Evaluating the use of casuistry during moral case deliberation in the ICU: A multiple qualitative case study.

Intensive care unit (ICU) professionals engage in ethical decision making under conditions of high stakes, great uncertainty, time-sensitivity and frequent irreversibility of action. Casuistry is a way by which actionable knowledge is obtained through comparing a patient case to previous cases from experience in clinical practice. However, within the field of study as well as in practice, evidence-based medicine is the dominant epistemic framework. This multiple case study evaluated the use of casuistic reasoning by intensive care unit (ICU) professionals during moral case deliberation. It took place in two Dutch hospitals between June 2020 and June 2022. Twentyfive moral case deliberations from ICU practice were recorded and analyzed using discourse analysis. Additionally, 47 interviews were held with ICU professionals who participated in these deliberations, analyzed using thematic analysis. We found that ICU professionals made considerable use of case comparisons when discussing continuation, withdrawal or limitation. Analogies played a role in justifying or complicating moral judgements, and also played a role in addressing moral distress. The language of case-based arguments is most often not overtly normative. Rather, the data shows that casuistic reasoning deals with the medical, ethical and contextual elements of decisions in an integrated manner. Facilitators of MCD have an essential role in (supporting ICU professionals in) scrutinizing casuistic arguments. The data shows that during MCD, actual reasoning often deviated from principle- and rule-based reasoning which ICU professionals preferred themselves. Evidence-based arguments often gained the character of analogical arguments, especially when a patient-at-hand was seen as highly unique from the average patients in the literature. Casuistic arguments disguised as evidence-based arguments may therefore provide ICU professionals with a false sense of certainty. Within education, we should strive to train clinicians and ethics facilitators so that they can recognize and evaluate casuistic arguments.

Consensus-based indicators for evaluating and improving the quality of regional collaborative networks of intensive care units: Results of a nationwide Delphi study.

PURPOSE: To select a consensus-based set of relevant and feasible indicators for monitoring and improving the quality of regional ICU network collaboratives. METHODS: A three-round Delphi study was conducted in the Netherlands between April and July 2022. A multidisciplinary expert panel prioritized potentially relevant and feasible indicators in two questionnaire rounds with two consensus meetings between both rounds. The RAND/UCLA appropriateness method was used to categorize indicators and synthesize results. A core set of highest ranked indicators with consensus-based levels of relevance and feasibility were finally tested in two ICU networks to assess their measurability. RESULTS: Twenty-four indicators were deemed as relevant and feasible. Seven indicators were selected for the core set measuring the standardized mortality rate in the region (n = 1) and evaluating the presence, content and/or follow-up of a formal plan describing network structures and policy agreements (n = 3), a long-term network vision statement (n = 1), and network meetings to reflect on and learn from outcome data (n = 2). The practice tests led to minor reformulations. CONCLUSIONS: This study generated relevant and feasible indicators for monitoring and improving the quality of ICU network collaboratives based on the collective opinion of various experts. The indicators may help to effectively govern such networks.

Development of Moral Injury in ICU Professionals During the COVID-19 Pandemic: A Prospective Serial Interview Study.

OBJECTIVES: During the COVID-19 pandemic, ICU professionals have faced moral problems that may cause moral injury. This study explored whether, how, and when moral injury among ICU professionals developed in the course of the COVID-19 pandemic. DESIGN: This is a prospective qualitative serial interview study. SETTING: Two hospitals among which one university medical center and one teaching hospital in the Netherlands. SUBJECTS: Twenty-six ICU professionals who worked during the COVID-19 pandemic. INTERVENTIONS: None. MEASUREMENTS MAIN RESULTS: In-depth interviews with follow-up after 6 and 12 months. In total, 62 interviews were conducted. ICU professionals narrated about anticipatory worry about life and death decisions, lack of knowledge and prognostic uncertainty about COVID-19, powerlessness and failure, abandonment or betrayal by society, politics, or the healthcare organization, numbness toward patients and families, and disorientation and self-alienation. Centrally, ICU professionals describe longitudinal processes by which they gradually numbed themselves emotionally from patients and families as well as potentially impactful events in their work. For some ICU professionals, organizational, societal, and political responses to the pandemic contributed to numbness, loss of motivation, and self-alienation. CONCLUSIONS: ICU professionals exhibit symptoms of moral injury such as feelings of betrayal, detachment, self-alienation, and disorientation. Healthcare organizations and ICU professionals themselves should be cognizant that these feelings may indicate that professionals might have developed moral injury or that it may yet develop in the future. Awareness should be raised about moral injury and should be followed up by asking morally injured professionals what they need, so as to not risk offering unwanted help.

