Table 0; documenting the steps to go from clinical database to research dataset.

OBJECTIVES: Data-driven decision support tools have been increasingly recognized to transform health care. However, such tools are often developed on predefined research datasets without adequate knowledge of the origin of this data and how it was selected. How a dataset is extracted from a clinical database can profoundly impact the validity, interpretability and interoperability of the dataset, and downstream analyses, yet is rarely reported. Therefore, we present a case study illustrating how a definitive patient list was extracted from a clinical source database and how this can be reported. STUDY DESIGN AND SETTING: A single-center observational study was performed at an academic hospital in the Netherlands to illustrate the impact of selecting a definitive patient list for research from a clinical source database, and the importance of documenting this process. All admissions from the critical care database admitted between January 1, 2013, and January 1, 2023, were used. RESULTS: An interdisciplinary team collaborated to identify and address potential sources of data insufficiency and uncertainty. We demonstrate a stepwise data preparation process, reducing the clinical source database of 54,218 admissions to a definitive patient list of 21,553 admissions. Transparent documentation of the data preparation process improves the quality of the definitive patient list before analysis of the corresponding patient data. This study generated seven important recommendations for preparing observational health-care data for research purposes. CONCLUSION: Documenting data preparation is essential for understanding a research dataset originating from a clinical source database before analyzing health-care data. The findings contribute to establishing data standards and offer insights into the complexities of preparing health-care data for scientific investigation. Meticulous data preparation and documentation thereof will improve research validity and advance critical care.

The association between coronary artery calcification and vectorcardiography in mechanically ventilated COVID-19 patients: the Maastricht Intensive Care COVID cohort.

BACKGROUND: Coronary artery calcification (CAC) is associated with poor outcome in critically ill patients. A deterioration in cardiac conduction and loss of myocardial tissue could be an underlying cause. Vectorcardiography (VCG) and cardiac biomarkers provide insight into these underlying causes. The aim of this study was to investigate whether a high degree of CAC is associated with VCG-derived variables and biomarkers, including high-sensitivity troponin-T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). METHODS: Mechanically ventilated coronavirus-19 (COVID-19) patients with an available chest computed tomography (CT) and 12-lead electrocardiogram (ECG) were studied. CAC scores were determined using chest CT scans. Patients were categorized into 3 sex-specific tertiles: low, intermediate, and high CAC. Daily 12 leads-ECGs were converted to VCGs. Daily hs-cTnT and NT-proBNP levels were determined. Linear mixed-effects regression models examined the associations between CAC tertiles and VCG variables, and between CAC tertiles and hs-cTnT or NT-proBNP levels. RESULTS: In this study, 205 patients (73.2% men, median age 65 years [IQR 57.0; 71.0]) were included. Compared to the lowest CAC tertile, the highest CAC tertile had a larger QRS area at baseline (6.65 µVs larger [1.50; 11.81], p = 0.012), which decreased during admission (- 0.27 µVs per day [- 0.43; - 0.11], p = 0.001). Patients with the highest CAC tertile also had a longer QRS duration (12.02 ms longer [4.74; 19.30], p = 0.001), higher levels of log hs-cTnT (0.79 ng/L higher [0.40; 1.19], p < 0.001) and log NT-proBNP (0.83 pmol/L higher [0.30; 1.37], p = 0.002). CONCLUSION: Patients with a high degree of CAC had the largest QRS area and higher QRS amplitude, which decreased more over time when compared to patients with a low degree of CAC. These results suggest that CAC might contribute to loss of myocardial tissue during critical illness. These insights could improve risk stratification and prognostication of patients with critical illness.

Off-the-Shelf Synthetic Biodegradable Grafts Transform In Situ into a Living Arteriovenous Fistula in a Large Animal Model.

