough investigation included electroencephalography, two lumbar punctures, as well as computed tomography cerebral angiography and cerebral magnetic resonance studies. At the end of the investigation, the final diagnosis was nonepileptic seizure.

cerebral oxygenation, cerebral perfusion, exercise, postconcussion syndrome

PMC6087580_01

Male

A 45-year-old male sustained a traumatic work-related patellar tendon rupture from the inferior pole of the patella while exiting a vehicle. The patient had a past medical history of diabetes mellitus type II. The patient was evaluated within 22 days of his injury and initially treated with primary repair 81 days after the injury. The tendon was repaired with two number 2 nonabsorbable sutures in a Krackow suture configuration throughout the length of the patellar tendon and anchored through bone tunnels in the patella. This patellar height was corrected to an Insall-Salvati Index (ISI) and Caton-Deschamps Index (CDI) of 1.23 and 1.14 (Figure 1) from 1.4 and 1.34, respectively (Figure 2). His knee was immobilized in a locking brace for two weeks, and then physical therapy was initiated for range of motion at two weeks postoperatively. The patient progressed slowly through physical therapy gaining 100 degrees of active leg flexion but developed significant quadriceps atrophy, patella alta, and 10 degrees of an extensor lag at 7 months following the procedure. The patient was compliant with the standard rehabilitation protocol and had no history of traumatic reinjury. Eleven months after the primary procedure, the patient was referred to our clinic for persistent pain, pain with squatting and kneeling, instability, and stagnation in functional recovery which prevented him from returning to work up to this point. Subjectively, he reported a 4/10 pain level at rest. Clinical examination revealed proximal migration of the patella, 2+ coarse patellar crepitus, full active range of motion, 3+/5 quadriceps strength, and a 10-degree lag with single leg raise. T2-weighted MRI and lateral knee radiograph at 11-month follow-up confirmed patella alta deformity (CDI = 1.51, ISI = 1.55), an intact albeit lax patellar tendon, and cartilage fissuring near the inferior patellar apex (Figure 3). There was no additional ligamentous injury noted on MRI. His preoperative patient-reported outcome scores can be found in Table 1. A collective decision was made with the patient at this time to proceed with revision patellar tendon repair with the goal of returning to work at some capacity and resuming his normal activities of daily living. The previous midline incision was dissected to visualize and confirm obvious redundancy and thinning of the patellar tendon. A 2 x 4 x 1 cm rectangular block of redundant patellar tendon tissue was outlined and resected to correct the degree of patella alta. The patella was mobilized using blunt dissection. The suture material from the index repair was removed, and the distal patellar footprint was prepared. Two 2.5 PEEK corkscrew anchors (Arthrex, Naples, FL) were anchored 2 cm apart on the distal patellar footprint. Krackow sutures were passed through the midsubstance of the patellar tendon, and with the opposite limb of each stitch, a half hitch was made such that a pulley mechanism was created (Figure 4). The tendon was reapproximated, and final fixation was secured with four mattress anchor knots with five alternating half hitches. The knee was brought to 30 degrees of flexion and the construct was stable. The wound was closed with a standard layered closure. Postoperative lateral knee radiograph displayed a CDI of 1.09 and an ISI of 1.16 (Figure 5), which confirmed that patella alta had been corrected. At 18-month follow-up, the patient had a repeat MRI performed which demonstrated a CDI of 1.35 (Figure 6). Following the operation, a locked extension brace was applied for full-time use, and he began physical therapy two weeks postoperatively. The patient was compliant with his rehabilitation protocol and did not suffer any setbacks in the postoperative period. At his 1-year follow-up examination, the patient did not appear in acute distress, had no joint effusion, did not have patellar apprehension, demonstrated a nonantalgic gait, showed full active range of motion with no lag (Figure 7), displayed a negative Clarke exam, and had 4/5 quadriceps strength. In addition, the patient had 5 mm of anterior translation bilaterally on KT-1000 arthrometry testing and 20.6 pounds of force on maximal muscle testing of leg extension on the right compared to 21.3 pounds on the left as measured by a handheld dynamometer. The patient reported a pain level of 2/10 with activity, which was a decrease from his preoperative pain level (4/10). He reported occasional use of Tylenol for pain. His PRO scores at 1-year follow-up can be found in Table 1. Despite a relatively benign physical exam (Figure 7) and subjective reporting of satisfaction with the revision procedure and his outcome, the patient reported moderate functional limitations. Permanent work-duty restrictions were subsequently outlined as a functional capacity examination, and patient reported outcomes did not permit return to his full occupational capacity.

PMC5338911_01

Female

A 25 Year old woman, with no premorbid illnesses presented with a history of cough during eating for 3 months duration and mucoid,non blood tinged sputum production for 1 month. She reported an 8 kg weight loss. There was no history of shortness of breath,chestpain,vomiting or choking. There was also no history of foreign body aspiration, ingestion of toxic or corrosive substances or any surgical procedures in past. Her younger sister was detected to have pulmonary tuberculosis 1 yr back and completed antituberculous treatment. She was not evaluated for Tuberculosis at the time of her sister's diagnosis. She had been married for 9 months, had regular menstrual cycles and no history of high risk behaviour. On examination she exhibited mild pallor. There was no icterus, cyanosis, clubbing or lymph node enlargement. Pulse rate - 86/min, regular; Blood pressure - 110/70 mmHg; respiratory rate - 16/min; and she was afebrile. Cardiovascular,respiratory,gastrointestinal,nervous system examination were within normal limits. Investigations showed WBC 11,200/cmm, with 64% neutrophils and 31% lymphocytes, Hgb - 10 g/dL, platelet count 230,000/cmm and ESR was 55 mm/h. Renal and liver function tests were within normal limits.Retroviral screening and autoimmune markers were negative.Sputum AFB was negative.Tuberculin skin test showed an induration measuring 15 x 15 mm. Barium swallow showed a fistulous communication between esophagus and bronchial tree (Fig. 1). Esophagoscopy was performed which revealed a 30 mm ulcer with irregular borders with communication into respiratory tract, 25 cm from the oral cavity. Computed tomography scan of thorax with three dimensional reconstruction was done which showed mediastinal lymphadenopathy, with erosion of posterior wall of left main bronchus, with a fistulous tract into anterolateral wall of esophagus (Fig. 2A-C). There was also centrilobular nodules in bilateral lung parenchyma with tree in bud appearance. Bronchoscopy revealed inflamed mucosa which revealed granulomatous inflammation on biopsy.AFB staining of bronchial secretions was negative,but tested positive for M.tuberculosis by PCR. Cultures done on bronchial secretions showed growth of M. tuberculosis. She was started on antituberculous treatment modified according to weight and nasogastric feeding started. Treatment comprised of an intensive phase for the first two months in which four antituberculous drugs (Isoniazid, Rifampicin, Pyrazinamide, Ethambutol) were given. This was followed by a continuation phase for next four months consisting of two drugs (Isoniazid and Rifampicin). Bronchoscopy was done after completing 4 months of treatment and showed normal bronchial lumen with disappearance of fistulous tract.Computed tomography of thorax showed resolution of lung lesions without any fistula. She completed 6 months of antituberculous treatment and remains asymptomatic till date.

bronchoesophageal fistula, tuberculosis

PMC3905907_01

Female

A 72-year-old female was referred to our hospital after having experienced fever and abdominal pain for 5 days and a skin rash for 3 days before admission. She also complained of polyarthralgia, predominantly on her distal extremities. At admission, her body temperature was 38.8 C and she had a skin rash composed of exudative maculopapules and erythema multiforme over most of her body. Based on a consultation with a dermatologist who made a tentative diagnosis, we suspended loxoprofen and famotidine, medications she had been taking, because of the suspicion that the eruptions may have been drug-induced. Concomitantly, she received antibiotic therapy (meropenem) under adequate hydration, and underwent repeated blood and stool cultures. Laboratory data showed systemic inflammatory response represented by an increased WBC, 7380/muL, and moderately elevated CRP, 7.74 mg/dL. Her computed tomography (CT) scan demonstrated thickening of mucosa and enlarged mesenteric lymph nodes (Figure 1). A colonoscopy examination showed a round mucosal elevation with hemorrhagic erosion and ulceration at the terminal ileum and cecum (Figure 2), for which the pathological finding was suspicious malignant lymphoma with an infiltration of atypical lymphocytes into necrotic mucosa (Figure 3). Immunohistochemistry determined CD3+ T-cell distribution in the submucosal tissue, but did not confirm clonality of lymphocytes. Based on the pathology results, we performed an 18-fluoro-deoxyglucose positron emission tomography (FDG-PET)/CT scan, which drew an accumulation of FDG isotopes into regional mesenteric lymph nodes (SUV max 2.6). In addition, an increased level of soluble interleukin-2 receptor (sIL-2R), 3095 IU/mL, and an expansion of a lymphocyte subset expressing gammadelta T-cell receptor in peripheral blood and bone marrow (10.9% and 3.9%, respectively) supported the diagnosis of malignant lymphoma. These results led to a tentative diagnosis of enteropathy-associated T-cell lymphoma (EATL, or gammadeltaT-cell lymphoma). The patient's febrile and abdominal symptoms ameliorated rapidly a few days after antibiotics were initiated, and her skin eruptions improved over the following 7 days. Since we could not obtain a confirmation of the pathological diagnosis, we reevaluated all aberrant clinical findings after the remission of the patient's symptoms. Within the 2-week treatment course, her laboratory data recovered to normal ranges. The sIL-2R level decreased to 483 IU/mL, and gammadelta T cells in peripheral blood were almost nonexistent (0.04%). A CT scan and colonoscopy conducted a few weeks after onset revealed slight swelling of the mesenteric lymph nodes and completely normal mucosa. During the second evaluation of the tentative diagnosis, Yersinia pseudotuberculosis was identified from her stool culture at admission. In light of all of the findings, we made the final diagnosis of Yersinia enterocolitis.

PMC6369518_01

Female

The patient was born full term at 40 weeks via normal spontaneous vaginal delivery to a 32-year old mother and 33-year old father. There were no perinatal complications and the Apgar scores were 4 and 9 at 5 and 10 minutes of life, respectively. She was small for gestational age with a birth weight of 5 lbs. 2 oz. at the 5th percentile and birth length of 18.5 inches between the 5th and 10th percentile. The patient was noted as having dysmorphic features including hypertelorism, low-set ears, epicanthal folds and a flat nasal bridge. During her first year of life she was diagnosed with failure to thrive, including a progressive deceleration in growth rate and global developmental delay. At 14 months of age, her facial dysmorphism, poor growth and developmental delay prompted additional evaluation including a karyotype that revealed tetrasomy X (Figure 1A). The parents' karyotypes were normal. A SNP array was also performed to evaluate the characteristics of the extra X chromosomes (Figure 1B). Her laboratory evaluation was remarkable for a low IGF-1 of 37ng/mL (reference range 49-342 ng/mL) and her bone age was delayed (1 month at chronological age of 17 months (Figure 2A). She also underwent a brain and pituitary MRI which showed delayed demyelination and an 8 x 4 x 13 mm cystic lesion in the sella turcica, indicating a Rathke's cleft cyst (Figure 2B). With progressively declining growth rate, a low IGF-1 and a Rathke's cleft cyst in the pituitary gland, growth hormone deficiency was strongly suspected, although this could not be confirmed via the growth hormone stimulation test due to difficulties in securing vascular access. Therefore, under clinical suspicion, she was diagnosed with growth hormone deficiency and at 21 months of age she started treatment requiring a low dose of growth hormone (0.13 mg/kg/week), to which she responded with improvement in IGF-1 and growth velocity, as is typical in this management of growth hormone deficiency (Figure 3A). At the time, her thyroid function tests and cortisol peak of 35.1 ug/dL after the standard 250 mcg ACTH stimulation test were appropriately within normal range. Serial MRIs performed over the years showed no change in the size of the cyst (Figure 2C). At her 8 years and 8 months follow-up visit, she again presented with height deceleration. On further evaluation, diurnal TSH showed a peak increment TSH of 41%, suggesting central hypothyroidism (normal increment >48%). Her ACTH stimulation test showed a peak cortisol of 13.9 mcg/dL at 60 minutes, indicating partial adrenal insufficiency. A physiologic dose of hydrocortisone and of levothyroxine replacement were initiated and her growth improved accordingly (Figure 3B). At age 8, she was prescribed aripiprazole for behavioral outbursts and subsequently had significant weight gain, her BMI percentile increasing from 50th to 85th. The patient had minimal breast development in addition to lipomastia at age 8 years, which was thought to be secondary to peripheral conversion of estrogen from extra adipose tissue: her breasts gradually regressed with dietary control. Her estradiol level was below detection limits. She restarted breast development at age 10 and reached Tanner 3 at age 11 years and 9 months. At that time, she developed an episode of vaginal bleeding which lasted 5 days but did not recur. Her LH was 5.9 U/L, FSH was 2.6 U/L and estradiol was 31.6 pg/mL (Table 1).

PMC10130361_01

Male

The patient was a 50-year-old man. The patient's father passed away due to tuberculosis and respiratory failure, while his mother remains in good health. The patient has two sisters and a half-brother, all of whom are healthy. At present, the patient does not have any children. He presented with chest tightness, chest and back pain, cough, blood in the sputum, and hypodynamia. The patient had a smoking history of 20 years before developing lung disease. Before the development of the disease, the patient had good health and no reported history of occupational exposure or genetic predisposition within the family. Contrast-enhanced computed tomography (CT) examination of the chest at presentation showed an upper left lung mass shadow (10.7 cm x 8.5 cm x 10.5 cm). The margin was poorly demarcated from the mediastinal pleura comprising multiple flaky low-density necrotic areas. The CT value ranged from 19 to 33 Hu. Whole-body positron emission tomography (PET)-CT scan revealed a mass hypermetabolic lesion in the upper left lung (SUV 8.5) and was considered upper left lung cancer. The lesion was infiltrated along the adjacent bronchial and pleural. And it was intricately related to the aortic arch with peripheral obstructive inflammation. Mild hypermetabolism (SUV 3.0) of left hilar and mediastinal lymph nodes (groups 5 and 6) reflected lymph node metastasis. No metastases were seen elsewhere throughout the body. Blood tumor markers (CEA, NSE, and CYFRA21-1) were normal. Examination of fine-needle aspiration biopsy of the lesion via CT revealed that tumor cells were spindle-shaped or oval, with diffuse infiltrative growth, necrosis of a small number of cartilage components, and loose interstitium. The tumor tissue consisted of both epithelial and mesenchymal tissues, with the epithelial component exhibiting features of low-grade adenocarcinoma. The mesenchymal component, on the other hand, exhibited characteristics of sarcoma with cartilage metaplasia, as illustrated in Figure 1 . This was consistent with the diagnosis of PB. Immunohistochemistry revealed epithelial components: CK (+), TTF1 (+), CEA (-), CK7 focal (+), CK5/6 focal (+), S-100 focal (+), EMA focal (+); mesenchymal components: Vim (+), S-100 focal (+), Des small (+), CD99 individual (+), CD34 vascular (+), MC (-), Napsin A (-), and Ki-67 (30% +) ( Figure 2 ). Due to the limited tissue sample available, certain immunotherapy predictors, including PD-L1, tumor mutation burden (TMB), and microsatellite stability (MSS), were not evaluated. The diagnosis was classic biphasic PB, and the clinical tumor stage was cT4N2M0 IIIB. The tumor could not be resected because the patient's tumor was closely related to the aortic arch. Therefore, the multiple disciplinary teams (MDTs) believed that radical surgery could be performed. The first-line chemotherapy regimen included paclitaxel 175 mg/m2 (day 1) + cisplatin 25 mg/m2 (day 1-day 3), with a total of four cycles. Chest radiotherapy was given one month after chemotherapy at a dose of 75 Gy/35f, and efficacy was assessed as partial response (PR) after sequential chemoradiotherapy. Follow-up was repeated every three months following the first-line treatment, and PFS was 12.3 months. The patient reported worsening chest pain, with the chest CT showing that the lesion was progressing. The left upper lung lesion was markedly enlarged, and solid changes appeared. The patient experienced difficulty falling asleep due to chest pain, requiring Oxycodone Hydrochloride Controlled-release Tablets at a dosage of 360 mg q12 h to achieve a Numerical Rating Scale (NRS) score below 3. This pain level significantly impacted the patient's ability to work and carry out daily activities. As a distinct subtype of NSCLC, classical biphasic PB (CBPB) poses challenges for second-line chemotherapy alone, and no known driver gene mutation is currently suitable for targeted therapy in this condition. Previous reports have demonstrated that PD-L1 expression was observed in roughly 12% of PPB patients. Furthermore, case studies have identified high PD-L1 expression in patients with CBPB. As such, the combination of chemotherapy and ICIs was considered a potential treatment approach. The treatment was changed to gemcitabine 1250 mg/m2 (d1, 8) and sintilimab 200 mg (d1). After one cycle of treatment, the patient developed third-degree neutropenia, a second-degree rash, and anorexia; we attributed these side effects to gemcitabine. Gemcitabine chemotherapy was discontinued at the patient's insistence, and only sintilimab immunomonotherapy was administered. Over time, the patient's chest pain gradually subsided, and they were able to resume daily activities. The dosage of Oxycodone Hydrochloride Controlled-release Tablets was consequently reduced to 80 mg q12 h. No significant adverse effects were observed during this treatment period. Based on imaging evaluations, the patient's disease state remained stable, classified as stable disease (SD) (see Figure 3 ). The patient is currently receiving sintilimab for 27 months. His condition was stable, with a performance status (PS) score of 1. The patient has been alive for nearly 40 months and has a good quality of life.

pd-1/pd-l1 axis, checkpoint inhibition, immunotherapy, pulmonary blastoma, sintilimab

PMC9270248_01

Male

A 52-year-old male presented to the emergency department with complaints of back pain that started after approximately one hour of heavy lifting. He stated that the pain was located in his lower back, characterized it as dull, and specified that it did not radiate. The back pain was said to have had an insidious onset and progressively worsened. The patient denied noticing any aggravating or relieving factors, as well as having similar pain in the past. He had not experienced any trauma to the affected area prior to the onset of symptoms, nor did he have a history of associated fever, numbness, tingling, weakness of his extremities, constipation, or urine retention. Additionally, he complained of chest pain that started roughly the same time as the back pain. Although, he endorsed previously experiencing the same type of chest pain recurrently for several months. The chest pain was described as sharp, pleuritic in nature, moderate severity, and had no known relieving factors. He denied chest pain with exertion, cough, sputum production, and shortness of breath. The patient's past medical history was notable for hypertension, schizophrenia, hepatitis C, questionable COPD/asthma, and alcohol abuse. He had a 30 pack-year smoking history and was still smoking at the time of presentation. His medications included amlodipine, hydrochlorothiazide, lisinopril, and naproxen for pain, and he had no known drug allergies. He was unemployed at the time of presentation but had worked as a mechanic previously. His diet consisted mainly of well-cooked meats, potatoes, and beans. Notably, the patient had no history of eating raw fish or fishing. Physical examination at time of arrival was significant for low grade fever and tachycardia. No obvious neurological deficits were appreciated. Laboratory tests collected included a complete blood count, a comprehensive metabolic panel, and blood cultures. A computerized tomography (CT) scan of the lumbar spine was obtained and revealed an L3-L5 epidural abscess with L5-S1 discitis. A CT scan of the thorax showed a right upper lobe pulmonary nodule measuring 4.2 x 3.2 cm. This nodule was seen a year earlier and measured about 1.7 x 0.9 cm, but the patient had elected against further surveillance/workup at that time. Other, less characterized, findings on the CT scan included a small liver nodule and a small mass in the pancreatic head (imaging not published per patient's family request). General serum tests including blood cultures, inflammatory markers, complete blood count, and metabolic profile were collected. They were significant for elevated values of ESR (78 mm/h), CRP (33 mg/dl), and white blood count (17.1 x 10[9]/L). Overnight, the two sets of blood cultures grew with 4 of 4 bottles showing Enterococcus species. Subsequently, the patient was started on intravenous (IV) vancomycin, and L3-L5 hemi-laminectomies were performed for evacuation of the abscess and culture of aspirate. An acid-fast bacillus concentration and smear with mycobacterium tuberculosis by polymerase chain reaction (PCR) came back negative. The remaining laboratory results were unremarkable. Over the next 2 days, blood cultures further speciated to L. Garvieae (identified by MALDI-TOF). In addition, the epidural abscess culture also grew L. garvieae, likely from hematologic seeding. Susceptibility testing showed it was susceptible to penicillin (MIC 0.8 mug/ml), ceftriaxone (MIC 0.6 mug/ml), vancomycin (MIC 0.8 mug/ml) and levofloxacin (MIC 2.2 mug/ml). The patient's antibiotic regimen was then switched to IV ceftriaxone and azithromycin and repeat blood cultures returned no growth. A transthoracic echocardiogram was obtained and was negative for any vegetation. In view of the spinal involvement, the patient was prescribed a total of 6 weeks of antibiotics to be completed outpatient as recommended by the infectious disease team. CT guided biopsy of the lung nodule was also performed, and pathology results showed invasive adenocarcinoma of the lung. Upon discharge, the patient was scheduled for a PET scan with further treatment recommendations to be provided based on imaging results. In view of the L. garvieae bacteremia, an outpatient colonoscopy was scheduled to rule out colon cancer, as the patient had never been scoped, and the organism had been reported in numerous patients with occult colon cancer. However, shortly after being discharged to complete antibiotics outpatient, the patient unfortunately and unexpectedly passed away from unrelated causes before further workup could be obtained.

adenocarcinoma, cancer, garvieae, lactococcus, raw fish

PMC6664517_01

Male

A 20-year-old male was transferred to our tertiary level one trauma center from an outlying community-based hospital following a noncontact basketball injury. Earlier that evening, the patient had been playing basketball at a local church when he jumped for a rebound and experienced severe pain in the left hip and thigh upon landing. He was unable to bear weight. At that time, he was taken to a local emergency department where he underwent immediate evaluation. Following the initial evaluation and review of radiographs, it was determined that the patient had sustained a subtrochanteric periprosthetic femur fracture. At that time, he was transferred to our facility for definitive management. After further investigation and questioning upon arrival at our facility, the patient reported a 5-6 month history of increasing left thigh pain prior to this injury. He had never received any medical care for the new onset thigh pain and attributed it to overuse. New radiographs obtained at our facility demonstrated a transverse periprosthetic femur fracture at the distal aspect of the previously placed dynamic hip screw. Nine years prior at the age of 11, the patient had been involved in a motor vehicle accident sustaining a subtrochanteric femur fracture which was addressed with reduction and placement of a dynamic hip screw (DHS). The surgery was noted to be performed flawlessly with no complications noted, but little is known about the details of the postoperative course as it was done at an outside facility. Despite discussions with the index surgeon to eventually remove the hardware, his case was never scheduled and the hardware was retained into skeletal maturity. Close inspection of imaging at the time of repeat injury showed evidence of a potential stress riser at the distal DHS/bone junction, with a significant amount of bony overgrowth of the DHS (Figure 1). Additionally, there was evidence of stress shielding with significant cortical thickening involving the entire lateral cortex seen on radiographs taken prior to injury (Figure 2). The patient was taken to the operating room for explant, fracture reduction, and insertion of a cephalomedullary nail. An extensile approach was necessary to completely expose the retained hardware. Gross intraoperative inspection showed extensive bony overgrowth of the implant (Figure 3). Osteotomies were utilized to remove the bony overgrowth to extract the hardware (Figures 4 and 5). After successful removal of the previous sliding hip screw, the fracture was exposed, reduced, and a long reamed cephalomedullary nail was placed with distal interlocking screws without difficulty (Figures 6(a)-6(c)). Postoperatively, his pain was initially controlled with IV pain medication and he was quickly transitioned to orals only. He was immediately weightbearing as tolerated with the aid of a walker. He progressed quickly with PT, working with them once a day. He was able to walk 120 feet with PT on postoperative day 2 with the use of a walker. He was placed on Lovenox for DVT prophylaxis until he was fully weightbearing using no assistance. He was discharged home on postoperative day #2. He presented to the emergency department two weeks postoperatively complaining of bloody drainage from the incision. The dressing was removed by the ED physician who noted no drainage and was unable to express any blood. The patient was otherwise feeling well. His pain had been controlled, and he denied fevers, chills, nausea, or vomiting. A new dressing was placed and he was discharged home with follow-up with the orthopedic surgeon who performed the case. In outpatient follow-up, the patient continued with Lovenox for DVT prophylaxis as well as physical therapy until he was weightbearing as tolerated without the use of aids. At subsequent postoperative follow-up visits, radiographic imaging revealed complete union of the previous fracture with an abundant amount of bridging callus (Figures 7(a) and 7(b)). The patient reported no other postoperative complications.

PMC8329520_01

Male

A 47-year-old man presented to the clinic with two weeks of headaches, progressive diplopia and right eyelid ptosis. He had no other neurological symptoms and review of systems was negative. He was a 10 pack-year smoker but had no past medical history, prior medication use or allergies. He had no ocular history. His family history was non-contributory. His sexual history was significant for unprotected same-sex intercourse with multiple partners over the past 10 years but no history of sexually transmitted infections. His vision was 20/30 in the right eye and 20/20 in the left. Examination revealed 80 prism diopters of exotropia with significant hypotropia and severe elevation, adduction and depression deficits (no movements from primary position) in the right eye. Abduction and incyclotorsion were preserved. The right pupil was dilated and poorly reactive to light and accommodation. No relative afferent pupillary defect was seen. Examination of the remaining cranial nerves revealed no abnormalities. Anterior segment and fundus examination was normal bilaterally. Neurological examination did not reveal ataxia, tremor or hemiparesis. Right isolated complete pupil-involving ONP was diagnosed. Given the clinical presentation, aneurysmal compression was suspected and urgent brain computed tomography angiography (CTA) was obtained but came back normal. Brain magnetic resonance imaging (MRI) revealed thickening and enhancement of the right oculomotor nerve at the level of the interpeduncular and suprasellar cisterns (Fig. 1). There was no leptomeningeal enhancement nor other cranial nerve enhancement. Complete blood count, glycated hemoglobin, erythrocyte sedimentation rate and C-reactive protein serum levels were normal. Chest radiography did not reveal hilar adenopathy or signs of tuberculosis. The initial treponemal test (Treponema pallidum enzyme immunoassay) was reactive and was confirmed by a positive rapid plasma reagin test (at a 1:16 titer). Testing for human immunodeficiency virus (HIV) and tuberculosis (interferon gamma release assay, IGRA) was negative. Cerebrospinal fluid (CSF) analysis demonstrated elevated protein levels (0.83 g/L, normal: 0.15 - 0.40) and lymphocytic pleocytosis (30 x 106/L, normal: < 5). A Venereal Disease Research Laboratory (VDRL) test performed on the CSF sample was reactive (at a 1:2 titer). Early neurosyphilis was diagnosed. The patient was treated with intravenous penicillin G, 4 million units every four hours administered at-home through a peripherally inserted central catheter for a total duration of 2 weeks. At the completion of treatment, symptomatic improvement was noted but the patient was lost to follow-up before a second ophthalmological assessment could be performed.

cns infections, cranial nerve palsy, neurology, neuroradiology, neurosyphilis, oculomotor nerve palsy, ophthalmology, sexually transmitted infections

PMC10284151_01

Male

A 56-year-old white man with a history of essential hypertension controlled with atenolol received the first ChAdOx1 nCov-19 vaccine in early May 2021. Four days after vaccination, he developed fever, malaise, and persistent headache. On the fifth day following vaccination, he presented with nausea, vomiting, fall from his height, generalized skin rash on the lower limbs, and ecchymosis. He was promptly admitted. His platelet count was 17,000/mm3 (150,000-450,000/mm3), D-dimer 41,000 ng/ml (<500 ng/ml), and fibrinogen 121 mg/dl (200-400 mg/dl). Peripheral smear showed no platelet clumps or schistocytes. Brain computed tomography (CT) examination identified right frontal heterogeneous intraparenchymal hematoma, measuring approximately 6.4 cm x 5.2 cm x 4.8 cm with a thin hypodense halo, causing mass effect with a local reduction in the amplitude of the sulci, compression over the right lateral ventricle resulting in contralateral deviation of midline structures by 0.7 cm, in addition to areas of bilateral frontoparietal subarachnoid hemorrhage. He also presented with a massive ventricular hemorrhage filling in the right lateral ventricle, the posterior horn of the left lateral ventricle, and the fourth ventricle, and bleeding in the right Sylvian cistern and perimesencephalic cistern. There was no evidence of aneurysmal dilatation. The CT angiogram the following day identified thrombosis in the superior sagittal sinus. Also, a lower extremities Doppler ultrasound showed right arterial and venous thrombosis. He underwent urgent neurosurgery for hematoma drainage and decompressive craniectomy. A few hours after the procedure, he developed new bleeding and bilateral cerebral edema and received plasma, cryoprecipitate, fibrinogen concentrate, platelet transfusions, and 70 g (1 g/kg) intravenous immunoglobulin. Despite all measures, the patient died with refractory intracranial hypertension on day 13 after vaccination. Patient's relatives and healthy unvaccinated controls provided written informed consent approved by the local Ethics Committee for clinical and laboratory investigations (CAAE #68118417.6.0000.5248 and #48532621.8.0000.5262, respectively). SARS-CoV-2 RT-PCR of the nasopharyngeal swab and serology to dengue, Chikungunya, Zika, HIV, hepatitis B and C, Cytomegalovirus (CMV), Epstein-Barr virus (EBV), toxoplasmosis, and rubella were negative. Relatives denied any past COVID-19 infection or heparin exposure. There was no personal or family history of thrombosis or miscarriages. IgG anti-PF4 antibodies were detected with a 3.33 optical density (reference <= 0.4). A flow cytometry-based assay to detect platelet-activating antibodies was performed according to Handtke et al. (Figure 1A). When added to healthy donor platelets, patient plasma elicited increased expression of CD62p to a greater extent than plasma from healthy heterologous donors. However, in the presence of high concentrations of heparin, which can destabilize PF4/adenovector aggregates due to its higher affinity to PF4, platelet activation levels were reduced to control levels, confirming the presence of platelet-activating immunocomplexes in the patient's plasma. Elevated plasmatic levels of CD62p, released by activated platelets and endothelial cells, and of tissue factor (TF, coagulation factor III), the primary activator of the extrinsic pathway of the coagulation cascade, corroborate the extensive platelet activation and clot formation (Figures 1B,C). Additional laboratory results are characterized in Table 1. The results of other blood tests were unremarkable except for increased alanine aminotransferase, C-reactive protein, IL-1beta, and caspase-1. Antinuclear antibodies, anti-cardiolipin IgG and IgM, lupus anticoagulant, and beta-2 glycoprotein 1 IgG were not detected. We performed genetic analysis using the Axiom Human Genotyping SARS-CoV-2 Research Array, which genotypes more than 870,000 single-nucleotide polymorphisms (SNPs) in the human genome. The first strategy consisted of screening mutations in 232 autosomal genes essential for thrombotic syndromes, to inflammatory disorders, and related to type I interferon (IFN) signaling (Table 2). Aiming to select rare variants, the minor allele frequency up to 0.01 in European or African populations was settled as a cutoff. Six thousand four hundred sixty-six related SNPs were present in the array, and 5,953 are described in the 1KGP database. From the selected SNPs, 689 and 845 rare putative variants were found in databases of African and European populations, respectively. Among them, 68 were found in heterozygosity in the patient. From these, seven SNPs have been studied in clinical conditions; four were considered benign; one likely benign; one, rs116667976, in the Factor XI gene (F11) with conflicting interpretations of pathogenicity; and the last one, rs2884737, in the VKORC1 gene, associated with Warfarin drug response. A descriptive analysis of the SNPs is depicted in Table 3. In addition to the search for rare variants, a second strategy was employed. We performed a screening of common mutations in the European or African populations that were in homozygosity in the patient. We assessed classical hereditary thrombophilia-associated mutations: Factor V Leiden G1691A (rs6025), Factor II G20210A (rs1799963), and methylenetetrahydrofolate reductase (MTHFR), C677T (rs1801133) and A1298C (rs1801131), in addition to distinct mutations on F11 and genes related to type I IFN. The patient was homozygous for the missense MTHFR variant c.665C > T chr1-11856378 G > A p.Ala222Val NM_005957.5 rs1801133, with clinical relevance for methotrexate drug response, with a general population frequency of approximately 0.3. His medical records from January 2021 and 2008 showed normal levels of folic acid and homocysteine, respectively. Also, he was not on vitamin B12 supplementation or had ever had hemolysis. Furthermore, he was homozygous for the variants in FXI rs2036914 and rs4253405; in TLR3 rs6849187 and rs6857595; in IFNW1 rs7852828; in TBK1/RASSF3 rs1245035 and rs1520765; in TICAM1 rs4807643 and rs8102626; and in IFNAR2 rs2252650. Besides rs2036914, classified as benign, none of these variants have been described as associated with clinical diseases (Table 3 in gray).

