Tsuchiura Kyodo General Hospital

Morbidity and mortality rates after surgery in patients with perforated peptic ulcer (PPU) remain high. Although several scoring systems have been proposed, only a few machine learning models have been designed to predict postoperative adverse events. This study aimed to develop and deploy a predictive model for the risk of postoperative adverse events in patients with PPU. We analyzed data from the Perforated Peptic Ulcer Analyzing Project, which is a retrospective survey of adult patients with PPU in seven participating institutions in Japan between January 2011 and December 2022. The postoperative adverse events were defined as complications with a Clavien-Dindo classification of Grade III or higher. The variables were selected based on permutation feature importance derived from a random forest algorithm using bootstrap sampling. Internal-external cross-validation was conducted to develop and evaluate the model's performance. The final model was deployed as an interactive web application. Of the 702 potentially eligible patients, 425 were treated surgically. Of these, 78 patients (18.3%) experienced postoperative adverse events. Ten variables were selected and used to develop a random forest model that displayed favorable discriminatory ability, with a pooled area under the receiver operating characteristic curve (AUROC) of 0.83. Compared to the other systems, the random forest model outperformed the PULP (AUROC, 0.79) and Boey scores (AUROC, 0.67). In this study, a machine learning model was developed and deployed to predict postoperative adverse events in patients with PPU. Further external validation is required for clinical use.

Abstract Introduction: Aneurysmal subarachnoid hemorrhage (aSAH) carries high early mortality and long-term functional impairment. Although early mobilization (EM) may enhance recovery, concerns regarding cerebral perfusion instability and delayed cerebral ischemia often limit its implementation. Objective physiological indicators to guide safe EM in aSAH remain limited. Methods: In this prospective, single-center exploratory study, 27 patients with aSAH during the cerebral vasospasm period underwent standardized EM delivered by a multidisciplinary team. Regional cerebral oxygen saturation (rSO₂) was continuously monitored using near-infrared spectroscopy (NIRS), along with mean arterial pressure (MAP), heart rate (HR), and peripheral oxygen saturation (SpO₂). Patients were categorized into low (< 63%, n = 10) and high (≥ 63%, n = 17) baseline rSO₂ groups. Changes in rSO₂ and systemic hemodynamics during postural transition from supine to sitting were analyzed. Results: Baseline rSO₂ was significantly lower in the low rSO₂ group in both the supine (61.2 ± 1.1 vs. 67.2 ± 3.3, p < 0.001) and sitting positions (59.9 ± 2.7 vs. 65.7 ± 4.0, p < 0.001), with no significant group-by-posture interaction. MAP demonstrated a significant group-by-position interaction (p = 0.033), whereas HR and SpO₂ showed no significant interactions. Conclusion: EM was associated with modest, posture-related reductions in cerebral oxygenation that were not accompanied by major systemic instability. NIRS monitoring may provide useful physiological information during EM and support the development of individualized mobilization strategies in patients with aSAH.

To investigate clinical outcomes, treatment, and survival rates of men aged ≥75 years with prostate cancer in Japan. The study used data from the Prostate Cancer Research International: Active Surveillance (PRIAS)-JAPAN, a nationwide, multicentre prospective cohort study of men with clinically localised prostate cancer managed with active surveillance (AS). The original eligibility criteria were clinical stage T1c-T2 disease, prostate-specific antigen (PSA) level ≤10 ng/mL, PSA density (PSAD) <0.20 ng/mL/mL, and Gleason Score ≤3 + 3 with two or fewer positive biopsy cores. In 2021, magnetic resonance imaging use expanded eligibility to include patients with a PSA level ≤20 ng/mL, PSAD <0.25 ng/mL/mL, and Gleason Score ≤3 + 4 with <50% of biopsy cores positive. PSA was monitored every 3-6 months, and biopsies were scheduled at 1, 4, 7, and 10 years, and every 5 years thereafter. The outcomes in those aged ≥75 years (older group) were compared with those aged <75 years (younger group). Of the 1274 eligible patients enrolled by 29 February 2024, 231 were in the older group and 1043 were in the younger group. In the older group, the median age at enrolment was 77 years. At diagnosis, patients in the older group had significantly larger prostate volumes, higher proportion of Gleason Score 3 + 4, and more T2 disease than those in the younger group. The protocol biopsy acceptance rate decreased over time (first: 82.9%, second: 63.6%, third: 42.2%, fourth: 22.4%), with no significant difference between age groups. The 10-year AS persistence rate in the older group was 8.8%. The overall survival was significantly lower in the older group than in the younger group (hazard ratio: 0.32, 95% confidence interval 0.14-0.74); however, the 10-year metastasis-free survival and cancer-specific survival rates in the older group were both 100%. In some patients aged ≥75 years an observation-focused management approach may be appropriate, in which AS is initiated as a structured monitoring phase with planned de-intensification and transition to watchful waiting, to prevent overtreatment while maintaining excellent cancer-specific outcomes.

