Longer ICU stay and invasive mechanical ventilation accelerate telomere shortening in COVID-19 patients 1 year after recovery.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes virus-induced-senescence. There is an association between shorter telomere length (TL) in coronavirus disease 2019 (COVID-19) patients and hospitalization, severity, or even death. However, it remains unknown whether virus-induced-senescence is reversible. We aim to evaluate the dynamics of TL in COVID-19 patients 1 year after recovery from intensive care units (ICU). Longitudinal study enrolling 49 patients admitted to ICU due to COVID-19 (August 2020 to April 2021). Relative telomere length (RTL) quantification was carried out in whole blood by monochromatic multiplex real-time quantitative PCR (MMqPCR) assay at hospitalization (baseline) and 1 year after discharge (1-year visit). The association between RTL and ICU length of stay (LOS), invasive mechanical ventilation (IMV), prone position, and pulmonary fibrosis development at 1-year visit was evaluated. The median age was 60 years, 71.4% were males, median ICU-LOS was 12 days, 73.5% required IMV, and 38.8% required a prone position. Patients with longer ICU-LOS or who required IMV showed greater RTL shortening during follow-up. Patients who required pronation had a greater RTL shortening during follow-up. IMV patients who developed pulmonary fibrosis showed greater RTL reduction and shorter RTL at the 1-year visit. Patients with longer ICU-LOS and those who required IMV had a shorter RTL in peripheral blood, as observed 1 year after hospital discharge. Additionally, patients who required IMV and developed pulmonary fibrosis had greater telomere shortening, showing shorter telomeres at the 1-year visit. These patients may be more prone to develop cellular senescence and lung-related complications; therefore, closer monitoring may be needed.

Relative telomere length impact on mortality of COVID-19: Sex differences.

Increasing age is associated with severity and higher mortality of COVID-19. Telomere shortening is associated with higher risk of infections and may be used to identify those patients who are more likely to die. We evaluated the association between relative telomere length (RTL) and COVID-19 mortality. RTL was measured in patients hospitalized because of COVID-19. We used Kaplan-Meier method to analyze survival probabilities, and Cox regression to investigate the association between RTL and mortality (30 and 90 days). Six hundred and eight patients were included in the analysis (mean age =72.5 years, 41.1% women, and 53.8% Caucasic). During the study period, 75 people died from COVID-19 and 533 survived. Lower RTL was associated with a higher risk of death in women either at 30 (adjusted hazard ratio [HR] (aHR) = 3.33; 95% confidence interval [CI] = 1.05-10.00; p = 0.040) and at 90 days (aHR = 3.57; 95%CI = 1.23-11.11; p = 0.019). Lower RTL was associated with a higher risk of dying of COVID-19 in women. This finding suggests that RTL has an essential role in the prognosis of this subset of the population.

Promoting networks between evidence-based medicine and values-based medicine in continuing medical education.

BACKGROUND: In recent years, medical practice has followed two different paradigms: evidence-based medicine (EBM) and values-based medicine (VBM). There is an urgent need to promote medical education that strengthens the relationship between these two paradigms. This work is designed to establish the foundations for a continuing medical education (CME) program aimed at encouraging the dialogue between EBM and VBM by determining the values relevant to everyday medical activities. METHODS: A quasi-experimental, observational, comparative, prospective and qualitative study was conducted by analyzing through a concurrent triangulation strategy the correlation between healthcare personnel-patient relationship, healthcare personnel's life history, and ethical judgments regarding dilemmas that arise in daily clinical practice.In 2009, healthcare personnel working in Mexico were invited to participate in a free, online clinical ethics course. Each participant responded to a set of online survey instruments before and after the CME program. Face-to-face semi-structured interviews were conducted with healthcare personnel, focusing on their views and representations of clinical practice. RESULTS: The healthcare personnel's core values were honesty and respect. There were significant differences in the clinical practice axiology before and after the course (P <0.001); notably, autonomy climbed from the 10th (order mean (OM) = 8.00) to the 3rd position (OM = 5.86). In ethical discernment, the CME program had an impact on autonomy (P ≤0.0001). Utilitarian autonomy was reinforced in the participants (P ≤0.0001). Regarding work values, significant differences due to the CME intervention were found in openness to change (OC) (P <0.000), self-transcendence (ST) (P <0.001), and self-enhancement (SE) (P <0.019). Predominant values in life history, ethical discernment and healthcare personnel-patient relation were beneficence, respect and compassion, respectively. CONCLUSIONS: The healthcare personnel participating in a CME intervention in clinical ethics improved high-order values: Openness to change (OC) and Self Transcendence (ST), which are essential to fulfilling the healing ends of medicine. The CME intervention strengthened the role of educators and advisors with respect to healthcare personnel. The ethical values developed by healthcare professionals arise from their life history and their professional formation.

