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Abstract Background Cardiopulmonary resuscitation in mountain environment is challenging. Continuous chest compressions during transport or hoist rescue are almost impossible without mechanical chest compression devices. Current evidence is predominantly based on studies conducted by urbane ambulance service. Therefore, we aimed to investigate the feasibility of continuous mechanical chest compression during alpine terrestrial transport using three different devices. Methods Randomized triple crossover prospective study in an alpine environment. Nineteen teams of the Austrian Mountain Rescue Service trained according to current ERC guidelines performed three runs each of a standardised alpine rescue-scenario, using three different devices for mechanical chest compression. Quality of CPR, hands-off-time and displacement of devices were measured. Results The primary outcome of performed work (defined as number of chest compressions x compression depth) was 66,062 mm (2832) with Corpuls CPR, 65,877 mm (6163) with Physio-Control LUCAS 3 and 40,177 mm (4396) with Schiller Easy Pulse. The difference both between LUCAS 3 and Easy Pulse (Δ 25,700; 95% confidence interval 21,118 – 30,282) and between Corpuls CPR and Easy Pulse (Δ 25,885; 23,590 – 28,181) was significant. No relevant differences were found regarding secondary outcomes. Conclusion Mechanical chest compression devices provide a viable option in the alpine setting. For two out of three devices (Corpuls CPR and LUCAS 3) we found adequate quality of CPR. Those devices also maintained a correct placement of the piston even during challenging terrestrial transport. Adequate hands-off-times and correct placement could be achieved even by less trained personnel.

Background: The limited applicability of evidence from RCTs in real-word practice is considered a potential bottleneck for evidence-based practice but rarely systematically assessed. Using our failure to recruit patients into a perioperative beta-blocker trial, we set out to analyse the restrictiveness and generalisability of trial eligibility criteria in a real-world cohort., Methods: We prospectively included adult patients (≥18 yr) scheduled for elective noncardiac surgery at an academic tertiary care facility who were screened for inclusion in a planned perioperative beta-blocker RCT, which was terminated owing to recruitment failure. The primary outcome was the proportion of screened patients who matched the eligibility criteria of 36 published RCTs included in a large Cochrane meta-analysis on perioperative beta-blocker therapy. The pragmatic/explanatory level of each RCT was assessed using the PRagmatic-Explanatory Continuum Indicator Summary 2 (PRECIS-2) score, which ranges from 9 points (indicating a very explanatory study) to 45 points (indicating a very pragmatic study)., Results: A total of 2241 patients (54% female, n=1215; 52 [standard deviation, 20] yr) were included for the assessment of trial eligibility between October 2015 and January 2016. Only a small proportion of patients matched the inclusion and exclusion criteria for each of the 36 RCTs, ranging from 53% to 0%. The average proportion of patients who did match the eligibility criteria of all 36 RCTs was 6.5% (n=145; 95% confidence interval, 6.3-6.6). A higher PRECIS-2 score was associated with a higher proportion of matching patients (P<0.001)., Conclusions: Trial eligibility criteria in perioperative beta-blocker therapy trials are overly restrictive and not generalisable to a real-world surgical population., Clinical Trial Registration: EudraCT#: 2015-002366-23., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: A considerable proportion of patients with angina-like symptoms in an emergency department have very low pretest probability for acute myocardial infarction (AMI). Numerous algorithms exist for the exclusion of AMI, usually including laboratory tests. We aimed to investigate whether patients with very low risk can safely be identified by ECG and clinical information without biomarker testing, contributing to saving time and costs., Methods: Prospective diagnostic test accuracy study. We included all consecutive patients presenting with angina at the department of emergency medicine of a tertiary care hospital during a 1-year period. Using clinical information without biomarker testing and ECG, the "Mini-GRACE score," based on the well-established GRACE-score without using laboratory parameters was calculated. In a cohort design we compared the index test Mini-GRACE to AMI as reference standard in the final diagnosis using standard measures of diagnostic test accuracy., Results: We included 2755 patients (44% female, age 44 ± 17 years). AMI was diagnosed in 103 (4%) patients, among those 44% with STEMI. Overall 2562 patients (93%) had a negative "Mini-GRACE," four (0.2%) of these patients had myocardial infarction, and this results in a sensitivity of 96.1% (95% CI 90.4%-98.9%), specificity 96.5% (95.7%-97.1%), positive predictive value 51.3% (46.3%-56.3%) and negative predictive value 99.8% (99.6%-99.9%). Model performance according to C statistic (0.90) and Brier score (0.0045) was excellent. In rule-out patients 30-day mortality was 0.3% and 1-year mortality was 0.8%., Conclusions: Patients with very low risk of AMI can be identified with high certainty using clinical information without biomarker testing and ECG. Cardiac biomarkers might be avoided in such cases, potentially leading to a significant cost reduction., (© 2020 The Authors. International Journal of Clinical Practice published by John Wiley & Sons Ltd.)