Abstract Triage tools in routine emergency care are largely static, failing to exploit simple behavioral cues clinicians notice in real time. Here, we developed a Bayesian, sequentially updating framework that integrates incoming cues to produce calibrated, time-consistent risk. Using a prospective single-center cohort of ambulance arrivals in Japan (February–August 2025; n=2,221), we evaluated time to first urination (TTU) as a proof-of-concept bedside cue for predicting hospital admission. Population-level fit to the cumulative admission curve was excellent (integrated squared error 0.002; RMSE 0.003; Kolmogorov–Smirnov 0.008; coverage 0.98). At the patient level, performance improved markedly with age/sex adjustment (AUC(t) 0.70 vs. 0.50 unadjusted), with lower Brier scores and positive calibration slopes. Platt recalibration refined probability scaling without altering discrimination, and decision-curve analysis showed small, favorable net benefit at common thresholds. This framework is readily extensible to multimodal inputs and external validation and is designed to complement, not replace, existing triage systems.

Abstract Background Left atrial calcification (LAC) after atrial fibrillation (AF) ablation has recently been described, but its clinical significance and determinants remain insufficiently defined. Methods Among 1,741 patients who underwent first-time radiofrequency AF ablation between 2011 and 2018, 231 patients underwent both pre- and post-ablation chest CT. Patients were classified into an LAC group (n=71) and a non-LAC group (n=160). Baseline characteristics, ablation parameters, and calcification sites were analyzed. Independent predictors of LAC formation were identified using Cox proportional hazards models. Clinical outcomes, including heart failure (HF) hospitalization, stroke, and a composite endpoint of all-cause mortality, HF, stroke, or coronary intervention, were compared during long-term follow-up. Results Over a mean follow-up of 9.5 ± 2.7 years, LAC was detected in 31% of patients, typically 7.3 ± 3.1 years after ablation. LAC occurred most frequently at the lateral mitral annulus and right pulmonary veins. Independent predictors of LAC formation were non-paroxysmal AF (HR 1.7, 95% CI 1.0–2.8, p=0.04), LA diameter &gt;50 mm (HR 2.7, 95% CI 1.3–5.5, p&lt;0.01), and ablation beyond the pulmonary veins (HR 2.3, 95% CI 1.3–4.2, p=0.04). Kaplan–Meier analysis showed significantly higher HF hospitalization in the LAC group (log-rank p=0.02), while stroke incidence was similar between groups (p=0.50). The composite endpoint occurred more frequently in the LAC group (p=0.05). Conclusion LAC is a not uncommon late finding after AF ablation, particularly in patients with advanced atrial remodeling or extensive ablation. Its presence is associated with a higher risk of HF hospitalization, underscoring the importance of procedural planning and long-term imaging surveillance in AF ablation patients.

Cough reflex and vagal reflex-induced bradycardia are important to predict and prevent prior to PFA to ensure procedural safety and efficacy. However, no studies have yet investigated differences in their incidence among the various PFA systems. We aimed to evaluate the incidence, predictors, and system-specific differences of cough reflex and vagal response during PFA in a large multicenter cohort. Data from 1715 patients undergoing PFA using either PulseSelect, Farapulse, or Varipulse systems at 13 centers were analyzed. Cough reflex was defined as any episode requiring procedure interruption or physical restraint, while a vagal response was defined as sinus arrest or atrioventricular block lasting ≥ 5s. Pulmonary vein isolation was achieved in all patients except for one case. Complications were rare and did not differ significantly among the PFA systems. Cough reflex occurred in 49.3% of patients, most frequently in the left superior pulmonary vein. Compared with Farapulse, the risk of cough reflex was higher with PulseSelect (odds ratio [OR] 1.648, 95% confidence interval [CI] 1.321-2.057) and Varipulse (OR 1.645, 95% CI 1.019-2.657). Patient-related factors such as male sex, asthma, heart failure, and hypertension increased the risk, whereas general anesthesia significantly reduced it (OR 0.236, 95% CI 0.174-0.318). Vagal response occurred in 15.2% of patients, with no significant differences among the PFA systems, and the sequence of pulmonary vein isolation did not affect its occurrence. Prophylactic atropine reduced the risk of vagal response. Cough reflex may vary across PFA systems, while vagal response may remain consistent.

