Cardiac Rehabilitation Using the Family-Centered Empowerment Model is Effective in Improving Long-term Mortality in Patients with Myocardial Infarction: A 10-year Follow-Up Randomized Clinical Trial.

INTRODUCTION: Cardiac rehabilitation (CR) play a critical role in reducing the risk of future cardiovascular events and enhancing the quality of life for individuals who have survived a heart attack. AIM: To assess the mortality rates and stability of the effects in myocardial infarction (MI) survivors after implementing a Family-Centered Empowerment Model (FCEM)-focused hybrid cardiac rehabilitation program. METHODS: This double-blind randomized controlled clinical trial, conducted at Shariati Hospital, an academic teaching hospital in Tehran, Iran (2012-2023), involved 70 MI patients and their families. Participants were randomly assigned to an FCEM intervention group or standard CR control group. The intervention commenced after the MI patient's safe discharge from the CCU and continued for the entire 10-year follow-up period. Various questionnaires were utilized to collect data on mortality rates and health-related quality of life (HRQoL). RESULTS: The 10-year follow-up period revealed lower mortality rates in the intervention group (5.7%, 11.4%, and 17.1% at 5, 7, and 10 years, respectively) compared to the control group (20%, 37.1%, and 48.9%). After adjusting for age, gender, and BMI, the control group had a four times higher mortality risk (HR: 4.346, 95% CI 1.671-7.307, P = 0.003). The FCEM-focused program demonstrated a significant and sustained positive impact on participants' quality of life for 48 months, with greater improvement compared to the control group. CONCLUSION: This study highlights the effectiveness of FCEM-based hybrid CR programs in enhancing long-term patient outcomes and reducing mortality rates among MI survivors. Further research is needed to explore the potential benefits in larger samples and diverse populations. TRIAL REGISTRATION: This study (Identifier: NCT02402582) was registered in the ClinicalTrials.gov on 03/30/2015.

What factors are effective on the CPR duration of patients under extracorporeal cardiopulmonary resuscitation: a single-center retrospective study.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is an alternative method for patients with reversible causes of cardiac arrest (CA) after conventional cardiopulmonary resuscitation (CCPR). However, cardiopulmonary resuscitation (CPR) duration during ECPR can vary due to multiple factors. Healthcare providers need to understand these factors to optimize the resuscitation process and improve outcomes. The aim of this study was to examine the different variables impacting the duration of CPR in patients undergoing ECPR. METHODS: This retrospective, single-center, observational study was conducted on adult patients who underwent ECPR due to in-hospital CA (IHCA) or out-of-hospital CA (OHCA) at Hamad General Hospital (HGH), the tertiary governmental hospital of Qatar, between February 2016 and March 2020. Univariate and multivariate binary logistic regression analyses were performed to identify the prognostic factors associated with CPR duration, including demographic and clinical variables, as well as laboratory tests. RESULTS: The mean ± standard division age of the 48 participants who underwent ECPR was 41.50 ± 13.15 years, and 75% being male. OHCA and IHCA were reported in 77.1% and 22.9% of the cases, respectively. The multivariate analysis revealed that several factors were significantly associated with an increased CPR duration: higher age (OR: 1.981, 95%CI: 1.021-3.364, P = 0.025), SOFA score (OR: 3.389, 95%CI: 1.289-4.911, P = 0.013), presence of comorbidities (OR: 3.715, 95%CI: 1.907-5.219, P = 0.026), OHCA (OR: 3.715, 95%CI: 1.907-5.219, P = 0.026), and prolonged collapse-to-CPR time (OR: 1.446, 95%CI:1.092-3.014, P = 0.001). Additionally, the study found that the initial shockable rhythm was inversely associated with the duration of CPR (OR: 0.271, 95%CI: 0.161-0.922, P = 0.045). However, no significant associations were found between laboratory tests and CPR duration. CONCLUSION: These findings suggest that age, SOFA score, comorbidities, OHCA, collapse-to-CPR time, and initial shockable rhythm are important factors influencing the duration of CPR in patients undergoing ECPR. Understanding these factors can help healthcare providers better predict and manage CPR duration, potentially improving patient outcomes. Further research is warranted to validate these findings and explore additional factors that may impact CPR duration in this population.

Prognostic effects of cardiopulmonary resuscitation (CPR) start time and the interval between CPR to extracorporeal cardiopulmonary resuscitation (ECPR) on patient outcomes under extracorporeal membrane oxygenation (ECMO): a single-center, retrospective observational study.

