Prediction of emergency department presentations for acute coronary syndrome using a machine learning approach.

The relationship between weather and acute coronary syndrome (ACS) incidence has been the subject of considerable research, with varying conclusions. Harnessing machine learning techniques, our study explores the relationship between meteorological factors and ACS presentations in the emergency department (ED), offering insights into seasonal variations and inter-day fluctuations to optimize patient care and resource allocation. A retrospective cohort analysis was conducted, encompassing ACS presentations to Dutch EDs from 2010 to 2017. Temporal patterns were analyzed using heat-maps and time series plots. Multivariable linear regression (MLR) and Random Forest (RF) regression models were employed to forecast daily ACS presentations with prediction horizons of one, three, seven, and thirty days. Model performance was assessed using the coefficient of determination (R²), Mean Absolute Error (MAE), and Mean Absolute Percentage Error (MAPE). The study included 214,953 ACS presentations, predominantly unstable angina (UA) (94,272; 44%), non-ST-elevated myocardial infarction (NSTEMI) (78,963; 37%), and ST-elevated myocardial infarction (STEMI) (41,718; 19%). A decline in daily ACS admissions over time was observed, with notable inter-day (estimated median difference: 41 (95%CI = 37-43, p = < 0.001) and seasonal variations (estimated median difference: 9 (95%CI 6-12, p = < 0.001). Both MLR and RF models demonstrated similar predictive capabilities, with MLR slightly outperforming RF. The models showed moderate explanatory power for ACS incidence (adjusted R² = 0.66; MAE (MAPE): 7.8 (11%)), with varying performance across subdiagnoses. Prediction of UA incidence resulted in the best-explained variability (adjusted R² = 0.80; MAE (MAPE): 5.3 (19.1%)), followed by NSTEMI and STEMI diagnoses. All models maintained consistent performance over extended prediction horizons. Our findings indicate that ACS presentation exhibits distinctive seasonal changes and inter-day differences, with marked reductions in incidence during the summer months and a distinct peak prevalence on Mondays. The predictive performance of our model was moderate. Nonetheless, we obtained good explanatory power for UA presentations. Our model emerges as a potentially valuable supplementary tool to enhance ED resource allocation or future predictive models predicting ACS incidence in the ED.

A comparison between invasive and noninvasive measurement of the Hypotension Prediction Index: A post hoc analysis of a prospective cohort study.

BACKGROUND: Clinical trials and validation studies demonstrate promising hypotension prediction capability by the Hypotension Prediction Index (HPI). Most studies that evaluate HPI derive it from invasive blood pressure readings, but a direct comparison with the noninvasive alternative remains undetermined. Such a comparison could provide valuable insights for clinicians in deciding between invasive and noninvasive monitoring strategies. OBJECTIVES: Evaluating predictive differences between HPI when obtained through noninvasive versus invasive blood pressure monitoring. DESIGN: Post hoc analysis of a prospective observational study conducted between 2018 and 2020. SETTING: Single-centre study conducted in an academic hospital in the Netherlands. PATIENTS: Adult noncardiac surgery patients scheduled for over 2 h long elective procedures. After obtaining informed consent, 91 out of the 105 patients had sufficient data for analysis. MAIN OUTCOME MEASURES: The primary outcome was the difference in area under the receiver-operating characteristics (ROC) curve (AUC) obtained for HPI predictions between the two datasets. Additionally, difference in time-to-event estimations were calculated. RESULTS: AUC (95% confidence interval (CI)) results revealed a nonsignificant difference between invasive and noninvasive HPI, with areas of 94.2% (90.5 to 96.8) and 95.3% (90.4 to 98.2), respectively with an estimated difference of 1.1 (-3.9 to 6.1)%; P = 0.673. However, noninvasive HPI demonstrated significantly longer time-to-event estimations for higher HPI values. CONCLUSION: Noninvasive HPI is reliably accessible to clinicians during noncardiac surgery, showing comparable accuracy in HPI probabilities and the potential for additional response time. TRIAL REGISTRATION: Clinicaltrials.gov (NCT03795831) on 10 January 2019. https://clinicaltrials.gov/study/NCT03795831.

Defining Postinduction Hemodynamic Instability With an Automated Classification Model.

