Cardiac Adverse Events and Remdesivir in Hospitalized Patients With COVID-19: A Post Hoc Safety Analysis of the Randomized DisCoVeRy Trial.

BACKGROUND: We aimed to evaluate the cardiac adverse events (AEs) in hospitalized patients with coronavirus disease 2019 (COVID-19) who received remdesivir plus standard of care (SoC) compared with SoC alone (control), as an association was noted in some cohort studies and disproportionality analyses of safety databases. METHODS: This post hoc safety analysis is based on data from the multicenter, randomized, open-label, controlled DisCoVeRy trial in hospitalized patients with COVID-19. Any first AE that occurred between randomization and day 29 in the modified intention-to-treat (mITT) population randomized to either remdesivir or control group was considered. Analysis was performed using Kaplan-Meier survival curves, and Kaplan-Meier estimates were calculated for event rates. RESULTS: Cardiac AEs were reported in 46 (11.2%) of 410 and 48 (11.3%) of 423 patients in the mITT population (n = 833) enrolled in the remdesivir and control groups, respectively. The difference between both groups was not significant (hazard ratio [HR], 1.0; 95% confidence interval [CI], .7-1.5; P = .98), even when serious and nonserious cardiac AEs were evaluated separately. The majority of reports in both groups were of arrhythmic nature (remdesivir, 84.8%; control, 83.3%) and were associated with a favorable outcome. There was no significant difference between the two groups in the occurrence of cardiac AE subclasses, including arrhythmic events (HR, 1.1; 95% CI, .7-1.7; P = .68). CONCLUSIONS: Remdesivir treatment was not associated with an increased risk of cardiac AEs compared with control in patients hospitalized with moderate or severe COVID-19. These results are consistent with other randomized, controlled trials and meta-analyses. Clinical Trials Registration. NCT04315948; EudraCT 2020-000936-23.

Cardiac Tamponade Complicating Extracorporeal Membrane Oxygenation: An Extracorporeal Life Support Organization Registry Analysis.

OBJECTIVES: Cardiac tamponade is a potentially life-threatening complication during extracorporeal membrane oxygenation (ECMO). In this study, the authors assessed the incidence, patient characteristics, and risk factors for mortality of cardiac tamponade during ECMO. DESIGN: The authors queried the Extracorporeal Life Support Organization (ELSO) Registry from 1997 to 2021 for all adults with cardiac tamponade as a reported complication during ECMO. PARTICIPANTS: Cardiac tamponade was reported in 2,176 (64% men; 53.8 ± 0.33 years) of 84,430 adults (2.6%). MEASUREMENTS AND MAIN RESULTS: Venoarterial ECMO was the main configuration (78%), followed by venovenous ECMO (VV ECMO) (18%), for cardiac (67%), pulmonary (21%) support, and extracorporeal cardiopulmonary resuscitation (ECPR) (12%). Percutaneous cannulation was performed in 51%, with the femoral vein and femoral artery as the most common sites for drainage and return cannulae, with dual-lumen cannulae in 39% of VV ECMO. Hospital survival was lower (35% v 49%; p < 0.01) when compared with that of all adults from the ELSO Registry. In multivariate analysis, age, aortic dissection and/or rupture, COVID-19, ECPR, pre-ECMO renal-replacement therapy, and prone position are associated with hospital mortality, whereas ECMO for pulmonary support is associated with hospital survival. Similarly, renal, cardiovascular, metabolic, neurologic, and pulmonary complications occurred more frequently in nonsurvivors. CONCLUSIONS: Cardiac tamponade is a rare complication during ECMO that, despite being potentially reversible, is associated with high hospital mortality. Venoarterial ECMO is the most common configuration. ECMO for pulmonary support was associated with higher survival, and ECPR was associated with higher mortality. In these patients, other ECMO-related complications were frequently reported and associated with hospital mortality.

Ultrasonography to Access Diaphragm Dysfunction and Predict the Success of Mechanical Ventilation Weaning in Critical Care: A Narrative Review.

