An in vivo duck hepatitis B virus model recapitulates key aspects of nucleic acid polymer treatment outcomes in chronic hepatitis B patients.

Nucleic acid polymers (NAPs) are an attractive treatment modality for chronic hepatitis B (CHB), with REP2139 and REP2165 having shown efficacy in CHB patients. A subset of patients achieve functional cure, whereas the others exhibit a moderate response or are non-responders. NAP efficacy has been difficult to recapitulate in animal models, with the duck hepatitis B virus (DHBV) model showing some promise but remaining underexplored for NAP efficacy testing. Here we report on an optimized in vivo DHBV duck model and explore several characteristics of NAP treatment. REP2139 was efficacious in reducing DHBV DNA and DHBsAg levels in approximately half of the treated ducks, whether administered intraperitoneally or subcutaneously. Intrahepatic or serum NAP concentrations did not correlate with efficacy, nor did the appearance of anti-DHBsAg antibodies. Furthermore, NAP efficacy was only observed in experimentally infected ducks, not in endogenously infected ducks (vertical transmission). REP2139 add-on to entecavir treatment induced a deeper and more sustained virological response compared to entecavir monotherapy. Destabilized REP2165 showed a different activity profile with a more homogenous antiviral response followed by a faster rebound. In conclusion, subcutaneous administration of NAPs in the DHBV duck model provides a useful tool for in vivo evaluation of NAPs. It recapitulates many aspects of this class of compound's efficacy in CHB patients, most notably the clear division between responders and non-responders.

Novel non-HAP class A HBV capsid assembly modulators have distinct in vitro and in vivo profiles.

IMPORTANCE: Chronic hepatitis B is the most important cause of liver cancer worldwide and affects more than 290 million people. Current treatments are mostly suppressive and rarely lead to a cure. Therefore, there is a need for novel and curative drugs that target the host or the causative agent, hepatitis B virus itself. Capsid assembly modulators are an interesting class of antiviral molecules that may one day become part of curative treatment regimens for chronic hepatitis B. Here we explore the characteristics of a particularly interesting subclass of capsid assembly modulators. These so-called non-HAP CAM-As have intriguing properties in cell culture but also clear virus-infected cells from the mouse liver in a gradual and sustained way. We believe they represent a considerable improvement over previously reported molecules and may one day be part of curative treatment combinations for chronic hepatitis B.

Class A capsid assembly modulator RG7907 clears HBV-infected hepatocytes through core-dependent hepatocyte death and proliferation.

BACKGROUND AND AIMS: Effective therapies leading to a functional cure for chronic hepatitis B are still lacking. Class A capsid assembly modulators (CAM-As) are an attractive modality to address this unmet medical need. CAM-As induce aggregation of the HBV core protein (HBc) and lead to sustained HBsAg reductions in a chronic hepatitis B mouse model. Here, we investigate the underlying mechanism of action for CAM-A compound RG7907. APPROACH AND RESULTS: RG7907 induced extensive HBc aggregation in vitro , in hepatoma cells, and in primary hepatocytes. In the adeno-associated virus (AAV)-HBV mouse model, the RG7907 treatment led to a pronounced reduction in serum HBsAg and HBeAg, concomitant with clearance of HBsAg, HBc, and AAV-HBV episome from the liver. Transient increases in alanine transaminase, hepatocyte apoptosis, and proliferation markers were observed. These processes were confirmed by RNA sequencing, which also uncovered a role for interferon alpha and gamma signaling, including the interferon-stimulated gene 15 (ISG15) pathway. Finally, the in vitro observation of CAM-A-induced HBc-dependent cell death through apoptosis established the link of HBc aggregation to in vivo loss of infected hepatocytes. CONCLUSIONS: Our study unravels a previously unknown mechanism of action for CAM-As such as RG7907 in which HBc aggregation induces cell death, resulting in hepatocyte proliferation and loss of covalently closed circular DNA or its equivalent, possibly assisted by an induced innate immune response. This represents a promising approach to attain a functional cure for chronic hepatitis B.