BACKGROUND: Postinduction hypotension (PIH) may be associated with increased morbidity and mortality. In earlier studies, the definition of PIH is solely based on different absolute or relative thresholds. However, the time-course (eg, how fast blood pressure drops during induction) is rarely incorporated, whereas it might represent the hemodynamic instability of a patient. We propose a comprehensive model to distinguish hemodynamically unstable from stable patients by combining blood pressure thresholds with the magnitude and speed of decline. METHODS: This prospective study included 375 adult elective noncardiac surgery patients. Noninvasive blood pressure was continuously measured between 5 minutes before up to 15 minutes after the first induction agent had been administered. An expert panel rated whether the patient experienced clinically relevant hemodynamic instability or not. Interrater correlation coefficient and intraclass correlation were computed to check for consistency between experts. Next, an automated classification model for clinically relevant hemodynamic instability was developed using mean, maximum, minimum systolic, mean, diastolic arterial blood pressure (SAP, MAP, and DAP, respectively) and their corresponding time course of decline. The model was trained and tested based on the hemodynamic instability labels provided by the experts. RESULTS: In total 78 patients were classified as having experienced hemodynamic instability and 279 as not. The hemodynamically unstable patients were significantly older (7 years, 95% confidence interval (CI), 4-11, P < .001), with a higher prevalence of chronic obstructive pulmonary disease (COPD) (3% higher, 95% CI, 1-8, P = .036). Before induction, hemodynamically unstable patients had a higher SAP (median (first-third quartile): 161 (145-175) mm Hg vs 150 (134-166) mm Hg, P < .001) compared to hemodynamic stable patients. Interrater agreement between experts was 0.92 (95% CI, 0.89-0.94). The random forest classifier model showed excellent performance with an area under the receiver operating curve (AUROC) of 0.96, a sensitivity of 0.84, and specificity of 0.94. CONCLUSIONS: Based on the high sensitivity and specificity, the developed model is able to differentiate between clinically relevant hemodynamic instability and hemodynamic stable patients. This classification model will pave the way for future research concerning hemodynamic instability and its prevention.

Microcirculatory Perfusion Disturbances During Veno-Arterial Extracorporeal Membrane Oxygenation: A Systematic Review.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used in case of potentially reversible cardiac failure and restores systemic hemodynamics. However, whether this is followed by improvement of microcirculatory perfusion is unknown. Moreover, critically ill patients have possible pre-existing microcirculatory perfusion disturbances. Therefore, this review provides an overview of alterations in sublingual microcirculatory perfusion in critically ill adult patients receiving VA-ECMO support. Pubmed, Embase (Ovid), Cochrane Central Register of Controlled Trials, and Web of Science were systematically searched according to PRISMA guidelines. Studies reporting sublingual microcirculatory perfusion measurements in adult patients supported by VA-ECMO were included. Outcome parameters included small vessel density (SVD), perfused vessel density (PVD), perfused small vessel density (PSVD), proportion of perfused vessels (PPV), microvascular flow index (MFI) and the heterogeneity index (HI). The protocol was registered at PROSPERO (CRD42021243930). The search identified 1215 studies of which 11 were included. Cardiogenic shock was the most common indication for VA-ECMO (n=8). Three studies report increased PSVD, PPV, and MFI 24 hours after initiation of ECMO compared to pre-ECMO. Nonetheless, microcirculatory perfusion stabilized thereafter. Four out of four studies showed higher PSVD and PPV in survivors compared to non-survivors. Over time, survivors showed recovery of microcirculatory perfusion within hours of initiation of ECMO, whereas this was absent in non-survivors. Notwithstanding the limited sample, VA-ECMO seems to improve microcirculatory perfusion shortly after initiation of ECMO, especially in survivors. Further research in larger cohorts is needed to clarify the longitudinal effects of ECMO on microcirculatory perfusion.

A Randomized Embedded Multifactorial Adaptive Platform for Extra Corporeal Membrane Oxygenation (REMAP ECMO) - Design and Rationale of the Left Ventricular Unloading trial domain.

