Hanno Ulmer

Efficacy and safety of the pulsed infusions of levosimendan in outpatients with advanced heart failure (LevoRep) study: a multicentre randomized trial

The aim of this study was to determine whether intermittent ambulatory treatment with levosimendan would improve functional capacity, quality of life, and event‐free survival in patients with advanced heart failure.

Systemic levels of vascular endothelial growth factor before and after intravitreal injection of aflibercept or ranibizumab in patients with age‐related macular degeneration: a randomised, prospective trial

To evaluate the changes of vascular endothelial growth factor (VEGF) plasma levels after intravitreal injections of aflibercept or ranibizumab in patients with exudative age‐related macular degeneration (AMD).

Motor events during healthy sleep: a quantitative polysomnographic study.

STUDY OBJECTIVESnMany sleep disorders are characterized by increased motor activity during sleep. In contrast, studies on motor activity during physiological sleep are largely lacking. We quantitatively investigated a large range of motor phenomena during polysomnography in physiological sleep.nnnDESIGNnProspective polysomnographic investigation.nnnSETTINGnAcademic referral sleep laboratory.nnnPARTICIPANTSnOne hundred healthy sleepers age 19-77 y were strictly selected from a representative population sample by a two-step screening procedure.nnnINTERVENTIONSnN/A.nnnMEASUREMENTS AND RESULTSnPolysomnography according to American Academy of Sleep Medicine (AASM) standards was performed, and quantitative normative values were established for periodic limb movements in sleep (PLMS), high frequency leg movements (HFLM), fragmentary myoclonus (FM), neck myoclonus (NM), and rapid eye movement (REM)-related electromyographic (EMG) activity. Thirty-six subjects had a PLMS index > 5/h, 18 had a PLMS index > 15/h (90th percentile: 24.8/h). Thirty-three subjects had HFLM (90th percentile: four sequences/night). All subjects had FM (90th percentile 143.7/h sleep). Nine subjects fulfilled AASM criteria for excessive FM. Thirty-five subjects had NM (90th percentile: 8.8/h REM sleep). For REM sleep, different EMG activity measures for the mentalis and flexor digitorum superficialis muscles were calculated: the 90th percentile for phasic mentalis EMG activity for 30-sec epochs according to AASM recommendation was 15.6%, and for tonic mentalis EMG activity 2.6%. Twenty-five subjects exceeded the recently proposed phasic mentalis cutoff of 11%. None of the subjects exceeded the tonic mentalis cutoff of 9.6%.nnnCONCLUSIONnQuantification of motor phenomena is a basic prerequisite to develop normative values, and is a first step toward a more precise description of the various motor phenomena present during sleep. Because rates of motor events were unexpectedly high even in physiological sleep, the future use of normative values for both research and clinical routine is essential.

Changes of Body Mass Index in Relation to Mortality: Results of a Cohort of 42,099 Adults

Background High Body-Mass-Index (BMI) is associated with increased all-cause mortality, but little is known about the effect of short- and long-term BMI change on mortality. The aim of the study was to determine how long-term weight change affects mortality. Methods and findings Within a population-based prospective cohort of 42,099 Austrian men and women (mean age 43 years) with at least three BMI measurements we investigated the relationship of BMI at baseline and two subsequent BMI change intervals of five years each with all-cause mortality using Cox proportional Hazard models. During median follow-up of 12 years 4,119 deaths were identified. The lowest mortalities were found in persons with normal weight or overweight at baseline and stable BMI over 10 years. Weight gain (≥0.10 kg/m2/year) during the first five years was associated with increased mortality in overweight and obese people. For weight gain during both time intervals mortality risk remained significantly increased only in overweight (Hazard Ratio (HR): 1.39 (95% confidence interval: 1.01; 1.92)) and obese women (1.85 (95% confidence interval: 1.18; 2.89)). Weight loss (< −0.10 kg/m2/year) increased all-cause mortality in men and women consistently. BMI change over time assessed using accepted World Health Organisation BMI categories showed no increased mortality risk for people who remained in the normal or overweight category for all three measurements. In contrast, HRs for stable obese men and women were 1.57 (95% CI: 1.31; 1.87) and 1.46 (95% CI: 1.25; 1.71) respectively. Conclusion Our findings highlight the importance of weight stability and obesity avoidance in prevention strategy.

