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Background: Approximately 5% of COVID-19 patients develop respiratory failure and need ventilatory support, yet little is known about the impact of mechanical ventilation strategy in COVID-19. Our objective was to describe baseline characteristics, ventilatory parameters, and outcomes of critically ill patients in the largest referral center for COVID-19 in Sao Paulo, Brazil, during the first surge of the pandemic. Methods: This cohort included COVID-19 patients admitted to the intensive care units (ICUs) of an academic hospital with 94 ICU beds, a number expanded to 300 during the pandemic as part of a state preparedness plan. Data included demographics, advanced life support therapies, and ventilator parameters. The main outcome was 28-day survival. We used a multivariate Cox model to test the association between protective ventilation and survival, adjusting for PF ratio, pH, compliance, and PEEP. Results: We included 1503 patients from March 30 to June 30, 2020. The mean age was 60 ± 15 years, and 59% were male. During 28-day follow-up, 1180 (79%) patients needed invasive ventilation and 666 (44%) died. For the 984 patients who were receiving mechanical ventilation in the first 24 h of ICU stay, mean tidal volume was 6.5 ± 1.3 mL/kg of ideal body weight, plateau pressure was 24 ± 5 cmH2O, respiratory system compliance was 31.9 (24.4–40.9) mL/cmH2O, and 82% of patients were ventilated with protective ventilation. Noninvasive ventilation was used in 21% of patients, and prone, in 36%. Compliance was associated with survival and did not show a bimodal pattern that would support the presence of two phenotypes. In the multivariable model, protective ventilation (aHR 0.73 [95%CI 0.57–0.94]), adjusted for PF ratio, compliance, PEEP, and arterial pH, was independently associated with survival. Conclusions: During the peak of the epidemic in Sao Paulo, critically ill patients with COVID-19 often required mechanical ventilation and mortality was high. Our findings revealed an association between mechanical ventilation strategy and mortality, highlighting the importance of protective ventilation for patients with COVID-19. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is responsible for the novel coronavirus disease 2019 (COVID-19). An appealing antiviral drug target is the coronavirus 3C-like protease (3CLpro) that is responsible for the processing of the viral polyproteins and liberation of functional proteins essential for the maturation and infectivity of the virus. In this study, multiple thermal analytical techniques have been implemented to acquire the thermodynamic parameters of 3CLpro at different buffer conditions. 3CLpro exhibited relatively high thermodynamic stabilities over a wide pH range; however, the protease was found to be less stable in the presence of salts. Divalent metal cations reduced the thermodynamic stability of 3CLpro more than monovalent cations; however, altering the ionic strength of the buffer solution did not alter the stability of 3CLpro. Furthermore, the most stable thermal kinetic stability of 3CLpro was recorded at pH 7.5, with the highest enthalpy of activation calculated from the slope of Eyring plot. The biochemical and biophysical properties of 3CLpro explored here may improve the solubility and stability of 3CLpro for optimum conditions for the setup of an enzymatic assay for the screening of inhibitors to be used as lead candidates in the discovery of drugs and design of antiviral therapeutics against COVID-19. [ABSTRACT FROM AUTHOR]

Background: Protective mechanical ventilation is recommended for patients with acute respiratory distress syndrome (ARDS), but it usually requires controlled ventilation and sedation. Using neurally adjusted ventilatory assist (NAVA) or pressure support ventilation (PSV) could have additional benefits, including the use of lower sedative doses, improved patient–ventilator interaction and shortened duration of mechanical ventilation. We designed a pilot study to assess the feasibility of keeping tidal volume (VT) at protective levels with NAVA and PSV in patients with ARDS. Methods: We conducted a prospective randomized crossover trial in five ICUs from a university hospital in Brazil and included patients with ARDS transitioning from controlled ventilation to partial ventilatory support. NAVA and PSV were applied in random order, for 15 min each, followed by 3 h in NAVA. Flow, peak airway pressure (Paw) and electrical activity of the diaphragm (EAdi) were captured from the ventilator, and a software (Matlab, Mathworks, USA), automatically detected inspiratory efforts and calculated respiratory rate (RR) and VT. Asynchrony events detection was based on waveform analysis. Results: We randomized 20 patients, but the protocol was interrupted for five (25%) patients for whom we were unable to maintain VT below 6.5 mL/kg in PSV due to strong inspiratory efforts and for one patient for whom we could not detect EAdi signal. For the 14 patients who completed the protocol, VT was 5.8 ± 1.1 mL/kg for NAVA and 5.6 ± 1.0 mL/kg for PSV (p = 0.455) and there were no differences in RR (24 ± 7 for NAVA and 23 ± 7 for PSV, p = 0.661). Paw was greater in NAVA (21 ± 3 cmH2O) than in PSV (19 ± 3 cmH2O, p = 0.001). Most patients were under continuous sedation during the study. NAVA reduced triggering delay compared to PSV (p = 0.020) and the median asynchrony Index was 0.7% (0–2.7) in PSV and 0% (0–2.2) in NAVA (p = 0.6835). Conclusions: It was feasible to keep VT in protective levels with NAVA and PSV for 75% of the patients. NAVA resulted in similar VT, RR and Paw compared to PSV. Our findings suggest that partial ventilatory assistance with NAVA and PSV is feasible as a protective ventilation strategy in selected ARDS patients under continuous sedation. Trial registration ClinicalTrials.gov (NCT01519258). Registered 26 January 2012, https://clinicaltrials.gov/ct2/show/NCT01519258 [ABSTRACT FROM AUTHOR]

To assess epidemiology and management practices of Latin America Pediatric Rheumatologists (LAPR) about childhood-onset systemic lupus erythematosus (cSLE). A cross-sectional study was performed in 288 LAPR PANLAR members based on online survey about cSLE practices. The response rate of web-based survey by LAPR was 170/288(59%) and the majority worked in university hospitals (63%). The ACR and/or SLICC classification criteria (99%) and disease activity tools (97%) were almost universally used by LAPR, whereas damage index (70%) and CHAQ (58%) instruments were less frequently used. Laboratory exams, diagnostic imaging, and biopsies were generally available (> 75%), however low availability for densitometry (66%). Drug access was excellent for the most common prescribed medications (> 75%), except for belimumab (11%). Emerging mosquito-borne diseases were also reported: dengue (20%), chikungunya (11%), and Zika (8%). Groups were further divided in two, according to the median number of cSLE patients followed by LAPR in the last year: groups A and B (≥ 25 and < 25, respectively). Frequencies of condom in combination with other contraceptive methods were significantly higher in group A than B (p = 0.01). The frequencies of reported pregnancy (p < 0.001) and non-adherence to therapy were significantly higher in group A (p = 0.023). Alcohol intake (p = 0.004) and illicit drug use (p = 0.007) were also reported more frequently by LAPR of group A in at least one cSLE patient. This first large web-based survey demonstrated an overall excellent access for diagnosis and therapy by LAPR, probably related to their high rate of practices in tertiary care of university hospitals. Adherence to therapy, pregnancy, and substance abuse was identified as major challenges in this population, particularly in larger centers. [ABSTRACT FROM AUTHOR]