In-hospital versus after-discharge complete revascularization in patients with ST segment elevation myocardial infarction and multivessel disease. REVIVA-ST trial.

INTRODUCTION: Complete revascularization (CR) in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD), is associated with a reduction in major adverse cardiovascular events (MACE). However, there is uncertainty about whether nonculprit-lesion revascularization should be performed, during index hospitalization or delayed, especially regarding health care resources utilization. In this study, we aimed to evaluate the impact of in-hospital nonculprit-lesion revascularization vs. delayed (after discharge) revascularization on the length of index hospitalization. METHODS: In this single-center study, we randomly assigned patients with STEMI and MVD who underwent successful culprit-lesion PCI to a strategy of either CR during in-hospital admission or a delayed CR after discharge. The first primary endpoint was the length of hospital stay. The second endpoint was the composite of cardiovascular death, myocardial infarction or ischemia-driven revascularization at 12 months (MACE). RESULTS: From January 2018 to December 2022, we enrolled 258 patients (131 allocated to CR during in-hospital admission and 127 to an after-discharge CR). We found a significant reduction in the length of hospital stay in those assigned to after-discharge CR strategy [4 days (3-5) versus 7 days (5-9); p = 0.001]. At 12-month of follow-up, no differences were found in the occurrence of MACE, 7 (5.34%) patients in in-hospital CR and 4 (3.15%) in after-discharge CR strategy; (hazard ratio, 0.59; 95% confidence interval, 0.17 to 2.02; p = 0.397). CONCLUSIONS: In STEMI patients with MVD, an after-discharge CR strategy reduces the length of index hospitalization without an increased risk of MACE after 12 months of follow-up. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT04743154.

Long-term recurrent events in ST-elevation myocardial infarction and multivessel disease. The impact of different revascularization strategies.

INTRODUCTION: The benefit of complete revascularization (CR) on long-term total event reduction in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD), still remains unclear. We assessed the efficacy of three different revascularization strategies on long-term total recurrent events. METHODS: We retrospectively analyzed 414 consecutive patients admitted with STEMI and MVD who were categorized according to the revascularization strategy used: culprit-vessel-only percutaneous coronary intervention (PCI) (n=163); in-hospital CR (n=136); and delayed CR (n=115). The combined endpoint assessed was all-cause mortality, the total number of myocardial infarctions, ischemia-driven revascularizations or strokes. Negative binomial regression was used to assess the association between the revascularization strategy and total events; risk estimates were expressed as an incidence rates ratio (IRR). RESULTS: At a median follow-up of four years (1.2-6), rates of the combined endpoint per 10 patient-years were 18, 0.8, and 0.6 in culprit-vessel-only PCI, in-hospital CR, and delayed CR strategies, respectively (p<0.001). After multivariable adjustment and when compared with culprit-vessel-only PCI, both in-hospital and delayed CR strategies were significantly associated with a reduction in the combined endpoint (IRR=0.40: 95% confidence interval (CI), 0.25-0.64; p<0.001; and IRR 0.40: 95% CI, 0.24-0.62; p<0.001, respectively). No differences were observed across in-hospital and delayed CR strategies. CONCLUSIONS: Complete revascularization of non-culprit lesions in patients with STEMI and MVD reduces the risk of total recurrent events during long-term follow-up. No differences between in-hospital and delayed CR strategies were found.

Inaccuracy of a non-invasive estimation of pulmonary vascular resistance assessed by cardiovascular magnetic resonance in heart failure patients.

Pulmonary vascular resistance (PVR) is a marker of pulmonary vascular remodeling. A non-invasive model assessed by cardiovascular magnetic resonance (CMR) has been proposed to estimate PVR. However, its accuracy has not yet been evaluated in patients with heart failure. We prospectively included 108 patients admitted with acute heart failure (AHF), in whom a right heart catheterization (RHC) and CMR were performed at the same day. PVR was estimated by CMR applying the model: PVR = 19.38 - [4.62 × Ln pulmonary artery average velocity (in cm/s)] - [0.08 × right ventricle ejection fraction (in %)], and by RHC using standard formulae. The median age of the cohort was 67 years (interquartile range 58-73), and 34% were females. The median of PVR assessed by RHC and CMR were 2.2 WU (1.5-4) and 5 WU (3.4-7), respectively. We found a weak correlation between invasive PVR and PVR assessed by CMR (Spearman r = 0.21, p = 0.02). The area under the ROC curve for PVR assessed by CMR to detect PVR ≥ 3 WU was 0.57, 95% confidence interval (CI): 0.47-0.68. In patients with AHF, the non-invasive estimation of PVR using CMR shows poor accuracy, as well as a limited capacity to discriminate increased PVR values.

