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Aflibercept (AFL) plus FOLFIRI prolongs overall survival (OS) in patients with metastatic colorectal cancer (mCRC). However, there is limited evidence on the efficacy and safety of AFL plus FOLFIRI previously treated with anti‐epidermal growth factor receptor (EGFR) agents. Therefore, we conducted a prospective open‐label phase II trial evaluating the efficacy and safety of AFL plus FOLFIRI in Japanese patients with mCRC failing a prior oxaliplatin‐based chemotherapy plus an anti‐EGFR agent. AFL (4 mg/kg iv) followed by FOLFIRI (irinotecan 180 mg/m2, leucovorin 200 mg/m2 iv, bolus 5‐fluorouracil [5‐FU] 400 mg/m2, and infusional 5‐FU 2400 mg/m2/46 h) was given every 2 weeks until progression or unacceptable toxicities. The primary endpoint was progression‐free survival (PFS) rate at 6 months. Forty three patients were enrolled between November 2019 and October 2022. The primary endpoint was met: 6‐month PFS rate was 58.8% (90% confidence interval [CI], 45.7%–72.0%). Median PFS and OS were 7.3 months (95% CI, 5.5–11.0 months) and 18.8 months (95% CI, 12.9–26.6 months), respectively. The overall response rate was 20.9% (95% CI, 10.0–36.0%) and disease control rate was 88.4% (95% CI, 74.9–96.1%). The main grade ≥3 adverse events included hypertension (62.8%), neutropenia (55.8%), leukopenia (25.6%), febrile neutropenia (11.6%), fatigue (9.3%), anorexia (9.3%), proteinuria (9.3%), and diarrhea (7.0%). No deaths and no new safety signals with a causal relation to the study treatment were observed. This study suggests that AFL plus FOLFIRI shows a high response rate and a manageable safety profile in Japanese patients with mCRC who failed prior oxaliplatin‐based chemotherapy plus an anti‐EGFR agent. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusions Fecal incontinence (FI) is a debilitating condition defined as recurrent uncontrolled passage of fecal material according to Rome IV. Although FI greatly impacts patients' health‐related quality of life (HRQOL), there have been few studies about the prevalence of FI in the Japanese general population. The aim of this study was to investigate the epidemiology of FI using Rome IV criteria in Japan.This was a cross‐sectional internet survey for Japanese individuals aged 18 to 79 years using a questionnaire about demographics, comorbidities, lifestyle, abdominal symptoms, bowel habits, HRQOL, and disorders of gut–brain interaction according to Rome IV diagnostic criteria. Multivariate linear regression analysis identified factors associated with FI fulfilling Rome IV criteria (Rome IV FI).Overall, 9995 subjects were analyzed. Of which, 9.5% of the participants had at least one episode of FI in the last 3 months, and the prevalence of Rome IV FI was 1.2%. HRQOL was significantly impaired in patients with Rome IV FI compared to continent individuals. Major functional bowel disorders overlapped with 39.5% of Rome IV FI where functional diarrhea (25.8%) was the most predominant. The overlap further impaired HRQOL in Rome IV FI patients. Alcohol consumption (odds ratio 1.82, 95% CI 1.24–2.66, p = 0.002) was independently related to Rome IV FI apart from gastroesophageal reflux disease, irritable bowel syndrome, functional abdominal bloating/distension, and functional diarrhea.The prevalence of Rome IV FI was 1.2% in Japan. Further study is warranted to investigate the effect of lifestyle modification on the management of FI. [ABSTRACT FROM AUTHOR]

The current literature on the effects of clozapine on pregnancy is limited, and no cases of pregnant Japanese women have been reported. Decreased variability in the fetal heart rate due to clozapine exposure has been reported in countries other than Japan, but its association with serum concentrations of clozapine has not been documented. In this case, a 29‐year‐old Japanese primipara with treatment‐resistant schizophrenia taking clozapine 250 mg/day experienced pregnancy. The pregnancy progressed without complications. At 40 weeks and 2 days of gestation, the patient developed premature rupture of membranes, and decreased variability in the fetal heart rate and variable deceleration were observed, leading to an emergency cesarean section. The neonate had no congenital malformations, metabolic disorders, seizures, floppy infant syndrome, leukopenia, or neutropenia. Serum concentrations of clozapine and norclozapine (N‐desmethylclozapine), measured in the mother and in the neonate immediately after birth, suggested that clozapine and norclozapine were transported to the fetus during pregnancy. Based on these observations, the present case suggests that high fetal serum concentrations of clozapine and norclozapine may affect fetal heart rate. This case report concludes that, with careful monitoring, Japanese women taking clozapine can deliver successfully and emphasizes the importance of monitoring serum clozapine concentrations and fetal cardiac function throughout pregnancy, with particular attention to the later stages. [ABSTRACT FROM AUTHOR]

Background: KEYNOTE-A33 (NCT04317066) is an open-label, single-arm, phase 1 trial designed to evaluate the safety and efficacy of pembrolizumab in Japanese patients with relapsed or refractory (R/R) primary mediastinal large B-cell lymphoma (PMBCL). Methods: Patients received pembrolizumab 200 mg every 3 weeks for up to 35 cycles. The primary endpoints were safety and objective response rate (ORR) per International Working Group 2007 criteria by independent central review. The secondary endpoint was disease control rate (DCR). Duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were exploratory. Results: Seven patients were enrolled and treated; the median age was 32 years (range 26–43) and 86% were female. The median time from the first dose to data cutoff (April 12, 2022) was 5.6 months (range 2.4–21.2). Grade 3–5 treatment-related adverse events (AEs) occurred in 2 patients (29%; 2 grade 4 neutropenia, 1 grade 3 febrile neutropenia); however, no patient discontinued pembrolizumab or died because of treatment-related AEs. The ORR was 43% [95% confidence interval (CI) 10–82]. DCR was 57% (95% CI 18–90). Median DOR was not reached (NR). Four (57%) patients had a reduction in target lesion size of ≥ 50%. The median PFS was 2.9 months (95% CI 2.6–NR). The median OS was 17.5 months (95% CI NE–NE), and the 12 months OS rate was 100%. Conclusion: Overall, pembrolizumab had manageable safety and clinically meaningful antitumor activity in Japanese patients with R/R PMBCL, results that were consistent with those observed in prior global studies. Trial Registry: Registry and the Registration No. of the study/trial: Clinicaltrials.gov: NCT04317066. [ABSTRACT FROM AUTHOR]

Background: The association between the molecular profiles and prognosis of Stage II colorectal cancer remains unclear. This study aimed to examine the risk factors for relapse of Stage II colorectal cancer using molecular profiling. Methods: We retrospectively enrolled patients with pStage II colorectal cancer who did not receive perioperative adjuvant therapy and whose surgically resected specimens were evaluated using gene expression and whole-exome analyses between January 2014 and December 2018. We evaluated the long-term outcomes and examined the risk factors for relapse-free survival. Results: We evaluated 322 patients with pStage II colorectal cancer, including 126 (39.1%) with right colon cancer. Eighty-seven patients (27.0%) had pT4 tumor, 175 (54.3%) had positive venous invasion, 120 (37.3%) had positive lymphatic invasion, and 68 (21.1%) had perineural invasion. The presence of mutations in key genes for colorectal cancer development based on whole-exome analyses was as follows: APC, 245 (76.1%); TP53, 208 (64.6%); and KRAS, 134 (41.6%). According to the consensus molecular subtype classification based on gene expression, 76 patients (23.6%) had consensus molecular subtype 4 and a significantly lower relapse-free survival than the other patients (5-year relapse-free survival: 83.8% vs. 92.9%, p = 0.017). Perineural invasion (hazard ratio: 5.316, p < 0.001) and consensus molecular subtype 4 (hazard ratio: 2.399, p = 0.020) were identified as independent risk factors for relapse-free survival. Conclusions: Molecular profiling of Stage II colorectal cancer to assess the risk factors for relapse may contribute to the indication and drug selection for adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Previously reported results from phase III KEYNOTE-048 demonstrated similar or improved overall survival (OS) with pembrolizumab or pembrolizumab-chemotherapy versus cetuximab-chemotherapy (EXTREME) in Japanese patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). We report results in Japanese patients from KEYNOTE-048 after 5 years of follow-up. Methods: Patients with R/M HNSCC of the oropharynx, oral cavity, hypopharynx, or larynx were randomly assigned 1:1:1 to pembrolizumab, pembrolizumab-chemotherapy, or EXTREME. Primary endpoints were OS and progression-free survival. Efficacy was evaluated in the programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥ 20, PD-L1 CPS ≥ 1, and total Japanese populations. Results: In Japan, 67 patients were enrolled (pembrolizumab, n = 23; pembrolizumab-chemotherapy, n = 25; EXTREME, n = 19). Median follow-up was 71.0 months (range, 61.2–81.5); data cutoff, February 21, 2022. 5-year OS rates with pembrolizumab versus EXTREME were 35.7% versus 12.5% (hazard ratio [HR] 0.38; 95% CI 0.13–1.05), 23.8% versus 12.5% (HR 0.70; 95% CI 0.34–1.45), and 30.4% versus 10.5% (HR 0.54; 95% CI 0.27–1.07) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. 5-year OS rates with pembrolizumab-chemotherapy versus EXTREME were 20.0% versus 14.3% (HR 0.79; 95% CI 0.27–2.33), 10.5% versus 14.3% (HR 1.18; 95% CI 0.56–2.48), and 8.0% versus 12.5% (HR 1.11; 95% CI 0.57–2.16) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. Conclusion: After 5 years of follow-up, pembrolizumab and pembrolizumab-chemotherapy showed long-term clinical benefits; results further support these treatments as first-line options for Japanese patients with R/M HNSCC. Clinical trial registration: NCT02358031. [ABSTRACT FROM AUTHOR]

