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Purpose Trials of tocilizumab in patients with severe COVID-19 pneumonia have demonstrated mixed results, and the role of tocilizumab in combination with other treatments is uncertain. Here we evaluated whether tocilizumab plus remdesivir provides greater benefit than remdesivir alone in patients with severe COVID-19 pneumonia. Methods This randomized, double-blind, placebo-controlled, multicenter trial included patients hospitalized with severe COVID-19 pneumonia requiring > 6 L/min supplemental oxygen. Patients were randomly assigned (2:1 ratio) to receive tocilizumab 8 mg/kg or placebo intravenously plus ≤ 10 days of remdesivir. The primary outcome was time from randomization to hospital discharge or “ready for discharge” (defined as category 1, assessed by the investigator on a 7-category ordinal scale of clinical status) to day 28. Patients were followed for 60 days. Results Among 649 enrolled patients, 434 were randomly assigned to tocilizumab plus remdesivir and 215 to placebo plus remdesivir. 566 patients (88.2%) received corticosteroids during the trial to day 28. Median time from randomization to hospital discharge or “ready for discharge” was 14 (95% CI 12–15) days with tocilizumab plus remdesivir and 14 (95% CI 11–16) days with placebo plus remdesivir [log-rank P  = 0.74; Cox proportional hazards ratio 0.97 (95% CI 0.78–1.19)]. Serious adverse events occurred in 128 (29.8%) tocilizumab plus remdesivir and 72 (33.8%) placebo plus remdesivir patients; 78 (18.2%) and 42 (19.7%) patients, respectively, died by day 28. Conclusions Tocilizumab plus remdesivir did not shorten time to hospital discharge or “ready for discharge” to day 28 compared with placebo plus remdesivir in patients with severe COVID-19 pneumonia.

Background Noradrenaline is currently the first-line vasopressor in treatment of circulatory failure. Its dose reflects illness severity, and together with dopamine, dobutamine and adrenaline, it is used in the Sequential Organ Failure Assessment (SOFA) score to grade cardiovascular dysfunction. Over the years, noradrenaline use has increased and it has largely replaced dopamine. As part of the SOFA-2 update, we conducted a systematic review and dose-response meta-analysis to assess the association between noradrenaline dose and mortality. Methods We searched MEDLINE, Embase, and Web of Science from 1 January 2013 to 30 October 2024 for studies reporting mortality by noradrenaline dose in critically ill adults. The primary outcome was mortality. We generated pooled relative risks (RR) and assessed linear and non-linear dose–response relationships. Mortality was also analysed by SOFA-2 noradrenaline categories. The study followed PRISMA guidelines and was registered with PROSPERO (CRD42024501533). Results Nineteen studies, including totally 29,935 patients, were included in the systematic review, and six in the meta-analysis. We observed a consistent increase in mortality: the relative risk escalated by a factor of 1.5 for every 0.1 µg/kg/min increase in peak noradrenaline dose. We did not find inflection points in the dose-mortality curve. In SOFA-2 categories, hospital mortality was 16.5% in the dose category ≤ 0.2 µg/kg/min, 31.9% in the category > 0.2 to 0.4 µg/kg/min, and 40.3% in the category > 0.4 µg/kg/min ( p  < 0.001). Conclusions In critically ill patients, escalating doses of noradrenaline correlate with an exponentially rising relative risk of mortality. This dose-dependent pattern reinforces the role of noradrenaline dose as a marker of cardiovascular failure severity.

The rapid development of efficacious and safe vaccines against coronavirus disease 2019 (COVID-19) has been instrumental in mitigating the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Moreover, the emergence of SARS-CoV-2 variants raised concerns on the efficacy of these vaccines. Herein, we report two cases of breakthrough infections with the P1 variant in patients vaccinated with CoronaVac, which is one of the two vaccines authorized for emergency use in the Brazilian immunization program. Our observations suggest that the vaccine reduced the severity of the disease and highlight the potential risk of illness following vaccination and subsequent infection with the P1 variant as well as for continued efforts to prevent and diagnose infection in vaccinated persons.

