Effect of immediate initiation of invasive ventilation on mortality in acute hypoxemic respiratory failure: a target trial emulation.

PURPOSE: Invasive ventilation is a fundamental treatment in intensive care but its precise timing is difficult to determine. This study aims at assessing the effect of initiating invasive ventilation versus waiting, in patients with hypoxemic respiratory failure without immediate reason for intubation on one-year mortality. METHODS: Emulation of a target trial to estimate the benefit of immediately initiating invasive ventilation in hypoxemic respiratory failure, versus waiting, among patients within the first 48-h of hypoxemia. The eligible population included non-intubated patients with SpO2/FiO2 ≤ 200 and SpO2 ≤ 97%. The target trial was emulated using a single-center database (MIMIC-IV) which contains granular information about clinical status. The hourly probability to receive mechanical ventilation was continuously estimated. The hazard ratios for the primary outcome, one-year mortality, and the secondary outcome, 30-day mortality, were estimated using weighted Cox models with stabilized inverse probability weights used to adjust for measured confounding. RESULTS: 2996 Patients fulfilled the inclusion criteria of whom 792 were intubated within 48 h. Among the non-invasive support devices, the use of oxygen through facemask was the most common (75%). Compared to patients with the same probability of intubation but who were not intubated, intubation decreased the hazard of dying for the first year after ICU admission HR 0.81 (95% CI 0.68-0.96, p = 0.018). Intubation was associated with a 30-day mortality HR of 0.80 (95% CI 0.64-0.99, p = 0.046). CONCLUSION: The initiation of mechanical ventilation in patients with acute hypoxemic respiratory failure reduced the hazard of dying in this emulation of a target trial.

First-year outcomes of very low birth weight preterm singleton infants with hypoxemic respiratory failure treated with milrinone and inhaled nitric oxide (iNO) compared to iNO alone: A nationwide retrospective study.

BACKGROUND: Inhaled nitric oxide (iNO) has a beneficial effect on hypoxemic respiratory failure. The increased use of concurrent iNO and milrinone was observed. We aimed to report the trends of iNO use in the past 15 years in Taiwan and compare the first-year outcomes of combining iNO and milrinone to the iNO alone in very low birth weight preterm (VLBWP) infants under mechanical ventilation. METHODS: This nationwide cohort study enrolled preterm singleton infants with birth weight <1500g treated with iNO from 2004 to 2019. Infants were divided into two groups, with a combination of intravenous milrinone (Group 2, n = 166) and without milrinone (Group 1, n = 591). After propensity score matching (PSM), each group's sample size is 124. The primary outcomes were all-cause mortality and the respiratory condition, including ventilator use and duration. The secondary outcomes were preterm morbidities within one year after birth. RESULTS: After PSM, more infants in Group 2 needed inotropes. The mortality rate was significantly higher in Group 2 than in Group 1 from one month after birth till 1 year of age (55.1% vs. 13.5%) with the adjusted hazard ratio of 4.25 (95%CI = 2.42-7.47, p <0.001). For infants who died before 36 weeks of postmenstrual age (PMA), Group 2 had longer hospital stays compared to Group 1. For infants who survived after 36 weeks PMA, the incidence of moderate and severe bronchopulmonary dysplasia (BPD) was significantly higher in Group 2 than in Group 1. For infants who survived until one year of age, the incidence of pneumonia was significantly higher in Group 2 (28.30%) compared to Group 1 (12.62%) (p = 0.0153). CONCLUSION: Combined treatment of iNO and milrinone is increasingly applied in VLBWP infants in Taiwan. This retrospective study did not support the benefits of combining iNO and milrinone on one-year survival and BPD prevention. A future prospective study is warranted.

Trophic Nutrition in ICU Patients Undergoing High-Flow Oxygen Therapy and/or Noninvasive Mechanical Ventilation: The Nutri-Trophic Study.

