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The pipeline for new drugs against multidrug-resistant Pseudomonas aeruginosa remains limited, highlighting the urgent need for innovative treatments. New strategies, such as membrane-targeting molecules acting as adjuvants, aim to enhance antibiotic effectiveness and combat resistance. RW01, a cyclic peptide with low antimicrobial activity, was selected as an adjuvant to enhance drug efficacy through membrane permeabilization. RW01's activity was evaluated via antimicrobial susceptibility testing in combination with existing antibiotics on 10 P. aeruginosa strains and analog synthesis. Synergy was assessed using checkerboard assays, and one-step mutants were generated to identify altered pathways through whole-genome sequencing and variant analysis. Permeabilizing activity was studied using flow cytometry and real-time fluorescence measurement. In vivo toxicity was assessed in female C57BL/6J mice, and possible interaction with mouse serum was also evaluated. Susceptibility testing revealed specific synergy with tetracyclines, with up to a 16-fold reduction in minimum inhibitory concentrations. Sequencing revealed that resistance to the RW01-minocycline combination involved mutations in the pmrB gene, affecting outer membrane lipopolysaccharide composition. This was further confirmed by the identification of cross-resistance to colistin in these mutants. RW01 reduced the mutant prevention concentration of minocycline from 64 to 8 mg/L. RW01 was demonstrated to enhance membrane permeabilization and therefore minocycline uptake with statistical significance. Synthetic derivatives of RW01 showed a complete loss of activity, highlighting the importance of RW01's D-proline(NH2) residue. No acute or cumulative in vivo toxicity was observed in mice. These findings suggest that RW01 could revitalize obsolete antimicrobials and potentially expand therapeutic options against multidrug-resistant P. aeruginosa ., Competing Interests: The authors declare no conflict of interest.

Burkitt lymphoma (BL) is an aggressive B-cell lymphoma associated with poor outcomes in patients with relapsed/refractory disease. This multicenter, retrospective study evaluated real-world CD19 CAR T-cell therapy outcomes in patients with relapsed/refractory BL using data abstracted from the medical records. In total, 31 patients received CAR T-cells after a median of 3 prior therapies (range 1-6). Patients received axi-cel (n = 19), liso-cel (n = 4), tisa-cel (n = 4) or other agents (n = 4). Grade 1-2 CRS occurred in 83.9% of patients (grade ≥3 6.5%), and grade 1-2 ICANS occurred in 29% of patients (grade ≥3 19.4%). Twenty-eight-day mortality was 16.1%, including one patient who died from grade 5 ICANS. The overall response rate at 1 month was 58.0% with a complete response (CR) rate of 41.9%, however the 6-month CR rate was only 25.8%. Median progression-free survival was 2.3 months (95% CI 1.0 - 9.0), and median overall survival was 6.0 months (95% CI 1.9 - 11.5). Three patients (9.7%) received consolidative allogeneic stem cell transplants, but all subsequently relapsed. In conclusion, CD19 CAR T-cell therapy infrequently delivers long term disease control in BL. Further investigation is needed to determine the most effective alternative management of these patients., (Copyright © 2025 American Society of Hematology.)

Objectives: To synthesise existing evidence on transitional care programmes for young people with juvenile-onset rheumatic and musculoskeletal diseases (jRMDs), focusing on their structure and implementation, the qualitative experiences and perceptions of those involved, and the quantitative outcomes associated with these programmes. Together with additional information, these insights have informed the European Alliance of Associations for Rheumatology (EULAR) Points to Consider for patient education in physical activity and self-management of pain in jRMDs during transitional care., Methods: A systematic literature review was conducted with a broadened scope beyond patient education in physical activity and self-management of pain to provide a comprehensive overview of transitional care in rheumatology, aiming to optimise current strategies, support evidence-based approaches, and identify areas for clinical improvement. The search was conducted in PubMed and the Cochrane Library from inception until November 1, 2023. Descriptive, qualitative, and quantitative studies were included. Two researchers independently conducted the search, screening, data extraction, and quality assessment., Results: From 31 studies, we identified 18 transitional care programmes with key approaches, including individualised and developmentally appropriate plans that often integrate educational strategies. These programmes, which generally aim to increase readiness to transfer, health-related quality of life, and continuity of care, frequently involved multidisciplinary teams and early intervention strategies. Young people with jRMDs and their families reported satisfaction with these transitional care experiences, particularly valuing early self-management support. While these programmes showed potential in promoting positive health outcomes and clinical practices, quantitative evidence supporting their effectiveness is limited, with few experimental studies confirming consistent benefits., Conclusions: This systematic review highlights the diverse yet fragmented approaches in transitional care for jRMDs, emphasising the need for stronger quantitative evidence. Thus, it is important to conduct further experimental research to optimise existing programmes or develop new ones, ultimately contributing to a smoother transition to adult care and improved long-term outcomes., Competing Interests: Competing interests DC: Speaker bureau–Pfizer, Novartis and Roche, KM: Honoraria from Amgen, Pfizer, Novartis and Medac. JCI, RPM, EBV, PAV, SA, JA, IB, MC, WC, DDC, AD, LL, AM, AFM, AN, SO, GP, ZS, TV, NW, AZ, YP, LC, and FEL have no conflicts of interest to declare., (Copyright © 2025. Published by Elsevier B.V.)

Background: Patients perceive high levels of weight prejudice, stigma, and discrimination within health systems, affecting their ability to manage their obesity and related chronic conditions. Scientific and patient obesity associations worldwide have prioritized the reduction of weight stigma to improve patient experiences in health systems and overall health outcomes. Since a significant proportion of the population is now living with multiple chronic diseases related to obesity, healthcare systems must shift toward multi-disease management frameworks incorporating person-centered and non-stigmatizing clinical conversations. Motivational Interviewing (MI) has the potential to transform clinical interactions by using non-stigmatizing language, communication, and practices. Studies using MI in obesity management have solely focused on weight loss outcomes, while other patient experience related outcomes would also be relevant to evaluate., Methods: A narrative review was undertaken to critically analyze the potential impact of MI on obesity and chronic disease management practices and experiences., Findings: An analysis and contextualization of the MI theoretical framework for obesity management, based on the philosophy of motivational spirit, was reviewed, assessing micro skills or strategies., Conclusion: MI may assist healthcare professionals conduct non-stigmatizing clinical conversations in accordance with basic principles of collaborative therapeutic alliances. A proposal for research considerations that can help illuminate the potential for of MI in obesity management is also outlined., Competing Interests: The authors declare no conflicts of interest., (© 2025 The Author(s). Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

There needs to be increased awareness of the long-term implications of prematurity to ensure optimal follow-up of these babies and design studies to obtain an evidence base for the development of improved guidelines https://bit.ly/46cdVtJ., Competing Interests: Conflicts of interest: A. Agustí reports grants paid to his institution from GlaxoSmithKline, AstraZeneca, Menarini, Chiesi and Sanofi; consulting fees from GlaxoSmithKline, AstraZenenca, Chiesi, Menarini and Sanofi; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from GlaxoSmithKline, AstraZeneca, Chiesi, Menarini and Zambon; and is Chair of the Board of Directors of the Global Initiative for Chronic Obstructive Lung Disease and Co-Chair of CADSET (both unpaid positions), all in the past 36 months. E. Baraldi reports payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, Sanofi and Chiesi; and participation on a data safety monitoring or advisory board for AstraZeneca and Sanofi, all in the past 36 months. F. Bianco is an employee of Chiesi Farmaceutici. A. Greenough reports a grant from Chiesi to support research on LISA and payment for a lecture at the ERS Congress from Chiesi, in the past 36 months. The remaining authors have nothing to disclose., (Copyright ©The authors 2025.)

Liver transplantation (LT) has been accepted as a cornerstone of care in hepatocellular carcinoma (HCC) for almost three decades. In recent years, its role has been evolving to include patients with disease burden beyond the widely used Milan criteria. The integration of dynamic biomarkers such as alpha-fetoprotein together with downstaging approaches and tumor evolution after enlistment has allowed the selection of patients most likely to benefit, resulting in 5-year survival rates greater that 70%. With the increasing use of immune checkpoint inhibitors (ICIs) across all stages of disease, alone or in combination with locoregional therapies, there is now the potential to further expand the patient population with HCC who may benefit from LT. This brings challenges, given the global shortage of organs and the need to better understand the optimal use of ICIs before transplantation. Furthermore, the field of transplant oncology awaits additional biomarkers that can predict those likely to benefit from ICIs. More than ever, a multidisciplinary approach for liver cancer management is critical to ensure all patients are considered for LT where appropriate, and do not miss the opportunity for long-term survival.

