Sapporo Minami Hospital

Approximately 30% of patients with depression suffer from treatment-resistant depression (TRD). Ketamine has shown antidepressant efficacy for TRD. While glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) has been demonstrated to play crucial roles in the process of pharmacological action of ketamine in experimental animals, it remains elusive how ketamine exhibits its efficacy through changes in AMPAR dynamics in patients with TRD. In this study, using a positron emission tomography (PET) tracer, [11C]K-2, which depicts AMPAR density in the living human brain, we detected a negative correlation between AMPAR density and illness severity and differences in AMPAR distribution between patients with TRD and healthy participants. Furthermore, we detected brain areas where ketamine administration altered AMPAR density in significant correlations with ketamine-induced antidepressant effect in patients with TRD. AMPAR density alteration in these regions partially rescued AMPAR phenotype in the affected areas. Thus, AMPAR dynamics underlies the antidepressant effect of ketamine in patients with TRD.

Chemotherapy-induced nausea and vomiting (CINV) remain major challenges during concurrent chemoradiotherapy (CCRT) for cervical cancer. Mannitol and furosemide are agents widely used to prevent cisplatin-induced nephrotoxicity; however, the differences in their effect on CINV have not been characterized. This study aimed to evaluate the impact of concomitant diuretic administration (mannitol versus furosemide) on the incidence and timing of vomiting in patients with cervical cancer undergoing CCRT. This multicenter, retrospective study evaluated the impact of concomitant diuretic administration on CINV in 485 patients receiving weekly, cisplatin-based CCRT between 2016 and 2024, including 206 who received mannitol and 279 who received furosemide. Vomiting occurred more frequently in the mannitol group than in the furosemide group (18.4% vs. 10.4%). Time-to-event analysis found that vomiting occurred earlier with mannitol during the entire CCRT course. These findings may reflect mannitol's osmotic properties and the increased, intestinal permeability associated with CCRT-related mucosal injury. To the best of our knowledge, this study is the largest investigation to date comparing diuretic agents in this setting. The results suggested that furosemide may be a more appropriate option for patients with a high risk of CINV.

BackgroundThe post-discharge period following psychiatric hospitalization is a high-risk period for suicide attempts. This risk is substantially higher for patients admitted for suicidal behavior. Despite the urgent need for effective countermeasures, evidence-based interventions specifically designed to prevent suicide reattempts in this high-risk population remain limited. Although assertive case management is recognized as an effective intervention, its feasibility, safety, and efficacy for patients in psychiatric hospitals remain uninvestigated. The ACTION-JP study aims to evaluate the feasibility, safety, and efficacy of such an intervention adapted for patients in Japan admitted to psychiatric hospitals following a suicide attempt.MethodsThe ACTION-JP study is a multicenter, single-arm clinical trial. A total of 220 adult patients admitted to participating psychiatric hospitals following a suicide attempt will be enrolled. The intervention comprises two main components: a psychoeducation program conducted during hospitalization and an 18-month structured assertive case management follow-up. The primary outcome is the change from baseline in the Columbia-Suicide Severity Rating Scale total score at the 6-month follow-up. Secondary outcomes include the incidence of suicide reattempts and self-harm, as well as changes in Beck Depression Inventory-II and Global Assessment of Functioning Scale scores.DiscussionThis study protocol describes the essential first step in developing an evidence-based suicide prevention strategy for psychiatric inpatients. This study will provide important data on the intervention’s feasibility, safety, and efficacy. The findings are expected to offer important insights into the potential effectiveness of assertive case management for reducing suicide risk post-discharge. The successful implementation of this study will provide the necessary basis for designing a future large-scale randomized controlled trial that may help to establish a new standard of care in psychiatric hospitals.Trial registrationThis trial was registered on the University Hospital Medical Information Network clinical trials registry: UMIN000057009 (Date of registration: April 1, 2025) and the Japan Registry for Clinical Trials: jRCT1010250041 (Date of registration: October 20, 2025).Supplementary informationThe online version contains supplementary material available at 10.1186/s12888-025-07554-0.

This study evaluated the 1-year improvement in blood pressure (BP), glucose metabolism (GM), and lipid metabolism (LM) abnormalities detected during health check-ups, and identified factors associated with improvement. This retrospective cohort study used data from a University Health Care Centre between April 2008 and March 2023. Adults with BP, GM, or LM abnormalities at baseline who attended the following year's check-ups were included. The abnormalities were defined according to the criteria of the Japan Society of Ningen Dock. The primary outcome was improvement in abnormalities at the subsequent check-up, defined as no longer meeting the abnormality criteria. Multivariable logistic regression was used to examine factors associated with improvement. We analysed 2727 participants with BP abnormalities (mean age: 55.4 ± 9.0 years; 71.1% males), 1506 with GM (55.8 ± 8.5 years; 74.9% males), and 3793 with LM (52.4 ± 8.7 years; 61.0% males). Improvement occurred in 57.4% (BP), 29.3% (GM), and 57.5% (LM). Use of corresponding medication at baseline (odds ratios [ORs]: 0.38, 0.33, and 0.14, for BP, GM, and LM, respectively, p < 0.05) and 1-year weight loss (ORs: 1.08, 1.24, and 1.12, respectively, p < 0.05) were associated with improvement across all three domains, whereas use of corresponding medication at the subsequent check-up was associated with improvement in BP and LM (ORs: 2.22 and 14.97, respectively, p < 0.001). In this large health check-up cohort, over half of BP and LM, and approximately one-third of GM abnormalities improved within 1 year. Associations between improvement and both weight reduction and pharmacological treatment highlight the importance of lifestyle modification and timely medical management.