Background: The phase 3 CheckMate 274 trial demonstrated superiority of adjuvant nivolumab over placebo after radical surgery in patients with high-risk urothelial carcinoma (UC). However, real-world data on the efficacy and safety profile of adjuvant nivolumab in Japan have not been reported. Methods: This retrospective study enrolled patients with high-risk UC who received adjuvant nivolumab therapy following radical surgery between 2022 and 2024 at our institution. We evaluated immune-related adverse events (irAEs) according to the Common Terminology Criteria for Adverse Events, version 5.0. Kaplan–Meier curves were used to assess disease-free survival (DFS) and overall survival (OS). Results: Thirty-three patients with high-risk UC receiving adjuvant nivolumab therapy following radical surgery were identified, and median follow-up was 11 months. Three patients experienced grade 3 irAEs, and 8 discontinued adjuvant nivolumab therapy due to irAEs. No grade 4 or 5 irAEs were observed. Eight patients have completed 1 year of treatment, and nine are currently on treatment. Nine patients had recurrences and one died of cancer. Of the nine patients with recurrences, six relapsed while on adjuvant nivolumab therapy, two relapsed after completing 1 year of treatment, and one relapsed after discontinuation of irAE. The 1- and 2-year OS rates were 100% and 90%, respectively, and median OS was not reached. The 1- and 2-year DFS rates were 70% and 60%, respectively, and median DFS was 26 months. Conclusions: Adjuvant nivolumab appears to have some efficacy in Japanese patients. Since this is a postoperative adjuvant therapy, careful patient selection is warranted. [ABSTRACT FROM AUTHOR]

Background: Cutaneous melanoma (CM) is the most common type in Caucasians, while acral melanoma (AM) and mucosal melanoma (MM), which are resistant to immunotherapies and BRAF/MEK-targeted therapies, are more common in East Asians. Genomic profiling is essential for treating melanomas, but such data are lacking in Japan. Methods: Comprehensive genomic profiling data compiled in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) were analyzed. Results: A total of 380 melanomas was analyzed, including 136 CM, 46 AM, 168 MM, and 30 uveal melanoma (UM). MM included conjunctival, sinonasal, oral, esophageal, anorectal, and vulvovaginal melanomas. No significant difference in the median tumor mutational burden (TMB) of CM (3.39 mutations/megabase), AM (2.76), and MM (3.78) was the key finding. Microsatellite instability-high status was found in one case. BRAF V600E/K was found in only 45 patients (12%). Key driver mutations in CM were BRAF (38%), NRAS (21%), NF1 (8%), and KIT (10%), with frequent copy number alterations (CNAs) of CDKN2A, CDKN2B, and MYC. AM was characterized by altered KIT (30%), NRAS (26%), and NF1 (11%) and CDKN2A, CDKN2B, CDK4, MDM2, and CCND1 CNAs. MM was characterized by altered NRAS (24%), KIT (21%), and NF1 (17%) and MYC, KIT, and CDKN2A CNAs, with differences based on anatomical locations. UM bore GNAQ or GNA11 driver mutations (87%) and frequent mutations in SF3B1 or BAP1. Conclusion: The distinct genomic profiling in Japanese patients, including lower TMB, compared to Caucasians, is associated with poorer treatment outcomes. This result underscores the need for more effective therapeutic agents. [ABSTRACT FROM AUTHOR]

Background: Bronchopulmonary dysplasia (BPD) has a lasting effect on the respiratory function of infants, imposing chronic health burdens. BPD is influenced by various prenatal, postnatal, and genetic factors. This study explored the connection between BPD and home oxygen therapy (HOT), and then we examined the association between HOT and a specific single-nucleotide polymorphism (SNP) in the hyaluronan and proteoglycan link protein 1 (HAPLN1) gene among premature Japanese infants. Materials and methods: Prenatal and postnatal data from 212 premature infants were collected and analyzed by four SNPs (rs975563, rs10942332, rs179851, and rs4703570) around HAPLN1 using the TaqMan polymerase chain reaction method. The clinical characteristics and genotype frequencies of HAPLN1 were assessed and compared between HOT and non-HOT groups. Results: Individuals with AA/AC genotypes in the rs4703570 SNP exhibited significantly higher HOT rates at discharge than those with CC homozygotes (odds ratio, 1.20, 95% confidence interval, 1.07–1.35, p =.038). A logistic regression analysis determined that CC homozygotes in the rs4703570 SNP did not show a statistically significant independent association with HOT at discharge. Conclusions: Although our study did not reveal a correlation between HAPLN1 and the onset of BPD, we observed that individuals with CC homozygosity at the rs4703570 SNP exhibit a reduced risk of HOT. [ABSTRACT FROM AUTHOR]

Summary: The association of renal function with fracture incidence during teriparatide or alendronate treatment in elderly Japanese women was examined. Fracture incidence differed by fracture type, renal function, and treatment protocol. The results provide important information on pharmacotherapy in clinical practice for osteoporosis. Purpose: Incidence rate of morphometric vertebral fracture was lower under treatment with once-weekly teriparatide (TPTD) followed by alendronate (ALN) than under treatment with ALN throughout the study among elderly Japanese women at high fracture risk in JOINT-05. This is an exploratory subgroup analysis according to chronic kidney disease (CKD) status at baseline. Methods: Participants received sequential therapy with TPTD for 72 weeks, followed by ALN for 48 weeks (TPTD-ALN group, N = 483) or ALN monotherapy for 120 weeks (ALN group, N = 496). Baseline CKD status was classified by the estimated glomerular filtration rate (eGFR) and categorized as: CKD 1/2 (eGFR ≥ 60 mL/min/1.73 m2), CKD 3a (eGFR 45–59 mL/min/1.73 m2), or CKD 3b/4 (eGFR < 45 mL/min/1.73 m2). Incidences of vertebral fractures including morphometric fractures, non-vertebral fractures, and all fractures were evaluated during follow-up. Results: Baseline characteristics were not different between treatment groups. Higher stages of CKD were associated with age and number of prevalent vertebral fracture. In CKD 1/2 patients (N = 556 with 90 incidents of morphometric vertebral fracture), the incidence of vertebral fractures was lower in the TPTD-ALN group than in the ALN group (p = 0.01). In CKD 3b/4 patients (N = 112 with 10 incidents of non-vertebral fracture), the incidence of non-vertebral fractures was lower in the ALN group than in the TPTD-ALN group, although the number of fractures was small. In the ALN group, the incidences of vertebral fractures, non-vertebral fractures, and all fractures remained constant across CKD stages. Conclusion: This exploratory analysis showed that fracture incidence on ALN was constant regardless of renal function. It also suggested that the incidence of vertebral fractures on TPTD-ALN was lower than ALN monotherapy in CKD 1/2 patients. These results provide important information for drug selection in the clinical practice of osteoporosis. [ABSTRACT FROM AUTHOR]

The Japanese people played a much more important role in shaping events during the Allied Occupation of Japan (1945-1952) than is often recognized. This article examines the movement for democratization of the labor unions in order to demonstrate the extent to which the Japanese shaped their own destiny. Domestic politics is often overlooked due to an emphasis on the start of the Cold War in this period. Indeed, US policy is usually given the predominant role in narratives of the period and is blamed for the decline of mass movements such as the labor movement but an examination of the evidence for Supreme Commander for the Allied Powers (SCAP) involvement in the period reveals that the Occupation authorities, especially those in the General Headquarters (GHQ) of SCAP, played a much smaller role than has been alleged. [ABSTRACT FROM AUTHOR]

This study reports a rare case of a dentigerous cyst in a malformed tooth in the mandible of a 5-year-old Japanese boy. Panoramic radiography revealed a cystic lesion with hard tissues inside. The patient underwent surgery under general anesthesia. The histopathological diagnosis was dentigerous cyst associated with a malformed tooth. [ABSTRACT FROM AUTHOR]

PURPOSE: Clinical utility of comprehensive genomic profiling (CGP) for precision medicine has become evident. Although there are several reports on the genomic landscape of GI stromal tumors (GISTs), large-scale data specific to GIST are limited, especially in Asia. Additionally, the applicability of molecular-targeted agents identified using CGP has not been extensively examined. We investigated the status of genomic alterations in Japanese patients with advanced GISTs using the National Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database to identify novel treatment strategies and drug development. MATERIALS AND METHODS: We retrospectively reviewed the clinical and CGP data of patients with advanced-stage GIST registered in the C-CAT database to assess the genomic landscape and potential actionable alterations. RESULTS: Data from 144 patients were reviewed. Oncogenic alterations were detected frequently in KIT (78%), CDKN2A (37%), CDKN2B (29%), RB1 (11%), STK11 (10%), TP53 (9%), PDGFRA (6%), and SDHB (6%). Loss of CDKN2A / CDKN2B was only observed in KIT/PDGFRA -mutated GISTs, while alterations in SDHA/SDHB were only detected in KIT/PDGFRA wild-type GISTs. Among 119 KIT/PDGFRA -mutated GISTs, 95 (80%) had oncogenic genomic alterations and 29 (24%) had actionable alterations, excluding KIT and PDGFRA. However, among 25 KIT/PDGFRA wild-type GISTs, 22 (88%) had oncogenic alterations and 11 (44%) had actionable alterations. Representative candidate drugs for genome-matched therapies in KIT/PDGFRA -mutated and wild-type GISTs were as follows: pembrolizumab for tumor mutation burden–high in one and two patients, respectively; poly-adenosine diphosphate ribose polymerase inhibitors for alterations related to homologous recombination deficiency in 12 and one patient, respectively; NTRK inhibitor for ETV6-NTRK3 fusion in one with KIT/PDGFRA wild-type GIST; and human epidermal growth factor receptor 2-antibody-drug conjugate in one with KIT/PDGFRA -mutated GIST. CONCLUSION: This study highlights the genomic landscape of advanced GISTs and the important role of CGP in identifying rational molecular-targeted therapeutic options. [ABSTRACT FROM AUTHOR]

