Mutación en SF3B1: pronóstico de los pacientes con síndrome mielodisplásico de bajo grado

[Resumen] Introducción: La mutación en el SF3B1 define a un subgrupo de pacientes con síndrome mielodisplásico (SMD-SF3B1mut) asociados generalmente con pronóstico no desfavorable. Sin embargo, los pacientes con SMD- SF3B1mut constituyen un grupo ampliamente heterogéneo en función de la presencia de alteraciones genéticas adicionales y según el hotspot afectado (K700E vs. otros). Objetivos: Evaluar el impacto pronóstico en términos de supervivencia global (SG) y riesgo de progresión leucémica según el tipo de mutación en SF3B1 a partir de la estratificación pronóstica de los pacientes con SMD- SF3B1mut por el IPSS-M. Material y Métodos: Estudio retrospectivo, unicéntrico de 46 pacientes con SMD-SF3B1mut. Se realizará un análisis descriptivo e inferencial. La función de supervivencia de los pacientes con SMD-SF3B1mut se ha estimado utilizando el estimador de Kaplan-Meier (SPSS® versión 26.0.0). Conclusión: El grupo de pacientes con mutación en SF3B1 es heterogéneo desde el punto de vista clínico. Este estudio pretende destacar la importancia de conocer el subtipo de mutación en SF3B1 para la evaluación del riesgo de SMD.[Resumo] Introdución: A mutación SF3B1 define un subgrupo de pacientes con síndrome mielodisplásico (MDS-SF3B1mut) xeralmente asociado cun prognóstico non desfavorable. Non obstante, os pacientes con MDSSF3B1mut constitúen un grupo amplamente heteroxéneo dependendo da presenza de alteracións xenéticas adicionais e segundo o hotspot afectado (K700E vs. outros). Obxetivo: Avaliar o impacto prognóstico en termos de supervivencia global (SO) e probabilidade de progresión leucémica dacordo con o tipo de mutación de SF3B1 en función da estratificación prognóstica dos pacientes con MDS-SF3B1mut pola IPSS-M. Metodoloxía: Estudo retrospectivo, monocéntrico, de 46 pacientes con SMD-SF3B1mut. Realizarase unha análise descritiva e inferencial. A análise de supervivencia realizouse mediante o método de Kaplan-Meier (SPSS® versión 26.0.0). Conclusión: os pacientes con mutación SF3B1 son clinicamente heteroxéneos. Este estudo destaca a importancia do subtipo de mutación SF3B1 na avaliación do risco de MDS.[Abstract] Introduction: The SF3B1 mutation defines a subgroup of patients with myelodysplastic syndrome (MDS-SF3B1mut) generally associated with a not unfavorable prognosis. However, patients with MDS-SF3B1mut constitute a heterogeneous group depending on the presence of additional genetic alterations and according to the affected hotspot (K700E vs. others). Objectives: To evaluate the prognostic impact in terms of overall survival (OS) and risk of leukemic progression according to the type of SF3B1 mutation from the prognostic stratification of patients with MDS-SF3B1mut by the IPSS-M. Material and Methods: Retrospective, single-center study of 46 patients with SMD-SF3B1mut. A descriptive and inferential analysis will be carried out. The survival function of patients with SMD-SF3B1mut has been estimated using the estimator of Kaplan-Meier (SPSS version 26.0.0). Conclusion: Patients with SF3B1 mutation is clinically heterogeneous. This study highlights the importance of the SF3B1 mutation subtype in MDS risk assessment.Traballo fin de mestrado (UDC.FCS). Asistencia e investigación sanitaria. Especialidade en investigación clínica. Curso 2022/2023

La hora de inicio de la cirugía como factor de riesgo para la infección de prótesis articular.: resultados de un estudio descriptivo.

La infección de prótesis articular (IPA) es una complicación relacionada con múltiples factores de riesgo. Nos proponemos analizar si la hora a la que se realiza una artroplastia puede ser un factor de riesgo para desarrollar una IPA. Material y método. Estudio observacional retrospectivo de una serie de pacientes que se sometieron a una cirugía de artroplastia de cadera o rodilla en el año 2010 en el Hospital Príncipe de Asturias de Alcalá de Henares (Madrid). Resultados. Durante el período de estudio se analizaron 362 cirugías de artroplastia de rodilla y cadera, 19 de las cuales desarrollaron IPA (incidencia 5,2%). Mediante análisis de regresión logística se observó un incremento estadísticamente significativo de la incidencia de IPA en las cirugías realizadas entre las 12 y las 14 horas (Odds Ratio [OR] 3,4; intervalo de confianza del 95% [IC 95%] 1,1 a 11,3, p=0,04) y menor en las realizadas entre las 8 y las 10 de la mañana (OR 0,2; IC 95% 0,04 a 0,91; p= 0,04). Conclusión. En nuestro estudio, los pacientes intervenidos al final de la mañana tuvieron un riesgo tres veces superior de desarrollar IPA, mientras que operarse a primera hora fue un factor protector.The prosthetic joint infection (PJI) is a complication with multiple risk factors described. We pro - pose to analyze if the hour of start time of surgery may be a risk for developing PJI. Materials and methods. We retrospectively analyze known risk factors in patients who underwent implantation of knee or hip arthroplasty in Principe de Asturias Hospital from January 2010 to December 2010 and the time of performance of the sur - gery. Results. During the study period 362 surgeries were analyzed, of which 19 developed PJI (incidence 5,2%). Logistic regression analysis showed more frequency of PJI incidence in surgeries started between 12 and 14pm (odds ratio [OR] 3,4; confidence interval [CI] 95% 1,1 to 11,3, p=0,04) and less frequent between 8 and 10 am (OR 0,2, CI 95% 0,04 to 0,91, p=0,04). Conclusion. In our study the patients undergoing surgery at the end of the morning had a threefold increased risk of developing PJI, while early surgery was a protective facto