BACKGROUND: The impact of the chronological sequence of events, including cardiac arrest (CA), initial cardiopulmonary resuscitation (CPR), return of spontaneous circulation (ROSC), and extracorporeal cardiopulmonary resuscitation (ECPR) implementation, on clinical outcomes in patients with both out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA), is still not clear. The aim of this study was to investigate the prognostic effects of the time interval from collapse to start of CPR (no-flow time, NFT) and the time interval from start of CPR to implementation of ECPR (low-flow time, LFT) on patient outcomes under Extracorporeal Membrane Oxygenation (ECMO). METHODS: This single-center, retrospective observational study was conducted on 48 patients with OHCA or IHCA who underwent ECMO at Hamad General Hospital (HGH), the tertiary governmental hospital of Qatar, between February 2016 and March 2020. We investigated the impact of prognostic factors such as NFT and LFT on various clinical outcomes following cardiac arrest, including 24-hour survival, 28-day survival, CPR duration, ECMO length of stay (LOS), ICU LOS, hospital LOS, disability (assessed using the modified Rankin Scale, mRS), and neurological status (evaluated based on the Cerebral Performance Category, CPC) at 28 days after the CA. RESULTS: The results of the adjusted logistic regression analysis showed that a longer NFT was associated with unfavorable clinical outcomes. These outcomes included longer CPR duration (OR: 1.779, 95%CI: 1.218-2.605, P = 0.034) and decreased survival rates for ECMO at 24 h (OR: 0.561, 95%CI: 0.183-0.903, P = 0.009) and 28 days (OR: 0.498, 95%CI: 0.106-0.802, P = 0.011). Additionally, a longer LFT was found to be associated only with a higher probability of prolonged CPR (OR: 1.818, 95%CI: 1.332-3.312, P = 0.006). However, there was no statistically significant connection between either the NFT or the LFT and the improvement of disability or neurologically favorable survival after 28 days of cardiac arrest. CONCLUSIONS: Based on our findings, it has been determined that the NFT is a more effective predictor than the LFT in assessing clinical outcomes for patients with OHCA or IHCA who underwent ECMO. This understanding of their distinct predictive abilities enables medical professionals to identify high-risk patients more accurately and customize their interventions accordingly.

Risk factors for neurological disability outcomes in patients under extracorporeal membrane oxygenation following cardiac arrest: An observational study.

OBJECTIVES: This study aimed to identify factors associated with neurological and disability outcomes in patients who underwent ECMO following cardiac arrest. METHODS: This retrospective, single-center, observational study included adult patients who received ECMO treatment for in-hospital cardiac arrest (IHCA) or out-of-hospital cardiac arrest (OHCA) between February 2016 and March 2020. Factors associated with neurological and disability outcomes in these patients who underwent ECMO were assessed. SETTING: Hamad General Hospital, Qatar. MAIN OUTCOME MEASURES: Neurological disability outcomes were assessed using the Modified Rankin Scale (mRS) and the Cerebral Performance Category (CPC) scale. RESULTS: Among the 48 patients included, 37 (77 %) experienced OHCA, and 11 (23 %) had IHCA. The 28-day survival rate was 14 (29.2 %). Of the survivors, 9 (64.3 %) achieved a good neurological outcome, while 5 (35.7 %) experienced poor neurological outcomes. Regarding disability, 5 (35.7 %) of survivors had no disability, while 9 (64.3 %) had some form of disability. The results showed significantly shorter median time intervals in minutes, including collapse to cardiopulmonary resuscitation (CPR) (3 vs. 6, P = 0.001), CPR duration (12 vs. 35, P = 0.001), CPR to extracorporeal cardiopulmonary resuscitation (ECPR) (20 vs. 40, P = 0.001), and collapse-to-ECPR (23 vs. 45, P = 0.001), in the good outcome group compared to the poor outcome group. CONCLUSION: This study emphasizes the importance of minimizing the time between collapse and CPR/ECMO initiation to improve neurological outcomes and reduce disability in cardiac arrest patients. However, no significant associations were found between outcomes and other demographic or clinical variables in this study. Further research with a larger sample size is needed to validate these findings. IMPLICATIONS FOR CLINICAL PRACTICE: The study underscores the significance of reducing the time between collapse and the initiation of CPR and ECMO. Shorter time intervals were associated with improved neurological outcomes and reduced disability in cardiac arrest patients.

Evaluation of psychological distress, burnout and structural empowerment status of healthcare workers during the outbreak of coronavirus disease (COVID-19): a cross-sectional questionnaire-based study.

