Indicator for patient safety: Readmission within 30 days for nosocomial infection.

Objetivos: Describir la frecuencia de reingresos en 30 días por infección nosocomial en el “Hospital Torrecárdenas” de Almería. Materiales y métodos: 25.653 episodios. El reingreso por infección nosocomial (IN): proporción de pacientes al alta de cada uno de los episodios hospitalarios durante el periodo de estudio que son reingresados de modo urgente en 30 días con IN, ya conste como diagnóstico principal del nuevo ingreso. Resultados: Proporción de reingresos por IN es 2,6‰ (IC95% 2,0 – 3,3), que supone un total de 67 episodios de reingreso por IN (5,0% del total). Unidad con mas reingresos por IN: UGC de urología 9,7‰ (IC95% 1,9 – 17,4)). Mayor probabilidad de reingreso se asocia al sexo masculino, a una mayor edad, a determinados diagnósticos y servicio al alta. Las unidades de hospitalización con más reingresos: salud mental, obstetricia, oncología radioterápica, oncología y reumatología, sin embargo, las unidades con mas reingresos por IN: urología, angiología y C.Vascular, oncología, neumología y cardiología. Las enfermedades que destacan como reingreso por IN: “otras alteraciones de uretra y vías urinaria” “infección postoperatoria, no clasificada en otro lugar”. Discusión y conclusiones: Se ha caracterizado el patrón de reingresos por IN en el hospital de Torrecárdenas, utilizándose para ser utilizado para implementar acciones preventivas y como un indicador de calidad asistencial.Objectives: To describe the frequency of readmission within 30 days for nosocomial infection at the “Hospital Torrecardenas” of Almeria. Material and methods: The source is from 1/1/2007 to 31/1/2008 CMBDh, analyzed 25,653 episodes. Readmissions for nosocomial infection (NI): proportion of patients at discharge for each hospital episode during the study period that are so urgently readmitted in 30 days with IN, and is credited as the primary diagnosis of new entry or as a diagnosis secondary. Descriptive analysis of variables such as age, sex, high service, month high, episode duration and primary diagnosis, using association between variables.Results: The proportion of readmissions by IN is 2.6 ‰ (IC95% 2,0–3,3), representing a total of 67 episodes of readmission for IN (5.0% of readmissions). The unit with more readmissions for IN was the hospital's urology unit (9.7 ‰ (IC95% 1,9–17,4)). A higher probability of readmission was associated with male gender, older age, certain diagnostic and service to hospital discharge. Inpatient units with more readmissions: mental health, obstetrics, radiation oncology, oncology and rheumatology, however, drives with more readmissions IN: urology, Angiology and Vascular C., oncology, pulmonology and cardiology. The diseases that stand out as readmission for IN are “other disorders of urethra and urinary tract” “postoperative infection, not elsewhere classified”. Conclusions: We have characterized the pattern of readmissions due to infections in the hospital Torrecárdenas, used to be used to implement preventive measures as an indicator of quality

s1a 5 molecular stratification of autoimmune diseases based on epigenetic profiles

Systemic autoimmune diseases (SADs) are a group of chronic inflammatory conditions with autoimmune aetiology and many common clinical features, leading to a difficult diagnosis or deciding the appropriate treatment. Finding new treatments or applying the existing ones in a more effective way is especially hard in SADs due to the heterogeneity of molecular mechanisms within the same disease class. Based on this premise, the first step towards establishing a precision medicine strategy for SADs is to reclassify these conditions at the molecular level, which might result in a more homogenous stratification in terms of pathological molecular pathways. It is well known that the interplay of DNA methylation patterns and environmental factors, and between these, is determinant in the regulation of the immune system. This, along with the fact that the genetic contribution to disease is dependent on regulatory variants with very small effects, and the low concordance for autoimmunity in monozygotic twins suggests that epigenetic regulation may play an important role in the development of these diseases. Thus, DNA methylation information might be a valuable marker to reclassify the autoimmune disorders molecularly. We performed an unsupervised clustering analysis of genome-wide DNA methylation profiling of 437 cases distributed across 7 different clinical entities (rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, primary Sjogren´s syndrome, primary antiphospholipid antibody syndrome, mixed connective tissue disease and undifferentiated connective tissue disease) and 115 healthy individuals. In this analysis we were able to identify new groups of patients composed of the different clinical diagnoses but with common biological features

Molecular stratification of autoimmune diseases based on epigenetic profiles

International audienc

Molecular stratification of autoimmune diseases based on epigenetic profiles

International audienc

Polymorphisms within the ARNT2 and CX3CR1 Genes Are Associated with the Risk of Developing Invasive Aspergillosis.

Invasive aspergillosis (IA) is a life-threatening infection that affects an increasing number of patients undergoing chemotherapy or allo-transplantation, and recent studies have shown that genetic factors contribute to disease susceptibility. In this two-stage, population-based, case-control study, we evaluated whether 7 potentially functional single nucleotide polymorphisms (SNPs) within the ARNT2 and CX3CR1 genes influence the risk of IA in high-risk hematological patients. We genotyped selected SNPs in a cohort of 500 hematological patients (103 of those had been diagnosed with proven or probable IA), and we evaluated their association with the risk of developing IA. The association of the most interesting markers of IA risk was then validated in a replication population, including 474 subjects (94 IA and 380 non-IA patients). Functional experiments were also performed to confirm the biological relevance of the most interesting markers. The meta-analysis of both populations showed that carriers of the ARNT2rs1374213G, CX3CR1rs7631529A, and CX3CR1rs9823718G alleles (where the RefSeq identifier appears as a subscript) had a significantly increased risk of developing IA according to a log-additive model (P value from the meta-analysis [PMeta] = 9.8 · 10-5, PMeta = 1.5 · 10-4, and PMeta =7.9 · 10-5, respectively). Haplotype analysis also confirmed the association of the CX3CR1 haplotype with AG CGG with an increased risk of IA (P = 4.0 · 10-4). Mechanistically, we observed that monocyte-derived macrophages (MDM) from subjects carrying the ARNTR2rs1374213G allele or the GG genotype showed a significantly impaired fungicidal activity but that MDM from carriers of the ARNT2rs1374213G and CX3CR1rs9823718G or CX3CR1rs7631529A alleles had deregulated immune responses to Aspergillus conidia. These results, together with those from expression quantitative trait locus (eQTL) data browsers showing a strong correlation of the CX3CR1rs9823718G allele with lower levels of CX3CR1 mRNA in whole peripheral blood (P = 2.46 · 10-7) and primary monocytes (P = 4.31 · 10-7), highlight the role of the ARNT2 and CX3CR1 loci in modulating and predicting IA risk and provide new insights into the host immune mechanisms involved in IA development

