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VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is caused by UBA1 somatic mutations and is characterized by late-onset systemic autoimmune inflammation and blood abnormalities such as cytopenia, vacuolation of myeloid/erythroblastic cells, and myelodysplastic syndrome (MDS). It is often resistant to immunosuppressive therapy, and no treatment strategy has been established. A 65-year-old man presented with palpable erythema, fever, macrocytic anemia, and arthralgia. He was subsequently diagnosed with MDS complicated by Sweet's disease. Treatment with azacitidine was initiated due to suspected skin invasion by MDS cells and resistance of the skin rash to steroid therapy. Next-generation sequencing of bone marrow samples prior to treatment initiation revealed the presence of UBA1 p.M41L (VAF 0.38) and DNMT3A p.L605fs mutations (VAF 0.184). Based on the findings of systemic inflammation, a diagnosis of VEXAS syndrome was made. The fever and skin rash improved with azacitidine therapy. In conclusion, somatic mutations in UBA1 should be explored in patients with MDS exhibiting systemic autoimmune inflammation. Furthermore, azacitidine may be a good treatment option for systemic autoinflammation in MDS associated with VEXAS syndrome.

Background Due to potentially fatal consequences of missed bacteremia, blood cultures are often overused. While there are several prediction models that can be used to identify patients who truly need blood cultures, physicians often rely on their gestalt. We evaluated the diagnostic performance of physician gestalt for bacteremia in comparison with 2 existing prediction models: Takeshima and Shapiro. Methods The study enrolled consecutive adult patients with suspected infection who were in the process of being admitted to the general medicine department at 2 hospitals between April 2017 and January 2019. Attending physicians provided gestalt regarding risk of bacteremia (0%–100%). Patients with a Results Among 2014 patients, 292 (14.5%) were diagnosed with bacteremia. The safety of physician gestalt and the Takeshima and Shapiro models was 3.7% (95% confidence interval [CI], 2.2% to 5.7%), 6.5% (95% CI, 5.0% to 7.9%), and 10.8% (95% CI, 9.4% to 12.3%), whereas the efficiency of each strategy was 22.4% (95% CI, 22.5% to 26.3%), 52.7% (95% CI, 50.5% to 54.9%), and 87.8% (95% CI, 86.3% to 89.2%), respectively. Conclusions Physician gestalt was safer but less efficient than existing models. Clinical prediction models could help reduce the overuse of blood cultures.

ImportanceQuality of life (QOL) of patients with atopic dermatitis (AD) is reported to be the lowest among skin diseases. To our knowledge, mindfulness and self-compassion training has not been evaluated for adults with AD.ObjectiveTo evaluate the efficacy of mindfulness and self-compassion training in improving the QOL for adults with AD.Design, Setting, and ParticipantsThis randomized clinical trial conducted from March 2019 through October 2022 included adults with AD whose Dermatology Life Quality Index (DLQI) score, a skin disease–specific QOL measure, was greater than 6 (corresponding to moderate or greater impairment). Participants were recruited from multiple outpatient institutes in Japan and through the study’s social media outlets and website.InterventionsParticipants were randomized 1:1 to receive eight 90-minute weekly group sessions of online mindfulness and self-compassion training or to a waiting list. Both groups were allowed to receive any dermatologic treatment except dupilumab.Main Outcomes and MeasuresThe primary outcome was the change in the DLQI score from baseline to week 13. Secondary outcomes included eczema severity, itch- and scratching-related visual analog scales, self-compassion and all of its subscales, mindfulness, psychological symptoms, and participants’ adherence to dermatologist-advised treatments.ResultsThe study randomized 107 adults to the intervention group (n = 56) or the waiting list (n = 51). The overall participant mean (SD) age was 36.3 (10.5) years, 85 (79.4%) were women, and the mean (SD) AD duration was 26.6 (11.7) years. Among participants from the intervention group, 55 (98.2%) attended 6 or more of the 8 sessions, and 105 of all participants (98.1%) completed the assessment at 13 weeks. The intervention group demonstrated greater improvement in the DLQI score at 13 weeks (between-group difference estimate, −6.34; 95% CI, −8.27 to −4.41; P d) at 13 weeks was −1.06 (95% CI, −1.39 to −0.74). All secondary outcomes showed greater improvements in the intervention group than in the waiting list group.Conclusions and RelevanceIn this randomized clinical trial of adults with AD, integrated online mindfulness and self-compassion training in addition to usual care resulted in greater improvement in skin disease–specific QOL and other patient-reported outcomes, including eczema severity. These findings suggest that mindfulness and self-compassion training is an effective treatment option for adults with AD.Trial Registrationhttps://umin.ac.jp/ctr Identifier: UMIN000036277

Background Chronic prostatitis (CP) can impair health-related quality of life (QOL), but the full impact of CP, including the impact of CP-like symptoms in men who have no CP diagnosis (CPS), is unknown. We estimated the impact of diagnosed CP (DCP) and CPS on Health-related QOL. Methods From a representative nationwide survey of men aged 20–84 in Japan, we determined the prevalence of DCP and also of CPS. For CPS, we used Nickel’s criteria, which were used previously to estimate the prevalence of CP and are based on the NIH Chronic Prostatitis Symptom Index. To test the robustness of Nickel’s criteria, we used two other definitions of CPS (two sensitivity analyses). We measured QOL with the Short-Form 12-Item Health Survey. We compared the participants’ QOL scores with the national-norm scores, and with the scores of men who had benign prostatic hyperplasia (BPH). Results Among the 5 010 participants, 1.4% had DCP and 3.7% had CPS. The sensitivity analyses resulted in CPS prevalence estimates of 3.1% and 4.5%. CPS was particularly common in younger participants (5.7% of those in their 30 s had CPS). QOL was very low among men with CP: In most areas (domains) of QOL, their scores were more than 0.5 standard deviation below the national-norm mean. Their mental-health scores were lower than those of men with BPH. The lowest scores among all 8 QOL domains were in role-functioning. Conclusions CP is common, but it is underdiagnosed, particularly in younger men. Whether diagnosed or only suspected, CP’s impact on QOL is large. Because CP is common, and because it substantially impairs individuals’ QOL and can also reduce societal productivity, it requires more attention. Specifically, needed now is a simple tool for urologists and for primary care providers, to identify men, particularly young men, whose QOL is impaired by CP.

Although respiratory rate has been a sensitive predictor for prognosis in acute settings, resting respiratory rate (RRR) is undervalued in chronic care. The clinical significance of RRR among older people is not well documented.We investigated the association between RRR and all-cause mortality among older outpatients.A retrospective cohort study exhaustively included patients who had undergone medical checkups in a facility between April 2017 and March 2018 and followed up for at least 2 years. We excluded patients who were less than 60 years of age or had not undergone regular outpatient appointments. Sex, age, smoking habits, history of hospitalization, polypharmacy, long-term care insurance certification status, Mazzaglia index, pulse rate, systolic blood pressure, and Charlson Comorbidity Index were measured at the baseline medical checkup. Survival was confirmed by chart review and by contacting physicians in charge. The risk ratios were estimated by converting the odds ratios derived from the multivariable logistic regression models.Of the 853 patients who underwent baseline checkups, 749 were enrolled in the analyses; death occurred in 53 patients (7.1%), with no loss to follow-up. The RRR was independently associated with all-cause mortality after adjusting for covariates [adjusted risk ratio of RRR per 1 bpm = 1.14, 95% confidence interval (CI): 1.06 - 1.22].Given the independent association of RRR for existing predictors, this simple index seems worthy of consideration in further studies aimed at defining its predictive role in older people and in different settings.RRR was independently associated with all-cause mortality.

