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Objectives: This study aimed to assess the prognostic value of routinely collected laboratory parameters, specifically lactate, troponin-T, and CK-MB, in predicting mortality in patients with surgically treated endocarditis. Additionally, the study evaluated the effectiveness of two mortality scores, EuroSCORE II and ACEF II Score, in this clinical context., Methods: We retrospectively analyzed data from 130 patients diagnosed with endocarditis who underwent surgery at a single tertiary center over nine years. The study utilized preoperative mortality scores and laboratory parameters collected within the first 24 h post-surgery. Statistical analyses included AUROC curves, Kaplan-Meier survival analyses, and correlation analyses to determine predictive values and associations with patient outcomes., Results: Among the 130 patients, 28 (21.5%) died within one year post-surgery. Elevated postoperative lactate levels were significantly associated with increased short- and long-term mortality, with AUROC values indicating strong predictive capability. The ACEF II Score also demonstrated significant predictive value for mortality at various time points, outperforming EuroSCORE II. Higher lactate levels and ACEF II Scores correlated with increased hazard ratios for mortality. Kaplan-Meier analyses revealed significant survival differences based on lactate and ACEF II Score thresholds., Conclusion: Postoperative lactate levels and the ACEF II Score are robust predictors of mortality in patients undergoing cardiac surgery for endocarditis. Integrating these parameters into clinical practice can enhance risk stratification and guide therapeutic decisions, improving patient outcomes through personalized care. Further studies are needed to validate these findings across diverse populations and explore additional biomarkers for refined predictive accuracy., (© 2024. The Author(s).)

Background: Sarcopenia, characterized by the loss of skeletal muscle mass, is an emerging comorbidity associated with poor outcomes in cardiovascular surgery. Its impact on mortality in patients undergoing valve surgery for infective endocarditis (IE) remains underexplored. This study investigates the relationship between sarcopenia, measured by the Psoas muscle area index (PMAi), and mortality in patients with IE undergoing valve surgery. Materials and Methods: We retrospectively analyzed 68 patients with IE who underwent valve surgery at a tertiary care center from 2013 to 2021. Sarcopenia was defined as being in the lowest quartile of PMAi, measured via preoperative computed tomography (CT). Baseline characteristics, survival outcomes, and factors influencing mortality were analyzed using Kaplan-Meier survival curves and Cox proportional hazards regression. The predictive value of PMAi for 1-year and 3-year mortality was assessed via receiver operating characteristic (ROC) curves. Results: Sarcopenia was strongly associated with increased mortality at both 1-year (HR: 0.378, p = 0.010) and 3-year follow-ups (HR: 0.457, p = 0.012). Female sex (OR: 275.748, p < 0.001) and older age (OR: 9.995, p = 0.003) were significant predictors of sarcopenia. Chronic kidney insufficiency (CKI) and the use of heart failure medication therapy also significantly impacted survival outcomes. Conclusions: Sarcopenia is a strong independent predictor of short- and mid-term mortality in patients undergoing valve surgery for IE. Routine radiological assessment of sarcopenia using PMAi could improve risk stratification and guide preoperative interventions. Tailored management strategies, especially in older women and patients with CKI, may enhance outcomes in this high-risk population.

Background: There is currently no practice-based, multicenter database of poisoned patients admitted to intensive care units (ICUs). The INTOXICATE study, endorsed by the ESICM and EAPCCT, aimed to determine the rate of eventful admissions among acutely intoxicated adult ICU patients., Methods: Ethical approval was obtained for this multicenter, prospective observational study, and data-sharing agreements were signed with each participating center. An electronic case report form was used to collect data on patient demographics, exposure, clinical characteristics, investigations, treatment, and in-hospital mortality data. The primary outcome, 'eventful admission', was a composite outcome defined as the rate of patients who received any of the following treatments in the first 24 h after the ICU admission: oxygen supplementation with a FiO2 > 40%, mechanical ventilation, vasopressors, renal replacement therapy (RRT), cardiopulmonary resuscitation, antidotes, active cooling, fluid resuscitation (> 1.5 L of intravenous fluid of any kind), sedation, or who died in the hospital., Results: Seventy-eight ICUs, mainly from Europe, but also from Australia and the Eastern Mediterranean, participated. A total of 2,273 patients were enrolled between November 2020 and June 2023. The median age of the patients was 41 years, 72% were exposed to intoxicating drugs. The observed rate of patients with an eventful ICU admission was 68% (n = 1546/2273 patients). The hospital mortality was 4.5% (n = 103/2273)., Conclusions: The vast majority of patients survive, and approximately one third of patients do not receive any ICU-specific interventions after admission in an intensive care unit for acute intoxication. High-quality detailed clinical data have been collected from a large cohort of acutely intoxicated ICU patients, providing information on the pattern of severe acute poisoning requiring intensive care admission and the outcomes of these patients., Trial Registration: OSF registration ID: osf.io/7e5uy., (© 2024. The Author(s).)

Background/Objectives : Infective endocarditis (IE) often requires surgical intervention, with postoperative acute kidney injury (AKI), posing a significant concern. This retrospective study aimed to investigate AKI incidence, its impact on short-term mortality, and identify modifiable factors in patients with IE scheduled for valve surgery. Methods : This single-center study enrolled 130 consecutive IE patients from 2013 to 2021 undergoing valve surgery. The creatinine levels were monitored pre- and postoperatively, and AKI was defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Patient demographics, comorbidities, procedural details, and complications were recorded. Primary outcomes included AKI incidence; the relevance of creatinine levels for AKI detection; and the association of AKI with 30-, 60-, and 180-day mortality. Modifiable factors contributing to AKI were explored as secondary outcomes. Results : Postoperatively, 35.4% developed AKI. The highest creatinine elevation occurred on the second postoperative day. Best predictive value for AKI was a creatinine level of 1.35 mg/dL on the second day (AUC: 0.901; sensitivity: 0.89, specificity: 0.79). Elevated creatinine levels on the second day were robust predictors for short-term mortality at 30, 60, and 180 days postoperatively (AUC ranging from 0.708 to 0.789). CK-MB levels at 24 h postoperatively and minimum hemoglobin during surgery were identified as independent predictors for AKI in logistic regression. Conclusion s : This study highlights the crucial role of creatinine levels in predicting short-term mortality in surgical IE patients. A specific threshold (1.35 mg/dL) provides a practical marker for risk stratification, offering insights for refining perioperative strategies and optimizing outcomes in this challenging patient population.

Severe aortic valve stenosis (AS) and pulmonary hypertension (PH) are life-threatening cardiovascular conditions, necessitating early detection and intervention. Recent studies have explored the role of Insulin-like Growth Factor-Binding Protein 2 (IGF-BP2) in cardiovascular pathophysiology. Understanding its involvement may offer novel insights into disease mechanisms and therapeutic targets for these conditions. A total of 102 patients (46 female, 56 male) with severe AS undergoing a transcatheter aortic valve replacement (TAVR) in a single-center study were classified using echocardiography tests to determine systolic pulmonary artery pressure (sPAP) and the presence (sPAP ≥ 40 mmHg) or absence (sPAP < 40 mmHg) of PH. Additionally, serial laboratory determinations of IGF-BP2 before, and at 24 h, 96 h, and 3 months after intervention were conducted in all study participants. Considering the entire cohort, patients with PH had significant and continuously higher serum IGF-BP2 concentrations over time than patients without PH. After subdivision by sex, it could be demonstrated that the above-mentioned results were only verifiable in males, but not in females. In the male patients, baseline IGF-BP2 levels before the TAVR was an isolated risk factor for premature death after intervention and at 1, 3, and 5 years post-intervention. The same was valid for the combination of male and echocardiographically established PH patients. The predictive role of IGF-BP2 in severe AS and concurrent PH remains unknown. A more profound comprehension of IGF-BP2 mechanisms, particularly in males, could facilitate the earlier consideration of the TAVR as a more effective and successful treatment strategy.