BACKGROUND: The use of Extracorporeal Membrane Oxygenation (ECMO) remains associated with high rates of complications, weaning failure and mortality which can be partly explained by a knowledge gap on how to properly manage patients on ECMO support. To address relevant patient management issues, we designed a "Randomized Embedded Multifactorial Adaptive Platform (REMAP)" in the setting of ECMO (REMAP ECMO) and a first embedded randomized controlled trial (RCT) investigating the effects of routine early left ventricular (LV) unloading through intra-aortic balloon pumping (IABP). METHODS: REMAP ECMO describes a registry-based platform allowing for the embedding of multiple response adaptive RCTs (trial domains) which can perpetually address the effect of relevant patient management issues on ECMO weaning success. A first trial domain studies the effects of LV unloading by means of an IABP as an adjunct to veno-arterial (V-A) ECMO versus V-A ECMO alone on ECMO weaning success at 30 days in adult cardiogenic shock patients admitted to the Intensive Care Unit (ICU). The primary outcome of this trial is "successful weaning from ECMO" being defined as a composite of survival without the need for mechanical circulatory support, heart transplantation, or left ventricular assist device (LVAD) at 30 days after initiation of ECMO. Secondary outcomes include the need for interventional escalation of LV unloading strategy, mechanistic endpoints, survival characteristics until one year after ECMO initiation, and quality of life. Trial data will be analysed using a Bayesian statistical framework. The adaptive design allows for a high degree of flexibility, such as response adaptive randomization and early stopping of the trial for efficacy or futility. The REMAP ECMO LV unloading study is approved by the Medical Ethical Committee of the Erasmus Medical Center and is publicly registered. CONCLUSION: This REMAP ECMO trial platform enables the efficient roll-out of multiple RCTs on relevant patient management issues. A first embedded trial domain will compare routine LV unloading by means of an IABP as an adjunct to V-A ECMO versus V-A ECMO alone. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05913622.

How I diagnose and treat cardiorespiratory complications of transfusion.

Cardiorespiratory complications after blood transfusion are the leading cause of transfusion related morbidity and mortality world-wide. Transfusion-related acute lung injury (TRALI) and transfusion associated circulatory overload (TACO) form the top two most frequently reported cardiorespiratory complications, both with clear pathophysiology-based treatment algorithms. In the past decades translational research has increased understanding of mechanisms in place including patient and transfusion risk factors. This has led to updated international definitions, biomarker-based diagnostics, intervention and risk mitigation. Preventive measures have led to a significant reduction in TRALI and TACO prevention is increasingly highlighted within hemovigilance. In this paper clinical case scenarios illustrate the challenges of diagnosing, treating and finally classifying cardiorespiratory complications of transfusion. A background on current definitions, diagnostics and pathophysiological mechanisms will be given; as well as how to deal with cases where TRALI/ TACO mechanisms are both present and need for combination therapies. Hemovigilance systems world-wide are essential to provide insight into the incidence of transfusion complications. Furthermore, these systems provide a basis to discover new patient and transfusion risk factors and to better balance the down- and upside of a transfusion for a patient. Finally, we discuss future challenges and research priorities in the field of cardiorespiratory transfusion complications.

Quality of care after a horizontal merger between two large academic hospitals.

Background: Hospital mergers remain common, but their influence on healthcare quality varies. Data on effects of European hospital mergers are ill defined, and academic hospitals in particular. This case study assesses early quality of care changes in two formerly competing Dutch academic hospitals that merged on June 6, 2018. Methods: Statistical process control and interrupted time series analysis were performed. All adult, non-psychiatric patients, admitted between 01-03-2016 and 01-10-2022 were eligible for analysis. Primary outcome measure was all cause in-hospital mortality (or hospice), secondary outcomes were unplanned 30-day readmissions to same hospital, length of stay, and patients' hospital rating. Data were obtained from electronic health records, and patient experience surveys. Findings: The mean (SD) age of the 573 813 included patients was 54·3 (18·9) years. The minority was female (277 817, 48·4 %), and most admissions were acute (308 597, 53·8 %). No merger related change in mortality was found in the first 20 months post-merger (limited to the pre-Covid-19 era). For this same period, the 30-day readmission incidence changed to a downward slope post-merger, and the length of stay shortened (immediate level-change -3·796 % (95 % CI, -5·776 % to -1·816 %) and trend-change -0·150 % per month (95 % CI, -0·307 % to 0·007 %)). Patients' hospital ratings seemed to improve post-merger. Interpretation: In this quality improvement study, a full- and gradual post-merger integration strategy for a Dutch academic hospital merger was not associated with changes in in-hospital mortality, and yielded slight improved results for secondary quality of care outcomes.