BACKGROUND: In light of several recent studies, there is evidence that the coronavirus disease 2019 (COVID-19) pandemic has caused various mental health concerns in the general population, as well as among healthcare workers (HCWs). The main aim of this study was to assess the psychological distress, burnout and structural empowerment status of HCWs during the COVID-19 outbreak, and to evaluate its predictors. METHODS: This multi-center, cross-sectional web-based questionnaire survey was conducted on HCWs during the outbreak of COVID-19 from August 2020 to January 2021. HCWs working in hospitals from 48 different countries were invited to participate in an online anonymous survey that investigated sociodemographic data, psychological distress, burnout and structural empowerment (SE) based on Depression Anxiety and Stress Scale 21 (DASS-21), Maslach Burnout Inventory (MBI) and Conditions for work effectiveness questionnaire (CWEQ_II), respectively. Predictors of the total scores of DASS-21, MBI and CWEQ-II were assessed using unadjusted and adjusted binary logistic regression analysis. RESULTS: Out of the 1030 HCWs enrolled in this survey, all completed the sociodemographic section (response rate 100%) A total of 730 (70.9%) HCWs completed the DASS-21 questionnaire, 852 (82.6%) completed the MBI questionnaire, and 712 (69.1%) completed the CWEQ-II questionnaire. The results indicate that 360 out of 730 responders (49.3%) reported severe or extremely severe levels of stress, anxiety, and depression. Additionally, 422 out of 851 responders (49.6%) reported a high level of burnout, while 268 out of 712 responders (37.6%) reported a high level of structural empowerment based on the DASS-21, MBI, and CWEQ-II scales, respectively. In addition, the analysis showed that HCWs working in the COVID-19 areas experienced significantly higher symptoms of severe stress, anxiety, depression and higher levels of burnout compared to those working in other areas. The results also revealed that direct work with COVID-19 patients, lower work experience, and high workload during the outbreak of COVID-19 increase the risks of negative psychological consequences. CONCLUSION: Health professionals had high levels of burnout and psychological symptoms during the COVID-19 emergency. Monitoring and timely treatment of these conditions is needed.

A Path towards Timely VAP Diagnosis: Proof-of-Concept Study on Pyocyanin Sensing with Cu-Mg Doped Graphene Oxide.

In response to the urgent requirement for rapid, precise, and cost-effective detection in intensive care units (ICUs) for ventilated patients, as well as the need to overcome the limitations of traditional detection methods, researchers have turned their attention towards advancing novel technologies. Among these, biosensors have emerged as a reliable platform for achieving accurate and early diagnoses. In this study, we explore the possibility of using Pyocyanin analysis for early detection of pathogens in ventilator-associated pneumonia (VAP) and lower respiratory tract infections in ventilated patients. To achieve this, we developed an electrochemical sensor utilizing a graphene oxide-copper oxide-doped MgO (GO - Cu - Mgo) (GCM) catalyst for Pyocyanin detection. Pyocyanin is a virulence factor in the phenazine group that is produced by Pseudomonas aeruginosa strains, leading to infections such as pneumonia, urinary tract infections, and cystic fibrosis. We additionally investigated the use of DNA aptamers for detecting Pyocyanin as a biomarker of Pseudomonas aeruginosa, a common causative agent of VAP. The results of this study indicated that electrochemical detection of Pyocyanin using a GCM catalyst shows promising potential for various applications, including clinical diagnostics and drug discovery.

Anticoagulation and Bleeding during Veno-Venous Extracorporeal Membrane Oxygenation: Insights from the PROTECMO Study.

Rationale: Definitive guidelines for anticoagulation management during veno-venous extracorporeal membrane oxygenation (VV ECMO) are lacking, whereas bleeding complications continue to pose major challenges. Objectives: To describe anticoagulation modalities and bleeding events in adults receiving VV ECMO. Methods: This was an international prospective observational study in 41 centers, from December 2018 to February 2021. Anticoagulation was recorded daily in terms of type, dosage, and monitoring strategy. Bleeding events were reported according to site, severity, and impact on mortality. Measurements and Main Results: The study cohort included 652 patients, and 8,471 days on ECMO were analyzed. Unfractionated heparin was the initial anticoagulant in 77% of patients, and the most frequently used anticoagulant during the ECMO course (6,221 d; 73%). Activated partial thromboplastin time (aPTT) was the most common test for monitoring coagulation (86% of days): the median value was 52 seconds (interquartile range, 39 to 61 s) but dropped by 5.3 seconds after the first bleeding event (95% confidence interval, -7.4 to -3.2; P < 0.01). Bleeding occurred on 1,202 days (16.5%). Overall, 342 patients (52.5%) experienced at least one bleeding event (one episode every 215 h on ECMO), of which 10 (1.6%) were fatal. In a multiple penalized Cox proportional hazard model, higher aPTT was a potentially modifiable risk factor for the first episode of bleeding (for 20-s increase; hazard ratio, 1.07). Conclusions: Anticoagulation during VV ECMO was a dynamic process, with frequent stopping in cases of bleeding and restart according to the clinical picture. Future studies might explore lower aPTT targets to reduce the risk of bleeding.