Introduction: Misdiagnosis of bipolar disorder (BD) can lead to ineffective treatment, increased risk of manic episodes, and increased severity. Objective diagnostic tests or precise tools to diagnose BD and distinguish it from major depressive disorder (MDD) in depressed patients are lacking., Aim: To assess the external diagnostic validity of a blood-based test using an RNA epigenetic signature for the differential diagnosis of BD versus MDD in patients with depression., Methods and Analysis: Multicentre cross-sectional study including an adult sample of inpatients or outpatients diagnosed with BD or MDD, currently treated for a major depressive episode. A structured diagnostic interview based on validated scales will be conducted. Sociodemographic variables, clinical history, toxic consumption, current treatment and quality of life will be assessed. Blood samples will be obtained and stored at -80 °C until RNA sequencing analysis. The EDIT-B is a blood-based test that combines RNA editing biomarkers and individual data (e.g., age, sex, and tobacco consumption). The clinical validation performance of the EDIT-B will be evaluated using the area under the curve, sensitivity, specificity, positive and negative predictive values, and likelihood ratios., Ethics and Dissemination: The principles of the Declaration of Helsinki 2013, precision psychiatry research and good clinical practice will be followed. The Research Ethics Committees of the participating centres approved the study. Participants will receive an information sheet and must sign the informed consent before the interview. Participants' data will be pseudonymized at the research sites. Any publication will use fully anonymized data. Publications with the final study results will be disseminated in international peer-reviewed journals and presented at international conferences., Study Registration: This study has been registered on clinicaltrials.gov (NCT05603819). Registration date: 28-10-2022., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval has been obtained in France by the research ethics committee Ile-de-France X (ID 2021-A-03194-37), in Spain by the research ethics committees of the Hospital Clinic of Barcelona (ID HCB/2022/0042) and the Sant Joan de Déu Foundation (PS-05-22) and in Denmark by the De Videnskabsetiske Komiteer for Region Hovedstaden (the Scientific Ethics Committees for the Capital Region of Denmark) (ID H-22010899). Consent for publication: Not applicable. Competing interests: Alcediag is an innovative diagnostic company that focuses on mental health, developing and commercializing innovative in vitro diagnostic tests. Alcediag has developed the EDIT-B test, which is based on proprietary RNA editing biomarkers. DW is the CSO of Alcediag. EV has received grants and served as consultant, advisor or CME speaker for the following entities outside the submitted work: AB-Biotics, AbbVie, Adamed, Angelini, Biogen, Beckley-Psytech, Biohaven, Boehringer-Ingelheim, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, HMNC, Idorsia, Johnson & Johnson, Lundbeck, Luye Pharma, Medincell, Merck, Newron, Novartis, Orion Corporation, Organon, Otsuka, Roche, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, Teva, and Viatris. AG-P has received CME-related honoraria or consulting fees from Janssen-Cilag, Lundbeck, Casen Recordati, the LCN, Rovi and Angelini, outside the submitted work. JZP has received honoraria from Lundbeck Pharma A/S within the last three years, outside the submitted work. LVK has received honoraria from Lundbeck Pharma and Teva within the last three years, outside the submitted work., (© 2025. The Author(s).)

Fitness assessment in patients with acute myeloid leukemia (AML) is critical to deliver the right therapy to the right patient. While several scoring systems are available to aid in determining fitness, the absence of validation studies has resulted in the lack of universally accepted assessment procedures. This limitation, combined with the increasing availability of novel agents expanding the spectrum of less-intensive options, has introduced additional complexity to the fitness assessment process. In this evolving context, fitness should reflect eligibility for a specific treatment among the several available, rather than a generic binary classification of eligibility for intensive chemotherapy. Moreover, the growing emphasis on patient-centered care, further highlights the importance of integrating quality of life, patients' preferences, patients' self-reported physical and social functioning status, social support, and early integration of palliative care into the assessment framework. A modern interpretation of fitness assessment should incorporate a comprehensive evaluation that extends beyond traditional clinical and biological disease characteristics. Thus, fitness assessment in patients with AML represents only one piece of a larger puzzle, encompassing the patient's overall capacity to sustain and benefit from a specific therapeutic program., (Copyright © 2025 American Society of Hematology.)

Post-transplant cyclophosphamide (PTCY) is increasingly used as effective graft-versus-host disease (GvHD) prophylaxis in allogeneic hematopoietic-cell transplantation (allo-HCT). However, PTCY is associated with toxicities. Whether patients with specific comorbidities are more vulnerable to cyclophosphamide-induced toxicity is unclear. We retrospectively evaluated the impact of individual organ dysfunctions for non-relapse mortality (NRM) risk and overall survival (OS) among 5888 adults who underwent PTCY-based allo-HCT for acute myeloid leukemia between 2010 and 2023. In multivariable analyses 5 of the comorbidities (renal, moderate/severe hepatic, cardiac including arrhythmia/valvular disease, severe pulmonary, infection) were independently associated with adverse NRM and OS without influencing relapse rate. A simplified model using the absence (n = 4390), presence of 1 (n = 1229) or presence of 2 or 3 (n = 269) of the comorbidities which were determined individually to contribute to NRM stratified patients into 3 NRM risk (16.2% vs. 21.6% vs. 36%, retrospectively) and OS categories (64% vs. 56% vs. 36.4%, retrospectively). In Cox model, recipients with 2 or 3 comorbidities had an increased hazard ratio for NRM of 2.38 (95% confidence interval [CI], 1.89-3) and for OS of 1.96 (95% CI 1.64-2.33). Whether patients with concomitant diagnoses, as determined here, may benefit from a reduced PTCY dose remains to be evaluated in prospective clinical trials., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Endovascular treatment (EVT) of stroke with large-vessel occlusion is known to be safe and effective. The effect of EVT for occlusion of medium or distal vessels is unclear., Methods: We randomly assigned participants with an isolated occlusion of medium or distal vessels (occlusion of the nondominant or codominant M2 segment of the middle cerebral artery [MCA]; the M3 or M4 segment of the MCA; the A1, A2, or A3 segment of the anterior cerebral artery; or the P1, P2, or P3 segment of the posterior cerebral artery) to receive EVT plus best medical treatment or best medical treatment alone within 24 hours after the participant was last seen to be well. The primary outcome was the level of disability at 90 days, as assessed with the modified Rankin scale score., Results: A total of 543 participants (women, 44%; median age, 77 years) were included in the analysis: 271 were assigned to receive EVT plus best medical treatment and 272 to receive best medical treatment alone. The median score on the National Institutes of Health Stroke Scale (range, 0 to 42, with higher scores indicating more severe symptoms) at admission was 6 (interquartile range, 5 to 9). Intravenous thrombolysis was given to 65.4% of the participants. The predominant occlusion locations were the M2 segment (in 44.0% of the participants), M3 segment (in 26.9%), P2 segment (in 13.4%), and P1 segment (in 5.5%). In the comparison between EVT plus best medical treatment and best medical treatment alone, no significant difference in the distribution of modified Rankin scale scores was observed at 90 days (common odds ratio for improvement in the score, 0.90; 95% confidence interval, 0.67 to 1.22; P = 0.50). All-cause mortality was similar in the two groups (15.5% with EVT plus best medical treatment and 14.0% with best medical treatment alone), as was the incidence of symptomatic intracranial hemorrhage (5.9% and 2.6%, respectively)., Conclusions: In persons with stroke with occlusion of medium or distal vessels, EVT did not result in a lower level of disability or a lower incidence of death than best medical treatment alone. (Funded by the Swiss National Science Foundation and others; DISTAL ClinicalTrials.gov number, NCT05029414.)., (Copyright © 2025 Massachusetts Medical Society.)

