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Background: Trastuzumab-deruxtecan (T-DXd) was approved for the treatment of HER2-positive patients with advanced gastric cancer in Japan based on the results of the DESTINY-Gastric01 trial. This study aimed to collect real-world data and evaluate the effectiveness and safety of T-DXd. Methods: Patients aged ≥ 20 years at the start of T-DXd administration with a histopathologically confirmed diagnosis of HER2-positive unresectable advanced or recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma that had worsened after chemotherapy were enrolled in this retrospective cohort study. Key outcomes included T-DXd treatment status, overall survival (OS), real-world progression-free survival (rwPFS), time to treatment failure (TTF), objective response rate and frequency of grade ≥ 3 adverse events (AEs). Results: Of the 312 patients included in the analysis, 75.3% were male, the median (range) age was 70.0 (27.0–89.0) years, 12.2% had an ECOG PS ≥ 2, 43.3% had ascites and the initial T-DXd dose was > 5.4– ≤ 6.4 mg/kg in 78.2% of patients. The median (95% confidence interval) OS, rwPFS and TTF (months) was 8.9 (8.0–11.0), 4.6 (4.0–5.1) and 3.9 (3.4–4.2), respectively. The response rate was 42.9% in patients with a target lesion. In total, 48.4% of patients experienced a grade ≥ 3 AE, 2.6% experienced grade 5 AEs and 60.9% experienced AEs leading to T-DXd dose adjustments (reduction: 36.9%, interruption: 34.0% or discontinuation: 23.7%). No new safety signals were detected. Conclusions: T-DXd was effective and had a manageable safety profile as a third- or later-line treatment for patients with HER2-positive gastric or GEJ cancer in Japanese clinical practice. Clinical trial registration: UMIN000049032 [ABSTRACT FROM AUTHOR]

Summary: This study compared the effectiveness and cardiovascular safety of romosozumab and teriparatide. The main finding was that there were no significant differences between the two drugs in fracture prevention and risk of major adverse cardiac events. This suggests that romosozumab and teriparatide are comparable options for treating osteoporosis. Purpose: This study aimed to determine the preventive effects of romosozumab versus teriparatide on fractures and the risk of cardiovascular events in patients initiating these drugs. Methods: We conducted an active comparator, a new user cohort design, with confounding controlled by inverse probability of treatment weighting using a Japanese administrative claims database (March 2019 to October 2022). This cohort study included 49,104 patients aged 50 years or older who initiated romosozumab (n = 16,125) or teriparatide (n = 32,979) for osteoporosis. The study exposure was the initiation of romosozumab or teriparatide. Effectiveness outcomes were nonvertebral fracture and hip fracture. The safety outcome was major adverse cardiac events (MACE). Follow-up period was 365 days. Results: The weighted incidence rate difference (IRD) for nonvertebral fracture between romosozumab versus teriparatide was –0.08 (95% confidence interval [CI], –0.34 to 0.17) events per 100 person-years (weighted hazard ratio [HR], 0.95 [95% CI, 0.81 to 1.12]); weighted IRD for hip fracture was 0.00 (95% CI, –0.16 to 0.16) events per 100 person-years (weighted HR, 0.99 [95% CI, 0.76 to 1.29]); and weighted IRD for MACE was –0.06 (95% CI, –0.20 to 0.09) events per 100 person-years (weighted HR, 0.90 [95% CI, 0.68 to 1.19]). Conclusion: In patients with osteoporosis, there was no significant difference in the prevention of nonvertebral fracture and hip fracture between romosozumab and teriparatide. In addition, the risk of MACE was comparable between the two drugs. [ABSTRACT FROM AUTHOR]

Japanese adults typically have healthier lipid profiles than American and European adults and a lower prevalence and later onset of atherosclerotic cardiovascular disease (ASCVD). Many Japanese also have uniquely elevated levels of high-density lipoprotein cholesterol (HDL-C). The following analysis examined the relationship between HDL-C level and HDL-C peroxide content, a bioindicator of unhealthy lipid metabolism in Japanese adults. Blood samples were collected from 463 participants, 31–84 years of age, who lived in Tokyo. A second blood sample was collected 5 years later from 241 of the participants, allowing us to evaluate the temporal stability of the inverse correlation between HDL-C level and HDL-C peroxide content. Glucoregulation and inflammatory activity were assessed because both can be associated with dyslipidemia and HDL-C dysfunction. Obesity and central adiposity were also considered. Overall, women had healthier HDL-C profiles than men. Elevated HDL-C (>90 mg/dL) was common (16.6%) and found more often in women. Higher HDL-C peroxide content was associated with older age and central adiposity and incremented further when HA1c and CRP were higher. When assessed 5 years later, lower HDL-C peroxide content continued to be evident in adults with higher HDL-C. While similar associations have been described for other populations, most Japanese adults typically had healthier levels of HDL-C with lower HDL-C peroxide content than previously reported for American adults. [ABSTRACT FROM AUTHOR]

Context.--: Endocervical adenocarcinoma is divided into human papillomavirus (HPV)-associated (HPVA) and HPV-independent (HPVI) in the 5th edition of the World Health Organization (WHO) tumor classification launched in 2020. However, the validity of the morphologic criteria used for biopsy specimens in real-world practice remains undetermined. Objective.--: To validate the utility of the 5th edition of the WHO classification for biopsy samples, focusing on its diagnostic criteria with the aid of ancillary studies. Design.--: We retrieved 217 cases of endocervical adenocarcinoma from 6 institutions, in which glass slides of both biopsy and resection specimens were available for review. Concordance between the biopsy and resection specimen diagnoses was evaluated. For discordant diagnoses, an algorithmic approach with ancillary studies proposed by the international group was applied to confirm their utility to improve the accuracy of biopsy diagnosis. Results.--: The biopsy diagnosis matched the resection specimen diagnosis in 197 cases (concordance rate, 91%; k = 0.75). The concordance rate was significantly higher for HPVA than HPVI (95% versus 81%, P = .001). There were no significant differences in the proportions of HPVA and HPVI or the accuracy of biopsy diagnosis between the participating institutions. All 19 discordant cases with unstained glass slides available were accurately recategorized as HPVA or HPVI using HPV in situ hybridization; p16 immunohistochemistry was positive in 3 of 9 cases of gastric-type HPVI that were negative by in situ hybridization. Conclusions.--: The 5th edition of the WHO criteria for biopsy diagnosis of endocervical adenocarcinoma distinguishes HPVA from HPVI well when ancillary studies are adequately applied. [ABSTRACT FROM AUTHOR]

Objectives: The present study aims to examine sociodemographic correlates and comorbid mental disorders among adult with autism spectrum disorders (ASD) and attention deficit hyperactivity disorders (ADHD) using the national representative data of Japan. Methods: Analysis was conducted on the cross-sectional data derived from the World Mental Health Japan Survey 2, whose participants were community residents aged 20-75 years old. Multiple logistic regression was conducted on the data of those who were assessed for adult ASD (N = 2227) and ADHD (N = 2297). The association of adult ASD/ADHD with sociodemographics, mood disorders, anxiety disorders, substance use disorders, suicide ideation, hikikomori (social withdrawal), and internet addiction was examined, adjusting for sex and age. Gender difference in the association was also assessed based on the interaction terms of sex. Results: None of the sociodemographics characteristics were significantly associated with adult ASD/ADHD. ADHD had increased risks for a variety of mental disorders, having the highest odds ratios for social phobia. However, a significant positive association was limited to social phobia and to drug abuse and dependence among those with adult ASD. Hikikomori and internet addiction were positively associated with ASD/ADHD, while suicide ideation was only associated with ADHD. Women with ADHD were more likely to have any one of mental disorders, as well as alcohol abuse and dependence, compared to men with ADHD. Conclusions: Adults with ASD/ADHD in Japan had increased mental health needs. The specific needs of women with ADHD should be also considered in future clinical work and research.

The present study examined the relationship between multisensory integration and the temporal binding window (TBW) for multisensory processing in adults with Autism spectrum disorder (ASD). The ASD group was less likely than the typically developing group to perceive an illusory flash induced by multisensory integration during a sound-induced flash illusion (SIFI) task. Although both groups showed comparable TBWs during the multisensory temporal order judgment task, correlation analyses and Bayes factors provided moderate evidence that the reduced SIFI susceptibility was associated with the narrow TBW in the ASD group. These results suggest that the individuals with ASD exhibited atypical multisensory integration and that individual differences in the efficacy of this process might be affected by the temporal processing of multisensory information.