Current vascular access options require frequent interventions. In situ tissue engineering (TE) may overcome these limitations by combining the initial success of synthetic grafts with long-term advantages of autologous vessels by using biodegradable grafts that transform into autologous vascular tissue at the site of implantation. Scaffolds (6 mm-Ø) made of supramolecular polycarbonate-bisurea (PC-BU), with a polycaprolactone (PCL) anti-kinking-coil, are implanted between the carotid artery and jugular vein in goats. A subset is bio-functionalized using bisurea-modified-Stromal cell-derived factor-1α (SDF1α) derived peptides and ePTFE grafts as controls. Grafts are explanted after 1 and 3 months, and evaluated for material degradation, tissue formation, compliance, and patency. At 3 months, the scaffold is resorbed and replaced by vascular neo-tissue, including elastin, contractile markers, and endothelial lining. No dilations, ruptures, or aneurysms are observed and grafts are successfully cannulated at termination. SDF-1α-peptide-biofunctionalization does not influence outcomes. Patency is lower in TE grafts (50%) compared to controls (100% patency), predominantly caused by intimal hyperplasia. Rapid remodeling of a synthetic, biodegradable vascular scaffold into a living, compliant arteriovenous fistula is demonstrated in a large animal model. Despite lower patency compared to ePTFE, transformation into autologous and compliant living tissue with self-healing capacity may have long-term advantages.

Deep embedded clustering generalisability and adaptation for integrating mixed datatypes: two critical care cohorts.

We validated a Deep Embedded Clustering (DEC) model and its adaptation for integrating mixed datatypes (in this study, numerical and categorical variables). Deep Embedded Clustering (DEC) is a promising technique capable of managing extensive sets of variables and non-linear relationships. Nevertheless, DEC cannot adequately handle mixed datatypes. Therefore, we adapted DEC by replacing the autoencoder with an X-shaped variational autoencoder (XVAE) and optimising hyperparameters for cluster stability. We call this model "X-DEC". We compared DEC and X-DEC by reproducing a previous study that used DEC to identify clusters in a population of intensive care patients. We assessed internal validity based on cluster stability on the development dataset. Since generalisability of clustering models has insufficiently been validated on external populations, we assessed external validity by investigating cluster generalisability onto an external validation dataset. We concluded that both DEC and X-DEC resulted in clinically recognisable and generalisable clusters, but X-DEC produced much more stable clusters.

Pericardial Fat Is Associated With Less Severe Multiorgan Failure Over Time in Patients With Coronavirus Disease-19: The Maastricht Intensive Care COVID Cohort.

PURPOSE: Pericardial fat (PF) and epicardial adipose tissue (EAT) may enhance the proinflammatory response in corona virus-19 (COVID-19) patients. Higher PF and EAT volumes might result in multiorgan failure and explain unfavorable trajectories.The aim of this study was to examine the association between the volume of PF and EAT and multiorgan failure over time. MATERIALS AND METHODS: All mechanically ventilated COVID-19 patients with an available chest computed tomography were prospectively included (March-June 2020). PF and EAT volumes were quantified using chest computed tomography scans. Patients were categorized into sex-specific PF and EAT tertiles. Variables to calculate Sequential Organ Failure Assessment (SOFA) scores were collected daily to indicate multiorgan failure. Linear mixed-effects regression was used to investigate the association between tertiles for PF and EAT volumes separately and serial SOFA scores over time. All models were adjusted. RESULTS: Sixty-three patients were divided into PF and EAT tertiles, with median PF volumes of 131.4 mL (IQR [interquartile range]: 115.7, 143.2 mL), 199.8 mL (IQR: 175.9, 221.6 mL), and 318.8 mL (IQR: 281.9, 376.8 mL) and median EAT volumes of 69.6 mL (IQR: 57.0, 79.4 mL), 107.9 mL (IQR: 104.6, 115.1 mL), and 163.8 mL (IQR: 146.5, 203.1 mL). Patients in the highest PF tertile had a statistically significantly lower SOFA score over time (1.3 [-2.5, -0.1], P =0.033) compared with the lowest PF tertile. EAT tertiles were not significantly associated with SOFA scores over time. CONCLUSION: A higher PF volume is associated with less multiorgan failure in mechanically ventilated COVID-19 patients. EAT volumes were not associated with multiorgan failure.

Bilateral Femoral Cannulation Is Associated With Reduced Severe Limb Ischemia-Related Complications Compared With Unilateral Femoral Cannulation in Adult Peripheral Venoarterial Extracorporeal Membrane Oxygenation: Results From the Extracorporeal Life Support Registry.

