Impact of donor type on the outcomes of acute graft versus host disease to systemic corticosteroid therapy.

Systemic corticosteroid therapy is a well-established first-line treatment for grades II-IV acute graft-versus-host disease (aGVHD). Recently, several developments have occurred, including the introduction of transplantation from human leukocyte antigen (HLA) haploidentical donors using post-transplant cyclophosphamide (PTCY-Haplo), and improvements in prognosis after cord blood transplantation (CBT) in Japan. This study aimed to analyze the association between donor sources and outcomes in patients with aGVHD. Our study included 2732 patients who developed grades II-IV aGVHD, and were treated with systemic corticosteroids. We compared HLA-matched related donors (MRD), HLA-matched unrelated donors (MUD), PTCY-Haplo, and CBT. We set endpoint as response rate, 1-year cumulative incidence of non-relapse mortality (NRM), and overall survival (OS). The adjusted odds ratios for a complete response (CR) were 0.99 (95% confidence interval [CI]: 0.74-1.31, P = 0.925) for MUD, 2.08 (95% CI: 1.35-3.25, P = 0.001) for PTCY-Haplo, and 1.08 (95% CI: 0.83-1.41, P = 0.550) for CBT compared with MRD. A significant increase in response rates for PTCY were only found in a single-organ involvement. No significant association was observed between the donor source and NRM or OS. In conclusion, PTCY-Haplo is associated with a high response rate in patients with a single-organ aGVHD; however, MUD and CBT were not associated with treatment response.

Preoperative treatment response prediction for pancreatic cancer by multiple microRNAs in plasma exosomes: Optimization using machine learning and network analysis.

BACKGROUND/OBJECTIVES: MicroRNAs (miRNAs) are involved in chemosensitivity through their biological activities in various malignancies, including pancreatic cancer (PC). However, single-miRNA models offer limited predictability of treatment response. We investigated whether a multiple-miRNA prediction model optimized via machine learning could improve treatment response prediction. METHODS: A total of 20 and 66 patients who underwent curative resection for PC after gemcitabine-based preoperative treatment were included in the discovery and validation cohorts, respectively. Patients were classified according to their response to preoperative treatment. In the discovery cohort, miRNA microarray and machine learning were used to identify candidate miRNAs (in peripheral plasma exosomes obtained before treatment) associated with treatment response. In the validation cohort, miRNA expression was analyzed using quantitative reverse transcription polymerase chain reaction to validate its ability to predict treatment response. RESULTS: In the discovery cohort, six and three miRNAs were associated with good and poor responders, respectively. The combination of these miRNAs significantly improved predictive accuracy compared with using each single miRNA, with area under the curve (AUC) values increasing from 0.485 to 0.672 to 0.909 for good responders and from 0.475 to 0.606 to 0.788 for poor responders. In the validation cohort, improved predictive performance of the miRNA combination over single-miRNA prediction models was confirmed, with AUC values increasing from 0.461 to 0.669 to 0.777 for good responders and from 0.501 to 0.556 to 0.685 for poor responders. CONCLUSIONS: Peripheral blood miRNA profiles using an optimized combination of miRNAs may provide a more advanced prediction model for preoperative treatment response in PC.

Extensive ablation for elderly patients with persistent atrial fibrillation: insights from the EARNEST-PVI prospective randomized trial.

BACKGROUND: In patients with persistent atrial fibrillation (AF), extensive ablation for substrate modification, such as linear ablation or complex fractionated atrial electrogram ablation in addition to pulmonary vein isolation (PVI) remains controversial. Previous studies investigating extensive ablation have demonstrated its varying efficacy, suggesting the possible heterogeneity of its efficacy. Aging is a major risk factor for AF and is associated with atrial remodeling. We aimed to compare the efficacy and safety of the extensive ablation strategy compared with PVI alone strategy between young and elderly patients. METHODS: This study is a post-hoc analysis of the multicenter, randomized controlled, noninferiority trial investigating the efficacy and safety of PVI-only (PVI-alone arm) compared with extensive ablation (PVI-plus arm) in patients with persistent AF (EARNEST-PVI trial). We divided the overall population into 2 groups based on age and assessed treatment effects. RESULTS: In the young group (age <65 years, N = 206), there was no significant difference in the recurrence rate between the PVI-alone group and PVI-plus group [hazard ratio (HR): 1.00, 95 % CI: 0.57-1.73, p = 0.987], whereas the recurrence rate was significantly lower in the PVI-plus group compared to the PVI-alone group in the elderly group (age ≥65 years, N = 291) (HR: 0.47, 95 % CI: 0.29-0.76, p = 0.0021) (p for interaction = 0.0446). There were no fatal procedural complications. CONCLUSION: In patients with persistent AF, the extensive ablation strategy was more effective than the PVI-alone strategy in elderly patients, while the effectiveness of both approaches was comparable in young patients. TRIAL REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT03514693. URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000022454 Unique ID issued by UMIN: UMIN000019449.