Background: It is widely recognized that periodontal disease is associated with diabetes mellitus. Periodontal disease is accompanied by inflammation of the periodontal tissue, impaired masticatory function, and the presence of periodontopathic bacteria, all of which may affect glycemic control. However, the exact relationship between these factors and glycemic control has not yet been established. In this study, we aimed to investigate the relationship between periodontal disease-related factors and glycemic control in Japanese community-dwelling individuals. Methods: We conducted a cross-sectional study involving 671 participants aged 29–92 (65.3 ± 12.1) years, using data from the Nagasaki Islands Study. Participants underwent routine medical examinations, including body mass index (BMI) and hemoglobin A1c (HbA1c) levels. Information on the participants' demographics (age and sex) and whether they were on diabetes medications, had an exercise habit, consumed alcohol, engaged in late-night eating, had regular dental checkups, and smoked was obtained using a self-administered questionnaire. Dental examinations were performed to examine dentition status, probing pocket depth, clinical attachment level (CAL), and bleeding on probing. Functional tooth units (FTUs), defined as pairs of occluding posterior teeth, were used as an indicator of occlusal support area. Saliva samples were collected and levels of two species of periodontopathic bacteria (Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans) were determined using real-time polymerase chain reaction. We analyzed the association between HbA1c levels and variables related to periodontal status, masticatory function, and salivary levels of periodontopathic bacteria. Results: Bivariate analysis showed that HbA1c levels were significantly associated with age, sex, exercise habit, BMI, diabetes medications, CAL, salivary P. gingivalis level, number of teeth, and three FTU subcategories. In the multiple regression analysis, age, BMI, diabetes medications, and total FTU score (i.e., including natural teeth, implant-supported artificial teeth, fixed prostheses, and removable dentures) remained associated with HbA1c levels (B = 0.23, 0.14, 0.52, and − 0.12; p < 0.001, p < 0.001, p < 0.001, and p = 0.008, respectively). Conclusions: In this community-based cross-sectional study, total FTU was significantly associated with HbA1c levels, independent of other risk factors. This suggests that reconstructed occlusal support areas, including dentures, are associated with glycemic control in the older population. [ABSTRACT FROM AUTHOR]

Aim: Few studies have investigated the relationship between low dietary variety and clearly defined social isolation by gender. This study explored the association between dietary variety and social isolation, classified by operational definition, separately by gender in community‐dwelling older adults. Methods: This cross‐sectional study recruited respondents via mail. A total of 4798 participants aged ≥65 years participated in the on‐site assessment. Social isolation was assessed by "lack of conversation," "lack of passive support," "lack of offering support," and "lack of social participation." Dietary variety was evaluated using the Dietary Variety Score (DVS). Results: The participants' median age was 73 (interquartile range 25–75: 69–77) years, and 2147 (44.7%) were male. After adjusting for covariates, with regard to male participants, a lack of offering support (β = −0.051, P = 0.019) and a lack of social participation (β = −0.089, P < 0.001) were associated with a low DVS. For female participants, only a lack of social participation was related to a low DVS (β = −0.067, P < 0.001). A lack of conversation and passive support were not associated with a low DVS for both genders (P >0.05). Conclusion: The results indicate that encouraging social participation, regardless of gender, as well as preventing a lack of offering support for others among men, may contribute to improving individuals' DVS. Geriatr Gerontol Int 2024; 24: 930–938. [ABSTRACT FROM AUTHOR]

Epidemiological studies have reported that Asian dust (AD), a type of desert dust, has harmful effects on human health. This study aimed to examine the association between AD exposure and hospitalization due to pneumonia. Data on patients in Western Japan admitted for pneumonia were included from a real-world database derived from electronic medical records. We used the meteorological observatory data of the most populous city in each prefecture, in which AD event was defined as a loss of visibility from a distance ≤10 km. A case-crossover design and conditional logistic regression model were used. Overall, 12 938 patients were included, and AD exposure events were observed for 557 days. Exposure to an AD event five days prior to hospitalization was significantly associated with hospitalization for pneumonia after adjusting for weather variables (odds ratio = 1.17). These findings suggest that AD exposure is associated with an increased rate of admission for pneumonia in Western Japan. [ABSTRACT FROM AUTHOR]

Objectives: The association between loneliness and disability is a growing public health priority. While the University of California Los Angeles Loneliness Scale (UCLA‐LS) has been internationally used as an indicator for assessing loneliness, its optimal cutoff point in relation to disability occurrence has not yet been examined. Therefore, we aimed to determine the optimal cutoff point of the UCLA‐LS regarding future disability. Methods: This longitudinal cohort study was conducted in Tokai City, Aichi Prefecture, Japan. Overall, 4536 community‐dwelling older adults (age: 73.8 ± 5.5 years; females: 55.2%) were followed up for 2 years. The area under the curve of the receiver operating characteristic analysis was calculated to evaluate the optimal cutoff point of the UCLA‐LS in relation to future disability occurrence using the Youden index, which maximized the sensitivity and specificity of the UCLAS‐LS. A survival analysis was conducted to test this cutoff value's external validity, using the presence or absence of disability occurrence as the dependent variable. Results: The cutoff score of the UCLA‐LS in relation to future disability was 44 points. An association was found between new disability occurrence and loneliness based on this cutoff value (hazard ratio: 1.67, 95% confidence interval: 1.29–2.16). Conclusions: Although cultural context should be taken into account, the optimal cutoff scores for the loneliness scale related to disability identified in this study may be a useful indicator for early recognition of loneliness as a global public health problem and for promoting social participation as one of the disability prevention strategies. [ABSTRACT FROM AUTHOR]

Aim: To date, there are limited clinical studies and real‐world evidence investigating whether sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) are associated with improved hepatic steatosis. This study aimed to evaluate the effectiveness of SGLT2i compared with that of dipeptidyl peptidase‐4 inhibitors (DPP4i) in improving the fatty liver index (FLI) in patients with type 2 diabetes mellitus (T2DM) and metabolic dysfunction‐associated steatotic liver disease (MASLD). Materials and Methods: This retrospective cohort study included new users of SGLT2i or DPP4i with T2DM and MASLD from a large claims database (JMDC Claims Database). The primary outcome was the incidence of improvement of the FLI. Cox proportional hazard models, weighted using propensity scores for predicting the initiation of treatment, were fitted to estimate hazard ratios with 95% confidence intervals (CIs). Time‐course changes in the FLI values were also assessed. Results: This study included 9127 SGLT2i and 12 286 DPP4i initiators. SGLT2i showed a higher incidence of improvement in the FLI (≥30%, ≥40% and ≥50% reduction from baseline FLI) compared with DPP4i, and the weighted hazard ratios were 1.27 (95% CI 1.18‐1.38), 1.24 (95% CI 1.13‐1.37) and 1.19 (95% CI 1.05‐1.33), respectively. SGLT2i indicated a greater decreased in FLI values compared with DPP4i at up to 3 years of the follow‐up period. Conclusion: SGLT2is use appeared to be associated with a greater improvement of the FLI than DPP4i use in patients with T2DM and MASLD. In the absence of direct head‐to‐head comparisons from clinical studies, our study, using real‐world data, may support physicians' decision‐making in clinical practice. [ABSTRACT FROM AUTHOR]

Proton pump inhibitor (PPI) use may be associated with renal dysfunction. Renal dysfunction in PPI users requires evaluation of development and progression risks simultaneously, using estimated glomerular filtration rate (eGFR) slope, which indicates changes in eGFR per year. To the best of our knowledge, no studies have evaluated eGFR slope in PPI users. This study investigated the association between PPI use and renal dysfunction using eGFR slope. A single-center cohort study was conducted using the health records data at Hamamatsu University Hospital in Japan. Participants were defined as first users of acid-suppressing drugs (PPIs or Histamine H2 receptor antagonists (H2RAs)) from 2010 to 2021 and continuously prescribed for ≥ 90 days. The H2RA group was used for the propensity-score matching (PSM) to the PPI group to minimize the effects of confounders. The eGFR slope was estimated using a linear mixed effects model. Participants were stratified by baseline eGFR and age, respectively, as subgroup analyses. A total of 4,649 acid-suppressing drug users met the inclusion criteria, including 950 taking H2RAs and 3,699 PPIs. After PSM, 911 patients were assigned to each group. The eGFR slopes of the PPI and H2RA users were -4.75 (95% CI: -6.29, -3.20) and -3.40 (-4.38, -2.42), respectively. The difference between the groups was not significant. Significant declines in eGFR were observed with PPIs with baseline eGFR ≥ 90 and age < 65. PPI use for ≥ 90 days may hasten eGFR decline compared to H2RA use, especially in patients with eGFR ≥ 90 or age < 65. [ABSTRACT FROM AUTHOR]