BACKGROUND: Although bystanders' performance is important to improve outcomes of patients after cardiac arrests, few studies have investigated the barriers of bystanders, including those who could not perform cardiopulmonary resuscitation or any other rescue actions in emergency situations. This study aimed to assess the relationship between the psychological barriers of laypersons who encountered emergency situations and their rescue actions.Methods and Results:A questionnaire survey was conducted and this included laypersons who had encountered emergency situations during the last 5 years. Six questions were about the psychological barriers and 8 questions were about the laypersons' rescue actions. The primary outcome was any rescue actions performed by laypersons in an actual emergency situation. Overall, 7, 827 (92.8%) of 8, 430 laypersons responded; of them, 1, 361 (16.1%) had encountered emergency situations during the last 5 years, and 1, 220 (14.5%) were eligible for inclusion in the analyses. Of the 6 psychological barriers, "fear of approaching a collapsed person" (adjusted odds ratio [AOR] 0.50; 95% confidence interval [95% CI] 0.32-0.79) and "difficulties in judging whether to perform any rescue action" (AOR 0.63; 95% CI 0.40-0.99) were significantly associated with performing any rescue actions. CONCLUSIONS: The fear of approaching a collapsed person and difficulties in judging whether to take any actions were identified as the psychological barriers in performing any rescue actions by laypersons who encountered emergency situations.

This paper reports on gas sensing based on near-infrared (NIR) reconstructive spectroscopy using a surface plasmon resonance (SPR) photodetector. The reconstructive spectrometer consists of an Au g...

Background Although corticosteroid therapy with dose tapering is the most commonly used treatment for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF), there is no consensus on the tapering regimen. This study aimed to investigate the association between early corticosteroid dose tapering and in-hospital mortality in patients with AE-IPF. Methods In this retrospective cohort study, we analyzed the data of a cohort from eight Japanese tertiary care hospitals and routinely collected administrative data from a cohort from 185 Japanese hospitals. Patients with AE-IPF were classified into the early and non-early tapering groups depending on whether the maintenance dose of corticosteroids was reduced within two weeks of admission. Propensity score analysis with inverse probability weighting (IPW) was performed to estimate the effect of early corticosteroid dose tapering. Results The multi-center cohort included 153 eligible patients, of whom 47 (31%) died, whereas the administrative cohort included 229 patients, of whom 51 (22%) died. Patients with early tapering tended to have a better prognosis than those without it (unadjusted hazard ratio [95% confidence interval] 0.41 [0.22–0.76] and 0.65 [0.36–1.18] in the multi-center and administrative cohorts, respectively). After IPW, the early tapering group had a better prognosis than the non-early tapering group (IPW-adjusted hazard ratio [95% confidence interval] 0.37 [0.14–0.99] and 0.27 [0.094–0.83] in the multi-center and administrative cohorts, respectively). Conclusion Early corticosteroid dose tapering was associated with a favorable prognosis in patients with AE-IPF. Further studies are warranted to confirm the effects of early corticosteroid dose tapering in patients with AE-IPF.

Background: The relationship between advance care planning and religious beliefs, which are important for palliative care, is controversial in Western countries and has not been verified in Asian countries. Aim: To investigate the association between advance care planning discussions and religious beliefs in Japan. Design: A nationwide survey conducted in 2016 using a quota sampling method to obtain a representative sample of Japan’s general population. Setting/participants: We analyzed responses from 3167 adults aged 20–84 years (mean age ± standard deviation, 50.9 ± 16.8 years). The outcome was measured by asking whether the respondents had ever discussed advance care planning, and the main exposure by whether they had any religious beliefs or affiliations, and if so, their degree of devoutness. We analyzed religious beliefs, affiliations, and devoutness in relation to the occurrence of discussions using multivariable logistic regression models adjusted for possible sociodemographic covariates. Results: Compared with respondents without, those with religious beliefs had significantly higher odds of having had discussions (adjusted odds ratio: 1.45, 95% confidence interval: 1.22–1.73). The devoutness of religious belief was proportional to the propensity of the occurrence of discussions ( p for trend < 0.001). In addition, Buddhists and Christians had higher odds of having had discussions than did nonbelievers. Conclusion: The results suggest that holding religious beliefs, especially in Japanese Buddhism and Christianity, facilitates advance care planning discussions among Japanese adults, and thus, may help health-care providers identify those prioritized for facilitating engagement in advance care planning, especially in palliative and spiritual care settings.

New 4,8,12-trioxotriangulene (TOT) neutral radical derivatives having three methoxy and hydroxy groups at the α-positions were synthesized, and the substituent effects on the electronic spin and redox properties were elucidated in the theoretical and experimental methods. Due to the small SOMO coefficients at the α-positions of TOT, the methoxy groups in the TOT neutral radical had negligible effects on the electronic spin structure and redox ability. On the other hand, methoxy groups greatly increased the LUMO energy having large coefficients at α-positions and, thus, caused a remarkable negative-potential shift of the redox wave of anion species involving the dianion and trianion species. Converting the methoxy groups to hydroxy groups caused a dramatic change in the electronic structure of TOT, where the intramolecular hydrogen bonds between hydroxy groups and oxo groups strongly attracted a minus charge on the TOT skeleton. The HOMO energy of the monoanion species was significantly reduced, causing a blue shift of the HOMO-LUMO transition and an anodic shift of the redox potential. In addition, due to the steric repulsion smaller than that of the methoxy group, the hydroxy derivative showed a more planar molecular structure and a strong π-stacking ability.

Primary tumor resection (PTR) before commencing systemic chemotherapy in patients with stage IV colorectal cancer and unresectable metastases (mCRC) remains controversial. This study aimed to assess whether PTR before systemic chemotherapy is associated with mortality in mCRC patients, after adjusting for confounding factors, such as the severity of the primary tumor and metastatic lesions. We analyzed hospital-based cancer registries from nine designated cancer hospitals in Fukushima Prefecture, Japan. Patients were divided into two groups (PTR and non-PTR), based on whether PTR was performed as initial therapy for mCRC or not. The primary outcome was all-cause mortality. Kaplan–Meier survival analysis was performed, and survival estimates were compared using the log-rank test. Adjusted hazard ratios were calculated using Cox regression to adjust for confounding factors. All tests were two-sided; P-values

Introduction Helicobacter pylori eradication therapy requires a complex prescribing schedule combining clarithromycin, amoxicillin, and a proton-pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB, vonoprazan). To reduce the burden of complex prescribing and increase adherence, a vonoprazan triple-drug blister pack comprising all three medications was launched in June 2016. This study aimed to assess the impact of the combination blister pack on eradication success rate in Japan immediately after launch. Methods We performed an interrupted time series analysis using a large administrative claims database of 7,300,000 insured individuals. We identified 36,570 patients who received first-line clarithromycin triple therapy from June 2015 to May 2016 (prelaunch) and 35,721 who received the same therapy from July 2016 to June 2017 (post-launch). The primary outcome was the success rate of clarithromycin triple therapy and the secondary outcomes were proportion of vonoprazan use and proportion of combination blister pack use. Results The success rate of clarithromycin triple therapy increased by 2.44% (95% confidence interval [CI] 1.36–3.52; P

