Robin Ristl

Heparin-bonded covered stents versus bare-metal stents for complex femoropopliteal artery lesions: the randomized VIASTAR trial (Viabahn endoprosthesis with PROPATEN bioactive surface [VIA] versus bare nitinol stent in the treatment of long lesions in superficial femoral artery occlusive disease).

OBJECTIVES The hypothesis that endovascular treatment with covered stents has equal risks but higher efficacy than bare-metal stents (BMS) in long femoropopliteal artery disease was tested. BACKGROUND Although endovascular treatment of short superficial femoral artery lesions revealed excellent results, efficacy in long lesions remains unsatisfactory. METHODS In a prospective, randomized, single-blind, multicenter study, 141 patients with symptomatic peripheral arterial disease were assigned to treatment with heparin-bonded, covered stents (Viabahn 72 patients) or BMS (69 patients). Clinical outcomes and patency rates were assessed at 1, 6, and 12 months. RESULTS Mean ± SD lesion length was 19.0 ± 6.3 cm in the Viabahn group and 17.3 ± 6.6 cm in the BMS group. Major complications within 30 days were observed in 1.4%. The 12-month primary patency rates in the Viabahn and BMS groups were: intention-to-treat (ITT) 70.9% (95% confidence interval [CI]: 0.58 to 0.80) and 55.1% (95% CI: 0.41 to 0.67) (log-rank test p = 0.11); treatment per-protocol (TPP) 78.1% (95% CI: 0.65 to 0.86) and 53.5% (95% CI: 0.39 to 0.65) (hazard ratio: 2.23 [95% CI: 1.14 to 4.34) (log-rank test p = 0.009). In lesions ≥20 cm, (TransAtlantic Inter-Society Consensus class D), the 12-month patency rate was significantly longer in VIA patients in the ITT analysis (VIA 71.3% vs. BMS 36.8%; p = 0.01) and the TPP analysis (VIA 73.3% vs. BMS 33.3%; p = 0.004). Freedom from target lesion revascularization was 84.6% for Viabahn (95% CI: 0.72 to 0.91) versus 77.0% for BMS (95% CI: 0.63 to 0.85; p = 0.37). The ankle-brachial index in the Viabahn group significantly increased to 0.94 ± 0.23 compared with the BMS group (0.85 ± 0.23; p < 0.05) at 12 months. CONCLUSIONS This randomized trial in symptomatic patients with peripheral arterial disease who underwent endovascular treatment for long femoropopliteal lesions demonstrated significant clinical and patency benefits for heparin-bonded covered stents compared with BMS in lesions ≥20 cm and for all lesions in the TPP analysis. In the ITT analysis for all lesions, which was flawed by major protocol deviations in 8.5% of the patients, the difference was not significant. (GORE VIABAHN® endoprosthesis with bioactive propaten surface versus bare nitinol stent in the treatment of TASC B, C and D lesions in superficial femoral artery occlusive disease; ISRCTN48164244).

The right heart in heart failure with preserved ejection fraction: insights from cardiac magnetic resonance imaging and invasive haemodynamics.

Recent data indicate that right ventricular systolic dysfunction (RVSD) by cardiac magnetic resonance imaging (CMR) is a strong predictor of outcome in heart failure. However, the prognostic significance of RVSD by CMR in heart failure with preserved ejection fraction (HFpEF) is unknown.

Thymoquinone attenuates tumor growth in ApcMin mice by interference with Wnt-signaling

