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Journal: The Tohoku journal of experimental medicine

183

The Coronavirus Disease 2019 (COVID-19) pandemic has killed many people worldwide since December 2019, and Iran has been among the most affected countries. In this retrospective study, we aimed to determine the prognostic factors associated with mortality in COVID-19 patients by analyzing 396 survived and 63 non-survived patients in Shahid Modarres Hospital, Tehran, Iran, from January 30th until April 5th, 2020. As the results, the BMI > 35 (p = 0.0003), lung cancer (p = 0.007), chronic kidney disease (p = 0.002), Immunocompromised condition (p = 0.003), and diabetes (p = 0.018) were more frequently observed in the expired group. The history of statins use was more common in the discharged group (p = 0.002), while there was no significant difference in the drug history of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, nonsteroidal anti-inflammatory drugs, aspirin, and/or steroids, and in the past-year influenza vaccination. Multivariable regression demonstrated rising odds of in-hospital death related with age (odds ratio (OR) = 1.055, p = 0.002), levels of C-reactive protein (CRP) (OR = 2.915, p < 0.001), creatinine (OR = 1.740, p = 0.023), lymphocyte count (OR = 0.999, p = 0.008), and magnesium level (OR = 0.032, p < 0.001) on admission. In conclusion, the patients with older age and higher BMI with lymphopenia, hypomagnesemia, elevated CRP and/or raised creatinine on admission are at higher risk of mortality due to the COVID-19 infection, which requires the physicians to use timely and strong therapeutic measures for such patients.

126

Pneumocystis jirovecii pneumonia (PJP) occurs in immunocompromised hosts and is classified as PJP with human immunodeficiency virus (HIV) infection (HIV-PJP) and PJP without HIV infection (non-HIV PJP). Non-HIV PJP rapidly progresses to respiratory failure compared with HIV-PJP possibly due to the difference in immune conditions; namely, the prognosis of non-HIV PJP is worse than that of HIV PJP. However, the diagnosis of non-HIV PJP at the early stage is difficult. Herein, we report a case of severe non-HIV PJP successfully managed with veno-venous extracorporeal membrane oxygenation (V-V ECMO). A 54-year-old woman with neuromyelitis optica was treated with oral corticosteroid, azathioprine, and methotrexate. She admitted to our hospital for fever, dry cough, and dyspnea which developed a week ago. On admission, she required endotracheal intubation and invasive ventilation for hypoxia. A chest computed tomography (CT) scan revealed ground-glass opacity and consolidation in the both lungs. Grocott staining and PCR analysis of bronchoalveolar lavage fluid indicated the presence of fungi and Pneumocystis jirovecii, respectively, whereas serum HIV-antibody was negative. The patient was thus diagnosed with non-HIV PJP and was treated with intravenous pentamidine and corticosteroid pulse therapy for PJP. However, hypoxia was worsened; consequently, V-V ECMO assistance was initiated on day 7. The abnormal chest CT findings and hypoxia were gradually improved. The V-V ECMO support was successfully discontinued on day 14 and mechanical ventilation was discontinued on day 15. V-V ECMO could be a useful choice for respiratory assistance in severe cases of PJP among patients without HIV infection.

6

The novel coronavirus disease 2019 (COVID-19) is now officially declared as a pandemic by the World Health Organization (WHO), and most parts of the world are taking drastic measures to restrict human movements to contain the infection. Millions around the world are wondering, if there is anything that could be done, other than maintaining high personal hygiene, and be vigilant of the symptoms, to reduce the spread of the disease and chances of getting infected, or at least to lessen the burden of the disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The National and International health agencies, including the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the WHO have provided clear guidelines for both preventive and treatment suggestions. In this article, I will briefly discuss, why keeping adequate zinc balance might enhance the host response and be protective of viral infections.

3

Japan is still a patriarchal society. There is an increasing number of female doctors who wish to follow a career path in surgery. This new generation of female surgeons need support not only in their career but also in work-life balance, especially after they have a family. We founded the Japan Association of Women Surgeons (JAWS) with the aims to advance females in surgery by providing networking and to develop leadership, mentorship, education, expertise and advocacy. This article describes our philosophy and activities, and our concept of role modeling. To find a single perfect role model is impossible in Japan, because lifestyle and family situations are quite different among individuals. Many young doctors in Japan find difficulties in identifying role models appropriate to their own situations. Our concept of remote role modeling is to identify multiple outstanding persons with excellent roles that one wishes to emulate; classify them by field of work, lifestyle, family situations, and others; then select the parts that one needs and assemble them to customize one’s own ideal role model. This type of role modeling is probably the most practical approach. While modern technology is good for communication, meeting role models in person at meetings and social occasions is important in building an ideal role model.