Factores de riesgo para destete fallido de la ventilación mecánica en adultos

Introducción: El destete o liberación de la ventilación mecánica (VM) es un proceso complejo y cuando es fallido aumentará los riesgos de complicaciones y gastos. Objetivo: Identificar factores de riesgo modificables para destete fallido en adultos con VM. Materiales y Métodos: Estudio de casos y controles realizado en pacientes ≥ 18 años ingresados en la unidad de cuidados intensivos de un hospital de tercer nivel. Los casos se identificaron como destete fallido (DF) del VM y los controles como destete simple. Se excluyeron los pacientes procedentes de otro hospital con VM. Los factores estudiados fueron el alto riesgo nutricional por el Nutric score modificado, la nutrición enteral tardía, el balance hídrico (BH) positivo y la ausencia de fisioterapia previos al destete. Se calculo el OR con una significancia < 0,05 para el análisis bivariado, multivariado y ajustado. Resultados: Se incluyeron 105 pacientes, 35 casos y 70 controles. El análisis bivariado encontró que el alto riesgo nutricional (OR = 2.5; IC 95% = 1,1 5,9; p=0,027) fue factor de riesgo, pero el análisis multivariado no lo confirmó. La nutrición enteral tardía (OR = 1,2; IC 95% = 0,4 3,4), el BH positivo (OR = 0,7; IC 95% = 0,3 1,7) y la ausencia de fisioterapia respiratoria (OR = 0,2; IC 95% = 0,004 0,011) no fueron factores de riesgo para DF. Conclusiones: El alto riesgo nutricional, la nutrición enteral tardía, el BH positivo y la ausencia de fisioterapia respiratoria antes del destete no fueron factores de riesgo para DF.

Background: Weaning of the mechanical ventilation (MV) is a complex process and when it fails, it can increase the risks of complications and expenses in health systems. Objective: To identify risk factors for failed weaning in adults with MV. Materials and Methods: Case-control study carried out in patients older than 18 years admitted to the intensive care unit of a tertiary care hospital. Cases were identified as failed weaning (FW) of MV, and controls were simple weaning. Patients from another hospital with MV were excluded. Risk factors studied were high nutritional risk by the modified Nutric score, late enteral nutrition, positive water balance (WB) and the absence of physical therapy prior to weaning. OR was calculated with a significance < 0.05 for bivariate, multivariate, and adjusted analysis. Results: 105 patients were included, 35 cases and 70 controls. The bivariate analysis found that high nutritional risk (OR = 2.5; 95% CI = 1.1 5.9; p = 0.027) was a risk factor, but the multivariate analysis did not confirm it. Late enteral nutrition (OR = 1.2; 95% CI = 0.4 3.4), positive WB (OR = 0.7; 95% CI = 0.3 1.7) and the absence of respiratory physiotherapy (OR = 0.2; 95% CI = 0.004 0.011) were not risk factors for FW. Conclusions: High nutritional risk, late enteral nutrition, positive BH and the absence of respiratory physiotherapy before weaning were not risk factors for FW.

Nivel de conocimiento sobre donación de órganos y factores sociodemográficos en los estudiantes de Medicina: estudio transversal