Background: H. pylori is a common bacterial infection that can cause gastritis, peptic ulcers, and cancer. The distribution of H. pylori infection is not uniform and can vary based on socio-economic factors. The aim of this study was to investigate the relationship between H. pylori infection and educational status in Central Europe. If the prevalence of H. pylori infection was found to be exceptionally high in one particular educational stratum, then systematic screening in this population group could be a sensible strategy., Methods: Participants were included from the Salzburg Colon Cancer Prevention Initiative (Sakkopi) cohort, consisting of 5313 asymptomatic Austrian patients. Clinical and laboratory parameters and the biopsy proven presence of H. pylori during an esophagoduodenoscopy were obtained, and patients' educational status was categorized into lower (38%), medium (54%), and higher (9%) education. Logistic regression models were fitted to evaluate the relationship between H. pylori infection and educational status., Results: Compared to patients with lower educational status (21%), patients with medium (17%) and higher (15%) educational status were less often infected with H. pylori (P<0.001). This association remained after adjustment for age, sex, and concomitant diagnosis of metabolic syndrome in multivariable logistic regression models. Sensitivity analysis showed lower odds for H. pylori infection with both medium and higher education in most strata., Conclusions: We discovered a statistically significant association between low educational status and an elevated risk for H. pylori infection. Nonetheless, the absolute difference is not enough to advocate for partially population-based screening in a specific education status group. As a result, we believe that the information linking low educational attainment to higher H. pylori prevalence should primarily be taken into account in clinical decision-making, but should not replace the existing testing approach for H. pylori, which is based on clinical reasoning and symptoms.

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression by binding to target messenger RNAs (mRNAs). miRNAs have been implicated in a variety of cardiovascular and neurological diseases, such as myocardial infarction, cardiomyopathies of various geneses, rhythmological diseases, neurodegenerative illnesses and strokes. Numerous studies have focused on the expression of miRNA patterns with respect to atrial fibrillation (AF) or acute ischemic stroke (AIS) However, only a few studies have addressed the expression pattern of miRNAs in patients with AF and AIS in order to provide not only preventive information but also to identify therapeutic potentials. Therefore, the aim of this review is to summarize 18 existing manuscripts that have dealt with this combined topic of AF and associated AIS in detail and to shed light on the most frequently mentioned miRNAs-1, -19, -21, -145 and -146 with regard to their molecular mechanisms and targets on both the heart and the brain. From this, possible diagnostic and therapeutic consequences for the future could be derived.

Purpose To perform a systematic review to assess the diagnostic and prognostic value of cardiac MRI after sudden cardiac arrest (SCA). Materials and Methods PubMed and Cochrane Library databases were systematically searched for studies investigating cardiac MRI after SCA in adult patients (≥18 years of age). The time frame of the encompassed studies spans from January 2012 to January 2023. The study protocol was preregistered in OSF Registries (www.osf.io/nxaev) , and the systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of the included studies was evaluated using the Newcastle-Ottawa quality assessment scale. Results Fourteen studies involving 1367 individuals, 1257 (91.9%) of whom underwent cardiac MRI, were included. Inconsistent findings were reported on the diagnostic value of cardiac MRI-specific findings. The included studies demonstrated the following main findings: (a) cardiac MRI led to a new or alternative diagnosis in patients with SCA; (b) cardiac MRI identified pathologic or arrhythmogenic substrates; (c) cardiac MRI helped detect myocardial edema (potentially reversible); (d) cardiac MRI provided evidence for the occurrence of adverse events; and (e) functional markers or ventricular dimensions were considered prognostically relevant in a few studies. Relevant challenges in this systematic review were the lack of comparators and reference standards relative to cardiac MRI as the index test and patient selection bias. Conclusion Cardiac MRI following SCA can contribute to the diagnostic process and offer supplementary information essential for treatment planning. Limitations of the review include studies with insufficient comparators and potential bias in patient selection. Systematic review registration link: osf.io/nxaev Keywords: Cardiac MRI, Cardiovascular Disease, Cardiomyopathy, Ischemia, Myocardial Edema, Sudden Cardiac Arrest © RSNA, 2024.

Introduction: Selection in patients with functional mitral regurgitation (MR) to identify responders to interventions is challenging. In these patients, frailty might be used as a multidimensional parameter to summarize the resilience to stressors. Our objective was to evaluate frailty as a predictor of outcome in patients with moderate to severe secondary MR., Methods: We conducted a single-center retrospective observational cohort study and included 239 patients with moderate to severe secondary MR aged 65 years or older between 2014 and 2020. Echocardiography was performed at baseline; frailty was evaluated using the clinical frailty scale (CFS). The combined primary endpoint was hospitalization for heart failure and all-cause mortality., Results: A total of 53% (127) of all patients were classified as CFS 4 (living with mild frailty) or higher. Frail patients had a higher risk for the combined endpoint (hazard ratio, HR 3.70, 95% confidence interval, CI 2.12-6.47; p < 0.001), 1‑year mortality (HR 5.94, 95% CI 1.76-20.08; p < 0.001) even after adjustment for EuroSCORE2. The CFS was predictive for the combined endpoint (AUC 0.69, 95% CI 0.62-0.75) and outperformed EuroSCORE2 (AUC 0.54, 95% CI 0.46-0.62; p = 0.01). In sensitivity analyses, we found that frailty was associated with adverse outcomes at least in trend in all subgroups., Conclusion: For older, medically treated patients with moderate to severe secondary mitral regurgitation, frailty is an independent predictor for the occurrence of death and heart failure-related readmission within 1 year and outperformed the EuroSCORE2. Frailty should be assessed routinely in patients with heart failure to guide clinical decision making for mitral valve interventions or conservative treatment., (© 2023. The Author(s).)

Background: Previous studies have been inconclusive about racial disparities in sepsis. This study evaluated the impact of ethnic background on management and outcome in sepsis and septic shock., Methods: This analysis included 17,146 patients suffering from sepsis and septic shock from the multicenter eICU Collaborative Research Database. Generalized estimated equation (GEE) population-averaged models were used to fit three sequential regression models for the binary primary outcome of hospital mortality., Results: Non-Hispanic whites were the predominant group (n = 14,124), followed by African Americans (n = 1,852), Hispanics (n = 717), Asian Americans (n = 280), Native Americans (n = 146) and others (n = 830). Overall, the intensive care treatment and hospital mortality were similar between all ethnic groups. This finding was concordant in patients with septic shock and persisted after adjusting for patient-level variables (age, sex, mechanical ventilation, vasopressor use and comorbidities) and hospital variables (teaching hospital status, number of beds in the hospital)., Conclusion: We could not detect ethnic disparities in the management and outcomes of critically ill septic patients and patients suffering from septic shock. Disparate outcomes among critically ill septic patients of different ethnicities are a public health, rather than a critical care challenge., (© 2023. The Author(s).)

Severe hyperlactatemia (>10mmol/L) or impaired lactate metabolism are known to correlate with increased mortality. The maximum lactate concentration on day 1 of 10,724 septic patients from the eICU Collaborative Research Database was analyzed and patients were divided into three groups based on maximum lactate in the first 24 h (<5mmol/l; ≥5mmol/l & <10mmol/l; ≥10mmol/l). In addition, delta lactate was calculated using the following formula: (maximum lactate day 1 minus maximum lactate day 2) divided by maximum lactate day 1. A multilevel regression analysis was performed, with hospital mortality serving as the primary study end point. Significant differences in hospital mortality were found in patients with hyperlactatemia (lactate ≥10mmol/l: 79%, ≥5mmol/l & <10mmol/l: 43%, <5mmol/l, 13%; p<0.001). The sensitivity of severe hyperlactatemia (≥10mmol/l) for hospital mortality was 17%, the specificity was 99%. In patients with negative delta lactate in the first 24 h, hospital mortality was excessive (92%). In conclusion, mortality in patients with severe hyperlactatemia is very high, especially if it persists for more than 24 h. Severe hyperlactatemia, together with clinical parameters, could therefore provide a basis for setting treatment limits., (© 2022. The Author(s).)