Plasma miRNA profile at COVID-19 onset predicts severity status and mortality.

BACKGROUND: MicroRNAs (miRNAs) have a crucial role in regulating immune response against infectious diseases, showing changes early in disease onset and before the detection of the pathogen. Thus, we aimed to analyze the plasma miRNA profile at COVID-19 onset to identify miRNAs as early prognostic biomarkers of severity and survival. METHODS AND RESULTS: Plasma miRNome of 96 COVID-19 patients that developed asymptomatic/mild, moderate and severe disease was sequenced together with a group of healthy controls. Plasma immune-related biomarkers were also assessed. COVID-19 patients showed 200 significant differentially expressed (SDE) miRNAs concerning healthy controls, with upregulated putative targets of SARS-CoV-2, and inflammatory miRNAs. Among COVID-19 patients, 75 SDE miRNAs were observed in asymptomatic/mild compared to symptomatic patients, which were involved in platelet aggregation and cytokine pathways, among others. Moreover, 137 SDE miRNAs were identified between severe and moderate patients, where miRNAs targeting the SARS CoV-2 genome were the most strongly disrupted. Finally, we constructed a mortality predictive risk score (miRNA-MRS) with ten miRNAs. Patients with higher values had a higher risk of 90-days mortality (hazard ratio = 4.60; p-value < 0.001). Besides, the discriminant power of miRNA-MRS was significantly higher than the observed for age and gender (AUROC = 0.970 vs. 0.881; p = 0.042). CONCLUSIONS: SARS-CoV-2 infection deeply disturbs the plasma miRNome from an early stage of COVID-19, making miRNAs highly valuable as early predictors of severity and mortality.

Metabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation.

Background: metabolic changes through SARS-CoV-2 infection has been reported but not fully comprehended. This metabolic dysregulation affects multiple organs during COVID-19 and its early detection can be used as a prognosis marker of severity. Therefore, we aimed to characterize metabolic and cytokine profile at COVID-19 onset and its relationship with disease severity to identify metabolic profiles predicting disease progression. Material and Methods: we performed a retrospective cross-sectional study in 123 COVID-19 patients which were stratified as asymptomatic/mild, moderate and severe according to the highest COVID-19 severity status, and a group of healthy controls. We performed an untargeted plasma metabolic profiling (gas chromatography and capillary electrophoresis-mass spectrometry (GC and CE-MS)) and cytokine evaluation. Results: After data filtering and identification we observed 105 metabolites dysregulated (66 GC-MS and 40 CE-MS) which shown different expression patterns for each COVID-19 severity status. These metabolites belonged to different metabolic pathways including amino acid, energy, and nitrogen metabolism among others. Severity-specific metabolic dysregulation was observed, as an increased transformation of L-tryptophan into L-kynurenine. Thus, metabolic profiling at hospital admission differentiate between severe and moderate patients in the later phase of worse evolution. Several plasma pro-inflammatory biomarkers showed significant correlation with deregulated metabolites, specially with L-kynurenine and L-tryptophan. Finally, we describe a strong sex-related dysregulation of metabolites, cytokines and chemokines between severe and moderate patients. In conclusion, metabolic profiling of COVID-19 patients at disease onset is a powerful tool to unravel the SARS-CoV-2 molecular pathogenesis. Conclusions: This technique makes it possible to identify metabolic phenoconversion that predicts disease progression and explains the pronounced pathogenesis differences between sexes.

Are Reduced Levels of Coagulation Proteins Upon Admission Linked to COVID-19 Severity and Mortality?