BackgroundPatients with familial adenomatous polyposis (FAP) are at increased risk for the development of colorectal cancer. Surgery and chemoprevention are the most effective means to prevent cancer development. Thymoquinone (TQ) is considered the main compound of the volatile Nigella sativa seed oil and has been reported to possess anticarcinogenic properties. In this study we evaluated the chemopreventive properties of TQ in a mouse model of FAP.MethodsAPCMin mice were fed with chow containing 37.5 mg/kg or 375 mg/kg TQ for 12 weeks. H&E stained intestine tissue sections were assessed for tumor number, localization, size, and grade. Immunohistochemistry for β-catenin, c-myc, Ki-67 and TUNEL-staining was performed to investigate TQ’s effect on major colorectal cancer pathways. TQ’s impact on GSK-3β and β-catenin were studied in RKO cells.Results375 mg/kg but not 37.5 mg/kg TQ decreased the number of large polyps in the small intestine of APCMin mice. TQ induced apoptosis in the neoplastic tissue but not in the normal mucosa. Furthermore, upon TQ treatment, β-catenin was retained at the membrane and c-myc decreased in the nucleus, which was associated with a reduced cell proliferation in the villi. In vitro, TQ activated GSK-3β, which induced membranous localization of β-catenin and reduced nuclear c-myc expression.ConclusionsIn summary, TQ interferes with polyp progression in ApcMin mice through induction of tumor-cell specific apoptosis and by modulating Wnt signaling through activation of GSK-3β. Nigella sativa oil (or TQ) might be useful as nutritional supplement to complement surgery and chemoprevention in FAP.

Antibiotics and their effects: what do patients know and what is their source of information?

BACKGROUND The Eurobarometer 2010 report on antimicrobial resistance included a survey on the knowledge of Europeans about antibiotics. Austria was ranked at the bottom of the EU27 countries. Based on these alarming results, it was the aim of this study to analyse demographic characteristics of patients and general practitioners in Austria to assess possible predictors for this outcome as well as to assess the main source of information related to antibiotics. METHODS This cross-sectional study was conducted within the context of the European APRES project. An additional 12-item questionnaire was developed asking for the knowledge about antibiotics, demographic data and the source of information. Statistical analyses included subgroup analyses and linear mixed regression models. RESULTS Overall, 3280 questionnaires were analysed. On average, 2.78 (standard deviation 1.69) out of the six knowledge questions were answered correctly. The main predictors for a low knowledge score were low educational level, age, speaking another language than German and male sex. In all, 55.6% of the participants marked the general practitioner as main source of information. However, the source was less important for the knowledge score than their highest educational level. CONCLUSION The Eurobarometer report result for Austrians could be confirmed and important associations and predictors could be identified: a multifaceted and evidence informed strategy is needed to improve the situation, which should both focus on target-group-specific interventions at the individual level to increase the knowledge of people with the highest needs as well as on strengthening the primary health care and educational sector at the system level.

Ustekinumab treatment in severe atopic dermatitis: Down-regulation of T-helper 2/22 expression

Background: It has recently been suggested that patients with moderate to severe atopic dermatitis (AD) may profit from anti‐interleukin (IL)‐12/‐23 p40 therapy. Objective: We sought to assess the immunologic effects of ustekinumab treatment on AD skin and to correlate them with the clinical efficacy of this drug. Methods: We investigated the course of 3 patients with severe AD who were administered 45 mg of subcutaneous ustekinumab over a period of 16 weeks. Clinical scores and skin biopsy specimens, taken at baseline and at week 8, were used to assess changes in disease severity. Results: All patients showed a gradual improvement of the disease, achieving a 50% reduction in the Eczema Area and Severity Index score by week 16. Immunohistology of skin biopsy specimens revealed a significant decrease in the degree of epidermal hyperplasia/proliferation and the number of infiltrating dermal T cells, dendritic cells, and mast cells after treatment. Using quantitative real‐time polymerase chain reaction of lesional skin, we found a clear reduction of T‐helper 2‐/22‐associated molecules after therapy. Limitations: The small number of patients (n = 3) limits efficacy analysis and warrants prospective placebo‐controlled studies in larger patient cohorts. Conclusion: Blocking IL‐12/‐23 p40 could be beneficial for a subgroup of patients with severely infiltrated AD.

