Donostia Unibertsitate Ospitalea

Circulating recombinant forms (CRFs) are important components of the HIV-1 pandemic. Previous studies have reported the propagation of diverse HIV-1 CRFs of South American origin in Europe. Here, through protease-reverse transcriptase (Pr-RT) and integrase sequence analyses, we identify a Spanish cluster (BC3) branching with a Brazilian virus (10BR_RJ009) previously classified as CRF146_BC. In Pr-RT, BC3 comprised 14 viruses and was nested within a larger cluster, comprising 22 Brazilian viruses and 1 Spanish virus branching outside of BC3. Near full-length genome analyses of five BC3 viruses revealed mosaic structures identical to 10BR_RJ009, with two breakpoints delimiting a ~0.3 kb subtype B fragment within an otherwise subtype C genome. Two other Brazilian viruses previously classified as CRF146_BC (10BR_RJ039 and 01_BR_RGS69) had one and two additional short subtype B fragments, respectively, and failed to group with the 10BR_RJ009/BC3 cluster in subtype C fragments. Based on these results, we contend that 10BR_RJ009 and BC3 viruses, but not 10BR_RJ039 and 01_BR_RGS69, should be classified as CRF146_BC. Bayesian analyses estimated the CRF146_BC emergence in Brazil to be around 1999 and its introduction in Europe around 2011. CRF146_BC is the 10th CRF of South American origin reported to circulate in Europe, reflecting the relationship between South American and European HIV-1 epidemics.

BackgroundThere is substantial heterogeneity in clinical presentation of genetic Frontotemporal Dementia (FTD), even within the same family. This suggests that additional heritability may exist and contribute to this variable presentation. We examined whether gene‐based aggregate burden of genome‐wide rare variants (minor allele frequency [MAF]: ≤1%) contribute to variation in regional cortical and subcortical grey matter volumes, after controlling for effects of causative mutations in GRN, MAPT, and C9orf72.MethodThis study was embedded within the GENetic Frontotemporal dementia Initiative (GENFI), which recruits genetic FTD cases and their asymptomatic at‐risk family members, both carriers and non‐carriers of FTD mutations. We included 518 participants with genotype (Neurochip; imputed against TOPMed), and T1w‐MRI brain volumetric data. Gene‐based burden tests that aggregate the number of rare variants by gene were used to examine the association of rare variants (MAF: ≤1%) with regional cortical and subcortical grey matter volumes (70 regions of interest [ROIs]), controlling for age, sex, total intracranial volume, mutation status, scanner site, population stratification, and family membership (kinship matrix) using RVTests. Annotations for loss of function mutations (LOF): start gain, stop loss, start loss, essential splice site, stop gain, normal splice site, and non‐synonymous. Multiple testing correction accounted for the number of genes and number of independent grey matter volumes as calculated by matSpD (p‐value threshold: 0.05/(17,053x42) = 6.98 x10‐8).ResultAggregate burden of LOF mutations (DNAJB8‐AS1, WDR26, RDM1P5, BSND, CNOT2, DDA1, ASAH2B, PPM1A, HOXD13, ALDH1A1, CENATAC, ANKRD45) was associated with significantly lower volumes within the left temporal lobe (ROIs: left temporal and lateral temporal left), and greater volume in the putamen bilaterally (TSACC). All genes are protein coding, except the DNAJB8‐AS1 (antisense RNA) and RDM1P5 (pseudogene), and are variably expressed in the brain. Molecular functions of significant genes involve regulation of gene expression, transcription, and cell cycle, ion channel function, and chromosomal segregation. WDR26 and CNOT2 genes have been implicated in neurodevelopment and neurological disorders respectively; BSND gene is involved in neurotransmission.ConclusionIdentification of deleterious or protective rare variants contributing to FTD imaging phenotypes may help identify genetic modifiers of familial FTD. Replication in larger cohorts is needed.