Enteral nutrition (EN) therapy in ICU patients requiring oxygen therapy with high-flow nasal cannula (HFNC) and/or noninvasive mechanical ventilation (NIMV) is controversial. A prospective, cohort, observational, and multicenter study was conducted in 10 ICUs in Spain to analyze the 90-day mortality, tolerance, side effects, and infectious complications of trophic EN in patients requiring HFNC therapy and/or NIVM. A total of 149 patients were enrolled. The mean age, severity scores, tracheobronchitis, bacteremia, and antimicrobial therapy were significantly higher in deceased than in living patients (p < 0.05), and the mortality rate was 14.8%. A total of 110 patients received oral trophic feedings, 36 patients received nasogastric tube feedings (NGFs), and 3 received mixed feedings. Trophic EN was discontinued in only ten (14.9%) patients because of feeding-related complications. The variables selected for the multivariate logistic regression on feeding discontinuation were SOFA upon admission (OR per unit = 1.461) and urea (OR per mg/dL = 1.029). There were no significant differences in the development of new infections according to the route of EN administration. Early trophic feeding administered to patients with acute respiratory failure requiring noninvasive ventilation is safe and feasible, and is associated with few dietary and infectious complications in a mortality, setting comparable to similar studies.

High-Flow Nasal Cannula Versus Noninvasive Ventilation as Initial Treatment in Acute Hypoxia: A Propensity Score-Matched Study.

IMPORTANCE: Patients presenting to the emergency department (ED) with hypoxemia often have mixed or uncertain causes of respiratory failure. The optimal treatment for such patients is unclear. Both high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) are used. OBJECTIVES: We sought to compare the effectiveness of initial treatment with HFNC versus NIV for acute hypoxemic respiratory failure. DESIGN SETTING AND PARTICIPANTS: We conducted a retrospective cohort study of patients with acute hypoxemic respiratory failure treated with HFNC or NIV within 24 hours of arrival to the University of Michigan adult ED from January 2018 to December 2022. We matched patients 1:1 using a propensity score for odds of receiving NIV. MAIN OUTCOMES AND MEASURES: The primary outcome was major adverse pulmonary events (28-d mortality, ventilator-free days, noninvasive respiratory support hours) calculated using a win ratio. RESULTS: A total of 1154 patients were included. Seven hundred twenty-six (62.9%) received HFNC and 428 (37.1%) received NIV. We propensity score matched 668 of 1154 (57.9%) patients. Patients on NIV versus HFNC had lower 28-day mortality (16.5% vs. 23.4%, p = 0.033) and required noninvasive treatment for fewer hours (median 7.5 vs. 13.5, p < 0.001), but had no difference in ventilator-free days (median [interquartile range]: 28 [26, 28] vs. 28 [10.5, 28], p = 0.199). Win ratio for composite major adverse pulmonary events favored NIV (1.38; 95% CI, 1.15-1.65; p < 0.001). CONCLUSIONS AND RELEVANCE: In this observational study of patients with acute hypoxemic respiratory failure, initial treatment with NIV compared with HFNC was associated with lower mortality and fewer composite major pulmonary adverse events calculated using a win ratio. These findings underscore the need for randomized controlled trials to further understand the impact of noninvasive respiratory support strategies.

Use of CPAP Ventilation in Non-ICU Wards May Influence Outcomes in Patients with Severe Respiratory COVID-19.

Background and Objectives: The COVID-19 disease has significantly burdened the healthcare system, including all units of severe patient treatment. Non-intensive care units were established to rationalize the capacity within the Intensive Care Unit (ICU) and to create a unit where patients with Acute Respiratory Distress Syndrome (ARDS) could be treated with non-invasive Continuous Positive Air Pressure (CPAP) outside the ICU. This unicentric retrospective study aimed to assess the efficacy of NIV Treatment in Patients of the fourth pandemic wave and how its application affects the frequency and mortality of ICU-treated patients at University Hospital Rijeka compared to earlier waves of the COVID-19 pandemic. Furthermore, the study showcases the effect of the Patient/Nurse ratio (P/N ratio) on overall mortality in the ICU. Materials and Methods: The study was conducted on two groups of patients with respiratory insufficiency in the second and third pandemic waves, treated in the COVID Respiratory Centre (CRC) (153 patients). We also reviewed a cohort of patients from the fourth pandemic wave who were initially hospitalized in a COVID-6 non-intensive unit from 1 October 2021 to 1 November 2022 (102 patients), and some of them escalated to CRC. Results: The introduction of the CPAP non-invasive ventilation method as a means of hypoxic respiratory failure treatment in non-intensive care units has decreased the strain, overall number of admissions, and CRC patient mortality. The overall fourth wave mortality was 29.4%, compared to the 58.2% overall mortality of the second and third waves. Conclusions: As a result, this has decreased CRC patient admissions and, by itself, overall mortality.

