Letermovir at a Prophylactic Dose for Cytomegalovirus Infection in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Retrospective Study in Japan.

Cytomegalovirus (CMV) infection is a major complication of hematopoietic stem cell transplantation (HSCT). Previous studies in adults demonstrated that letermovir prophylaxis for 100 d after HSCT reduces the occurrence of CMV infection; however, studies in children are limited. In this study, we aimed to examine the incidence of CMV infection in children who underwent allogeneic HSCT with prophylactic letermovir therapy. A single-center retrospective study was conducted among patients aged ≤17 who underwent allogeneic HSCT. We compared the cumulative incidence of CMV infection, mainly monitored by pp65-antigenemia, after HSCT between patients with and without letermovir prophylaxis (10-12 or 5-6 mg/kg/d when co-administered with cyclosporine) using Gray's test. We analyzed 79 patients with a median follow-up period of 126 d. The median age of these patients was 8.3 years (Interquartile range, 3.7-12.4). Prophylactic letermovir was used in 25 patients. Twenty-five patients developed CMV infection, and the cumulative incidence was 38.9% (95% confidence intervals, 25.0-52.5). The cumulative incidence of CMV infection was not significantly different between the letermovir and no-letermovir groups (33.1 vs. 36.6%, p = 0.228). Meanwhile, the cumulative incidence of CMV infection up to 100 d following HSCT was significantly lower in the letermovir group than in the no-letermovir group (8.0 vs. 32.8%, p = 0.026). Most patients experienced no noticeable adverse effects associated with letermovir; however, one patient discontinued letermovir because of nausea and anorexia. In conclusion, the results of this study suggest that letermovir prophylaxis against CMV infection may be effective in children without severe adverse effects.

Radiation-Induced Childhood Thyroid Cancer after the Fukushima Daiichi Nuclear Power Plant Accident.

After the Fukushima Nuclear Power Plant accident in March 2011, a large-scale ultrasound examination of childhood thyroid cancer for all Fukushima residents aged 18 years old or younger was initiated. Fukushima was divided into four areas according to the external radioactivity released by the accident: the highest (A), high-intermediate (B), low-intermediate (C), and the lowest (D). Five rounds of surveys were carried out from October 2011 to March 2023. The annual incidence rates of the "Common Case" not affected by the accident were able to be estimated. The difference between the incidence rate of whole patients and the "Common Case" is that of the "Radiation-induced Case". The annual incidence rate of the "Radiation-induced Case" began to increase immediately after the accident, where the highest level was seen in A area, and the order was A > B > C > D. It showed that the development of childhood thyroid cancer was affected by the radiation released by the accident. The effect of the radiation consisted of two phases: the first phase may have been due to the damage to the immune system, and the second phase may have been due to the genetic mutation in the children who were youngest at the time of the accident.

Intergenerational Chain of Violence, Adverse Childhood Experiences, and Elder Abuse Perpetration.

Importance: It is widely known that individuals with adverse childhood experiences (ACEs) have an increased risk of abusing their own children, thereby perpetuating the cycle of violence. However, the association between ACEs and elder abuse perpetration has not been fully examined. Objective: To examine the association between ACEs and elder abuse and the mediating factors. Design, Setting, and Participants: This cross-sectional study used data collected via the self-administered Japan COVID-19 and Society Internet Survey from September 12 to October 19, 2022. Men and women aged 20 to 64 years who responded to related questions were included. Data were analyzed from July 2023 to April 2024. Exposures: ACEs, defined as the experience of any of 7 items-interpersonal loss (parental loss and parental divorce), family psychopathology (parental mental disease and violence in family), abuse (physical and psychological abuse), and neglect-before the age of 18 years. Main Outcomes and Measures: The primary outcome was the perpetration of physical and/or psychological abuse against an older person (aged ≥65 years) self-reported via questionnaire. The direct and indirect effect estimates were determined using logistic regression analyses. Results: Of a total of 13 318 participants (mean [SD] age, 41.1 [12.1] years; 6634 female [49.8%]), 1133 (8.5%) reported perpetrating violence against older adults. Compared with individuals without ACEs, the odds ratios (ORs) for perpetrating violence were 3.22 (95% CI, 2.74-3.79) for those with 1 ACE and 7.65 (95% CI, 6.41-9.13) for those with 2 or more ACEs. In the mediation analysis, factors with large indirect effect estimates included depression (OR, 1.13; 95% CI, 1.11-1.14; proportion mediated [PM], 18.6%), mental illness other than depression (OR, 1.12; 95% CI, 1.10-1.14; PM, 17.3%), and self-rated health (OR, 1.04; 95% CI, 1.03-1.05; PM, 6.0%). Conclusions and Relevance: These findings suggest that intergenerational cycles of violence may extend to any vulnerable group, not only children but also older adults. Further research into the prevention of ACEs and breaking these cycles of violence is warranted.