Background: High quality cardiopulmonary resuscitation is a key factor in survival with good overall quality of life after out-of-hospital cardiac arrest. Current evidence is predominantly based on studies conducted at low altitude, and do not take into account the special circumstances of alpine rescue missions. We therefore aimed to investigate the influence of physical strain at high altitude on the quality of cardiopulmonary resuscitation., Methods: Alpine field study. Twenty experienced mountaineers of the Austrian Mountain Rescue Service trained in Basic Life Support (BLS) performed BLS on a manikin in groups of two for 16 min. The scenario was executed at baseline altitude and immediately after a quick ascent over an altitude difference of 1200 m at 3454 m above sea level. The sequence of scenarios was randomised for a cross over analysis. Quality of CPR and exhaustion of participants (vital signs, Borg-Scale, Nine hole peg test) were measured and compared between high altitude and baseline using random-effects linear regression models., Results: The primary outcome of chest compression depth significantly decreased at high altitude compared to baseline by 1 cm (95% CI 0.5 to 1.3 cm, p < 0.01). There was a significant reduction in the proportion of chest compressions in the target depth (at least 5 cm pressure depth) by 55% (95% CI 29 to 82%, p < 0.01) and in the duration of the release phase by 75 ms (95% CI 48 to 101 ms, p < 0.01). No significant difference was found regarding hands-off times, compression frequency or exhaustion., Conclusion: Physical strain during a realistic alpine rescue mission scenario at high altitude led to a significant reduction in quality of resuscitation. Resuscitation guidelines developed at sea level are not directly applicable in the mountain terrain.

Objective: Risk assessment plays a decisive role in the management of acute coronary syndrome (ACS). The GRACE and the CRUSADE scores are among the most frequently used risk assessment tools. We aimed to compare the performance of the GRACE and CRUSADE risk scores to predict in-hospital mortality and major bleeding in a contemporary ACS population at a high-volume academic hospital., Methods: All patients treated for ACS from January 1, 2006 to December 31, 2015 at a tertiary care centre were prospectively enrolled. We calculated GRACE and CRUSADE risk scores. We compared the discrimination capacity of both scores for in-hospital mortality and major bleeding., Results: In total 4087 patients (1151 [28.2%] female; age 62 ± 14 years) were included. Among these 2218 (54.3%) were diagnosed with ST-elevation myocardial infarction, 113 (2.8%) died in hospital and major bleeding occurred in 65 (1.6%). Discrimination capacity for in-hospital mortality of the GRACE score was superior to the CRUSADE score (receiver operator characteristic area under the curve (AUC) 0.91 (95% CI 0.89-0.93) vs 0.83 (95% CI 0.80-0.86); P < .01). Performance for major bleeding differed but was poor for both scores (AUC 0.71 [0.65-0.76] for GRACE vs 0.61 [0.55-0.68] for CRUSADE; P < .01)., Conclusion: The GRACE score appears to be superior over CRUSADE to predict in-hospital mortality. Major bleeding is rare in the era of primary PCI and performance of both scores for this outcome was poor., (© 2019 The Authors. International Journal of Clinical Practice published by John Wiley & Sons Ltd.)