2

As Japan’s population ages, there is a growing interest in regional health care coordination. Our study aimed to evaluate whether the interval between onset and admission to convalescent rehabilitation wards (onset-admission) was associated with outcomes in ischemic stroke patients. We conducted a retrospective cohort study in a single rehabilitation hospital. Ischemic stroke patients consecutively admitted to the wards were eligible to enroll. Outcomes included Functional Independence Measure (FIM)-motor gain, the Food Intake Level Scale (FILS) and a discharge rate to home. FIM assesses functional independence, including motor (FIM-motor) and cognitive domains, and is a measure of activities of daily living (ADLs). The FIM-motor gain indicates the difference between the FIM-motor scores at admission and discharge. FILS is a 10-point observer-rated scale to measure swallowing. After enrollment, 481 patients (mean age 74.4 years; 45.7% women) were included. The median [interquartile range] onset-admission interval was 13 [10-20] days and the median National Institute of Health Stroke Scale score, a measure of stroke severity, was 8 [3-13]. In multivariate analysis, the onset-admission interval was independently associated with FIM-motor gain (β = -0.107, p = 0.024), FILS score at discharge (β = -0.159, p = 0.041), and the rate of discharge to home (odds ratio: 0.946, p = 0.032). In conclusion, a shorter interval between stroke onset and admission to convalescent rehabilitation wards contributes to improved outcomes, including ADLs, dysphagia, and a discharge rate to home, in ischemic stroke patients, regardless of stroke severity.

0

Juvenile idiopathic arthritis (JIA) is a heterogeneous autoimmune disease characterized by arthritis of unknown etiology. JNK pathway-associated phosphatase (JKAP) is reported to be a negative regulator of T-cell activation, but its clinical role in JIA is unknown. This study aimed to investigate the correlation of JKAP with disease activity and treatment response to a tumor necrosis factor (TNF) inhibitor, etanercept (ETN), in JIA patients. Totally, 104 JIA patients (6.9 ± 2.7 years old) and 100 age- and sex-matched healthy controls (HCs) (7.2 ± 2.4 years old) were enrolled, and their serum samples were collected for measuring JKAP by enzyme-linked immunoassay. In JIA patients, after 24-week ETN treatment, clinical response was assessed based on the American College of Rheumatology pediatric criteria (ACRpedi) 50 criteria. Results showed that JKAP levels were significantly lower in JIA patients compared with HCs, and of good value in differentiating JIA patients from HCs. Among JIA patients, higher JKAP levels were associated with lower disease activity indexes, including C-reactive protein, number of joints with active arthritis, physician’s global assessment of disease activity, and the present history of disease-modifying antirheumatic drugs; higher baseline JKAP levels were correlated with worse ACRpedi 50 response to ETN at week 24, and was also an independent predictive factor for worse ACRpedi 50 response to ETN. Thus, it may be inappropriate to use ETN for JIA patients with higher JKAP levels. In conclusion, serum JKAP is a potential biomarker for JIA activity and treatment response to a TNF inhibitor.

0

In esophageal squamous cell carcinoma (ESCC) comprising 90% of cases with esophageal cancer, endoscopic resection (ER) is recommended for patients with negligible risk of ESCC-related mortality. In fact, a main cause of death in patients underwent ER is not ESCC. We thus aimed to clarify the predictors for early and late mortality among patients underwent ER of ESCC between 2005 and 2018 at our institution. In this retrospective cohort study, we investigated the prognosis and predictors of early and late mortality with the cut-off value of 3 years. We enrolled 407 patients with a median 69 months follow-up. The 5-year overall survival and disease-specific survival, an indicator of ESCC-related mortality, were 83.4% and 98.4%, respectively. In multivariate Cox analyses, Eastern Cooperative Oncology Group performance status (ECOG-PS), consisting of six grades by a patient’s level of activity, ≥ 2 was a predictor for early and late morality [hazard ratio (HR), 7.21 (P = 0.007) and 15.62 (P = 0.021), respectively]. Charlson comorbidity index (CCI), which is an index for predicting mortality by comorbid conditions, ≥ 2 was also a predictor for both mortality [HR, 2.97 (P = 0.017) and 1.90 (P = 0.019), respectively]. However, age was a predictor only for late mortality [HR, 3.08 (P = 0.010) in 80-84 years and 8.38 (P < 0.001) in ≥ 85 years]. Considering the predictive ability for early mortality, we propose that ECOG-PS and/or CCI are better indices compared with age in deciding treatment strategy after ER for ESCC.