INTRODUCTION: Weaning failure is common in mechanically ventilated patients, and whether ultrasound (US) can predict weaning outcome remains controversial. This review aims to evaluate the diaphragmatic function measured by US as a predictor of weaning outcome. METHODS: PubMed was searched to identify original articles about the use of diaphragmatic US in ICU patients. A total of 61 citations were retrieved initially; available data of 26 studies were included in this review. RESULTS: To assess diaphragmatic dysfunction in adults, six studies evaluated excursion, five evaluated thickening fraction, and both in nine. Despite heterogeneity in the diagnostic accuracy of diaphragm US among the studies, the sonographic indices showed good diagnostic performance for predicting weaning outcome. CONCLUSIONS: Diaphragmatic US can be a useful and accurate tool to detect diaphragmatic dysfunction in critically ill patients and predict weaning outcome.

Evaluation of urinary cysteinyl leukotrienes as biomarkers of severity and putative therapeutic targets in COVID-19 patients.

BACKGROUND: Cysteinyl leukotrienes (CysLT) are potent inflammation-promoting mediators, but remain scarcely explored in COVID-19. We evaluated urinary CysLT (U-CysLT) relationship with disease severity and their usefulness for prognostication in hospitalized COVID-19 patients. The impact on U-CysLT of veno-venous extracorporeal membrane oxygenation (VV-ECMO) and of comorbidities such as hypertension and obesity was also assessed. METHODS: Blood and spot urine were collected in "severe" (n = 26), "critically ill" (n = 17) and "critically ill on VV-ECMO" (n = 17) patients with COVID-19 at days 1-2 (admission), 3-4, 5-8 and weekly thereafter, and in controls (n = 23) at a single time point. U-CysLT were measured by ELISA. Routine markers, prognostic scores and outcomes were also evaluated. RESULTS: U-CysLT did not differ between groups at admission, but significantly increased along hospitalization only in critical groups, being markedly higher in VV-ECMO patients, especially in hypertensives. U-CysLT values during the first week were positively associated with ICU and total hospital length of stay in critical groups and showed acceptable area under curve (AUC) for prediction of 30-day mortality (AUC: 0.734, p = 0.001) among all patients. CONCLUSIONS: U-CysLT increase during hospitalization in critical COVID-19 patients, especially in hypertensives on VV-ECMO. U-CysLT association with severe outcomes suggests their usefulness for prognostication and as therapeutic targets.

Treatment of invasive candidiasis in the era of Candida resistance.

PURPOSE OF REVIEW: The increasing incidence of drug-resistant Candida brings a new challenge to the treatment of invasive candidiasis. Although cross-resistance among azoles and echinocandins was generally uncommon, reports of multidrug-resistant (MDR) Candida markedly increased in the last decade. The purpose of this review is to understand mechanisms and risk factors for resistance and how to tackle antifungal resistance. RECENT FINDINGS: The paper describes the action of the three main classes of antifungals - azoles, echinocandins and polyenes - and Candida's mechanisms of resistance. The current evolution from cross-resistance to multiresistance among Candida explains the modern glossary - multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) - imported from bacteria. MDR Candida most commonly involves acquired resistance in species with intrinsic resistance, therefore it mostly involves C. glabrata, C. parapsilosis, C. krusei, C guilliermondii or C. auris , which is intrinsically multidrug resistant. Finally, strategies to tackle antifungal resistance became clearer, ideally implemented through antifungal stewardship. SUMMARY: Avoiding antifungal's overuse and selecting the best drug, dose and duration, when they are needed, is fundamental. Knowledge of risk factors for resistance, microbiological diagnosis to the species, use of susceptibility test supported by antifungal stewardship programs help attaining effective therapy and sustaining the effectiveness of the current antifungal armamentarium.

Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial.

BACKGROUND: Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants. METHODS: Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. RESULTS: Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49-69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI - 0.1% [- 8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (- 3.2% [- 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities. CONCLUSION: This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies. Trial registration Bari-SolidAct is registered at NCT04891133 (registered May 18, 2021) and EUClinicalTrials.eu ( 2022-500385-99-00 ).

Creatinine Clearance in Acute Brain Injury: A Comparison of Methods.