Background: The link between coagulation system disorders and COVID-19 has not yet been fully elucidated. Aim: Evaluating the association of non-previously reported coagulation proteins with COVID-19 severity and mortality. Design: Cross-sectional study of 134 COVID-19 patients recruited at admission and classified according to the highest COVID-19 severity reached (asymptomatic/mild, moderate, or severe) and 16 healthy control individuals. Methods: Coagulation proteins levels (antithrombin, prothrombin, factor_XI, factor_XII, and factor_XIII) and CRP were measured in plasma by the ProcartaPlex Panel (Invitrogen) multiplex immunoassay upon diagnosis. Results: We found higher levels of antithrombin, prothrombin, factor XI, factor XII, and factor XIII in asymptomatic/mild and moderate COVID-19 patients compared to healthy individuals. Interestingly, decreased levels of antithrombin and factors XI, XII, and XIII were observed in those patients who eventually developed severe illness. Additionally, survival models showed us that patients with lower levels of these coagulation proteins had an increased risk of death. Conclusion: COVID-19 provokes early increments of some specific coagulation proteins in most patients. However, lower levels of these proteins at diagnosis might "paradoxically" imply a higher risk of progression to severe disease and COVID-19-related mortality.

Characteristics of patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) from the ARIAM-SEMICYUC registry: development of a score for predicting MINOCA.

BACKGROUND: Acute myocardial infarction (AMI) with no evidence of relevant stenosis of the coronary artery, known as myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA), has a prevalence of up to 14%. The various causes of MINOCA lead to damage of the myocardium, and there are marked differences in diagnoses, prognoses, and treatments. Although the number of patients affected is considerable owing to the high prevalence of acute coronary syndrome (ACS), the causes of MINOCA have received little attention with the result that some patients may not receive appropriate treatment. Awareness of this disease among clinicians has started only to improve since the beginning of the current century. The aim of this study was to develop a score that enables patients with MINOCA to be distinguished from patients with MI with coronary artery disease (MI-CAD) and thus to facilitate appropriate diagnosis and therapy. PATIENTS AND METHODS: A multicenter observational cohort study was designed. All patients aged ≥18 years from the ARIAM-SEMICYUC (Analysis of Delay in AMI-Spanish Society of Intensive Care Medicine and Coronary Unit) registry, diagnosed with AMI, and admitted to critical care units or coronary care units (CCUs) were included. Patients were classified into two groups: MINOCA, comprising patients with no significant lesions on angiography, and MI-CAD, comprising patients with lesions of the coronary artery tree. RESULTS: A score based on standard variables to assess the probability of MINOCA on admission was designed, showing a maximum value corresponding to a 40% probability of MINOCA. The discriminative power of the model was 0.756 (P-value for the Hosmer-Lemeshow test was >0.05). At 30-day follow-up, the mortality rate was higher for MI-CAD patients. CONCLUSION: Patients with MINOCA constitute a population that differs from other patients with AMI. Their differential characteristics require a certain diagnostic effort to align therapy with the disease causing the ischemic event. This score could prove useful in establishing additional diagnostic procedures.

[Influence of the combination of antiplatelet agents on the occurrence of early left ventricular insufficiency in patients with acute coronary syndromes without persistent ST-segment elevation]. / Insuficiencia ventricular izquierda precoz en pacientes con síndrome coronario agudo sin elevación persistente del segmento ST: primera descripción y evaluación de los factores asociados.

BACKGROUND AND OBJECTIVE: The frequency of left ventricular failure (LVF) in the early stages of non-ST-segment elevation acute coronary syndrome (NSTE ACS) has not been described so far. The objective of this study is to describe for the first time the frequency of LVF in the early course of NSTE ACS and to assess its association with other interventions. PATIENTS AND METHOD: Observational prospective cohort multicenter study in intensive and coronary care units (ICCU). Patients with NSTE ACS admitted within 24h after onset were included. Main outcome was the occurrence of LVF. We evaluated the association between LVF and clinical and therapeutic variables. RESULTS: LVF occurred in 15.6% of patients. Coronary angiography (CA) during admission to the ICCU was a protective variable against the main outcome, performed before 72h (odds ratio [OR] 0.47; 95% confidence interval [95% CI] 0.25-0.89; P=.022) and later (OR 0,39; 95% CI 0,15-0,98; P=.044). The administration of beta-blockers was a protective variable against the occurrence of LVF (OR 0,54; 95% CI 0,32-0,87; P=.013). Patients receiving acetylsalicylic acid before admission to the ICCU had a higher risk of developing LVF (OR 1.74; 95% CI 1.06-2.86; P=.028). Age was also a factor of risk for LVF (OR 1.02; 95% CI 1.00-1.05; P=.032). CONCLUSIONS: CA and beta-blockers can decrease the occurrence of LVF. The association between previous administration of acetylsalicylic acid and age with the occurrence of LVF may reflect long-standing cardiovascular disease.