Skeletal muscle atrophy often complicates idiopathic pulmonary fibrosis (IPF). IPF patients frequently experience acute exacerbation (AE), but the association between skeletal muscle atrophy and mortality remains unknown in AE-IPF patients. Herein, cross-sectional areas of the erector spinae muscle (ESMCSA) and the pectoralis muscle (PMCSA) of AE-IPF patients were analysed via computed tomography. Primary outcome was 90-day mortality. Survival probability was estimated using the Kaplan–Meier method, and the log-rank test was used between the low and high groups of ESMCSA and PMCSA. We used multivariable Cox proportional-hazards models to evaluate the association between ESMCSA and PMCSA and prognosis. Among the 212 patients, 94 (44%) died during the observation period. The low ESMCSA group (2) had a significantly worse prognosis than the high group (≥ 25.6 cm2) (hazard ratio (HR) [95% confidence interval (CI)]: 1.52 [1.00–2.33], p = 0.049). Multivariable analyses showed that all-cause mortality was associated with low ESMCSA (model 1, adjusted HR [95% CI]: 1.59 [0.98–2.60]; model 2, 1.55 [0.95–2.56] and model 3, 1.67 [1.00–2.78]). A similar trend was observed between low PMCSA and poor prognosis (HR [95% CI]: 1.39 [0.88–2.20]). In conclusion, low ESMCSA is associated with high 90-day mortality in AE-IPF patients.

ObjectiveAlthough mindfulness and self-compassion programs have been applied in clinical settings, no studies have reported their benefits for atopic dermatitis (AD). The aim of the study was to evaluate the feasibility and acceptability of an online group format of 8 weekly 90-minute sessions of a mindfulness and self-compassion program for adults with AD.ResultsIn this single-arm, open label pre-post comparison study design, 15 adults (10 women; mean age, 38.3 ± 8.98 years) completed the intervention and assessment. The primary outcome was disease-specific quality of life (QOL) (Dermatology Life Quality Index and Skindex-16) at the 20-week follow-up. The secondary outcomes were other self-reported questionnaires, and descriptive feedback of the program. Assessments were conducted at baseline, mid-treatment, post-intervention, and at follow-up. Overall, there were no significant improvements. However, of the four participants whose QOL was largely impacted due to AD, the scores improved significantly, with minimal clinically important difference or greater change. All participants were satisfied with the program. This program could benefit adults with AD by improving QOL. Randomized controlled trials are warranted to elucidate the efficacy of the program. This study has been registered at the UMIN Clinical Trials Registry (ID: UMIN000030484).

Background The effect of ICU admission time on patient outcomes has been shown to be controversial in several studies from a number of countries. The imbalance between ICU staffing and medical resources during off-hours possibly influences the outcome for critically ill or injured patients. Here, we aimed to evaluate the association between ICU admission during off-hours and in-hospital mortality in Japan. Methods This study was an observational study using a multicenter registry (Japanese Intensive care PAtient Database). From the registry, we enrolled adult patients admitted to ICUs from April 2015 to March 2019. Patients with elective surgery, readmission to ICUs, or ICU admissions only for medical procedures were excluded. We compared in-hospital mortalities between ICU patients admitted during off-hours and office-hours, using a multilevel logistic regression model which allows for the random effect of each hospital. Results A total of 28,200 patients were enrolled with a median age of 71 years (interquartile range [IQR], 59 to 80). The median APACHE II score was 18 (IQR, 13 to 24) with no significant difference between patients admitted during off-hours and those admitted during office-hours. The in-hospital mortality was 3399/20,403 (16.7%) when admitted during off-hours and 1604/7797 (20.6%) when admitted during office-hours. Thus, off-hours ICU admission was associated with lower in-hospital mortality (adjusted odds ratio 0.91, [95% confidence interval, 0.84–0.99]). Conclusions ICU admissions during off-hours were associated with lower in-hospital mortality in Japan. These results were against our expectations and raised some concerns for a possible imbalance between ICU staffing and workload during office-hours. Further studies with a sufficient dataset required for comparing with other countries are warranted in the future.

To investigate whether lower limb arterial calcification (LLAC) quantified using computed tomography (CT) was a risk factor for bilateral severe knee osteoarthritis (OA).This cross-sectional study included patients who were scheduled for surgical treatment of primary varus knee OA. Knee OA was evaluated using the Kellgren-Lawrence (KL) classification, KL grades 3 and 4 were defined as severe OA. The LLAC score in the bilateral whole leg CT was quantitatively measured and categorized into low or high groups based on the median value. A modified Poisson regression model was used to examine the relationship between the categorized LLAC score and the presence of bilateral severe knee OA with adjustment for possible confounders.Of a total of 252 patients examined, multivariable modified Poisson regression analysis showed a significant association between higher LLAC score and the presence of bilateral severe knee OA (adjusted risk ratio = 1.28; 95% confidence interval [CI], 1.12-1.48;LLAC was associated with bilateral severe knee OA, and the LLAC score may be a useful measurement to identify patients at risk of bilateral severe knee OA.

Context Advance care planning (ACP) is vital for end-of-life care management. Experiences as informal family caregivers might act as a catalyst to promote ACP. Objectives We investigated the association between ACP discussions and caregiving experiences. Methods A nationwide survey in Japan was conducted in December 2016 using a quota sampling method to select a sample representative of the general Japanese population. The responses of 3167 individuals aged 20–84 years (mean age: 50.9 ± 16.8) were analyzed. The outcome was measured by asking if respondents had ever engaged in ACP discussions. The exposure was measured by asking whether and for how long respondents had experience as informal caregivers for family members. We analyzed informal caregiving experience related to the occurrence of ACP discussions using multivariable logistic regression models that adjusted for possible covariates. Results Respondents with informal caregiving experience had significantly higher odds of having ACP discussions than those without caregiving experience (adjusted odds ratio: 1.93, 95% CI = 1.63, 2.29). Stronger effects were identified in younger adults (aged 20–65 years) and those with a higher education level (education duration > 12 years) than in older adults (aged ≥65 years) and those with a lower education level, respectively. Conclusion Experiences as informal caregivers for family members may facilitate ACP discussions among Japanese adults, especially younger adults with higher educational attainment. Our findings may help health-care providers screen those at risk for inadequate ACP discussions, and informal caregiving experience should be considered when health-care providers initiate discussions of end-of-life care.