OBJECTIVES: Peripheral venoarterial extracorporeal membrane oxygenation (ECMO) with femoral access is obtained through unilateral or bilateral groin cannulation. Whether one cannulation strategy is associated with a lower risk for limb ischemia remains unknown. We aim to assess if one strategy is preferable. DESIGN: A retrospective cohort study based on the Extracorporeal Life Support Organization registry. SETTING: ECMO centers worldwide included in the Extracorporeal Life Support Organization registry. PATIENTS: All adult patients (≥ 18 yr) who received peripheral venoarterial ECMO with femoral access and were included from 2014 to 2020. INTERVENTIONS: Unilateral or bilateral femoral cannulation. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the occurrence of limb ischemia defined as a composite endpoint including the need for a distal perfusion cannula (DPC) after 6 hours from implantation, compartment syndrome/fasciotomy, amputation, revascularization, and thrombectomy. Secondary endpoints included bleeding at the peripheral cannulation site, need for vessel repair, vessel repair after decannulation, and in-hospital death. Propensity score matching was performed to account for confounders. Overall, 19,093 patients underwent peripheral venoarterial ECMO through unilateral ( n = 11,965) or bilateral ( n = 7,128) femoral cannulation. Limb ischemia requiring any intervention was not different between both groups (bilateral vs unilateral: odds ratio [OR], 0.92; 95% CI, 0.82-1.02). However, there was a lower rate of compartment syndrome/fasciotomy in the bilateral group (bilateral vs unilateral: OR, 0.80; 95% CI, 0.66-0.97). Bilateral cannulation was also associated with lower odds of cannulation site bleeding (bilateral vs unilateral: OR, 0.87; 95% CI, 0.76-0.99), vessel repair (bilateral vs unilateral: OR, 0.55; 95% CI, 0.38-0.79), and in-hospital mortality (bilateral vs unilateral: OR, 0.85; 95% CI, 0.81-0.91) compared with unilateral cannulation. These findings were unchanged after propensity matching. CONCLUSIONS: This study showed no risk reduction for overall limb ischemia-related events requiring DPC after 6 hours when comparing bilateral to unilateral femoral cannulation in peripheral venoarterial ECMO. However, bilateral cannulation was associated with a reduced risk for compartment syndrome/fasciotomy, lower rates of bleeding and vessel repair during ECMO, and lower in-hospital mortality.

Evaluation of pliable bioresorbable, elastomeric aortic valve prostheses in sheep during 12 months post implantation.

Pliable microfibrous, bioresorbable elastomeric heart valve prostheses are investigated in search of sustainable heart valve replacement. These cell-free implants recruit cells and trigger tissue formation on the valves in situ. Our aim is to investigate the behaviour of these heart valve prostheses when exposed to the high-pressure circulation. We conducted a 12-month follow-up study in sheep to evaluate the in vivo functionality and neo-tissue formation of these valves in the aortic position. All valves remained free from endocarditis, thrombotic complications and macroscopic calcifications. Cell colonisation in the leaflets was mainly restricted to the hinge area, while resorption of synthetic fibers was limited. Most valves were pliable and structurally intact (10/15), however, other valves (5/15) showed cusp thickening, retraction or holes in the leaflets. Further research is needed to assess whether in-situ heart valve tissue engineering in the aortic position is possible or whether non-resorbable synthetic pliable prostheses are preferred.

Coronary Artery Calcifications Are Associated With More Severe Multiorgan Failure in Patients With Severe Coronavirus Disease 2019 Infection: Longitudinal Results of the Maastricht Intensive Care COVID Cohort.

PURPOSE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is regarded as a multisystemic disease. Patients with preexisting cardiovascular disease have an increased risk for a more severe disease course. This study aimed to investigate if a higher degree of coronary artery calcifications (CAC) on a standard chest computed tomography (CT) scan in mechanically ventilated patients was associated with a more severe multiorgan failure over time. MATERIALS AND METHODS: All mechanically ventilated intensive care unit patients with SARS-CoV-2 infection who underwent a chest CT were prospectively included. CT was used to establish the extent of CAC using a semiquantitative grading system. We categorized patients into 3 sex-specific tertiles of CAC: lowest, intermediate, and highest CAC score. Daily, the Sequential Organ Failure Assessment (SOFA) scores were collected to evaluate organ failure over time. Linear mixed-effects regression was used to investigate differences in SOFA scores between tertiles. The models were adjusted for age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, cardiovascular risk factors, and chronic liver, lung, and renal disease. RESULTS: In all, 71 patients were included. Patients in the highest CAC tertile had, on average, over time, 1.8 (0.5-3.1) points higher SOFA score, compared with the lowest CAC tertile ( P =0.005). This association remained significant after adjustment for age, sex, and APACHE II score (1.4 [0.1-2.7], P =0.042) and clinically relevant after adjustment for cardiovascular risk factors (1.3 [0.0-2.7], P =0.06) and chronic diseases (1.3 [-0.2 to 2.7], P =0.085). CONCLUSION: A greater extent of CAC is associated with a more severe multiorgan failure in mechanically ventilated coronavirus disease 2019 patients.