Bovine rhinitis B virus (BRBV) (genus Aphthovirus, family Picornaviridae) is a significant etiological agent of the bovine respiratory disease complex. Despite global reports on BRBV, genomic data for Japanese strains are not available. In this study, we aimed to obtain genomic information on BRBV in Japan and analyze its genetic characteristics. In nasal swabs from 66 cattle, BRBV was detected in 6 out of 10 symptomatic and 4 out of 56 asymptomatic cattle. Using metagenomic sequencing and Sanger sequencing, the nearly complete genome sequences of two Japanese BRBV strains, IBA/2211/2 and LAV/238002, from symptomatic and asymptomatic cattle, respectively, were determined. These viruses shared significant genetic similarity with known BRBV strains and exhibited unique mutations and recombination events, indicating dynamic evolution, influenced by regional environmental and biological factors. Notably, the leader gene was only approximately 80% and 90% identical in its nucleotide and amino acid sequence, respectively, to all of the BRBV strains with sequences in the GenBank database, indicating significant genetic divergence in the Japanese BRBV leader gene. These findings provide insights into the genetic makeup of Japanese BRBV strains, enriching our understanding of their genetic diversity and evolutionary mechanisms. [ABSTRACT FROM AUTHOR]

Background: Although basic laparoscopic hepatectomy (LH) has become the standard procedure for hepatectomy, the safety of advanced LH remains to be clarified, especially in elderly patients. We investigated the safety of advanced LH in elderly Japanese patients. Methods: Elderly patients (≥ 65 years) who underwent advanced LH between 2016 and 2021 were analyzed using a nationwide claims database in Japan. The perioperative outcomes of patients who underwent open hepatectomy (OH group) or LH (LH group) were compared using propensity score matching (PSM). The primary outcome was in-hospital mortality. The E-value method was performed to assess the strength of the outcome point estimates against possible unmeasured confounding factors. Results: Among 5,021 patients, eligible patients were classified into the OH (n = 4,152) and LH (n = 527) groups. The median patient age was 74 years in both groups. Hepatocellular carcinoma and metastatic liver tumors were the major indications for hepatectomy (OH: 52.5% versus 30.6%; LH: 60.7% versus 26.4%). After PSM, in-hospital mortality rates for OH and LH were 1.7 and 0.76%, respectively. The risk ratio was 0.45 (95% confidence interval, 0.16–1.25; E-value = 3.87). Compared with OH, LH was associated with a longer anesthesia time (411 versus 432 min), lower rate of blood product use (red blood concentrate: 33.5% versus 20.3%; fresh frozen plasma: 29.2% versus 17.1%), and shorter hospital stay (13 versus 12 days). Conclusions: In elderly patients, the safety of advanced LH was similar to that of advanced OH, or might be better in Japan under the current policy of hospital accreditation. [ABSTRACT FROM AUTHOR]

Introduction: The incidence of steatotic liver disease has increased in recent years. Thus, steatotic liver disease is a major public health issue in Japan. This study investigated the association between weight reduction and the remission of metabolic dysfunction-associated steatotic liver disease (MASLD)/Metabolic and alcohol related/associated liver disease (MetALD) in Japanese individuals undergoing health checkups. Methods: This retrospective observational study included 8,707 Japanese patients with MASLD/MetALD who underwent health checkups from May 2015 to March 2023. The participants were monitored for its remission at their subsequent visit. MASLD was diagnosed on abdominal ultrasonography and based on the presence of at least one of five metabolic abnormalities. The impact of body mass index (BMI) reduction on MASLD/MetALD remission was assessed via logistic regression analysis and using receiver operating characteristic curves. Results: Logistic regression analysis revealed that weight loss was significantly associated with MASLD/MetALD remission. Other factors including exercise habits and reduced alcohol consumption were significant predictors of MASLD/MetALD remission in the overall cohort and in male patients. The optimal BMI reduction cutoff values for MASLD/MetALD remission were 0.9 kg/m2 and 4.0% decrease in the overall cohort, 0.85 kg/m2 and 3.9% decrease in males, and 1.2 kg/m2 and 4.5% decrease in females. In participants with a BMI of 23 kg/m2, the cutoff values were 0.75 kg/m2 and 2.7% BMI reduction. Discussion: Weight reduction plays an important role in both MASLD and MetALD remission among Japanese individuals. That is, targeting specific BMI reduction is effective. This underscores the importance of targeted weight management strategies in preventing and managing MASLD/MetALD in the Japanese population. [ABSTRACT FROM AUTHOR]

Environmental DNA (eDNA) is a promising tool for the continuous monitoring of fish ecology and diversity. However, its potential for describing the phenological activity of fish has rarely been examined. This study aimed to elucidate a linkage between the spatiotemporal distribution of eDNA and the phenology of an amphidromous fish, ayu Plecoglossus altivelis altivelis, in a river in Hokkaido, Japan, which is its northernmost distributional area. A significant positive correlation between eDNA concentration and catch per unit effort of P. a. altivelis in the river confirmed the use of eDNA as a surrogate for the abundance of P. a. altivelis. eDNA of P. a. altivelis was first detected in late April on a sandy beach adjacent to the river mouth. Subsequent to its first detection at the lowest site in the river in early May, eDNA spread throughout the river, indicating the upstream migration of P. a. altivelis. Spawning activity was also represented by a rapid increase in eDNA concentration and its surge at night in the lowest reaches of the river during September and October. These results suggest that upstream migration and spawning primarily commenced when the water temperature reached 10°C and decreased below 20°C, respectively. This observation is consistent with the behavioral responses observed in P. a. altivelis populations from other regions of Japan. Consequently, this study demonstrated that eDNA distribution was closely linked to the phenological activity of P. a. altivelis and that eDNA is a powerful tool for studying the phenology of migratory fishes. [ABSTRACT FROM AUTHOR]

The magnitude of the effect of human T‐lymphotropic virus 1 (HTLV‐1) infection on uveitis remains unclear. We conducted a cross‐sectional study in a highly endemic area of HTLV‐1 in Japan. The study included 4265 residents (men, 39.2%), mostly middle‐aged and older individuals with a mean age of 69.9 years, who participated in our surveys between April 2016 and September 2022. We identified HTLV‐1 carriers by screening using chemiluminescent enzyme immunoassays and confirmatory tests, and the proportion of carriers was 16.1%. Participants with uveitis were determined from the medical records of all hospitals and clinics where certified ophthalmologists practiced. We conducted logistic regression analyses in an age‐ and sex‐adjusted model to compute the odds ratio (OR) and 95% confidence interval (CI) of uveitis according to HTLV‐1 infection status. Thirty‐two (0.8%) participants had uveitis. For HTLV‐1 carriers, the age‐ and sex‐adjusted OR (95% CI) of uveitis was 3.27 (1.57–6.72) compared with noncarriers. In conclusion, HTLV‐1 infection was associated with a higher risk of uveitis among mostly middle‐aged and older Japanese residents in a highly endemic HTLV‐1 area. Our findings suggest that physicians who treat HTLV‐1 carriers should assess ocular symptoms, and those who diagnose patients with uveitis should consider HTLV‐1 infection. [ABSTRACT FROM AUTHOR]

Objective: To revise the 2017 clinical practice guidelines (CPG) for the management of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) to reflect advancements in the field. Methods: Similar to the 2017 CPG, the Grading of Recommendations, Assessment, Development, and Evaluation system was adopted for this revision. The intended users of this CPG include patients diagnosed with MPA or GPA in Japan and their families and healthcare professionals, including specialists and non-specialists. Based on a scoping review, four clinical questions (CQs) of the 2017 guidelines were modified, and six new CQs were added. Results: We suggest a combination of glucocorticoid and cyclophosphamide or rituximab for remission induction therapy. In cases where cyclophosphamide or rituximab is used, we suggest the use of avacopan over high-dose glucocorticoid. Furthermore, we suggest against the use of plasma exchange in addition to the standard treatment in severe cases of MPA/GPA. Finally, we suggest the use of glucocorticoid and rituximab over glucocorticoid and azathioprine for remission maintenance therapy. Conclusions: The recommendations have been updated based on patient preference, certainty of evidence, benefit and risk balance, and cost. [ABSTRACT FROM AUTHOR]