Background: Tei index (TI) is a combined myocardial performance index for overall cardiac function, the sensitivity of which seems to be better than that of systolic and diastolic parameters alone. Evidence for TI in the context of Takotsubo syndrome (TTS) is currently limited, which is why we chose to investigate this parameter in affected patients., Subjects and Methods: Patients with TTS (n = 51), acute coronary syndrome (ACS; n = 29), and controls (n = 58) were retrospectively investigated. Laboratory and echocardiographic parameters including TI were analyzed for their ability to discriminate TTS in the total study cohort., Results: TI was the highest, and thus most pathological, in patients with TTS (median 0.516 vs. ACS: 0.355 vs. control: 0.313, p < 0.0001) and showed the best discriminatory ability for TTS (AUC: 0.836, p < 0.0001). A cut-off for diagnosis of TTS was calculated at ≥0.418 (specificity: 83.5% and sensitivity: 74.0%) by means of the Youden index., Conclusion: The discriminatory ability of TI was better than that of other echocardiographic parameters such as LV systolic function. Due to the simple, fast, and inexpensive way of calculating TI, diagnostic workup with conventional parameters could be complemented by TI in patients with suspected TTS., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Objectives: Helicobacter pylori (H. pylori) and colorectal neoplasia (CRN) are frequent entities. Epidemiological data suggest an association between H. pylori positivity (H. pylori +) and CRN, whereas pathophysiologic considerations substantiate a possible causal relationship. However, the relationship between CRN and H. pylori + may also be mediated by shared risk factors. Therefore, the aim of this cross-sectional study was to evaluate a possible independent relationship between H. pylori and CRN in a Central European cohort., Methods: We included 5,707 asymptomatic patients. All patients underwent screening colonoscopy and upper gastrointestinal endoscopy. We assessed the association between any CRN and advanced CRN with H. pylori + using multilevel logistic regression. We adjusted for age, sex, a positive family history of colorectal cancer, and cardiovascular risk., Results: 1,082 patients (19%) were H. pylori + and 4,625 (81%) H. pylori -. Patients with both CRN and H. pylori had more cardiometabolic risk factors. In univariate (aOR 1.20; 1.10-1.31) and multivariable analysis (aOR 1.20; 1.08-1.32), H. pylori + was associated with the diagnosis of any CRN. However, H. pylori + was associated with the presence of advanced CRN (aOR 1.26; 0.96-1.64) only in trend., Conclusions: We found a clustered co-occurrence of CRN and H. pylori. This association persisted after correction for shared cardiometabolic risk factors. We suggest that our analysis emphasizes the clinical value of H. pylori eradication. Whether "test and treat" H. pylori is warranted to prevent CRN remains unclear but is at least a possibility given the simplicity of "test and treat.", (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background: The association between Helicobacter pylori (Hp) infection and non-alcoholic fatty liver disease (NAFLD) is subject of a contentious debate. Data mainly stem from Asian cohorts whereas European data are scarce. We, therefore, investigated an Austrian colorectal cancer screening cohort for an association between Hp and NAFLD., Methods: In total, 5338 consecutive participants undergoing screening colonoscopy at a single center in Austria were evaluated in this cross-sectional study. The primary risk factor was being Hp negative or positive. The primary endpoint was the presence of NAFLD defined by ultrasound (NAFLD; primary endpoint). Uni- and multivariable logistic regression models were fitted to obtain odds ratios (OR) and 95% confidence intervals (95%CI). Finally, this association was analyzed in a subgroup of 1128 patients in whom NAFLD was diagnosed by transient elastography (TE, secondary endpoint)., Results: NAFLD prevalence defined by ultrasound did not differ between Hp positive (48%) and negative patients (45%, P=0.097). Accordingly, in uni- (OR 1.12 95% CI 0.98-1.29; P=0.098) and multivariable analysis adjusting for different risk factors (aOR 0.96 95%CI 0.82-1.13; P=0.601) no independent association was found. On subgroup analysis, NAFLD diagnosed by TE was more prevalent in the Hp positive compared to the Hp negative group (49% vs. 38%, P=0.004) and these patients also had higher steatosis grades. However, after adjustment for risk factors, no independent association between Hp positivity and NAFLD diagnosed by TE (aOR 1.26 95%CI 0.89-1.78; P=0.194) was confirmed., Conclusions: In this Central European cohort, Hp-positivity was not associated with the diagnosis of NAFLD. Although Hp positive patients seem to be more likely to have a concomitant NAFLD diagnosis, this association might rather relate to a cardiometabolic risk phenotype than causality.

Introduction: The role of erythrocytes in the acute coronary syndrome (ACS) is complex. The aim of this review in terms of PICO (P: patients; I: intervention; C: comparison; O: outcome) was to summarize systematic reviews in patients (P) with acute coronary syndrome, evaluating the effects of (I) 1) iron deficiency, 2) administration of an erythropoiesis-stimulating agent (ESA), 3) anemia on admission, 4) red blood cell transfusion, 5) a restrictive transfusion strategy in comparison (C) to 1) no iron deficiency, 2) no ESA 3) no anemia on admission, 4) no red blood cell transfusion, 5) a liberal transfusion strategy on mortality (O)., Methods: We used AMSTAR2 to assess the methodological quality of systematic reviews and grade the available research. The primary endpoint was all-cause mortality., Results: Using the data from 2,787,005 patients, the following conditions were associated with worse outcome in patients with ACS: anemia on admission (RR 2.08 95%CI 1.70-2.55) and transfusion (1.93 95%CI 1.12-3.34) of red blood cells. A liberal transfusion (RR 0.86 95%CI 0.70-1-05), administration of ESA (RR 0.55 95%CI 0.22-1.33) and iron deficiency (OR 1.24 95%CI 0.12-13.13) were not associated with altered all-cause mortality., Conclusion: Patients suffering from ACS and anemia on admission are at particular risk for adverse outcome. There is evidence of associations between adverse outcomes and receiving red blood cell transfusions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

(1) Double-stranded DNA (dsDNA) and deoxyribonuclease (DNase) as surrogate parameters for accumulating inflammatory hazards are insufficiently studied in resuscitation research. (2) Blood samples of 76 individuals after CA were analyzed 24 and 96 h after ICU admission. Plasma levels of dsDNA, interleukin-8, and monocyte chemoattractant protein-1 and activity of DNase were assessed along with baseline characteristics, intensive care measures, and outcome data. DsDNA/DNase ratio was used as main prognostication parameter. After calculating an optimal empirical cut-off for outcome prediction (death or Cerebral Performance Category ≥3 at 6 months), multivariable logistic regression was applied. (3) Using receiver operating characteristic (ROC) analysis, an area under the curve (AUC) of 0.65 (95% CI 0.50-0.79) was found for dsDNA/DNase after 24 h versus 0.83 (95% CI 0.73-0.92) after 96 h ( p = 0.03). The empirical cut-off for dsDNA/DNase ratio after 96 h was 149.97 (Youden). DsDNA/DNase ratio was associated with unfavorable outcome at six months (aOR 1.006, 95% CI 1.0017-1.0094, p = 0.005). In multivariable analysis, the association of dsDNA/DNase ratio independently predicted outcome as a continuous variable (aOR 1.004, 95% CI 1.0004-1.0079, p = 0.029) after adjusting for potential confounders. (4) DsDNA/DNase ratio at 96 h demonstrates good predictive performance for estimating outcome after CA.

In Europe, tax-based healthcare systems (THS) and social health insurance systems (SHI) coexist. We examined differences in 30-day mortality among critically ill patients aged ≥ 70 years treated in intensive care units in a THS or SHI. Retrospective cohort study. 2406 (THS n = 886; SHI n = 1520) critically ill ≥ 70 years patients in 129 ICUs. Generalized estimation equations with robust standard errors were chosen to create population average adjusted odds ratios (aOR). Data were adjusted for patient-specific variables, organ support and health economic data. The primary outcome was 30-day-mortality. Numerical differences between SHI and THS in SOFA scores (6 ± 3 vs. 5 ± 3; p = 0.002) were observed, but clinical frailty scores were similar (> 4; 17% vs. 14%; p = 0.09). Higher rates of renal replacement therapy (18% vs. 11%; p < 0.001) were found in SHI (aOR 0.61 95%CI 0.40-0.92; p = 0.02). No differences regarding intubation rates (68% vs. 70%; p = 0.33), vasopressor use (67% vs. 67%; p = 0.90) and 30-day-mortality rates (47% vs. 50%; p = 0.16) were found. Mortality remained similar between both systems after multivariable adjustment and sensitivity analyses. The retrospective character of this study. Baseline risk and mortality rates were similar between SHI and THS. The type of health care system does not appear to have played a role in the intensive care treatment of critically ill patients ≥ 70 years with COVID-19 in Europe., (© 2022. The Author(s).)

