Incidencia de trombosis venosa profunda en pacientes con síndrome de distrés respiratorio agudo secundario a COVID-19, bajo tromboprofilaxis con dosis intermedia de heparina de bajo peso molecular / Deep venous thrombosis incidence in patients with COVID-19 acute respiratory distress syndrome, under intermediate dose of chemical thromboprophylaxis

Resumen A pesar de la tromboprofilaxis estándar, el diagnóstico de trombosis es común en pacientes críticos con COVID-19. El objetivo del presente estudio fue evaluar la incidencia de trombosis venosa profunda (TVP) en pacientes con neumonía grave por COVID-19 con requerimientos de asistencia respiratoria mecánica, bajo tromboprofilaxis química con dosis intermedia (1 mg/kg/día) de heparina de bajo peso molecular (enoxaparina). Se trató de un estudio unicéntrico, descriptivo y de corte transversal de datos recopilados en forma prospectiva. Se realizó búsqueda activa y sistemática de TVP en miembros inferiores (o en confluente yúgulosubclavio en su defecto) mediante doppler venoso cada 7 días. Se continuó con la evaluación por doppler semanal hasta la finalización de la ventilación mecánica, el cum plimiento de los 28 días de internación en unidad de cuidados intensivos, el fallecimiento o la suspensión de la tromboprofilaxis con enoxaparina por cualquier causa. Se incluyeron 46 pacientes. Se realizó diagnóstico de TVP en 5 (3 en miembros inferiores y 2 en con fluente yúgulosubclavio). Tres diagnósticos de TVP fueron asociados a la presencia de catéter venoso central (2 en miembros inferiores y 1 en el confluente yúgulosubclavio), dos fallecieron durante el seguimiento por causas vinculadas al síndrome de distrés respiratorio agudo (SDRA) pero no por eventos trombóticos o de sangrado mayor. En todos los casos, los eventos trombóticos fueron asintomáticos. En nuestra serie de pacientes con SDRA moderado/grave secundario a neumonía por COVID-19, la incidencia de TVP fue del 10.9% en aquellos bajo tromboprofilaxis con dosis intermedia (1 mg/kg/día) de enoxaparina.

Abstract Despite standard thrombo prophylaxis, venous thrombosis is common in critically ill patients with COVID-19. The objective of this study was to evaluate deep venous thrombosis (DVT) incidence in patients with severe COVID-19 pneumonia with mechanical ventilation requirements under intermediate dose of chemical thromboprophylaxis (1 mg/kg/day of enoxaparin). This was a single-center, descriptive, cross-sectional study of prospectively collected data. An active and systematic protocol with venous doppler was carried out for DVT diagnosis in lower limbs (or in jugulo-subclavian venous confluence) every 7 days. Weekly doppler evaluation was continued until the end of mechanical ventilation, up to 28 days of intensive care unit admission, until death or until the thromboprophylaxis suspension for any cause. Forty-six patients were included. DVT was diagnosed in 5 (3 in lower limbs and 2 in jugulo-subclavian conflu ent). In 3 cases, DVT was catheter-related (2 in lower limbs and 1 in jugulo-subclavian confluent), 2 died during follow-up due to acute respiratory distress syndrome (ARDS) complications without thrombotic events or major bleeding. All thrombotic events were asymptomatic. In our series of patients with moderate/severe COVID-19 ARDS, DVT incidence was 10.9% under thromboprophylaxis with intermediate dose (1 mg/kg/ day) of enoxaparin.

[Deep venous thrombosis incidence in patients with COVID-19 acute respiratory distress syndrome, under intermediate dose of chemical thromboprophylaxis]. / Incidencia de trombosis venosa profunda en pacientes con síndrome de distrés respiratorio agudo secundario a COVID-19, bajo tromboprofilaxis con dosis intermedia de heparina de bajo peso molecular.

Despite standard thromboprophylaxis, venous thrombosis is common in critically ill patients with COVID-19. The objective of this study was to evaluate deep venous thrombosis (DVT) incidence in patients with severe COVID-19 pneumonia with mechanical ventilation requirements under intermediate dose of chemical thromboprophylaxis (1 mg/kg/day of enoxaparin). This was a single-center, descriptive, cross-sectional study of prospectively collected data. An active and systematic protocol with venous doppler was carried out for DVT diagnosis in lower limbs (or in jugulo-subclavian venous confluence) every 7 days. Weekly doppler evaluation was continued until the end of mechanical ventilation, up to 28 days of intensive care unit admission, until death or until the thromboprophylaxis suspension for any cause. Forty-six patients were included. DVT was diagnosed in 5 (3 in lower limbs and 2 in jugulo-subclavian confluent). In 3 cases, DVT was catheter-related (2 in lower limbs and 1 in jugulo-subclavian confluent), 2 died during follow-up due to acute respiratory distress syndrome (ARDS) complications without thrombotic events or major bleeding. All thrombotic events were asymptomatic. In our series of patients with moderate/severe COVID-19 ARDS, DVT incidence was 10.9% under thromboprophylaxis with intermediate dose (1 mg/kg/ day) of enoxaparin.

