Hospital of Bruneck

Brunico - Bruneck, Italy

Hospital of Bruneck

Brunico - Bruneck, Italy
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Pechlaner R.,Innsbruck Medical University | Tsimikas S.,University of California at San Diego | Yin X.,King's College London | Willeit P.,Innsbruck Medical University | And 10 more authors.
Journal of the American College of Cardiology | Year: 2017

Background Routine apolipoprotein (apo) measurements for cardiovascular disease (CVD) are restricted to apoA-I and apoB. Here, the authors measured an unprecedented range of apolipoproteins in a prospective, population-based study and relate their plasma levels to risk of CVD. Objectives This study sought to measure apolipoproteins directly by mass spectrometry and compare their associations with incident CVD and to obtain a system-level understanding of the correlations of apolipoproteins with the plasma lipidome and proteome. Methods Associations of 13 apolipoproteins, 135 lipid species, and 211 other plasma proteins with incident CVD (91 events), defined as stroke, myocardial infarction, or sudden cardiac death, were assessed prospectively over a 10-year period in the Bruneck Study (N = 688) using multiple-reaction monitoring mass spectrometry. Changes in apolipoprotein and lipid levels following treatment with volanesorsen, a second-generation antisense drug targeting apoC-III, were determined in 2 human intervention trials, one of which was randomized. Results The apolipoproteins most significantly associated with incident CVD were apoC-II (hazard ratio per 1 SD [HR/SD]: 1.40; 95% confidence interval [CI]: 1.17 to 1.67), apoC-III (HR/SD: 1.38; 95% CI: 1.17 to 1.63), and apoE (HR/SD: 1.31; 95% CI: 1.13 to 1.52). Associations were independent of high-density lipoprotein (HDL) and non-HDL cholesterol, and extended to stroke and myocardial infarction. Lipidomic and proteomic profiles implicated these 3 very-low-density lipoprotein (VLDL)-associated apolipoproteins in de novo lipogenesis, glucose metabolism, complement activation, blood coagulation, and inflammation. Notably, apoC-II/apoC-III/apoE correlated with a pattern of lipid species previously linked to CVD risk. ApoC-III inhibition by volanesorsen reduced plasma levels of apoC-II, apoC-III, triacylglycerols, and diacylglycerols, and increased apoA-I, apoA-II, and apoM (all p < 0.05 vs. placebo) without affecting apoB-100 (p = 0.73). Conclusions The strong associations of VLDL-associated apolipoproteins with incident CVD in the general community support the concept of targeting triacylglycerol-rich lipoproteins to reduce risk of CVD. © 2017 The Authors

Gruber E.,Hospital of Bruneck | Oberhammer R.,Hospital of Bruneck | Balkenhol K.,EURAC Institute of Mountain Emergency Medicine | Strapazzon G.,EURAC Institute of Mountain Emergency Medicine | And 4 more authors.
Resuscitation | Year: 2014

Objective: In some emergency situations resuscitation and ventilation may have to be performed by basic life support trained personnel, especially in rural areas where arrival of advanced life support teams can be delayed. The use of advanced airway devices such as endotracheal intubation has been deemphasized for basically-trained personnel, but it is unclear whether supraglottic airway devices are advisable over traditional mask-ventilation. Methods: In this prospective, randomized clinical single-centre trial we compared airway management and ventilation performed by nurses using facemask, laryngeal mask Supreme (LMA-S) and laryngeal tube suction-disposable (LTS-D). Basic life support trained nurses (n= 20) received one-hour practical training with each device. ASA 1-2 patients scheduled for elective surgery were included (n= 150). After induction of anaesthesia and neuromuscular block nurses had two 90-second attempts to manage the airway and ventilate the patient with volume-controlled ventilation. Results: Ventilation failed in 34% of patients with facemask, 2% with LMA-S and 22% with LTS-D (P<0.001). In patients who could be ventilated successfully mean tidal volume was 240±210ml with facemask, 470±120ml with LMA-S and 470±140ml with LTS-D (P<0.001). Leak pressure was lower with LMA-S (23.3±10.8cm H2O, 95% CI 20.2-26.4) than with LTS-D (28.9±13.9cm·H2O, 95% CI 24.4-33.4; P=0.047). Conclusions: After one hour of introductory training, nurses were able to use LMA-S more effectively than facemask and LTS-D. High ventilation failure rates with facemask and LTS-D may indicate that additional training is required to perform airway management adequately with these devices. High-level trials are needed to confirm these results in cardiac arrest patients. © 2014 Elsevier Ireland Ltd.