Background: Previous studies reported regional differences in end-of-life care (EoLC) for critically ill patients in Europe., Objectives: The purpose of this post-hoc analysis of the prospective multicentre COVIP study was to investigate variations in EoLC practices among older patients in intensive care units during the coronavirus disease 2019 pandemic., Methods: A total of 3105 critically ill patients aged 70 years and older were enrolled in this study (Central Europe: n = 1573; Northern Europe: n = 821; Southern Europe: n = 711). Generalised estimation equations were used to calculate adjusted odds ratios (aORs) to population averages. Data were adjusted for patient-specific variables (demographic, disease-specific) and health economic data (gross domestic product, health expenditure per capita). The primary outcome was any treatment limitation, and 90-day mortality was a secondary outcome., Results: The frequency of the primary endpoint (treatment limitation) was highest in Northern Europe (48%), intermediate in Central Europe (39%) and lowest in Southern Europe (24%). The likelihood for treatment limitations was lower in Southern than in Central Europe (aOR 0.39; 95% confidence interval [CI] 0.21-0.73; p = 0.004), even after multivariable adjustment, whereas no statistically significant differences were observed between Northern and Central Europe (aOR 0.57; 95%CI 0.27-1.22; p = 0.15). After multivariable adjustment, no statistically relevant mortality differences were found between Northern and Central Europe (aOR 1.29; 95%CI 0.80-2.09; p = 0.30) or between Southern and Central Europe (aOR 1.07; 95%CI 0.66-1.73; p = 0.78)., Conclusion: This study shows a north-to-south gradient in rates of treatment limitation in Europe, highlighting the heterogeneity of EoLC practices across countries. However, mortality rates were not affected by these results., (© 2022 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: Patients with severe aortic valve stenosis (AS) frequently present with pulmonary hypertension (PH). The gold standard for detection of pulmonary hypertension is right heart catheterization, which is not routinely performed as a preoperative standard in cardiology centers today, neither before surgical valve replacement nor before transcatheter aortic valve replacement (TAVR) procedure. Echocardiographic determination of systolic pulmonary artery pressure (sPAP) provides an opportunity to assess the presence or absence of PH. The aim of the present study was to investigate the extent to which plasma levels of common cardiovascular biomarkers behave in patients with severe AS and an sPAP < 40 mmHg in comparison to patients with an sPAP ≥ 40 mmHg., Methods: 179 patients with echocardiographic evidence of severe AS before TAVR procedure were divided into 2 groups based on sPAP. An sPAP of 40 mmHg was considered the cut-off value, with absence of PH defined by an sPAP < 40 mmHg (n = 82) and presence of PH defined by an sPAP ≥ 40 mmHg (n = 97). Directly before TAVR, a blood sample was drawn from each patient, and plasma concentrations of the cardiovascular biomarkers Soluble Suppression of Tumorigenicity-2 (sST2), Growth/Differentiation of Factor-15 (GDF-15), Heart-Type Fatty-Acid Binding Protein (H-FABP), Insulin Like Growth Factor Binding Protein 2 (IGF-BP2), Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR), Brain Natriuretic Peptide (BNP) and Cardiac Troponin I (cTnI) were determined., Results: Patients with an sPAP ≥ 40 mmHg had significantly higher sST2 ( p = 0.010), GDF-15 ( p = 0.005), IGF-BP2 ( p = 0.029), suPAR ( p = 0.018), BNP ( p < 0.001) and cTnI ( p = 0.039) plasma levels. Only for H-FABP ( p = 0.069), no significant differences were discernible between the two groups. In addition, cut-off values were calculated to predict an sPAP ≥ 40 mmHg. Significant results were shown with 16045.84 pg/mL for sST2 ( p = 0.010), with 1117.54 pg/mL for GDF-15 ( p = 0.005), with 107028.43 pg/mL for IGF-BP2 ( p = 0.029), with 3782.84 pg/mL for suPAR ( p = 0.018), with 2248.00 pg/mL for BNP ( p < 0.001) and with 20.50 pg/mL for cTnI ( p = 0.002)., Conclusions: sPAP as an echocardiographic parameter in combination with supplementary use of cardiovascular biomarkers presented here have the potential to provide more detailed information about the presence or absence of PH in a non-invasive way., Competing Interests: The authors declare no conflict of interest. Michael Lichtenauer is serving as one of the Guest editors of this journal. We declare that Michael Lichtenauer had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Dinesh Kalra., (Copyright: © 2022 The Author(s). Published by IMR Press.)

Aims: Patients with acute coronary syndrome (ACS) frequently suffer from anaemia, but its role in patients admitted to an intensive care unit (ICU) is unclear. This analysis evaluates the prognostic relevance of different degrees of anaemia and their specific impact on disease severity and the outcome in critically ill ACS patients., Methods and Results: and results The multi-centre electronic Intensive Care Unit Collaborative Research Database was used, and all patients admitted with ACS were included in a retrospective analysis. Anaemia and its degrees were defined according to the criteria by the World Health Organization. A multi-level logistic regression analysis was used to fit three sequential regression models for the binary primary outcome of hospital mortality. A total of 7418 patients were included; 3437 patients (46%) had anaemia on admission. Patients with anaemia were significantly older [61 (53-70) vs. 70 (61-78) years, P < 0.001], more often female ( P  < 0.001), and required an increased rate of vasopressor use ( P  < 0.001) and mechanical ventilation ( P  < 0.001). With the higher Sequential organ failure assessment score (1 vs. 2; P  < 0.001) and Acute Physiology And Chronic Health Evaluation (35 vs. 47; P  < 0.001) scores, a higher degree of anaemia was associated with prolonged ICU stay (2 vs. 5 days, P  < 0.001). Even patients with mild anaemia needed significantly from more intensive treatment and suffered worse outcome. Intensive care unit and hospital mortality were inversely associated with haemoglobin levels., Conclusion: Nearly half of critically ill patients with ACS suffer from anaemia, which is associated with increased illness severity, complex ICU procedures, and mortality-even in mild anaemia. Haemoglobin on admission is an independent factor for adverse outcome., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: The European Society of Cardiology endorsed SCORE2 to assess cardiovascular risk. The aim of this observational, retrospective study was to assess whether SCORE2 is associated with colorectal neoplasia in an asymptomatic screening population. Further, we evaluated if SCORE2 predicts tumor-related mortality. Methods: We included 3408 asymptomatic patients who underwent a screening colonoscopy. We calculated SCORE2 for each participant and stratified patients according to their predicted 10-year risk of cardiovascular disease: SCORE2 0−4.9%, SCORE2 5−9.9%, and SCORE2 ≥ 10%. We assessed the association between SCORE2 as a continuous variable, the presence of colorectal neoplasia using multilevel logistic regression, and SCORE2 and mortality using Cox regression. Results: In total, 1537 patients had a SCORE2 of 0−4.9%, 1235 a SCORE2 of 5−9.9%, and 636 a SCORE2 ≥ 10%. The respective rates of colorectal neoplasia were 20%, 37%, and 44%. SCORE2 was associated with the presence of any (OR 1.11 95%CI 1.09−1.12; p < 0.001) and advanced colorectal neoplasia (OR 1.06 95%CI 1.08−1.13; p < 0.001) in univariate analysis. After multivariable adjustment (age, sex, family history, and metabolic syndrome) a higher SCORE2 remained associated with higher odds for any (aOR 1.04 95%CI 1.02−1.06; p = 0.001) and advanced (aOR 1.06 95%CI 1.03−1.10; p < 0.001) colorectal neoplasia. SCORE2 was associated with both all-cause (HR 1.11 95%CI 1.09−1.14; p < 0.001) and tumor-related mortality (HR 1.10 95%CI 1.05−1.14; p < 0.001). Conclusions: We found that SCORE2 is associated with the presence of colorectal neoplasia. Clinicians could kill two birds with one stone calculating SCORE2. In patients with a high SCORE2, screening colonoscopy aside from cardiovascular risk mitigation could improve outcomes.

Background: Endovascular embolization techniques are nowadays well established in the management of acute arterial bleedings. However, the education and training of the next generation of interventionalists are still based on the traditional apprenticeship model, where the trainee learns and practices directly at the patient, which potentially affects the patient's safety. The objective of this study was to design and develop a standardized endovascular simulation concept for the training of acute bleeding embolizations, based on real-life cases., Results: An adaptable and cost-effective endovascular simulator was developed using an in-house 3D print laboratory. All thoracic and abdominal acute bleeding embolizations over more than a year with appropriate pre-interventional computed tomography scans were included to manufacture 3D printed vascular models. A peristaltic pump was used to generate pulsatile flow curves. Forty embolization cases were engaged in this study, and 27 cases were fully reproduced in the simulation setting (69.23%). The simulation success was significantly lower in pulmonary embolizations (p = 0.031) and significantly higher in soft tissue (p = 0.032) and coil embolizations (p = 0.045). The overall simulation success was 7.8 out of 10 available points., Conclusions: Using stereolithography 3D printing in a standardized simulation concept, endovascular embolization techniques for treating acute internal hemorrhages in the chest and abdomen can be simulated and trained based on the patient-specific anatomy in a majority of the cases and at a broad spectrum of different causes., (© 2022. The Author(s).)