BACKGROUND: Currently, the measurement of glomerular filtration rate is very complex and costly, so its daily evaluation is performed using endogenous markers, of which creatinine is the most frequently used. It allows the estimation of glomerular filtration rate by means of its clearance or by formulas based on its serum and urine concentration. Augmented renal clearance (ARC) is frequent among critically ill patients and is defined as creatinine clearance (CrCl) > 130 ml/min/1.73 m2. The aim of this study was to compare measured CrCl (MCC) and estimated CrCl obtained with the Cockcroft-Gault formula (CG), the Modification of Diet in Renal Disease Study equation (MDRD), and the Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI) in patients with severe traumatic brain injury and nontraumatic subarachnoid hemorrhage. The second aim was to assess the incidence of ARC in this population of neurocritical patients. METHODS: This was a prospective, observational, single center study from a cohort of 74 patients admitted to the neurocritical intensive care unit due to traumatic brain injury or subarachnoid hemorrhage. Serum creatinine (at 7 a.m.) and a 6-h urine collection were analyzed, and CrCl was measured and estimated by using CG, MDRD, and CKD-EPI. The intraclass correlation coefficient (ICC) was evaluated for each pair, and Bland-Altman plots were used to assess clinical significance. RESULTS: Among 74 patients, the median age was 53 (interquartile range [IQR] 36-65), and the median Glasgow Coma Scale score at admission was 6. The median MCC at admission was 176 (IQR 135-214). The medians of CG, MDRD and CKD-EPI were, respectively, 129 ml/min/1.73 m2 (IQR 95-176), 158 (IQR 115-202), and 116 (97-132). An ICC was applied to evaluate the correlation between MCC and estimated methods and showed a weak correlation between MCC and estimated CrCl obtained with the three different methods. The strongest ICC statistical correlation was found between MCC and MDRD, and the weakest correlation was found between MCC and CKD-EPI. Bland-Altman plots showed that differences between each pair were not clinically acceptable. ARC was present in 78% of measurements, using MCC. A weak correlation was observed between MCC and calculated CrCl. CG, MDRD, and CKD-EPI overestimated MCC when MCC ≤ 130 ml/min/1.73 m2 and underestimated it when MCC > 130 ml/min/1.73 m2. CONCLUSIONS: In this population, there was a weak statistical correlation between measured and estimated methods. In patients with ARC, formulas underestimated MCC. MCC should probably be the preferred methodology for renal function assessment in the clinical setting to better adjust drug dosage and guarantee drug effectiveness.

Effect of remdesivir on viral dynamics in COVID-19 hospitalized patients: a modelling analysis of the randomized, controlled, open-label DisCoVeRy trial.

BACKGROUND: The antiviral efficacy of remdesivir in COVID-19 hospitalized patients remains controversial. OBJECTIVES: To estimate the effect of remdesivir in blocking viral replication. METHODS: We analysed nasopharyngeal normalized viral loads from 665 hospitalized patients included in the DisCoVeRy trial (NCT04315948; EudraCT 2020-000936-23), randomized to either standard of care (SoC) or SoC + remdesivir. We used a mathematical model to reconstruct viral kinetic profiles and estimate the antiviral efficacy of remdesivir in blocking viral replication. Additional analyses were conducted stratified on time of treatment initiation (≤7 or >7 days since symptom onset) or viral load at randomization (< or ≥3.5 log10 copies/104 cells). RESULTS: In our model, remdesivir reduced viral production by infected cells by 2-fold on average (95% CI: 1.5-3.2-fold). Model-based simulations predict that remdesivir reduced time to viral clearance by 0.7 days compared with SoC, with large inter-individual variabilities (IQR: 0.0-1.3 days). Remdesivir had a larger impact in patients with high viral load at randomization, reducing viral production by 5-fold on average (95% CI: 2.8-25-fold) and the median time to viral clearance by 2.4 days (IQR: 0.9-4.5 days). CONCLUSIONS: Remdesivir halved viral production, leading to a median reduction of 0.7 days in the time to viral clearance compared with SoC. The efficacy was larger in patients with high viral load at randomization.

