Search

Introduction/aims: Amyotrophic lateral sclerosis (ALS) is characterized by profound muscle weakness, including diaphragmatic weakness resulting in hypercapnic respiratory failure. While non-invasive ventilation (NIV) is usually initiated in the home, patients presenting with hypercapnic respiratory failure may be at high risk of adverse outcomes with delays in treatment. We aim to describe the clinical utility of transcutaneous CO 2 (TCO 2 ) to assess the need for inpatient initiation of NIV., Methods: Eight patients from the University of Michigan Pranger ALS clinic were directly admitted to the hospital for urgent initiation of NIV between May 2020-May 2021. A retrospective review of electronic medical records, including pre-hospital pulmonary function assessments, hospitalization blood gases, and NIV use metrics was performed., Results: All eight patients had symptoms of respiratory insufficiency at time of admission, although not all patients had forced vital capacity (FVC) measurements that would identify need for NIV. All patients had measured TCO 2  > 45 mmHg. Seven of eight patients had worsening hypercapnia after admission, indicating advanced respiratory failure. All patients were titrated to tolerance of continuous nocturnal NIV while in the hospital, with an average length of stay of 6.5 days (range, 3-8). All patients demonstrated compliance with NIV, >4 h, at post-hospital follow-up., Discussion: Many current ambulatory measurements underestimate, or incompletely evaluate, respiratory dysfunction, and arterial blood gases are not typically readily available. Outpatient TCO 2 measurements can serve as a useful screening tool to identify ALS patients who would benefit from inpatient initiation and titration of NIV., (© 2022 Wiley Periodicals LLC.)

Objectives: This study's purpose is to evaluate the incidence, predictors, and outcomes of patients presenting to the cardiac catheterization laboratory with takotsubo syndrome complicated by respiratory failure or shock., Background: The presentation of takotsubo syndrome mimics acute myocardial infarction. It is often diagnosed in the cardiac catheterization laboratory when no coronary obstruction is found. A subset of these patients develops shock or respiratory failure., Methods: This is a retrospective study of patients who underwent cardiac catheterization at the Kaiser Permanente Southern California health system with takotsubo syndrome between 2006 to 2016. Medical records were manually reviewed to identify patient characteristics, treatment, and clinical outcomes., Results: Among 530 patients with takotsubo syndrome, 56 (10.6%) developed shock or respiratory failure and required mechanical or inotropic support. A higher proportion of these patients were men (14.3% vs 5.7%) and Black (10.7% vs 7.0%). In multivariate logistic regression analyses, factors associated with respiratory failure or shock were age (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.94-0.99; P=.02), chronic obstructive pulmonary disease (OR, 1.9; 95% CI, 1.1-3.5; P=.02), chronic kidney disease (OR, 2.6; 95% CI, 1.3-5.3; P=.01), physical trigger (OR, 5.7; 95% CI, 3.0-10.8; P<.01), and ST elevation on the presenting electrocardiogram (OR, 2.5; 95% CI, 1.4-4.8; P=.04). Patients who required mechanical ventilation or inotropic support had significantly higher mortality (hazard ratio, 3.9; 95% CI, 2.1-7.1; P<.001)., Conclusion: Shock or respiratory failure occur in 10.6% of patients presenting with takotsubo syndrome. Men and patients with baseline respiratory or renal disease were disproportionally affected. These patients have significantly worse clinical outcomes.

Background: Pulse oximeters may produce less accurate results in non-White patients., Research Question: Do pulse oximeters detect arterial hypoxemia less effectively in Black, Hispanic, and/or Asian patients than in White patients in respiratory failure and about to undergo extracorporeal membrane oxygenation (ECMO)?, Study Design and Methods: Data on adult patients with respiratory failure readings 6 h before ECMO were provided by the Extracorporeal Life Support Organization registry. Data was collected from 324 centers between January 2019 and July 2020. Our primary analysis was of rates of occult hypoxemia-low arterial oxygen saturation (Sao 2  ≤ 88%) on arterial blood gas measurement despite a pulse oximetry reading in the range of 92% to 96%., Results: The rate of pre-ECMO occult hypoxemia, that is, arterial oxygen saturation (Sao 2 ) ≤ 88%, was 10.2% (95% CI, 6.2%-15.3%) for 186 White patients with peripheral oxygen saturation (Spo 2 ) of 92% to 96%; 21.5% (95% CI, 11.3%-35.3%) for 51 Black patients (P = .031 vs White); 8.6% (95% CI, 3.2%-17.7%) for 70 Hispanic patients (P = .693 vs White); and 9.2% (95% CI, 3.5%-19.0%) for 65 Asian patients (P = .820 vs White). Black patients with respiratory failure had a statistically significantly higher risk of occult hypoxemia with an OR of 2.57 (95% CI, 1.12-5.92) compared with White patients (P = .026). The risk of occult hypoxemia for Hispanic and Asian patients was equivalent to that of White patients. In a secondary analysis of patients with Sao 2  ≤ 88% despite Spo 2 > 96%, Black patients had more than three times the risk compared with White patients (OR, 3.52; 95% CI, 1.12-11.10; P = .032)., Interpretation: Compared with White patients, the prevalence of occult hypoxemia was higher in Black patients than in White patients about to undergo ECMO for respiratory failure, but it was comparable in Hispanic and Asian patients compared with White patients., (Copyright © 2021 American College of Chest Physicians. All rights reserved.)

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., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Gerome Breen has sat on pre-clinical advisory boards for Compass Pathways Ltd and Otsuka Ltd. Michael J Griffiths has received research supported by Fast Track Diagnostics, Luxembourg and consultancy fees from Siemens Healthineers. There are no other conflicts to disclose.

Objective: To present an uncommon but serious, recently identified complication of checkpoint inhibitor therapy in a patient treated with pembrolizumab infusion for disseminated recurrent respiratory papillomatosis (RRP)., Methods: Case report., Results: A 43-year-old woman with underlying asthma developed acute hypoxic respiratory failure within 24 hours of her third infusion of pembrolizumab for treatment of intractable, disseminated recurrent respiratory papillomatosis. Pulmonary function testing revealed a severe intra-thoracic obstructive ventilatory defect. Discontinuation of pembrolizumab, ventilatory support, and treatment with systemic and inhaled corticosteroids resulted in resolution of respiratory failure; however, her underlying asthma remains poorly controlled., Conclusion: To our knowledge, this case is the first report of pembrolizumab-induced obstructive respiratory failure in a patient being treated for RRP.