Exploring the Impact of Extracorporeal Membrane Oxygenation on the Endothelium: A Systematic Review.

Extracorporeal membrane oxygenation (ECMO) is a life-saving intervention for patients with circulatory and/or pulmonary failure; however, the rate of complications remains high. ECMO induces systemic inflammation, which may activate and damage the endothelium, thereby causing edema and organ dysfunction. Advancing our understanding in this area is crucial for improving patient outcomes during ECMO. The goal of this review is to summarize the current evidence of the effects of ECMO on endothelial activation and damage in both animals and patients. PubMed and Embase databases were systematically searched for both clinical and animal studies including ECMO support. The outcome parameters were markers of endothelial activation and damage or (in)direct measurements of endothelial permeability, fluid leakage and edema. In total, 26 studies (patient n = 16, animal n = 10) fulfilled all eligibility criteria, and used VA-ECMO (n = 13) or VV-ECMO (n = 6), or remained undefined (n = 7). The most frequently studied endothelial activation markers were adhesion molecules (ICAM-1) and selectins (E- and P-selectin). The levels of endothelial activation markers were comparable to or higher than in healthy controls. Compared to pre-ECMO or non-ECMO, the majority of studies showed stable or decreased levels. Angiopoietin-2, von Willebrand Factor and extracellular vesicles were the most widely studied circulating markers of endothelial damage. More than half of the included studies showed increased levels when compared to normal ranges, and pre-ECMO or non-ECMO values. In healthy animals, ECMO itself leads to vascular leakage and edema. The effect of ECMO support in critically ill animals showed contradicting results. ECMO support (further) induces endothelial damage, but endothelial activation does not, in the critically ill. Further research is necessary to conclude on the effect of the underlying comorbidity and type of ECMO support applied on endothelial dysfunction.

Developments in Transfusion Medicine: Pulmonary Transfusion Reactions and Novel Blood Cell Labeling Techniques.

Staying updated on advancements in transfusion medicine is crucial, especially in critical care and perioperative setting, where timely and accurate transfusions can be lifesaving therapeutic interventions. This narrative review explores the landscape of transfusion-related adverse events, focusing on pulmonary transfusion reactions such as transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI). TACO and TRALI are the leading causes of transfusion-related morbidity and mortality; however, specific treatments are lacking. Understanding the current incidence, diagnostic criteria, pathogenesis, treatment, and prevention strategies can equip clinicians to help reduce the incidence of these life-threatening complications. The review discusses emerging pathogenic mechanisms, including the possible role of inflammation in TACO and the mechanisms of reverse TRALI and therapeutic targets for TACO and TRALI, emphasizing the need for further research to uncover preventive and treatment modalities. Despite advancements, significant gaps remain in our understanding of what occurs during transfusions, highlighting the necessity for improved monitoring methods. To address this, the review also presents novel blood cell labeling techniques in transfusion medicine used for improving monitoring, quality assessment, and as a consequence, potentially reducing transfusion-related complications. This article aims to provide an update for anesthesiologists, critical care specialists, and transfusion medicine professionals regarding recent advancements and developments in the field of transfusion medicine.

The Prognostic Value of Troponin-T in Out-of-Hospital Cardiac Arrest Without ST-Segment Elevation: A COACT Substudy.

Background: In out-of-hospital cardiac arrest (OHCA) without ST-elevation, predictive markers that can identify those with a high risk of acute coronary syndrome are lacking. Methods: In this post hoc analysis of the Coronary Angiography after Cardiac Arrest (COACT) trial, the baseline, median, peak, and time-concentration curves of troponin-T (cTnT) (T-AUC) in OHCA patients without ST-elevation were studied. cTnT values were obtained at predefined time points at 0, 3, 6, 12, 24, 36, 28, and 72 hours after admission. All patients who died within the measurement period were not included. The primary outcome was the association between cTnT and 90-day survival. Secondary outcomes included the association of cTnT and acute thrombotic occlusions, acute unstable lesions, and left ventricular function. Results: In total, 352 patients were included in the analysis. The mean age was 64 ± 13 years (80.4% men). All cTnT measures were independent prognostic factors for mortality after adjustment for potential confounders age, sex, history of coronary artery disease, witnessed arrest, time to BLS, and time to return of spontaneous circulation (eg, for T-AUC: hazard ratio, 1.44; 95% CI, 1.06-1.94; P = .02; P value for all variables ≤.02). Median cTnT (odds ratio [OR], 1.58; 95% CI, 1.18-2.12; P = .002) and T-AUC (OR, 2.03; 95% CI, 1.25-3.29; P = .004) were independent predictors for acute unstable lesions. Median cTnT (OR, 1.62; 95% CI, 1.17-2.23; P = .003) and T-AUC (OR, 2.16; 95% CI, 1.27-3.68; P = .004) were independent predictors for acute thrombotic occlusions. CTnT values were not associated with the left ventricular function (eg, for T-AUC: OR, 2.01; 95% CI, 0.65-6.19; P = .22; P value for all variables ≥.14). Conclusion: In OHCA patients without ST-segment elevation, cTnT release during the first 72 hours after return of spontaneous circulation was associated with clinical outcomes.