Association between alcohol consumption and incidence of type 2 diabetes in middle-aged Japanese from Panasonic cohort study 12.

This retrospective cohort study aimed to investigate the association between alcohol consumption and the onset of type 2 diabetes in middle-aged Japanese individuals. Participants were aged 40 and above from Panasonic Corporation, Osaka, Japan's medical health checkup program from 2008 to 2021. Alcohol consumption was calculated by converting the quantity consumed into daily ethanol consumption. We assessed the association between alcohol consumption and the onset of type 2 diabetes using Cox regression analysis. The total and median follow-up duration was 13 years and 7 (3-13) years (748,090 person-years). Among 102,802 participants, 7,510 participants (7.3%) developed type 2 diabetes during the study period. Alcohol consumption at the level of 0 < to < 22 g/day and 22 to < 39 g/day were negatively associated with developing type 2 diabetes compared to complete alcohol abstainers. Alcohol consumption at levels of 39 to < 66 g/day and at levels of ≥ 66 g/day were positively associated with developing type 2 diabetes in participants with BMI < 25 kg/m2. All levels of alcohol consumption were negatively associated with developing type 2 diabetes in participants with BMI ≥ 25 kg/m2. Moderate-to-heavy alcohol consumption were positively associated with developing type 2 diabetes for participants with BMI < 25 kg/m2, whereas alcohol intake was negatively associated with developing type 2 diabetes among participants with BMI ≥ 25 kg/m2.

Impact of the Coronavirus Disease 2019 Pandemic on Outpatient Visits for Diabetic Retinopathy in Japan: A Retrospective Cohort Study.

Purpose: Long-term ramifications of the coronavirus disease 2019 pandemic on various care-seeking characteristics of patients with diabetic retinopathy remain unclear. This study aimed to identify risk factors for dropout from regular fundus examinations (RFEs) in patients with diabetic retinopathy in Japan. Methods: We extracted demographic and health checkup data (April 2018 to March 2021) from the JMDC database. Patients with diabetes identified using diagnosis-related and medication codes were included. The dropout and continuation groups included patients who discontinued and continued to undergo RFEs during the coronavirus disease 2019 pandemic, respectively. Results: The number of RFEs was significantly lower during the mild lockdown period (April and May 2020) than during the prepandemic period. Of the 14,845 patients with diabetes, 2333 (15.7%) dropped out of RFEs during the pandemic, whereas before the pandemic, of the 11,536 patients with diabetes, 1666 (14.4%) dropped out of RFEs (P = 0.004). Factors associated with dropout in the multivariate logistic regression analysis included younger age, male sex, high triglyceride levels, high γ-glutamyl transpeptidase levels, smoking habit, alcohol consumption, weight gain of more than 10 kg since the age of 20 years, and certain stages of lifestyle improvement. Factors associated with continuation included low body mass index and high glycosylated hemoglobin levels. Conclusions: Our findings can assist in identifying patients with diabetes at risk of dropout. Translational Relevance: These results have implications for public health and identifying patients with diabetes at risk of dropout. Education and tailored monitoring regimens could be pivotal role in fostering adherence.

The effect of management of older patients with heart failure by general physicians on mortality and hospitalization rates: a retrospective cohort study.