Background: The COVID 19 pandemic has had a crucial effect on the patterns of disease and treatment in the healthcare system. This study examines the effect of the COVID-19 pandemic on respiratory ED visits and admissions broken down by age group and respiratory diagnostic category., Methods: Data on non-COVID related ED visits and hospitalizations from the ED were obtained in a retrospective analysis for 29 acute care hospitals, covering 98% of ED beds in Israel, and analyzed by 5 age groups: under one-year-old, 1-17, 18-44, 45-74 and 75 and over. Diagnoses were classified into three categories: Upper respiratory tract infections (URTI), pneumonia, and COPD or asthma. Data were collected for the whole of 2020, and compared for each month to the average number of cases in the three pre-COVID years (2017-2019)., Results: In 2020 compared to 2017-2019, there was a decrease of 34% in non-COVID ED visits due to URTI, 40% for pneumonia and a 35% decrease for COPD and asthma. Reductions occurred in most age groups, but were most marked among infants under a year, during and following lockdowns, with an 80% reduction. Patients over 75 years old displayed a marked drop in URTI visits. Pediatric asthma visits fell during lockdowns, but spiked when restrictions were lifted, accompanied by a higher proportion admitted. The percent of admissions from the ED visits remained mostly stable for pneumonia; the percent of young adults admitted with URTI decreased significantly from March to October., Conclusions: Changing patterns of ED use were probably due to a combination of a reduced rate of viral diseases, availability of additional virtual services, and avoidance of exposure to the ED environment. Improved hygiene measures during peaks of respiratory infections could be implemented in future to reduce respiratory morbidity; and continued provision of remote health services may reduce overuse of ED services for mild cases., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Most patients infected with SARS-CoV-2 (COVID-19) experience mild, non-specific symptoms, but many develop severe symptoms associated with an excessive inflammatory response. Elevated plasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) provide early warning of progression to severe respiratory failure (SRF) or death, but access to suPAR testing may be limited. The Severe COvid Prediction Estimate (SCOPE) score, derived from circulating concentrations of C-reactive protein, D- dimers, interleukin-6, and ferritin among patients not receiving non-invasive or invasive mechanical ventilation during the SAVE-MORE study, offers predictive accuracy for progression to SRF or death within 14 days comparable to that of a suPAR concentration of ≥6 ng/mL (area under receiver operator characteristic curve 0.81 for both). The SCOPE score is validated in two similar independent cohorts. A SCOPE score of 6 or more is an alternative to suPAR for predicting progression to SRF or death within 14 days of hospital admission for pneumonia, and it can be used to guide treatment decisions., Competing Interests: E.J.G.-B. has received honoraria from Abbott CH, bioMérieux, Brahms GmbH, GSK, InflaRx GmbH, Sobi, and XBiotech, Inc.; independent educational grants from Abbott CH, AxisShield, bioMérieux, InflaRx GmbH, Johnson & Johnson, MSD, Sobi, and XBiotech, Inc.; and funding from the Horizon 2020 Marie-Curie Project European Sepsis Academy (granted to the National and Kapodistrian University of Athens) and the Horizon 2020 European Grants ImmunoSep and RISCinCOVID (granted to the Hellenic Institute for the Study of Sepsis). G.P. has received independent educational grants from Pfizer, MSD, Angelini, and Bio-Rad. H.M. reports receiving honoraria, consulting fees, and non-financial support from health care companies, including Amgen, Angelini, Bayer, Mylan, MSD, Pfizer, and Servier. L.D. has received consultation honoraria from SOBI. M.B. has received funds for research grants from and/or has been an advisor/consultant and/or speaker/chairman for Angelini, Astellas, Bayer, bioMérieux, Cidara, Cipla, Gilead, Menarini, MSD, Pfizer, Roche, Shionogi, and Nabriva. P.P. has received honoraria from GILEAD Sciences, Janssen, and MSD. G.N.D. is an advisor or lecturer for Ipsen, Pfizer, Genkyotex, Novartis, and Sobi; received research grants from Abbvie and Gilead; and has served as PI in studies for Abbvie, Novartis, Gilead, Novo Nordisk, Genkyotex, Regulus Therapeutics, Inc., Tiziana Life Sciences, Bayer, Astellas, Pfizer, Amyndas Pharmaceuticals, CymaBay Therapeutics, Inc., Sobi, and Intercept Pharmaceuticals. M.G.N. is supported by an ERC advanced grant (833247) and a Spinoza grant of the Netherlands Organization for Scientific Research. M.G.N. is a scientific founder of TTxD and he has received independent educational grants from TTxD, GSK, Ono Pharma, and ViiV HealthCare. The other authors declare no competing interests., (© 2022 The Author(s).)

Background: Respiratory failure is a common complication of Guillain-Barré syndrome (GBS). This study aimed to determine the clinical predictors and electrodiagnostic (EDx) characteristics in patients with Guillain-Barré syndrome (GBS) with respiratory failure., Methods: The retrospective study included 29 confirmed GBS cases with respiratory failure and age- (±5 years) and sex-matched controls (1:1). The dependent t -test and McNemar-Bowker test were used to analyse the continuous and categorical data, respectively. In addition, a multiple logistic regression analysis was used to analyse the predictive factors for respiratory failure., Results: Among both cases and controls, the majority were male (72.4%), and the average age was 50.9 years. The data showed that patients with respiratory failure had higher GBS disability scores, lower motor power (≤3) of the hip flexors and ankle dorsiflexors, and experienced facial and bulbar palsy. In the multivariate analysis, the significant predictive factors were bulbar palsy (AOR 10.4 [95% CI [2.6-41.4]) and motor power of hip flexors ≤ 3 (AOR 31.4 [95% CI [3.1-314.5]). Patients with respiratory failure had lower compound muscle action potential amplitude of the ulnar and tibial nerves. The median, ulnar, and tibial nerve conduction studies were more likely to reflect inexcitability. The GBS subtypes in GBS patients with and without respiratory failure were not significantly different., Conclusions: Bulbar palsy and motor power of the hip flexors ≤ 3 were significant predictors for respiratory failure. The GBS subtypes in patients with and without respiratory failure were not significantly different., Competing Interests: The authors declare there are no competing interests., (©2022 Charoentanyarak et al.)

Background: Respiratory failure worsens the outcome of acute pancreatitis (AP) and underlying factors might be early detectable., Aims: To evaluate the prevalence and prognostic relevance of early pleuropulmonary pathologies and pre-existing chronic lung diseases (CLD) in AP patients., Methods: Multicentre retrospective cohort study. Caudal sections of the thorax derived from abdominal contrast enhanced computed tomography (CECT) performed in the early phase of AP were assessed. Independent predictors of severe AP were identified by binary logistic regression analysis. A one-year survival analysis using Kaplan-Meier curves and log rank test was performed., Results: 358 patients were analysed, finding pleuropulmonary pathologies in 81%. CECTs were performed with a median of 2 days (IQR 1-3) after admission. Multivariable analysis identified moderate to severe or bilateral pleural effusions (PEs) (OR = 4.16, 95%CI 2.05-8.45, p<0.001) and pre-existing CLD (OR = 2.93, 95%CI 1.17-7.32, p = 0.022) as independent predictors of severe AP. Log rank test showed a significantly worse one-year survival in patients with bilateral compared to unilateral PEs in a subgroup., Conclusions: Increasing awareness of the prognostic impact of large and bilateral PEs and pre-existing CLD could facilitate the identification of patients at high risk for severe AP in the early phase and thus improve their prognosis., Competing Interests: The authors have declared that no competing interests exist.