A pesar de la tromboprofilaxis estándar, el diagnóstico de tromb osis es común en pacientes críticos con COVID-19. El objetivo del presente estudio fue evaluar la incidencia de trombosis venosa profunda (TVP) en pacientes con neumonía grave por COVID-19 con requerimientos de asistencia respiratoria mecánica, bajo tromboprofilaxis química con dosis intermedia (1 mg/kg/día) de heparina de bajo peso molecular (enoxaparina). Se trató de un estudio unicéntrico, descriptivo y de corte transversal de datos recopilados en forma prospectiva. Se realizó búsqueda activa y sistemática de TVP en miembros inferiores (o en confluente yúgulosubclavio en su defecto) mediante doppler venoso cada 7 días. Se continuó con la evaluación por doppler semanal hasta la finalización de la ventilación mecánica, el cum plimiento de los 28 días de internación en unidad de cuidados intensivos, el fallecimiento o la suspensión de la tromboprofilaxis con enoxaparina por cualquier causa. Se incluyeron 46 pacientes. Se realizó diagnóstico de TVP en 5 (3 en miembros inferiores y 2 en confluente yúgulosubclavio). Tres diagnósticos de TVP fueron asociados a la presencia de catéter venoso central (2 en miembros inferiores y 1 en el confluente yúgulosubclavio), dos fallecieron durante el seguimiento por causas vinculadas al síndrome de distrés respiratorio agudo (SDRA) pero no por eventos trombóticos o de sangrado mayor. En todos los casos, los eventos trombóticos fueron asintomáticos. En nuestra serie de pacientes con SDRA moderado/grave secundario a neumonía por COVID-19, la incidencia de TVP fue del 10.9% en aquellos bajo tromboprofilaxis con dosis intermedia (1 mg/kg/día) de enoxaparina.

Echocardiographic findings in patients under mechanical ventilation with COVID-19 acute respiratory distress syndrome / Hallazgos ecocardiográficos en pacientes bajo ventilación mecánica con síndrome de dificultad respiratoria aguda por COVID-19

Abstract Coronavirus disease 2019 (COVID-19) produces a significant burden to severely ill patients affected by acute respiratory failure. The aim of this study was to describe echocardiographic findings in a series of mechanically ventilated patients with moderate and severe acute respiratory distress syndrome (ARDS) due to COVID-19. This was a single center, descriptive and cros s-sectional study of prospectively collected data. Patients had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate or severe ARDS. Initial echocardiogram was performed within 7 days of intensive care unit admission and every 15 days until mechanical ventilation ended, 28 days or death. Time spent by the physician for each study was measured. Multiple echographic measurements were acquired; 33 patients were analyzed. Total number of echocardiograms performed was 76. The median imaging time required to complete a standard study was 13 [10-15] minutes. Chronic structural abnormalities were present in 16 patients (48%), being LV hypertrophy the main finding in 11 patients (33%). The most frequent acute or dynamic finding was RV enlargement (43%) when considering all echocardiograms performed from admission to day 28 of follow-up. Other findings were: pulmonary hypertension (15%), new or dynamic left ventricle (LV) regional wall motion abnormalities (15%), new or dynamic LV global contractility deterioration (6%) and hypercontractility (12%).