Objective The aim of the present study was to validate the Simplified Acute Physiology Score II (SAPS II) and 3 (SAPS 3), the Mortality Probability Models III (MPM 0 -III), and the Cancer Mortality Model (CMM) in patients with cancer admitted to several intensive care units (ICU). Design Prospective multicenter cohort study. Setting Twenty-eight ICUs in Brazil. Patients Seven hundred and seventeen consecutive patients (solid tumors 93%; hematological malignancies 7%) included over a 2-month period. Interventions None. Measurements and main results Discrimination was assessed by area under receiver operating characteristic (AROC) curves and calibration by Hosmer–Lemeshow goodness-of-fit test. The main reasons for ICU admission were postoperative care (57%), sepsis (15%) and respiratory failure (10%). The ICU and hospital mortality rates were 21 and 30%, respectively. When all 717 patients were evaluated, discrimination was superior for both SAPS II (AROC = 0.84) and SAPS 3 (AROC = 0.84) scores compared to CMM (AROC = 0.79) and MPM 0 -III (AROC = 0.71) scores ( P  < 0.05 in all comparisons). Calibration was better using CMM and the customized equation of SAPS 3 score for South American countries (CSA). MPM 0 -III, SAPS II and standard SAPS 3 scores underestimated mortality (standardized mortality ratio, SMR > 1), while CMM tended to overestimation (SMR = 0.48). However, using the SAPS 3 for CSA resulted in more precise estimations of the probability of death [SMR = 1.02 (95% confidence interval = 0.87–1.19)]. Similar results were observed when scheduled surgical patients were excluded. Conclusions In this multicenter study, the customized equation of SAPS 3 score for CSA was found to be accurate in predicting outcomes in cancer patients requiring ICU admission.

Background Non-alcoholic fatty liver disease (NAFLD) associated with obesity comprises pathological changes ranging from steatosis to steatohepatitis; these can evolve to cirrhosis and hepatocellular carcinoma. Objectives The objectives of this study are to assess the prevalence of and predictive markers for steatohepatitis in obese patients undergoing bariatric surgery. Methods A prospective study of 184 morbidly obese patients undergoing bariatric surgery formed the study cohort. Patients taking potentially hepatotoxic medications and those with viral diseases and a history of excessive alcohol consumption were excluded. Liver biopsies were performed during surgery with a “Trucut” needle. Patients were classified into the following groups according to the histopathological findings: normal, steatosis, mild steatohepatitis, and moderate-severe steatohepatitis. Factors associated with steatohepatitis were evaluated using logistic regression. p values <0.05 were considered significant. Results The prevalence of NAFLD was 84 % (steatosis, 22.0 %; mild steatohepatitis, 30.8 %; moderate-severe steatohepatitis, 32.0 %). Independent predictive factors for steatohepatitis were age (odds ratio (OR), 1.05; 95 % confidence interval (CI), 1.01–1.09; p  = 0.011), waist circumference (OR, 1.03; 95 % CI, 1.00–1.06; p  = 0.021), serum alanine aminotransferase (ALT) levels (OR, 1.04; 95 % CI, 1.01–1.08; p  = 0.005), and serum triglyceride levels (OR, 1.01; 95 % CI, 1.00–1.01; p  = 0.042). Score values for each predictor were derived from regression coefficients and odds ratio, and a total (risk) score was obtained from the sum of the points to evaluate the probability of having steatohepatitis. Conclusion Age, waist circumference, serum ALT levels, and serum triglyceride levels are efficient and non-invasive predictive markers for the diagnosis and management of steatohepatitis in morbidly obese patients.

Background The gold-standard method for establishing a microbiological diagnosis of COVID-19 is reverse-transcriptase polymerase chain reaction (RT-PCR). This study aimed to evaluate the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of a set of clinical-radiological criteria for COVID-19 screening in patients with severe acute respiratory failure (SARF) admitted to intensive care units (ICUs), using reverse-transcriptase polymerase chain reaction (RT-PCR) as the reference standard. Methods Diagnostic accuracy study including a historical cohort of 1009 patients consecutively admitted to ICUs across six hospitals in Curitiba (Brazil) from March to September, 2020. The sample was stratified into groups by the strength of suspicion for COVID-19 (strong versus weak) using parameters based on three clinical and radiological (chest computed tomography) criteria. The diagnosis of COVID-19 was confirmed by RT-PCR (referent). Results With respect to RT-PCR, the proposed criteria had 98.5% (95% confidence interval [95% CI] 97.5–99.5%) sensitivity, 70% (95% CI 65.8–74.2%) specificity, 85.5% (95% CI 83.4–87.7%) accuracy, PPV of 79.7% (95% CI 76.6–82.7%) and NPV of 97.6% (95% CI 95.9–99.2%). Similar performance was observed when evaluated in the subgroups of patients admitted with mild/moderate respiratory disfunction, and severe respiratory disfunction. Conclusion The proposed set of clinical-radiological criteria were accurate in identifying patients with strong versus weak suspicion for COVID-19 and had high sensitivity and considerable specificity with respect to RT-PCR. These criteria may be useful for screening COVID-19 in patients presenting with SARF.