Genome-Scale Metabolic Model of Xanthomonas phaseoli pv. manihotis: An Approach to Elucidate Pathogenicity at the Metabolic Level.

Xanthomonas phaseoli pv. manihotis (Xpm) is the causal agent of cassava bacterial blight, the most important bacterial disease in this crop. There is a paucity of knowledge about the metabolism of Xanthomonas and its relevance in the pathogenic process, with the exception of the elucidation of the xanthan biosynthesis route. Here we report the reconstruction of the genome-scale model of Xpm metabolism and the insights it provides into plant-pathogen interactions. The model, iXpm1556, displayed 1,556 reactions, 1,527 compounds, and 890 genes. Metabolic maps of central amino acid and carbohydrate metabolism, as well as xanthan biosynthesis of Xpm, were reconstructed using Escher (https://escher.github.io/) to guide the curation process and for further analyses. The model was constrained using the RNA-seq data of a mutant of Xpm for quorum sensing (QS), and these data were used to construct context-specific models (CSMs) of the metabolism of the two strains (wild type and QS mutant). The CSMs and flux balance analysis were used to get insights into pathogenicity, xanthan biosynthesis, and QS mechanisms. Between the CSMs, 653 reactions were shared; unique reactions belong to purine, pyrimidine, and amino acid metabolism. Alternative objective functions were used to demonstrate a trade-off between xanthan biosynthesis and growth and the re-allocation of resources in the process of biosynthesis. Important features altered by QS included carbohydrate metabolism, NAD(P)+ balance, and fatty acid elongation. In this work, we modeled the xanthan biosynthesis and the QS process and their impact on the metabolism of the bacterium. This model will be useful for researchers studying host-pathogen interactions and will provide insights into the mechanisms of infection used by this and other Xanthomonas species.

Opioids for the management of dyspnea in patients with heart failure: a systematic review of the literature / Opioides para el manejo de la disnea en pacientes con insuficiencia cardiaca: Revisión sistemática de la literatura

Abstract Introduction: Heart failure is a chronic, progressive, prevalent disease, with a high impact on health systems and on the quality of life of patients and families. Dyspnea is a common symptom and management with opioids has been proposed. Objective: To conduct a systematic review of the literature pertaining to the use of opioids for the management of dyspnea in patients with stable chronic heart failure, functional class New York Heart Association (NYHA) II, III, or IV. Materials and methods: A systematic review was conducted in the MEDLINE, Embase, Cochrane, OVID, LILACS, and PROSPERO databases of articles published in 5 languages between January 1, 1995 and July 31, 2018. Studies describing the administration of any type of opioid for the management of dyspnea in patients with stable chronic heart failure NYHA II, III, or IV were included. Results: Four clinical trials were obtained for the final analysis with a total number of 70 patients, describing opioid administration for the management of dyspnea in patients with stable chronic heart failure, NYHA II, III, or IV. Conclusion: In adult patients with compensated chronic heart failure under optimum treatment, there is low-quality evidence that shows benefit with the use of opioids for the management of dyspnea. For a stronger recommendation, controlled, randomized studies with a larger number of subjects are required.

Resumen Introducción: La insuficiencia cardiaca es una enfermedad crónica, progresiva, prevalente, con un alto impacto en los sistemas de salud y en la calidad de vida de los pacientes y sus familias, la disnea es un síntoma común y se ha planteado el uso de opioides para su control. Objetivo: Revisión sistemática de la literatura sobre el uso de opioides en el manejo de la disnea en pacientes con insuficiencia cardiaca crónica estable con clase funcional NYHA II, III o IV. Materiales y métodos: Se realizó una revisión sistemática de los artículos encontrados en las bases de datos MEDLINE, Embase, Cochrane, OVID, LILACS, PROSPERO a partir del 1 de enero del 1995 hasta el 31 de julio del 2018, publicados en cinco idiomas. Se incluyeron aquellos estudios en los cuales se describe la administración de cualquier tipo de opioide para el manejo de la disnea en pacientes con insuficiencia cardiaca crónica estable, NYHA II, III o IV. Resultados: Se incluyeron cuatro ensayos clínicos para el análisis final, con un numero total de 70 pacientes, en los cuales se describe la administración de opioides para el manejo de la disnea en pacientes con insuficiencia cardiaca crónica estable, NYHA II, III, o IV. Conclusiones: En pacientes adultos con insuficiencia cardiaca crónica compensada en tratamiento óptimo, existe evidencia de baja calidad que muestra beneficio para el manejo de la disnea con opioides, deben realizarse estudios aleatorizados controlados con una cantidad de individuos mayor para poder generar una recomendación más fuerte.