Insuficiencia ventricular izquierda precoz en pacientes con síndrome coronario agudo sin elevación persistente del segmento ST: primera descripción y evaluación de los factores asociados / Influence of the combination of antiplatelet agents on the occurrence of early left ventricular insufficiency in patients with acute coronary syndromes without persistent ST-segment elevation

Fundamento y objetivo: La frecuencia de la insuficiencia ventricular izquierda ( IVI ) en las fases precoces del síndrome coronario agudo sin elevación del segmento ST (SCASEST) no está descrita en la actualidad. El objetivo de este estudio es describir por vez primera la frecuencia de esta complicación en la evolución inicial del SCASEST y evaluar su asociación a otras intervenciones. Pacientes y método: Estudio observacional de cohortes prospectivo y multicéntrico realizado en unidades de cuidados intensivos y coronarios (UCIC). Se incluyeron pacientes con SCASEST ingresados en las primeras 24 h de evolución. El desenlace principal fue la aparición de IVI . Se evaluó la asociación entre esta y variables clínicas y terapéuticas. Resultados: Se produjo IVI en el 15,6% de los pacientes. La realización de angiografía coronaria (AC) durante el ingreso en la UCIC fue una variable protectora frente al desenlace principal, realizada tanto antes de las 72 horas (odds ratio [OR] 0,47; intervalo de confianza del 95% [IC 95%] 0,25-0,89; p = 0,022), como más tarde (OR 0,39; IC 95% 0,15-0,98; p = 0,044). La administración de betabloqueantes se mostró como variable protectora frente a la aparición de IVI (OR 0,54; IC 95% 0,32-0,87; p = 0,013). La toma de ácido acetilsalicílico antes del ingreso en la UCIC supuso un mayor riesgo de IVI (OR 1,74; IC 95% 1,06-2,86; p = 0,028). La edad fue factor de riesgo de presentar IVI (OR 1,02; IC 95% 1,00-1,05; p = 0,032). Conclusiones: La realización de AC precoz y la administración de betabloqueantes aparecen como capaces de disminuir la aparición de IVI . La toma previa de ácido acetilsalicílico y la edad se asociaron a la aparición de IVI , pudiendo reflejar enfermedad cardiovascular de larga evolución (AU)

Fundamento y objetivo: La frecuencia de insuficiencia ventricular izquierda (FVI) en las primeras etapas de la elevación del síndrome coronario agudo sin elevación del segmento ST (SCASEST) no se ha descrito hasta el momento. El objetivo de este estudio es describir por primera vez la frecuencia de LVF en el curso temprano de SCASEST y evaluar su asociación con otras intervenciones. Pacientes y método: Estudio multicéntrico observacional prospectivo de cohortes en las unidades de cuidados intensivos y coronarios (ICCU). Los pacientes con SCASEST ingresados dentro de las 24 horas después de la aparición se incluyeron. Resultado principal fue la aparición de LVF. Se evaluó la asociación entre la LVF y variables clínicas y terapéuticas. Resultados: LVF se produjo en el 15,6% de los pacientes. La angiografía coronaria (CA) durante el ingreso en la UCCI fue una variable protectora contra el resultado principal, realizado antes de las 72 h (odds ratio [OR] 0,47; intervalo de confianza del 95% [IC 95%] 0,25 hasta 0,89; P = 0.022) y más tarde (OR 0,39, IC 95% 0,15-0,98; P = 0,044). La administración de este tratamiento fue una variable protectora frente a la ocurrencia de LVF (OR 0,54, IC 95% 0,32-0,87; P = 0,013). Los pacientes que reciben ácido acetilsalicílico antes de su ingreso en la UCCI tenían un mayor riesgo de desarrollar LVF (OR 1.74, IC del 95%: 1,06 a 2,86; P = 0,028).La edad también fue un factor de riesgo para la LVF (OR 1.02, IC del 95%: 1,00 a 1,05; P = 0,032). Conclusiones: CA y beta-bloqueantes pueden disminuir la aparición de LVF. La asociación entre la anterior administración de ácido acetilsalicílico y la edad a la ocurrencia de LVF puede reflejar la enfermedad cardiovascular de larga data (AU)