Citations

Objective: This post hoc analysis of the CHAMPION-NMOSD trial evaluated the safety and efficacy of ravulizumab in patients with aquaporin-4 antibody-positive (AQP4-Ab+) neuromyelitis optica spectrum disorder (NMOSD) previously exposed or naïve to rituximab (RTX). Methods: Patients received weight-based intravenous ravulizumab with a loading dose followed by maintenance dosing every 8 weeks. Patients were stratified by prior RTX exposure: no RTX exposure (RTX-naïve) vs RTX exposure > 3 months before initiating ravulizumab (RTX-exposed). Key outcomes included treatment-emergent adverse events (TEAEs), serious TEAEs (TESAEs), relapse rates, and vaccination timing from the last RTX dose. Results: Of the 58 patients enrolled, 89.7% were female, with a mean age of 47.4 years, and 21/58 (36.2%) were RTX-exposed. Relapses occurred in 12/21 (57.1%) RTX-exposed patients between their first RTX dose and study entry. The safety profile of ravulizumab was generally similar between RTX-exposed and RTX-naïve groups. Common TEAEs included COVID-19, headache, urinary tract infection, and upper respiratory tract infection. UTIs were more frequent in RTX-exposed individuals. One patient in each group experienced a meningococcal infection. No adjudicated on-trial relapses were reported while on ravulizumab. Conclusions: Following initiation of ravulizumab, RTX-exposed and RTX-naïve patients with AQP4-Ab+ NMOSD achieved sustained disease control and demonstrated a manageable safety profile. Clinical Trial Information: The CHAMPION-NMOSD Trial; ClinicalTrials.gov identifier: NCT04201262 (registered October 06, 2020).

Abstract Background NRG/RTOG 1010 evaluated trastuzumab added to trimodality therapy for HER2+ localized esophageal adenocarcinoma (EAC) management. Secondary PRO objectives assessed improvement in the FACT‐Esophageal Cancer Subscale (ECS), version 4, with trastuzumab, and if improved ECS correlated with pathologic complete response (pCR). Methods Patients were randomized to weekly paclitaxel/carboplatin/radiation (chemoradiation, CRT) followed by surgery ± trastuzumab (CRT + Tras). Disease‐free survival (DFS) was the primary end point. The projected PRO sample size of 158 patients, based on an 80% participation rate of the DFS primary endpoint sample size of 197 HER2+ patients, would provide ≥ 89% power to detect ≥25% increase in the proportion of CRT + Tras patients with ECS improvement from baseline to 6–8 weeks post‐CRT; one‐sided α = 0.05, using a χ 2 test. Improvement in ECS and its swallowing index (SI) and eating index (EI) was defined as 5‐, 2‐, and 2‐point increases, respectively, from baseline to 6–8 weeks post‐CRT. Univariate logistic regression was assessed if pCR was associated with improved ECS. Results From 2010 to 2015, 203 HER2+ patients were randomized and 194 were eligible. Of 171 PRO consenting patients, the ECS was completed by 162 (95%) at baseline, 108 (64%) 6–8 weeks, 82 (49%) 1 year, and 55 (33%) at 2 years. The proportion of patients with an improvement in 6–8 weeks ECS was higher on the CRT + Tras arm (46% vs. 38%), although not significantly different ( p = .39). There was no correlation between pCR and ECS scores at 1 year, with 39% and 37% of pCR and non‐pCR patients, respectively, having improved 1‐year ECS scores. Conclusions The addition of trastuzumab to CRT for localized HER2+ EAC did not improve PROs.

Artificial intelligence (AI) and machine learning have emerged as transformative analytic methods capable of identifying patterns and proposing treatment strategies from complex, heterogeneous data generated in patient care settings. However, translating reports of AI tools into clinical decision-making requires careful interpretation and contextualization. Here, we present a structured framework (ABCDEFG framework) for clinicians to critically appraise studies reporting AI tools using a high-profile reinforcement learning analysis of vasopressin initiation in septic shock as a case example. We highlight key methodological strengths including adherence to reporting standards, alignment with clinical outcomes, and external validation. We also identify limitations related to causal inference, reward structure design, assumptions about state representation, and implementation readiness. Our framework emphasizes the importance of rigorous, clinically grounded critique before integrating AI tools into practice, and provides a roadmap for clinicians to assess the reliability and relevance of emerging AI-based decision support.