chadox1 ncov-19 vaccine, vitt, anti-pf4 antibodies, genetic predisposition, polymorphisms, vaccine-induced thrombotic thrombocytopenia

PMC9592748_01

Unknown

In late February 2022, a wave of SARS-CoV-2 infection rapidly appeared in Shanghai as of May 4, 2022, and 601,942 patients were diagnosed with SARS-CoV-2 infections, including 503 deaths. All the new viral genomes in Shanghai were clustered into the SARS-CoV-2 BA.2.2 sublineage. Patients under 18 years old, including several patients with congenital heart disease (CHD), were admitted to the quarantine ward in Shanghai Children's Medical Center affiliated with Shanghai Jiaotong University School of Medicine during this outbreak in Shanghai. To the authors' knowledge, there have been no reports of Omicron variant infections among the pediatric CHD population. We presented the first single-center case series study of the clinical features of CHD children with Omicron infections.

omicron, children, congenital heart disease, coronavirus, infectious disease

PMC9640602_01

Male

The patient is an 80-year-old male, height: 166 cm, weight: 57 kg, nationality: Han nationality, occupation: freelancer. He was admitted to the hospital because of "progressive dysuria for more than 10 years, aggravating for more than 1 month." About 10 years ago, the patient developed progressive dysuria without obvious incentives, such as waiting for urination, labored urination, thinning of the urination line, and incomplete urination. In 2015, he underwent transurethral resection of the prostate in our hospital and was discharged after his condition improved. About a month ago, the above symptoms aggravated, and the effect of oral "anti-inflammatory drugs" at home was not obvious. Now the patient came to our hospital for further diagnosis and treatment. After the outpatient examination, he was admitted to the Urology Department of our hospital with "prostatic hyperplasia and cystitis." Since the onset of the disease, the patient has had no chills, no fever, normal diet and sleep, normal bowel movements, normal urination as described above, and no significant change in weight. The patient's previous physical condition was good. In 1970, the patient underwent subtotal gastrectomy for "peptic ulcer," and the postoperative recovery was satisfactory. In 2015, the patient underwent transurethral resection of the prostate due to benign prostatic hyperplasia, and the postoperative recovery was satisfactory. The patient denied the history of hypertension, diabetes, coronary heart disease, viral hepatitis, tuberculosis infectious disease and close contact, denied any history of major trauma or blood transfusion and denied any history of drug or food allergies. Vaccination history unknown. Parents are not consanguineous, deny family history of disease and similar medical history. The patient is in fair general condition, temperature: 36 C, pulse: 67 beats/min, respiration: 18 breaths/min, blood pressure: 169/97 mmHg. Abdomen is flat, no varices or scarring of the abdominal wall, no gastrointestinal pattern or peristaltic waves, soft to palpation, no pressure or rebound pain in the abdomen, liver and spleen are not palpable under the ribs, no percussion pain in the liver or kidney area, negative mobile turbid sounds, normal bowel sounds, no significant abnormalities in the bladder area. Rectal palpation: enlarged prostate, about 5*5*6 cm, tough, no hard nodules, no pressure pain, superficial central sulcus. Ancillary examination: PSA assay: TPSA: 1.91 ng/ml, FPSA: 0.56 ng/ml. urine routine: BACT-M: 879/ul, WBC: 98.0/ul, BC: 2 +, BLD: 1 +, PRO: 4 +, NIT: 1 +, no abnormalities in the rest of the indicators. Coagulation analysis + D-dimer assay: DD: 0.63 mg/L, the remaining indicators were not abnormal. Liver function + cardiac enzyme assay: TP: 60.1 g/L, ALB: 34.9 g/L, CKMB: 33.2 U/L, no abnormalities in the remaining indicators. Urine culture + colony count: no bacterial growth in urine culture of the middle urine. Urology ultrasound shows prostate size is about 5*5*6 cm, the volume of diverticular urine was about 184 ml and the volume of residual urine in the bladder was about 125 ml. CT scan of the kidney and ureter and bladder + enhanced CT of the lower abdomen showed that the bladder was full, multiple stones were seen in the bladder, the larger one was about 2.7*3.6 cm; the bladder wall was thickened and strengthened, and multiple cystic pouch shadows were seen in part of the bladder wall protruding outwards with clear borders, the larger one was about 10.5*6.5 cm in size. The larger one is about 10.5*6.5 cm in size and contains stones. The prostate was enlarged and multiple foci of calcification were seen (Figure 2A). Diagnostic imaging: (1) bladder stones, cystitis and multiple diverticula formation. (2) prostatic hyperplasia and calcification. Cardiac ultrasound and cardiac function measurements: degenerative aortic lesion with a small amount of regurgitation, calcification of the posterior mitral leaflet annulus with a small amount of regurgitation, a small amount of tricuspid regurgitation, and left ventricular hypo-diastolic function. Pulmonary mediastinal CT scan: (1) multiple foci of fibrosis and microscopic sclerotic foci in the lungs, (2) double pulmonary emphysema, (3) calcification of the aortic and coronary artery walls. Pulmonary function measurements: normal ventilation, mildly reduced small airway function, normal ventilation reserve function. Electrocardiogram suggests: sinus rhythm; high voltage on the left ventricular surface and ST-T changes. Ultrasound of the liver, gallbladder, spleen and kidney: no significant abnormalities on ultrasound of the liver, gallbladder, spleen and kidney. Combining the patient's history, physical examination and ancillary examination, the initial diagnosis was: (i) prostatic hyperplasia; (ii) cystitis; (iii) bladder stones; (iv) bladder diverticulum; (v) bladder diverticulum stones; (vi) emphysema; (vii) post-gastrectomy for most of the stomach. The diagnosis of this patient is relatively easy, with typical clinical symptoms and imaging examinations. It should be noted that the clinical symptoms of bladder diverticula are generally not obvious. Larger bladder diverticula are prone to secondary infection, stone formation, and even tumor occurrence. The diagnosis is mainly based on imaging examinations. In addition, bladder stones in middle-aged and elderly people need to consider whether there is prostatic hyperplasia, because bladder stones are often secondary to urinary tract obstruction caused by prostatic hyperplasia. The patient's diagnosis and treatment process were shown in Figure 1. As the patient has cystitis as well as bladder stones, he has been advised to drink more water to dilute the urine and reduce bladder irritation, and also to use the antibiotic cefotaxime sodium (2g, bid) reasonably to fight infection and treat cystitis.

giant diverticulum of the bladder, turp, benign prostatic hyperplasia, bladder stones, case report, diverticular calculi, minimally invasive, one-stage surgery

PMC7658487_01

Female

A 65-year-old woman with no medical history visited our hospital with an abnormal chest shadow. Her physical findings were normal including peripheral edema, digital clubbing, cyanosis, or sicca syndrome, and her blood test findings including tumor markers and a respiratory function test were also normal. Her chest CT showed a ground glass nodule with a diameter of 1.5cm in the lower lobe (S6) of the right lung (Fig. 1). Because we suspected lung cancer, a transbronchial lung biopsy (TBLB) was performed: the specimen showed atypical cells with no obvious malignant findings. Three months later, the size of the nodule had increased slightly. For a definitive diagnosis, video-assisted thoracoscopic surgery was performed, and the pathological findings showed diffuse lymphoid follicular hyperplasia, infiltration of the alveolar septum by small lymphocytes and plasma cells, and follicular bronchiolitis (Fig. 2A). There were many lymphoid follicles in the tissue and lymphocyte exudation was present in the alveolar space (Fig. 2B). Immunohistochemically, the follicular area was CD20 positive, and CD3 positive T cells had infiltrated into the alveolar walls (Fig. 3). There was no monoclonal growth of kappa or lambda positive cells. There were a few lymphoepithelial lesions, and lymphocyte infiltration was observed between the bronchiole epithelium. Based on these pathological findings, a LIP pattern was considered. There were no physical or serological findings associated with collagen disease. Seven months after surgery, new localized ground glass shadows appeared (Fig. 4), and they gradually increased on the basal lesion of the lung for four years (Fig. 5). However, because she had no respiratory symptoms and normal respiratory function, she was observed with no medication. In addition, no other underlying diseases associated with LIP developed.

ground glass nodule, idiopathic interstitial pneumonias, lymphocytic interstitial pneumonia, video-assisted thoracoscopic surgery (vats)

High resolution CT shows a diffuse a ground-glass nodule in the lower lobe of the right lung near the seventh to ninth thoracic vertebrae (arrow).

PMC7658487_01

Female

A 65-year-old woman with no medical history visited our hospital with an abnormal chest shadow. Her physical findings were normal including peripheral edema, digital clubbing, cyanosis, or sicca syndrome, and her blood test findings including tumor markers and a respiratory function test were also normal. Her chest CT showed a ground glass nodule with a diameter of 1.5cm in the lower lobe (S6) of the right lung (Fig. 1). Because we suspected lung cancer, a transbronchial lung biopsy (TBLB) was performed: the specimen showed atypical cells with no obvious malignant findings. Three months later, the size of the nodule had increased slightly. For a definitive diagnosis, video-assisted thoracoscopic surgery was performed, and the pathological findings showed diffuse lymphoid follicular hyperplasia, infiltration of the alveolar septum by small lymphocytes and plasma cells, and follicular bronchiolitis (Fig. 2A). There were many lymphoid follicles in the tissue and lymphocyte exudation was present in the alveolar space (Fig. 2B). Immunohistochemically, the follicular area was CD20 positive, and CD3 positive T cells had infiltrated into the alveolar walls (Fig. 3). There was no monoclonal growth of kappa or lambda positive cells. There were a few lymphoepithelial lesions, and lymphocyte infiltration was observed between the bronchiole epithelium. Based on these pathological findings, a LIP pattern was considered. There were no physical or serological findings associated with collagen disease. Seven months after surgery, new localized ground glass shadows appeared (Fig. 4), and they gradually increased on the basal lesion of the lung for four years (Fig. 5). However, because she had no respiratory symptoms and normal respiratory function, she was observed with no medication. In addition, no other underlying diseases associated with LIP developed.

ground glass nodule, idiopathic interstitial pneumonias, lymphocytic interstitial pneumonia, video-assisted thoracoscopic surgery (vats)

After 7 months, high resolution CT showed a ground glass shadow on the dorsal side of the left lower lung field.

PMC5320300_01

Male

A 42-year-old nonsmoking Saudi man with a history of type 1 diabetes was referred to our institution for investigation of a chronic cough and mild exertional dyspnea. He denied a history of hemoptysis, weight loss, night sweats, or change in appetite. A physical examination revealed a temperature of 37.0 C, respiratory rate of 20 breaths/min, heart rate of 70 beats/min, blood pressure of 110/70 mmHg and oxygen saturation of 96% on room air. A chest examination was entirely normal. There was no lymphadenopathy. The rest of examination was unremarkable. A complete blood count, liver function test, erythrocyte sedimentation rate and C-reactive protein were within normal limits. The chest-X-ray was unremarkable. The Computed Tomography (CT) scan revealed a lobulated round nodule in the left upper lobe adjacent to the bronchus, measuring 1.8 x 1.6 cm with an absence of significant lymph nodes (Figure 1). Flexible bronchoscopy revealed a swollen endobronchial lesion at the apical posterior segment of left upper lobe of the lung (Figure 2). Cytology and brushing were negative for malignant cells. Acid fast bacilli and MT-PCR were positive and later, the Mycobacterium tuberculosis culture was also positive. Multiple biopsies were taken from the endobronchial lesion and histopathology was consistent with the diagnosis of squamous papilloma (Figure 3). There was no evidence of dysplasia, malignancy, or granuloma in all biopsies taken from the endobronchial lesion. HPV in situ hybridization was negative. The patient completed a 6-month course of anti-TB treatment. A follow-up CT chest redemonstrated the same lobulated round nodule in the left upper lobe, almost stable from the previous study (Figure 4). Repeated flexible bronchoscopy showed the same findings. Multiple transbronchial biopsies were consistent with the diagnosis of well-differentiated squamous cell carcinoma (Figure 5). The patient had a left upper lobectomy and biopsies of the mediastinal lymph nodes did not reveal any malignancy or granulomas (T3N0M0). The patient was treated with 6 cycles of chemotherapy and he was considered cured. He underwent a surveillance program with no evidence of recurrence after three years of follow-up.

PMC6355664_01

Female

An 8-year-old girl for first-cousin parents, she is the second child among four girls of a Syrian family having a refugee-status at a camp in Sulaymaniyah, northern Iraq, since 2014. Our patient was born uneventfully in August 2010 and received BCG vaccine, according to the schedule at 7th day of age. Two months later, she developed ipsilateral axillary lymphadenitis followed by generalized lymphadenopathy. Meanwhile, features of disseminated BCG infection, including fever, weight loss, disseminated maculopapular rash, and hepatosplenomegaly, were manifested, and managed by a prolonged course of anti-TB medicines including isoniazid, and rifampin. According to the history taken from the mother, our patient had repeated episodes of non-specific illnesses, in form of relapsing/remitting maculopapular skin rash, oral thrush, respiratory infection, gastroenteritis, and urinary tract infections that were treated in an outpatient setting, in addition to one episode of meningitis treated at a hospital in Syria. At 4-year-old, as the family fled the war in Syria to a camp in northern Iraq, the child's condition was severely deteriorated and she became seriously ill with fever, night sweating, diarrhea, and poor appetite. Thus, she was referred to the intensive care unit at Hiwa Hospital in Sulaymaniyah, the northern province in Iraq. Upon admission she was toxic, cachexic, and feverish, with generalized lymphadenopathy including cervical, axillary, inguinal and epitrochlear lymph nodes. The lymph nodes were multiple, asymmetrical, and visibly enlarged with the biggest about (3.5 x 3 cm) at left axilla, firm in consistency, not tender, and discrete. The abdomen was distended with the presence of hepatosplenomegaly and ascites, in addition to right lung crepitation. The patients' growth parameters were below the third centile. Investigations showed an erythrocyte sedimentation rate (ESR) of 110 (normal range 3-13) millimeters/hour (mm/h), along with hypochromic microcytic anemia, leukocytosis, and high immunoglobulin-G assay. Ascetic fluid showed lymphocytic predominance with a serum-to-ascites albumin gradient of < 1.1 gm/dl, normal liver, and renal function tests. HIV and hepatitis screening were negative. Chest X-ray and computed tomography (CT) of the chest and abdomen showed a pulmonary consolidation at the right lower lung, in addition to mesenteric lymphadenitis disclosed by CT. Although microbiological and histopathological evaluations were not done, there was a high index of suspicion of mycobacterial infection, either in the form of relapsing disseminated BCG disease or active TB, based on the TB-prevalent situation at the area of the camp. Furthermore, the patient did not respond to an initial course of broad-spectrum antibiotics. Thus, she was treated empirically with 4 anti-TB medications for 12 months, including; isoniazid, rifampin, pyrazinamide, and streptomycin that was later changed to ethambutol. She showed a very good clinical and laboratory responses. Several months later, after stopping anti-TB therapy, she relapsed with generalized lymphadenopathy and maculopapular skin rash (Figure 1). She also had episodes of abdominal pain and bloody diarrhea, disturbed sleep, and weight loss. Our patient underwent several excisional biopsies from axillary, cervical, and groin lymph nodes, in Syria and in Iraq, but the results were non-conclusive. Moreover, during the periods of suspected infection with leukocytosis and lymph node neutrophilic infiltration, culture was not regularly done, mostly because of the limited laboratory facilities and being treated in an out-patient setting. There was no history of BCG disease or TB, among family members. On most occasions the patient had an ESR of >= 100 mm/h, hypochromic microcytic anemia, leukocytosis, neutrophilia, lymphopenia with hypercellular marrow examination, and low CD3 and CD4 by flowcytometry. Antinuclear antibody, in addition to toxoplasmosis, rubella, cytomegalovirus, herpes simplex, HIV, and syphilis, as well as the culture for TB, were all negative. Thyroid, liver, and renal function tests were normal.

bacillus calmette-guérin (bcg), flinders technology associates (fta), il12rb1 deficiency, iraq, mendelian susceptibility to mycobacterial diseases (msmd), non-tuberculous mycobacteria (ntm), tuberculosis (tb), whole exome sequencing (wes)

PMC9725122_01

Female

Table 2 presents the demographic details of respondents. According to the respondents, they initially migrated to the study area from the surrounding districts to secure livelihoods and explore earning opportunities. Among respondents, thirty-seven lived in the city for the last 12 years, while twenty-four respondents lived in the area for 5 to 7 years. Fifty-six respondents lived for the last two to four years while 28 respondents were relatively new in the locality. Majority of the participants (66.20%) lived in joint families while a few working women lived as a single parent family. Majority of the participants was in the age group range of 21-30 and 31-40 years old. The demographic details of respondents also highlighted their average family size is 6.8 per household and that they have either no schooling or less than primary level education. Out of 54 respondents, 21 worked as housemaids, 16 as laundry-maids, twelve as cooks, and five as child caregivers. Number of persons who earn ranged from 1-4 person per household with each household having high level of dependent members (see Table 3). In majority cases, the spouses of all the respondents worked as street vendors, taxi drivers, construction labors, juice sellers and garbage collectors. In 25 households, children were also working to earn for their families. In most cases, children were enrolled in schools while only 23 respondents reported that their children were studying in government schools. Out of 54 respondents, forty-seven respondents had rented accommodation. Majority of rented houses were single room with kitchen facility while a few respondents were living in the servant quarters of the households where they worked. The rent of accommodations ranged from US $55 to $65 per month. Only five respondents had bank accounts, all the respondents had mobile phones, and 36 respondents had domestic animals for meeting their milk needs. COVID-19 severely disrupted access to services and resources. Respondents highlighted that after the emergence of COVID-19 and subsequent lockdowns, majority of basic services were closed. For instance, the National Command and Operation Center (NCOC) directed to civil administration on the closure of economic activities, banned inter and intra city mobility, suspended educational facilities and reduced health services to a minimum. Respondents highlighted that the implementation of such kind of restrictions created a stressful environment, and everyone showed his/her concern. Particularly, those who were already suffering from limited access to services and opportunities were in trouble. Women domestic workers documented that they faced difficulty in access to basic services during lockdown. During lockdown, life became very challenging, because everything that you need was inaccessible and shut down. For people like us who are totally dependent on their daily earnings were in serious trouble. Mostly, we don't keep enough food items stocked at home. When the lockdown was announced, everyone rushed to the groceries stores and purchased enough food items for themselves. But people like us who don't have enough money and hardly manage their home were at risk to face severe problems to feed themselves and their dependents. The disruption in social services and market closure pushed people to experience an unprecedented situation. The respondents highlighted that chaos ensued without any alternative arrangements. For instance, people were informed not to come to work due to market closure and fear of being infected by others, the suspension of basic services such as transport, education and most importantly health services generated a crisis for them which was never experienced before. One of the childcare giver women workers reported, My mother has serious health issues; she needs frequent checkups from physicians. But during the lockdown, health services were limited to only emergency services. We visited the health facility several times but were not allowed to have an appointment. She suffered a lot and became weaker day by day. Because I could not afford the private clinic expenses, we mostly relied on old medication, but for me it was very hard to purchase medicines. Furthermore, the closure of private clinics also made it challenging for poor families who had limited resources and access to quality health care services. These private clinics operated by healthcare practitioners provided health services relatively cheaper. Restrictions and bans on these private clinics put the poor families at disadvantage. COVID-19 indiscriminately affected the livelihood of women domestic workers engaged in informal sector. The primary data revealed that in most cases, women domestic workers relied on their own earnings to support their families. Before COVID-19, these domestic workers were dependent on the households where they offered their services in different capacities for fixed hours in a day. For instance, one respondent highlighted that they mostly worked at three to four households at the same time and visited them in fixed hours. While working, the households facilitated them in kind such as food items, cloths, vegetables, fruits and supported them financially at the time of any emergency. Women domestic workers documented that the outbreak of COVID-19 and the subsequent unprecedented situation of lockdown has adversely affected their livelihood options. One of the housemaids expressed during interview: I worked as a housemaid in three different households. Since the government announced the lockdown, I have been informed by the families not to come for work. Initially, I thought that it might be for one or two days but as the days passed, the period became longer. Hence, I was worried about our livelihood because I had no income throughout the lockdown period. In addition, at home, we don't have sufficient amount of money to meet our needs. Therefore, at that time I was struggling to find any alternative. The interview details also revealed that COVID-19 outbreak created a sense of worry among respondents regarding their livelihood. They faced an array of problems to manage their livelihood during COVID-19. For instance, majority of the women domestic workers whose husbands earned to support their families reported that restrictions on transport services further exacerbated their livelihood opportunities. My husband is a taxi driver and he used to go to work regularly. Since the lockdown was imposed, he could not find work. During the lockdown, he tried several times but was unable to get enough customers. During that period, he mostly returned home empty handed with zero earnings. Domestic women workers from single parent families were adversely affected by lockdown. Most of these families were unable to pay for their daily expenses. Though they were supported by other family members such as fraternal and maternal relatives and in-laws, but they hardly met their basic needs. One respondent recalled that time and documented, There were no food items left at home to eat. I remember one morning when I woke up early and went out to find something for breakfast. After one and half hour struggle, I knocked at a door hopelessly and requested them to give something for breakfast. Thankfully, that family gave me adequate amount of grocery items and vegetables. Most of the respondents illustrated that they borrowed money from relatives, neighbors, and friends to meet the daily expenses. The lockdown and the subsequent crisis impoverished women domestic workers and their families. Although the intensity of these problems varies across families, but the adverse effects are more pronounced in single parent families and in families with more dependent family members. After one week of lockdown, I was really worried how to manage the required groceries until I could resume work. Because, we have more family members, I used to buy wheat flour, sugar, edible oil etc., from a nearby grocery store at the corner of our street. But during the lockdown when shops were allowed to be open only for certain hours, I visited many times, but the owner refused to give me required food items on credit. Majority respondents reported the loss of livelihood opportunities resulting from the shutdown of economic activities. A sense of worry was reported by all the respondents over their retention of jobs and earnings, debt repayment, and restoration of livelihoods opportunities. The interview details revealed that majority of the respondents disproportionately experienced financial hardship during COVID-19. In most cases, women domestic workers lost their jobs and earnings which directly affected their household expenditures. Though they were working with households for many years, they received minimum financial support from the employers. The respondents reported that in many cases they were forced to leave their jobs while others lost their jobs due to unavailability of intra city transport which restricted their travel to the workplaces. The lost jobs and lack of earning opportunities resulted into debt which put the women domestic workers under pressure and vulnerable to economic hardships. For instance, majority of respondents was worried about the repayment of debt that compelled them to make different compromises. They were struggling to readjust their household expenditures and cut down on food choices, health services, leisure activities, recharging of mobile and cable television (in few cases), participation in family and social gatherings, and personal expenses. One of the women domestic workers documented that: Having no job and minimum earnings compels you to revisit all of your life choices. We experienced it for the first time and were confused what to do when everyone around us had the similar economic conditions. The lockdown period drastically affected our economic position. The respondents highlighted that the economic hardships vary by families and social arrangements. For instance, in the first case, those women domestic workers who had more working family members were relatively in a better position to absorb economic shocks. While in the second case, women domestic workers who were sole bread earners or had more dependent family members were in serious economic trouble. In both cases, majority respondents agreed that economic hardships severely and adversely affected their overall wellbeing and family welfare. We had a cow and a goat to meet our milk needs. But I sold the goat for a very cheap price because I had no money in hand to feed my family. The interview details also revealed that lost job and reduction in earnings affected the household dynamics such as shrinking of household earnings, withered savings, increased debt, difficulty in management of household expenditure, and changing nature of family relationships. Respondents documented that the sudden reduction in economic resources and subsequent economic constraints made the life of women domestic workers stressful and challenging. We hardly managed our household expenditures, and the overall quality of life has deteriorated. We faced difficulty in payment of rent, food intake got restricted, marital relationships were stressed. Due to indebtedness, families became economically under-pressure which led to financial insecurities; therefore, families were forced to sell their personal assets. In addition, women domestic workers complained that increase in prices of basic commodities further aggravated their hardship. The pandemic and resulting lockdown created both long- and short-term economic hardships for domestic women workers. In the short term, they had to restore the household expenditures while in the long run they had to manage their economic resources in such a way that enabled them to minimize their economic insecurities and hardships. The government Ehsas Emergency Cash program was launched just after the introduction of lockdown. The purpose of the program was to facilitate those vulnerable groups of society who were experiencing economic hardship during the pandemic. Government allocated 203 billion Pakistani Rupees to provide direct cash assistance of Rupees 12000 (equal to $75 US dollar @160 = 1$) to more than 15 million families across the country. Out of 54 respondents, 27 women domestic workers or their family members received the assistance. My friend shared the details of the government direct cash assistance program. I sent my information. After a few hours, I received the message that I was eligible for the program. I thought it might not work but after one and a half week, I received a detailed message on mobile to visit the specific location and collect the money. Upon further probing that majority of respondents did not get the government assistance, it was revealed that most respondents were either unaware or could not follow the process for getting registered in the system. When I was informed by my neighbor that such kind of cash program was launched, I tried to send my details, but it was too late. The financial assistance support by the government was utilized by women domestic workers and their families in purchasing food items, payment of rent, and other utilities. The women domestic workers lamented over the selection process and the cash transfer mechanism. They perceived that the system in place has certain deficiencies such as available data in the system which disqualified majority of the poor families and there was no redressing mechanism for any complaint. Other than the government social support system, women domestic workers received help and assistance from charitable organizations, philanthropists, and the local community. Domestic workers received ration bags, vegetables, cooked food items, and clothes as a one-time support or help. It was also revealed during interviews that majority respondents did not ask anyone for assistance and help in the crucial time to avoid exposing their poverty and lowering their dignity; they only relied on the money they earned by working in houses, and on those house owners who provided cash and other items without even asking. Though the government assistance and social support received from different actors were considered necessary initiatives, but they were not sufficient for overall uplifting of the lives of these women domestic workers in the post lockdown situation. The lockdown left poor communities, especially the domestic women workers, marginalized and vulnerable to many challenges. These challenges ranged from personal, economic, social and psychological challenges. At personal level the respondents reported stress, anxiety, and depression which adversely affected the marital relationship in many households. Conflicts at the household level were reported among couples which led to stress in marital relationship and subsequently led to domestic violence in many cases. My husband is a chain smoker, he needs two packets of cigarettes daily. I managed it for one and a half week but then it was difficult for me to manage such amount of money every day. My husband asked for money, but I refused many times, and told him that we are going short of money, and it was difficult to manage the household expenditures. Gradually, he became annoyed and aggressive. He attempted three times to beat me, but I luckily managed to escape. The economic hardships resulted in the domestic workers getting laid off and suddenly losing earnings which compelled them into many compromises including cutting down on many household expenditures, food choices, health services, and pushed families into indebtedness. Due to the financial constraints, the women domestic workers restricted their social relationships and avoided participation in family and social gatherings which they perceived as adverse effects on their social standing and arrangements. Participation in family and social gatherings needs financial resources. But when your life is at risk and you are struggling to feed yourself and other family members, how can one participate in any kind of event? Though it negatively affects your family relationship with your relatives and others, but you have to set your priorities because once you are in a crisis, very few people will get you out of trouble. The respondents illustrated that they were suffering from psychological problems. For instance, stress, depression, and anxiety were common issues. I did not pay attention to my household chores. Through I tried it several times, but I always found myself absentminded and sometimes very worried about how things will settle down. Even my children complained so many times, but it was difficult to manage myself. The nature of psychological problems these women domestic workers experienced vary by family arrangements. However, these psychological issues also created personal health issues among women domestic workers which they perceived were caused by the strain in the earnings and household expenditures.

