Articles científics - HVH

Osmotic Fragility in Leukodepleted Stored Red Blood Cells: Implications for Neurocritical Care Transfusion Strategies

2026-03-11T13:02:33Z

Osmotic Fragility in Leukodepleted Stored Red Blood Cells: Implications for Neurocritical Care Transfusion Strategies Peris, Marta; Pons Escoll, Veronica; Rodríguez-Borrero, Nuria; Jurado, Desiree; Parra, Rafael; Rierola, Marina; Poca, Maria A.; Ortuño Cabrero, Ana; Sahuquillo, Juan Hemoglobina lliure; Fragilitat osmòtica; Emmagatzematge de glòbuls vermells; Hemoglobina libre; Fragilidad osmótica; Almacenamiento de glóbulos rojos; Free hemoglobin; Osmotic fragility; Red blood cell storage; Background: Anemia is frequent in critically ill patients with traumatic brain injury (TBI) and worsens neurological outcomes. Red blood cell (RBC) transfusion is a cornerstone of management, but storage-related biochemical and structural changes may impair oxygen delivery. This study examined the effect of storage duration on osmotic fragility (OF) and free hemoglobin (fHb) in leukodepleted packed RBCs (pRBCs) as indicators of membrane stability and hemolysis. Methods: Twenty-four leukodepleted pRBC units in SAGM (saline, adenine, glucose, and mannitol) solution were analyzed from Day 3 to Day 42. OF was assessed by Beutler’s method with H50 values derived from logistic models, and fHb was quantified spectrophotometrically. Flow cytometry with phosphate-buffered saline (PBS)-induced osmotic stress provided complementary OF data. Results: OF increased significantly beyond 28 days, with Week 6 H50 values exceeding those at Weeks 2 and 4 (p < 0.0001). fHb rose progressively with storage: 7.3 ± 4.3 µmol/L (Week 2), 14.6 ± 7.9 (Week 4), and 25.7 ± 12.1 (Week 6) (p < 0.0001). Hemolysis remained below the 0.8% threshold but increased from 0.09% to 0.29% (p < 0.0001). Conclusions: pRBC storage beyond 28 days leads to greater OF and fHb release, reflecting reduced membrane stability. These changes may compromise transfusion efficacy and oxygen delivery in neurocritical care.

Consolidation deficits in episodic memory define distinct clinical and neurodegenerative profiles in Huntington’s disease

2026-03-11T13:12:48Z

Consolidation deficits in episodic memory define distinct clinical and neurodegenerative profiles in Huntington’s disease Quevedo-García, Angela; Sampedro, Frederic; Oltra-Cucarella, Javier; Perez-Perez, Jesus; Martinez-Horta, Saul; Puig Davi, Arnau Episodic memory; Hippocampus; Huntington’s disease; Memoria episódica; Hipocampo; Enfermedad de Huntington; Memòria episòdica; Hipocamp; Malaltia de Huntington; Background Huntington’s disease (HD) is primarily associated with executive dysfunction, but episodic memory impairment is also present. Traditionally, these memory deficits have been attributed to retrieval difficulties linked to fronto-striatal dysfunction, rather than to disruptions in encoding or consolidation processes. However, the specific nature and diversity of memory impairments in HD remain underexplored. Objective To characterize the profile of episodic memory impairment in HD, identify distinct cognitive phenotypes, and examine their clinical, neuroanatomical, and biomarker correlates. Methods We assessed episodic memory in HD patients and healthy controls using the Free and Cued Selective Reminding Test (FCSRT), complemented by Item-Specific Deficit Approach (ISDA) indices to quantify encoding, consolidation, and retrieval deficits. Structural MRI was used to identify gray matter volume correlates, and plasma neurofilament light chain (NfL) was measured as a marker of neuroaxonal injury. Results Compared to controls, HD patients showed marked impairments in free recall with preserved cued recall, suggesting predominant retrieval deficits. However, nearly one-third of patients exhibited global impairments across all FCSRT components, mainly driven by consolidation deficits consistent with medial temporal lobe dysfunction. This subgroup also showed worse cognitive and functional performance and significant atrophy in the hippocampus, entorhinal cortex, and parahippocampal gyrus. Conclusion Episodic memory dysfunction in HD is heterogeneous and includes both retrieval-related and consolidation-driven profiles. These profiles reflect distinct neurodegenerative patterns, emphasizing the importance of cognitive subtyping for improving clinical characterization and biomarker development in HD.; The present study was funded from Fondo de Investigaciones Sanitarias (FIS) from the Instituto de Salud Carlos III (Grant number: PI21/01758) and Fondos FEDER.