A conceptual framework for advance care planning is lacking in societies like Japan's valuing family-centered decision-making.A consensus definition of advance care planning with action guideline adapted to Japanese society.We conducted a multidisciplinary modified Delphi study 2020-2022. Thirty physicians, 10 healthcare and bioethics researchers, six nurses, three patient care managers, three medical social workers, three law experts, and a chaplain evaluated, in 7 rounds (including two web-based surveys where the consensus level was defined as ratings by ≥70% of panelists of 7-9 on a nine-point Likert scale), brief sentences delineating the definition, scope, subjects, and action guideline for advance care planning in Japan.The resulting 29-item set attained the target consensus level, with 72%-96% of item ratings 7-9. Advance care planning was defined as "an individual's thinking about and discussing with their family and other people close to them, with the support as necessary of healthcare providers who have established a trusting relationship with them, preparations for the future, including the way of life and medical treatment and care that they wish to have in the future." This definition/action guideline specifically included support for individuals hesitant to express opinions to develop and express preparations for the future.Adaptation of advance care planning to Japanese culture by consciously enhancing and supporting individuals' autonomous decision-making may facilitate its spread and establishment in Japan and other societies with family-centered decision-making cultures.

Fat accumulation in the liver, pancreas, skeletal muscle, and visceral bed relates to type-2 diabetes (T2D). However, the distribution of fat among these compartments is heterogenous and it is unclear whether specific distribution patterns indicate high T2D risk. We therefore investigated fat-distribution patterns and their link to future T2D. From 2168 individuals without diabetes who underwent computed tomography in Japan, this case-cohort study included 658 randomly selected individuals and 146 incident cases of T2D over 6 years of follow-up. Using data-driven analysis (k-means) based on fat content in the liver, pancreas, muscle, and visceral bed, we identified four fat-distribution clusters: Hepatic steatosis, Pancreatic steatosis, Trunk myosteatosis, and Steatopenia. Compared with the Steatopenia cluster, the adjusted hazard ratios (95% CIs) for incident T2D were 4.02 (2.27-7.12) for the Hepatic steatosis cluster, 3.38 (1.65-6.91) for the Pancreatic steatosis cluster, and 1.95 (1.07-3.54) for the Trunk myosteatosis cluster. The clusters were replicated in 319 German individuals without diabetes who underwent magnetic resonance imaging and metabolic phenotyping. The distribution of AUC-glucose across the four clusters found in Germany was similar to the distribution of T2D risk across the four clusters in Japan. Insulin sensitivity and insulin secretion differed across the four clusters. Thus, we identified patterns of fat distribution with different T2D risks presumably due to differences in insulin sensitivity and insulin secretion.

Objective: Fat accumulation in liver, pancreas, skeletal muscle, and visceral bed relates to type 2 diabetes (T2D) . However, distribution of fat in these compartments is heterogenous and it is unclear if specific distribution patterns indicate high T2D risk. We therefore investigated fat distribution patterns and their link to future T2D. Methods: From 2168 individuals without diabetes undergoing computed tomography in Japan, this case-cohort study included 658 randomly selected individuals and 146 incident cases of T2D with a 6-year follow-up. Data-driven analysis (k-means) was applied to develop clusters based on fat content in liver, pancreas, muscle, and visceral bed. Hazard ratios (HRs) for association of clusters and incident T2D were estimated using weighted Cox regression. In 3 individuals without diabetes with magnetic resonance imaging and metabolic phenotyping in Germany, cluster validation with additional assessment of glycemic traits from OGTTs was conducted. Results: We identified four clusters of fat distribution: cluster 1 (Hepatic steatosis cluster) , cluster 2 (Pancreatic steatosis cluster) , cluster 3 (Myosteatosis dominant cluster) , cluster 4 (Steatopenic cluster) . Compared with Steatopenic cluster, the adjusted-HRs (95%CIs) for incident T2D were 4.02 (2.27-7.12) in Hepatic steatosis cluster, 3.38 (1.65-6.91) in Pancreatic steatosis cluster, and 1.95 (1.07-3.54) in Myosteatosis dominant cluster. The clusters were replicated in the German cohort with similar distribution of AUC-glucose to the diabetes hazard in the Japanese cohort. Insulin sensitivity and insulin secretion were different across clusters with the lowest insulin sensitivity and highest insulin secretion in Hepatic steatosis cluster. Conclusions: Extending evidence about fat accumulation in single compartments, we identified specific patterns of fat distribution with different T2D risk presumably due to differences in insulin sensitivity and insulin secretion. Disclosure H.Yamazaki: None. N.Stefan: Advisory Panel; Gilead Sciences, Inc., GlaxoSmithKline plc., Sanofi, Consultant; AstraZeneca, Intercept Pharmaceuticals, Inc., Novo Nordisk, Pfizer Inc., Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck Sharp & Dohme Corp. A.Fritsche: Advisory Panel; Boehringer Ingelheim International GmbH, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. A.L.Birkenfeld: None. R.Wagner: Advisory Panel; Akcea Therapeutics, Daiichi Sankyo, Sanofi-Aventis Deutschland GmbH, Speaker's Bureau; Lilly, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. M.Heni: Advisory Panel; Boehringer Ingelheim International GmbH, Research Support; Boehringer Ingelheim International GmbH, Sanofi, Speaker's Bureau; Amryt Pharma Plc, Boehringer Ingelheim International GmbH, Novo Nordisk. S.Tauchi: None. J.Machann: None. T.Haueise: None. Y.Yamamoto: None. M.Dohke: None. N.Hanawa: None. Y.Kodama: Other Relationship; Eisai Co., Ltd. A.Katanuma: None. Funding the German Center for Diabetes Research (DZD, 01GI0925) , the state of Baden-Württemberg (32-5400/58/2, Forum Gesundheitsstandort Baden-Württemberg) , and JSPS KAKENHI Grant Number 19K16978

BackgroundData on the effects of intraoperative end-tidal carbon dioxide (EtCO2) levels on postoperative organ dysfunction are limited. Thus, this study was designed to investigate the relationship between the intraoperative EtCO2 level and postoperative organ dysfunction in patients who underwent major abdominal surgery under general anesthesia.MethodsWe conducted a retrospective cohort study involving patients who underwent major abdominal surgery under general anesthesia at Kyoto University Hospital. We classified those with a mean EtCO2 of less than 35 mmHg as low EtCO2. The time effect was determined as the minutes when the EtCO2 value was below 35 mmHg, whereas the cumulative effect was evaluated by measuring the area below the 35-mmHg threshold. The outcome was postoperative organ dysfunction, defined as a composite of at least one organ dysfunction among acute renal injury, circulatory dysfunction, respiratory dysfunction, coagulation dysfunction, and liver dysfunction within 7 days after surgery.ResultsOf the 4,171 patients, 1,195 (28%) had low EtCO2, and 1,428 (34%) had postoperative organ dysfunction. An association was found between low EtCO2 and increased postoperative organ dysfunction (adjusted risk ratio, 1.11; 95% confidence interval [CI], 1.03–1.20; p = 0.006). Additionally, long-term exposure to EtCO2 values of less than 35 mmHg (≥224 min) was associated with postoperative organ dysfunction (adjusted risk ratio, 1.18; 95% CI, 1.06–1.32; p = 0.003) and low EtCO2 severity (area under the threshold) (adjusted risk ratio, 1.13; 95% CI, 1.02–1.26; p = 0.018).ConclusionsIntraoperative low EtCO2 of below 35 mmHg was associated with increased postoperative organ dysfunction.