PubMed | University of Verona, Hospital of Bruneck, Innsbruck Medical University and King's College London
Type: Journal Article | Journal: Diabetes/metabolism research and reviews | Year: 2016

Type 2 diabetes mellitus (T2DM) is closely associated with elevated body iron stores. The hormone hepcidin is the key regulator of iron homeostasis. Inadequately low hepcidin levels were recently reported in subjects with manifest T2DM. We investigated whether alterations of hepcidin levels precede the manifestation of T2DM and predict T2DM development independently of established risk conditions.This prospective population-based study included 675 subjects aged 50-89 years, 51.9% of whom were female. Hepcidin levels were measured by gold standard tandem mass spectrometry. Diabetes was diagnosed according to American Diabetes Association criteria, and incident diabetes was recorded between baseline in 2000 and 2010.The baseline hepcidin-to-ferritin ratio in subjects that subsequently developed diabetes during follow-up was reduced on average by 29.8% as compared with subjects with normal glucose tolerance (95% confidence interval, -50.7% to -0.2%; p=0.049). After adjustment for age, sex, and serum ferritin, higher hepcidin levels were associated with reduced risk of incident diabetes (hazard ratio per 1-unit higher log2 hepcidin, 0.80; 95% confidence interval, 0.64-0.98; p=0.035; 33 events). Additional adjustment for established diabetes risk factors and determinants of hepcidin concentration did not appreciably change these results (HR, 0.81; 95% CI, 0.66-0.99). Likewise, inadequately low hepcidin levels were also detected in subjects with prevalent T2DM (n=76).Hepcidin levels that are inadequately low in relation to body iron stores are an independent predictor for incident T2DM and may contribute to diabetes-related tissue iron overload. Copyright 2015 John Wiley & Sons, Ltd.

PubMed | Study Center Confraternitaet Vienna, Innsbruck Medical University, Leiden University, VU University Amsterdam and 2 more.
Type: Journal Article | Journal: Movement disorders : official journal of the Movement Disorder Society | Year: 2016

The aim of this study was to evaluate odor identification testing as a quick, cheap, and reliable tool to identify PD.Odor identification with the 16-item Sniffin Sticks test (SS-16) was assessed in a total of 646 PD patients and 606 controls from three European centers (A, B, and C), as well as 75 patients with atypical parkinsonism or essential tremor and in a prospective cohort of 24 patients with idiopathic rapid eye movement sleep behavior disorder (center A). Reduced odor sets most discriminative for PD were determined in a discovery cohort derived from a random split of PD patients and controls from center A using L1-regularized logistic regression. Diagnostic accuracy was assessed in the rest of the patients/controls as validation cohorts.Olfactory performance was lower in PD patients compared with controls and non-PD patients in all cohorts (each P < 0.001). Both the full SS-16 and a subscore of the top eight discriminating odors (SS-8) were associated with an excellent discrimination of PD from controls (areas under the curve 0.90; sensitivities 83.3%; specificities 82.0%) and from non-PD patients (areas under the curve 0.91; sensitivities 84.1%; specificities 84.0%) in all cohorts. This remained unchanged when patients with >3 years of disease duration were excluded from analysis. All 8 incident PD cases among patients with idiopathic rapid eye movement sleep behavior disorder were predicted with the SS-16 and the SS-8 (sensitivity, 100%; positive predictive value, 61.5%).Odor identification testing provides excellent diagnostic accuracy in the distinction of PD patients from controls and diagnostic mimics. A reduced set of eight odors could be used as a quick tool in the workup of patients presenting with parkinsonism and for PD risk indication. 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Mahlknecht P.,Innsbruck Medical University | Mahlknecht P.,University College London | Seppi K.,Innsbruck Medical University | Frauscher B.,Innsbruck Medical University | And 12 more authors.
Movement Disorders | Year: 2015

Background: The prevalence of rapid eye movement sleep behavior disorder (RBD) and its association with markers of neurodegeneration in the general population are poorly defined. Methods: We assessed the prevalence of probable RBD defined by two validated questionnaires, the RBD Screening Questionnaire (RBDSQ) and the Innsbruck RBD-Inventory (RBD-I), and studied its associations with clinical and imaging markers for neurodegeneration in the Bruneck Study cohort aged 60 y or older. Results: Of the 456 participants without Parkinson's disease, 4.6% (RBDSQ; 95%CI, 3.0%-7.0%) and 7.7% (RBD-I; 95%CI, 5.6%-10.5%) had probable RBD. Probable RBD diagnosed with either of the questionnaires was associated with hyposmia (trend; P < 0.1), anxiety (P < 0.05), depression (P < 0.05), antidepressant use (P < 0.05), and self-reported non-motor symptoms (P < 0.01), specifically, dribbling saliva, memory problems, apathy, concentration problems, and anxiety. Conclusions: Our findings may provide a basis for future studies intending to identify cohorts at risk for Lewy body diseases through screening of the general elderly population for RBD. © 2015 International Parkinson and Movement Disorder Society.