Epigenetic age acceleration in surviving versus deceased COVID-19 patients with acute respiratory distress syndrome following hospitalization.

BACKGROUND: Aging has been reported as a major risk factor for severe symptoms and higher mortality rates in COVID-19 patients. Molecular hallmarks such as epigenetic alterations and telomere attenuation reflect the biological process of aging. Epigenetic clocks have been shown to be valuable tools for measuring biological age in various tissues and samples. As such, these epigenetic clocks can determine accelerated biological aging and time-to-mortality across various tissues. Previous reports have shown accelerated biological aging and telomere attrition acceleration following SARS-CoV-2 infection. However, the effect of accelerated epigenetic aging on outcome (death/recovery) in COVID-19 patients with acute respiratory distress syndrome (ARDS) has not been well investigated. RESULTS: In this study, we measured DNA methylation age and telomere attrition in 87 severe COVID-19 cases with ARDS under mechanical ventilation. Furthermore, we compared dynamic changes in epigenetic aging across multiple time points until recovery or death. Epigenetic age was measured using the Horvath, Hannum, DNAm skin and blood, GrimAge, and PhenoAge clocks, whereas telomere length was calculated using the surrogate marker DNAmTL. Our analysis revealed significant accelerated epigenetic aging but no telomere attrition acceleration in severe COVID-19 cases. In addition, we observed epigenetic age deceleration at inclusion versus end of follow-up in recovered but not in deceased COVID-19 cases using certain clocks. When comparing dynamic changes in epigenetic age acceleration (EAA), we detected higher EAA using both the Horvath and PhenoAge clocks in deceased versus recovered patients. The DNAmTL measurements revealed telomere attrition acceleration in deceased COVID-19 patients between inclusion and end of follow-up and a significant change in dynamic telomere attrition acceleration when comparing patients who recovered versus those who died. CONCLUSIONS: EAA and telomere attrition acceleration were associated with treatment outcomes in hospitalized COVID-19 patients with ARDS. A better understanding of the long-term effects of EAA in COVID-19 patients and how they might contribute to long COVID symptoms in recovered individuals is urgently needed.

Ambulatory extracorporeal membrane oxygenation simulator: The next frontier in clinical training.

BACKGROUND: Current medical simulators for extracorporeal membrane oxygenation (ECMO) are expensive and rely on low-fidelity methodologies. This creates a challenge that demands a new approach to eliminate high costs and integrate with critical care environments, especially in light of the scarce resources and supplies available after the COVID-19 pandemic. METHODS: To address this challenge, we examined the current state-of-the-art medical simulators and collaborated closely with Hamad Medical Corporation (HMC), the primary healthcare provider in Qatar, to establish criteria for advancing the cutting-edge ECMO simulation. This article presents a comprehensive ambulatory high-realism and cost-effective ECMO simulator. RESULTS: Over the past 3 years, we have surveyed relevant literature, gathered data, and continuously developed a prototype of the system modules and the accompanying tablet application. By doing so, we have successfully addressed the issue of cost and fidelity in ECMO simulation, providing an effective tool for medical professionals to improve their understanding and treatment of patients requiring ECMO support. CONCLUSIONS: This paper will focus on presenting an overall ambulatory ECMO simulator, detailing the various sub-systems and emphasizing the modular casing of the physical components and the simulated patient monitor.

Body composition and muscle strength at the end of ICU stay are associated with 1-year mortality, a prospective multicenter observational study.