Objetivo: Establecer el nivel de conocimiento sobre donación de órganos (NCD) de los estudiantes del décimo semestre de la carrera profesional de Medicina Humana y su relación con algunas variables sociodemográficas. Materiales y métodos: Se realizó un estudio transversal, tipo encuesta, en el cual se incluyeron 121 alumnos de una universidad peruana. Se utilizó un cuestionario que contiene 5 características sociodemográficas y 10 preguntas acerca del NCD. Además del análisis descriptivo, se comparó el NCD con las características sociodemográficas, para lo cual se utilizó el estadístico ji al cuadrado, considerando una relación significativa cuando el valor de p fue menor de 0,05. Resultados: La edad promedio de los alumnos fue de 23 ± 2,3 años, 51,2 % fueron de sexo masculino, 78,5 % profesaban alguna religión, 83,5 % adquirieron sus conocimientos de un entorno académico y 24,8 % tuvieron un familiar o amigo cercano que necesitaba trasplante de órganos. El 47 % registraron un NCD alto; 42 %, medio, y 11 %, bajo. En el análisis bivariado no se encontró relación entre el NCD según el grupo etario (p = 0,696), el sexo (p = 0,794), el origen de su conocimiento (p = 0,734) o si tuvieron un contacto cercano relacionado a donación (p = 0,269); pero sí se relacionó favorablemente (p = 0,008; IC 95% 0,008-0,011) con profesar alguna religión. Conclusiones: La mayoría de los alumnos del décimo semestre de la carrera de Medicina Humana tuvieron un NCD alto, y este hallazgo estuvo relacionado a que los alumnos profesaban alguna religión.

Objective: To determine the level of knowledge of organ donation (LKD) in tenth-semester Human Medicine students and its relationship with some sociodemographic variables. Materials and methods: A cross-sectional survey study conducted with 121 students from a Peruvian university. A questionnaire consisting of five sociodemographic characteristics and 10 questions about LKD was used. Besides the descriptive analysis, a chi-square test was used to compare LKD with the sociodemographic characteristics, considering a significant relationship when the p value was less than 0.05. Results: The average age of the students was 23 ± 2.3 years, 51.2 % were males, 78.5 % practiced a religion, 83.5 % acquired their knowledge in an academic environment and 24.8 % had a family member or close friend who needed an organ transplant. Forty-seven percent (47 %), 42 % and 11 % of the students had a high, medium and low LKD, respectively. According to the bivariate analysis, there was no relationship between LKD and the age group of the students (p = 0.696), their sex (p = 0.794), the origin of their knowledge (p = 0.734) or having an acquaintance who needed an organ donation (p = 0.269); however, it was related (p = 0.008; 95% CI 0.008 - 0.011) to practicing a religion. Conclusions: Most tenth-semester Human Medicine students had a high LKD, which was related to practicing a religion.

Nutrición en la educación médica: Estudio transversal en una universidad de Perú

Estudios recientes han encontrado que los estudiantes de medicina afirman haber recibido una educación nutricional insuficiente. Objetivos: Describir la percepción de la formación, actitudes y competencias, conocimientos adquiridos y las barreras en estudiantes de medicina, y establecer la correlación entre la formación y el conocimiento en nutrición. Método: Estudio transversal, observacional y correlacional, aplicando una encuesta de 47 preguntas a alumnos de 6to año de una escuela de medicina. El análisis incluyó frecuencias con proporciones y la mediana con rango intercuartílico. La correlación entre la formación recibida y los conocimientos adquiridos se realizó con el coeficiente Rho de Spearman con significancia <0,05. Resultados: Se incluyeron 75 alumnos, la mediana etárea fue 24 años. La mayoría percibió su formación como no suficiente, cerca del 90% tenía una actitud positiva hacia la enseñanza de nutrición y sus conocimientos oscilaron entre el 16 a 95%. Se identificó una correlación directa y significativa entre la formación y el conocimiento (Spearman= 0,278, p= 0,013). Conclusiones: La percepción de los estudiantes de medicina sobre su formación en nutrición fue baja, a pesar de una actitud proactiva y los conocimientos tuvieron resultados contrastantes. Se estableció una correlación directa entre la percepción de su formación y el conocimiento en nutrición.