Pechlaner R.,Innsbruck Medical University | Kiechl S.,Innsbruck Medical University | Willeit P.,Innsbruck Medical University | Willeit P.,University of Cambridge | And 8 more authors.
Journal of the American Heart Association | Year: 2014

Background-Haptoglobin (Hp) is an abundant plasma protein with antioxidant properties. The Hp 2-2 genotype has previously been linked to coronary heart disease risk in individuals with elevated glycosylated hemoglobin (HbA1c). We investigated the association of Hp and HbA1c with cardiovascular disease (CVD) in the longitudinal, population-based Bruneck Study. Methods and Results-Hp genotype was determined by polymerase chain reaction according to standard procedures and HbA1c concentration by a Diabetes Control and Complications Trial-aligned assay. HbA1c was measured in 1995, 2000, and 2005. Occurrence of the combined CVD endpoint of myocardial infarction or stroke was recorded between 1995 and 2010. Outcome analyses employed the Cox proportional hazards model with HbA1c category as time-varying covariate. At baseline in 1995, 806 subjects (male sex, 49.3%; age, mean ± standard deviation, 62.70 ± 11.08 years) were included. During follow-up, 123 subjects experienced at least 1 CVD event (48 suffered myocardial infarction, 68 stroke, and 7 both). Among subjects with HbA1c≥6.5% (≥48 mmol/mol), those with the Hp 2-2 genotype did not show an elevated risk of incident CVD compared with those with other genotypes (age- and sex-adjusted hazard ratio [95% CI], 0.47 [0.19, 1.13], P=0.092) and a null association was also observed in subjects with HbA1c<6.5% (1.10 [0.75, 1.62], P=0.629) (P for interaction=0.082). Conclusions-Subjects with the Hp 2-2 genotype and elevated HbA1c compared with subjects with other Hp genotypes and elevated HbA1c did not show increased CVD risk. © 2014 The Authors.

Mahlknecht P.,Innsbruck Medical University | Mahlknecht P.,University College London | Kiechl S.,Innsbruck Medical University | Stockner H.,Innsbruck Medical University | And 4 more authors.
Parkinsonism and Related Disorders | Year: 2015

Objective: Mild parkinsonian signs (MPS) are common in the elderly population and are associated with a wide range of adverse health outcomes, including incident Parkinson's disease (PD). We aimed to prospectively evaluate potential risk factors for incident MPS. Methods: Participants of the population-based Bruneck Study representative for the general elderly community underwent a baseline assessment of substantia nigra (SN)-echogenicity with transcranial sonography, olfactory function with the Sniffin' Sticks identification test and vascular risk according to the Framingham risk score as well as a baseline and 5-year follow-up neurological examination. MPS were defined according to established criteria based on the entire motor section of the Unified PD Rating Scale. Participants with PD at baseline or follow-up and subjects with MPS at baseline were excluded. A logistic regression analysis adjusted for age and sex was used to detect risk factors for incident MPS in the remaining 393 participants. Results: SN-hyperechogenicity and hyposmia were related to the development of MPS with odds ratios of 2.0 (95%CI, 1.1-3.7) and 1.6 (95%CI, 1.0-2.7), respectively, while increased vascular risk was not. Having both, SN-hyperechogenicity and hyposmia, was associated with an odds ratio of 3.0 (95%CI, 1.2-7.7) for incident MPS. Among the various motor domains, increased SN-echogenicity predicted the development of bradykinesia and rigidity, whereas diminished olfactory function predicted the development of impaired axial motor function. Conclusions: In addition to their established roles as risk factors for PD, SN-hyperechogenicity and hyposmia are associated with an increased risk for MPS in the general elderly community. © 2015 Elsevier Ltd.