Family participation in essential care activities: Needs, perceptions, preferences, and capacities of intensive care unit patients, relatives, and healthcare providers-An integrative review.

BACKGROUND: Family participation in essential care activities may benefit both patients and relatives. OBJECTIVES: In this integrative review, we aimed to identify needs, perceptions, preferences, and capacities regarding family participation in essential care in intensive care units (ICUs) from the patient's, relatives', and ICU healthcare providers' perspective. REVIEW METHOD USED: An integrative review method was used. DATA SOURCES: PubMed, CINAHL, EMBASE, MEDLINE, Cochrane, Web of Science, and reference lists of included articles were searched, from inception to January 25, 2021. REVIEW METHODS: We included studies on family participation in essential care activities during ICU stay which reported associated needs, perceptions, preferences and capacities. Quality assessment was performed with the Kmet Standard Quality Assessment Criteria developed for evaluating primary research papers in a variety of fields, and an extensive qualitative thematic analysis was performed on the results. RESULTS: Twenty-seven studies were included. Quality scores varied from 0.45 to 0.95 (range: 0-1). Patients' needs, perceptions, preferences, and capacities are largely unknown. Identified themes on needs and perceptions were relatives' desire to help the patient, a mostly positive attitude among all involved, stress regarding patient safety, perceived beneficial effects, relatives feeling in control-ICU healthcare providers' concerns about loss of control. Preferences for potential essential care activities vary. Relatives want an invitation and support from ICU healthcare providers. Themes regarding capacities were knowledge, skills, education and training, and organisational conditions. CONCLUSIONS: Implementation of family participation in essential care requires education and training of relatives and ICU healthcare providers to address safety and quality of care concerns, though most studies lack further specification.

POCUS in dyspnea, nontraumatic hypotension, and shock; a systematic review of existing evidence.

BACKGROUND: Point-of-care ultrasound (POCUS) has been adopted as a powerful tool in acute medicine. This systematic review aims to critically appraise the existing literature on point-of-care ultrasound in respiratory or circulatory deterioration. METHODS: Original studies on POCUS and dyspnea, nontraumatic hypotension, and shock from March 2002 until March 2022 were assessed in the PubMed and Embase Databases. Two reviewers independently screened articles for inclusion, extracted data, and assessed the quality of included studies using an established checklist. RESULTS: We included 89 articles in this review. Point-of-care ultrasound in the initial workup increases the diagnostic accuracy in patients with dyspnea, nontraumatic hypotension and shock in the ED, ICU and medical ward setting. No improvement is found in patients with severe sepsis in the ICU setting. POCUS is capable of narrowing the differential diagnoses and is faster, and more feasible in the acute setting than other diagnostics available. Results on outcome measures are heterogenous. The quality of the included studies is considered low most of the times, mainly because of performance and selection bias and absence of a gold standard as the reference test. CONCLUSION: We conclude that POCUS contributes to a higher diagnostic accuracy in dyspnea, nontraumatic hypotension, and shock. It aides in narrowing the differential diagnoses and shortening the time to correct diagnosis and effective treatment. TRIAL REGISTRY: INPLASY; Registration number: INPLASY202220020; URL: https://inplasy.com/.

