Secondary spontaneous pneumothorax in a patient with resistant Mycobacterium abscessus infection and systemic sclerosis-associated interstitial lung disease: A case report.

Mycobacterium abscessus subsp. abscessus (MABA) is refractory and sometimes fatal especially in an immunocompromised patient. Also, MABA-associated pneumothorax is an extremely rare complication. We report a case of MABA pulmonary infection complicated pneumothorax treated successfully. A 69-year-old Japanese female with immunosuppressed systemic sclerosis-associated interstitial lung disease experienced left-sided secondary spontaneous pneumothorax. MABA was detected in the pleural effusion and blood culture. Microbial sensitivity test showed the MABA was sensitive to only amikacin, sitafloxacin, and clofazimine. Combination therapy with these antibiotics including azithromycin achieved remission within three weeks. In the treatment of MABA infection, compliance with microbial sensitivity test is crucial.

Evaluation of coagulation status using clot waveform analysis in general ward patients with COVID-19.

Coronavirus disease (COVID-19)-related systemic cytokine response induces the production of procoagulant factors, which predisposes patients to a prothrombotic state. Viscoelastic testing can identify the degree of hypercoagulability, which is related to outcomes. We aimed to study the changes in clot waveform analysis (CWA) parameters in COVID-19 patients on hospital admission compared to those in a group of healthy individuals. We conducted a retrospective study of COVID-19 patients admitted to general wards and evaluated demographic and clinical parameters as well as laboratory parameters, including coagulation parameters. CWA data from patients (n = 62) with COVID-19 prior to the initiation of anticoagulation therapy were compared with those from healthy controls (n = 67). The measured CWA parameters were min1, min2, max2, and delta change. CWA, fibrinogen, and D-dimer values were higher in COVID-19 patients than in healthy controls (p < 0.001). CWA profiles were consistent with hypercoagulability and characterized by an increase in density, velocity, and acceleration of clot formation. Activated partial thromboplastin time, fibrinogen, D-dimer, and C-reactive protein (CRP) values were higher in patients in whom all CWA parameters were raised than in patients with just a few elevated CWA parameters, while Sequential Organ Failure Assessment scores, prothrombin time, fibrin degradation product levels and platelet counts did not differ between the two groups. CWA variables showed hypercoagulopathy on admission in COVID-19 patients who were hospitalized in the general ward, and this pattern was more pronounced in critically ill patients with elevated fibrinogen, D-dimer, and CRP levels. Our results may help identify patients at high risk of thromboembolism.

[Three cases of COVID-19 in elderly patients with delayed release from isolation due to persistent positive polymerase chain reaction findings].

The coronavirus disease 2019 (COVID-19) infection has spread worldwide, with no sign of its control in Japan yet. Eight elderly COVID-19 patients over 90 years of age were treated at our hospital. We herein report three cases with characteristic progression. Case 1 was a 91-year-old female patient diagnosed with bacterial pneumonia previously who did not show improvement with medication; thus, she was transferred to our hospital 16 days after the onset. She was diagnosed with COVID-19 using the SARS-CoV-2 polymerase chain reaction (PCR) test. Favipiravir, methylprednisolone, and unfractionated heparin were administered, but she only tested negative 68 days after the onset, at which point she was discharged. However, she was transferred back to our hospital 80 days after the onset since she tested positive again. She was transferred to another hospital 110 days after the onset without testing negative. Case 2 was a 102-year-old female. Despite being a mild case, it took 32 days to obtain negative PCR findings, leading to a decline in the activities of daily living. Case 3 was a 90-year-old male patient treated with favipiravir, dexamethasone, and unfractionated heparin, but his condition deteriorated. He never tested negative for PCR and ultimately died 20 days after the onset. Reports suggest that PCR positivity does not necessarily indicate infectivity, but there are no clear criteria for lifting a quarantine. Therefore, PCR negativity is often sought for "peace of mind." In the current situation where hospitals are fully occupied, clear criteria for lifting the quarantine should be promptly determined. After the completion of treatment, it is more important to monitor symptoms and take standard precautions, such as daily health monitoring, wearing a mask, and keeping an appropriate distance from others, than to obtain a negative PCR result.