Objective: The objective was to determine the mortality rate as well as the causes and predictors of mortality in antiphospholipid antibody (aPL)-positive patients with/without APS classification., Methods: The inclusion criteria for the multicenter international APS ACTION registry are positive aPL according to the Revised Sapporo Classification Criteria tested within one year prior to enrollment. Patients are followed every 12 ± 3 months with clinical data and blood collection. For this prospective analysis, firstly we analyzed the causes of death for patients reported as "deceased". Secondly, we analyzed risk factors for mortality using adjusted Cox proportional hazards model, and calculated the survival probability by Kaplan-Meier model based on different age groups., Results: Of 967 patients, 43 (5%) were deceased after a median follow-up of 5.3 years. Based on the univariate analysis, deceased patients, compared to non-deceased, were more likely to be older and have a history of arterial thrombosis, catastrophic APS (CAPS), concomitant systemic autoimmune diseases (SAIDx), and baseline cardiovascular disease (CVD) risk factors. Based on the cox proportional hazards model adjusted for age and for each of the strongest predictors of mortality, arterial thrombosis (HR 2.94, 95% CI 1.50-5.76), concomitant SAIDx (HR 2.97, 95% 1.56-5.63), and baseline any CVD risk factor (HR 2.43, 95% CI 1.05-5.71) were significantly associated with mortality., Conclusion: In our cohort of persistently aPL-positive patients, the mortality rate was 5% after a median follow-up of five years, highest for patients over 60 years-old at registry entry. History of arterial thrombosis, concomitant SAIDx, and baseline any CVD risk factor independently predicted future mortality., (This article is protected by copyright. All rights reserved.)

Chronic rhinosinusitis with nasal polyps (CRSwNP) often co-exists with asthma and non-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD), creating a more severe phenotype and an additional burden compared with CRSwNP disease alone. The relationship between these diseases in terms of shared immunological disbalance has been coined in the literature as "global airway disease" or "unified airway disease" and requires integrated treatment strategies. Our post hoc analysis of the Phase III randomised, double-blind, placebo-controlled, multicentre SYNAPSE study (GSK ID: 205687; NCT03085797) assessed the efficacy of mepolizumab, an anti-interleukin-5 monoclonal antibody, in simultaneously improving both CRSwNP and asthma outcomes versus placebo. By utilising a combined measure that accounts for quality of life, sinonasal symptoms and asthma control, we aimed to validate the potential of mepolizumab as an effective therapeutic option for global airway disease.

Objective: As a result of conflicting, inadequate or controversial data in the literature, several issues concerning the management of patients with abdominal aortic aneurysms (AAAs) remain unanswered. The aim of this international, expert-based Delphi consensus document was to provide some guidance for clinicians on these controversial topics., Methods: A three-round Delphi consensus document was produced with 44 experts on 6 prespecified topics regarding the management of AAAs. All answers were provided anonymously. The response rate for each round was 100%., Results: Most participants (42 of 44 [95.4%]) agreed that a minimum case volume per year is essential (or probably essential) for a center to offer open or endovascular AAA repair (EVAR). Furthermore, 33 of 44 (75.0%) believed that AAA screening programs are (probably) still clinically effective and cost effective. Additionally, most panelists (36 of 44 [81.9%]) voted that surveillance after EVAR should be (or should probably be) lifelong. Finally, 35 of 44 participants (79.7%) thought that women smokers should (or should probably/possibly) be considered for screening at 65 years of age, similar to men. No consensus was achieved regarding lowering the threshold for AAA repair and the need for deep venous thrombosis prophylaxis in patients undergoing EVAR., Conclusions: This expert-based Delphi consensus document provides guidance for clinicians regarding specific unresolved issues. Consensus could not be achieved on some topics, highlighting the need for further research in those areas., Competing Interests: Disclosures A.K. has received speaker fees from Cook Inc., & W.L. Gore & Associates, and is a consultant for Bentley Innomed. M.A.F. has received clinical trial support and is a Consultant for Cook, W. L. Gore & Associates, Getinge, and ViTAA. He has received research support from Cook and has stock options in Centerline Biomedical. M.E. is a paid consultant for W. L. Gore & Associates and Silk Road Medical. M.G. is a consultant for Cook Medical, W. L. Gore & Associates and Medtronic and a proctor for Cook Medical., (Copyright © 2024 Society for Vascular Surgery. All rights reserved.)

Mathematical models of thrombin generation (TG) that have been developed are based on a systems biology approach. Although this approach provides important information about the coagulation system, its clinical applicability is limited by its complexity and number of input variables required. The aim of this study was to develop a semimechanistic model able to describe TG in trauma and control patients. A dataset containing longitudinal data of TG assays and coagulation factors from 40 trauma patients and 20 control patients was used for model building. The model considered three fundamental processes: the degradation of tissue factor (TF) through a first-order process, the activation of factor II by the TF through a first-order process, and the degradation of thrombin through a first-order process. Model fitting was performed using a nonlinear mixed-effects approach. The condition of the patient (trauma and control) and coagulation factors were modelled as covariates. Model building demonstrated the presence of two additional processes that improved the predictive capacity of the model: the activation of factor II by TF governed by a second-order constant and, a mechanism of factor II activation by TF characterized by a 7-compartment transit chain governed by a second-order constant. In the covariate model only the inclusion of patient condition was significant. Model evaluation demonstrated excellent performance in describing the temporal pattern of TG in trauma and control patients. Thrombin generation can be adequately modelled using a semimechanistic approach. Its application in practice could help to better assess the risk of hemorrhage and/or thrombosis in different settings., (© 2024 The Author(s). Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

In the last decades, various types of endoscopic sinus surgery (ESS) have emerged as treatments for chronic rhinosinusitis (CRS), particularly with the development of personalized, endotype-driven approaches targeting mucosal inflammation and remodeling. Despite these advancements, the literature reports heterogeneous and often divergent outcomes, leaving the actual benefit of more extensive surgical approaches in CRS control a matter of ongoing debate. This discrepancy stems from inconsistent definitions of surgical techniques, leading to variations in osseous and mucosal resections depending on patient phenotype, disease severity and surgeon preference. To address this inconsistency, the Japanese Rhinology Society introduced a classification based on procedure extent, but it lacks details on anatomical structures and mucosal treatment. Similarly, the ACCESS system measures ESS extent with postoperative CT-scans but overlooks mucosal interventions.