Different epidemiology of bloodstream infections in COVID-19 compared to non-COVID-19 critically ill patients: a descriptive analysis of the Eurobact II study.

BACKGROUND: The study aimed to describe the epidemiology and outcomes of hospital-acquired bloodstream infections (HABSIs) between COVID-19 and non-COVID-19 critically ill patients. METHODS: We used data from the Eurobact II study, a prospective observational multicontinental cohort study on HABSI treated in ICU. For the current analysis, we selected centers that included both COVID-19 and non-COVID-19 critically ill patients. We performed descriptive statistics between COVID-19 and non-COVID-19 in terms of patients' characteristics, source of infection and microorganism distribution. We studied the association between COVID-19 status and mortality using multivariable fragility Cox models. RESULTS: A total of 53 centers from 19 countries over the 5 continents were eligible. Overall, 829 patients (median age 65 years [IQR 55; 74]; male, n = 538 [64.9%]) were treated for a HABSI. Included patients comprised 252 (30.4%) COVID-19 and 577 (69.6%) non-COVID-19 patients. The time interval between hospital admission and HABSI was similar between both groups. Respiratory sources (40.1 vs. 26.0%, p < 0.0001) and primary HABSI (25.4% vs. 17.2%, p = 0.006) were more frequent in COVID-19 patients. COVID-19 patients had more often enterococcal (20.5% vs. 9%) and Acinetobacter spp. (18.8% vs. 13.6%) HABSIs. Bacteremic COVID-19 patients had an increased mortality hazard ratio (HR) versus non-COVID-19 patients (HR 1.91, 95% CI 1.49-2.45). CONCLUSIONS: We showed that the epidemiology of HABSI differed between COVID-19 and non-COVID-19 patients. Enterococcal HABSI predominated in COVID-19 patients. COVID-19 patients with HABSI had elevated risk of mortality. Trial registration ClinicalTrials.org number NCT03937245 . Registered 3 May 2019.

Genomic prediction and genetic correlations estimated for milk production and fatty acid traits in Walloon Holstein cattle using random regression models.

The aims of this study were to: (1) estimate genetic correlation for milk production traits (milk, fat and protein yields and fat and protein contents) and fatty acids (FA: C16:0, C18:1 cis-9, LCFA, SFA, and UFA) over days in milk, (2) investigate the performance of genomic predictions using single-step GBLUP (ssGBLUP) based on random regression models (RRM), and (3) identify the optimal scaling and weighting factors to be used in the construction of the H matrix. A total of 302 684 test-day records of 63.875 first lactation Walloon Holstein cows were used. Positive genetic correlations were found between milk yield and fat and protein yield (rg from 0.46 to 0.85) and between fat yield and milk FA (rg from 0.17 to 0.47). On the other hand, negative correlations were estimated between fat and protein contents (rg from -0.22 to -0.59), between milk yield and milk FA (rg from -0.22 to -0.62), and between protein yield and milk FA (rg from -0.11 to -0.19). The selection for high fat content increases milk FA throughout lactation (rg from 0.61 to 0.98). The test-day ssGBLUP approach showed considerably higher prediction reliability than the parent average for all milk production and FA traits, even when no scaling and weighting factors were used in the H matrix. The highest validation reliabilities (r2 from 0.09 to 0.38) and less biased predictions (b1 from 0.76 to 0.92) were obtained using the optimal parameters (i.e., ω = 0.7 and α = 0.6) for the genomic evaluation of milk production traits. For milk FA, the optimal parameters were ω = 0.6 and α = 0.6. However, biased predictions were still observed (b1 from 0.32 to 0.81). The findings suggest that using ssGBLUP based on RRM is feasible for the genomic prediction of daily milk production and FA traits in Walloon Holstein dairy cattle.

Random regression test-day models to describe milk production and fatty acid traits in first lactation Walloon Holstein cows.

