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Diabetes mellitus is associated with 90-day mortality in old critically ill COVID-19 patients: a multicenter prospective observational cohort study.
Mayerhöfer, T, Klein, S, Wernly, B, Flaatten, H, Guidet, B, De Lange, DW, Fjølner, J, Leaver, S, Beil, M, Sviri, S, et al
Infection. 2023;(5):1407-1415
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Abstract
BACKGROUND Several studies have found an association between diabetes mellitus, disease severity and outcome in COVID-19 patients. Old critically ill patients are particularly at risk. This study aimed to investigate the impact of diabetes mellitus on 90-day mortality in a high-risk cohort of critically ill patients over 70 years of age. METHODS This multicentre international prospective cohort study was performed in 151 ICUs across 26 countries. We included patients ≥ 70 years of age with a confirmed SARS-CoV-2 infection admitted to the intensive care unit from 19th March 2020 through 15th July 2021. Patients were categorized into two groups according to the presence of diabetes mellitus. Primary outcome was 90-day mortality. Kaplan-Meier overall survival curves until day 90 were analysed and compared using the log-rank test. Mixed-effect Weibull regression models were computed to investigate the influence of diabetes mellitus on 90-day mortality. RESULTS This study included 3420 patients with a median age of 76 years were included. Among these, 37.3% (n = 1277) had a history of diabetes mellitus. Patients with diabetes showed higher rates of frailty (32% vs. 18%) and several comorbidities including chronic heart failure (20% vs. 11%), hypertension (79% vs. 59%) and chronic kidney disease (25% vs. 11%), but not of pulmonary comorbidities (22% vs. 22%). The 90-day mortality was significantly higher in patients with diabetes than those without diabetes (64% vs. 56%, p < 0.001). The association of diabetes and 90-day mortality remained significant (HR 1.18 [1.06-1.31], p = 0.003) after adjustment for age, sex, SOFA-score and other comorbidities in a Weibull regression analysis. CONCLUSION Diabetes mellitus was a relevant risk factor for 90-day mortality in old critically ill patients with COVID-19. STUDY REGISTRATION NCT04321265, registered March 19th, 2020.
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Simvastatin in Critically Ill Patients with Covid-19.
, , Hills, TE, Lorenzi, E, Berry, LR, Shyamsundar, M, Al-Beidh, F, Annane, D, Arabi, Y, Aryal, D, Au, C, et al
The New England journal of medicine. 2023;(25):2341-2354
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BACKGROUND The efficacy of simvastatin in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS In an ongoing international, multifactorial, adaptive platform, randomized, controlled trial, we evaluated simvastatin (80 mg daily) as compared with no statin (control) in critically ill patients with Covid-19 who were not receiving statins at baseline. The primary outcome was respiratory and cardiovascular organ support-free days, assessed on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support through day 21 in survivors; the analyis used a Bayesian hierarchical ordinal model. The adaptive design included prespecified statistical stopping criteria for superiority (>99% posterior probability that the odds ratio was >1) and futility (>95% posterior probability that the odds ratio was <1.2). RESULTS Enrollment began on October 28, 2020. On January 8, 2023, enrollment was closed on the basis of a low anticipated likelihood that prespecified stopping criteria would be met as Covid-19 cases decreased. The final analysis included 2684 critically ill patients. The median number of organ support-free days was 11 (interquartile range, -1 to 17) in the simvastatin group and 7 (interquartile range, -1 to 16) in the control group; the posterior median adjusted odds ratio was 1.15 (95% credible interval, 0.98 to 1.34) for simvastatin as compared with control, yielding a 95.9% posterior probability of superiority. At 90 days, the hazard ratio for survival was 1.12 (95% credible interval, 0.95 to 1.32), yielding a 91.9% posterior probability of superiority of simvastatin. The results of secondary analyses were consistent with those of the primary analysis. Serious adverse events, such as elevated levels of liver enzymes and creatine kinase, were reported more frequently with simvastatin than with control. CONCLUSIONS Although recruitment was stopped because cases had decreased, among critically ill patients with Covid-19, simvastatin did not meet the prespecified criteria for superiority to control. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.).