Introduction: Intoxications are common in intensive care units (ICUs). The number of causative substances is large, mortality usually low. This retrospective cohort study aims to characterize differences of intoxicated compared to general ICU patients, point out variations according to causative agents, as well as to highlight differences between survivors and non-survivors among intoxicated individuals in a large-scale multi-center analysis., Methods: A total of 105,998 general ICU patients and 4,267 individuals with the admission diagnoses "overdose" and "drug toxicity" from the years 2014 and 2015 where included from the eICU Collaborative Research Database. In addition to comparing these groups with respect to baseline characteristics, intensive care measures and outcome parameters, differences between survivors and non-survivors from the intoxication group, as well as the individual groups of causative substances were investigated., Results: Intoxicated patients were younger (median 41 vs. 66 years; p<0.001), more often female (55 vs. 45%; p<0.001), and normal weighted (36% vs. 30%; p<0.001), whereas more obese individuals where observed in the other group (37 vs. 31%; p<0.001). Intoxicated individuals had a significantly lower mortality compared to general ICU patients (1% vs. 10%; aOR 0.07 95%CI 0.05-0.11; p<0.001), a finding which persisted after multivariable adjustment (aOR 0.17 95%CI 0.12-0.24; p<0.001) and persisted in all subgroups. Markers of disease severity (SOFA-score: 3 (1-5) vs. 4 (2-6) pts.; p<0.001) and frequency of vasopressor use (5 vs. 15%; p<0.001) where lower, whereas rates of mechanical ventilation where higher (24 vs. 26%; p<0.001) in intoxicated individuals. There were no differences with regard to renal replacement therapy in the first three days (3 vs. 4%; p=0.26). In sensitivity analysis (interactions for age, sex, ethnicity, hospital category, maximum initial lactate, mechanical ventilation, and vasopressor use), a trend towards lower mortality in intoxicated patients persisted in all subgroups., Conclusion: This large-scale retrospective analysis indicates a significantly lower mortality of intoxicated individuals compared to general ICU patients., (© 2022. The Author(s).)

Background: Higher survival has been shown for overweight septic patients compared with normal or underweight patients in the past. This study aimed at investigating the management and outcome of septic ICU patients in different body mass index (BMI) categories in a large multicenter database., Methods: In total, 16,612 patients of the eICU collaborative research database were included. Baseline characteristics and data on organ support were documented. Multilevel logistic regression analysis was performed to fit three sequential regression models for the binary primary outcome (ICU mortality) to evaluate the impact of the BMI categories: underweight (<18.5 kg/m 2 ), normal weight (18.5 to < 25 kg/m 2 ), overweight (25 to < 30 kg/m 2 ) and obesity (≥ 30 kg/m 2 ). Data were adjusted for patient level characteristics (model 2) as well as management strategies (model 3)., Results: Management strategies were similar across BMI categories. Underweight patients evidenced higher rates of ICU mortality. This finding persisted after adjusting in model 2 (aOR 1.54, 95% CI 1.15-2.06; p = 0.004) and model 3 (aOR 1.57, 95%CI 1.16-2.12; p = 0.003). No differences were found regarding ICU mortality between normal and overweight patients (aOR 0.93, 95%CI 0.81-1.06; p = 0.29). Obese patients evidenced a lower risk of ICU mortality compared to normal weight, a finding which persisted across all models (model 2: aOR 0.83, 95%CI 0.69-0.99; p = 0.04; model 3: aOR 0.82, 95%CI 0.68-0.98; p = 0.03). The protective effect of obesity and the negative effect of underweight were significant in individuals > 65 years only., Conclusion: In this cohort, underweight was associated with a worse outcome, whereas obese patients evidenced lower mortality. Our analysis thus supports the thesis of the obesity paradox., (© 2021. The Author(s).)

Background: Mortality in sepsis remains high. Studies on small cohorts have shown that red cell distribution width (RDW) is associated with mortality. The aim of this study was to validate these findings in a large multicenter cohort., Methods: We conducted this retrospective analysis of the multicenter eICU Collaborative Research Database in 16,423 septic patients. We split the cohort in patients with low (≤15%; n = 7,129) and high (>15%; n = 9,294) RDW. Univariable and multivariable multilevel logistic regressions were used to fit regression models for the binary primary outcome of hospital mortality and the secondary outcome intensive care unit (ICU) mortality with hospital unit as random effect. Optimal cutoffs were calculated using the Youden index., Results: Patients with high RDW were more often older than 65 years (57% vs. 50%; p < 0.001) and had higher Acute Physiology and Chronic Health Evaluation (APACHE) IV scores (69 vs. 60 pts.; p < 0.001). Both hospital (adjusted odds ratios [aOR] 1.18; 95% CI: 1.16-1.20; p < 0.001) and ICU mortality (aOR 1.16; 95% CI: 1.14-1.18; p < 0.001) were associated with RDW as a continuous variable. Patients with high RDW had a higher hospital mortality (20 vs. 9%; aOR 2.63; 95% CI: 2.38-2.90; p < 0.001). This finding persisted after multivariable adjustment (aOR 2.14; 95% CI: 1.93-2.37; p < 0.001) in a multilevel logistic regression analysis. The optimal RDW cutoff for the prediction of hospital mortality was 16%., Conclusion: We found an association of RDW with mortality in septic patients and propose an optimal cutoff value for risk stratification. In a combined model with lactate, RDW shows equivalent diagnostic performance to Sequential Organ Failure Assessment (SOFA) score and APACHE IV score., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Prognostication after cardiopulmonary resuscitation (CPR) is complex. Novel biomarkers like soluble suppression of tumorigenicity 2 (sST2) may provide an objective approach. A total of 106 post-CPR patients were included in this single-center observational prospective study. Serum sST2 levels were obtained 24 h after admission. Individuals were assigned to two groups: patients below and above the overall cohort's median sST2 concentration. Primary outcome was a combined endpoint at 6 months (death or Cerebral Performance Category > 2); secondary endpoint 30-day mortality. A uni- and multivariate logistic regression analysis were conducted. Elevated sST2-levels were associated with an increased risk for the primary outcome (OR 1.011, 95% CI 1.004-1.019, p = 0.004), yet no patients with poor neurological outcome were observed at 6 months. The optimal empirical cut-off for sST2 was 46.15 ng/ml (sensitivity 81%, specificity 53%, AUC 0.69). Levels above the median (> 53.42 ng/ml) were associated with higher odds for both endpoints (death or CPC > 2 after 6 months: 21% vs. 49%, OR 3.59, 95% CI 1.53-8.45, p = 0.003; death after 30 days: 17% vs. 43.3%, OR 3.75, 95% CI 1.52-9.21, p = 0.003). A positive correlation of serum sST2 after CPR with mortality at 30 days and 6 months after cardiac arrest could be demonstrated., (© 2021. The Author(s).)

Background: Intensivists keep getting challenged with prognostication after cardiopulmonary resuscitation (CPR). The model for end-stage liver disease, excluding INR (MELD-XI) Score has proven valuable for assessing illness severity. Serum lactate is a readily available and established indicator of general stress and tissue hypoxia. We aimed to evaluate the prognostic value of MELD-XI combined with serum lactate in patients after CPR., Methods: A retrospective analysis on 106 patients after CPR was performed. Multivariable Cox regression was performed to evaluate associations with 30-day mortality and neurological outcome by means of cerebral performance category (CPC). An optimal cut-off was calculated by means of the Youden Index. Patients were then divided into subgroups based on the optimal cut-offs for MELD-XI and serum lactate., Results: MELD-XI and lactate were independently associated with mortality. The respective cut-offs were MELD-XI>12 and lactate ≥2.5 mmol/L. Patients were split into three groups: lactate <2.5 mmol/L and MELD-XI≤12 (low-risk; N.=32), lactate ≥2.5 mmol/L or MELD-XI>12 (medium-risk; N.=39), and lactate ≥2.5 mmol/L and MELD-XI >12 (high-risk; N.=33). The mortality rates were 6%, 26% and 61% in the low, medium and high-risk group. This combined model yielded in the highest predictive abilities (AUC=0.78 95%CI: 0.68-0.85; P=0.03 vs. AUC=0.66 for SOFA Score). Worse neurological outcome (CPC 3 or 4) was more common in the medium and high-risk group (6.25%, 10.3% and 9.1%)., Conclusions: The combination of MELD-XI and lactate concentration at ICU admission was superior to the more complex SOFA Score for prediction of mortality after CPR.

