Improved Electrochemical Peptide Synthesis Enabled by Electron-Rich Triaryl Phosphines.

While remarkable progress has been made in the development of peptide medicines, many problems related to peptide synthesis remain unresolved. Previously, we reported electrochemical peptide synthesis using a phosphine as a potentially recyclable coupling reagent. However, there was room for improvement from the point of view of reaction efficiency, especially in the carboxylic acid activation step and the peptide bond formation step. To overcome these challenges, we searched for the optimal phosphine. Among phosphines with various electronic properties, we found that electron-rich triaryl phosphines improved the reaction efficiency. Consequently, we successfully performed electrochemical peptide synthesis on sterically hindered and valuable amino acids. We also synthesized oligopeptides that were challenging with our previous method. Finally, we examined the effect of substituents on the phosphine cations, and gained some insights into reactivity, which will aid researchers designing reactions involving phosphine cations.

Influence of different standing positions on anatomical parameters of coronal whole-leg weight-bearing radiographs in preoperative planning for high tibial osteotomy.

Purpose: The purpose of this study was to assess the differences in lower limb global alignment and anatomical parameters of coronal whole-leg radiographs, which were generally used in preoperative planning for high tibial osteotomy (HTO), according to different weight-bearing standing positions. Methods: Between April 2021 and December 2022, 176 patients (60 males and 116 females) were investigated. Full-weight-bearing coronal whole-leg radiographs were obtained with the patella centred on the femoral condyle. Patients were divided by Kellgren-Lawrence grade (KL-0, KL-I, KL-II and KL-III) and assessed in two standing positions: legs closed and legs spread. Patients with flexion contractures or those unable to stand with full weight bearing were excluded. The mechanical distal femoral angle, medial proximal tibial angle (MPTA), femorotibial angle, joint line convergence angle, percentage weight-bearing line (%WBL) and hip-knee-ankle angle (HKAA) were measured. The Student's t test was used to compare the two standing positions. A p value < 0.05 indicated a statistically significant difference. Results: The MPTAs of legs closed standing and legs spread standing were 84.9 ± 2.6° and 85.1 ± 2.4° in KL-0, 84.7 ± 2.0° and 84.9 ± 2.1° in KL-I and 85.0 ± 2.43° and 85.4 ± 2.4° in KL-II, respectively. There were statistically significant differences in the MPTA between the two standing positions in KL-0, KL-I and KL-II. In contrast, the %WBL and HKAA did not change regardless of the standing position. In the KL-III group, no statistical significance was observed for any of the anatomical parameters. Conclusion: Several anatomical parameters were changed between the legs closed standing and the legs spread standing positions. It was suggested that the standing position should be taken into consideration in the planning for HTO. Level of Evidence: Level IV, Case series with no comparison group.

High tibial osteotomy alone does not decrease medial meniscus extrusion in the setting of medial meniscus posterior root tear: A cadaveric study.

PURPOSE: This study investigated whether inducing valgus alignment and shifting the load laterally through high tibial osteotomy (HTO) alone decreases the extent of medial meniscus extrusion (MME) in the setting of medial meniscus posterior root tear(MMPRT) using ultrasound evaluation. METHODS: Eight fresh-frozen human cadaveric knee specimens were tested using a six-degree-of-freedom robotic testing system and ultrasound. Each specimen was tested in five conditions: (1) intact, (2) MMPRT, (3) medial meniscus repair (MMR), (4) combined medial open-wedge HTO + MMR, and (5) HTO + MMPRT. Measurements were obtained over the medial collateral ligament (MCL, central image) and posterior to the MCL (posterior image) with a 250 N axial load at 0°, 30°, and 90° of knee flexion. Statistical analysis was performed using a two-factor repeated-measures ANOVA. RESULTS: MME was significantly greater in HTO + MMPRT(0°: 2.44 ± 0.41mm, 30°: 2.47 ± 0.37mm, 90°: 2.41 ± 0.28mm) than HTO + MMR in central images (mean difference +0.83 mm, p < .001). No significant difference was found between HTO + MMPRT and MMPRT in MME . MMR had significantly less MME than MMPRT (mean difference -0.58mm, p < .001, posterior image at 0°and central image at 90°, p=.002). HTO + MMR showed significantly less MME than MMR alone at 30° and 90° knee flexion in central image (30°: -0.38 ± 0.05mm, 90°: -0.45 ± 0.06mm, p < .001) and 90° knee flexion in posterior image (-0.38 ± 0.08mm, p = .004). CONCLUSION: HTO alone did not decrease MME in the setting of MMPRT, while MMR alone decrease MME after MMPRT. Additionally, HTO + MMR decreases MME aftrer MMPRT compared to MMR alone, although the clinical significance was uncertain. CLINICAL RELEVANCE: The findings of this study provide clinicians with valuable insights for improving MME. HTO alone does not decrease MME in cases of MMPRT.

