Search

Background: Capacity strain negatively impacts patient outcome, and the effects of patient surge are a continuous threat during the COVID-19 pandemic. Evaluating changes in mortality over time enables evidence-based resource planning, thus improving patient outcome. Our aim was to describe baseline risk factors associated with mortality among COVID-19 hospitalized patients and to compare mortality rates over time. Methods: We conducted a retrospective cohort study in the largest referral hospital for COVID-19 patients in Sao Paulo, Brazil. We investigated risk factors associated with mortality during hospitalization. Independent variables included age group, sex, the Charlson Comorbidity Index, admission period according to the stage of the first wave of the epidemic (early, peak, and late), and intubation. Results: We included 2949 consecutive COVID-19 patients. 1895 of them were admitted to the ICU, and 1473 required mechanical ventilation. Median length of stay in the ICU was 10 (IQR 5–17) days. Overall mortality rate was 35%, and the adjusted odds ratios for mortality increased with age, male sex, higher Charlson Comorbidity index, need for mechanical ventilation, and being admitted to the hospital during the wave peak of the epidemic. Being admitted to the hospital during the wave peak was associated with a 33% higher risk of mortality. Conclusions: In-hospital mortality was independently affected by the epidemic period. The recognition of modifiable operational variables associated with patient outcome highlights the importance of a preparedness plan and institutional protocols that include evidence-based practices and allocation of resources. [ABSTRACT FROM AUTHOR]

Introduction: Targeted therapy and immune checkpoint inhibitors (ICI) have drastically improved outcomes of metastatic non-small cell lung cancer (NSCLC) patients in outpatient settings. Because trials on critically ill patients are improbable, little is known about their efficacy among patients admitted to intensive care units (ICU). Methods: We retrospectively analyzed the clinical outcomes of critically-ill NSCLC patients receiving either ICI or targeted therapy during ICU admission at the MD Anderson Cancer Center from April 2016 to August 2020. We collected data on ICU admission diagnoses, sequential organ failure assessment (SOFA), previous cancer therapies, tumor gene mutations or translocations, and PD-Ll expression. Overall survival (OS) was calculated from the date of drug initiation using the Kaplan-Meier method. Results: Of 9898 ICU admissions, 9 patients with metastatic NSCLC who received either targeted therapy (5) or PD-' ICI (4) during ICU admission were included. The most common reasons for ICU admissions were tumor visceral crisis (3/9) and sepsis (3/9). The median (range) admission SOFA was 4 (2-11). Six patients were naive to systemic therapy. Five patients required mechanical ventilation. The median OS was 77 days (95%CI, 36-NA), and 5 patients were discharged alive (all received targeted therapy). The median OS of patients who received ICI was 25.5 days (95%CI, 8-NA) and for those who received targeted therapy was 2' 8 days (95%CI, 77-NA). At 6 and '2 months follow-up, 3 and 2 patients who received targeted therapy were still alive, respectively. Conclusions: Our exploratory findings indicate a possible benefit of targeted therapy but suggest a lack of clinical utility of PD-1 ICI for critically ill metastatic NSCLC patients. Because of the small sample size, further studies are needed to expand on this topic. [ABSTRACT FROM AUTHOR]

Background: High‐grade neuroendocrine carcinoma of the larynx (HG‐NECL) is rare and aggressive with limited data regarding response to systemic therapy. We evaluated clinicopathological features, therapeutic approaches, and outcomes in patients with laryngeal or hypopharyngeal HG‐NECL. Methods: Data were retrospectively collected through 1997–2020. Median disease‐free (mDFS), progression‐free (mPFS), and overall survival (mOS) were estimated using the Kaplan–Meier method. Results: Fifteen patients were identified; most had locoregional (N = 7) or metastatic disease (N = 5). The main curative‐intent treatment was chemoradiation concurrent with platinum‐based chemotherapy; the rate of complete response was 78%. Most patients (80%) developed recurrence; the mDFS was 13.1 months. For the first‐line palliative therapy, the ORR and mPFS were 50% and 3.1 months, respectively. For all patients, the mOS was 17.8 months, and 8.6 months for metastatic disease. Conclusion: Laryngeal HG‐NEC is associated with high relapse rates and dismal prognosis for those with recurrent/metastatic disease. Novel therapeutic strategies are needed. [ABSTRACT FROM AUTHOR]