Abstract Background Post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) is an established prognostic physiological marker after revascularization, used to assess stenting success and predict long-term outcomes. While post-PCI FFR's prognostic value is recognized, its optimal cutoff value has shown considerable variability across studies. We hypothesized that this variability may be partly explained by differences in perfused myocardial mass between the left anterior descending artery (LAD) and non-LAD territories. Purpose We aimed to investigate the vessel-specific prognostic cutoff value of post-PCI FFR. Methods This subanalysis of the International Post-PCI FFR Extended Registry included 2128 patients who underwent successful drug-eluting stent (DES) implantation. Post-PCI FFR was measured immediately after the procedure, and patients were stratified according to the target vessel (LAD or non-LAD). The primary endpoint was target vessel failure (TVF), a composite of cardiac death, target vessel-related myocardial infarction, and target vessel revascularization at 5 years. Hazard ratios (HRs) for TVF were calculated per 0.01 unit decrease in post-PCI FFR using univariate and multivariate Cox proportional hazards models. Results The median post-PCI FFR overall was 0.88 (LAD: 0.87 vs. non-LAD: 0.94). A significant inverse relationship was observed between post-PCI FFR and TVF risk. Restricted cubic spline analysis identified vessel-specific optimal post-PCI FFR cutoff values: 0.86 for LAD and 0.93 for non-LAD vessels, with the LAD cutoff being significantly lower (p&amp;lt;0.05). Multivariate analysis confirmed these findings, showing similar optimal cutoff values (LAD: 0.87 vs. non-LAD: 0.93) after adjusting for confounders. Conclusion These results demonstrate that optimal post-PCI FFR cutoff values are vessel-dependent, emphasizing the importance of vessel-specific risk stratification and tailored post-PCI management strategies.Figure1:Histogram of post-PCI FFR

Abstract Background Coronary microvascular dysfunction (CMD) can be classified into two endotypes: endogenous and classical.1 The first subtype, termed "endogenous-type" CMD, is characterized by a relatively high baseline flow with a reduced coronary flow reserve (CFR). The "classical-type" CMD, exhibits elevated hyperemic resistance and a reduced CFR. While the presence of CMD post-percutaneous coronary intervention (PCI) has been reported to be linked to worse outcomes, the differential impact of these distinct CMD subtypes remains largely unexplored. Purpose This study aimed to evaluate the prognostic implications of these two CMD endotypes, classified using stress transthoracic doppler echocardiography (S-TDE)-derived flow velocity, in patients with chronic coronary syndrome after PCI. Methods We retrospectively studied 205 patients who underwent elective PCI for lesions in left anterior descending artery (LAD). Coronary diastolic peak flow velocity (DPV) in LAD was measured at rest and during hyperemia using S-TDE. Post-PCI CMD was defined as coronary flow velocity reserve (CFVR) ≤ 2.0 and further classified into endogenous or classical types based on resting DPV cutoff of 33 cm/s. This cutoff was determined based on the 34.6th percentile of sorted DPV values, corresponding to reduced CFVR (≤ 2.0) distribution. (Figure 1) We assessed the association between post-PCI CMD endotypes and major adverse cardiac events (MACE), defined as composite of cardiac death, myocardial infarction, heart failure hospitalization, and target vessel revascularization. Results During median follow-up of 2.3 years, 30 (14.6%) patients experienced MACE. The cumulative MACE rate was significantly worse in the CMD group with low CFVR (P=0.037). Among endogenous-type CMD, classical-type CMD, and non-CMD, prognosis was significantly different (P&amp;lt;0.001). Post-hoc analysis revealed worse prognosis for endogenous-type CMD compared to classical-type (P=0.033) and non-CMD (P=0.0018). (Figure 2) Multivariate Cox proportional hazard analysis showed endogenous-type CMD was independently associated with MACE (hazard ratio (HR), 3.28; 95% confidence interval (CI), 1.53-7.04; P=0.0022). Multivariate logistic regression analysis showed pre-PCI resting DPV (HR, 1.05; 95% CI, 1.02-1.09; P=0.0012) and pre-PCI average E/e’ (HR, 1.08; 95% CI, 1.01-1.16; P=0.029) were independently associated with post-PCI endogenous-type CMD. Conclusions Endogenous-type CMD, compared with classical type CMD, is independently associated with MACE. The use of pre-PCI S-TDE measurements, especially resting DPV and average E/e’, may help identify individuals at high risk of developing endogenous-type CMD post-PCI. Identification of CMD endotype post-PCI using S-TDE may help identify high-risk patients for MACE and guide personalized management strategies following FFR-guided PCI.Figure 1 Figure 2

One of the challenges in clinical genetics for rare diseases and personalized medicine is evaluating isoform alterations arising from heterozygous putative splicing variants at the allele level. Our aim was to analyze these variants by dividing cDNA or direct RNA nanopore long reads into two alleles, referencing whole-genome sequencing data containing allele-informative single nucleotide variants and then comparing the allele-separated reads using Full-Length Alternative Isoform analysis of RNA (FLAIR), a previously published bioinformatics tool for isoform analysis. In this study, we developed an allele-separative bioinformatics pipeline and described its performance. We applied our pipeline to previously published nanopore direct RNA sequencing data, as well as 5’ cap-trapping full-length cDNA nanopore sequencing (CTR-seq) data from blood samples of three individuals. We successfully identified heterozygous splicing variants associated with significant isoform differences between alleles. Furthermore, we uncovered the effects of a novel pathogenic splicing variant in PYGM on isoforms in a compound-heterozygous case of McArdle disease using nanopore cDNA amplicon and targeted genomic sequencing. This study demonstrates the utility of nanopore long-read sequencing for isoform analysis at the allele level, providing a valuable approach to evaluating the direct consequences of heterozygous splicing variants in individuals.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-14566-z.