Purpose Healthy lifestyle is related to quality of life (QOL) after cancer diagnosis and prognosis. However, there are few reports on patients conscious of healthy lifestyle and patients requiring medical providers’ attention regarding healthy lifestyle. We aimed to develop a healthy lifestyle consciousness index (HLCI) for cancer patients and evaluated its validity in gynecological cancer patients. Methods The HLCI was designed to assess degree of healthy lifestyle consciousness, including items regarding “diet,” “exercise,” “body weight,” and “sleep.” Exploratory factor analysis was performed for dimensionality of the scale; Cronbach’s alpha was calculated to assess internal-consistency reliability. For criterion-based validity, we calculated proportions of stage III/IV gynecological malignancies in those with categorized HLCI scores based on tertiles. Concurrent validity was evaluated between HLCI and other quality of life (QOL) scales including European Organization for Research and Treatment of Cancer QLQ-C30 in limited patients. Results HLCI comprised five 10-point items (0–45); higher values implied improved healthy lifestyle consciousness. Data from 108 gynecological malignancy patients at Kyoto University Hospital were analyzed. The mean age of subjects was 55.8 years; 36.1% of them had uterine corpus cancer; 34.3% were at stage III/IV of gynecological malignancy. The factor analysis revealed HLCI was unidimensional; the reliability based on Cronbach’s alpha was satisfactory (0.88). The proportions of stage III/IV gynecological malignancies were 25.7%, 33.3%, and 44.4% in those with first (7–24 points), second (25–30 points), and third (31–46 points) tertiles of HLCI score, respectively. For patients with other QOL scales (n = 25), the mean scores of global health status of QLQ-C30 were 33.3, 50.0, and 83.3 for first, second, and third tertiles of HLCI score, respectively. Conclusion HLCI was successfully validated; thus, patients with advanced stages or higher QOL might have strong consciousness regarding healthy lifestyle. HLCI may be useful in precision care for improved lifestyles and QOL.

Objectives:To assess the impact of nationwide outpatient antimicrobial stewardship interventions in the form of financial incentives for providers and provider education when antimicrobials are deemed unnecessary for uncomplicated respiratory infections and acute diarrhea.Methods:We collected data from a large claims database from April 2013 through March 2020 and performed a quasi-experimental, interrupted time-series analysis. The outcome of interest was oral antimicrobial prescription rate defined as the number of monthly antimicrobial prescriptions divided by the number of outpatient visits each month. We examined the effects of financial incentive to providers (ie, targeted prescriptions for those aged ≤2 years) and provider education (ie, targeted prescriptions for those aged ≥6 years) on the overall antimicrobial prescription rates and how these interventions affected different age groups before and after their implementation.Results:In total, 21,647,080 oral antimicrobials were prescribed to 2,920,381 unique outpatients during the study period. At baseline, prescription rates for all age groups followed a downward trend throughout the study period. Immediately after the financial incentive implementation, substantial reductions in prescription rates were observed among only those aged 0–2 years (−47.5 prescriptions per 1,000 clinic visits each month; 95% confidence interval, −77.3 to −17.6; P = .003), whereas provider education immediately reduced prescription rates in all age groups uniformly. These interventions did not affect the long-term trend for any age group.Conclusion:These results suggest that the nationwide implementation of financial incentives and provider education had an immediate effect on the antimicrobial prescription but no long-term effect.

Aim There is growing recognition of the need to hold advance care planning discussions. Older adults who have direct interpersonal involvement with dying family members might begin to consider their own end-of-life care. This study examined the associations between experiences of being with a dying family member and advance care planning discussions among Japanese older adults. Methods This study examined data from a previous self-administered questionnaire survey carried out among outpatients aged ≥65 years. All participants were visitors of a community hospital in Japan, with data being collected over a 1-week period in July 2016. The main exposure was experiences of being with dying family members, while the outcome was advance care planning discussions with the family members and/or their physician. We analyzed the associations between experiences of being with dying family members and advance care planning discussions through log-binomial regression models adjusted for possible sociodemographic confounders. Results Of the 302 respondents included for analysis, 96 (32%) had experiences of being with dying family members, while 179 (59%) held advance care planning discussions. Respondents with said experiences were more likely to have discussions than those without experiences (fully adjusted prevalence ratio 1.31, 95% confidence interval 1.04-1.65). Subgroup analyses showed no significant interaction effects between experiences of being with dying family members and the covariates. Conclusions Direct interpersonal involvement with dying family members might facilitate advance care planning discussions among Japanese older adults. Our results should help healthcare providers recognize individuals who are unlikely to have discussions. Geriatr Gerontol Int 2021; 21: 197-202.

Background Although hospitalized patients with acute decompensated heart failure (ADHF) have severe physical dysfunction, little data are available on the comparative effectiveness of early versus late rehabilitation. This study examined the relationship between early compared to late rehabilitation and physical function among older patients hospitalized for ADHF. Methods In a retrospective cohort study, independent patients aged ≥65 years at baseline who were hospitalized for ADHF from 2012 to 2014 and underwent inpatient rehabilitation were identified using Emergency Department visit data and electronic medical records at two hospitals. Patients were classified into those who underwent early rehabilitation (initiated within 72 hours of admission) and late rehabilitation (after 72 hours). Primary outcome was length of time from admission until the patient was able to walk independently. Multivariable competing-risk regression with death as the competing event was used to adjust for potential confounding factors, and multiple imputation (MI) analysis was performed. Results Of 259 individuals, 30 (11.6%) commenced rehabilitation within 72 hours after admission while 229 (88.4%) did so 72 hours after admission. Patients who received early rehabilitation had a higher rate of unassisted walking for at least 40 m by 30 days after admission (hazard ratio: 8.03; 95% confidence interval: 2.15 to 29.98; P = .002 in the multivariable adjusted model) than those who received late rehabilitation. Similar findings were observed on MI analysis. Conclusion Early rehabilitation therapy commenced within 72 hours of admission was associated with a higher rate of recovery of an activity of daily living (independent walking on a level surface).

Background: To evaluate the diagnostic accuracy and clinical utility of the acute aortic dissection detection risk score (ADD-RS) alone or with D-dimer as a screening test to exclude acute aortic syndrome. Methods: We conducted a systematic review and meta-analysis of studies examining the diagnostic accuracy of ADD-RS. We searched MEDLINE, Embase and Cochrane Controlled Register of Trials up to 12 December 2018. Results: We identified nine studies involving 26,598 patients for ADD-RS alone and 3421 patients with D-dimer. Overall, the methodological quality based on the Quality Assessment of Diagnostic Accuracy Studies 2 was moderate to high. Bivariate meta-analyses showed that the pooled sensitivities were 0.94 (95% confidence interval (CI) 0.90, 0.96) at the threshold of ADD-RS ≥1, 0.46 (95% CI, 0.34, 0.59) at ADD-RS ≥2, 1.00 (95% CI 0.99, 1.00) at ADD-RS ≥1 with D-dimer and 0.99 (95% CI 0.97, 1.00) at ADD-RS ≥2 with D-dimer. For the low prevalence population, failure rate and efficiency were 0.8% and 38.3% at ADD-RS ≥1, 0.03% and 14.5% at ADD-RS ≥1 with D-dimer, and 0.1% and 33.6% at ADD-RS ≥2 with D-dimer, respectively. For the high prevalence population, failure rate and efficiency were 3.8% and 33.3% at ADD-RS ≥1, 0.2% and 12.3% at ADD-RS ≥1 with D-dimer and 0.6% and 28.4% at ADD-RS ≥2 with D-dimer, respectively. Conclusions: ADD-RS alone or with D-dimer was a useful screening test with high sensitivity to exclude acute aortic syndrome. However, the optimal threshold of ADD-RS alone or with D-dimer may depend on the clinical setting.