Mortality after partner's cancer diagnosis or death: A population-based prospective cohort study in Japan.

BACKGROUND: The health statuses of closely connected individuals are interdependent. Little is known about mortality risk associated with partner's cancer diagnosis and cause-specific mortality risk associated with partner's death. METHODS: Relative risks for all-cause and cause-specific mortality following a partner's cancer diagnosis or death compared to the period when the partner is cancer-free and alive were investigated in the population-based prospective cohort study that enrolled 140,420 people at the age between 40-69 in 1990-1994. RESULTS: 55,050 participants (27,665 men and 27,385 women) who were identified as married couples were followed-up for 1,073,746.1 (518,368.5 in men and 555,377.6 in women) person-years, during which 9,816 deaths (7,217 in men and 2,599 in women) were observed. After a partner's cancer diagnosis, the mortality rate ratio (MRR) of all-cause mortality was not increased among both men and women, while an increase of externally-caused MRR was observed. The suicide MRR significantly increased among men (MRR = 2.90 [95% CI, 1.70-4.93]) and it persisted for more than 5 years. After a partner's death, the MRRs of all-cause, cardiovascular disease (CVD), respiratory disease (RD), and externally-caused mortality significantly increased only among men. Stratified analysis by smoking status among men showed significantly increased MRRs of CVD and RD mortality among former/current smokers, but not among never-smokers. CONCLUSION: Partner's cancer diagnosis did not increase all-cause mortality risk, but increased externally-caused mortality risk, especially suicide among men. The impact of partner's death on mortality risk differed by the mortality causes and sex, and smoking affected some of cause-specific mortality risk.

Post-discharge functional outcomes in older patients with sepsis.

BACKGROUND: The post-discharge prognosis of patients with sepsis remains a crucial issue; however, few studies have investigated the relationship between pre-sepsis health status and subsequent prognosis in a large population. This study aimed to examine the effect of the pre-sepsis care needs level on changes in care needs and mortality in patients with sepsis 1 year post-discharge. METHODS: This was a population-based retrospective cohort study including twelve municipalities in Japan that participated in the Longevity Improvement & Fair Evidence study between April 2014 and March 2022, with a total of 1,491,608 persons. The pre-hospitalization levels of care needs (baseline) were classified from low to high, as no care needs, support level and care needs level 1, care needs levels 2-3, and care needs levels 4-5 (fully dependent). The outcomes were changes in care needs level and mortality 1 year post-discharge, assessed by baseline care needs level using Cox proportional hazard models. RESULTS: The care needs levels of 17,648 patients analyzed at baseline were as follows: no care needs, 7982 (45.2%); support level and care needs level 1, 3736 (21.2%); care needs levels 2-3, 3089 (17.5%); and care needs levels 4-5, 2841 (16.1%). At 1 year post-discharge, the distribution of care needs were as follows: no care needs, 4791 (27.1%); support level and care needs level 1, 2390 (13.5%); care needs levels 2-3, 2629 (14.9%); care needs levels 4-5, 3373 (19.1%); and death, 4465 (25.3%). Patients with higher levels of care needs exhibited an increased association of all-cause mortality 1 year post-discharge after adjusting for confounders [hazard ratios and 95% confidence intervals: support level and care needs level 1, 1.05 (0.96, 1.15); care needs levels 2-3, 1.46 (1.33, 1.60); and care needs levels 4-5, 1.92 (1.75, 2.10); P for trend < 0.001]. CONCLUSIONS: Elevated care needs and mortality were observed in patients with sepsis within 1 year post-discharge. Older patients with sepsis and higher baseline levels of care needs had a high association of all-cause mortality 1 year post-discharge.