We investigated the use of different Legendre polynomial orders to estimate genetic parameters for milk production and fatty acid (FA) traits in the first lactation Walloon Holstein cows. The data set comprised 302,684 test-day records of milk yield, fat and protein contents, and FAs generated by mid-infrared (MIR) spectroscopy, C16:0 (palmitic acid), C18:1 cis-9 (oleic acid), LCFAs (long-chain FAs), SFAs (saturated FAs) and UFAs (unsaturated FAs) were studied. The models included random regression coefficients for herd-year of calving (h), additive genetic (a) and permanent environment (p) effects. The selection of the best random regression model (RRM) was based on the deviance information criterion (DIC), and genetic parameters were estimated via a Bayesian approach. For all analysed random effects, DIC values decreased as the order of the Legendre polynomials increased. Best-fit models had fifth-order (degree 4) for the p effect and ranged from second- to fifth-order (degree 1-4) for the a and h effects (LEGhap: LEG555 for milk yield and protein content; LEG335 for fat content and SFA; LEG545 for C16:0 and UFA; and LEG535 for C18:1 cis-9 and LCFA). Based on the best-fit models, an effect of overcorrection was observed in early lactation (5-35 days in milk [DIM]). On the contrary, third-order (LEG333; degree 2) models showed flat residual trajectories throughout lactation. In general, the estimates of genetic variance tended to increase over DIM, for all traits. Heritabilities for milk production traits ranged from 0.11 to 0.58. Milk FA heritabilities ranged from low-to-high magnitude (0.03-0.56). High Spearman correlations (>0.90 for all bulls and >0.97 for top 100) were found among breeding values for 155 and 305 DIM between the best RRM and LEG333 model. Therefore, third-order Legendre polynomials seem to be most parsimonious and sufficient to describe milk production and FA traits in Walloon Holstein cows.

Searching for causal relationships among latent variables concerning performance, carcass, and meat quality traits in broilers.

In causal relationship studies, the latent variables may summarize the phenotypes in theoretical traits according to their phenotypic correlations, improving the understanding of causal relationships between broilers phenotypes. In this study, we aimed to investigate potential causal relationships among latent variables in broilers using a structural equation model in the context of genetic analysis. The data used in this study comprised 14 traits in broilers with 2,017 records each, and 104,154 animals in pedigree. Four latent variables (WEIGHT, LOSSES, COLOUR, and VISCERA) were defined and validated using Bayesian Confirmatory Factor Analysis. Subsequently, a search for causal linkage structures was performed, obtaining a single causal link structure between the latent variables. Then, this information was used to fit the structural equation model (SEM). The results from the SEM indicated positive causal effects of the variables WEIGHT and LOSSES on the variables VISCERA and COLOUR, respectively, with structural coefficient estimates of 1.006 and 0.040, respectively. On the other hand, an antagonist causal effect of the variable WEIGHT on the variable LOSSES was verified, with a structural coefficient estimate of -4.333. These results highlight the causal relationship between performance and meat quality traits, which may be associated with the natural processes involved in the conversion of muscle into meat and the structural changes in muscle tissues due to intense selection for high growth rates in broilers.

Depressive and Anxiety Symptoms in Severe COVID-19 Survivors: A Prospective Cohort Study.

The coronavirus disease 2019 (COVID-19) has rapidly spread worldwide, leading to increased concerns about long-term patients' neuropsychiatric consequences. This study aims to describe the presence of depressive and anxiety symptoms in severe COVID-19 survivors and to identify associated baseline, in-hospital and post-discharge factors. This study is part of the MAPA longitudinal project conducted with severe COVID-19 patients admitted in Intensive Care Medicine Department (ICMD) of a University Hospital (CHUSJ) in Porto, Portugal. Patients with ICMD length of stay ≤ 24 h, terminal illness, major auditory loss or inability to communicate at follow-up assessment were excluded. All participants were assessed by telephone post-discharge (median = 101 days), with a comprehensive protocol assessing depressive and anxiety symptoms, cognition, Intensive Care Unit (ICU) memories recall and health-related quality of life. Out of a sample of 56 survivors (median age = 65; 68% males), 29% and 23% had depressive and anxiety symptoms, respectively. Depressive and anxiety symptoms were significantly more prevalent among younger survivors and were associated with cognitive complaints, emotional and delusions ICU memories and fear of having COVID-19 sequelae, sleep problems and pain after discharge (all p < 0.05). An important proportion of these survivors suffers from depression and anxiety symptoms post-discharge, namely younger ones and those who reported more cognitive complaints, ICU memories, fear of having COVID-19 sequelae, sleep problems and pain. These findings highlight the importance of psychological consequences assessment and planning of appropriate and multidisciplinary follow-up care after hospitalization due to COVID-19.