Ischaemic electrocardiogram patterns and its association with survival in out-of-hospital cardiac arrest patients without ST-segment elevation myocardial infarction: a COACT trials' post-hoc subgroup analysis.

AIMS: ST-depression and T-wave inversion are frequently present on the post-resuscitation electrocardiogram (ECG). However, the prognostic value of ischaemic ECG patterns is unknown. METHODS AND RESULTS: In this post-hoc subgroup analysis of the Coronary Angiography after Cardiac arrest (COACT) trial, the first in-hospital post-resuscitation ECG in out-of-hospital cardiac arrest patients with a shockable rhythm was analysed for ischaemic ECG patterns. Ischaemia was defined as ST-depression of ≥0.1 mV, T-wave inversion in ≥2 contiguous leads, or both. The primary endpoint was 90-day survival. Secondary endpoints were rate of acute unstable lesions, levels of serum troponin-T, and left ventricular function. Of the 510 out-of-hospital cardiac arrest patients, 340 (66.7%) patients had ischaemic ECG patterns. Patients with ischaemic ECG patterns had a worse 90-day survival compared with those without [hazard ratio 1.51; 95% confidence interval (CI) 1.08-2.12; P = 0.02]. A higher sum of ST-depression was associated with lower survival (log-rank = 0.01). The rate of acute unstable lesions (14.5 vs. 15.8%; odds ratio 0.90; 95% CI 0.51-1.59) did not differ between the groups. In patients with ischaemic ECG patterns, maximum levels of serum troponin-T (µg/L) were higher [0.595 (interquartile range 0.243-1.430) vs. 0.359 (0.159-0.845); ratio of geometric means 1.58; 1.13-2.20] and left ventricular function (%) was worse (44.7 ± 12.5 vs. 49.9 ± 13.3; mean difference -5.13; 95% CI -8.84 to -1.42). Adjusted for age and time to return of spontaneous circulation, ischaemic ECG patterns were no longer associated with survival. CONCLUSION: Post-arrest ischaemic ECG patterns were associated with worse 90-day survival. A higher sum of ST-depression was associated with lower survival. Adjusted for age and time to return of spontaneous circulation, ischaemic ECG patterns were no longer associated with survival.

Morisprudence: a theoretical framework for studying the relationship linking moral case deliberation, organisational learning and quality improvement.

There is a claim that clinical ethics support services (CESS) improve healthcare quality within healthcare organisations. However, there is lack of strong evidence supporting this claim. Rather, the current focus is on the quality of CESS themselves or on individual learning outcomes. In response, this article proposes a theoretical framework leading to empirical hypotheses that describe the relationship between a specific type of CESS, moral case deliberation and the quality of care at the organisational level. We combine insights from the literature on CESS, organisational learning and quality improvement and argue that moral case deliberation causes healthcare professionals to acquire practical wisdom. At the organisational level, where improving quality is a continuous and collective endeavour, this practical wisdom can be aggregated into morisprudence, which is an ongoing formulation of moral judgements across cases encountered within the organisation. Focusing on the development of morisprudence enables refined scrutinisation of CESS-related quality claims.

Prospective Multicenter Observational Cohort Study on Time to Death in Potential Controlled Donation After Circulatory Death Donors-Development and External Validation of Prediction Models: The DCD III Study.