Purpose: Old (>64 years) and very old (>79 years) intensive care patients with sepsis have a high mortality. In the very old, the value of critical care has been questioned. We aimed to compare the mortality, rates of organ support, and the length of stay in old vs. very old patients with sepsis and septic shock in intensive care. Methods: This analysis included 9,385 patients, from the multi-center eICU Collaborative Research Database, with sepsis; 6184 were old (aged 65-79 years), and 3,201 were very old patients (aged 80 years and older). A multi-level logistic regression analysis was used to fit three sequential regression models for the binary primary outcome of ICU mortality. A sensitivity analysis in septic shock patients ( n = 1054) was also conducted. Results: In the very old patients, the median length of stay was shorter (50 ± 67 vs. 56 ± 72 h; p < 0.001), and the rate of a prolonged ICU stay was lower (>168 h; 9 vs. 12%; p < 0.001) than the old patients. The mortality from sepsis was higher in very old patients (13 vs. 11%; p = 0.005), and after multi-variable adjustment being very old was associated with higher odds for ICU mortality (aOR 1.32, 95% CI 1.09-1.59; p = 0.004). In patients with septic shock, mortality was also higher in the very old patients (38 vs. 36%; aOR 1.50, 95% CI 1.10-2.06; p = 0.01). Conclusion: Very old ICU-patients suffer from a slightly higher ICU mortality compared with old ICU-patients. However, despite the statistically significant differences in mortality, the clinical relevance of such minor differences seems to be negligible., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bruno, Wernly, Mamandipoor, Rezar, Binnebössel, Baldia, Wolff, Kelm, Guidet, De Lange, Dankl, Koköfer, Danninger, Szczeklik, Sigal, van Heerden, Beil, Fjølner, Leaver, Flaatten, Osmani and Jung.)

Background: Mechanical Ventilation (MV) is a complex and central treatment process in the care of critically ill patients. It influences acid-base balance and can also cause prognostically relevant biotrauma by generating forces and liberating reactive oxygen species, negatively affecting outcomes. In this work we evaluate the use of a Recurrent Neural Network (RNN) modelling to predict outcomes of mechanically ventilated patients, using standard mechanical ventilation parameters., Methods: We performed our analysis on VENTILA dataset, an observational, prospective, international, multi-centre study, performed to investigate the effect of baseline characteristics and management changes over time on the all-cause mortality rate in mechanically ventilated patients in ICU. Our cohort includes 12,596 adult patients older than 18, associated with 12,755 distinct admissions in ICUs across 37 countries and receiving invasive and non-invasive mechanical ventilation. We carry out four different analysis. Initially we select typical mechanical ventilation parameters and evaluate the machine learning model on both, the overall cohort and a subgroup of patients admitted with respiratory disorders. Furthermore, we carry out sensitivity analysis to evaluate whether inclusion of variables related to the function of other organs, improve the predictive performance of the model for both the overall cohort as well as the subgroup of patients with respiratory disorders., Results: Predictive performance of RNN-based model was higher with Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) of 0.72 (± 0.01) and Average Precision (AP) of 0.57 (± 0.01) in comparison to RF and LR for the overall patient dataset. Higher predictive performance was recorded in the subgroup of patients admitted with respiratory disorders with AUC of 0.75 (± 0.02) and AP of 0.65 (± 0.03). Inclusion of function of other organs further improved the performance to AUC of 0.79 (± 0.01) and AP 0.68 (± 0.02) for the overall patient dataset and AUC of 0.79 (± 0.01) and AP 0.72 (± 0.02) for the subgroup with respiratory disorders., Conclusion: The RNN-based model demonstrated better performance than RF and LR in patients in mechanical ventilation and its subgroup admitted with respiratory disorders. Clinical studies are needed to evaluate whether it impacts decision-making and patient outcomes., Trial Registration: NCT02731898 ( https://clinicaltrials.gov/ct2/show/NCT02731898 ), prospectively registered on April 8, 2016.

Etiological, microbiological and epidemiological factors changed over time, but mortality rates remain high in infective endocarditis (IE). Healthcare-associated IE is nowadays responsible for a significant proportion of cases due to increasing numbers of cardiac devices. Cardiac implantable electronic devices, transcatheter aortic valve replacement, and percutaneous valve repair are meanwhile used, especially in old and sick patients. In suspected IE modified Duke criteria, integrating clinical results, imaging, and biomarkers are traditionally applied. Newer imaging technologies such as multi-slice computed tomography, photon-emission computed tomography, and magnetic resonance imaging might add value to conventional echocardiography in diagnosis and management of IE. Treatment consists of long-term antibiotic therapy, infectiological source control and/or cardiac surgery. Recently, antibiotic parenteral outpatient regimens and partial oral treatment strategies were shown to shorten hospital stays in patients suffering from IE. However, it remains unclear how to best select patients for partial oral therapy. This review describes new trends in diagnosing, imaging, and treating IE in a changing patient collective with particular focus on patients with implantable cardiac devices., (Copyright © 2020 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Background: Performing cardiopulmonary resuscitation (CPR) and postresuscitation care in the intensive care unit (ICU) are standardized procedures; however, there is evidence suggesting sex-dependent differences in clinical management and outcome variables after cardiac arrest (CA)., Methods: A prospective analysis of patients who were hospitalized at a medical ICU after CPR between December 2018 and March 2020 was conducted. Exclusion criteria were age < 18 years, hospital length of stay < 24 h and traumatic CA. The primary study endpoint was mortality after 6 months and the secondary endpoint neurological outcome assessed by cerebral performance category (CPC). Differences between groups were calculated by using U‑tests and χ 2 -tests, for survival analysis both univariate and multivariable Cox regression were fitted., Results: A total of 106 patients were included and the majority were male (71.7%). No statistically significant difference regarding 6‑month mortality between sexes could be shown (hazard risk, HR 0.68, 95% confidence interval, CI 0.35-1.34; p = 0.27). Neurological outcome was also similar between both groups (CPC 1 88% in both sexes after 6 months; p = 1.000). There were no statistically significant differences regarding general characteristics, pre-existing diseases, as well as the majority of clinical and laboratory parameters or measures performed on the ICU., Conclusion: In a single center CPR database no statistically significant sex-specific differences regarding post-resuscitation care, survival and neurological outcome after 6 months were observed.

Background: The growing proportion of elderly intensive care patients constitutes a public health challenge. The benefit of critical care in these patients remains unclear. We compared outcomes in elderly versus very elderly subjects receiving mechanical ventilation., Methods: In total, 5,557 mechanically ventilated subjects were included in our post hoc retrospective analysis, a subgroup of the VENTILA study. We divided the cohort into 2 subgroups on the basis of age: very elderly subjects (age ≥ 80 y; n = 1,430), and elderly subjects (age 65-79 y; n = 4,127). A propensity score on being very elderly was calculated. Evaluation of associations with 28-d mortality was done with logistic regression analysis., Results: Very elderly subjects were clinically sicker as expressed by higher SAPS II scores (53 ± 18 vs 50 ± 18, P < .001), and their rates of plateau pressure < 30 cm H 2 O were higher, whereas other parameters did not differ. The 28-d mortality was higher in very elderly subjects (42% vs 34%, P < .001) and remained unchanged after propensity score adjustment (adjusted odds ratio 1.31 [95% CI 1.16-1.49], P < .001)., Conclusions: Age was an independent and unchangeable risk factor for death in mechanically ventilated subjects. However, survival rates of very elderly subjects were > 50%. Denial of critical care based solely on age is not justified. (ClinicalTrials.gov registration NCT02731898.)., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2021 by Daedalus Enterprises.)