Prostate cancer, prostate cancer death, and death from other causes, among men with metabolic aberrations.

Background: Few previous studies of metabolic aberrations and prostate cancer risk have taken into account the fact that men with metabolic aberrations have an increased risk of death from causes other than prostate cancer. The aim of this study was to calculate, in a real-life scenario, the risk of prostate cancer diagnosis, prostate cancer death, and death from other causes. Methods: In the Metabolic Syndrome and Cancer Project, prospective data on body mass index, blood pressure, glucose, cholesterol, and triglycerides were collected from 285,040 men. Risks of prostate cancer diagnosis, prostate cancer death, and death from other causes were calculated by use of competing risk analysis for men with normal (bottom 84%) and high (top 16%) levels of each factor, and a composite score. Results: During a mean follow-up period of 12 years, 5,893 men were diagnosed with prostate cancer, 1,013 died of prostate cancer, and 26,328 died of other causes. After 1996, when prostate-specific antigen testing was introduced, men up to age 80 years with normal metabolic levels had 13% risk of prostate cancer, 2% risk of prostate cancer death, and 30% risk of death from other causes, whereas men with metabolic aberrations had corresponding risks of 11%, 2%, and 44%. Conclusions: In contrast to recent studies using conventional survival analysis, in a real-world scenario taking risk of competing events into account, men with metabolic aberrations had lower risk of prostate cancer diagnosis, similar risk of prostate cancer death, and substantially higher risk of death from other causes compared with men who had normal metabolic levels.

A prospective study on metabolic risk factors and gallbladder cancer in the metabolic syndrome and cancer (Me-Can) collaborative study.

Objective To investigate the association between metabolic risk factors (individually and in combination) and risk of gallbladder cancer (GBC). Methods The metabolic syndrome and cancer project (Me-Can) includes cohorts from Norway, Austria, and Sweden with data on 578,700 men and women. We used Cox proportional hazard regression models to calculate relative risks of GBC by body mass index (BMI), blood pressure, and plasma levels of glucose, cholesterol, and triglycerides as continuous standardised variables and their standardised sum of metabolic syndrome (MetS) z-score. The risk estimates were corrected for random error in measurements. Results During an average follow-up of 12.0 years (SDu200a=u200a7.8), 184 primary gallbladder cancers were diagnosed. Relative risk of gallbladder cancer per unit increment of z-score adjusted for age, smoking status and BMI (except for BMI itself) and stratified by birth year, sex and sub-cohorts, was for BMI 1.31 (95% confidence interval 1.11, 1.57) and blood glucose 1.76 (1.10, 2.85). Further analysis showed that the effect of BMI on GBC risk is larger among women in the premenopausal age group (1.84 (1.23, 2.78)) compared to those in the postmenopausal age group (1.29 (0.93, 1.79)). For the other metabolic factors no significant association was found (mid blood pressure 0.96 (0.71, 1.31), cholesterol 0.84 (0.66, 1.06) and serum triglycerides 1.16 (0.82, 1.64)). The relative risk per one unit increment of the MetS z-score was 1.37 (1.07, 1.73). Conclusion This study showed that increasing BMI and impaired glucose metabolism pose a possible risk for gallbladder cancer. Beyond the individual factors, the results also showed that the metabolic syndrome as an entity presents a risk constellation for the occurrence of gallbladder cancer.

Female gender may predict response to FOLFIRINOX in patients with unresectable pancreatic cancer: A single institution retrospective review