Background: Increased fructose intake has been associated with metabolic consequences such as impaired hepatic lipid metabolism and development of nonalcoholic fatty liver disease (NAFLD)., Objectives: The aim of this study was to investigate the role of fructose in glucose and lipid metabolism in the liver, heart, skeletal muscle, and adipose tissue., Methods: Ten healthy subjects (age: 28 ± 19 y; BMI: 22.2 ± 0.7 kg/m2) underwent comprehensive metabolic phenotyping prior to and 8 wk following a high-fructose diet (150 g daily). Eleven patients with NAFLD (age: 39.4 ± 3.95 y; BMI: 28.4 ± 1.25) were characterized as "positive controls." Insulin sensitivity was analyzed by a 2-step hyperinsulinemic euglycemic clamp, and postprandial interorgan crosstalk of lipid and glucose metabolism was evaluated, by determining postprandial hepatic and intra-myocellular lipid and glycogen accumulation, employing magnetic resonance spectroscopy (MRS) at 7 T. Myocardial lipid content and myocardial function were assessed by 1H MRS imaging and MRI at 3 T., Results: High fructose intake resulted in lower intake of other dietary sugars and did not increase total daily energy intake. Ectopic lipid deposition and postprandial glycogen storage in the liver and skeletal muscle were not altered. Postprandial changes in hepatic lipids were measured [Δhepatocellular lipid (HCL)&#95;healthy&#95;baseline: -15.9 ± 10.7 compared with ± ΔHCL&#95;healthy&#95;follow-up: -6.9 ± 4.6; P = 0.17] and hepatic glycogen (Δglycogen&#95;baseline: 64.4 ± 14.1 compared with Δglycogen&#95;follow-up: 51.1 ± 9.8; P = 0.42). Myocardial function and myocardial mass remained stable. As expected, impaired hepatic glycogen storage and increased ectopic lipid storage in the liver and skeletal muscle were observed in insulin-resistant patients with NAFLD., Conclusions: Ingestion of a high dose of fructose for 8 wk was not associated with relevant metabolic consequences in the presence of a stable energy intake, slightly lower body weight, and potentially incomplete absorption of the orally administered fructose load. This indicated that young, metabolically healthy subjects can at least temporarily compensate for increased fructose intake. This trial was registered at www.clinicaltrials.gov as NCT02075164., (Copyright © The Author(s) 2019.)

Purpose: To investigate [ 11 C]acetate PET-surrogate parameter of fatty acid synthase activity-as suitable tool for diagnosis and monitoring of liver steatosis., Methods: In this retrospective study, data were obtained from 83 prostatic carcinoma patients from 1/2008 to 1/2014. Mean HU was calculated from unenhanced CT of all patients from liver with liver HU less than 40 as threshold for liver steatosis. SUV max of the liver and of the blood pool in thoracic aorta (as background for calculation of a liver/background ratio [SUV l/b ]) was measured. t test was used with a P < 0.05 considered as statistically significant difference and ROC analysis was used for calculating specificity and sensitivity., Results: 19/83 patients (20%) had diagnosis of hepatic steatosis according to CT. Uptake of [ 11 C]acetate was significantly higher in patients with hepatic steatosis as compared to control group (SUV max 7.96 ± 2.0 vs. 5.48 ± 2.3 [P < 0.001]). There was also a significant correlation between both SUV max (r = - 0.52, P < 0.001) and SUV l/b (r = - 0.59, P < 0.001) with the density (HU) of the liver. In ROC analysis for detection of liver steatosis SUV max (threshold: 5.86) had a sensitivity of 94% and specificity of 69% with an AUC of 0.81. Increasing body mass index is correlated with the severity of steatosis., Conclusion: We showed for the first time that hepatic steatosis associates with increased [ 11 C]acetate uptake. Also, severity of steatosis correlates with [ 11 C]acetate uptake. [ 11 C]acetate uptake PET seems promising for the assessment of liver steatosis.