Background/Objectives: In 2019, the European Society of Gynaecological Oncology (ESGO) published a set of quality indicators (QIs) for the surgical management of cervical cancer with the aim of improving clinical practice. The objective of this study is to evaluate the influence of ESGO QIs and clinicopathological factors on progression-free survival (PFS) in patients with early-stage cervical cancer in a retrospective cohort. Methods: A retrospective study was conducted in patients with early-stage cervical cancer who underwent radical surgery with pelvic lymph node assessment at La Paz University Hospital between 2005 and 2022. The cohort was divided into two groups according to the timing of surgery (before vs. after 2010), when MRI was implemented as a standardized diagnostic tool and the multidisciplinary tumor board was established. Univariate and multivariate Cox regression analyses were performed, including demographic and histopathological variables, as well as adherence to ESGO QIs, focusing on those related to the overall management. Hazard ratios and 95% confidence intervals were estimated. Kaplan-Meier survival curves were generated and compared between groups. Results: The implementation of systematic MRI and a multidisciplinary tumor board at our center was associated with a significant reduction in positive surgical margins (p = 0.003) and parametrial invasion (p < 0.001), as well as improved diagnostic accuracy, lowering the rate of upstaging from 31.6% before 2010 to 4.4% thereafter (p < 0.001). PFS in the post-2010 cohort was significantly improved (log-rank p = 0.0408), although no differences in overall survival (OS) were observed (log-rank p = 0.2602). Additionally, cervical conization prior to radical hysterectomy was associated with a markedly reduced risk of recurrence (HR 0.12, p < 0.001), representing the most significant prognostic factor for PFS in our cohort. Conclusions: The correct application of ESGO QIs, along with appropriate staging and pathological assessment, is essential to improve prognosis in cervical cancer. Systematic implementation of these standards is recommended to optimize clinical care.

The number of elderly patients who could benefit from an allogeneic hematopoietic stem cell transplantation (allo-HSCT) is continuously increasing; however, the most appropriate way to select elderly candidates for this procedure is still a matter of debate. We report the clinical outcomes of a group of 529 patients aged 65 y and older who received a first allo-HSCT between 2011 and 2020 and were reported to the Grupo Español de Trasplante Hematopoyético y Terapia Celular database. The median age was 67.2 y (range, 65-82) and 54 patients (10.2%) were 70 y and older. The 4-y cumulative incidence (CI) of nonrelapse mortality was 32.0% (95% confidence interval [CI], 28-36), CI of relapse was 29.1% (95% CI, 25-33), of overall survival was 43.4% (95% CI, 39-48), of progression-free survival was 38.9% (95% CI, 35-43), and of graft-versus-host disease (GvHD)-free, relapse-free survival was 23.7% (95% CI, 20-28). The 100-d CI of grades II-IV and III-IV acute GvHD was 34.7% (95% CI, 31-39) and 10.4% (95% CI, 8-13), respectively, and the 2-y CI of moderate-severe chronic GvHD was 21.0% (95% CI, 18-25). In the multivariate analysis, a hematopoietic cell transplantation-specific comorbidity index of ≥3 and a high/very high disease risk index were associated with worse overall survival; however, age did not influence the outcomes. Advanced age alone should not serve as an exclusion criterion for allo-HSCT, as the procedure can be both safe and effective in elderly patients with careful candidate selection and optimized transplant strategies.

Se presenta la actuación arqueológica de urgencia desarrollada con motivo de la aparición, en el año 2014, de un conjunto de restos humanos en las obras de reposición de la tubería de la conducción de agua que abastece el barrio El Carrascal en el municipio de Unzué. Se descubrió una fosa común simultánea con diez individuos masculinos de edades jóvenes con lesiones por impacto de arma de fuego. Por otro lado, se recuperaron cuatro proyectiles esféricos de avancarga, alojados en fémur, cráneo y mandíbula de tres de ellos. La exhumación ha permitido documentar un hecho violento en el contexto de la Guerra de la Independencia, producto de una acción por sorpresa, que podría coincidir con la emboscada que realiza el Corso Terrestre, al mando de Javier Mina, probablemente el 12 de agosto de 1809 a diez artilleros franceses en El Carrascal.