FOLFIRINOX is a highly active regimen for the treatment of patients with unresectable pancreatic cancer. However, treatment with FOLFIRINOX is associated with relevant toxicity and predictors for response to therapy are warranted. We retrospectively analyzed 49 patients with unresectable pancreatic cancer treated with FOLFIRINOX in order to evaluate a possible predictive role of clinical parameters and tumor characteristics for response to chemotherapy. Tumor samples were characterized histopathologically before treatment and expression of p53 and Ki67 was analyzed using automated immunohistochemistry. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. The overall objective response rate was 55.1%, the disease control rate was 70.6%. Female gender was associated with a significantly higher disease control rate of 91.7 compared to 48.0% in male patients (p=0.001) which reached 100% in female patients when primarily treated compared to treatment after surgical resection and relapse (77.8%, p=0.057). For all patients median PFS was 3.5 months (95% CI, 2.7-4.3 months) and median OS was 13 months (95% CI, 9.4-16.6 months). Female patients showed a tendency towards a longer median PFS (5.0 months, 95% CI, 3.6-6.4 months) compared to males (3.0 months, 95% CI, 2.4-3.6 months) (p=0.099). Serum levels of CA19.9 and CEA were significantly higher in female patients compared to male patients (p=0.037, p=0.05). Tumors of patients with response to FOLFIRINOX showed a higher expression level of p53 and Ki67 as well as higher serum levels of CA19.9 compared to non-responders, which was statistically not significant. Our study indicates that female gender is a positive predictor for therapy response to FOLFIRINOX in patients with unresectable pancreatic cancer. Female gender in turn was associated with increased levels of tumor markers CEA and CA19.9 and patients with higher serum levels of CA19.9 were more responsive to FOLFIRINOX.

The faster the better: anastomosis time influences patient survival after deceased donor kidney transplantation

Despite a continuously growing knowledge of the impact of factors on kidney graft function, such as donor age, body mass index, and cold ischemia time, few data are available regarding anastomosis time (AT) and its impact on long‐term results. We investigated whether surgical AT correlates with patient and graft survival after kidney transplantation performing a retrospective analysis of 1245 consecutive deceased donor kidney transplantations between 01/2000 and 12/2010 at Innsbruck Medical University. Kaplan–Meier and log‐rank analyses were carried out for 1‐ and 5‐year patient and graft survival. AT was defined as time from anastomosis start until reperfusion. Median AT was 30 min. Five‐year survival of allografts with an AT >30 min was 76.6% compared with 80.6% in the group with AT <30 min (P = 0.027). Patient survival in the group with higher AT similarly was inferior with 85.7% after 5 years compared with 89.6% (P < 0.0001) [Correction added on February 18, 2015, after first online publication: the percentage value for patient survival was previously incorrect and have now been changed to 89.6%]. Cox regression analysis revealed AT as an independent significant factor for patient survival (HR 1.021 per minute; 95% CI 1.006–1.037; P = 0.006). As longer AT closely correlates with inferior long‐term patient survival, it has to be considered as a major risk factor for inferior long‐term results after deceased donor kidney transplantation.

Secretoneurin as a marker for hypoxic brain injury after cardiopulmonary resuscitation.

PurposeThe neuropeptide secretoneurin (SN) shows widespread distribution in the brain. We evaluated whether SN is elevated after cardiopulmonary resuscitation (CPR) and could serve as a potential new biomarker for hypoxic brain injury after CPR.MethodsThis was a prospective observational clinical study. All patients admitted to a tertiary medical intensive care unit after successful CPR with expected survival of at least 24xa0h were consecutively enrolled from September 2008 to April 2013. Serum SN and neuron-specific enolase were determined in 24xa0h intervals starting with the day of CPR for 7xa0days. Neurological outcome was assessed with the Cerebral Performance Categories Scale (CPC) at hospital discharge.ResultsA total of 134 patients were included with 49xa0% surviving to good neurological outcome (CPC 1–2). SN serum levels peaked within the first 24xa0h showing on average a sixfold increase above normal. SN levels were significantly higher in patients with poor (CPC 3–5) than in patients with good neurological outcome [0–24xa0h: 75 (43–111) vs. 38 (23–68)xa0fmol/ml, pxa0<xa00.001; 24–48xa0h: 45 (24–77) vs. 23 (16–39)xa0fmol/ml, pxa0<xa00.001]. SN determined within the first 48xa0h showed a receiver operating characteristic (ROC) area under the curve (AUC) of 0.753 (0.665–0.841). NSE in the first 72xa0h had a ROC-AUC of 0.881 (0.815–0.946). When combining the two biomarkers an AUC of 0.925 (0.878–0.972) for outcome prediction could be reached.ConclusionsSN is a promising early biomarker for hypoxic brain injury. Further studies will be required for confirmation of these results.

