ECG changes in patients with acute ethanol intoxication

Objectives. To assess how ethanol in potential lethal serum concentrations affects features of the ECG that may be associated with cardiac arrhythmias. Design. We included 84 patients, who were hospitalised with assumed acute ethanol intoxication. In the emergency room resting ECG was recorded and blood was collected for serum osmolality measurement used as a proxy for ethanol level. Thirty-two also had ECG recorded at discharge. Twenty-seven hospitalised patients without known alcohol ingestion served as controls. ECG segment durations were compared with controls and related to intoxication level. Results. In subjects with moderately elevated to high serum osmolality, the P wave and QTc intervals were prolonged compared with sober subjects. P wave, PR, QRS and QTc intervals were longer when the subjects had high blood ethanol levels (at admission) than at discharge (p-values: 0.0001, 0.0002, 0.010 and < 0.0001 for P wave, PR, QRS and QTc intervals. n = 32). Conclusions. Ethanol at high to very high blood concentration causes several changes in the ECG that might be associated with increased risk of arrhythmias.     

Comparison of the centrifugal and roller pump in elective coronary artery bypass surgery—a prospective,randomized study with special emphasis upon platelet activation

Objective—Evaluation of the centrifugal pump vs roller pump concerning effects upon platelet function, hemolysis and clinical outcome in elective coronary artery bypass surgery.

Design—Thirty‐four patients were randomized to centrifugal or roller pump. Platelet activation was studied by flow cytometry before, during and up to 3 days after bypass.

Results—Duration of bypass, ischemic period, peripheral anastomoses, hospital stay and mortality did not differ. In roller pump patients, platelet aggregates increased by 250% between end of bypass and 3?h postoperatively (p?<?0.001). A secondary, fivefold increase in number of platelet aggregates was found on the 3rd postoperative day (p?<?0.001). In the centrifugal pump group, these changes were not significant. Hemolysis increased (20%) at end of bypass and 3?h postoperatively (p?<?0.005), and decreased to preoperative levels the next day without group difference.

Conclusion—Platelet aggregation was significantly increased in roller compared with centrifugal pump patients, indicating higher susceptibility to postoperative thrombotic complications with the roller pump. Otherwise, there was no clinical evidence for superiority of the centrifugal pump.     

Nonlinear model predictive control based on constraint transformation

The paper presents a constraint transformation approach for nonlinear model predictive control (MPC) subject to a class of state and control constraints. The approach uses a two‐stage transformation technique to incorporate the constraints into a new unconstrained MPC formulation with new variables. As part of the stability analysis, the relationship of the new unconstrained MPC scheme to an interior penalty formulation in the original variables is discussed. The approach is combined with an unconstrained gradient method that allows for computing the single MPC iterations in a real‐time manner. The applicability of the approach, for example, to fast mechatronic systems, is demonstrated by numerical as well as experimental results. Copyright © 2015 John Wiley & Sons, Ltd.     

Cost‐effectiveness of treating vascular leg ulcers with UrgoStart® and UrgoCell® Contact

Although chronic wounds have a high socio‐economic impact, data on comparative effectiveness of treatments are rare. UrgoStart^® is a hydroactive dressing containing a nano‐oligosaccharide factor (NOSF). This study aimed at evaluating the cost‐effectiveness of this NOSF‐containing wound dressing in vascular leg ulcers compared with a similar neutral foam dressing (UrgoCell^® Contact) without NOSF. Cost‐effectiveness analysis from the perspective of the German statutory health care system was performed using a decision tree model for a period of 8 weeks. Cost and outcome data were derived from the clinical study ‘Challenge’ suggesting a response rate (≥40% wound size reduction) of UrgoStart^® of 65·6% versus 39·4% for the comparator. In the treatment model, effect‐adjusted costs of €849·86 were generated after 8 weeks for treatment with UrgoStart^® versus €1335·51 for the comparator resulting in an effect‐adjusted cost advantage of €485·64 for UrgoStart^®. In linear sensitivity analyses, the outcomes were stable for varying assumptions on prices and response rates. In an 8‐week period of treatment for vascular leg ulcers, UrgoStart^® shows superior cost‐effectiveness when compared with the similar neutral foam dressing without any active component (NOSF). As demonstrated within a randomised, double‐blind clinical trial, UrgoStart^® is also more effective in wound area reduction than the neutral foam dressing. Wound healing was not addressed in this clinical trial. Follow‐up data of 12 months to allow for reulceration assessment were not generated.     