The optimal administration of inotrope after cardiac surgery is unknown. This study aimed to investigate the impact of postoperative inotrope on clinical outcomes in adult elective cardiac surgery patients. Data from the Blood Pressure and Relative Optimal Target after Heart Surgery in Epidemiologic Registry study were analyzed, employing propensity score considering the hospital of admission. The primary outcome was the length of hospital stay evaluated using quantile regression. Secondary outcomes were kidney injury progression, renal replacement therapy, atrial fibrillation, mortality, mechanical ventilation duration, and length of intensive care unit (ICU) stay. Among 870 patients from 14 ICUs in Japan, 535 received inotropes within 24 h of ICU admission, with usage rates ranging from 40 to 100% among facilities. After propensity score matching, 218 patients were included in each group. The inotrope group had a significantly longer hospital stay compared to the control group (16 days vs. 14 days; median difference 1.78 [95% confidence interval [CI] 0.31–3.24]; p = 0.018). However, no significant differences were observed in the secondary outcomes, except for mechanical ventilation duration. The results of the sensitivity analysis using a mixed-effects quantile regression analysis considering the hospital of admission for length of hospital stay in the original cohort were consistent with the results of the propensity analyses (median difference in days, 2.35 [95% CI, 0.35–4.36]; p = 0.022). The use of inotropes within 24 h of ICU admission in adult elective cardiac surgery patients was associated with an extended hospitalization period of approximately 2 days, without offering any prognostic benefit. Clinical trial registration: UMIN-CTR, https://www.umin.ac.jp/ctr/index-j.htm, UMIN000037074. [ABSTRACT FROM AUTHOR]

Introduction: Food protein-induced enterocolitis syndrome (FPIES) is a form of non-IgE-mediated gastrointestinal food allergy. FPIES is considered a rare food allergy disorder and is often under-recognized. Therefore, clinicians should have a better understanding of its manifestations and maintain a high index of suspicion for a correct diagnosis. To this end, information about differences in the characteristics of caregiver-reported and physician-diagnosed FPIES is important. Methods: The present, national, multicentric, prospective birth cohort study, called the Japan Environment and Children's Study (JECS), enrolled a general population of 104,062 fetal records. The characteristics of FPIES in 1.5-year-old children were categorized as cases reported by caregivers or as those diagnosed by a physician using questionnaire data. Results: The prevalence of caregiver-reported and physician-diagnosed FPIES cases was 0.69% and 0.06%, respectively. Among the former, the most common causative food was hen's egg (HE), and the second most common causative food was cow's milk (CM) (51.0% and 17.1% of patients responded to HE and CM, which accounted for 46% and 15% of all the causative foods, respectively). Conversely, among the physician-diagnosed cases, the most common causative food was CM followed by HE (57.7% and 36.5% of patients responded to CM and HE, which accounted for 46% and 29% of all the causative foods, respectively). CM accounted for a significantly higher proportion of causative foods in physician-diagnosed FPIES while HE accounted for a significantly higher proportion of caregiver-reported FPIES (p < 0.05). Conclusion: A discrepancy was found in reports of the most common causative food between caregiver-reported and physician-diagnosed cases of FPIES. [ABSTRACT FROM AUTHOR]

The Akoya pearl oyster (Pinctada fucata (Gould)) is the most important species for pearl cultivation in Japan. Mass mortality of 0-year-old juvenile oysters and anomalies in adults, known as summer atrophy, have been observed in major pearl farming areas during the season when seawater temperatures exceed about 20 _C since 2019. In this study, we identified a novel birnavirus as the pathogen of summer atrophy and named it Pinctada birnavirus (PiBV). PiBV was first presumed to be the causative agent when it was detected specifically and frequently in the infected oysters in a comparative metatranscriptomics of experimentally infected and healthy pearl oysters. Subsequently, the symptoms of summer atrophy were reproduced by infection tests using purified PiBV. Infection of juvenile oysters with PiBV resulted in an increase in the PiBV genome followed by the atrophy of soft body and subsequent mortality. Immunostaining with a mouse antiserum against a recombinant PiBV protein showed that the virus antigen was localized mainly in the epithelial cells on the outer surface of the mantle. Although the phylogenetic analysis using maximum likelihood method placed PiBV at the root of the genus Entomobirnavirus, the identity of the bi-segmented, genomic RNA to that of known birnaviruses at the full-length amino acid level was low, suggesting that PiBV forms a new genus. The discovery of PiBV will be the basis for research to control this emerging disease. [ABSTRACT FROM AUTHOR]

Understanding the regeneration and succession of belowground communities, particularly in forests, is vital for maintaining ecosystem health. Despite its importance, there is limited knowledge regarding how fungal communities change over time during ecosystem development, especially under different forest restoration strategies. In this study, we focused on two restoration methods used in northern Japan: monoculture planting and natural regeneration. We examined the responses of the fungal community to monoculture plantations (active tree planting) and naturally regenerated (passive regeneration) forests over a 50-year chronosequence, using natural forests as a reference. Based on DNA metabarcoding, we assessed the richness of fungal Operational Taxonomic Units (OTUs) and their dissimilarity. Our findings revealed that soil fungal richness remained stable after natural regeneration but declined in monoculture plantations, from 354 to 247 OTUs. While the compositional dissimilarity of fungal assemblages between monoculture plantations and natural forests remained consistent regardless of the time since tree planting, it significantly decreased after natural regeneration, suggesting recovery to a state close to the reference level. Notably, the composition of key functional fungal groups—saprotrophic and ectomycorrhizal— has increasingly mirrored that of natural forests over time following passive natural regeneration. In summary, our study suggests that monoculture plantations may not be effective for long-term ecosystem function and service recovery because of their limited support for soil fungal diversity. These results underscore the importance of natural regeneration in forest restoration and management strategies. [ABSTRACT FROM AUTHOR]

Background: Diabetic kidney disease (DKD) is the most common disease among patients requiring dialysis for the first time in Japan. Multidisciplinary care (MDC) may prevent the progression of kidney failure. However, the effectiveness and timing of MDC to preserve kidney function in patients with DKD is unclear. Therefore, the aim of this study was to investigate whether MDC for patients with DKD affects the preservation of kidney function as well as the timing of MDC in clinical practice. Methods: In this retrospective cohort study, we identified patients with type 2 diabetes mellitus and DKD from April 2012 to January 2020 using a nationwide Japanese healthcare record database. The fee code for medical guidance to prevent dialysis in patients with diabetes was used to distinguish between the MDC and non-MDC groups. The primary outcome was a 40% decline in the estimated glomerular filtration rate, and secondary outcomes were death, hospitalization, permanent dialysis, kidney failure with replacement therapy, and emergency temporary catheterization. Propensity score matching was performed, and Kaplan–Meier and multivariable Cox regression analyses were performed. Results: Overall, 9,804 eligible patients met the inclusion criteria, of whom 5,614 were matched for the main analysis: 1,039 in the MDC group, and 4,575 in the non-MDC group. The primary outcome did not differ between the groups (hazard ratio: 1.18, [95% confidence interval: 0.99–1.41], P = 0.07). The groups also did not differ in terms of the secondary outcomes. Most patients with DKD received their first MDC guidance within 1 month of diagnosis, but most received guidance only once per year. Conclusions: Although we could not demonstrate the effectiveness of MDC on kidney function in patients with DKD, we clarified the characteristics of such patients assigned the fee code for medical guidance to prevent dialysis related to diabetes. [ABSTRACT FROM AUTHOR]