Introduction: Migraine is a debilitating headache disorder with a high prevalence in Japan that imposes significant societal burden. Although the Japanese Clinical Practice Guideline for Headache Disorders 2021 recommends both acute and preventive migraine treatments, the usage of preventive treatments is still limited. Therefore, it is crucial to understand the treatment preferences of patients with migraine pertaining to both acute and preventive treatments. Methods: A mixed-methods study including a discrete choice experiment (DCE) was conducted with Japanese patients with migraine (10 for the qualitative interviews, and 400 for the DCE) who were recruited from the Rakuten Insight panel. The DCE presented hypothetical treatment options including oral acute, oral preventive, and injectable preventive medications. Six attributes (method of delivery, reduction of pain, impact of headaches on daily routines, dosage adjustability, and temporary and persistent side effects) each with three levels were included in the survey. A hierarchical Bayesian model was used to estimate relative attribute importance scores (RAI) for all attributes. Results: For the 400 participants in the DCE, the most common age bracket was 40–49 years old, and the majority were female (66.75%). RAI estimates indicated that "method of delivery" was the most important attribute for patients (RAI 51.92, SD = 10.20), followed by "reduction of pain when experiencing a headache" (RAI 17.00, SD = 7.74). Oral preventive treatments were preferred over injectable preventive treatments. The qualitative interviews showed that patients prefer oral medications to injectable treatments, and a lack of awareness regarding preventive treatments. Conclusion: This study found that the "method of delivery" was the most important driver of treatment preferences of patients with migraine in Japan, with oral acute medications being preferred. Oral preventive treatments were found to be preferred over injectable treatments. These results may indicate the need for increased education regarding preventive treatments, as well as the need for further development of these treatments. [ABSTRACT FROM AUTHOR]

Background and Objective: Inadequate response to antidepressant monotherapy is common among patients with major depressive disorder (MDD). The efficacy and safety of adjunctive brexpiprazole 2 mg/day has recently been confirmed during the 6-week, randomized, placebo-controlled phase 2/3 (BLESS) study, which evaluated brexpiprazole at 1 mg/day and 2 mg/day versus placebo as adjunctive therapy to antidepressant therapies in 740 Japanese patients with MDD and an inadequate response to antidepressant monotherapy. This study evaluated the long-term safety and efficacy of adjunctive fixed-dose brexpiprazole 2 mg/day in Japanese patients with MDD. Methods: An open-label, 52-week study enrolled rollover patients who completed the 6-week, double-blind, randomized, placebo-controlled phase 2/3 BLESS study (NCT03697603), and de novo patients aged ≥ 65 years. Patients were titrated to fixed-dose brexpiprazole 2 mg/day from Week 1. Safety assessments included treatment-emergent adverse events (TEAEs; primary outcome) and clinical and laboratory variables. Efficacy was assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS), Clinical Global Impression-Improvement (CGI-I) scale, Hamilton Depression Rating Scale (HAM-D) 17-item total score, and Sheehan Disability Scale (SDS) score. Results: In total, 247 patients [rollover, n = 216; de novo (previously unexposed), n = 31] were included in the safety/efficacy populations, and 138 (rollover, n = 132; de novo, n = 6; 55.9%) completed the study. Common TEAEs (incidence ≥ 10%) were weight gain [33.2% (n = 82)], akathisia [23.5% (n = 58)], nasopharyngitis [21.1% (n = 52)], and somnolence [10.5% (n = 26)]. TEAEs leading to treatment discontinuation occurred in 26.7% of patients receiving brexpiprazole and 58.1% of de novo patients. The mean (SD) increase in body weight from baseline to Week 52 [observed cases (OC)] was 4.2 (6.5) kg (n = 138); 44.5% (n = 110) had weight gain ≥ 7% at any postbaseline visit. There were no cases of tardive dyskinesia and no AEs related to suicide/suicide attempts. One death occurred (unknown cause), which was unrelated to study treatment. Improvements in the MADRS total score were observed from baseline over the course of the 52-week study [mean (SD) change at Week 52 (OC): − 7.3 (8.7)] for all patients receiving brexpiprazole. The overall MADRS response rate and remission rate in patients receiving brexpiprazole was 41.3% (n = 57) and 34.8% (n = 48), respectively, at Week 52 (OC). Improvements in CGI-S, HAM-D 17 item total score, and SDS mean scores were also observed from baseline over the 52-week study, with a mean (SD) change from baseline at Week 52 (OC) of − 0.8 (1.0), − 5.9 (6.3), and − 1.0 (2.2), respectively, indicating a sustained improvement in symptoms with long-term brexpiprazole treatment. Conclusions: This is the first study to evaluate the safety profile of brexpiprazole 2 mg/day in Japanese patients with MDD, including older adults, which is similar to previous reports, with no new safety risks, and continued efficacy over 52 weeks. Study Registration: ClinicalTrials.gov (NCT03737474; registered on 29 July 2018). [ABSTRACT FROM AUTHOR]

Aim: To explore the efficacy and safety of once‐weekly insulin icodec (icodec) in Japanese adults (≥20 years old) with type 2 diabetes from the global ONWARDS 1, 2 and 4 trials. Materials and Methods: Insulin‐naive (ONWARDS 1) and insulin‐experienced (ONWARDS 2 and 4) individuals were randomized to icodec or a once‐daily insulin comparator: insulin glargine U100 [ONWARDS 1 (basal insulin only) and 4 (basal–bolus regimen)] or insulin degludec [ONWARDS 2 (basal insulin only)]. The primary outcome was change in glycated haemoglobin from baseline to end of treatment (EOT) (ONWARDS 1: Week 52; ONWARDS 2 and 4: Week 26). Here, we present the Japanese subgroup results. Results: Similar reductions in glycated haemoglobin from baseline to EOT were observed in each trial for icodec and comparators. The proportion of time in range (blood glucose 3.9–10.0 mmol/L) at EOT was also comparable across treatment groups (time in range: 58%–68%), as was time spent with blood glucose below 3.0 mmol/L (<1.0%). Combined clinically significant (blood glucose <3.0 mmol/L) or severe (requiring external assistance for recovery) hypoglycaemia rates were low, with no severe events (ONWARDS 1 and 2) or a single severe event (ONWARDS 4; icodec group) reported. These results generally aligned with findings from the respective global populations. No new safety issues were identified. Conclusions: Icodec improved glycaemic control to a similar degree as once‐daily basal insulin comparators while maintaining low levels of clinically significant or severe hypoglycaemia. The findings support icodec use in Japanese individuals with different levels of type 2 diabetes progression. [ABSTRACT FROM AUTHOR]

NRAS Q61 mutations are driver genetic alterations associated with common melanocytic nevi. Herein, we describe a case of NRAS‐mutant melanocytic tumor with a blue nevus‐like morphology. A 71‐year‐old Japanese man presented with a 4.6‐mm nodule on his back. Histopathological examination revealed a dense distribution of spindle‐shaped melanocytes in the upper dermis and a sparse distribution of dendritic melanocytes in the mid‐dermis. The vertical periadnexal extension reached the deep dermis at the center of the tumor. A small junctional component, hyperpigmentation, sclerotic stroma, mild nuclear atypia, and a few mitotic figures were observed. Immunohistochemical examination revealed no PRAME expression and preserved p16 expression. Diffuse RASQ61R immunoreactivity was observed in these tumor cells. Nuclear β‐catenin expression was not observed. Targeted RNA sequencing revealed two mutations, NRAS c.182A>G (Q61R) and FGFR2 c.‐157A>G, but no other pathogenic alterations such as BRAF, GNAQ, GNA11, CTNNB1, PRKAR1A, or IDH1 mutations or kinase gene fusions. The histopathology fits that of compound‐type blue nevus, which is called "Kamino nevus"; however, this tumor was genetically considered to be on the spectrum of conventional acquired melanocytic nevi but not on that of blue nevi. Morphologically, NRAS‐driven melanocytic nevi resemble blue nevi without IDH1R132C coexistence. [ABSTRACT FROM AUTHOR]

