02.07.01. Investigación y comunicación científica

Phase IIB, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Intravenous Defibrotide for the Prevention and Treatment of Respiratory Distress and Cytokine Release Syndrome in COVID-19

2026-08-03T10:48:15Z

Phase IIB, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Intravenous Defibrotide for the Prevention and Treatment of Respiratory Distress and Cytokine Release Syndrome in COVID-19 Jara-Rubio, Rubén; Martínez-Mellado, Antonio-José; Kiwitt-Cardenas, Jonathan; Clavel, José-G; García-Pérez, Bartolomé; Castro, Pedro; Díaz-Ricart, Maribel; Carrillo-Alcaraz, Andrés; López-Bernus, Amparo; Bernal-Morell, Enrique; Roura, Aychel; Marín, Sonia; Ruiz-López, Francisco-José; Solana-Martínez, Elena; Martínez-Baño, Domingo; Albacete-Moreno, Carlos-L; Andreu-Soler, Enriqueta; Tellez-Santoyo, Adrián; Fernández-Méndez, Sara; Noguera-Velasco, José-Antonio; Cebreiros-López, Iria; Parrilla, Andrés; Espuny-Miró, Alberto; García-Bernal, David; Blanquer-Blanquer, Miguel; Sánchez-Salinas, Andrés; Iniesta-Martínez, Francisca; Hernández-García, Cristina; Muro-Amador, Manuel; Minguela-Puras, Alfredo; Moreno-Docón, Antonio; Torres-Cantero, Alberto; Muñoz-García, María; Serrano, Manuel; Iacobelli, Massimo; Carlo-Stella, Carmelo; Wei, Lee-Jen; Richardson, Paul-G; Moraleda-Jiménez, José-María INTRODUCTION: Endothelial dysfunction is key in COVID-19 pathogenesis. This randomized, double-blind phase IIb trial investigated continuous intravenous infusion of defibrotide in patients hospitalized with SARS-CoV-2 infection and respiratory failure. METHODS: One-hundred and fifty patients were randomized (2:1) to defibrotide or placebo, stratified by disease severity (WHO COVID-19 severity scale 4/5 vs. 6). The primary endpoint was clinical improvement time (days from first improvement through Day 30). RESULTS: Median clinical improvement time was not significantly different with defibrotide versus placebo (15.0 [IQR: 0-24] vs. 20.0 [IQR: 9-25] days; p = 0.10). Day-30 (23.0% vs. 22.0%) and Day-60 (26.0% vs. 22.0%) mortality, reduction in mean fraction of inspired oxygen during treatment, and median duration of hospitalization did not differ with defibrotide versus placebo. Defibrotide demonstrated favorable safety, with no differences versus placebo in serious adverse events (34.0% vs. 36.0%), hypotension (16.0% vs. 12.0%), or hemorrhage (13.0% vs. 8.0%). Exploratory pre-specified biomarker analyses showed greater early d-dimer reduction and lymphocyte recovery with defibrotide, although these results require validation. CONCLUSION: Continuous intravenous infusion of defibrotide was safe but did not improve clinical outcomes in severe COVID-19. Further analyses will explore mechanistic actions and pharmacokinetics of defibrotide and the pathophysiology of endothelial dysfunction in COVID-19. TRIAL REGISTRATION: EudraCT identifier: 2020-001409-21. CLINICALTRIALS: gov identifier: NCT04348383.

Combined versus Sequential Surgery in Lamellar Macular Holes: A Multicenter Observational Study