PMC5567942_02

Male

A 53-year-old male known with HIV infection since 2010 was admitted to hospital in April 2014 with symptoms of vomiting and abdominal pains for three days prior. It was associated with nausea and the vomitus contained food, was non-blood stained and occurred 3-4 times a day. He also complained of dizziness, some cough and had recently noted that his urine output had reduced without change in colour. He however had no history of diarrhoea or fever. He had been started on first line drugs; zidovudine (AZT), 3TC and EFV in 2010 and also put on cotrimoxazole prophylaxis of 960mg daily. He had a history of tuberculosis treatment the same year, for which he completed medication. In 2012, he was switched to second line treatment of ritonavir-boosted lopinavir (LPV/r), 3TC and TDF due to drug failure. His most recent viral load in 2013 was undetectable. On admission, he was very pale with oral thrush, was severely wasted and volume depleted; and had no oedema. His blood pressure was 100/60 and temperature 36.1 degrees. His systemic exam was otherwise unremarkable. Laboratory tests revealed the following: white cell count of 2,350/mul, hemoglobin of 3.8g/dL and a platelet count of 353,000/mul. Creatinine was 559mumol/l, urea 55mmol/l, potassium 4.5mmol/l and sodium of 114mmol/l. He had hepatitis B surface antigen positivity. He was put on antibiotics, fluconazole, rehydrated and transfused. TDF was discontinued and replaced by ABC, 3TC was renal dosed, LPV/r continued and cotrimoxazole dose halved. On the third day, the creatinine level was 541mumol/l, urea 35mmol/l, potassium 2.5mmol/l, chloride 86mmol/l and sodium122mmol/l. He was managed for hypokalemia. Over the next few days the creatinine levels reduced progressively and at discharge the creatinine level was down to 216mumol/l and urea to 33mmol/l. He was followed up and a month later, his renal function had normalized.

case report, hiv/aids, nephrotoxicity, reversal, tenofovir

PMC9937678_01

Male

A 22-year-old male patient presented to the emergency department with complaints of gradually progressive breathlessness for three months, which had increased significantly over the last 10 days, dry cough, fever, vomiting, and loss of appetite. The patient also reported chronic complaints of left-sided chest pain and weight loss for eight months. Given his worsening oxygenation situation, the patient was admitted to the intensive care unit and started on non-invasive ventilation with oxygen support. On obtaining the patient's detailed history, it was revealed that he was well eight months ago before he developed left-sided chest pain, which varied in intensity, and was admitted to a private hospital, where a chest radiograph was conducted and revealed left-sided moderate pleural effusion. Therapeutic thoracentesis was done, and approximately 1000 mL of hemorrhagic pleural fluid was drained. Pleural fluid cytology revealed a lymphocyte-predominant pleural fluid with high cellularity, but no evidence of malignancy was reported by the cytopathologist. The patient had no history of comorbid conditions apart from chronic alcohol consumption for four years. On general examination, his findings were as follows: pulse rate: 128 beats/minute; respiratory rate: 28 breaths/minute; blood pressure: 90/50 mm Hg; and oxygen saturation (SpO2 %): 88% on room air. Pallor was present, while icterus was absent, and chest auscultation revealed the presence of bilateral crepitations. A chest X-ray with a posteroanterior (PA) view was done on admission and revealed bilateral miliary opacities with symmetrical distribution (Figure 1). For further evaluation of the abnormal chest X-ray findings, a contrast-enhanced computerized tomography (CT) scan of the thorax was performed, revealing the presence of multiple centrilobular nodules arranged in random distribution with tree-in-bud appearance and lymphadenopathy. The left upper lobe showed consolidation with focal changes of bronchiectasis, and these CT features were suggestive of miliary TB (Figure 2). For further evaluation, a flexible fiber optic bronchoscopy was done, which showed the presence of thick mucopurulent secretions present in the left bronchial tree. No visible endobronchial mass or anatomical abnormality was observed. The reports of various other investigations done for the patient are summarized in Table 1. After starting non-invasive ventilation (NIV) support and anti-tubercular therapy (ATT), the patient started to show improvement in the oxygenation status and blood parameters and was gradually weaned from oxygen support and shifted to the general ward. The patient was discharged after 21 days on ATT with a standard four-drug regimen of Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), and Ethambutol (E), which are to be continued for six months. The patient was asked for a follow-up after seven days but was lost to the follow-up. This loss was probably a result of the considerable geographical distance between the patient's hometown and our hospital. Hence, no follow-up radiological investigations could be conducted to assess improvements. A differential diagnosis of malignancy was ruled out through a cytological analysis of the pleural fluid and the bronchoalveolar lavage fluid for malignant cells. A proper history ruled out other etiologies such as occupational lung diseases and hypersensitivity pneumonitis.

acute respiratory distress syndrome, antitubercular therapy, dexamethasone, hyponatremia, miliary tuberculosis

PMC6262779_01

Female

A woman with no medical history was seen in our department for the first time in 2001 at the age of 62 with erythematous slightly squamous plaques on the right arm and back (Fig 1, A). Skin biopsy was suggestive for sarcoidosis with well-formed noncaseating granulomas. Neither Ziehl Neelsen staining, tissue culture, nor DNA analysis was performed. No systemic involvement was found. From 2001 to 2009, she received successive treatments including hydroxychloroquine, thalidomide, doxycycline, methotrexate, colchicine, and systemic steroids. The lesions failed to respond and were slowly extending centrifugally with atrophic zones, without any systemic involvement (Fig 1, B and C). This treatment failure led to the introduction of adalimumab in 2009. Chest radiograph at this time was normal and QuantiFERON-TB was negative. Adalimumab induced painful ulcerations limited to the plaques that regressed within a few days after stopping the treatment. From 2009 to 2015, she received short courses of oral steroids, dapsone, and doxycycline, without any efficacy. Skin lesions were stable, and there were no symptoms suggestive of internal organ involvement. A new extracutaneous staging was performed in September 2015, including thoraco-abdomino-pelvic computed tomography scan, which was normal, and there was only a slightly high level of serum angiotensin-converting enzyme. Mycophenolate mofetil (MM) was started in November 2015 to treat what was considered to be recalcitrant sarcoidosis. Six months later, the plaques suddenly worsened and became erosive and extensive (Fig 2, A). New extracutaneous staging, including chest radiograph, was normal, and QuantiFERON-TB was negative. A new skin biopsy of ulcerative lesions showed an inflammatory infiltrate in the dermis with an ill-defined noncaseating granuloma (Fig 2, B). Stains for mycobacteria, bacteria, and fungi were negative. The first 24-hour polymerase chain reaction (PCR) (GenoQuick MTB, Hain Lifescience) was negative. After 5 weeks, tissue culture was positive for a mycobacterium from the tuberculosis complex. DNA analysis by PCR (Genotype MTBC, Hain Lifescience) identified an M bovis that was sensitive to rifampicin, ethambutol, and isoniazid, but resistant to pyrazinamide. MM was discontinued, and a triple therapy comprising isoniazid, rifampicin, and ethambutol was administered for 2 months, followed by isoniazid and rifampicin for 4 months. The ulceration rapidly healed and the lesions gradually resolved and cleared, with only hypertrophic scars remaining at the end of treatment (Fig 2, C) without recurrence after 18 months of follow-up.

mm, mycophenolate mofetil, mycobacterium bovis, pcr, polymerase chain reaction, cutaneous tuberculosis, lupus vulgaris, sarcoidosis

PMC3912988_01

Male

Two males participants with non-fluent aphasia took part in this study. The protocol was approved by Macquarie University and the participants and their primary caregivers gave informed consent. The Western Aphasia Battery (WAB) was used to assess both participants' speech and language function. Participant GOE was 65 years old and 18 months post left fronto-temporal stroke (see Figure 1 for structural image). The WAB assessment classified GOE as having moderate non-fluent Broca's aphasia. GOE also presented with moderate right hemiparesis. Participant AMC was 49 years old and 20 months post left fronto-temporal stroke (see Figure 1). AMC had a titanium mesh plate inserted in his temporal region following the stroke. The WAB assessment classified AMC as having moderate-to-severe non-fluent Broca's aphasia with difficulties in auditory-verbal comprehension. AMC also presented with moderate right hemiparesis and moderate right visual neglect. GOE had knowledge of MIT through his group therapy sessions and AMC had been undergoing MIT for a year prior to participating in the study. The participants were both asked to halt all speech and language therapy for the duration of this study. GOE and AMC were right-handed prior to the stroke and both were native speakers of English. Language function was first assessed 1 week prior to commencing the study (baseline 1) and immediately before the first treatment session was conducted (baseline 2). After the study commenced, language testing was conducted after each treatment session and 1 week following the completion of the study. The language assessment tasks included the automatic production of verbal sequences (i.e., counting from 1 to 21, reciting the days of the week, reciting the months of the year, reciting the alphabet, and listing as many animals as possible within 1 min) and a phrase repetition task. There were 51 phrases in the phrase repetition task (see Table A1 for phrases). These phrases had no more than 4 syllables (e.g., "I love you," "Goodbye," "Pass the salt," "Hi"). The verbal output for both the phrase repetition and verbal fluency tasks was recorded and later transcribed. The phrases used during the repetition task were divided into 3 lists of 17 phrases that were matched for utterance length, syntactic structure, and frequency/imageability. Each of these lists was randomly assigned to one of 3 conditions for each participant: rTMS-treated, sham-rTMS treated, and untreated. The rTMS-treated list was used by the clinician to provide MIT following rTMS, whilst the sham-rTMS treated list was used by the clinician to provide MIT following sham-rTMS. The untreated list was not practiced during MIT. The phrases practiced during MIT were, therefore, a subset of the phrases presented in the repetition task for language assessment. Anatomical and functional images were collected at Macquarie University Hospital, Sydney, using a 3 Tesla Siemens MagnetonVerio scanner with a 32-channel head coil. First, an alignment scan was performed for head position adjustments so that the AC-PC reference line was as close as possible to the vertical axis of the scanner. Second, a T1-weighted anatomical image was obtained using the following parameters: TR/TE = 2000 ms/900 ms, FOV = 250 mm, flip angle = 9 degrees and voxel size = 1 mm3. Third, T2-weighted functional images were acquired using the following parameters: TR/TE = 3000 ms/32 ms, FOV = 240 mm, flip angle = 80 degrees, gap = 0.5, number of slices = 78 and voxel size = 2.5 mm2. The order of acquisition was ascending, interleaved. All sessions were started with 2 dummy scans. Brain activation was measured by adopting the blood oxygenation level-dependent (BOLD) effect with optimal contrast (Ogawa et al.,). The collected images were preprocessed using the Statistical Parametric Mapping software (SPM8; http://www.fil.ion.ucl.ac.uk/spm). Corrections were made for the time delay in acquisition of the different slices, and the images were realigned onto the mean image for head-motion correction and spatially normalized into a standard stereotaxic space with voxel size of 3 mm3 using the Montreal Neurological Institute (MNI) template. A spatial smoothing filter was employed for each volume by using an isotropic Gaussian kernel (FWHM = 6 mm). Participants underwent an fMRI session one week prior to the start of the study and 1 week following the end of the study. The scans were used to localize Broca's homolog for targeted stimulation in the rTMS portion of the treatment and to track any functional cortical reorganization occurring during the study. Participants were asked to complete two tasks in the scanner: an automatic speech task and a naming/reading task. All stimuli were projected onto a screen and viewed through a mirror mounted on the head coil. Verbal responses were recorded using a FOMR-III MRI compatible microphone (Optoacoustics Ltd) attached to the head coil in the scanner. The overt responses were also transcribed at the time of scanning. Stimulus presentation and recording of the verbal responses was controlled by Presentation (Neurobehavioral Systems Inc). The participants were trained on each task prior to the fMRI sessions. A block-design was used to present the tasks in the scanner because it permits an examination of overt speech in participants with aphasia despite the false-starts and hesitations found in such participants (Martin et al.,). Such designs also have excellent statistical power (Aguirre et al.,). In the automatic speech task, participants were required to count from 1 to 21 and recite the days of the week, months of the year and the alphabet. When completing this task (see Figure 2A), participants saw a category label appear on the screen for 3 s (e.g., NUMBERS) followed by three examples of the category sequence (e.g., 1, 2, 3) that appeared for 1.5 s each. Participants were given 20 s to recite (in correct order) each item in the category. The order of the categories was randomized. There were two runs of this task. Each run consisted of 4 trials that were separated by a 20 s fixation. In the naming/reading task, participants were asked to name a picture or read a word. There were 10 items that appeared as both pictures and words. The items were selected from The International Picture Naming Project database (http://crl.ucsd.edu/experiments/ipnp/; Szekely et al.,) based on length (one syllable), frequency (high) and percent of dominant response (100% of participants produced the dominant name). When completing this task (see Figure 2B), participants saw an instruction label appear on the screen for 3 s (e.g., PICTURE or WORD) followed by 5 items (e.g., king, bat, leaf, map, egg) that each appeared for 1.5 s. Participants were given 4 s to name each picture or read each word. The pictures appeared in a separate block to the words. Block order was counterbalanced. Each block was separated by a 20 s fixation. There were four blocks in each run. Participants completed two runs. Both GOE and AMC participated in two phases of the TMS protocol: rTMS and sham-TMS. The order of the two phases was counterbalanced across participants and was separated by a 1-week break. GOE first went through the rTMS phase, whereas AMC first went through the sham-TMS phase. Each phase consisted of three treatment sessions that were separated by 3 days (see Table 1 for treatment schedule). Surface electromyography (EMG) electrodes were placed over the first dorsal interosseous (FDI) of the left hand. Single-pulse TMS was performed to establish active motor threshold (AMT) using a Magstim Rapid stimulator. Stimulation was conducted using a 70 mm figure-8 coil. The coil was placed with the handle pointing occipitally at an angle of approximately 45 to the mid-sagittal line over the primary motor cortex in the right hemisphere at the optimal site for obtaining an MEP in the FDI. After AMT was established, intermittent theta-burst stimulation (iTBS), a form of high frequency rTMS, was performed using Magstim Rapid2 with intensity set at 80% of AMT. The iTBS consisted of bursts of 3 pulses at 50 Hz given every 200 ms in 2 s trains, repeated every 10 s over 200 s for a total of 600 pulses. Coil position for iTBS was determined by examining the T2-weighted MRI scans of each participant. The target site for stimulation was selected by identifying a peak of frontal activity (separately for each participant) within the anatomical territory of pars triangularis (GOE) or pars opercularis (AMC) in the right inferior frontal gyrus. This peak voxel activity was elicited by the automatic speech task. The surface distance measurements method was used to identify the location of the selected region on the head of each participant (Weiduschat et al.,). The same iTBS procedure was used in the sham-rTMS phase, but a sham TMS coil was substituted for the real TMS coil. The sham coil mimics a real TMS coil by producing the same clicking sound, but, unlike a real TMS coil, the sham coil does not cause any change in neural activity. Each rTMS session lasted 5-min and was followed by a 5-min break. Participants completed a 40-min MIT session after the break, which was administered by a clinician. Participants and the clinician were blind to stimulation condition. The MIT session followed the format of a typical MIT protocol with phrases trained using a hierarchical series of steps (Norton et al.,). Each phrase was intoned on the minor third interval with regular syllable durations of 1 s.

aphasia, fmri, rtms, rehabilitation, stroke

PMC7783366_01

Male

The patient is a 48-year-old married man, with secondary level education, of middle socioeconomic status, with well-adjusted premorbid functioning. The patient was diagnosed with COVID-19 for which he was required hospitalisation for the initial part of his illness and was managed conservatively and improved after 12 days of admission and eventually recovered. His mother, in her 60s, was also diagnosed with COVID-19, and during the hospitalisation, her physical condition deteriorated rapidly, requiring mechanical ventilation. While the patient was hospitalised, his mother passed away due to the illness, and her last rites were conducted by his other family members. The patient came to know of his mother's demise only after his discharge and was shocked on hearing the news. He expressed guilt for not being able to give his mother company in the last few days of her life and not participating in her funeral rites. His family members tried to console him, but he was not reassured. He would remain tearful throughout the day and preferred to stay isolated. His sleep, appetite and self-care were normal during this period. After 2 weeks, patient's sleep gradually reduced to 1.5-2 hours/day. Despite not sleeping, the patient would appear active throughout the day. He also became more talkative and would constantly talk about his mother. He would also appear authoritative to his family members and order them to follow his instructions. He would be constantly engaged in household chores, even when they had already been done by his wife. His predominant mood was irritable, and he would have anger outbursts. He would try to go out of the house despite the lockdown, saying that he was going to the Prime Minister's office to instruct him on how to control the pandemic. If family members stopped him, he would try to run out of the house and become verbally aggressive. Because of unmanageability, he was brought by his family to the outpatient services of our psychiatry department. History revealed that the patient's father suffered from mental illness suggestive of bipolar disorder, which was never treated, and he had expired at the age of 64 years. However, the patient had not suffered from any mental illness in the past. General physical examination and systemic examination revealed no abnormality. His blood pressure (BP) was 110/70 mm Hg, pulse rate (PR) was 81/min, respiratory rate (RR) was 14/min and body mass index (BMI) was 23.9. On mental status examination (MSE), he was mildly unkempt, authoritative towards the interviewer, eye-to-eye contact (ETEC) was made but not sustained and rapport could not be established. His speech was spontaneous with increased rate, tone and volume. His affect was irritable, and he reported ideas of grandiosity. His attention and concentration were aroused but ill-sustained, and his judgement was impaired. Based on his history and MSE findings, a diagnosis of first-episode mania was entertained as per ICD-10 (International Classification of Disorders). Young Mania Rating Scale (YMRS) was applied, which yielded a score of 27. The patient was started on a daily dose of 15 mg olanzapine and 1 mg clonazepam optimised over 1 week. He showed clinical response over the next 2 weeks on the above-mentioned medications. His sleep increased to 6-7 hours/day; there was a reduction in irritability, anger outburst and increased talkativeness, but the ideas of grandiosity and increased psychomotor activity persisted. The YMRS score was reduced to 16 after 2 weeks of pharmacological management.

adolescent psychiatry, behavioural symptoms, conflict, psychological, psychological trauma

PMC7783366_02

Female

The patient is a 14-year-old girl, a student of class 9, belonging to a Hindu nuclear family of low socioeconomic status. She had an easy temperament, no medical comorbidity and no history or family history of mental illness. The patient was studying in a private school, and she was considered as a meritorious student by her teachers and family members and participated in extracurricular activities. Since March 2020, with the imposition of nationwide lockdown, her school has been closed, and all academic activities were conducted through online learning. Although the patient's father possessed a smartphone with an internet connection, she did not have access to a computer or laptop. The patient was required to attend online classes regularly as organised by her school authorities. She also received online assignments through email, which had to be completed and mailed back within the stipulated period. The patient would try to attend the online classes on her father's phone, but she was unable to complete her assignments. Both her parents were not educated beyond middle school and could not assist her in her academics. The patient would remain constantly preoccupied with her inability to follow the curriculum. She would express apprehensions regarding her schoolwork. She would frequently report to her family members that she would lag behind her other peers and would not be able to clear her exams. She started reporting intermittent anxiety symptoms, crying spells and sleep disturbance for the next 2.5 months. Then, 10 days prior to the assessment, the patient's mother noticed that she would not sleep at night and appear fearful. She would not interact with family members and have unprovoked anger outbursts. Occasionally, she was seen muttering to herself. Her appetite and self-care also deteriorated significantly following which she was brought to the OPD. General physical examination revealed mild pallor. Her BP was 90/70 mm Hg, PR was 98/min, RR was 16/min and BMI was 18.4. Blood investigations revealed no abnormality. On MSE, she was unkempt, appearing fearful and muttering to self intermittently. ETEC was not made or sustained and psychomotor activity was increased. Her attituded towards the interview was guarded. Her affect was irritable and speech was irrelevant with increased rate, tone and volume, and she was not cooperative for further interviews and would become verbally aggressive. Based on the history and clinical evaluation, a diagnosis of acute transient psychotic disorder was made as per ICD-10, and the patient was started on a daily dose of risperidone 2 mg and lorazepam 1 mg over which her family members reported mild improvement in fearfulness, muttering to self and anger outburst over next 1 week. There was also improvement in her sleep and self-care.

adolescent psychiatry, behavioural symptoms, conflict, psychological, psychological trauma

PMC7783366_03

Female

The patient is a 9-year-old girl, dropped out of school, belonging to lower socioeconomic status, with no significant medical or psychiatric history in the family, was brought to OPD during the lockdown. The child's functioning before the illness was adequate with good academic performance. The family members gave a history of sudden onset spells of unresponsiveness that were usually preceded by a stressful event and were often associated with concomitant symptoms of headache, light-headedness and palpitations. These spells had been occurring intermittently over the last year, during which period, her family had sought consultation from a neurologist. She was diagnosed with psychogenic non-epileptic seizures; her EEG revealed no abnormality, and she was not on any pharmacological treatment. During the lockdown, the garment factory in which her father worked was shut down, because of which he lost his job. This led to a financial crisis in the family as her father was the chief earning member, and they faced difficulties in paying their rent and meeting the expenditure for daily essentials. The patient was exposed to discussions among parents over money matters. She would be constantly preoccupied with the financial issues of the family. She became anxious and upset when she came to know that her mother was contemplating working as a domestic help to meet the financial needs of the family. She would repeatedly ask her family members to allow her to share the workload at home. Even though she was a student of primary school, she tried to tutor students younger to her in her neighbourhood, as an attempt to earn money for the family. She would remain anxious most of the time and have a sudden outburst of crying. This would often be followed by an unresponsive spell. Previously, these episodes would occur one to two times in a month, whereas now they started to occur three to four times/day. The family members initially sought help from a local faith healer, but after perceiving no improvement, she was brought to the psychiatry OPD. Her general and systemic physical examination did not reveal any abnormality. Her BP was 100/60 mm Hg, PR was 88/min, RR was 16/min and BMI was 17.9. Blood investigations revealed no abnormality. On MSE, she was well kempt, ETEC was made but not sustained and rapport could be established with great difficulty. Her affect was constricted. She reported preoccupations with the financial problems of the family and ideas of guilt about not being able to contribute to the family. Based on the history and clinical assessment, a diagnosis of conversion disorder with seizures was made as per ICD-10. A differential diagnosis of syndromal depressive or anxiety disorder in addition to her pre-existing conversion symptoms was also entertained; however, on evaluation, she did not fulfil the criteria for a separate comorbid diagnosis. The patient was referred to a clinical psychologist for psychotherapeutic intervention. Psychosocial stressors were explored in detail. On Children's Apperception Test, the major themes obtained were of uncertainty, loss of finances and lack of food, failure and poor problem solving ability. The intervention focused on teaching emotional self-regulation skills and breathing exercises for relaxation. The child was asked to keep a record of the frequency of episodes and skill practice. After the initial three sessions, the next sessions were conducted telephonically to enable the family to save travel fare. By the fifth week of treatment, the patient's episodes of headache and unresponsive spells had reduced to one to two times per week.

adolescent psychiatry, behavioural symptoms, conflict, psychological, psychological trauma

PMC10282642_01

Male

A 7-year-old boy was admitted to the hospital for a fever with a maximum temperature of 38.1 C and paroxysmal coughing, dyspnea, and cyanosis of the lips for two days, without spasmodic coughing, wheezing, digestive symptoms, or joint pain. Self-measured SPO2 was 89%. Therefore, he was admitted to a hospital and underwent intravenous administration of amoxicillin and clavulanate potassium for one day, meropenem once, and nebulization, mask, and high-flow oxygen therapy. Still, his condition did not improve, so he was transferred to our hospital for treatment. Past medical history: The patient had a history of multiple episodes of wheezing and "asthma " but had not experienced wheezing attacks in the past two years. He underwent tonsil and adenoidectomy surgery three years ago. There was no history of immunodeficiency, no use of immunosuppressive drugs, and no contact with patients infected with T whipplei. Physical examination on admission: temperature 38.1 C, pulse 136 bpm, respiratory rate 34 bpm, blood pressure 118/67 mmHg, SPO2 96% (mask oxygen inhalation 6 L/min), clear consciousness, low spirit, rapid breathing, three depressions sign, low breath sounds in the left lung, no rhonchi and crackles heard in both lungs and no abnormalities found in cardiac and abdominal examinations. The laboratory test in another hospital revealed blood routine: white blood cell 20.1 x 10 9/L, neutrophil 92.6%, lymphocyte 4.3%, C-reactive protein 1.2 mg/L. Blood gas analysis in another hospital showed a PH 7.387, PaCO2 39.2 mmHg, PaO2 56 mmHg, HCO3- 21.9 mmol/L, BE -0.31, Lac 2.1 mmol/L. The chest CT from our emergency department revealed consolidation in the left lung and occlusion of the left upper lobe bronchus (Figure 1). After admission, several examinations were completed. Complete blood count showed white blood cell 21.11 x 109/L, with 96.4% neutrophil and 2.3% lymphocyte, and C-reactive protein 11.81 mg/L. Arterial blood gas analysis showed a pH of 7.42, PaCO2 34.4 mmHg, PaO2 78.9 mmHg, HCO3- 22 mmol/L, BE -1.8, and Lac 4.3 mmol/L. The patient's procalcitonin level was 0.325 ng/ml. Immunoglobulin and lymphocyte subgroup tests were normal, suggesting no immunodeficiency. Pathogen tests examinations for influenza A and B, respiratory syncytial virus, adenovirus, Chlamydia, coronavirus, rhinovirus, Mycoplasma pneumoniae, human metapneumovirus, Bocavirus, parainfluenza virus, Ureaplasma urealyticum, and Chlamydia trachomatis were negative. EB virus antibody and tuberculosis-related tests were negative. The G and GM tests were negative, and the pharyngeal swab and lavage culture was normal. The patient received nasal high-flow warm and humidified oxygen therapy upon admission. On the same day, bronchoalveolar lavage was performed, and sputum plugs were removed. Metagenomic Next-Generation Sequencing was performed on the lavage fluid, and a follow-up chest x-ray showed increased transparency in the left lung (Figure 2). Subsequently, the patient received intravenous azithromycin to fight off infection, methylprednisolone to suppress inflammation, ambroxol to liquefy sputum, and nebulized inhalation. The results on day 3 showed T whipplei (with a sequence count of 261) and Streptococcus mitis (with a sequence count of 6) in the lavage fluid. So azithromycin was discontinued (after three days of administration) and replaced with intravenous piperacillin-tazobactam for five days (150 mg/kg.d). After five days of anti-infection treatment, the patient's blood test results were normal. The patient was discharged on the eighth day of treatment. The re-examed chest x-ray on the day of discharge suggested that the left lung lesion had significantly improved (Figure 3). The patient continued to take oral amoxicillin and clavulanate potassium for four days after discharge. Discharge diagnoses were respiratory failure, severe pneumonia, and plastic bronchitis. One-month follow-up after discharge showed no cough and fever and normal symmetrical breathing sounds in the lungs, and the condition did not recur.

children, neat-generation sequencing, piperacillin-tazobactam, plastic bronchitis, tropheryma whipplei

Ct scan on the day of admission (complete consolidation of the left upper lobe, bronchial obstruction of the left upper lobe, and large areas of high-density shadows in the left lower lobe).

PMC6349633_01

Female

A 71-year-old woman was found to have a solitary pulmonary nodule in the right lower lobe on computed tomography (CT) scans during work-up for an episode of pleuritic chest pain. This 1.4-cm, 18F-fluorodeoxyglucose-avid (maximum standardized uptake value: 5.5) lesion was biopsied, and results revealed a high-grade neuroendocrine tumor. Multiple extrapulmonary lesions on positron emission tomography, including a colonic lesion and adenopathy within the mediastinum and abdomen, were biopsied and found to be consistent with the patient's history of sarcoidosis. Postbiopsy, the patient developed a pneumothorax requiring a chest tube and 2-day hospital admission. Given the patient's poor pulmonary function (forced expiratory volume in 1 second: 1.1 L; 43% of predicted), the patient was deemed medically inoperable. She was referred to radiation and medical oncology where options including radiation therapy alone, sequential chemoradiotherapy, and concurrent chemoradiotherapy were discussed. The patient refused any treatment involving chemotherapy, and given the size and location of the lesion, the patient consented to move forward with SABR of 6000 cGy delivered over 8 fractions on alternate days. A 4-dimensional CT simulation was performed on a 16-slice Philips Big Bore CT Scanner (Philips Healthcare, Cleveland, OH). During respiration, the tumor moved 11 mm in the superoinferior direction, greater than our institutional standard of 10 mm for requiring respiratory gating. The internal target volume (ITV) was delineated on the axial slices of a subset average CT scan, composed of phases between 40% and 60% of the respiratory cycle. The planning target volume (PTV) was created using a 5 mm uniform margin around the ITV (Fig 1). The ITV and PTV were 4.2 cm3 and 17.0 cm3, respectively. A dose of 6000 cGy was prescribed to the PTV using a single isocenter, with a maximum point dose of 8170 cGy within the ITV. Treatment was delivered on alternate days, with daily cone beam CT, gated 2-dimensional kV/kV image guidance, and respiratory gating. After four fractions, cone beam CT scans revealed a change in location, shape, and size of the lung mass. The treating radiation oncologist decided to replan the patient using the same technique described previously. At the time of re-simulation, the GTV was determined to have shifted approximately 8 mm inferiorly, 9 mm posteriorly, and 1 mm laterally (3-dimensional distance: 12 mm; Fig 2). The new ITV and PTV were 1.4 cm3 and 9.0 cm3, respectively. The patient completed the remaining four fractions without incident, and her treatment was restarted 4 days after re-simulation was initiated.

PMC6699325_01

Female

A 24-year-old girl, born to 4th degree consanguineous parents of Turkish origin, was admitted to our hospital with complaints of pain, swelling, and limited movement of left elbow, ankles, and both knees since the age of 11 years. Following a diagnosis of juvenile idiopathic arthritis, treatment with corticosteroids, methotrexate, and sulfasalazine was given at public hospital. As she was not responding to these treatments, she was hospitalized for further examination and therapy at our University Hospital Pediatric Rheumatology Clinic 12 years ago. Her developmental milestones were normal for age. She had cataract surgery at the age of ten. She had been diagnosed with bilaterally hand and foot onychomycosis for at least five years and received antifungal therapies with no improvement although any fungus could be identified in cultures. Her sister had been diagnosed with juvenile idiopathic arthritis at seven years of age and deceased due to chronic renal failure at the age of 13. On her first physical examination [at first admission, her weight was 24 kg (<3 percentile) and height 132 cm (<3 percentile)] she had failure to thrive. There was limitation in left elbow dorsiflexion and in hip abduction and swelling in both knees. There was also heel pain with tenderness of achilles tendon. Besides articular findings, the most important symptoms were dystrophic nails of hand and feet with onychomycosis. Dermatologic consultation revealed that she had nail psoriasis accompanied by onychomycosis (Figure 1). According to the consultation report, there were lesions in the nail matrix (leukonychia and nail plate crumbling) and separation of the nail plate from underlying nail bed (onycholysis). Her nails were painful and were causing restrictions in her daily activities. Laboratory examinations were as follows: white blood cells 7960/mm3 (polymorphonuclear leukocytes 56%, lymphocytes 44%), hemoglobin 10.6 g/dl, hematocrit 32.8%, platelets 392000/mm3, C-reactive protein 5 mg/dl (normal <0.5 mg/dl), erythrocyte sedimentation rate 105 mm/hr (normal <15 mm/hr), and normal renal and liver function tests. Serum immunoglobulins (Ig) were very high as compared to age matched controls (IgG 2230 mg/dl, IgM 242 mg/dl, IgA 201 mg/dl) revealing hypergammaglobulinemia. The search for anti-nuclear antibodies and rheumatoid factor was negative. Abdominal and renal ultrasonography were normal. Some of the microbiologic tests were as follows: anti-HBs (-), HbsAg(-), anti-HIV (-), Brucella agglutination test (-), CMV IgM (-), and IgG(+). Total IgE levels, eosinophil counts, absolute counts, and percentages of lymphocyte subsets and the oxidative burst activity of granulocytes were normal. She was evaluated for tuberculosis and was found to have two BCG (Bacillus Calmette-Guerin) scars, a negative tuberculin response, and a negative QuantiFERON assay result (Qiagen, Chadstone, Australia). At the beginning of the long term follow-up (totally 12 years) she was diagnosed with refractory polyarticular juvenile idiopathic arthritis and nail psoriasis with onychomycosis. She was started on treatment with etanercept (Enbrel), methotrexate, and itraconazole with good response for a while for arthritic problems, but not for dermatologic disorders. Then, because of inadequate response, prednisolone at a dose of 1 mg/kg/day was added and also resulted in substantial improvement. She had experienced recurrent urinary tract infections and Klebsiella pneumonia was isolated from urine. Scintigraphic examinations, voiding cystography, and ultrasonography for kidneys were normal. Urine acid-fast bacilli test was negative. She did not have recurrent sinopulmonary infections. Then, Candida albicans was isolated from swab material of nail. She was given local and systemic antifungal medications for onychomycosis with no response. As she had nail psoriasis with refractory onychomycosis, molecular genetic analyses for chronic mucocutaneous candidiasis and APECED syndrome were performed. CARD9, AIRE, and STAT1 genes were found to be wild-type.