Impact of the Aortomitral Positional Anatomy on Atrioventricular Conduction Disorder Following Mitral Valve Surgery.

BACKGROUND: Variations in the aortomitral positional anatomy, including aortic root rotation appear to be related to variations in the location of the conduction system, including the bundle of His. However, little is known about their clinical significance. METHODS AND RESULTS: This study included 147 patients with normal ECGs who underwent mitral valve surgery. The aortomitral anatomy was classified using preoperative 3-dimensional transesophageal echocardiography, and postoperative conduction disorders, including atrioventricular block and bundle branch block, were analyzed. Variations classified as aortomitral appearance were designated as having a center appearance (85.7%, n=126/147) or lateral appearance (14.3%, n=21/147) on the basis of whether the aortic root was located at the center or was shifted to the left fibrous trigone side. Subsequently, those with a center appearance, aortic root rotation was classified as having a center rotation (83.3% [n=105/126]), in which the commissure of the left and noncoronary aortic leaflet was located at the center, lateral rotation (14.3% [n=18/126]), rotated to the left trigone side, or medial rotation (2.4% [n=3/126]), rotated to the right. The incidence of 3-month persistent new-onset conduction disorder was higher in the lateral appearance than the center appearance group (21.1% versus 5.0%; P=0.031) and higher in the lateral rotation than in the center or medial rotation groups (29.4% versus 1.0% versus 0.0%, respectively; P<0.001). CONCLUSIONS: Aortomitral variations can be classified using 3-dimensional transesophageal echocardiography. Lateral appearance and lateral rotation are risk factors for conduction disorders in mitral valve surgery.

Association of Statin Use with Dementia Risk Among Older Adults in Japan: A Nested Case-Control Study Using the LIFE Study.

Background: Previous studies have shown a possible association between statin use and a decreased risk of dementia, but the association has not been sufficiently established, especially in the super-aging society of Japan. Objective: This study aimed to determine the association between statin use and the risk of dementia among Japanese participants aged> =65 years old. Methods: Data from the Longevity Improvement and Fair Evidence (LIFE) Study were utilized, including medical and long-term care (LTC) claim data from 17 municipalities between April 2014 and December 2020. A nested case-control study was conducted with one case matched to five controls based on age, sex, municipality, and year of cohort entry. We used a conditional logistic regression model to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: This study included 57,302 cases and 283,525 controls, with 59.7% of the participants being woman. After adjusting for potential confounders, statin use was associated with a lower risk of dementia (OR, 0.70; 95% CI: 0.68-0.73) and Alzheimer's disease (OR: 0.66; 95% CI: 0.63-0.69). Compared with non-users, the ORs of dementia were as follows: 1.42 (1.34-1.50) for 1-30 total standardized daily dose (TSDD), 0.91 (0.85-0.98) for 31-90 TSDD, 0.63 (0.58-0.69) for 91-180 TSDD, and 0.33 (0.31-0.36) for >180 TSDD in dose-analysis. Conclusions: Statin use is associated with a reduced risk of dementia and Alzheimer's disease among older Japanese adults. A low cumulative statin dose is associated with an increased risk of dementia, whereas a high cumulative statin dose is a protective factor against dementia.

Postdischarge functional outcomes in older patients with acute heart failure in Japan: the Longevity Improvement & Fair Evidence study.

BACKGROUND: The association between care needs level (CNL) at hospitalisation and postdischarge outcomes in older patients with acute heart failure (aHF) has been insufficiently investigated. METHODS: This population-based cohort study was conducted using health insurance claims and CNL data of the Longevity Improvement & Fair Evidence study. Patients aged ≥65 years, discharged after hospitalisation for aHF between April 2014 and March 2022, were identified. CNLs at hospitalisation were classified as no care needs (NCN), support level (SL) and CNL1, CNL2-3 and CNL4-5 based on total estimated daily care time as defined by national standard criteria, and varied on an ordinal scale between SL&CNL1 (low level) to CNL4-5 (fully dependent). The primary outcomes were changes in CNL and death 1 year after discharge, assessed by CNL at hospitalisation using Cox proportional hazard models. RESULTS: Of the 17 724 patients included, 7540 (42.5%), 4818 (27.2%), 3267 (18.4%) and 2099 (11.8%) had NCN, SL&CNL1, CNL2-3 and CNL4-5, respectively, at hospitalisation. One year after discharge, 4808 (27.1%), 3243 (18.3%), 2968 (16.7%), 2505 (14.1%) and 4200 (23.7%) patients had NCN, SL&CNL1, CNL2-3, CNL4-5 and death, respectively. Almost all patients' CNLs worsened after discharge. Compared to patients with NCN at hospitalisation, patients with SL&CNL1, CNL2-3 and CNL4-5 had an increased risk of all-cause death 1 year after discharge (hazard ratio [95% confidence interval]: 1.19 [1.09-1.31], 1.88 [1.71-2.06] and 2.56 [2.31-2.84], respectively). CONCLUSIONS: Older patients with aHF and high CNL at hospitalisation had a high risk of all-cause mortality in the year following discharge.