Introduction Although predialysis hemoglobin concentration is affected by interdialytic weight gain (IDWG), the interaction between these parameters is not well understood. Methods Using data from the Dialysis Outcomes and Practice Pattern Study in Japan (J-DOPPS) phases 1, 2, 3, 4, and 5, we analyzed patients who underwent maintenance hemodialysis. The exposure variable was hemoglobin concentration, and the effect modifier was IDWG at baseline. These 2 categorical variables were then combined and analyzed. The primary outcome was major adverse cardiovascular events (MACEs). Hazard ratios (HRs) were estimated using a Cox model for the association between exposure and MACEs after adjusting for potential confounders. We examined additive interactions between hemoglobin concentration and IDWG by calculating the relative excess risk due to interaction (RERI), which is defined as a departure from the additivity of effects. Results A total of 8234 patients were enrolled. During a median follow-up of 2.1 years, 1062 (12.9%) patients developed MACEs. As the IDWG increased, the lowest point estimation in each IDWG category tended to shift to the lower hemoglobin concentration categories. In IDWG categories of ≥6%, point estimation of MACEs with hemoglobin concentration of ≥10.0 g/dl to, Graphical abstract

We used 2‐D shear wave elastography to quantify lymph node hardness, from the shear wave velocity, to determine the presence or absence of metastatic lymphadenopathy in the inguinal lymph nodes of five patients with malignant melanoma and squamous cell carcinoma. The shear wave velocity accurately identified all cases of metastasis confirmed by histology, compared with two false‐positive and one false‐negative finding with positron emission tomography/computed tomography. 2‐D shear wave elastography would be useful to evaluate inguinal lymph node metastasis.

BACKGROUND Taxanes are the current first-line treatment for advanced cutaneous angiosarcoma (CAS) for patients who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity. However, no effective second-line therapy for such patients has been established. METHODS We designed a single-arm prospective observational study of eribulin mesylate (ERB) administered at a dose of 1·4 mg m-2 on days 1 and 8 in a 21-day cycle. Patients with advanced CAS who were previously treated with a taxane and were scheduled to begin ERB treatment were enrolled. The primary endpoint was overall survival (OS) and the secondary endpoints were response rate (RR), progression-free survival (PFS) and toxicity assessment. RESULTS We enrolled a total of 25 patients. The median OS and PFS were 8·6 months and 3·0 months, respectively. The best overall RR was 20% (five of 25). In total, 16 grade 3/4 severe adverse events (SAEs) occurred; however, all patients recovered. Patients who achieved partial response or stable disease as best response had longer OS than those with progressive disease (median OS not reached and 3·3 months, respectively; P < 0·001). Patients who did not experience SAEs showed longer OS than those who did (median OS 18·8 months and 7·5 months, respectively; P < 0·05). Patients with distant metastasis had shorter median OS than those with locoregional disease, but without statistically significant difference. CONCLUSIONS ERB showed a promising RR and is a potential candidate for second-line treatment for patients with CAS, after treatment with taxanes. However, owing to the occurrence of SAEs in over half of the participants, caution should be exercised regarding ERB use in elderly patients. What is already known about this topic? Taxanes are the current first-line treatment for patients with advanced cutaneous angiosarcoma (CAS) who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity. No effective therapy for taxane-resistant CAS has been established thus far. Eribulin suppresses microtubule polymerization and elicits an antitumour effect similar to that of taxanes. What does this study add? In our single-arm prospective observational study to evaluate the efficacy of eribulin for treating patients with advanced CAS who previously received taxanes, the median overall survival and progression-free survival were 8·6 and 3·0 months, respectively. Response rates at weeks 7, 13 and 25 were 20%, 17% and 14%, respectively. Although 16 grade 3/4 severe adverse events occurred, all patients recovered. Eribulin showed a promising response rate and is a potential candidate for second-line treatment in CAS after taxane treatment. Linked Comment: Smrke and Benson. Br J Dermatol 2020; 183:797-798.

Background: Although advance care planning discussions are increasingly accepted worldwide, their ideal timing is uncertain and cultural factors may pertain. Aim: To evaluate timing and factors affecting initiation of advance care planning discussions for adult patients in Japan and Taiwan. Design: Mixed-methods questionnaire survey to quantitatively determine percentages of patients willing to initiate advance care planning discussions at four stages of illness trajectory ranging from healthy to undeniably ill, and to identify qualitative perceptions underlying preferred timing. Setting/participants: Patients aged 40–75 years visiting outpatient departments at four Japanese and two Taiwanese hospitals were randomly recruited. Results: Overall (of 700 respondents), 72% (of 365) in Japan and 84% (of 335) in Taiwan ( p Conclusion: The majority of patients are willing to begin discussion before their health is severely compromised; about one out of five patients are unwilling to begin until clearly facing death. To promote advance care planning, healthcare providers must be mindful of patients’ preferences and factors associated with acceptance and reluctance to initiate advance care planning.

Malignant melanoma (MM) is the most life‐threatening disease among all skin malignancies, and recent genome‐wide studies reported BRAF, RAS, and NF1 as the most frequently mutated driver genes. While epigenetic aberrations are known to contribute to the oncogenic activity seen in various cancers, their role in MM has not been fully investigated. To investigate the role of epigenetic aberrations in MM, we performed genome‐wide DNA methylation analysis of 51 clinical MM samples using Infinium 450k beadarray. Hierarchical clustering analysis stratified MM into two DNA methylation epigenotypes: high‐ and low‐methylation subgroups. Tumor thickness was significantly greater in case of high‐methylation tumors than low‐methylation tumors (8.3 ± 5.3 mm vs 4.5 ± 2.9 mm, P = .003). Moreover, prognosis was significantly worse in high‐methylation cases (P = .03). Twenty‐seven genes were found to undergo significant and frequent hypermethylation in high‐methylation subgroup, where TFPI2 was identified as the most frequently hypermethylated gene. MM cases with lower expression levels of TFPI2 showed significantly worse prognosis (P = .001). Knockdown of TFPI2 in two MM cell lines, CHL‐1 and G361, resulted in significant increases of cell proliferation and invasion. These indicate that MM can be stratified into at least two different epigenetic subgroups, that the MM subgroup with higher DNA methylation shows a more progressive phenotype, and that methylation of TFPI2 may contribute to the tumor progression of MM., We conducted DNA methylome analysis using 51 clinical malignant melanoma samples, and focused on aberrant DNA hypermethylation in promoter CpG islands, which are critical regions that result in gene silencing. We found that malignant melanoma can be stratified into at least two subgroups based on promoter methylation status, and that High‐methylation subgroup involving TFPI2 methylation exhibits advanced tumor phenotypes, characterized by thicker progression and worse prognosis.