Psychological Effects on Healthcare Workers during the COVID-19 Outbreak: A Single-center Study at a Tertiary Hospital in Tokyo, Japan.

Objective The present study analyzed the psychological status of healthcare workers in Japan and the influencing factors during the 2019 coronavirus disease pandemic. Methods An online survey was conducted from July 22 to August 21, 2020. A total of 328 of the 1,029 medical staff members in our university hospital participated in the study. Their mental health was assessed using the 12-item General Health Questionnaire. A multivariate regression analysis was performed to identify the factors associated with the mental health outcomes. Results Of the respondents, 78.0% reported psychological distress. Overall, we found that women, non-physicians, those who lived alone, and younger respondents had significantly greater psychological distress than their counterparts. The multivariate regression analysis showed that four factors were extracted as independent 12-item General Health Questionnaire-related factors: the lack of a sense of mission as a medical professional, the burden of the change in the quality of work, the lack of understanding about virus infectivity, and a strong sense of duty. Conclusion In summary, we found a high prevalence of psychological distress among healthcare workers during the 2019 coronavirus disease outbreak in Japan. Independent risk factors for psychological distress were the burden of the change in the quality of work, the lack of understanding about virus infectivity, a sense of responsibility, and the lack of a strong motivation and drive to help.

A population-based cross-sectional study of the association between periodontitis and arterial stiffness among the older Japanese population.

OBJECTIVE: To investigate the potential association between periodontitis and arterial stiffness among the older Japanese population. BACKGROUND: The prevalence of periodontitis is increasing in Japanese older adults. Arterial stiffness increases the risks of cardiovascular events and death, morbidity, and dementia. METHODS: This secondary analysis of data from a cross-sectional study evaluated the periodontal inflamed surface area (PISA), reflecting the amount of inflamed periodontal tissue that was estimated by a full-mouth periodontal examination. Severe periodontitis was defined per the parameters provided by the Centers for Disease Control/American Academy of Periodontology. The Cardio-Ankle Vascular Index (CAVI) was used for measuring the overall stiffness of the artery, and higher CAVI indicated increased arterial stiffness. An ordinal logistic regression model was used to evaluate the association between periodontitis and arterial stiffness. RESULTS: The analysis included 185 Japanese adults [35% men; age, mean (standard deviation) 80.2 (4.4) years]. The average PISA and the prevalence of severe periodontitis were 64.4 mm2 and 27.6%, respectively; 54 (29.2%), 56 (30.3%), and 75 (40.5%) participants were stratified to the CAVI < 9, 9 ≤ CAVI <10, and CAVI ≥ 10 groups, respectively. After adjusting for potential confounders, the odds ratio of the prevalence and severity of arterial stiffness evaluated using CAVI was 1.06 [95% confidence interval (CI) 1.01 to 1.10] for PISA per 10 mm2 and 2.12 (95% CI 1.09 to 4.11) for severe periodontitis. CONCLUSION: Periodontitis was associated with arterial stiffness among Japanese older adults. Further studies are needed to investigate whether arterial stiffness is an intermediate factor in the pathway between periodontitis and systemic diseases, including cardiovascular disease and dementia.

Type 1 Diabetes, ACTH Deficiency, and Hypothyroidism Simultaneously Induced by Nivolumab Therapy in a Patient with Gastric Cancer: A Case Report.

Nivolumab, a fully human IgG4 immune checkpoint inhibitor (ICI) antibody, has been approved for a variety of cancers. Several endocrine-associated immune-related adverse events have been reported, but the incidence rate is relatively low. This is a case of a patient with gastric cancer who underwent nivolumab therapy, leading to type 1 diabetes as well as adrenocorticotropic hormone (ACTH) deficiency and hypothyroidism almost simultaneously. A 70-year-old man with no previous history of diabetes was treated with nivolumab monotherapy for gastric cancer in November 2018. After 8 courses of nivolumab, he was diagnosed with type 1 diabetes associated with ICI; consequently, insulin therapy was initiated in March 2019. In April 2019, he was transported to hospital due to suffering from prolonged hypoglycemia, disturbed consciousness, and fever. He frequently experienced episodes of hypoglycemia, with poor controlled glycemia. His disturbed consciousness and fever also sustained. Further investigation of his hormones revealed low cortisol and ACTH levels, as well as hypothyroidism. His blood glucose control was improved after the introduction of hydrocortisone and thyroid hormone; he became alert and afebrile. In January 2020, he received a followed-up in an outpatient setting under insulin, hydrocortisone, and thyroid replacement therapy. Endocrine defect associated with ICIs, especially type 1 diabetes or ACTH deficiency, is a rare condition. To the best of our knowledge, this is the 1st case of multiple endocrinopathies simultaneously induced by nivolumab. Various endocrine concomitant defects should be taken into consideration when treating with nivolumab.