Resumen La enfermedad por coronavirus 2019 (COVID-19) produce una carga significativa para los pacientes gravemente enfermos afectados por insuficiencia respiratoria aguda. El objetivo de este estudio fue describir los hallazgos ecocardiográficos en una serie de pacientes ventilados mecánicamente con síndrome de dificultad respiratoria aguda (SDRA) moderado y grave debido a COVID-19. Se trata de un estudio unicéntrico, descriptivo y de corte transversal de datos recopilados en forma prospectiva. Los pacientes tenían una infección por el coronavirus SARS-Cov-2 y SDRA moderado o grave. El ecocardiogra ma inicial se realizó dentro de los 7 días del ingreso en la unidad de cuidados intensivos y luego cada 15 días hasta finalizar la ventilación mecánica, 28 días o fallecimiento. Se midió el tiempo empleado por el operador en cada estudio. Se adquirieron múltiples medidas ecográficas. Se analizaron 33 pacientes. El número total de ecocardiogramas realizados fue de 76. El tiempo necesario (mediana [RIQ]) para la obtención de las imágenes de un estudio estándar fue de 13 [10-15] minutos. Las anomalías estructurales crónicas estuvieron presentes en 16 pacientes (48%), siendo la hipertrofia ventricular izquierda la principal (11 pacientes, 33%). El hallazgo agudo o dinámico más frecuente fue el agrandamiento del ventrículo derecho (VD) (43%) al considerar todos los ecocardiogramas realizados desde el ingreso hasta el día 28 de seguimiento. Otros hallazgos fueron: hipertensión pulmonar (15%), anomalías del movimiento de la pared regional del VI nuevas o dinámicas (15%), deterioro de la contractilidad global del ventrículo izquierdo, nuevo o dinámico (6%), e hipercontractilidad (12%).

Echocardiographic findings in patients under mechanical ventilation with COVID-19 acute respiratory distress syndrome.

Coronavirus disease 2019 (COVID-19) produces a significant burden to severely ill patients affected by acute respiratory failure. The aim of this study was to describe echocardiographic findings in a series of mechanically ventilated patients with moderate and severe acute respiratory distress syndrome (ARDS) due to COVID-19. This was a single center, descriptive and cros s-sectional study of prospectively collected data. Patients had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate or severe ARDS. Initial echocardiogram was performed within 7 days of intensive care unit admission and every 15 days until mechanical ventilation ended, 28 days or death. Time spent by the physician for each study was measured. Multiple echographic measurements were acquired; 33 patients were analyzed. Total number of echocardiograms performed was 76. The median imaging time required to complete a standard study was 13 [10-15] minutes. Chronic structural abnormalities were present in 16 patients (48%), being LV hypertrophy the main finding in 11 patients (33%). The most frequent acute or dynamic finding was RV enlargement (43%) when considering all echocardiograms performed from admission to day 28 of follow-up. Other findings were: pulmonary hypertension (15%), new or dynamic left ventricle (LV) regional wall motion abnormalities (15%), new or dynamic LV global contractility deterioration (6%) and hypercontractility (12%).

La enfermedad por coronavirus 2019 (COVID-19) produce una carga significativa para los pacientes gravemente enfermos afectados por insuficiencia respiratoria aguda. El objetivo de este estudio fue describir los hallazgos ecocardiográficos en una serie de pacientes ventilados mecánicamente con síndrome de dificultad respiratoria aguda (SDRA) moderado y grave debido a COVID-19. Se trata de un estudio unicéntrico, descriptivo y de corte transversal de datos recopilados en forma prospectiva. Los pacientes tenían una infección por el coronavirus SARS-Cov-2 y SDRA moderado o grave. El ecocardiograma inicial se realizó dentro de los 7 días del ingreso en la unidad de cuidados intensivos y luego cada 15 días hasta finalizar la ventilación mecánica, 28 días o fallecimiento. Se midió el tiempo empleado por el operador en cada estudio. Se adquirieron múltiples medidas ecográficas. Se analizaron 33 pacientes. El número total de ecocardiogramas realizados fue de 76. El tiempo necesario (mediana [RIQ]) para la obtención de las imágenes de un estudio estándar fue de 13 [10-15] minutos. Las anomalías estructurales crónicas estuvieron presentes en 16 pacientes (48%), siendo la hipertrofia ventricular izquierda la principal (11 pacientes, 33%). El hallazgo agudo o dinámico más frecuente fue el agrandamiento del ventríc ulo derecho (VD) (43%) al considerar todos los ecocardiogramas realizados desde el ingreso hasta el día 28 de seguimiento. Otros hallazgos fueron: hipertensión pulmonar (15%), anomalías del movimiento de la pared regional del VI nuevas o dinámicas (15%), deterioro de la contractilidad global del ventrículo izquierdo, nuevo o dinámico (6%), e hipercontractilidad (12%).

High- Versus Low-Dose Dexamethasone for the Treatment of COVID-19-Related Acute Respiratory Distress Syndrome: A Multicenter, Randomized Open-Label Clinical Trial.