Prevalence of wheezing and atopic diseases in Austrian schoolchildren in conjunction with urban, rural or farm residence

SummaryBackgroundA large number of studies have consistently shown that children growing up on a farm have a reduced prevalence of allergic disorders. The GABRIEL Advanced Study was conducted in five rural areas of southern Germany, Switzerland, Austria and Poland to shed light on the protective ‘farm effect’ on asthma and atopic disease. Whereas, the GABRIEL Advanced Study focussed on rural children only, the present study incorporates data from Innsbruck town children also.MethodsA screening questionnaire was developed to identify children with and without atopic disease within their living environment. Children were stratified into farm children, rural children and Innsbruck-town children. Within the farming environment, regular exposure to the following key factors of interest was predefined: the animal shed, the hay loft and farm milk. Wheezing in the past 12 months (W12), doctor-diagnosed (dd)-asthma, dd-allergic rhinitis and dd-atopic dermatitis were evaluated by using standardized questions from the International Study of Asthma and Allergies in Childhood (ISAAC)ResultsFarm children with regular exposure showed a lower risk for W12 (odds ratios (OR)xa0=xa00.3; 95xa0%; confidence interval (CI) 0.2–0.5), dd-asthma (ORxa0=xa00.4; 95xa0% CI 0.2–0.9) and dd-hay fever (OR 0.2; 95xa0% CI 0.1–0.4). The protective effect of regular exposure extended to rural children but included W12 and dd-hay fever only. Multivariate logistic regression analysis for children being regularly exposed revealed protective attributes for the animal shed, the hay loft and farm milk.ConclusionThese data show that regular exposure to a farming environment protects against wheezing, asthma and hay fever. Regarding wheezing and hay fever, this effect was not restricted to children living on a farm but also notable in rural children with regular farm contact.ZusammenfassungHintergrundIn den letzten Jahren konnten zahlreiche Studien zeigen, dass Kinder, die am Bauernhof aufwachsen, seltener an atopischen Erkrankungen leiden. Die GABRIEL Advanced Multicenterstudie, durchgeführt in Deutschland, Schweiz, Österreich und Polen, hat sich zum Ziel gesetzt mögliche protektive Faktoren betreffend den „Bauernhof-Effekt“ aufzudecken. Während die GABRIEL Advanced Studie ausschließlich die am Land lebenden Kinder inkludierte, wurden in der vorliegenden Arbeit auch die Daten von Stadtkindern (Innsbruck) in die Analyse mit einbezogen.MethodikMittels Screening-Fragebogen wurden Kinder je nach Lebensraum in Bauernhofkinder, Landkinder und Innsbruck-Stadtkinder stratifiziert und dieser Lebensraum dann mit der Prävalenz atopischer Erkrankungen korreliert. Am Bauernhof wurden als mögliche protektive Faktoren regelmäßiger Kontakt zu Tierstall und/oder Futterscheune (Heustall) und der regelmäßige Konsum von Bauernhofmilch prädefiniert. Die Prävalenz von ärztlich diagnostiziertem (doctor diagnosed=dd) Asthma, dd-allergischer Rhinitis, dd atopischer Dermatitis, als auch Wheezing in den letzten 12 Monaten (W12), wurden mittels standardisiertem ISAAC Fragebogen erhoben.ErgebnisseBauernhofkinder mit regelmäßiger Exposition zu Tierstall, Futterscheune oder regelmäßigem Konsum von Bauernhofmilch hatten ein deutlich geringeres Risiko für W12 (ORxa0=xa00,3; 95xa0% CI 0,2–0,5), dd-Asthma (ORxa0=xa00,4; 95xa0% CI 0,2–0,9) und dd-allergischer Rhinitis (OR 0,2; 95xa0% CI 0,1–0,4). Der protektive Effekt einer regelmäßigen Exposition erstreckte sich auch auf Landkinder, allerdings beschränkt auf W12 und dd-allergische Rhinits. Auch die multivariate logistische Regressionsanalyse zeigte protektive Attribute für Stall, Scheune als auch für Bauernhofmilch, mit jedoch unterschiedlichem Potential auf die einzelnen Outcomeparameter.SchlussfolgerungDie vorliegenden Daten bestätigen, dass regelmäßige Bauernhofexposition im Kindesalter sich protektiv auf Wheezing, Asthma und allergische Rhinits auswirkt. Dieser Effekt zeigte sich nicht nur für die am Bauernhof lebenden Kindern, sondern erstreckte sich auch auf Kinder im ländlichen Umfeld mit regelmäßigem Bauernhofkontakt.