PMC7876440_01

Female

A 23-year-old woman presented to our hospital with involuntary movement attacks, which she had exhibited for about 20 years. The patient has an unremarkable family history, and her antenatal and perinatal histories and postnatal development were uneventful. At the age of 2, she underwent her first non-febrile generalized seizure. She was administered sodium valproate for 1 year. While another seizure occurred at the age of 12, the patient had since remained seizure-free. At the age of 3 years, involuntary movement attacks without impairment of consciousness began to occur after prolonged exercise or fasting. Attacks were characterized by intermittent dystonia of right unilateral limbs, manifesting as elbow joint, wrist joint, knee joint alternating flexion, twist, and adduction, especially the upper limb. Left limbs were involved occasionally. The involuntary movements lasted from 3 to 5 min. The episodes occurred only one or two times every month. She was diagnosed with dystonia, but no drugs were prescribed. The attacks often occurred before menstruation since her adolescence. At the age of 21 years, the pattern of attacks did not change, but it occurred more frequently than before, about once a week. The patient received a prescription for oxcarbazepine; while the drug helped to control the symptoms at first, it gradually became unhelpful. Four months before admission, the patient's manifestations became less associated with exercise or fasting, and the frequency increased to two to three times weekly. Oxcarbazepine was replaced with carbamazepine. Two months before admission, the symptom worsened after a trip to the seaside: the patient experienced continuous attacks, presenting as involuntary movements of the right upper and lower limbs, with affected limbs becoming painful. The degree of movement was similar to previous attacks; however, the episodes lasted from 3 to 30 min with intervals of 15-20 min; carbamazepine combined with Madopar could not relieve her PDs. Her head circumference was normal. Psychomotor development did not show any abnormalities according to her parents. The timeline of the patient's symptom is shown in Figure 1. Neurological examination revealed positive bilateral Hoffman signs and decreased muscle tone. Cranial nerves, motor strength, and sensory examination were normal. Brain and spine magnetic resonance imaging, lung computed tomography, and laboratory blood exams (including the assessments of ceruloplasmin and erythrocyte sedimentation rates) were unremarkable. Prolonged electroencephalogram monitoring showed sharp-slow and delta waves in the bilateral frontal area (Figure 2). Considering the worsening of her symptoms after her travels and a low fever of under 38.0 C, which had begun 4 days before admission to our hospital, we supposed that the worsened dyskinesia could be attributed to infectious factors. After written informed consent was obtained from the patient, lumbar puncture was performed, which showed a white blood cell (WBC) count of 20 x 106/L and a glucose concentration of 1.9 mmol/L (reference value: 2.3-4.1 mmol/L) in CSF; before the lumbar puncture, the patient's blood glucose concentration was 4.39 mmol/L. The CSF:blood glucose ratio was 0.43 (normal range: 0.62-0.68) [3]. These findings informed a speculative diagnosis of intracranial infection. However, antibody testing for M. tuberculosis and viruses in the blood and smear tests for M. tuberculosis and Cryptococcus in CSF showed negative results. A second lumbar puncture was performed 6 days later, showing a WBC of 2 x 106/L and a glucose concentration of 2.0 mmol/L in CSF. Tested the same morning, the patient's blood glucose concentration was 4.50 mmol/L; the ratio of CSF to blood glucose concentration was 0.44. Though the WBC in the CSF decreased to normal levels, the patient's symptoms did not abate fully. Her symptoms, medical history, and persistent reduced CSF:blood glucose ratios together suggested a neurometabolic disorder. We therefore subjected the patient and her parents to genetic analyses and identified a heterozygous point mutation (c.940G>A) in exon 7 of the SLC2A1 gene, which causes a substitution of amino acid 314 from glycine to serine (p.Gly314Ser). The mutation was not found in her parents. Ultimately, the genetic analysis informed a diagnosis of Glut1-DS. The patient began a ketogenic diet (KD), and the PDs disappeared within 3 months.

glut1-ds, slc2a1, intracranial infection, ketogenic diet, paroxysmal exercise-induced dyskinesia, paroxysmal non-kinesigenic dyskinesia

PMC7640539_01

Male

A 37-year-old male with an active history of IDU and alcoholism presented with a two day history of low-grade fever and an episode of massive hemoptysis. The hemoptysis was characterized as being bright red in color and approximately 350 mL in volume. Surgical history was significant for open-heart surgery two years prior for tricuspid valve replacement due to infective endocarditis. On admission, he was febrile (38.4 C), but hemodynamically stable. On general inspection, the patient was jaundiced with a visible sternotomy scar on the chest. Basal lung crackles were appreciated on auscultation. The patient was admitted with the impression of recurrent IE versus tuberculosis or pneumonia as top differentials. Laboratory results were remarkable for anemia with a hemoglobin level of 8 g/dL, prolonged prothrombin time at 16.8 s, elevated C-reactive protein (CRP) level at 160.5 mg/L, elevated erythrocyte sedimentation rate (ESR) at 90 mm/h and elevated serum procalcitonin at 4.49 ng/mL. Blood cultures grew Staphylococcus aureus colonies. Serologic tests were positive for hepatitis B virus (HBV) and hepatitis C virus (HCV), but negative for human immunodeficiency virus (HIV). A chest x-ray showed patchy areas of reticulation with ground-glass opacities in both lower lung zones and mild obliteration of the left costophrenic angle (Fig. 1). An echocardiogram was obtained and showed normal systolic function, normal ejection fraction of 55-60% and no regional wall motion abnormality. Remarkable findings included multiple vegetations attached to the tricuspid bio-prosthesis, the largest of which was attached to the valve ring on the ventricular side measuring 25 mm in length. Moreover, another mobile vegetation was attached to the right ventricular outflow tract wall measuring 20 mm in length. Computed tomography (CT) of the chest revealed a 2.7x2.4 cm lobulated lesion in the right lower lung lobe, with an iso-dense attenuation to the contrast medium and apparent topographic continuity with the pulmonary vessels (Fig. 2). The diagnosis of recurrent infective endocarditis of the tricuspid valve with ruptured right lower lobe pulmonary pseudoaneurysm was made. A multi-disciplinary team meeting was convened, and it was decided to manage the case with coiling of the pulmonary artery aneurysm followed by a redo tricuspid valve replacement. Two days into the admission, the patient successfully underwent aneurysm coiling by interventional radiology through a right transfemoral approach, using the Seldinger technique with an 18G needle and subsequent insertion of a 5F arterial sheath. Coils (Interlock , Boston Scientific) were inserted into the aneurysm and stasis was achieved (Fig. 3). Eight days later, the patient underwent scheduled open cardiac surgery under general anesthesia for a re-do tricuspid valve replacement. Intracardiac vegetations were found on the previously implanted artificial tricuspid valve and two other larger ones on the ventricular aspect. The whole 29 mm prosthetic valve (Pericarbon More, Sorin Group) was removed along with the vegetations (Fig. 4) and replaced with a 27 mm biological valve (MOSIAC 310 CINCH, Medtronic). The valve was secured to the anulus by a 2/0 non-absorbable suture (polyester suture) and closure of the right atriotomy was achieved using a 4/0 suture (polyester suture), followed by removal of the aortic cross clamp. The patient was subsequently weaned off cardiopulmonary bypass with no complications and transferred to the cardiac care unit in stable condition. Post-surgery, the patient had a normal sinus rhythm with a heart rate of 80/ minute and blood pressure of 110/70 mmHg, and he was started on gentamicin, cefazolin and rifampicin for six weeks. After 14 days, patient recovered successfully, and his laboratory tests were within reference range (CRP 0.40 mg/L, ESR 35 mm/h, procalcitonin <0.02 ng/mL) and was subsequently discharged after clinical and radiological improvement. He was followed up in the cardiac surgery clinic, and enrolled in a rehabilitation program to manage his drug addiction. After one year of follow-up, the patient is currently doing well from a clinical standpoint, no recurrence of hemoptysis or fever. Follow-up by echocardiograph and chest x-ray showed no vegetations, good cardiac function and no changes or issues were noted with the intra-aneurysmal coils.

infective endocarditis, intravenous drug use, mycotic pulmonary artery aneurysms

PMC6151194_01

Female

A 52-year-old postmenopausal female of Filipino origin presented to hospital with a three-day history of increasing abdominal bloating, vomiting, and fevers. She denied urinary or bowel symptoms. This patient had no significant past medical or family history and was a nonsmoker. She moved to Australia from the Philippines in 2015 and worked as a nurse in both countries. On admission, she had a temperature of 39.9 C, a heart rate of 127, and a respiratory rate of 35. Her abdomen was markedly distended. There was a palpable tender mass in the right lower quadrant, with guarding and rebound tenderness. Initial investigations showed mildly deranged liver enzymes, an elevated CRP, and slightly elevated CA-125 and CA-19.9 (Table 1). CT scan showed a 22 x 13 cm multiseptated cystic lesion almost certainly of ovarian aetiology, as well as omental fat hazing, raising the possibility of an acute omental infarction (Figures 1(a) and 1(b)). She was admitted for observation and intravenous antibiotics. Her fever resolved, and she was discharged home with a plan to follow-up in outpatient clinic for elective ovarian cystectomy. Ten days later, the patient re-presented to hospital with severe abdominal pain and ongoing fevers. Repeat laboratory results showed worsening liver enzymes and a further rise of CRP (Table 1). A repeat CT scan showed the large ovarian cyst had likely ruptured with new generalised ascites and peritoneal enhancement, concerning for disseminated disease (Figures 2(a) and 2(b)). The patient underwent emergency laparotomy with total abdominal hysterectomy, bilateral salpingo-oophorectomy, infracolic omentectomy, and appendectomy. The cyst had a small leak, and 3.5 L of fluid was drained from the cyst and sent for histology (Figure 3(a)). A further 200 ml of ascitic fluid was collected. Inflammatory changes on the surface of the pelvis, and multiple inflammatory deposits overlying small bowel mesentery were noted (Figure 3(b)). Histology of the cyst showed a benign mucinous cystadenoma. The uterus, ovarian cyst, omentum, and appendix contained florid granulomatous inflammation and caseous necrosis. Peritoneal fluid cultured Mycobacterium tuberculosis. A chest CT confirmed lymph node calcification consistent with previous tuberculosis, with no evidence of active infection. Her postoperative recovery was uneventful, and she was commenced on isoniazid, rifampicin, ethambutol, and pyrazinamide under guidance of the Infectious Disease team. The patient remained well at a recent 3-month follow-up.

PMC5328352_01

Male

In April 2013, in Northern Norway, a 24 year-old Caucasian healthy male soldier participated in a qualifying ski march to become a combat officer in the Norwegian Defence Forces. He was wearing full winter protection gear including wind protectors over his gloves. Earlier that day the weather conditions were fine with an air temperature around -5 C and a light southerly breeze. During the ski march, he felt warm and took of his gloves. The weather deteriorated rapidly in the afternoon. Air temperatures dropped to around -15 C and a forceful wind was now blowing towards his right side. Although he noticed a chilling of his hands from the wind, he still felt subjectively warm. After approximately 90 minutes, he decided to put on his gloves again and noticed that the skin of his hands had turned a blue-grey colour. His fingers felt numb with loss of finger dexterity. Having put on his gloves, he continued marching. After 2 hours, he felt a burning pain in his hands and noticed that the fingers were swollen and that blisters had developed on his fingers, especially on the right hand side. Strongly motivated to pass the test, he did not seek medical attention and continued the march. His fingers became more painful and he felt loss of sensation. After the exercise, he was diagnosed with second-degree frostbite injuries to his hands and was treated conservatively. The blisters were covered with paraffin gauze and a dry bulky dressing was applied. The wound dressings were continued until the wounds had healed. Due to cold hypersensitivity and pain when exposed to even a mild cold challenge, he was assigned to indoor duties. In 2014, he wanted to qualify for a higher rank in a combat group. The training for this takes place in Northern Norway with more than 6 months of winter during which temperatures may reach -40 C. In the autumn of 2014 he reported that his fingers still became rapidly cold, pale and totally numb as soon they were exposed to cold, even at a temperature of +5 C. He felt a constant pain and loss of sensation in his fingers resulting in reduced finger dexterity. He was deemed unfit for outdoor military service and had to leave the combat unit. In May 2015, he was referred to the outpatient clinic for Plastic Surgery at the University Hospital North Norway. He was diagnosed with sequelae from frostbite. To exclude other pathological conditions further investigations were carried out. Angiography of the upper extremities showed open arteries on the lower arms, but all digital arteries were described as very thin with no dilatation after heat stimulation or hand/finger movements. No other pathology was found. Dynamic Infrared Thermography (DIRT) was performed to test the patient's response to a cold challenge. This involved measuring the skin temperature of the dorsal aspect of both hands before, immediately after and for 3 minutes following a mild cold challenge (1 min. immersion of the hand in water at 20 C). During the immersion, each hand was covered by a thin plastic bag to avoid it becoming wet. The skin temperatures were measured with a high definition infrared camera. The patient was wearing outdoor winter clothing to stimulate peripheral vasodilation. Prior to the cold challenge, the patient reported that he felt warm. Additional obtained facial thermographic images showed the nose was vaso-dilated, presumably due to open arterio-venous anastomoses. DIRT showed a rapid onset of cooling and slow rewarming of the fingers after the cold challenge, similar to the slow warming subjects reported by Brandstrom. However, in our patient we performed a mild cold challenge, resulting in a clear difference between the right and left hand, the right hand being cooler. Quantitative Sensory Testing (QST) indicated a loss of function with regard to non-painful stimuli in the mechanical and thermal domain (cold-, mechanical-, and vibration detection threshold). These findings corresponded well with the patients' symptoms, namely loss of sensation in his fingers and reduced finger dexterity. The soldier was interested in receiving treatment. He was informed on the off label use of BTX-A to treat vasospastic disorders and nociceptive/neuropathic pain disorders. He consented to a treatment with BTX-A. Each 100 unit vial of BTX-A (Allergan, Inc. Irvine, CA) was prepared in a standard manner with a concentration of 40 units/ml. The injections were administered at the neurovascular bundles in the palm of each hand at the level of the metacarpophalangeal joints (60 Units BTX-A per hand). This resulted in a dose of 12 units of BTX-A just at or proximal to the annular pulley A1 of the flexor tendon sheath of each finger. At 3 weeks follow up the patient reported that he had less pain, warmer hands and improved sensory function, based on his own subjective evaluation. In November 2015, during the winter period, the patient reported improved cold tolerance and was able to perform normal outdoor activities. Angiography, DIRT and QST were repeated and the results were compared to the pre-treatment results. Angiography showed that the digital arteries were more dilated and more clearly visible (Figure 1). DIRT showed rapid and improved rewarming of all fingers compared to the pre-treatment examination although the rewarming of the right hand was still a bit slower compared to the left hand at all time points during the examinations (Figure 2). QST showed a normalisation of sensory function apart from a marginal reduction of the ability to detect vibration (Figure 3). Based on the encouraging results it was agreed to repeat the treatment. The same procedure with the same dose of BTX-A of 60 U (40U/per ml) per hand was used as during the first treatment. At 6 weeks follow-up in January 2016, the patient reported even further improvement. The only side effect of both BTX-A treatments was a temporary weakness of the intrinsic muscles of each hand, the lumbrical and interosseous muscles to the 2-5 finger and the flexor pollicis breves, the opponents and adductor muscles of the thumb. This transitional weakness lasted about 3 weeks.

frostbite, angiography, army, botulinum toxin, cold injury, military, non-freezing cold injury, quantitative sensory testing, thermography, vasospastic disorder

PMC3090634_01

Male

A 40-year-old man of Albanian descent, living in Athens the last 20 years, was admitted on February 2008. His symptoms began one year prior to admission with dry cough and gradual weight loss of a total of 30 kg. Night sweats and scant hemoptysis appeared the last month. A limited workup 6 months ago had revealed the presence of chronic active hepatitis B. The patient was working in a restaurant, was a nonsmoker, and had no other remarkable medical history. Clinical examination revealed cachexia, hepatosplenomegaly, and small, discrete, and nontender axillary and cervical lymph nodes. There were no clinical signs of liver failure or portal hypertension such as jaundice, palmar erythema, spider nevi, encephalopathy, or ascites. Laboratory tests showed pancytopenia, elevated hepatic aminotransferases (3-4 times the upper limit) and polyclonal hypergammaglobulinemia. Erythrocyte Sedimentation Rate was 100 mm/h. Serum albumin, bilirubin and prothrombin time, were within normal limits. HIV was tested negative by ELISA twice by three months apart. Antibodies against Hepatitis C virus were negative as well. An abdominal ultrasound revealed increased dimensions of the liver and spleen and the presence of enlarged lymph nodes at the hepatic hilum. Diameter and flow through the portal vein were normal, and no ascites was detected. A Computerized Tomography scan of the chest revealed limited adenopathy; a 2 x 1 cm mass at the right hilum, and a 1.2 cm right lower paratracheal lymph node with hypodense centre. On bronchoscopy, epistaxis and pharyngeal inflammation consistent with candidiasis were noticed. There was mild diffuse redness throughout the tracheobronchial tree. Inflammation was more prominent on the medial aspect of the bronchus intermedius extending into the middle lobe bronchus. Interestingly, a discreet mucosal polypoid lesion was observed on the middle lobe carina (Figure 1). Bronchial biopsies taken from this lesion revealed epithelial hyperplasia and several Leishmania amastigotes within histiocytes (Figures 2(a) and 2(b)). Transbronchial needle biopsies (TBNB) targeted at the right lower paratracheal lymph node also revealed histiocytes containing abundant Leishmania amastigotes (Figure 3). A bone marrow biopsy was also positive for Leishmania amastigotes, as was a liver biopsy. In the latter, there was considerable hepatic inflammation, attributed to both Leishmania and HBV infection, along with minimal fibrosis but not cirrhosis. Fluorescent antibodies against Leishmania were positive in high titers of >=1/640. The patient was treated with IV liposomal Amphotericin B with prompt clinical and laboratory improvement. Six months later, white blood cell count and differential, lymphocyte subpopulations, and immunoglobulin levels were within normal limits. Due to the persistence of increased hepatic aminotransferases (1.5 times the upper limit) the patient began treatment with telbivudine. On the first and second year follow up, the patient remained in excellent clinical condition and had normal laboratory values.

PMC6854222_01

Male

A 53-year-old Sri Lankan male with a background history of diabetes and hypertension for 14 years presented with left side (non dominant) isolated hand swelling for a 7-month duration. Its progressive enlargement was associated with pain and restriction of movements. There were no other small or large joint symptoms. He did not have episodes of fever, and he maintained good physical well-being in terms of appetite and weight. He did not give any past history of chronic productive cough, pulmonary tuberculosis, or any contact history. On examination, there was a swelling near the wrist joint and carpal region both volar and dorsal aspects (Figure 1). The area was not warm, and mild tenderness was elicited. Flexion extension and circumduction movements were reduced. Distal neurovascular examination was unremarkable. His ESR was 98 mm/hr with full blood count and other biochemical investigations within the normal range. Initial digital X-ray of the hand showed destructive type lytic lesions involving mainly the carpal bones and bases of the 2nd to 5th metacarpals with sparing of the radiocarpal and distal radioulnar joints (Figure 2). His chest X-ray was normal. He underwent a magnetic resonance (MR) scan of the hand which showed multiple destructive lesions in the carpal bones, surrounding focal fluid collections with narrowing of the intercarpal and carpometacarpal joints (Figure 3). Flexor muscle tendons were intact. Upon initial assessment with basic investigations and imaging, a conclusive diagnosis was not achieved. A decision was made to go ahead with a synovial biopsy, and an intraoperative caseous material was noted. After the new finding, other investigations in relation to caseous necrosis were carried out. His Mantoux test was positive with 12 mm of induration. Serological assessment for melioidosis was negative. Histology sample showed multiple Langhans type of giant cell associated with caseating granulomas, and the Xpert MTB/RIF test was positive. He was started on antituberculosis treatment with hand physiotherapy and occupational therapy. He was improved in terms of pain and swelling with antituberculosis treatment without any significant side effects of the treatment, and his culture was also positive for Mycobacterium tuberculosis.

PMC517508_01

Male

A 29-year-old previously healthy immigrant male patient from Kazakhstan was admitted to hospital with new-onset severe hemoptysis, macroscopic hematuria and extensive cutaneous petechiae on lower extremities. He appeared ill and poorly nourished. The patient was oriented and well cooperated, and there was no previous history of hematologic or liver or another disease and recent medication. He presented with unexplained weight loss of 2 months duration along with intermittent fever, night sweats and cough. The physical examination revealed a blood pressure of 100/70 mm/Hg, pulse 100/min, a temperature 37.2 C, extensive cutaneous petechiae on lower extremities, hemorrhagic bulla on tongue and on mucosa of oral cavity, and amphoric souffle on apex of right chest. No organomegaly or lymphadenomegaly or evidence of another disease such as chronic liver disease was detectable. The initial complete blood count revealed a white blood cell 25.1 x 109/l (58% neutrophils, 29% bants, 9% lymphocytes and 4% monocytes), hemoglobin 11.2 gr/dl, hematocrit 36%, MCV 84 fl, reticulocytes 1% and platelet count 7.6 x 109/l. Erythrocyte sedimentation rate was 110 mm/h. A peripheral smear was remarkable for a paucity of platelets. Coagulation profile [prothrombin time (PT), activated-partial thromboplastin time (aPTT), fibrin degradation products (FDP)] were normal. A bone marrow aspiration demonstrated hypercellularity of all cell lines with normal maturation of myeloid and erythroid precursors. Megakaryocytes were increased in number with normal morphology. On bone marrow aspiration hemophagocytosis was not observed. A chest X-ray (Figure 1) and computed tomography (CT) (Figure 2) demonstrated bilateral patchy infiltrates and walled cavities on left and right upper lobes. Acid-fast bacilli were strongly positive in sputum (Figure 3). Bone marrow aspirate and urine for acid-fast bacilli were negative. Sputum culture yielded mycobacterium tuberculosis complex. The following laboratory studies were normal or negative: biochemical tests (glucose, urea, creatinine, uric acid, sodium, potassium, calcium, chloride, phosphorus, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, bilirubin, total protein and albumin), rheumatoid factor, anti-nuclear antibody, anti-platelet specific antibodies, Coomb's tests, HIV, hepatitis B and C virus, blood culture, bone marrow aspirate culture and abdominopelvic CT. No granuloma or hemophagocytosis was detected on bone marrow biopsy. The patient was started on rifampin 10 mg/kg/d, isoniazid 5 mg/kg/d, ethambutol 25 mg/kg/d, pyrazinamide 40 mg/kg/d, pyridoxine 75 mg/d and intravenous immune globulin (IVIg) 1 g/kg/d given for 2 days. On day 2 of hospitalization and treatment of anti-tuberculous therapy prednisolone 1 mg/kg/d was added. On day 8, platelet counts started to increase and on day 12 of the treatment it reached to 187 x 109/l level. Patient improved on day 10 and he did not have any complaints on day 14; at time of discharge. He received a total of 6 red blood cell (RBC) units throughout hospitalization. During his hospitalization findings of hemolysis or gastrointestinal bleeding and massive bleeding in another site except hematuria and hemoptysis were not established. A complete blood count at discharge demonstrated a WBC 17 x 109/l, Hb 9.6 g/dl, and platelet count 310 x 109/l (Table 1). Corticosteroids were discontinued on day 14 of therapy and the patient was discharged and recurrent thrombocytopenia was not established after withdrawal of corticosteroid therapy. Ninety days after discharge, the patient was well with a platelet count of 300 x 109/l (Table 1) and he had no side effect thought to be secondary to anti-tuberculous drugs.

CT showing cavitary lesions in both lungs.

PMC6968688_01

Male

A fully functional 90-year-old Hispanic male presented to the emergency department with 1 day of nausea and vomiting. He had non-radiating, periumbilical and upper abdominal pain with non-bilious, non-bloody emesis. He has no blood or coffee-ground material in his vomitus. He denied any diarrhea or constipation. He had been unable to tolerate oral intake of any amount or consistency. These symptoms occurred acutely without any notable inciting factors. He denied subjective fevers, night sweats, or subjective weight loss, but had a recorded five pounds weight loss over 1 month. He had a good appetite prior to the onset of his symptoms, but he had been unable to eat or drink due to nausea and vomiting. The patient has a past medical history of coronary artery disease, hypertension, hyperlipidemia, aortic regurgitation, mitral regurgitation, hypothyroidism, asthma, and pre-diabetes. He has a family history of thyroid disease, but he does not have a family history of cancers. He denies tobacco, alcohol, or recreational drug use. On presentation, his vital signs were within normal limits. On examination, he appeared lean and comfortable without evidence of distress or diaphoresis. He was alert and oriented to person, time, and place. His heart and lung exams were unremarkable. He had a soft abdomen with normoactive bowel sounds and mild tenderness to palpation of his periumbilical region and bilateral upper quadrants of his abdomen. He has no rebound tenderness and no guarding. His lower extremities had 2+ pitting edema to the mid-calves. Laboratory testing revealed no significant abnormalities on basic metabolic panel, complete blood count, and thyroid function panel. His CT of the abdomen and pelvis with intravenous contrast showed a mild ileus with diffuse wall thickening, edema and mucosal thickening of small bowel loops and colon concerning for enterocolitis, significant diverticulosis, and moderate ascites. He was started on intravenous piperacillin-tazobactam and metronidazole with some improvement in symptoms, and he was able to tolerate oral intake with decreased emesis. He was discharged on oral ciprofloxacin and metronidazole, but returned to the hospital the same day and was readmitted hours later for recurrent symptoms. The patient was started on several antiemetics, including scheduled ondansetron and prochlorperazine with as needed metoclopramide, trimethobenzamide, and promethazine for symptomatic control. Despite that, he was still unable to tolerate any oral intake and continued to have nausea and vomiting of clear-yellow fluid and feeding materials without hematemesis and coffee-ground contents. Gastroenterology consultation was obtained on hospital day three. It was thought that he most likely had viral gastroenteritis. The team therefore discontinued antibiotics and monitored him clinically. By hospital day 5, the patient showed no improvement, and a repeat CT of the abdomen and pelvis with intravenous contrast was performed, which showed persistent gastric antral wall thickening and narrowed lumen suspicious for gastric malignancy, diffuse omental infiltration, and concerns for linitis plastica (Figure 1). He subsequently underwent esophagogastroduodenoscopy (EGD), which showed severe reflux esophagitis from recurrent emesis, a 2-cm hiatal hernia, delayed gastric emptying, extrinsic compression on lesser curvature of stomach, and white nummular lesions in the gastric antrum. Biopsy of the stomach was performed, which later showed no malignant cells. Serial abdominal x-ray found no obstruction. The patient's hospital course was complicated by intermittent, self-limiting fevers, and his vomiting progressed to copious bilious emesis. Blood culture, urinalysis, and chest x-ray showed no source of infection. An abdominal ultrasound showed no biliary obstruction or cirrhosis but again demonstrated ascites. Due to his fever and ascites, paracentesis was performed to evaluate for spontaneous bacterial peritonitis. His ascites fluid analysis was unremarkable for infection, with a serum-ascites albumin gradient of 0.4 g/dL and total protein of ascitic fluid of 3.2 g/dL, which was concerning for either tuberculosis or peritoneal carcinomatosis. His ascites fluid, however, did not show any organisms on acid-fast bacilli smear and culture and had no malignant cells on cytological analysis. His clinical status continued to decline, with ongoing emesis and inability to have oral intake. A nasogastric tube was placed for enteral feeding, which was intermittently held due to ongoing emesis that occurred shortly after being on enteral feeds. CT enterography demonstrates progressive dilatation of the second and third duodenal segments with transition to a nondilated, thick-walled distal fourth duodenal and jejunal segments suspicious for possible primary bowel malignancy. Along with the multifocal liver lesions, moderate ascites, and distinctive reticular infiltration of the omentum also seen on CT, this was highly suggestive of enteropathic non-Hodgkin's lymphoma (Figure 2). Given the rapid progression over a period of 3 weeks, however, these findings were thought to be more consistent with an infectious or inflammatory process rather than an aggressive neoplastic process with metastasis. Repeat esophagogastroduodenoscopy with push enteroscopy showed Grade D esophagitis, gastritis, and jejunal inflammation with edema and erythema (Figure 3). The obtained biopsy from this procedure demonstrated a transition from normal jejunal mucosa to pathologically-involved and distorted mucosa, which was characterized by diffuse infiltrate of large neoplastic cells with highly irregular nuclei, moderate amount of cytoplasm, and centroblastic morphology. Immunohistochemistry identified sheets of B cells expressing CD45, CD20, CD79a, and BCL6 (subset), but not CD10, MUM1, CD138, cyclin D1, and cytokeratin AE1/AE3. This therefore affirmed the diagnosis of DLBCL, specifically the germinal center B cell type based on the Hans algorithm. The proliferation index (Ki-67) was approximately 90% (Figure 4). Due to the patient's continued emesis, he developed a fever and was found to have aspiration pneumonia on chest x-ray. He was treated with a 7-day course of ampicillin-sulbactam and was started on partial parenteral nutrition. Palliative care and hematology/oncology consultation services were involved in his care. After a discussion with the patient and his family, it was decided that due to his poor nutritional status and deconditioned state, he would not pursue aggressive therapies such as surgery or chemotherapy. The patient received a peripherally inserted central catheter for total parenteral nutrition on hospital day 24 and was discharged the following day for home hospice. He did not receive any follow-up after discharge and eventually expired.

non-hodgkin’s lymphoma, extranodal diffuse large b cell lymphoma, gastrointestinal lymphoma

PMC8053430_01

Female

A 36-year-old right-handed woman presented with a few days' history of cough, diarrhea, and fever. Medical history was significant for hypertension and polycystic ovary syndrome, for which the patient took anti-hypertensive medications and oral contraceptives. A nasopharyngeal swab showed that the patient was positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The patient was prescribed Azithromycin and sent home to quarantine. On the 8th day of home quarantine, the patient was found to have right-sided weakness and facial droop and was brought to the emergency department 8 h post-ictus. She had sustained wakefulness and was able to localize to pain, and her pupils were equal and briskly reactive to light. She also had hemiplegia and right central facial palsy. The NIHSS score was 25. Cranial CT scan showed a hypodensity at the left ICA territory without midline shift and an Alberta Stroke Program Early CT Score of 0 [Figure 1]. She was admitted to the ICU and started on medical decompression. Admission D-dimer and C-reactive protein (CRP) were elevated. A 24-h monitoring CT scan showed an increased degree of hypodensity in the left ICA distribution, as well as a midline shift of 7.3 mm. In view of this finding, DH was recommended, but there was no consent. Shortly after, the patient was found to have tachycardia, labored breathing, and decrease in sensorium. She was only able to open her eyes to painful stimuli and withdraw to pain, and her left pupil became dilated. She was intubated, and then brought to the operating room for DH after consent was secured. Postoperatively, the patient's sensorium improved, and she was able to open her eyes to speech and localize to pain. The anisocoria was reversed. However, the patient continued to have fever, tachycardia, and tachypnea despite ventilatory support. Chest radiograph showed bilateral pneumonia with consolidation. The levels of the inflammatory markers D-dimer and CRP were higher than on admission, and ferritin and LDH levels were elevated as well. After 2 weeks, a repeat nasopharyngeal swab showed that the patient was negative for SARS-CoV-2. A tracheostomy was performed. Over the course of her ICU stay, the patient also developed ventilator-associated Acinetobacter baumannii pneumonia and pulmonary tuberculosis. She had persistent desaturation and hypoxia, making it difficult to wean her off ventilatory support. The patient succumbed to chronic respiratory failure 25 days post-ictus.

acute ischemic stroke, coronavirus disease 2019 infection, decompressive hemicraniectomy, infarct, severe acute respiratory syndrome coronavirus 2

PMC8138197_01

Male

A healthy 30-year-old man with a history of prior PKP for hereditary corneal dystrophy performed 12 months before in another institution, presented to our ophthalmological emergency office with an open globe following accidental contusive trauma with a ball, while he was playing football. The double running corneal suture was removed 7 days before the trauma occurrence. At slit-lamp evaluation, complete dehiscence of the wound at the graft-host junction and complete corneal button loss was evident, with partial uveal tissue and vitreous protrusion, and traumatic aphakia. At that time, the donor button was not found. The patient was provided with comprehensive counselling preoperatively. The patient was then immediately taken to the operating room, but a donor cornea was not available since it was night and the local eye bank was closed. A Wide-Field Landers temporary kerato-prosthesis (Ocular Instruments, Bellevue, WA, USA) was then applied after uveal tissue repositioning and anterior vitrectomy. The patient was examined the day after (shown in Fig. 1a, b), and through the temporary kerato-prosthesis, it was possible to partially explore the retina, which appeared adherent as far as it was possible to visualize. The same day a new donor button was available, and we proceeded to remove the temporary kerato-prosthesis and applied a full-thickness corneal graft of 8.50 mm sutured with 16 detached 10-0 nylon stitches while maintaining a constant 23-gauge pars plana infusion throughout the surgery. Meanwhile, the old corneal graft was found attached to a patient's shoe.

corneal button loss, temporary kerato-prosthesis, trauma

PMC6838525_01

Female

The patient is a 56-year-old female who visited the primary care clinic to request a Mantoux or tuberculin skin test (TST), a test that required to update her nursing school file. She is in perfect health condition, with no symptoms or complaints of any sort. She was born in Cuba, where she was vaccinated with the Bacillus Calmette-Guerin (BCG) at birth. She migrated to the United States three years ago. The patient denied having any history of or being in close contacts with anyone with tuberculosis disease or a chronic cough. She does not have a cough, night-time fever, fatigue or chills, working or residing in facilities or institutions with people who are at high risk for TB such as hospitals that care for TB patients, homeless shelters, correctional facilities, nursing homes, or residential facilities for patients with HIV infection/AIDS. She also denied having any previous or current diagnosis of silicosis, diabetes mellitus, chronic renal failure or on hemodialysis, gastrectomy, jejunoileal bypass, solid organ transplant, or head cancer. The urine drug test was negative (Center for Disease Control and Prevention USA). Her past medical history is unremarkable except for a history of papillary thyroid cancer. Her thyroid was removed via 131 radioactive iodides (thyroid ablation) 35 years ago. Since then she has been taking thyroxin replacements (Thyroxin-T4; 100 mug) once/day. She also suffers from gastroesophageal reflux and is on Omeprazole 1 capsule/day for over seven years now. In 2017 she had a gastroscopy, and a colonoscopy performed that revealed standard results. She had a hysterectomy 16 years ago due to massive intramural fibroids. She does not drink or smoke. She has no history of any allergies and is not known to be on any habit-forming medications. She is a very highly educated lady who lives with family members. Her father died 31 years ago from liver cancer and her mother two years ago from a thrombotic stroke. She is the last of four living siblings, all in good health conditions. Her current physical examination was satisfactory. She is in no form of distress. She has normal vital signs with a bodyweight of 162 pounds. Her laboratory results such as full blood count, urea, electrolytes, and liver function tests are unremarkable. Her chest X-Ray reveals standard cardiac size and configuration. The lungs are clear and expanded. She has no active disease and no radiographic evidence of active or prior primary tuberculosis. Quantiferon Gold test was negative three years ago, and this year was still negative. The tuberculin skin test (TST) done this year was positive. The diameter of the skin induration was 15 mm (Fig. 1).