Background: Noninvasive respiratory support is frequently needed for patients with acute hypoxemic respiratory failure due to coronavirus disease 19 (COVID-19). Helmet noninvasive ventilation has multiple advantages over other oxygen support modalities but data about effectiveness are limited., Methods: In this multicenter randomized trial of helmet noninvasive ventilation for COVID-19 patients, 320 adult ICU patients (aged ≥14 years or as per local standards) with suspected or confirmed COVID-19 and acute hypoxemic respiratory failure (ratio of arterial oxygen partial pressure to fraction of inspired oxygen < 200 despite supplemental oxygen with a partial/non-rebreathing mask at a flow rate of 10 L/min or higher) will be randomized to helmet noninvasive ventilation with usual care or usual care alone, which may include mask noninvasive ventilation, high-flow nasal oxygen, or standard oxygen therapy. The primary outcome is death from any cause within 28 days after randomization. The trial has 80% power to detect a 15% absolute risk reduction in 28-day mortality from 40 to 25%. The primary outcome will be compared between the helmet and usual care group in the intention-to-treat using the chi-square test. Results will be reported as relative risk  and 95% confidence interval. The first patient was enrolled on February 8, 2021. As of August 1, 2021, 252 patients have been enrolled from 7 centers in Saudi Arabia and Kuwait., Discussion: We developed a detailed statistical analysis plan to guide the analysis of the Helmet-COVID trial, which is expected to conclude enrollment in November 2021., Trial Registration: ClinicalTrials.gov NCT04477668 . Registered on July 20, 2020., (© 2022. The Author(s).)

Background: Postoperative respiratory failure, defined as ventilator dependency for more than 48 hours or unplanned reintubation within 30 days, is a costly complication of cardiac surgery that increases mortality and length of stay. Stratification of patients by risk upon intensive care unit admission could identify cases requiring early measures to prevent respiratory failure. This study aimed to develop and validate a risk score for postoperative respiratory failure after cardiac surgery., Methods: This retrospective analysis of 4262 patients admitted to the cardiovascular intensive care unit after major cardiac surgery between January 2013 and December 2017, used The Society of Thoracic Surgeons database and ventilator data from the respiratory therapy department. Patients were randomly and equally assigned to development and validation cohorts. Covariates used in the multivariable models were assigned weighted points proportional to their β regression coefficient values to create the risk score, which categorized patients into low, medium, and high risk of postoperative respiratory failure., Results: In both cohorts, postoperative respiratory failure risk was significantly different between risk categories. Compared with low-risk patients, moderate-risk patients had a 2 times greater risk, and high-risk patients had a 4-7 times greater risk. Body mass index, previous cardiac surgery, cardiopulmonary bypass, cardiogenic shock, pulmonary disease presence, baseline functional status, hemodynamic instability, and number of blood products used intraoperatively were significant predictors of respiratory failure., Conclusions: This risk score can stratify patients by risk for developing postoperative respiratory failure after major cardiac surgery, which may help in the development of preventive measures., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Guillain-Barré syndrome (GBS) is a common peripheral neuropathy with relatively heterogenous clinical manifestations. In severe cases, it can result in disabling neuromuscular symptoms and respiratory failure. In this study, we assessed whether the systemic immune-inflammation index (SII) is associated with respiratory failure in GBS patients., Methods: We retrospectively analyzed clinicopathological data from GBS patients diagnosed in the First Affiliated Hospital of Kunming Medical University. SII was calculated based on counts of neutrophils (N), platelets (P), and lymphocytes (L). Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff values for SII, N, P, and L. Univariate and multivariate logistic regression were performed to determine the ability of the SII to predict respiratory failure., Results: Among the 369 GBS patients in this study, 61 (16.5%) suffered respiratory failure. Multivariate logistic regression showed that N ≥ 6.03 × 10 9 /l, Hughes Functional Grading Scale (HFGS) score ≥ 3 at admission, and SII ≥ 863.04 × 10 9 /l can independently predict respiratory failure in GBS patients. SII showed higher predictive ability than N, based on area under the ROC curve (0.75 vs. 0.72)., Conclusion: SII may be a novel independent prognostic indicator of respiratory failure in GBS patients, helping physicians identify those at risk in a timely manner., (© 2021. Fondazione Società Italiana di Neurologia.)

Objective: This study aims to summarize the risk factors of type II respiratory failure in patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD), to guide clinical treatment in time, and consequently reduce the serious impact of COPD on human health., Methods: Five databases were searched for relevant articles on risk factors of acute exacerbation of COPD combinate with type II respiratory failure. We calculated the standard mean difference (SMD), odds ratio (OR), and their 95% confidence interval (95% CI) utilizing a fixed-effect model or a random-effect model according to the level of heterogeneity., Results: As of 14 May 2021, 13 articles were included in our meta-analysis. The results showed that low albumin and uric acid levels were the risk factors for type II respiratory failure in acute exacerbation of COPD patients, and the differences were statistically significant (albumin: SMD = -2.03, 95% CI: -2.81, -1.26; uric acid: SMD = -1.28, 95% CI: -1.41, -1.15). Besides, 10 other systematic markers have been reported to be the risk factors for type II respiratory failure of patients with acute exacerbation of COPD, but only in single study., Conclusion: The meta-analysis results further confirm that low albumin and uric acid levels are risk factors for type II respiratory failure in acute exacerbation of COPD patients. Additionally, this analysis also summarizes many emerging inflammatory indicators, nutritional indicator, and cardiovascular system indicators to predict the progression of acute exacerbation of COPD to type II respiratory failure but only in single study., (© 2022 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Objective: To assess the association between the timing of surgery relative to the development of Covid-19 and the risks of postoperative complications., Summary Background Data: It is unknown whether patients who recovered from Covid-19 and then underwent a major elective operation have an increased risk of developing postoperative complications., Methods: The risk of postoperative complications for patients with Covid-19 undergoing 18 major types of elective operations in the Covid-19 Research Database was evaluated using multivariable logistic regression. Patients were grouped by time of surgery relative to SARS-CoV-2 infection; that is, surgery performed: (1) before January 1, 2020 ("pre-Covid-19"), (2) 0 to 4 weeks after SARS-CoV-2 infection ("peri-Covid-19"), (3) 4 to 8 weeks after infection ("early post-Covid-19"), and (4) ≥8 weeks after infection ("late post-Covid-19")., Results: Of the 5479 patients who met study criteria, patients with peri-Covid-19 had an elevated risk of developing postoperative pneumonia [adjusted odds ratio (aOR), 6.46; 95% confidence interval (CI): 4.06-10.27], respiratory failure (aOR, 3.36; 95% CI: 2.22-5.10), pulmonary embolism (aOR, 2.73; 95% CI: 1.35-5.53), and sepsis (aOR, 3.67; 95% CI: 2.18-6.16) when compared to pre-Covid-19 patients. Early post-Covid-19 patients had an increased risk of developing postoperative pneumonia when compared to pre-Covid-19 patients (aOR, 2.44; 95% CI: 1.20-4.96). Late post-Covid-19 patients did not have an increased risk of postoperative complications when compared to pre-Covid-19 patients., Conclusions: Major, elective surgery 0 to 4 weeks after SARS-CoV-2 infection is associated with an increased risk of postoperative complications. Surgery performed 4 to 8 weeks after SARS-CoV-2 infection is still associated with an increased risk of postoperative pneumonia, whereas surgery 8 weeks after Covid-19 diagnosis is not associated with increased complications., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: During COVID-19 surges, medical trainees may perform patient care outside typical clinical responsibilities. While respiratory failure in pediatric patients secondary to COVID-19 is rare, it is critical that providers can effectively care for these children while protecting the health care team. Simulation is an important tool for giving learners a safe environment in which to learn and practice these new skills., Methods: In this simulation, learners provided care to a 13-year-old male with obesity, COVID-19 pneumonia, status asthmaticus, and respiratory failure. Target learners were pediatric emergency medicine fellows and emergency medicine residents. Providers were expected to identify the signs and symptoms of status asthmaticus, pneumonia, and respiratory failure and demonstrate appropriate evaluation and management while minimizing COVID-19 exposure. Participants completed a postsimulation survey on their satisfaction and confidence in performing the objectives., Results: Twenty-eight PGY 1-PGY 6 learners participated in this simulation. The postsimulation survey showed that most learners felt the simulation was effective in teaching the evaluation and management of respiratory failure due to COVID-19 ( M = 5.0; 95% CI, 4.9-5.0) and was relevant to their work ( M = 5.0; 95% CI, 5.0-5.0)., Discussion: Learners felt that the case was effective in teaching the skills needed to care for a child with COVID-19 pneumonia, status asthmaticus, and respiratory failure. Future directions include updating the case with new COVID-19 knowledge and personal protective equipment practices gained over time, using hybrid telesimulation to increase learners' exposure to the case, and adapting the case for other health care providers., (© 2022 Tsao et al.)