Acute respiratory failure due to pulmonary exacerbation in children with cystic fibrosis admitted in a pediatric intensive care unit: outcomes and factors associated with mortality.

BACKGROUND: Children with advanced pulmonary disease due to cystic fibrosis (CF) are at risk of acute respiratory failure due to pulmonary exacerbations leading to their admission to pediatric intensive care units (PICU). The objectives of this study were to determine short and medium-term outcomes of children with CF admitted to PICU for acute respiratory failure due to pulmonary exacerbation and to identify prognosis factors. METHODS: This retrospective monocentric study included patients less than 18 years old admitted to the PICU of a French university hospital between 2000 and 2020. Cox proportional hazard regression methods were used to determine prognosis factors of mortality or lung transplant. RESULTS: Prior to PICU admission, the 29 patients included (median age 13.5 years) had a severe lung disease (median Forced Expiratory Volume in 1 s percentage predicted at 29%). Mortality rates were respectively 17%, 31%, 34%, 41% at discharge and at 3, 12 and 36 months post-discharge. Survival rates free of lung transplant were 34%, 32%, 24% and 17% respectively. Risk factors associated with mortality or lung transplant using the univariate analysis were female sex and higher pCO2 and chloride levels at PICU admission, and following pre admission characteristics: home respiratory and nutritional support, registration on lung transplant list and Stenotrophomonas Maltophilia bronchial colonization. CONCLUSION: Children with CF admitted to PICU for acute respiratory failure secondary to pulmonary exacerbations are at high risk of death, both in the short and medium terms. Lung transplant is their main chance of survival and should be considered early.

Hospitalizaciones y eventos por insuficiencia cardiaca sistólica y diastólica en España entre 2016 y 2019. Un estudio de base poblacional / Hospital admissions and outcomes for systolic and diastolic heart failure in Spain between 2016 and 2019: A population-based study

Antecedentes y objetivos: En España carecemos de datos poblacionales de hospitalizaciones por insuficiencia cardiaca (IC) según sea sistólica o diastólica. Analizamos las diferencias clínicas, en mortalidad intrahospitalaria y reingresos de causa cardiovascular a los 30 días entre ambos tipos. Métodos: Estudio observacional retrospectivo de pacientes dados de alta con el diagnóstico principal de IC de los hospitales del Sistema Nacional de Salud entre 2016 y 2019, distinguiendo entre IC sistólica y diastólica. La fuente de datos fue el conjunto mínimo básico de datos del Ministerio de Sanidad. Se calcularon las razones de mortalidad intrahospitalaria y de reingreso a los 30 días estandarizadas por riesgo usando sendos modelos de regresión logística multinivel de ajuste de riesgo. Resultados: Se seleccionaron 190.200 episodios de IC. De ellos, 163.727 (86,1%) fueron por IC diastólica y se caracterizaron por presentar mayor edad, mayor proporción de mujeres, de diabetes y de insuficiencia renal que los de IC sistólica. Según los modelos de ajuste de riesgo la IC diastólica, frente a la sistólica, se comportó como un factor protector de mortalidad intrahospitalaria (odds ratio [OR]: 0,79; intervalo de confianza del 95% [IC 95%]: 0,75-0,83; p<0,001) y de reingreso de causa cardiovascular a los 30 días (OR: 0,93; IC 95%: 0,88-0,97; p0,002). Conclusiones: En España, entre 2016 y 2019, los episodios de hospitalización por IC fueron mayoritariamente por IC diastólica. Según los modelos de ajuste de riesgo la IC diastólica, con respecto a la sistólica, fue un factor protector de mortalidad intrahospitalaria y de reingreso de causa cardiovascular a los 30 días.(AU)