BACKGROUND: The prevalence of heart failure is increasing owing to the aging of the population, resulting in growing medical costs and an increasing number of patients with multimorbidity. The optimal management of heart failure by general physicians in addition to internal medicine physicians, such as cardiologists, is essential, although the specifics are unclear. In this study, we aimed to determine the differences in heart failure management outcomes among older patients between those managed by general physicians and those managed by internal medicine physicians, especially in terms of hospitalization and mortality rates. METHODS: This was a retrospective cohort study of patients with heart failure who visited a community hospital in Japan. Patients with heart failure were selected based on International Classification of Diseases codes from electronic medical record data over 9 years, from September 2015 to August 2023. The independent variables were whether a general physician treated the patient; the primary outcome was death; the secondary outcome was hospitalization; and the covariates were patient background, including comorbidities. Multiple logistic regression analysis was used to evaluate the association between being managed by a general physician and death and hospitalization, after adjusting for confounding factors. RESULTS: A total of 1032 patients with heart failure were identified, with a mean age of 82.4 years, and 48.9% were men. Patients treated by general physicians were older, were more likely to have dementia and were more likely to need care than those treated by internal medicine physicians. Being treated by a general physician was significantly negatively associated with death (odds ratio [OR], 0.62) and hospitalization (OR, 0.73). CONCLUSIONS: In Japan, where medical specialties are increasingly differentiated, the comprehensive management of older patients with heart failure and multiple comorbidities by general physicians may reduce hospitalization and mortality rates. Appropriate education of general physicians and an increase in their numbers may prove essential for the successful management of patients with heart failure in aging communities.

Association of Suicidal Ideation With Physical Health Conditions, Mental Health Conditions, and Multimorbidity and the Modifying Role of Emotional Social Support: A Cross-Sectional Study in Japan.

INTRODUCTION: It is unclear whether the risk of suicide differs among individuals with only physical health condition, those with only mental health conditions, and those with both types of conditions (multimorbidity) and how emotional social support modifies these associations. This study aimed to examine differences in the association of suicidal ideation with the presence of only physical health conditions, only mental health conditions, and multimorbidity and the modifying role of emotional social support in these associations. METHODS: A cross-sectional survey was conducted between August and September 2023 in a Japanese rural town to collect data. The exposure variable was the health condition, and it was classified into 4 groups: disease-free, only physical health conditions, only mental health conditions, and multimorbidity. The outcome variable was suicidal ideation. The data collected were analyzed using multivariate logistic regression analysis and stratified analysis. RESULTS: Suicidal ideation was found to have a significant positive association with the presence of only mental health conditions and multimorbidity. These associations remained unchanged in the absence of emotional social support. However, the odds ratio for the only mental health conditions group decreased in the presence of emotional social support, while the odds ratio for the multimorbidity group remained significantly higher. CONCLUSIONS: Suicidal ideation is positively associated with the presence of only mental health conditions and multimorbidity, but emotional social support modifies only the association between suicidal ideation and the presence of only mental health conditions. These results suggest that it may be important to identify the type of social support one needs based on one's health condition to prevent suicide.

Association of Clopidogrel with Interstitial Lung Disease: Gaining Insight Through the Japanese Pharmacovigilance Database.

Background: The P2Y12 receptor inhibitors clopidogrel and prasugrel are widely used. Clopidogrel and prasugrel have different metabolic pathways, but whether their adverse event (AE) profiles differ significantly is unclear. Objective: This study aimed to compare the possible AEs induced by clopidogrel and prasugrel and to assess the rank-order of their AEs submitted to a spontaneous reporting database. Materials and Methods: Data were extracted from the Japanese Adverse Drug Event Report database (JADER). Reports of AEs associated with clopidogrel and prasugrel were analyzed to calculate the reporting odds ratios (RORs) and 95% confidence intervals (CIs). Results: Based on 5869 reports for clopidogrel (69.6%, men) and 513 reports for prasugrel (74.1%, men), 703 and 135 different AEs were identified, respectively. Bleeding complications including hemorrhage were commonly reported for both clopidogrel and prasugrel. As for AEs related to clopidogrel, unexpected AEs such as interstitial lung disease (227 reports; ROR, 1.77; 95% CI, 1.49-2.10), abnormal hepatic function (137 reports; ROR, 1.27; 95% CI, 1.07-1.51), and hepatocellular injury (96 reports; ROR, 120.0; 95% CI, 94.9-151.8) ranked at relatively high positions based on the number of occurrences, unlike prasugrel. Conclusion: This analysis of the national pharmacovigilance database highlights distinct AE profiles for clopidogrel and prasugrel. Unexpected AEs associated with clopidogrel were identified, providing valuable insights for clinical monitoring and patient safety.

The Impact of Japanese Dietary Patterns on Metabolic Dysfunction-Associated Steatotic Liver Disease and Liver Fibrosis.