bacillus calmette-guerin, gold, isoniazid, mantoux test, purified protein derivative, quantiferon, tuberculin skin test, tuberculosis

PMC9487515_01

Male

In November 2014, a 30-year-old male wheelchair athlete (ID: BL) with SCI classified as ASIA C contacted our university and asked for support regarding his athletic orientation toward paratriathlon (Figure 1). BL had participated in professional wheelchair basketball for a decade and had already finished several triathlons including national championships. He wanted to have guidance in sport-specific training and testing to achieve his ultimate goal: participating in the Paralympic Games in either Rio de Janeiro (2016) or Tokyo (2020). The athlete gave written informed consent to take part in this study. Standardized guidelines for reporting were used (refer to Supplementary Material 1). From 1990 to 2003, BL participated in motocross races. In March 2003, at the age of 18 years, he was involved in a quad bike accident that caused lumbar spine compression (ICD10-S32.01), kidney contusion (ICD10-S37.01), and incomplete paraplegia (ICD10-S34.71) with neurogenic bladder dysfunction (ICD10-N31.1) that required the permanent use of a wheelchair (ICD10-Z99.3). Immediate surgery stabilized the spine by internal fixation of the thoracolumbar junction. BL received physiotherapy, ergotherapy, and medical care during acute rehabilitation up to June 2004. He started wheelchair basketball soon after rehabilitation and played for several teams at the national level. Regular medical check-ups remained unsuspicious. In August 2013, he participated in his first sprint-distance paratriathlon.

trimp, case report, chronic myeloid leukemia (cml), paratriathlon, performance, srpe, spinal cord injury (sci), training

PMC5744188_01

Female

The 56-year-old patient was diagnosed with CIDP in 1999 with a typical manifestation consisting of distal and proximal weakness and sensory dysfunction of all extremities. The clinical evaluation revealed generally absent deep tendon reflexes, distal and proximal weakness, large fiber sensory involvement, and a tremor of the right arm. Nerve conduction studies revealed primary demyelinating neuropathy (Table 1). She had suffered from tuberculosis infection 1965, 1974, and 1978. In 2002, she was diagnosed with breast cancer treated by tamoxifen. The patient received intravenous immunoglobulins (IVIG) treatment since 2004 with a dosage of 50 g at 4-10 weeks of treatment intervals (0.77 g/kg body weight) and was clinically stable for more than 10 years. In 2014, she subacutely developed progressive vertigo and a tendency to fall to the right side combined with nausea. In addition, she suffered from increasing problems with walking and climbing stairs. Clinical examination revealed a clear deterioration of the paresis but no nystagmus or other signs for vestibular involvement. Ear-nose-throat examination was without pathological finding. MRI demonstrated a right-sided pontocerebellar lesion adjacent to the upper cerebellar peduncle with incomplete peripheral enhancement. There was no concurrent pathological meningeal enhancement (Figure 1A). As differential diagnosis tuberculoma, metastasis, sarcoidosis, MS, as well as central manifestation of CIDP were discussed and further diagnostic tests were performed. For that, CSF showed mild pleocytosis (seven cells) and elevated protein (136 mg/dl) with normal lactate levels, negative oligoclonal bands (OCB) without evidence for infection. Borrelia screening was negative. CT scan of the thorax showed two old, unchanged calcified granulomas in the left upper field of lung compatible with previous tuberculosis infection, there were no signs of lymphadenopathy. In addition, extensive tests revealed no sign for recurrence of breast carcinoma. Importantly, before the patient developed the clinical manifestation of the brainstem symptoms we had demonstrated positive NF155- (mean 17.5 IFN-gamma spots/106 MNCs) as well as NF186-specific T cell response (28.33 IFN-gamma spots/106 MNCs) compared to CEF peptide pool specific IFN-gamma response (1,062 IFN-gamma spots/106 MNCs) by ELISPOT assay (Figure 1B). In comparison, 16 patients with non-immune neuropathy revealed no NF155 (mean 0.5 IFN-gamma spots/106 MNCs) and NF186 (mean 0 IFN-gamma spots/106 MNCs) with CEF peptide pool specific IFN-gamma response (519 IFN-gamma spots/106 MNCs). Interestingly, NF155 as well as NF186 antibodies measured by ELISA according to the protocol of Ng et al. were negative. In the synopsis of all findings, we diagnosed a subacute central manifestation of CIDP and escalated the immunomodulatory treatment by increasing the dosage of IVIG up to 2 g/kg body weight once followed by 1.4 g/kg BW. The patient recovered over 6 months reaching complete remission state of vertigo and improvement of gait ataxia. Follow-up MRI scan 18 months later revealed a new, non-enhancing lesion within the middle cerebellar peduncle and the adjacent pons, the previously diagnosed lesion was not did no longer show gadolinium enhancement (Figure 1C). A follow-up Elispot assay did not show NF-specific T cell response any more (0 IFN-gamma spots/106 MNCs), while the IFN-gamma response against the CEF control peptide pool was also reduced (mean 169 IFN-gamma spots/106 MNCs; Figure 1D). NF-specific antibodies remained negative. Follow-up CSF remained unchanged with a mild pleocytosis and elevated protein (129 mg/dl) without OCB.

ccpd, cidp, atypical, neurofascin, neurofascin 155

PMC6039750_01

Male

A 59-year-old man who appeared healthy without any underlying disease, visited our hospital with a cough and sputum that had persisted for more than a month. The patient had undergone chest computed tomography (CT) after abnormal findings on chest X-ray at another hospital. Based on the chest CT results, he was diagnosed with pneumonia in the right upper lobe and was admitted to that hospital. He was treated with intravenous injections of third-generation cephalosporin antibiotics for 3 weeks. However, after the treatment, there was no improvement in the lesion. Hence, he was transferred to our hospital. He had a 40-pack-years smoking history and no family history. He also had a working history of iron welding in the preceding 5 months. He was alert, and the following findings were noted in the physical examinations upon admission: blood pressure, 140/70 mmHg; pulse rate, 85 beats per minute; respiratory rate, 20 breaths per minute; and body temperature, 36.8 C. He had a chronically ill appearance. His conjunctiva was not anemic and his sclera was not icteric. Clear breathing sounds were auscultated on both lung fields and his heartbeats were regular without murmur upon auscultation. The other examination results were also within normal limits. The following were the results of a laboratory examination: hemoglobin and hematocrit levels, normal; white blood cell count, 11,670/muL: differential count, 52.4% neutrophils, 31.7% lymphocytes, 12.5% monocytes, and 3.2% eosinophils; platelet count 292 x 109/L; C-reactive protein levels, slightly elevated at 32 mg/L (normal range 0-5 mg/L); serum ferritin levels, 151.4 mug/L (normal range 30-400 mug/L); serum transferrin saturation levels 31.1% (normal range 20-50% in males); and renal and liver function tests, normal. Arterial blood examination while breathing room air showed a blood pH of 7.44, a PaO2 of 71.0 mmHg, a PaCO2 of 36.7 mmHg, and HCO3 of 24.7 mM/L, with 96% oxygen saturation. Pulmonary function studies revealed results within a normal range. Forced vital capacity (FVC) of 4.19 liters (96% of predicted) and forced expiratory volume-one second (FEV1) of 3.16 liters (102% of predicted) were observed. To examine the possible source of infection, he underwent recurrent sputum analysis. However, the bacterial, viral, fungal and acid fast bacilli cultures from sputum were all negative. Three months before admission, he had undergone a chest X-ray at our hospital. At that time, his chest X-ray showed normal images. When he was admitted, his chest X-ray showed a pattern of consolidation in the right upper lung field (Fig. 1). A CT scan of the chest showed peribronchial distribution with peripheral segmental air-space consolidation in the right upper posterior segment, and small ill-defined nodules. It also showed centrilobular emphysema in both the upper and mid-lung zones. The air space consolidation on right upper lung field was increased compared with previous study results (Fig. 2). Bronchoscopy was performed 3 days after admission and there was no endobronchial lesion observed. Bronchial washing was performed in the right upper lobe and bronchoalveolar lavage (BAL) was performed in the right middle lobe. Retrieved lavage fluid volume was 60ml (31%). Cytospin examination showed 4% neutrophils, 6% lymphocytes, 88% alveolar cells, and 2% eosinophils. Photomicrographic findings after bronchoalveolar lavage revealed many alveolar macrophage-containing iron particles. The intracellular iron particles were markedly positive upon Prussian blue staining (x 1000) (Fig. 3). Moreover, no malignant cells were observed. Acid-fast bacilli cultures and smears, tuberculosis detection PCR, bacterial detection Gram stain and cultures, and bronchoalveolar lavage fluid fungus cultures also presented negative results. We did not measure the ferritin levels in bronchoalveolar lavage fluid. CT-guided trans thoracic needle biopsy was performed for histological confirmation. The biopsy specimen also showed alveolar, macrophage-containing, Prussian blue-positive iron particles in the alveolar space (Fig. 4). No evidence of vasculitis and malignancy was observed in the histological examination. Serum ANCA levels were also measured and confirmed to be negative. Based on the patient's occupational exposure history and test results, the diagnosis of pulmonary siderosis (welder's lungs) was confirmed. Subsequently, we advised him to discontinue his job and discharged him from the hospital. No specific treatment was administered and only medications to control symptoms were prescribed. One month later, we performed bronchoalveolar lavage again. Two months later, a chest X-ray was performed in the outpatient clinic. The consolidation lesion observed in the right upper lobe had slightly improved (Fig. 1). The patient is currently undergoing observation, and has not shown any special symptoms.

bronchoalveolar lavage, pulmonary siderosis, transthoracic lung biopsy

PMC6942715_01

Male

A 72-year-old man was addressed to the nephrology department for acute kidney injury with increased creatininemia at 2.2 mg/dL (N: 0.72-1.17) corresponding to an estimated glomerular filtration rate (eGFR) of 30 mL/min/1.73 m2 according to the CKD-EPI formula. He was asymptomatic. He had no personal or family history of kidney disease. He did not travel, had no allergies, and had no known contact with ill patients. He was not taking any nonsteroidal anti-inflammatory drugs. His medical history comprised of pleural tuberculosis treated 20 years before, well controlled hypertension under treatment with calcium antagonists and glaucoma treated by monthly intravitreal injections of bevacizumab in the past 6 months. Physical examination and blood pressure were normal. There was no swelling. Laboratory investigations did not show any sign of TMA, with normal haemoglobin and platelet count. Immunological testing was positive only for antiphospholipid antibodies. Infectious serology was negative. The urinalysis showed no haematuria but increase of albuminuria from 2.9 to 226 mg/g of creatinine (N: <30). Urine cultures were negative. Kidney ultrasound was normal. A renal biopsy performed two weeks after showed ten glomeruli. Two of them were obsolescent glomeruli with complete glomerulosclerosis. The other glomeruli demonstrated thickening of capillary wall (Figure 1(a)). There were segmental glomerular capillary microaneurysms, filled with pale material, and segmental hyaline thickening of the glomerular basement membrane (Figure 1(b)). Silver staining showed some double contours (Figure 1(c)). Mild focal interstitial fibrosis and tubular atrophy with a mononuclear cells infiltrate were seen. Immunofluorescence for IgA, IgG, IgM, C1q, kappa, and lambda was negative. However, C3 immunofluorescence showed a sparse endothelial positivity in arterioles (not shown). On electron microscopy, the endothelial cells showed irregularities, and focal loss of fenestrations. Subendothelial space expansion by electron-lucent material was visible (Figure 1(d)). This was consistent with signs of endothelial injury. Intravitreal injections of anti-VEGF were suspended. Four months after withdrawal, serum creatinine was of 1.20 mg/dL, and albuminuria normalized, supporting our hypothesis of intravitreal anti-VEGF induced renal microangiopathy. One year after bevacizumab was stopped, serum creatinine was of 0.95 mg/dL, and urinary albumin-creatinine ratio was of 3.3 mg/g. The patient did not present any thromboembolic event.

PMC3253394_01

Male

A 70-year-old male was treated with conservative management for a minor case of hemoptysis. However, massive hemoptysis (about 500 mL/24 hours) and hypoxemia occurred and the patient deteriorated. The patient had a history of pulmonary tuberculosis about 30 years prior, had suffered from congestive heart failure with arrhythmia for ten years, and had been treated for upper thoracic tuberculous spondylitis with posterior spinal fusion for the last 15 days. A chest radiograph revealed severe destructive changes of both upper lobes, secondary emphysematous changes of both lower lobes and recent development of bilateral consolidations due to aspirated blood. Embolization treatment was performed with a 5-Fr catheter and a coaxial 2.5-Fr microcatheter (Renegade; Boston Scientific, Watertown, MA) for both bronchial and other possible systemic arteries with polyvinyl alcohol (PVA) particles, 350-500 microm in diameter (Contour; Boston Scientific, Watertown, MA) and microcoils (Tornado embolization microcoil: Cook, Bloomington, IN). Two days later, the patient suffered massive hemoptysis. No evidence of recanalization of previously embolized arteries on angiography was found and additional embolization of both upper lobar pulmonary arteries was performed, because radiologically undetectable pulmonary artery bleeding was suspected. However, the patient continued to suffer from hemoptysis. On the third trial of angiography, five hours after the second embolization, coronary angiography showed a CBF (proximal left circumflex arterial branch) from the left circumflex coronary artery to the left bronchial artery combined with a severe pulmonary artery shunt at the left upper lung. The CBF was embolized after superselection across the CBF to prevent embolization of the coronary artery (Fig. 1). Hemoptysis was stopped immediately after the third embolization but the patient died 12 hours later due to further deterioration of hypoxemia despite intensive ventilator care.

bronchial artery, coronary artery, embolization, hemoptysis, pulmonary tuberculosis

PMC3253394_02

Male

A 57-year-old male arrived at the emergency room due to cardiac arrest. He had a history of diabetes and pneumonia six and two years prior, respectively, and underwent embolization treatment for hemoptysis five days prior and was discharged one day earlier. He was diagnosed with pulmonary and endobronchial tuberculosis and was prescribed medications for tuberculosis. About one hour before arriving at the emergency room, about 700 mL of hemoptysis occurred. For the first angiography performed five days prior, the right interocostobronchial artery to the left lower lung, aberrant bronchial arteries from the left internal mammary artery supplying the left upper lung, and several left posterior intercostal arteries supplying the left lower lung were successfully embolized with PVA particles. Computed tomography (CT) showed no enlarged bronchial arteries, and angiography of the descending thoracic aorta and left subclavian artery showed no systemic hypervascularization in either lung. Both coronary angiographies showed a CBF (sinoatrial nodal artery) from the right coronary artery coursing along the left main bronchus (Fig. 2). However, cannulation and embolization of CBF failed due to spastic changes of CBF and tachycardia. Bleeding through the endotracheal tube and hypoxemia persisted despite intensive care resulting in death two days after embolization.

bronchial artery, coronary artery, embolization, hemoptysis, pulmonary tuberculosis

Chest CT and angiography of right coronary artery in 57-year-old male, case 2. second. embolization treatments. Right lung lesions were improving but left lung lesions changed into cavitary lesions.

PMC3253394_02

Male

A 57-year-old male arrived at the emergency room due to cardiac arrest. He had a history of diabetes and pneumonia six and two years prior, respectively, and underwent embolization treatment for hemoptysis five days prior and was discharged one day earlier. He was diagnosed with pulmonary and endobronchial tuberculosis and was prescribed medications for tuberculosis. About one hour before arriving at the emergency room, about 700 mL of hemoptysis occurred. For the first angiography performed five days prior, the right interocostobronchial artery to the left lower lung, aberrant bronchial arteries from the left internal mammary artery supplying the left upper lung, and several left posterior intercostal arteries supplying the left lower lung were successfully embolized with PVA particles. Computed tomography (CT) showed no enlarged bronchial arteries, and angiography of the descending thoracic aorta and left subclavian artery showed no systemic hypervascularization in either lung. Both coronary angiographies showed a CBF (sinoatrial nodal artery) from the right coronary artery coursing along the left main bronchus (Fig. 2). However, cannulation and embolization of CBF failed due to spastic changes of CBF and tachycardia. Bleeding through the endotracheal tube and hypoxemia persisted despite intensive care resulting in death two days after embolization.

bronchial artery, coronary artery, embolization, hemoptysis, pulmonary tuberculosis

Chest CT and angiography of right coronary artery in 57-year-old male, case 2. Right coronary angiography (C, D) shows coronary to bronchial artery fistula with spastic change from proximal right coronary artery running along superior and inferior walls of left main bronchus (arrows).

PMC3253394_02

Male

A 57-year-old male arrived at the emergency room due to cardiac arrest. He had a history of diabetes and pneumonia six and two years prior, respectively, and underwent embolization treatment for hemoptysis five days prior and was discharged one day earlier. He was diagnosed with pulmonary and endobronchial tuberculosis and was prescribed medications for tuberculosis. About one hour before arriving at the emergency room, about 700 mL of hemoptysis occurred. For the first angiography performed five days prior, the right interocostobronchial artery to the left lower lung, aberrant bronchial arteries from the left internal mammary artery supplying the left upper lung, and several left posterior intercostal arteries supplying the left lower lung were successfully embolized with PVA particles. Computed tomography (CT) showed no enlarged bronchial arteries, and angiography of the descending thoracic aorta and left subclavian artery showed no systemic hypervascularization in either lung. Both coronary angiographies showed a CBF (sinoatrial nodal artery) from the right coronary artery coursing along the left main bronchus (Fig. 2). However, cannulation and embolization of CBF failed due to spastic changes of CBF and tachycardia. Bleeding through the endotracheal tube and hypoxemia persisted despite intensive care resulting in death two days after embolization.

bronchial artery, coronary artery, embolization, hemoptysis, pulmonary tuberculosis

Chest CT and angiography of right coronary artery in 57-year-old male, case 2. Right coronary angiography (C, D) shows coronary to bronchial artery fistula with spastic change from proximal right coronary artery running along superior and inferior walls of left main bronchus (arrows).

PMC3253394_03

Female

A 68-year-old female experienced four episodes of hemoptysis (more than 400 mL/48 hours). She had a history of pulmonary tuberculosis that was diagnosed about 50 years prior and had underwent embolization of both bronchial arteries and multiple systemic collaterals due to recurrent hemoptysis (seven times) over the five years prior to presentation. Serial chest radiographs and CT showed severe destructive changes with bronchiectasis and cavitary lesions at the left lung. Because bronchial or systemic arteries causing hemoptysis were not found, right and left coronary angiographies were performed. The coronary angiography revealed two CBFs from both coronary arteries (sinoatrial nodal artery from right coronary artery and distal left circumflex arterial branch) to the left upper and lower lung as well as a massive pulmonary artery shunt (Fig. 3). After careful selection of CBFs as far from the coronary arterial branches as possible with a microcatheter, an embolization was performed with PVA particles and small amounts of Gelfoam particles, resulting in no visible residual hypervascularization or pulmonary artery shunt. The patient was asymptomatic without hemoptysis, but abnormal electrocardiography (EKG) (unusual P axis and short PR, probably junctional tachycardia) and increased cardiac enzyme (serum creatine kinase 375 IU/L, normal range 22-269; creatine kinase-MB 33.0 ng/mL, normal range 0.0-3.4; troponin-I 11.04 ng/mL, normal range 0.0-0.3) were noted the next day. Echocardiography showed normal left ventricular systolic function and EKG was normalized on the sixth day post-embolization. The patient was discharged without any symptoms.

bronchial artery, coronary artery, embolization, hemoptysis, pulmonary tuberculosis

Chest CT and angiographies of both coronary arteries in 68-year-old female, case 3. . A, B. Chest CT images prior to embolization treatment. Small tortuous coronary to bronchial artery fistula is suspected to be traversing right main pulmonary artery (thin arrows,.

PMC3253394_03

Female

A 68-year-old female experienced four episodes of hemoptysis (more than 400 mL/48 hours). She had a history of pulmonary tuberculosis that was diagnosed about 50 years prior and had underwent embolization of both bronchial arteries and multiple systemic collaterals due to recurrent hemoptysis (seven times) over the five years prior to presentation. Serial chest radiographs and CT showed severe destructive changes with bronchiectasis and cavitary lesions at the left lung. Because bronchial or systemic arteries causing hemoptysis were not found, right and left coronary angiographies were performed. The coronary angiography revealed two CBFs from both coronary arteries (sinoatrial nodal artery from right coronary artery and distal left circumflex arterial branch) to the left upper and lower lung as well as a massive pulmonary artery shunt (Fig. 3). After careful selection of CBFs as far from the coronary arterial branches as possible with a microcatheter, an embolization was performed with PVA particles and small amounts of Gelfoam particles, resulting in no visible residual hypervascularization or pulmonary artery shunt. The patient was asymptomatic without hemoptysis, but abnormal electrocardiography (EKG) (unusual P axis and short PR, probably junctional tachycardia) and increased cardiac enzyme (serum creatine kinase 375 IU/L, normal range 22-269; creatine kinase-MB 33.0 ng/mL, normal range 0.0-3.4; troponin-I 11.04 ng/mL, normal range 0.0-0.3) were noted the next day. Echocardiography showed normal left ventricular systolic function and EKG was normalized on the sixth day post-embolization. The patient was discharged without any symptoms.

bronchial artery, coronary artery, embolization, hemoptysis, pulmonary tuberculosis

Chest CT and angiographies of both coronary arteries in 68-year-old female, case 3. C, D. Early and late phases of right coronary angiography show enlarged coronary to bronchial artery fistula from proximal right coronary artery and massive pulmonary artery shunt (thick arrows).

PMC3253394_03

Female

A 68-year-old female experienced four episodes of hemoptysis (more than 400 mL/48 hours). She had a history of pulmonary tuberculosis that was diagnosed about 50 years prior and had underwent embolization of both bronchial arteries and multiple systemic collaterals due to recurrent hemoptysis (seven times) over the five years prior to presentation. Serial chest radiographs and CT showed severe destructive changes with bronchiectasis and cavitary lesions at the left lung. Because bronchial or systemic arteries causing hemoptysis were not found, right and left coronary angiographies were performed. The coronary angiography revealed two CBFs from both coronary arteries (sinoatrial nodal artery from right coronary artery and distal left circumflex arterial branch) to the left upper and lower lung as well as a massive pulmonary artery shunt (Fig. 3). After careful selection of CBFs as far from the coronary arterial branches as possible with a microcatheter, an embolization was performed with PVA particles and small amounts of Gelfoam particles, resulting in no visible residual hypervascularization or pulmonary artery shunt. The patient was asymptomatic without hemoptysis, but abnormal electrocardiography (EKG) (unusual P axis and short PR, probably junctional tachycardia) and increased cardiac enzyme (serum creatine kinase 375 IU/L, normal range 22-269; creatine kinase-MB 33.0 ng/mL, normal range 0.0-3.4; troponin-I 11.04 ng/mL, normal range 0.0-0.3) were noted the next day. Echocardiography showed normal left ventricular systolic function and EKG was normalized on the sixth day post-embolization. The patient was discharged without any symptoms.

bronchial artery, coronary artery, embolization, hemoptysis, pulmonary tuberculosis

Chest CT and angiographies of both coronary arteries in 68-year-old female, case 3. C, D. Early and late phases of right coronary angiography show enlarged coronary to bronchial artery fistula from proximal right coronary artery and massive pulmonary artery shunt (thick arrows).

PMC3253394_03

Female

A 68-year-old female experienced four episodes of hemoptysis (more than 400 mL/48 hours). She had a history of pulmonary tuberculosis that was diagnosed about 50 years prior and had underwent embolization of both bronchial arteries and multiple systemic collaterals due to recurrent hemoptysis (seven times) over the five years prior to presentation. Serial chest radiographs and CT showed severe destructive changes with bronchiectasis and cavitary lesions at the left lung. Because bronchial or systemic arteries causing hemoptysis were not found, right and left coronary angiographies were performed. The coronary angiography revealed two CBFs from both coronary arteries (sinoatrial nodal artery from right coronary artery and distal left circumflex arterial branch) to the left upper and lower lung as well as a massive pulmonary artery shunt (Fig. 3). After careful selection of CBFs as far from the coronary arterial branches as possible with a microcatheter, an embolization was performed with PVA particles and small amounts of Gelfoam particles, resulting in no visible residual hypervascularization or pulmonary artery shunt. The patient was asymptomatic without hemoptysis, but abnormal electrocardiography (EKG) (unusual P axis and short PR, probably junctional tachycardia) and increased cardiac enzyme (serum creatine kinase 375 IU/L, normal range 22-269; creatine kinase-MB 33.0 ng/mL, normal range 0.0-3.4; troponin-I 11.04 ng/mL, normal range 0.0-0.3) were noted the next day. Echocardiography showed normal left ventricular systolic function and EKG was normalized on the sixth day post-embolization. The patient was discharged without any symptoms.

bronchial artery, coronary artery, embolization, hemoptysis, pulmonary tuberculosis

Chest CT and angiographies of both coronary arteries in 68-year-old female, case 3. E. Left coronary angiography shows another enlarged coronary to bronchial artery fistula (thick arrow) that showed severe pulmonary artery shunt at left lower lung (not shown).

PMC9553233_01

Male

The patient is a 37-year-old Chinese male. In April 2014, he was diagnosed with brucellosis due to fever and fatigue, and his symptoms disappeared after anti-brucellosis medications for three months. In October 2014, the patient developed left hip pain, worsened by weight-bearing, and was admitted to the orthopedics department of our hospital in December 2014 due to the deterioration of symptoms. He is a sheep herdsman without any history of trauma, alcoholism, or hormone use. Physical examination revealed that the active and passive motion of the left hip was somewhat restricted due to pain. X-ray demonstrated that the left femoral head exhibited a strip-like low-density area but no evidence of stenosis (Figure 1A and B). CT scan revealed cavity necrosis in the left femoral head (Figure 1C). MRI revealed necrosis of the left femoral head, and effusion in the left joint cavity (Figure 1D and E). Blood test showed WBC 6.85 x 109/L with neutrophils accounted for 61.8%, CRP 3.5 mg/L, ESR 2.00 mm/h. SAT was positive at a titer of 1:320, and all tests for tuberculosis and rheumatoid arthritis were negative. Having been diagnosed with brucellar hip arthritis complicated by osteonecrosis of the left femoral head, the patient underwent puncture and irrigation of the left hip joint and core decompression and bone grafting. B. melitensis was detected in hip joint effusion and osteonecrosis of femoral head by real-time PCR. HE staining of a core biopsy of the left femoral head revealed amorphous necrotic material (Figure 2A); Giemsa staining can demonstrate scattered positive Brucella (Figure 2B). Triple anti-infective therapy was administered after the operation: rifampicin (0.6g po qd; Guangdong Hengjian Pharmaceuticals), doxycycline (0.1g po bid; Jiangsu Lianhuan Pharmaceuticals), and levofloxacin (0.2g ivgtt bid; Yangtze River Pharmaceuticals). Upon discharge from the hospital two weeks after the operation, his left hip pain was substantially relieved, and the antibiotic regimen was adjusted to rifampicin (0.6g po qd; Guangdong Hengjian Pharmaceuticals) and doxycycline (0.1g po bid; Jiangsu Lianhuan Pharmaceuticals) for six months. In follow-up, the symptoms of left hip pain and movement limitation disappeared almost half a year later, and there was no obvious abnormality in the blood test or hip X-ray (Figure 1F). In the telephone follow-up in April 2022, the patient's recovery proceeded well.

brucella, case series, core decompression, femoral head necrosis, total hip arthroplasty

PMC9553233_02

Male

The patient is a 33-year-old Chinese male. He was diagnosed with brucellosis in a local hospital in October 2017 due to right hip pain and wavy fever. Following the administration of anti-brucellosis drugs, the fever subsided, but the pain in the right hip did not. In January 2018, the patient visited the orthopedic department of our hospital due to aggravation of right hip pain and decreased hip joint mobility. History indicates that the patient's family raised sheep for a long time, and there was no history of trauma, alcohol consumption, or hormone use. The physical examination revealed severe tenderness in the right hip region, longitudinal percussion pain in the right lower limb, and limited passive and active movement of the right hip. There was no abnormality in the chest X-ray or CT. X-ray of the hip joint showed low signal on the right femoral head, joint narrowing and even invagination of the joint space (Figure 3A). CT showed cavity necrosis and low-density patches of shadows in the right femoral head (Figure 3B). MRI of the hip joint indicates effusion of the right hip joint complicated by necrosis of the right femoral head, and the inflammatory fluid diffused with extra-articular (Figure 3C). Blood tests indicated WBC 4.60x109/L with neutrophils accounting for 61.1%, CRP59.3mg/L, ESR29.0mm/hr, and procalcitonin (PCT) 0.05ng/mL. T-SPOT.TB assay (T-SPOT), as well as serum anti-tuberculosis antibody tests, were negative. RBPT was positive, and SAT was positive at a titer of 1:640. The above examination eliminated tuberculosis, and a preliminary diagnosis of brucellar hip arthritis and osteonecrosis of the femoral head was made. Despite taking anti-brucellosis medications for two weeks, which included rifampicin (0.6g po qd; Guangdong Hengjian Pharmaceuticals), doxycycline (0.1g po bid; Jiangsu Lianhuan Pharmaceuticals), and levofloxacin (0.2g ivgtt bid; Yangtze River Pharmaceuticals), the right hip's symptoms did not improve. This patient underwent puncture and irrigation of the right hip joint and core decompression with bone grafting of the femoral head. Using real-time PCR, B. melitensis was detected in joint effusions and osteonecrosis of the femoral head. HE staining in osteonecrosis of the femoral head revealed partial dead bone and inflammatory cellulose exudate (Figure 4A); Giemsa staining showed scattered positive Brucella (Figure 4B). When discharged from the hospital three weeks after surgery, the patient's right hip pain was significantly reduced; blood tests showed a CRP level of 24.7mg/L and an ESR level of 18.00mm/hr. The antibiotic regimen was adjusted to rifampicin (0.6g po qd; Guangdong Hengjian Pharmaceuticals) and doxycycline (0.1g po bid; Jiangsu Lianhuan Pharmaceuticals) after discharge, with a total therapy duration of six months. Following a follow-up four years later, the pain in the right hip had completely disappeared, and the hip joint was no longer limited in movement; neither the blood tests nor the imaging examinations (Figure 3D-F) revealed any abnormalities.

brucella, case series, core decompression, femoral head necrosis, total hip arthroplasty

PMC2808615_01

Male

A 47-yr-old man suffering from tenesmus and mucoid stool was admitted to our hospital via a local clinic. He had smoked one pack of cigarettes daily for 20 yr and he did not drink alcohol. He had a history of pulmonary tuberculosis 20 yr ago that was treated with anti-tuberculosis medication for 9 months. On admission, he appeared in good health without any complaints of weight loss, fever and night sweats. His blood pressure was 110/90 mmHg, his pulse rate was 78/min, body temperature was 36.2C and respirations were 18/min. On physical examination, the patient appeared normal and showed no remarkable findings except a depressed anterior chest wall. No lymphadenopathy was detected. His breath sounds were clear and his heart sounds were regular without any murmurs. The laboratory findings included hemoglobin 13.4 g/dL, white blood cells 4,600/microL, platelets 305,000/microL, AST 22 IU/L, ALT 35 IU/L, ALP 47 IU/L, GGT 42 IU/L, LDH 393 U/L, BUN 14.8 mg/dL, creatinine 1.0 mg/dL, uric acid 6.2 mg/dL and calcium 3.6 mg/dL. A radiograph of the chest showed a white lesion in the right upper lung field; this was thought to be a healed scar from pulmonary tuberculosis. The upper gastrointestinal endoscopic examination revealed an healed ulcer in the duodenal bulb. Rapid urease test for Helicobacter pylori gave a negative result. Colonoscopic examination revealed two lesions 1) a granular & reddish mucosal thickening at the just above rectum (Fig. 1A), and 2) a reddish inflammatory mucosa without elevation or depression at the appendiceal orifice (Fig. 1B). Microscopic examination of the mucosal lesions of the colon and rectum showed lymphoepithelial lesions consisting of diffuse proliferation of small lymphocytes and some glandular destruction by lymphocytes (Fig. 2A). Immunohistochemistry showed the neoplastic cells were positive for CD20 (Fig. 2B) but negative for CD5, CD10, and cyclin D1. We then started to perform the staging evaluation of non-Hodgkin's lymphoma (NHL). The titer of beta2-microglobulin was 1,770 microg/L and this was in the normal range. The proteins showed a pattern of polyclonal gammopathy upon serum protein electrophoresis. Computed tomography of abdomen revealed no lymphadenopathy. A bone marrow aspiration and biopsy was performed and they revealed no remarkable findings. He was diagnosed with a low grade MALT lymphoma of stage IE (using Ann-Arbor staging) and stage II (using St. Jude Children's Research Hospital staging). He had received anticancer chemotherapy (cyclophosphamide 1,200 mg, adriamycin 80 mg, vincristine i.v. and prednisolone 100 mg p.o. for 5 days every month for 4 months) with involved field radiation therapy (3,000 cGy at the colon and 150 cGy at the rectum with 10 MV radiography 2 ports for 20 times during 29 days). His presenting symptoms, including the tenesmus and mucoid stools subsided after treatment. Three months after treatment, a follow-up colonoscopy revealed no abnormal mucosa (Fig. 3).

