Repositori Obert UdL

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Open Access
Rare Genetic Variants in Young Adults Requiring Pacemaker Implantation
(Elsevier, 2024) Ochoa, Juan Pablo; Espinosa, M. Ángeles; Gayán-Ordas, Jara; Fernández-Valledor, Andrea; Gallego-Delgado, María; Tirón, Coloma; Lozano-Ibañez, Adrián; García Pinilla, José Manuel; Rodríguez-Palomares, José F.; Larrañaga-Moreira, José María; Llamas-Gómez, Helena; Ripoll-Vera, Tomas; Braza-Boïls, Aitana; Vilches, Silvia; Méndez, Irene; Bascompte-Claret, Ramón; García-Álvarez, Ana; Villacorta, Eduardo; Fernandez-Lozano, Ignacio; Lara-Pezzi, Enrique; Garcia-Pavia, Pablo
BACKGROUND Genetic disease has recently emerged as a cause of cardiac conduction disorders (CCDs), but the diagnostic yield of genetic testing and the contribution of the different genes to CCD is still unsettled. OBJECTIVES This study sought to determine the diagnostic yield of genetic testing in young adults with CCD of unknown etiology requiring pacemaker implantation. We also studied the prevalence of rare protein-altering variants across individual genes and functional gene groups. METHODS We performed whole exome sequencing in 150 patients with CCD of unknown etiology who had permanent pacemaker implanted at age #60 years at 14 Spanish hospitals. Prevalence of rare protein-altering variants in patients with CCD was compared with a reference population of 115,522 individuals from gnomAD database (control subjects). RESULTS Among 39 prioritized genes, patients with CCD had more rare protein-altering variants than control subjects (OR: 2.39; 95% CI: 1.75-3.33). Significant enrichment of rare variants in patients with CCD was observed in all functional gene groups except in the desmosomal genes group. Rare variants in the nuclear envelope genes group exhibited the strongest association with CCD (OR: 6.77; 95% CI: 3.71-13.87). Of note, rare variants in sarcomeric genes were also enriched (OR: 1.73; 95% CI: 1.05-3.10). An actionable genetic variant was detected in 21 patients (14%), with LMNA being the most frequently involved gene (4.6%). CONCLUSIONS Unrecognized rare genetic variants increase the risk of CCD in young adults with CCD of unknown etiology. Genetic testing should be performed in patients age #60 years with CCD of unknown etiology. The role of genetic variants in sarcomeric genes as a cause of CCD should be further investigated
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Experiences and challenges of refugees from Ukraine in accessing healthcare and social services during their integration in Lithuania
(Frontiers Media, 2024) Urbanavice, Rita; El Arab, Rabie Adel; Hendrixson, Vaiva; Austys, Donatas; Jakavonyte-Akstiniene, Agne; Skvarcevskaja, Marija; Istomina, Natalja
Background: The influx of Ukrainian refugees to Lithuania due to the ongoing conflict has created substantial challenges in healthcare and social services. Objective: To identify the key challenges faced by Ukrainian refugees in accessing healthcare and social services in Lithuania. Methods: A qualitative study was conducted using semi-structured interviews with 22 Russian-speaking female Ukrainian refugees residing in various regions of Lithuania. Data were collected between July and October 2022 and analyzed using inductive qualitative content analysis to identify key themes related to healthcare access, social services, and integration. Findings: Refugees reported significant barriers, including language difficulties, long waiting times for healthcare services, and inconsistent access to social services, particularly in smaller municipalities. Despite access to free healthcare, the quality and timeliness of services were often inadequate, exacerbating challenges for those with pre-existing health conditions. Psychological support services were underutilized, and language barriers impeded access to both healthcare and employment opportunities. Coordination between social and healthcare services was lacking, creating further difficulties for refugees in navigating essential services. Conclusion: While Lithuanian authorities have provided critical support, significant gaps remain in healthcare access and social service coordination. Urgent improvements are needed in language support, psychological care, and healthcare accessibility, particularly in smaller municipalities. These findings highlight the need for targeted policies to address these challenges and ensure equitable access to services for all refugees. Future research should include more diverse refugee populations to guide comprehensive policy development.