Background:EGFR L858R mutation is associated with poorer efficacy of EGFR-tyrosine kinase inhibitors (TKIs) than EGFR Ex19del in patients with non-small cell lung cancer (NSCLC). However, ramucirumab (RAM) + erlotinib (ERL) therapy exhibited comparable efficacy between patients with L858R mutation and Ex19del mutation (median progression-free survival (PFS): 19.6 vs 19.4 months) in the RELAY study, with favorable PFS for both gene mutations at 19.4 months in the Japanese subset. Meanwhile, the FLAURA study revealed shorter PFS with osimertinib (OSI) for L858R mutation than Ex19del mutation, with poorer PFS in the Japanese subset than in the overall population. The treatment discontinuation rates of RAM + ERL and OSI in Japanese patients were 18% and 29%, respectively. Consequently, RAM + ERL may exhibit superior efficacy and safety in Japanese patients with the L858R mutation.Objectives:To evaluate the therapeutic efficacy and safety of RAM + ERL as a first-line treatment for advanced or recurrent NSCLC harboring the L858R mutation in Japanese patients.Design:A multicenter, noninterventional, retrospective cohort study.Methods and analysis:This study will involve patients with advanced or recurrent NSCLC (ECOG PS score 0–2) with L858R mutation who received RAM + ERL between November 1, 2020 and August 31, 2023, with the planned sample size of 200 patients. The primary endpoint is time to treatment failure, and the secondary endpoints are overall survival, PFS, PFS2, time to discontinuation of any EGFR-TKI, time to failure of strategy, objective response rate, disease control rate, and safety. Exploratory endpoints are effects of ERL and RAM on PD-L1 expression and neutrophil-to-lymphocyte ratio.Discussion:To the best of our knowledge, this is the first retrospective study focusing on L858R mutations associated with the RELAY regimen, providing the corresponding real-world data.Trial registration:UMIN Clinical Trials Registry identifier: UMIN000052047.

Programmed death ligand 1 (PD-L1) serves as a crucial biomarker for predicting the efficacy of immune checkpoint inhibitors in patients with non-small cell lung cancer (NSCLC). This study aimed to identify the most suitable first-line treatment regimen for patients with PD-L1 expression <1% (PD-L1-negative) NSCLC by comparing nivolumab plus ipilimumab (NI), NI combined with chemotherapy (NICT), and pembrolizumab and chemotherapy (PCT). We analyzed data from 141 patients with PD-L1-negative NSCLC treated with NI, NICT, or PCT at 14 Japanese institutions between December 2020 and November 2022. Propensity score analysis was employed to minimize selection bias, and Kaplan-Meier analysis and Cox proportional hazards regression were used to evaluate progression-free survival (PFS) and overall survival (OS). Neither NI nor NICT demonstrated superior PFS or OS than PCT. Subgroup analyses revealed no significant differences between treatment groups across age, histological subtypes, or clinical features. Results from propensity score matching and inverse probability of treatment weighting were consistent with those observed in the overall cohort. Moreover, safety profiles showed that PCT was associated with the lowest rates of treatment discontinuation and immune-related adverse events requiring systemic corticosteroid therapy. In patients with PD-L1-negative NSCLC, the efficacy of NI and NICT was not superior to that of PCT. Thus, we concluded that PCT could be a favorable treatment option for this patient population.

A 55-year-old male construction worker presented with multiple fractures after falling downstairs and striking his forehead on a concrete wall, an incident preceded by consuming approximately 50 g of alcohol. Initial evaluation revealed a contaminated 7 cm forehead laceration and a depressed frontal bone fracture, with no neurological deficits or intracranial bleeding on computed tomography (CT), leading to discharge with follow-up instructions despite mild intoxication. The next day, neck pain prompted further imaging, uncovering a complex injury pattern: frontal bone fracture, occipital base fracture, C1 anterior arch fracture, and C4 vertebral body and spinous process fractures, with magnetic resonance imaging (MRI) excluding intervertebral disc injury. Conservative management with a Philadelphia collar for two months, followed by a soft collar for three months, and teriparatide to aid bone healing resulted in the patient returning to work symptom-free after six months. Follow-up imaging at one year (CT) showed no displacement and partial bone healing, while a three-year MRI confirmed no posttraumatic complications. This case illustrates a rare sequential fracture pattern from head trauma, resembling a billiard-like chain reaction where indirect axial force cascades through the frontal bone, occipital base, and cervical spine. Alcohol likely delayed pain recognition by elevating the pain threshold, highlighting the need for comprehensive cervical imaging in head trauma patients - especially those with intoxication or altered consciousness - to prevent missed diagnoses and ensure timely intervention.