Qualitative and Quantitative Assessment of Atrial Functional Mitral Regurgitation: analysis from the REVEAL-AFMR registry.

Background: The prevalence, characteristics, and prognosis of atrial functional mitral regurgitation (AFMR) based on severity remain unclear. No studies have systematically evaluated quantitative thresholds, such as effective regurgitant orifice area (EROA) or regurgitant volume, in relation to outcomes in AFMR. This multicenter study aimed to clarify the clinical implications of both qualitative and quantitative assessments of AFMR severity.

Phase IV adaptive randomised clinical trials evaluating efficacy and cost-efficacy of pre-emptive pharmacogenetic genotyping strategies in the Spanish National Health System: iPHARMGx Master Protocol and PREVESTATGx nested clinical trial.

Introduction: Genetic variations impact drug response, driving the need for personalised medicine through pre-emptive pharmacogenetic testing. However, the adoption of pre-emptive pharmacogenetic testing for commonly prescribed drugs, such as statins, outside of tertiary hospitals is limited due to a lack of pharmacoeconomic evidence to support widespread implementation by healthcare policy-makers. The Spanish Consortium for the Implementation of Pharmacogenetics (iPHARMGx Consortium) addresses this by developing a clinical trial master protocol that will govern multiple nested adaptive clinical trials that compare genotype-guided treatments to standard care in specific drug-gene-population triads, asses their cost-efficacy and identify novel biomarkers through advanced sequencing techniques.

Prognostic Expression Signature of , , and Genes in Patients with Metastatic Hormone-sensitive Prostate Cancer Treated with Androgen Receptor Pathway Inhibitors.

Unlabelled: Alterations in the tumor suppressor genes (TSGs) , , and are associated with treatment resistance, worse survival, and aggressive variants of prostate cancer (AVPC). We previously developed and validated a signature reflecting low TSG expression (TSG) that was associated with poor outcomes in patients with metastatic hormone-sensitive prostate cancer (mHSPC) treated with androgen deprivation therapy (ADT) ± docetaxel. The aim of this multicenter retrospective study was to validate the TSG signature in patients with mHSPC treated with ADT and an androgen receptor pathway inhibitor (ARPI) and to explore clinical characteristics at progression according to TSG status.

Plasma acellular transcriptome contains Parkinson's disease signatures that can inform clinical diagnosis.

We aimed to identify plasma cell-free transcripts (cfRNA) associated with Parkinson's disease (PD) that also have a high predictive value to differentiate PD from healthy controls. Leveraging two independent populations from two different movement disorder centers we identified 2,188 differentially expressed cfRNAs after meta-analysis. The identified transcripts were enriched in PD relevant pathways, such as PD (p=9.

Effectiveness of endoscopic ultrasound-guided simple puncture-aspiration (non-stenting) in the management of abdominal collections.

Background: Endoscopic management of abdominal collections includes endoscopic ultrasound (EUS)-guided transmural drainage, transpapillar via endoscopic retrograde cholangiopancreatography (ERCP), and EUS-guided simple puncture-aspiration (SPA). The latter is little reported, and there are some doubts about its real usefulness.

Objectives: The aim of this study was to assess the effectiveness of EUS-guided SPA as a first-line approach for treatment in selected abdominal collections.

ACTIV trials: Lessons learned in trial design in the setting of an emergent pandemic.

Accelerating COVID-19 Treatment Interventions and Vaccines (ACTIV) was initiated by the US government to rapidly develop and test vaccines and therapeutics against COVID-19 in 2020. The ACTIV Therapeutics-Clinical Working Group selected ACTIV trial teams and clinical networks to expeditiously develop and launch master protocols based on therapeutic targets and patient populations. The suite of clinical trials was designed to collectively inform therapeutic care for COVID-19 outpatient, inpatient, and intensive care populations globally.

A phase 2, multicenter, clinical trial of CPX-351 in older patients with secondary or high-risk acute myeloid leukemia: PETHEMA-LAMVYX.

Background: LAMVYX was a multicenter, single-arm, phase 2 trial designed to validate the safety and efficacy of CPX-351 in patients aged 60-75 years with newly diagnosed, secondary acute myeloid leukemia and to generate evidence on key issues not addressed in the preceding regulatory pivotal trial.