Voriconazole pharmacokinetics (PK) are known to be affected by genetic polymorphisms of drug-metabolizing enzymes such as CYP2C19 ; however, such information is limited for the pediatric population. The primary aim of this study is to establish a voriconazole PK model incorporating CYP2C19 phenotypes in Japanese children with malignancy or inborn errors of immunity. CYP2C19 genotypes were assessed by whole-genome genotyping and defined as follows: *17/*17: ultrarapid metabolizer (URM), *1/*17: rapid metabolizer (RM), *1/*1:normal metabolizer (NM), *1/*2, *1/*3, *2/*17:intermediate metabolizer (IM), and *2/*2, *2/*3, *3/*3: poor metabolizer (PM). Population PK analysis was performed. The voriconazole serum concentration profile was described by a two-compartment model with first-order absorption, mixed linear and nonlinear (Michaelis-Menten) elimination. Voriconazole concentration data were available from 60 patients with a median age of 5.3 years. The phenotypes predicted from CYP2C19 genotypes were RM in 1 (2 %), NM in 21 (35 %) patients, IM in 27 (45 %) patients, and PM in 11 (18 %) patients. Underlying diseases included 38 (63%) patients with hematological malignancy and 18 (30 %) patients with inborn errors of immunity. Among the CYP2C19 phenotypes, PM was predicted to show complete inhibition (the degree of V max inhibition [V max, inh ] = 100 %; V max = 0). The estimated parameters of V max,inh were +0.8 higher in patients with gamma-glutamyl transpeptidase (γ-GTP) Grade 2 or higher and +2.7 higher when C -reactive protein (CRP) levels were 2.0 mg/dL or higher. CYP2C19 genetic polymorphisms, γ-GTP, and CRP affect V max,inh of voriconazole in children with malignancy or inborn errors of immunity. [ABSTRACT FROM AUTHOR]

Cefmetazole (CMZ) is a carbapenem-sparing option in the treatment of extended-spectrum beta-lactamase (ESBL)-producing bacterial infection. In this pilot study, we aimed to compare the effects of antimicrobial treatment (meropenem [MP] and CMZ) with those of no antimicrobial treatment (control group) on the microbiome. The study was a multicenter, prospective, observational pilot study conducted from October 2020 to October 2022. Feces and saliva samples were collected for microbiome analyses at two time points (early-period: days 1–3; and late-period: days 4–30) for the antimicrobial treatment group, and at one time point for the control group. Five feces (MP-F and CMZ-F) and five saliva (MP-S and CMZ-S) samples were included in the MP and the CMZ groups. Ten feces (C–F) and saliva (C–S) samples were included in the control group. Group α diversity was notably lower in the late-period MP-F group than the control group as determined with the Shannon richness index. β diversity analysis of the feces samples based on weighted and unweighted UniFrac distances revealed distinctions in both the late-period CMZ-F and MP-F groups compared with the control group. Weighted UniFrac analysis showed that only the early-period MP-F group differed from the control group. In the saliva samples, weighted and unweighted UniFrac analyses showed significant differences between the control group and the early CMZ, late CMZ, and late MP groups. MP treatment may cause larger impact on the feces microbiome than CMZ in Japanese patients. [ABSTRACT FROM AUTHOR]

Background: Previous clinical trials presented efficacy and safety of Janus kinase 1 inhibitor upadacitinib through 52weeks for moderate-to-severe atopic dermatitis (AD). Objectives: To assess the effectiveness and safety of upadacitinib through 48weeks in real-world clinical practice for Japanese AD patients (aged ≥12years). Methods: This retrospective study included 287 patients with moderate-to severe AD treated with 15mg (n=216) or 30mg (n=71) of upadacitinib daily. Effectiveness was assessed using eczema area severity index (EASI) scores, atopic dermatitis control tool (ADCT), peak pruritus-numerical rating scale (PP-NRS), and investigator’s global assessment (IGA). Safety was evaluated through the incidence of treatment-emergent adverse events. Results: From baseline, EASI, ADCT, PP-NRS, and IGA rapidly reduced at week 4, and the reduction was maintained until week 48 of treatment with upadacitinib at both doses. Achievement rates of EASI 75, EASI 90, and EASI 100 at week 48 were 63.5, 30.2, and 7.9 in 15mg group, and 77.4, 54.8, and 3.2% in 30mg group, respectively. Acne and herpes zoster were frequent, but no serious adverse events occurred. Conclusions: Upadacitinib was therapeutically effective and tolerable for moderate-to-severe AD through 48weeks in real-world clinical practice. [ABSTRACT FROM AUTHOR]

Background: Deucravacitinib is a selective oral tyrosine kinase 2 (TYK2) inhibitor recently approved for psoriasis. Objectives: We aimed to evaluate the real-world effectiveness and safety of deucravacitinib for psoriasis. Methods: We analyzed 33 Japanese patients with psoriasis (23 with plaque psoriasis, eight with psoriatic arthritis, and two with erythrodermic psoriasis) from January 2023 to October 2023. All patients received deucravacitinib 6mg daily until week 16. Results: At week 8, 12, or 16, the achievement rate of PASI 75 was 60.9%, 73.9%, or 78.3%, that of PASI 90 was 13.0%, 39.1%, or 52.2%, that of PASI 100 was 0%, 8.7%, or 13.0%, that of absolute PASI ≤2 was 34.8%, 65.2%, or 78.3%, respectively. The achievement rate of dermatology life quality index 0/1 at week 16 was 42.9%. Fourteen patients (42%) complained pruritus. Peak pruritus-numerical rating scale in patients with pruritus decreased by median [interquartile] 71.4 [50–80] % of baseline at week 2. Adverse events occurred in 18.2% of patients, which were mild and manageable. Conclusions: Deucravacitinib for patients with psoriasis was well-tolerated and gave favorable therapeutic effects in the real-world practice. Deucravacitinib treatment rapidly reduced pruritus. [ABSTRACT FROM AUTHOR]

The 2024 Noto Peninsula Earthquake significantly affected the Noto Peninsula, Japan, where foreign nationals, mainly foreign technical intern trainees, reside. They represent a minority in Japanese society in terms of language and religion, which may render them vulnerable to disasters. Muslim communities centered in mosques have supported such minorities in past natural hazard-related disasters. However, in Japan, these activities have rarely been investigated immediately after a disaster event. This study aims to provide a prompt report on the initial responses of three mosques (1. Kanazawa Mosque, 2. Al-Faruq Mosque, and 3. Toyama Mosque) in Ishikawa and Toyama Prefectures, which were significantly affected by the 2024 Noto Peninsula Earthquake. To this end, we conducted interviews mainly with the (deputy) representatives of the target mosques until approximately two months after the earthquake. Consequently, all three mosques functioned as evacuation shelters for traveling or nearby affected Muslims in the immediate aftermath of the earthquake. In addition, both the Kanazawa Mosque and Al-Faruq Mosque provided relief supplies to foreign technical intern trainees (Indonesian Muslims) in the Noto Peninsula within approximately one week of the earthquake; they continued providing support thereafter. Al-Faruq Mosque also provided soup kitchens to Japanese individuals (non-Muslims) and the technical intern trainees. Such mosque functions and activities have been observed in past natural hazard-related disasters; thus, these findings are highly generalizable. These findings may be useful for the government and other stakeholders when considering how to support affected minorities in the future. [ABSTRACT FROM AUTHOR]

Background: The prognosis of patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer has improved significantly since the advent of EGFR tyrosine kinase inhibitors (EGFR-TKIs). We aimed to investigate the relationship between patient characteristics, EGFR genotype, therapeutic agents, and the prognosis of the patients with EGFR mutation-positive lung cancer. Methods: This retrospective cohort study analyzed 198 Japanese patients with unresectable EGFR mutation-positive lung cancer who were treated with EGFR-TKIs at Toho University Sakura Medical Center from April 2006 to December 2021. Factors associated with overall survival (OS) were analyzed using Cox proportional hazards analysis. Results: Patients who received osimertinib had a significantly longer OS than did those not receiving it (median OS, 36.2 versus 20.7 months; p < 0.001).There were significant differences in OS between patients with EGFR mutation who received osimertinib as first-line treatment, T790M-positive patients who received osimertinib as second- or later-line treatment, and those who did not receive it (median OS, 28.2 versus 40.2 versus 20.7 months; p = 0.003). However, in T790M-negative patients, no significant difference in OS was noted between those who did and did not receive osimertinib as post-treatment (median OS, 28.0 versus 40.0 months; p = 0.619). Multivariate Cox proportional hazards analysis showed that osimertinib treatment was associated with longer OS (hazard ratio, 0.480; 95% confidence interval, 0.326–0.707; p < 0.001). Conclusion: The patients who were T790M-positive in the first-line treatment with first or second-generation EGFR-TKIs and were given osimertinib as the second or later line treatment had a better prognosis than the patients who were T790M-negative in the first-line treatment with first or second-generation EGFR-TKIs and could not receive osimertinib. [ABSTRACT FROM AUTHOR]

Introduction: Functional decline occurs during dialysis initiation, particularly in unplanned cases. To prevent unplanned hemodialysis, we aimed to identify associated factors from the first referral to the nephrology department to hemodialysis initiation and assess patient prognosis post‐unplanned hemodialysis initiation. Methods: This retrospective study involved 257 Japanese patients initiating hemodialysis and compared patient characteristics based on whether hemodialysis was planned or unplanned at a single center. Patient outcomes were evaluated in collaboration with maintenance hemodialysis centers. Results: Unplanned hemodialysis initiation correlated with heart failure history (p < 0.05) and infections like pneumonia (p < 0.001). Patients with unplanned hemodialysis initiation had a worse prognosis than those with planned initiation (p < 0.001), and multivariable Cox regression showed it as an independent risk factor for death (p < 0.05). Conclusions: Hygiene and careful attention to heart failure may reduce unplanned hemodialysis and improve patient well‐being and healthcare efficiency. This retrospective analysis highlights crucial considerations for optimizing the initiation of hemodialysis. [ABSTRACT FROM AUTHOR]