Adverse cardiovascular magnetic resonance phenotypes are associated with greater likelihood of incident coronavirus disease 2019: findings from the UK Biobank.

BACKGROUND: Coronavirus disease 2019 (COVID-19) disproportionately affects older people. Observational studies suggest indolent cardiovascular involvement after recovery from acute COVID-19. However, these findings may reflect pre-existing cardiac phenotypes. AIMS: We tested the association of baseline cardiovascular magnetic resonance (CMR) phenotypes with incident COVID-19. METHODS: We studied UK Biobank participants with CMR imaging and COVID-19 testing. We considered left and right ventricular (LV, RV) volumes, ejection fractions, and stroke volumes, LV mass, LV strain, native T1, aortic distensibility, and arterial stiffness index. COVID-19 test results were obtained from Public Health England. Co-morbidities were ascertained from self-report and hospital episode statistics (HES). Critical care admission and death were from HES and death register records. We investigated the association of each cardiovascular measure with COVID-19 test result in multivariable logistic regression models adjusting for age, sex, ethnicity, deprivation, body mass index, smoking, diabetes, hypertension, high cholesterol, and prior myocardial infarction. RESULTS: We studied 310 participants (n = 70 positive). Median age was 63.8 [57.5, 72.1] years; 51.0% (n = 158) were male. 78.7% (n = 244) were tested in hospital, 3.5% (n = 11) required critical care admission, and 6.1% (n = 19) died. In fully adjusted models, smaller LV/RV end-diastolic volumes, smaller LV stroke volume, and poorer global longitudinal strain were associated with significantly higher odds of COVID-19 positivity. DISCUSSION: We demonstrate association of pre-existing adverse CMR phenotypes with greater odds of COVID-19 positivity independent of classical cardiovascular risk factors. CONCLUSIONS: Observational reports of cardiovascular involvement after COVID-19 may, at least partly, reflect pre-existing cardiac status rather than COVID-19 induced alterations.

Brain Multimodal Monitoring in Severe Acute Brain Injury: Is It Relevant to Patient Outcome and Mortality?

INTRODUCTION: Advanced multimodal monitoring (MMM) of the brain is recommended as a tool to manage severe acute brain injury in intensive care units (ICUs) and prevent secondary lesions. The aim of this study was to determine if MMM has implications for patient outcome and mortality. METHODS: We analyzed data on 389 patients admitted with a subarachnoid hemorrhage (SAH) or traumatic brain injury (TBI) to two general ICUs and one neurocritical care ICU (NCCU) between March 2014 and October 2016, and their subsequent outcomes. RESULTS: The study population consisted of 259 males and 130 females. Group 1, which comprised 69 patients with MMM admitted to the NCCU, was compared with group 2, which comprised patients managed without MMM. With the exceptions of the Simplified Acute Physiology Score (SAPS II) and Glasgow Coma Scale (GCS) scores, there were no differences between the two groups. Group 1 had significantly better outcomes at ICU discharge, at 28 days, and at 3 months, and also had a lower mortality rate (P < 0.05). When outcomes were adjusted for SAPS II scores, patients who had MMM had better outcomes (odds ratios 0.215 at ICU discharge, 0.234 at 28 days, 0.338 at 3 months, and 0.474 at 6 months) but no difference in mortality. CONCLUSION: Use of MMM in patients with SAH or TBI is associated with better outcomes and should be considered in the management of these patients.

Cardiac Tamponade Complicating Extracorporeal Membrane Oxygenation: A Single-Centre Experience.