Purpose To generate consensus and provide expert clinical practice statements for the management of adult sepsis in resource-limited settings. Methods An international multidisciplinary Steering Committee with expertise in sepsis management and including a Delphi methodologist was convened by the Asia Pacific Sepsis Alliance (APSA). The committee selected an international panel of clinicians and researchers with expertise in sepsis management. A Delphi process based on an iterative approach was used to obtain the final consensus statements. Results A stable consensus was achieved for 30 (94%) of the statements by 41 experts after four survey rounds. These include consensus on managing patients with sepsis outside a designated critical care area, triggers for escalating clinical management and criteria for safe transfer to another facility. The experts agreed on the following: in the absence of serum lactate, clinical parameters such as altered mental status, capillary refill time and urine output may be used to guide resuscitation; special considerations regarding the volume of fluid used for resuscitation, especially in tropical infections, including the use of simple tests to assess fluid responsiveness when facilities for advanced hemodynamic monitoring are limited; use of Ringer’s lactate or Hartmann’s solution as balanced salt solutions; epinephrine when norepinephrine or vasopressin are unavailable; and the administration of vasopressors via a peripheral vein if central venous access is unavailable or not feasible. Similarly, where facilities for investigation are unavailable, there was consensus for empirical antimicrobial administration without delay when sepsis was strongly suspected, as was the empirical use of antiparasitic agents in patients with suspicion of parasitic infections. Conclusion Using a Delphi method, international experts reached consensus to generate expert clinical practice statements providing guidance to clinicians worldwide on the management of sepsis in resource-limited settings. These statements complement existing guidelines where evidence is lacking and add relevant aspects of sepsis management that are not addressed by current international guidelines. Future studies are needed to assess the effects of these practice statements and address remaining uncertainties.

Hypothermia occurs commonly during surgery and can cause postoperative complications. We aimed to describe the characteristics and outcomes of hypothermia in patients undergoing major surgeries. This prospective, observational, multicenter study of a nationally representative sample included all patients over 18 years of age admitted to an intensive care unit (ICU). Thirty ICUs were selected randomly at national level. The main outcome measure was the proportion of patients who developed postoperative hypothermia in the first 24 hours of ICU admission. Patients were divided into three groups based on temperature: <35°C, <36°C, and ≥36°C (no hypothermia). Patients' characteristics, postoperative complications, and risk factors were evaluated in all groups. To verify whether hypothermia was a strong risk factor for postoperative complications, a Kaplan-Meier curve was generated and adjusted using a Cox regression model. In total, 738 patients had their temperatures measured. The percentage of patients with temperature <35°C (median [Q1-Q3], 34.7°C [34.3-34.9°C]) was 19.1% (95% confidence interval [CI] = 16.1-22.5) and that of patients with temperature <36°C (median [Q1-Q3], 35.4°C [35.0-35.8°C]) was 64% (95% CI = 58.3-70.0). The percentage of surgical complications was 38.9%. Patients with hypothermia were older, had undergone abdominal surgeries, had undergone procedures of longer duration, and had more comorbidities. A postoperative temperature ≤35°C was an independent risk for composite postoperative complications (hazard ratio = 1.523, 95% CI = 1.15-2.0), especially coagulation and infection. Inadvertent hypothermia was frequent among patients admitted to the ICU and occurred more likely after abdominal surgery, after a long procedure, in elderly patients, and in patients with a higher number of comorbidities. Low postoperative temperature was associated with postoperative complications.

The aim of the study was to characterize the practices of Brazilian ICU physicians toward sedation and delirium. A cross-sectional survey was conducted among a convenience sample of critical care physicians between April and June 2008. One thousand fifteen critical care physicians responded. Sedation scoring systems were used by 893 (88.3%) of the respondents. The Ramsay and Richmond Agitation-Sedation Scale were used by 81.9% and 6.8% of the respondents, respectively. Most respondents did not discuss sedation targets (62.8%) or practice daily sedative interruption (68.3%) in most patients. More than half of the respondents (52.7%) used a sedation protocol, and the most used sedatives were midazolam (97.8%), fentanyl (91.5%), and propofol (55%). A significant rate of the respondents (42.7%) estimated that more than 25% of patients under mechanical ventilation have delirium, but 53.5% occasionally assessed patients for delirium. Thirteen percent used specific delirium scales, with the Confusion Assessment Method for intensive care unit (ICU) being the most applied. Delirium was often treated with haloperidol (88.1%); however, atypical antipsychotics (36.3%) and benzodiazepines (42.3%) were also used. Despite the recent advances in knowledge of sedation and delirium, most of them are still not translated into clinical practice. Significant variation in practice is observed among ICU physicians and represents a potential target for future research and educational interventions.