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BACKGROUND: The emergence of SARS-CoV-2 variants led to subsequent waves of COVID-19 worldwide. In many countries, the second wave of COVID-19 was marked by record deaths, raising the concern that variants associated with that wave might be more deadly. Our aim was to compare outcomes of critically-ill patients of the first two waves of COVID-19. METHODS: This retrospective cohort included critically-ill patients admitted between March-June 2020 and April-July 2021 in the largest academic hospital in Brazil, which has free-access universal health care system. We compared admission characteristics and hospital outcomes. The main outcome was 60-day survival and we built multivariable Cox model based on a conceptual causal diagram in the format of directed acyclic graph (DAG). RESULTS: We included 1583 patients (1315 in the first and 268 in the second wave). Patients in the second wave were younger, had lower severity scores, used prone and non-invasive ventilatory support more often, and fewer patients required mechanical ventilation (70% vs 80%, p<0.001), vasopressors (60 vs 74%, p<0.001), and dialysis (22% vs 37%, p<0.001). Survival was higher in the second wave (HR 0.61, 95%CI 0.50-0.76). In the multivariable model, admission during the second wave, adjusted for age, SAPS3 and vaccination, was not associated with survival (aHR 0.85, 95%CI 0.65-1.12). CONCLUSIONS: In this cohort study, patients with COVID-19 admitted to the ICU in the second wave were younger and had better prognostic scores. Adjusted survival was similar in the two waves, contrasting with record number of hospitalizations, daily deaths and health system collapse seen across the country in the second wave. Our findings suggest that the combination of the burden of severe cases and factors such as resource allocation and health disparities may have had an impact in the excess mortality found in many countries in the second wave.

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Objective. Understanding a patient's respiratory effort and mechanics is essential for the provision of individualized care during mechanical ventilation. However, measurement of transpulmonary pressure (the difference between airway and pleural pressures) is not easily performed in practice. While airway pressures are available on most mechanical ventilators, pleural pressures are measured indirectly by an esophageal balloon catheter. In many cases, esophageal pressure readings take other phenomena into account and are not a reliable measure of pleural pressure.Approach.A system identification approach was applied to provide accurate pleural measures from esophageal pressure readings. First, we used a closed pressurized chamber to stimulate an esophageal balloon and model its dynamics. Second, we created a simplified version of an artificial lung and tried the model with different ventilation configurations. For validation, data from 11 patients (five male and six female) were used to estimate respiratory effort profile and patient mechanics.Main results.After correcting the dynamic response of the balloon catheter, the estimates of resistance and compliance and the corresponding respiratory effort waveform were improved when compared with the adjusted quantities in the test bench. The performance of the estimated model was evaluated using the respiratory pause/occlusion maneuver, demonstrating improved agreement between the airway and esophageal pressure waveforms when using the normalized mean squared error metric. Using the corrected muscle pressure waveform, we detected start and peak times 130 ± 50 ms earlier and a peak amplitude 2.04 ± 1.46 cmH2O higher than the corresponding estimates from esophageal catheter readings.Significance.Compensating the acquired measurements with system identification techniques makes the readings more accurate, possibly better portraying the patient's situation for individualization of ventilation therapy.

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BACKGROUND: Survivors of chronic critical illness often experience weakness and functional dependence to various degrees after their intensive care unit (ICU) stay. Evaluating their functional status with the traditional six-minute walk test is challenging due to space constraints or patient intolerance. OBJECTIVE: Our aim was to evaluate the feasibility of using the six-minute step test (6MST) as a measure of functional capacity in chronically critically ill patients early after ICU discharge. METHODS: This prospective study was undertaken in a private Brazilian hospital. From July 2019 to July 2020, all chronically critically ill patients were asked to participate 48 hours after ICU discharge. On the day of study inclusion and a week later, those who consented underwent functional assessment comprised of the 6MST, peripheral muscle strength using handgrip strength (HGS), and mobility using the ICU mobility scale (IMS). RESULTS: A total of 40 patients were included. The 6MST was feasible in 40% on the first evaluation and 57% on the second. The median 6MST was 0 [0-5] on the first evaluation and 3.5 [0-7.75] on the second (P = 0.005). The median HGS increased from 11.50 [9.25-18] on the first evaluation to 14.5 [10-20] on the second (P = 0.006). The median IMS was 4.5 [3.25-7] on the first evaluation and 6 [3.25-7] on the second (P<0.001). Despite the significant improvement, all parameters measured remained well below normal. CONCLUSION: The 6MST was a feasible measure of functional capacity in chronically critically ill patients early after ICU discharge. Patients had functional capacity well below predicted values.

