A Randomized Trial of Lipid Metabolism Modulation with Fenofibrate for Acute Coronavirus Disease 2019.

Background Abnormal cellular lipid metabolism appears to underlie SARS-CoV-2 cytotoxicity and may involve inhibition of peroxisome proliferator activated receptor alpha (PPARα). Fenofibrate, a PPAR-α activator, modulates cellular lipid metabolism. Fenofibric acid has also been shown to affect the dimerization of angiotensin-converting enzyme 2, the cellular receptor for SARS-CoV-2. Fenofibrate and fenofibric acid have been shown to inhibit SARS-CoV-2 replication in cell culture systems in vitro . Methods We randomly assigned 701 participants with COVID-19 within 14 days of symptom onset to 145 mg of fenofibrate (nanocrystal formulation with dose adjustment for renal function or dose-equivalent preparations of micronized fenofibrate or fenofibric acid) vs. placebo for 10 days, in a double-blinded fashion. The primary endpoint was a ranked severity score in which participants were ranked across hierarchical tiers incorporating time to death, duration of mechanical ventilation, oxygenation parameters, subsequent hospitalizations and symptom severity and duration. ClinicalTrials.gov registration: NCT04517396. Findings: Mean age of participants was 49 ± 16 years, 330 (47%) were female, mean BMI was 28 ± 6 kg/m 2 , and 102 (15%) had diabetes mellitus. A total of 41 deaths occurred. Compared with placebo, fenofibrate administration had no effect on the primary endpoint. The median (interquartile range [IQR]) rank in the placebo arm was 347 (172, 453) vs. 345 (175, 453) in the fenofibrate arm (P = 0.819). There was no difference in various secondary and exploratory endpoints, including all-cause death, across randomization arms. These results were highly consistent across pre-specified sensitivity and subgroup analyses. Conclusion Among patients with COVID-19, fenofibrate has no significant effect on various clinically relevant outcomes.

A randomized clinical trial of lipid metabolism modulation with fenofibrate for acute coronavirus disease 2019.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cytotoxicity may involve inhibition of peroxisome proliferator-activated receptor alpha. Fenofibrate activates peroxisome proliferator-activated receptor alpha and inhibits SARS-CoV-2 replication in vitro. Whether fenofibrate can be used to treat coronavirus disease 2019 (COVID-19) infection in humans remains unknown. Here, we randomly assigned inpatients and outpatients with COVID-19 within 14 d of symptom onset to 145 mg of oral fenofibrate nanocrystal formulation versus placebo for 10 d, in a double-blinded fashion. The primary endpoint was a severity score whereby participants were ranked across hierarchical tiers incorporating time to death, mechanical ventilation duration, oxygenation, hospitalization and symptom severity and duration. In total, 701 participants were randomized to fenofibrate (n = 351) or placebo (n = 350). The mean age of participants was 49 ± 16 years, 330 (47%) were female, mean body mass index was 28 ± 6 kg/m2 and 102 (15%) had diabetes. Death occurred in 41 participants. Compared with placebo, fenofibrate had no effect on the primary endpoint. The median (interquartile range) rank in the placebo arm was 347 (172, 453) versus 345 (175, 453) in the fenofibrate arm (P = 0.819). There was no difference in secondary and exploratory endpoints, including all-cause death, across arms. There were 61 (17%) adverse events in the placebo arm compared with 46 (13%) in the fenofibrate arm, with slightly higher incidence of gastrointestinal side effects in the fenofibrate group. Overall, among patients with COVID-19, fenofibrate has no significant effect on various clinically relevant outcomes ( NCT04517396 ).

Continuation versus discontinuation of renin-angiotensin system inhibitors in patients admitted to hospital with COVID-19: a prospective, randomised, open-label trial.