Performance of a Large Language Model in Screening Citations.

Importance: Large language models (LLMs) are promising as tools for citation screening in systematic reviews. However, their applicability has not yet been determined. Objective: To evaluate the accuracy and efficiency of an LLM in title and abstract literature screening. Design, Setting, and Participants: This prospective diagnostic study used the data from the title and abstract screening process for 5 clinical questions (CQs) in the development of the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock. The LLM decided to include or exclude citations based on the inclusion and exclusion criteria in terms of patient, population, problem; intervention; comparison; and study design of the selected CQ and was compared with the conventional method for title and abstract screening. This study was conducted from January 7 to 15, 2024. Exposures: LLM (GPT-4 Turbo)-assisted citation screening or the conventional method. Main Outcomes and Measures: The sensitivity and specificity of the LLM-assisted screening process was calculated, and the full-text screening result using the conventional method was set as the reference standard in the primary analysis. Pooled sensitivity and specificity were also estimated, and screening times of the 2 methods were compared. Results: In the conventional citation screening process, 8 of 5634 publications in CQ 1, 4 of 3418 in CQ 2, 4 of 1038 in CQ 3, 17 of 4326 in CQ 4, and 8 of 2253 in CQ 5 were selected. In the primary analysis of 5 CQs, LLM-assisted citation screening demonstrated an integrated sensitivity of 0.75 (95% CI, 0.43 to 0.92) and specificity of 0.99 (95% CI, 0.99 to 0.99). Post hoc modifications to the command prompt improved the integrated sensitivity to 0.91 (95% CI, 0.77 to 0.97) without substantially compromising specificity (0.98 [95% CI, 0.96 to 0.99]). Additionally, LLM-assisted screening was associated with reduced time for processing 100 studies (1.3 minutes vs 17.2 minutes for conventional screening methods; mean difference, -15.25 minutes [95% CI, -17.70 to -12.79 minutes]). Conclusions and Relevance: In this prospective diagnostic study investigating the performance of LLM-assisted citation screening, the model demonstrated acceptable sensitivity and reasonably high specificity with reduced processing time. This novel method could potentially enhance efficiency and reduce workload in systematic reviews.

External Validation of Updated Prediction Models for Neurological Outcomes at 90 Days in Patients With Out-of-Hospital Cardiac Arrest.

BACKGROUND: Few prediction models for individuals with early-stage out-of-hospital cardiac arrest (OHCA) have undergone external validation. This study aimed to externally validate updated prediction models for OHCA outcomes using a large nationwide dataset. METHODS AND RESULTS: We performed a secondary analysis of the JAAM-OHCA (Comprehensive Registry of In-Hospital Intensive Care for Out-of-Hospital Cardiac Arrest Survival and the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest) registry. Previously developed prediction models for patients with cardiac arrest who achieved the return of spontaneous circulation were updated. External validation was conducted using data from 56 institutions from the JAAM-OHCA registry. The primary outcome was a dichotomized 90-day cerebral performance category score. Two models were updated using the derivation set (n=3337). Model 1 included patient demographics, prehospital information, and the initial rhythm upon hospital admission; Model 2 included information obtained in the hospital immediately after the return of spontaneous circulation. In the validation set (n=4250), Models 1 and 2 exhibited a C-statistic of 0.945 (95% CI, 0.935-0.955) and 0.958 (95% CI, 0.951-0.960), respectively. Both models were well-calibrated to the observed outcomes. The decision curve analysis showed that Model 2 demonstrated higher net benefits at all risk thresholds than Model 1. A web-based calculator was developed to estimate the probability of poor outcomes (https://pcas-prediction.shinyapps.io/90d_lasso/). CONCLUSIONS: The updated models offer valuable information to medical professionals in the prediction of long-term neurological outcomes for patients with OHCA, potentially playing a vital role in clinical decision-making processes.