Background & Aims: With the rising prevalence of non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) non-invasive tools obtaining pathomechanistic insights to improve risk stratification are urgently needed. We therefore explored high- and ultra-high-field magnetic resonance spectroscopy (MRS) to obtain novel mechanistic and diagnostic insights into alterations of hepatic lipid, cell membrane and energy metabolism across the spectrum of NAFLD., Methods: MRS and liver biopsy were performed in 30 NAFLD patients with NAFL (n=8) or NASH (n=22). Hepatic lipid content and composition were measured using 3-Tesla proton ( 1 H)-MRS. 7-Tesla phosphorus ( 31 P)-MRS was applied to determine phosphomonoester (PME) including phosphoethanolamine (PE), phosphodiester (PDE) including glycerophosphocholine (GPC), phosphocreatine (PCr), nicotinamide adenine dinucleotide phosphate (NADPH), inorganic phosphate (Pi), γ-ATP and total phosphorus (TP). Saturation transfer technique was used to quantify hepatic ATP flux., Results: Hepatic steatosis in 1 H-MRS highly correlated with histology (P<.001) showing higher values in NASH than NAFL (P<.001) without differences in saturated or unsaturated fatty acid indices. PE/TP ratio increased with advanced fibrosis (F3/4) (P=.002) whereas GPC/PME+PDE decreased (P=.05) compared to no/mild fibrosis (F0-2). γ-ATP/TP was lower in advanced fibrosis (P=.049), while PCr/TP increased (P=.01). NADPH/TP increased with higher grades of ballooning (P=.02). Pi-to-ATP exchange rate constant (P=.003) and ATP flux (P=.001) were lower in NASH than NAFL., Conclusions: Ultra-high-field MRS, especially saturation transfer technique uncovers changes in energy metabolism including dynamic ATP flux in inflammation and fibrosis in NASH. Non-invasive profiling by MRS appears feasible and may assist further mechanistic and therapeutic studies in NAFLD/NASH., (© 2017 The Authors Liver International Published by John Wiley & Sons Ltd.)

Background: Bariatric patients often suffer from vitamin D deficiency (VDD), and both, morbid obesity and VDD, are related to non-alcoholic fatty liver disease. However, limited data are available regarding best strategies for treating VDD, particularly, in bariatric patients undergoing omega-loop gastric bypass (OLGB). Therefore, we examined the efficacy and safety of a forced vitamin D dosing regimen and intervention effects in liver fibrotic patients., Methods: In this double-blind, randomized, placebo-controlled trial, 50 vitamin D-deficient patients undergoing OLGB were randomly assigned to receive, in the first month postoperatively, oral vitamin D 3 (≤3 doses of 100,000 IU; intervention group) or placebo as loading dose (control group) with subsequent maintenance dose (3420 IU/day) in both groups until 6-month visit., Results: Compared with control group, higher increase of 25(OH)D (67.9 (21.1) vs. 55.7 nmol/L (21.1); p = 0.049) with lower prevalence of secondary hyperparathyroidism (10 vs. 24 %; p = 0.045) was observed in intervention group. No (serious) adverse events related to study medication were found. The loading dose regimen was more effective in increasing 25(OH)D in patients with significant liver fibrosis while this was not the case for conventional supplementation (placebo with maintenance dose) (71.5 (20.5) vs. 22.5 nmol/L (13.8); p = 0.022; n = 14)., Conclusions: Our findings indicate that a high vitamin D 3 loading dose, in the first month postoperatively, with subsequent maintenance dose is effective and safe in achieving higher vitamin D concentrations in OLGB patients. Unexpectedly, it is more effective in patients with significant liver fibrosis which is of potentially high clinical relevance and requires further investigation.