This study aimed to investigate the effect of Japanese dietary patterns on metabolic dysfunction-associated steatotic liver disease (MASLD) and liver fibrosis. After excluding factors affecting the diagnosis of hepatic steatosis, 727 adults were analyzed as part of the Health Promotion Project. The dietary patterns of the participants were classified into rice, vegetable, seafood, and sweet based on their daily food intake. Liver stiffness measurements and controlled attenuation parameters were performed using FibroScan. Energy and nutrient intake were calculated using the Brief-type Self-administered Diet History Questionnaire. Univariate and multivariate analyses were used to identify the risk factors for liver fibrosis within the MASLD population. The vegetable group had significantly lower liver fibrosis indicators in the MASLD population than the rice group. The multivariate analysis identified a body mass index ≥ 25 kg/m2 (odds ratio [OR], 1.83; 95% confidence interval [CI], 1.01-1.83; p = 0.047) and HOMA-IR ≥ 1.6 (OR, 3.18; 95% CI, 1.74-5.78; p < 0.001) as risk factors for liver fibrosis, and vegetable group membership was a significant low-risk factor (OR, 0.38; 95% CI, 0.16-0.88; p = 0.023). The multivariate analysis of nutrients in low-risk foods revealed high intake of α-tocopherol (OR, 0.74; 95% CI, 0.56-0.99; p = 0.039) as a significant low-risk factor for liver fibrosis. This study suggests that a vegetable-based Japanese dietary pattern, through the antioxidant effects of α-tocopherol, may help prevent liver fibrosis in MASLD and the development of MASLD.

A pharmacovigilance study on clinical factors of active vitamin D3 analog-related acute kidney injury using the Japanese Adverse Drug Event Report Database.

Acute kidney injury (AKI) due to vitamin D therapy for osteoporosis is encountered in clinical practice, but epidemiological studies are scarce. We aimed to determine the association between AKI and vitamin D therapy and to identify risk factors for AKI using the Japanese Adverse Drug Event Report database. We used reporting odds ratios (RORs) to detect signals and evaluate risk factors using multiple logistic regression analysis. Among 298,891 reports from April 2004 to September 2023, 1071 implicated active vitamin D3 analogs as suspect drugs for adverse events. There was a significant association between AKI and active vitamin D3 analogs (ROR [95% confidence interval {CI}], eldecalcitol: 16.75 [14.23-19.72], P < 0.001; alfacalcidol: 5.29 [4.07-6.87], P < 0.001; calcitriol: 4.46 [1.88-10.59], P < 0.001). The median duration of administration before AKI onset was 15.4 weeks. Multiple logistic regression analysis showed a significant association between AKI and age ≥ 70 years (odds ratio [95% CI], 1.47 [1.04-2.07]; P = 0.028), weight < 50 kg (1.55 [1.12-2.13]; P = 0.007), hypertension (1.90 [1.42-2.54]; P < 0.001), and concomitant use of nonsteroidal anti-inflammatory drugs (1.58 [1.10-2.25], P = 0.012) and magnesium oxide (1.96 [1.38-2.78]; P < 0.001). Our results suggest that active vitamin D3 analogs are associated with AKI development. Physicians prescribing these medications to patients with risk factors should consider the possibility of AKI, especially during the first 6 months.

Spatiotemporal analysis of the association between Kawasaki disease incidence and PM2.5 exposure: a nationwide database study in Japan.

BACKGROUND: Kawasaki disease (KD) is an acute vasculitis primarily affecting children. While some studies suggest a link between KD and PM2.5 exposure, findings remain inconsistent. This study aimed to perform spatiotemporal analysis to investigate the impact of monthly and annual exposure to PM2.5 and other air pollutants on the incidence of KD before and after the advent of the COVID-19 pandemic. METHODS: In this retrospective analysis, we used the Japanese administrative claims database to identify the incidence of KD in children under age 5 in 335 secondary medical care areas across Japan before (from July 2014 to December 2019) and during (from January 2020 to December 2021) the COVID-19 pandemic. For each of these periods, we developed hierarchical Bayesian models termed conditional autoregressive (CAR) models that can address the spatiotemporal clustering of KD to investigate the association between the monthly incidence of KD and exposure to PM2.5, NO, NO2 and SO2 over 1-month and 12-month durations. The pollution data were collected from publicly available data provided by the National Institute for Environmental Studies. RESULTS: In the before-pandemic and during-pandemic periods, 55 289 and 14 023 new cases of KD were identified, respectively. The CAR models revealed that only 12-month exposure to PM2.5 was consistently correlated with KD incidence, and each 1 µg/m3 increase in annual PM2.5 exposure corresponded to a 3%-10% rise in KD incidence. Consistent outcomes were observed in the age-stratified sensitivity analysis. CONCLUSIONS: Annual exposure to PM2.5 was robustly linked with the onset of KD. Further research is needed to elucidate the underlying mechanism by which the spatiotemporal distribution of PM2.5 is associated with KD.