Association between the severity of hypothermia and in-hospital mortality in patients with infectious diseases: The J-Point registry.

Aim: Hypothermia is associated with poor prognosis in patients with sepsis. However, no studies have explored the correlation between the severity of hypothermia and prognosis. Methods: Using data from the Japanese accidental hypothermia network registry (J-Point registry), we examined adult patients aged ≥18 years with infectious diseases whose initial body temperature was ≤35°C from April 1, 2011 to March 31, 2016, in 12 centers. Patients were divided into three groups according to their body temperature: Tertile 1 (T1) (32.0-35.0°C), Tertile 2 (T2) (28.0-31.9°C), and Tertile 3 (T3) (<28.0°C). In-hospital mortality was employed as a metric to assess outcomes. We conducted a multivariate logistic regression analysis to investigate the relationship between the three categories and the occurrence of in-hospital mortality. Results: A total of 572 patients were registered, and 170 eligible patients were identified. Of these patients, 55 were in T1 (32.0-35.0°C), 76 in T2 (28.0-31.9°C), and 39 in T3 (<28.0°C) groups. The overall in-hospital mortality rate in accidental hypothermia (AH) patients with infectious diseases was 34.1%. The in-hospital mortality rates in the T1, T2, and T3 groups were 34.5%, 36.8%, and 28.2%, respectively. The multivariable analysis demonstrated no significant differences regarding in-hospital mortality among the three groups (T2 vs. T1, adjusted odds ratio [OR]: 1.29; 95% confidence interval [CI]: 0.58-2.89 and T3 vs. T1, adjusted OR: 0.83; 95% CI: 0.30-2.31). Conclusion: In this multicenter retrospective observational study, hypothermia severity was not associated with in-hospital mortality in AH patients with infectious diseases.

Association between eGFR and neurological outcomes among patients with out-of-hospital cardiac arrest: A nationwide prospective study in Japan.

Aim: We aimed to investigate the association between estimated glomerular filtration rate and prognosis in out-of-hospital cardiac arrest patients and explore the heterogeneity of the association. Methods: Patients experiencing out-of-hospital cardiac arrest due to medical causes and registered in the JAAM-OHCA Registry between June 2014 and December 2019 were stratified into shockable rhythm, pulseless electrical activity, and asystole groups according to the cardiac rhythm at the scene. The primary outcome was a 1-month favorable neurological status. Adjusted odds ratios with 95% confidence intervals were calculated to investigate the association between estimated glomerular filtration rate and outcomes using a logistic model. Results: Of the 19,443 patients included, 2769 had initial shockable rhythm at the scene, 5339 had pulseless electrical activity, and 11,335 had asystole. As the estimated glomerular filtration rate decreased, the adjusted odds ratio for a 1-month favorable neurological status decreased among those with initial shockable rhythm (estimated glomerular filtration rate, adjusted odds ratio [95% CI]: 45-59 mL/min/1.73 m2, 0.61 [0.47-0.79]; 30-44 mL/min/1.73 m2, 0.45 [0.32-0.62]; 15-29 mL/min/1.73 m2, 0.35 [0.20-0.63]; and <15 mL/min/1.73 m2, 0.14 [0.07-0.27]). Estimated glomerular filtration rate was associated with neurological outcomes in patients aged <65 years with initial shockable rhythm but not in those aged >65 years or patients with initial pulseless electrical activity or asystole. Conclusion: The estimated glomerular filtration rate is associated with neurological prognosis in out-of-hospital cardiac arrest patients with initial shockable rhythm at the scene but not in those with initial non-shockable rhythm.

Non-linear association between the time required to reaching temperature targets and the neurological outcome in patients undergoing targeted temperature management after out-of-hospital cardiac arrest: Observational multicentre cohort study.