Serial Assessment of Myocardial Injury Markers in Mechanically Ventilated Patients With SARS-CoV-2 (from the Prospective MaastrICCht Cohort).

Myocardial injury in COVID-19 is associated with in-hospital mortality. However, the development of myocardial injury over time and whether myocardial injury in patients with COVID-19 at the intensive care unit is associated with outcome is unclear. This study prospectively investigates myocardial injury with serial measurements over the full course of intensive care unit admission in mechanically ventilated patients with COVID-19. As part of the prospective Maastricht Intensive Care COVID cohort, predefined myocardial injury markers, including high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and electrocardiographic characteristics were serially collected in mechanically ventilated patients with COVID-19. Linear mixed-effects regression was used to compare survivors with nonsurvivors, adjusting for gender, age, APACHE-II score, daily creatinine concentration, hypertension, diabetes mellitus, and obesity. In 90 patients, 57 (63%) were survivors and 33 (37%) nonsurvivors, and a total of 628 serial electrocardiograms, 1,565 hs-cTnT, and 1,559 NT-proBNP concentrations were assessed. Log-hs-cTnT was lower in survivors compared with nonsurvivors at day 1 (ß -0.93 [-1.37; -0.49], p <0.001) and did not change over time. Log-NT-proBNP did not differ at day 1 between both groups but decreased over time in the survivor group (ß -0.08 [-0.11; -0.04] p <0.001) compared with nonsurvivors. Many electrocardiographic abnormalities were present in the whole population, without significant differences between both groups. In conclusion, baseline hs-cTnT and change in NT-proBNP were strongly associated with mortality. Two-thirds of patients with COVID-19 showed electrocardiographic abnormalities. Our serial assessment suggests that myocardial injury is common in mechanically ventilated patients with COVID-19 and is associated with outcome.

Cardiovascular outcome 6 months after severe coronavirus disease 2019 infection.

OBJECTIVES: In coronavirus disease 2019 (COVID-19), cardiovascular risk factors and myocardial injury relate to increased mortality. We evaluated the extent of cardiac sequelae 6 months after hospital discharge in patients surviving ICU hospitalization for COVID-19. METHODS: All survivors of Maastricht-ICU were invited for comprehensive cardiovascular evaluation 6 months after discharge from ICU. Cardiac screening included an electrocardiogram, cardiac biomarkers, echocardiography, cardiac magnetic resonance (CMR) and, wherever indicated, cardiac computed tomography or coronary angiogram. RESULTS: Out of 52 survivors, 81% ( n  = 42) participated to the cardiovascular follow-up [median follow-up of 6 months, interquartile range (IQR) 6.1-6.7]. Eight patients (19%) had newly diagnosed coronary artery disease (CAD), of which two required a percutaneous intervention. Echocardiographic global longitudinal strain (GLS) was abnormal in 24% and CMR-derived GLS was abnormal in 12%, despite normal left ventricular ejection fraction in all. None of the patients showed elevated T 1 relaxation times and five patients (14%) had an elevated T 2 relaxation time. Late gadolinium enhancement (LGE) reflecting regional myocardial fibrosis was increased in eight patients (21%), of which three had myocarditis and three had pericarditis. CONCLUSION: Cardiovascular follow-up at 6 months after ICU-admission for severe COVID-19 revealed that one out of five invasively mechanically ventilated survivors had CAD, a quarter had subclinical left ventricular dysfunction defined as reduced echocardiographic GLS, and 42% of the patients had CMR abnormalities (reduced LVEF, reduced GLS, LGE presence, and elevated T 2 ). On the basis of these findings, long-term cardiovascular follow-up is strongly recommended in all post-IC COVID-19 patients. CLINICAL TRIAL REGISTRATION: Trial Register number [NL8613]) https://www.trialregister.nl/trial/8613Video abstract:http://links.lww.com/HJH/B899 .