Extensive ablation for persistent atrial fibrillation patients with mitral regurgitation: Insights from the EARNEST-PVI prospective randomized trial.

BACKGROUND: Extensive ablation in addition to pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF) has not yielded consistent results, indicating diversity in their efficacy. Mitral regurgitation (MR) associated with AF may indicate a higher prevalence of arrhythmogenic substrate, suggesting potential benefits of extensive ablation for these patients. METHODS: This post-hoc analysis of the EARNEST-PVI trial compared PVI alone versus an extensive ablation strategy (PVI-plus) in persistent AF patients, stratified by MR presence. The primary endpoint of the study was the recurrence of AF. The secondary endpoints included death, cerebral infarction, and procedure-related complications. RESULTS: The trial included 495 eligible patients divided into MR and non-MR groups. The MR group consisted of 192 patients (89 in the PVI-alone arm and 103 in the PVI-plus arm), while the non-MR group had 303 patients (158 in the PVI-alone arm and 145 in the PVI-plus arm). In the non-MR group, recurrence rates were similar between PVI-alone and PVI-plus arms (Log-rank P = 0.47, Hazard ratio = 0.85 [95%CI: 0.54-1.33], P = 0.472). However, in the MR group, PVI-plus was significantly more effective in preventing AF recurrence (Log-rank P = 0.0014, Hazard ratio = 0.40 [95%CI: 0.22-0.72], P = 0.0021). No significant differences were observed in secondary endpoints between the two arms. CONCLUSIONS: For persistent AF patients with mild or greater MR, receiving PVI-plus was superior to PVI-alone in preventing AF recurrence. Conversely, for patients without MR, the effectiveness of extensive ablation was not demonstrated. These findings suggest tailoring ablation strategies based on MR presence can lead to better outcomes in AF management.

Effects of Concomitant Traumatic Spinal Cord and Brain Injury on In-Hospital Mortality: A Retrospective Analysis of a Nationwide Trauma Registry in Japan.

Isolated traumatic spinal cord injury (t-SCI) and traumatic brain injury (TBI) represent significant public health concerns, resulting in long-term disabilities and necessitating sophisticated care, particularly when occurring concurrently. The impact of these combined injuries, while crucial in trauma management, on clinical, socioeconomic, and health care outcomes is largely unknown. To address this gap, our secondary retrospective cohort study used data from the Japan Trauma Data Bank, covering patients enrolled over a 13-year period (2006-2018), to elucidate the effects of concurrent t-SCI and TBI on in-hospital mortality. Data on patient demographics, injury characteristics, treatment modalities, and outcomes were analyzed. Multivariate logistic regression analysis was performed to examine prognostic variables associated with in-hospital mortality, including interaction terms between t-SCI severity and TBI presence. This study included 91,983 patients with neurotrauma, with a median age of 62 years (69.7% men). Among the patients, 9,018 (9.8%) died in the hospital. Concomitant t-SCI and TBI occurred in 2,954 (3.2%) patients. t-SCI only occurred in 9,590 (10.4%) patients, whereas TBI only occurred in the majority of these cases (79,439, 86.4%). Multivariate logistic regression analysis revealed age; sex; total number of comorbidities; systolic blood pressure at presentation; Glasgow coma scale score at presentation; and Abbreviated Injury Scale (AIS) scores for head, face, chest, abdomen, cervical-SCI, thoracic-SCI, and lumbar-SCI as significant independent factors for in-hospital mortality. The odds ratio of cervical-SCI × head AIS as an interaction term was 0.85 (95% confidence interval: 0.77-0.95), indicating a negative interaction. In conclusion, we identified 12 factors associated with in-hospital mortality in patients with t-SCI. In addition, the negative interaction between cervical t-SCI and TBI suggests that the presence of t-SCI in patients with TBI may be underestimated. This study highlights the importance of early recognition and comprehensive management of these complex trauma conditions while considering the possibility of concomitant t-SCI in patients with TBI.