Purpose: We evaluated associations between outcomes and time to achieving temperature targets during targeted temperature management of out-of-hospital cardiac arrest. Methods: Using Comprehensive Registry of Intensive Care for out-of-hospital cardiac arrest Survival (CRITICAL) study, we enrolled all patients transported to participating hospitals from 1 July 2012 through 31 December 2017 aged ≥ 18 years with out-of-hospital cardiac arrest of cardiac aetiology and who received targeted temperature management in Osaka, Japan. Primary outcome was Cerebral Performance Category scale of 1 or 2 one month after cardiac arrest, designated as "one-month favourable neurological outcome". Non-linear multivariable logistic regression analyses assessed the primary outcome based on time to reaching temperature targets. In patients subdivided into quintiles based on time to achieving temperature targets, multivariable logistic regression calculated adjusted odds ratios and 95% confidence intervals. Results: We analysed 473 patients. In non-linear multivariable logistic regression analysis, p value for non-linearity was < 0.01. In the first quintile (< 26.7 minutes), second quintile (26.8-89.9 minutes), third quintile (90.0-175.1 minutes), fourth quintile (175.2-352.1 minutes), and fifth quintile (≥ 352.2 minutes), one-month favourable neurological outcome was 32.6% (31/95), 40.0% (36/90), 53.5% (53/99), 57.4% (54/94), and 37.9% (36/95), respectively. Adjusted odds ratios with 95% confidence intervals for one-month favourable neurological outcome in the first, second, third, and fifth quintiles compared with the fourth quintile were 0.38 (0.20 to 0.72), 0.43 (0.23 to 0.81), 0.77 (0.41 to 1.44), and 0.46 (0.25 to 0.87), respectively. Conclusion: Non-linear multivariable logistic regression analysis could clearly describe the association between neurological outcome in patients with out-of-hospital cardiac arrest and the time from the introduction of targeted temperature management to reaching the temperature targets.

Association between gasping and survival among out-of-hospital cardiac arrest patients undergoing extracorporeal cardiopulmonary resuscitation: The SOS-KANTO 2017 study.

Aim: This study aimed to assess the association between gasping and survival among out-of-hospital cardiac arrest (OHCA) patients requiring extracorporeal cardiopulmonary resuscitation (ECPR). Methods: This prospective, multicenter, observational study was conducted between 2019 and 2021. We categorized adult patients requiring ECPR into those with or without gasping prior to hospital arrival. The primary outcome was the 30-day survival. We performed multivariable logistic regression analyses fitted with generalized estimating equations and subgroup analyses based on the initial rhythm and age. Results: Of the 9,909 patients with OHCA requiring ECPR, 332 were enrolled in the present study, including 92 (27.7%) and 240 (72.3%) with and without gasping, respectively. The 30-day survival was higher in patients with gasping than in those without gasping (35.9% [33/92] vs. 16.2% [39/240]). In the logistic regression analysis, gasping was significantly associated with improved 30-day survival (adjusted odds ratio: 3.01; 95% confidence interval, 1.64-5.51). Subgroup analyses demonstrated similar trends in patients with an initial non-shockable rhythm and older age. Conclusions: Gasping was associated with improved survival in OHCA patients requiring ECPR, even those with an initial non-shockable rhythm and older age. Clinicians may select the candidates for ECPR appropriately based on the presence of gasping.

Evaluating the impact of ELSO guideline adherence on favorable neurological outcomes among patients requiring extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest.

AIM: Selecting the appropriate candidates for extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA) is challenging. Previously, the Extracorporeal Life Support Organization (ELSO) guidelines suggested the example of inclusion criteria. However, it is unclear whether patients who meet the inclusion criteria of the ELSO guidelines have more favorable outcomes. We aimed to evaluate the relationship between the outcomes and select inclusion criteria of the ELSO guidelines. METHODS: We conducted a post-hoc analysis of a multicenter prospective study conducted between 2019 and 2021. Adult patients with OHCA treated with ECPR were included. The primary outcome was a favorable neurological outcome (Cerebral Performance Category of 1 or 2) at 30 days. An ELSO criteria score was assigned based on four criteria: (i) age < 70 years; (ii) witness; (iii) bystander CPR; and (iv) low-flow time (<60 min). Subgroup analysis based on initial cardiac rhythm was performed. RESULTS: Among 9,909 patients, 227 with OHCA were included. The proportion of favorable neurological outcomes according to the number of ELSO criteria met were: 0.0% (0/3), 0 points; 0.0% (0/23), 1 point; 3.0% (2/67), 2 points; 7.3% (6/82), 3 points; and 16.3% (7/43), 4 points. A similar tendency was observed in patients with an initial shockable rhythm. However, no such relationship was observed in those with an initial non-shockable rhythm. CONCLUSION: Patients who adhered more closely to specific inclusion criteria of the ELSO guidelines demonstrated a tendency towards a higher rate of favorable neurological outcomes. However, the relationship was heterogeneous according to initial rhythm.