Small-volume blood sample collection tubes in adult intensive care units: A rapid practice guideline.

BACKGROUND: This Intensive Care Medicine Rapid Practice Guideline (ICM-RPG) provides an evidence-based recommendation to address the question: in adult patients in intensive care units (ICUs), should we use small-volume or conventional blood collection tubes? METHODS: We included 23 panelists in 8 countries and assessed and managed financial and intellectual conflicts of interest. Methodological support was provided by the Guidelines in Intensive Care, Development, and Evaluation (GUIDE) group. We conducted a systematic review, including evidence from observational and randomized studies. Using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, we evaluated the certainty of evidence and developed recommendations using the Evidence-to-Decision framework. RESULTS: We identified 8 studies (1 cluster and 2 patient-level randomized trials; 5 observational studies) comparing small-volume to conventional tubes. We had high certainty evidence that small-volume tubes reduce daily and cumulative blood sampling volume; and moderate certainty evidence that they reduce the risk of transfusion and mean number of red blood cell units transfused, but these estimates were limited by imprecision. We had high certainty that small-volume tubes have a similar rate of specimens with insufficient quantity. The panel considered that the desirable effects of small-volume tubes outweigh the undesirable effects, are less wasteful of resources, and are feasible, as demonstrated by successful implementation across multiple countries, although there are upfront implementation costs to validate small-volume tubes on laboratory instrumentation. CONCLUSION: This ICM-RPG panel made a strong recommendation for the use of small-volume sample collection tubes in adult ICUs based on overall moderate certainty evidence.

Health-related quality of life one year after refractory cardiac arrest treated with conventional or extracorporeal CPR; a secondary analysis of the INCEPTION-trial.

Background: Prospective, trial-based data comparing health-related quality of life (HRQoL) in patients surviving out-of-hospital cardiac arrest (OHCA) through extracorporeal cardiopulmonary resuscitation (ECPR) or conventional CPR (CCPR) are scarce. We aimed to determine HRQoL during 1-year after refractory OHCA in patients treated with ECPR and CCPR. Methods: We present a secondary analysis of the multicenter INCEPTION-trial, which studied the effectiveness of ECPR versus CCPR in patients with refractory OHCA. HRQoL was prospectively assessed using the EQ-5D-5L questionnaire. Poor HRQoL was pragmatically defined as an EQ-5D-5L health utility index (HUI) > 1 SD below the age-adjusted norm. We used mixed linear models to assess the difference in HRQoL over time and univariable analyses to assess factors potentially associated with poor HRQoL. Results: A total of 134 patients were enrolled, and hospital survival was 20% (27 patients). EQ-5D-5L data were available for 25 patients (5 ECPR and 20 CCPR). One year after OHCA, the estimated mean HUI was 0.73 (0.05) in all patients, 0.84 (0.12) in ECPR survivors, and 0.71 (0.05) in CCPR survivors (p-value 0.31). Eight (32%) survivors had a poor HRQoL. HRQoL was good in 17 (68%) patients, with 100% in ECPR survivors versus 60% in CCPR survivors (p-value 0.14). Conclusion: One year after refractory OHCA, 68% of the survivors had a good HRQoL. We found no statistically significant difference in HRQoL one year after OHCA in patients treated with ECPR compared to CCPR. However, numerical differences may be clinically relevant in favor of ECPR.

Heterogeneity of treatment effect of vilobelimab in COVID-19: a secondary analysis of a randomised controlled trial.