Background: During the COVID-19 pandemic, creating tools to assess disease severity is one of the most important aspects of reducing the burden on emergency departments. Lung ultrasound has a high accuracy for the diagnosis of pulmonary diseases; however, there are few prospective studies demonstrating that lung ultrasound can predict outcomes in COVID-19 patients. We hypothesized that lung ultrasound score (LUS) at hospital admission could predict outcomes of COVID-19 patients. This is a prospective cohort study conducted from 14 March through 6 May 2020 in the emergency department (ED) of an urban, academic, level I trauma center. Patients aged 18 years and older and admitted to the ED with confirmed COVID-19 were considered eligible. Emergency physicians performed lung ultrasounds and calculated LUS, which was tested for correlation with outcomes. This protocol was approved by the local Ethics Committee number 3.990.817 (CAAE: 30417520.0.0000.0068). Results: The primary endpoint was death from any cause. The secondary endpoints were ICU admission and endotracheal intubation for respiratory failure. Among 180 patients with confirmed COVID-19 who were enrolled (mean age, 60 years; 105 male), the average LUS was 18.7 ± 6.8. LUS correlated with findings from chest CT and could predict the estimated extent of parenchymal involvement (mean LUS with < 50% involvement on chest CT, 15 ± 6.7 vs. 21 ± 6.0 with > 50% involvement, p < 0.001), death (AUC 0.72, OR 1.13, 95% CI 1.07 to 1.21; p < 0.001), endotracheal intubation (AUC 0.76, OR 1.17, 95% CI 1.09 to 1.26; p < 0.001), and ICU admission (AUC: 0.71, OR 1.14, 95% CI 1.07 to 1.21; p < 0.001). Conclusions: In COVID-19 patients admitted in ED, LUS was a good predictor of death, ICU admission, and endotracheal intubation. [ABSTRACT FROM AUTHOR]

Background: The first cases of coronavirus disease (COVID-19) in Brazil were diagnosed in February 2020. Our Emergency Department (ED) was designated as a COVID-19 exclusive service. We report our first 500 confirmed COVID-19 pneumonia patients. Methods: From 14 March to 16 May 2020, we enrolled all patients admitted to our ED that had a diagnosis of COVID-19 pneumonia. Infection was confirmed via nasopharyngeal swabs or tracheal aspirate PCR. The outcomes included hospital discharge, invasive mechanical ventilation, and in-hospital death, among others. Results: From 2219 patients received in the ED, we included 506 with confirmed COVID-19 pneumonia. We found that 333 patients were discharged home (65.9%), 153 died (30.2%), and 20 (3.9%) remained in the hospital. A total of 300 patients (59.3%) required ICU admission, and 227 (44.9%) needed invasive ventilation. The multivariate analysis found age, number of comorbidities, extension of ground glass opacities on chest CT and troponin with a direct relationship with all-cause mortality, whereas dysgeusia, use of angiotensin converting enzyme inhibitor or angiotensin-ii receptor blocker and number of lymphocytes with an inverse relationship with all-cause mortality Conclusions: This was a sample of severe patients with COVID-19, with 59.2% admitted to the ICU and 41.5% requiring mechanical ventilator support. We were able to ascertain the outcome in majority (96%) of patients. While the overall mortality was 30.2%, mortality for intubated patients was 55.9%. Multivariate analysis agreed with data found in other studies although the use of angiotensin converting enzyme inhibitor or angiotensin-ii receptor blocker as a protective factor could be promising but would need further studies. Trial registration: The study was registered in the Brazilian registry of clinical trials: RBR-5d4dj5. [ABSTRACT FROM AUTHOR]

The following information is missing from the Funding statement: This study was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) in the form of a grant awarded to ITV (2016/14566-4). Reference 1 Brandão Neto RA, Marchini JF, Marino LO, Alencar JCG, Lazar Neto F, Ribeiro S, et al. (2021) Mortality and other outcomes of patients with coronavirus disease pneumonia admitted to the emergency department: A prospective observational Brazilian study. [Extracted from the article]