Myeloid cells in vascular dementia and Alzheimer's disease: Possible therapeutic targets?

Growing evidence supports the suggestion that the peripheral immune system plays a role in different pathologies associated with cognitive impairment, such as vascular dementia (VD) or Alzheimer's disease (AD). The aim of this review is to summarize, within the peripheral immune system, the implications of different types of myeloid cells in AD and VD, with a special focus on post-stroke cognitive impairment and dementia (PSCID). We will review the contributions of the myeloid lineage, from peripheral cells (neutrophils, platelets, monocytes and monocyte-derived macrophages) to central nervous system (CNS)-associated cells (perivascular macrophages and microglia). Finally, we will evaluate different potential strategies for pharmacological modulation of pathological processes mediated by myeloid cell subsets, with an emphasis on neutrophils, their interaction with platelets and the process of immunothrombosis that triggers neutrophil-dependent capillary stall and hypoperfusion, as possible effector mechanisms that may pave the way to novel therapeutic avenues to stop dementia, the epidemic of our time.Spanish Ministry of Science and Innovation (MCIN), Grant/Award Number: PID2019-106581RB-I00; Leducq Foundation for Cardiovascular Research, Grant/Award Numbers: TNE19CVD01, TNE-21CVD04; Instituto de Salud Carlos III (ISCIII) and cofinanced by the European Development Regional Fund “A Way to Achieve Europe”, Grant/Award Numbers: PI20/00535, RICORSICTUSRD21/0006/0001; Severo Ochoa Center of Excellence, Grant/Award Number: CEX2020-001041-S.S

SF3B1, RUNX1 and TP53 Mutations Significantly Impact the Outcome of Patients With Lower-Risk Myelodysplastic Syndrome

[Introduction] Prognosis of patients with myelodysplastic syndrome (MDS), particularly the group with lower-risk disease (LR-MDS) is very heterogeneous. Several studies have described the prognostic value of recurrent somatic mutations in MDS including all risk categories. Recently, the incorporation of genomic data to clinical parameters defined the new Molecular International Prognostic Scoring System (IPSS-M).[Materials and Methods] In this study, we evaluated the impact of molecular profile in a series of 181 patients with LR-MDS and non-proliferative chronic myelomonocytic leukemia.[Results] Epigenetic regulators (TET2, ASXL1) and splicing (SF3B1) were the most recurrent mutated pathways. In univariate analysis, RUNX1 or TP53 mutations correlated with lower median overall survival (OS). In contrast, SF3B1 mutation was associated with prolonged median OS [95 months (95% IC, 32-157) vs. 33 months (95% CI, 19-46) in unmutated patients (P < 0.01)]. In a multivariate Cox regression model, RUNX1 mutations independently associated with shorter OS, while SF3B1 mutation retained its favorable impact on outcome (HR: 0.24, 95% CI, 0.1-0.5; P = 0.001). In addition, TP53 or RUNX1 mutations were identified as predictive covariates for the probability of leukemic progression (P < 0.001).[Conclusion] Incorporation of molecular testing in LR-MDS identified a subset of patients with expected poorer outcome, either due to lower survival or probability of leukemic progression.Peer reviewe

Evolution of antibody titers after two doses of mRNA Pfizer-BioNTech vaccine and effect of the third dose in nursing home residents.

ObjectivesWe evaluated the IgG antibody titer against SARS-CoV-2 in 196 residents of a Spanish nursing home after the second dose of the BNT162b2 vaccine and the evolution of this titer over time. The role of the third dose of the vaccine on immune-response is also analysed in 115 of participants.MethodsVaccine response was evaluated 1, 3 and 6 months after second dose of Pfizer-BioNTech COVID-19 Vaccine and 30 days after booster vaccination. Total anti-RBD (receptor binding domain) IgG immunoglobulins were measured to assess response. Six month after the second dose of vaccine and previously to the booster, T-cell response was also measured in 24 resident with different antibody levels. T-spot Discovery SARS-CoV-2 kit was used to identify cellular immunogenicity.ResultsAs high as 99% of residents demonstrated a positive serological response after second dose. Only two patients showed no serologic response, two men without records of previous SARS-CoV-2 infection. A higher immune response was associated with prior SARS-CoV-2 infection regardless of the gender or age. The anti-S IgG titers decreased significantly in almost all the participants (98.5%) after six months of vaccination whatever previous COVID-infection. The third dose of vaccine increased antibody titers in all patients, although initial vaccination values were not restored in the majority of cases.ConclusionThe main conclusion of the study is that vaccine resulted in good immunogenicity in this vulnerable population. Nevertheless more data are needed on the long-term maintenance of antibody response after booster vaccination