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Open Access
Hormonal biomarkers remain prognostically relevant within the molecular subgroups in endometrial cancer
(Elsevier, 2024) Vrede, Stephanie W.; Van Weelden, Willem Jan; Bulten, Johan; Gilks, C. Blake; Teerenstra, Steven; Huvila, Jutta; Matias-Guiu, Xavier; Gil-Moreno, Antonio; Asberger, Jasmin; Sweegers, Sanne; van der Putten, Louis J. M.; Küsters-Vandevelde, Heidi V. N; Reijnen, Casper; Colás, Eva; Hausnerova, Jitka; Weinberger, Vit; Snijders, Marc P. L. M.; Vinklerova, Petra; Ravaggi, Antonella; Odicino, Franco; Bignotti, Eliana; McAlpine, Jessica N.; Kruitwagen, Roy; Pijnenborg, Johanna M. A.
Objective: The prognostic relevance of hormonal biomarkers in endometrial cancer (EC) has been well-established. A refined three-tiered risk model for estrogen receptor (ER)/progesterone receptor (PR) expression was shown to improve prognostication. This has not been evaluated in relation to the molecular subgroups. This study aimed to evaluate the ER/PR expression within the molecular subgroups in EC. Methods: A retrospective multicenter cohort study was performed and data from the European Network for Individualized Treatment centers and Vancouver, Canada were used. ER/PR immunohistochemical expression was grouped as: ER/PR 0-10 %, 20-80 % or 90-100 %. Molecular subgroups were determined with full next-generation sequencing or combined with immunohistochemistry: POLEmut, mismatch repair deficient (MMRd), p53mut and no-specific molecular profile (NSMP). Results: A total of 739 patients were included (median follow-up 5.0 years). Tumors were classified as POLEmut in 9.1 %(N = 67), MMRd in 27.6 %(N = 204), p53mut in 20.8 %(N = 154) and NSMP in 42.5 %(N = 314). Among all molecular subgroups, patients with ER/PR 90-100 % expression revealed the best disease-specific survival (DSS). Within p53mut, PR 90-100 % expression showed a 5-year DSS of 100.0 %. ER expression is prognostic more relevant in MMRd and NSMP tumors while PR expression in p53mut and NSMP tumors. Across all molecular subgroups, PR 0-10 %, p53mut, lympho-vascular space invasion and FIGO stage III-IV remained independently prognostic for reduced DSS Whereas PR 90-100 % and POLEmut remained independently prognostic for improved DSS. Conclusion: We demonstrated that ER/PR expression remain prognostically relevant within the molecular subgroups, and that a three-tiered cutoff refines prognostication. These data support incorporating routine evaluation of ER/PR expression in clinical practice.
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Open Access
La apnea obstructiva del sueño y la hipoxemia nocturna aumentan el riesgo cardiovascular basal en población chilena
(Sociedad Médica de Santiago, 2024) Labarca, Gonzalo; Henríquez Beltrán, Mario; Jorquera-Díaz, Jorge; Dreyse, Jorge; Jorquera, Jorge
La coexistencia de apnea obstructiva del sueño (AOS) y el riesgo cardiovascular (CV) han sido descrito asiduamente. Sin embargo, las implicancias de métricas novedosas usadas en el diagnóstico de la AOS en pacientes con riesgo CV son escasa en población hispano/latino. Objetivo: Determinar la asociación entre el índice de eventos respiratorios (IER) y el tiempo de desaturación bajo 90% de SpO2 (CT90%) con riesgo CV mediante el modelo predictivo de Framingham 2008. Además, analizamos el rendimiento diagnóstico del modelo de riesgo CV basal, ajustado por IER, CT90% y su combinación para predecir mortalidad CV en pacientes con sospecha clínica de AOS. Método: Estudio monocéntrico de cohorte, prospectivo. 1560 pacientes fueron evaluados para el presente estudio, todos los pacientes fueron sometidos a una evaluación clínica sugerente de AOS, presión arterial y variables antropométricas. Para determinar la asociación de los índices de interés con el riesgo CV, se realizó una regresión multivariada linear entre el porcentaje de riesgo CV y el puntaje de IER o CT90%. Todos los análisis se realizaron en el software R (R-project) y se estableció un valor p < 0.05 como estadísticamente significativo. Resultados: IER y CT90% mostraron diferencias significativas para el CV (p-valor= <0.001). Además, se observó un incremento porcentual en cada cuartil del IER y CT90% (p-valor= <0.001). Conclusiones: El IER y CT90% mostraron una asociación significativa e incremental con el riesgo CV de la cohorte. Sin embargo, los análisis predictivos de mortalidad CV usando el IER y CT90% no fueron significativos.