Purpose: Home non-invasive ventilation (NIV) is recommended in patients with COPD and hypercapnic chronic respiratory failure (HCRF). The mechanism by it can improve alveolar ventilation during spontaneous breathing is not yet completely explained. Our aim is to evaluate the impact of on diaphragm muscle function in a series of patients with HCRF., Patients and Methods: Observational, longitudinal, prospective study of a series of patients with very severe chronic obstruction to airflow treated with home high imntensity NIV (HINIV). Patients underwent a baseline and after 12 months assessment including adherence to treatment, quality of life, respiratory function tests and diaphragmatic ultrasound. SPSS v.26 software was used for statistical analysis., Results: We studied 30 patients, 63% male, the mean age was 60.8 (±6.4) years old. Patients had a severe obstructive ventilatory pattern [FEV1 21.8 (±6.1)%] and hypercapnia [pCO2 56.4 (±7.2) mmHg]. After 12 months of HINIV, we observed significant increases in FVC of 9.2% (p = 0.002), FEV1 of 3.5% (p = 0.04), MIP of 9.4% (p = 0.006), and 6-minute-walking test (6MWT) of 31.9 m (p = 0.001), as well as decreases in paCO2 of 12.5 mmHg (p = 0.001), HCO3 of 4.7 mmol/L (p = 0.001) and BODE index from 7 to 6. Diaphragmatic ultrasound demonstrated an increase in the thickening fraction of 14% (p = 0.002). Respiratory symptoms (p = 0.04), physical function (p = 0.03), and sleep (p = 0.04) also improved., Conclusion: In patients with HCRF due to very severe chronic obstruction to airflow, long-term HINIV can improve respiratory performance by improving the function of the diaphragmatic musculature. Larger multicenter clinical trials are needed to confirm the results suggested in this study., Competing Interests: Dr Javier Sayas Catalan reports grants from Menarini, personal fees from Resmed, personal fees from Philips Respironics, outside the submitted work. The authors report no cother conflicts of interest in this work., (© 2022 Hernandez-Voth et al.)

The article provides a review of the literature on the development of chronic respiratory failure in patients with chronic cicatricial stenosis of the larynx and cervical trachea. The authors provide data on the etiology, pathogenetic features of the course of cicatricial stenosis of the larynx and trachea, the reasons for the development of chronic respiratory failure, the effect of hypoxemia on general metabolic processes in the body and on regeneration processes, as well as on methods of their correction and improvement of the postoperative period. The methods of respiratory impact on chronic respiratory failure in these patients are considered, based on the experience of a number of researchers and technical advances in recent years.

A 38-year-old pregnant woman presented at 30 weeks gestation in respiratory distress with pre-eclampsia. This was on the background of slowly progressive dyspnoea over six years, with generalised weakness and previous surgery for ptosis and prognathia. After successful caesarean delivery at 31 weeks, the patient was found to have a homozygous likely pathogenic variant in the MYOD1 gene. This case presents a milder phenotype for MYOD1 congenital myopathy, usually associated with diaphragmatic defects, respiratory insufficiency and dysmorphic facies. It also highlights the difficulties of managing an undiagnosed patient through pregnancy.

Background: Coronavirus disease 2019 (COVID-19) has spread globally, and many patients with severe cases have received oxygen therapy through a high-flow nasal cannula (HFNC)., Objectives: We assessed the efficacy of HFNC for treating patients with COVID-19 and risk factors for HFNC failure., Methods: We searched PubMed, Embase, and the Cochrane Central Register of randomized controlled trials (RCTs) and observational studies of HFNC in patients with COVID-19 published in English from January 1st, 2020 to August 15th, 2021. The primary aim was to assess intubation, mortality, and failure rates in COVID-19 patients supported by HFNC. Secondary aims were to compare HFNC success and failure groups and to describe the risk factors for HFNC failure., Results: A total of 25 studies fulfilled selection criteria and included 2851 patients. The intubation, mortality, and failure rates were 0.44 (95% confidence interval (CI): 0.38-0.51, I 2  = 84%), 0.23 (95% CI: 0.19-0.29, I 2  = 88%), and 0.47 (95% CI: 0.42-0.51, I 2  = 56%), respectively. Compared to the success group, age, body mass index (BMI), Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACHE) II score, D-dimer, lactate, heart rate, and respiratory rate were higher and PaO 2 , PaO 2 /FiO 2 , ROX index (the ratio of SpO 2 /FiO 2 to respiratory rate), ROX index after the initiation of HFNC, and duration of HFNC were lower in the failure group (all Ps < 0.05). There were also more smokers and more comorbidities in the failure group (all Ps < 0.05). Pooled odds ratios (ORs) revealed that older age (OR: 1.04, 95% CI: 1.01-1.07, P = 0.02, I 2  = 88%), a higher white blood cell (WBC) count (OR: 1.06, 95% CI: 1.01-1.12, P = 0.02, I 2  = 0%), a higher heart rate (OR: 1.42, 95% CI: 1.15-1.76, P < 0.01, I 2  = 0%), and a lower ROX index(OR: 0.61, 95% CI: 0.39-0.95, P = 0.03, I 2  = 93%) after the initiation of HFNC were all significant risk factors for HFNC failure., Conclusions: HFNC is an effective way of providing respiratory support in the treatment of COVID-19 patients. Older age, a higher WBC count, a higher heart rate, and a lower ROX index after the initiation of HFNC are associated with an increased risk of HFNC failure.

Objectives: A systematic review and meta-analysis were performed to compare the effects of high-flow nasal oxygen cannula (HFNC) and noninvasive ventilation (NIV) in extubated patients with respiratory insufficiency., Methods: The Cochrane Library, PubMed, and ClinicalTrials.gov were searched from inception to 28 February 2021, to identify randomized controlled trials. The primary outcome was reintubation within 24-72 hours after a planned extubation. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated., Results: Six articles with1746 patients were included. The effect of HFNC on the reintubation rate was noninferior to that of NIV (OR = 1.11, 95% CI: 0.85-1.44). The rate of treatment failure was 20.40% with HFNC versus 20.92% with NIV; this difference was nonsignificant (OR = 0.97, 95% CI: 0.72-1.32, P = 0.85). HFNC reduced the rates of skin lesion occurrence (10.28% versus 23.82%, OR = 0.37, 95% CI: 0.26-0.53, P < 0.00001) and post-extubation respiratory failure (23.76% versus 25.56%, OR = 0.64, 95% CI: 0.46-0.88, P = 0.006), compared with NIV., Conclusions: In extubated patients, HFNC was noninferior to NIV in the rate of reintubation and treatment failure. Compared with NIV, HFNC decreased the occurrence of skin lesions and post-extubation respiratory failure.