Wickerhamiella is a genus of budding yeast that is mainly isolated from environmental samples, and 40 species have been detected. The yeast isolated from human clinical samples usually only contain three species: W. infanticola, W. pararugosa and W. sorbophila. In this study, we isolated W. tropicalis from a blood sample of a six-year-old female with a history of B-cell precursor lymphoblastic leukemia in Japan in 2022. Though the strain was morphologically identified as Candida species by routine microbiological examinations, it was subsequently identified as W. tropicalis by sequencing the internal transcribed spacer (ITS) of ribosomal DNA (rDNA). The isolate had amino acid substitutions in ERG11 and FKS1 associated with azole and echinocandin resistance, respectively, in Candida species and showed intermediate-resistant to fluconazole and micafungin. The patient was successfully treated with micafungin. Furthermore, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) detected three novel peaks that are specific for W. tropicalis, indicating that MALDI-MS analysis is useful for rapid detection of Wickerhamiella species in routine microbiological examinations. [ABSTRACT FROM AUTHOR]

(1) Background: Although the diagnostic criteria for massive hemorrhage with organ dysfunction, such as disseminated intravascular coagulation associated with delivery, have been empirically established based on clinical findings, strict logic has yet to be used to establish numerical criteria. (2) Methods: A dataset of 107 deliveries with >2000 mL of blood loss, among 13,368 deliveries, was obtained from nine national perinatal centers in Japan between 2020 and 2023. Twenty-three patients had fibrinogen levels <170 mg/dL, which is the initiation of coagulation system failure, according to our previous reports. Three of these patients had hematuria. We used six machine learning methods to identify the borderline criteria dividing the fibrinogen/fibrin/fibrinogen degradation product (FDP) planes, using 15 coagulation fibrinolytic factors. (3) Results: The boundaries of hematuria development on a two-dimensional plane of fibrinogen and FDP were obtained. A positive FDP–fibrinogen/3–60 (mg/dL) value indicates hematuria; otherwise, the case is nonhematuria, as demonstrated by the support vector machine method that seemed the most appropriate. (4) Conclusions: Using artificial intelligence, the borderline criterion was obtained, which divides the fibrinogen/FDP plane for patients with hematuria that could be considered organ dysfunction in massive hemorrhage during delivery; this method appears to be useful. [ABSTRACT FROM AUTHOR]

This study investigated the leftover rate of side dishes in school lunches provided by communal kitchens in Japan's Chugoku region, with a focus on vegetable dishes supplied in containers and three types of menu items served daily to 20 elementary and junior high schools in communal kitchen A for 116 days. First, the leftovers in the containers that were returned to the communal kitchen were weighed and combined. The study then compared outside temperature, distance from communal kitchen A, school type, number of students per class, assignment of nutrition teachers, and time elapsed after cooking. Finally, we examined the relationship between these factors and the leftover rate using multiple regression analysis. The median leftover rate was 20.1% (0–96.9) for 250 side dishes with a high leftover rate; however, this was widely distributed. The number of students per class, assignment of nutrition teachers, and time elapsed after cooking were strongly related to the leftover rate; the adjusted coefficient of determination, R2, was 0.236. The regression results indicated that regarding the side dish leftover rate, the standardized coefficient, β, was 0.414, 0.215, 0.107, 0.093, and 0.094 for the number of students per class, assignment of nutrition teacher, the time elapsed after the end of cooking, distance from communal kitchen A, and presence of seaweed, respectively (p<0.001). Dietary education by homeroom and nutrition teachers and reducing the time elapsed after cooking impacts students' awareness and preferences, which may decrease the leftover rate. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between atomoxetine or methylphenidate use and arrhythmia, heart failure (HF), stroke, and myocardial infarction (MI) in attention-deficit/hyperactivity disorder (ADHD) patients mainly focused on the people of working age. Methods: In a self-controlled case series study using a Japanese claims database, we identified events of arrhythmia, HF, stroke, and MI among 15,472 atomoxetine new users and 12,059 methylphenidate new users. Adjusted incidence rate ratios (aIRRs) of outcome events were estimated using multivariable conditional Poisson regression. Results: An increased risk of arrhythmia was observed during the first 7 days after the initial atomoxetine exposure (aIRR 6.22, 95% CI [1.90, 20.35]) and in the subsequent exposure (3.23, [1.58, 6.64]). No association was found between methylphenidate exposure and arrhythmia, nor between atomoxetine or methylphenidate exposure and HF. The limited number of stroke and MI cases prevented thorough analysis. Conclusions: Clinicians should consider monitoring for arrhythmia after patients initiating or re-initiating atomoxetine. [ABSTRACT FROM AUTHOR]

Background: Team-level job crafting has been put forward as a method to promote nurses' mental health. However, a longitudinal association is unclear. Therefore, the objective of this study was to investigate the association between team job crafting at baseline and work engagement, work performance, psychological distress, and intention to leave at three-month and six-month follow-ups among Japanese hospital nurses. Also, whether an increase in the team job crafting during 3 or 6 months was associated with an increase in the work engagement during 3 or 6 months of individual nurses was examined. Methods: A multilevel prospective cohort study was conducted. Data were collected from nurses of five hospitals in Japan at baseline (T1) and follow-ups at 3-months (T2) and 6-months (T3). A total of 2,478 nurses were included. The team job crafting scale for nurses and its three subscales were measured for the independent variables. Ward-means were used as ward-level variables. The dependent variables were work engagement, work performance, psychological distress, and intention to leave. Hierarchical Linear Modeling (HLM) was used to examine the multilevel association. The study protocol was registered at the UMIN Clinical Trials Registry (ID = UMIN000047810) (May 22, 2022). Results: A total of 460 nurses completed the T1 survey (response rate = 18.6%), and data from 391 nurses nested in 30 wards were included in the analyses. The intraclass correlation coefficients (ICCs) at T1 were 0.02 for work engagement and 0.07 for team job crafting. The HLM revealed that ward-level team job crafting at T1 was not significantly associated with work engagement, work performance, psychological distress, and intention to leave at T2 or T3. The ward-level change (T3-T1) of "crafting for the task considering the team's growth" (subscale for team job crafting) was significantly and positively associated with the change (T3-T1) in work engagement. Conclusions: Ward-level team job crafting at baseline did not predict nurses' work engagement, work performance, psychological distress, or intention to leave at a three-month or six-month follow-up. The impact of ward-level team job crafting may attenuate over several months. [ABSTRACT FROM AUTHOR]

Background: Although there is insufficient evidence for the treatment of older patients with advanced gastric cancer, fluorouracil combined with platinum chemotherapy has been recognized as a standard first-line treatment for such populations in Japan despite the lack of efficacy and toxicity data. Methods: Patients aged 75 years or older with advanced gastric cancer were enrolled. S-1 plus docetaxel (docetaxel: 40 mg/m2, day 1; S-1: 80 mg/m2, days 1–14; q21 days) was repeated every 3 weeks. The primary endpoint was overall response rate. Secondary endpoints were safety, progression-free survival, time to treatment failure, and overall survival. The sample size was calculated as 30 under the hypothesis of an expected response rate of 40% and a threshold response rate of 20%, at a power of 90% and a two-sided alpha value of 5%. Results: From February 2010 to January 2015, 31 patients were enrolled and assessed for efficacy and toxicity. The response rate was 45.2% (95% CI 27.3%–64.0%; p = 0.001) and it exceeded the expected response rate set at 40%. Median progression-free survival was 5.8 months, the 1-year survival rate was 58.1%, and the median survival time was 16.1 months. The major grade 3/4 adverse events were neutropenia (58%), febrile neutropenia (13%), anemia (10%), anorexia (10%), and fatigue (6%). Conclusions: These findings indicate that S-1 plus docetaxel as first-line treatment for older patients is feasible and that it has promising efficacy against advanced gastric cancer. [ABSTRACT FROM AUTHOR]

Aim: To investigate the association between maternal combined spinal‐epidural analgesia during vaginal delivery and neurodevelopment in 3‐year‐old children. Methods: Using data from the Japan Environment and Children's Study, a birth cohort study on pregnant women and their offspring, we described the background, perinatal outcomes, and neurodevelopmental outcomes of participants with a singleton pregnancy who received combined spinal‐epidural analgesia during vaginal delivery and those who did not. The association between maternal combined spinal‐epidural analgesia and abnormalities in five domains of the Ages and Stages Questionnaire, Third Edition, was analyzed using univariable and multivariable logistic regression analyses. Crude and adjusted odds ratios with 95% confidence intervals (95% CI) were calculated. Results: Among 59 379 participants, 82 (0.1%) children (exposed group) were born to mothers who received combined spinal‐epidural analgesia during vaginal delivery. In the exposed versus control groups, 1.2% versus 3.7% had communication abnormalities (adjusted odds ratio [95% CI]: 0.30 [0.04–2.19]), 6.1% versus 4.1% exhibited gross‐motor abnormalities (1.36 [95% CI: 0.55–3.36]), 10.9% vs. 7.1% had fine‐motor abnormalities (1.46 [95% CI: 0.72–2.96]), 6.1% vs. 6.9% showed difficulties with problem‐solving (0.81 [95% CI: 0.33–2.01]), and 2.4% vs. 3.0% had personal‐social problems (0.70 [95% CI: 0.17–2.85]). Conclusions: Exposure to combined spinal‐epidural analgesia during vaginal delivery was not associated with the risk of neurodevelopmental abnormalities; however, the sample size of our study might not be appropriate for the study design. [ABSTRACT FROM AUTHOR]