Recent studies have found that medical students claim to have received insufficient nutritional education. Objectives: To describe the perception of training, attitudes and skills, knowledge and barriers acquired, and the correlation between nutrition training and knowledge. Methods: Cross-sectional, observational and correlational study, using a survey of 47 questions to 6th year students of a medical school. The analysis included frequencies, proportions, median and interquartile ranges. The correlation between the training received and the knowledge acquired was estimated using Spearman's Rho coefficient with a significance of p<0.05. Results: Seventy-five students were included with a median age of 24 years. Most students perceived their nutrition training as not sufficient. About 90% had a positive attitude towards nutrition education. Nutrition knowledge ranged from 16 to 95%. A direct correlation (Spearman's Rho= 0.278) was found to be significant (p= 0.013) between the training received and knowledge. Conclusions: The perception of medical student about their training in nutrition was low, despite having a proactive attitude; knowledge had contrasting results. A direct correlation was established between the perception of nutrition training and knowledge.

The establishment of public health policies and the burden of non-alcoholic fatty liver disease in the Americas.

Non-alcoholic fatty liver disease (NAFLD) affects 20-25% of the general population and is associated with morbidity, increased mortality, and elevated health-care costs. Most NAFLD risk factors are modifiable and, therefore, potentially amenable to being reduced by public health policies. To date, there is no information about NAFLD-related public health policies in the Americas. In this study, we analysed data from 17 American countries and found that none have established national public health policies to decrease NAFLD-related burden. There is notable heterogeneity in the existence of public health policies to prevent NAFLD-related conditions. The most common public health policies were related to diabetes (15 [88%] countries), hypertension (14 [82%] countries), cardiovascular diseases (14 [82%] countries), obesity (nine [53%] countries), and dyslipidaemia (six [35%] of countries). Only seven (41%) countries had a registry of the burden of NAFLD, and efforts to raise awareness in the Americas were scarce. The implementation of public health policies are urgently needed in the Americas to decrease the burden of NAFLD.

Methylene blue for the treatment of refractory septic shock secondary to listeriosis in a paediatric patient.

Current therapies frequently used for refractory septic shock include hydrocortisone, vasopressin, extracorporeal membrane oxygenation (ECMO) support, inodilators, levosimendan and methylene blue. The evidence for these treatments is very limited. We present a case of a 5-year-old patient with refractory septic shock, secondary to Listeria monocytogenes meningitis. She presented with status epilepticus and developed septic shock. Shock persisted despite multiple high-dose vasoactive medications. ECMO support was not available. The medical team decided to use methylene blue to revert the vasoplegia, with excellent results. Shortly after the administration, vasopressors were weaned off and the high lactate cleared. She developed severe neurological sequelae due to brain haemorrhage secondary to the Listeria meningitis. The evidence supporting methylene blue for refractory septic shock in paediatric patients is limited. This case represents the effectiveness of this therapy without secondary effects.

GASTRIC AND ORAL FEEDING IN SEVERE ACUTE PANCREATITIS.

BACKGROUND: There is controversy about the initiation of gastric or oral feeding in patients with severe acute pancreatitis (SAP) because they could increase pancreatic stimulation and exacerbate symptoms and complications. OBJECTIVE: To describe the clinical characteristics and results of patients with SAP who underwent gastric tube or oral feeding versus parenteral or jejunal feeding. METHODS: A retrospective study was carried out on patients over 18 years old with SAP diagnostic, who had been treated in critical care units. We excluded patients coming from other hospitals and those with incomplete medical records. RESULTS: Thirty patients with SAP were included, fifty three percent of them tolerated the gastric tube or oral feeding, and most of them were females and older than patients who received parenteral or jejunal feeding. Other clinical characteristics and outcomes were similar in both groups. Conclusion: Gastric tube or oral feeding is no absolute contraindication for SAP.