Case Report: An Unusual Cause for Recurrent Hemopericardium in a Patient With Dyspnea.

The case concerns a female presenting with dyspnoea resulting from recurrent hemopericardium. Pericardiocentesis, coronary angiography, and extensive laboratory and imaging studies did not reveal the underlying etiology of the hemopericardium. Only after repeat and exploratory surgery, diffuse venous pericardial hemorrhages with localized thrombi typical of angiosarcoma were discovered.

Radiation Induces Valvular Interstitial Cell Calcific Response in an in vitro Model of Calcific Aortic Valve Disease.

Background: Mediastinal ionizing radiotherapy is associated with an increased risk of valvular disease, which demonstrates pathological hallmarks similar to calcific aortic valve disease (CAVD). Despite advances in radiotherapy techniques, the prevalence of comorbidities such as radiation-associated valvular disease is still increasing due to improved survival of patients receiving radiotherapy. However, the mechanisms of radiation-associated valvular disease are largely unknown. CAVD is considered to be an actively regulated disease process, mainly controlled by valvular interstitial cells (VICs). We hypothesize that radiation exposure catalyzes the calcific response of VICs and, therefore, contributes to the development of radiation-associated valvular disease. Methods and Results: To delineate the relationship between radiation and VIC behavior (morphology, calcification, and matrix turnover), two different in vitro models were established: (1) VICs were cultured two-dimensional (2D) on coverslips in control medium (CM) or osteogenic medium (OM) and irradiated with 0, 2, 4, 8, or 16 Gray (Gy); and (2) three-dimensional (3D) hydrogel system was designed, loaded with VICs and exposed to 0, 4, or 16 Gy of radiation. In both models, a dose-dependent decrease in cell viability and proliferation was observed in CM and OM. Radiation exposure caused myofibroblast-like morphological changes and differentiation of VICs, as characterized by decreased αSMA expression. Calcification, as defined by increased alkaline phosphatase activity, was mostly present in the 2D irradiated VICs exposed to 4 Gy, while after exposure to higher doses VICs acquired a unique giant fibroblast-like cell morphology. Finally, matrix turnover was significantly affected by radiation exposure in the 3D irradiated VICs, as shown by decreased collagen staining and increased MMP-2 and MMP-9 activity. Conclusions: The presented work demonstrates that radiation exposure enhances the calcific response in VICs, a hallmark of CAVD. In addition, high radiation exposure induces differentiation of VICs into a terminally differentiated giant-cell fibroblast. Further studies are essential to elucidate the underlying mechanisms of these radiation-induced valvular changes.

Systemic inflammation down-regulates glyoxalase-1 expression: an experimental study in healthy males.

BACKGROUND: Hypoxia and inflammation are hallmarks of critical illness, related to multiple organ failure. A possible mechanism leading to multiple organ failure is hypoxia- or inflammation-induced down-regulation of the detoxifying glyoxalase system that clears dicarbonyl stress. The dicarbonyl methylglyoxal (MGO) is a highly reactive agent produced by metabolic pathways such as anaerobic glycolysis and gluconeogenesis. MGO leads to protein damage and ultimately multi-organ failure. Whether detoxification of MGO into D-lactate by glyoxalase functions appropriately under conditions of hypoxia and inflammation is largely unknown. We investigated the effect of inflammation and hypoxia on the MGO pathway in humans in vivo. METHODS: After prehydration with glucose 2.5% solution, ten healthy males were exposed to hypoxia (arterial saturation 80-85%) for 3.5 h using an air-tight respiratory helmet, ten males to experimental endotoxemia (LPS 2 ng/kg i.v.), ten males to LPS+hypoxia and ten males to none of these interventions (control group). Serial blood samples were drawn, and glyoxalase-1 mRNA expression, MGO, methylglyoxal-derived hydroimidazolone-1 (MG-H1), D-lactate and L-lactate levels, were measured serially. RESULTS: Glyoxalase-1 mRNA expression decreased in the LPS (ß (95%CI); -0.87 (-1.24; -0.50) and the LPS+hypoxia groups; -0.78 (-1.07; -0.48) (P<0.001). MGO was equal between groups, whereas MG-H1 increased over time in the control group only (P=0.003). D-Lactate was increased in all four groups. L-Lactate was increased in all groups, except in the control group. CONCLUSION: Systemic inflammation downregulates glyoxalase-1 mRNA expression in humans. This is a possible mechanism leading to cell damage and multi-organ failure in critical illness with potential for intervention.