PMC6560984_01

Female

A 43-year-old woman presented to the emergency department with cough, weight loss and progressive difficulty with breathing of 2 months. Cough was insidious in onset, productive of copious thick whitish sputum, which was not foul-smelling but worse early in the morning. There was a history of fever, but no hemoptysis, drenching night sweats or contact with persons with chronic cough. At about the same period, she developed difficulty with breathing which was gradual in onset, provoked by ordinary activities such as walking and doing house chores. Difficulty with breathing progressively worsened, and became present even at rest which made her present at the emergency department. There was associated easy fatigability and orthopnea, but no Paroxysmal Nocturnal Dyspnea. She had bilateral leg and abdominal swelling, but no swelling in other parts of the body and no change in urine volume or frequency. She also complained of unintentional weight loss. Prior to the current bout of symptoms, she has been having recurrent cough for 22 years and had received four courses of anti-tuberculosis medications in the past;1st treatment in 1996, 2nd treatment in 2001, 3rd treatment in 2007 and 4th treatment in 2013. The basis of pulmonary Tuberculosis (PTB) diagnosis could not be ascertained in all cases and she did not complete 6 months of treatment in at least 2 of the courses. There is history of use of firewood for cooking for about 25 years, but no history of cigarette-smoking. She is not diabetic or hypertensive. No history of chronic use of immunosuppressives, exposure to asbestos, sharing of sharps, multiple sexual partners or blood transfusion. She is not a known asthmatic and no history of atopy. No history of recurrent joint pains, skin rash, mucosal sores, recurrent sinusitis or symptoms suggestive of malabsorption. No history of recurrent childhood upper respiratory tract infections. Immunization history could not be ascertained. She does not take alcohol. She is a petty trader and has been divorced for over 5 years due to recurrent ill health and has 4 children. Over the years, she has been patronizing patent medicine dealers, and has been to several hospitals where she had repeated chest x-rays and been on medications including courses of antibiotics with short lived clinical improvement. She also had several courses of antibiotics in the current illness with no improvement prior to presentation. At presentation, she was ill-looking, in respiratory distress, not pale, febrile (38.2 C.), anicteric, cyanosed, not dehydrated, no asterexis, no peripheral lymphadenopathy, had grade 1 finger clubbing and bilateral pitting pedal edema up to the knee. SpO2 was 84%, weight was 47kg, and height was 1.65m with BMI of 17.3kg /m2. Chest examinations revealed respiratory rate of 32cpm. Modified medical research council (MMRC) dyspnea scale was 4. Other findings were bibasal coarse crepitations and left lower lobe consolidation. Cardiovascular examination revealed pulse rate of 110 bpm with regular rate and rhythm, Blood pressure 120/70 mmHg, elevated Jugular venous pressure with distended neck veins, Apex beat is displaced laterally with left parasternal heave. She has a third heart sound with loud P2 and pansystolic murmur loudest in the tricuspid area. There was tender hepatomegaly but neurological and musculoskeletal examinations were normal. The most recent Chest X-ray (CXR) done three days prior to presentation showed reticulonodular opacities, cystic lesions especially in the mid to lower zones, moderate cardiomegaly with mild vascular engorgement with perivascular cuffing (Figure 1). Differentials at presentation were PTB complicated by cor pulmonale with superimposed bacterial infection, Post-TB Bronchiectasis, Chronic Obstructive Pulmonary Disease (COPD), Congestive heart failure secondary to valvular heart disease and Interstitial lung disease. Patient was admitted and various investigations were ordered. She was nursed in cardiac position and the following treatments were commenced; Intranasal oxygen at 5L/min, intravenous (IV) Frusemide 60mg daily, Tab Spironolactone 25mg daily, IV Augmentin 1.2g 12 hourly, Tab clarithromycin 500mg bd and chest physiotherapy. Chest Computerized Tomography (CT) scan revealed lung fields showing mosaic pattern with patchy areas of ground glass attenuation. Multiple poorly defined nodules of varying sizes and shapes are seen in a random distribution in all the lung segments with upper lobe predominance. Conferencing nodules are seen in the apical segment of the right lung, apicoposterior segement of left lung with extension into the oblique fissure and lateral aspect of superior lingular segment. Generalized cylindrical, varicoid and cystic bronchiectatic changes with signet ring sign is seen in both lung fields but worse at the right middle lobe and left lingular segments. There is thickening of the intralobular septae and the walls of the dilated bronchi. The impression was Bronchiectasis with mosaic perfusion and randomly distributed pulmonary nodules most likely to Post infectious (Figure 2, Figure 3, Figure 4). Sputum studies microscopy, culture and sensitivity yielded growth of upper respiratory flora; AFB and GeneXpert were negative for MTB. Blood culture yielded no growth. Fingerstick glucose was 6.6mmol/L at presentation. Basal metabolic panel was within normal limit (HCO3: 28 mmol/L, Na:128 mmol/L, K: 3.5 mmol/L, Urea: 2.4 mmol/L, Cr:81 umol/L). FBC revealed PCV: 42%; WBC: 12,000 cells/mm3, Platelets: 372,000 cells/mm3, Neutrophil: 84%, Lymphocytes: 44%, Eosinophils: 02%. ESR was 33mm/hr (westergren method). ECG showed Sinus tachycardia and Right axis deviation. Echocardiography revealed Right heart disease. Anti-nuclear antibody and HIV screening were both negative. Serum proteins were within normal limits. Spirometry revealed obstructive pattern (Table 1). Based on the Chest CT scan findings and result of other investigations, a diagnosis of Bronchiectasis probably post-PTB or secondary to poorly treated pneumonia, with infective exacerbation, complicated by corpulmonale was made. Nebulized salbutamol was added to her current treatment regimen. After 6 days on admission, patients condition deteriorated evidenced by persistent fever, respiratory distress, confusion and hypoxia (SpO2 82%) and was considered for Intensive care unit admission, bronchoscopic sampling of the lower respiratory tract, while IV Augmentin was changed to IV Cefepim. The relatives however, objected to further treatment due to financial constraint and was subsequently discharged against medical advice. She was also advised to get multivalent pneumococcal polyvalent vaccine at the nearest primary health care center upon discharge.

bronchiectasis, morbidity, pathogenetic mechanisms

Chest CT scan scannogram reveals severe honeycombing especially in the middle and upper lobes of both lung fields from combination of tramline and bronchial thickening.

PMC6560984_01

Female

A 43-year-old woman presented to the emergency department with cough, weight loss and progressive difficulty with breathing of 2 months. Cough was insidious in onset, productive of copious thick whitish sputum, which was not foul-smelling but worse early in the morning. There was a history of fever, but no hemoptysis, drenching night sweats or contact with persons with chronic cough. At about the same period, she developed difficulty with breathing which was gradual in onset, provoked by ordinary activities such as walking and doing house chores. Difficulty with breathing progressively worsened, and became present even at rest which made her present at the emergency department. There was associated easy fatigability and orthopnea, but no Paroxysmal Nocturnal Dyspnea. She had bilateral leg and abdominal swelling, but no swelling in other parts of the body and no change in urine volume or frequency. She also complained of unintentional weight loss. Prior to the current bout of symptoms, she has been having recurrent cough for 22 years and had received four courses of anti-tuberculosis medications in the past;1st treatment in 1996, 2nd treatment in 2001, 3rd treatment in 2007 and 4th treatment in 2013. The basis of pulmonary Tuberculosis (PTB) diagnosis could not be ascertained in all cases and she did not complete 6 months of treatment in at least 2 of the courses. There is history of use of firewood for cooking for about 25 years, but no history of cigarette-smoking. She is not diabetic or hypertensive. No history of chronic use of immunosuppressives, exposure to asbestos, sharing of sharps, multiple sexual partners or blood transfusion. She is not a known asthmatic and no history of atopy. No history of recurrent joint pains, skin rash, mucosal sores, recurrent sinusitis or symptoms suggestive of malabsorption. No history of recurrent childhood upper respiratory tract infections. Immunization history could not be ascertained. She does not take alcohol. She is a petty trader and has been divorced for over 5 years due to recurrent ill health and has 4 children. Over the years, she has been patronizing patent medicine dealers, and has been to several hospitals where she had repeated chest x-rays and been on medications including courses of antibiotics with short lived clinical improvement. She also had several courses of antibiotics in the current illness with no improvement prior to presentation. At presentation, she was ill-looking, in respiratory distress, not pale, febrile (38.2 C.), anicteric, cyanosed, not dehydrated, no asterexis, no peripheral lymphadenopathy, had grade 1 finger clubbing and bilateral pitting pedal edema up to the knee. SpO2 was 84%, weight was 47kg, and height was 1.65m with BMI of 17.3kg /m2. Chest examinations revealed respiratory rate of 32cpm. Modified medical research council (MMRC) dyspnea scale was 4. Other findings were bibasal coarse crepitations and left lower lobe consolidation. Cardiovascular examination revealed pulse rate of 110 bpm with regular rate and rhythm, Blood pressure 120/70 mmHg, elevated Jugular venous pressure with distended neck veins, Apex beat is displaced laterally with left parasternal heave. She has a third heart sound with loud P2 and pansystolic murmur loudest in the tricuspid area. There was tender hepatomegaly but neurological and musculoskeletal examinations were normal. The most recent Chest X-ray (CXR) done three days prior to presentation showed reticulonodular opacities, cystic lesions especially in the mid to lower zones, moderate cardiomegaly with mild vascular engorgement with perivascular cuffing (Figure 1). Differentials at presentation were PTB complicated by cor pulmonale with superimposed bacterial infection, Post-TB Bronchiectasis, Chronic Obstructive Pulmonary Disease (COPD), Congestive heart failure secondary to valvular heart disease and Interstitial lung disease. Patient was admitted and various investigations were ordered. She was nursed in cardiac position and the following treatments were commenced; Intranasal oxygen at 5L/min, intravenous (IV) Frusemide 60mg daily, Tab Spironolactone 25mg daily, IV Augmentin 1.2g 12 hourly, Tab clarithromycin 500mg bd and chest physiotherapy. Chest Computerized Tomography (CT) scan revealed lung fields showing mosaic pattern with patchy areas of ground glass attenuation. Multiple poorly defined nodules of varying sizes and shapes are seen in a random distribution in all the lung segments with upper lobe predominance. Conferencing nodules are seen in the apical segment of the right lung, apicoposterior segement of left lung with extension into the oblique fissure and lateral aspect of superior lingular segment. Generalized cylindrical, varicoid and cystic bronchiectatic changes with signet ring sign is seen in both lung fields but worse at the right middle lobe and left lingular segments. There is thickening of the intralobular septae and the walls of the dilated bronchi. The impression was Bronchiectasis with mosaic perfusion and randomly distributed pulmonary nodules most likely to Post infectious (Figure 2, Figure 3, Figure 4). Sputum studies microscopy, culture and sensitivity yielded growth of upper respiratory flora; AFB and GeneXpert were negative for MTB. Blood culture yielded no growth. Fingerstick glucose was 6.6mmol/L at presentation. Basal metabolic panel was within normal limit (HCO3: 28 mmol/L, Na:128 mmol/L, K: 3.5 mmol/L, Urea: 2.4 mmol/L, Cr:81 umol/L). FBC revealed PCV: 42%; WBC: 12,000 cells/mm3, Platelets: 372,000 cells/mm3, Neutrophil: 84%, Lymphocytes: 44%, Eosinophils: 02%. ESR was 33mm/hr (westergren method). ECG showed Sinus tachycardia and Right axis deviation. Echocardiography revealed Right heart disease. Anti-nuclear antibody and HIV screening were both negative. Serum proteins were within normal limits. Spirometry revealed obstructive pattern (Table 1). Based on the Chest CT scan findings and result of other investigations, a diagnosis of Bronchiectasis probably post-PTB or secondary to poorly treated pneumonia, with infective exacerbation, complicated by corpulmonale was made. Nebulized salbutamol was added to her current treatment regimen. After 6 days on admission, patients condition deteriorated evidenced by persistent fever, respiratory distress, confusion and hypoxia (SpO2 82%) and was considered for Intensive care unit admission, bronchoscopic sampling of the lower respiratory tract, while IV Augmentin was changed to IV Cefepim. The relatives however, objected to further treatment due to financial constraint and was subsequently discharged against medical advice. She was also advised to get multivalent pneumococcal polyvalent vaccine at the nearest primary health care center upon discharge.

bronchiectasis, morbidity, pathogenetic mechanisms

Chest CT scan showing Signet ring appearance in both lung fields in the upper lobes.

PMC6560984_01

Female

A 43-year-old woman presented to the emergency department with cough, weight loss and progressive difficulty with breathing of 2 months. Cough was insidious in onset, productive of copious thick whitish sputum, which was not foul-smelling but worse early in the morning. There was a history of fever, but no hemoptysis, drenching night sweats or contact with persons with chronic cough. At about the same period, she developed difficulty with breathing which was gradual in onset, provoked by ordinary activities such as walking and doing house chores. Difficulty with breathing progressively worsened, and became present even at rest which made her present at the emergency department. There was associated easy fatigability and orthopnea, but no Paroxysmal Nocturnal Dyspnea. She had bilateral leg and abdominal swelling, but no swelling in other parts of the body and no change in urine volume or frequency. She also complained of unintentional weight loss. Prior to the current bout of symptoms, she has been having recurrent cough for 22 years and had received four courses of anti-tuberculosis medications in the past;1st treatment in 1996, 2nd treatment in 2001, 3rd treatment in 2007 and 4th treatment in 2013. The basis of pulmonary Tuberculosis (PTB) diagnosis could not be ascertained in all cases and she did not complete 6 months of treatment in at least 2 of the courses. There is history of use of firewood for cooking for about 25 years, but no history of cigarette-smoking. She is not diabetic or hypertensive. No history of chronic use of immunosuppressives, exposure to asbestos, sharing of sharps, multiple sexual partners or blood transfusion. She is not a known asthmatic and no history of atopy. No history of recurrent joint pains, skin rash, mucosal sores, recurrent sinusitis or symptoms suggestive of malabsorption. No history of recurrent childhood upper respiratory tract infections. Immunization history could not be ascertained. She does not take alcohol. She is a petty trader and has been divorced for over 5 years due to recurrent ill health and has 4 children. Over the years, she has been patronizing patent medicine dealers, and has been to several hospitals where she had repeated chest x-rays and been on medications including courses of antibiotics with short lived clinical improvement. She also had several courses of antibiotics in the current illness with no improvement prior to presentation. At presentation, she was ill-looking, in respiratory distress, not pale, febrile (38.2 C.), anicteric, cyanosed, not dehydrated, no asterexis, no peripheral lymphadenopathy, had grade 1 finger clubbing and bilateral pitting pedal edema up to the knee. SpO2 was 84%, weight was 47kg, and height was 1.65m with BMI of 17.3kg /m2. Chest examinations revealed respiratory rate of 32cpm. Modified medical research council (MMRC) dyspnea scale was 4. Other findings were bibasal coarse crepitations and left lower lobe consolidation. Cardiovascular examination revealed pulse rate of 110 bpm with regular rate and rhythm, Blood pressure 120/70 mmHg, elevated Jugular venous pressure with distended neck veins, Apex beat is displaced laterally with left parasternal heave. She has a third heart sound with loud P2 and pansystolic murmur loudest in the tricuspid area. There was tender hepatomegaly but neurological and musculoskeletal examinations were normal. The most recent Chest X-ray (CXR) done three days prior to presentation showed reticulonodular opacities, cystic lesions especially in the mid to lower zones, moderate cardiomegaly with mild vascular engorgement with perivascular cuffing (Figure 1). Differentials at presentation were PTB complicated by cor pulmonale with superimposed bacterial infection, Post-TB Bronchiectasis, Chronic Obstructive Pulmonary Disease (COPD), Congestive heart failure secondary to valvular heart disease and Interstitial lung disease. Patient was admitted and various investigations were ordered. She was nursed in cardiac position and the following treatments were commenced; Intranasal oxygen at 5L/min, intravenous (IV) Frusemide 60mg daily, Tab Spironolactone 25mg daily, IV Augmentin 1.2g 12 hourly, Tab clarithromycin 500mg bd and chest physiotherapy. Chest Computerized Tomography (CT) scan revealed lung fields showing mosaic pattern with patchy areas of ground glass attenuation. Multiple poorly defined nodules of varying sizes and shapes are seen in a random distribution in all the lung segments with upper lobe predominance. Conferencing nodules are seen in the apical segment of the right lung, apicoposterior segement of left lung with extension into the oblique fissure and lateral aspect of superior lingular segment. Generalized cylindrical, varicoid and cystic bronchiectatic changes with signet ring sign is seen in both lung fields but worse at the right middle lobe and left lingular segments. There is thickening of the intralobular septae and the walls of the dilated bronchi. The impression was Bronchiectasis with mosaic perfusion and randomly distributed pulmonary nodules most likely to Post infectious (Figure 2, Figure 3, Figure 4). Sputum studies microscopy, culture and sensitivity yielded growth of upper respiratory flora; AFB and GeneXpert were negative for MTB. Blood culture yielded no growth. Fingerstick glucose was 6.6mmol/L at presentation. Basal metabolic panel was within normal limit (HCO3: 28 mmol/L, Na:128 mmol/L, K: 3.5 mmol/L, Urea: 2.4 mmol/L, Cr:81 umol/L). FBC revealed PCV: 42%; WBC: 12,000 cells/mm3, Platelets: 372,000 cells/mm3, Neutrophil: 84%, Lymphocytes: 44%, Eosinophils: 02%. ESR was 33mm/hr (westergren method). ECG showed Sinus tachycardia and Right axis deviation. Echocardiography revealed Right heart disease. Anti-nuclear antibody and HIV screening were both negative. Serum proteins were within normal limits. Spirometry revealed obstructive pattern (Table 1). Based on the Chest CT scan findings and result of other investigations, a diagnosis of Bronchiectasis probably post-PTB or secondary to poorly treated pneumonia, with infective exacerbation, complicated by corpulmonale was made. Nebulized salbutamol was added to her current treatment regimen. After 6 days on admission, patients condition deteriorated evidenced by persistent fever, respiratory distress, confusion and hypoxia (SpO2 82%) and was considered for Intensive care unit admission, bronchoscopic sampling of the lower respiratory tract, while IV Augmentin was changed to IV Cefepim. The relatives however, objected to further treatment due to financial constraint and was subsequently discharged against medical advice. She was also advised to get multivalent pneumococcal polyvalent vaccine at the nearest primary health care center upon discharge.

bronchiectasis, morbidity, pathogenetic mechanisms

Chest Axial CT scan showing cystic and cylindrical dilatation of the bronchi with bronchial wall thickening centrally, more severe on the left.

PMC9850026_01

Female

A 37-year-old, Gravida 4 Para 3 living 3 at 19 weeks' gestation age with three previous caesarean scars, a known patient with chronic hypertension. She presented at our facility with complain of vaginal bleeding for 4 h prior to arrival, which was characterized by minimal bleeding with clots, she changed two pads. This was accompanied by lower abdominal pain that was intermittent and cramping in nature. It was non progressive with no specific periodicity. She had no preceding vaginal discharge or leakage. She did not report of awareness of heartbeat, loss of consciousness, or dizziness. On review of other system was uneventful. She has no known drug or food allergy. She booked at 12 weeks and was prescribed methyldopa 500 mg thrice daily for her chronic hypertension, which she has been using with good compliance and her blood pressure was well controlled. The pregnancy was uneventful until the time of admission. She is a non-smoker and reports no alcohol use during pregnancy. On examination: she was ill looking, alert, afebrile, not pale, not dyspnoeic with no lower limb oedema. Her vitals on admission were a blood pressure reading of 139/86 mmHg, a pulse rate of 86 beats per minute, a temperature of 36.6 C saturating 99 % on room air. Her abdominal examination revealed a gravid abdomen, had an old sub-umbilical midline incision scar, fundal height was 20 cm, with variable lie. The abdomen was not tense, and mild tenderness was elicited. Foetal heart rate was 168 beats per minute. Sterile speculum examination was done a healthy cervix was visualized which was closed with fresh blood oozing from the cervical OS. Review of other systems was unremarkable. Obstetric ultrasound was performed initially, showed a single viable foetus with estimate weight of 330 g, foetal heart rate were 172 beats per minutes, posterior placenta with a heterogenous echotexture extending to anterior aspect (Fig. 1, Fig. 2). Initial blood work up revealed a Haemoglobin level of 11.5 g/dl, Haematocrit of 36 %, Platelets count of 161 x 109/l. Our provisional diagnosis at this point was threatened abortion at 19 weeks and chronic hypertension with differential diagnosis of low-lying placenta. She was initiated on Progesterone (ethyl oleate progesterone) 100 mg intramuscular, intravenous Tranexamic acid 1000 mg, Intravenous paracetamol 1 g. 7 h post admission, she was reviewed once more by a resident of Obstetrics and Gynaecology reported she had developed per vaginal bleeding, with soaked one maternity pad and accompanied with awareness of her heartbeat. On examination: she was pale, tachycardic with a heart rate of 120. Foetal heart rate was not picked on doppler assessment, other vital signs were stable. Per abdominal exam revealed fundal height had significantly increased from 20 cm to 30 cm and tenderness elicited over the uterus. Hemoperitoneum of about 200 ml with fresh blood and clots Uterus found measuring about 30 cm fundal height Uterus had a distinct white and blueish discoloration resembling that of a Couvelaire uterus (Fig. 5) Ovaries and fallopian tubes appeared normal The urinary bladder was normal, but the bladder peritoneum was adhered to the lower part of the uterus. Repeat Full blood picture showed Haemoglobin of 8.8 g/dl, Haematocrit of 25.7 % and Platelets count of 47 x 109/l. She was transfused with two units of packed red cells and four units of platelets. Our current diagnosis at this point was an Abruptio placenta. She consented for emergency exploratory laparotomy and was taken for surgery. Intra-operative under aseptic technique abdominal incision was made through old sub-umbilical midline incision scar and findings were Hysterotomy performed and delivery of a 260 g foetus with no signs of life. There were multiple heavy clots in the uterus, about 1000 ml of clots were evacuated. Uterine muscles were lax and there was intractable bleeding despite administration of 40 IU oxytocin in 500 ml of Normal Saline. Given that the levels of Platelet count pre-operatively was 57 and the continued bleeding seen at the incision site the decision was made for subtotal hysterectomy. Subtotal hysterectomy was done, the uterine stump sutured, and haemostasis achieved. There was significant bleeding from the left ovarian vessels therefore left oophorectomy was done as well. The abdomen was then closed in layers. Patient was the sent to the Intensive Care Unit for close monitoring whilst receiving two units of packed red cells, four units of Platelets and two units of fresh whole blood. On day four post operation she was discharged in good condition. Her outpatient follow up was uneventful.

couvelaire uterus, placenta abruption, previable pregnancy

PMC5924802_01

Male

This study was approved by the Ben Taub Hospital IRB, and each participant signed a consent form, and gave written permission to publish their de-identified results. The participants were not compensated for their participation in this study. Patient 1 was a 39-year-old male patient hospitalized with a traumatic SCI C4-5 resulting in quadriplegia and respiratory failure requiring trachiotomy (breathing through a hole in his throat) after falling out of 4 story building (apparent suicide attempt) 2 weeks prior to the current study. The fall/accident resulted in C6/C7 Burst Fracture, C4/C5 Spinous Process Fractures, C5/C6 Transverse Process Fractures, SCI, and right 8th through 11th rib fractures. Psychological assessments determined that the patient was clinically depressed, and had high anxiety associated with the traumatic event that left him paralyzed with a SCI. He could not remember anything about events leading up to his fall out of a building and he did not have any PTSD symptoms. Patient 2 suffered a SCI after jumping out of a moving vehicle, in an attempted suicide. Due to damage to the spine including a C7 fracture, the hospitalized patient had bilateral hand numbness and parasthesias, and paresis (partial paralysis of his legs). Both patients were treated by the first author of this paper (AF). The psychotherapist (AF) has a Ph.D. in clinical psychology and had been working with SCI patients as a clinical psychologist at Ben Taub for several years, at the time this study was conducted. This was a within-subject design case study with key measures administered before and after each VR DBT mindfulness training session. Patients received VR DBT Mindfulness training sessions after they were cleared by the acute surgery team to participate in this study. Patients were also free from infection at the time of the intervention. The measures were administered before and after each VR intervention. During the VR+DBT skills learning interventions, the participant looked into a pair of wide field of view Oculus Rift DK2 VR goggles (100 field of view diagonal, per eye), and had the illusion of floating down a 3-D computer-generated river (created and owned by bigenvironments.com, see also vrpain.com) while listening to one of three DBT mindfulness skills training audio tracks. All audio tracks and verbal DBT treatments used in this study are copyrighted by Marsha Linehan. See below a brief description of each audio track as well as the VR system. Track 1: Observing Sound (Linehan,; 8.5 min total). Here is an excerpt "what we are going to do now is practice observing sound....the idea is not to think about sound, the idea is to just notice it...I am going to start by ringing the bell three times....just listen to the bells, how long they last, how they go from loud to soft, just listen, as you focus on your breath coming in and breath coming out. If your mind wanders, bring it back." Track 2: Observing visuals: (adapted from Linehan,; 10 min total) The observing visuals script was adapted to synchronize with images the patient sees in the VR goggles when they are listening to the audio (Navarro-Haro et al.,). Exerpt: "Notice what you see as you float down the river, observe the serenity of the water, attend to what you see in the present moment. If your mind wanders away, just bring it back, gently...to the river." Track 3: Wise Mind; (adapted from Linehan,; 8 min long) The patient listened to these audio instructions while in VR floating down the river in virtual reality. Here is an excerpt "Imagine that you are a small flake of stone, flat, and light. You are now floating slowly and gently through the clear blue water, toward your wise mind...notice what you see, what you feel, as you are floating down toward your wise mind. As you float down the river, observe the serenity of the river, be aware of the calmness, and settle your attention there, within yourself." "As you reach the center of your self, focus your attention there, in your center, in your wise mind. Come back...to the river..if you find your mind wandering." Each participant sat in their hospital bed. After filling out the pre-treatment psychological measures, the patient looked into a pair of Oculus Rift DK2 VR goggles. Patient one had a breathing tube in his neck, and was not allowed to move his head, so the therapist held the VR goggles near his face. Patient 2 wore the VR goggles on his head, and was able to look around in the VR world. Head tracking allowed him to look around the 3D computer virtual world. While looking into the virtual reality goggles, each patient looked down river. Near the beginning of the VR session, the patients stayed in one place at the top of the virtual river, as they received verbal DBT mindfulness skills training exercise instructions from the therapist. Then, the patient began descending slowly down the river while listening to audio instructions directing the patient how to practice mindfulness. Each participant sat in their hospital bed and looked into a pair of head mounted Oculus Rift DK2 VR goggles with 100 diagonal field of view per eye and 960 by 1,080 pixels resolution per eye (75 hz). The goggles were plugged into an MSI GT Series GT72 Dominator Pro G-1252 Gaming Laptop 6th Generation Intel Core i7 6700HQ (2.60 GHz) 16 GB Memory 1 TB HDD 512 GB SSD NVIDIA GeForce GTX 980M 4 GB GDDR5 17.3" Windows 10 Home 64-Bit. The VR world was designed to give the patient the illusion of going inside the 3D computer generated world, where they floated slowly down a computer generated river in VR, with trees, boulders, and mountains. Each patient listened to mindfulness training instructions followed by sounds of birds and crickets chirping, and water sounds, in an immersive computer simulation of floating down a 3-D computer-generated river during the VR DBT mindfulness intervention (see Figure 1). Patient 1 listened to Observing and Wise Mind audios while in virtual reality. The patient received "observing visuals" for session 1, "observing sounds" for session 2, and "wise mind" for session 3, and "observing visuals" again, for session 4. While in VR, Patient 2 received "observing visuals," and "observing sound". He only had two sessions of VR because his health improved sufficiently that he was discharged before a third session was implemented (i.e., he did not receive the "wise mind" VR DBT session). The current study used a measure designed specifically for medical patients. BDI -FastScreen is a reliable 7-item self-report instrument valuable for measuring the severity of the patient's depression (Beck et al.,). The BDI Fast Screen has been shown to have concurrent and discriminative validity (Benedict et al.,). The BDI Medical Fast Screen is an abbreviated version of the longer Beck Depression Inventory (Beck et al.,). Patients respond to multiple choice questions to measure the severity of the patient's depression. The questions ask patients to rate their hopelessness, irritability, feelings of guilt, etc. The Spielberger State-Trait Anxiety Inventory (STAI-Y). Internal consistency coefficients range from 0.86 to 0.95, and it has good test-retest reliability coefficients ranging from 0.65 to 0.75 (Spielberger et al.,; Spielberger,). The 10 item "STAI-Y short" used in the current study produced scores similar to those obtained with the full form of the STAI-Y (Bergua et al.,). Previous VR DBT studies used diary based measures of negative and positive emotions (Navarro-Haro et al.,; Gomez et al.,). The current study introduces new measures using a Graphic Rating Scales question format (Jensen,). The Graphic Rating Scale is a 10-unit horizontal line labeled with number and word descriptors. Patients can easily answer these GRS ratings despite having no previous experience (Tesler et al.,). Using single GRS questions, patients rated how "depressed" and "nervous/anxious" and how "emotionally upset" they felt before and after each VR session. Before and after each VR DBT Mindfulness Skills Training session, each patient also briefly rated on a scale from 0 to 10 the intensity of several primary emotions (sadness, fear, anger, guilt, shame, disgust, and joy, see Ekman,; Linehan,; Navarro-Haro et al.,; Gomez et al.,). To measure acute stress disorder/PTSD symptoms, we created a new Graphic Rating Scale of current ASD/PTSD symptoms, adapted from the diagnostic criteria of the DSM-4 (American Psychiatric Association,).

dialectical behavior therapy, emotions, mindfulness training, spinal cord injury (sci), virtual reality therapy

PMC5088547_01

Female

The patient (patient 1) was a 2-year-old Japanese girl who was the first child of healthy non-consanguineous parents. Her younger brother had no proteinuria or hematuria. Her maternal aunt had an episode of nephritis, and a renal biopsy was performed during childhood, but the findings were uncertain. At 14 months of age, patient 1 was referred to our hospital because of microscopic hematuria that had persisted from the neonatal period. She had no clinically detectable hearing loss or ocular abnormalities. A urine culture revealed no infection. At 15 months of age, enalapril malate was initiated for proteinuria, with a urinary protein/creatinine ratio (P/Cr) of 1.3-3.6 g/gCr. At 21 months of age, she was admitted to our hospital for a renal biopsy. On admission, a urinalysis showed 2+ proteinuria (P/Cr, 1.3 g/gCr) and 3+ hematuria, with the urine sediment containing >100 red cells per high-power field. Her blood urea nitrogen (BUN) level was 17.7 mg/dL, serum creatinine level was 0.22 mg/dL, serum total protein level was 5.9 g/dL, and albumin level was 3.7 g/dL. Serum C3 and C4 levels were 118.2 mg/dL and 24.8 mg/dL, respectively. Antinuclear antibodies were negative. Renal ultrasonography was unremarkable. Her mother (patient 2) also had a history of proteinuria and hematuria without renal dysfunction, deafness, or ocular abnormalities. The pedigree of her family is shown in Fig. 1a. At 34 years of age, she was admitted to our hospital along with her daughter (patient 1) for a renal biopsy. A urinalysis showed 3+ proteinuria (P/Cr, 1.7 g/gCr) and 2+ hematuria, with the sediment containing 10-19 red cells per high-power field. Her BUN level was 20.0 mg/dL, serum creatinine level was 0.59 mg/dL, serum total protein level was 6.8 g/dL, and albumin level was 4.0 g/dL. Serum C3 and C4 levels were 134.4 mg/dL and 34.2 mg/dL, respectively. Antinuclear antibodies were negative. Renal ultrasonography showed a cystic lesion in the right kidney. The renal biopsy findings of the two patients are shown in Fig. 2. In patient 1, 29 glomeruli were observed on light microscopy; the glomerulus, tubules, and interstitium showed no significant alterations. Immunofluorescence (IF) staining for alpha 5 chains of type IV collagen showed segmental and mosaic patterns in the glomerular basement membrane (GBM). Electron microscopy (EM) demonstrated diffusely thinned-out GBMs (139-143 nm) with focal lamellation and splitting. In patient 2, 40 glomeruli were observed on light microscopy, two of which were globally sclerotic. IF staining for alpha 5 chains of type IV collagen showed segmental and mosaic patterns in the GBM, Bowman's capsule, and distal tubular basement membrane (TBM). EM demonstrated diffusely thinned-out GBMs (149-166 nm) with dense granules and splitting. In both patients, the merged IF staining images for alpha 2 and 5 chains of type IV collagen clarified the findings of segmental and mosaic patterns in the GBM. A sequence analysis of COL4A5 in the index patient and her mother was performed. The study was approved by the Institutional Review Board of Kobe University School of Medicine, and written informed consent was obtained. Genomic DNA was isolated from each patient's peripheral blood leukocytes using the Quick Gene Mini 80 System (Kurabo Industries, Tokyo, Japan), according to the manufacturer's instructions. Mutational analyses of COL4A5 were performed using polymerase chain reaction (PCR) and direct sequencing of genomic DNA of all exons and exon-intron boundaries. All 51 specific exons of COL4A5 were amplified by PCR. The PCR-amplified products were then purified and subjected to direct sequencing using a Dye Terminator Cycle Sequencing Kit (Amersham Biosciences, Piscataway, USA) with an automatic DNA sequencer (ABI Prism 3130; Perkin Elmer Applied Biosystems, Foster City, USA). The analysis revealed that both patients had a heterozygous mutation (c.2767G>C) in exon 32 (Fig. 1a). To investigate X chromosome inactivation, the human androgen receptor (HUMARA) assay was performed in both patients. Genomic DNA was digested by a methylation-sensitive enzyme, HpaII, at 37 C for 18 hours followed by PCR using DNA with HUMARA primers, as described previously. A DNA fragment analysis was performed on a 310 Genetic Analyzer (Thermo Fisher Scientific, Waltham, USA). Fragment data analyses were performed using the Gene Mapper Software program (Thermo Fisher Scientific). The HUMARA assay for patients 1 and 2 revealed that the X chromosome inactivation pattern was 77:23 and 31:69, respectively (Fig. 1b).