Background: The Severe Respiratory Insufficiency Questionnaire (SRI) is a multidimensional instrument for health-related quality of life (HRQL) assessment in patients with chronic respiratory failure (CRF). The SRI has originally been developed in German in 2003, but 15 translated versions have been created during the last 18 years with the exclusion of the Italian translation., Aims of the Study: The present project was aimed at creating an Italian version of the SRI., Methods: Professional forward-translation and back-translation procedures have been provided based on the original German version by independent translators, and this was followed by final reconciliation., Results: The Italian SRI contains 49 items covering 7 different subscales which can summarize to one Summary Score., Conclusions: The Italian SRI is a multidimensional instrument, which can be used for HRQL assessment in Italian-speaking patients with CRF. Validation of the Italian version of the questionnaire is formally required in the future., (© 2022 S. Karger AG, Basel.)

Context: Respiratory dysfunction is a component of every organ failure scoring system developed, reflecting the significance of the lung in multiple organ dysfunction syndrome. However, existing systems do not reflect current practice and are not consistently evidence based., Objective: We aimed to review the literature to identify the components of respiratory failure associated with outcomes in children, with the purpose of developing an operational and evidence-based definition of respiratory dysfunction., Data Sources: Electronic searches of PubMed and Embase were conducted from 1992 to January 2020 by using a combination of medical subject heading terms and text words to define respiratory dysfunction, critical illness, and outcomes., Study Selection: We included studies of critically ill children with respiratory dysfunction that evaluated the performance of metrics of respiratory dysfunction and their association with patient-centered outcomes. Studies in adults, studies in premature infants (≤36 weeks' gestational age), animal studies, reviews and commentaries, case series with sample sizes ≤10, and studies not published in English in which we were unable to determine eligibility criteria were excluded., Data Extraction: Data were abstracted into a standard data extraction form., Results: We provided binary (no or yes) and graded (no, nonsevere, or severe) definitions of respiratory dysfunction, prioritizing oxygenation and respiratory support. The proposed criteria were approved by 82% of members in the first round, with a score of 8 of 9 (interquartile range 7-8)., Limitations: Exclusion of non-English publications, heterogeneity across the pediatric age range, small sample sizes, and incomplete handling of confounders are limitations., Conclusions: We propose definitions for respiratory dysfunction in critically ill children after an exhaustive literature review., Competing Interests: FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Background: Use of noninvasive ventilation (NIV) in patients with moderate to severe ARDS is controversial. We aimed to use HACOR (combination of heart rate, acidosis, consciousness, oxygenation and respiratory rate) score to comprehensively assess the efficacy of NIV in ARDS patients with PaO 2 /FiO 2  ⩽ 150 mmHg., Methods: Secondary analysis was performed using the data collected from two databases. We screened the ARDS patients who used NIV as a first-line therapy. Patients with PaO 2 /FiO 2  ⩽ 150 mmHg were enrolled. NIV failure was defined as requirement of intubation., Results: A total of 224 moderate to severe ARDS patients who used NIV as a first-line therapy were enrolled. Of them, 125 patients (56%) experienced NIV failure and received intubation. Among the intubated patients, the survivor had shorter time from initiation of NIV to intubation than nonsurvivors (median 10 vs 22 h, p  < 0.01). The median differences of HACOR score before and 1-2 h of NIV were 1 point (interquartile range: 0-3). We defined the patients with △HACOR >1 as responders (n  = 102) and the rest to non-responders (n  = 122). Compared to non-responders, the responders had higher HACOR score before NIV. However, the HACOR score was lower in the responders than non-responders after 1-2 h, 12 h, and 24 h of NIV. The responders also had lower NIV failure rate (36% vs 72%, p  < 0.01) and lower 28-day mortality (32% vs 47%, p  = 0.04) than non-responders., Conclusions: NIV failure was high among patients with moderate to severe ARDS. Delayed intubation is associated with increased mortality. The reduction of HACOR score after 1-2 h of NIV can identify the patients who respond well to NIV.

Objectives: Pneumonia is a significant cause of morbidity and mortality in solid-organ transplant recipients. We studied the demographic characteristics, respiratory management, and outcomes of solid-organ transplant recipients with pneumonia in an intensive care unit., Materials and Methods: There have been 2857 kidney, 687 liver, and 142 heart transplants performed between October 16, 1985, and February 28, 2021, at our center. We retrospectively analyzed records for 51 of 193 recipients with pneumonia during the posttransplant period between January 1, 2016, and December 31, 2018., Results: Fifty-one of 193 recipients were followed in the intensive care unit. Mean age was 45.4 ± 16.6 years among 42 male (82.4%) and 9 female (17.6%) recipients. Twenty-six patients (51%) underwent kidney transplant, 14 (27.5%) liver transplant, 7 (13.7%) heart transplant, and 4 (7.8%) combined kidney and liver transplant. Most pneumonia episodes occurred 6 months after transplant (70.6%) with acute hypoxemic respiratory failure. Mean Acute Physiology and Chronic Health Evaluation System II score was 18.9 ± 7.7, and the Sequential Organ Failure Assessment score was 8.5 ± 3.9 at intensive care unit admission. Whereas 66.7% of pneumonia cases were nosocomial acquired, 33.3% were community acquired. The intensive care unit and 28-day mortality rates were 39.2% and 64.7%, respectively., Conclusions: Solid-organ transplant recipients with pneumonia have been associated with poor prognosis. Our cohort followed in the intensive care unit comprised mostly patients with nosocomial pneumonia with acute hypoxemic respiratory failure, hospitalized 6 months after transplant with high Acute Physiology and Chronic Health Evaluation System II scores predictive of mortality. In this high-risk patient group, careful follow-up, early discovery of warning signs, and rapid treatment initiation could improve the outcomes in the intensive care unit.