Heart failure with preserved ejection fraction (HFpEF) is now the most common form of heart failure (HF). This syndrome is associated with an elevated morbi-mortality, and effective therapies are urgently needed. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are the first pharmacological class that has demonstrated to reduce hospitalization and cardiovascular mortality in large clinical trials in HFpEF. Furthermore, the dual SGLT 1/2 inhibitor sotagliflozin has shown a reduction in cardiovascular outcomes in diabetic HF patients, regardless of ejection fraction Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure (SOLOIST-WHF) Trial, and prevents the development of HF in patients with diabetes and chronic kidney disease Sotagliflozin on Cardiovascular and Renal Events in Patients with Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk (SCORED) trial. The major objective of the Sotagliflozin in Heart Failure With Preserved Ejection Fraction Patients (SOTA-P-CARDIA) trial (NCT05562063) is to investigate whether the observed cardiorenal benefits of sotagliflozin in HF patients with diabetes can be extended to a non-diabetic population. The SOTA-P-CARDIA is a prospective, randomized, double-blinded, placebo-controlled study that will randomize non-diabetic patients with the universal definition of HFpEF (ejection fraction > 50% assessed the day of randomization). Qualifying patients will be randomized, in blocks of 4, to receive either sotagliflozin or placebo for a period of 6 months. The primary outcome is changes in left ventricular mass by cardiac magnetic resonance from randomization to end of the study between the groups. Secondary end points include changes in peak VO 2 ; myocardial mechanics, interstitial myocardial fibrosis, and volume of epicardial adipose tissue; distance in the 6-min walk test; and quality of life. Finally, the authors expect that this trial will help to clarify the potential benefits of the use of sotagliflozin in non-diabetic HFpEF patients., Competing Interests: Declarations. Ethics Approval: All procedures performed in studies involving human participants are in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The protocol was approved by the Mount Sinai Institutional Review Board (GCO 22–0574) and received IND 165123 by the FDA. Consent to Participate: Informed consent is obtained from all individual participants included in the study. Consent for Publication: Not applicable. Competing Interests: This study has been funded by an Investigator-Initiated Grant to Dr. Badimon by Lexicon Pharmaceuticals, Inc., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Bacterial pulmonary superinfections develop in a substantial proportion of mechanically ventilated COVID-19 patients and are associated with prolonged mechanical ventilation requirements and increased mortality. Albeit recommended, evidence supporting the use of empirical antibiotics at intubation is weak and of low quality. The aim of this study was to elucidate the effect of empirical antibiotics, administered within 24 h of endotracheal intubation, on superinfections, duration of mechanical ventilation, and mortality in mechanically ventilated patients with COVID-19., Methods: Emulated targeted trial by means of a propensity score-matched analysis of a prospective multicentre cohort study of consecutive mechanically ventilated patients admitted to 62 Spanish intensive care units suffering from COVID-19 between March 2020 and February 2021., Results: Overall, 8532 critically ill COVID-19 patients were included, of which 2580 mechanically ventilated patients remained after matching. Empirical antibiotics were prescribed to 1665 (64%) at intubation. Pulmonary superinfections developed in 39% and 47% of patients treated with and without empirical antibiotics, respectively (p<0.01). Patients treated with empirical antibiotics had a shorter duration of mechanical ventilation (incidence risk ratio: 0.85 [95% confidence interval (CI), 0.78 - 0.94], p<0.01) and a reduced stay in the intensive care unit (incidence risk ratio: 0.89 [95% CI, 0.82 - 0.97] days, p<0.01). Mortality 28 days after endotracheal intubation was 28% in patients treated with empirical antibiotics as opposed to 32% in patients treated without (odds ratio: 0.76 [95% CI, 0.61 - 0.94], p<0.01)., Conclusion: The administration of empirical antibiotics at intubation in mechanically ventilated COVID-19 patients was associated with a reduced incidence of pulmonary superinfections, a shorter duration of mechanical ventilation and intensive care unit stay, and a lower mortality rate. Notwithstanding these benefits, the applicability of these findings to other viral pneumonias and beyond the pandemic context remains uncertain., Registration: www., Clinicaltrials: gov (NCT04457505)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Functioning is the reason to be of rehabilitation as it is essential to the lives of people who suffer from a disease. The International Classification of Functioning, Disability and Health (ICF) can help in designing a functioning profile of a patient, identifying needs for rehabilitation plans and measuring the results of an intervention., Objective: To identify the outcome measurement instruments reported in clinical studies in muscular dystrophies (MDs) and provide an ICF content analysis., Method: A systematic literature review was conducted until October 2022, using Medline, PubMed, and Scopus databases. Papers assessing outcomes related to functioning in patients with MDs were included., Results: A total of 116 papers were included and all identified outcome measures were linked to the ICF. Inter-researcher agreement for the linking process was 0.82. The analysed instruments focused mainly on aspects of body functions, followed by activities and participation. General scales were more comprehensive than specific., Conclusions: The application of ICF in this research enhances the understanding of functioning of patients with MDs and the need to develop more specific but comprehensive scales tailored to the needs of MD patients, and can guide clinicians in a assessing patients through a biopsychosocial perspective.

Purpose of Review: Protein intake is recognized as a key nutritional factor crucial for optimizing Metabolic Bariatric Surgery (MBS) outcomes by preventing protein malnutrition, preserving fat-free mass, and inducing satiety. This paper discusses the current evidence regarding protein intake and its impact on clinical outcomes following MBS., Recent Findings: There are considerable gaps in the understanding of protein requirements following MBS, as existing guidelines are based on limited and inconsistent reports. This highlights the urgent need for updated clinical practice recommendations grounded in high-quality evidence. Further investigation using robust methodologies is essential to address existing research gaps related to the individualization of protein requirements following MBS. Future research should consider factors such as the time elapsed since surgery, the form and quantity of protein consumed, and necessary adjustments for physical activity. Ultimately, in alignment with recent literature, a more specific and personalized dietary protein approach should be examined., Competing Interests: Compliance with Ethical Standards. Ethical Approval: Ethical approval was not required for this type of article as it does not involve original research with human neither animal subjects. Conflict of Interest: The authors declare no competing interests. Human and Animal Rights and Informed Consent: This article does not contain any studies with human or animal subjects performed by any of the authors., (© 2025. The Author(s).)

Objective: Self-harm is common in adolescents and a major public health concern. Evidence for effective interventions that stop repetition is lacking. This individual-participant-data (IPD) meta-analysis of randomised controlled trials (RCTs) aimed to provide robust estimates of therapeutic intervention effects and explore which treatments are best suited to different subgroups., Method: We searched databases and trial registers, to January-2022. RCTs compared therapeutic intervention to control, targeted adolescents aged 11-18 with a history of self-harm and receiving clinical care and reported on outcomes related to self-harm or suicide attempt. Primary outcome was repetition of self-harm at 12 months post-randomization . Two-stage random-effects IPD meta-analyses were conducted overall and by intervention. Secondary analyses incorporated aggregate data (AD) from RCTs without IPD. PROSPERO registration: CRD42019152119., Results: We identified 39 eligible studies; 26 provided IPD (3,448 participants), 7 provided AD (698 participants). There was no evidence that intervention/s were more or less effective than controls at preventing repeat self-harm by 12 months in IPD (odds ratio (OR)=1.06 [95% CI 0.86, 1.31], studies=20, n=2,949) or IPD+AD (OR=1.02 [95% CI 0.82, 1.27], studies=22, n=3,117) meta-analyses and no evidence of heterogeneity of treatment effects on study and treatment factors. Across all interventions, participants with multiple prior self-harm episodes showed evidence of improved treatment effect on self-harm repetition 6-12 months after randomization (OR=0.33 [95% CI 0.12, 0.94], studies=9, n=1,771)., Conclusion: This large-scale meta-analysis of RCTs provided no evidence that therapeutic intervention was more, or less, effective than control for reducing repeat self-harm. We observed evidence indicating more effective interventions within youth with two or more self-harm incidents. Funders and researchers need to agree on a core set of outcome measures to include in subsequent studies., (Copyright © 2025. Published by Elsevier Inc.)

Background: Severe alcohol-associated hepatitis (AH) is rising in incidence with a high mortality burden. While corticosteroids are recommended for eligible patients with severe AH, no guidance exists for the timing of steroid initiation, tapering regimens, and surveillance of adverse events., Objective: We aim to systematically review these variables and provide evidence-based recommendations for the inpatient and outpatient management of severe AH., Design: We performed a literature search from inception to 5/30/2024 to include clinical trials published in full form and assessed the quality of evidence using the Cochrane Risk of Bias tool. Data were collected on the timing of initiation, rate, and complications following steroid therapy, and taper regimens in the setting of severe AH., Results: Of 28 studies that fulfilled our inclusion criteria, median time from admission to steroid initiation was 6.5 days. The most common steroid dosing regimen was prednisolone 40 mg daily for 28 days. Twenty-five studies containing 3,196 subjects reported adverse events, with exactly 50% in the steroid arm and the other half in the comparison arm. Infections, gastrointestinal bleeds, and renal impairment were the most frequently reported adverse events. Most infections occurred within the first month of the study. A two-week steroid taper was the most frequently reported regimen., Conclusion: We recommend taking up to a week to systematically and thoroughly evaluate patients before initiating steroids, and vigilant monitoring in the first month of treatment. We also recommend the lowest possible steroid exposure with a two-week steroid taper and close outpatient follow-up., (Copyright © 2025 American Association for the Study of Liver Diseases.)