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Beyond the Wild MRSA: Genetic Features and Phylogenomic Review of mecC-Mediated Methicillin Resistance in Non-aureus Staphylococci and Mammaliicocci
(Multidisciplinary Digital Publishing Institute (MDPI), 2024-01-01) Abdullahi, I.N.; Latorre-Fernández, J.; Reuben, R.C.; Trabelsi, I.; González-Azcona, C.; Arfaoui, A.; Usman, Y.; Lozano, C.; Zarazaga, M.; Torres, C.
Methicillin resistance, mediated by the mecA gene in staphylococci and mammaliicocci, has caused tremendous setbacks in the use of antibiotics in human and veterinary medicine due to its high potential of presenting the multidrug resistance (MDR) phenotype. Three other mec analogs exist, of which the mecC has evolutionary been associated with methicillin-resistant Staphylococcus aureus (MRSA) in wild animals, thus loosely referred to as the wild MRSA. In this study, we present an epidemiological review and genomic analysis of non-aureus staphylococci and mammaliicocci that carry the mecC-mediated methicillin resistance trait and determine whether this trait has any relevant link with the One Health niches. All previous studies (2007 till 2023) that described the mecC gene in non-aureus staphylococci and mammaliicocci were obtained from bibliometric databases, reviewed, and systematically analyzed to obtain the antimicrobial resistance (AMR) and virulence determinants, mobilome, and other genetic contents. Moreover, core genome single-nucleotide polymorphism analysis was used to assess the relatedness of these strains. Of the 533 articles analyzed, only 16 studies (on livestock, environmental samples, milk bulk tanks, and wild animals) were eligible for inclusion, of which 17 genomes from 6 studies were used for various in silico genetic analyses. Findings from this systematic review show that all mecC-carrying non-aureus staphylococci were resistant to only beta-lactam antibiotics and associated with the classical SCCmec XI of S. aureus LGA251. Similarly, two studies on wild animals reported mecC-carrying Mammaliicoccus stepanovicii associated with SCCmec XI. Nevertheless, most of the mecC-carrying Mammaliicoccus species presented an MDR phenotype (including linezolid) and carried the SCCmec-mecC hybrid associated with mecA. The phylogenetic analysis of the 17 genomes revealed close relatedness (<20 SNPs) and potential transmission of M. sciuri and M. lentus strains in livestock farms in Algeria, Tunisia, and Brazil. Furthermore, closely related M. sciuri strains from Austria, Brazil, and Tunisia (<40 SNPs) were identified. This systematic review enhances our comprehension of the epidemiology and genetic organization of mecC within the non-aureus staphylococci and mammaliicocci. It could be hypothesized that the mecC-carrying non-aureus staphylococci are evolutionarily related to the wild MRSA-mecC. The potential implications of clonal development of a lineage of mecA/mecC carrying strains across multiple dairy farms in a vast geographical region with the dissemination of MDR phenotype is envisaged. It was observed that most mecC-carrying non-aureus staphylococci and mammaliicocci were reported in mastitis cases. Therefore, veterinarians and veterinary microbiology laboratories must remain vigilant regarding the potential existence of mecA/mecC strains originating from mastitis as a potential niche for this resistance trait.