Impact of pre-existing medical conditions on mortality in geriatric trauma: a nationwide study in Japan.

PURPOSE: To investigate the relationship between pre-existing medical conditions and outcomes in elderly trauma patients in Japan. METHODS: This multicenter observational study utilized data from the Japan Trauma Data Bank (JTDB) from 2019 to 2020. The primary outcome was in-hospital mortality. Factors associated with in-hospital mortality were identified using multivariate logistic regression analysis, from which adjusted odds ratios (AOR) and 95% confidence intervals (CI) were determined. RESULTS: Of the participants during the study period, 19,598 patients were included in the analysis. Among the pre-existing medical conditions, moderate or severe liver disease showed the strongest positive association with in-hospital mortality (AOR: 7.087, 95% CI: 3.194-15.722), followed by multiple malignancies (AOR: 3.490, 95% CI: 1.046-11.641), congestive heart failure (AOR: 2.572, 95% CI: 1.920-3.445), and moderate or severe renal disease (AOR: 2.256, 95% CI: 1.584-3.215). CONCLUSION: Data from JTDB suggests that pre-existing conditions like moderate or severe liver disease, congestive heart failure, and moderate or severe renal disease in elderly trauma patients are positively correlated with in-hospital mortality.

Factors associated with difficulty in hospital acceptance during the COVID-19 pandemic period in Osaka Prefecture, Japan: a population-based study.

Background: In many countries, emergency medical systems were responsible for initial treatment of patients with COVID-19. Generally, acceptance by medical institutions may not be sufficient, and it may take much time to determine the medical institution to which to transport the patient. This problem is termed "difficulty in hospital acceptance (DIH)," and it is used as a key performance indicator in the assessment of the EMS in Japan. The purpose of this study was to reveal the factors associated with the DIH during the COVID-19 pandemic using dataset in the ORION (Osaka emergency information Research Intelligent Operation Network system). Methods: This was a retrospective descriptive study with a 3-year study period from January 1, 2019 to December 31, 2021. We included patients who were recorded in the ORION system during the study period. The primary endpoint was defined as DIH. Multivariable logistic regression model was used to assess factors associated with DIH during the COVID-19 pandemic and calculated their adjusted odds ratio (AOR) and associated 95% confidence interval (CI). Results: 1,078,850 patients included in this study. Of them, 41,140 patients (3.8%) experienced DIH and 1,037,710 patients (96.2%) did not experience DIH. The median age was 71 years (IQR: 45-82), and 543,760 patients (50.4%) were male. In this study, SpO2, body temperature, and epidemic period of COVID-19 were associated with difficulty in hospital acceptance. The highest AOR of SpO2 was 80% or less (AOR: 1.636, [95% CI: 1.532-1.748]), followed by 81-85% (AOR: 1.584, [95% CI: 1.459-1.721]). The highest AOR of body temperature was 38.0-38.9°C (AOR: 1.969 [95% CI: 1.897-2.043]), followed by 39°C or higher (AOR: 1.912 [95% CI: 1.829-1.998]). The highest AOR of epidemic period of COVID-19 was the 4th wave (AOR: 2.134, [95% CI: 2.065-2.205]), followed by the 3rd wave (AOR: 1.842, [95% CI: 1.785-1.901]). Conclusion: In this study, we revealed factors associated with the DIH during the COVID-19 pandemic. As various factors are involved in the spread of an unknown infectious disease, it is necessary not only to plan in advance but also to take appropriate measures according to the situation in order to smoothly accept emergency patients.

Statin use and risk of Parkinson's disease among older adults in Japan: a nested case-control study using the Longevity Improvement and Fair Evidence study.