Ovarian Mesonephric-like Adenocarcinoma: Its Prevalence in a Japanese High-Volume Cancer Center and a Literature Review on Therapeutic Targets.

BACKGROUND: Ovarian mesonephric-like adenocarcinoma (MLA) is a newly described histological type known for its aggressive behavior. This study aims to determine the frequency of ovarian MLA, review the existing literature, and elucidate its clinicopathological characteristics, including the potential therapeutic targets. METHODS: We retrospectively reviewed the pathological diagnoses of 501 primary ovarian cancer surgical cases at our institution from 2010 to 2023. MLAs exhibiting typical morphological and immunohistochemical features were included. The frequency and clinicopathological characteristics of these cases were summarized. Additionally, we conducted a literature search using PubMed to collect and summarize previously reported cases of ovarian MLAs. RESULTS: Among the 501 primary ovarian cancer cases, we identified 3 cases (0.6%) of MLA. The patients were 52-76 years old, and the initial FIGO stages were IC1 (two cases) and IIIB (one case). All the cases exhibited HRP, pMMR, PD-L1 negativity (CPS < 1), and low HER2 expression. Two cases experienced metastatic recurrence. A literature review identified 97 cases of MLA. The MLAs frequently exhibited KRAS mutations (90%, 38/42), with a recurrence rate of 39% (26/67). CONCLUSION: MLAs accounted for 0.6% of malignant ovarian tumors at our institution, all of which were advanced or recurrent cases. These cases showed HRP, pMMR, and PD-L1 negativity, indicating a lack of current therapeutic targets. The literature also reported a high incidence of advanced and recurrent cases, highlighting the need for accurate diagnosis and the development of new treatments. The frequent KRAS mutations suggest a potential therapeutic target for recurrent or metastatic MLA.

Development of a predictive scoring system for vitamin D deficiency 'Vitamin D Deficiency Predicting Scoring (ViDDPreS)' based on the vitamin D status in young Japanese women: a nationwide cross-sectional study.

OBJECTIVE: Vitamin D deficiency (VDD) is common among young women and causes various health problems, including those that occur during pregnancy and childbirth. Thus, we investigated the risk factors for VDD in young Japanese women and developed a simple risk scoring system called Vitamin D Deficiency Predicting Scoring (ViDDPreS). DESIGN: A cross-sectional study, using the following factors for multivariate logistic regression analysis to create the ViDDPreS score: residential area, season, cumulative ambient ultraviolet-B irradiation, BMI, vitamin D supplement use, sun exposure habits, frequency of habitual food intake and eating habits. The subjects were randomly divided into development and test sets for analysis. Serum 25-hydroxivitamin D concentration of less than 20 ng/ml was defined as VDD. SETTING: Four regions (Hokkaido/Tohoku, Kanto, Chubu/Kinki/Shikoku and Kyushu/Okinawa) in Japan. PARTICIPANTS: Five hundred and eighty-three healthy women aged 18-40 years. RESULTS: In the development set, the VDD group (68·4 %) had higher proportions of the following variables than the non-VDD group: residential area outside the Kanto region; blood samples obtained in winter; low BMI (<18·5 kg/m2); vitamin D supplement non-users; short time regularly spent outside on weekdays; intake of fish, vitamin D-abundant fish, dried fish and redfish less than once a week. VDD risk was classified as low, medium or high according to the ViDDPreS scores including these contributing factors, with a test set C-index of 0·671. CONCLUSION: We identified the risk factors for VDD in young Japanese women and developed a simple risk scoring system that enables us to assess VDD risk and aid in the development of appropriate prevention and treatment strategies for this population.

Characteristic features of late-onset systemic lupus erythematosus: An observational study of data from the Lupus Registry of Nationwide Institutions.