Long-term outcomes and predictors of morbi-mortality according to age in stemi patients with multivessel disease: Impact of an incomplete revascularization.

BACKGROUND: Optimal management strategy for patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) still remains unclear, especially in the elderly population. The aim of this study was to assess long-term outcomes and predictors of morbi-mortality according to age in patients with a STEMI and MVD. METHODS: We prospectively included 381 consecutive patients with a STEMI who underwent primary angioplasty and showed MVD in the angiogram. 111 (29.1%) patients were older than 75 (≥75) years and 270 (70.9%) were younger than 75 (<75) years. The co-primary outcomes were the incidence of all-cause mortality and major adverse cardiac events (MACE) during follow-up. RESULTS: During a median follow-up of 22 months, patients ≥75 years showed a higher incidence of all-cause mortality and MACE, as compared to younger patients. On multivariate analysis, incomplete revascularization (IR) was only an independent predictor of MACE (HR = 3.1, CI 95%:1.9-4.7; P = .02) in younger patients; whereas in the elderly group severely depressed ejection fraction was the unique independent predictor of MACE (HR = 2.7, CI 95%:1.5-4.8; P = .001). IR was not associated with the risk of all-cause mortality in any group. CONCLUSION: This study confirms the relevant prevalence of MVD in STEMI patients, as well as the difference in outcomes of an IR strategy between both age-groups, being only independently associated with MACE in younger patients. This finding supports that a routine complete revascularization (CR) strategy seems to be the best therapeutic option in younguer patients, whereas in the elderly population may not confer a clear clinical benefit during a long-term follow-up.

Inheritance patterns in metabolism and growth in diallel crosses of Arabidopsis thaliana from a single growth habitat.

Metabolism is a key determinant of plant growth and modulates plant adaptive responses. Increased metabolic variation due to heterozygosity may be beneficial for highly homozygous plants if their progeny is to respond to sudden changes in the habitat. Here, we investigate the extent to which heterozygosity contributes to the variation in metabolism and size of hybrids of Arabidopsis thaliana whose parents are from a single growth habitat. We created full diallel crosses among seven parents, originating from Southern Germany, and analysed the inheritance patterns in primary and secondary metabolism as well as in rosette size in situ. In comparison to primary metabolites, compounds from secondary metabolism were more variable and showed more pronounced non-additive inheritance patterns which could be attributed to epistasis. In addition, we showed that glucosinolates, among other secondary metabolites, were positively correlated with a proxy for plant size. Therefore, our study demonstrates that heterozygosity in local A. thaliana population generates metabolic variation and may impact several tasks directly linked to metabolism.

Novel allelic variants in ACD6 cause hybrid necrosis in local collection of Arabidopsis thaliana.

Hybrid necrosis is a common type of hybrid incompatibility in plants. This phenomenon is caused by deleterious epistatic interactions, resulting in spontaneous activation of plant defenses associated with leaf necrosis, stunted growth and reduced fertility in hybrids. Specific combinations of alleles of ACCELERATED CELL DEATH 6 (ACD6) have been shown to be a common cause of hybrid necrosis in Arabidopsis thaliana. Increased ACD6 activity confers broad-spectrum resistance against biotrophic pathogens but reduces biomass production. We generated 996 crosses among individuals derived from a single collection area around Tübingen (Germany) and screened them for hybrid necrosis. Necrotic hybrids were further investigated by genetic linkage, amiRNA silencing, genomic complementation and metabolic profiling. Restriction site associated DNA (RAD)-sequencing was used to understand genetic diversity in the collection sites containing necrosis-inducing alleles. Novel combinations of ACD6 alleles found in neighbouring stands were found to activate the A. thaliana immune system. In contrast to what we observed in controlled conditions, necrotic hybrids did not show reduced fitness in the field. Metabolic profiling revealed changes associated with the activation of the immune system in ACD6-dependent hybrid necrosis. This study expands our current understanding of the active role of ACD6 in mediating trade-offs between defense responses and growth in A.  thaliana.