Background and purpose: In Spain there is a lack of population data that specifically compare hospitalization for systolic and diastolic heart failure (HF). We assessed clinical characteristics, in-hospital mortality and 30-day cardiovascular readmission rates differentiating by HF type. Methods: We conducted a retrospective observational study of patients discharged with the principal diagnosis of HF from The National Health System’ acute hospital during 2016-2019, distinguishing between systolic and diastolic HF. The source of the data was the Minimum Basic Data Set. The risk-standardized in-hospital mortality ratio and risk-standardized 30-day cardiovascular readmission ratio were calculated using multilevel risk adjustment models. Results: The 190,200 episodes of HF were selected. Of these, 163,727 (86.1%) were classified as diastolic HF and were characterized by older age, higher proportion of women, diabetes mellitus, dementia and renal failure than those with systolic HF. In the multilevel risk adjustment models, diastolic HF was a protective factor for both in-hospital mortality (odds ratio [OR]: 0.79; 95% confidence interval [CI]: 0.75-0.83; P<.001) and 30-day cardiovascular readmission versus systolic HF (OR: 0.93; 95% CI: 0.88-0.97; P=.002). Conclusions: In Spain, between 2016 and 2019, hospitalization episodes for HF were mostly due to diastolic HF. According to the multilevel risk adjustment models, diastolic HF compared to systolic HF was a protective factor for both in-hospital mortality and 30-day cardiovascular readmission.(AU)

Effect of Helmet Noninvasive Ventilation vs Usual Respiratory Support on Mortality Among Patients With Acute Hypoxemic Respiratory Failure Due to COVID-19: The HELMET-COVID Randomized Clinical Trial.

Importance: Helmet noninvasive ventilation has been used in patients with COVID-19 with the premise that helmet interface is more effective than mask interface in delivering prolonged treatments with high positive airway pressure, but data about its effectiveness are limited. Objective: To evaluate whether helmet noninvasive ventilation compared with usual respiratory support reduces mortality in patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. Design, Setting, and Participants: This was a multicenter, pragmatic, randomized clinical trial that was conducted in 8 sites in Saudi Arabia and Kuwait between February 8, 2021, and November 16, 2021. Adult patients with acute hypoxemic respiratory failure (n = 320) due to suspected or confirmed COVID-19 were included. The final follow-up date for the primary outcome was December 14, 2021. Interventions: Patients were randomized to receive helmet noninvasive ventilation (n = 159) or usual respiratory support (n = 161), which included mask noninvasive ventilation, high-flow nasal oxygen, and standard oxygen. Main Outcomes and Measures: The primary outcome was 28-day all-cause mortality. There were 12 prespecified secondary outcomes, including endotracheal intubation, barotrauma, skin pressure injury, and serious adverse events. Results: Among 322 patients who were randomized, 320 were included in the primary analysis, all of whom completed the trial. Median age was 58 years, and 187 were men (58.4%). Within 28 days, 43 of 159 patients (27.0%) died in the helmet noninvasive ventilation group compared with 42 of 161 (26.1%) in the usual respiratory support group (risk difference, 1.0% [95% CI, -8.7% to 10.6%]; relative risk, 1.04 [95% CI, 0.72-1.49]; P = .85). Within 28 days, 75 of 159 patients (47.2%) required endotracheal intubation in the helmet noninvasive ventilation group compared with 81 of 161 (50.3%) in the usual respiratory support group (risk difference, -3.1% [95% CI, -14.1% to 7.8%]; relative risk, 0.94 [95% CI, 0.75-1.17]). There were no significant differences between the 2 groups in any of the prespecified secondary end points. Barotrauma occurred in 30 of 159 patients (18.9%) in the helmet noninvasive ventilation group and 25 of 161 (15.5%) in the usual respiratory support group. Skin pressure injury occurred in 5 of 159 patients (3.1%) in the helmet noninvasive ventilation group and 10 of 161 (6.2%) in the usual respiratory support group. There were 2 serious adverse events in the helmet noninvasive ventilation group and 1 in the usual respiratory support group. Conclusions and Relevance: Results of this study suggest that helmet noninvasive ventilation did not significantly reduce 28-day mortality compared with usual respiratory support among patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. However, interpretation of the findings is limited by imprecision in the effect estimate, which does not exclude potentially clinically important benefit or harm. Trial Registration: ClinicalTrials.gov Identifier: NCT04477668.

