Deciphering the Role of microRNAs: Unveiling Clinical Biomarkers and Therapeutic Avenues in Atrial Fibrillation and Associated Stroke-A Systematic Review.

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.

Insulin-like Growth Factor-Binding Protein 2 in Severe Aortic Valve Stenosis and Pulmonary Hypertension: A Gender-Based Perspective.

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.

The impact of ethnic background on ICU care and outcome in sepsis and septic shock - A retrospective multicenter analysis on 17,949 patients.

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.

The Association between Helicobacter pylori and Colorectal Neoplasia.

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."

Tei Index Complements Conventional Echocardiographic Parameters in Diagnostic Workup of Suspected Takotsubo Syndrome.

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.

Variations in end-of-life care practices in older critically ill patients with COVID-19 in Europe.

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.

Systolic Pulmonary Artery Pressure and Cardiovascular Biomarkers-New Non-Invasive Ways to Detect Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis Undergoing TAVR?

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.

Management of intoxicated patients - a descriptive outcome analysis of 4,267 ICU patients.

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.

Red Cell Distribution Width Is Independently Associated with Mortality in Sepsis.

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.

Machine learning predicts mortality based on analysis of ventilation parameters of critically ill patients: multi-centre validation.

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.

Short-term dual antiplatelet therapy (DAPT) followed by P2Y12 monotherapy versus traditional DAPT in patients undergoing percutaneous coronary intervention: meta-analysis and viewpoint.

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 P2Y12 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 P2Y12 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 I2 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 P2Y12 inhibitor monotherapy versus DAPT, there were similar rates of major bleeding (RR 0.67 95%CI 0.34-1.32; p = 0.25; I2 75%), mortality (RR 0.92 95%CI 0.78-1.09; p = 0.33; I2 0%) and stroke (RR 0.97 95%CI 0.52 - 0.18; p = 0.92; I2 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; I2 0%) and stent thrombosis (RR 1.03 95%CI 0.74-1.44; p = 0.87; I2 0%). The experimental treatment with P2Y12 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.

Regenerative Cardiovascular Therapies: Stem Cells and Beyond.

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.

Cardiac MRI after Sudden Cardiac Arrest: A Systematic Review.

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.

Beyond the Valve: Incidence, Outcomes, and Modifiable Factors of Acute Kidney Injury in Patients with Infective Endocarditis Undergoing Valve Surgery-A Retrospective, Single-Center Study.

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. Conclusions: 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.

Hyperlactatemia and altered lactate kinetics are associated with excess mortality in sepsis : A multicenter retrospective observational study.

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.

Frailty as a predictor of mortality and readmission rate in secondary mitral regurgitation.

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), 1­year 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.

Assessing the association between H. pylori infection and educational status: implications for screening strategies?

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.

Underweight but not overweight is associated with excess mortality in septic ICU patients.

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/m2), normal weight (18.5 to < 25 kg/m2), overweight (25 to < 30 kg/m2) and obesity (≥ 30 kg/m2). 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.

Relevance of pre-existing anaemia for patients admitted for acute coronary syndrome to an intensive care unit: a retrospective cohort analysis of 7418 patients.

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 role of anemia on admission in acute coronary syndrome - An umbrella review of systematic reviews and meta-analyses.

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.