Understanding Flexdispersion: Structure-Function Relationship Studies of Organic Amphiphilic Ligands.

Since inorganic nanoparticles have unique properties that differ from those of bulk materials, their material applications have attracted attention in various fields. In order to utilize inorganic nanoparticles for functional materials, they must be dispersed without agglomeration. Therefore, the surfaces of inorganic nanoparticles are typically modified with organic ligands to improve their dispersibility. Nevertheless, the relationship between the tail group structure in organic ligands and the dispersibility of inorganic nanoparticles in organic solvents remains poorly understood. We previously developed amphiphilic ligands that consist of ethylene glycol chains and alkyl chains to disperse inorganic nanoparticles in a variety of organic solvents. However, the structural requirements for amphiphilic ligands to "flexibly" disperse nanoparticles in less polar to polar solvents are still unclear. Here, we designed and synthesized several phosphonic acid ligands for structure-function relationship studies of flexdispersion. Dynamic light scattering analysis and visible light transmittance measurements revealed that the ratio of alkyl/ethylene glycol chains in organic ligands alone does not determine the dispersibility of the nanoparticles in organic solvents, but the arrangement of the individual chains also has an effect. From a practical application standpoint, it is preferable to design ligands with ethylene glycol chains on the outside relative to the particle surface.

Global real-world experiences with pembrolizumab in advanced urothelial carcinoma after platinum-based chemotherapy: the ARON-2 study.

BACKGROUND: Immune checkpoint inhibitors have changed previous treatment paradigm of advanced urothelial carcinoma (UC). The ARON-2 study (NCT05290038) aimed to assess the real-world effectiveness of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy. PATIENTS AND METHODS: Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were retrospectively collected from 88 institutions in 23 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS) and overall response rate (ORR). Cox proportional hazards models were adopted to explore the presence of prognostic factors. RESULTS: In total, 836 patients were included: 544 patients (65%) received pembrolizumab after progression to first-line platinum-based chemotherapy in the metastatic setting (cohort A) and 292 (35%) after recurring within < 12 months since the completion of adjuvant or neoadjuvant chemotherapy (cohort B). The median follow-up time was 15.3 months. The median OS and the ORR were 10.5 months and 31% in the overall study population, 9.1 months and 29% in cohort A and 14.6 months and 37% in cohort B. At multivariate analysis, ECOG-PS ≥ 2, bone metastases, liver metastases and pembrolizumab setting (cohort A vs B) proved to be significantly associated with worst OS and PFS. Stratified by the presence of 0, 1-2 or 3-4 prognostic factors, the median OS was 29.4, 12.5 and 4.1 months (p < 0.001), while the median PFS was 12.2, 6.4 and 2.8 months, respectively (p < 0.001). CONCLUSIONS: Our study confirms that pembrolizumab is effective in the advanced UC real-world context, showing outcome differences between patients recurred or progressed after platinum-based chemotherapy.

Impact of time to revascularization on outcomes in patients after out-of-hospital cardiac arrest with STEMI.