BACKGROUND: Biological considerations suggest that renin-angiotensin system inhibitors might influence the severity of COVID-19. We aimed to evaluate whether continuing versus discontinuing renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) affects outcomes in patients admitted to hospital with COVID-19. METHODS: The REPLACE COVID trial was a prospective, randomised, open-label trial done at 20 large referral hospitals in seven countries worldwide. Eligible participants were aged 18 years and older who were admitted to hospital with COVID-19 and were receiving a renin-angiotensin system inhibitor before admission. Individuals with contraindications to continuation or discontinuation of renin-angiotensin system inhibitor therapy were excluded. Participants were randomly assigned (1:1) to continuation or discontinuation of their renin-angiotensin system inhibitor using permuted block randomisation, with allocation concealed using a secure web-based randomisation system. The primary outcome was a global rank score in which participants were ranked across four hierarchical tiers incorporating time to death, duration of mechanical ventilation, time on renal replacement or vasopressor therapy, and multiorgan dysfunction during the hospitalisation. Primary analyses were done in the intention-to-treat population. The REPLACE COVID trial is registered with ClinicalTrials.gov, NCT04338009. FINDINGS: Between March 31 and Aug 20, 2020, 152 participants were enrolled and randomly assigned to either continue or discontinue renin-angiotensin system inhibitor therapy (continuation group n=75; discontinuation group n=77). Mean age of participants was 62 years (SD 12), 68 (45%) were female, mean body-mass index was 33 kg/m2 (SD 8), and 79 (52%) had diabetes. Compared with discontinuation of renin-angiotensin system inhibitors, continuation had no effect on the global rank score (median rank 73 [IQR 40-110] for continuation vs 81 [38-117] for discontinuation; ß-coefficient 8 [95% CI -13 to 29]). There were 16 (21%) of 75 participants in the continuation arm versus 14 (18%) of 77 in the discontinuation arm who required intensive care unit admission or invasive mechanical ventilation, and 11 (15%) of 75 participants in the continuation group versus ten (13%) of 77 in the discontinuation group died. 29 (39%) participants in the continuation group and 28 (36%) participants in the discontinuation group had at least one adverse event (χ2 test of adverse events between treatment groups p=0·77). There was no difference in blood pressure, serum potassium, or creatinine during follow-up across the two groups. INTERPRETATION: Consistent with international society recommendations, renin-angiotensin system inhibitors can be safely continued in patients admitted to hospital with COVID-19. FUNDING: REPLACE COVID Investigators, REPLACE COVID Trial Social Fundraising Campaign, and FastGrants.

Vocación médica, más allá del deber de cuidar: Revisión de la literatura desde el aspecto ético y filosófico

En este artículo de revisión, se examina la vocación médica como un fenómeno que va más allá del simple deber de cuidar a los pacientes y se centra en la importancia del compromiso ético, la empatía y la resiliencia en la práctica médica. Se discuten las implicaciones para la formación de médicos y la práctica clínica.

This review article explores medical vocation as a phenomenon that extends beyond the mere duty of caring for patients, focusing on the significance of ethical commitment, empathy, and resilience in medical practice. The implications for medical training and clinical practice are discussed.

Relación entre los grupos sanguíneos A, B y O y mortalidad por infección con SARS-CoV-2 en pacientes hospitalizados

El objetivo del estudio fue investigar la relación entre los grupos sanguíneos A, B y O y la mortalidad en pacientes hospitalizados por una infección grave por SARS-CoV-2. La investigación fue observacional retrospectiva en un hospital de tercer nivel en Lima, Perú. Se incluyó a 203 pacientes, con una edad media de 62,58 ± 16,45 años, y el 71,92 % eran varones. La frecuencia de los grupos sanguíneos O, A y B fue del 75,37 %, 17,24 % y 7,39 %, respectivamente. Se encontró asociación con la mortalidad por infección grave por COVID-19 con los grupos sanguíneos que no son A (grupo O, grupo B), con un PR (razón de prevalencia) de 2,25 IC (intervalo de confianza) 95 % 1,07-4,71. Al ajustar por las principales variables, la asociación con RP persistió en 2,78 IC 95 % 1,06-7,24. En conclusión, en los pacientes hospitalizados por una infección grave por SARS-CoV-2, los grupos sanguíneos O y B estarían asociados con una mayor mortalidad que los pacientes del grupo sanguíneo A.

This study aimed to determine the relationship between ABO blood groups and mortality in patients hospitalized for severe SARS-CoV-2 infection. An observational and retrospective research was conducted in a tertiary care hospital in Lima, Peru. A total of 203 patients with a mean age of 62.58 ± 16.45 years were included in the research, out of whom 71.92 % were males. The frequency of O, A and B blood groups were 75.37 %, 17.24 % and 7.39 %, respectively. An association with mortality from severe COVID-19 infection was found with non-A blood groups (O group or B group), with a PR (prevalence ratio) of 2.25 and 95% CI (confidence interval) of 1.07 - 4.71. When adjusting the main variables, the association with PR remained in 2.78 and 95% CI in 1.06 - 7.24. In conclusion, patients hospitalized for severe SARS-CoV-2 infection with O and B blood groups seem to be associated with higher mortality rates than those with A blood group.