Effect of High-Flow Nasal Cannula Oxygen vs Standard Oxygen Therapy on Mortality in Patients With Respiratory Failure Due to COVID-19: The SOHO-COVID Randomized Clinical Trial.

Importance: The benefit of high-flow nasal cannula oxygen (high-flow oxygen) in terms of intubation and mortality in patients with respiratory failure due to COVID-19 is controversial. Objective: To determine whether the use of high-flow oxygen, compared with standard oxygen, could reduce the rate of mortality at day 28 in patients with respiratory failure due to COVID-19 admitted in intensive care units (ICUs). Design, Setting, and Participants: The SOHO-COVID randomized clinical trial was conducted in 34 ICUs in France and included 711 patients with respiratory failure due to COVID-19 and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen equal to or below 200 mm Hg. It was an ancillary trial of the ongoing original SOHO randomized clinical trial, which was designed to include patients with acute hypoxemic respiratory failure from all causes. Patients were enrolled from January to December 2021; final follow-up occurred on March 5, 2022. Interventions: Patients were randomly assigned to receive high-flow oxygen (n = 357) or standard oxygen delivered through a nonrebreathing mask initially set at a 10-L/min minimum (n = 354). Main Outcomes and Measures: The primary outcome was mortality at day 28. There were 13 secondary outcomes, including the proportion of patients requiring intubation, number of ventilator-free days at day 28, mortality at day 90, mortality and length of stay in the ICU, and adverse events. Results: Among the 782 randomized patients, 711 patients with respiratory failure due to COVID-19 were included in the analysis (mean [SD] age, 61 [12] years; 214 women [30%]). The mortality rate at day 28 was 10% (36/357) with high-flow oxygen and 11% (40/354) with standard oxygen (absolute difference, -1.2% [95% CI, -5.8% to 3.4%]; P = .60). Of 13 prespecified secondary outcomes, 12 showed no significant difference including in length of stay and mortality in the ICU and in mortality up until day 90. The intubation rate was significantly lower with high-flow oxygen than with standard oxygen (45% [160/357] vs 53% [186/354]; absolute difference, -7.7% [95% CI, -14.9% to -0.4%]; P = .04). The number of ventilator-free days at day 28 was not significantly different between groups (median, 28 [IQR, 11-28] vs 23 [IQR, 10-28] days; absolute difference, 0.5 days [95% CI, -7.7 to 9.1]; P = .07). The most common adverse events were ventilator-associated pneumonia, occurring in 58% (93/160) in the high-flow oxygen group and 53% (99/186) in the standard oxygen group. Conclusions and Relevance: Among patients with respiratory failure due to COVID-19, high-flow nasal cannula oxygen, compared with standard oxygen therapy, did not significantly reduce 28-day mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT04468126.

Proteome-wide Mendelian randomization identifies causal links between blood proteins and severe COVID-19.