BACKGROUND & AIMS: After a prolonged intensive care unit (ICU) stay patients experience increased mortality and morbidity. The primary aim of this study was to assess the prognostic value of nutritional status, body mass composition and muscle strength, as assessed by body mass index (BMI), bioelectrical impedance analysis (BIA), handgrip (HG) test, and that of the biological features to predict one-year survival at the end of a prolonged ICU stay. METHODS: This was a multicenter prospective observational study. Survivor patients older than 18 years with ICU length of stay >72 h were eligible for inclusion. BIA and HG were performed at the end of the ICU stay. Malnutrition was defined by BMI and fat-free mass index (FFMI). The primary endpoint was one-year mortality. Multivariable logistic regression was performed to determine parameters associated with mortality. RESULTS: 572 patients were included with a median age of 63 years [53.5; 71.1], BMI of 26.6 kg/m2 [22.8; 31.3], SAPS II score of 43 [31; 58], and ICU length of stay of 9 days [6; 15]. Malnutrition was observed in 142 (24.9%) patients. During the 1-year follow-up after discharge, 96 (18.5%) patients died. After adjustment, a low HG test score (aOR = 1.44 [1.11; 1.89], p = 0.01) was associated with 1-year mortality. Patients with low HG score, malnutrition, and Albuminemia <30 g/L had a one-year death rate of 41.4%. Conversely, patients with none of these parameters had a 1-year death rate of 4.1%. CONCLUSION: BIA to assess FFMI, HG and albuminemia at the end of ICU stay could be used to predict 1-year mortality. Their ability to identify patients eligible for a structured recovery program could be studied.

A Prospective Cohort Study (OUTSTRIP-COVID) on Functional and Spirometry Outcomes in COVID-19 ICU Survivors at 3 Months.

Purpose: COVID-19 pandemic resulted in a significant number of critical care admissions secondary to severe pneumonia and acute respiratory distress syndrome. We evaluated the short-, medium- and long-term outcomes of lung function and quality of life in this prospective cohort study and reported the outcomes at 7 weeks and 3 months from discharge from intensive care unit. Methods: A prospective cohort study of ICU survivors with COVID-19 was conducted from August 2020 to May 2021 to evaluate baseline demographic and clinical variables as well as determine lung function, exercise capacity, and health-related quality of life (HRQOL) using spirometry and 6-minute walk test (6MWT) conducted in accordance with American Thoracic Society standards, and SF-36 (Rand), respectively. SF-36 is a generic 36 question standardized health survey. Descriptive and inferential statistics (alpha = 0.05) were used to analyse the data. Results: At baseline, 100 participants were enrolled in the study of whom 76 followed up at 3 months. Majority of the patients were male (83%), Asians (84%) and less than 60 years of age (91%). HRQOL showed significant improvement in all domains of SF-36, except in emotional wellbeing. Spirometry variables also showed significant improvement in all variables over time with greatest improvement in percentage predicted Forced expiratory volume 1 (79% vs 88% p < 0.001). 6MWT showed significant improvement in variables of walk distance, dyspnea, and fatigue with greatest improvement in change in oxygen saturation (3% vs 1.44% p < 0.001). Intubation status did not impact the changes in SF-36, spirometry or 6MWT variables. Conclusion: Our findings suggest that ICU survivors of COVID-19 have significant improvement in their lung function, exercise capacity and HRQOL within 3 months of ICU discharge regardless of intubation status.

Outcomes of Patients With in- and out-of-hospital Cardiac Arrest on Extracorporeal Cardiopulmonary Resuscitation: A Single-center Retrospective Cohort Study.

Extracorporeal membrane oxygenation (ECMO) support has been suggested to improve the survival rate in patients with refractory in- and out-of-hospital cardiac arrest (IHCA and OHCA). Several factors predict outcome in these patients, including initial heart rhythm and low-flow time. Literature shows variable survival rates among patients who received extracorporeal cardiopulmonary resuscitation (EPCR). The objective of this study is to analyze the outcomes (survival rate as well as neurological and disability outcomes) of patients treated with ECPR following refractory OHCA and IHCA. This single-center, retrospective cohort study was conducted on patients with refractory cardiac arrest treated with ECPR between February 2016 and March 2020. The primary outcomes were 24-hour, hospital discharge and 1-year survival after CA and the secondary endpoints were neurological and disability outcomes. Forty-eight patients were included in the analysis. 11/48 patients are In Hospital Cardiac Arrest (IHCA) and 37/48 patients are Out of Hospital Cardiac Arrest (OHCA). Time from collapse to CPR for 79.2% of the patients was less than 5 minutes. The median CPR duration and collapse to ECMO were 40 and 45 minutes, respectively. The rate of survival was significantly higher in patient who presented with initial shockable rhythm (P = 0.006) and to whom targeted temperature management (TTM) post cardiac arrest was applied (P = 0.048). This first descriptive study about ECPR in the middle east region shows that 20.8% of ECPR patients survived until hospital discharge. Our analysis revealed that initial shockable rhythm and TTM are most important prognostic factors that predicts favorable neurological survival.

Pharmacokinetics, Pharmacodynamics, and Dosing Considerations of Novel ß-Lactams and ß-Lactam/ß-Lactamase Inhibitors in Critically Ill Adult Patients: Focus on Obesity, Augmented Renal Clearance, Renal Replacement Therapies, and Extracorporeal Membrane Oxygenation.