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ESICM guidelines on acute respiratory distress syndrome: definition, phenotyping and respiratory support strategies.
Grasselli, G, Calfee, CS, Camporota, L, Poole, D, Amato, MBP, Antonelli, M, Arabi, YM, Baroncelli, F, Beitler, JR, Bellani, G, et al
Intensive care medicine. 2023;(7):727-759
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Abstract
The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients' representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research.
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Detailed stratified GWAS analysis for severe COVID-19 in four European populations.
Degenhardt, F, Ellinghaus, D, Juzenas, S, Lerga-Jaso, J, Wendorff, M, Maya-Miles, D, Uellendahl-Werth, F, ElAbd, H, Rühlemann, MC, Arora, J, et al
Human molecular genetics. 2022;(23):3945-3966
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Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a ~0.9-Mb inversion polymorphism that creates two highly differentiated haplotypes and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative including non-Caucasian individuals, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.
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Noninvasive ventilation in COVID-19 patients aged ≥ 70 years-a prospective multicentre cohort study.
Polok, K, Fronczek, J, Artigas, A, Flaatten, H, Guidet, B, De Lange, DW, Fjølner, J, Leaver, S, Beil, M, Sviri, S, et al
Critical care (London, England). 2022;(1):224
Abstract
BACKGROUND Noninvasive ventilation (NIV) is a promising alternative to invasive mechanical ventilation (IMV) with a particular importance amidst the shortage of intensive care unit (ICU) beds during the COVID-19 pandemic. We aimed to evaluate the use of NIV in Europe and factors associated with outcomes of patients treated with NIV. METHODS This is a substudy of COVIP study-an international prospective observational study enrolling patients aged ≥ 70 years with confirmed COVID-19 treated in ICU. We enrolled patients in 156 ICUs across 15 European countries between March 2020 and April 2021.The primary endpoint was 30-day mortality. RESULTS Cohort included 3074 patients, most of whom were male (2197/3074, 71.4%) at the mean age of 75.7 years (SD 4.6). NIV frequency was 25.7% and varied from 1.1 to 62.0% between participating countries. Primary NIV failure, defined as need for endotracheal intubation or death within 30 days since ICU admission, occurred in 470/629 (74.7%) of patients. Factors associated with increased NIV failure risk were higher Sequential Organ Failure Assessment (SOFA) score (OR 3.73, 95% CI 2.36-5.90) and Clinical Frailty Scale (CFS) on admission (OR 1.46, 95% CI 1.06-2.00). Patients initially treated with NIV (n = 630) lived for 1.36 fewer days (95% CI - 2.27 to - 0.46 days) compared to primary IMV group (n = 1876). CONCLUSIONS Frequency of NIV use varies across European countries. Higher severity of illness and more severe frailty were associated with a risk of NIV failure among critically ill older adults with COVID-19. Primary IMV was associated with better outcomes than primary NIV. Clinical Trial Registration NCT04321265 , registered 19 March 2020, https://clinicaltrials.gov .
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Vasculitis changes in COVID-19 survivors with persistent symptoms: an [18F]FDG-PET/CT study.
Sollini, M, Ciccarelli, M, Cecconi, M, Aghemo, A, Morelli, P, Gelardi, F, Chiti, A
European journal of nuclear medicine and molecular imaging. 2021;48(5):1460-1466
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Plain language summary
The SARS-CoV-2 infection manifests with a broad spectrum of clinical patterns ranging from minimally or asymptomatic cases to mild illness, to severe infection, to critical disease. The aim of this study was to evaluate whether the radiopharmaceutical, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), was able to demonstrate a persistent inflammatory process in the vascular epithelium or in any other site. The study included Covid-19 patients who recovered but complained of unexplained persisting symptoms for more than 30 days during the follow-up visits. The patients where divided into two groups; the long Covid and control group. Results indicate that although the total vascular score was similar in the two groups, the target-to-blood pool ratio was significantly higher in three vascular regions (thoracic aorta, right iliac artery, and femoral arteries) in the long Covid than in controls. Authors conclude that their findings suggest that SARS-CoV-2 induces vascular inflammation, which may be responsible for persisting symptoms.