2026-08-03T10:48:58Z

Combined versus Sequential Surgery in Lamellar Macular Holes: A Multicenter Observational Study López-Arbues, Santiago; Gómez-Rivera, Susana; Rodríguez, Ibai-Tamayo; Arredondo-Montero, Javier; Selles-Navarro, Inmaculada; Montoliu-antón, Ana; Bilbao-Malave, Valentina; González-Zamora, Jorge; García-Layana, Alfredo; Aliseda-Pérez-de-Madrid, Daniel PURPOSE: To compare 1-year best-corrected visual acuity (BCVA) after pars plana vitrectomy (PPV) for lamellar macular hole (LMH) between combined phacovitrectomy and sequential strategies, and to explore factors associated with postoperative visual outcome. METHODS: Multicenter observational study of adults with optical coherence tomography (OCT)-confirmed LMH undergoing PPV. Surgical sequence was classified as combined surgery or sequential surgery (PPV?phacoemulsification, PPV in pseudophakic eyes, or PPV without subsequent cataract extraction). LMHs were classified as tractional, mixed, or degenerative based on OCT criteria. BCVA (logMAR) was recorded preoperatively and at 1 year. Ceiling effect was defined as achieving 1-year BCVA ?0.22 logMAR. Independent predictors of 1-year BCVA were assessed using a linear mixed-effects model with a random intercept for patient. RESULTS: A total of 175 eyes from 167 patients were included; 1-year BCVA was available for 126 eyes (72.0%), whereas 49 eyes (28.0%) had missing 1-year BCVA. Among eyes with recorded 1-year BCVA, no statistically significant differences were detected between combined and sequential surgery (0.2 [0.1-0.3] vs 0.2 [0.1-0.3]; p = 0.939) or among LMH subtypes. Overall, BCVA improved from 0.4 (IQR 0.3-0.5) to 0.2 (0.1-0.3) at 1 year. In ceiling-effect analysis, baseline BCVA (p = 0.013) and the presence of isolated epiretinal membrane (p = 0.032) were associated with achieving BCVA ?0.22 logMAR. In the mixed-effects model, baseline BCVA was the only independent predictor of 1-year BCVA (? = 0.60; 95% CI 0.32-0.89; p < 0.001). CONCLUSION: PPV for LMH was associated with visual improvement at 1 year, and the study did not detect statistically significant differences in final BCVA between combined and sequential strategies or among LMH subtypes. Baseline BCVA was the main determinant of 1-year outcomes, supporting individualized selection of surgical sequence based on lens status and shared patient-surgeon preferences.

Postmortem genetic testing in sudden death: clinical and medico-legal implications

2026-08-03T10:47:20Z

Postmortem genetic testing in sudden death: clinical and medico-legal implications Sabater-Molina, María; Nicolás-Rocamora, Elisa; Munteanu, Serena; Fuentes-Bermejo, María-Dolores; Osuna-Carrillo-Albornoz, Eduardo; Pérez-Cárceles, María-Dolores; Pastor-Quirante, Francisco; Gimeno-Blanes, Juan-Ramón; Hernández-del-Rincón, Juan-Pedro BACKGROUND: Anatomopathological autopsy and postmortem genetic testing play a crucial role in forensic medicine, particularly in elucidating the causes of sudden death (SD) that remain unexplained by conventional methods. This study explores their value in detecting inherited cardiac conditions with medico-legal and preventive implications. METHODS: From a 15-year forensic cohort, 12 cases of sudden unexpected death in which conventional autopsy was inconclusive or where a hereditary cardiac condition was suspected, were analyzed. Each case underwent histology, toxicology, and targeted next-generation sequencing panels covering genes associated with channelopathies and cardiomyopathies. Variants were classified according to ACMG/AMP guidelines, and family studies were performed when feasible. RESULTS: Integrated pathological and genetic analysis identified pathogenic or likely pathogenic variants in several cases, notably in RYR2 and CALM2 (channelopathies) and FLNC and PPP1R13L (cardiomyopathies). In these cases, genetic findings confirmed the diagnosis, while variants of uncertain significance were detected in others. Postmortem genetic testing proved essential in cases with structurally normal hearts or sub-diagnostic findings, such as concealed arrhythmogenic cardiomyopathy. Familial cascade testing uncovered additional carriers, enabling targeted surveillance and preventive measures. CONCLUSION: Combining pathological autopsy and postmortem genetic testing significantly improves the diagnostic yield in unexplained SD, uncovers hidden hereditary cardiac conditions, and provides critical information for risk assessment in relatives. Beyond clinical implications, these findings contribute to accurate forensic determinations and prevention of miscarriages of justice. Integrating genetic studies into forensic protocols should become standard practice to ensure both scientific rigor and legal fairness. CLINICAL TRIAL REGISTRATION: Not applicable.