OBJECTIVE: Dose optimization of novel ß-lactam antibiotics (NBLA) has become necessary given the increased prevalence of multidrug-resistant infections in intensive care units coupled with the limited number of available treatment options. Unfortunately, recommended dose regimens of NBLA based on PK/PD indices are not well-defined for critically ill patients presenting with special situations (i.e., obesity, extracorporeal membrane oxygenation (ECMO), augmented renal clearance (ARC), and renal replacement therapies (RRT)). This review aimed to discuss and summarize the available literature on the PK/PD attained indices of NBLA among critically ill patients with special circumstances. DATA SOURCES: PubMed, MEDLINE, Scopus, Google Scholar, and Embase databases were searched for studies published between January 2011 and May 2022. STUDY SELECTION AND DATA EXTRACTION: Articles relevant to NBLA (i.e., ceftolozane/tazobactam, ceftazidime/avibactam, cefiderocol, ceftobiprole, imipenem/relebactam, and meropenem/vaborbactam) were selected. The MeSH terms of "obesity", "augmented renal clearance", "renal replacement therapy", "extracorporeal membrane oxygenation", "pharmacokinetic", "pharmacodynamic" "critically ill", and "intensive care" were used for identification of articles. The search was limited to adult humans' studies that were published in English. A narrative synthesis of included studies was then conducted accordingly. DATA SYNTHESIS: Available evidence surrounding the use of NBLA among critically ill patients presenting with special situations was limited by the small sample size of the included studies coupled with high heterogeneity. The PK/PD target attainments of NBLA were reported to be minimally affected by obesity and/or ECMO, whereas the effect of renal functionality (in the form of either ARC or RRT) was more substantial. CONCLUSION: Critically ill patients presenting with special circumstances might be at risk of altered NBLA pharmacokinetics, particularly in the settings of ARC and RRT. More robust, well-designed trials are still required to define effective dose regimens able to attain therapeutic PK/PD indices of NBLA when utilized in those special scenarios, and thus aid in improving the patients' outcomes.

High-temporal resolution profiling reveals distinct immune trajectories following the first and second doses of COVID-19 mRNA vaccines.

Knowledge of the mechanisms underpinning the development of protective immunity conferred by mRNA vaccines is fragmentary. Here, we investigated responses to coronavirus disease 2019 (COVID-19) mRNA vaccination via high-temporal resolution blood transcriptome profiling. The first vaccine dose elicited modest interferon and adaptive immune responses, which peaked on days 2 and 5, respectively. The second vaccine dose, in contrast, elicited sharp day 1 interferon, inflammation, and erythroid cell responses, followed by a day 5 plasmablast response. Both post-first and post-second dose interferon signatures were associated with the subsequent development of antibody responses. Yet, we observed distinct interferon response patterns after each of the doses that may reflect quantitative or qualitative differences in interferon induction. Distinct interferon response phenotypes were also observed in patients with COVID-19 and were associated with severity and differences in duration of intensive care. Together, this study also highlights the benefits of adopting high-frequency sampling protocols in profiling vaccine-elicited immune responses.

DNA methylation predicts the outcome of COVID-19 patients with acute respiratory distress syndrome.

BACKGROUND: COVID-19 infections could be complicated by acute respiratory distress syndrome (ARDS), increasing mortality risk. We sought to assess the methylome of peripheral blood mononuclear cells in COVID-19 with ARDS. METHODS: We recruited 100 COVID-19 patients with ARDS under mechanical ventilation and 33 non-COVID-19 controls between April and July 2020. COVID-19 patients were followed at four time points for 60 days. DNA methylation and immune cell populations were measured at each time point. A multivariate cox proportional risk regression analysis was conducted to identify predictive signatures according to survival. RESULTS: The comparison of COVID-19 to controls at inclusion revealed the presence of a 14.4% difference in promoter-associated CpGs in genes that control immune-related pathways such as interferon-gamma and interferon-alpha responses. On day 60, 24% of patients died. The inter-comparison of baseline DNA methylation to the last recorded time point in both COVID-19 groups or the intra-comparison between inclusion and the end of follow-up in every group showed that most changes occurred as the disease progressed, mainly in the AIM gene, which is associated with an intensified immune response in those who recovered. The multivariate Cox proportional risk regression analysis showed that higher methylation of the "Apoptotic execution Pathway" genes (ROC1, ZNF789, and H1F0) at inclusion increases mortality risk by over twofold. CONCLUSION: We observed an epigenetic signature of immune-related genes in COVID-19 patients with ARDS. Further, Hypermethylation of the apoptotic execution pathway genes predicts the outcome. TRIAL REGISTRATION: IMRPOVIE study, NCT04473131.