This study aimed to elucidate the clinical features, outcomes and risk factors of flares in patients with systemic lupus erythematosus (SLE). Data were collected from patients with newly diagnosed SLE at the Fukushima Medical University Hospital between 2011 and 2022. Patients who experienced a flare during the study period constituted the flare group, and their clinical features were compared with those of the no-flare group. The cumulative flare-free survival regarding several clinical items was compared between the two groups using Kaplan–Meier's curves. Among 387 patients with SLE, 83 patients with newly diagnosed SLE were included. Their mean age was 37.9 years, and 29 patients experienced flares during the study period. The general characteristics were similar between the two groups, with the exception of the observation period and anti-SS-A antibody positivity. Regarding therapy, a significantly increased frequency of hydroxychloroquine intake and combination with immunosuppressive agents were observed in the no-flare group. The Kaplan–Meier analysis revealed a significantly higher cumulative flare-free survival in the anti-SS-A negative group and combination immunosuppressive therapy group. In conclusion, anti-SS-A positivity may be a risk factor for SLE flare. In turn, combination immunosuppressive therapy may be beneficial for SLE treatment in daily clinical practice. [ABSTRACT FROM AUTHOR]

The reading ability of English readers has been shown to correlate with psychophysical measurements of dynamic visual information processing. This study investigated the relationship between reading ability and dynamic visual information processing in healthy adult native Japanese readers (n = 46). Reading ability was assessed using three different tests: the Japanese Adult Reading Test (JART), transposed-letter detection task, and oral reading. Principal component analysis was performed on the scores on the three reading tests to quantify reading ability. Psychophysical thresholds were measured for contrast detection and speed discrimination with a drifting grating stimulus as well as for tracking two targets among concentrically revolving objects, providing an upper speed limit for attentional tracking. Simple correlation analysis revealed that one of the principal components correlated with the tracking speed limit. In addition, another principal component correlated with the speed-discrimination threshold, which is consistent with previous findings in English readers. These results suggest that Japanese reading ability involves at least two different processes, each sharing underlying mechanisms with visual motion and attentional processing. [ABSTRACT FROM AUTHOR]

Background: Physical activity (PA) and sedentary behaviour have important health implications. Self-reported measures of PA and sitting time (ST) such as questionnaires are most commonly used in public health studies and surveillance, but their accuracy might be affected by cultural differences between countries. The aim of the present study was to examine the correlation between the self-administered Global PA Questionnaire - Japanese version (GPAQ-J) and accelerometer in Japanese adults. Methods: A cross-sectional comparative study was conducted to examine the last 7 days PA by GPAQ-J, comparing with accelerometer data. A convenience sample of 181 women and 85 men were included. Results: Significant positive correlations using Spearman's rank correlation were observed between total moderate-to-vigorous PA (MVPA) by GPAQ-J and both of accelerometer-measured total MVPA and 10-minute bouts of MVPA in both women and men, with a higher correlation in men (total MVPA: ρ = 0.375, 10-minute bouts of MVPA: ρ = 0.419). GPAQ-J transportation MVPA was significantly correlated with all types of variables for accelerometer-measured MVPA for men, particularly with ambulatory MVPA (ρ = 0.615). On the other hand, for women, a significant positive correlation was observed between GPAQ-J recreation MVPA and accelerometer-measured 10-minute bouts of MVPA. Average MVPA with GPAQ-J was between the accelerometer-measured total MVPA and the 10 min bouts of MVPA in both genders. A significant positive correlation was only observed between ST by accelerometer and the GPAQ-J question in men (ρ = 0.332), not women (ρ = 0.004). Conclusions: The GPAQ-J has weak or moderate validity for evaluating both total and 10-minute bouts of MVPA in Japanese women and men. ST by the GPAQ-J has moderate validity only in men. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) presents with a broad spectrum of clinical manifestations, including an increased risk of tumor development and hypertension. Comprehensive data on genotype‒phenotype correlations in patients with NF1 are limited. Therefore, in this study, we aimed to elucidate the detailed genetic and clinical characteristics of NF1 in a hereditary tumor cohort. We performed sequencing and copy number assays in a clinical laboratory and analyzed the clinical data of 44 patients with suspected NF1. Germline pathogenic variants were detected in 36 patients (81.8%), and 20.7% of the variants were novel. Notably, 40.0% of adult patients presented with malignancies; female breast cancer occurred in 20.0% of patients, which was a higher rate than that previously reported. Hypertension was observed in 30.6% of the adult patients, with one patient experiencing sudden death and another developing pheochromocytoma. Three patients with large deletions in NF1 exhibited prominent cutaneous, skeletal, and neurological manifestations. These results highlight the importance of regular surveillance, particularly for patients with malignancies and hypertension. Our findings provide valuable insights for genetic counseling and clinical management, highlighting the multiple health risks associated with NF1 and the need for comprehensive and multidisciplinary care. NF1 Patients Face Increased Cancer and Hypertension Risks: Neurofibromatosis type 1 (NF1) is a genetic disorder that causes skin changes and tumors. This study explores the genetic and physical characteristics of NF1 in Japanese patients. Researchers collected data from 44 patients with suspected NF1 between 2020 and 2024. They used genetic tests to identify changes in the NF1 gene, which is crucial for tumor suppression. The study found that 92.3% of suspected patients with NF1 had detectable genetic changes linked to NF1. These changes included various types of variants, such as truncating, missence and large deletion variants. The study showed that patients with large deletion had more severe symptoms, including tumors and developmental issues. The findings suggest that understanding these genetic differences can help improve patient care and monitoring. In conclusion, this research highlights the importance of genetic testing in managing NF1. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author. [ABSTRACT FROM AUTHOR]

Background: Diffusion-weighted magnetic resonance imaging (DWI) is essential for diagnosing Creutzfeldt–Jakob disease (CJD). Thalamic lesions are rarely detected by DWI in sporadic CJD (sCJD) cases with methionine homozygosity at polymorphic codon 129 (129MM) of the prion protein (PrP) gene. Here, we describe an unusual sCJD case, characterized by prolonged isolated thalamic diffusion hyperintensities and atypical brain pathology, in combination with the 129MM genotype. Case presentation: A 72-year-old Japanese man developed a mild unsteady gait that had persisted for 1 year. DWI revealed isolated thalamic diffusion hyperintensities. Over the following 4 years, his condition progressed to include ataxia and cognitive decline. Repeated cerebrospinal fluid tests were negative for 14-3-3 protein, total tau protein, and real-time quaking-induced conversion assay. Electroencephalography did not show periodic sharp wave complexes or generalized periodic discharges. Despite these findings, thalamic DWI abnormalities persisted and evolved to include cortical lesions in the later stage of the disease. Genetic testing confirmed a 129MM genotype with no pathogenic PrP gene variants. Brain autopsy identified type 2 pathogenic PrP and the absence of the M2-thalamic prion strain, suggesting an MM2-cortical (MM2C)-subtype of sCJD. Histopathology revealed small vacuoles (sv) and patchy-perivacuolar PrP deposits without large vacuoles (lv). Patchy-perivacuolar deposits are a characteristic feature of the MM2C (lv) subtype and indicate MM2C (lv) pathology. Thus, this case was classified as a rare MM2C (sv + lv) subtype. No PrP protein staining was observed in the thalamus, despite spongiform changes with small vacuoles. Conclusions: This case underscores the diagnostic challenges of atypical CJD with isolated thalamic abnormalities on DWI. Despite negative cerebrospinal fluid findings and clinical diagnostic criteria, persistent DWI abnormalities and evolving clinical symptoms continued to raise suspicion of CJD. A definitive diagnosis, being the MM2C (sv + lv) subtype of sCJD, was confirmed upon pathological examination. Even when atypical findings, such as isolated thalamic abnormalities, are observed and various tests are negative, if suspicion of CJD cannot be ruled out, it is important to confirm the diagnosis and pathological subtypes via postmortem analysis. [ABSTRACT FROM AUTHOR]

Skin aging is a multifaceted process influenced by genetic, environmental, and immunological factors, resulting in visible changes such as wrinkles, pigmentation, and alterations in skin texture. Despite its high relevance, there is a paucity of large-scale studies focusing on visible age-related changes in facial skin among Japanese populations, particularly by region. This study aims to address these gaps by examining age- and sex-specific skin changes in a large cohort of 2,543 Japanese subjects using advanced skin imaging techniques. The study included subjects aged 17–71 years who provided informed consent. The imaging system captures facial images using standard light, UV light, and two types of polarized light, applying deep learning techniques to analyze various skin parameters. Statistical analysis was performed to evaluate correlations between age, gender, and skin characteristics. Results indicated significant correlations between age and skin color across all domains, with large pores on the nose showing the highest correlation with age. Sebum and porphyrin levels exhibited a decreasing trend with age, though correlation coefficients were low. Cheek gloss, both in area and color, showed relatively high correlation coefficients. Pigmentation-related items, such as spots and melanin, demonstrated significant age correlations, particularly in areas like the corners of the eyes, under the eyes, and cheeks. Wrinkles and fine wrinkles correlated with age in various regions, though not on the forehead. The findings highlight the importance of understanding regional and demographic variations in skin aging to develop effective anti-aging treatments. [ABSTRACT FROM AUTHOR]