Factores asociados a mortalidad en enfermedad SARS-CoV-2 grave de un hospital peruano / Factors associated with mortality in severe SARS-CoV-2 infection in a Peruvian hospital

Objetivo: Determinar factores asociados a mortalidad en pacientes con enfermedad grave por SARS-CoV-2. Material y métodos: Estudio retrospectivo en pacientes mayores de 18 años hospitalizados por enfermedad grave (saturación periférica de Oxígeno < 93% o compromiso radiológico pulmonar > 30%) y prueba molecular positiva en hisopado nasofaríngeo; en el hospital Rebagliati entre marzo y mayo de 2020. Se revisó historia clínica electrónica, resultados de análisis (de laboratorio y radiológicos) al ingreso y tratamiento recibido. Se realizó estadística bivariada y multivariada utilizando regresión de cox. Resultados: Se incluyeron 337 pacientes, de los cuales 215 fallecieron (63.8%). Fueron de sexo masculino 72.1%, edad promedio 63.6 años (DS 15.3), tiempo de enfermedad 7.4 días, estancia hospitalaria 10.3 días y 48.8% ingresó a ventilación mecánica invasiva. El análisis multivariado encontró significancia en edad > 60 años (HR 1.76, IC95% 1.26-2.45), antecedente de diabetes mellitus tipo 2 (HR 1.63, IC95% 1.14-2.32), compromiso radiológico pulmonar > 75% (HR 1.87, IC95% 1.37-2.56), leucocitosis > 14000 x mm3 (HR 1.59, IC95% 1.15-2.20), albúmina sérica < 4.0 g/dL (HR 2.49, IC95% 1.30-4.75) y lactato > 1.5 mmol/L (HR: 1.766 IC95% 1.25-2.49). Conclusiones: La edad mayor de 60 años, diabetes mellitus tipo 2, compromiso pulmonar severo, leucocitosis, albúmina baja y lactato elevado al ingreso hospitalario, son factores asociados a mortalidad en pacientes con enfermedad grave por SARS-CoV-2.

Objetive:To determine factors associated with mortality in patients with severe SARS-CoV-2 disease. Materials and methods: Retrospective study in patients older than 18 years hospitalized with severe disease (peripheral oxygen saturation <93% or radiological lung involvement > 30%) and a positive RT-PCR nasopharyngeal swab; in the Rebagliati hospital between March and May 2020. We reviewed electronic medical record, results of admission studies (laboratory and radiological) and treatment received. Bivariate and multivariate analysis were performed using cox regression. Results: 337 patients were studied, 215 of them died (63.8%). 72.1% were male, mean age was 63.6 years (SD 15.3), time of disease evolution was 7.4 days, hospital stay 10.3 days, and 48.8% were on mechanical ventilation. Multivariate analysis found significance in age > 60 years (HR 1.76, IC95% 1.26-2.45), history of type 2 Diabetes (HR 1.63, IC95% 1.14-2.32), pulmonary involvement > 75% (HR 1.87, IC95% 1.37-2.56), leukocytes > 14000 x mm3 (HR 1.59, IC95% 1.15-2.20), serum albumin < 4.0 g/dL(HR 2.49, IC95% 1.30-4.75) and lactate > 1.5 mmol/L(HR: 1.766 IC95% 1.25-2.49). Conclusions: Age older than 60 years, type 2 diabetes mellitus, severe pulmonary involvement, leukocytosis, low albumin, and high lactate at admission are factors associated with mortality in patients with severe SARS-CoV-2 disease.

Shock críptico, diagnóstico incipiente / Shock Cryptic, emerging diagnostic

El shock críptico es una entidad clínica poco identificada, describe aún paciente con signos de hipoperfusión tisular sin afectación de la presión arterial. En el departamento de emergencia es importante identificar signos de hipoperfusión y evaluar diversas fuentes ocultas de infección realizando una historia clínica completa, un examen físico exhaustivo y de ser necesario imagenología avanzada. Es necesario concluir que la importancia del diagnóstico oportuno de esta entidad clínica ayuda a mejorar significativamente el pronóstico.