BACKGROUND: Acceptance of organs from controlled donation after circulatory death (cDCD) donors depends on the time to circulatory death. Here we aimed to develop and externally validate prediction models for circulatory death within 1 or 2 h after withdrawal of life-sustaining treatment. METHODS: In a multicenter, observational, prospective cohort study, we enrolled 409 potential cDCD donors. For model development, we applied the least absolute shrinkage and selection operator (LASSO) regression and machine learning-artificial intelligence analyses. Our LASSO models were validated using a previously published cDCD cohort. Additionally, we validated 3 existing prediction models using our data set. RESULTS: For death within 1 and 2 h, the area under the curves (AUCs) of the LASSO models were 0.77 and 0.79, respectively, whereas for the artificial intelligence models, these were 0.79 and 0.81, respectively. We were able to identify 4% to 16% of the patients who would not die within these time frames with 100% accuracy. External validation showed that the discrimination of our models was good (AUCs 0.80 and 0.82, respectively), but they were not able to identify a subgroup with certain death after 1 to 2 h. Using our cohort to validate 3 previously published models showed AUCs ranging between 0.63 and 0.74. Calibration demonstrated that the models over- and underestimated the predicted probability of death. CONCLUSIONS: Our models showed a reasonable ability to predict circulatory death. External validation of our and 3 existing models illustrated that their predictive ability remained relatively stable. We accurately predicted a subset of patients who died after 1 to 2 h, preventing starting unnecessary donation preparations, which, however, need external validation in a prospective cohort.

Cost Analysis From a Randomized Comparison of Immediate Versus Delayed Angiography After Cardiac Arrest.

Background In patients with out-of-hospital cardiac arrest without ST-segment elevation, immediate coronary angiography did not improve clinical outcomes when compared with delayed angiography in the COACT (Coronary Angiography After Cardiac Arrest) trial. Whether 1 of the 2 strategies has benefits in terms of health care resource use and costs is currently unknown. We assess the health care resource use and costs in patients with out-of-hospital cardiac arrest. Methods and Results A total of 538 patients were randomly assigned to a strategy of either immediate or delayed coronary angiography. Detailed health care resource use and cost-prices were collected from the initial hospital episode. A generalized linear model and a gamma distribution were performed. Generic quality of life was measured with the RAND-36 and collected at 12-month follow-up. Overall total mean costs were similar between both groups (EUR 33 575±19 612 versus EUR 33 880±21 044; P=0.86). Generalized linear model: (ß, 0.991; 95% CI, 0.894-1.099; P=0.86). Mean procedural costs (coronary angiography and percutaneous coronary intervention, coronary artery bypass graft) were higher in the immediate angiography group (EUR 4384±3447 versus EUR 3028±4220; P<0.001). Costs concerning intensive care unit and ward stay did not show any significant difference. The RAND-36 questionnaire did not differ between both groups. Conclusions The mean total costs between patients with out-of-hospital cardiac arrest randomly assigned to an immediate angiography or a delayed invasive strategy were similar during the initial hospital stay. With respect to the higher invasive procedure costs in the immediate group, a strategy awaiting neurological recovery followed by coronary angiography and planned revascularization may be considered. Registration URL: https://trialregister.nl; Unique identifier: NL4857.

Perceived Burden Due to Registrations for Quality Monitoring and Improvement in Hospitals: A Mixed Methods Study.

BACKGROUND: Quality indicators are registered to monitor and improve the quality of care. However, the number and effectiveness of quality indicators is under debate, and may influence the joy in work of physicians and nurses. Empirical data on the nature and consequences of the registration burden are lacking. The aim of this study was to identify and explore healthcare professionals' perceived burden due to quality registrations in hospitals, and the effect of this burden on their joy in work. METHODS: A mixed methods observational study, including participative observations, a survey and semi-structured interviews in two academic hospitals and one teaching hospital in the Netherlands. Study participants were 371 healthcare professionals from an intensive care unit (ICU), a haematology department and others involved in the care of elderly patients and patients with prostate or gastrointestinal cancer. RESULTS: On average, healthcare professionals spend 52.3 minutes per working day on quality registrations. The average number of quality measures per department is 91, with 1380 underlying variables. Overall, 57% are primarily registered for accountability purposes, 19% for institutional governance and 25% for quality improvement objectives. Only 36% were perceived as useful for improving quality in everyday practice. Eight types of registration burden were identified, such as an excessive number of quality registrations, and the lack of usefulness for improving quality and inefficiencies in the registration process. The time healthcare professionals spent on quality registrations was not correlated with any measure of joy in work. Perceived unreasonable registrations were negatively associated with healthcare professionals' joy in work (intrinsic motivation and autonomy). Healthcare professionals experienced quality registrations as diverting time from patient care and from actually improving quality. CONCLUSION: Registering fewer quality indicators, but more of what really matters to healthcare professionals, is key to increasing the effectiveness of registrations for quality improvement and governance. Also the efficiency of quality registrations should be increased through staffing and information and communications technology solutions to reduce the registration burden experienced by nurses and physicians.