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OBJECTIVE: COVID-19 has been associated with a significant burden to those who survive the acute phase. We aimed to describe the quality of life and symptoms of anxiety, depression, and posttraumatic stress disorder (PTSD) at 90 days after hospital discharge of COVID-19 patients. METHODS: Patients with COVID-19 admitted to a private hospital in the city of São Paulo, Brazil, between April of 2020 and April of 2021 were interviewed by telephone at 30 and 90 days after discharge to assess the quality of life and symptoms of depression, anxiety, and PTSD. RESULTS: A total of 2,138 patients were included. The mean age was 58.6 ± 15.8 years, and the median length of hospital stay was 9.0 (5.0-15.8) days. Between the two time points, depression increased from 3.1% to 7.2% (p < 0.001), anxiety increased from 3.2% to 6.2% (p < 0.001), and PTSD increased from 2.3% to 5.0% (p < 0.001). At least one physical symptom related to COVID-19 diagnosis persisted in 32% of patients at day 90. CONCLUSIONS: Persistence of physical symptoms was high even at 90 days after discharge. Although the prevalence of symptoms of anxiety, depression, and PTSD was low, these symptoms persisted for three months, with a significant increase between the time points. This finding indicates the need to identify at-risk patients so that they can be given an appropriate referral at discharge.

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BACKGROUND: Patient-ventilator asynchronies are usually detected by visual inspection of ventilator waveforms but with low sensitivity, even when performed by experts in the field. Recently, estimation of the inspiratory muscle pressure (Pmus) waveforms through artificial intelligence algorithm has been proposed (Magnamed®, São Paulo, Brazil). We hypothesized that the display of these waveforms could help healthcare providers identify patient-ventilator asynchronies. METHODS: A prospective single-center randomized study with parallel assignment was conducted to assess whether the display of the estimated Pmus waveform would improve the correct identification of asynchronies in simulated clinical scenarios. The primary outcome was the mean asynchrony detection rate (sensitivity). Physicians and respiratory therapists who work in intensive care units were randomized to control or intervention group. In both groups, participants analyzed pressure and flow waveforms of 49 different scenarios elaborated using the ASL-5000 lung simulator. In the intervention group the estimated Pmus waveform was displayed in addition to pressure and flow waveforms. RESULTS: A total of 98 participants were included, 49 per group. The sensitivity per participant in identifying asynchronies was significantly higher in the Pmus group (65.8 ± 16.2 vs. 52.94 ± 8.42, p < 0.001). This effect remained when stratifying asynchronies by type. CONCLUSIONS: We showed that the display of the Pmus waveform improved the ability of healthcare professionals to recognize patient-ventilator asynchronies by visual inspection of ventilator tracings. These findings require clinical validation. TRIAL REGISTRATION: ClinicalTrials.gov: NTC05144607. Retrospectively registered 3 December 2021.

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INTRODUCTION: In COVID-19-related acute respiratory distress syndrome (ARDS), the clot play a role in gas exchange abnormalities. Fibrinolytic therapy can improve alveolar ventilation by restoring blood flow. In this systematic review and meta-analysis protocol, we aim to assess the safety and efficacy of fibrinolytic therapy in such a population. METHODS: We will perform a systematic search in MEDLINE, EMBASE, Cochrane CENTRAL and LILACS databases without language restrictions for relevant randomised controlled trials (RCTs) and quasi-RCTs. Two review authors will independently perform data extraction and quality assessments of data from included studies. In case of divergence, a third author will be contacted. The Cochrane handbook will be used for guidance. If the results are not appropriate for a meta-analysis, a descriptive analysis will be performed. DISCUSSION: This systematic review and meta-analysis protocol will provide current evidence about the safety and efficacy of fibrinolytic therapy in patients with COVID-19 and ARDS. These findings will provide if fibrinolytic therapy might be an option for a desperate clinical setting, where all medical efforts have been used. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020187482. ETHICS AND DISSEMINATION: Ethics committee approval is not necessary. We intend to update the public registry, report any protocol amendments and publish the results in a widely accessible journal.