Outcome in Heart Failure with Preserved Ejection Fraction: The Role of Myocardial Structure and Right Ventricular Performance

Background Heart failure with preserved ejection fraction (HFpEF) is recognized as a major cause of cardiovascular morbidity and mortality. Thus, a profound understanding of the pathophysiologic changes in HFpEF is needed to identify risk factors and potential treatment targets in this specific patient population. Therefore, we aimed to comprehensively assess the impact of left- and right-ventricular function and hemodynamics on long-term mortality and morbidity in order to improve risk prediction in patients with HFpEF. Methods and Results We prospectively included 142 consecutive patients with HFpEF into our observational, non-interventional registry. Echocardiography, cardiac magnetic resonance imaging and invasive hemodynamic assessments including myocardial biopsy were performed at baseline. We detected significant correlations between left ventricular extracellular matrix and left ventricular end-diastolic diameter (r = -0.64;p = 0.03) and stroke volume (r = -0.53;p = 0.04). Hospitalization for heart failure and/or cardiac death was observed over a median follow up of 10 months. The strongest risk factors were reduced right ventricular function (adj. HR 6.62;95%CI 3.12- 14.02;p<0.001), systolic pulmonary arterial pressure (adj. HR per 1-SD 1.55;95%CI 1.15- 2.09;p = 0.004) and the pulmonary artery wedge pressure (adj. HR per 1-SD 1.51;95%CI 1.09–2.08; p = 0.012). The area under the ROC curve for right ventricular function was 0.63, for systolic pulmonary arterial pressure 0.75, and for pulmonary artery wedge pressure 0.68. Conclusion The current study emphasizes the importance of right ventricular function and pulmonary pressures on outcome in patients with HFpEF providing pathophysiological insights into the hemodynamic changes in HFpEF.

Depression and anxiety among migrants in Austria: A population based study of prevalence and utilization of health care services

BACKGROUND Although migrants form a large part of the Austrian population, information about mental health of migrants in Austria is scarce. Therefore, we compared the prevalence of dysphoric disorders (depression and anxiety) and the corresponding utilization of health care services of Eastern European, western and other migrants with the non-migrant population in Austria. METHODS We performed a telephone survey on a random sample of the general population of Austria aged 15 years and older (n=3509) between October 2010 and September 2011. Depression and anxiety were measured with the Patient Health Questionnaire-4 and utilization of health care services in the last 4 weeks was inquired. RESULTS 15.0% of our sample had a migration background. Female migrants from Eastern Europe, first and second generation, had a higher prevalence of dysphoric disorders (29.7% and 33.4% respectively) than Austrian women (15.2%) (p<0.001). The prevalence in the other migrant groups did not differ significantly from the Austrian population. There was no gender difference in dysphoric disorders in the Austrian population. After adjustment for age and chronic diseases, having a dysphoric disorder was associated with a higher utilization of health care services among migrant and Austrian women, but not among men. LIMITATIONS Because of the explorative nature of the study multiple testing correction was not performed. The reason for health care utilization was not assessed. CONCLUSIONS Mental health of female migrants from Eastern Europe should be studied in more detail; men could be an underserved group, both in migrants and Austrians.

Secretomes of apoptotic mononuclear cells ameliorate neurological damage in rats with focal ischemia

The pursuit of targeting multiple pathways in the ischemic cascade of cerebral stroke is a promising treatment option. We examined the regenerative potential of conditioned medium derived from rat and human apoptotic mononuclear cells (MNC), rMNC apo sec and hMNC apo sec, in experimental stroke. We performed middle cerebral artery occlusion on Wistar rats and administered apoptotic MNC-secretomes intraperitoneally in two experimental settings. Ischemic lesion volumes were determined 48 hours after cerebral ischemia. Neurological evaluations were performed after 6, 24 and 48 hours. Immunoblots were conducted to analyze neuroprotective signal-transduction in human primary glia cells and neurons. Neuronal sprouting assays were performed and neurotrophic factors in both hMNC apo sec and rat plasma were quantified using ELISA. Administration of rat as well as human apoptotic MNC-secretomes significantly reduced ischemic lesion volumes by 36% and 37%, respectively. Neurological examinations revealed improvement after stroke in both treatment groups. Co-incubation of human astrocytes, Schwann cells and neurons with hMNC apo sec resulted in activation of several signaling cascades associated with the regulation of cytoprotective gene products and enhanced neuronal sprouting in vitro. Analysis of neurotrophic factors in hMNC apo sec and rat plasma revealed high levels of brain derived neurotrophic factor (BDNF). Our data indicate that apoptotic MNC-secretomes elicit neuroprotective effects on rats that have undergone ischemic stroke.