In November 2021, the COVID-19 pandemic death toll surpassed five million individuals. We applied Mendelian randomization including >3,000 blood proteins as exposures to identify potential biomarkers that may indicate risk for hospitalization or need for respiratory support or death due to COVID-19, respectively. After multiple testing correction, using genetic instruments and under the assumptions of Mendelian Randomization, our results were consistent with higher blood levels of five proteins GCNT4, CD207, RAB14, C1GALT1C1, and ABO being causally associated with an increased risk of hospitalization or respiratory support/death due to COVID-19 (ORs = 1.12-1.35). Higher levels of FAAH2 were solely associated with an increased risk of hospitalization (OR = 1.19). On the contrary, higher levels of SELL, SELE, and PECAM-1 decrease risk of hospitalization or need for respiratory support/death (ORs = 0.80-0.91). Higher levels of LCTL, SFTPD, KEL, and ATP2A3 were solely associated with a decreased risk of hospitalization (ORs = 0.86-0.93), whilst higher levels of ICAM-1 were solely associated with a decreased risk of respiratory support/death of COVID-19 (OR = 0.84). Our findings implicate blood group markers and binding proteins in both hospitalization and need for respiratory support/death. They, additionally, suggest that higher levels of endocannabinoid enzymes may increase the risk of hospitalization. Our research replicates findings of blood markers previously associated with COVID-19 and prioritises additional blood markers for risk prediction of severe forms of COVID-19. Furthermore, we pinpoint druggable targets potentially implicated in disease pathology.

Psychological Dimensions of Palliative Care Consultation: Approaches to Seriously Ill Patients at the End of Life.

Mental health clinicians often hear seriously ill patients ask the unanswerable: Why did this happen? What is the meaning of my suffering? In the inpatient setting, general medical ward, or oncology unit, patients are confronted with their mortality in new, urgent ways. Palliative medicine, or the specialized, comprehensive care of patients facing a life-limiting illness, occupies a unique and liminal space. Although often practiced by clinicians with non-mental health training backgrounds, there exists ample psychological content to be explored in the palliative care encounter. In this article, we present the case of a husband and international businessperson who experienced terminal complications from an advanced stage lung cancer. His illness was not responsive to multiple cancer-directed treatments, and he developed respiratory failure requiring high levels of supplemental oxygen support, from which he was unable to wean. Palliative care consultation was sought with the multiple objectives of ameliorating his severe death anxiety and persistent dyspnea as well as assisting in the clarification of his end-of-life wishes. Our goal with this case presentation and related discussion is to introduce the psychological aspects of palliative medicine to psychiatrists and psychotherapists.

New risk scoring system for predicting 3-month mortality after acute exacerbation of idiopathic pulmonary fibrosis.

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is often fatal. A straightforward staging system for AE-IPF would improve prognostication, guide patient management, and facilitate research. The aim of study is to develop a multidimensional prognostic AE-IPF staging system that uses commonly measured clinical variables. This retrospective study analyzed data from 353 consecutive patients with IPF admitted to our hospital during the period from January 2008 through January 2018. Multivariate analysis of information from a database of 103 recorded AE-IPF cases was used to identify factors associated with 3-month mortality. A clinical prediction model for AE-IPF was developed by using these retrospective data. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of this model. Logistic regression analysis showed that PaO2/FiO2 ratio, diffuse HRCT pattern, and serum C-reactive protein (CRP) were significantly associated with 3-month mortality; thus, PaO2/FiO2 ratio < 250 (P), CRP ≥ 5.5 (C), and diffuse HRCT pattern (radiological) (R) were included in the final model. A model using continuous predictors and a simple point-scoring system (PCR index) was developed. For the PCR index, the area under the ROC curve was 0.7686 (P < 0.0001). The sensitivity of the scoring system was 78.6% and specificity was 67.8%. The PCR index identified four severity grades (0, 1, 2, and 3), which were associated with a 3-month mortality of 7.7%, 29.4%, 54.8%, and 80%, respectively. The present PCR models using commonly measured clinical and radiologic variables predicted 3-month mortality in patients with AE-IPF.

Noninvasive ventilation and high-flow nasal cannula in patients with acute hypoxemic respiratory failure by covid-19: A retrospective study of the feasibility, safety and outcomes.