Methods: The primary end point of the study was the complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate after induction. Eligible patients were recommended to undergo allogeneic hematopoietic stem cell transplantation after the first consolidation cycle.

Validation of the Valve Academic Research Consortium High Bleeding Risk Definition in Patients Undergoing TAVR.

The Valve Academic Research Consortium for High Bleeding Risk (VARC-HBR) has recently introduced a consensus document that outlines risk factors to identify high bleeding risk (HBR) in patients undergoing transcatheter aortic valve replacement (TAVR). The objective of the present study was to evaluate the prevalence and predictive value of the VARC-HBR definition in a contemporary, large-scale TAVR population. Multicenter study including 10,449 patients undergoing TAVR.

Development and validation of the post-CAR prognostic index for large B-cell lymphoma patients after CAR-T progression in third or later line treatment.

Chimeric antigen receptor (CAR) T-cell therapy fails to achieve durable responses in over 60% of relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients in the third or later line setting. After CAR-T failure, survival outcomes are heterogeneous and a prognostic model in this patient population is lacking. A training cohort of 216 patients with progressive disease (PD) after CAR-T from 12 Spanish centers was used to develop the Post-CAR Prognostic Index (PC-PI); primary endpoint was overall survival (OS) from CAR-T progression.

Design and cohort characteristics of TRACK, a prospective study of hyperkalaemia management decision-making.

Background: Guideline-recommended hyperkalaemia management includes dietary potassium (K) restriction, bicarbonate correction, diuretics and K binders with dose reduction of renin-angiotensin-aldosterone system inhibitors as a last resort. The extent to which these recommendations are implemented is uncertain, as real-world data on hyperkalaemia management are limited. The Tracking Treatment Pathways in Adult Patients with Hyperkalemia (TRACK) study is a multinational, prospective, longitudinal study that is being conducted to address this knowledge gap.

Treatment of atopic dermatitis with abrocitinib in real practice in Spain: efficacy and safety results from a 24-week multicenter study.

Background: Abrocitinib, a selective JAK 1 inhibitor, was recently approved in Europe. Despite its approval, real-world data on its efficacy and safety in treating moderate-to-severe atopic dermatitis (AD) remains limited.

Objectives: This study aimed to evaluate the short-term effectiveness and safety of abrocitinib in a real-life setting for patients with moderate-to-severe AD.

Novel prognostic factors and therapeutic advances in adult acute lymphoblastic leukemia.

The prognosis of adult patients with acute lymphoblastic leukemia (ALL) has improved in the last decades. This has been due to the sum of several factors including more precise recognition of the ALL subtypes, refinement of the assessment of prognostic factors, improvement in pediatric-inspired chemotherapy regimens and especially to the incorporation of novel targeted and immune therapeutics, as well as engineered cellular therapies, among others. These therapies were initially developed for relapsed or refractory patients but are now being incorporated into frontline treatment and represent a major step forward in ALL therapy.

Beyond myeloid neoplasms germline guidelines: Validation of the thresholds criteria in the search of germline predisposition variants.

Introduction: Germline predisposition to myeloid neoplasms can be suspected in patients younger than 50 years or when harboring mutations with a variant allele frequency (VAF) higher than 30% for point mutations in specific genes. To investigate the VAF thresholds' accuracy we have explored the prevalence of germline variants below the 30% VAF threshold.

Methods: A total of 40 variants with VAF lower than 30% in bone marrow samples of myeloid neoplasm patients were selected and studied in CD3 cells.

Altered tubulin detyrosination due to SVBP malfunction induces cytokinesis failure and senescence, underlying a complex hereditary spastic paraplegia.

Senescence, marked by permanent cell cycle arrest may contribute to the decline in regenerative potential and neuronal function, thereby promoting neurodegenerative disorders. In this study, we employed whole exome sequencing to identify a previously unreported biallelic missense variant in SVBP (p.Leu49Pro) in six patients from three unrelated families.

Reliability and Validity of Ultrasound in Identifying Anatomical Landmarks for Diagnosing A2 Pulley Ruptures: A Cadaveric Study.

: Rock climbing is becoming more popular, leading to an increased focus on diagnosing and treating related injuries. Finger pulley and flexor tendon injuries are common among climbers, with the A2 pulley being the most frequently affected. High-resolution ultrasound (US) is the preferred method for detecting pulley injuries.