ABSTRACT Patients with neuromyelitis optica spectrum disorder (NMOSD) may experience increased signs and symptoms of their underlying disease when vaccinated against meningococcal disease before receiving complement component 5 inhibitor therapies. This retrospective analysis indicated an overall low relapse incidence (mean [range], 3.3% [0.7%–10.6%]) of physician‐reported relapses occurring within 4 weeks of meningococcal vaccination in those screened in CHAMPION‐NMOSD (NCT04201262), randomized to eculizumab or placebo in PREVENT (NCT01892345), and from the Japanese postmarketing surveillance of eculizumab in patients with anti‐aquaporin‐4 antibody‐positive NMOSD. Further studies are needed to determine if postvaccination relapses are attributable to vaccination or inherent relapse risk among these patients.

Background Effective patient education is critical for informed decision-making and adherence in kidney transplantation. Generative artificial intelligence (AI), particularly large language models (LLMs), has the potential to enhance patient education in kidney transplantation; however, its factual accuracy and readability remain incompletely characterized. Methods We evaluated the performance of the GPT-5.1 (2025) model in generating plain-language explanations for 100 clinically relevant kidney transplantation terms. Explanations were generated using a standardized prompt (first round) and a revised prompt explicitly requesting an eighth-grade reading level or lower (second round). Accuracy was assessed by expert reviewers using a 5-point Likert scale, while readability was evaluated using the Flesch Reading Ease (higher score indicated easier readability of the text) and Flesch–Kincaid Grade Level (higher score indicated higher education level required to understand the text) score. The study was conducted in November 2025. Results All AI-generated explanations demonstrated high accuracy, with no clinically significant errors. In the first round, the mean Flesch Reading Ease score was 23.6 ± 23.4, indicating very difficult readability, and 46% of explanations required a college-level reading ability (mean Flesch–Kincaid Grade Level 13.4 ± 4.8). Following prompt revision, readability improved substantially. The mean Flesch Reading Ease score increased to 62.4 ± 7.5, corresponding to standard readability, and all explanations were written at a middle school level or below (mean Flesch–Kincaid Grade Level 6.3 ± 1.1). Conclusion GPT-5.1 generated highly accurate explanations of kidney transplantation terms across prompting strategies. Explicit readability-focused prompting substantially improved readability without compromising accuracy, underscoring the importance of prompt design when deploying LLMs for patient-centered education in transplantation.

Background Chronic graft versus host disease (cGVHD) is a complex post-transplant complication resulting in varying degrees of musculoskeletal (MSK) manifestations, including sclerosis-type skin conditions, fasciitis, and osteopenia, avascular necrosis affecting the shoulder, elbow and hands apart from other joints of the body. A large proportion of these can often miss out on the expertise of upper limb therapists. Study Objectives This paper aims to outline upper limb cGVHD manifestations to raise awareness among upper limb physiotherapists and rehabilitation specialists, so that patients can receive more focused, optimal care. Methods An electronic search was conducted across a wide database covering the period from 1990 to 2025. Further manual search used Google Scholar to help identify relevant articles. Boolean operators ‘AND’ and ‘OR’ combined keywords such as chronic graft versus host disease, acute graft versus host disease, allogenic hematopoietic stem cell transplantation, hematopoietic cell transplantation, stem cell transplant, bone marrow transplant, physiotherapy, upper limb specialist, musculoskeletal, fasciitis, and scleroderma. Results A total of 4,393 titles were screened against the pre-set inclusion and exclusion criteria, and only 3 articles were found to be suitable for this narrative review. All 3 articles were case studies of upper limb cGVHD and rehabilitation reporting positive outcomes on patients’ upper and lower limb range of motion, function, and quality of life (QoL). Conclusion cGVHD can cause various MSK issues, especially in the upper limbs. It is important to collaborate with upper limb physiotherapy and occupational therapy experts to improve awareness and patient outcomes.

Abstract Platinum-based chemotherapy remains a cornerstone of treatment for triple-negative breast cancer (TNBC), yet the molecular determinants governing platinum response remain poorly defined. By leveraging the randomized Phase II INFORM trial, which compared neoadjuvant cisplatin to anthracycline-based therapy in BRCA1/2 -mutant breast cancer—we identified miR-362-3p as a specific regulator of cisplatin sensitivity. Higher plasma miR-362-3p expression was exclusively associated with favorable clinical outcome in the cisplatin arm, with no association observed in the AC arm, decoupling platinum-specific vulnerability from general chemotherapy response. We used gain- and loss-of-function TNBC models to establish that miR-362-3p functions as a potent sensitizer to cisplatin in vitro and in vivo . Integrated TCGA analysis and experimental validation identified BCLAF1, a key regulator of DNA damage response, as a direct repression target of miR-362-3p. We uncovered a novel role for the miR-362-3p/ BCLAF1 axis in overcoming platinum resistance in TNBC.