BACKGROUND: Noninvasive ventilation (NIV) and High-flow nasal cannula (HFNC) are the main forms of treatment for acute respiratory failure. This study aimed to evaluate the effect, safety, and applicability of the NIV and HFNC in patients with acute hypoxemic respiratory failure (AHRF) caused by COVID-19. METHODS: In this retrospective study, we monitored the effect of NIV and HFNC on the SpO2 and respiratory rate before, during, and after treatment, length of stay, rates of endotracheal intubation, and mortality in patients with AHRF caused by COVID-19. Additionally, data regarding RT-PCR from physiotherapists who were directly involved in assisting COVID-19 patients and non-COVID-19. RESULTS: 62.2 % of patients were treated with HFNC. ROX index increased during and after NIV and HFNC treatment (P < 0.05). SpO2 increased during NIV treatment (P < 0.05), but was not maintained after treatment (P = 0.17). In addition, there was no difference in the respiratory rate during or after the NIV (P = 0.95) or HFNC (P = 0.60) treatment. The mortality rate was 35.7 % for NIV vs 21.4 % for HFNC (P = 0.45), while the total endotracheal intubation rate was 57.1 % for NIV vs 69.6 % for HFNC (P = 0.49). Two adverse events occurred during treatment with NIV and eight occurred during treatment with HFNC. There was no difference in the physiotherapists who tested positive for SARS-COV-2 directly involved in assisting COVID-19 patients and non-COVID-19 ones (P = 0.81). CONCLUSION: The application of NIV and HFNC in the critical care unit is feasible and associated with favorable outcomes. In addition, there was no increase in the infection of physiotherapists with SARS-CoV-2.

Toxicity assessment of gelsenicine and the search for effective antidotes.

BACKGROUND: Gelsenicine, one of the most toxic alkaloids of Gelsemium elegans Benth (G. elegans), causes severe respiratory depression. However, its toxicity mechanisms are yet to be elucidated and no effective antidotes are available. OBJECTIVE: This study aimed to analyse the toxicity characteristics of gelsenicine. METHODS: Both acute and sub-acute toxicities were evaluated. Gelsenicine distribution and elimination in the central nervous system (CNS) and blood were observed. Effective antidotes for gelsenicine poisoning were screened. RESULTS: In the acute toxicity study, gelsenicine was highly toxic, and female rats exhibited greater sensitivity to gelsenicine than male rats (LD50 0.520 mg/kg vs 0.996 mg/kg, respectively). Death was primarily caused by respiratory failure. However, in the sub-acute toxicity study, no significant organ damage was observed. Gelsenicine was easily absorbed from the gastrointestinal tract and penetrated the blood-brain barrier, reaching peak concentrations in the CNS within 15 min and rapidly decreasing thereafter. Flumazenil or diazepam combined with epinephrine reversed gelsenicine toxicity and significantly improved survival rate in mice. CONCLUSIONS: Gelsenicine is a highly toxic substance that affects nerve conduction without causing damage; the potential toxic mechanism is possibly associated with GABAA receptors. Our findings provide insights into the clinical treatment of gelsenicine-related poisoning and its toxicity mechanisms.

Effect of mortality from COVID-19 on inpatient outcomes.

When hospitals first encountered coronavirus disease 2019 (COVID-19), there was a dearth of therapeutic options and nearly 1 in 3 patients died from the disease. By the summer of 2020, as deaths from the disease declined nationally, multiple single-center studies began to report declining mortality of patients with COVID-19. To evaluate the effect of COVID-19 on hospital-based mortality, we searched the Vizient Clinical Data Base for outcomes data from approximately 600 participating hospitals, including 130 academic medical centers, from January 2017 through December 2020. More than 32 million hospital admissions were included in the analysis. After an initial spike, mortality from COVID-19 declined in all regions of the country to under 10% by June 2020 and remained constant for the remainder of the year. Despite this, inpatient, all-cause mortality has increased since the beginning of the pandemic, even those without respiratory failure. Inpatient mortality has particularly increased in elderly patients and in those requiring intubation for respiratory failure. Since June 2020, COVID-19 kills one in every 10 patients admitted to the hospital with this diagnosis. The addition of this new disease has raised overall hospital mortality especially those who require intubation for respiratory failure.