OBJECTIVE: To determine whether high-dose dexamethasone increases the number of ventilator-free days (VFD) among patients with acute respiratory distress syndrome (ARDS) caused by COVID-19. DESIGN: Multicenter, randomized, open-label, clinical trial. PARTICIPANTS: Consecutive patients with confirmed COVID-19-related ARDS were enrolled from June 17, 2020, to March 27, 2021, in four intensive care units (ICUs) in Argentina. INTERVENTION: 16 mg of dexamethasone intravenously daily for five days followed by 8 mg of dexamethasone daily for five days or 6 mg of dexamethasone intravenously daily for 10 days. MAIN OUTCOME AND MEASURES: The primary outcome was ventilator-free days during the first 28 days. The secondary outcomes were all-cause mortality at 28 and 90 days, infection rate, muscle weakness, and glycemic control in the first 28 days. RESULTS: Data from 98 patients who received at least one dose of dexamethasone were analyzed. The trial was prematurely terminated due to low enrollment rate. At 28 days after randomization, there was no difference between high- and low-dose dexamethasone groups in VFD (median, 0 [interquartile range [IQR] 0-14] vs. 0 [IQR 0-1] days; P = .231), or in the mean duration of mechanical ventilation (19 ± 18 vs. 25 ± 22 days; P = .078). The cumulative hazard of successful discontinuation from mechanical ventilation was increased by the high-dose treatment (adjusted sub-distribution hazard ratio: 1.84; 95% CI: 1.31 to 2.5; P < .001). None of the prespecified secondary and safety outcomes showed a significant difference between treatment arms. CONCLUSIONS: Among patients with ARDS due to COVID-19, the use of higher doses of dexamethasone compared with the recommended low-dose treatment did not show an increase in VFD. However, the higher dose significantly improved the time required to liberate them from the ventilator.

High dose dexamethasone treatment for Acute Respiratory Distress Syndrome secondary to COVID-19: a structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The aim of this study is to explore the effectiveness and safety of high dose dexamethasone treatment for Acute Respiratory Distress Syndrome secondary to SARS-Cov-2 pneumonia. TRIAL DESIGN: Multicentre, randomized clinical trial, controlled, open label, parallel group, to evaluate the effectiveness and safety of high dose dexamethasone in adult patients with confirmed COVID-19, with Acute Respiratory Distress Syndrome. PARTICIPANTS: We will include patients with SARS-Cov-2 pneumonia who develop acute respiratory distress syndrome, in several intensive care units (ICU) in Buenos Aires, Argentina (CEMIC, Clinica Bazterrica, Sanatorio Sagrado Corazon) Inclusion criteria: Men and women, age ≥ 18 years old. Confirmed diagnosis of SARS-CoV-2 infection, by RT-PCR. Diagnosis of Acute Respiratory Distress Syndrome (hypoxemic respiratory failure not explained by cardiac disease + PaO2/FiO2 ratio < 300 with a Positive End-Expiratory Pressure ≥ 5 cm H2O + bilateral pulmonary infiltrates) Length of mechanical ventilation of at least 72 hours Informed consent (next of kin / legal guardian) Exclusion criteria: Pregnant or breast-feeding women. Terminal disease (advanced cancer; under palliative care; cardiovascular, respiratory, or renal disease with a life expectancy less ≤ 1 year). Therapeutic limitation (advance directives or do not resuscitate order) Severe immunosuppression (HIV infection, long-term use of immunosuppressive agents, active cancer). Patients under chronic treatment with glucocorticoids for other diseases (≥ 8 mg prednisone, or equivalent) Participation in another randomized clinical trial. INTERVENTION AND COMPARATOR: Eligible patients will be randomized to receive standard ICU patient care (group 1) or standard ICU patient care plus high dose dexamethasone (group 2). Group 1: dexamethasone up to 6 mg/24 hours for up to 10 days + ventilatory, hemodynamic, nutritional, and antimicrobial support according to international guidelines. Group 2: dexamethasone 16 mg/24 hours for 5 days followed by dexamethasone 8 mg/24 hours for 5 days + ventilatory, hemodynamic, nutritional, and antimicrobial support according to international guidelines. MAIN OUTCOME: The main result is ventilator-free days at 28 days (Days without ventilator support in the first 28 days following randomization). Secondary outcomes are 28-days and 90-days mortality, frequency of nosocomial infections in the first 28 days after randomization, Sequential Organ Failure Assessment (SOFA) score variation and prone position in the first 10-days, viral shedding 28-days after randomization, and delirium and muscle weakness at ICU discharge. RANDOMISATION: Treatment will be assigned according to site stratified randomization by permuted random blocks sequence 1:1 generated with a table in R language concealed in a randomization tool in REDCap (Research Electronic Data CAPture) platform. BLINDING (MASKING): This is an open trial, so no masking of treatment assignment will be used. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Assuming a 3 days difference in ventilator-free days between treatment groups, with a mean of 9 days, and a standard deviation of 9 days; the necessary sample size would be 284 subjects (142 per group), with a power of 80% and a two-tailed alpha error of 0.05. TRIAL STATUS: The protocol with code 1264, version 3.0 on date: May 13, 2020 is approved by the local Ethics Committee. The trial is in the recruitment phase. Recruitment began May 22, 2020 and is anticipated to be complete by the end of December 2021. TRIAL REGISTRATION: The trial was registered under the title "Dexamethasone for COVID-19 Related ARDS: a Multicenter, Randomized Clinical Trial" with ClinicalTrials number NCT04395105, https://clinicaltrials.gov/ct2/show/NCT04395105 , registered on 20 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Hepatitis E infection is an infrequent cause of acute hepatitis in the metropolitan area of Buenos Aires.