Objectives: The quality of telephone-assisted cardiopulmonary resuscitation (CPR) needs improvement. This study investigates whether a dispatchers' perception is an adequate measure of the actual quality of CPR provided by laypersons., Material and Methods: Individual participant data from 3 randomized simulation trials, with identical methodology but different interventions, were combined for this analysis. Professional dispatchers gave telephone assistance to laypersons, who each provided 10 minutes of CPR on a manikin. Dispatchers were requested to classify the quality of providers' CPR as adequate or inadequate. Based on actual readings from manikins we classified providers' performance as adequate at 5-6 cm for depth and 100-120 compressions per minute (cpm) for rate. We calculated metrics of dispatcher accuracy., Results: Six dispatchers rated the performance of 94 laypersons (38 women [42%]) with a mean (SD) age of 37 (14) years. In 905 analyzed minutes of telephone-assisted CPR, the mean compression depth and rate was 41 (13) mm and 98 (24) cpm, respectively. Analysis of dispatchers' diagnostic test accuracy for adequate compression depth yielded a sensitivity of 65% (95 CI 36%-95%) and specificity of 42% (95% CI, 32%-53%). Analysis of their assessment of adequate compression rate yielded a sensitivity of 75% (95% CI, 64%-86%) and specificity of 42% (95% CI, 32%-52%). Although dispatchers always underestimated the actual values of CPR parameters, the female dispatchers evaluations were less inaccurate than the evaluations of make dispatchers; the dispatchers overall (males and females together) underestimated the adequacy of female laypersons' CPR performance to a greater degree than female dispatchers did., Conclusion: The ability of dispatchers to estimate the quality of telephone-assisted CPR is limited. Dispatchers estimates of CPR adequacy needs to be studied further in order to find ways that telephone-assisted CPR might be improved.

Introduction: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is multifactorial including metabolic, genetic (e.g. PNPLA3 [patatin-like phospholipase domain-containing 3 gene]), viral factors and drugs. Besides, there is evidence for a role of copper deficiency. Aim of the study was to evaluate the role of hepatic copper content, PNPLA3 in NAFLD patients with and without metabolic syndrome (MetS)., Methods: One-hundred seventy-four NAFLD patients, who underwent liver biopsy for diagnostic work-up, were studied. Diagnosis of MetS was based on the WHO Clinical Criteria. Steatosis was semiquantified as percentage of fat containing hepatocytes and was graded according to Brunt. Histological features of non-alcoholic steatohepatitis (NASH) were assessed using the Bedossa classification. Hepatic copper content (in μg/g dry weight) was measured by flame atomic absorption spectroscopy. SNP rs738409 in PNPLA3 was investigated by RT-PCR., Results: Mean hepatic copper content was 22.3 (19.6-25.1) μg/g. The mean percentage of histologically lipid containing hepatocytes was 42.2% (38.3-46.0) and correlated inversely with hepatic copper content (ρ=-0.358, P<0.001). By subgroup analysis this inverse correlation remained significant only in patients without MetS (OR: 0.959 [CI95%: 0.926-0.944], P=0.020). Presence of minor allele (G) of PNPLA3 was also associated with moderate/severe steatosis (≥33%) both in patients with (OR: 2.405 [CI95%: 1.220-4.744], P=0.011) and without MetS (OR: 2.481 [CI95%: 1.172-5.250], P=0.018), but was only associated with NASH (OR: 2.002 [CI95%: 1.062-3.772], P=0.032) and liver fibrosis (OR: 2.646 [CI95%: 1.299-5.389], P=0.007) in patients without MetS., Conclusion: Hepatic copper content and PNPLA3 mutations are associated with disease activity in NAFLD patients without MetS. Presence of MetS appears to mask the effects of hepatic copper and PNPLA3., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Background: Morbidly obese patients are at risk for non-alcoholic fatty liver disease (NAFLD) and vitamin D deficiency (VDD). Non-alcoholic steatohepatitis (NASH) is the progressive variant of NAFLD and can advance to fibrosis, cirrhosis, and liver cancer. We aimed to examine prevalence of liver fibrosis and its non-invasive predictors in bariatric patients