The association between statin use and the risk of Parkinson's disease remains inconclusive, particularly in Japan's super-ageing society. This study aimed to investigate the potential association between statin use and the risk of Parkinson's disease among Japanese participants aged ≥65 years. We used data from the Longevity Improvement and Fair Evidence Study, which included medical and long-term care claim data from April 2014 to December 2020 across 17 municipalities. Using a nested case-control design, we matched one case to five controls based on age, sex, municipality and cohort entry year. A conditional logistic regression model was used to estimate the odds ratios with 95% confidence intervals. Among the 56 186 participants (9397 cases and 46 789 controls), 53.6% were women. The inverse association between statin use and Parkinson's disease risk was significant after adjusting for multiple variables (odds ratio: 0.61; 95% confidence interval: 0.56-0.66). Compared with non-users, the dose analysis revealed varying odds ratios: 1.30 (1.12-1.52) for 1-30 total standard daily doses, 0.77 (0.64-0.92) for 31-90 total standard daily doses, 0.62 (0.52-0.75) for 91-180 total standard daily doses and 0.30 (0.25-0.35) for >180 total standard daily doses. Statin use among older Japanese adults was associated with a decreased risk of Parkinson's disease. Notably, lower cumulative statin doses were associated with an elevated risk of Parkinson's disease, whereas higher cumulative doses exhibited protective effects against Parkinson's disease development.

External Validation of Updated Prediction Models for Neurological Outcomes at 90 Days in Patients With Out-of-Hospital Cardiac Arrest.

BACKGROUND: Few prediction models for individuals with early-stage out-of-hospital cardiac arrest (OHCA) have undergone external validation. This study aimed to externally validate updated prediction models for OHCA outcomes using a large nationwide dataset. METHODS AND RESULTS: We performed a secondary analysis of the JAAM-OHCA (Comprehensive Registry of In-Hospital Intensive Care for Out-of-Hospital Cardiac Arrest Survival and the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest) registry. Previously developed prediction models for patients with cardiac arrest who achieved the return of spontaneous circulation were updated. External validation was conducted using data from 56 institutions from the JAAM-OHCA registry. The primary outcome was a dichotomized 90-day cerebral performance category score. Two models were updated using the derivation set (n=3337). Model 1 included patient demographics, prehospital information, and the initial rhythm upon hospital admission; Model 2 included information obtained in the hospital immediately after the return of spontaneous circulation. In the validation set (n=4250), Models 1 and 2 exhibited a C-statistic of 0.945 (95% CI, 0.935-0.955) and 0.958 (95% CI, 0.951-0.960), respectively. Both models were well-calibrated to the observed outcomes. The decision curve analysis showed that Model 2 demonstrated higher net benefits at all risk thresholds than Model 1. A web-based calculator was developed to estimate the probability of poor outcomes (https://pcas-prediction.shinyapps.io/90d_lasso/). CONCLUSIONS: The updated models offer valuable information to medical professionals in the prediction of long-term neurological outcomes for patients with OHCA, potentially playing a vital role in clinical decision-making processes.

Association between the severity of hypothermia and in-hospital mortality in patients with infectious diseases: The J-Point registry.

Aim: Hypothermia is associated with poor prognosis in patients with sepsis. However, no studies have explored the correlation between the severity of hypothermia and prognosis. Methods: Using data from the Japanese accidental hypothermia network registry (J-Point registry), we examined adult patients aged ≥18 years with infectious diseases whose initial body temperature was ≤35°C from April 1, 2011 to March 31, 2016, in 12 centers. Patients were divided into three groups according to their body temperature: Tertile 1 (T1) (32.0-35.0°C), Tertile 2 (T2) (28.0-31.9°C), and Tertile 3 (T3) (<28.0°C). In-hospital mortality was employed as a metric to assess outcomes. We conducted a multivariate logistic regression analysis to investigate the relationship between the three categories and the occurrence of in-hospital mortality. Results: A total of 572 patients were registered, and 170 eligible patients were identified. Of these patients, 55 were in T1 (32.0-35.0°C), 76 in T2 (28.0-31.9°C), and 39 in T3 (<28.0°C) groups. The overall in-hospital mortality rate in accidental hypothermia (AH) patients with infectious diseases was 34.1%. The in-hospital mortality rates in the T1, T2, and T3 groups were 34.5%, 36.8%, and 28.2%, respectively. The multivariable analysis demonstrated no significant differences regarding in-hospital mortality among the three groups (T2 vs. T1, adjusted odds ratio [OR]: 1.29; 95% confidence interval [CI]: 0.58-2.89 and T3 vs. T1, adjusted OR: 0.83; 95% CI: 0.30-2.31). Conclusion: In this multicenter retrospective observational study, hypothermia severity was not associated with in-hospital mortality in AH patients with infectious diseases.

