https://hdl.handle.net/10259/11209 2026-10-18T11:54:52Z https://hdl.handle.net/10259/12199 Use of Venetoclax in Patients with Relapsed or Refractory Acute Myeloid Leukemia: The PETHEMA Registry Experience Labrador, Jorge; Saiz Rodríguez, Miriam; de Miguel, Dunia; de Laiglesia, Almudena; Rodríguez Medina, Carlos; Vidriales, María Belén; Pérez Encinas, Manuel; Sánchez Sánchez, María José; Cuello, Rebeca; Roldán Pérez, Alicia; Vives, Susana; Benzo Callejo, Gonzalo; Colorado, Mercedes; García Fortes, María; Sayas, María José; Olivier, Carmen; Recio, Isabel; Conde Royo, Diego; Bienert García, Álvaro; Vahi, María; Muñoz García, Carmen; Seri Merino, Cristina; Tormo, Mar; Vall llovera, Ferran; Foncillas, María Ángeles; Martínez Cuadrón, David; Sanz, Miguel Ángel; Montesinos, Pau The effectiveness of venetoclax (VEN) in relapsed or refractory acute myeloid leukemia (RR-AML) has not been well established. This retrospective, multicenter, observational database studied the effectiveness of VEN in a cohort of 51 RR-AML patients and evaluated for predictors of response and overall survival (OS). The median age was 68 years, most were at high risk, 61% received ≥2 therapies for AML, 49% had received hypomethylating agents, and ECOG was ≥2 in 52%. Complete remission (CR) rate, including CR with incomplete hematological recovery (CRi), was 12.4%. Additionally, 10.4% experienced partial response (PR). The CR/CRi was higher in combination with azacitidine (AZA; 17.9%) than with decitabine (DEC; 6.7%) and low-dose cytarabine (LDAC; 0%). Mutated NPM1 was associated with increased CR/CRi. Median OS was 104 days (95% CI: 56–151). For the combination with AZA, DEC, and LDAC, median OS was 120 days, 104 days, and 69 days, respectively; p = 0.875. Treatment response and ECOG 0 influenced OS in a multivariate model. A total of 28% of patients required interruption of VEN because of toxicity. Our real-life series describes a marginal probability of CR/CRi and poor OS after VEN-based salvage. Patients included had very poor-risk features and were heavily pretreated. The small percentage of responders did not reach the median OS 2022-03-01T00:00:00Z https://hdl.handle.net/10259/12198 Role of Pharmacogenetics in the Treatment of Acute Myeloid Leukemia: Systematic Review and Future Perspectives Pinto Merino, Álvaro; Labrador, Jorge; Zubiaur, Pablo; Alcaraz, Raquel; Herrero, María José; Montesinos, Pau; Abad Santos, Francisco; Saiz Rodríguez, Miriam Acute myeloid leukemia (AML) is a heterogeneous disease characterized by remarkable toxicity and great variability in response to treatment. Plenteous pharmacogenetic studies have already been published for classical therapies, such as cytarabine or anthracyclines, but such studies remain scarce for newer drugs. There is evidence of the relevance of polymorphisms in response to treatment, although most studies have limitations in terms of cohort size or standardization of results. The different responses associated with genetic variability include both increased drug efficacy and toxicity and decreased response or resistance to treatment. A broad pharmacogenetic understanding may be useful in the design of dosing strategies and treatment guidelines. The aim of this study is to perform a review of the available publications and evidence related to the pharmacogenetics of AML, compiling those studies that may be useful in optimizing drug administration. 