Background/Objectives Methods Results Conclusion Leisure activities provide various health benefits for older adults. However, few studies have examined changes in leisure activities and health. This study aimed to determine the association among changes in leisure activities, subsequent all‐cause mortality, and functional disability.Using a longitudinal, prospective cohort design, we analyzed data from the Japan Gerontological Evaluation Study (JAGES) in 2010 and 2013 merged with government data on death and long‐term care needs by 2020. Changes in leisure activity were defined as four‐category exposure based on a question about leisure activities: those with leisure activities in both 2010 and 2013, those who started leisure activities in 2013, those without leisure activities in both 2010 and 2013 (reference group), and those who stopped leisure activities in 2013. All‐cause mortality and functional disability were defined as onset during the 6‐year follow‐up from the 2013 survey. We applied the inverse probability of censoring and treatment‐weighted methods for analyses using Cox proportional hazards models, where missingness was addressed using multiple imputation.The study included 38,125 participants with a mean age of 72.8 ± 5.5 years at baseline, and 46.9% were male. Among those without leisure activities between 2010 and 2013 and those who started leisure activities in 2013, mortality rates by 2020 were 28.6% and 21.1%, and functional disability rates were 24.6% and 18.1%, respectively; and in analyses with the inverse probability of censoring and treatment‐weighted methods, the hazard ratio for mortality was 0.82 (95% confidence interval (CI), 0.75–0.90) and 0.89 (95% CI, 0.79–1.01) for functional disability, respectively.Initiation of leisure activities among the older adults was associated with a lower risk of mortality and functional disability over the subsequent 6 years compared to older adults who did not report initiating any leisure activities. [ABSTRACT FROM AUTHOR]

Young children socially learn “what to eat” and “what not to eat” by observing others’ preferences for, and aversions to, specific food items. However, it is not clear which learning children prioritize more – learning “what to eat” or “what not to eat.” To answer this question, we compared young Japanese children’s memory of novel foods that were preferred and disliked by others. In Experiment 1, 4–5-year-olds (N = 24) preferentially remembered novel foods disliked by others more than those preferred by others. In Experiment 2, children in the same age group (N = 29) better remembered specific evaluations of foods disliked by others than those preferred by others. Thus, these findings reveal that young Japanese children show heightened memories of foods disliked by others over those liked by others. In addition, food neophobia was higher in children with a poorer memory for specific evaluations of foods preferred by others. Our results suggest that learning “what not to eat” is a priority task for young children. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims/Introduction Materials and Methods Results Conclusions This analysis seeks to evaluate the cost‐effectiveness of urine albumin‐to‐creatinine ratio testing compared with urine protein‐creatinine ratio testing and no urine testing for the identification of kidney damage in individuals with type 2 diabetes who have, or are at risk of, chronic kidney disease in Japan.A health‐economic model estimated the clinical and economic consequences of different tests to evaluate kidney damage in line with Japanese guidelines, taking a Japanese healthcare perspective. Differences in the diagnostic performance of tests were considered by the integration of real‐world Japanese data. Outcomes were considered over a lifetime horizon, and included costs, prevented dialyses, life years gained, quality‐adjusted life years, and incremental cost‐effectiveness ratios.Repeated urine albumin‐to‐creatinine ratio testing was found to be cost‐effective compared with both urine protein‐creatinine ratio testing and no urine testing, yielding incremental cost‐effectiveness ratios of ¥2,652,693 and ¥2,460,453, respectively.Repeated urine albumin‐to‐creatinine ratio testing is cost‐effective compared with urine protein‐creatinine ratio testing and no urine testing in Japanese individuals with type 2 diabetes, supporting existing clinical evidence that albumin‐to‐creatinine ratio testing should be used more widely, particularly compared with other urine tests such as urine protein‐creatinine ratio testing. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims/Introduction Materials and Methods Results Conclusions Leukocyte cell‐derived chemotaxin 2 (LECT2) is an obesity‐associated hepatokine that causes skeletal muscle insulin resistance. Since LECT2 is up‐regulated by the inactivation of the energy sensor AMPK in the liver, we hypothesized that LECT2 has potential as a biomarker for metabolic dysfunction‐associated steatotic liver disease (MASLD). Therefore, we investigated whether circulating LECT2 levels are associated with insulin sensitivity, liver enzymes, and MASLD.This cross‐sectional study included 138 Japanese individuals. Plasma LECT2 levels were measured using fasting blood samples. B‐mode ultrasonography was used to assess hepatic steatosis.The mean age and body mass index (BMI) of participants were 63.5 ± 10.2 years and 23.0 ± 3.1 kg/m2, respectively. Higher LECT2 levels positively correlated with homeostatic model assessment for insulin resistance (HOMA‐IR) values and negatively correlated with the quantitative insulin sensitivity check index (QUICKI) among all participants (HOMA‐IR; non‐standardized β (B) = 6.38, P < 0.01: QUICKI; B = −161, P < 0.01). These correlations were stronger in the low BMI group (HOMA‐IR; B = 13.85, P < 0.01: QUICKI; B = −180, P < 0.01). LECT2 levels also positively correlated with gamma‐glutamyl transferase levels (B = 0.01, P = 0.01) and alanine aminotransferase levels (B = 0.33, P = 0.02). Higher LECT2 levels correlated with the prevalence of MASLD (odds ratio = 1.14, P = 0.02).The present results suggest the potential of plasma LECT2 levels as a biomarker for insulin resistance in individuals who are not overweight and the prevalence of MASLD in the general population. [ABSTRACT FROM AUTHOR]

Japanese patients with polycystic ovary syndrome (PCOS) exhibit distinct body type characteristics, such that the rate of overweight/obese women is remarkably low. In addition, hyperandrogenism is relatively rare among Japanese PCOS patients. Therefore, these factors are considered in PCOS diagnostic criteria used in Japan. Diagnostic criteria for PCOS were recently revised by the Japan Society of Obstetrics and Gynecology based on a nationwide survey of PCOS and released on December 5, 2023 (JSOG2024). JSOG2024 criteria diagnosed PCOS according to the following three items: (1) irregular menstrual cycle/chronic anovulation, (2) polycystic ovarian morphology or elevated serum anti‐Müllerian hormone (AMH) level, and (3) hyperandrogenism or high luteinizing hormone. The presence of all three items is required to diagnose PCOS, after excluding other diseases with symptoms similar to PCOS. We also established AMH cut‐off values by age and a system for evaluating ovarian findings useful for both the JSOG2024 and Rotterdam criteria. We anticipate that the JSOG2024 criteria with cut‐off values will enhance the treatment of Japanese patients with PCOS and those of other ethnicities with low obesity and hirsutism. [ABSTRACT FROM AUTHOR]

Red complex bacteria (Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia) have high virulence in periodontal disease. In the present study, we aimed to elucidate the detailed symbiotic relationships between the red complex and other oral bacteria in older Japanese individuals. Polymerase chain reaction was performed using dental plaque from 116 subjects and specific primers for ten periodontal pathogens. The detection rate of Prevotella intermedia and Capnocytophaga sputigena was significantly higher in P. gingivalis-positive subjects than in P. gingivalis-negative subjects (p < 0.05). The detection rate of Campylobacter rectus, Prevotella nigrescens, Capnocytophaga ochracea, and Eikenella corrodens was significantly higher in T. forsythia-positive subjects than in T. forsythia-negative subjects (p < 0.01). In a comprehensive analysis of oral microbiomes, three red complex species-positive subjects had significantly higher α-diversity than only P. gingivalis-positive subjects (p < 0.05) and had significantly lower β-diversity than only T. forsythia-positive subjects (p < 0.01). In the taxonomy analysis, Porphyromonas was significantly higher in three red complex species-positive subjects than in only P. gingivalis-positive and only T. forsythia-positive subjects (p < 0.01). These results suggest that each red complex species forms a unique oral microbiome and individuals positive for all red complex bacteria may harbor oral bacteria that confer a significant advantage in developing periodontal disease. [ABSTRACT FROM AUTHOR]

Objective: We aimed to determine whether the severity of acute Kawasaki disease (KD) can be predicted based on whether a patient remains febrile or becomes afebrile immediately after the completion of initial immunoglobulin treatment (IVIG). Methods: This retrospective cohort study at a single institution involved 306 patients with KD. They were categorized into four groups according to their fever status at two specific time points (end of the initial IVIG treatment and 24–36 h later): Group F-F, patients who remained febrile at both time points; Group F-AF, patients who were febrile at the end of the initial IVIG treatment but became afebrile 24–36 h later; Group AF-F, patients who were afebrile at the end of the initial IVIG treatment but became febrile 24–36 h later; and Group AF-AF, patients who remained afebrile at both time points. The clinical characteristics of the groups were compared. Results: Group F-F (n = 38) showed a significantly higher incidence of CAAs compared to Group AF-F (n = 37), 55.3% vs. 0.0% (p < 0.0001), although both groups were classified as resistant to the initial IVIG. Conclusions: In Japanese patients with acute KD, the presence or absence of fever at the completion of initial IVIG treatment may serve as an early predictor of the occurrence of CAAs. An earlier secondary treatment may be warranted for patients who are in a febrile state immediately after the completion of the initial IVIG treatment. Future research should include a prospective cohort study with a larger number of KD cases across multiple institutions to analyze the effects of other contributing factors related to CAL formation. [ABSTRACT FROM AUTHOR]