with VDD (<75 nmol/l)., Methods: Baseline liver biopsy of a randomized controlled trial was performed in 46 patients with omega loop gastric bypass. Clinical, laboratory, and histological data were examined and tested with univariate and multivariable analysis., Results: In total, 80 % were females, aged 42 (SD 13) years with BMI 44 (4) kg/m(2). Twenty-six percent had diabetes mellitus (DM) and 44 % metabolic syndrome (MeS). Seventy-two percent had NASH, 11 % simple steatosis, and 17 % normal liver. In total, 30 % demonstrated significant fibrosis (F ≥ 2) with 9 % of advanced (F3) and 4 % cirrhosis (F4). Increased stages of fibrosis were primarily associated with higher levels of HOMA2-insulin resistance (IR), procollagen type I propeptide (P1NP), lower osteocalcin, albumin-corrected calcium, parathyroid hormone, vitamin D, male sex, and higher age. Other independent risk factors for advanced fibrosis were MeS (OR = 9.3 [0.99-87.5], p = 0.052) and DM (OR = 12.8 [1.2-137.4], p = 0.035). The fibrosis FIB-4 index <10.62 and NAFLD fibrosis score <-26.93 had a negative predictive value of 100 and 96 %, respectively., Conclusions: Liver fibrosis is frequent in morbidly obese patients with concurrent DM and/or MeS. Increased serum levels of IR, P1NP, lower osteocalcin, and VDD are clinically relevant predictors of fibrosis. Consequently, we suggest that patients with preoperative presence of these markers are at increased risk for liver fibrosis and should be monitored closely., Competing Interests: Compliance with Ethical StandardsInformed consent was obtained from each patient included in the study. The trial was approved by the local Ethical Committee of the Medical University of Vienna (Ref No.: 1899/2013) and the Austrian Competent Authority (Ref. No.: LCM-718280-0001) and conforms to the ethical guidelines of the 1975 Declaration of Helsinki [12]. Furthermore, the protocol was registered at clinicaltrials.gov (NCT02092376) and the European Clinical Trials Database (EudraCT: 2013-003546-16). The study methods are in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines for reporting randomized trials [13].DisclosuresThe authors ML, RK, CK, ST, FL, KS, TW, FW, and BL have no commercial associations that might be a conflict of interest in relation to this article. MT reports grants and personal fees from Albireo, Gilead, MSD, Falk, and Intercept, personal fees from Janssen and Novartis, and grants from Takeda outside the submitted work. In addition, MT is listed as a co-inventor in a patent on the Medical use of nor-UDCA licensed to Med Univ Graz. GP reports educational grant from Medtronic outside the submitted work.

Background: Omega-loop gastric bypass (OLGB) results in weight loss (WL) but data on its impact on liver and glucose metabolism compared to Roux-en-Y gastric bypass (RYGB) is lacking. Therefore, the aim of this study was to compare the development of hepatic and metabolic markers as well as WL between the above-mentioned surgical groups during the first postoperative year., Methods: We retrospectively evaluated the respective parameters in non-diabetic morbidly obese patients who underwent either RYGB (n = 25) or OLGB (n = 25)., Results: Compared to RYGB, OLGB showed a greater WL percentage. Liver transaminases dropped in RYGB, while rose in OLGB. No correlation between aspartate transaminase, alanine transaminase, and WL could be detected. Gamma-glutamyltransferase decreased significantly in RYGB over the first 3 months, while it increased in OLGB. We found higher levels of triglycerides, insulin, homeostasis model assessment of insulin resistance (HOMA2-IR), and liver fat percentage in RYGB at baseline, despite matching the groups for age, sex, and BMI. Those differences disappeared, except for triglycerides, within 1 year. All metabolic parameters correlated with WL., Conclusion: OLGB results in greater WL but transiently deteriorated several liver parameters in the first postoperative year. This was not associated with WL. The impact of these results on hepatic outcomes such as non-alcoholic steatohepatitis and fibrosis progression requires further studies. In both groups, improved insulin resistance and sensitivity were correlated with higher WL and lower liver fat percentage, respectively.