BACKGROUND: International guidelines recommend emergency coronary angiography in patients after out-of-hospital cardiac arrest (OHCA) with ST-segment elevation on 12­lead electrocardiography. However, the association between time to revascularization and outcomes remains unknown. This study aimed to evaluate the association between time to revascularization and outcomes in patients with OHCA due to ST-segment-elevation myocardial infarction (STEMI) who underwent percutaneous coronary intervention (PCI). METHODS: This multicenter, retrospective, nationwide observational study included patients aged ≥18 years with OHCA due to STEMI who underwent PCI between 2014 and 2020. The time of the first return of spontaneous circulation (ROSC) was defined as the time of first ROSC during resuscitation, regardless of the pre-hospital or in-hospital setting. The primary outcome was a 1-month favorable neurological outcome, defined as cerebral performance category 1 or 2. Multivariable logistic regression analysis was used to assess the association between the time to revascularization and favorable neurological outcomes. RESULTS: A total of 547 patients were included in this analysis. The multivariable logistic regression analysis showed that a shorter time from the first ROSC to revascularization was associated with 1-month favorable neurological outcomes (63/86 [73.3%] in the time from the first ROSC to revascularization ≤60 min group versus 98/193 [50.8%] in the >120 min group; adjusted OR, 0.26; 95% CI, 0.11-0.56; P for trend, 0.015). CONCLUSIONS: Shorter time to revascularization was significantly associated with 1-month favorable neurological outcomes in patients with OHCA due to STEMI who underwent PCI.

Machine learning prediction of refractory ventricular fibrillation in out-of-hospital cardiac arrest using features available to EMS.

Background: Shock-refractory ventricular fibrillation (VF) or ventricular tachycardia (VT) is a treatment challenge in out-of-hospital cardiac arrest (OHCA). This study aimed to develop and validate machine learning models that could be implemented by emergency medical services (EMS) to predict refractory VF/VT in OHCA patients. Methods: This was a retrospective study examining adult non-traumatic OHCA patients brought into the emergency department by Singapore EMS from the Pan-Asian Resuscitation Outcomes Study (PAROS) registry. Data from April 2010 to March 2020 were extracted for this study. Refractory VF/VT was defined as VF/VT persisting or recurring after at least one shock. Features were selected based on expert clinical opinion and availability to dispatch prior to arrival at scene. Multivariable logistic regression (MVR), LASSO and random forest (RF) models were investigated. Model performance was evaluated using receiver operator characteristic (ROC) area under curve (AUC) analysis and calibration plots. Results: 20,713 patients were included in this study, of which 860 (4.1%) fulfilled the criteria for refractory VF/VT. All models performed comparably and were moderately well-calibrated. ROC-AUC were 0.732 (95% CI, 0.695 - 0.769) for MVR, 0.738 (95% CI, 0.701 - 0.774) for LASSO, and 0.731 (95% CI, 0.690 - 0.773) for RF. The shared important predictors across all models included male gender and public location. Conclusion: The machine learning models developed have potential clinical utility to improve outcomes in cases of refractory VF/VT OHCA. Prediction of refractory VF/VT prior to arrival at patient's side may allow for increased options for intervention both by EMS and tertiary care centres.

Relationship between increased knee joint line obliquity after medial open-wedge high tibial osteotomy and patient-reported outcome measures.

INTRODUCTION: This study evaluated the correlation between postoperative knee joint line obliquity after medial open-wedge high tibial osteotomy and patient-reported outcome measures excluding excessively overcorrected knees. This study further identified preoperative radiological factors related to the increased postoperative knee joint line obliquity. MATERIALS AND METHODS: We retrospectively evaluated patients who underwent medial open-wedge high tibial osteotomy between March 2013 and March 2021. Postoperative excessively overcorrected knees with hip-knee-ankle angle > 7° were excluded. We investigated radiological parameters and patient-reported outcome measures preoperatively and at the last follow-up. The following radiologic parameters were measured: hip-knee-ankle angle, weight-bearing line ratio, mechanical medial proximal tibial angle, mechanical lateral distal femoral angle, lateral distal tibial angle, joint line convergent angle, knee joint line obliquity, ankle joint line obliquity, hip abduction angle, tibial posterior slope, Carton-Deschamps index, and patella tilting angle. Clinical outcomes were evaluated using Japanese knee outcome measures. This assessment criterion is based on the Western Ontario McMaster Universities Arthritis Index and MOS Short Form 36. Multiple regression analysis was performed to evaluate the association between postoperative knee joint line obliquity and patient-reported outcome measures or preoperative radiological factors (P < .05). RESULTS: A total of 52 knees were included. The mean age at the time of the surgery was 61.6 ± 9.0 years and the mean follow-up period was 30.6 ± 10.1 months. Increased postoperative knee joint line obliquity was associated with lower Japanese knee outcome measures. The preoperative hip-knee-ankle angle was significantly associated with postoperative knee joint line obliquity. CONCLUSIONS: Increased knee joint line obliquity after medial open-wedge high tibial osteotomy is associated with inferior clinical outcomes. Care should be given to the center of the rotational angulation in around-knee osteotomy to avoid postoperative increased knee joint line obliquity. LEVEL OF EVIDENCE: Retrospective comparative study, Level III.