Alimentação oral e gástrica na pancreatite aguda grave / Gastric and oral feeding in severe acute pancreatitis

ABSTRACT BACKGROUND: There is controversy about the initiation of gastric or oral feeding in patients with severe acute pancreatitis (SAP) because they could increase pancreatic stimulation and exacerbate symptoms and complications. OBJECTIVE: To describe the clinical characteristics and results of patients with SAP who underwent gastric tube or oral feeding versus parenteral or jejunal feeding. METHODS: A retrospective study was carried out on patients over 18 years old with SAP diagnostic, who had been treated in critical care units. We excluded patients coming from other hospitals and those with incomplete medical records. RESULTS: Thirty patients with SAP were included, fifty three percent of them tolerated the gastric tube or oral feeding, and most of them were females and older than patients who received parenteral or jejunal feeding. Other clinical characteristics and outcomes were similar in both groups. Conclusion: Gastric tube or oral feeding is no absolute contraindication for SAP.

RESUMO CONTEXTO Há controvérsias sobre o início da alimentação gástrica ou oral em pacientes com pancreatite aguda grave (PAG), pois elas podem aumentar a estimulação pancreática e exacerbar os sintomas e complicações. OBJETIVO Descrever as características clínicas e os resultados de pacientes com PAG submetidos à alimentação por sonda gástrica ou via oral versus alimentação parenteral ou jejunal. MÉTODOS Foi realizado um estudo retrospectivo em pacientes maiores de 18 anos com diagnóstico de PAG, atendidos em unidades de terapia intensiva. Excluímos pacientes procedentes de outros hospitais e aqueles com prontuário incompleto. RESULTADOS Trinta pacientes com PAG foram incluídos, 53% deles toleravam a sonda gástrica ou alimentação via oral, e a maioria era do sexo feminino e tinha mais idade do que os pacientes que receberam alimentação parenteral ou jejunal. Outras características clínicas e resultados foram semelhantes em ambos os grupos. CONCLUSÃO A sonda gástrica ou alimentação oral não é contra-indicação absoluta para PAG.

Comparison of different prognostic scores for patients with cirrhosis hospitalized with SARS-CoV-2 infection.

INTRODUCTION AND OBJECTIVES: Viral infections have been described to increase the risk of decompensation in patients with cirrhosis. We aimed to determine the effect of SARS-CoV-2 infection on outcome of hospitalized patients with cirrhosis and to compare the performance of different prognostic models for predicting mortality. PATIENTS: We performed a prospective cohort study including 2211 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through October 1, 2020 in 38 Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters of patients with and without cirrhosis. All patients were followed until discharge or death. We evaluated the prognostic performance of different scoring systems to predict mortality in patients with cirrhosis using ROC curves. RESULTS: Overall, 4.6% (CI 3.7-5.6) subjects had cirrhosis (n = 96). Baseline Child-Turcotte-Pugh (CTP) class was assessed: CTP-A (23%), CTP-B (45%) and CTP-C (32%); median MELD-Na score was 19 (IQR 14-25). Mortality was 47% in patients with cirrhosis and 16% in patients without cirrhosis (P < .0001). Cirrhosis was independently associated with death [OR 3.1 (CI 1.9-4.8); P < .0001], adjusted by age, gender, and body mass index >30. The areas under the ROC curves for performance evaluation in predicting 28-days mortality for Chronic Liver Failure Consortium (CLIF-C), North American Consortium for the Study of End-Stage Liver Disease (NACSELD), CTP score and MELD-Na were 0.85, 0.75, 0.69, 0.67; respectively (P < .0001). CONCLUSIONS: SARS-CoV-2 infection is associated with elevated mortality in patients with cirrhosis. CLIF-C had better performance in predicting mortality than NACSELD, CTP and MELD-Na in patients with cirrhosis and SARS-CoV-2 infection. Clinicaltrials.gov:NCT04358380.