Background: Robust collateral circulation has been linked with better reperfusion and clinical outcomes. It remains unclear how individual assessments of collateral circulation may be translated into clinical practice., Methods: The pooled Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) angiography dataset was analyzed by a centralized, independent imaging core blinded to other clinical data. Conventional angiography was acquired immediately prior to endovascular therapy. Collaterals were graded with the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN) system and associated with baseline patient characteristics, reperfusion, and day 90 modified Rankin Score (mRS). Both 90-day all-cause mortality and day 90 mRS were modeled via multivariable logistic regression., Results: Angiography was available in 376/605 (62%) patients. Baseline ASPECTS (Alberta Stroke Program Early CT Score) (p=0.043), history of diabetes mellitus (p=0.048), site of occlusion (p<0.001), and degree of subsequent Thrombolysis in Cerebral Infarction (TICI) reperfusion (p<0.001) were associated with collateral grades. ASITN collateral grade was strongly associated with ordinal mRS from baseline to 90 days in an unadjusted analysis (p<0.001). Multivariable regression demonstrated that collateral status is a strong determinant of mRS outcome in the presence of other predictors (OR=1.37 per grade, 95% CI [1.05 to 1.74], p=0.018). By comparing ORs, 1 unit of ASITN was determined to be approximately equivalent to 4.5 points of NIHSS, 11 years of age, 1.5 points of ASPECTS, or 100 min less delay from onset to puncture, in terms of impact on mRS., Conclusions: Individual collateral physiology may contribute significantly to reperfusion success and clinical outcomes after acute ischemic stroke. Building a consensus for the role of angiographic collateral assessment in the allocation of adjuvant reperfusion therapies may help galvanize a precision medicine approach in stroke., Competing Interests: Competing interests: DSL reports having received grant funding from NINDS and consulting fees as an imaging core laboratory from Cerenovus, Genentech, Medtronic, Stryker, and Rapid Medical. RJ reports consulting with Phenox Medical, Microvention Terumo, and RapidPulse Inc. CBLMM reports having received grant funding from the CVON/Dutch Heart Foundation, Healthcare Evaluation Netherlands, European Commission, TWIN Foundation, and unrestricted grants from Stryker and Boehringer Ingelheim (all paid to institution) and is shareholder of Nicolab (minority interest). AvdL reports consulting fees from Stryker and grant funding from the Dutch Heart Foundation, AngioCare BV, Medtronic/Covidien/EV3®, MEDAC Gmbh/LAMEPRO, Penumbra Inc., Top Medical/Concentric, and Stryker, received by the Erasmus University Medical Center. LSR serves on a Data and Safety Monitoring Board (DSMB) for somatosensory evoked potentials (SEP) monitoring in patients with acute ischemic stroke and large anterior vessel occlusion undergoing endovascular thrombectomy. A clinical validation of the Brain20® medical device, Promise20. AD reports grants from the Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organisation for Health Research and Development, Health Holland Top Sector Life Sciences & Health and unrestricted grants from Penumbra Inc., Stryker, Medtronic, and Thrombolytic Science, all for research. JLS reports consulting fees for advising on rigorous and safe clinical trial design and conduct from Abbott, Acticor, Aeromics, Amgen, Argenica, Astrocyte, Bayer, Biogen, Boehringer Ingelheim, BrainsGate, BrainQ, CSL Behring, Filterlex, Genentech, Johnson & Johnson, MindRhythm, Medtronic, NeuroMerit, Neuronics, Novo Nordisk, Occlutech, Phenox, Phillips, QuantalX, Rapid Medical, Roche, and Stream Biomedical. PJM reports unrestricted institutional scientific grants from Stryker and Medtronic. KWM reports consultancies with Boehringer Ingelheim, Biogen, Hyperfine, and lecture fees from Boehringer Ingelheim, IschemaView, and Brainomix. PW discloses institutional research grant support within the last 2 years from Microvention Terumo. He declares the following relevant professional relationships: Chair of the European Society of Minimally Invasive Neurotherapeutics Guidelines Committee, sits on the Policy Working Group for Thrombectomy of NHS England, and represents the Royal College of Radiologists on the UK Intercollegiate Stroke Working party - none of these are associated with financial reimbursement. He reports the following modest consultancy work: member of Stryker’s Global Hemorrhagic Stroke Advisory Board and educational consultancy work for Microvention Terumo. He has no other interests to declare. MG reports being the principal investigator of an unrestricted research grant to the University of Calgary for the HERMES collaboration by Medtronic. He also reports consulting services with Medtronic, Stryker, Microvention, and Cerenovus, and a licensing agreement with GE Healthcare regarding systems of acute stroke diagnosis., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Female recipients of allogeneic hematopoietic stem cell transplantation are at high risk of developing human papillomavirus (HPV)-associated lesions and (pre)cancer. We describe the results of a cervical cancer screening program in these women., Methods: From 2010 to 2022, 70 female recipients of allogeneic hematopoietic stem cell transplantation in our institution entered a standardized protocol of gynecological evaluation. HPV testing, Papanicolaou smear, and thorough gynecological examinations were conducted in all the women., Results: The cumulative prevalence of HPV infection was 21.4% (15/70). Ten of 70 women (14.3%) had a positive HPV test result in the first gynecological evaluation and 5 additional women (7.1%) became positive during follow-up. Thirteen women (18.5%) presented cytohistological lesions (3 high-grade lesions and 10 low-grade lesions). Twenty-nine women (41.4%) showed HPV-negative reactive atypical abnormalities related to the conditioning treatment, which closely mimicked HPV-associated lesions, which spontaneously disappeared during follow-up., Conclusions: Gynecological evaluation should be maintained over time, as a significant proportion of these women may become HPV positive during follow-up. Reactive benign, atypical changes related to the treatment, which closely mimic HPV-associated lesions, are a frequent finding in these women. HPV testing is a key tool for the evaluation of these patients, as it allows for identifying women at risk and excluding cytological mimickers., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Previous studies have reported that chronic lymphocytic leukemia (CLL) shows a de novo chromatin activation pattern as compared to normal B cells. Here, we explored whether the level of chromatin activation is related to the clinical behavior of CLL. We identified that in some regulatory regions, increased de novo chromatin activation is linked to clinical progression whereas, in other regions, it is associated with an indolent course. We next developed two prognostic scores for progressive and indolent disease, respectively, calculated a single score representing the balance between them, and further generated surrogate scores based on gene and protein expression of the target genes. The balance score outperformed the clinical impact of the two individual scores, as it seemed to capture the prognostic information provided by each of them. Biologically, CLLs with higher balance score showed increased activation of TNF-α/NF-κB and mTOR signaling pathways. Regulatory programs related to progression were predominantly activated in the lymph node microenvironment, whereas those linked to indolent disease appeared to be microenvironment-independent. Finally, we thoroughly validated the balance score as a powerful and independent quantitative prognostic factor for time to first treatment across independent CLL cohorts and data modalities such as chromatin, transcriptome or proteome data. Our findings support the concept that de novo acquisition of chromatin changes in CLL cells plays a dual biological role, and that the balance between pro-progression and pro-indolence is a strong independent determinant of CLL prognosis., (Copyright © 2025 American Society of Hematology.)

Background: This study examines the management and outcomes of large paranasal sinus osteomas (PSO), especially those abutting or encasing critical structures of the skull base and orbit., Methodology: A multicentric retrospective analysis was conducted between June 2007 and September 2023. The study included surgically treated (regardless the type of approach chosen) PSO, exceeding 3 cm in diameter and/or located in critical anatomical areas. An analysis was performed to assess the association between the critical relationships, size, presence of residual disease, and incidence of intra- and postoperative complications., Results: The series included 160 patients. Most PSO were diagnosed due to clinical symptoms, predominantly for those located in the frontal sinus. Residual disease was observed in 9.4% of patients, with its occurrence influenced by PSO size and relationships with specific anatomical structures. Thirty-five/160 (21.9%) of patients experienced one or more intra- and/or postoperative complications. Intraoperative complications were associated with the proximity of PSO to the cribriform plate. Long-term complications were more frequently observed in cases involving the anterior and posterior plate of the frontal bone., Conclusions: This study highlights the complexities involved in managing large PSO, demonstrating that size and anatomical relationships of these osteomas can critically influence surgical decisions, residual disease, and complication rate. The study's retrospective design limited the collection of standardized symptom outcomes, highlighting the need for future studies to address this apect.