Appropriateness of empirical antibiotic therapy and added value of adjunctive gentamicin in patients with septic shock: a prospective cohort study in the ICU.

OBJECTIVES: To determine the appropriateness of empiric antibiotic therapy and the possible benefit of adding short-course gentamicin in septic shock patients with abdominal, urogenital, or an unknown focus. Secondary objectives were the effect of gentamicin addition on shock reversal and the incidence of a fungal infection. METHODS: Microbiological cultures, antibiotic treatment, and antibiotic resistance patterns of the cultured microorganisms were recorded during the first 5 days of admission. Inappropriate antibiotic therapy was defined as a prescription within the first 24 h that did not cover cultured bacteria during the first 5 days of admission and was determined in the overall group and in patients receiving adjunctive gentamicin (combination therapy) versus patients receiving monotherapy. Binomial logistic regression analysis was used to investigate the association of gentamicin addition with shock reversal. RESULTS: Of 203 septic shock patients, with abdominal (n = 143), urogenital (n = 27) or unknown (n = 33) focus, 115 patients received monotherapy, and 88 patients received combination therapy. Inappropriate therapy occurred in 29 patients (14%), more frequently in monotherapy (17%) versus combination therapy (10%). Combination therapy would have been effective in 55% of patients with inappropriate monotherapy. We found no association between gentamicin addition and shock reversal (p = .223). A fungal infection was present in 22 patients (11%). CONCLUSION: Inappropriate empirical antibiotic therapy occurs in 17% of septic shock patients receiving monotherapy. In 55% of these patients, additional gentamicin would have resulted in appropriate therapy. When clinical course is unfavourable, lowering the threshold for administering adjunctive aminoglycoside and antifungal therapy should be considered.

Early ICU-mortality in sepsis - causes, influencing factors and variability in clinical judgement: a retrospective cohort study.

BACKGROUND: Sepsis is a global health care problem with a high mortality. Early death seems common; however, data are sparse. The objective of the present study was to report causes and influencing factors of early death in sepsis and septic shock. METHODS: All septic ICU patients were included from 2012 to 2017. Early death was predefined as occurring within 48 h. Causes and factors leading up to death were reported by a panel of four intensivists, independently reviewing the medical files. Following factors were assessed: (1) delay in ICU admission; (2) futile ICU treatment; (3) missed diagnosis or inadequate treatment on the ICU. Fleiss kappa was used to assess inter-observer agreement. RESULTS: 1107 septic patients (APACHE II score 25 ± 8) were included. 344 patients died of which 97 (28%) within 48 h. In 33% an autopsy was performed. Primary causes of early death were multiple organ failure, mesenteric ischaemia and death after cardio-pulmonary resuscitation (CPR). Delay in ICU admission was scored in 32% of early deaths with slight agreement (κ = 0.180), futile ICU treatment in 29% with moderate agreement (κ = 0.415) and missed diagnosis or treatment in 7% of cases with slight agreement (κ = 0.122). CONCLUSIONS: Early death after ICU admission in sepsis is common and primarily caused by multiple organ failure, mesenteric ischaemia and death after unsuccessful CPR. Influencing factors were delay in ICU admission and futile ICU admission. Fleiss kappa indicates substantial variability in clinical judgement between intensivists, strengthening the necessity for shared decision making.

Clinical diagnoses vs. autopsy findings in early deceased septic patients in the intensive care: a retrospective cohort study.