Reactividad de sueros de ratones inmunizados con vesículas de membrana externa derivadas de Salmonella entérica / Reactivity of sera from mice immunized with outer membrane vesicles derived from Salmonella enterica

La fiebre tifoidea causada por Salmonella Paratyphi A (fiebre paratifoidea) es indistinguible de la producida por Salmonella Typhi y el grado de incidencia ha aumentado en los últimos años, especialmente en el sudeste asiático. Por otro lado, la diarrea y otras complicaciones entéricas causadas por Salmonella Enteritidis y Salmonella Typhimurium continúan siendo un problema de salud grave, especialmente en países subdesarrollados. Las vacunas continúan siendo la forma más efectiva de prevenir estas enfermedades. Existen vacunas basadas en el polisacárido capsular de Salmonella Typhi que protegen contra la fiebre tifoidea; sin embargo, no hay vacunas efectivas licenciadas para uso en humanos que prevengan las enfermedades producidas por los serotipos de Salmonella no tifoideas. El desarrollo de una formulación con capacidad para proteger contra estas enfermedades sigue siendo un desafío para la comunidad científica. En este trabajo se evaluó, mediante Western blot, la reactividad de los sueros de ratones inmunizados por vía subcutánea con formulaciones basadas en vesículas de membrana externa derivadas de Salmonella Paratyphi A, Salmonella Enteritidis y Salmonella Typhimurium, contra los respectivos lisados celulares, para identificar la formulación que induce la mejor respuesta inmunológica cruzada. Los resultados obtenidos indicaron una alta reactividad de todos los sueros a los lisados, sin una diferencia aparente entre ellos. Sin lugar a dudas, se deberán realizar pruebas de inmunogenicidad seguidas de pruebas de retos cruzados para identificar un candidato vacunal. Estos resultados sugieren que las vesículas de membrana externa empleadas en este estudio están compuestas por antígenos posiblemente conservados en los tres serotipos de Salmonella y que pueden inducir una respuesta inmune de amplio espectro y protección cruzada(AU)

Typhoid fever caused by Salmonella Paratyphi A (paratyphoid fever) is indistinguishable from that caused by Salmonella Typhi and the degree of incidence has increased in recent years, especially in Southeast Asia. On the other hand, diarrhea and other enteric complications caused by Salmonella Enteritidis and Salmonella Typhimurium continue to be a serious health problem, especially in underdeveloped countries. Vaccines continue to be the most effective way to prevent these diseases. There are vaccines based on Salmonella Typhi capsular polysaccharide, which protects against typhoid fever; however, there are no effective vaccines licensed for use in humans to prevent disease caused by nontyphoidal Salmonella serotypes. Developing a formulation capable of protecting against these diseases remains a challenge for the scientific community. In this work, the reactivity of the sera of mice immunized subcutaneously with formulations based on Outer Membrane Vesicles (OMV) derived from Salmonella Paratyphi A, Salmonella Enteritidis and Salmonella Typhimurium, was evaluated by Western blot, against the respective cell lysates to identify the formulation that induces the best cross immune response. The results obtained indicated a high reactivity of all the sera to the lysates; without an apparent difference between them. Undoubtedly, immunogenicity tests followed by cross-challenge tests should be performed to identify a vaccine candidate. These results suggest that the OMV used in this study are composed of possibly conserved antigens in the three Salmonella serotypes and that they can induce a broad-spectrum immune response and cross protection(AU)

Uso de antirreumáticos en covid-19 desde la hidroxicloroquina hasta la anakinra pasando por tocilizumab y baricitinib: Una revisión de la literatura / Use of antirheumatic drugs in covid-19 from hydroxychloroquine to anakinra through tocilizumab and baricitinib: A review of the literature

Actualmente nos encontramos en una pandemia mundial causada por el coronavirus 2019 o COVID­19, presentando diferentes desafíos para el sistema de salud debido a que no se cuenta aún con alguna vacuna ni con un tratamiento que haya demostrado su eficacia en totalidad, siendo el manejo actual preventivo y de soporte. Por lo que, en esta revisión se estudiará a los fármacos antirreumáticos más resaltantes que tengan un probable efecto farmacológico, como son la hidroxicloroquina, el tocilizumab, el anakinra y el baricitinib, frente al COVID­19. Se espera que brinde apoyo para futuros tratamientos e investigaciones sobre la enfermedad.