Liver stiffness values assessed with 2-D shear wave elastography (SWE), transient elastography (TE) and simple serologic tests were compared with respect to non-invasive assessment in a cohort of 127 consecutive patients with chronic liver diseases. The rate of reliable liver stiffness measurements was significantly higher with 2-D SWE than with TE: 99.2% versus 74.8%, p < 0.0001 (different reliability criteria used, according to current recommendations). In univariate analysis, liver stiffness measured with 2-D SWE correlated best with fibrosis stage estimated with TE (r = 0.699, p < 0.0001), followed by Forns score (r = 0.534, p < 0.0001) and King's score (r = 0.512, p < 0.0001). However, in multivariate analysis, only 2-D SWE-measured values remained correlated with fibrosis stage (p < 0.0001). The optimal 2-D SWE cutoff values for predicting significant fibrosis were 8.03 kPa for fibrosis stage ≥2 (area under the receiver operating characteristic curve = 0.832) and 13.1 kPa for fibrosis stage 4 (area under the receiver operating characteristic curve = 0.915), respectively. In conclusion, 2-D SWE can be used to obtain reliable liver stiffness measurements in almost all patients and performs very well in predicting the presence of liver cirrhosis., (Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: Beyond its classical role in calcium homoeostasis and bone metabolism, vitamin D deficiency has been found to be associated with several diseases, including diabetes, non-alcoholic fatty liver disease, and even obesity itself. Importantly, there are limited data on therapeutic strategies for vitamin D deficiency in bariatric patients, and the procedure-specific guidelines may not be sufficient. To improve long-term outcomes, nutritional screening and appropriate supplementation to prevent nutrient deficiencies are urgently needed. Therefore, the aim of this study is to examine effects and safety of a forced dosing regimen of vitamin D versus conventional dose supplementation on vitamin D levels and other parameters in bariatric patients., Methods/design: The study includes loading plus repeat dosing compared with repeated administration of vitamin D without a loading dose, according to guidelines, in a prospective, double-blind, randomized controlled trial. Up to a triple oral loading dose is given on day 1, then 2 and 4 weeks after surgery (100,000 IU dose each time), followed by an oral maintenance dose (3420 IU/day). The control group (n = 25) will receive placebo, followed by administration of a standard dose (3420 IU/day). We hypothesize that a significant increase in vitamin D levels will occur in patients in the treatment group (n = 25) by 24 weeks after surgery. Further measurements are aimed at evaluating changes in inflammation, bone turnover, insulin resistance, blood pressure, liver, mental health, and gut microbiota of patients undergoing omega-loop gastric bypass surgery. Furthermore, possible associations between concentrations of vitamin D, the involved enzymes, or vitamin D receptor in adipose and/or liver tissues will be determined., Discussion: To our knowledge, this trial is the first of its kind with this type of vitamin D supplementation in bariatric patients. Its major strength is the design and implementation of evaluation of influencing factors such as liver function, bone health, inflammation, insulin resistance, blood pressure, symptoms of depression, or microbiota. This alternative vitamin D dosing regimen has the potential to be a safe, fast, evidence-based treatment of vitamin D deficiency in bariatric patients. Owing to the increasing number of bariatric patients, it is also of interest to elucidate the link between obesity and vitamin D., Trial Registration: ClinicalTrials.gov identifier: NCT02092376 . Registered on 17 March 2014.