Tranexamic acid-induced fixed drug eruption confirmed by the drug lymphocyte transformation test.

We present the first case of multiple fixed drug eruption caused by tranexamic acid, which was confirmed by the LTT. This case was difficult to diagnose because the drug-induced aseptic meningitis by loxoprofen was occurred simultaneously.

Sleep quality among elderly high-altitude dwellers in Ladakh.

It has been already known that people who temporarily stay at high altitude may develop insomnia as a symptom of acute mountain sickness. However, much less is known about people living at high altitude. The aim of this study was to determine the effect of high altitude environment on sleep quality for the elderly who have been living at high altitude for their whole lives. A cross-sectional study was conducted in Domkhar valley at altitudes of 2800-4200m, Ladakh. Sleep quality was assessed using Insomnia Severity Index (ISI). Measurement items include body mass index, blood pressure, blood sugar, hemoglobin, timed Up and Go test, oxygen saturation during wakefulness, respiratory function test, Oxford Knee Score (OKS), and Geriatric Depression Scale (GDS), and so on. The participants were Ladakhi older adults aged 60 years or over (n=112) in Domkhar valley. The participation rate was 65.1% (male: female=47:65, mean age: 71.3 years and 67.9 years, respectively). The prevalence of the high score of ISI (8 or more) was 15.2% (17 out of 112). Altitude of residence was significantly correlated with ISI. Stepwise multiple regression analysis showed that OKS and altitude of residence were significantly related with ISI.

Glucose intolerance associated with hypoxia in people living at high altitudes in the Tibetan highland.

OBJECTIVES: To clarify the association between glucose intolerance and high altitudes (2900-4800 m) in a hypoxic environment in Tibetan highlanders and to verify the hypothesis that high altitude dwelling increases vulnerability to diabetes mellitus (DM) accelerated by lifestyle change or ageing. DESIGN: Cross-sectional epidemiological study on Tibetan highlanders. PARTICIPANTS: We enrolled 1258 participants aged 40-87 years. The rural population comprised farmers in Domkhar (altitude 2900-3800 m) and nomads in Haiyan (3000-3100 m), Ryuho (4400 m) and Changthang (4300-4800 m). Urban area participants were from Leh (3300 m) and Jiegu (3700 m). MAIN OUTCOME MEASURE: Participants were classified into six glucose tolerance-based groups: DM, intermediate hyperglycaemia (IHG), normoglycaemia (NG), fasting DM, fasting IHG and fasting NG. Prevalence of glucose intolerance was compared in farmers, nomads and urban dwellers. Effects of dwelling at high altitude or hypoxia on glucose intolerance were analysed with the confounding factors of age, sex, obesity, lipids, haemoglobin, hypertension and lifestyle, using multiple logistic regression. RESULTS: The prevalence of DM (fasting DM)/IHG (fasting IHG) was 8.9% (6.5%)/25.1% (12.7%), respectively, in all participants. This prevalence was higher in urban dwellers (9.5% (7.1%)/28.5% (11.7%)) and in farmers (8.5% (6.1%)/28.5% (18.3%)) compared with nomads (8.2% (5.7%)/15.7% (9.7%)) (p=0.0140/0.0001). Dwelling at high altitude was significantly associated with fasting IHG+fasting DM/fasting DM (ORs for >4500 and 3500-4499 m were 3.59/4.36 and 2.07/1.76 vs <3500 m, respectively). After adjusting for lifestyle change, hypoxaemia and polycythaemia were closely associated with glucose intolerance. CONCLUSIONS: Socioeconomic factors, hypoxaemia and the effects of altitudes >3500 m play a major role in the high prevalence of glucose intolerance in highlanders. Tibetan highlanders may be vulnerable to glucose intolerance, with polycythaemia as a sign of poor hypoxic adaptation, accelerated by lifestyle change and ageing.