We are currently in a global pandemic caused by the coronavirus 2019 or COVID-19, presenting different challenges for the health system due to the fact that there is still no vaccine or a treatment that has proven its effectiveness in its entirety, being the management current preventive and supportive. Therefore, this review will study the most prominent antirheumatic drugs that have a probable pharmacological effect, such as hydroxychloroquine, tocilizumab, anakinra and baricitinib, against COVID-19. It is expected that they will provide support for future treatments. and research on the disease

Uso de antirreumáticos en covid-19 desde la hidroxicloroquina hasta la anakinra pasando por tocilizumab y baricitinib: Una revisión de la literatura / Use of antirheumatic drugs in covid-19 from hydroxychloroquine to anakinra through tocilizumab and baricitinib: A review of the literature

RESUMEN Actualmente nos encontramos en una pandemia mundial causada por el coronavirus 2019 o COVID-19, presentando diferentes desafíos para el sistema de salud debido a que no se cuenta aún con alguna vacuna ni con un tratamiento que haya demostrado su eficacia en totalidad, siendo el manejo actual preventivo y de soporte. Por lo que, en esta revisión se estudiará a los fármacos antirreumáticos más resaltantes que tengan un probable efecto farmacológico, como son la hidroxicloroquina, el tocilizumab, el anakinra y el baricitinib, frente al COVID-19. Se espera que brinde apoyo para futuros tratamientos e investigaciones sobre la enfermedad.

ABSTRACT We are currently in a global pandemic caused by the coronavirus 2019 or COVID- 19, presenting different challenges for the health system due to the fact that there is still no vaccine or a treatment that has proven its effectiveness in its entirety, being the management current preventive and supportive. Therefore, this review will study the most prominent antirheumatic drugs that have a probable pharmacological effect, such as hydroxychloroquine, tocilizumab, anakinra and baricitinib, against COVID-19. It is expected that they will provide support for future treatments. and research on the disease.

Prospective Latin American cohort evaluating outcomes of patients with COVID-19 and abnormal liver tests on admission.

INTRODUCTION & OBJECTIVES: The independent effect of liver biochemistries as a prognostic factor in patients with COVID-19 has not been completely addressed. We aimed to evaluate the prognostic value of abnormal liver tests on admission of hospitalized patients with COVID-19. MATERIALS & METHODS: We performed a prospective cohort study including 1611 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through July 31, 2020 in 38 different Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters, including liver function tests, on admission and during hospitalization. All patients were followed until discharge or death. We fit multivariable logistic regression models, further post-estimation effect through margins and inverse probability weighting. RESULTS: Overall, 57.8% of the patients were male with a mean age of 52.3 years, 8.5% had chronic liver disease and 3.4% had cirrhosis. Abnormal liver tests on admission were present on 45.2% (CI 42.7-47.7) of the cohort (n = 726). Overall, 15.1% (CI 13.4-16.9) of patients died (n = 244). Patients with abnormal liver tests on admission presented higher mortality 18.7% (CI 15.9-21.7), compared to those with normal liver biochemistries 12.2% (CI 10.1-14.6); P < .0001). After excluding patients with history of chronic liver disease, abnormal liver tests on admission were independently associated with death [OR 1.5 (CI 1.1-2.0); P = 0.01], and severe COVID-19 (2.6 [2.0-3.3], P < .0001), both adjusted by age, gender, diabetes, pneumonia and body mass index >30. CONCLUSIONS: The presence of abnormal liver tests on admission is independently associated with mortality and severe COVID-19 in hospitalized patients with COVID-19 infection and may be used as surrogate marker of inflammation. CLINICALTRIALS.GOV: NCT04358380.

Neutrophils Fuel Effective Immune Responses through Gluconeogenesis and Glycogenesis.