Early death in sepsis occurs frequently; however, specific causes are largely unknown. An autopsy can contribute to ascertain causes of death. The objective of the study was to determine discrepancies in clinical diagnosis and postmortem findings in septic intensive care unit (ICU) patients deceased within 48 h after ICU admission. All septic ICU patients who deceased within 48 h after ICU admission were identified and included. Four intensivists determined the clinical cause of death by medical record review. An autopsy was performed within 24 h of death. Clinical diagnosis and postmortem findings were compared and classified as autopsy-identified missed clinical diagnoses and autopsy-refuted diagnoses. Class I and II missed major diagnoses using the Goldman criteria were scored. Between 2012 and 2017, 1107 septic patients were admitted to ICU. Of these, 344 patients (31%) died, of which 97 patients (28%) deceased within 48 h. In 32 (33%) early deceased patients, an autopsy was agreed. There were 26 autopsy-identified missed clinical diagnoses found, mostly myocardial infarction (n = 4) and pneumonia (n = 4). In four patients (13%), a class I discrepancy was found. In fourteen patients (42%), a class II discrepancy was found. In conclusion, an autopsy is an important diagnostic tool that can identify definite causes of death. These diagnoses deviate from diagnoses established during admission in early deceased sepsis patients.

Veno-Arterial Extracorporeal Life Support in Heart Transplant and Ventricle Assist Device Centres. Meta-analysis.

AIMS: Because reported mortality on veno-arterial (V-A) extracorporeal life support (ECLS) substantially varies between centres, the aim of the current analysis was to assess the outcomes between units performing heart transplantation and/or implanting ventricular assist device (HTx/VAD) vs. non-HTx/VAD units in patients undergoing V-A ECLS for cardiogenic shock. METHODS AND RESULTS: Systematic search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was performed using PubMed/MEDLINE databases until 30 November 2019. Articles reporting in-hospital/30-day mortality and centre's HTx/VAD status were included. In-hospital outcomes and long-term survival were analysed in subgroup meta-analysis. A total of 174 studies enrolling n = 13 308 patients were included with 20 series performed in non-HTx/VAD centres (1016 patients, 7.8%). Majority of patients underwent V-A ECLS for post-cardiotomy shock (44.2%) and acute myocardial infarction (20.7%). Estimated overall in-hospital mortality was 57.2% (54.9-59.4%). Mortality rates were higher in non-HTx/VAD [65.5% (59.8-70.8%)] as compared with HTx/VAD centres [55.8% (53.3-58.2%)], P < 0.001. Estimated late survival was 61.8% (55.7-67.9%) without differences between non-HTx/VAD and HTx/VAD centres: 66.5% (30.3-1.02%) vs. 61.7% (55.5-67.8%), respectively (P = 0.797). No differences were seen with respect to ECLS duration, limb complications, and reoperations for bleeding, kidney injury, and sepsis. Yet, weaning rates were higher in HTx/VAD vs. non-HTx/VAD centres: 58.7% (56.2-61.1%) vs. 48.9% (42.0-55.9%), P = 0.010. Estimated rate of bridge to heart transplant was 6.6% (5.2-8.3%) with numerical, yet not statistically significant, difference between non-HTx/VAD [2.7% (0.8-8.3%)] as compared with HTx/VAD [6.7% (5.3-8.6%)] (P = 0.131). CONCLUSIONS: Survival after V-A ECLS differed according to centre's HTx/VAD status. Potentially different risk profiles of patients must be taken account for before definite conclusions are drawn.

Serial measurements in COVID-19-induced acute respiratory disease to unravel heterogeneity of the disease course: design of the Maastricht Intensive Care COVID cohort (MaastrICCht).

INTRODUCTION: The course of the disease in SARS-CoV-2 infection in mechanically ventilated patients is unknown. To unravel the clinical heterogeneity of the SARS-CoV-2 infection in these patients, we designed the prospective observational Maastricht Intensive Care COVID cohort (MaastrICCht). We incorporated serial measurements that harbour aetiological, diagnostic and predictive information. The study aims to investigate the heterogeneity of the natural course of critically ill patients with a SARS-CoV-2 infection. METHODS AND ANALYSIS: Mechanically ventilated patients admitted to the intensive care with a SARS-CoV-2 infection will be included. We will collect clinical variables, vital parameters, laboratory variables, mechanical ventilator settings, chest electrical impedance tomography, ECGs, echocardiography as well as other imaging modalities to assess heterogeneity of the course of a SARS-CoV-2 infection in critically ill patients. The MaastrICCht is also designed to foster various other studies and registries and intends to create an open-source database for investigators. Therefore, a major part of the data collection is aligned with an existing national intensive care data registry and two international COVID-19 data collection initiatives. Additionally, we create a flexible design, so that additional measures can be added during the ongoing study based on new knowledge obtained from the rapidly growing body of evidence. The spread of the COVID-19 pandemic requires the swift implementation of observational research to unravel heterogeneity of the natural course of the disease of SARS-CoV-2 infection in mechanically ventilated patients. Our study design is expected to enhance aetiological, diagnostic and prognostic understanding of the disease. This paper describes the design of the MaastrICCht. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the medical ethics committee (Medisch Ethische Toetsingscommissie 2020-1565/3 00 523) of the Maastricht University Medical Centre+ (Maastricht UMC+), which will be performed based on the Declaration of Helsinki. During the pandemic, the board of directors of Maastricht UMC+ adopted a policy to inform patients and ask their consent to use the collected data and to store serum samples for COVID-19 research purposes. All study documentation will be stored securely for fifteen years after recruitment of the last patient. The results will be published in peer-reviewed academic journals, with a preference for open access journals, while particularly considering deposition of the manuscripts on a preprint server early. TRIAL REGISTRATION NUMBER: The Netherlands Trial Register (NL8613).