In a phase 3 trial (PANAMO, NCT04333420), vilobelimab, a complement 5a (C5a) inhibitor, reduced 28-day mortality in mechanically ventilated COVID-19 patients. This post hoc analysis of 368 patients aimed to explore treatment heterogeneity through unsupervised learning. All available clinical variables at baseline were used as input. Treatment heterogeneity was assessed using latent class analysis (LCA), Ward's hierarchical clustering (HC) and the adjudication to previously described clinical sepsis phenotypes. The primary outcome was 28-day mortality. For LCA, a 2-class latent model was deemed most suitable. In the LCA model, 82 (22%) patients were assigned to class 1 and 286 (78%) to class 2. Class 1 was defined by more severely ill patients with significantly higher mortality. In an adjusted logistic regression, no heterogeneity of treatment effect (HTE) between classes was observed (p = 0.998). For HC, no significant classes were found (p = 0.669). Using the previously described clinical sepsis subtypes, 41 patients (11%) were adjudicated subtype alpha (α), 17 (5%) beta (ß), 112 (30%) delta (δ) and 198 (54%) gamma (γ). HTE was observed between clinical subtypes (p = 0.001) with improved 28-day mortality after treatment with vilobelimab for the δ subtype (OR = 0.17, 95% CI 0.07-0.40, p < 0.001). No signal for harm of treatment with vilobelimab was observed in any class or clinical subtype. Overall, treatment effect with vilobelimab was consistent across different classes and subtypes, except for the δ subtype, suggesting potential additional benefit for the most severely ill patients.

A quality improvement study on how a simulation model can help decision making on organization of ICU wards.

BACKGROUND: Intensive Care Unit (ICU) capacity management is essential to provide high-quality healthcare for critically ill patients. Yet, consensus on the most favorable ICU design is lacking, especially whether ICUs should deliver dedicated or non-dedicated care. The decision for dedicated or non-dedicated ICU design considers a trade-off in the degree of specialization for individual patient care and efficient use of resources for society. We aim to share insights of a model simulating capacity effects for different ICU designs. Upon request, this simulation model is available for other ICUs. METHODS: A discrete event simulation model was developed and used, to study the hypothetical performance of a large University Hospital ICU on occupancy, rejection, and rescheduling rates for a dedicated and non-dedicated ICU design in four different scenarios. These scenarios either simulate the base-case situation of the local ICU, varying bed capacity levels, potential effects of reduced length of stay for a dedicated design and unexpected increased inflow of unplanned patients. RESULTS: The simulation model provided insights to foresee effects of capacity choices that should be made. The non-dedicated ICU design outperformed the dedicated ICU design in terms of efficient use of scarce resources. CONCLUSIONS: The choice to use dedicated ICUs does not only affect the clinical outcome, but also rejection- rescheduling and occupancy rates. Our analysis of a large university hospital demonstrates how such a model can support decision making on ICU design, in conjunction with other operation characteristics such as staffing and quality management.

Incidence of catheter-related thrombosis and its association with outcome in critically ill patients: A prospective observational study.

BACKGROUND: Incidence of central venous catheter (CVC)-related thrombosis in critically ill patients remains ambiguous and its association with potential hazardous sequelae unknown. The primary aim of the study was to evaluate the epidemiology of CVC-related thrombosis; secondary aims were to assess the association of catheter-related thrombosis with catheter-related infection, pulmonary embolism and mortality. METHODS: This was a single-center, prospective observational study conducted at a tertiary intensive care unit (ICU) in the Netherlands. The study population consisted of CVC placements in adult ICU patients with a minimal indwelling time of 48 h. CVC-related thrombosis was diagnosed with ultrasonography. Primary outcomes were prevalence and incidence, incidence was reported as the number of cases per 1000 indwelling days. RESULTS: 173 CVCs in 147 patients were included. Median age of patients was 64.0 [IQR: 52.0, 72.0] and 71.1 % were male. Prevalence of thrombosis was 0.56 (95 % CI: 0.49, 0.63) and incidence per 1000 indwelling days was 65.7 (95 % CI: 59.0, 72.3). No association with catheter-related infection was found (p = 0.566). There was a significant association with pulmonary embolism (p = 0.022). All 173 CVCs were included in the survival analysis. Catheter-related thrombosis was associated with a lower 28-day mortality risk (hazard ratio: 0.39, 95 % CI: 0.17, 0.87). CONCLUSION: In critically ill patients, prevalence and incidence of catheter-related thrombosis were high. Catheter-related thrombosis was not associated with catheter-related infections, but was associated with pulmonary embolism and a decreased mortality risk.

