Características clínico-microbiológicas y del manejo diagnóstico y terapéutico de la bacteriemia por S. aureus en un hospital terciario.

Antecedentes: Las bacteriemias por S. aureus (BSA) son infecciones graves que asocian una morbi-mortalidad importante que va a depender principalmente de las circunstancias del huésped y del abordaje diagnóstico y terapéutico realizado. Objetivos: Describir las características clínicas y microbiológicas de las bacteriemias por S. aureus en un hospital terciario. Métodos: Estudio observacional retrospectivo unicéntrico en el Hospital Clínico Universitario Lozano Blesa de Zaragoza. La población a estudio son los pacientes ≥ 14 años del HCLB con BSA entre septiembre de 2015 y abril de 2016. Se revisaron las historias clínicas de los pacientes para registrar las diferentes variables relacionadas con paciente, microbiológicas, del manejo, tratamiento y evolución. Desde el punto de vista clínico se estudió la comorbilidad de los pacientes, la gravedad y foco de la infección así como el presumible lugar de adquisición. Desde el punto de vista diagnóstico se evaluó el grado de cumplimiento de la obtención de hemocultivos de control y de la realización de ecocardiograma. Desde el punto de vista terapéutico se analizó la duración del tratamiento antibiótico así como la utilización de betalactámicos antiestafilocócicos en las cepas sensibles a cloxacilina. Resultados: El 58% eran pacientes mujeres. La media de edad fue 69,91 años. Se incluyeron 26 pacientes, el 62% de las cepas eran SASM y el 38% SARM. De forma global el 50% de las cepas (n=13) tenían una CMI >1, el 43,75% (n=7) de las SASM y el 60% (n=10) de las SARM. La mayoría de las BSA (n=13; 46,15%) estaban relacionadas con la asistencia sanitaria (IRAS) mientras que 9 (34,62%) y 4 (15,38%) fueron nosocomiales o comunitarias respectivamente. El principal foco fue el catéter central (23,07%). El 38,46% presentaron sepsis grave. Se realizaron hemocultivos de control en el 80% de los pacientes, ecocardiograma transtorácico (ETT) en el 48% (n=12) y ecocardiograma transesofágico en el 16% (n=4). De las 16 cepas SASM el 31,25% (n=5) se trataron con cloxacilina, antibiótico de elección para este microorganismo y el 50% (n=8) con cefazolina, que se considera de eficacia similar. La mortalidad al mes fue 29,17%. Conclusiones: La BSA en nuestro hospital ocurre sobre pacientes ancianos y con importante comorbilidad. La frecuencia de BSA por SARM es elevada, muy por encima de la frecuencia de SARM entre S. aureus. Se cumplen las recomendaciones para la duración del tratamiento. La mortalidad observada está dentro del rango descrito en las series de nuestro entorno, pero en el límite alto. Hay una mayor mortalidad por SARM cuando la CMI a vancomicina es >1,5 mg/L. Los principales aspectos de mejora son la optimización de la obtención de hemocultivos de control y la selección de β-lactámicos antiestafilocócicos en pacientes con SASM. Interesa realizar en un futuro una evaluación de asociaciones entre distintos factores de riesgo de mortalidad

Theoretical Higgs Mass Bounds in the Standard Model and Supersymmetric Extensions

These lectures provide a very basic introduction to different theoretical limits on the mass of Higgs scalars. Particular attention is devoted to the pure Standard Model and its Minimal Supersymmetric extension (MSSM). [Lectures presented at the XXIV ITEP Winter School, Snegiri (Russia), February 96]Comment: 37 pages, TeX, 15 postscript figures include

Evaluation of aflatoxin and fumonisin co-exposure in urine samples from healthy volunteers in northern Mexico

Aflatoxins (AF) and fumonisins (FB) are common contaminants of maize and have been associated with cancer, immune suppression, and growth stunting. In this work, AFM(1) and FB(1) were measured in urine samples of healthy volunteers from the metropolitan area of Monterrey, Mexico, while AF and FB were detected in foods collected near the sampling zone. Urine samples from 106 adults were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry and toxins in foods were measured by fluorometry. The mean value of AFM(1) and FB(1) was 4.3 pg/mg creatinine from 76 samples (72 %), and 50 pg/mg creatinine from 75 samples (71 %), respectively. More than half of the samples (n = 56, 53 %) had detectable levels of both AFM(1) and FB(1). No differences in toxin levels were found between males and females or between age groups, but AFM(1) and FB(1) levels were higher (p < 0.01) when detected as a single exposure compared to co-exposed. Some significant results were found when comparing AFM(1) and FB(1) levels among groups of people assigned to levels of food consumption. Food samples had average concentrations of 5.3 μg/kg for AF and 800 μg/kg for FB. The results showed that co-exposure to AF and FB is common in the metropolitan area of Monterrey