Despite advancements in medical technology, the challenges of diagnosing fever of unknown origin (FUO) and inflammation of unknown origin (IUO) persist. Positron emission tomography/computed tomography (PET/CT) has been used to assess these conditions; however, it is unclear which patients most benefit from this approach. This study aimed to assess the clinical value and optimal use of fluorine-18-labelled-fluorodeoxyglucose (18F-FDG)-PET/CT in patients with FUO/IUO. We reviewed FDG-PET/CT scans conducted at our department between January 2014 and December 2020 to further assess FUO/IUO. FUO was defined as a fever lasting over three weeks without a diagnosis based on conventional assessment. IUO was defined as prolonged inflammation with a body temperature below 38.3 ℃ and without a diagnosis after conventional diagnostic procedures. The efficacy of FDG-PET/CT was determined based on the diagnostic outcomes achieved by integrating imaging findings with histopathological or microbiological evidence, clinical criteria, or follow-up assessments. We conducted crude and age-sex adjusted logistic regression for potential risk factors to determine the degree of burden on demographic and clinical characteristics. Forty-five patients with FUO/IUO underwent FDG-PET/CT, and final diagnoses were made in 32 patients (71.1%). The percentages of diagnostic categories were 53.3%, 8.9%, and 6.7% for non-infectious inflammatory diseases, malignancy, and infection, respectively. In multivariable logistic regression analysis, IUO was the only independent predictor of the efficacy of FDG-PET/CT in the final diagnosis (odds ratio, 67.02; 95% confidence interval, 4.02–1119). Our results indicate that IUO was associated with a higher diagnostic yield compared to those with FUO. [ABSTRACT FROM AUTHOR]

Because of shifting social circumstances, a growing number of businesses are implementing work at home options. Working at home enhances work-life balance but blurs the line between work and personal life, making it challenging for workers to psychologically detach from work outside of their designated hours. This blurring of boundaries between work and personal life is thought to potentially increase work engagement. Moreover, achieving psychological detachment from work and disengaging from work-related thoughts outside of working hours are thought to demand high levels of thought control ability. This study hypothesized that (1) compared to office workers, those who work at home struggle more to detach from work and exhibit higher levels of work engagement, (2) higher levels of thought control ability reduce work-related thoughts. This study employed a combination of a cross-sectional survey design and an experimental approach using a cognitive task to examine the research questions. Focusing on Japanese workers, the results confirmed that home workers face challenges in detaching from work and show higher work engagement, identifying work from home as a potential stressor and a factor that may increase work involvement. On the other hand, the study found no link between elevated thought control ability and reduced work-related thoughts during cognitive tasks. [ABSTRACT FROM AUTHOR]

Background: The receptor for advanced glycation end product (RAGE) is a transmembrane receptor accelerating a pro-inflammatory signal. RAGE signalling is promoted by decreased soluble isoform of RAGE (sRAGE), which is a decoy receptor for RAGE ligands, and RAGE SNP rs2070600 minor allele. In Caucasian and Japanese cohorts, low circulatory sRAGE levels and presence of the minor allele are associated with poor survival of idiopathic pulmonary fibrosis (IPF) and increased disease susceptibility to interstitial lung disease, respectively. However, whether sRAGE and RAGE SNP rs2070600 are associated with acute exacerbation of IPF (AE-IPF) is unclear. Methods: This retrospective cohort study evaluated the association between the onset of AE-IPF and serum sRAGE levels in 69 German and 102 Japanese patients with IPF. The association of AE-IPF with RAGE SNP rs2070600 in 51 German and 84 Japanese patients, whose DNA samples were stored, was also investigated. Results: In each cohort, the incidence of AE-IPF was significantly and reproducibly higher in the patients with sRAGE < 467.1 pg/mL. In a pooled exploratory analysis, the incidence of AE-IPF was lowest in the patients with higher sRAGE levels and rs2070600 minor allele, although no significant difference in the incidence was observed between the patients with and without the rs2070600 minor allele. Conclusions: Low sRAGE levels were associated with increased incidence of AE-IPF in two independent cohorts of different ethnicities. The combination of rs2070600 and sRAGE levels may stratify patients with IPF for the risk of AE. [ABSTRACT FROM AUTHOR]

Optimal ligament balance is crucial for successful total knee arthroplasty (TKA), which is a standard procedure for managing end-stage knee osteoarthritis. However, the reported values of ligament balance vary due to different methodologies and population differences, which requires further studies. This study aimed to investigate the varus-valgus ligament balance in healthy knees of Japanese individuals and its relationship with lower limb alignment. The studyanalyzed64 knees from 33 healthy young adults using stress radiographs to measure varus-valgus laxity. The mechanical hip-knee-ankle angle, medial proximal tibial angle, and lateral distal femoral angles were determined using digital long-leg radiographs. Varus and valgus laxities were compared, and the relationship between ligament balance and alignment parameters was analyzed. Mean varus laxity (3.6°± 1.3°) was significantly greater than mean valgus laxity(2.9°± 1.0°) (p<0.0001). No significant association was observed between ligament balance and alignment parameters. Healthy knees of Japanese individuals exhibited slightly greater varus laxity (0.7°) than valgus laxity, with no correlation observed between ligament balance and lower limb alignment. The finding underscores the importance of recognizing alignment diversity while noting that alignment does not influence ligament balance; this is particularly relevant in modern TKA techniques focusing on patient-specific joint and ligament reconstructions. The study's findings could help formulate strategies benefiting knee osteoarthritis management. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the relationship between low-dose prednisolone (PSL) and the incidence of hypokalaemia at abiraterone acetate (abiraterone) plus PSL combination therapy targeting Japanese patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: This retrospective observational study included 153 Japanese patients treated with abiraterone and PSL for mCRPC at Kariya Toyota General Hospital and Gifu General Medical Center between September 2014 and October 2022. The incidence of grade ≥ 2 hypokalaemia as well as serum potassium level variations and the continuous combination therapy duration were compared between the low-dose (5 mg/day of PSL) and the standard-dose (10 mg/day of PSL) groups. Results: This study included 153 patient of which 95 were matched to establish the analysis population. The low-dose and the standard-dose groups consisted of 13 and 82 patients, respectively. No significant difference in the incidence of grade ≥ 2 hypokalaemia was observed between the two groups [15.4% (2/13 patients) in the low-dose group and 12.2% (10/82 patients) in the standard-dose group, P = 0.667]. The low-dose group exhibited a decrease in serum potassium levels from 4.63 on day − 7 − 0 to 4.16 mmol/L on day 84 ± 10 (n = 7, P = 0.066), and serum potassium levels from day − 7 − 0 to 84 ± 10 in the low-dose group appeared to be great in the standard-dose group (n = 37, P = 0.475). The Kaplan–Meier curves for continuity of abiraterone and PSL therapy were not significantly different between the low-dose group (n = 13) and standard-dose group (n = 82, P = 0.427). Conclusion: Combination therapy with abiraterone and 5 mg/day of PSL in Japanese patients with mCRPC did not change the incidence of grade ≥ 2 hypokalaemia. However, although not significant, 5 mg/day of PSL demonstrated a decreasing trend in serum potassium levels with a larger degree of change than that of 10 mg/day of PSL. Therefore, the combination of abiraterone and 5 mg/day PSL can be administered to Japanese patients with mCRPC. The patients must be monitored for hypokalaemia through measurement of serum potassium levels and observation of subjective symptoms such as muscle weakness, convulsion etc. In addition, the doctor or the pharmacist must explain these symptoms to the patient and instruct them to consult their medical staff immediately in the event of development of such symptoms. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims/Introduction Materials and Methods Results Conclusions We evaluated the effect of the MiniMed™ 770G, an insulin pump using hybrid closed‐loop technology, on blood glucose management and quality of life in Japanese people with type 1 diabetes.This was a 52‐week, prospective, observational study. Fifty Japanese people with type 1 diabetes switched from the MiniMed™ 640G to 770G, and we analyzed the continuous glucose monitoring data of 24 subjects who used auto mode throughout the study. We also analyzed the scores of the Diabetes Therapy‐Related Quality of Life questionnaire completed by 26 auto‐mode users before and after the treatment change.The baseline time in range 70–180 mg/dL was 67.3 (54.8–78.4)%, with a significant improvement beginning 8 weeks after the switch and lasting until 52 weeks. The baseline time below range <70 mg/dL was 1.9 (0.6–3.6)%, with a significant increase at week 8; however, the mean value was less than 4% throughout the study period. On the other hand, the number of blood glucose measurements significantly increased. While there was no significant difference in the overall change in the total Diabetes Therapy‐Related Quality of Life score, there was a significant decrease in the treatment satisfaction score.Use of the MiniMed™ 770G improved continuous glucose monitoring metrics. However, treatment satisfaction decreased, probably due to the increased frequency of blood glucose monitoring necessary to maintain auto mode. [ABSTRACT FROM AUTHOR]