Single, remote-magnetic catheter approach for pulmonary vein isolation in patients with paroxysmal and non-paroxysmal atrial fibrillation.

BACKGROUND The aim of the study was to investigate the safety and efficacy of a single, remote-magnetic catheter navigation system (MNS) for pulmonary vein isolation (PVI). METHODS A total of 107 PVI procedures in 71 patients with paroxysmal (32%), persistent (38%) and longstanding-persistent (30%) atrial fibrillation (AF) were analyzed. A wide area circumferential radiofrequency ablation PVI was performed with either an 8mm MNS (first 35 procedures) or an irrigated MNS (last 36 procedures) catheter. Electrical isolation was confirmed with circular pacing/sensing using the MNS catheter and a coronary sinus catheter. Our follow-up strategy in the first year and upon symptoms thereafter was: clinical check plus 12-lead ECG (100%) and 24 h-ECG recordings (76%) at 3 month intervals, trans-telephonic ECG (79%) twice daily and upon symptoms (4 weeks every 3 months), or ECG monitoring via implanted devices (9%). RESULTS The mean procedure time at 1st PVI was 247±61 min, and mean fluoroscopy time was 44±18 min. The overall complication rate was 2%. Success rates did not differ at the 1st PVI regarding catheter type (p=0.931) but were dependent on history of AF: patients with paroxysmal AF had the highest success rates of 58% and 29% after 1 and 3 years of follow-up, respectively (p=0.0084). CONCLUSION PVI with a single MNS catheter is safe and is associated with short fluoroscopy exposition. Despite a rigorous follow-up strategy success rates favorably compare with recently published data on hand-held PVI. Thus, multipolar catheters or a 2nd trans-septal puncture may not be mandatory.

Impact of preoperative serum creatinine on short- and long-term mortality after cardiac surgery: a cohort study

BACKGROUND Preoperative renal insufficiency is an important predictor of mortality after cardiac surgery. This retrospective cohort study was designed to identify the optimal cut-off for baseline serum creatinine (bSCr) and estimated glomerular filtration rate (eGFR) to predict survival. Furthermore, we investigated the potential confounding effect of other perioperative risk indicators on short- and long-term survival. METHODS Data of 9490 cardiac surgical patients were prospectively collected between 1997 and 2008 (follow up to 2010) at the Medical University Vienna. We identified bSCr cut-off values and calculated uni- and multivariate hazard models for short- and long-term survival and compared the results with a validation set from Zurich. The estimated survival curves defined a distinct period of increased mortality until 150 days. RESULTS Cut-off values of >115 µmol litre(-1) for bSCr and ≤50 ml min(-1) for eGFR were identified. Increased bSCr, associated with higher mortality [hazard ratio (HR) 2.61, 95% confidence interval (CI) 2.43-2.80, P<0.0001], was present in 19.5% of patients and remained predictive for short- (HR 1.59, 95% CI 1.38-1.83, P=0.0027) and long-term survival (HR 1.46, 95% CI 1.32-1.62, P<0.0001) in the multivariate hazard models. A cut-off of >120 µmol litre(-1) for bSCr was determined for the validation set. Decreased eGFR was present in 23.6% (HR 2.86, 95% CI 2.67-3.06, P<0.0001). CONCLUSIONS In our patients, increased bSCr was an independent predictor of mortality, which may critically influence risk evaluation and perioperative treatment guidance.