Polymorphisms within the ARNT2 and CX3CR1 Genes Are Associated with the Risk of Developing Invasive Aspergillosis

Invasive aspergillosis (IA) is a life-threatening infection that affects an increasing number of patients undergoing chemotherapy or allo-transplantation, and recent studies have shown that genetic factors contribute to disease susceptibility. In this two-stage, population-based, case-control study, we evaluated whether 7 potentially functional single nucleotide polymorphisms (SNPs) within the ARNT2 and CX3CR1 genes influence the risk of IA in high-risk hematological patients. We genotyped selected SNPs in a cohort of 500 hematological patients (103 of those had been diagnosed with proven or probable IA), and we evaluated their association with the risk of developing IA. The association of the most interesting markers of IA risk was then validated in a replication population, including 474 subjects (94 IA and 380 non-IA patients). Functional experiments were also performed to confirm the biological relevance of the most interesting markers. The meta-analysis of both populations showed that carriers of the ARNT2rs1374213G, CX3CR1rs7631529A, and CX3CR1rs9823718G alleles (where the RefSeq identifier appears as a subscript) had a significantly increased risk of developing IA according to a log-additive model (P value from the meta-analysis [PMeta]\u2009=\u20099.8 \ub7 10-5, PMeta\u2009=\u20091.5 \ub7 10-4, and PMeta\u2009=7.9 \ub7 10-5, respectively). Haplotype analysis also confirmed the association of the CX3CR1 haplotype with AG CGG with an increased risk of IA (P\u2009=\u20094.0 \ub7 10-4). Mechanistically, we observed that monocyte-derived macrophages (MDM) from subjects carrying the ARNTR2rs1374213G allele or the GG genotype showed a significantly impaired fungicidal activity but that MDM from carriers of the ARNT2rs1374213G and CX3CR1rs9823718G or CX3CR1rs7631529A alleles had deregulated immune responses to Aspergillus conidia. These results, together with those from expression quantitative trait locus (eQTL) data browsers showing a strong correlation of the CX3CR1rs9823718G allele with lower levels of CX3CR1 mRNA in whole peripheral blood (P\u2009=\u20092.46 \ub7 10-7) and primary monocytes (P\u2009=\u20094.31 \ub7 10-7), highlight the role of the ARNT2 and CX3CR1 loci in modulating and predicting IA risk and provide new insights into the host immune mechanisms involved in IA development

Polymorphisms within the ARNT2 and CX3CR1 Genes Are Associated with the Risk of Developing Invasive Aspergillosis.

Invasive aspergillosis (IA) is a life-threatening infection that affects an increasing number of patients undergoing chemotherapy or allo-transplantation, and recent studies have shown that genetic factors contribute to disease susceptibility. In this two-stage, population-based, case-control study, we evaluated whether 7 potentially functional single nucleotide polymorphisms (SNPs) within the ARNT2 and CX3CR1 genes influence the risk of IA in high-risk hematological patients. We genotyped selected SNPs in a cohort of 500 hematological patients (103 of those had been diagnosed with proven or probable IA), and we evaluated their association with the risk of developing IA. The association of the most interesting markers of IA risk was then validated in a replication population, including 474 subjects (94 IA and 380 non-IA patients). Functional experiments were also performed to confirm the biological relevance of the most interesting markers. The meta-analysis of both populations showed that carriers of the ARNT2rs1374213G, CX3CR1rs7631529A, and CX3CR1rs9823718G alleles (where the RefSeq identifier appears as a subscript) had a significantly increased risk of developing IA according to a log-additive model (P value from the meta-analysis [PMeta] = 9.8 · 10-5, PMeta = 1.5 · 10-4, and PMeta =7.9 · 10-5, respectively). Haplotype analysis also confirmed the association of the CX3CR1 haplotype with AG CGG with an increased risk of IA (P = 4.0 · 10-4). Mechanistically, we observed that monocyte-derived macrophages (MDM) from subjects carrying the ARNTR2rs1374213G allele or the GG genotype showed a significantly impaired fungicidal activity but that MDM from carriers of the ARNT2rs1374213G and CX3CR1rs9823718G or CX3CR1rs7631529A alleles had deregulated immune responses to Aspergillus conidia. These results, together with those from expression quantitative trait locus (eQTL) data browsers showing a strong correlation of the CX3CR1rs9823718G allele with lower levels of CX3CR1 mRNA in whole peripheral blood (P = 2.46 · 10-7) and primary monocytes (P = 4.31 · 10-7), highlight the role of the ARNT2 and CX3CR1 loci in modulating and predicting IA risk and provide new insights into the host immune mechanisms involved in IA development.status: Published onlin

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease

Transcriptome and Methylome Integrative Molecular Analysis Uncovers a New Systemic Autoimmune Disease Classification

International audienc