BACKGROUND: Cardiac tamponade is a potential complication during extracorporeal membrane oxygenation (ECMO). METHOD: This study assessed the incidence, clinical presentation, therapeutic approach, and outcome of cardiac tamponade at a single ECMO centre during a 10-year period. RESULTS: Cardiac tamponade occurred in 11 adults (seven men; age 53 years [range, 48-60]) of 566 patients (1.9%), after 10 days (range, 3-16) of ECMO support: eight veno-venous (VV) and three veno-arterial (VA). Cardiac tamponade was suspected due to haemodynamic deterioration or collapse, and was confirmed by bedside echocardiography. In five of eight VV-ECMO (62%) patients, circulatory arrest ensued and immediate VA-ECMO conversion was performed. Definitive treatment of cardiac tamponade consisted of surgical pericardiotomy in 10 cases: sternotomy (n=8), left minithoracotomy (n=1) and subxiphoid approach (n=1); and pericardiocentesis in one patient. Cardiovascular perforation repair was performed in five patients: two right atrium, two superior vena cava and one pulmonary artery. In the remaining six patients, cardiac tamponade was associated with recent cardiac surgery (n=2), prolonged cardiopulmonary resuscitation (n=1), thoracic trauma (n=1), myopericarditis (n=1), and acute myocardial infarction (n=1). Nine (9) patients (82%) were weaned from ECMO (20 days [range, 11-25]) and eight patients (73%) survived intensive care unit (ICU) (29 days [range, 26-61]) and hospital (34 days [range, 29-81]). CONCLUSION: Cardiac tamponade is a rare but life-threatening complication during both VV-ECMO and VA-ECMO. Echocardiography plays a major role in timely diagnosis and treatment. Immediate conversion to VA-ECMO when circulatory collapse ensued and emergency sternotomy for cardiovascular perforation repair gave favourable outcomes in a high proportion of patients.

Random-effect meta-analysis of genetic parameter estimates for carcass and meat quality traits in beef cattle.

Considerable variability of genetic parameter estimates is observed among different studies for the same trait, which is associated with the distinct effects included in the statistical model, population breed, and sample sizes. The random-effect meta-analysis summarizes genetic parameters considering the heterogeneity among studies. Therefore, the aim of this study was to perform a random-effect meta-analysis of heritability and genetic correlation estimates for carcass and meat quality traits in beef cattle. A total of 152 estimates of heritability and 83 genetic correlations for longissimus muscle area (LMA), back fat thickness (BFT), and marbling score (MRB) were used. High heterogeneity among published studies was observed for all traits, indicating the need of a random-effects model to perform the analysis. Estimates of heritability through the meta-analysis using the random-effects model were high (0.30 to 0.34), indicating that fast genetic progress can be obtained for these traits. However, genetic correlations had low magnitude (lower than 0.25), which suggested that all three traits should be included in the selection scheme.

Subclinical Changes in Cardiac Functional Parameters as Determined by Cardiovascular Magnetic Resonance (CMR) Imaging in Sleep Apnea and Snoring: Findings from UK Biobank.

Background and Objectives: Obstructive sleep apnea (OSA) is a common disorder with an increased risk for left ventricular and right ventricular dysfunction. Most studies to date have examined populations with manifest cardiovascular disease using echocardiography to analyze ventricular dysfunction with little or no reference to ventricular volumes or myocardial mass. Our aim was to explore these parameters with cardiac MRI. We hypothesized that there would be stepwise increase in left ventricular mass and right ventricular volumes from the unaffected, to the snoring and the OSA group. Materials and Methods: We analyzed cardiac MRI data from 4978 UK Biobank participants free from cardiovascular disease. Participants were allocated into three cohorts: with OSA, with self-reported snoring and without OSA or snoring (n = 118, 1886 and 2477). We analyzed cardiac parameters from balanced cine-SSFP sequences and indexed them to body surface area. Results: Patients with OSA were mostly males (47.3% vs. 79.7%; p < 0.001) with higher body mass index (25.7 ± 4.0 vs. 31.3 ± 5.3 kg/m²; p < 0.001) and higher blood pressure (135 ± 18 vs. 140 ± 17 mmHg; p = 0.012) compared to individuals without OSA or snoring. Regression analysis showed a significant effect for OSA in left ventricular end-diastolic index (LVEDVI) (ß = -4.9 ± 2.4 mL/m²; p = 0.040) and right ventricular end-diastolic index (RVEDVI) (ß = -6.2 ± 2.6 mL/m²; p = 0.016) in females and for right ventricular ejection fraction (RVEF) (ß = 1.7 ± 0.8%; p = 0.031) in males. A significant effect was discovered in snoring females for left ventricular mass index (LVMI) (ß = 3.5 ± 0.9 g/m²; p < 0.001) and in males for left ventricular ejection fraction (LVEF) (ß = 1.0 ± 0.3%; p = 0.001) and RVEF (ß = 1.2 ± 0.3%; p < 0.001). Conclusion: Our study suggests that OSA is highly underdiagnosed and that it is an evolving process with gender specific progression. Females with OSA show significantly lower ventricular volumes while males with snoring show increased ejection fractions which may be an early sign of hypertrophy. Separate prospective studies are needed to further explore the direction of causality.