Development and validation of a scoring system for in-hospital mortality following band ligation in esophageal variceal bleeding.

OBJECTIVES: We aimed to develop and validate a simple scoring system to predict in-hospital mortality after endoscopic variceal ligation (EVL) for esophageal variceal bleeding. METHODS: Data from a 13-year study involving 46 Japanese institutions were split into development (initial 7 years) and validation (last 6 years) cohorts. The study subjects were patients hospitalized for esophageal variceal bleeding and treated with EVL. Variable selection was performed using least absolute shrinkage and selection operator regression, targeting in-hospital all-cause mortality as the outcome. We developed the Hospital Outcome Prediction following Endoscopic Variceal Ligation (HOPE-EVL) score from ß coefficients of multivariate logistic regression and assessed its discrimination and calibration. RESULTS: The study included 980 patients: 536 in the development cohort and 444 in the validation cohort. In-hospital mortality was 13.6% and 10.1% for the respective cohorts. The scoring system used five variables: systolic blood pressure (<80 mmHg: 2 points), Glasgow Coma Scale (≤12: 1 point), total bilirubin (≥5 mg/dL: 1 point), creatinine (≥1.5 mg/dL: 1 point), and albumin (<2.8 g/dL: 1 point). The risk groups (low: 0-1, middle: 2-3, high: ≥4) in the validation cohort corresponded to observed and predicted mortality probabilities of 2.0% and 2.5%, 19.0% and 22.9%, and 57.6% and 71.9%, respectively. In this cohort, the HOPE-EVL score demonstrated excellent discrimination ability (area under the curve [AUC] 0.890; 95% confidence interval [CI] 0.850-0.930) compared with the Model for End-stage Liver Disease score (AUC 0.853; 95% CI 0.794-0.912) and the Child-Pugh score (AUC 0.798; 95% CI 0.727-0.869). CONCLUSIONS: The HOPE-EVL score practically and effectively predicts in-hospital mortality. This score could facilitate the appropriate allocation of resources and effective communication with patients and their families.

Prognostic value of micrometric substaging in pT1 bladder cancer patients treated with en-bloc transurethral resection.

AIMS: We aimed to assess the oncological impact of micrometric extent of invasion in patients with pT1 bladder cancer (BCa) who underwent en-bloc resection for bladder tumour (ERBT). METHODS AND RESULTS: We retrospectively analysed the records and specimens of 106 pT1 high-grade BCa patients who underwent ERBT. The extent of invasion, such as depth from basal membrane, number of invasive foci, maximum width of invasive focus, muscularis mucosae invasion and infiltration pattern (pattern A: solid sheet-like, nodular or nested growth, pattern B: trabecular, small cluster or single-cell pattern) were evaluated by a single genitourinary pathologist. The end-points were recurrence-free (RFS) and progression-free survival (PFS). Within a median follow-up of 23 months, overall, 36 patients experienced recurrence and 13 patients experienced disease progression. The 2-year PFS differed significantly depending on depth from basal membrane (< 1.3 mm: 94.8% versus ≧ 1.3 mm: 65.2%, P = 0.005), maximum width of invasive focus (< 4 mm: 91.7% versus ≧ 4 mm: 62.3%, P < 0.001), muscularis mucosae (MM) invasion (above MM = 96.1% versus into or beyond MM = 64.8%, P = 0.002) and infiltration pattern (pattern A: 100% versus pattern B: 83.3%, P = 0.037). In a multivariable analysis, MM invasion [hazard ratio (HR) = 4.54, 95% confidence interval (CI) = 1.25-16.5] and maximum width of invasive focus ≧ 4 mm (HR = 4.79, 95% CI = 1.25-16.5) were independent prognostic factors of progression. CONCLUSIONS: En-bloc resection facilitates the evaluation of pathologic variables that might be useful in predicting disease recurrence and progression. In particular, not only the MM invasion but also the maximum width of invasion focus, reflecting the invasive volume, appear to be reliable prognosticators for disease progression.