The lipid accumulation product (LAP) is a novel, sex-specific indicator of lipid accumulation. While previous studies have investigated the relationship between LAP and diabetes, they have not specifically addressed potential sex differences in this association. The present study explores the potential sex-specific differences in the relationship between LAP and diabetes mellitus (DM) risk in the Japanese population. From 2004 to 2015, a total of 15,263 Japanese individuals without DM underwent physical assessments at Murakami Memorial Hospital. The association between LAP and incident diabetes was analyzed using Cox proportional hazards regression models, incorporating cubic spline functions and smooth curve fitting to identify potential non-linear relationships. Subgroup and sensitivity analysis assessments were conducted to validate the robustness of our findings. After adjusting for covariates, a positive association between LAP and DM risk was observed in both females (HR: 1.02, 95% CI: 1.00-1.03, P = 0.0138) and males (HR: 1.01, 95% CI: 1.00-1.01, P = 0.0314). A non-linear association between LAP and incident DM was identified for both sexes. The inflection points for LAP were 16.58 for females and 11.11 for males. In females, the HR to the left and right of the inflection point were 1.09 (95% CI: 1.02–1.17) and 1.01 (95% CI: 1.00-1.03), respectively. In males, the HR to the left and right of the inflection point were 0.92 (95% CI: 0.86–0.98) and 1.01 (95% CI: 1.00-1.01), respectively. Sensitivity analysis indicated a stronger association between LAP and DM risk. Elevated baseline LAP levels were associated with an increased risk of incident DM, with the relationship exhibiting non-linear characteristics. These findings suggest that maintaining lower LAP levels may help mitigate the risk of developing diabetes. [ABSTRACT FROM AUTHOR]

Background: The copy number status (CNS) of the survival motor neuron (SMN) gene may influence the risk and prognosis of amyotrophic lateral sclerosis (ALS) and lower motor neuron diseases (LMND) other than spinal muscular atrophy (SMA). However, previous studies of this association, mainly from Europe, have yielded controversial results, suggesting possible regional differences. Here, we investigated the effect of the SMN gene in Japanese patients with ALS and LMND. Methods: We examined the SMN copy numbers and clinical histories of 487 Japanese patients with sporadic ALS (281 men; mean age at onset 61.5 years), 50 with adult LMND (50 men; mean age at onset 58.4 years) and 399 Japanese controls (171 men; mean age 62.2 years). Patients with pathogenic mutations in ALS-causing genes were excluded. SMN1 and SMN2 copy numbers were determined using the droplet digital polymerase chain reaction. Results: The frequency of a copy number of one for the SMN2 gene was higher in patients with ALS (38.0%) than in healthy controls (30.8%) (odds ratio (OR) = 1.37, 95% confidence interval (CI) = 1.04–1.82, p < 0.05). The SMN2 copy number affected the survival time of patients with ALS (median time: 0 copies, 34 months; 1 copy, 39 months; 2 copies, 44 months; 3 copies, 54 months; log-rank test, p < 0.05). Cox regression analysis revealed that the SMN2 copy number was associated with increased mortality (hazard ratio = 0.84, 95% CI = 0.72–0.98, p < 0.05). Also, null SMN2 cases were significantly more frequent in the LMND group (12.0%) than in the control group (4.8%) (OR = 2.73, 95% CI = 1.06–6.98, p < 0.05). Conclusions: Our findings suggest that SMN2 copy number reduction may adversely affect the onset and prognosis of MND, including ALS and LMND, in Japanese. [ABSTRACT FROM AUTHOR]

Renal medullary carcinoma is a rare, high‐grade carcinoma arising in the renal medulla, which is usually associated with sickle cell trait, and there are very few documented cases in the Japanese population. We report a case of renal medullary carcinoma, immunohistochemically defined as SMARCB1 deficient, in a 67‐year‐old Japanese woman without a history of sickle cell trait. Somatic mutation of SMARCB1 and an EML4::ALK fusion gene were identified by comprehensive genomic profiling. Computed tomography revealed metastatic lesions in the retrocaval lymph nodes, liver, and bronchus. Six cycles of the dose‐dense methotrexate, vinblastine, adriamycin, and cisplatin‐combined chemotherapy were completed after an ultrasound‐guided percutaneous biopsy of the renal tumor. After chemotherapy, the size of the original tumor in the right kidney had decreased in size, as well as the other metastatic lesions. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Methods Results Conclusion Northern Japanese children tend to have larger physiques; however, the underlying cause remains unknown. Previous geographical correlation analyses revealed an unusual trend; effective day length was negatively correlated with height and positively correlated with weight (adjusted for height). This paradoxical relationship suggests a thyroid hormone‐like effect and possible photoperiodic response. This study aimed to determine whether this phenomenon remains consistent over time and across different regions of Japan.We used geographically and temporally weighted regression (GTWR) to examine whether the relationship between height and effective day length, which differs from the relationship between weight and effective day length, varies by location and time. GTWR models each observation point separately, allowing for spatial and temporal variations. The analysis included the average height and weight data of children and adolescents by prefecture from 1989 to 2019, along with effective day length considering illuminance above 5000 lx derived from the agrometeorological grid square data.Height was used as the dependent variable, whereas weight and effective day length were used as independent variables. For height estimation, the coefficients of weight and effective day length were consistently positive and negative, respectively, although the regression coefficients showed minor geographical and temporal variations.The opposite correlation between height and effective day length and that between weight and effective day length were consistent. This suggests that the phenomenon is more likely driven by environmental factors than by economic or genetic influences. [ABSTRACT FROM AUTHOR]

Background: Augmented renal clearance (ARC) decreases the therapeutic concentration of drugs excreted by the kidneys in critically ill patients. Several ARC prediction models have been developed and validated; however, their usefulness in Japan has not been comprehensively investigated. Thus, we developed a unique ARC prediction model for a Japanese mixed intensive care unit (ICU) population and compared it with existing models. Methods: This retrospective study enrolled a mixed ICU population in Japan from January 2019 and June 2022. The primary outcome was the development and validation of a model to predict ARC onset based on baseline information at ICU admission. Patients admitted until May 2021 were included in the training set, and external validation was performed on patients admitted thereafter. A multivariate logistic regression model was used to develop an integer-based predictive scoring system for ARC. The new model (the JPNARC score) was externally validated along with the ARC and Augmented Renal Clearance in Trauma Intensive Care (ARCTIC) scores. Results: A total of 2,592 critically ill patients were enrolled initially, with 651 patients finally included after excluding 1,941 patients. The training and validation datasets comprised 456 and 195 patients, respectively. Multivariate analysis was performed to develop the JPNARC score, which incorporated age, sex, serum creatinine, and diagnosis upon ICU admission (trauma or central nervous system disease). The JPNARC score had a larger area under the receiver operating characteristic curve than the ARC and ARCTIC scores in the validation dataset (0.832, 0.633, and 0.740, respectively). Conclusions: An integer-based scoring system was developed to predict ARC onset in a critically ill Japanese population and showed high predictive performance. New models designed to predict the often-unrecognized ARC phenomenon may aid in the decision-making process for upward drug dosage modifications, especially in resource- and labor-limited settings. [ABSTRACT FROM AUTHOR]

Background and Aims The efficacy and safety of early sacubitril/valsartan (Sac/Val) initiation after acute heart failure (AHF) has not been demonstrated outside North America. The present study aimed to evaluate the effect of in-hospital Sac/Val therapy initiation after an AHF episode on N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in Japanese patients. Methods This was an investigator-initiated, multicentre, prospective, randomized, open-label, blinded-endpoint pragmatic trial. After haemodynamic stabilization within 7 days after hospitalization, eligible inpatients were allocated to switch from angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to Sac/Val (Sac/Val group) or to continue angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (control group). The primary efficacy endpoint was the 8-week proportional change in geometric means of NT-proBNP levels. Results A total of 400 patients were equally randomized, and 376 (median age 75 years, 31.9% women, de novo heart failure rate 55.6%, and median left ventricular ejection fraction 37%) were analysed. The per cent changes in NT-proBNP level geometric means at Weeks 4/8 were −35%/−45% (Sac/Val group) and −18%/−32% (control group), and their group ratio (Sac/Val vs. control) was 0.80 (95% confidence interval 0.68–0.94; P =.008) at Week 4 and 0.81 (95% confidence interval 0.68–0.95; P =.012) at Week 8, respectively. In the pre-specified subgroup analyses, the effects of Sac/Val were confined to patients with a left ventricular ejection fraction < 40% and were more evident in those in sinus rhythm and taking mineralocorticoid receptor antagonists. No adverse safety signal was evident. Conclusions In-hospital Sac/Val therapy initiation in addition to contemporary recommended therapy triggered a greater NT-proBNP level reduction in Japanese patients hospitalized for AHF. These findings may expand the evidence on Sac/Val therapy in this clinical situation outside North America. Clinical Trial Registration ClinicalTrial.gov (NCT05164653) and Japan Registry of Clinical Trials (jRCTs021210046). [ABSTRACT FROM AUTHOR]

Background: Studies have reported that depressive symptoms in individuals who witness workplace bullying are worsening. Consequently, companies in Japan were legally obligated to implement the necessary employment management regulations to prevent workplace bullying in 2019. Notably, assertion and physical activities can reduce depressive symptoms. This study examined the effects of assertion video viewing and physical activity interventions on depressive symptoms in workers who witnessed workplace bullying. Methods: Forty-five Japanese adults participated in this study. After viewing the workplace bullying video, the participants were randomly divided into three groups: assertion video viewing, physical activity, and control. Depressive symptoms were assessed by the Multiple Mood Scale before the intervention (T1), after viewing the video (T2), and immediately after the intervention (T3). Two-factor analysis of variance was conducted with group and time as independent variables and depressive symptoms as the dependent variable. Results: Analysis of variance revealed that the interaction effect was significant. Simple main effect analysis revealed that depressive symptom scores at T3 were significantly lower than those at T2 in the assertion group and that depressive symptom scores at T3 were significantly lower than those at T1 and T2 in the physical activity group. Conclusions: Video viewing and physical activity may ameliorate depressive symptoms in workers who have witnessed workplace bullying. [ABSTRACT FROM AUTHOR]