Cardiovascular magnetic resonance reference values of mitral and tricuspid annular dimensions: the UK Biobank cohort.

BACKGROUND: Mitral valve (MV) and tricuspid valve (TV) apparatus geometry are essential to define mechanisms and etiologies of regurgitation and to inform surgical or transcatheter interventions. Given the increasing use of cardiovascular magnetic resonance (CMR) for the evaluation of valvular heart disease, we aimed to establish CMR-derived age- and sex-specific reference values for mitral annular (MA) and tricuspid annular (TA) dimensions and tethering indices derived from truly healthy Caucasian adults. METHODS: 5065 consecutive UK Biobank participants underwent CMR using cine balanced steady-state free precession imaging at 1.5 T. Participants with non-Caucasian ethnicity, prevalent cardiovascular disease and other conditions known to affect cardiac chamber size and function were excluded. Absolute and indexed reference ranges for MA and TA diameters and tethering indices were stratified by gender and age (45-54, 55-64, 65-74 years). RESULTS: Overall, 721 (14.2%) truly healthy participants aged 45-74 years (54% women) formed the reference cohort. Absolute MA and TA diameters, MV tenting length and MV tenting area, were significantly larger in men. Mean ± standard deviation (SD) end-diastolic and end-systolic MA diameters in the 3-chamber view (anteroposterior diameter) were 2.9 ± 0.4 cm (1.5 ± 0.2 cm/m2) and 3.3 ± 0.4 cm (1.7 ± 0.2 cm/m2) in men, and 2.6 ± 0.4 cm (1.6 ± 0.2 cm/m2) and 3.0 ± 0.4 cm (1.8 ± 0.2 cm/m2) in women, respectively. Mean ± SD end-diastolic and end-systolic TA diameters in the 4-chamber view were 3.2 ± 0.5 cm (1.6 ± 0.3 cm/m2) and 3.2 ± 0.5 cm (1.7 ± 0.3 cm/m2) in men, and 2.9 ± 0.4 cm (1.7 ± 0.2 cm/m2) and 2.8 ± 0.4 cm (1.7 ± 0.3 cm/m2) in women, respectively. With advancing age, end-diastolic TA diameter became larger and posterior MV leaflet angle smaller in both sexes. Reproducibility of measurements was good to excellent with an inter-rater intraclass correlation coefficient (ICC) between 0.92 and 0.98 and an intra-rater ICC between 0.90 and 0.97. CONCLUSIONS: We described age- and sex-specific reference ranges of MA and TA dimensions and tethering indices in the largest validated healthy Caucasian population. Reference ranges presented in this study may help to improve the distinction between normal and pathological states, prompting the identification of subjects that may benefit from advanced cardiac imaging for annular sizing and planning of valvular interventions.

High impact of COVID-19 in long-term care facilities, suggestion for monitoring in the EU/EEA, May 2020.

Residents in long-term care facilities (LTCF) are a vulnerable population group. Coronavirus disease (COVID-19)-related deaths in LTCF residents represent 30-60% of all COVID-19 deaths in many European countries. This situation demands that countries implement local and national testing, infection prevention and control, and monitoring programmes for COVID-19 in LTCF in order to identify clusters early, decrease the spread within and between facilities and reduce the size and severity of outbreaks.