Background: Performing hemodialysis without heparin is still challenging. The objective of the present work was to evaluate the impact on thrombogenicity of the hemodialysis circuit using synthetic membranes compared to the asymmetric cellulose triacetate (ATA) membrane., Methods: Prospective, multicenter, randomized, crossover, open-label study. In each of the two phases of the study, six consecutive hemodialysis sessions were performed over two weeks, in which the patients were dialyzed with the dialyzer randomly assigned (synthetic vs asymmetric cellulose triacetate membrane). During the six sessions of both phases, the heparin dose was progressively reduced from the full usual heparin dose in the first session to zero heparin in the sixth session. After each session, visual inspection of the venous chamber and dialyzer was performed, and a coagulation score was assigned. A micro- computed tomography (CT) scanning of some dialyzers was also executed at Ghent University., Results: Comparison of the last completed sessions shows that there were significant differences depending on the dialyzer used: 60% of dialysis sessions with asymmetric cellulose triacetate could be completed without heparin versus 24% with synthetic membranes (p = 0.01). We also found differences in the number of sessions completed: 46% with the asymmetric cellulose triacetate membrane and 7% with the synthetic membrane (p = 0.001). The results obtained with the micro-CT analysis were also better with the asymmetric cellulose triacetate., Conclusions: Our findings strongly suggest that asymmetric cellulose triacetate membranes may be useful in situations in which dialysis should be performed without heparin or with low-dose heparins., Trail Registry: NCT06505616., Competing Interests: Declarations. Conflict of interest: P.S. reports honorarium for conferences, consulting fees and advisory boards from Amgen, Astellas, Astra Zeneca, Baxter, Braun, Fresenius, Nipro, Vifor-Pharma. P.M. reports honorarium for conferences and consulting fee from Nipro. F.M. has received consultancy and lecture fees from Baxter, Fresenius Medical Care, Medtronic, Nipro, Toray, and Vifor. The remaining authors declare no potential conflicts of interest related to the contents of this article. Ethical approval: The study was approved by the local Ethics Committee, and it was conducted according to the principles of the Declaration of Helsinki. Informed consent: All patients who participated in the study provided signed informed consent., (© 2025. The Author(s).)

Background: The HER2DX assay predicts long-term prognosis and pathologic complete response (pCR) in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving neoadjuvant systemic therapy but has not been evaluated in inflammatory breast cancer (IBC)., Patients and Methods: HER2DX was analyzed in baseline biopsy tissues from 23 patients with stage III HER2-positive IBC on a phase II trial (NCT01796197) treated with neoadjuvant trastuzumab, pertuzumab, and paclitaxel (THP). To assess the assay's predictive accuracy for pCR in IBC, clinical-pathological features and outcomes from this IBC cohort were compared with 156 patients with stage III HER2-positive non-IBC from four different cohorts. Comparative analyses included HER2DX scores, gene signatures, and expression of individual genes between patients with IBC and non-IBC., Results: Notable differences in clinicopathological characteristics included higher pertuzumab and chemotherapy usage and lower axillary burden in patients with IBC compared with non-IBC. In the combined cohort (n = 179), HER2DX pCR score and pertuzumab use were significant predictors of pCR, but not IBC status. The pCR rates in patients treated with trastuzumab-based chemotherapy (including IBC and non-IBC) were 68.9%, 58.5%, and 16.3% in the HER2DX pCR-high, -medium, and -low groups, respectively. Comparative gene expression analysis indicated minor differences between IBC and non-IBC affecting individual HER2, immune, and proliferation genes., Conclusions: The HER2DX pCR score could predict pCR in stage III HER2-positive IBC following treatment with de-escalated neoadjuvant systemic therapy and in stage III HER2-positive non-IBC. Elevated pCR rates in HER2-positive IBC with high HER2DX pCR scores suggest there may be a role for treatment de-escalation in these patients and confirmatory studies are justified., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In the last decades, research from cognitive science, clinical psychology, psychiatry, and social neuroscience has provided mounting evidence that several social cognitive abilities are impaired in people with schizophrenia and contribute to functional difficulties and poor clinical outcomes. Social dysfunction is a hallmark of the illness, and yet, social cognition is seldom assessed in clinical practice or targeted for treatment. In this article, 17 international experts, from three different continents and six countries with expertise in social cognition and social neuroscience in schizophrenia, convened several meetings to provide clinicians with a summary of the most recent international research on social cognition evaluation and treatment in schizophrenia, and to lay out primary recommendations and procedures that can be integrated into their practice. Given that many extant measures used to assess social cognition have been developed in North America or Western Europe, this article is also a call for researchers and clinicians to validate instruments internationally and we provide preliminary guidance for the adaptation and use of social cognitive measures in clinical and research evaluations internationally. This effort will assist promoting scientific rigor, enhanced clinical practice, and will help propel international scientific research and collaboration and patient care.

Aims: To evaluate the association between transcatheter edge-to-edge repair (TEER) and outcomes in patients with significant mitral regurgitation (MR) following acute myocardial infarction (MI), focusing on the aetiology of acute post-MI MR in high-risk surgical patients., Methods and Results: The International Registry of MitraClip in Acute Mitral Regurgitation following Acute Myocardial Infarction (IREMMI) includes 187 patients with severe MR post-MI managed with TEER. Of these, 176 were included in the analysis, 23 (13%) patients had acute papillary muscle rupture (PMR) and 153 (87%) acute secondary MR. The mean age was 70 ± 10 years and 41% were female. PMR patients had fewer cardiovascular risk factors: hypertension (52% vs. 73%, p = 0.04), diabetes (26% vs. 48%, p < 0.01) but a higher left ventricular ejection fraction (45±  15% vs.35±  10%, p < 0.01) compared secondary MR patients. PMR patients were more likely to present in cardiogenic shock (91% vs. 51%, p = 0.001), require mechanical circulatory support (74% vs. 34%, p = 0.01), and had a higher EuroSCORE II (23±  13% vs. 13±  11%, p = 0.011). The median time from MI to TEER was shorter in PMR (6 days) versus secondary MR (20 days) (p < 0.01). Procedural success was similar (87% vs. 92%, p = 0.49) with comparable MR grade reduction. However, PMR patients had significantly higher in-hospital mortality rates (adjusted odds ratio [OR] 3.05, 95% confidence interval [CI] 1.15-8.12, p = 0.02), 30-day mortality rates (unadjusted OR 3.99, 95% CI 1.42-11.26, p = 0.01) and a higher rate of conversion to surgical mitral valve replacement (22% vs. 3%, p < 0.01) (unadjusted OR 8.17, 95% CI 2.15-30.96, p < 0.001). Aetiology of MR, cardiogenic shock, and procedure timing significantly impacted in-hospital mortality. After adjusting for EuroSCORE II and cardiogenic shock, MR aetiology remained the strongest predictor (adjusted OR 6.71; 95% CI 2.06-21.86, p < 0.01)., Conclusion: Transcatheter edge-to-edge repair may be considered a salvage or bridge procedure in decompensated post-MI MR patients of both aetiologies; however, patients with PMR have a higher risk of mortality and conversion to surgery., (© 2025 European Society of Cardiology.)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. In multiple myeloma (MM), measurable residual disease (MRD) is assessed in bone marrow (BM). However, less invasive evaluation of peripheral residual disease (PRD) in blood could be advantageous and less cumbersome. We investigated the prognostic value of PRD monitoring after 24 cycles of maintenance in 138 transplant-eligible patients with MM enrolled in the GEM2012MENOS65/GEM2014MAIN clinical trials. PRD was assessed using next-generation flow (NGF) and mass spectrometry (MS). Positive PRD by NGF in 16/138 (11.5%) patients was associated with a 13-fold increased risk of progression and/or death; median progression-free survival (PFS) and overall survival (OS) were 2.5 and 47 months, respectively. Considering patients' MRD status in BM as the reference, PRD detection using NGF showed positive and negative predictive values of 100% and 73%, respectively. Presence of PRD helped identifying patients at risk of imminent progression among those with positive MRD in BM. Patients with undetectable PRD according to both NGF and MS showed 2-year PFS and OS rates of 97% and 100%, respectively. In multivariate analyses including the Revised International Staging System and the complete remission status, only MRD in BM and PRD by NGF showed independent prognostic value for PFS. This study supports the use of less invasive PRD monitoring during maintenance or observation in transplant-eligible patients with MM.

