Intubation Decision Based on Illness Severity and Mortality in COVID-19: An International Study.

OBJECTIVES: To evaluate the impact of intubation timing, guided by severity criteria, on mortality in critically ill COVID-19 patients, amidst existing uncertainties regarding optimal intubation practices. DESIGN: Prospective, multicenter, observational study conducted from February 1, 2020, to November 1, 2022. SETTING: Ten academic institutions in the United States and Europe. PATIENTS: Adults (≥ 18 yr old) confirmed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and hospitalized specifically for COVID-19, requiring intubation postadmission. Exclusion criteria included patients hospitalized for non-COVID-19 reasons despite a positive SARS-CoV-2 test. INTERVENTIONS: Early invasive mechanical ventilation (EIMV) was defined as intubation in patients with less severe organ dysfunction (Sequential Organ Failure Assessment [SOFA] < 7 or Pa o2 /F io2 ratio > 250), whereas late invasive mechanical ventilation (LIMV) was defined as intubation in patients with SOFA greater than or equal to 7 and Pa o2 /F io2 ratio less than or equal to 250. MEASUREMENTS AND MAIN RESULTS: The primary outcome was mortality within 30 days of hospital admission. Among 4464 patients, 854 (19.1%) required mechanical ventilation (mean age 60 yr, 61.7% male, 19.3% Black). Of those, 621 (72.7%) were categorized in the EIMV group and 233 (27.3%) in the LIMV group. Death within 30 days after admission occurred in 278 patients (42.2%) in the EIMV and 88 patients (46.6%) in the LIMV group ( p = 0.28). An inverse probability-of-treatment weighting analysis revealed a statistically significant association with mortality, with patients in the EIMV group being 32% less likely to die either within 30 days of admission (adjusted hazard ratio [HR] 0.68; 95% CI, 0.52-0.90; p = 0.008) or within 30 days after intubation irrespective of its timing from admission (adjusted HR 0.70; 95% CI, 0.51-0.90; p = 0.006). CONCLUSIONS: In severe COVID-19 cases, an early intubation strategy, guided by specific severity criteria, is associated with a reduced risk of death. These findings underscore the importance of timely intervention based on objective severity assessments.

Impact of Isolated Exercise-Induced Small Airway Dysfunction on Exercise Performance in Professional Male Cyclists.

BACKGROUND: Professional cycling puts significant demands on the respiratory system. Exercise-induced bronchoconstriction (EIB) is a common problem in professional athletes. Small airways may be affected in isolation or in combination with a reduction in forced expiratory volume at the first second (FEV1). This study aimed to investigate isolated exercise-induced small airway dysfunction (SAD) in professional cyclists and assess the impact of this phenomenon on exercise capacity in this population. MATERIALS AND METHODS: This research was conducted on professional cyclists with no history of asthma or atopy. Anthropometric characteristics were recorded, the training age was determined, and spirometry and specific markers, such as fractional exhaled nitric oxide (FeNO) and immunoglobulin E (IgE), were measured for all participants. All of the cyclists underwent cardiopulmonary exercise testing (CPET) followed by spirometry. RESULTS: Compared with the controls, 1-FEV3/FVC (the fraction of the FVC that was not expired during the first 3 s of the FVC) was greater in athletes with EIB, but also in those with isolated exercise-induced SAD. The exercise capacity was lower in cyclists with isolated exercise-induced SAD than in the controls, but was similar to that in cyclists with EIB. This phenomenon appeared to be associated with a worse ventilatory reserve (VE/MVV%). CONCLUSIONS: According to our data, it appears that professional cyclists may experience no beneficial impacts on their respiratory system. Strenuous endurance exercise can induce airway injury, which is followed by a restorative process. The repeated cycle of injury and repair can trigger the release of pro-inflammatory mediators, the disruption of the airway epithelial barrier, and plasma exudation, which gradually give rise to airway hyper-responsiveness, exercise-induced bronchoconstriction, intrabronchial inflammation, peribronchial fibrosis, and respiratory symptoms. The small airways may be affected in isolation or in combination with a reduction in FEV1. Cyclists with isolated exercise-induced SAD had lower exercise capacity than those in the control group.

Predicting the Outcome of Patients with Severe COVID-19 with Simple Inflammatory Biomarkers: The Utility of Novel Combined Scores-Results from a European Tertiary/Referral Centre.