Extracorporeal cardiopulmonary resuscitation versus conventional CPR in cardiac arrest: an updated meta-analysis and trial sequential analysis.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) may reduce mortality and improve neurological outcomes in patients with cardiac arrest. We updated our existing meta-analysis and trial sequential analysis to further evaluate ECPR compared to conventional CPR (CCPR). METHODS: We searched three international databases from 1 January 2000 through 1 November 2023, for randomised controlled trials or propensity score matched studies (PSMs) comparing ECPR to CCPR in both out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). We conducted an updated random-effects meta-analysis, with the primary outcome being in-hospital mortality. Secondary outcomes included short- and long-term favourable neurological outcome and survival (30 days-1 year). We also conducted a trial sequential analysis to evaluate the required information size in the meta-analysis to detect a clinically relevant reduction in mortality. RESULTS: We included 13 studies with 14 pairwise comparisons (6336 ECPR and 7712 CCPR) in our updated meta-analysis. ECPR was associated with greater precision in reducing overall in-hospital mortality (OR 0.63, 95% CI 0.50-0.79, high certainty), to which the trial sequential analysis was concordant. The addition of recent studies revealed a newly significant decrease in mortality in OHCA (OR 0.62, 95% CI 0.45-0.84). Re-analysis of relevant secondary outcomes reaffirmed our initial findings of favourable short-term neurological outcomes and survival up to 30 days. Estimates for long-term neurological outcome and 90-day-1-year survival remained unchanged. CONCLUSIONS: We found that ECPR reduces in-hospital mortality, improves neurological outcome, and 30-day survival. We additionally found a newly significant benefit in OHCA, suggesting that ECPR may be considered in both IHCA and OHCA.

The Neurorehabilitation of Neurological Movement Disorders Requires Rigorous and Sustained Research.

Movement disorders that stem from neurological conditions such as stroke, cerebral palsy, multiple sclerosis (MS), Parkinson's disease (PD), and spinocerebellar degeneration (SCD) can significantly impair a person's activities of daily living (ADL) [...].

Overview and future prospects of out-of-hospital cardiac arrest registries in Japan.

Aim: Out-of-hospital cardiac arrest (OHCA) is a life-threatening emergency with high mortality. The "chain of survival" is critical to improving patient outcomes. To develop and enhance this chain of survival, measuring and monitoring the resuscitation processes and outcomes are essential for quality assurance. In Japan, several OHCA registries have successfully been implemented at both local and national levels. We aimed to review and summarise the conception, strengths, and challenges of OHCA registries in Japan. Method and results: The following representing registries in Japan were reviewed: the All-Japan Utstein registry, the Utstein Osaka Project/the Osaka-CRITICAL study, the SOS-KANTO study, the JAAM-OHCA study, and the SAVE-J II study. The All-Japan Utstein registry, operated by the Fire and Disaster Management Agency of Japan and one of the largest nationwide population-based registries in the world, collects data concerning all patients with OHCA in Japan, excluding in-hospital data. Other research- and hospital-based registries collect detailed out-of-hospital and in-hospital data. The Osaka-CRITICAL study and the SOS-KANTO study are organized at regional levels, and hospitals in the Osaka prefecture and in the Kanto area participate in these registries. The JAAM-OHCA study is managed by the Japanese Association of Acute Medicine and includes 107 hospitals throughout Japan. The Save-J II study focuses on patients with OHCA treated with extracorporeal cardiopulmonary resuscitation. Conclusion: Each OHCA registry has its own philosophy, strengths, perspectives, and challenges; however, all have been successful in contributing to the improvement of emergency medical service (EMS) systems through the quality improvement process. These registries are expected to be further utilized to enhance EMS systems and improve outcomes for patients with OHCA, while also contributing to the field of resuscitation science.