Blood urea nitrogen (BUN) was reported to be associated with mortality in heart failure patients. We aimed to evaluate admission BUN concentration in a heterogeneous critically ill patient collective ...admitted to an intensive care unit (ICU) for prognostic relevance.
A total of 4176 medical patients (67±13 years) admitted to a German ICU between 2004 and 2009 were included. Follow-up of patients was performed retrospectively between May 2013 and November 2013. Association of admission BUN and both intra-hospital and long-term mortality were investigated by Cox regression. An optimal cut-off was calculated by means of the Youden-Index.
Patients with higher admission BUN concentration were older, clinically sicker and had more pronounced laboratory signs of multi-organ failure including kidney failure. Admission BUN was associated with adverse long-term mortality (HR 1.013; 95%CI 1.012-1.014; p<0.001). An optimal cut-off was calculated at 28 mg/dL which was associated with adverse outcome even after correction for APACHE2 (HR 1.89; 95%CI 1.59-2.26; p<0.001), SAPS2 (HR 1.85; 95%CI 1.55-2.21; p<0.001) and several parameters including creatinine in an integrative model (HR 3.34; 95%CI 2.89-3.86; p<0.001). We matched 614 patients with admission BUN >28 mg/dL to case-controls ≤ 28mg/dL corrected for APACHE2 scores: BUN above 28 mg/dL remained associated with adverse outcome in a paired analysis with the difference being 5.85% (95%CI 1.23-10.47%; p = 0.02).
High BUN concentration at admission was robustly associated with adverse outcome in critically ill patients admitted to an ICU, even after correction for co-founders including renal failure. BUN might constitute an independent, easily available and important parameter for risk stratification in the critically ill.
Objectives This study investigated the effect of catheter-based renal sympathetic denervation (RD) on left ventricular hypertrophy (LVH) and systolic and diastolic function in patients with resistant ...hypertension. Background LVH and diastolic dysfunction are associated with elevated sympathetic activity and increased morbidity and mortality. The effect of RD on LVH and LV function is unclear. Methods Forty-six patients underwent bilateral RD, and 18 patients served as controls. Transthoracic echocardiography was performed at baseline, and after 1 month and 6 months. Results Besides reduction of systolic and diastolic blood pressure (−22.5/−7.2 mm Hg at 1 month and −27.8/−8.8 mm Hg at 6 months, p < 0.001 at each time point), RD significantly reduced mean interventricular septum thickness from 14.1 ± 1.9 mm to 13.4 ± 2.1 mm and 12.5 ± 1.4 mm (p = 0.007), and LV mass index from 53.9 ± 15.6 g/m2.7 (112.4 ± 33.9 g/m2 ) to 47.0 ± 14.2 g/m2.7 (103.6 ± 30.5 g/m2 ) and 44.7 ± 14.9 g/m2.7 (94.9 ± 29.8 g/m2 ) (p < 0.001) at 1 month and 6 months, respectively. The mitral valve lateral E/E′ decreased after RD from 9.9 ± 4.0 to 7.9 ± 2.2 at 1 month and 7.4 ± 2.7 at 6 months (p < 0.001), indicating reduction of LV filling pressures. Isovolumic relaxation time shortened (baseline 109.1 ± 21.7 ms vs. 85.6 ± 24.4 ms at 6 months, p = 0.006), whereas ejection fraction significantly increased after RD (baseline: 63.1 ± 8.1% vs. 70.1 ± 11.5% at 6 months, p < 0.001). No significant changes were obtained in control patients. Conclusions Besides the known effect on blood pressure, our study showed for the first time that RD significantly reduces LV mass and improves diastolic function, which might have important prognostic implications in patients with resistant hypertension at high cardiovascular risk.
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.
Mitochondrial Ca2+ handling plays an important role in energy production and various cellular signaling processes. Mitochondrial Ca2+ uptake is regulated by the mitochondrial Ca2+ uniporter (MCU), at ...least one non‐MCU Ca2+ channel and possibly a mitochondrial ryanodine receptor. Two distinct mechanisms mediate Ca2+ outward transport, the Na+‐dependent (mNCX) and the Na+‐independent Ca2+ efflux. In recent years we gained more insight into the regulation and function of these different Ca2+ transport mechanisms. However, the precise physiological role and the molecular structure of all mitochondrial Ca2+ transporters and channels still has to be determined.
Neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) are associated with the severity of various diseases. The aim of this study was to demonstrate the relationship of NLR and ...MLR with the severity of myocarditis. 202 consecutive patients with myocarditis were retrospectively enrolled in this study. Laboratory parameters and clinical data were extracted from hospital records and discharge letters. Median NLR was 2.48 (IQR 1.55-4.58) and median MLR was 0.42 (IQR 0.39-0.58). NLR and MLR correlated with HF, CRP and leukocyte count, MLR further correlated inversely with LV systolic function (rs = - 0.379, p = 0.030). Both ratios correlated better with length of hospital stay (NLR: rs = 0.435, p = 0.003; MLR: rs = 0.534, p < 0.0001) than CRP, leukocyte count, IL-6 or procalcitonin. AUCs for the prediction of prolonged hospital stay (NLR = 0.75, MLR = 0.80), and optimal cut-offs therefor were calculated. Patients who had in-hospital complications showed a higher NLR, however, this remained statistically insignificant. NLR and MLR correlated with the length of stay, as well as with several clinical and laboratory parameters in patients with myocarditis. Since white blood cell differentials are relatively easy and fast to perform, both ratios could facilitate further risk stratification in affected patients.
The lactate/albumin ratio has been reported to be associated with mortality in pediatric patients with sepsis. We aimed to evaluate the lactate/albumin ratio for its prognostic relevance in a larger ...collective of critically ill (adult) patients admitted to an intensive care unit (ICU). A total of 348 medical patients admitted to a German ICU for sepsis between 2004 and 2009 were included. Follow-up of patients was performed retrospectively between May 2013 and November 2013. The association of the lactate/albumin ratio (cut-off 0.15) and both in-hospital and post-discharge mortality was investigated. An optimal cut-off was calculated by means of Youden's index. The lactate/albumin ratio was elevated in non-survivors (
< 0.001). Patients with an increased lactate/albumin ratio were of similar age, but clinically in a poorer condition and had more pronounced laboratory signs of multi-organ failure. An increased lactate/albumin ratio was associated with adverse in-hospital mortality. An optimal cut-off of 0.15 was calculated and was associated with adverse long-term outcome even after correction for APACHE2 and SAPS2. We matched 99 patients with a lactate/albumin ratio >0.15 to case-controls with a lactate/albumin ratio <0.15 corrected for APACHE2 scores: The group with a lactate/albumin ratio >0.15 evidenced adverse in-hospital outcome in a paired analysis with a difference of 27% (95%CI 10-43%;
< 0.01). Regarding long-term mortality, again, patients in the group with a lactate/albumin ratio >0.15 showed adverse outcomes (
< 0.001). An increased lactate/albumin ratio was significantly associated with an adverse outcome in critically ill patients admitted to an ICU, even after correction for confounders. The lactate/albumin ratio might constitute an independent, readily available, and important parameter for risk stratification in the critically ill.
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
Changes of lactate concentration over time were reported to be associated with survival in septic patients. We aimed to evaluate delta-lactate (ΔLac) 24 h after admission (Δ24Lac) to an ...intensive care unit (ICU) in critically ill patients for short- and long-term prognostic relevance.
Methods
In total, 26,285 lactate measurements of 2191 patients admitted to a German ICU were analyzed. Inclusion criterion was a lactate concentration at admission above 2.0 mmol/L. Maximum lactate concentrations of day 1 and day 2 were used to calculate Δ24Lac. Follow-up of patients was performed retrospectively. Association of Δ24Lac and both in-hospital and long-term mortality were investigated. An optimal cut-off was calculated by means of the Youden index.
Results
Patients with lower Δ24Lac were of similar age, but clinically sicker. As continuous variable, higher Δ24Lac was associated with decreased in-hospital mortality (per 1% Δ24Lac; HR 0.987 95%CI 0.985–0.990;
p
< 0.001) and an optimal Δ24Lac cut-off was calculated at 19%. Δ24Lac ≤ 19% was associated with both increased in-hospital (15% vs 43%; OR 4.11; 95%CI 3.23–5.21;
p
< 0.001) and long-term mortality (HR 1.54 95%CI 1.28–1.87;
p
< 0.001), even after correction for APACHE II, need for catecholamines and intubation. We matched 256 patients with Δ24Lac ≤ 19% to case–controls > 19% corrected for APACHE II scores, baseline lactate level and sex: Δ24Lac ≤ 19% remained associated with lower in-hospital and long-term survival.
Conclusions
Lower Δ24Lac was robustly associated with adverse outcome in critically ill patients, even after correction for confounders. Δ24Lac might constitute an independent, easily available and important parameter for risk stratification in the critically ill.
Although current guidelines endorse early beta-blocker therapy in stable patients with STEMI, there is no clear recommendation on the early use of these drugs in patients with NSTEMI.
Literature ...search was conducted by 3 independent researchers using PubMed/MEDLINE, CDSR, CENTRAL, CCAs, EBM Reviews, Web of Science and LILACS. Studies were eligible if (P) patients included were ≥ 18 years of age and had non-ST-segment elevation myocardial infarction (NSTEMI), (I) early (<24 h) treatment with intravenous or oral beta-blockers was compared to (C) no treatment with beta-blockers and data on (O) in-hospital mortality and/or in-hospital cardiogenic shock were depicted. Odds ratios and 95% confidence intervals were calculated using random effects models with the Mantel–Haenszel method. The Hartung-Knapp-Sidik-Jonkman method was used as estimator for τ2.
977 records were screened for eligibility, which led to the inclusion of 4 retrospective, nonrandomized, observational cohort studies comprising a total of N = 184,951 patients. After pooling of the effect sizes, early therapy with beta-blockers resulted in a reduction of in-hospital mortality (OR 0.43 0.36–0.51, p = 0.0022) despite no significant effect on the prevalence of cardiogenic shock (OR 0.36 0.07–1.91, p = 0.1196).
Early treatment with beta-blockers was associated with an attenuation of in-hospital mortality despite no increase in cardiogenic shock. Thus, early therapy with these drugs could elicit beneficial effects on top of reperfusion therapy, similar to the effects seen in STEMI-patients. The low number of studies (k = 4) has to be considered when interpreting the findings of this analysis.
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•To date, there is no recommendation on early beta-blocker therapy (BB) in NSTEMI.•A meta-analysis was conducted, 4 retrospective cohort studies were included.•Early BBs reduced mortality (OR 0.43, p = 0.0022) despite no effect on shock.•In NSTEMI, BB could elicit beneficial effects on top of reperfusion like in STEMI.
MELD-XI, an adapted version of Model for End-stage Liver Disease (MELD) score excluding INR, was reported to predict outcomes e.g. in patients with acute heart failure. We aimed to evaluate MELD-XI ...in critically ill patients admitted to an intensive care unit (ICU) for prognostic relevance.
A total of 4381 medical patients (66±14 years, 2862 male) admitted to a German ICU between 2004 and 2009 were included and retrospectively investigated. Admission diagnoses were e.g. myocardial infarction (n = 2034), sepsis (n = 694) and heart failure (n = 688). We divided our patients in two cohorts basing on their MELD-XI score and evaluated the MELD-XI score for its prognostic relevance regarding short-term and long-term survival. Optimal cut-offs were calculated by means of the Youden-Index.
Patients with a MELD-XI score >12 had pronounced laboratory signs of organ failure and more comorbidities. MELD-XI >12 was associated with an increase in short-term (27% vs 6%; HR 4.82, 95%CI 3.93-5.93; p<0.001) and long-term (HR 3.69, 95%CI 3.20-4.25; p<0.001) mortality. In a univariate Cox regression analysis for all patients MELD-XI was associated with increased long-term mortality (changes per score point: HR 1.06, 95%CI 1.05-1.07; p<0.001) and remained to be associated with increased mortality after correction in a multivariate regression analysis for renal failure, liver failure, lactate concentration, blood glucose concentration, oxygenation and white blood count (HR 1.04, 95%CI 1.03-1.06; p<0.001). Optimal cut-off for the overall cohort was 11 and varied remarkably depending on the admission diagnosis: myocardial infarction (9), pulmonary embolism (9), cardiopulmonary resuscitation (17) and pneumonia (17). We performed ROC-analysis and compared the AUC: SAPS2 (0.78, 95%CI 0.76-0.80; p<0.0001) and APACHE (0.76, 95%CI 0.74-0.78; p<0.003) score were superior to MELD-XI (0.71, 95%CI 0.68-0.73) for prediction of mortality.
The easily calculable MELD-XI score is a robust and reliable tool to predict both intra-ICU and long-term mortality in critically ill medical patients admitted to an ICU. Optimal cut-off values for MELD-XI scores seem to depend on the primary disease and need to be validated in future prospective studies. Compared to SAPS2 and APACHE score, MELD-XI lacks precision but might have comparable and even additive value, as it is easily available and independent of subjective values.
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