Neumonía adquirida en la comunidad por Staphylococcus aureus resistente a meticilina / Community-Acquired Pneumonia Due to Methicillin-Resistant Staphylococcus aureus

Los casos de infecciones causadas por Staphylococcus aureus resistente a meticilina han aumentado durante la última década. Dentro de ellas, la neumonía necrotizante (NN) adquirida en la comunidad se ha encontrado en pacientes jóvenes, sanos y sin factores de riesgo, lo que ha generado cuadros de evolución rápida y potencialmente mortales. En este artículo se discuten factores epidemiológicos, fisiopatológicos, de diagnóstico, tratamiento y pronóstico de la NN por Staphylococcus aureus resistente a meticilina adquirida en la comunidad.

The cases oí iníections caused by methicillirvresistant Stapkylococcus aureus have íncreased over the last decade, within them necrotizmg community'acquired pneumonía has been íound in healthy, young and with no risk factors patients, developing dínícal symptoms rapidly evolving and threatening. This artide discussed epidemiológica!, pathophysiological, diagnostic, treatment, and prognosis oí necrotizing pneumonía by Staphyiococcus aureus methicillin resistant communitV' acquired.

ANALIZANDO DATOS DE RNA-Seq EN PROCARIOTAS: UNA REVISIÓN PARA NO EXPERTOS: A Review for Non-experts / RNA-Seq Data Analysis in Prokaryotes

La secuenciación de transcritos con RNA-Seq es hoy en día una de las técnicas más populares en los estudios transcriptómicos. Relativamente reciente, esta técnica ha permitido la secuenciación de transcritos de RNA en una escala y profundidad no alcanzada por otras técnicas anteriores. Sin embargo, el alcance de las conclusiones que se pueden sacar depende estrictamente de un proceso adecuado, desde el diseño experimental hasta el análisis bioinformático de los datos. Dadas las diferencias en el proceso transcripcional de las células eucariotas y procariotas, el análisis de RNA-Seq deberá tener ciertas consideraciones dependiendo del tipo de organismo estudiado. En esta revisión se exponen los principales factores a tener en cuenta para lograr un análisis de RNA-Seq consistente, replicable y concluyente, enfocándose específicamente en organismos procariotas.

RNA-Seq is nowadays the method of choice for the sequencing of transcripts and transcriptomes in the field of molecular biology and gene expression assays. Until recently, this technique has allowed for the sequencing of RNA transcripts in an unprecedented scale and depth never reached in previous years; nevertheless, the reach and validity of the conclusions generated will depend strictly on an adequate experimental design and a robust analysis of the data. Given the inherent differences between prokaryotes and eukaryotes, the RNA-Seq analysis should take into account the type of organism studied. In this review we present the main factors to take into consideration when designing a consistent analysis for this type of data in prokaryotes, from the experimental design to the in silico analysis of the generated data.

Mean platelet volume is associated with infarct size and microvascular obstruction estimated by cardiac magnetic resonance in ST segment elevation myocardial infarction.

Mean platelet volume (MPV) is an indicator of platelet activation. High MPV has been recently considered as an independent risk factor for poor outcomes after ST-segment elevation myocardial infarction (STEMI). We analyzed 128 patients diagnosed with first STEMI successfully reperfused during three consecutive years. MPV was measured on admission and a cardiac magnetic resonance (CMR) exam was performed within the first week in all patients. Myocardial necrosis size was estimated by the area of late gadolinium enhancement (LGE), identifying microvascular obstruction (MVO), if present. Clinical outcomes were recorded at 1 year follow-up. High MPV was defined as a value in the third tertile (≥9.5 fl), and a low MPV, as a value in the lower two. We found a slight but significant correlation between MPV and infarct size (r = 0.287, P = 0.008). Patients with high MPV had more extensive infarcted area (percentage of necrosis by LGE: 17.6 vs. 12.5%, P = 0.021) and more presence of MVO (patients with MVO pattern: 44.4 vs. 25.3%, P = 0.027). In a multivariable analysis, hazard ratio for major adverse cardiac events was 3.35 [95% confidence interval (CI) 1.1-9.9, P = 0.03] in patients with high MPV. High MPV in patients with first STEMI is associated with higher infarct size and more presence of MVO measured by CMR.