Introduction: Serum levels of FGF23 have been associated with adverse outcomes in cardiovascular diseases in patients with and without impaired renal function. Hence, this study aimed to explore the prognostic relevance of intact FGF23 (iFGF23) and its derivate C-terminal FGF23 (cFGF23) in patients undergoing transcatheter aortic valve replacement (TAVR) with regard to renal function., Methods: A total of 274 patients undergoing transfemoral TAVR were enrolled in this study. Blood samples were obtained preinterventionally and analyzed for iFGF23 and cFGF23 by means of enzyme linked immunosorbent assay (ELISA). Follow-up was obtained for 12 months., Results: Serum levels of cFGF23 and iFGF23 both correlated positively with serum creatinine and inversely with estimated glomerular filtration rate (eGFR). Cox regression analysis revealed a significant association of cFGF23 with 1-year-mortality in patients with eGFR ≥45ml/min/1.73m², but not in patients with an eGFR <45ml/min/1.73m². A cut-off was calculated for cFGF23 (6.82 pmol/l) and patients with eGFR ≥45ml/min/1.73m² were retrospectively divided into two groups (above/below cut-off). Patients above the cut-off had a significantly worse 1-year-mortality than patients below the cut-off (33.3% vs. 19.6%; OR 2.05 (95%CI 1.03-4.07), p= 0.038). The association of cFGF23 with 1-year-mortality in patients with eGFR ≥45ml/min/1.73m² remained statistically significant even after correction for possible confounders in a multivariate Cox regression analysis., Conclusion: cFGF23 could be an individual risk factor for mortality in patients undergoing TAVR with an eGFR ≥45ml/min/1.73m²., (Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Assuming that atrial fibrillation (AF) is associated with left atrial remodeling and dysfunction, we hypothesize that left atrial and left atrial appendage ejection fractions (LAEF and LAAEF) are useful and may be more sensitive outcome predictors of pulmonary vein isolation (PVI). Fifty patients who underwent PVI at our institution with available pre-interventional cardiac computed tomography (CT) for procedure planning were included in this retrospective study. The patients were separated into two groups by recurrence and non-recurrence of AF and subgroups of paroxysmal and persistent AF. Semiautomatic volumetric analysis of the left atrium was used to calculate morphological and functional parameters and optimal cut-offs were calculated using the Youden index. LAEF (accuracy 94%, sensitivity 67%) and LAAEF (accuracy 90%, sensitivity 67%) were significantly reduced in patients with AF recurrence (16% vs. 36%, p = 0.00002; 16% vs. 42%, p = 0.000002), and in the subgroup analysis, the functional parameters were independent from AF type (paroxysmal and persistent). With a cut-off of <23% for both LAEF and LAAEF (area under the curve (AUC) 0.94, 95%CI 0.84-0.99 and AUC 0.96, 95%CI 0.86-0.99, respectively), AF recurrence occurred in 77.8%, within a mean follow-up period of 229 days. In conclusion, left atrial function on prior cardiac CT offers useful parameters for predicting AF recurrence after PVI.

Background: Antimicrobial therapy is a cornerstone in the treatment of infective endocarditis (IE). Typically, intravenous (i.v.) therapy is given for 6 weeks or longer, leading to prolonged hospital stays and high costs. Several trials evaluating the efficacy of partial oral therapy (POT) have been published. This article aimed to review and meta-analyze studies comparing i.v. therapy versus POT in non-critically ill patients suffering from IE., Methods: A structured database search (based on PRISMA guidelines) regarding POT versus i.v. therapy in IE was conducted using PubMed/Medline. Primary endpoint was all-cause mortality and a secondary endpoint IE relapse. Risk rates were calculated using a random effects model (DerSimonian and Laird). Heterogeneity was assessed using the I 2 statistics., Results: After screening 1848 studies at title and abstract levels, 4 studies were included. A total of 765 patients suffered from primary left-sided IE, whereas right-sided IE was observed in 72 patients. Mortality rates were lower in POT versus i.v. therapy (risk ratio [RR] 0.38, 95% confidence interval, confidence interval [CI] 0.20-0.74; p = 0.004; I 2 0%). IE relapse rates were similar (RR 0.63, 95% CI 0.29-1.37; p = 0.24; I 2 0%)., Conclusion: Data comparing POT with standard care in IE is limited and to date only one sufficiently powered stand-alone trial exists to support its use. In this meta-analysis POT was non-inferior to i.v. therapy with respect to mortality and IE relapse in non-critically ill patients suffering from both left-sided and right-sided IE. These findings indicate that POT is a feasible treatment strategy in selected patients suffering from IE but further validation in future studies will be required.

Rationale and Objectives: Acidosis and hyperlactatemia predict outcome in critically ill patients. We assessed BE and pH for risk prediction capabilities in a sub-group of septic patients in the MIMIC-III database., Methods: Associations with mortality were assessed by logistic regression analysis in 5586 septic patients. Baseline parameters, lactate concentrations, pH, and BE were analyzed at baseline and after 6 hours., Measurements and Main Results: We combined acidosis (defined as either BE ≤-6 and/or pH ≤7.3) and hyperlactatemia and split the cohort into three subgroups: low-risk (no acidosis and lactate <2.3 mmol/L; n = 2294), medium-risk (either acidosis or lactate >2.3 mmol/L; n = 2125) and high-risk (both acidosis and lactate >2.3 mmol/L; n = 1167). Mortality was 14%, 20% and 38% (p<0.001) in low-risk, medium-risk and high-risk patients, respectively. The predictiveness of this model (AUC 0.63 95%CI 0.61-0.65) was higher compared to acidosis (AUC 0.59 95%CI 0.57-0.61; p<0.001) and lactate >2.3 mmol/L (AUC 0.60 95%CI 0.58-0.62; p<0.001) alone. Hyperlactatemia alone was only moderately predictive for acidosis (AUC 0.60 95%CI 0.59-0.62)., Conclusions: Acidosis and hyperlactatemia can occur independently to a certain degree. Combining acidosis and hyperlactatemia in a model yielded higher predictiveness for ICU-mortality. Septic patients with acidosis should be treated even more aggressively in the future., Competing Interests: Declaration of Competing Interest The authors whose names are listed immediately above certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: Heart failure with preserved ejection fraction (HFpEF) remains an ongoing therapeutic and diagnostic challenge to date. In this study we aimed for an analysis of the diagnostic potential of four novel cardiovascular biomarkers, GDF-15, H-FABP, sST2, and suPAR in HFpEF patients compared to controls as well as ICM, and DCM., Methods: In total, we included 252 stable outpatients and controls (77 DCM, 62 ICM, 18 HFpEF, and 95 controls) in the present study. All patients were in a non-decompensated state and on a stable treatment regimen. Serum samples were obtained and analyzed for GDF-15 (inflammation, remodeling), H-FABP (ischemia and subclinical ischemia), sST2 (inflammation, remodeling) and suPAR (inflammation, remodeling) by means of ELISA., Results: A significant elevation of GDF-15 was found for all heart failure entities compared to controls ( p < 0.005). Similarly, H-FABP evidenced a significant elevation in all heart failure entities compared to the control group ( p < 0.0001). Levels of sST2 were significantly elevated in ICM and DCM patients compared to the control group and HFpEF patients ( p < 0.0001). Regarding suPAR, a significant elevation in ICM and DCM patients compared to the control group ( p < 0.0001) and HFpEF patients ( p < 0.01) was observed. An AUC analysis identified H-FABP (0.792, 95% CI 0.713-0.870) and GDF-15 (0.787, 95% CI 0.696-0.878) as paramount diagnostic biomarkers for HFpEF patients., Conclusion: Based on their differences in secretion patterns, novel cardiovascular biomarkers might represent a promising diagnostic tool for HFpEF in the future.

Background: Chronic kidney disease (CKD) and cardiovascular diseases (CVD) often occur concomitantly, and CKD is a major risk factor for cardiovascular mortality. Since some of the most commonly used biomarkers in CVD are permanently elevated in patients with CKD, novel biomarkers are warranted for clinical practice. Methods: Plasma concentrations of five cardiovascular biomarkers (soluble suppression of tumorigenicity (sST2), growth differentiation factor 15 (GDF-15), heart-type fatty acid-binding protein (H-FABP), insulin-like growth factor-binding protein 2 (IGF-BP2), and soluble urokinase plasminogen activator receptor) were analyzed by means of enzyme-linked immunosorbent assay (ELISA) in 219 patients with CKD enrolled in the German Chronic Kidney Disease (GCKD) study. Results: Except for sST2, all of the investigated biomarkers were significantly elevated in patients with CKD (2.0- to 4.4-fold increase in advanced CKD (estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m² body surface area (BSA)) and showed a significant inverse correlation with eGFR. Moreover, all but H-FABP and sST2 were additionally elevated in patients with micro- and macro-albuminuria. Conclusions: Based on our findings, sST2 appears to be the biomarker whose diagnostic performance is least affected by decreased renal function, thus suggesting potential viability in the management of patients with CVD and concomitant CKD. The predictive potential of sST2 remains to be proven in endpoint studies.