Depression and Altitude: Cross-Sectional Community-Based Study Among Elderly High-Altitude Residents in the Himalayan Regions.

Suicide rates are higher at high altitudes, and some hypothesize that hypoxia is the cause. There may be a significant correlation between rates of depression and altitude, but little data exist outside the United States. The purpose of the present study is to conduct a survey of depression among the elderly highlanders in Asia. We enrolled 114 persons aged 60 years or older (mean, 69.2 ± 6.7 years; women, 58.8%) in Domkhar (altitude, 3800 m), Ladakh, India and 173 ethnic Tibetans (mean, 66.5 ± 6.1 years; women, 61.3%) in Yushu (altitude, 3700 m), Qinghai Province, China. The two-item Patient Health Questionnaire (PHQ-2) and the geriatric depression scale were administered. A psychiatrist interviewed the subjects who had a positive score on the PHQ-2. The results of the interview with the residents conducted by the specialist showed that two cases (1.8%) from Domkhar and four (2.3%) from Qinghai had depression. Despite the high altitude, the probability of depression was low in elderly highlander in Ladakh and Qinghai. Our finding seems to indicate that cultural factors such as religious outlook and social/family relationship inhibit the development of depression.

Prevalence of hypertension at high altitude: cross-sectional survey in Ladakh, Northern India 2007-2011.

OBJECTIVE: Prevalence of hypertension was examined in a widely dispersed (45 110 km(2)) representative group of Ladakhi in Northern India. The influence of hypoxic environment of wide-ranged altitude (2600-4900 m) and lifestyle change on hypertension was studied. METHODS: 2800 participants (age 20-94 years) were enrolled. Systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure of ≥90 mm Hg and/or taking current anti-hypertensive medicine was defined as hypertension. Height and weight for body mass index and SpO2 were examined. The rural population comprised six subdivisions with a distinct altitude, dietary and occupational pattern. Participants in the urban area of Leh consist of two groups, that is, migrants settled in Leh from the Changthang nomadic area, and dwellers born in Leh. The prevalence of hypertension in the two groups was compared with that in the farmers and nomads in rural areas. The effects of ageing, hypoxia, dwelling at high altitude, obesity, modernised occupation, dwelling in an urban area, and rural-to-urban migration to hypertension were analysed by multiple logistic regression. RESULTS: The prevalence of hypertension was 37.0% in all participants and highest in migrants settled in Leh (48.3%), followed by dwellers born in Leh town (41.1%) compared with those in rural areas (33.5). The prevalence of hypertension in nomads (all: 27.7%, Tibetan/Ladakhi: 19.7/31.9%)) living at higher altitude (4000-4900 m) was relatively low. The associated factors with hypertension were ageing, overweight, dwelling at higher altitude, engagement in modernised sedentary occupations, dwelling in urban areas, and rural-to-urban migration. The effects of lifestyle change and dwelling at high altitude were independently associated with hypertension by multivariate analysis adjusted with confounding factors. CONCLUSIONS: Socioeconomic and cultural factors play a big role with the effect of high altitude itself on high prevalence of hypertension in highlanders in Ladakh.

Vasodilatation of multiple cerebral arteries in early stage of stroke-like episode with MELAS.

We describe a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), with multiple cerebral vasodilatations in a stroke-like episode visualised by using magnetic resonance angiography (MRA) and CT angiography (CTA). In the acute stroke-like episode stage, T2-weighted and fluid-attenuated inversion recovery MRI showed high-intensity areas in the left occipital area. In addition, MRA and CTA revealed prominent dilatation of the left posterior cerebral artery and temporal branches of the middle cerebral artery with focal hyperperfusions using CT perfusion (CTP) that corresponded to the MRI. After 10 days, with the development of aphasia, MRI indicated the lesions had spread to the temporal and parietal regions, and this distribution was not confined to major vascular territories. The patient's symptoms gradually improved, accompanied by the attenuation of MRI, CTA, and CTP findings. These characteristic features along with the MRI changes that spread beyond vascular boundaries and the multiple cerebral vasodilatations prior to the development of clinical symptoms are not fully explained by the mitochondrial angiopathy or cytopathy theories. These findings provide further evidence supporting neuronal hyperexcitability in stroke-like episodes of MELAS.