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The study aimed to evaluate a quantification method of pulmonary perfusion with Dual-Energy CT Angiography (DE-CTA) normalized by lung density in the prediction of outcome in acute pulmonary embolism (PE). In this prospective study with CTA scans acquired with different breathing protocols, two perfusion parameters were calculated: %PBV (relative value of PBV, expressed per unit volume) and PBVm (PBV normalized by lung density, expressed per unit mass). DE-CTA parameters were correlated with simplified pulmonary embolism severity index (sPESI) and with outcome groups, alone and in combinationwith tomographic right-to-left ventricular ratios (RV/LV). PBVm showed significant correlation with sPESI. PBVm presented higher accuracy than %PBV In the prediction of ICU admission or death in patients with PE, with the best performance when combined with RV/LV volumetric ratio.

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ABSTRACT Objective: COVID-19 has been associated with a significant burden to those who survive the acute phase. We aimed to describe the quality of life and symptoms of anxiety, depression, and posttraumatic stress disorder (PTSD) at 90 days after hospital discharge of COVID-19 patients. Methods: Patients with COVID-19 admitted to a private hospital in the city of São Paulo, Brazil, between April of 2020 and April of 2021 were interviewed by telephone at 30 and 90 days after discharge to assess the quality of life and symptoms of depression, anxiety, and PTSD. Results: A total of 2,138 patients were included. The mean age was 58.6 ± 15.8 years, and the median length of hospital stay was 9.0 (5.0-15.8) days. Between the two time points, depression increased from 3.1% to 7.2% (p < 0.001), anxiety increased from 3.2% to 6.2% (p < 0.001), and PTSD increased from 2.3% to 5.0% (p < 0.001). At least one physical symptom related to COVID-19 diagnosis persisted in 32% of patients at day 90. Conclusions: Persistence of physical symptoms was high even at 90 days after discharge. Although the prevalence of symptoms of anxiety, depression, and PTSD was low, these symptoms persisted for three months, with a significant increase between the time points. This finding indicates the need to identify at-risk patients so that they can be given an appropriate referral at discharge.

RESUMO Objetivo: A COVID-19 tem sido associada a um fardo significativo para aqueles que sobrevivem à fase aguda. Nosso objetivo foi descrever a qualidade de vida e sintomas de ansiedade, depressão e transtorno de estresse pós-traumático (TEPT) 90 dias após a alta hospitalar em pacientes com COVID-19. Métodos: Pacientes com COVID-19 internados em um hospital privado na cidade de São Paulo (SP) entre abril de 2020 e abril de 2021 foram entrevistados por telefone 30 e 90 dias após a alta para avaliar a qualidade de vida e sintomas de depressão, ansiedade e TEPT. Resultados: Foram incluídos 2.138 pacientes. A média de idade foi de 58,6 ± 15,8 anos, e a mediana do tempo de internação hospitalar foi de 9,0 (5,0-15,8) dias. Entre os dois momentos, a depressão aumentou de 3,1% para 7,2% (p < 0,001), a ansiedade, de 3,2% para 6,2% (p < 0,001), e o TEPT, de 2,3% para 5,0% (p < 0,001). Pelo menos um sintoma físico relacionado ao diagnóstico de COVID-19 persistia em 32% dos pacientes no 90º dia. Conclusões: A persistência dos sintomas físicos foi elevada mesmo 90 dias após a alta. Embora a prevalência de sintomas de ansiedade, depressão e TEPT tenha sido baixa, esses sintomas persistiram por três meses, com aumento significativo entre os momentos. Esse achado indica a necessidade de identificar os pacientes de risco para que possam receber o encaminhamento adequado no momento da alta.

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OBJECTIVE: To compare the lung mechanics and outcomes between COVID-19-associated acute respiratory distress syndrome and non-COVID-19-associated acute respiratory distress syndrome. METHODS: We combined data from two randomized trials in acute respiratory distress syndrome, one including only COVID-19 patients and the other including only patients without COVID-19, to determine whether COVID-19-associated acute respiratory distress syndrome is associated with higher 28-day mortality than non-COVID-19 acute respiratory distress syndrome and to examine the differences in lung mechanics between these two types of acute respiratory distress syndrome. RESULTS: A total of 299 patients with COVID-19-associated acute respiratory distress syndrome and 1,010 patients with non-COVID-19-associated acute respiratory distress syndrome were included in the main analysis. The results showed that non-COVID-19 patients used higher positive end-expiratory pressure (12.5cmH2O; SD 3.2 versus 11.7cmH2O SD 2.8; p < 0.001), were ventilated with lower tidal volumes (5.8mL/kg; SD 1.0 versus 6.5mL/kg; SD 1.2; p < 0.001) and had lower static respiratory compliance adjusted for ideal body weight (0.5mL/cmH2O/kg; SD 0.3 versus 0.6mL/cmH2O/kg; SD 0.3; p = 0.01). There was no difference between groups in 28-day mortality (52.3% versus 58.9%; p = 0.52) or mechanical ventilation duration in the first 28 days among survivors (13 [IQR 5 - 22] versus 12 [IQR 6 - 26], p = 0.46). CONCLUSION: This analysis showed that patients with non-COVID-19-associated acute respiratory distress syndrome have different lung mechanics but similar outcomes to COVID-19-associated acute respiratory distress syndrome patients. After propensity score matching, there was no difference in lung mechanics or outcomes between groups.