Background Argentina is considered a region of low seroprevalence of hepatitis E virus (HEV), however; no studies have evaluated its burden among acute hepatitis cases. OBJECTIVES: We aimed to estimate the proportion of acute HEV and outcome in a cohort of patients with acute hepatitis from 6 liver units in the Metropolitan area of Buenos Aires (MABA). STUDY DESIGN: We performed a prospective cohort study including patients ≥18 years with acute hepatitis (increase in transaminases x 5 ULN) fromJuly 2016 to May 2018. Severe hepatitis was defined as acute hepatitis + INR> 1.5 and acute liver failure as severe hepatitis + encephalopathy. In patients in whom other etiologies were excluded, HEV tests were performed: anti-HEV IgM/G and HEV-RNA in serum and feces. RESULTS: Overall, 268 patients with acute hepatitis were included in the study. The most frequent etiologies of acute hepatitis were hepatitis B (67patients, 25 %), hepatotoxicity (65, 24 %) and autoimmune hepatitis (26, 10 %). Acute HEV infection was confirmed in 8 (2.98 %; 95 %CI 1.25-5.63) patients who tested positive for anti-HEV IgM. A total of 63 (23.5 %) patients were hospitalized and 9 (3.3 %) patients died. Overall, 48 (18 %) patients developed severe hepatitis, 6 (2.2 %) have acute liver failure, 6 (1.9 %) underwent liver transplantation and 9 (3.4 %) patients died. CONCLUSIONS: the proportion of acute HEV in MABA was low during the period studied. We believe our findings will aid physicians prioritize other etiologies of acute hepatitis over HEV in order to optimize diagnostic resources and offer better care to their patients.

Obesity Trends among Asthma Patients in the United States: A Population-based Study.

BACKGROUND: Obesity is strongly associated with worse asthma control and poorer quality of life. The current obesity epidemic has reached historically high levels, with an estimated prevalence rate of 37% in the general United States (US) population. However, less is known about trends in the prevalence of obesity among individuals with asthma or which sociodemographic groups are at higher risk for increased weight. METHODS: The study was conducted with data from the Behavioral Risk Factor Surveillance System (BRFSS) study, a nationally representative probability-based sample of the US population. We included participants ≥18 years of age who were interviewed between 1999 and 2016. Using stratified weighting, we estimated the annual prevalence of participants with, and without a diagnosis of asthma, classified according to their body mass index (BMI), into: normal weight (18.5-25 kg/m2), overweight (25-30 kg/m2), or obese (>30 kg/m2). We calculated the annual odds of obesity among participants with vs. without asthma to assess if trends among individuals with asthma followed those of the general US population. Nominal regression analysis assessed the association between age, sex, race/ethnicity, and income with prevalence of obesity among participants with asthma. RESULTS: Among the 543,574 BRSFF participants with asthma, the prevalence of overweight and obesity changed from 34.3% and 24.7% in 1999 to 28.8% and 41.1% in 2016, respectively. The odds ratio (OR) of obesity in patients with asthma compared to the general population without asthma, increased during the same period from 1.39 (95% confidence interval [CI]: 1.36-1.36) in 1999 to 1.75 (95% CI: 1.75-1.76) in 2016. Adjusted analysis showed that older (OR: 2.32, 95% CI: 2.32-2.33), Black (OR: 1.61, 95% CI: 1.61-1.61) and Hispanic (OR: 1.29, 95%. CI: 1.28-1.29) participants with asthma had higher rates of obesity. CONCLUSIONS: There has been a substantial increase in the prevalence of obesity among individuals with asthma in the last two decades, beyond what could be explained by general population trends. These results suggest that obesity is an increasing determinant of asthma morbidity and should be particularly targeted in minorities with asthma.