Importance: There is no systemic therapy for recurrent or metastatic adenoid cystic carcinoma (ACC) approved by the US Food and Drug Administration., Objective: To examine the efficacy, safety, and tolerability of vascular endothelial growth factor receptor (VEGFR) inhibitors in recurrent or metastatic ACC., Data Sources: PubMed, Embase, and Cochrane Library were systematically searched for studies of VEGFR inhibitors in recurrent or metastatic ACC from database inception to August 31, 2023., Study Selection: Inclusion criteria were prospective clinical trials of recurrent or metastatic ACC treated with VEGFR inhibitors, reporting at least 1 outcome of interest specifically for ACC. Of 1963 identified studies, 17 (0.9%) met inclusion criteria., Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) reporting guideline was followed to extract data. Data were pooled using a random-effects generalized linear mixed model with 95% CIs., Main Outcomes and Measures: The primary efficacy outcome was best overall response to VEGFR inhibitors, including objective response, stable disease, or progressive disease (PD). Safety and tolerability outcomes included incidence of grade 3 or higher adverse events, rates of exit from trial due to PD or drug-related toxic effects, and dose reduction rate (DRR)., Results: A total of 17 studies comprising 560 patients with recurrent or metastatic ACC treated with 10 VEGFR inhibitors were included. The objective response rate was 6% (95% CI, 3%-12%; I2 = 71%) and stable disease was the most frequent best overall response (82%; 95% CI, 74%-87%; I2 = 67%). The 6-month disease control (defined as objective response and stable disease) rate was 54% (95% CI, 45%-62%; I2 = 52%). The rate of grade 3 or higher adverse events was 53% (95% CI, 42%-64%; I2 = 81%) and of DRR was 59% (95% CI, 40%-76%). Most patients (57%; 95% CI, 44%-70%; I2 = 83%) continued therapy until PD; 21% (95% CI, 15%-28%; I2 = 62%) of patients suspended therapy for toxic effects. In subgroup analysis by specific VEGFR inhibitor, the objective response rate was 14% (95% CI, 7%-25%; I2 = 0%), stable disease rate was 76% (95% CI, 63%-85%; I2 = 0%), proportion treated until PD was 61% (95% CI, 14%-94%; I2 = 94%), and DRR was 78% (95% CI, 66%-87%; I2 = 39%) with lenvatinib. Corresponding axitinib results were objective response rate of 8% (95% CI, 4%-15%; I2 = 0%) and stable disease rate of 85% (95% CI, 72%-92%; I2 = 69%), with 73% (95% CI, 63%-82%; I2 = 0%) of patients treated until PD, and the DRR was 22% (95% CI, 12%-38%; I2 = 77%). Rivoceranib had the highest objective response rate (24%; 95% CI, 7%-57%) but high heterogeneity among studies (I2 = 95%) and the lowest rate of patients who continued therapy until PD (35%; 95% CI, 20%-55%; I2 = 90%)., Conclusions and Relevance: This systematic review and meta-analysis found that VEGFR inhibitors were associated with high rates of disease stabilization in recurrent or metastatic ACC. Of 10 included VEGFR inhibitors, lenvatinib and axitinib were associated with the best combined and consistent efficacy, safety, and tolerability profiles, substantiating their inclusion in treatment guidelines.

Background: A local increase in angiotensin 2 after inactivation of angiotensin-converting enzyme 2 by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may induce a redox imbalance in alveolar epithelium cells, causing apoptosis, increased inflammation and, consequently, impaired gas exchange. We hypothesized that N-acetylcysteine (NAC) administration could restore this redox homeostasis and suppress unfavorable evolution in patients with coronavirus disease 2019 (COVID-19)., Methods: This was a double-blind, randomized, placebo-controlled, single-center trial conducted at the Emergency Department of Hospital das Clínicas, São Paulo, Brazil, to determine whether NAC in high doses can avoid respiratory failure in patients with COVID-19. We enrolled 135 patients with severe COVID-19 (confirmed or suspected), with an oxyhemoglobin saturation <94% or respiratory rate >24 breaths/minute. Patients were randomized to receive NAC 21 g (~300 mg/kg) for 20 hours or dextrose 5%. The primary endpoint was the need for mechanical ventilation. Secondary endpoints were time of mechanical ventilation, admission to the intensive care unit (ICU), time in ICU, and mortality., Results: Baseline characteristics were similar between the 2 groups, with no significant differences in age, sex, comorbidities, medicines taken, and disease severity. Also, groups were similar in laboratory tests and chest computed tomography scan findings. Sixteen patients (23.9%) in the placebo group received endotracheal intubation and mechanical ventilation, compared with 14 patients (20.6%) in the NAC group (P = .675). No difference was observed in secondary endpoints., Conclusions: Administration of NAC in high doses did not affect the evolution of severe COVID-19., Clinical Trials Registration: Brazilian Registry of Clinical Trials (REBEC): U1111-1250-356 (http://www.ensaiosclinicos.gov.br/rg/RBR-8969zg/)., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: To evaluate the first-attempt success rates and complications of endotracheal intubation of coronavirus disease 2019 (COVID-19) patients by emergency physicians., Methods: This prospective observational study was conducted from March 24, 2020 through May 28, 2020 at the emergency department (ED) of an urban, academic trauma center. We enrolled patients consecutively admitted to the ED with suspected or confirmed COVID-19 submitted to endotracheal intubation. No patients were excluded. The primary outcome was first-attempt intubation success, defined as successful endotracheal tube placement with the first device passed (endotracheal tube) during the first laryngoscope insertion confirmed with capnography. Secondary outcomes included the following complications: hypotension, hypoxemia, aspiration, and esophageal intubation., Results: A total of 112 patients with confirmed or suspected COVID-19 were enrolled. Median age was 61 years and 61 patients (54%) were men. The primary outcome, first-attempt intubation success, was achieved in 82% of patients. Among the 20 patients who were not intubated on the first attempt, 75% were intubated on the second attempt and 20% on the third attempt; cricothyrotomy was performed in 1 patient. Forty-eight (42%) patients were hypotensive and required norepinephrine immediately post-intubation. Fifty-eight (52%) experienced peri-intubation hypoxemia, and 2 patients (2%) had cardiac arrest. There were no cases of failed intubation resulting in death up to 24 hours after the procedure., Conclusion: Emergency physicians achieve high success rates when intubating COVID19 patients, although complications are frequent. However, these findings should be considered provisional until their generalizability is assessed in their institutions and setting., (© 2020 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of the American College of Emergency Physicians.)