PMC3891416_01

Female

A 22-year-old woman presented with epigastric discomfort and intermittent dark-colored stools of two months duration. She had no previous illness and denied constitutional symptoms such as fever, weight loss, or night sweating. A physical examination detected no abdominal mass or tenderness, and no rebound tenderness. Laboratory studies showed a hemoglobin of 13.9 g/dL, leukocytes of 7,580/mm3, and an ESR of 17 mm/hr. Other biochemical tests results were within normal ranges, and anti-HIV Ab was negative. Stool occult blood was also negative. An esophagogastroduodenoscopic (EGD) examination revealed a round mass of about 3-cm at the duodenal bulb, with normal surrounding mucosa and central ulceration (Figure 1). Several red or black spots on the base of the ulceration evidenced recent bleeding. An endoscopic biopsy taken at the ulceration margin identified chronic duodenitis. Chest X-ray films showed inactive pulmonary tuberculosis at the left upper lobe, and abdominal computed tomography (CT) revealed a well-defined round mass that enhanced as gastric mucosa, at the posterior wall of the duodenal bulb suggestive of duodenal GIST (Figure 2). Endoscopic ultrasonography (EUS) showed an ulcerative hypoechogenic mass at the submucosal layer of the duodenal bulb (Figure 3). Exploratory laparotomy was performed to exclude the possibility of malignant GIST of the duodenum. During laparotomy, a solitary mass was detected around the hepatic artery, which penetrated the duodenal bulb. The mass was excised and a histopathological analysis revealed lymphadenopathy with caseous granuloma (Figure 4). Polymerase chain reaction of DNA extracted from the node was positive for tuberculosis and acid-fast bacilli were found by Ziehl-Neelsen tissue staining. The patient was diagnosed with solitary tuberculous lymphadenopathy and discharged on anti-tuberculosis medication. No evidence of recurrence has been observed during nine months of treatment.

PMC8116796_01

Female

The patient's clinical course was illustrated in Figure 1A . A 52-year-old female patient presented at the hospital in June, 2018 in a good physical condition, complaining of pain in the middle and upper abdomen accompanied by acid reflux and heartburn over the past 5 months. Her serum CA19.9, SCC, and CEA levels were 65.82 U/ml, 25.5 ng/ml, and 11.65 ng/ml, respectively. An abdomen computed tomography (CT) indicated a tumor measuring 7 x 6 cm located in the tail of the pancreas that invaded the posterior wall of the stomach and the splenic artery, accompanied by multiple hepatic and lymph node metastases in the left supraclavicular fossa ( Figure 1B ). Subsequently an endoscopic ultrasound (EUS)-guided biopsy was performed on the pancreatic lesion and the histological and immunohistochemically tests confirmed a cT4N1M1 primary pure squamous cell carcinoma ( Figure 2A ). A sequencing performed on the biopsied specimen revealed a stop-gain mutation in BRCA2 exon 11 (c.1830A>T, p.K944*) ( Figure S1 ), which has been reported as a pathogenic germline mutation. In addition, the patient had a tumor mutational burden (TMB) of 5.4 mut/Mb and a stable microsatellite status (MSS). Based on the genetic results, a regimen of nanoparticle albumin-bound paclitaxel (125 mg/m2) combined with cisplatin (75 mg/m2) was eventually decided after a multi-disciplinary panel discussion. The combined chemotherapy was initiated in July, 2018 ( Figure 1A ). After five cycles of treatment, the patient achieved partial response (PR) on primary pancreatic and metastatic lesions revealed by a total abdomen CT scan ( Figure 1B ) and the serum biomarkers (CA19.9, SCC, and CEA) declined into a normal range. She remained as PR after eight cycles. A magnetic resonance imaging (MRI) was performed in March, 2019 after 10 cycles of combined chemotherapy and showed that both hepatic and lymph node metastases (regional and distanced lymph nodes) achieved complete response (CR) and the primary pancreatic lesion shrank from the initial 5.7 to 1.5 cm in diameter ( Figure 1B ). Since the imaging examination indicated tumor downstaging, which might be qualified for surgical resection, a preoperative laparoscopy was conducted in April, 2019, and detected multiple nodules on the liver surface. No hepatic space-occupying lesion was detected by the intraoperative US. The nodules on hepatic segments 2, 3, and 4 were resected and sent for histopathological test, and results showed a few malignant tumor cells in the S2 nodule. A laparotomy continued under the request of the patient's family and revealed a lesion of 4 x 3cm in the pancreatic tail and multiple hepatic lesions. Subsequently, a posterior radical antegrade modular pancreatosplenectomy was performed and hepatic metastatic lesions were also resected. Histological examination of the resected specimens revealed severe tumor degeneration after the combined chemotherapy ( Figure 2B ) with vital tumor cells present only in small areas of primary and liver metastatic lesions. Two of the four peripancreatic lymph nodes had severe degeneration; no residual tumor cells were found in lymph nodes (n = 12). The pathological classification of pT3N0M1 was defined. The sequencing on the tumor tissue showed the retaining of BRCA2 K944*, a TMB of 8 mut/Mb and MSS. The patient experienced postoperative thrombocytopenia (platelet account: 6-9 x 109/L) of unknown cause and the platelet account returned to normal (50-60 x 109/L) 3 months later without any treatment. A repeat PET-CT in July, 2019 showed a liver recurrent lesion of 3.3 cm in diameter. The patient was then treated with olaparib (200 mg per day) combined with pembrolizumab (100 mg per 21 days) and achieved stable disease (SD) on her liver lesion 6 months later. The plasma and matched white blood cell samples of the patient were sent for sequencing using a panel with 520-cancer-related genes. The results confirmed BRCA2 K944* as a somatic mutation, and showed a TMB of 7.98 mut/Mb and MSS status. The patient experienced hepatic artery embolization and severe low platelet count. She died from a cerebral hemorrhage in March, 2020 with an OS of 21 months.

brca2 mutation, cisplatin, nanoparticle albumin-bound paclitaxel, overall survival, pancreatic squamous cell carcinoma

PMC6302580_01

Male

Candida auris, first reported in Japan in 2009, is an emerging pathogen that has caused severe disease in hospitalized patients in many countries, including India, South Africa, Spain, the United Kingdom, the United States, and Venezuela. In July 2015, a 65-year-old man from Kenya visiting Australia for the first time sought treatment in Perth, Western Australia, Australia, for chronically discharging sternal sinus persisting for >1 year. His active medical problems included severe hypercapneic chronic obstructive pulmonary disease with pulmonary hypertension, ischemic heart disease, and chronic kidney impairment. In July 2012, he had unstable angina treated by coronary stenting that was complicated by cardiac arrest with cardiopulmonary resuscitation, which resulted in sternal injuries and a 3-month intensive care unit hospitalization in Nairobi, Kenya. At hospital admission, computed tomography scan of the chest showed a 3.3-cm subcutaneous collection and bony changes from chronic sternal osteomyelitis (Figure). Surgical debridement confirmed sternal osteomyelitis with parasternal abscesses. Posaconazole was given as pragmatic oral therapy, and trough serum levels of 2.0 mg/L at week 2 and 2.60 mg/L at week 4 were achieved. The patient died from progressive cardiorespiratory failure 3 months later. Deep operative sternal bone samples yielded a yeast on Difco CHROMagar Candida medium (Becton Dickinson, https://www.bd.com/) that did not produce pseudohyphae or germ tubes. The isolate grew well at 40 C and 42 C but not 45 C. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI version 3.1; Bruker Daltonics, https://www.bruker.com/) identified the pathogen as Candida auris (score >2.1). Sequencing of the 18S rDNA internal transcribed region and 28S rDNA D1-D2 regions confirmed pathogen identification (Appendix Figure 1). We edited the DNA sequences, assembled consensus sequences using SeqScape (Applied Biosystems, https://www.thermofisher.com/us/en/home/brands/applied-biosystems.html), and performed sequence alignments with BLAST (https://blast.ncbi.nlm.nih.gov/Blast.cgi). The internal transcribed regions of our isolate matched 100% with C. auris reference strain KP131674.1. The D1-D2 regions of the isolate also matched 100% with those of multiple C. auris isolates (GenBank accession nos. JQ219331-2, KM000828, KM000830, KU321688). Susceptibility testing with the Sensititre YeastOne YO10 panel (Trek Diagnostic Systems, https://www.thermofisher.com/) showed fluconazole resistance (MIC >256 mg/L) and posaconazole susceptibility (MIC 0.06 mg/L) (Appendix Table). We performed whole-genome sequencing (WGS) on the isolate (FSMC57608) using the NextSeq platform (Illumina, https://www.illumina.com/) and then assembled Illumina paired-end sequencing data using SPAdes, St. Petersburg genome assembler 3.1.1 (http://spades.bioinf.spbau.ru/release3.1.1/manual.html). We identified core genome single-nucleotide polymorphisms (SNPs) using Snippy version 4.0 (http://www.vicbioinformatics.com/software.snippy.shtml), using the C. auris B8441 genome for reference and previously described methods, and mapped 97.77% of the reads. A maximum-parsimony phylogenetic tree was constructed by using MEGA version 7.0 (https://www.megasoftware.net/) and 10 other C. auris genomes. Results showed that FSMC57608 (GenBank accession no. SRP156632) is a South Africa clade III isolate (Appendix Figure 2) with SNPs V125A and F126L and at wild-type amino acid positions 132 and 143 of Erg11 (gene associated with azole class antifungal drug resistance) (Appendix Figure 3). Extensive nosocomial transmission of C. auris has been documented, and mortality rates of 40%-60% have been reported for patients with candidemia. C. auris can colonize human skin for months (,). Of 620 cases of C. auris infection linked to outbreaks in Europe during 2013-2017, a total of 466 (75.2%) patients became colonized. We postulate that our patient became colonized in 2012 in an intensive care unit in Kenya. This case also illustrates that clinical manifestations of C. auris infection can progress slowly for >12 months. C. auris is multidrug resistant and, therefore, poses a risk for all patients, given the limited antifungal options available. Tentative C. auris-specific MIC breakpoints exist, pending further correlation between MICs and clinical outcomes. Proposed breakpoints are derived from expert opinion and/or those of closely related Candida species for antimicrobial drugs (e.g., amphotericin B) that do not have breakpoints. Despite breakpoint uncertainty and concerns about emergent multidrug resistance among C. auris isolates, we had prescribed oral posaconazole for our patient because of the in vitro MIC results and his strong preference for oral antifungal therapy. WGS results show C. auris isolates fall into 4 distinct clades that appear to have emerged almost simultaneously in different geographic regions of the globe. Isolate FSMC57608 has SNPs V125A and F126L in Erg11, the latter SNP, F126L, having been described in previous investigations (J.F. Munoz, unpub. data, https://doi.org/10.1101/299917) (,). This isolate was also wild type at amino acid positions 132 and 143 of Erg11, as seen in Africa isolates (J.F. Munoz, unpub. data, https://doi.org/10.1101/299917), further supporting that the infection originated in Africa. In summary, we describe a case of travel-linked C. auris infection manifesting as chronic sternal osteomyelitis, diagnosed in Australia in 2015. The patient had a history of intensive care treatment in Kenya, a country with documented C. auris transmission, he required treatment in Australia 3 years later and exhibited clinically significant disease associated with South Africa clade III C. auris infection.

australia, candida auris, erg11, kenya, maldi-tof ms, south africa clade iii, antimicrobial resistance, bone, cardiorespiratory failure, multidrug resistant, sternal osteomyelitis, whole-genome sequencing, yeast

PMC6469747_01

Unknown

The CoD as described in hospital registers were retrospectively coded using the ICD-10-CM codes. Cause-specific mortality proportions were derived as the fraction of total deaths possibly associated to specific conditions, using hospital-based ICD-10-CM list diagnoses. Here, owing to the complexity associated with defining infections with pneumococcal aetiology, we limit our perspectives only on pneumococcal-related causes of deaths defined as follow: ALRI: Diagnosis of pneumonia based on medical declaration as cause of death (i.e. any Acute Lower Respiratory Tract Infection (ALRI) or pneumonia including all diagnosis of ALRI); or Clinically severe pneumonia: Death resulting from cough or difficult breathing as admission symptoms for child 1-59 months old residing in study area, A): Clinical pneumococcal infections And with either - A respiratory rate >= 40/minute, or temperature >38.5 C, or refusing to feed, or vomiting and/or lower chest in-drawing Culture-positive invasive pneumococcal disease Culture-negative polymerase chain reaction (PCR) or antigen test positive invasive pneumococcal disease B): Laboratory confirmed infections Radiologically confirmed pneumonia i.e. Chest X-ray-Community Acquired Pneumonia compatible with endpoint consolidation Radiologically confirmed pneumonia i.e. Chest X-ray-Community Acquired Pneumonia with any radiologic abnormality C): Radiologically confirmed infections Clinical cases of pneumococcal infections, which did not meet these criteria, were considered as non-confirmed pneumococcal diseases (unspecified). D): Causes of deaths not related to pneumococcus These included other biologically related causes of under-five deaths apart from those due to pneumococcal infections e.g. Tuberculosis (TB), HIV or malaria and others. E): Deaths due to injuries This consisted of under-five deaths with non-biological causes such as those resulting from injuries or accidents.

PMC9894277_01

Male

A 25-year-old male, non-smoker with no other co-morbidities initially reported at a peripheral hospital with history of cough and weight loss of 1 month duration. The cough was insidious in onset with mucoid expectoration and history of weight loss of 05 kilograms with reduced appetite and generalized malaise. On examination, he had bronchial breath sounds in left infraclavicular and interscapular area, and crackles were heard in right mammary area. On evaluation, there was thrombocytosis and raised erythrocyte sedimentation rate, with normal haemoglobin, liver and renal function tests. His chest radiograph showed dense acinar radiopacities in the left upper zone and superior part of Left middle zone, suggestive of active pulmonary tuberculosis [Figure 1a]. On sputum smear, Ziehl-Neelsen (ZN) stain 2+ acid-fast bacilli (AFB) were seen (RNCTP grading). He was diagnosed as sputum smear positive pulmonary tuberculosis and was initially started on first-line antitubercular drugs. He showed features of clinical deterioration with no weight gain, worsening of his chest radiograph and continued to be sputum smear positive even after one month of ATT. He was further evaluated at our centre, his sputum CBNAAT (gene Xpert) showed presence of Mycobacterium (MTB detected high), and rifampicin resistance was also present [Table 1]. His sputum MTB LJ medium culture showed positive growth for MTB with resistance to isoniazid, rifampicin, pyrazinamide, levofloxacin and ethambutol. The first-line probe assay (LPA-1) confirmed the rifampicin resistance (presence of rpoB mutation) and resistance to isoniazid (presence of katG mutation), while the second-line probe assay (LPA-2) showed fluoroquinolone resistance but sensitive to aminoglycosides. The patient was diagnosed as a case of pre-extensively drug-resistant tuberculosis and was started on bedaquiline-based therapy consisting of bedaquiline, linezolid, clofazimine, cycloserine and levofloxacin. However, he had suboptimal response and continued to have productive cough and radiological progression of disease even after 04 months of the above regime. In view of his worsening of disease, he was started on delamanid-based therapy. He showed significant clinical response in form amelioration of his cough and weight gain of 13 kilograms. He became sputum and culture negative after one month of delamanid therapy. His repeat chest radiograph showed significant improvement [Figure 1b]. His delamanid was stopped after 06 months, and he was discharged on continuation phase of ATT.

delamanid, extensively drug-resistant tuberculosis, sputum smear positive pulmonary tuberculosis

PMC9894277_02

Male

A 34-year-old male with no previous known co-morbidities initially reported to a peripheral hospital with history of cough with mucoid expectoration, dyspnoea and weight loss of 14 kilograms in 1 month. On examination, he was cachectic (weight: 34 kilograms) and had pallor. The chest examination showed decreased expansion on right side with bronchial breath sounds on auscultation over right infra- and interscapular areas. On evaluation, he has anaemia (haemoglobin 9 mg/dl) and thrombocytosis, while rest of the biochemical parameters were within normal limits [Table 1]. He was also found to have positive hepatitis B antigen. His sputum ZN staining showed presence of AFB (2+), and sputum CBNAAT (gene Xpert) confirmed the presence of AFB but showed high-level rifampicin resistance. The chest radiograph showed non-homogenous opacity with extensive cavitary involvement of right upper and mid-zone [Figure 2a]. He was diagnosed as a case of sputum smear positive rifampicin-resistant pulmonary tuberculosis and was transferred to our centre for further management. At our centre, he underwent sputum LPA-1 which confirmed rifampicin and isoniazid resistance, and LPA-2 showed resistance to fluoroquinolone but sensitive to aminoglycoside. He was managed as case of pre-XDR tuberculosis and was started on bedaquiline-based ATT. He showed suboptimal response to the therapy and continued to be symptomatic with radiological worsening. He also developed secondary spontaneous pneumothorax on right side which was managed with chest tube drainage, and later pleurodesis was also done with 2.5% povidone iodine. In view of clinical and radiological deterioration, delamanid was added to the therapy. The patient showed significant response to the ATT and attained smear conversion after two months and culture conversion after five months [Figure 2b]. Due to his extensive disease, the patient had developed post-tuberculosis sequelae which was confirmed by computed tomography of chest. His CT chest showed marked tubular, varicose and cylindrical bronchiectasis with bronchial wall thickening in segmental and subsegmental bronchi of all the lobes of both lungs with more conspicuous involvement of right upper and middle lobes. There were areas of consolidation on both sides. The spirometry showed mixed defect-moderate restriction (FVC-3.76 L (53.8%) and obstruction (FEV1/FVC-50.2%), FEV1-3.23L (46.6%). His DLCO was reduced suggestive of mild diffusion defect. The patient was given 06 months of bedaquiline and delamanid and was later continued continuation phase of ATT with total duration of ATT for 18 months.

delamanid, extensively drug-resistant tuberculosis, sputum smear positive pulmonary tuberculosis

PMC3755699_01

Female

A 78-year-old woman, postmenopausal for the last 30 years, presented to our gynecology outpatient department with symptoms of vaginal discharge for the last 3 weeks, associated with weakness and fever. The discharge was foul smelling and yellowish with a reddish tinge. There was no history of urinary frequency, diabetes, or tuberculosis. Her parity score was P4L4, with all 4 pregnancies being full-term vaginal delivery and the last pregnancy was 50 years ago. The patient underwent tubal ligation 46 years ago and also gave a history of surgery for intertrochanteric fracture of the femur neck, which was uneventful. On examination, the patient was moderately built and moderately nourished, with mild pallor. The abdomen was soft and non-tender. Per-speculum examination revealed the cervix, which was bleeding on touch. On vaginal examination, 6-8 weeks anteverted uterus with parametrial tenderness was noted. Lab test revealed 11.3 gm% hemoglobin with 11800/cumm total leucocyte count, with other parameters being normal. Radiological examination was advised and the MRI result was reported as a mass lesion in the cervix, with irregular margins extending into two-thirds of the myometrium superiorly and the upper one-third of the vagina inferiorly, with loss of fat planes between the uterus and posterior wall of the bladder and anterior wall of the rectum (Figure 1). In view of clinical and radiological findings, a preoperative diagnosis of cervical carcinoma was made. Cervical and endometrial biopsies were taken under anesthesia and sent for histopathological examination. Intra-operatively, 15cc of pus was drained from the endometrial cavity and sent for microbiological examination, which was found to be positive for gram-positive cocci. Microscopic sections obtained from the tissue received for histopathological examination showed endometrial tissue with few glands and sheets of lipid containing foamy histiocytes in the stroma, along with diffuse infiltration by inflammatory cells (lymphocytes and plasma cells). A few areas of histiocytic aggregates were seen infiltrating the myometrium (Figures 2-5). Ziehl-Neelsen, PAS, and GMS staining revealed no specific organism. Cervical biopsy revealed acute inflammation with regenerative atypia in the squamous epithelium. However, extensive study of endometrial and endocervical tissue revealed no evidence of malignancy.

cervical carcinoma, histiocytic endometritis, xanthogranulomatous endometritis

PMC8647993_01

Male

An 8-month-old infant was referred by a paediatrician to a dermatology outpatient clinic due to disseminated blisters and erosions failing to respond to treatment. The skin lesions were presented for about 5 weeks. According to the mother, the parents and elder brother of the boy had suffered from gastroenterocolitis at that time. All the family members presented fever of 38-38.5 C accompanied by diarrhoea and abdominal pain. On the third day of gastroenterocolitis, our patient started to present non-itchy erythematous plaques on the palms and soles, with solitary vesicles, accompanied by loss of appetite. The patient was consulted by a paediatrician, who suspected the Boston disease with secondary bacterial infection and administered an analgetic (acetaminophen), an antibiotic (amoxycillin with clavulanic acid), topical glucocorticosteroids (fluticasone and hydrocortisone), and dimetindene (oral solution). After 7 days of application, there was no response to that treatment regime. The boy was referred to a hospital, where he was consulted by another paediatrician, who administered clarithromycin. The treatment with clarithromycin was discontinued after few days, as according to the mother, erythematous circular plaques started to spread from palms and soles proximally, affecting forearms, arms, shins, thighs, and the trunk (Figure 1A). Moreover, tense blisters and vesicles on the erythematous background, initially located on distal parts of upper and lower limbs (Figure 1B), were gradually spreading to the periumbilical area (Figure 1C), the whole trunk, and the face. The skin of the scalp and diaper area was spared. There was no family history of atopic diseases. The boy was breastfed since birth and mother did not have to use any kind of elimination diet, and the diet was expanded according to the guidelines without any disturbing symptoms. A family history of autoimmune blistering skin diseases and chronic diseases was negative. There was no recent history of vaccination prior to the onset of lesions. The boy was vaccinated only on the first day of life (against hepatitis B and tuberculosis), while other mandatory vaccinations were postponed due to mild but frequent oropharyngeal infections, transmitted mostly by older brother of the patient. Although our patient presented new blisters every day, with some of them turning into oozing erosions covered with yellowish crusts, the boy was in a good general condition, without any additional systemic symptoms, such as fever, weakness, or pruritus. A chest X-ray ordered by a paediatrician showed slight inflammatory lesions pericardially and in the upper lung fields. Abdomen ultrasound did not reveal any abnormalities. Interestingly, mother of the boy decided to check if the family members had COVID-19 infection, and about 4 weeks after the onset of gastrointestinal symptoms, the pertinent blood tests were performed. It turned out that our patient, older brother, and father all had IgG antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (determined by CMIA:chemiluminescent microparticle immunoassay--235 BAU/ml), while mother of the boy had a positive SARS-CoV-2 reverse transcription PCR (RT-PCR) test. Our patient was referred to a dermatologist who suspected erythema multiforme or Kaposi varicelliform eruption with secondary infection and prescribed topical treatment with fucidic acid combined with hydrocortisone, cleansing with sodium hypochlorite, and systemic treatment with acyclovir. As there was no improvement after 2 days of this treatment and the boy started to refuse to eat or drink, the dermatologist decided to refer the infant to a hospital. Laboratory findings showed slightly increased levels of platelets (480 x 109 per L), slight microcytic anaemia, higher levels of eosinophils (7%) in a complete blood count with differential leukocyte count, slightly elevated C-reactive protein (12 mg/dl) with negative procalcitonin (0.04 ng/ml), slightly higher D-dimer (11.64 mg/L), and slightly lower level of serum IgA (24 mg/dl). Culture from blister fluid showed growth of Streptococcus pyogenes. The RT-PCR test for the SARS-CoV-2 was negative. At last, the consulting dermatologist suspected an autoimmune blistering skin disease and took a biopsy from peribullous skin for direct immunofluorescence (DIF). DIF revealed linear deposits of IgG (+), IgG1 (+) (Figure 1D), and C3 (++) along the DEJ. No deposits of IgA, IgM, and IgG4 were found. Multiplex ELISA (Euroimmun, Germany) detected the markedly increased level of IgG antibodies against BP180 (9.81), whereas the levels of antibodies against BP230, desmoglein 1, desmoglein 3, type VII collagen, and envoplakin were within normal range (negative level ratio <1). Thus, BP was diagnosed. Treatment with systemic methylprednisolone intravenously at a single 40 mg dose, intravenous immunoglobulin (1.5 g/kg bwt, the dose was administered within 2 days), amoxicillin (due to secondary bacterial infection of blisters with Streptococcus pyogenes), and a pain reliever (paracetamol) were introduced. A very fast improvement of skin condition was observed during the treatment. After a 5-day hospital stay, our patient was discharged home, and systemic treatment with oral prednisolone and amoxicillin was continued. The doses of prednisone were tapered gradually, about 2.5 mg every 2 weeks, and the treatment was discontinued after 6 weeks. Aggravation of the disease when tapering the dose of prednisone was not observed. With total resolution of lesions that left only discreet post-inflammatory discolorations, the boy remains in good condition.

covid-19, rt-pcr, autoimmune blistering, bullous pemphigoid, infants

PMC9772812_01

Male

A 46-year-old Japanese man was referred to our hospital in 2017 after developing Raynaud's symptoms on his fingers, taut facial skin and heartburn. Significant skin sclerosis had spread from his fingers to his entire body. Although the patient did not have digital ulceration, pigmentation over his trunk was observed. His modified Rodnan's skin score (mRSS) was 36/51 points. Respiratory symptoms such as cough and shortness of breath were absent, but chest CT showed interstitial pneumonia in both lungs (Fig. 1A). Forced vital capacity (FVC) was 4.13 l (predicted value 4.2 l) and remained stable. His anti-topoisomerase I antibody titre was >=850.0 U/ml (normal <10.0 U/ml). Based on these findings, he was diagnosed with SSc. Combination therapy with oral prednisolone (PSL) 30 mg/day and monthly intravenous cyclophosphamide (IVCY) was started. His skin symptoms gradually improved and the lung lesions did not progress (Fig. 1B). PSL was gradually tapered to 2 mg/day and after six courses the IVCY was changed to tacrolimus. The mRSS improved to 4/51 points and in June 2021 his condition had stabilized following PSL (2 mg) and tacrolimus therapy. In August 2021 he was vaccinated twice with the anti-SARS-CoV-2 mRNA vaccine (Pfizer-BioNTech) at an interval of 3 weeks. Two weeks after the first vaccination he had difficulty bending his fingers and upper limbs and felt that his facial skin was taut. After the second vaccination, the skin symptoms worsened and dyspnoea on effort appeared. His mRSS at the time he visited our outpatient clinic, 1 month after the second injection, was 16/51 points. His KL-6 increased to 502 U/ml from 292 U/ml (normal range 105.3-401.2) and chest CT showed ground glass opacities in the lower lobe pleura bilaterally (Fig. 1C). His FVC had decreased to 3.35 l. A treatment regimen of four weekly rituximab infusions (375 mg/m2) was started. The symptoms improved over 2 months, including dyspnoea on effort and difficulty bending the fingers. The mRSS also improved to 10/51 points. The SARS-CoV-2 pandemic has led to the active promotion of the anti-SARS-CoV-2 mRNA vaccination worldwide. Although systemic symptoms, such as fever, chills, myalgia, arthralgia, headache and malaise, are commonly reported in vaccinated individuals, rigorous investigation of the effects of the vaccines on rheumatic disease activity, including SSc, have failed to identify any impact. The anti-SARS-CoV-2 vaccine is considered safe for patients with rheumatic disease. Machado et al. studied 4604 patients with inflammatory rheumatic and musculoskeletal diseases (RMDs), including 62 scleroderma patients, vaccinated with the anti-SARS-CoV-2 vaccine and reported a flare rate of 4.4% and an occasionally severe flare rate of 0.6%. Connolly et al. studied 1377 patients with RMDs, including 14 with scleroderma, who received the anti-SARS-CoV-2 vaccine. While there were no cases of severe flare, 11% of patients had a flare requiring treatment. Post-vaccine RMD relapse was more common in patients with a prior SARS-CoV-2 diagnosis or flare within the 6 months before vaccination. Our patient had stable disease activity for >2 years and no history of SARS-CoV-2 infection. A small number of cases of rheumatic disease, both new-onset and relapse, have been reported after anti-SARS-CoV-2 vaccination. Cole et al. reported a case of new-onset scleroderma in a patient vaccinated with the ChAdOx1 nCOV-19 vaccine. They hypothesized that a recombinant adenovirus vector encoding the SARS-CoV-2 spike protein antigen triggered an immune response that led to the development of scleroderma. Regarding mRNA vaccination, a patient with discoid lupus developed overlap syndrome comprising scleroderma and myositis after vaccination. It has been reported that myocarditis may occur, although rarely, after two doses of SARS-CoV-2 mRNA vaccine, especially in young males. The mRNA vaccine is composed of mRNA encapsulated in lipid nanoparticles (LNPs), and the LNPs are thought to cause myocarditis directly or indirectly by triggering an immune response. Moreover, SARS-CoV-2 mRNA vaccination is thought to elicit CD4+ and CD8+ T cell responses and elevate cytokine levels. The exacerbation of skin and lung lesions after vaccination in our patient suggests that the resultant immune responses triggered the SSc flare. The efficacy of rituximab in SSc has been recently demonstrated and is consistent with the improvement of scleroderma. In our patient, scleroderma progressed rapidly after vaccination but gradually improved after rituximab administration. Thus rituximab is also effective against scleroderma induced by anti-SARS-CoV-2 mRNA vaccination. This is the first report of SSc exacerbation following anti-SARS-CoV-2 mRNA vaccination. While RMD patients should be vaccinated, given their higher rates of SARS-CoV-2 infection, SARS-CoV-2-related mortality and the rarity of relapse, SSc patients should be monitored for worsening symptoms after the vaccine.