The emotional responses to achievement contexts of 149 preschool children from three cultural groups were observed. The children were Japanese (N = 32), African American (N = 63) and White American of mixed European ancestry (N = 54). The results showed that Japanese children differed from American children in expressing less shame, pride, and sadness, but more of both exposure and evaluative embarrassment. African American and White American children did not differ from one another. American children however showed more evaluative as opposed to exposure embarrassment. This finding supports the idea that success and failure are interpreted differently by Japanese children during the preschool years. The low amount of sadness and shame expression, and the limited range of number of different expressions observed in the Japanese children agree with the general finding that East Asian infants and young children differ from Western infants and children primarily in the display of negative expressions. These results demonstrate that cultural differences, whether due to temperament or direct socialization of cultural values, influence how children respond to achievement situations. (Contains 4 tables, 1 figure and 1 footnote.)

Background: Sensitive gag reflexes prevent dental patients from receiving appropriate treatment. Aromatherapy helps patients relax during dental procedures. However, the effect of aromatherapy on the gag reflex caused by the stimulation of the oral cavity is unknown. This study aimed to evaluate whether aromatherapy reduces gag reflexes during oral stimulation. Methods: In this randomized, placebo-controlled, single-blind, crossover study, the gag reflexes of 24 healthy individuals (12 females and 12 males; mean age: 34.3 ± 9.5 years) were quantified. A standard saliva ejector was slowly guided down the participant's throat to determine the maximum tolerance of the gag reflex, and the insertion distance was measured to quantify the gag reflex. All individuals participated in an aromatherapy session with peppermint essential oil and a placebo session with distilled water. The gag reflex was quantified before (baseline) and after each session. Another measurement was performed using nitrous oxide/oxygen inhalation as a positive control. Results: Gag reflex values significantly increased after aromatherapy with both peppermint essential oil and placebo compared to baseline values (paired t-test, P < 0.001 and P = 0.014, respectively). The gag reflex value also increased significantly during nitrous oxide/oxygen inhalation (paired t-test, P < 0.001). There was no significant difference in the increase rate of gag reflex values between the positive control and aromatherapy interventions, but it was significantly lower after the placebo intervention (repeated measures analysis of variance, P = 0.003; post-hoc test, P = 0.83 and P = 0.02). Conclusion: Aromatherapy with peppermint essential oil has the potential for reducing gag reflex during dental procedures. Trial registration: The study was registered in the University hospital Medical Information Network Clinical Trials Registry under the code UMIN000050616 (approved 17/03/2023). [ABSTRACT FROM AUTHOR]

Simple Summary: Cervical lymph node (LN) metastasis is a critical prognostic factor for patients with head and neck squamous cell carcinoma (HNSCC), rendering accurate diagnosis of LN metastasis crucial for improving patient outcomes. Our study aimed to develop deep learning models for metastatic LN detection using YOLOv7, the fastest single-stage object detection model, on B-mode and power Doppler (D-mode) ultrasonography in patients with HNSCC and investigate their utility in supporting the diagnosis by comparing their performance to that of highly experienced radiologists and less experienced residents. A total of 462 B- and D-mode ultrasound images were used to train, validate, and test the B- and D-mode models, respectively. The detection performances of the B- and D-mode models for metastatic LNs were higher than those of less experienced residents; the performance of the D-mode model was comparable to that of highly experienced radiologists, suggesting that YOLOv7-based models are useful for supporting the diagnosis. Ultrasonography is the preferred modality for detailed evaluation of enlarged lymph nodes (LNs) identified on computed tomography and/or magnetic resonance imaging, owing to its high spatial resolution. However, the diagnostic performance of ultrasonography depends on the examiner's expertise. To support the ultrasonographic diagnosis, we developed YOLOv7-based deep learning models for metastatic LN detection on ultrasonography and compared their detection performance with that of highly experienced radiologists and less experienced residents. We enrolled 462 B- and D-mode ultrasound images of 261 metastatic and 279 non-metastatic histopathologically confirmed LNs from 126 patients with head and neck squamous cell carcinoma. The YOLOv7-based B- and D-mode models were optimized using B- and D-mode training and validation images and their detection performance for metastatic LNs was evaluated using B- and D-mode testing images, respectively. The D-mode model's performance was comparable to that of radiologists and superior to that of residents' reading of D-mode images, whereas the B-mode model's performance was higher than that of residents but lower than that of radiologists on B-mode images. Thus, YOLOv7-based B- and D-mode models can assist less experienced residents in ultrasonographic diagnoses. The D-mode model could raise the diagnostic performance of residents to the same level as experienced radiologists. [ABSTRACT FROM AUTHOR]

Background In recent years, due to the global shortage of helium gas, the development of gas chromatography (GC) analytical methods using alternatives to helium carrier gases is necessary. Objective The objective of this study was to examine the applicability of hydrogen and nitrogen as alternative carrier gases using the test method for azo compounds in the Act on Control of Household Products Containing Harmful Substances of Japan. Method The gas chromatograph mass spectrometer (GC-MS) analytical method using hydrogen and nitrogen as alternative carrier gases was compared with a method using helium for 26 primary aromatic amines (PAAs) originated from azo dyes. Results When hydrogen and nitrogen were used as carrier gases under the same conditions used during analysis using helium (same column, gas flow rate, oven temperature conditions, etc.), sufficient peak separation of 26 PAAs was obtained. The sensitivities of the methods using helium and hydrogen were comparable, whereas the sensitivity was lower when nitrogen was used, with the detection limits ranging from 1/220 to 1/25. However, all carrier gases achieved quantification at concentrations below the standard value (30 μg/g) of the Act on Control of Household Products Containing Harmful Substances, and the results were in agreement with the standard value for the target product. Conclusions Our results indicated that hydrogen or nitrogen can be used as alternative carrier gases to helium for GC-MS analysis of azo compounds producing specific aromatic amines. Highlights Using hydrogen or nitrogen as an alternative carrier gas to helium, azo compounds could be quantified with excellent accuracy. [ABSTRACT FROM AUTHOR]

Background: Pediatric allergic rhinitis (AR), including cedar pollinosis (CP), is increasing in Japan. We investigated the effects of sublingual immunotherapy (SLIT), which has limited studies of its effectiveness in real‐world settings, on children with CP. Methods: This retrospective cohort study used a claim database in 2018–2021. Children aged ≤15 years with CP records in 2019 were eligible and were followed up through 2021. We included 2962 CP children undergoing SLIT and 547 who were not. The medication score was used to evaluate SLIT effectiveness in the cedar pollen dispersal season each year. Adverse events and the occurrence of allergic diseases were also evaluated. Results: Medication score was higher in the SLIT group during the index period but lower in 2021 compared to the non‐SLIT group (mean ± standard deviation: 5.17 ± 2.39 and 4.74 ± 2.38 in 2019, 3.13 ± 2.30 and 3.55 ± 2.48 in 2021, respectively). The adjusted mean difference between groups from 2019 to 2021 was −0.62 (95% confidence interval: −0.86 to −0.39, p <.0001), and the medication score was reduced in the SLIT group (risk ratio: 1.2: 1.1 to 1.3). The occurrence of adverse events involving abdominal disorders (adjusted odds ratio [aOR]: 0.64: 0.51 to 0.81), asthma exacerbation (aOR: 0.37: 0.24 to 0.57), and allergic diseases involving hay fever unrelated to CP (aOR: 0.60: 0.45 to 0.80) or asthma (aOR: 0.71: 0.58 to 0.86) was lower in the SLIT group. Conclusion: In children with CP, SLIT is effective, well tolerated, and could decrease the occurrence of other allergic diseases. [ABSTRACT FROM AUTHOR]