Background: The clinical significance of combinations of inflammatory biomarkers in severe COVID-19 infection is yet to be proved. Although several studies have evaluated the prognostic value of biomarkers in patients with COVID-19, there are limited data regarding the value of the combination scores that could take full advantage of the prognostic value of several biomarkers and that could account for the heterogeneity of patients with severe COVID-19. We investigated the prognostic value of combination scores of admission values of inflammatory biomarkers in adults with severe COVID-19. Methods: Adults admitted to the Department of Respiratory Medicine of the UHL with severe COVID-19 (April-September 2021, NCT05145751) were included. Demographics, medical history, laboratory tests and outcome (high-flow nasal cannula (HFNC), admission to Intensive Care Unit (ICU) or death) were recorded. The optimal cut-off points of on admission values of C-reactive protein (CRP), CRP to lymphocyte ratio (CLR), lymphocyte to neutrophil ratio (LNR) and derived variation of neutrophil to lymphocyte ratio (dv-NLR (neutrophil/white blood count-lymphocyte)) for the predetermined outcome were defined. Based on the cut-off of CRP, LNR, dv-NLR and CLR, which were found to be predictors for HFNC, 3 scores were defined: CRP and LNR (C-CRP #1), CRP and dv-NLR (C-CRP #2), CRP and CLR (C-CRP #3). Likewise, based on the cut-off of CRP and CLR, which were found to be predictors for death, the score of CRP and CLR (C-CRP #3*) was defined. The combination scores were then classified as: 2 points (both biomarkers elevated); 1 point (one biomarker elevated) and 0 points (normal values). None of the biomarkers was predictive for the ICU admission, so no further analysis was performed. Binomial logistic regression analysis was used to establish the predictive role for each biomarker. Results: One hundred and fifteen patients (60% males, mean age 57.7 years) were included. Thirty-seven (32.2%) patients required HFNC, nine (7.8%) died and eight (7%) were admitted to ICU, respectively. As far as HFNC is concerned, the cut-off point was 3.2 for CRP, 0.231 for LNR, 0.90 for dv-NLR and 0.004 for CLR. Two points of C-CRP #1 and 2 points of C-CRP #3 predicted HFNC with a probability as high as 0.625 (p = 0.005) and 0.561 (p < 0.001), respectively. Moreover, 1 point of C-CRP #2 and 2 points of C-CRP #2 predicted HFNC with a probability of 0.333 and 0.562, respectively. For death, the optimal cut-off point for CRP was 1.11 and for CLR 3.2*1033. Two points of C-CRP #3* with an accuracy of 0.922 predicted mortality (p = 0.0038) in severe COVID-19. Conclusions: The combination scores of CRP and inflammatory biomarkers, based on admission values, are promising predictors for respiratory support using HFNC and for mortality in patients suffering from severe COVID-19 infection.

Evaluating the diagnostic and prognostic ability of ischemia modified albumin in COVID-19.

BACKGROUND: Patients with COVID-19 can rapidly deteriorate and develop acute hypoxic respiratory failure. Prominent features of the disease include severe inflammation, endotheliitis, and thrombosis. OBJECTIVES: The aim of the study was to evaluate the diagnostic and prognostic effectiveness of ischemia modified albumin (ΙΜΑ) in a cohort of COVID-19 patients. METHODS: This prospective observational study included adults with SARS-CoV-2 infection confirmed by reverse transcription polymerase chain reaction test, who were hospitalized specifically for COVID-19. The outcomes of interest were progression to severe acute respiratory failure during the index hospitalization defined as partial pressure of oxygen/fraction of inspired oxygen lower or equal to 150, admission to the intensive care unit (ICU) and in-hospital mortality. Admission IMA levels were determined using the commercially available "IMA Assay Kit" method (Abbexa LTD, Cambridge, UK). Adults without SARS-CoV-2 infection were used as controls. RESULTS: 135 COVID-19 patients and 64 controls were included. Admission IMA levels were significantly higher in COVID-19 patients compared to controls [[24.38 (11.94) ng/ml vs. 14.69 (3.52) ng/ml, p < 0.01]. Receiver operating characteristic analysis of admission IMA showed an area under the curve (AUC) of 94% (p < 0.0001) for COVID-19 diagnosis (cut-off value: 17.5 ng/ml; sensitivity: 90.37%; specificity: 87.5%). Admission IMA was also associated with mortality (AUC: 68%, p = 0.01). However, it was not associated with severe acute respiratory failure (AUC: 47%, p = 0.53) or ICU admission (AUC: 58%, p = 0.41). CONCLUSION: Admission IMA was significantly increased in COVID-19 patients and was associated with in-hospital mortality.

Nasal high flow or noninvasive ventilation? navigating hypercapnic COPD exacerbation treatment: A randomized noninferiority clinical trial.

BACKGROUND: Noninvasive ventilation (NIV) has been the cornerstone for managing acute exacerbations of COPD (AECOPD) with hypercapnic respiratory failure. Nasal high flow (NHF) oxygen therapy has emerged as a potential alternative, offering a more tolerable modality with promising outcomes. The aim of the present study was to evaluate whether NHF respiratory support is noninferior to NIV with respect to treatment failure, in patients with mild-to-moderate hypercapnic AECOPD. METHODS: In this multi-center, randomized, noninferiority trial, 105 patients with AECOPD and respiratory failure type II were enrolled. Participants were randomly assigned to receive either NHF therapy or NIV. The primary endpoint was the frequency of treatment failure, defined as the need for intubation and invasive mechanical ventilation or a switch to the alternative treatment group. Secondary endpoints included changes in respiratory parameters, patient comfort indicators, and the occurrence of complications. RESULTS: The findings revealed no significant difference in the primary outcome between the groups, with a treatment failure rate of 19.6 % (10 out of 51) in the NHF group and 14.8 % (8 out of 54) in the NIV group. Interestingly, NHF users reported significantly lower levels of dyspnea and discomfort at multiple follow-up points. Despite the differences in patient comfort, respiratory parameters such as respiratory rate, arterial blood gases, and use of accessory muscles of respiration showed no significant disparities between the groups throughout the study period. CONCLUSIONS: NHF therapy was similar to NIV in preventing treatment failure among patients with hypercapnic AECOPD, offering a viable alternative with enhanced comfort. TRIAL REGISTRATION: The study was prospectively registered in ClinicalTrials.gov (Identifier: NCT03466385) on March 15, 2018.

Sodium Glucose Co-Transporter 2 Inhibitors and the Cardiovascular System: Current Knowledge and Future Expectations.

Diabetic cardiomyopathy is a well-recognized clinical entity and reflects a complex relationship between metabolic substrates and myocardial function. Sodium glucose co-transporter 2 (SGLT2) inhibitors are antidiabetic agents that are found to exert multiple cardioprotective effects. Large clinical trials showed their beneficial effects on patients with heart failure, reducing the rates of rehospitalizations and improving kidney function. The aim of this review is to summarize the latest evidence in the literature regarding the multiple effects of SGLT2 inhibitors on patients across the spectrum of cardiovascular diseases.