Bleeding assessment following central venous catheter placement, a direct comparison of prospective and retrospective analyses.

BACKGROUND: Reported bleeding incidences following central venous catheter (CVC) placement highly depend on methods of bleeding assessment. To determine the direction and magnitude of the bias associated with retrospective data collection, we used data from the PACER randomized controlled trial and a previous retrospective cohort study. STUDY DESIGN AND METHODS: A patient-level comparison of CVC-related bleeding severity was made among (1) the prospectively collected clinical bleeding assessment of the PACER trial, (2) centralized assessment of CVC insertion site photographs, and (3) retrospective chart review. Interrater reliability for photographic bleeding assessment and retrospective chart review was assessed using Cohen's κ. The magnitude of underreporting of both methods compared to prospective clinical bleeding assessment at different cutoff points of clinically relevant bleeding was assessed using McNemar's test. RESULTS: Interrater reliability was acceptable for both methods (κ = 0.583 and κ = 0.481 for photographic assessment and retrospective chart review, respectively). Photographic bleeding assessment led to significant underreporting of bleeding complications at all cutoff points. Retrospective chart review led to significant underreporting of minor bleeding complications, with an odds ratio (95% CI) of 0.17 (0.044-0.51) for the cutoff point grade 1 (i.e., self-limiting or requiring at most 20 min of manual compression) or higher. There was no significant underreporting of major bleeding complications with retrospective chart review. DISCUSSION: Centralized photographic bleeding assessment and retrospective chart review lead to biased bleeding assessment compared to prospective clinical bleeding assessment.

Towards personalized medicine: a scoping review of immunotherapy in sepsis.

Despite significant progress in our understanding of the pathophysiology of sepsis and extensive clinical research, there are few proven therapies addressing the underlying immune dysregulation of this life-threatening condition. The aim of this scoping review is to describe the literature evaluating immunotherapy in adult patients with sepsis, emphasizing on methods providing a "personalized immunotherapy" approach, which was defined as the classification of patients into a distinct subgroup or subphenotype, in which a patient's immune profile is used to guide treatment. Subgroups are subsets of sepsis patients, based on any cut-off in a variable. Subphenotypes are subgroups that can be reliably discriminated from other subgroup based on data-driven assessments. Included studies were randomized controlled trials and cohort studies investigating immunomodulatory therapies in adults with sepsis. Studies were identified by searching PubMed, Embase, Cochrane CENTRAL and ClinicalTrials.gov, from the first paper available until January 29th, 2024. The search resulted in 15,853 studies. Title and abstract screening resulted in 1409 studies (9%), assessed for eligibility; 771 studies were included, of which 282 (37%) were observational and 489 (63%) interventional. Treatment groups included were treatments targeting the innate immune response, the complement system, coagulation and endothelial dysfunction, non-pharmalogical treatment, pleiotropic drugs, immunonutrition, concomitant treatments, Traditional Chinese Medicine, immunostimulatory cytokines and growth factors, intravenous immunoglobulins, mesenchymal stem cells and immune-checkpoint inhibitors. A personalized approach was incorporated in 70 studies (9%). Enrichment was applied using cut-offs in temperature, laboratory, biomarker or genetic variables. Trials often showed conflicting results, possibly due to the lack of patient stratification or the potential influence of severity and timing on immunomodulatory therapy results. When a personalized approach was applied, trends of clinical benefit for several interventions emerged, which hold promise for future clinical trials using personalized immunotherapy.

Favorable resuscitation characteristics in patients undergoing extracorporeal cardiopulmonary resuscitation: A secondary analysis of the INCEPTION-trial.