To evaluate the status of lupus nephritis treatment particularly regarding the need for intensification of treatment in Japan from 2010 to 2019 using a large-scale claims database. This descriptive study included adult lupus nephritis patients who were administered glucocorticoid equivalent to ≥15 mg prednisolone as the initial dose. After summarizing patient characteristics, we assessed the rate of treatment intensification using the Kaplan–Meier method among six groups based on initial dose of glucocorticoid. We identified 403 patients (mean age, 42.7 years; 68.5% women) with the median initial glucocorticoid dose of 30 mg/day prednisolone equivalent. We observed 56 treatment intensifications; the incidence rate was 71.3 per 1,000 person-years (95% confidence interval: 52.6–90.0). The rate in higher glucocorticoid dose groups was higher than that in lower glucocorticoid dose groups. We found that the rate of treatment intensification was higher in the high-dose glucocorticoid groups than in the low-dose glucocorticoid groups. Further studies are needed to clarify the relationship between the initial dose of glucocorticoids and the prognosis of lupus nephritis patients. [ABSTRACT FROM AUTHOR]

Although intraoperative intravenous fluids are commonly administered to reverse intraoperative hypotension during cardiac surgery, the appropriate volume remains unclear. This study aimed to evaluate the relationship between the intraoperative fluid balance and sequential organ failure assessment (SOFA) score in patients undergoing cardiac surgery to determine the impact of intraoperative intravenous fluids on their organs. This was a post hoc analysis using data from a multicenter, retrospective, observational study across 14 intensive care units (ICUs) in Japan. Adult patients admitted to ICUs after elective coronary artery bypass grafting or valve surgery from January 1 to December 31, 2018 were enrolled. We compared patients with intraoperative fluid balance < 20 ml/kg to those with fluid balance ≥ 20 ml/kg and conducted a multiple regression analysis for the SOFA score within 24 h of ICU admission. Of the 1567 included patients, 870 met the eligibility criteria. A total of 725 patients (83%) had an intraoperative fluid balance of ≥ 20 ml/kg. In the univariate analysis, the SOFA score (interquartile range) was 7 (6–8) and 7 (6–9) in the intraoperative fluid balance < 20 ml/kg and ≥ 20 ml/kg groups, respectively (p = 0.017). Multiple regression analysis showed a positive association between intraoperative fluid balance and SOFA score within 24 h of ICU admission [standardized coefficient 0.0065 (95% confidence interval 0.0036–0.0095), p < 0.001]. Intraoperative fluid balance in patients undergoing cardiac surgery was significantly associated with higher SOFA scores within 24 h of ICU admission. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is a global health concern; Enterobacterales resistant to third-generation cephalosporins (3GCs) and carbapenems are of the highest priority. Here, we conducted genome sequencing and standardized quantitative antimicrobial susceptibility testing of 4,195 isolates of Escherichia coli and Klebsiella pneumoniae resistant to 3GCs and Enterobacterales with reduced meropenem susceptibility collected across Japan. Our analyses provided a complete classification of 3GC resistance mechanisms. Analyses with complete reference plasmids revealed that among the blaCTX-M extended-spectrum β-lactamase genes, blaCTX-M-8 was typically encoded in highly similar plasmids. The two major AmpC β-lactamase genes were blaCMY-2 and blaDHA-1. Long-read sequencing of representative plasmids revealed that approximately 60% and 40% of blaCMY-2 and blaDHA-1 were encoded by such plasmids, respectively. Our analyses identified strains positive for carbapenemase genes but phenotypically susceptible to carbapenems and undetectable by standard antimicrobial susceptibility testing. Systematic long-read sequencing enabled reconstruction of 183 complete plasmid sequences encoding three major carbapenemase genes and elucidation of their geographical distribution stratified by replicon types and species carrying the plasmids and potential plasmid transfer events. Overall, we provide a blueprint for a national genomic surveillance study that integrates standardized quantitative antimicrobial susceptibility testing and characterizes resistance determinants. Kayama et al. present a blueprint for a national genomic surveillance study that conducts genome sequencing of thousands of strains, integrates standardized quantitative antimicrobial susceptibility testing, and characterizes antimicrobial resistance determinants. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study aimed to examine the association between ABCDEF bundles and long-term postintensive care syndrome (PICS)-related outcomes. DESIGN: Secondary analysis of the J-PICS study. SETTING: This study was simultaneously conducted in 14 centers and 16 ICUs in Japan between April 1, 2019, and September 30, 2019. PATIENTS: Adult ICU patients who were expected to be on a ventilator for at least 48 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Bundle compliance for the last 24 hours was recorded using a checklist at 8:00 am The bundle compliance rate was defined as the 3-day average of the number of bundles performed each day divided by the total number of bundles. The relationship between the bundle compliance rate and PICS prevalence (defined by the 36-item Short Form Physical Component Scale, Mental Component Scale, and Short Memory Questionnaire) was examined. A total of 191 patients were included in this study. Of these, 33 patients (17.3%) died in-hospital and 48 (25.1%) died within 6 months. Of the 96 patients with 6-month outcome data, 61 patients (63.5%) had PICS and 35 (36.5%) were non-PICS. The total bundle compliance rate was 69.8%; the rate was significantly lower in the 6-month mortality group (66.6% vs 71.6%, p = 0.031). Bundle compliance rates in patients with and without PICS were 71.3% and 69.9%, respectively (p = 0.61). After adjusting for confounding variables, bundle compliance rates were not significantly different in the context of PICS prevalence (p = 0.56). A strong negative correlation between the bundle compliance rate and PICS prevalence (r = –0.84, R² = 0.71, p = 0.035) was observed in high-volume centers. CONCLUSIONS: The bundle compliance rate was not associated with PICS prevalence. However, 6-month mortality was lower with a higher bundle compliance rate. A trend toward a lower PICS prevalence was associated with higher bundle compliance in high-volume centers. [ABSTRACT FROM AUTHOR]

Japan is prone to natural disasters such as earthquakes and torrential rains. Since those disasters have become more severe, extending the life of infrastructure is an urgent issue. Modern sewer system in Japan have been constructed since 1884, and regular inspection, cleaning, and repair are essential to prolonging the life of sewage pipes. Manholes, which are entrances to sewage systems, can be regarded to be one of the important structures that support our safe, secure, and comfortable lives. In this paper, two main parts composed of a manhole, a cover and its bottom, are introduced. The cover made of spheroidal graphite cast iron (cast iron cover) and the manhole bottom made of resin concrete have been developed to extend the life and performance of manholes. The cast iron cover has been made lighter by optimizing the material and structure, does not rattle even when automobiles pass through it at high speed, and automatically releases pressure when the pressure in pipe rises. In addition, the introduction of resin concrete compensates for the shortcomings of cement concrete, such as low curing speed, salt damage, and freezethaw characteristics. Finally, examples of implementations and achievements with the developed materials and structures are presented and discussed. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate the real‐world clinical practice of estrogen and progestogen prescriptions for menopausal women. Methods: Using a health care database in Japan, we conducted a cross‐sectional study on estrogen prescriptions and detailed analyses of newly initiated estrogens and concomitant prescriptions of progestogens. Data between January 2005 and December 2021 were analyzed. Results: In 2021, the proportion of women aged 45–49 years receiving estrogens was 25.8 [95% confidence interval (CI): 25.3, 26.3] per 1000 women, while it was 6.4 [95% CI: 6.0, 6.7] for those aged ≥60 years. The prescription of estrogens gradually increased in women aged 50–59 years after 2009. In women without a history of hysterectomy, transdermal estradiol was the primary form of estrogens prescribed for ≥180 days, in women aged <60 years. The proportion of transdermal estradiol gradually increased each year, whereas that of oral‐conjugated equine estrogens decreased. Among progestogen, the proportions of dydrogesterone and transdermal norethisterone acetate increased over time, while that of medroxyprogesterone acetate decreased. Approximately 30% of women prescribed estrogens for ≥180 days did not initiate progestogen concurrently. In women undergoing hysterectomy, progestogen was not initiated in >90% of cases, and transdermal estradiol was prescribed in approximately 80% of cases in 2021. Conclusions: This study reviewed the prescription of estrogens in menopausal women in Japan. A considerable number of women with a uterus are receiving estrogen therapy rather than estrogen‐progestogen therapy (EPT), despite the guidelines recommending the use of EPT in these women. [ABSTRACT FROM AUTHOR]