OBJECTIVE: Late-onset systemic lupus erythematosus (LoSLE) is known to possess characteristics different from those of early-onset SLE (EoSLE), thereby making their diagnosis difficult. This study aimed to assess the characteristic features of LoSLE in Japan, a model country with a super-aged society. METHODS: Data were obtained from the Lupus Registry of Nationwide Institutions, which includes a multicenter cohort of patients with SLE in Japan who satisfied the 1997 American College of Rheumatology revised classification criteria for SLE. Data were compared between patients with LoSLE (≥50 years old at onset) and EoSLE (<50 years old at onset). To identify factors associated with LoSLE, binary logistic regression was used for the multivariate analysis, and missing values were complemented by multiple imputations. We also conducted a sub-analysis for patients diagnosed within 5 years of onset. RESULTS: Out of 929 enrolled patients, 34 were excluded owing to a lack of data regarding onset age. Among the 895 remaining patients, 100 had LoSLE, whereas 795 had EoSLE. The male-to-female ratio was significantly higher in the LoSLE group than in the EoSLE group (0.32 vs 0.11, p < 0.001). With respect to SLEDAI components at onset, patients with LoSLE exhibited a higher frequency of myositis (11.9% vs 3.75%, p = 0.031), lower frequency of skin rash (33.3% vs 67.7%, p < 0.001), and lower frequency of alopecia (7.32% vs 24.7%, p = 0.012). No significant differences in overall disease activity at onset were observed between the two groups. Regarding medical history, immunosuppressants were more commonly used in EoSLE. A multivariate analysis revealed that a higher male proportion and a lower proportion of new rash at onset were independent characteristic features of LoSLE. We also identified late onset as an independent risk factor for a high SDI score at enrollment and replicated the result in a sub-analysis for the population with a shorter time since onset. CONCLUSIONS: We clarified that LoSLE was characterized by a higher male proportion, a lower frequency of skin rash and a tendency to organ damage. Now that the world is faced with aging, our results may be helpful at diagnosis of LoSLE.

Small Vessel Disease Burden Predicts Incident Dementia and Poor Functional Outcome in Independent Outpatients.

Background: Total small vessel disease (SVD) score is used to measure the burden of SVD. Objective: This study aimed to clarify the predictive value of total SVD score for incident dementia and functional outcomes in independent outpatients with vascular risk factors. Methods: We derived data from a Japanese cohort in which patients underwent magnetic resonance imaging and cognitive examinations. They were followed up until March 2023. The primary outcomes was dementia. Secondary outcome was functional outcomes. We measured a modified Rankin scale (mRS) score at the last visit and defined poor functional outcomes as mRS score ≥3. Results: After excluding those with a mRS score ≥2, Mini-Mental State Examination score in Japanese version < 24, and missing T2* images, 692 patients were included. During a median follow-up period of 4.6 years, dementia occurred in 31 patients. In multivariate analysis, the score 4 group showed a significantly higher risk of incident dementia than the score 0-3 groups (adjusted hazard ratio, 6.25; 95% CI, 1.83-21.40, p = 0.003). The total SVD score was also independently related to poor functional outcome. Conclusions: The total SVD score of 4, and ≥1 could predict dementia and poor functional outcomes, respectively. Our results suggest intensive management of patients with SVD to prevent dementia and to maintain independent activities of daily living.

Abdominal visceral-to-subcutaneous fat ratio in the prediction of metabolic syndrome risk in Japanese Americans followed prospectively for 10-years loses information.

AIMS: Visceral fat predicts the development of metabolic syndrome (MetS), but it is not known whether the visceral to subcutaneous fat area ratio (VSR) measured using imaging predicts MetS risk as well or better. Thus, we aimed to examine if VSR predicted future risk of MetS over 10-years. METHODS: We followed 329 participants in the longitudinal Japanese American Community Diabetes Study without MetS at baseline for its development over 10 years. Intra-abdominal (VFA) and subcutaneous abdominal (SFA) fat areas were measured at baseline and 10-years and used to calculate VSR. Logistic regression was used to estimate the odds of incident MetS by baseline and 10-year change in VSR and other adipose depots with and without adjustment for baseline MetS features. Areas under ROC curves were calculated in predicting the development of MetS. RESULTS: 99 participants developed MetS over 10-years. Logistic regression models showed a higher odds of incident MetS with greater VSR and 10-year VSR change (OR = 1.67, 95 % CI 1.11-2.51; OR = 1.46, 95 % CI 1.06-2.01, respectively) adjusting for age, sex, and MetS features at baseline. However, VSR alone performed poorly at discriminating (AUROC 0.5807) compared to VFA (AUROC 0.6970, p < 0.001) or a logistic model incorporating VFA and SFA (AUROC 0.7221, p = 0.001). CONCLUSIONS: VSR and VFA predict 10-year MetS risk in Japanese Americans, confirming the importance of relatively greater fat distribution in the visceral depot in the development of MetS. However, VSR is a weaker predictor of MetS development and provides less information compared to VFA alone, and its further use in predicting metabolic abnormalities is not recommended.

