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

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Diseño y validación de la escala THRISOL para el triaje de riesgo social en hospitales de grupo I

Social risk is defined as the possibility of one person from being injured because of any reason related to a social problem. Some studies points out that praecox identification of social risk and its priorization by health professionals in hospitals reduce the number of hospital inpatients stays which must be prorogued because of social reasons, but nowadays, there is no validated questionnaire for social risk triage in hospitalized patients. Objective: to design and validate a social risk triage scale (THRISOL scale) to be applied in people attended in group I hospitals. Social risk triage in hospitals will allow the selection and classification of patients in several risk levels so that an appropriate attention related to the identified social risk level could be developed. Methodology: the scale design will have to stages: first of all, a bibliographic review will be performed to identify social risk indicators which, afterwards, will be evaluated by social workers in order to assign a scalar value to each item. The pilot version of the scale will be applied in a sample of patients and a factorial analysis will be performed to identify the underlying structure of the scale, removing those items with low saturation. The final version will be applied in other sample of patients to estimate its validity, reliability and the proportion of correct classifications and the cut-off points will be stablished, giving priority to the sensibility of the scale. Relevance. Social risk triage provide the systematic valuation of the social patron of the patient. Besides, praecox identification of a possible social risk will improve the social functioning of the patient on discharge and it will ensure a better continuity of care.El riesgo social es definido como la posibilidad de que una persona sufra un daño que tiene su origen en una causa social. Algunos estudios señalan que la identificación precoz del riesgo social y la priorización del mismo por parte del personal sanitario en el ámbito hospitalario reducen el número de estancias que se deben prolongar por criterios sociales, pero actualmente no existe ningún cuestionario validado para el triaje de riesgo social en pacientes hospitalizados. Objetivo: diseñar y validar una escala de triaje de riesgo social (escala THRISOL) para su aplicación en personas atendidas en hospitales de grupo I. Metodología. El diseño de la escala tendrá dos etapas: en primer lugar, se realizará una revisión bibliográfica para identificar indicadores de riesgo social que, posteriormente, serán valorados por trabajadores sociales con el fin de asignar a cada ítem un valor escalar. Se validará la versión piloto de la escala en una muestra de pacientes y se realizará un análisis factorial para identificar la estructura subyacente de la escala, eliminando aquellos ítems con baja saturación. La versión definitiva será aplicada a otra muestra de pacientes para calcular su validez y fiabilidad y la proporción de clasificaciones correctas y se fijarán puntos de corte priorizando la sensibilidad de la escala. Relevancia. El triaje de riesgo social facilitará la valoración sistemática del patrón social del paciente. Además, la identificación precoz de un posible riesgo social mejorará el funcionamiento social del paciente al alta y garantizará una mejor continuidad asistencial

Identification and validation of clinical phenotypes with prognostic implications in patients admitted to hospital with COVID-19: a multicentre cohort study