Intestinal Bacteria Fluctuating in Early-Stage Colorectal Cancer Carcinogenesis are Associated with Diet in Healthy Adults.

This hospital-based, cross-sectional study aimed to explore the association between diet and fluctuating intestinal bacteria in early-stage colorectal cancer (CRC) (Atopobium parvulum, Actinomyces odontolyticus, Solobacterium moorei, and Bifidobacterium longum). Healthy participants (n = 212) who underwent total colonoscopy at National Cancer Center Hospital (Tokyo, Japan) were divided into two groups according to the relative abundance of bacteria in their feces: those in the top 25% of relative bacterial abundance as cases and the bottom 25% as controls. The participants were divided into three groups (low, medium, and high) according to their intake of food groups associated with CRC. Multivariable logistic regression analysis was conducted to estimate the association between dietary intake and higher relative abundance of bacteria. Dairy products were inversely associated with a higher relative abundance of A. parvulum, A. odontolyticus, and S. moorei, with odds ratios (high vs. low) and 95% confidence interval as follows: 0.16 (0.06-0.44), 0.25 (0.08-0.82), and 0.29 (0.11-0.78), respectively. Additionally, dietary fiber was inversely associated with a higher relative abundance of S.moorei (0.29 [0.11-0.78]). No association was observed between diet and B.longum. In conclusion, healthy adults with a higher intake of dairy products and fiber had lower odds of having a higher relative abundance of CRC-associated microbiota.

Non-linear association between the time required to reaching temperature targets and the neurological outcome in patients undergoing targeted temperature management after out-of-hospital cardiac arrest: Observational multicentre cohort study.

Purpose: We evaluated associations between outcomes and time to achieving temperature targets during targeted temperature management of out-of-hospital cardiac arrest. Methods: Using Comprehensive Registry of Intensive Care for out-of-hospital cardiac arrest Survival (CRITICAL) study, we enrolled all patients transported to participating hospitals from 1 July 2012 through 31 December 2017 aged ≥ 18 years with out-of-hospital cardiac arrest of cardiac aetiology and who received targeted temperature management in Osaka, Japan. Primary outcome was Cerebral Performance Category scale of 1 or 2 one month after cardiac arrest, designated as "one-month favourable neurological outcome". Non-linear multivariable logistic regression analyses assessed the primary outcome based on time to reaching temperature targets. In patients subdivided into quintiles based on time to achieving temperature targets, multivariable logistic regression calculated adjusted odds ratios and 95% confidence intervals. Results: We analysed 473 patients. In non-linear multivariable logistic regression analysis, p value for non-linearity was < 0.01. In the first quintile (< 26.7 minutes), second quintile (26.8-89.9 minutes), third quintile (90.0-175.1 minutes), fourth quintile (175.2-352.1 minutes), and fifth quintile (≥ 352.2 minutes), one-month favourable neurological outcome was 32.6% (31/95), 40.0% (36/90), 53.5% (53/99), 57.4% (54/94), and 37.9% (36/95), respectively. Adjusted odds ratios with 95% confidence intervals for one-month favourable neurological outcome in the first, second, third, and fifth quintiles compared with the fourth quintile were 0.38 (0.20 to 0.72), 0.43 (0.23 to 0.81), 0.77 (0.41 to 1.44), and 0.46 (0.25 to 0.87), respectively. Conclusion: Non-linear multivariable logistic regression analysis could clearly describe the association between neurological outcome in patients with out-of-hospital cardiac arrest and the time from the introduction of targeted temperature management to reaching the temperature targets.

Maternal diabetes and risk of offspring congenital heart diseases: the Japan Environment and Children's Study.