Only a few studies have longitudinally evaluated whether fatty pancreas increases the risk of type-2 diabetes (T2D), and their results were inconsistent. Fatty pancreas is closely linked to overweight and obesity, but previous studies did not exclude overweight or obese individuals. Therefore, in this cohort study, we investigated the association between fatty pancreas and T2D incidence in lean individuals. Between 2008 and 2013, 1478 nondiabetic lean individuals (i.e. body-mass index

Objective This study aimed to evaluate the influence of advanced glycation end-product (AGE) accumulation on the prevalence and severity of overactive bladder (OAB) in community-dwelling elderly adults. Methods We conducted a cross-sectional study involving 269 Japanese community dwellers aged ≥75 years in 2015. AGE accumulation was non-invasively measured via skin autofluorescence (SAF) values using AGE Reader. The primary and secondary outcomes were the presence and severity of OAB evaluated using the Overactive Bladder Symptom Score (OABSS). Individuals with an urgency score of ≥2 and sum score of ≥3 were considered to have OAB. The associations of SAF with the prevalence and severity of OAB were assessed using logistic and linear regression models, respectively, adjusted for clinically important confounders. Results The median age of participants was 78 years. Of 269 participants, 110 (40.9%) were men and 75 (27.9%) had OAB. The median SAF was 2.2 AU (arbitrary units). Increasing median SAF was observed with increasing age. Multivariable analysis revealed that SAF was not associated with either the likelihood of having OAB (odds ratio per 1 AU = 0.77, 95% confidence interval: 0.37–1.62) or the natural log-transformed OABSS (β per 1 AU = −0.07, 95% confidence interval: −0.26–0.12). Conclusions In this study, AGE accumulation, as assessed by SAF, was not associated with the prevalence and severity of OAB in Japanese community-dwelling elderly people aged ≥75 years.

Background: Early detection of cognitive decline allows timely intervention to delay progression of dementia. However, current cognitive evaluation tools often include items delivered via verbal forms of instruction, which can cause poor performance in patients with hearing loss. Objective: To develop and validate a cognitive screening battery, the Reading Cognitive Test Kyoto (ReaCT Kyoto), comprising test items given through non-verbal instruction. Methods: A cross-sectional and multi-center study was conducted in the three medical institutes. ReaCT Kyoto was designed to evaluate domains of “registration,” “repetition,” “delayed recall,” “visuospatial recognition,” “orientation in time and place,” and “executive function.” The Japanese version of the Mini-Mental State Examination Test (MMSE-J) and ReaCT Kyoto were applied by experienced psychotherapists. Concurrent validity was evaluated between the ReaCT Kyoto Test and MMSE-J and between the ReaCT Kyoto Test and physician-diagnosed dementia. Results: ReaCT Kyoto was validated in a sample of 115 participants. The mean age of subjects was 81.0±6.4 years, and the sample comprised 53.0% females. The area under the receiver operating curves was 0.95 for detecting physician-diagnosed dementia. When classifying patients in accordance with presence or absence of hearing loss, the AUCs were 0.93 and 0.97 for those with and without hearing loss, respectively. With a cut-off score of

Introduction: Patients undergoing hemodialysis (HD) have higher predialysis plasma osmolality. Several studies have suggested lower osmolality to be associated with worse outcomes in patients not undergoing HD. However, no studies have examined the association between osmolality and mortality among patients undergoing HD. Objective: We aimed to examine the association between predialysis plasma calculated osmolality and all-cause mortality. Methods: This was a prospective cohort study of 1,240 patients undergoing HD participating in the Japanese Dialysis Outcomes and Practice Patterns Study phase 5 (2012–2015). The exposure was predialysis plasma osmolality, calculated as 2 × (serum sodium concentration [mmol/L]) + (serum urea nitrogen [mg/dL])/2.8 + (serum glucose [mg/dL])/18. The primary outcome was all-cause mortality. The secondary outcome was the change in systolic blood pressure (SBP) during HD. We used a marginal structural model with stabilized weights to estimate the association between calculated osmolality and all-cause mortality in the presence of time-varying confounders affected by prior exposure. Results: Mean baseline plasma calculated osmolality was 306.8 ± 8.6 mOsm/kg. Low predialysis calculated osmolality was associated with higher mortality (adjusted hazard ratio 1.52, 95% confidence interval [CI]: 1.30–1.78 by each 10 mOsm/L lower osmolality). The association was consistent across clinically relevant subgroups. Predialysis osmolality was significantly associated with intradialytic SBP change (mean difference 0.96 [95% CI: 0.05–1.88] mm Hg per each 10 mOsm/L lower osmolality). Conclusions: Low predialysis calculated osmolality was an independent risk factor of all-cause mortality.

Background Solitary death is an emerging public health problem in developed countries. Alcohol abuse is associated with social isolation and excess mortality. However, data on the association between alcohol abuse and solitary death are limited. Our purposes were to assess whether alcohol abuse is associated with a long interval from death to discovery among people living alone. Methods This is a cross-sectional study using the data on subjects from the largest forensic database in Kyoto, Japan, from February 2012 to December 2015. Solitary death was defined as a phenomenon of dying alone at home and remaining undiscovered for more than 1 week. All the subjects who lived alone and aged over 18 at the time of death were included in the study. The presence of alcohol abuse was identified via an investigation during home visits. Proportional ratios were calculated using a fitted logit model to evaluate the association of alcohol abuse on solitary death after adjusting for possible confounders. Results A total of 235 subjects were included in the analysis. The mean age (standard deviation) of subjects at the time of death was 63.4 (15.1) years, and approximately 61.8% and 38.9% of subjects in the alcohol and non-alcohol abuse groups, respectively, experienced solitary death. Multivariable analyses revealed that alcohol abuse was associated with solitary death (adjusted proportion ratio: 1.50; 95% confidence interval: 1.12–2.00). Conclusions The findings of this study could help identify individuals at higher risk of solitary death. Moreover, calling the attention of people with alcohol abuse may be beneficial to prevent solitary death.

Malignant melanomas often present with irregular shapes and in multiple shades of brown under white light. Dermoscopy is used to diagnose malignant melanomas; nevertheless, it is often difficult to differentiate malignant melanoma from healthy pigmented skin. The DZ-D100 dermoscope (Casio Computer) is a digital camera equipped with a white light-emitting diode (LED) and a violet LED, which can capture non-polarized/polarized conventional dermoscopy images (CDS) as well as violet-light dermoscopy (VLD) images. Since the absorption wavelength of melanin approaches that of ultraviolet rays, VLD with a wavelength of 405 nm can be used to visualize it. This camera allows three images with the same composition to be captured simultaneously. In this case, we performed dermoscopy with DZ-D100 to determine the surgical resection margins of a melanoma of the heel in a 76-year-old woman. The pale-colored lesions that were difficult to demarcate by CDS were clearly visible by VLD, presenting as dark areas in the grayscale images. Preoperatively determined lesion boundaries with CDS in combination with VLD were histologically more accurate than those with conventional CDS alone. Therefore, the combination of CDS and VLD may reveal the distribution of subtle pigmentation of fine melanin in the skin, making it easier to distinguish between lesions and healthy skin. As one of the limitations, parts of the heel with thick stratum corneum were also observed to be dark gray in the VLD images. Therefore, the evaluation of pigment lesion should be performed by comparing both CDS and VLD.