Genetic Diversity and Geographic Population Structure of Bovine Neospora caninum Determined by Microsatellite Genotyping Analysis

The cyst-forming protozoan parasite Neospora caninum is one of the main causes of bovine abortion worldwide and is of great economic importance in the cattle industry. Recent studies have revealed extensive genetic variation among N. caninum isolates based on microsatellite sequences (MSs). MSs may be suitable molecular markers for inferring the diversity of parasite populations, molecular epidemiology and the basis for phenotypic variations in N. caninum, which have been poorly defined. In this study, we evaluated nine MS markers using a panel of 11 N. caninum-derived reference isolates from around the world and 96 N. caninum bovine clinical samples and one ovine clinical sample collected from four countries on two continents, including Spain, Argentina, Germany and Scotland, over a 10-year period. These markers were used as molecular tools to investigate the genetic diversity, geographic distribution and population structure of N. caninum. Multilocus microsatellite genotyping based on 7 loci demonstrated high levels of genetic diversity in the samples from all of the different countries, with 96 microsatellite multilocus genotypes (MLGs) identified from 108 N. caninum samples. Geographic sub-structuring was present in the country populations according to pairwise FST. Principal component analysis (PCA) and Neighbor Joining tree topologies also suggested MLG segregation partially associated with geographical origin. An analysis of the MLG relationships, using eBURST, confirmed that the close genetic relationship observed between the Spanish and Argentinean populations may be the result of parasite migration (i.e., the introduction of novel MLGs from Spain to South America) due to cattle movement. The eBURST relationships also revealed genetically different clusters associated with the abortion. The presence of linkage disequilibrium, the co-existence of specific MLGs to individual farms and eBURST MLG relationships suggest a predominant clonal propagation for Spanish N. caninum MLGs in cattle.Fil: Regidor Cerrillo, Javier. Universidad Complutense de Madrid; EspañaFil: Díez Fuertes, Francisco. Universidad Complutense de Madrid; EspañaFil: García Culebras, Alicia. Universidad Complutense de Madrid; EspañaFil: Moore, Dadin Prando. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: González Warleta, Marta. Agricultural Research Center of Mabegondo; EspañaFil: Cuevas, Carmen. Universidad Complutense de Madrid; EspañaFil: Schares, Gereon. Agricultural Research Center of Mabegondo; EspañaFil: Katzer, Frank. Moredun Research Institute; Reino UnidoFil: Pedraza Diaz, Susana. Universidad Complutense de Madrid; EspañaFil: Mezo, Mercedes. Agricultural Research Center of Mabegondo; EspañaFil: Ortega Mora, Luis M.. Universidad Complutense de Madrid; Españ

Relationships among the <i>N</i><i>. caninum</i> MLGs (n = 82) estimated by eBURST analysis.

<p>Each complete MLG is represented by a dot and the genotype number assigned in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072678#pone.0072678.s003" target="_blank">Table S1</a> (Numbers 1-11 represent worldwide MLGs; 12-64 Spanish MLGs; 65-80 Argentinean MLGs; 81-88 Scottish MLGs; and 89-95 German MLGs). MLG dots were also coloured according to their geographical origin (see legend). The dot diameter is proportional to the number of samples with identical MLG (see legend). Single locus variants (SLV) are connected by black lines and double loci variants (DLV) by blue lines. MLGs clusters (n=9) are represented. Main MLGs clusters (n=3) are showed by clear circles. Number and name in the squares identifies the herd origin and worldwide isolates, respectively (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072678#pone.0072678.s003" target="_blank">Table S1</a>). Note that singletons were excluded from the snapshot representation (worldwide n=7; Spanish n=7; Argentinean n=2; Scottish n=3; and German n=2).</p

Clustering of <i>N</i><i>. caninum</i> country populations based on Principal Component Analysis (PCA) and Neighbor Joining (NJ).

<p>(A) Graphics represent the genetic relationships between the MLGs from each country population based on a covariance matrix. Colours indicate geographic origin (see legend). The proportion of variation in the dataset for each axis is indicated in parentheses. (B) Unrooted NJ tree inferred from allele shared genetic distances. Each tip represents a single MLG. Woldwide MLGs are identified by isolate name. Colour of circles in terminal branches indicates geographic origin (see legend). Percentage bootstrap values were generated from 1,000 replicates. Bootstrap values ≥70% are shown in black circles. Scale bar represents branch lengths. NJ tree based in Cavalli-Sforza distances depicted similar topologies (data not shown).</p