Expression of transforming growth factor-beta receptor type 1 and type 2 in human sporadic vestibular Schwannoma

Expression of the transforming growth factor-beta (TGF-beta) protein family in the peripheral nervous system is well established, but the role of their cognate receptors TGF-beta receptor type 1 (R1) and type 2 (R2) has been less well studied. TGF-beta plays an essential role in Schwann cell proliferation and differentiation, and is involved in neurotrophic effects of several neurotrophic substances. TGF-beta is also expressed in benign peripheral nervous system tumors such as vestibular schwannomas. In the present study, we aimed to detect TGF-beta R1 and R2 in a total of 40 sporadic vestibular schwannomas using immunohistochemistry, and correlated the findings to essential clinicopathologic data. TGF-beta, TGF-beta R1, and TGF-beta R2 mRNA was further analyzed by RT-PCR in six vestibular schwannomas. TGF-beta R1 immunoexpression was found in about 95% of the tumors. TGF-beta R1 was equally present in Antoni A and Antoni B areas of the tumors. TGF-beta R2 was found immunohistochemically in 77%. In addition, all tumors showed strong expression of TGF-beta. No correlation between TGF-beta R1 or R2 expression and clinicopathologic parameters such as age, sex, clinical symptoms, growth pattern, and proliferation acitivity as measured by Ki-67 (MIB-1) staining was found. Moreover, all schwannomas studied contained TGF-beta, TGF-beta R1, and TGF-beta R2 mRNA. Therefore, the TGF-beta/TGF-beta R1 and -R2 system is present in human schwannomas, but its biologic role for tumor development and growth remains unclear.     

Hypophosphorylated TCR/CD3zeta signals through a Grb2-SOS1-Ras pathway in Lck knockdown cells

Despite the loss of proximal TCR-dependent signaling events, downstream T cell responses are paradoxically augmented in T cells with siRNA-mediated Lck knockdown (Methi et al., J. Immunol. 2005. 175: 7398-7406). This indicates that alternative Lck-independent pathways of T cell activation exist or that low levels of Lck elicit other signals than normal T cell activation. Here we report the recruitment of Grb2-SOS1 to CD3zeta of the TCR complex after prolonged anti-CD3 (OKT3) stimulation in T cells with Lck knockdown. Grb2 bound to incompletely phosphorylated ITAM1 with the pY-Y configuration in a solid-phase assay, but was excluded by ZAP-70 in the doubly phosphorylated pY-pY conformation. Ras and ERK1/2 activation was augmented after prolonged stimulation in T cells with Lck knockdown compared to control, leading to increased activation of the proximal IL-2 promoter (NFAT-AP-1). Finally, the phosphorylation of Ras-GAP was strongly suppressed in Lck knockdown cells, indicating that a Ras negative feedback mechanism is dependent on Lck.     

Statins and Angiotensin‐Converting Enzyme Inhibitors are Associated with Reduced Mortality and Morbidity in Chronic Liver Disease

Liver fibrosis is a common response to many chronic liver diseases. The aim of our study was to explore whether pharmacotherapy for concurrent diseases affects overall mortality, liver‐related mortality and liver‐related morbidity in patients with chronic liver disease. We performed a register‐based cohort study of all patients with a first‐time diagnosis of chronic liver disease between 2005 and 2012 in Sweden (n = 70 546). Data from the Patient Register, the Prescribed Drug Register and the Death Certificate Register were linked . We studied whether the use of statins, angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers and antibiotics affected the risk of total mortality, liver‐specific mortality and morbidity. We found a reduction in mortality risk for statin users (n = 11,245) with hazard ratios from 0.57 (95% CI: 0.32–0.99) for patients with autoimmune hepatitis to 0.84 (95% CI: 0.75–0.95) for patients with alcoholic liver disease. There was a significantly reduced liver‐related mortality for patients with alcoholic liver disease who used angiotensin‐converting enzyme inhibitors, 0.85 (95% CI: 0.65–0.96). There were increased overall mortality risks for antibiotic users (n = 44,572), with hazard ratios up to 1.67 (95% CI, 1.55–1.80) for viral hepatitis. Statin use was associated with decreased risks of liver‐specific mortality and morbidity, and reduced total mortality foremost among patients with alcoholic liver disease. Angiotensin ‐converting enzyme inhibitors was associated with reduced liver‐related mortality among patients with alcoholic liver disease.