Background: Heart failure (HF) remains one of the leading causes of death to date despite extensive research funding. Various studies are conducted every year in an attempt to improve diagnostic accuracy and therapy monitoring. The small cytoplasmic heart-type fatty acid-binding protein (H-FABP) has been studied in a variety of disease entities. Here, we provide a review of the available literature on H-FABP and its possible applications in HF. Methods: Literature research using PubMed Central was conducted. To select possible studies for inclusion, the authors screened all available studies by title and, if suitable, by abstract. Relevant manuscripts were read in full text., Results: In total, 23 studies regarding H-FABP in HF were included in this review., Conclusion: While, algorithms already exist in the area of risk stratification for acute pulmonary embolism, there is still no consensus for the routine use of H-FABP in daily clinical practice in HF. At present, the strongest evidence exists for risk evaluation of adverse cardiac events. Other future applications of H-FABP may include early detection of ischemia, worsening of renal failure, and long-term treatment planning., Competing Interests: The authors declare no conflict of interest.

The optimal duration dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) is subject to debate. A short-duration DAPT (one month to three months) followed by P2Y 12 monotherapy instead of standard 6 to 12 months DAPT followed by aspirin monotherapy after PCI has been suggested. We meta-analyzed studies comparing short-term (≤ 3 months) DAPT followed by P2Y 12 monotherapy versus standard DAPT in patients after PCI. In total, 2304 studies were screened at title and abstract level. The primary endpoint was major bleeding. Secondary endpoints included myocardial infarction, stent thrombosis, stroke, and all-cause mortality. Study level data were analyzed. Heterogeneity was assessed using the I 2 statistic. Risk rates (RR) were calculated using a random-effects model (DerSimonian and Laird) for clinical outcomes for each individual study and consecutive pooling. In total, 21970 patients from three studies were analyzed. Between P2Y 12 inhibitor monotherapy versus DAPT, there were similar rates of major bleeding (RR 0.67 95%CI 0.34-1.32; p = 0.25; I 2 75%), mortality (RR 0.92 95%CI 0.78-1.09; p = 0.33; I 2 0%) and stroke (RR 0.97 95%CI 0.52 - 0.18; p = 0.92; I 2 57%). Endpoints assessing thrombotic events showed no statistically significant difference including myocardial infarction (RR 0.99 95%CI 0.85-1.15; p = 0.86; I 2 0%) and stent thrombosis (RR 1.03 95%CI 0.74-1.44; p = 0.87; I 2 0%). The experimental treatment with P2Y 12 monotherapy after very short-term DAPT was not superior to standard DAPT. Our meta-analysis adds insight that DAPT might be safely shortened in selected patient strategies. However, DAPT remains the gold standard for antithrombotic treatment after PCI.

Background: MicroRNAs (miRNAs) are small, single-stranded RNA sequences that regulate gene expression on a post-transcriptional level. In the last few decades, various trials have investigated the diagnostic and therapeutic potential of miRNAs in several disease entities. Here, we provide a review of the available evidence on miRNAs in inflammatory heart diseases (myocarditis, endocarditis, and pericarditis) and sepsis-induced cardiac dysfunction., Methods: Systematic database research using the PubMed and Medline databases was conducted between July and September 2019 using predefined search terms. The whole review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines., Results: In total, 131 studies were screened, 96 abstracts were read, and 69 studies were included in the review., Discussion: In the future, circulating miRNAs could serve as biomarkers for diagnosis and disease monitoring in the context of inflammatory heart diseases and sepsis-induced cardiac dysfunction. Considering the promising results of different animal models, certain miRNAs could also emerge as novel therapeutic approaches in this setting.

Although reperfusion therapy has improved outcomes, acute myocardial infarction (AMI) is still associated with both significant mortality and morbidity. Once irreversible myocardial cell death due to ischemia and reperfusion sets in, scarring leads to reduction in left ventricular function and subsequent heart failure. Regenerative cardiovascular medicine experienced a boost in the early 2000s when regenerative effects of bone marrow stem cells in a murine model of AMI were described. Translation from an animal model to stem cell application in a clinical setting was rapid and the first large trials in humans suffering from AMI were conducted. However, high initial hopes were early shattered by inconsistent results of randomized clinical trials in patients suffering from AMI treated with stem cells. Hence, we provide an overview of both basic science and clinical trials carried out in regenerative cardiovascular therapies. Possible pitfalls in specific cell processing techniques and trial design are discussed as these factors influence both basic science and clinical outcomes. We address possible solutions. Alternative mechanisms and explanations for effects seen in both basic science and some clinical trials are discussed here, with special emphasis on paracrine mechanisms via growth factors, exosomes, and microRNAs. Based on these findings, we propose an outlook in which stem cell therapy, or therapeutic effects associated with stem cell therapy, such as paracrine mechanisms, might play an important role in the future. Optimizing stem cell processing and a better understanding of paracrine signaling as well as its effect on cardioprotection and remodeling after AMI might improve not only AMI research, but also our patients' outcomes.

Background: Excessive bleeding impairs outcome after coronary artery bypass grafting (CABG). Clopidogrel in combination with aspirin, given before percutaneous coronary intervention, have become the standard for stent thrombosis prevention. Some premedicated patients, however, are found to need surgical treatment, thus platelet inhibition caused by clopidogrel becomes a concern for post operation major bleeding., Aims: This study was designed to evaluate the impact of preoperative clopidogrel on bleeding and outcomes after coronary artery bypass graft surgery (CABG)., Methods: The study represent a observational retrospective analysis of collected data. The follow up of 223 treated with clopidogrel and aspirin and 77 patients not receiving treatment with platelet antagonist 7 days before CABG are analyzed., Results: The groups were comparable in age, gender, body surface area, preoperative hematocrit, preoperative prothrombin time and prior myocardial infarction. The clopidogrel group had higher12h and 24h mean chest tube output (at 12h mean 519.7ml vs 353.1 ml, p < 0.05, at 24h mean 756.6 ml vs 563.5 ml, p<0.05). Moreover, reoperation for bleeding was 4.5-fold higher in the clopidogrel group (5.9% vs. 1.3%, p <0.01), and more transfusions of red blood cells (3.23U vs 2.6 U, p<0.05), platelets (1.53U vs 1.23U, p<0.01) and fresh frozen plasma (0.84U vs 0.36 U, p<0.01). The clopidogrel group also showed a longer mechanical ventilation time (16.9h vs 12.9 h p = 0.03) and trend towards more prolonged stay in ICU (2.08 days vs 1.7 days p= 0.048)., Conclusions: Clopidogrel in combination with aspirin before CABG is associated with higher postoperative bleeding, exposure to blood products and morbidity. These findings raise concern regarding the routine administration of clopidogrel before anticipated but undecided coronary stent implantation.

Objective: Gaucher's disease is a rare genetic disorder that results in the accumulation of cerebrosides in the liver, spleen, kidneys, lungs, brain and bone marrow. The deficiency of the specific lysosomal enzyme glucocerebrosidase is considered as causative factor. The first effective treatment for the disease, the drug Ceredase, approved in 1995, was replaced in 2001 by the drug Cerezyme®., Methods: During the period 2004-2009 in our service 11 children were hospitalized and treated for Gaucher's disease: 9 children with type 1, and 2 children with type 3 of the disease. The enzymatic examinations of the biomarker chitotriosidase were performed in Sahlgren's University Hospital, Mölndal Sweden; the DNA analysis was performed in the Children's Hospital & Regional Medical Center, Seattle, USA., Findings: We are presenting the biological and genetic molecular data of the children. In our case series, one year after the treatment started, the hemoglobin level was normalized; the platelet count was normalized in 7 patients after one year of treatment, and in 9 patients after two years of treatment. The hemorrhagic syndrome stopped after 6 months of treatment. Chitotriosidase values decreased 10-20 times the initial value, after one year of treatment and in one case the value reached the normal range. The treatment with Cerezyme® has also improved the visceral and biological signs. Anomalies of the oculomotricity were less sensitive to the treatment., Conclusion: According to our experience, Chitotriosidase is a sensitive and specific marker in diagnosing and monitoring Gaucher's disease. The enzyme replacement therapy through Cerezyme® is an effective and safe treatment of Gaucher's disease. Blood signs (anemia, platelet count); visceral signs (splenomegaly, hepatomegaly) as well as bone involvement showed decisive improvement under the therapy.