Purpose of Review: We describe the evolution of caval valve implantation (CAVI) as a treatment for severe symptomatic tricuspid regurgitation (TR) in the high surgical risk patient., Recent Findings: Surgical treatment of severe TR is often limited by the high surgical risk of the patients who tend to develop severe secondary TR. Coaptation, annuloplasty, and orthotopic replacement strategies are all limited by annular and leaflet geometry, prior valve repair, and the presence of cardiac implantable device leads. CAVI appears to be a treatment strategy for severe symptomatic TR that improves functional capacity and quality of life while also reducing edema and ascites and improving cardiac output. Chronic kidney disease is a common comorbidity of patients with severe TR; zero-contrast CAVI has been described. Severe TR is undertreated, yet common in the elderly structural heart disease population. The evolution of CAVI as a viable treatment for severe TR underscores the deleterious systemic contribution of backwards flow to morbidity and mortality. There are good safety and efficacy outcomes from registry data using the TricValve platform. Randomized controlled trials for CAVI versus medical therapy for severe TR are ongoing., Competing Interests: Declarations. Human and Animal Rights and Informed Consent: All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines). Conflict of Interest: Drs. Puri and Altisent serve as a consultants to Products & Features. Dr. Puri is a consultant to VDyne, and PI of TRICAV-1 and TRICAV-2 trials. Dr. Chen has nothing to disclose. Key References: Blasco-Turrión S, Briedis K, Estévez-Loureiro R, Sánchez-Recalde A, Cruz-González I, Pascual I, et al. Bicaval TricValve Implantation in Patients With Severe Symptomatic Tricuspid Regurgitation. JACC Cardiovasc Interv. 2024;17:60–72. This Analysis Describes the 1-year Clinical Endpoints from the TricValve single-arm Interventional CAVI Experience. Denby K, Spilias N, Harb SC, Kapadia SR, Puri R. Contrast-Sparing Intravascular Ultrasound–Guided Caval Valve Implantation for Severe Symptomatic Tricuspid Regurgitation. JACC Case Rep. 2023;23:102007. This series describes contrast-sparing techniques for CAVI that utilize IVUS, important due to the prevalence of chronic kidney disease in patients with severe tricuspid regurgitation and right heart failure., (© 2024. The Author(s).)

Introduction: Liver transplantation (LT) provides significant survival benefits to patients with unresectable HCC. In the United States, organ allocation policies for HCCs within the United Network for Organ Sharing criteria do not prioritize patients based on their differences in oncological characteristics. This study assessed whether transplant-associated survival benefits (TASBs) vary among patients with different tumor burden scores (TBS) measured at the time of listing., Methods: We analyzed data from adults applying for HCC MELD exception points between 2002 and 2019, with follow-up until December 2023, using the Scientific Registry of Transplant Recipients. TBS was determined based on the largest tumor diameter and number of HCCs. Patients were categorized into low (≤3), intermediate (3.1-5), and high (>5) TBS groups. TASB was measured as the difference in 5-year survival with and without LT., Results: This study included 36,634 LT candidates. High-TBS patients had higher waitlist dropout rates and marginally lower post-transplant survival, resulting in a significantly greater TASB. The 5-year TASB for the low, intermediate, and high TBS groups were 15.7, 22.1, and 25.0 months, respectively. The adjusted survival benefit expressed in 5-year survival differences was 21.9%, 34.5%, and 39.4% in the low, intermediate, and high TBS groups, respectively (p<0.001)., Conclusions: Higher TBS during listing correlates with greater LT benefits for patients with unresectable HCC within UNOS criteria. We conclude that organ allocation policies in the United States should prioritize patients with high TBS due to their increased risk of dropout and comparable post-transplant survival when compared to patients with less advanced tumors., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Objective: To investigate the prevalence and patterns of social media use among gynecologic oncologists for professional and academic purposes., Methods: A prospective online survey between November and December 2022 targeted gynecologic oncology practitioners (gynecologic oncologists, surgical oncologists, medical oncologists, radiation/clinical oncologists, and onco-pathologists/pathologists). The survey, distributed via various social media platforms, included 40 questions to capture qualitative and quantitative data on social media use., Results: Of 131 respondents from 32 countries, 106 (80.9%) were gynecologic oncologists and affiliated with academic institutions (84.7%). Facebook (n=110, 83.9%), Twitter (n= 108, 82.4%), and Instagram (n=100, 76.3%) were the most used platforms. Respondents used social media to stay updated (n=101, 77.1%), network (n=97, 74%), learn about conferences and webinars (n=97, 74%), and engage in academic discussions (n=84, 64.1%). Following the COVID-19 pandemic, 100/129 (77.5%) reported increased social media use. However, only 32 (24.4%) used it to connect with patients, and concerns were raised about privacy and the need for separate professional and personal accounts. A quarter of respondents hesitated to share their opinions on social media due to the fear of controversy, with 26 (20%) experiencing cyberbullying, yet 120/130 (92.3%) believed it enabled junior professionals to express their views. Concerns about differentiating valid content, information reliability, and the professional perception of sourcing knowledge from social media were noted. Gender, age, specialty, and income level influenced patterns of social media use, with variations in preferences for platforms, content engagement, and purposes, highlighting a complex landscape of social media interaction among gynecologic oncologists., Conclusion: While the use of social media among gynecologic oncologists is prevalent, particularly for academic and professional development, challenges such as cyberbullying, privacy concerns, and the need for formal training in social media navigation persist. Tailored training programs and guidelines could enhance social media's effective and ethical use in this field, promoting a safe environment for professional expression and engagement., Competing Interests: Competing interests: JK-B is vice president of the European Network of Young Gynecologic Oncologists (ENYGO), ASJ is social media editor for IJGC, GN is Social media editor for Gynecologic Oncology Journal and treasure for Enhanced Recovery After Surgery (ERAS) Society., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Therapies derived from substances of human origin (SoHOs) such as organs, cells, and tissues provide life-saving or life-changing treatment for millions of people worldwide each year. However, many people lack timely access to SoHO-based therapies because of insufficient supplies of these exceptional health resources and/or broader barriers in access to healthcare. Despite well-established governmental commitments to promote health equity in general and equity of access to SoHOs in particular, information about inequities in access to most SoHO-based therapies is scarce. Furthermore, the issue of equitable allocation of SoHO-based therapies has received little attention from policymakers and ethicists, except in the context of organ allocation for transplantation. Consequently, the extent and nature of potential inequities within and between countries are largely unknown, and few sources of guidance are available to support progress toward equity in global access to SoHO-based therapies. We present here the findings of an international ethics working group convened in preparation for the 2023 Global Summit on Convergence in Transplantation, organized in Santander, Spain. The group sought to assess potential gaps in knowledge about inequities involving SoHO-based therapies, to elucidate systemic factors that may influence access to these therapies, and to consider how policies and frameworks governing access to and allocation of SoHO-based therapies may promote equity when it is necessary to define boundaries in access because of insufficiency of supply. In discussing these challenges, we also outline several recommendations for action by governments and health authorities., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Oligodendroglioma is an adult-type diffuse glioma defined by 1p/19q codeletion and IDH1/2 mutation. Treatment includes surgery followed by observation alone in select low-grade tumors, or combination radiation and chemotherapy with procarbazine, lomustine, and vincristine (PCV) or temozolomide (TMZ). While prospective studies investigating treatments for molecularly defined oligodendrogliomas are ongoing, this retrospective study analyzes the relationship between adjuvant regimens and progression-free survival (PFS)., Methods: Adults with IDH-mutant, 1p/19q codeleted oligodendroglioma (WHO grade 2 or 3) who underwent surgery between 2005 and 2021 were identified. Clinical data, disease characteristics, treatment, and outcomes were collected., Results: A total of 207 patients with grade 2 and 70 with grade 3 oligodendrogliomas were identified. Median (IQR) follow-up was 57 (87) months. Patients with grade 3 tumors who received adjuvant radiation and PCV had longer median PFS (> 110 months) than patients who received radiation and TMZ (52 months, p = 0.008) or no adjuvant chemoradiation (83 months, p = 0.03), which was not seen in grade 2 tumors (p = 0.8). In multivariate analysis, patients who received PCV chemotherapy (Relative Risk [95% CI] = 0.24[0.05-1.08] and radiotherapy (0.46[0.21-1.02]) trended towards longer PFS, independently of grade., Conclusion: Adjuvant radiation and PCV are associated with improved PFS over radiation with TMZ in patients with grade 3 molecularly defined oligodendrogliomas, and all-grade patients treated with PCV trended towards decreased risk of recurrence and progression. These results highlight the importance of ongoing clinical trials investigating these treatments., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Johns Hopkins Institutional Review Board (IRB00282685). Informed consent was waived due to the retrospective, non-interventional design of this study. Competing interests: On behalf of all authors, the corresponding author states no conflicts of interest. KJR: Research support from Elekta AB, Accuray and Canon; Data Safety Monitoring Board for BioMimetix; Travel expenses from Brainlab, Elekta AB, Accuray and Icotec; Consulting fees Icotec. MH: Parexel - data safety monitoring board; Advarra - data safety monitoring board; Bayer, AnHeart Therapeutics Inc, and Servier -- advisory board. Reporting guidelines: We found no applicable reporting guidelines that would apply to this article. By following the EQUATOR reporting guidelines decision tree, ( http://www.equatornetwork.org/wp-content/uploads/2013/11/20160226-RG-decision-tree-for-Wizard-CC-BY-26-February-2016.pdf ), we found that none of the most popular checklists are appropriate for our study design., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Acute myeloid leukemia (AML) with translocation t(8;16)(p11;p13) represents a rare entity that has been categorized as a disease-defining recurring cytogenetic abnormality with adverse risk in the 2022 European LeukemiaNet classification. This rating was mainly based on a retrospective analysis comprising patients from several large clinical trials, which, however, included only 21 patients treated with allogeneic stem cell transplantation (alloSCT). Therefore, the European Society for Blood and Marrow Transplantation performed a registry study on a larger cohort to evaluate the role of alloSCT in t(8;16) AML. Sixty transplant recipients with t(8;16) AML were identified. Two-year overall and leukemia-free survival (OS/LFS) was 43/39%. Patients transplanted in first complete remission (CR1, n = 44) achieved a 2-year OS/LFS of 48%/48%. Following alloSCT in CR1, the multivariable analysis identified a complex karyotype (CK) as a major risk factor for relapse (HR 4.17, p = .016), lower LFS (HR 3.38, p = .01), and lower OS (HR 3.08, p = .017). Two-year OS/LFS of patients with CK was 19%/19%, in contrast to 67%/67% in patients with t(8;16) outside a CK. Other factors for inferior outcomes were older age and secondary AML. In summary, alloSCT could mitigate the adverse risk of patients with t(8;16) AML not harboring a CK, particularly when performed in CR1., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)