Abstract
PURPOSE Several patients experience unexplained persistent symptoms after SARS-CoV-2 recovering. We aimed at evaluating if 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) was able to demonstrate a persistent inflammatory process. METHODS Recovered adult COVID-19 patients, who complained unexplained persisting symptoms for more than 30 days during the follow-up visits, were invited to participate in the study. Patients fulfilling inclusion criteria were imaged by [18F]FDG positron emission tomography/computed tomography ([18F]FDG-PET/CT). Whole-body [18F]FDG-PET/CT, performed according to good clinical practice, was qualitatively (comparison with background/liver) and semi-quantitatively (target-to-blood pool ratio calculated as average SUVmax artery/average SUVmean inferior vena cava) analyzed. Negative follow-up [18F]FDG-PET/CT images of oncologic patients matched for age/sex served as controls. Mann-Whitney test was used to test differences between groups. SPSS version 26 was used for analyses. RESULTS Ten recovered SARS-CoV-2 patients (seven male and three females, median age 52 years, range 46-80) with persisting symptoms were enrolled in the study. Common findings at visual analysis were increased [18F]FDG uptake in bone marrow and blood vessels (8/10 and 6/10 cases, respectively). [18F]FDG uptake in bone marrow did not differ between cases and controls (p = 0.16). The total vascular score was similar in the two groups (p = 0.95). The target-to-blood pool ratio resulted higher in recovered SARS-CoV-2 patients than in controls. CONCLUSION Although the total vascular score was similar in the two groups, the target-to-blood pool ratio was significantly higher in three vascular regions (thoracic aorta, right iliac artery, and femoral arteries) in the recovered COVID-19 cohort than in controls, suggesting that SARS-CoV-2 induces vascular inflammation, which may be responsible for persisting symptoms.
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Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016.
Author et al, , Bateman, RM, Sharpe, MD, Jagger, JE, Ellis, CG, Solé-Violán, J, López-Rodríguez, M, Herrera-Ramos, E, Ruíz-Hernández, J, Borderías, L, et al
Critical care (London, England). 2016;:347
Abstract
[This corrects the article DOI: 10.1186/s13054-016-1208-6.].
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Year in review in Intensive Care Medicine 2012: I. Neurology and neurointensive care, epidemiology and nephrology, biomarkers and inflammation, nutrition, experimentals.
Antonelli, M, Bonten, M, Cecconi, M, Chastre, J, Citerio, G, Conti, G, Curtis, JR, Hedenstierna, G, Joannidis, M, Macrae, D, et al
Intensive care medicine. 2013;(2):232-46
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Mowat-Wilson syndrome: facial phenotype changing with age: study of 19 Italian patients and review of the literature.
Garavelli, L, Zollino, M, Mainardi, PC, Gurrieri, F, Rivieri, F, Soli, F, Verri, R, Albertini, E, Favaron, E, Zignani, M, et al
American journal of medical genetics. Part A. 2009;(3):417-26
Abstract
Mowat-Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene, and characterized by typical face, moderate-to-severe mental retardation, epilepsy, Hirschsprung disease, and multiple congenital anomalies, including genital anomalies (particularly hypospadias in males), congenital heart defects, agenesis of the corpus callosum, and eye defects. Since the first delineation by Mowat et al. [Mowat et al. (1998); J Med Genet 35:617-623], approximately 179 patients with ZEB2 mutations, deletions or cytogenetic abnormalities have been reported primarily from Europe, Australia and the United States. Genetic defects include chromosome 2q21-q23 microdeletions (or different chromosome rearrangements) in few patients, and ZEB2 mutations in most. We report on clinical and genetic data from 19 Italian patients, diagnosed within the last 5 years, including six previously published, and compare them with patients already reported. The main purpose of this review is to underline a highly consistent phenotype and to highlight the phenotypic evolution occurring with age, particularly of the facial characteristics. The prevalence of MWS is likely to be underestimated. Knowledge of the phenotypic spectrum of MWS and of its changing phenotype with age can improve the detection rate of this condition.