PMC5368394_01

Male

A previously healthy 67-year-old male presented with a swollen left hand following a laceration to his third digit after working in soil in his yard in June 2013. He also managed three large hobby aquariums. A 10-day consecutive course of cefprozil and clindamycin marginally improved his swelling. However, he returned in October 2013 with worsening stiffness and digital and hand swelling, which resulted in a diagnosis of seronegative rheumatoid arthritis (RA) after consultation with rheumatology. All autoimmune serology was negative, and inflammatory markers were normal. His swollen left hand partially resolved after pulsed dose prednisone (20 mg daily/2 weeks) but worsened again. He then received prednisone (10 mg/day) and sulfasalazine (2 g/day) with incomplete improvement followed by progression with spread to his left elbow. Several aspirations and intra-articular steroid injections of left elbow, wrist, and MCP joints were attempted with minimal improvement. On the presumption that his rheumatoid arthritis was refractory, methotrexate and leflunomide were added. In January 2014, the patient evolved nodules located on the extensor surfaces of his left arm and hand. New nodules appeared on the ulnar aspect of his thumb, radial aspect of his index finger, styloid process, and mid shaft of the ulna. Due to ongoing disease, the biologic adalimumab (Humira) was started in February 2014. Prednisone and sulfasalazine were discontinued, but methotrexate and leflunomide were continued. Infectious prescreening for his biologic therapy screening occurred one week after receiving the first dose of Humira. A Mantoux test read at 9-millimetres was presumed to be falsely positive after a subsequent negative interferon-gamma release assay (IGRA) test (Quantiferon Gold In-Tube) was obtained. After three months of treatment, he continued to have a swollen left olecranon and developed lower extremity nodules also. Several joint aspirations were performed from his wrist and knee (due to swelling), but microscopy and bacterial cultures were negative. In December 2014 he had worsening of the swelling and pain in the left wrist, metacarpophalangeal joints, elbow, and left knee. Sulfasalazine and prednisone were restarted along with rotation of his biologic to etanercept. This resulted in dramatic worsening of his nodular lesions. An urgent biopsy of a left arm nodule and a synovial fluid aspirate of his left elbow were collected and were both positive for acid-fast bacilli consistent with mycobacterium. His immunosuppressants were immediately discontinued and he was urgently referred to the Tuberculosis clinic. Subsequently, the mycobacterial species was determined by mycobacterial growth indicator tube (MGIT) culture to be Mycobacterium marinum in two additional joint aspirates (left wrist and olecranon bursa) that were grown at reduced temperature. A summary of the patient's clinical course is depicted in Figure 1.

PMC4714624_01

Male

A 23-year-old man presented to the emergency department with the after being struck in the hand with a basketball. Clinical findings are seen in the image above. What is the nature of the injury seen above? What is the role of radiography in clinical workup? What are the common causes of failed reduction attempts in thumb interphalangeal (IP) joint dislocations? How are open thumb IP joint dislocations best managed?

ip dislocation of thumb, open thumb ipj dislocation, thumb ipj dislocation, thumb dislocation, thumb interphalangeal (ip) joint dislocation

PMC8725022_01

Female

A 48-year-old woman living with HIV ("case" patient) sought care in Georgia, USA for a chronic, left-sided breast lesion. She reported recurrent Staphylococcus aureus skin infections, including breast abscesses. She was born in the United States, never lived abroad, intermittently experienced homelessness, was not receiving antiretroviral therapy, and had never received bacillus Calmette-Guerin (BCG) vaccine. Signs of advanced HIV and left breast edema and tenderness were noted. An ultrasound showed an abscess and surgical intervention was warranted for source control. A chest computed tomography showed multiple enlarged intrathoracic lymph nodes and a pulmonary calcified granuloma. The CD4 count was 221 cells/mm3 and the HIV viral load was 3.74 logs. Multiple breast abscesses were found during operative debridement. Two surgical sample cultures on routine microbiologic media were positive for S aureus. The samples were also cultured on BD BACTEC MGIT and Middlebrook 7H11 agar medium. Breast tissue histopathology showed acute inflammation consistent with abscesses. No granulomas were described, and acid-fast staining was not performed. Forty days later, a single mycobacteria colony was noted on the 7H11 agar identified as Mycobacterium tuberculosis complex (MTBC) by high-performance liquid chromatography. The patient was referred to her local health department where treatment for tuberculosis and HIV were initiated. The isolate was subjected to routine, conventional genotyping (spoligotype and 24-locus MIRU-VNTR) by the Centers for Disease Control and Prevention and identified as Mycobacterium bovis BCG-type. We initiated an investigation for cross-contamination because the patient had never received BCG vaccine or chemotherapy. We identified a BCG-positive case ("source" patient) with a similar collection date by reviewing Georgia's State Electronic Notifiable Disease Surveillance System (SendSS) records. The source patient was undergoing surgical management of intra-abdominal infection, a complication of BCG intravesical instillation. The case and source patients' surgeries were performed at the same hospital, prompting review of laboratory records. However, the samples were processed at different times and laboratory cross-contamination was ruled out. Upon review of hospital records, we discovered the case patient's surgery was performed 48 hours after the source patient's surgery in the same operating room (OR). The source patient underwent an exploratory laparotomy, over 300 milliliters of pus were drained, and samples grew M. bovis BCG-type. Four other patients underwent surgery in the same OR between source and case patients' surgeries. No samples for microbiological tests were collected in the OR for these 4 cases. Review of state surveillance and hospital records as of September 2021 did not uncover any other suspected false-positive BCG cultures. Moreover, there was no documentation of surgical site complications secondary to infections. Of note, these 4 patients had no hardware or device implanted in the OR. We could not ascertain if any common surgical equipment was used for both patients. Operating rooms in this institution undergo turnover cleaning between cases and terminal cleaning at the end of the day. Turnover cleaning was performed with Sani-Cloth AF3 wipes and terminal cleaning was performed with Ecolab A-456 II disinfectant. The first product claims to have activity against M. bovis whereas the latter product does not mention M. bovis in its technical sheet. Two gaps in the OR cleaning process were identified in this investigation. First, the nurse circulator present during the source patient's surgery was unaware of turnover cleaning policy requiring the circulator to disinfect surgical equipment after each case. Second, the surgical table was disinfected as part of the turnover cleaning process and left draped at the end of the day and excluded as part of the terminal cleaning process. Both gaps were addressed by training the OR personnel who perform these turnover tasks. Globally, approximately 2% of all MTBC-positive cultures result from laboratory cross-contamination. Furthermore, 9% of all TB diagnoses may be incorrect due to laboratory cross-contamination. In addition to exposing patients to unneeded and potentially harmful treatment, false TB diagnoses may cost an average of $10 000 per patient in the United States. However, cross-contamination does not occur exclusively in the laboratory. We describe a case of a false-positive MTB culture attributed to cross-contamination of the environment from a previous patient who had surgery for a disseminated BCG infection in the same OR. Although fomites are not generally considered a source for transmission of MTBC, given the results of our investigation, it appears plausible that an OR table surface or tool was heavily contaminated with M. bovis, which can survive up to 4 months on dry, inanimate surfaces, and contaminated specimens placed on that table or touched by that tool 4 days later. Although fomite-based transmission following improper cleaning of bronchoscopes or infected cystoscopes is well established and has been associated with both false-positive cultures and potential exposure to M. tuberculosis, aside from this report, we did not find any other reports of MTBC false-positive cultures due to cross-contamination in the OR. While only our case patient's samples were cross-contaminated in this incident, it is plausible that any material or device on the OR table that was placed into another patient could have resulted in serious complications, including inoculation of M. bovis or contamination and infection of wound beds. Our report demonstrates the importance in thorough MTBC false-positive investigations in accordance with the CDC False-Positive Investigation Toolkit and warrants further investigation into OR cleaning protocols and procedures. This report is timely given the recent bone graft-related MTBC outbreak throughout the United States. Clinicians, public health, and infection control staff should be aware that MTBC cross-contamination in the OR, and perhaps fomite-based transmission, is an exceedingly rare, but possible, event.

bcg, mycobacterium bovis, mycobacterium tuberculosis, cross-contamination, false-positive, tuberculosis

PMC4857691_01

Male

A 47-year-old married male with acquired immune deficiency syndrome (AIDS) who was a shopkeeper by profession presented with skin lesions on both lower limbs for past 9 months. It was associated with mild itching and pain. There were no complaints of joint pain or redness of eyes. The patient was diagnosed with HIV in 2007 and first-line antiretroviral therapy (ART) (tenofovir, lamivudine, efavirenz) was started in 2009. He developed severe fatigue, weight loss, cough, and dyspnea, and CD4 count dropped to 50 cells/mm3 with plasma viral load of 157 copies/ml, 11 months ago in March 2015. Due to treatment failure, he was then put on second-line ART (abacavir, lamivudine, atazanavir, and ritonavir) and his CD4 count increased to 204 cells/mm3 with plasma viral load of 38 copies/ml in September 2015. The present skin lesions started 2 months after initiation of second-line ART. Patient also had history of pulmonary tuberculosis (TB) in 2007 when his CD4 count was 213 cells/mm3, and Herpes Zoster in 2012 when CD4 count was 78 for which treatment was taken. On general examination, patient was moderately built and nourished, and his vitals were within normal limits. Cutaneous examination revealed multiple well-defined nontender hyperpigmented papules and nodules on both ankles, dorsum of bilateral feet and soles [Figure 1a-c]. Inguinal lymph nodes were not palpable. There were no lesions elsewhere in the body. Hair, nail, and oral mucosa were normal. No ocular or systemic abnormality was noted. Differential diagnoses considered were Kaposi's sarcoma and immune reconstitution inflammatory syndrome (IRIS) related infection including cutaneous TB. His routine blood investigations showed hemoglobin 11.5 g%, total leukocyte count 4300/mm3; and differential count neutrophil 70%, lymphocytes 28%, eosinophils 1% and monocytes 1%, and platelets 287,000/mm3. Liver function tests and renal function tests were normal. Mantoux test, serological tests for syphilis (VDRL, TPHA), hepatitis B and C, and anti-nuclear antibodies were negative. Chest radiography and abdominal ultrasonography were normal. Biopsy taken from the nodular lesion on dorsum of left foot showed a diffused dense infiltrate in reticular dermis with mild fibroplasia. The infiltrate consisted of neutrophils and histiocytes with scattering of lymphocytes and plasma cells. The infiltrate surrounded small thickened vessels and extended extensively into the interstitium. Small amount of neutrophilic nuclear dust was also present within the infiltrate [Figure 2]. Overlying epidermis and dermoepidermal junction were largely spared. These features were suggestive of EED. Patient was started on oral dapsone 100 mg/day and then increased to 200 mg/day to which he is responding gradually.

eed, hiv/aids, iris

PMC9650543_01

Female

The patient was 77-year-old woman with a history of ischemic cardiomyopathy and severe functional mitral and tricuspid regurgitation. Two years prior, she had undergone coronary bypass surgery, mitral valve ring annuloplasty, and suture annuloplasty of the tricuspid valve (DeVega). The patient complained of worsening heart failure symptoms, particularly peripheral edema, decreased physical capacity, and shortness of breath (New York Heart Association (NYHA) Functional Class III). Upon admission, physical examination revealed marked peripheral edema, jugular venous distension, and irregular heartbeat. The electrocardiogram showed atrial fibrillation. NT-proB-type natriuretic peptide level was 2,270 pg/mL. Echocardiography demonstrated normal left ventricular function and mild mitral regurgitation after mitral ring annuloplasty but massive tricuspid regurgitation (vena contractae width of 15 mm) due to gradual dilation of the tricuspid annulus (diameter of 40 mm) (Supplementary Video S1). The patient was evaluated as to be at high risk for re-surgery of the tricuspid valve (EuroScore II 4.8%) and was considered for TTVr by the heart team. TEER was performed by using the TriClip device (Abbott, Vascular GmbH). During the TEER procedure, it was difficult to visualize the septal leaflet of the tricuspid valve in transesophageal echocardiography (TEE) due to shadowing from the annuloplasty ring on the mitral site. This was resolved by utilizing an atypically higher degree of probe rotation (Supplementary Video S2). Previous sutured annuloplasty of the tricuspid valve did not affect imaging of the valve or the procedure itself. The first device was used to grasp the anterior and septal leaflets. The second device was deployed to grasp the posterior and septal leaflets. Tricuspid regurgitation was reduced to a mild degree in postprocedural TEE (Figure 1), and in transthoracic echocardiography that was performed at the time of discharge (Supplementary Video S3). Hemodynamic improvement with slightly reduced left atrial pressure (from 12 mmHg before the procedure to 9 mmHg after the procedure) and markedly increased cardiac index (from 1.8 to 2.5 L min-1 m-2). After 1 month of follow-up, repeat echocardiography demonstrated tricuspid regurgitation grade 1 without stenosis (transvalvular gradient of 1 mmHg). The patient reported that physical capacity and dypnea had improved (to NYHA functional class I).

triclip, annuloplasty, percutaneous, surgery, tricuspid regurgitation

PMC4702151_01

Male

A 30-year-old man with an unremarkable medical history was admitted to the emergency room after experiencing numbness on the right side of his face and dizziness while playing basketball. He recounts that he quickly had a transient cold sensation on the right side of his face extending to his right arm and leg. These symptoms were followed by a cramp-like sensation on the right arm and weakness of the right leg. Afterward, the remaining symptoms were weakness/numbness on the right side of the face and difficulty with speech and swallowing. The patient recently had an uneventful upper respiratory tract infection and had no toxic habits. Family history was unremarkable. In the emergency room, he had right facial asymmetry with tongue deviation to the right and right hemiparesis. Laboratory values and the initial head computed tomography scan were unremarkable. Forty-eight hours later, magnetic resonance imaging (MRI) of the brain showed multiple recent infarcts at both cerebellar hemispheres, suggestive of a VAD (Figure 1). Magnetic resonance angiography (MRA) showed bilateral VAD (Figure 2). He was anticoagulated and required gastrostomy for severe dysphagia. The patient was admitted to an inpatient rehabilitation facility where he scored 81 on the Functional Independence Measure at initial evaluation. He was discharged after 16 days, with a score of 107. At 6 months, he was asymptomatic, and continues to work as a security guard.

basketball, spontaneous bilateral vertebral artery dissection, sports, stroke

PMC5352017_01

Female

A 15-year-old female patient (menarche one year earlier) presented with severe dysmenorrhoea with normal menstrual flow. On the abdominal examination, fullness and tenderness was seen in the left flank. There was no history of tuberculosis or any urinary complaints. Ultrasound revealed a septate uterus with heterogeneous collection in the left uterine cavity. There was a left-sided, complex cystic lesion with haematosalpinx. Both kidneys were normally visualized. MRI was performed in a 1.5T system (Achieva, Philips Medical Systems, The Netherlands), which showed a septate uterus with normal outer fundal contour of the uterus. The left-sided cavity was obstructed with associated hematometra. There was also left haematosalpinx and endometriomas in the left ovary with loculated, hemorrhagic fluid in the lower peritoneal cavity. The right-sided uterine cavity was seen to communicate with the single cervical canal (Figures 1, 2). The patient underwent exploratory laparotomy with excision of the left-sided uterine cavity and of the left adnexal endometriotic lesions. The postoperative course was uneventful with relief of dysmenorrhoea.

adnexa uteri, magnetic resonance imaging, mullerian ducts

PMC7395467_01

Female

Our patient is a 36-year-old female with a history of adult onset seizures. She was born and raised in Mexico and emigrated to the United States at the age of 8. Since arriving to the United States, she had never returned to Mexico. She had her first seizure about 10 years before presentation, at which point she was placed on anti-epileptic medications that were subsequently weaned off without any further seizure activity in the past several years. No prior imaging was available for our review, but the patient denied report of any intracranial lesions that could be identified as the culprit of the adult onset seizures. She initially presented to an outside institution with progressively worsening bilateral headaches over the past year that were associated with vertigo and intermittent nausea. The headaches were worse at night and on waking up in the morning, and they improved throughout the day. A computerized tomography (CT) scan demonstrated ventriculomegaly and transependymal flow, with evidence of obstruction at the level of the fourth ventricle. She was referred to our clinic by our neurology colleagues, where she was found to have no neurologic deficits on examination. Outpatient magnetic resonance imaging (MRI) demonstrated obstructed hydrocephalus secondary to a lobulated cystic mass within the fourth ventricle, with a streak of internal linear enhancement most consistent with racemose NCC. A worm was easily identified within the cyst on the MRI [Figure 1]. Given the chronic nature of the lesion and her benign clinical examination, she was scheduled for elective surgery a few weeks later. She underwent right frontal burr hole for endoscopic third ventriculostomy and placement of external ventricular drain (EVD), then she was positioned prone and underwent suboccipital craniotomy for resection of the fourth ventricular cystic mass followed by duraplasty. The cyst was removed as a single en bloc specimen, although during the process of removal, a small portion of the cyst ruptured into the ventricle - this was quickly suctioned and extensively irrigated. Gross examination [Figure 2] and pathology [Figure 3] demonstrated a mature T. solium plerocercoid larvae measuring 1.2 x 0.5 x 0.2 cm encased in a tan, gelatinous, cystic membrane. Postoperatively, she had no neurologic deficits. Her EVD was quickly weaned with minimal drainage and low intracranial pressure, so it was removed on postoperative day 2. She underwent ophthalmologic examination, demonstrating no evidence of an active ocular infection or involvement of NCC, but concern for a chronic, inactive choroidal inflammatory process. Our infectious disease colleagues were consulted and found no other risk factors for NCC aside from living in Mexico until the age of 8, and she was negative for tuberculosis infection. Given her longstanding history of seizures, but recent presentation with an active lesion, it was felt that she may have been auto-infecting. She underwent a 21-day course of albendazole with a 14-day dexamethasone taper for protection against aseptic meningitis. She was also prescribed a single dose of praziquantel at the end of her therapy given concerns for possible auto-infection from her gastrointestinal system. On discharge, her headaches, vertigo, and nausea had completely resolved.

hydrocephalus, intraventricular, neurocysticercosis, taenia solium, tapeworm

PMC6529843_01

Male

The patient is a Caucasian 3-years old male child, late-preterm born (36 weeks) from vaginal delivery, after a pregnancy complicated by placental detachment. Birth weight was 2,490 g (26 centile). He was the first child of an unrelated couple. Family history was negative for cardiac or hepatic disorders. The main stages of psychomotor development were delayed (sitting position at 8 months with hypotonia; walking at 18 months; speaking at 3 years). At 20 months of age a systolic murmur was found at the cardiac auscultation and heart ultrasound was performed, showing a mild stenosis of the pulmonary branches. Screening for metabolic diseases was negative, except for the finding of hypertransaminasemia. Because of dysmorphic facial features, delayed neurological development and elevated liver enzymes, a genetic condition was suspected and the patient was referred to the Clinical Genetics Unit of the Giovanni XXIII Children's Hospital in Bari. At referral, height, weight and head circumference were normal (>50 centile). He featured prominent frontal bossing, saddle nose with a bulbous tip, 2/VI systolic cardiac murmur, severe psychomotor retardation suggesting an autistic phenotype. His stools were hypocholic with remains of undigested food. Fundus oculi and brain resonance were normal. Karyotype and FRAXA analysis resulted negative. After patient's parents signed the informed consent, gene sequencing of JAG1 (NM_000214) was performed by Next Generation Sequencing. Target enrichment was done by TruSeq custom amplicon (Illumina, San Diego, CA, United States) according to the manufacturer's instructions. Template library was prepared and was sequenced using MiseqIllumina platform (Illumina, San Diego, CA, United States). Annotation and filtering of variants were performed with Illumina Variant Studio version 2.0, following recommended settings. To evaluate the completeness of the method for the screening of the targeted gene, the sequencing coverage of each amplicon was analyzed in detail using Integrative Genome Viewer version 2.3 (Broad Institute, Cambridge, MA). Variants and region with a depth coverage below 30x were confirmed by Sanger sequencing. The heterozygous sequence variant c.2026delT; p.Cys676AlafsTer67 in exon 16 was identified and confirmed using Sanger sequencing (Figure 1), also because the coverage in exon 16 was very low (<30 x). Primers sequences for PCR amplification of the exon 16 were designed using Primer3 software: Forward primer CCTGTCGTGAATGGTCCTG, Reverse primer CCAGGCCCAGAGAAATATCA. The variant was absent in both parents, arisen as a de novo variant, which determines the formation of a stop codon. Variant was checked for previously reported causative mutations in published works and mutation databases: Human Gene Mutation Database (HGMD) and Leiden Open Variation Database (LOVD) and it has never been described before. Moreover, variant was searched indbSNP, 1,000 Genomes and ExACdatbases, to exclude common single nucleotide polymorphism. The child started symptomatic therapy with ursodeoxycholic acid and multidisciplinary follow-up, in particular rehabilitative psychomotor follow-up.

alagille syndrome, jag1, next generation sequencing, hypertransaminasemia, stop codon mutation

PMC7364116_01

Female

The patient is a 40-year-old housewife, native of India, resident of the UAE for several years, who had been at her normal state of health up until a month before she presented to a local hospital with complaints of intermittent low grade fever, myalgia, headache, lethargy and behavioral changes in the form of increasing social withdrawal and self-neglect. There had been no known TB exposure or recent travel (her last trip was 5 months prior to presentation to Oman). She denied any personal or family history of autoimmune diseases or TB. On presentation, she was hemodynamicaly stable with a low-grade temperature (37.8C). She had a Glasgow Coma Score of 11/15. There were no meningeal signs and the remainder of the exam was unremarkable. Initial workup including metabolic profile, CBC and CXR were negative, and a lumbar puncture was performed due to abnormal GCS in the absence of other explanations. The initial cerebrospinal fluid analysis revealed pleocytosis (WBCs 88 cells/muL, lymphocytes 100 %), glucose 63.61 mg/dL (3.53 mmol/L), and elevated protein (404 mg/dL). Neither Gram stain nor acid-fast stain reveal any bacteria. Brain MRI showed diffuse leptomeningeal enhancement. At the time, given her 1 month history of intermittent low grade fevers, associated with headaches and her due to her being from a high risk area, anti-TB therapy was initiated (rifampin, isoniazid, pyrazinamide, ethambutol and dexamethasone 4 mg intravenous twice daily). After 14 days she had slight improvement in the level of consciousness but developed a severe drug eruption and all medications were discontinued. Her mental status declined over the ensuing days and was transferred to our facility for further care as a case of TB meningitis. She was admitted to our ICU as a case of meningitis/encephalitis, she was awake, lying curled on the bed with generalized rigidity. Her temp was 39C and she was saturating at 100 % on room air with normal other vital signs. Repeat investigations were done which included CT head and MRI brain, which were normal, as well as 24 h EEG monitoring which showed no epileptiform discharges. Repeat CSF analysis revealed normal glucose of 68.65 mg/dL (3.81 mmol/L), elevated protein (183 mg/dL), pleocytosis (11cells/muL, 99 % lymphocytes). The Meningitis/Encephalitis cerebrospinal fluid (CSF) panel was negative (Polymerase Chain Reaction (PCR) was done for: Escherichia coli, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis, Streptococcus agalactiae (Group B), Streptococcus pneumoniae, Cryptococcus gattii and neoformans, Cytomegalovirus, Herpes simplex virus 1 and 2, Human herpesvirus 6, Enterovirus, Human parechovirus, and Varicella zoster virus). Additional CSF studies included VDRL, mycobacterial PCR, Gram stain, and culture. Blood serology tested for human immunodeficiency virus (HIV), Brucella, syphilis and Lyme disease were all negative. Second-line regimen for TB was initiated (moxifloxacin, linezolid, amoxicillin/clavulanate, meropenem, and amikacin IV). Isoniazid was reintroduced slowly after obtaining verbal consent from the next of kin. Additionally, dexamethasone 0.3 mg/kg/day intravenously (IV) for two weeks, then the dose was tapered (0.2 mg/kg/day IV for a week, 0.1 mg/kg/day IV for the 4th week, then 4 mg per day orally and further tapered by 1 mg off the daily dose each week (total 8 weeks). However, the diagnosis of CNS tuberculosis came into question due to the lack of evidence from microbiology and failure of empiric treatment. Other investigations that were done included a quantiferon gold assay which was negative, a repeat CT head and MRI brain, which were normal, as well as CT of the chest, abdomen and pelvis which showed no evidence of related TB findings. The possibility of autoimmune disease was then considered. Laboratory tests results are displayed in Table 1. Based on the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE, our patient's clinical and biochemical picture fits with the diagnosis of SLE. The classification for SLE requires the presence of a positive antinuclear antibodies (ANA) as an entry criterion. Additive criteria consist of seven clinical (ie, constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal) and three immunologic (ie, antiphospholipid antibodies, complement proteins, SLE-specific antibodies) categories, each of which are weighted from 2 to 10. Patients are classified as having SLE with a score of 10 or more points. Our patient had positive ANA titers, which made her eligible for the 2019 EULAR/ARCP criteria. She presented with a one-month history of intermittent fevers (two points) associated with neuropsychiatric symptoms (three points). She had low C3 and C4 levels (four points), and positive anti-smith antibodies (six points). This gave her a total score of 15, consisted with SLE. Once her final AFB cultures came out and her rheumatology work up came highly suspicious for SLE. We discontinued her TB medications and started her on a tapering dose of Prednisolone starting at 40 mg daily with a 10 mg taper each week. She followed up with a rheumatologist at an outside hospital, which confirmed our diagnosis of SLE and stared her on hydroxychloroquine 200 mg per day and prednisone 5 mg daily. She is doing well and has returned to her baseline.

aseptic meningitis, chronic meningitis, systemic lupus erythematosus

PMC6301820_01

Female

A 49-year-old Chinese female was admitted in January, 2015 for painless mass in left breast. The subsequent biopsy demonstrated invasive breast carcinoma with immunohistochemical results of ER(-), PR(-), HER-2(3+), Ki67(+ 20%) and P53(+ 90%)(Figure1). Systemic evaluation showed bilateral lung metastases (0.1-0.9cm) and hepatic metastases (0.7-1.0cm) in addition with primary left breast cancer (33.9 x 18.3mm) and left axillary lymph node involvement (56.8 x 33.0mm). The patient refused molecular targeted therapy for economic reasons and underwent chemotherapy (six cycles of TAC: Pirarubicin, Cyclophosphamide, Paclitaxel and one cycle of T: Paclitaxel). The response was evaluated as partial remission (PR). In September, 2015, her hepatic metastases progressed rapidly (1.0-1.9cm). Then she was enrolled in the clinical trial and randomly assigned to the control group (Lapatinib plus Capecitabine). In March, 2017, she complained of dizziness. The brain MRI with contrast revealed a lesion measuring about 3.1 x 2.7cm located in the left frontal lobe with circular enhancement and edema around, consistent with metastasis (Figure 2A,B). Local radiotherapy with a dose of 48Gy/16f was performed to the single BM and her discomfort disappeared. However, 3 months later, her disease progressed (lung metastases: 0.2-2.7cm, liver metastases: 1.2-4.3cm) and the BM shrank to 1.5 x 1.5cm. In August, the patient experienced recurrence in the left chest wall and further progression of liver metastases. Systemic therapy was switched to NP (Vinorelbine and Cisplatin) plus Herceptin. The lesions demontrated PR response to 4 cycles of NP plus Herceptin. Due to gastrointestinal side effects and grade 3 myelosuppression, the fifth and sixth chemotherapy regimen was adjusted to NC (Vinorelbine and Carboplatin) and N (Vinorelbine), respectively. In February, 2018, she complained of aphasia and intermittent convulsion. The brain MRI with contrast manifested a lesion in the left frontal lobe with obvious ring enhancement. Flair-weighted MRI showed large area of PTBE, resulting in compression and deformation of bilateral ventricle and midline structure shift to the right (Figure 2E,F). Comparing with the brain MRI in November, 2017 (Figure 2C,D), the BM demonstrated slight increase (2.5 x 2.0cm to 3.8 x 2.2cm) while PTBE increased significantly. Conventional intervention with dehydration (mannitol: 250ml, q8h, from 02/01/2018 to 02/07/2018; 250mg, q6h, from 02/08/2018 to 02/10/2018; glycerol fructose: 250ml, q12h, from 02/01/2018 to 02/10/2018) and glucocorticoid (dexamethasone: 20mg daily, from 02/08/2018 to 02/10/2018) was given. However, there was no improvement. The patient developed progressive aphasia and right-side limb activity disorder. Apatinib, with a dose of 250mg daily, was initiated. Surprisingly, after 3 days of use, the aphasia disappeared and she could communicate with others normally. After 10 days of use, her right-side limb activity recovered completely. The subsequent brain MRI (March, 16, 2018) revealed remarkable shrinkage of PTBE and no obvious change in the BM lesion (Figure 2G,H). Now, she takes apatinib 250mg daily and no common apatinib related side effects were observed.

apatinib, tki, vegf, vegfr2, intractable, peritumoral brain edema, radiotherapy

PMC7232110_01

Male

A 55-year-old African man with a past medical history of hypertension presented to Parkland Memorial Hospital with a chief complaint of a worsening productive cough that was recurring for the past year. Cough was described as intermittent with occasional yellow sputum production and associated with shortness of breath and chest pain. He denied voice hoarseness, hemoptysis, melanoptysis, and wheezing. Patient also noted 5-pound weight loss over the past 2-3 months, but denied fever, chills, or night sweats. Patient was a recent immigrant from Nigeria where he worked as a mechanic and had a remote smoking history of ~1 pack/year in the early 1990s. He had no personal history tuberculosis nor he had known tuberculosis contacts. He had no personal or family history of cancer and he denied sick contacts. His surgical history was non-contributory. On physical exam he was afebrile with a regular respiratory rate and no adventitious lung sounds where noted. The patient had been seen for the same complaint at an outside primary care clinic two weeks prior and a chest X ray revealed a mild tracheal deviation to the right (Fig. 1A). A computed tomography (CT) of the chest with contrast was obtained (Fig. 1B & C) and it was notable for a 1.9 cm mass in the right mainstem bronchus with associated right lower lobe consolidation and bronchiectasis. Pulmonology was consulted and management options were discussed. The patient was ultimately recommended to undergo bronchoscopy for airway examination, biopsy of endobronchial lesion, and potential therapeutic intervention. Bronchoscopy showed a 90% obstructing mass in the proximal right mainstem bronchus and bronchus intermedius. The mass was large and circumferential, endobronchial, exophytic, and polypoid (Fig. 2A). The mass was too large to pass the therapeutic bronchoscope for assessment of the distal airways. The lesion was pretreated with epinephrine and cold saline. The tumor was then excised piecemeal using an electrocautery snare, forceps and suction. Tumor coagulation was performed using APC for hemostasis. Finally, balloon dilation was performed in the right mainstem bronchus and bronchus intermedius (Fig. 2B). The excised tissue was sent for histopathologic examination. Microscopic evaluation (Fig. 3) showed an infiltrating gland-forming neoplasm with two cell components: eosinophilic ducts, tightly coupled with a surrounding layer of myoepithelial cells with clear cytoplasm. Immunostains (Fig. 3) highlighted the two cell components, as the ducts were positive for AE1/AE3 and CD117 while the myoepithelial cells stained for SOX10, S100, p40 and p63.SMA was negative. The findings were diagnostic for epithelial-myoepithelial carcinoma. The tumor was interpreted as intermediate-grade on the basis of increased nuclear atypia and an elevated mitotic rate. Patient was discharged from the hospital with scheduled outpatient visits for monitoring of the carcinoma by pulmonology and thoracic surgery. He, unfortunately, was lost to follow up.

bronchus intermedius, electrocautery, interventional pulmonology, lung, right mainstem bronchus, salivary epithelial-myoepithelial carcinoma

Radiological Findings. [A] posterior-anterior plain chest film obtained 2 weeks prior to presentation with tracheal deviation to the right and hilar fullness. [B] Chest CT scan with contrast with axial view with right mainstem obstructing endobronchial mass (yellow arrow) [C] Coronal reconstruction with right mainstem endobronchial mass (yellow arrow) with evidence of post obstructive bronchiectasis. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article. ).