2022-03-01T00:00:00Z https://hdl.handle.net/10259/12173 Polymorphisms in the oxytocin receptor and their association with apathy and impaired social cognition in Huntington’s disease Saiz Rodríguez, Miriam; Gil Polo, Cecilia; Diez Fairen, Mónica; Martinez Horta, Saul Indra; Sampedro Santalo, Frederic; Calvo Simal, Sara; Alonso García, Esther; Riñones Mena, Esther; Aguado, Laura; Mariscal, Natividad; Muñoz Siscart, Ignacio; Piñeiro, Dolores; Rivadeneyra, Jessica; Cubo Delgado, Esther Background Huntington’s disease (HD) is a neurodegenerative disorder characterized by cognitive, motor, and neuropsychiatric manifestations. Oxytocin is a neuropeptide studied for its role as a neuromodulator regulating multiple behaviors linked to social cognition. Genetic variation of oxytocin receptor (OXTR) might interact in the etiology and development of several impaired social behaviors. Our aim was to study OXTR polymorphisms and their relationship with apathy and social cognition in HD. Methods OXTR was sequenced in 21 cases and 22 controls. We assessed apathy, anxiety, depression, and irritability (Hospital Anxiety and Depression Scale-Snaith Irritability scale, HADS-SIS) and social cognition (Ekman 60 faces test), motor symptoms and functionality with the total functional capacity (TFC), and the Unified HD rating Scale (UHDRS). Results We identified ten variants in OXTR. Three variants were classified as possibly damaging (p.Arg40Gly) or probably damaging (p.Leu46Pro, p.Thr102Asn). Subjects carrying the wild-type genotype of the synonymous variant p.Val45 showed a significantly lower score in the HADS-SIS scale, related to lower irritability (p = 0.013). The only subject carrying the heterozygous genotype of the synonymous variant p.Leu62 showed a significantly higher score on Ekman scale, compared to wild-type (p = 0.049); however, this finding was not confirmed after bootstrapping. Conclusion Variations in OXTR could have a relevant role in the correct development of social and cognitive functions. Future approaches will include the molecular study of p.Arg40Gly, p.Leu46Pro, and p.Thr102Asn to confirm their pathogenicity, as well as the validation of the influence of p.Val45 and p.Leu62 variants for their involvement in irritability and social cognition in HD. 2022-06-01T00:00:00Z https://hdl.handle.net/10259/12170 Impact of Melatonin Supplementation on Sports Performance and Circulating Biomarkers in Highly Trained Athletes: A Systematic Review of Randomized Controlled Trials Celorrio San Miguel, Ana M.; Roche, Enrique; Herranz López, María; Celorrio San Miguel, Marta; Mielgo Ayuso, Juan; Fernández Lázaro, Diego Melatonin (N-acetyl-5 methoxytryptamine) is an indolic neurohormone that modulates a variety of physiological functions due to its antioxidant, anti-inflammatory, and immunoregulatory properties. Therefore, the purpose of this study was to critically review the effects of melatonin supplementation in sports performance and circulating biomarkers related to the health status of highly trained athletes. Data were obtained by performing searches in the following three bibliography databases: Web of Science, PubMed, and Scopus. The terms used were “Highly Trained Athletes”, “Melatonin”, and “Sports Performance”, “Health Biomarkers” using “Humans” as a filter. The search update was carried out in February 2024 from original articles published with a controlled trial design. The PRISMA rules, the modified McMaster critical review form for quantitative studies, the PEDro scale, and the Cochrane risk of bias were applied. According to the inclusion and exclusion criteria, 21 articles were selected out of 294 references. The dose of melatonin supplemented in the trials ranged between 5 mg to 100 mg administered before or after exercise. The outcomes showed improvements in antioxidant status and inflammatory response and reversed liver damage and muscle damage. Moderate effects on modulating glycemia, total cholesterol, triglycerides, and creatinine were reported. Promising data were found regarding the potential benefits of melatonin in hematological biomarkers, hormonal responses, and sports performance. Therefore, the true efficiency of melatonin to directly improve sports performance remains to be assessed. Nevertheless, an indirect effect of melatonin supplementation in sports performance could be evaluated through improvements in health biomarkers. 2024-03-01T00:00:00Z