[A case of rubella encephalitis presenting as clinically mild encephalitis/encephalopathy with a reversible splenial lesion].

A 26-year-old male was admitted because of a fever, headache and disturbance of consciousness with lymph node swelling of the neck two days after developing a rash. A neurological examination revealed restlessness with irritability in response to sensory stimuli, such as an injection. Diffusion-weighted brain magnetic resonance imaging (MRI) revealed a hyperintense ovoid lesion in the splenium of the corpus callosum, which showed a low coefficient in the ADC map: the lesion disappeared after 22 days. An enzyme immunoassay (EIA) of the serum and cerebrospinal IgM were positive for rubella virus. The patient was therefore diagnosed with rubella encephalitis. He recovered gradually and was discharged on day 19 after the onset of symptoms without any sequelae. To our knowledge, this is the first case of rubella encephalitis presenting as clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). Although the exact mechanism underlying the development of rubella encephalitis is not well established, this case indicated that our patient had an immune-mediated secondary encephalitis. According to the survey of the pandemic of rubella from 2012 to April 2013 in Japan, the incidence of rubella encephalitis is thought to be relatively higher than was previously noted. This emphasizes the importance of vaccination for preventing encephalitis.

[Association between high altitude and depression in the Himalayas and the Andes].

AIM: Suicide rates in the United States are higher in higher altitude areas, and hypoxia has been cited as a factor in these higher rates. There may be a significant correlation between rates of depression and altitude, but little data exist outside the United States. The purpose of the present study is to conduct a survey of depression among the elderly residing in the Himalayas and the Andes. METHOD: We visited Ladakh (altitude 3,800-4,800 m) in India, Qinghai (3,700 m) in China and Puyca (3,600 m) in Peru between July 2009 and July 2011. We recruited 114 farmers from Domkhar in Ladakh (mean age, 69.2 years; female-male ratio, 58.8%), 206 nomads from Changthang in Ladakh (55.1 years; 43.7%), 173 Tibetan subjects from Qinghai (66.5 years; 61.3%) and 103 indigenous Andean subjects from Puyca (69.0 years; 68.0%). The two-item Patient Health Questionnaire (PHQ-2) was administered to the subjects. A psychiatrist interviewed the residents with single or double positive scores on the PHQ-2. RESULT: The ratio of subjects with one or more positive score in PHQ-2 was significantly higher in Qinghai than in other regions. (Domkhar vs. Changthang vs. Qinghai vs. Puyca = 7.0% vs. 5.3% vs. 36.9% vs. 15.5%, P<0.001). However, prevalence of depression by interview did not change in these regions. (1.8% vs. 1.9% vs. 2.3% vs. 2.9%). CONCLUSION: Despite the high altitude, the prevalence of depression was low in elderly highlanders in the Himalayas and the Andes. These results may relate to being presumed to related to a deep devotion to a religion and tight interpersonal networks.

Disaster-related psychiatric disorders among survivors of flooding in Ladakh, India.

BACKGROUND: Heavy rainfall in northern India in August 2010 caused flash floods, seriously damaging homes and infrastructure. There have been no major disasters in the history of Ladakh, and no surveys on post-disaster psychiatric disorders have been conducted in this area. AIMS AND METHODS: To examine the impact of this disaster in Ladakh one month post-disaster, we visited Choglamsar, located near the town of Leh, where the flood had the most severe impact. In total, 318 survivors (mean age: 58.6 years; female-male ratio: 59.7%; Tibetan refugees: 86.2%) participated in the survey. We used the two-item Patient Health Questionnaire (PHQ-2) along with questions covering background characteristics and disaster exposure. A psychiatrist interviewed the survivors with a single or double positive score in the PHQ-2 or with post-traumatic stress disorder (PTSD) symptoms. RESULTS AND CONCLUSION: There were only two PTSD cases and five of major depressive disorders. PTSD and depression were less common in the Tibetan cultural areas than in other areas. The social background and temperamental characteristics of the Tibetan culture may play a suppressive role in psychiatric disorders.