COVID 19 and the risk of gastro-intestinal perforation: A case series and literature review.

BACKGROUND: COVID19 is a viral disease with pneumonia as its most common presentation. Many presentations and complications have been reported, but gastro-intestinal perforation has not received much attention. METHODS: three cases from our hospital are presented, and the current literature was reviewed. RESULTS, CASES: All three patients were admitted to the ICU with respiratory failure due to COVID19 pneumonia and intubated. Our first patient was treated with steroids, and subsequently diagnosed with rectal perforation on day 34 of his hospital admission. The second patient was treated with steroids and tocilizumab, and diagnosed with colonic perforation 1 day after neostigmine administration, on day 14 of his hospital admission. Our third patient was treated with steroids and tocilizumab, and diagnosed colonic perforation 4 days after neostigmine administration, on day 14 of his hospital admission. RESULTS, LITERATURE: 25 more cases were found in current literature, both upper GI and lower GI perforations, either as a presenting symptom or during the course of hospitalization. These were often associated with treatment with steroids, interleukin 6 inhibitors, or both. CONCLUSIONS: Gastro-intestinal perforation is a rare but dangerous complication of COVID19. Treatment with tocilizumab and steroids may both increase the risk of this complication, and hamper diagnosis.

Targeted Temperature Management in Out-of-Hospital Cardiac Arrest With Shockable Rhythm: A Post Hoc Analysis of the Coronary Angiography After Cardiac Arrest Trial.

OBJECTIVES: The optimal targeted temperature in patients with shockable rhythm is unclear, and current guidelines recommend targeted temperature management with a correspondingly wide range between 32°C and 36°C. Our aim was to study survival and neurologic outcome associated with targeted temperature management strategy in postarrest patients with initial shockable rhythm. DESIGN: Observational substudy of the Coronary Angiography after Cardiac Arrest without ST-segment Elevation trial. SETTING: Nineteen hospitals in The Netherlands. PATIENTS: The Coronary Angiography after Cardiac Arrest trial randomized successfully resuscitated patients with shockable rhythm and absence of ST-segment elevation to a strategy of immediate or delayed coronary angiography. In this substudy, 459 patients treated with mild therapeutic hypothermia (32.0-34.0°C) or targeted normothermia (36.0-37.0°C) were included. Allocation to targeted temperature management strategy was at the discretion of the physician. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After 90 days, 171 patients (63.6%) in the mild therapeutic hypothermia group and 129 (67.9%) in the targeted normothermia group were alive (hazard ratio, 0.86 [95% CI, 0.62-1.18]; log-rank p = 0.35; adjusted odds ratio, 0.89; 95% CI, 0.45-1.72). Patients in the mild therapeutic hypothermia group had longer ICU stay (4 d [3-7 d] vs 3 d [2-5 d]; ratio of geometric means, 1.32; 95% CI, 1.15-1.51), lower blood pressures, higher lactate levels, and increased need for inotropic support. Cerebral Performance Category scores at ICU discharge and 90-day follow-up and patient-reported Mental and Physical Health Scores at 1 year were similar in the two groups. CONCLUSIONS: In the context of out-of-hospital cardiac arrest with shockable rhythm and no ST-elevation, treatment with mild therapeutic hypothermia was not associated with improved 90-day survival compared with targeted normothermia. Neurologic outcomes at 90 days as well as patient-reported Mental and Physical Health Scores at 1 year did not differ between the groups.

The effects of intensive care unit-initiated transitional care interventions on elements of post-intensive care syndrome: A systematic review and meta-analysis.