0

Glomerular inflammation is a putative aggravation factor for type 2 diabetic nephropathy and urinary thrombin is a novel marker of glomerular inflammation. To clarify the relationship between glomerular inflammation and progression of the nephropathy, we measured urinary thrombin in 118 patients with type 2 diabetic nephropathy at different stages. To investigate the implications of urinary thrombin in the nephropathy, we compared urinary thrombin with expression of tissue factor, the trigger of blood coagulation activation, in glomeruli and with markers of renal injury (estimated glomerular filtration rate (eGFR) and proteinuria). Urinary thrombin was found in 4.9% (3/61), 0.0% (0/12), 29.6% (8/27) and 50.0% (9/18) of patient groups at stages 1, 2, 3 and 4, respectively. Thus, urinary thrombin was negligible in the patients at early stages (stages 1 and 2), but was present predominantly in the patients at advanced stages (stages 3 and 4). Tissue factor was expressed in accumulated macrophages in glomeruli, which indicates that thrombin may be generated in inflamed glomeruli presumably via inflammation-induced activation of the exudated coagulation factors into glomerular tissues and then be excreted in urine. Urinary thrombin was significantly associated with both decreased eGFR and increased proteinuria in type 2 diabetic nephropathy. Therefore, increased urinary thrombin in patients with advanced stages of type 2 diabetic nephropathy suggests that glomerular inflammation may injure the tissues, thereby impairing renal function. Monitoring an effect of anti-diabetic treatments on glomerular inflammation in the patients with type 2 diabetic nephropathy may be a possible application of urinary thrombin.

0

Alanine aminotransferase (ALT) activity has been recognized as a marker for monitoring the risk of metabolic syndrome, diabetes and non-alcoholic fatty liver disease in children. Higher ALT activity was reported to be associated with eating fast in Japanese adults, but the association in children is unclear. Moreover, eating fast and eating until full are reported to be associated with being overweight. This study examined the association between elevated ALT and eating behaviors (eating fast and eating until full) among population-based schoolchildren (aged 9-10 years) in Ina Town, Saitama, Japan. Data for eating behaviors were obtained from a self-written questionnaire. Blood samples were drawn to measure ALT. Elevated ALT was defined as > 30 U/L in boys and > 19 U/L in girls. Logistic regression models and structural equation models were used to calculate the effect of eating behaviors on elevated ALT. Final data analysis was carried out for 1,870 boys and 1,739 girls. “Eating fast and eating until full” was significantly associated with elevated ALT in each sex. “Eating fast and not eating until full” was significantly associated with elevated ALT in boys, but after adjusting for exercise and body mass index, this association was not significant. In conclusion, “eating fast and eating until full” was associated with elevated ALT in schoolchildren. A sex difference in the association of “eating fast and not eating until full” with elevated ALT was observed. Modifying the behaviors of eating fast and eating until full is important for schoolchildren to prevent ALT elevation.

0

Alcohol use disorder is a serious health problem in college students. Alcohol Use Disorders Identification Test (AUDIT) is a 10-item screening tool to assess alcohol consumption, drinking behaviors, and alcohol-related problems. AUDIT-C is a short version of AUDIT, consisting of consumption items 1-3. However, the optimal cutoff values of AUDIT and AUDIT-C for detecting excessive drinking are not available for Japanese college students. The aim of this study was to evaluate the validity of cutoff points of AUDIT and AUDIT-C for detecting moderate drinking, heavy drinking and binge drinking among Japanese college students. The cross-sectional study was based on an anonymous, self-administered questionnaire. In January 2017, we sampled college students and graduate students aged 20 years or older during annual health examinations at Mie University in Japan. Two thousand students underwent health examinations, and the eligible subjects were 1,600, including 152 (9.5%) moderate drinkers, 58 (3.6%) heavy drinkers and 666 (41.6%) binge drinkers. ROC (receiver operating characteristic) curve analysis showed that the optimal cutoff values for moderate drinking, heavy drinking and binge drinking were 5, 8 and 5 for men and 4, 7 and 4 for women in AUDIT; and 4, 7 and 4 for men and 4, 7 and 4 for women in AUDIT-C, respectively. Moderate drinking is considered unsafe drinking. Therefore, the optimal cutoff values for moderate drinking (5 for men and 4 for women in AUDIT and 4 for both sexes in AUDIT-C) are important parameters for prevention of alcohol use disorder in Japanese college students.