Background: In CPR, sufficient compression depth is essential. The American Heart Association ("at least 5cm", AHA-R) and the European Resuscitation Council ("at least 5cm, but not to exceed 6cm", ERC-R) recommendations differ, and both are hardly achieved. This study aims to investigate the effects of differing target depth instructions on compression depth performances of professional and lay-rescuers., Methods: 110 professional-rescuers and 110 lay-rescuers were randomized (1:1, 4 groups) to estimate the AHA-R or ERC-R on a paper sheet (given horizontal axis) using a pencil and to perform chest compressions according to AHA-R or ERC-R on a manikin. Distance estimation and compression depth were the outcome variables., Results: Professional-rescuers estimated the distance according to AHA-R in 19/55 (34.5%) and to ERC-R in 20/55 (36.4%) cases (p=0.84). Professional-rescuers achieved correct compression depth according to AHA-R in 39/55 (70.9%) and to ERC-R in 36/55 (65.4%) cases (p=0.97). Lay-rescuers estimated the distance correctly according to AHA-R in 18/55 (32.7%) and to ERC-R in 20/55 (36.4%) cases (p=0.59). Lay-rescuers yielded correct compression depth according to AHA-R in 39/55 (70.9%) and to ERC-R in 26/55 (47.3%) cases (p=0.02)., Conclusion: Professional and lay-rescuers have severe difficulties in correctly estimating distance on a sheet of paper. Professional-rescuers are able to yield AHA-R and ERC-R targets likewise. In lay-rescuers AHA-R was associated with significantly higher success rates. The inability to estimate distance could explain the failure to appropriately perform chest compressions. For teaching lay-rescuers, the AHA-R with no upper limit of compression depth might be preferable., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

24-nor-ursodeoxycholic acid (norUDCA) is a side-chain shortened derivate of ursodeoxycholic acid (UDCA). Since norUDCA is only ineffectively conjugated with glycine or taurine, it has specific physicochemical and therapeutic properties distinct from UDCA. Nonamidated norUDCA undergoes cholehepatic shunting enabling 'ductular targeting' and inducing a bicarbonate-rich hypercholeresis, with cholangioprotective effects. At the same time it has direct anti-inflammatory, antilipotoxic, anti fibrotic, and antiproliferative properties targeting various liver cell populations. norUDCA appears to be one of the most promising novel treatment approaches targeting the liver and the bile duct system at multifactorial and multicellular levels. This review article is a summary of a lecture given at the XXIII International Bile Acid Meeting (Falk Symposium 194) on 'Bile Acids as Signal Integrators and Metabolic Modulators' held in Freiburg, October 8-9, 2014, and summarizes the recent progress with norUDCA as a novel therapeutic approach in cholestatic and metabolic (liver) disorders., (2015 S. Karger AG, Basel.)

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and comprises a liver disease spectrum ranging from steatosis to nonalcoholic steatohepatitis (NASH) with risk of progression to liver cirrhosis and hepatocellular carcinoma (HCC). Associated metabolic conditions and comorbidities such as obesity, diabetes and cardiovascular diseases are common and require concerted management. Adiponutrin (PNPLA3) variants may help to identify NAFLD patients at higher risk for liver disease progression towards advanced fibrosis and HCC. The therapeutic options in NAFLD/NASH include lifestyle modification, pharmacological treatment, bariatric surgery for patients with morbid obesity and treatment of complications of liver cirrhosis and HCC, including liver transplantation. Insulin sensitizers and antioxidative treatment strategies with vitamin E are among the best-established pharmacological approaches, but both drugs have long-term safety issues and there is limited evidence in cirrhotic patients. Treatment of concomitant/underlying metabolic conditions with statins or metformin may also have beneficial effects on portal hypertension, complications of liver cirrhosis and HCC prevention. The bile acid receptor FXR may be a promising novel therapeutic target for the treatment of NAFLD/NASH, fibrosis and portal hypertension, but the prognostic implications of associated changes in low- and high-density lipoprotein cholesterol require further studies. Morbidly obese NASH patients can benefit from bariatric surgery which may reduce liver fibrosis but carries a risk of decompensation in patients with advanced liver cirrhosis. When carefully selected, patients with NASH cirrhosis undergoing liver transplantation have a good outcome. This review summarizes recent progress in the management of patients with liver cirrhosis due to NASH., (© 2015 S. Karger AG, Basel.)