BACKGROUND: Few prospective cohort studies have examined the association between maternal diabetes, including pre-pregnancy and gestational diabetes, and the risk of congenital heart disease (CHD) in Asian offspring. METHODS: We examined the association between maternal diabetes and offspring CHD among 97,094 mother-singleton infant pairs in the Japan Environment and Children's Study (JECS) between January 2011 and March 2014. Odds ratios (OR) and 95% confidence intervals (CI) of offspring CHD based on maternal diabetes (pre-pregnancy diabetes and gestational diabetes) were estimated using logistic regression after adjusting for maternal age at delivery, pre-pregnancy body mass index (BMI), maternal smoking habits, alcohol consumption, annual household income, and maternal education. The diagnosis of CHD in the offspring was ascertained from the transcript of medical records. RESULTS: The incidence of CHD in the offspring was 1,132. Maternal diabetes, including both pre-pregnancy diabetes and gestational diabetes, was associated with a higher risk of offspring CHD: multivariable OR (95%CI) = 1.81 (1.40-2.33) for maternal diabetes, 2.39 (1.05-5.42) for pre-pregnancy diabetes and 1.77 (1.36-2.30) for gestational diabetes. A higher risk of offspring CHD was observed in pre-pregnancy BMI ≥25.0 kg/m2 (OR = 2.55, 95% CI: 1.74-3.75) than in pre-pregnancy BMI <25.0 kg/m2 (OR = 1.49, 95% CI: 1.05-2.10, p for interaction = 0.04). CONCLUSIONS: Maternal diabetes, including both pre-pregnancy and gestational, was associated with an increased risk of CHD in offspring.

Association between eGFR and neurological outcomes among patients with out-of-hospital cardiac arrest: A nationwide prospective study in Japan.

Aim: We aimed to investigate the association between estimated glomerular filtration rate and prognosis in out-of-hospital cardiac arrest patients and explore the heterogeneity of the association. Methods: Patients experiencing out-of-hospital cardiac arrest due to medical causes and registered in the JAAM-OHCA Registry between June 2014 and December 2019 were stratified into shockable rhythm, pulseless electrical activity, and asystole groups according to the cardiac rhythm at the scene. The primary outcome was a 1-month favorable neurological status. Adjusted odds ratios with 95% confidence intervals were calculated to investigate the association between estimated glomerular filtration rate and outcomes using a logistic model. Results: Of the 19,443 patients included, 2769 had initial shockable rhythm at the scene, 5339 had pulseless electrical activity, and 11,335 had asystole. As the estimated glomerular filtration rate decreased, the adjusted odds ratio for a 1-month favorable neurological status decreased among those with initial shockable rhythm (estimated glomerular filtration rate, adjusted odds ratio [95% CI]: 45-59 mL/min/1.73 m2, 0.61 [0.47-0.79]; 30-44 mL/min/1.73 m2, 0.45 [0.32-0.62]; 15-29 mL/min/1.73 m2, 0.35 [0.20-0.63]; and <15 mL/min/1.73 m2, 0.14 [0.07-0.27]). Estimated glomerular filtration rate was associated with neurological outcomes in patients aged <65 years with initial shockable rhythm but not in those aged >65 years or patients with initial pulseless electrical activity or asystole. Conclusion: The estimated glomerular filtration rate is associated with neurological prognosis in out-of-hospital cardiac arrest patients with initial shockable rhythm at the scene but not in those with initial non-shockable rhythm.

Active and passive smoking and breast cancer in Japan: a pooled analysis of nine population-based cohort studies.

BACKGROUND: Epidemiological studies have shown inconsistent results regarding the link between smoking and breast cancer risk, despite the biological plausibility of a positive association. METHODS: Participants were 166 611 women from nine prospective cohort studies in Japan which launched in 1984-1994 and followed for 8-22 years. Information on smoking and secondhand smoke was obtained through self-administered baseline questionnaires. Breast cancer was defined as code C50 according to the International Classification of Diseases for Oncology, 3rd Edition or the International Classification of Diseases, 10th Revision. After adjusting for several potential confounders, relative risks for breast cancer were calculated in the individual studies according to the current or previous status of active and passive smoking using Cox regression, followed by a summary estimate of hazard ratios using random-effects meta-analyses. RESULTS: Of the 60 441 participants who reported being premenopausal and 106 170 who reported being postmenopausal at baseline, 897 and 1168 developed breast cancer during follow-up, respectively. Compared with never smokers, current smokers had a higher risk of developing breast cancer before the age of 50 years. In addition, ever smokers who started smoking at 30 years of age or younger, or who started smoking before first childbirth, had a higher risk of developing breast cancer before the age of 50 years. No association between adulthood or childhood exposure to secondhand smoke and breast cancer was observed. CONCLUSION: Smoking may increase the risk of premenopausal breast cancer, and smoking earlier in life might be especially harmful. The impact of secondhand smoke needs further investigation.