Impact of prolonged requirement for insulin on 90-day mortality in critically ill patients without previous diabetic treatments: a post hoc analysis of the CONTROLING randomized control trial.

BACKGROUND: Stress hyperglycemia can persist during an intensive care unit (ICU) stay and result in prolonged requirement for insulin (PRI). The impact of PRI on ICU patient outcomes is not known. We evaluated the relationship between PRI and Day 90 mortality in ICU patients without previous diabetic treatments. METHODS: This is a post hoc analysis of the CONTROLING trial, involving 12 French ICUs. Patients in the personalized glucose control arm with an ICU length of stay ≥ 5 days and who had never previously received diabetic treatments (oral drugs or insulin) were included. Personalized blood glucose targets were estimated on their preadmission usual glycemia as estimated by their glycated A1c hemoglobin (HbA1C). PRI was defined by insulin requirement. The relationship between PRI on Day 5 and 90-day mortality was assessed by Cox survival models with inverse probability of treatment weighting (IPTW). Glycemic control was defined as at least one blood glucose value below the blood glucose target value on Day 5. RESULTS: A total of 476 patients were included, of whom 62.4% were male, with a median age of 66 (54-76) years. Median values for SAPS II and HbA1C were 50 (37.5-64) and 5.7 (5.4-6.1)%, respectively. PRI was observed in 364/476 (72.5%) patients on Day 5. 90-day mortality was 23.1% in the whole cohort, 25.3% in the PRI group and 16.1% in the non-PRI group (p < 0.01). IPTW analysis showed that PRI on Day 5 was not associated with Day 90 mortality (IPTWHR = 1.22; CI 95% 0.84-1.75; p = 0.29), whereas PRI without glycemic control was associated with an increased risk of death at Day 90 (IPTWHR = 3.34; CI 95% 1.26-8.83; p < 0.01). CONCLUSION: In ICU patients without previous diabetic treatments, only PRI without glycemic control on Day 5 was associated with an increased risk of death. Additional studies are required to determine the factors contributing to these results.

Recurrent Cardiac Arrests Due to Amniotic Fluid Embolism.

Amniotic fluid embolism (AFE) is a rare but devastating complication of pregnancy and is associated with high morbidity and mortality. Identifiable maternal risk factors for AFE include older age, multiparity, cesarean section, and placenta previa, while fetal factors include male gender, fetal distress, and death. AFE presents with respiratory distress, seizure, and circulatory collapse and can be complicated with disseminated intravascular coagulopathy, multiorgan failure, and death. In our case, we present a patient who underwent elective cesarean section for placenta previa, which was complicated by sudden cardiac arrest immediately after delivering the placenta in the operating theatre followed by disseminated intravascular coagulation (DIC). The patient developed massive post-partum hemorrhage secondary to the underlying DIC, which required a massive blood transfusion along with platelets, fresh frozen plasma (FFP), and tranexamic acid. The Society of Maternal-Fetal Medicine proposed criteria for the diagnosis of AFE, which include clinical features and laboratory findings. The presence of a DIC picture is considered to be the hallmark finding that helps to differentiate between AFE and other conditions with similar presentation. Treatment of amniotic fluid embolism depends on early recognition and supportive care.

Individualised versus conventional glucose control in critically-ill patients: the CONTROLING study-a randomized clinical trial.

PURPOSE: Hyperglycaemia is an adaptive response to stress commonly observed in critical illness. Its management remains debated in the intensive care unit (ICU). Individualising hyperglycaemia management, by targeting the patient's pre-admission usual glycaemia, could improve outcome. METHODS: In a multicentre, randomized, double-blind, parallel-group study, critically-ill adults were considered for inclusion. Patients underwent until ICU discharge either individualised glucose control by targeting the pre-admission usual glycaemia using the glycated haemoglobin A1c level at ICU admission (IC group), or conventional glucose control by maintaining glycaemia below 180 mg/dL (CC group). A non-commercial web application of a dynamic sliding-scale insulin protocol gave to nurses all instructions for glucose control in both groups. The primary outcome was death within 90 days. RESULTS: Owing to a low likelihood of benefit and evidence of the possibility of harm related to hypoglycaemia, the study was stopped early. 2075 patients were randomized; 1917 received the intervention, 942 in the IC group and 975 in the CC group. Although both groups showed significant differences in terms of glycaemic control, survival probability at 90-day was not significantly different (IC group: 67.2%, 95% CI [64.2%; 70.3%]; CC group: 69.6%, 95% CI [66.7%; 72.5%]). Severe hypoglycaemia (below 40 mg/dL) occurred in 3.9% of patients in the IC group and in 2.5% of patients in the CC group (p = 0.09). A post hoc analysis showed for non-diabetic patients a higher risk of 90-day mortality in the IC group compared to the CC group (HR 1.3, 95% CI [1.05; 1.59], p = 0.018). CONCLUSION: Targeting an ICU patient's pre-admission usual glycaemia using a dynamic sliding-scale insulin protocol did not demonstrate a survival benefit compared to maintaining glycaemia below 180 mg/dL.