Background The clinical presentation of COVID-19 in patients admitted to hospital is heterogeneous. We aimed to determine whether clinical phenotypes of patients with COVID-19 can be derived from clinical data, to assess the reproducibility of these phenotypes and correlation with prognosis, and to derive and validate a simplified probabilistic model for phenotype assignment. Phenotype identification was not primarily intended as a predictive tool for mortality. Methods In this study, we used data from two cohorts: the COVID-19@Spain cohort, a retrospective cohort including 4035 consecutive adult patients admitted to 127 hospitals in Spain with COVID-19 between Feb 2 and March 17, 2020, and the COVID-19@HULP cohort, including 2226 consecutive adult patients admitted to a teaching hospital in Madrid between Feb 25 and April 19, 2020. The COVID-19@Spain cohort was divided into a derivation cohort, comprising 2667 randomly selected patients, and an internal validation cohort, comprising the remaining 1368 patients. The COVID-19@HULP cohort was used as an external validation cohort. A probabilistic model for phenotype assignment was derived in the derivation cohort using multinomial logistic regression and validated in the internal validation cohort. The model was also applied to the external validation cohort. 30-day mortality and other prognostic variables were assessed in the derived phenotypes and in the phenotypes assigned by the probabilistic model. Findings Three distinct phenotypes were derived in the derivation cohort (n=2667)—phenotype A (516 [19%] patients), phenotype B (1955 [73%]) and phenotype C (196 [7%])—and reproduced in the internal validation cohort (n=1368)— phenotype A (233 [17%] patients), phenotype B (1019 [74%]), and phenotype C (116 [8%]). Patients with phenotype A were younger, were less frequently male, had mild viral symptoms, and had normal inflammatory parameters. Patients with phenotype B included more patients with obesity, lymphocytopenia, and moderately elevated inflammatory parameters. Patients with phenotype C included older patients with more comorbidities and even higher inflammatory parameters than phenotype B. We developed a simplified probabilistic model (validated in the internal validation cohort) for phenotype assignment, including 16 variables. In the derivation cohort, 30-day mortality rates were 2·5% (95% CI 1·4–4·3) for patients with phenotype A, 30·5% (28·5–32·6) for patients with phenotype B, and 60·7% (53·7–67·2) for patients with phenotype C (log-rank test p<0·0001). The predicted phenotypes in the internal validation cohort and external validation cohort showed similar mortality rates to the assigned phenotypes (internal validation cohort: 5·3% [95% CI 3·4–8·1] for phenotype A, 31·3% [28·5–34·2] for phenotype B, and 59·5% [48·8–69·3] for phenotype C; external validation cohort: 3·7% [2·0–6·4] for phenotype A, 23·7% [21·8–25·7] for phenotype B, and 51·4% [41·9–60·7] for phenotype C). Interpretation Patients admitted to hospital with COVID-19 can be classified into three phenotypes that correlate with mortality. We developed and validated a simplified tool for the probabilistic assignment of patients into phenotypes. These results might help to better classify patients for clinical management, but the pathophysiological mechanisms of the phenotypes must be investigated

Impact of uterine manipulator on oncological outcome in endometrial cancer surgery.

There are limited data available to indicate whether oncological outcomes might be influenced by the uterine manipulator, which is used at the time of hysterectomy for minimally invasive surgery in patients with endometrial cancer. The current evidence derives from retrospective studies with limited sample sizes. Without substantial evidence to support its use, surgeons are required to make decisions about its use based only on their personal choice and surgical experience. To evaluate the use of the uterine manipulator on oncological outcomes after minimally invasive surgery, for apparent early-stage endometrial cancer. We performed a retrospective multicentric study to assess the oncological safety of uterine manipulator use in patients with apparent early-stage endometrial cancer, treated with minimally invasive surgery. The type of manipulator, surgical staging, histology, lymphovascular space invasion, International Federation of Gynecology and Obstetrics stage, adjuvant treatment, recurrence, and pattern of recurrence were evaluated. The primary objective was to determine the relapse rate. The secondary objective was to determine recurrence-free survival, overall survival, and the pattern of recurrence. A total of 2661 women from 15 centers were included; 1756 patients underwent hysterectomy with a uterine manipulator and 905 without it. Both groups were balanced with respect to histology, tumor grade, myometrial invasion, International Federation of Gynecology and Obstetrics stage, and adjuvant therapy. The rate of recurrence was 11.69% in the uterine manipulator group and 7.4% in the no-manipulator group (P In this study, the use of a uterine manipulator was associated with a worse oncological outcome in patients with uterus-confined endometrial cancer (International Federation of Gynecology and Obstetrics I-II) who underwent minimally invasive surgery. Prospective trials are essential to confirm these results

VII Jornadas de Innovación Educativa de la Universidad de La Laguna: imaginar y comprender la innovación en la Universidad

The change of structure and process of the organizations of the current society has generated a great impact in the new way of working. Work teams coordination ensures that a team functions as a unitary whole; is identified as a key process to understand work team effectiveness. This paper presents a brief introduction of the recent research on Work teams in organizations and raises relevant issues about their implications for Pedagogy studies. This paper aims, first, to analyze the potential of team based organizations. And secondly, to examine the effects in pedagogy studies. Coordination is a process that involves the use of strategies and patterns of behavior aimed to integrate actions, knowledge and goals of interdependent members. The tasks have increased its difficulty, doing that individual resolution is very difficult or impossibleUniversidad de La Lagun