Cryptic shock is a poorly identified clinical entity, it still describes a patient with signs of tissue hypoperfusion without affecting blood pressure. In the emergency department, it is important to identify signs of hypoperfusion and evaluate various hidden sources of infection by taking a complete medical history, a thorough physical examination, and if necessary advanced imaging. It is necessary to conclude that the importance of the timely diagnosis of this clinical entity helps to significantly improve the prognosis.

Características y evolución de pacientes con litiasis urinaria en emergencia de un hospital terciario / Characteristics And Evolution Of Patients With Urinary Lithiasis In A Tertiary Hospital Emergency

Antecedentes: La sintomatología y complicaciones de litiasis urinaria son una causa frecuente de atención en emergencia. Objetivos: Determinar características y evolución de pacientes con litiasis urinaria atendidos en el servicio de emergencia de un hospital terciario de la seguridad social. Métodos: Estudio observacional realizado en el hospital Rebagliati Lima-Perú, durante el primer trimestre 2019. Se evaluó variables sociodemográficas, de tiempo e indicadores de emergencia del sistema estadístico institucional, realizando estadística descriptiva con IBM SPSS 25.0. Resultados: Se registraron 583 atenciones por litiasis urinaria (194 por mes), correspondiendo al 14% de la patología genito-urinaria vista en el servicio evaluado. 55% de sexo masculino, edad promedio 48 años (rango 14 a 92). Atendidos principalmente por tópico de cirugía y de prioridad 3, causas más frecuentes dolor, infección y hematuria. Tiempo de primera atención 4,8 horas, saliendo de alta el 70%. Se admitió a salas de observación 10,5% con estancia promedio de 77 horas (3,2 días), siendo hospitalizada 51%, de alta 31%, operada 3% y falleció 2%. Conclusión: La litiasis urinaria se presenta en 1 de cada 7 atenciones de patología genitourinaria del servicio de emergencia evaluado, predominando en varones, de edad media, el 10% es admitido a sala de observación, con corta estancia y baja mortalidad.

Background: The symptoms and complications of urinary lithiasis are a frequent cause of emergency care. Objectives: To determine characteristics and evolution of patients with urinary lithiasis attended in the emergency room of a tertiary social security hospital. Methods: Observational study carried out at the Rebagliati hospital Lima-Peru, during the first quarter of 2019. Sociodemographic variables, time and emergency indicators of the institutional statistical system were evaluated, performing descriptive statistics with IBM SPSS 25.0. Results: 583 attentions for urinary lithiasis (194 per month) were registered, corresponding to 14% of the genito-urinary pathology seen in the evaluated service. 55% male, average age 48 years (range 14 to 92). Mainly attended by surgical topic and priority 3, most frequent causes pain, infection and hematuria. Time of first attention 4.8 hours, leaving 70% of discharge. Observation rooms were admitted to 10.5% with an average stay of 77 hours (3.2 days), with 51% hospitalized, discharge 31%, operated 3% and 2% died. Conclusion: Urinary lithiasis occurs in 1 out of 7 genitourinary pathologies of the emergency room evaluated, predominantly in middle-aged men, 10% are admitted to the observation room, with a short stay and low mortality.

Coma mixedematoso, reporte de caso / Coma mixedematoso, case report

Paciente varón de 82 años que ingresa al Servicio de Emergencia por presentar un tiempo de enfermedad de 15 días con hiporexia, disartria, rigidez de miembros superiores e inferiores, en mal estado general, pícnico con edema, lesiones en piel y trastorno del sensorio, bradicardia sostenida; por lo cual al inicio se plantea como problema de insuficiencia respiratoria, trastorno del sensorio a descartar un accidente cerebro vascular. Paciente empeora con mayor compromiso del sensorio y hemodinámico se plantea diagnóstico de coma mixedematoso aplicando el Score Clínico de coma mixedematoso, se inicia tratamiento, paciente fallece.

Patient used for 82 years. Emergency service to present a time of illness of 15 days with hyporexia, dysarthria, rigidity of upper and lower limbs, general condition, periodic with edema, skin lesions and sensory disorder, bradycardia. sustained Therefore, at the beginning, it presents as a problem of respiratory insufficiency, sensory disorder to rule out a s troke. Patient worsens with greater sensory and hemodynamic compromise refers to myxedema coma by applying the Clinical Score of coma mixedematoso, treatment is started, patient dies.