Durvalumab in Advanced Biliary Tract Cancer: Real-World Data From a Large Cohort of Patients Across Multiple International Centers

2026-03-11T13:17:07Z

Durvalumab in Advanced Biliary Tract Cancer: Real-World Data From a Large Cohort of Patients Across Multiple International Centers Fornaro, Lorenzo; Ikeda, Masafumi; Abidoye, Oluseyi; Lucchetti, Jessica; rimini, margherita; Antonuzzo, Lorenzo; Castet, Florian Biliary tract cancer; Chemotherapy; Cholangiocarcinoma; Càncer de les vies biliars; Quimioteràpia; Colangiocarcinoma; Cáncer de las vías biliares; Quimioterapia; Colangiocarcinoma; Background We recently published the first real-world multicenter and multi-institutional study of cisplatin, gemcitabine, and durvalumab in patients with advanced biliary tract cancer (BTC). Here we present an expanded patient cohort with an increased sample size and longer median follow-up. Methods The study population included patients with advanced BTC, who received cisplatin/gemcitabine plus durvalumab at 55 centers across 12 countries in Europe, the United States, and Asia. The primary endpoints of the study were progression-free survival (PFS) and overall survival (OS). Secondary endpoints were overall response rate (ORR) and safety. Results Overall, 1358 patients were enrolled. Median PFS was 7.6 months (95% CI: 7.2–8.1), and median OS was 15.6 months (95% CI: 14.8–16.5). ORR was 35.6%, and DCR was 82.7%. Any grade AEs occurred in 1213 patients (89.3%). Grade 3–4 AEs occurred in 597 patients (43.2%). The rate of immune-related AEs (irAE) was 20.3%. Grade 3–4 irAE occurred in 3.0% of patients. At the multivariate analysis for OS, normal albumin level (HR 0.68, 95% CI 0.57–0.81, p < 0.0001), CEA levels within normal ranges (HR 0.68, 95% CI 0.57–0.82, p < 0.0001), NLR < 3 (HR 0.62, 95% CI 0.52–0.74, p < 0.0001), ECOG PS 0 (HR 0.51, 95% CI 0.42–0.61, p < 0.0001), and prior surgery (HR 0.80, 95% CI 0.65–0.99, p = 0.036) were positive prognostic factors. Conclusion The updated findings, derived from an expanded cohort, further support the adoption of durvalumab in combination with gemcitabine and cisplatin in routine clinical practice, reinforcing the efficacy and safety outcomes demonstrated in the phase III TOPAZ-1 trial.

Unbiased Artificial Intelligence: Addressing Bias in Computational Pathology

2026-03-11T12:47:32Z

Unbiased Artificial Intelligence: Addressing Bias in Computational Pathology Montezuma, Diana; Porz, Rouven; Ameisen, David; Serbanescu, Mircea-Sebastian; L'Imperio, Vincenzo; Temprana Salvador, Jordi Inteligencia artificial; Patología computacional; Intel·ligència artificial; Patologia computacional; Artificial intelligence; Computational pathology; This work was conducted independently and was fully funded by the European Society of Digital and Integrative Pathology (ESDIP).