Computational Characterization of The Dish-In-A-Dish, A High Yield Culture Platform for Endothelial Shear Stress Studies on the Orbital Shaker.

Endothelial cells sense and respond to shear stress. Different in vitro model systems have been used to study the cellular responses to shear stress, but these platforms do not allow studies on high numbers of cells under uniform and controllable shear stress. The annular dish, or dish-in-a-dish (DiaD), on the orbital shaker has been proposed as an accessible system to overcome these challenges. However, the influence of the DiaD design and the experimental parameters on the shear stress patterns is not known. In this study, we characterize different designs and experimental parameters (orbit size, speed and fluid height) using computational fluid dynamics. We optimize the DiaD for an atheroprotective flow, combining high shear stress levels with a low oscillatory shear index (OSI). We find that orbit size determines the DiaD design and parameters. The shear stress levels increase with increasing rotational speed and fluid height. Based on our optimization, we experimentally compare the 134/56 DiaD with regular dishes for cellular alignment and KLF2, eNOS, CDH2 and MCP1 expression. The calculated OSI has a strong impact on alignment and gene expression, emphasizing the importance of characterizing shear profiles in orbital setups.

The impact of Centre's heart transplant status and volume on in-hospital outcomes following extracorporeal membrane oxygenation for refractory post-cardiotomy cardiogenic shock: a meta-analysis.

BACKGROUND: Postcardiotomy cardiogenic shock (PCS) that is refractory to inotropic support remains a major concern in cardiac surgery and is almost universally fatal unless treated with mechanical support. While reported mortality rates on ECMO vary from center to center, aim of the current report is assess if the outcomes differ between centres according to volume and heart transplantation status. METHODS: A systematic search was performed according to PRISMA statement using PubMed/Medline databases between 2010 and 2018. Relevant articles were scrutinized and included in the meta-analysis only if reporting in-hospital/30-day mortality and heart transplantation status of the centre. Paediatric and congenital heart surgery-related studies along with those conducted in the setting of veno-venous ECMO for respiratory distress syndrome were excluded. Differences were assessed by means of subgroup meta-analysis and meta-regression. RESULTS: Fifty-four studies enrolling N = 4421 ECMO patients were included. Of those, 6 series were performed in non-HTx centres (204 pts.;4.6%). Overall 30-day survival (95% Confidence Intervals) was 35.3% (32.5-38.2%) and did not statistically differ between non-HTx: 33.3% (26.8-40.4%) and HTx centres: 35.7% (32.7-38.8%); Pinteraction = 0.531. There was no impact of centre volume on survival as well: ßcoef = 0.0006; P = 0.833. No statistical differences were seen between HTx and non-HTx with respect to ECMO duration, limb complications, reoperations for bleeding, kidney injury and sepsis. There were however significantly less neurological complications in the HTx as compared to non-HTx centres: 11.9% vs 19.5% respectively; P = 0.009; an inverse relationship was seen for neurologic complications in centres performing more ECMOs annually ßcoef = - 0.0066; P = 0.031. Weaning rates and bridging to HTx and/or VADs were higher in HTx facilities. CONCLUSIONS: There was no apparent difference in survival after ECMO implantation for refractory PCS according to centre's ECMO volume and transplantation status. Potentially different risk profiles of patients in these centres must be taken account for before definite conclusions are drawn.