Microbiological profiles and clinical outcomes of critically ill surgical patients with lower gastrointestinal perforation in Japan: a single-center retrospective observational study.

BACKGROUND: Lower gastrointestinal perforation (LGP) is a surgical emergency disease that can result in secondary bacterial peritonitis. Microbiological studies on LGP are rare. The present study aimed to ascertain the microbiological profile of LGP in patients admitted to the intensive care unit (ICU) at our institute after surgery. In addition, we investigated whether initial empirical therapy with vancomycin was associated with in-hospital mortality, duration of ICU stay, and duration of ventilator support. METHODS: This single-center, retrospective, observational study was conducted at Kobe City Medical Center General Hospital, Japan. The study population included all patients diagnosed with LGP who were admitted to the ICU after emergency surgery between 2017 and 2023. The primary outcome assessed was the microbiological profile of microorganisms isolated from ascites fluid and blood of the participants. The secondary end-points were in-hospital mortality, duration of ICU stay, and duration of ventilator support. We performed univariate and multivariate regression analyses to evaluate the end-points. RESULTS: During the study period, 89 patients were included in the analysis. The most commonly identified pathogen from the ascites cultures was Escherichia coli (65.2%), followed by Enterococcus spp. (51.7%). E. faecium was identified in 16 (18.0%) ascites samples. The microbiological profile of critically ill patients with LGP admitted to the ICU after surgery was similar to that of previous studies on intra-abdominal infection (IAI). Therefore, the initial empirical therapy in the IAI guidelines is more appropriate for LGP. Multivariate regression analysis suggested that the combination of initial empirical therapy with vancomycin was not associated with in-hospital mortality (odds ratio [OR] = 0.96, 95% confidence interval [CI] 0.23-3.00, p = 0.955), duration of ICU stay (coefficient=-0.92, 95% CI -3.04-1.21, p = 0.393), or duration of ventilator-support (coefficient=-9.03, 95%CI -49.69-31.63, p = 0.659). CONCLUSION: The microbiological profile of critically ill patients with LGP admitted to the ICU after surgery was similar to that of previous studies on IAI. However, the frequency of E. faecium in the present study was higher than that in previous studies. Initial empirical therapy with drugs such as meropenem in combination with vancomycin for E. faecium was not associated with in-hospital mortality, duration of ICU stay, and duration of ventilator support, after adjusting for confounding factors.

Loneliness and Social Isolation Factors Under the Prolonged COVID-19 Pandemic in Japan: 2-Year Longitudinal Study.

BACKGROUND: Worsening loneliness and social isolation during the COVID-19 pandemic have become serious public health concerns worldwide. Despite previous research reporting persistent loneliness and social isolation under repeated emergency declarations and prolonged pandemics, long-term studies are needed to identify the actual conditions of loneliness and social isolation, and the factors that explain them. OBJECTIVE: In this study, 3 web-based surveys were conducted at 1-year intervals during the 2 years after the first state of emergency to examine changes in loneliness and social isolation and the psychosocial factors associated with them in the Japanese population. METHODS: The first survey (phase 1, May 11-12, 2020) was conducted at the end of the first emergency declaration period, the second survey (phase 2, June 14-20, 2021) was conducted at the end of the third emergency declaration period, and the third survey (phase 3, May 13-30, 2022) was conducted when the state of emergency had not been declared but many COVID-19-positive cases occurred during this period. We collected data on 3892 inhabitants (n=1813, 46.58% women; age: mean 50.3, SD 13.4 y) living in the 4 prefectures where emergency declaration measures were applied in phases 1 and 2. A linear mixed model analysis was performed to examine the association between psychosocial variables as explanatory variables and loneliness scores as the dependent variable in each phase. RESULTS: While many psychosocial and physical variables showed improvement for the 2 years, loneliness, social isolation, and the relationship with familiar people deteriorated, and the opportunities for exercise, favorite activities, and web-based interaction with familiar people decreased. Approximately half of those experiencing social isolation in phase 1 remained isolated throughout the 2-year period, and a greater number of people developed social isolation than those who were able to resolve it. The results of the linear mixed model analysis showed that most psychosocial and physical variables were related to loneliness regardless of the phase. Regarding the variables that showed a significant interaction with the phase, increased altruistic preventive behavior and a negative outlook for the future were more strongly associated with severe loneliness in phase 3 (P=.01 to <.001), while the association between fewer social networks and stronger loneliness tended to be more pronounced in phase 2. Although the interaction was not significant, the association between reduced face-to-face interaction, poorer relationships with familiar people, and increased loneliness tended to be stronger in phase 3. CONCLUSIONS: This study found that loneliness and social isolation remained unresolved throughout the long-term COVID-19 pandemic. Additionally, in the final survey phase, these issues were influenced by a broader and more complex set of factors compared to earlier phases.