Effectiveness and Persistence of Long-Acting Injectable Cabotegravir and Rilpivirine in Migrant Individuals Living With HIV in Spain: Substudy of the RELATIVITY Cohort

2026-08-03T10:47:19Z

Effectiveness and Persistence of Long-Acting Injectable Cabotegravir and Rilpivirine in Migrant Individuals Living With HIV in Spain: Substudy of the RELATIVITY Cohort Llenas-García, Jara; Arcos-Rueda, María-del-Mar; Calderon-Hernaiz, Ruth; Pedrero-Tome, Roberto; Bisbal-Pardo, Otilia; Matarranz, Mariano; Torralba, Miguel; Galindo-Puerto, María-José; Rodríguez, Adrián; Penaranda-Vera, María; Sanjoaquin-Conde, Isabel; de-la-Fuente-Moral, Sara; Cabello-Úbeda, Alfonso; Navarro-San-Francisco, Carolina; Antelo-Cuellar, Karenina; Pedrosa-Aragon, Marc; Aguilera-García, María; Tiraboschi, Juan; Martínez-Álvarez, Rosa-María; Vivancos, María-Jesús; Montero-Hernández, Carmen; Bernal-Morell, Enrique; Cabello-Clotet, Noemi; Morano-Amado, Luis-Enrique; Gisbert-Pérez, Laura; Sepulveda, María-Antonia; Alemán-Valls, María-Remedios; Sánchez-Guirao, Antonio-Jesús; Fanciulli, Chiara; Escrig, Cristina; Ferreira-Pasos, Eva-María; Lucas-Dato, Ana; García-Torras, Sara; Hidalgo-Tenorio, Carmen; Estébanez, Miriam; Muelas-Fernández, Magdalena; Losa-García, Juan-Emilio; Cerezales-Calvino, Ana; Pino-Díaz, María-Elisa; Martínez-Montes, Clara; Arenas-García, Víctor; Arnaiz-de-las-Revillas, Francisco; Pernas-Pardavila, Hadrian; Padilla, Sergio; Garcinuno-Jiménez, María-Ángeles; Alonso-Alonso, Lucía; Ramos-Vicente, Noemi; Barragán-Gallo, Patricia; Cabo-Magadan, Rebeca; del-Alamo, Mikel; Egido-Murciano, Miguel-Vicente; Juárez-Toquero, Alberto; Romero-Palacios, Alberto; Clavero-Olmos, Marta; García-Navarro, María-del-Mar; Sanz, José; Gainzarain, Juan-Carlos; Milian-Sanz, Marta; de-la-Calle, Beatriz; Ferrero-Beneitez, Óscar-Luis; Troya, Jesús; Buzon-Martin, Luis INTRODUCTION: Migrants living with HIV often face high mobility, vulnerability and limited baseline information on HIV-1 genotype or treatment history. We aimed to assess the effectiveness and persistence of long-acting injectable cabotegravir and rilpivirine (LAI CAB+RPV) among migrants in Spain. METHODS: This multicentre cohort study across 58 Spanish hospitals included virologically suppressed adults switching to CAB+RPV LAI before January 2025. Data collection started in June 2023. Baseline characteristics and outcomes were compared by migrant status, and multivariate Cox proportional hazards regression models were fitted to assess factors associated with virological failure (VF) and discontinuation. Propensity score matching (PSM) by gender, age, known genotype and prior VF was employed to control for confounding. RESULTS: Of 3135 participants, 951 (30.3%) were migrants, predominantly from Latin America. Median follow-up was 13.8 months (interquartile range 8.91-19.1). VF occurred in 0.9% of migrants versus 0.5% of Spanish-born individuals (odds ratio 1.89, 95% confidence interval [CI] 0.69-5.03; p = 0.22). In adjusted models, migrant status showed a non-significant trend towards higher VF (adjusted hazard ratio [aHR] 2.16, 95% CI 0.89-5.22; p = 0.079). At 12 months, 95.8% of migrants (461/481) persisted on LAI CAB+RPV treatment versus 98.3% of Spanish-born individuals (1348/1372) (p = 0.005). Discontinuation due to any adverse event was more frequent in migrants (3.3% vs. 1.8%). Migrant status was significantly associated with discontinuation due to both local (aHR 2.63, 95% CI 1.33-5.26; p = 0.005) and systemic adverse events (aHR 3.33, 95% CI 1.45-7.69, p = 0.005). In the PSM cohort (n = 932 per group), migrant status was independently associated with increased risk of VF (aHR 3.51, 95% CI 0.95-12.98, p = 0.045) and discontinuation due to systemic adverse events (aHR 2.88, 95% CI 1.01-8.17, p = 0.047). CONCLUSIONS: Nearly one-third of participants switching to LAI CAB+RPV were migrants. While VF was rare overall, migrants had a significantly higher risk of treatment discontinuation, partly driven by adverse events. These findings highlight the need for closer monitoring and tailored strategies to optimize persistence with LAI regimens in migrant populations.