Anti-IgLON5 disease was identified 10 years ago, thanks to the discovery of IgLON5 antibodies and the joint effort of specialists in sleep medicine, neuroimmunology, and neuropathology. Without this collaboration, it would have been impossible to untangle fundamental aspects of this disease. After the seminal description in 2014, today there is growing evidence that most patients present a chronic progressive course with gait instability, abnormal movements, bulbar dysfunction, and a sleep disorder characterized by nonrapid eye movement and REM parasomnias, and obstructive sleep apnea with stridor. Unlike other autoimmune encephalitides, the response to immunotherapy is suboptimal. Neuropathologic studies in patients with a prolonged clinical course showed a novel 3-repeat and 4-repeat neuronal tauopathy mainly involving the hypothalamus and tegmentum of the brainstem. The absence of tau deposits in the brain of patients who died early, the demonstration that IgLON5 antibodies cause an irreversible decrease in cell-surface levels of IgLON5, and a disorganization of the neuronal cytoskeleton suggest that the disease is primarily autoimmune and the tauopathy a secondary event. After a decade, we now know the disease much better, but important issues still need to be addressed. We have to gather more information on the natural course of the disease, develop better treatments, and identify robust predictors of outcome. More basic research is needed on the physiology of IgLON5, how antibodies disrupt its function, and the downstream effects leading to neurodegeneration. Finally, better designed passive transfer and active immunization models are needed to confirm the pathogenic effect of IgLON5 antibodies.

Background: Driving pressure is thought to determine the effect of low tidal ventilation on survival in patients with acute respiratory distress syndrome. The leading cause of mortality in these patients is non-pulmonary multiorgan dysfunction, which is believed to worsen due to the biological response to mechanical ventilation (biotrauma). Therefore, we aimed to analyze the association between driving pressure, biotrauma, and non-pulmonary multiorgan dysfunction. Additionally, we analyzed this relationship for tidal volume/predicted body weight., Methods: Observational study that included adult patients with acute respiratory distress syndrome undergoing invasive mechanical ventilation admitted to the Hospital Clinic of Barcelona, Spain, between June 2019 and February 2021. We conducted mixed-effects models to assess the effects of driving pressure and tidal volume/predicted body weight on the evolution of 22 log-transformed biomarker variables during the first, third, and fifth days after study enrollment. These 22 systemic biomarkers characterized epithelial and endothelial pulmonary dysfunction, inflammation, and coagulation disorders in the included patients. In the same fashion, the association between driving pressure and non-pulmonary multiorgan dysfunction was evaluated by the non-pulmonary sequential organ failure assessment score (non-pulmonary SOFA) and its associated variables. Finally, we performed mediation analyses to assess whether the relationship between biomarkers and driving pressure was mediated by other ventilator-induced lung injury parameters., Results: Thirty-eight patients were included. Driving pressure was independently associated with soluble Receptor for advanced glycation end-products, Interleukin (IL)-8, IL-6, IL-10, IL-17, Interferon-ɣ, Chemokine (C-C motif)-2, Vascular endothelial growth factor, Tissue factor, Protein C, Protein S, and higher dose of norepinephrine. However, this relationship attenuated over time. In contrast, tidal volume/predicted body weight was not associated with any of the 22 biomarkers tested . A concomitant increase in positive end-inspiratory plateau pressure or tidal volume did not mediate the effect of driving pressure on biomarkers. Conversely, the association between compliance of the respiratory system and pulmonary epithelial dysfunction was primarily mediated by driving pressure., Conclusions: Driving pressure, but not tidal volume/predicted body weight, was correlated with epithelial and endothelial pulmonary dysfunction, inflammation, coagulation disorders, and hemodynamic dysfunction. However, this relationship diminished over time., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Société Française d'Anesthésie et de Réanimation (SFAR). Published by Elsevier Masson SAS. All rights reserved.)

Objectives: The AsseSSing Impact in pSoriatic Treatment (ASSIST) study investigated prescribing in routine PsA care and whether the patient-reported outcome-PsA Impact of Disease questionnaire (PsAID-12)-impacted treatment. This study also assessed a range of patient and clinician factors and their relationship to PsAID-12 scoring and treatment modification., Methods: Patients with PsA were selected across the UK and Europe between July 2021 and March 2022. Patients completed the PsAID questionnaire and the results were shared with their physician. Patient characteristics, disease activity, current treatment methods, treatment strategies, medication changes and patient satisfaction scores were recorded., Results: A total of 503 patients were recruited. Some 36.2% had changes made to treatment, and 88.8% of these had treatment escalation. Overall, the mean PsAID-12 score was higher for patients with treatment escalation; increase in PSAID-12 score is associated with increased odds of treatment escalation (odds ratio 1.58; P < 0.0001). However, most clinicians reported that PsAID-12 did not impact their decision to escalate treatment, instead supporting treatment reduction decisions. Physician's assessment of disease activity had the most statistically significant effect on likelihood of treatment escalation (odds ratio 2.68, per 1-point score increase). Escalation was more likely in patients not treated with biologic therapies. Additional factors associated with treatment escalation included: patient characteristics, physician characteristics, disease activity and disease impact., Conclusion: This study highlights multiple factors impacting treatment decision-making for individuals with PsA. PsAID-12 scoring correlates with multiple measures of disease severity and odds of treatment escalation. However, most clinicians reported that the PsAID-12 did not influence treatment escalation decisions. Psoriatic Arthritis Impact of Disease (PsAID) scoring could be used to increase confidence in treatment de-escalation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Women are known to have twice as much lifetime prevalence of post-traumatic stress disorder (PTSD) as men do. It has been reported that the risk genotype (CC) of a single nucleotide polymorphism (SNP) (rs2267735) in the pituitary adenylate cyclase-activating polypeptide (PACAP-PAC1R) system is associated with PTSD risk and altered fear conditioning and fear extinction in women. Surprisingly, no previous work has studied the effect of this SNP on fear conditioning, extinction, or generalization in non-traumatized/low trauma load women. Here, two separate groups of women underwent either a two-day fear conditioning and fear extinction paradigm, or a one-day fear conditioning and fear generalization paradigm. Results showed no significant differences between genotypes in conditioned stimulus discrimination, during fear acquisition, extinction, or generalization. These findings suggest that the previously reported fear processing impairments in traumatized CC women are not a consequence of this genotype alone, but likely dependent on the interaction between this genetic risk and the exposure to traumatic stressors., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest, (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)