In Japan, sexual offending, especially paraphilic sexual offending, has become a major problem, and approximately 3000 people are arrested for frotteuristic and voyeuristic behavior each year. Considering the repetitive nature of such behaviors, determining the recidivism risk is imperative. Globally, Static‐99 is one of the most widely used actuarial risk assessment tools to predict recidivism among sex offenders. However, sexual offending is largely influenced by social and cultural backgrounds, and whether risk factors identified in the West are applicable to other countries is unknown. Therefore, we developed a Japanese version of the Static‐99 and examined its reliability and validity with 167 Japanese paraphilic sex offenders. The results showed good internal consistency (Cronbach's alpha coefficient = 0.88) and predictive accuracy (area under the curve = 0.76). The results indicate that the Japanese Static‐99 can be used with Japanese sex offenders. Moreover, risk factors identified in the Western context are applicable to Japanese sex offenders despite the different nature and manifestations of their offending. [ABSTRACT FROM AUTHOR]

Objective: Recent advances in single‐cell RNA sequencing technology have improved our understanding of the immunological landscape of rheumatoid arthritis (RA). We aimed to stratify the synovium from East Asian patients with RA by immune cell compositions and gain insight into the inflammatory drivers of each synovial phenotype. Methods: Synovial tissues were obtained from East Asian patients in Japan with RA (n = 41) undergoing articular surgery. The cellular composition was quantified by a deconvolution approach using a public single‐cell–based reference. Inflammatory pathway activity was calculated by gene set variation analysis, and chromatin accessibility was evaluated using assay of transposase accessible chromatin–sequencing. Results: We stratified RA synovium into three distinct subtypes based on the hierarchical clustering of cellular composition data. One subtype was characterized by abundant HLA‐DRAhigh synovial fibroblasts, autoimmune‐associated B cells, GZMK+GZMB+ CD8+ T cells, interleukin (IL)1‐β+ monocytes, and plasmablasts. In addition, tumor necrosis factor (TNF)‐α, interferons (IFNs), and IL‐6 signaling were highly activated in this subtype, and the expression of various chemokines was significantly enhanced. Moreover, we found an open chromatin region overlapping with RA risk locus rs9405192 near the IRF4 gene, suggesting the genetic background influences the development of this inflammatory synovial state. The other two subtypes were characterized by increased IFNs and IL‐6 signaling, and expression of molecules associated with degeneration, respectively. Conclusion: This study adds insights into the synovial heterogeneity in East Asian patients and shows a promising link with predominant inflammatory signals. Evaluating the site of inflammation has the potential to lead to appropriate drug selection that matches the individual pathology. [ABSTRACT FROM AUTHOR]

Many models for predicting various disease prognoses have achieved high performance without laboratory test results. However, whether laboratory test results can improve performance remains unclear. This study aimed to investigate whether laboratory test results improve the model performance for coronavirus disease 2019 (COVID-19). Prediction models were developed using data from the electronic healthcare record database in Japan. Patients aged ≥18 years hospitalized for COVID-19 after February 11, 2020, were included. Their age, sex, comorbidities, laboratory test results, and number of days from February 11, 2020, were collected. We developed a logistic regression, XGBOOST, random forest, and neural network analysis and compared the performance with and without laboratory test results. The performance of predicting in-hospital death was evaluated using the area under the curve (AUC). Data from 8,288 hospitalized patients (females, 46.5%) were analyzed. The median patient age was 71 years. A total of 6,630 patients were included in the training dataset, and 312 (4.7%) died. In the logistic regression model, the area under the curve was 0.88 (95% confidence interval [CI] = 0.83–0.93) and 0.75 (95% CI = 0.68–0.81) with and without laboratory test results, respectively. The performance was not fundamentally different between the model types, and the laboratory test results improved the performance in all cases. The variables useful for prediction were blood urea nitrogen, albumin, and lactate dehydrogenase. Laboratory test results, such as blood urea nitrogen, albumin, and lactate dehydrogenase levels, along with background information, helped estimate the prognosis of patients hospitalized for COVID-19. [ABSTRACT FROM AUTHOR]

Introduction: Eldecalcitol (ELD) is an active vitamin D3 analog (AVD) commonly used to treat osteoporosis in Japan. Although routine monitoring of serum calcium levels during ELD therapy is recommended, little is known about the actual frequency and determinants of monitoring. Materials and methods: This was a descriptive cohort study using a Japanese electronic medical records database. We identified osteoporosis patients who initiated treatment with ELD or other AVDs (alfacalcidol and calcitriol) between April 1, 2011 and September 10, 2021. The index date for cohort entry was the first prescription date of ELD or other AVDs. The frequency of serum calcium monitoring was evaluated every 6 months. Determinants of serum calcium monitoring were identified using multivariable logistic regression models. We also calculated the incidence of hypercalcemia and the frequency of serum calcium monitoring within 6 months before hypercalcemia. Results: We identified 12,671 ELD users and 7867 other AVD users. Within 6 months after cohort entry, 45.9% of ELD users and 58.7% of other AVD users underwent serum calcium monitoring. Female sex, no use of systemic corticosteroids, moderate-to-good renal function, treatment in smaller hospitals, and treatment in orthopedic surgery departments were associated with a lower likelihood of receiving serum calcium monitoring during ELD therapy. The incidence of hypercalcemia among ELD users was 6.36 per 100 person-years, with 20.6% of cases not receiving serum calcium monitoring before hypercalcemia. Conclusion: Our findings suggest that serum calcium monitoring is not given adequate attention during ELD therapy in routine clinical practice. [ABSTRACT FROM AUTHOR]

To examine the association between hip fracture and associated factors, including polypharmacy, and develop an optimal predictive model, we conducted a population-based matched case–control study using the health insurance claims data on hip fracture among Japanese patients. We included 34,717 hospitalized Japanese patients aged ≥ 65 years with hip fracture and 34,717 age- and sex- matched controls who were matched 1:1. This study included 69,434 participants. Overall, 16 variable comorbidities and 60 variable concomitant medications were used as explanatory variables. The participants were added to early elderly and late elderly categories for further analysis. The odds ratio of hip fracture increased with the number of medications only in the early elderly. AUC was highest for early elderly (AUC, 0.74, 95% CI 0.72–0.76). Use of anti-Parkinson's drugs had the largest coefficient and was the most influential variable in many categories. This study confirmed the association between risk factors, including polypharmacy and hip fracture. The risk of hip fracture increased with an increase in medication number taken by the early elderly and showed good predictive accuracy, whereas there was no such association in the late elderly. Therefore, the early elderly in Japan should be an active target population for hip fracture prevention. [ABSTRACT FROM AUTHOR]

Background: An association between adrenergic alpha-1 receptor antagonists and delirium has been suggested, but the details are unclear. Aim: This study investigated the association between adrenergic alpha-1 receptor antagonists and delirium in patients with benign prostatic hyperplasia using the Japanese Adverse Drug Event Report database. Method: First, disproportionality analysis compared the frequency of delirium in the adrenergic alpha-1 receptor antagonists silodosin, tamsulosin, and naftopidil. Next, multivariate logistic analysis was performed to examine the association between delirium and adrenergic alpha-1 receptor antagonists where disproportionality was detected. Results: A disproportionality in delirium was observed in patients receiving tamsulosin (reporting odds ratio [ROR] 1.85, 95% confidence interval [CI] 1.38–2.44, P < 0.01) compared with those who did not, and also in patients receiving naftopidil (ROR 2.23, 95% CI 1.45–3.28, P < 0.01) compared with those who did not. Multivariate logistic analysis revealed that in addition to previously reported risk factors for delirium, delirium in patients receiving tamsulosin was significantly increased with concomitant use of anticholinergics (odds ratio 2.73, 95% CI 1.41–5.29, P < 0.01) and delirium in patients receiving naftopidil was significantly increased with concomitant use of beta3-adrenergic receptor agonists (odds ratio 4.19, 95% CI 1.66–10.6, P < 0.01). Conclusion: Anticholinergics or beta3-adrenergic receptor agonists to treat overactive bladder in patients receiving tamsulosin and naftopidil was strongly associated with delirium. Confirming the medical history and concomitant medications of patients receiving tamsulosin or naftopidil may contribute to preventing delirium in patients with benign prostatic hyperplasia and to improving their outcomes. [ABSTRACT FROM AUTHOR]