Predictive Biomarkers of Intensive Care Unit and Mechanical Ventilation Duration in Critically-Ill Coronavirus Disease 2019 Patients.

Introduction: Detection of early metabolic changes in critically-ill coronavirus disease 2019 (COVID-19) patients under invasive mechanical ventilation (IMV) at the intensive care unit (ICU) could predict recovery patterns and help in disease management. Methods: Targeted metabolomics of serum samples from 39 COVID-19 patients under IMV in ICU was performed within 48 h of intubation and a week later. A generalized linear model (GLM) was used to identify, at both time points, metabolites and clinical traits that predict the length of stay (LOS) at ICU (short ≤ 14 days/long >14 days) as well as the duration under IMV. All models were initially trained on a set of randomly selected individuals and validated on the remaining individuals in the cohort. Further validation in recently published metabolomics data of COVID-19 severity was performed. Results: A model based on hypoxanthine and betaine measured at first time point was best at predicting whether a patient is likely to experience a short or long stay at ICU [area under curve (AUC) = 0.92]. A further model based on kynurenine, 3-methylhistidine, ornithine, p-cresol sulfate, and C24.0 sphingomyelin, measured 1 week later, accurately predicted the duration of IMV (Pearson correlation = 0.94). Both predictive models outperformed Acute Physiology and Chronic Health Evaluation II (APACHE II) scores and differentiated COVID-19 severity in published data. Conclusion: This study has identified specific metabolites that can predict in advance LOS and IMV, which could help in the management of COVID-19 cases at ICU.

The first consecutive 5000 patients with Coronavirus Disease 2019 from Qatar; a nation-wide cohort study.

BACKGROUND: There are limited data on Coronavirus Disease 2019 (COVID-19) outcomes at a national level, and none after 60 days of follow up. The aim of this study was to describe national, 60-day all-cause mortality associated with COVID-19, and to identify risk factors associated with admission to an intensive care unit (ICU). METHODS: This was a retrospective cohort study including the first consecutive 5000 patients with COVID-19 in Qatar who completed 60 days of follow up by June 17, 2020. The primary outcome was all-cause mortality at 60 days after COVID-19 diagnosis. In addition, we explored risk factors for admission to ICU. RESULTS: Included patients were diagnosed with COVID-19 between February 28 and April 17, 2020. The majority (4436, 88.7%) were males and the median age was 35 years [interquartile range (IQR) 28-43]. By 60 days after COVID-19 diagnosis, 14 patients (0.28%) had died, 10 (0.2%) were still in hospital, and two (0.04%) were still in ICU. Fatal COVID-19 cases had a median age of 59.5 years (IQR 55.8-68), and were mostly males (13, 92.9%). All included pregnant women (26, 0.5%), children (131, 2.6%), and healthcare workers (135, 2.7%) were alive and not hospitalized at the end of follow up. A total of 1424 patients (28.5%) required hospitalization, out of which 108 (7.6%) were admitted to ICU. Most frequent co-morbidities in hospitalized adults were diabetes (23.2%), and hypertension (20.7%). Multivariable logistic regression showed that older age [adjusted odds ratio (aOR) 1.041, 95% confidence interval (CI) 1.022-1.061 per year increase; P < 0.001], male sex (aOR 4.375, 95% CI 1.964-9.744; P < 0.001), diabetes (aOR 1.698, 95% CI 1.050-2.746; P 0.031), chronic kidney disease (aOR 3.590, 95% CI 1.596-8.079, P 0.002), and higher BMI (aOR 1.067, 95% CI 1.027-1.108 per unit increase; P 0.001), were all independently associated with increased risk of ICU admission. CONCLUSIONS: In a relatively younger national cohort with a low co-morbidity burden, COVID-19 was associated with low all-cause mortality. Independent risk factors for ICU admission included older age, male sex, higher BMI, and co-existing diabetes or chronic kidney disease.