OBJETIVO: Comparar a mecânica pulmonar e os desfechos entre a síndrome do desconforto respiratório agudo associada à COVID-19 e a síndrome do desconforto respiratório agudo não associada à COVID-19. MÉTODOS: Combinamos dados de dois ensaios randomizados sobre a síndrome do desconforto respiratório agudo, um incluindo apenas pacientes com COVID-19 e o outro incluindo apenas pacientes sem COVID-19, para determinar se a síndrome do desconforto respiratório agudo associada à COVID-19 está associada à maior mortalidade aos 28 dias do que a síndrome do desconforto respiratório agudo não associada à COVID-19 e também examinar as diferenças na mecânica pulmonar entre esses dois tipos de síndrome do desconforto respiratório agudo. RESULTADOS: Foram incluídos na análise principal 299 pacientes com síndrome do desconforto respiratório agudo associada à COVID-19 e 1.010 pacientes com síndrome do desconforto respiratório agudo não associada à COVID-19. Os resultados mostraram que os pacientes sem COVID-19 utilizaram pressão positiva expiratória final mais alta (12,5cmH2O; DP 3,2 versus 11,7cmH2O; DP 2,8; p < 0,001), foram ventilados com volumes correntes mais baixos (5,8mL/kg; DP 1,0 versus 6,5mL/kg; DP 1,2; p < 0,001) e apresentaram menor complacência respiratória estática ajustada para o peso ideal (0,5mL/cmH2O/kg; DP 0,3 versus 0,6mL/cmH2O/kg; DP 0,3; p = 0,01). Não houve diferença entre os grupos quanto à mortalidade aos 28 dias (52,3% versus 58,9%; p = 0,52) ou à duração da ventilação mecânica nos primeiros 28 dias entre os sobreviventes (13 [IQ 5 - 22] dias versus 12 [IQ 6 - 26] dias; p = 0,46). CONCLUSÃO: Esta análise mostrou que os pacientes com síndrome do desconforto respiratório agudo não associada à COVID-19 têm mecânica pulmonar diferente, mas desfechos semelhantes aos dos pacientes com síndrome do desconforto respiratório agudo associada à COVID-19. Após pareamento por escore de propensão, não houve diferença na mecânica pulmonar e nem nos desfechos entre os grupos.

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Purpose: There is a significant lack of epidemiological data on hereditary cancer in Northeast Brazil. This is the largest study on the prevalence and mutational spectrum of cancer predisposition genes conducted in this region and the first in the State of Ceará. Methods: Patients ≥18 years of age that were referred to CHANCE (Grupo de Câncer Hereditário do Ceará) from March 2014 to December 2020 with testing criteria for breast cancer susceptibility genes according to NCCN v.1.2021 were eligible to participate. The inclusion of patients was limited to one individual per family and to those born in the State of Ceará. All patients underwent a hereditary cancer panel testing with at least 30 genes. Results: A total of 355 patients were included, and 97 (27.3%) carried a P/LP germline variant in 18 different genes. Among the 97 P/LP carriers, BRCA1 (31, 31.9%) and BRCA2 (25, 25.7%) were the most frequently mutated genes, followed by PALB2 (10, 10.3%), CHEK2 (7, 7.2%) and ATM (4, 4.1%). A small number of recurrent variants (detected in three or more individuals) in BRCA1, BRCA2, CHEK2 and ATM represented the majority of the P/LP variants described in this cohort. Conclusion: In this cohort, the prevalence of L/PL was high, particularly involving the BRCA1, BRCA2, PALB2, CHEK2 and ATM genes and, to a lesser extent than expected, the TP53 gene. A high frequency of recurrent variants was also observed, for which further and larger analyses should clarify the presence of any possible founder effect. Characterizing the mutational profile of cancer predisposition genes in diverse populations may contribute to cancer prevention and therapeutic management.