Mahlknecht P.,Innsbruck Medical University | Kiechl S.,Innsbruck Medical University | Bloem B.R.,Radboud University Nijmegen | Willeit J.,Innsbruck Medical University | And 5 more authors.
PLoS ONE | Year: 2013

Background:Although gait disorders are common in the elderly, the prevalence and overall burden of these disorders in the general community is not well defined.Methods:In a cross-sectional investigation of the population-based Bruneck Study cohort, 488 community-residing elderly aged 60-97 years underwent a thorough neurological assessment including a standardized gait evaluation. Gait disorders were classified according to an accepted scheme and their associations to falls, neuropsychological measures, and quality of life were explored.Results:Overall, 32.2% (95% confidence interval [CI] 28.2%-36.4%) of participants presented with impaired gait. Prevalence increased with age (p<0.001), but 38.3% (95%CI 30.1%-47.3%) of the subjects aged 80 years or older still had a normally preserved gait. A total of 24.0% (95%CI 20.4%-28.0%) manifested neurological gait disorders, 17.4% (14.3%-21.0%) non-neurological gait problems, and 9.2% (6.9%-12.1%) a combination of both. While there was no association of neurological gait disorders with gender, non-neurological gait disorders were more frequent in women (p = 0.012). Within the group of neurological gait disorders 69.2% (95%CI 60.3%-76.9%) had a single distinct entity and 30.8% (23.1%-39.7%) had multiple neurological causes for gait impairment. Gait disorders had a significant negative impact on quantitative gait measures, but only neurological gait disorders were associated with recurrent falls (odds ratio 3.3; 95%CI 1.4-7.5; p = 0.005 for single and 7.1; 2.7-18.7; p<0.001 for multiple neurological gait disorders). Finally, we detected a significant association of gait disorders, in particular neurological gait disorders, with depressed mood, cognitive dysfunction, and compromised quality of life.Conclusions:Gait disorders are common in the general elderly population and are associated with reduced mobility. Neurological gait disorders in particular are associated with recurrent falls, lower cognitive function, depressed mood, and diminished quality of life. © 2013 Mahlknecht et al.

Mahlknecht P.,Innsbruck Medical University | Seppi K.,Innsbruck Medical University | Stockner H.,Innsbruck Medical University | Nocker M.,Innsbruck Medical University | And 7 more authors.
Neurodegenerative Diseases | Year: 2013

Background: The clinical diagnosis of Parkinson's disease (PD) is currently anchored in its cardinal motor symptoms. According to hospital-based studies, an enlarged echogenicity in the area of the substantia nigra (SN) assessed with transcranial sonography (TCS) may represent a useful biomarker in the diagnosis of PD. Objective: To evaluate SN hyperechogenicity as a marker for PD in the Bruneck Study cohort, which is representative of the general elderly community. Methods: The diagnostic accuracy of TCS in distinguishing clinically diagnosed PD from nonparkinsonian subjects was assessed in 574 subjects from this cohort. Results: There was a good diagnostic accuracy of TCS in distinguishing PD subjects from nonparkin sonian subjects with an area under the curve value of 0.82. At a receiveroperating characteristic curve analysis-based cutoff value for SN hyperechogenicity of 0.18 cm 2 , TCS had a sensitivity of 88.2% (95% confidence interval, CI, 64.4-98.0), a specificity of 77.0% (95% CI 72.8-80.6), a positive predictive value of 12.7% (95% CI 7.8-20.0) and a negative predictive value of 99.4% (95% CI 97.8-100.0) for subjects with clinically definite PD at baseline. When analyzing the same population after 5 years with regard to the presence of known and newly diagnosed PD cases, baseline TCS yielded very similar diagnostic accuracy values. Conclusion: SN hyperechogenicity may represent a useful biomarker for PD not only in a hospital-based setting but also in the general community. Copyright © 2013 S. Karger AG, Basel.

PubMed | Hospital of Bruneck and Innsbruck Medical University
Type: Journal Article | Journal: Movement disorders : official journal of the Movement Disorder Society | Year: 2016

Recently, the International Parkinson and Movement Disorder Society has defined research criteria for prodromal Parkinsons disease (PD), but to date their predictive value has not yet been tested in population-based cohorts.We retrospectively applied these criteria to the longitudinal Bruneck Study cohort aged 55-94 years using recorded data on all included risk and prodromal markers that are quick and easily assessable.After excluding participants with idiopathic PD or secondary parkinsonism, prevalence of probable prodromal PD in the remaining 539 participants was 2.2% (95% confidence interval, 1.2%-3.9%). Of 488 participants followed up over 5 years, 11 developed incident PD. Sensitivity of probable prodromal PD status for incident PD was 54.6% (95% confidence interval, 28.0%-78.8%), specificity was 99.2% (97.8%-99.8%), positive predictive value was 60.0% (31.2%-83.3%), and negative predictive value was 99.0% (97.5%-99.6%).Our findings suggest that the new research criteria for prodromal PD are a promising tool to identify cases of incident PD over 5 years, arguing for their usefulness in defining target populations for disease-prevention trials. 2016 International Parkinson and Movement Disorder Society.

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