Ocular genetics in the Japanese population.

In today's globalized society, ophthalmologists can examine people of different ethnicities regardless of where they live. The frequency of disease-causing genes varies according to a patient's ethnic background. We explain genetic findings for Japanese patients with inherited eye diseases. Ocular genetics has made great advances over the past 30 years. For example, detecting mutations at nucleotide position 11778 in mitochondrial DNA was useful in the genetic diagnosis of Leber's hereditary optic neuropathy (LHON). I evaluated the genotype-phenotype relationship in cases of corneal dystrophy and inherited retinal dystrophy (IRD). I identified the entire exon sequence of the eyes shut homolog (EYS) gene in patients with autosomal recessive retinitis pigmentosa (RP). EYS gene mutations are the most frequent cause of autosomal recessive RP. RPGRIP1 may be a common causative gene with early-onset severe retinal dystrophy, including Leber congenital amaurosis. However, some genes have complex structures that are difficult to analyze, including the OPN1LW/OPN1MW gene cluster in blue cone monochromacy and the IKBKG/NEMO genes in incontinentia pigmenti. This review will also present two cases with uniparental disomy, a case of IRD with double mutations, and a case with RP complicated with LHON-like neuropathy. Precise understanding of the effects of genetic variants may reveal differences in the clinical characteristics of patients with the same variant. When starting genome medicine, accurately diagnosing the patient, making accurate prediction, determining the genetic pattern, and providing genetic counseling are important. Above all, that both the doctors and patients understand genetic diseases correctly is important.

Risk factors for post-coronavirus disease condition in the Alpha-, Delta-, and Omicron-dominant waves among adults in Japan: A population-based matched case-control study.

Vaccination is associated with a reduced risk of post-coronavirus disease (COVID-19) condition (PCC). Here, risk factors including vaccination for PCC in the Omicron-dominant waves among Japanese adults were investigated. This was a registry-based matched case-control study of individuals aged 18-79 years diagnosed with COVID-19 registered in a National database between March 2021 and April 2022 and matched noninfected individuals living in Yao City, Japan. A self-administered questionnaire was used to assess persistent symptoms and their risk factors. The COVID-19 vaccination status was obtained from the Vaccination Registry. PCC risk factors were analyzed using logistic regression after adjusting for potential confounding factors. Overall, 4185 infected (cases) and 3382 noninfected (controls) individuals were included in the analysis. The mean ages and proportions of women were 44.7 years and 60.2% and 45.5 years and 60.7% for cases and controls, respectively. A total of 3805 (90.9%) participants had asymptomatic or mild acute symptoms at the median (range) follow-up of 271 (185-605) days. The prevalence of PCC was 15.0% for cases while that of persistent symptoms was 4.4% for controls; among the cases, it was 27.0% in the Alpha- and Delta-dominant waves and 12.8% in the Omicron-dominant wave. Female sex, comorbidities, and hospitalization were positively associated with PCC. One or more vaccine doses of vaccination were inversely associated with PCC; the inverse association was stronger in the Alpha- and Delta-dominant waves (adjusted odds ratio [aOR]: 0.29, 95% confidence interval [CI]: 0.12-0.73) than in the Omicron-dominant wave (aOR: 0.79, 95% CI: 0.59-1.07).