Gauge unification and the supersymmetric light Higgs mass

We consider general supersymmetric models with: a) arbitrary matter content; and, b) gauge coupling Unification near the String scale $\sim 10^{17}$ GeV, and derive the absolute upper limit on the mass of the lightest Higgs boson. For a top-quark mass $M_t$= 175 GeV, and depending on the supersymmetric parameter $\tan\beta$, this mass bound can be as high as $\sim$ 200 GeV.Comment: 4 pages, revtex + psfig.sty, 2 figure

Clinical characteristics and prognosis of myocardial infarction with non-obstructive coronary arteries (MINOCA): A prospective single-center study

Background: A definition of myocardial infarction with non-obstructive coronary arteries (MINOCA) was published by European Society of Cardiology in 2016. The aim of this study is to analyze the clinical profile and prognosis of these patients in a prospective single-center study and compare it with the literature data. Methods: During a 3-year period, information from every consecutive MINOCA patient was gathered (n = 109). It was then compared with 412 contemporaneous patients with myocardial infarction and obstructive coronary arteries (MIOCA). Univariate and multivariate analyses were performed. Prognosis analysis was adjusted by age and cardiovascular risk factors (CVRF). Results: MINOCA represented 16.9% of the total of patients admitted for myocardial infarction. Compared with MIOCA, they had more psychosocial disorders (22.9% vs. 10.7%; p &lt; 0.01) and more pro-inflammatory conditions (34.9% vs. 14.0%; p &lt; 0.01). Atrial fibrillation was twice as frequent in MINOCA (14.7% vs. 7.3%; p = 0.016). Predictors of MINOCA were as follows: female gender, absence of diabetes, absence of tobacco use, tachycardia, troponin above 10 times the 99th percentile, and pro-inflammatory conditions. Median follow-up was 17.3 ± 9.3 months. Major adverse cardiovascular events (MACE; a composite of a recurrence of acute myocardial infarction, transient ischemic attack/stroke, or death from cardiovascular cause and death from any cause) occurred in 10.8% of the MINOCA group as compared with 10.7% in the MIOCA group (hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.58–2.45; p = 0.645). Cardiovascular re-admission rates were higher in the MINOCA group: 19.8% vs. 13.9% (HR 1.85; CI 1.06–3.21; p = 0.030). Conclusions: The frequency of MINOCA is high, with fewer CVRF, and it is linked to atrial fibrillation, psychosocial disorders, and pro-inflammatory conditions. Mid-term prognosis is worse than previously thought, with a similar proportion of MACE as compared to MIOCA, and even a higher rate of cardiovascular re-admissions

Spanish cohort of VEXAS syndrome : clinical manifestations, outcome of treatments and novel evidences about UBA1 mosaicism

The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic UBA1 variants. To investigate the presence of VEXAS syndrome among patients with adult-onset undiagnosed AID. Additional studies evaluated the mosaicism distribution and the circulating cytokines. Gene analyses were performed by both Sanger and amplicon-based deep sequencing. Patients' data were collected from their medical charts. Cytokines were quantified by Luminex. Genetic analyses of enrolled patients (n=42) identified 30 patients carrying UBA1 pathogenic variants, with frequencies compatible for postzygotic variants. All patients were male individuals who presented with a late-onset disease (mean 67.5 years; median 67.0 years) characterised by cutaneous lesions (90%), fever (66.7%), pulmonary manifestations (66.7%) and arthritis (53.3%). Macrocytic anaemia and increased erythrocyte sedimentation rate and ferritin were the most relevant analytical abnormalities. Glucocorticoids ameliorated the inflammatory manifestations, but most patients became glucocorticoid-dependent. Positive responses were obtained when targeting the haematopoietic component of the disease with either decitabine or allogeneic haematopoietic stem cell transplantation. Additional analyses detected the UBA1 variants in both haematopoietic and non-haematopoietic tissues. Finally, analysis of circulating cytokines did not identify inflammatory mediators of the disease. Thirty patients with adult-onset AID were definitively diagnosed with VEXAS syndrome through genetic analyses. Despite minor interindividual differences, their main characteristics were in concordance with previous reports. We detected for the first time the UBA1 mosaicism in non-haematopoietic tissue, which questions the previous concept of myeloid-restricted mosaicism and may have conceptual consequences for the disease mechanisms

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 +/- 19.2 years) recruited from 29 international centers. RESULTS At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% +/- 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of <= 35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe