Coronary artery disease (CAD) is one of the leading causes of death and disability in Europe and worldwide. For patients with multi-vessel CAD, coronary artery bypass graft (CABG) surgery is a common approach for coronary revascularization, and is of proven symptomatic and prognostic benefit. Due to an aging population, higher prevalence of co-morbidities (such as diabetes mellitus, heart failure, hypertension, and renal failure), and a growing requirement for concomitant surgical procedures (such as valve and aortic surgery), higher risk patients are undergoing surgery. ^1–3 This has resulted in an increased risk of peri-operative myocardial injury (PMI) ⁴ and Type 5 myocardial infarction (MI), both of which are associated with worsened clinical outcomes following CABG surgery. The aetiology and determinants of PMI and Type 5 MI are multi-factorial (see Tables 1 and 2 for summary). Although diagnostic criteria have been proposed for Type 5 MI (based on an elevation in cardiac biomarkers in the 48-h post-operative period and electrocardiogram/angiography/imaging evidence of MI ^{5, 13}), there is currently no clear definition for prognostically significant PMI, in terms of the level of post-operative cardiac biomarker elevation, which is associated with worsened clinical outcomes following CABG surgery.

Bcl-2 plays a key role in the regulation of apoptosis. We investigated the role of a novel regulatory single-nucleotide polymorphism (−938C>A) in the inhibitory P2 BCL2 promoter in B-cell chronic lymphocytic leukemia (B-CLL). The −938C allele displayed significantly increased BCL2 promoter activity and binding of nuclear proteins compared with the A allele. Concomitantly, Bcl-2 protein expression in B cells from CLL patients carrying the −938 AA genotype was significantly increased compared with CC genotypes. Genotype distribution between 123 CLL patients (42 AA, 55 AC, 26 CC) and 120 genotyped healthy controls (36 AA, 63 AC, 21 CC) was not significantly different, suggesting that genotypes of this polymorphism do not increase the susceptibility for B-CLL. However, median time from first diagnosis to initiation of chemotherapy and median overall survival were significantly shorter in patients with −938AA genotype (38 and 199 months, respectively) compared with AC/CC genotypes (120 and 321 months, respectively; P = .008 and P = .003, respectively). Multivariable Cox regression identified the BCL2−938AA genotype as an independent prognostic factor for the time to first treatment (hazard ratio [HR] 1.9; P = .034) together with disease stage at diagnosis (HR 2.5; P = .004) and ZAP-70 status (HR 3.0; P = .001). The BCL2−938AA genotype is associated with increased Bcl-2 expression and a novel unfavorable genetic marker in patients with B-CLL.

Extracorporeal membrane oxygenation (ECMO) is a life-saving therapy in acute respiratory distress syndrome (ARDS) patients but is associated with complications and costs. Here, we validate various scores supposed to predict mortality and develop an optimized categorical model. In a derivation cohort, 108 ARDS patients (2010–2015) on veno-venous ECMO were retrospectively analysed to assess four established risk scores (ECMOnet-Score, RESP-Score, PRESERVE-Score, Roch-Score) for mortality prediction (receiver operating characteristic analysis) and to identify by multivariable logistic regression analysis independent variables for mortality to yield the new PRESET-Score (PREdiction of Survival on ECMO Therapy-Score). This new score was then validated both in independent internal (n = 82) and external (n = 59) cohorts. The median (25%; 75% quartile) Sequential Organ Failure Assessment score was 14 (12; 16), Simplified Acute Physiology Score II was 62.5 (57; 72.8), median intensive care unit stay was 17 days (range 1–124), and mortality was 62%. Only the ECMOnet-Score (area under curve (AUC) 0.69) and the RESP-Score (AUC 0.64) discriminated survivors and non-survivors. Admission pH_a, mean arterial pressure, lactate, platelet concentrations, and pre-ECMO hospital stay were independent predictors of death and were used to build the PRESET-Score. The score’s internal (AUC 0.845; 95% CI 0.76–0.93; p < 0.001) and external (AUC 0.70; 95% CI 0.56–0.84; p = 0.008) validation revealed excellent discrimination. While our data confirm that both the ECMOnet-Score and the RESP-Score predict mortality in ECMO-treated ARDS patients, we propose a novel model also incorporating extrapulmonary variables, the PRESET-Score. This score predicts mortality much better than previous scores and therefore is a more precise choice for decision support in ARDS patients to be placed on ECMO.

The intrapulmonary renin–angiotensin systemviatissue concentration of angiotensin II or bradykinin may have multiple effects on pulmonary pathophysiology. Therefore, it was investigated whether the presence of the D allele of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism or the A allele of angiotensinogen (AGT) promoter polymorphism (-6)A/G are independent risk factors for 30-day survival in acute respiratory distress syndrome (ARDS) patients.In a prospective study, adults (Germans of Caucasian ethnicity)with ARDS (n = 84) were recruited from the current authors’ intensive care unit and genotyped for theACEI/D and theAGT(-6)A/G polymorphisms, as were 200 healthy Caucasian controls.Mortality was increased in theACEDD genotype compared with the I allele, and theACEI/D polymorphism was an independent prognostic factor for 30-day survival. Patients with a homozygous DD genotype were at highest risk for death (hazard ratio 5.7; 95% confidence interval 1.7–19.2) compared with the II genotype. In contrast, theAGT(-6)A/G polymorphism was neither associated with an increased risk for development of ARDS nor with outcome.In patients with acute respiratory distress syndrome, the angiotensin-converting enzyme insertion/deletion polymorphism but not the angiotensinogen (-6)A/G promoter polymorphism is an independent risk factor with a pronounced effect on 30-day survival.

Introduction: Established biomarkers for the diagnosis of sepsis are procalcitonin, interleukin 6, and C-reactive protein. Although sepsis evokes changes of coagulation and fibrinolysis, it is unknown whether thromboelastometry can detect these alterations. We investigated whether thromboelastometry variables are suitable as biomarkers for severe sepsis in critically ill adults. Methods: In the observational cohort study, blood samples were obtained from patients on the day of diagnosis of severe sepsis (n = 56) and from postoperative patients (n = 52), and clotting time, clot formation time, maximum clot firmness, alpha angle, and lysis index were measured with thromboelastometry. In addition, procalcitonin, interleukin 6, and C-reactive protein levels were determined. For comparison of biomarkers, receiver operating characteristic (ROC) curves were used, and the optimal cut-offs and odds ratios were calculated. Results: In comparison with postoperative controls, patients with sepsis showed an increase in lysis index (97% ± 0.3 versus 92 ± 0.5; P < 0.001; mean and SEM) and procalcitonin (2.5 ng/ml ± 0.5 versus 30.6 ± 8.7; P < 0.001). Clot-formation time, alpha angle, maximum clot firmness, as well as interleukin 6 and C-reactive protein concentrations were not different between groups; clotting time was slightly prolonged. ROC analysis demonstrated an area under the curve (AUC) of 0.901 (CI 0.838 - 0.964) for the lysis index, and 0.756 (CI 0.666 - 0.846) for procalcitonin. The calculated cut-off for the lysis index was > 96.5%, resulting in a sensitivity of 84.2%, and a specificity of 94.2%, with an odds ratio of 85.3 (CI 21.7 - 334.5). Conclusions: The thromboelastometry lysis index proved to be a more reliable biomarker of severe sepsis in critically ill adults than were procalcitonin, interleukin 6, and C-reactive protein. The results also demonstrate that early involvement of the hemostatic system is a common event in severe sepsis.