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used as a supportive treatment for refractory out-of-hospital cardiac arrest (OHCA). Still, there is a paucity of data evaluating favorable and unfavorable prognostic characteristics in patients considered for ECPR. Methods: We performed a previously unplanned post-hoc analysis of the multicenter randomized controlled INCEPTION-trial. The study group consisted of patients receiving ECPR, irrespective of initial group randomization. The patients were divided into favorable survivors (cerebral performance category [CPC] 1-2) and unfavorable or non-survivors (CPC 3-5). Results: In the initial INCEPTION-trial, 134 patients were randomized. ECPR treatment was started in 46 (66%) of 70 patients in the ECPR treatment arm and 3 (4%) of 74 patients in the conventional treatment arm. No statistically significant differences in baseline characteristics, medical history, or causes of arrest were observed between survivors (n = 5) and non-survivors (n = 44). More patients in the surviving group had a shockable rhythm at the time of cannulation (60% vs. 14%, p = 0.037), underwent more defibrillation attempts (13 vs. 6, p = 0.002), and received higher dosages of amiodarone (450 mg vs 375 mg, p = 0.047) despite similar durations of resuscitation maneuvers. Furthermore, non-survivors more frequently had post-ECPR implantation adverse events. Conclusion: The persistence of ventricular arrhythmia is a favorable prognostic factor in patients with refractory OHCA undergoing an ECPR-based treatment. Future studies are warranted to confirm this finding and to establish additional prognostic factors.Clinical trial Registration:clinicaltrials.gov registration number NCT03101787.

Biomarker patterns in patients with cardiogenic shock versus septic shock.

Background: In cardiogenic shock (CS), contractile failure is often accompanied by a systemic inflammatory response syndrome. In contrast, many patients with septic shock (SS) develop cardiac dysfunction. A similar hemodynamic support strategy is often deployed in both syndromes but it is unclear whether this is justified based on profiles of biomarkers expressing neurohormonal activation and cardiovascular stress. Methods: In this prospective, multicenter cohort, 111 patients with acute myocardial infarction related CS were identified, and matched to patients with SS. Clinical parameters were collected and blood samples were obtained on day 1-3 of Intensive Care admission. Results: In this shock cohort comprising 222 patients, with a mean age of 61 (±13.5) years and of whom 161 (37 %) were male, we found that despite obvious clinical disparities on admission, mortality at 30-days did not differ (CS: 40.5 % vs. SS 43.1 %, p = 0.56). Overall, plasma concentrations of all biomarkers were higher in SS patients, with the largest difference on the first day. However, only in CS patients the biomarker concentrations were associated with mortality. Conclusion: In this prospective, multicenter cohort SS and CS patients showed similarities in baseline conditions and had similar mortality. However, several biomarkers only showed prognostic value in CS.

A national multi centre pre-hospital ECPR stepped wedge study; design and rationale of the ON-SCENE study.

BACKGROUND: The likelihood of return of spontaneous circulation with conventional advanced life support is known to have an exponential decline and therefore neurological outcome after 20 min in patients with a cardiac arrest is poor. Initiation of venoarterial ExtraCorporeal Membrane Oxygenation (ECMO) during resuscitation might improve outcomes if used in time and in a selected patient category. However, previous studies have failed to significantly reduce the time from cardiac arrest to ECMO flow to less than 60 min. We hypothesize that the initiation of Extracorporeal Cardiopulmonary Resuscitation (ECPR) by a Helicopter Emergency Medical Services System (HEMS) will reduce the low flow time and improve outcomes in refractory Out of Hospital Cardiac Arrest (OHCA) patients. METHODS: The ON-SCENE study will use a non-randomised stepped wedge design to implement ECPR in patients with witnessed OHCA between the ages of 18-50 years old, with an initial presentation of shockable rhythm or pulseless electrical activity with a high suspicion of pulmonary embolism, lasting more than 20, but less than 45 min. Patients will be treated by the ambulance crew and HEMS with prehospital ECPR capabilities and will be compared with treatment by ambulance crew and HEMS without prehospital ECPR capabilities. The primary outcome measure will be survival at hospital discharge. The secondary outcome measure will be good neurological outcome defined as a cerebral performance categories scale score of 1 or 2 at 6 and 12 months. DISCUSSION: The ON-SCENE study focuses on initiating ECPR at the scene of OHCA using HEMS. The current in-hospital ECPR for OHCA obstacles encompassing low survival rates in refractory arrests, extended low-flow durations during transportation, and the critical time sensitivity of initiating ECPR, which could potentially be addressed through the implementation of the HEMS system. When successful, implementing on-scene ECPR could significantly enhance survival rates and minimize neurological impairment. TRIAL REGISTRATION: Clinicaltyrials.gov under NCT04620070, registration date 3 November 2020.