ObjectivesThis study aimed to investigate the association between kyphotic posture and future loss of independence (LOI) and mortality in community-dwelling older adults.DesignProspective cohort study.SettingTwo Japanese municipalities.ParticipantsWe enrolled 2193 independent community-dwelling older adults aged≥65 years at the time of their baseline health check-up in 2008. Kyphotic posture was evaluated using the wall-occiput test (WOT) and classified into three categories: non-kyphotic, mild (>0 and ≤4 cm) and severe (>4 cm).Primary and secondary outcome measuresThe primary outcome was mortality and the secondary outcomes were LOI (new long-term care insurance certification levels 1–5) and a composite of LOI and mortality. A Cox proportional hazards model was used to estimate the adjusted HRs (aHRs).ResultsOf the 2193 subjects enrolled, 1621 were included in the primary analysis. Among these, 272 (17%) and 202 (12%) were diagnosed with mild and severe kyphotic postures, respectively. The median follow-up time was 5.8 years. Compared with the non-kyphotic group, the aHRs for mortality were 1.17 (95% CI 0.70 to 1.96) and 1.99 (95% CI 1.20 to 3.30) in the mild and severe kyphotic posture groups, respectively. In the secondary analysis, a consistent association was observed for LOI (mild: aHR 1.70, 95% CI 1.13 to 2.55; severe: aHR 2.08, 95% CI 1.39 to 3.10) and the LOI-mortality composite (mild: aHR 1.27, 95% CI 0.90 to 1.79; severe: aHR 1.83, 95% CI 1.31 to 2.56).ConclusionKyphotic posture was associated with LOI and mortality in community-dwelling older adults. Identifying the population with kyphotic posture using the WOT might help improve community health.

The impact of prehospital notification by emergency medical services (EMS) on outcomes of endovascular therapy (EVT) for large vessel occlusion (LVO) remains unclear. We therefore explored the association between prehospital notification and clinical outcomes after EVT. In this single-center retrospective study from 2016 through 2020, we identified all LVO patients who received EVT. Based on the EMS’s usage of a prehospital stroke notification system, we categorized patients into two groups, Hotline and Non-hotline. The primary outcome was good neurological outcome at 90 days; other time metrics were also evaluated. Of all 312 LVO patients, the proportion of good neurological outcomes was 94/218 (43.1%) in the Hotline group and 8/34 (23.5%) in the Non-hotline group (adjusted odds ratio 2.86; 95% confidence interval 1.12 to 7.33). Time from hospital arrival to both tissue plasminogen activator and to groin puncture were shorter in the Hotline group (30 (24 to 38) min vs 48(37 to 65) min, p < 0.001; 40 (32 to 54) min vs 76 (50 to 97) min, p < 0.001), respectively. In conclusion, prehospital notification was associated with a reduction in time from hospital arrival to intervention and improved clinical outcomes in LVO patients treated with EVT. Non-standard Abbreviations and AcronymsEVT, endovascular therapy; t-PA, tissue plasminogen activator; LVO, large vessel occlusion; EMS, emergency medical services; mRS, modified Rankin scale; NIHSS, National Institute of Health Stroke Scale; ASPECTS, Alberta stroke program early computed tomography score; TICI, thrombolysis in cerebral infarction.

Diminishing homeostatic proliferation of memory T cells is essential for improving the efficacy of lymphoablation in transplant recipients. Our previous studies in a mouse heart transplantation model established that B lymphocytes secreting proinflammatory cytokines are critical for T cell recovery after lymphoablation. The goal of the current study was to identify mediators of B cell activation following lymphoablation in allograft recipients. Transcriptome analysis revealed that macrophage-inducible C-type lectin (Mincle, Clec4e) expression is up-regulated in B cells from heart allograft recipients treated with murine anti-thymocyte globulin (mATG). Recipient Mincle deficiency diminishes B cell production of pro-inflammatory cytokines and impairs T lymphocyte reconstitution. Mixed bone marrow chimeras lacking Mincle only in B lymphocytes have similar defects in T cell recovery. Conversely, treatment with a synthetic Mincle ligand enhances T cell reconstitution after lymphoablation in non-transplanted mice. Treatment with agonistic CD40 mAb facilitates T cell reconstitution in CD4 T cell-depleted, but not in Mincle-deficient, recipients indicating that CD40 signaling induces T cell proliferation via a Mincle-dependent pathway. These findings are the first to identify an important function of B cell Mincle as a sensor of damage-associated molecular patterns released by the graft and demonstrate its role in clinically relevant settings of organ transplantation.

PURPOSE Gynecologic laparoscopic surgery has a high incidence of postoperative nausea and vomiting (PONV). Studies suggest that low intraoperative end-tidal carbon dioxide (EtCO2) is associated with an increased incidence of PONV, but the results have not been consistent among studies. This study investigated the association between intraoperative EtCO2 and PONV in patients undergoing gynecologic laparoscopic surgeries under general anesthesia. METHODS This retrospective cohort study involved patients who underwent gynecologic laparoscopic surgeries under general anesthesia at Kyoto University Hospital. We defined hypocapnia as a mean EtCO2 of 2 and PONV two days after surgery and the postoperative length of hospital stay (PLOS). RESULTS Of the 739 patients, 120 (16%) had low EtCO2, and 430 (58%) developed PONV two days after surgery. There was no substantial association between low EtCO2 and increased incidence of PONV (adjusted risk ratio: 0.96; 95% confidence interval [CI]: 0.80–1.14; p = 0.658). Furthermore, there was no substantial association between low EtCO2 and prolonged PLOS (adjusted difference in PLOS: 0.13; 95% CI, −1.00 to 1.28; p = 0.816). CONCLUSION Intraoperative low EtCO2 was not substantially associated with either increased incidence of PONV or prolonged PLOS.

Objectives: The association between frailty and short-term prognosis has not been established in critically ill older adults presenting to the emergency department. We sought to examine the association between premorbid frailty and 30-day mortality in this patient population. Methods: This is a retrospective observational study on older adults aged over 75 who were triaged as Level 1 resuscitation with subsequent admissions to intermediate units or intensive care units (ICUs) in a single critical care center, from January to December 2019. We excluded patients with out-of-hospital cardiac arrest or those transferred from other hospitals. Frailty was evaluated by the Clinical Frailty Scale (CFS) from the patients' chart reviews. The primary outcome was 30-day mortality, and we examined the association between frailty scored on the CFS and 30-day mortality using a multivariable logistic regression model with CFS 1-4 as a reference. Results: A total of 544 patients, median age: 82 years (interquartile rang 78 to 87), were included in the study. Of these, 29% were in shock and 33% were in respiratory failure. The overall 30-day mortality was 15.1%. The adjusted risk difference (95% confidence interval [CI]) in mortality for CFS 5, CFS 6, and CFS 7-9 was 6.3% (-3.4 to 15.9), 11.2% (0.4 to 22.0), and 17.7% (5.3 to 30.1), respectively; and the adjusted risk ratio (95% CI) was 1.45 (0.87 to 2.41), 1.85 (1.13 to 3.03), and 2.44 (1.50 to 3.96), respectively. Conclusion: The risk of 30-day mortality increased as frailty advanced in critically ill older adults. Given this high risk of short-term outcomes, ED clinicians should consider goals of care conversations carefully to avoid unwanted medical care for these patients.