The course of COVID-19 is unpredictable, ranging from asymptomatic to respiratory failure and death. Prognostic biomarkers are urgently needed. We hypothesized that long pentraxin PTX3 could be a valuable plasma biomarker due to its essential role in inflammatory processes. In a prospective hospitalized COVID-19 derivation cohort (n = 126) during the spring of 2020, we measured PTX3 within 4 days of admission. The predictive value of mechanical ventilation (MV) and 30-day mortality compared with clinical parameters and other markers of inflammation were assessed by logistic regression analysis and expressed as odds ratio (OR) with 95% confidence interval (CI). Analyses were repeated in a prospective validation cohort (n = 112) of hospitalized patients with COVID-19 treated with remdesivir and dexamethasone. Thirty-day mortality in the derivation cohort was 26.2%. In patients who died, the median PTX3 concentration upon admission was 19.5 ng/mL (IQR: 12.5-33.3) versus 6.6 ng/mL (IQR 2.9-12.3) (p < 0.0001) for survivors. After adjustment for covariates, the odds of 30-day mortality increased two-fold for each doubling of PTX3 (OR 2.03 [95% CI: 1.23-3.34], p = 0.006), which was also observed in the validation cohort (OR 1.70 [95% CI: 1.09-2.67], p = 0.02). Similarly, PTX3 levels were associated with MV. After adjustment for covariates, OR of MV was 2.34 (95% CI: 1.33-4.12, p = 0.003) in the derivation cohort and 1.64 (95% CI: 1.03-2.62, p = 0.04) in the validation cohort. PTX3 appears to be a useful clinical biomarker to predict 30-day respiratory failure and mortality risk in COVID-19 patients treated with and without remdesivir and dexamethasone., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background: Opioid-induced respiratory depression (OIRD) is a serious complication that can lead to negative outcomes. There are known risk factors for OIRD; however, a lack of national guidelines for the prevention and early detection of OIRD exists., Methods: An evidence-based practice study was conducted to create an enhanced monitoring (EM) program. The EM program consisted of risk stratification of surgical spine patients, including the use of STOP-BANG screening for obstructive sleep apnea, capnography monitoring, use of home positive airway pressure therapy, capnography alarm optimization, hospitalist consultation, nursing education, and patient education., Results: Approximately 17% (N = 937/5,462) of surgical spine patients were enrolled in the EM program. Fifty-six percent of EM patients were monitored with capnography and had out of range end-tidal carbon dioxide levels 17% of the time. The rate of transfers to the intensive care unit (ICU) for OIRD decreased, though not statistically significant (p = .151)., Conclusions: The EM program with risk stratification was found to reduce transfers to the ICU for OIRD. Although not statistically significant, the decreased number of transfers was clinically significant. Engagement of the interprofessional team and capnography alarm parameter optimization helped to reduce nonactionable alarms., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 National Association for Healthcare Quality.)

Objective: Severe COVID-19 is characterized by a dysregulated immune response in which neutrophils play a critical role. Calprotectin reflects neutrophil activation and is involved in the self-amplifying thrombo-inflammatory storm in severe COVID-19. We aimed to evaluate the role of calprotectin in early prediction of severity in COVID-19 patients., Methods: This was a multicenter prospective observational study enrolling consecutive adult COVID-19 patients. On arrival to emergency department, blood samples were collected for laboratory tests, including serum calprotectin. The primary outcome was severe respiratory failure requiring invasive mechanical ventilation and the secondary outcome was need for Intensive Care Unit (ICU) admission., Results: Study population included 395 patients, 57 (14.4%) required invasive mechanical ventilation and 100 (25.3%) were admitted to ICU. Median serum calprotectin levels were significantly higher in intubated (3.73 mg/L vs. 2.63 mg/L; p < 0.001) and ICU patients (3.48 mg/L vs. 2.60 mg/L; p = 0.001). Calprotectin showed a significant accuracy to predict the need for invasive mechanical ventilation (ROC AUC 0.723) and ICU admission (ROC AUC 0.650). In multivariate analysis, serum calprotectin was an independent predictor of invasive mechanical ventilation (OR 1.161) and ICU admission (OR 1.068)., Conclusion: Serum calprotectin can be used as an early predictor of severity in COVID-19 patients., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Self-administration of helminths has gained attention among patients as a potential but unproven therapy for autoimmune disease. We present a case of rapidly progressive respiratory failure in a patient with systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH) as a result of self-administration of parasitic organisms., Case: A 45-year-old woman with a history of interstitial lung disease and PAH due to limited cutaneous SSc presented to pulmonary clinic with worsening dyspnea, cough, and new onset hypoxemia. Three months prior to presentation she started oral helminth therapy with Necator americanus as an alternative treatment for SSc. Laboratory evaluation revelaed eosinophilia and elevated IgE levels. IgG antibodies to Strongyloides were detected. High resolution computed tomography of the chest revealed progressive ILD and new diffuse ground glass opacities. Transthoracic echocardiogram and right heart catheterization illustrated worsening PAH and right heart failure. The patient was admitted to the hospital and emergently evaluated for lung transplantation but was not a candidate for transplantation due to comorbidities. Despite aggressive treatment for PAH and right heart failure, her respiratory status deteriorated, and the patient transitioned to comfort-focused care., Conclusion: Although ingestion of helminths poses a risk of infection, helminth therapy has been investigated as a potential treatment for autoimmune diseases. In this case, self-prescribed helminth ingestion precipitated fatal acute worsening of lung inflammation, hypoxemia, and right heart dysfunction, highlighting the risk of experimental helminth therapy in patients, especially those with underlying respiratory disease., (© 2021. The Author(s).)

Purpose: Both acute respiratory failure (ARF) and acute kidney injury (AKI) are two common complications in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Moreover, both ARF and AKI are reported as increasing the risk of mortality of patients with AECOPD. However, the interaction of ARF and AKI on the mortality of patients with AECOPD remains unknown. Therefore, the aim of this study is to investigate the joint effect of ARF and AKI on in-hospital mortality in AECOPD patients., Patients and Methods: We performed a retrospective, observational cohort study of data from Nanjing First Hospital. The effect of AKI and ARF on in-hospital mortality was assessed using a multivariate logistic regression model. Additive interaction was assessed with the relative excess risk due to interaction., Results: A total of 1647 participants were enrolled. ARF and AKI occurred in 515 (31.3%) and 357 (21.7%) patients, respectively. Overall, in-hospital mortality was 5.7%. The in-hospital mortality of the neither ARF nor AKI group, the ARF only group, the AKI only group, and both the ARF and AKI group were 0.8%, 7.0%, 7.5%, and 29.9%, respectively. After multivariate logistic regression analysis, the independent factors for in-hospital death included: albumin (OR 0.88, 95% CI 0.83-0.93, P < 0.001), ARF only (OR 8.53, 95% CI 3.64-19.99, P < 0.001), AKI only (OR 8.99, 95% CI 3.58-22.55, P < 0.001), and both ARF and AKI (OR 39.13, 95% CI 17.02-89.97, P < 0.001). The relative excess risk due to interaction was 22.62 (95% CI, 0.31 to 44.93), the attributable proportion due to interaction was 0.59 (95% CI, 0.36 to 0.79), and the synergy index was 2.46 (95% CI, 1.44 to 4.20), indicating ARF and AKI had a significant synergic effect on in-hospital mortality., Conclusion: ARF and AKI had a synergistic effect on in-hospital mortality in AECOPD patients., Competing Interests: The authors declare no conflicts of interest., (© 2021 Chen et al.)