OBJECTIVE: The aim of the study was to assess the effectiveness of intensive care unit (ICU)-initiated transitional care interventions for patients and families on elements of post-intensive care syndrome (PICS) and/or PICS-family (PICS--F). REVIEW METHOD USED: This is a systematic review and meta-analysis SOURCES: The authors searched in biomedical bibliographic databases including PubMed, Embase (OVID), CINAHL Plus (EBSCO), Web of Science, and the Cochrane Library and included studies written in English conducted up to October 8, 2020. REVIEW METHODS: We included (non)randomised controlled trials focussing on ICU-initiated transitional care interventions for patients and families. Two authors conducted selection, quality assessment, and data extraction and synthesis independently. Outcomes were described using the three elements of PICS, which were categorised into (i) physical impairments (pulmonary, neuromuscular, and physical function), (ii) cognitive impairments (executive function, memory, attention, visuo-spatial and mental processing speed), and (iii) psychological health (anxiety, depression, acute stress disorder, post-traumatic stress disorder, and depression). RESULTS: From the initially identified 5052 articles, five studies were included (i.e., two randomised controlled trials and three nonrandomised controlled trials) with varied transitional care interventions. Quality among the studies differs from moderate to high risk of bias. Evidence from the studies shows no significant differences in favour of transitional care interventions on physical or psychological aspects of PICS-(F). One study with a nurse-led structured follow-up program showed a significant difference in physical function at 3 months. CONCLUSIONS: Our review revealed that there is a paucity of research about the effectiveness of transitional care interventions for ICU patients with PICS. All, except one of the identified studies, failed to show a significant effect on the elements of PICS. However, these results should be interpreted with caution owing to variety and scarcity of data. PROSPERO REGISTRATION: CRD42020136589 (available via https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020136589).

Interferon gamma immunotherapy in five critically ill COVID-19 patients with impaired cellular immunity: A case series.

BACKGROUND: Prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding has been described in immunocompromised coronavirus disease 2019 (COVID-19) patients, resulting in protracted disease and poor outcome. Specific therapy to improve viral clearance and outcome for this group of patients is currently unavailable. METHODS: Five critically ill COVID-19 patients with severe defects in cellular immune responses, high SARS-CoV-2 viral RNA loads, and no respiratory improvement were treated with interferon gamma, 100 µg subcutaneously, thrice weekly. Bronchial secretion was collected every 48 h for routine diagnostic SARS-CoV-2 RT-PCR and viral culture. FINDINGS: Interferon gamma administration was followed by a rapid decline in SARS-CoV-2 load and a positive-to-negative viral culture conversion. Four patients recovered, and no signs of hyperinflammation were observed. CONCLUSIONS: Interferon gamma may be considered as adjuvant immunotherapy in a subset of immunocompromised COVID-19 patients. FUNDING: A.v.L. and R.v.C. are supported by National Institutes of Health (R01AI145781). G.J.O. and R.P.v.R. are supported by a VICI grant (016.VICI.170.090) from the Dutch Research Council (NWO). W.F.A. is supported by a clinical fellowship grant (9071561) of Netherlands Organization for Health Research and Development. M.G.N. is supported by an ERC advanced grant (833247) and a Spinoza grant of the Netherlands Organization for Scientific Research.

COVID-19 is associated with distinct myopathic features in the diaphragm of critically ill patients.