Respiratory events after intensive care unit discharge in trauma patients: Epidemiology, outcomes, and risk factors.

BACKGROUND: Respiratory complications are associated with significant morbidity and mortality in trauma patients. The care transition from the intensive care unit (ICU) to the acute care ward is a vulnerable time for injured patients. There is a lack of knowledge about the epidemiology of respiratory events and their outcomes during this transition. METHODS: Retrospective cohort study in a single Level I trauma center of injured patients 18 years and older initially admitted to the ICU from 2015 to 2019 who survived initial transfer to the acute care ward. The primary outcome was occurrence of a respiratory event, defined as escalation in oxygen therapy beyond nasal cannula or facemask for three or more consecutive hours. Secondary outcomes included unplanned intubation for a primary pulmonary cause, adjudicated via manual chart review, as well as in-hospital mortality and length of stay. Multivariable logistic regression was used to examine patient characteristics associated with posttransfer respiratory events. RESULTS: There were 6,561 patients that met the inclusion criteria with a mean age of 52.3 years and median Injury Severity Score of 18 (interquartile range, 13-26). Two hundred and sixty-two patients (4.0%) experienced a respiratory event. Respiratory events occurred early after transfer (median, 2 days, interquartile range, 1-5 days), and were associated with high mortality (16% vs. 1.8%, p < 0.001), and ICU readmission rates (52.6% vs. 4.7%, p < 0.001). Increasing age, male sex, severe chest injury, and comorbidities, including preexisting alcohol use disorder, congestive heart failure, and chronic obstructive pulmonary disease, were associated with increased odds of a respiratory event. Fifty-eight patients experienced an unplanned intubation for a primary pulmonary cause, which was associated with an in-hospital mortality of 39.7%. CONCLUSION: Respiratory events after transfer to the acute care ward occur close to the time of transfer and are associated with high mortality. Interventions targeted at this critical time are warranted to improve patient outcomes. LEVEL OF EVIDENCE: Prognostic and Epidemiological study, level III.

Low testosterone predicts hypoxemic respiratory insufficiency and mortality in patients with COVID-19 disease: another piece in the COVID puzzle.

PURPOSE: Hypogonadism was described in high number of male subjects with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this study, we investigated whether low testosterone (T) values may influence the clinical presentation and outcome of SARS-CoV-2-related pneumonia in a large population of adult males with coronavirus disease 19 (COVID-19). METHODS: Two hundred twenty one adult males hospitalized for COVID-19 at the IRCCS Humanitas Research Hospital, Rozzano-Milan (Italy) were consecutively evaluated for arterial partial pressure oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, serum T and inflammatory parameters at study entry, need of ventilation during hospital stay and in-hospital mortality. RESULTS: Subjects low T values (< 8 nmol/L; 176 cases) were significantly older (P = 0.001) and had higher serum interleukin-6 (P = 0.001), C-reactive protein (P < 0.001), lactate dehydrogenase (P < 0.001), ferritin (P = 0.012), lower P/F ratio (P = 0.001), increased prevalence of low T3 syndrome (P = 0.041), acute respiratory insufficiency (P < 0.001), more frequently need of ventilation (P < 0.001) and higher mortality rate (P = 0.009) compared to subjects with higher T values. In the multivariable regression analyses, T values maintained significant associations with acute respiratory insufficiency (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.79-0.94; P < 0.001 and in-hospital mortality (OR 0.80, 95% CI 0.69-0.95; P = 0.009), independently of age, comorbidities, thyroid function and inflammation. CONCLUSION: Low T levels values are associated with unfavorable outcome of COVID-19. Prospective studies are needed to evaluate the long-term outcomes of hypogonadism related to COVID-19 and the clinical impact of T replacement during and after acute illness.