Case Presentation: A 17-year-old previously healthy Taiwanese girl presented with syncope on a background of 1 month of weakness, polyarthritis, and heliotrope rash. Her presentation and investigations, which included an elevated creatine phosphokinase level and diffuse myositis on lower limb MRI, were consistent with juvenile dermatomyositis (JDM)., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Background: Titration of inspired oxygen is a challenge in preterm infants with hypoxemic respiratory failure (HRF). Monitoring of brain oxygen by near-infrared spectroscopy (NIRS) has been proven to minimize the burden of hyperoxia and hypoxemia; with a better understanding of cerebral autoregulation, integrating NIRS and pulse oximetry for titrating inspired oxygen in preterm infants is a novel approach., Methods: We studied the impact of integrated monitoring of oxygen saturation by pulse oximetry (SpO 2 ) and cerebral regional tissue oxygen (crRTO) by NIRS during a stepwise oxygen reduction test (ORT) on reducing oxygen requirement in preterm infants with HRF. The correlation between SpO 2 with crRTO, and fractional oxygen extraction (FOE) was assessed, concordance levels (r > 0.5) were determined during the assessment period and were considered as a sign of impaired autoregulation. The primary outcome was the achievement of significantly lower FiO 2 at 72 h after the start of the integrated monitoring., Results: A total of 38 preterm infants were included, 27 had normal cerebral autoregulation (CAR) (Group 1) in whom SpO 2 was poorly correlating with crRTO with (r < 0.5) and had a significantly greater percentage of reduction below baseline in FiO 2 (mean: 34%). Eleven infants had impaired CAR (Group 2) with SpO 2 significantly correlating with crRTO (r > 0.5) and had a linear trend of FOE inverse to SpO 2 and crRTO; this was considered as an arterial saturation dependent oxygen delivery (SadDO 2 )., Conclusion: Integrated monitoring of preterm infants by SpO 2 and crRTO was associated with easier weaning of oxygen with less burden of both hyperoxia and hypoxemia., (© 2021 Wiley Periodicals LLC.)

Introduction: Respiratory high dependency units (RHDUs) set up in European countries in the last decade are based on being a transitional step between the intensive care units (ICUs) and the conventional hospital ward in terms of staffing, level of monitoring, and patients' severity. In the pre-COVID-19 era, its main use has been the treatment of hypercapnic acute-on-chronic respiratory failure with noninvasive respiratory support, and more recently, for hypoxemic acute respiratory failure., Areas Covered: We searched the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, limited to the terms: COVID-19 and RHDU, Respiratory Intermediate care Unit, acute respiratory distress syndrome (ARDS), noninvasive ventilation (NIV), high flow nasal cannula (HFNC), prone position, and monitoring. In this review, we summarize RHDU´s dual purpose: on the one hand, to decrease the number of admissions into ICU, and on the other hand, early discharges of patients from ICU with prolonged admissions due to the need of care or laborious weaning from invasive mechanical ventilation. Although this dual purpose of RHDUs has contributed to decrease the overload of the ICUs during the pandemic, the hundreds of patients admitted in hospitals, with approximately 20%-30% needing critical care, has exceeded the forecasts of many hospitals., Expert Opinion: It seems clear that a reorganization and optimization of the care of patients with severe COVID-19 is necessary, minimizing admissions to the ICU and facilitating an early discharge. During the pandemic, several hospitals have spontaneously created new RHDUs or extended preexisting RHDUs or up-graded respiratory wards in order to receive less sick patients requiring lower levels of monitoring and nurse-to-patient ratios. This article reviews under a European expert perspective this topic and proposes an adaptation and optimization of the RHDUs to meet the emergent needs caused by the pandemic emphasizing the role of the expert application of noninvasive respiratory therapies in preventing intubation and ICU access.

Hierarchal clustering of amino acid metabolites may identify a metabolic signature in children with pediatric acute hypoxemic respiratory failure. Seventy-four immunocompetent children, 41 (55.4%) with pediatric acute respiratory distress syndrome (PARDS), who were between 2 days to 18 years of age and within 72 h of intubation for acute hypoxemic respiratory failure, were enrolled. We used hierarchal clustering and partial least squares-discriminant analysis to profile the tracheal aspirate airway fluid using quantitative LC-MS/MS to explore clusters of metabolites that correlated with acute hypoxemia severity and ventilator-free days. Three clusters of children that differed by severity of hypoxemia and ventilator-free days were identified. Quantitative pathway enrichment analysis showed that cysteine and methionine metabolism, selenocompound metabolism, glycine, serine and threonine metabolism, arginine biosynthesis, and valine, leucine, and isoleucine biosynthesis were the top five enriched, impactful pathways. We identified three clusters of amino acid metabolites found in the airway fluid of intubated children important to acute hypoxemia severity that correlated with ventilator-free days < 21 days. Further studies are needed to validate our findings and to test our models., (© 2021. The Author(s).)

Background: Several biomarkers have been identified to predict the outcome of COVID-19 severity, but few data are available regarding sex differences in their predictive role. Aim of this study was to identify sex-specific biomarkers of severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19., Methods: Plasma levels of sex hormones (testosterone and 17β-estradiol), sex-hormone dependent circulating molecules (ACE2 and Angiotensin1-7) and other known biomarkers for COVID-19 severity were measured in male and female COVID-19 patients at admission to hospital. The association of plasma biomarker levels with ARDS severity at admission and with the occurrence of respiratory deterioration during hospitalization was analysed in aggregated and sex disaggregated form., Results: Our data show that some biomarkers could be predictive both for males and female patients and others only for one sex. Angiotensin1-7 plasma levels and neutrophil count predicted the outcome of ARDS only in females, whereas testosterone plasma levels and lymphocytes counts only in males., Conclusions: Sex is a biological variable affecting the choice of the correct biomarker that might predict worsening of COVID-19 to severe respiratory failure. The definition of sex specific biomarkers can be useful to alert patients to be safely discharged versus those who need respiratory monitoring., (© 2021. The Author(s).)

Background: Non-invasive mechanical ventilation (NIV) use in patients admitted with acute respiratory failure due to COPD exacerbations (AECOPDs) varies significantly between hospitals. However, previous literature did not account for patients' illness severity. Our objective was to examine the variation in risk-standardized NIV use after adjusting for illness severity., Methods: We retrospectively analyzed AECOPD hospitalizations from 2011 to 2017 at 106 acute-care Veterans Health Administration (VA) hospitals in the USA. We stratified hospitals based on the percentage of NIV use among patients who received ventilation support within the first 24 hours of admission into quartiles, and compared patient characteristics. We calculated the risk-standardized NIV % using hierarchical models adjusting for comorbidities and severity of illness. We then stratified the hospitals by risk-standardized NIV % into quartiles and compared hospital characteristics between quartiles. We also compared the risk-standardized NIV % between rural and urban hospitals., Results: In 42,048 admissions for AECOPD over 6 years, the median risk-standardized initial NIV % was 57.3% (interquartile interval [IQI]=41.9-64.4%). Hospitals in the highest risk-standardized NIV % quartiles cared for more rural patients, used invasive ventilators less frequently, and had longer length of hospital stay, but had no difference in mortality relative to the hospitals in the lowest quartiles. The risk-standardized NIV % was 65.3% (IQI=34.2-84.2%) in rural and 55.1% (IQI=10.8-86.6%) in urban hospitals ( p =0.047), but hospital mortality did not differ between the two groups., Conclusion: NIV use varied significantly across hospitals, with rural hospitals having higher risk-standardized NIV % rates than urban hospitals. Further research should investigate the exact mechanism of variation in NIV use between rural and urban hospitals., Competing Interests: Dr Fortis reports grants from the Veterans Health Administration, has received grants from the American Thoracic Society and Fisher & Paykel to study the effect of heat-humidified high-flow air on COPD, and has served as a consultant for Genentech. Dr Amy MJ O’Shea reports grants from the VHA Office of Rural Health, during the conduct of the study. Mr Brice Beck reports receiving a salary from Iowa City VHA Research, during the conduct of the study. The authors have no other conflicts of interest germane to this manuscript. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States Government., (© 2021 Fortis et al.)

