Preventing exacerbations in chronic obstructive pulmonary disease (COPD) is a priority, as exacerbations accelerate progression, increase mortality, and impair quality of life. The use of biologics that act on specific inflammatory pathways through monoclonal antibodies in COPD offers a precision medicine strategy for high-risk patients who continue to experience frequent exacerbations despite optimal inhaled treatment. However, the use of these biologic therapies in COPD presents significant challenges, stemming from the clinical heterogeneity of the disease and the limited evidence available. Their indication and management must be personalized and precise, raising questions about how to implement a biologic therapy strategy in COPD in clinical practice. This clinical protocol focused on the use of biologic therapy in COPD sets out the objectives ("Why"), describes the selection of candidates ("In which patients"), the monitoring of response ("What should be measured") and how to implement it in clinical practice ("How") based on the available evidence and expert consensus.
BACKGROUND:Antitachycardia pacing (ATP) can prevent defibrillator shocks and associated adverse outcomes. Opportunities to enhance ATP performance exist, particularly for rapid monomorphic ventricular tachycardia (MVT). Intrinsic ATP (iATP) is the first closed-loop algorithm that designs and auto-adjusts ATP therapy in real time. OBJECTIVE:This study aimed to evaluate iATP performance in a large, real-world cohort. METHODS:This global, prospective, observational study enrolled patients with an iATP-enabled implantable cardioverter-defibrillator or cardiac resynchronization therapy-defibrillator device. The primary objective, to demonstrate iATP could effectively terminate >60% of MVT episodes in the fast ventricular tachycardia (VT) zone, was analyzed using the generalized estimating equations (GEE) method. Additional analyses included overall effectiveness and the rate of MVT acceleration resulting in shock. A post hoc analysis used GEE models to compare iATP data with standard ATP from a retrospective cohort. RESULTS:In total, 1875 enrolled patients were followed for a total of 3200 patient-years, yielding 2575 iATP-treated MVT episodes. Of 265 iATP-treated episodes in the fast VT zone (73 patients), the GEE-estimated success rate was 89.7% (95% confidence interval [CI] 83.6-93.7), exceeding the primary objective. The GEE-estimated rate of iATP-associated MVT acceleration resulting in shock was 2.3%. Compared with standard ATP, iATP almost doubled the odds of VT termination (adjusted odds ratio 1.87; 95% CI 1.32-2.66; P = .0005) and halved the odds of acceleration resulting in shock (adjusted odds ratio 0.43; 95% CI 0.25-0.74; P = .0026). CONCLUSION:In routine practice, iATP was highly effective and safe across all VT rates. Although exploratory, iATP had overall superior termination rates and a lower chance of acceleration resulting in shock than standard ATP.
Genomic surveillance of respiratory syncytial virus (RSV) enables detecting and monitoring of circulating lineages and the emergence of amino acid substitutions affecting transmission, severity, and treatment. We present a comprehensive workflow for RSV whole-genome sequencing, from sample processing to lineage classification. Tiling amplicon protocols adapted for Illumina and Oxford Nanopore Technologies sequencing approaches and an in-house bioinformatic pipeline were developed for the analysis of samples. We validated the workflow on clinical samples, and identified RSV sequences harbouring substitutions associated with monoclonal antibody resistance and the presence of coinfections.
In a large multicenter real-world cohort, we aimed to evaluate outcomes of FLAG-Ida salvage therapy for relapsed/refractory (R/R) acute myeloid leukemia (AML) and validated the SALFLAGE prognostic score. We analyzed 1079 adults with R/R AML treated across 112 PETHEMA institutions over 26 years (1998-2024), including patients with primary refractory disease (36.9%) and first relapse episode (63.1%), with a median age of 52 years. Complete remission composite (CRc) was achieved 56.8%, including complete remission (CR) in 51.0%, CR with incomplete recovery in 4.0%, and morphological-free-state in 1.8%, enabling 35.2% of patients and 62% of responders to proceed to allogeneic transplantation without morphological disease. With median follow-up of 50.9 months, median overall survival (OS) was 10.2 months, with 5-year OS rate of 21.6%. Prior allogeneic transplantation (HR 0.54; p < 0.001) and relapse-free interval ≥ 1 year (HR 0.75; p = 0.024) independently predicted improved OS, whereas modified high-risk cytogenetics including t(8; 21) (HR 3.58; p < 0.001), FLT3-ITD mutation at primary diagnosis (HR 1.61; p < 0.001), and age ≥ 60 (HR 1.43; p < 0.001) conferred inferior OS. Validation of the SALFLAGE score demonstrated moderate discrimination (C-index 0.67), with 5-year survival of 38.4%, 27.2%, and 12.7% across risk categories (p < 0.001). Outcomes improved over periods (1998-2005 vs. 2006-2016 vs. 2017-2024): 30-day mortality was 6.9% vs. 9.3% vs. 5.0%, respectively (p = 0.030), and median OS was 7.8 versus 9.4 versus 11.1 months, respectively (p = 0.16). We confirm FLAG-Ida as a reference salvage regimen in fit R/R AML and validate the SALFLAGE score in this setting.