Neutrophils can function and survive in injured and infected tissues, where oxygen and metabolic substrates are limited. Using radioactive flux assays and LC-MS tracing with U-13C glucose, glutamine, and pyruvate, we observe that neutrophils require the generation of intracellular glycogen stores by gluconeogenesis and glycogenesis for effective survival and bacterial killing. These metabolic adaptations are dynamic, with net increases in glycogen stores observed following LPS challenge or altitude-induced hypoxia. Neutrophils from patients with chronic obstructive pulmonary disease have reduced glycogen cycling, resulting in impaired function. Metabolic specialization of neutrophils may therefore underpin disease pathology and allow selective therapeutic targeting.

Gestantes con enfermedad por coronavirus 2019 y transmisión vertical intrauterina: una revisión sistemática / Pregnant women with coronavirus disease 2019 and intrauterine vertical transmission: a systematic review

Resumen Introducción . La enfermedad por coronavirus 2019 (COVID-19) es una enfermedad de las vías respiratorias potencialmente severa, producida por el coronavirus tipo 2 causante del síndrome respiratorio agudo grave (SARS-CoV-2). La transmisión intrauterina de la madre al feto es un motivo de debate. Objetivo. Identificar la evidencia disponible de transmisión vertical intrauterina en la gestante con COVID-19. Metodología. Revisión sistemática utilizando los términos: "Vertical transmission" AND "COVID-19" OR "SARS-CoV-2". Las bases de datos consultadas fueron MEDLINE/PubMed, Science Direct, Clinical Key, LILACS, SciELO, Google Scholar, medRxiv y SciELO Preprints. Resultados . Se identificaron 30 estudios que cumplieron los criterios de selección e incluían 476 gestantes. La infección se encontró en 9 neonatos (1,9%), el hisopado faríngeo en ellos se hizo dentro de las 48 horas del nacimiento. En 4 de ellos no se buscó la presencia del virus en otros tejidos y fluidos maternos, mientras que en los 5 casos restantes se identificó el ARN en la placenta de tres de ellos, en dos se encontró en el líquido amniótico y en uno en el canal vaginal. Los estudios fueron muy heterogéneos; así podemos mencionar la variedad de la población reportada, el número de muestras y momento de la toma en los neonatos, la falta de muestreo en los tejidos y fluidos maternos. Conclusiones . La transmisión vertical intrauterina del SARS-CoV-2 no ha sido demostrada de forma contundente debido a que la mayoría de las gestantes con la enfermedad ha tenido neonatos con la prueba molecular negativa (98,1%). Sin embargo, la heterogeneidad de los estudios tampoco permite descartar esta posibilidad.

ABSTRACT Introduction: Coronavirus disease 2019, also called COVID-19, is a potentially severe respiratory disease originated by the type 2 coronavirus that causes severe acute respiratory syndrome (SARS-CoV-2). Intrauterine transmission from mother to fetus is a matter of debate. Objective: To identify the available evidence of vertical intrauterine transmission in pregnant women with COVID-19. Methodology: A systematic review was performed using the terms: "Vertical transmission" AND "COVID-19" OR "SARSCoV-2" NOT "Review *". The databases consulted were MEDLINE/PubMed, Science Direct, Clinical Key, LILACS, SciELO, Google Scholar, medRxiv and SciELO Preprints. Results: Thirty primary studies met the selection criteria and included 476 pregnant women. Infection was found in 9 neonates (1.9%) in whom pharyngeal swabs were done within 48 hours of birth. In four of them the presence of the virus was not looked for in other maternal tissues and fluids; in the remaining 5 cases, the virus RNA was identified in the placenta of three of them, in two it was found in the amniotic fluid and in one in vaginal secretion. Studies were very heterogeneous, with great variety of the reported population, the number of samples and time of collection in neonates, the lack of sampling in maternal tissues and fluids. Conclusions: Vertical intrauterine transmission of SARS-CoV-2 has not been conclusively demonstrated in pregnant women with COVID-19 as the majority of patients with the disease had newborns with negative molecular test (98,1%). The heterogeneity of the studies does not allow to rule out this possibility either.