Background: The strength of association between preoperative natriuretic peptide levels and adverse outcomes after cardiac surgery recently has been studied in different research, but results still are diversely variable., Methods: Sixty-five consecutive patients undergoing elective off-pump coronary artery bypass grafting prospectively were recruited. Preoperative levels of NTproBNP were measured in venous blood samples collected before induction of anesthesia., Results: The average age was 57.62 ± 7.21. Of the patients, 86.15% were male. Euro-scoreII averaged 1.76 ± 0.34. The mean preoperative NTproBNP levels were 312.41 ± 329.93 pg/mL. Only two patients died (3%). Three patients required prolonged mechanical ventilation (4.6%). Four patients (6%) suffered from new onset postoperative AF. Five patients (7.6%) had low cardiac output, of which three needed IABP, and four patients (6%) had postoperative myocardial infarction. The mean ICU stay was 3.37 ± 0.84 days, and the mean hospital stay was 6.38 ± 1.3 days. There were no significant differences in preoperative NTproBNP levels in patients who had or didn't have any of the postoperative complications or in-hospital mortality (P > .05)., Conclusion: Our study showed no significant correlation between preoperative NTproBNP levels and postoperative low cardiac output, atrial fibrillation, postoperative myocardial infarction, length of ICU stay, prolonged mechanical ventilation, length of hospital stay as well as in-hospital mortality following elective off-pump CABG. Therefore, more prospective specific studies are needed to delineate the role of preoperative natriuretic peptides as significant predictors of poor outcomes after CABG surgery., (© 2021 Forum Multimedia Publishing, LLC)

Background Atrial fibrillation (AF) commonly occurs in the setting of acute conditions. We aimed to identify the acute conditions associated with secondary AF (AF precipitants) including pneumonia/sepsis, pneumothorax, respiratory failure, myocarditis, pericarditis, alcohol intoxication, thyrotoxicosis, cardiothoracic surgery, other surgery in patients with newly diagnosed AF and determine their association with subsequent oral anticoagulant use. Methods and Results We assembled a cohort of patients in the UMass Memorial Healthcare system with a new diagnosis of AF with and without AF precipitants. We used combinations of International Classification of Diseases , Tenth Revision ( ICD-10 ) codes, Current Procedural Terminology codes, laboratory values, imaging reports, and physician notes including discharge summary texts to identify AF precipitants. We then manually reviewed the individual charts to validate presence of AF precipitants. The study sample consisted of 185 patients with and 172 patients without AF precipitants. Pneumonia/sepsis, myocardial infarction, respiratory failure, and cardiothoracic surgery were the most common precipitants identified. In multivariable analyses adjusting for age, sex, patient comorbidities, left atrial enlargement, left ventricular ejection fraction, and antiplatelet use, patients with AF precipitants were less likely to receive subsequent anticoagulation therapy at 30 days after the initial AF diagnosis (odds ratio, 0.31; 95% CI, 0.19-0.52). The association was persistent after excluding men with CHA 2 DS 2 -VASc score <2 and women with CHA 2 DS 2 -VASc score <3. Conclusions Our study highlights lower usage of oral anticoagulant in secondary AF in contemporary clinical practice.

Competing Interests: Declaration of interests We declare no competing interests.

Various prediction models have been formulated to predict the need for mechanical ventilation (MV). In this study, we compare the sensitivity and specificity of Erasmus GBS Respiratory Insufficiency Score (EGRIS) and Sharshar score with single breath count (SBC) at 2 Hz to assess their usefulness in predicting MV and functional outcome. The primary outcome was prediction of MV and relative usefulness of all three models based on sensitivity and specificity. The secondary outcome was functional recovery at 6 months using the cut off points for MV and functional outcome at 6months was assessed using Hughes scale and categorized as good (<2) and poor (≥2). The median age was 30 years, and 64 (69.6%) were males. The sensitivity and specificity of EGRIS score was 78.1% and 67.2%, Sharshar score was 75.0% and 64.1%, and SBC at 2 Hz was 78.1% and 75.0%. The area under the receiver operating curves was maximum for SBC at 2 Hz (0.86) compared to other models, although insignificant. EGRIS score < 5 had better functional recovery compared to those with score ≥ 5 (66% vs 34%, p = 0.001). Similarly, in Sharshar score, 23/59 (39%) with score ≥ 4 had good recovery compared to 36 (61%) with score < 4 (p = 0.01). All the three models have comparable predictive values for MV. Outcome prediction is the best with EGRIS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The recent renascence of phenotypic drug discovery (PDD) is catalyzed by its ability to identify first-in-class drugs and deliver results when the exact molecular mechanism is partially obscure. Acute respiratory distress syndrome (ARDS) is a severe, life-threatening condition with a high mortality rate that has increased in frequency due to the COVID-19 pandemic. Despite decades of laboratory and clinical study, no efficient pharmacological therapy for ARDS has been found. An increase in endothelial permeability is the primary event in ARDS onset, causing the development of pulmonary edema that leads to respiratory failure. Currently, the detailed molecular mechanisms regulating endothelial permeability are poorly understood. Therefore, the use of the PDD approach in the search for efficient ARDS treatment can be more productive than classic target-based drug discovery (TDD), but its use requires a new cell-based assay compatible with high-throughput (HTS) and high-content (HCS) screening. Here we report the development of a new plate-based image cytometry method to measure endothelial barrier function. The incorporation of image cytometry in combination with digital image analysis substantially decreases assay variability and increases the signal window. This new method simultaneously allows for rapid measurement of cell monolayer permeability and cytological analysis. The time-course of permeability increase in human pulmonary artery endothelial cells (HPAECs) in response to the thrombin and tumor necrosis factor α treatment correlates with previously published data obtained by transendothelial resistance (TER) measurements. Furthermore, the proposed image cytometry method can be easily adapted for HTS/HCS applications.

Background: Defects in the RYR1 (OMIM#180901) gene lead to Ryanodine receptor type 1-related myopathies (RYR1-RM); the most common subgroup of congenital myopathies., Methods: Congenital myopathy presents a diagnostic challenge due to the need for multiple testing modalities to identify the many different genetic etiologies. In this case, the patient remained undiagnosed after whole-exome sequencing (WES), chromosomal microarray, methylation analysis, targeted deletion and duplication studies, and targeted repeat expansion studies. Clinical whole-genome sequencing (WGS) was then pursued as part of a research study to identify a diagnosis., Results: WGS identified compound heterozygous RYR1 intronic variants, RNA sequencing confirmed both variants to be pathogenic causing RYR1-RM in a phenotype of severe congenital hypotonia with respiratory failure from birth, neonatal brain hemorrhage, and congenital heart disease involving transposition of the great arteries., Conclusion: While there is an ongoing debate about the clinical superiority of WGS versus WES for patients with a suspected genetic condition, this scenario highlights a weakness of WES as well as the added cost and delay in diagnosis timing with having WGS follow WES or even ending further genetic testing with a negative WES. While knowledge gaps still exist for many intronic variants, transcriptome analysis provides a way of validating the resulting dysfunction caused by these variants and thus allowing for appropriate pathogenicity classification. This is the second published case report of a patient with pathogenic intronic variants in RYR1-RM, with clinical RNA testing confirming variant pathogenicity and therefore the diagnosis suggesting that for some patients careful analysis of a patient's genome and transcriptome are required for a complete genetic evaluation. The diagnostic odyssey experienced by this patient highlights the importance of early, rapid WGS., (© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)