INTRODUCTION: The diaphragm is the main muscle of inspiration, and its dysfunction contributes to adverse clinical outcomes in critically ill patients. We recently reported the infiltration of SARS-CoV-2, and the development of fibrosis, in the diaphragm of critically ill patients with COVID-19. In the current study, we aimed to characterise myofiber structure in the diaphragm of critically ill patients with COVID-19. METHODS: Diaphragm muscle specimens were collected during autopsy from patients who died of COVID-19 in three academic medical centres in the Netherlands in April and May 2020 (n=27). We studied diaphragm myofiber gene expression and structure and compared the findings obtained to those of deceased critically ill patients without COVID-19 (n=10). RESULTS: Myofibers of critically ill patients with COVID-19 showed on average larger cross-sectional area (slow-twitch myofibers: 2441±229 vs 1571±309 µm2; fast-twitch myofibers: 1966±209 vs 1225±222 µm2). Four critically ill patients with COVID-19 showed extremely large myofibers, which were splitting and contained many centralised nuclei. RNA-sequencing data revealed differentially expressed genes involved in muscle regeneration. CONCLUSION: Diaphragm of critically ill patients with COVID-19 has distinct myopathic features compared with critically ill patients without COVID-19, which may contribute to the ongoing dyspnoea and fatigue in the patients surviving COVID-19 infection.

The effect of immediate coronary angiography after cardiac arrest without ST-segment elevation on left ventricular function. A sub-study of the COACT randomised trial.

BACKGROUND: The effect of immediate coronary angiography and percutaneous coronary intervention (PCI) in patients who are successfully resuscitated after cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) on left ventricular function is currently unknown. METHODS: This prespecified sub-study of a multicentre trial evaluated 552 patients, successfully resuscitated from out-of-hospital cardiac arrest without signs of STEMI. Patients were randomized to either undergo immediate coronary angiography or delayed coronary angiography, after neurologic recovery. All patients underwent PCI if indicated. The main outcomes of this analysis were left ventricular ejection fraction and end-diastolic and systolic volumes assessed by cardiac magnetic resonance imaging or echocardiography. RESULTS: Data on left ventricular function was available for 397 patients. The mean (± standard deviation) left ventricular ejection fraction was 45.2% (±12.8) in the immediate angiography group and 48.4% (±13.2) in the delayed angiography group (mean difference: -3.19; 95% confidence interval [CI], -6.75 to 0.37). Median left ventricular end-diastolic volume was 177 ml in the immediate angiography group compared to 169 ml in the delayed angiography group (ratio of geometric means: 1.06; 95% CI, 0.95-1.19). In addition, mean left ventricular end-systolic volume was 90 ml in the immediate angiography group compared to 78 ml in the delayed angiography group (ratio of geometric means: 1.13; 95% CI 0.97-1.32). CONCLUSION: In patients successfully resuscitated after out-of-hospital cardiac arrest and without signs of STEMI, immediate coronary angiography was not found to improve left ventricular dimensions or function compared with a delayed angiography strategy. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register number, NTR4973.

Increased blood angiotensin converting enzyme 2 activity in critically ill COVID-19 patients.

Critically ill #COVID19 patients display markedly increased alternative angiotensin pathway activity compared to healthy controls, reflected by increased blood ACE2 levels as well as decreased angiotensin-II and enhanced angiotensin-1-7 formation https://bit.ly/2MU1z4z.

Dysregulated Innate and Adaptive Immune Responses Discriminate Disease Severity in COVID-19.

The clinical spectrum of COVID-19 varies and the differences in host response characterizing this variation have not been fully elucidated. COVID-19 disease severity correlates with an excessive proinflammatory immune response and profound lymphopenia. Inflammatory responses according to disease severity were explored by plasma cytokine measurements and proteomics analysis in 147 COVID-19 patients. Furthermore, peripheral blood mononuclear cell cytokine production assays and whole blood flow cytometry were performed. Results confirm a hyperinflammatory innate immune state, while highlighting hepatocyte growth factor and stem cell factor as potential biomarkers for disease severity. Clustering analysis revealed no specific inflammatory endotypes in COVID-19 patients. Functional assays revealed abrogated adaptive cytokine production (interferon-γ, interleukin-17, and interleukin-22) and prominent T-cell exhaustion in critically ill patients, whereas innate immune responses were intact or hyperresponsive. Collectively, this extensive analysis provides a comprehensive insight into the pathobiology of severe to critical COVID-19 and highlights potential biomarkers of disease severity.