Peter J. Meffert

Development, External Validation, and Comparative Assessment of a New Diagnostic Score for Hepatic Steatosis

OBJECTIVES:We used data from population-based studies to determine the accuracy of the Fatty Liver Index (FLI) and the Hepatic Steatosis Index (HSI) in determining individual risk of hepatic steatosis. We also developed a new risk scoring system and validated all three indices using external data.METHODS:We used data from the Study of Health in Pomerania (SHIP; n=4,222), conducted in North-eastern Germany, to validate the existing scoring systems and to develop our own index. Data from the South German Echinococcus Multilocularis and Internal Diseases in Leutkirch (EMIL) study (n=2,177) were used as an external validation data set. Diagnostic performance was evaluated in terms of discrimination (area under the receiver operating characteristic curve (AUC)) and calibration plots. We applied boosting for generalized linear models to select relevant diagnostic separators.RESULTS:The FLI accurately discriminated patients with fatty liver disease from those without (AUC=0.817) but had poor calibration, in that predicted risks differed considerably from observed risks, based on SHIP data. The FLI performed well in discrimination and calibration in the analysis of EMIL data (AUC=0.890). The HSI performed worse than the FLI in analysis of both data sets (SHIP: AUC=0.782 and EMIL: AUC=0.841), showing an extremely skewed calibration. Our newly developed risk score had a good performance in the development data set (SHIP: AUC=0.860) and also good discrimination ability in the validation data (EMIL: AUC=0.876), but it had low calibration based on the validation data set.CONCLUSIONS:We compared the ability of the FLI, HSI, and our own scoring system to determine the risk of hepatic steatosis using two population-based data sets (one for the development of our own system and one for validation). In the development and independent replication data set, all three indices discriminated well between patients with and without hepatic steatosis, but the predicted risks did not match well with the observed risks, when applied to external data. Scoring systems for fatty liver disease could depend on methodological standardization of ultrasound diagnosis and laboratory measurements.

Pancreatic Steatosis Demonstrated at MR Imaging in the General Population: Clinical Relevance

PURPOSE To determine the relationship between pancreatic fat content and type 2 diabetes and prediabetes. MATERIALS AND METHODS From the prospective population-based Study of Health in Pomerania (SHIP), 1367 volunteers (563 men, 678 women; median age, 50 years) underwent whole-body magnetic resonance (MR) imaging at 1.5 T, which included multiecho chemical shift-encoded acquisition of the abdomen. SHIP was approved by the institutional review board, and written informed consent was obtained from all participants. The proton density fat fraction (PDFF) was calculated after correction for T1 bias, T2* bias, multipeak spectral complexity of fat, and noise bias. On the basis of oral glucose tolerance test results, participants were grouped into those with normal glucose tolerance (n = 740), those with prediabetes (n = 431), and those with confirmed type 2 diabetes but without medication (n = 70). PDFF was assessed in the pancreatic head, body, and tail. Multivariable regression analysis was conducted to investigate possible relationships of PDFF with demographic factors, behavioral factors, and laboratory data associated with the metabolic syndrome. RESULTS In all subjects, the mean unadjusted pancreatic fat content was 4.4% (head, 4.6%; body, 4.9%; tail, 3.9%; being unequally distributed, P < .001). There was no significant difference in pancreatic PDFF among subjects with normal glucose tolerance, prediabetes, and type 2 diabetes (P = .980). Pancreatic PDFF showed a positive association with age and body mass index and a negative association with serum lipase activity (P < .001). CONCLUSION The presence of pancreatic fat is not related to prediabetes or diabetes, which suggests that it has little clinical relevance for an individuals glycemic status.

Prevalence of Fatty Liver Disease and Hepatic Iron Overload in a Northeastern German Population by Using Quantitative MR Imaging

Purpose To quantify liver fat and liver iron content by measurement of confounder-corrected proton density fat fraction (PDFF) and R2* and to identify clinical associations for fatty liver disease and liver iron overload and their prevalence in a large-scale population-based study. Materials and Methods From 2008 to 2013, 2561 white participants (1336 women; median age, 52 years; 25th and 75th quartiles, 42 and 62 years) were prospectively recruited to the Study of Health in Pomerania (SHIP). Complex chemical shift-encoded magnetic resonance (MR) examination of the liver was performed, from which PDFF and R2* were assessed. On the basis of previous histopathologic calibration, participants were stratified according to their liver fat and iron content as follows: none (PDFF, ≤5.1%; R2*, ≤41.0 sec-1), mild (PDFF, >5.1%; R2*, >41 sec-1), moderate (PDFF, >14.1%; R2*, >62.5 sec-1), high (PDFF: >28.0%; R2*: >70.1 sec-1). Prevalence of fatty liver diseases and iron overload was calculated (weighted by probability of participation). Clinical associations were identified by using boosting for generalized linear models. Results Median PDFF was 3.9% (range, 0.6%-41.5%). Prevalence of fatty liver diseases was 42.2% (1082 of 2561 participants); mild, 28.5% (730 participants); moderate, 12.0% (307 participants); high content, 1.8% (45 participants). Median R2* was 34.4 sec-1 (range, 14.0-311.8 sec-1). Iron overload was observed in 17.4% (447 of 2561 participants; mild, 14.7% [376 participants]; moderate, 0.8% [20 participants]; high content, 2.0% [50 participants]). Liver fat content correlated with waist-to-height ratio, alanine transaminase, uric acid, serum triglycerides, and blood pressure. Liver iron content correlated with mean serum corpuscular hemoglobin, male sex, and age. Conclusion In a white German population, the prevalence of fatty liver diseases and liver iron overload is 42.2% (1082 of 2561) and 17.4% (447 of 2561). Whereas liver fat is associated with predictors related to the metabolic syndrome, liver iron content is mainly associated with mean serum corpuscular hemoglobin.

Effects of water-filtered infrared-A and of heat on cell death, inflammation, antioxidative potential and of free radical formation in viable skin - First results

The effects of water-filtered infrared-A (wIRA) and of convective heat on viability, inflammation, inducible free radicals and antioxidative power were investigated in natural and viable skin using the ex vivo Bovine Udder System (BUS) model. Therefore, skin samples from differently treated parts of the udder of a healthy cow were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, by prostaglandin E2 (PGE2) measurement and by electron spin resonance (ESR) spectroscopy. Neither cell viability, the inflammation status, the radical status or the antioxidative defence systems of the skin were significantly affected by wIRA applied within 30 min by using an irradiance of 1900 W m(-2) which is of relevance for clinical use, but which exceeded the maximum solar IR-A irradiance at the Earths surface more than 5 times and which resulted in a skin surface temperature of about 45 °C without cooling and of about 37 °C with convective cooling by air ventilation. No significant effects on viability and on inflammation were detected when convective heat was applied alone under equivalent conditions in terms of the resulting skin surface temperatures and exposure time. As compared with untreated skin, free radical formation was almost doubled, whereas the antioxidative power was reduced to about 50% after convective heating to about 45 °C.

Magnetic Resonance Imaging of Changes in Abdominal Compartments in Obese Diabetics during a Low-Calorie Weight-Loss Program.

Objectives To investigate changes in the fat content of abdominal compartments and muscle area during weight loss using confounder-adjusted chemical-shift-encoded magnetic resonance imaging (MRI) in overweight diabetics. Methods Twenty-nine obese diabetics (10/19 men/women, median age: 59.0 years, median body mass index (BMI): 34.0 kg/m2) prospectively joined a standardized 15-week weight-loss program (six weeks of formula diet exclusively, followed by reintroduction of regular food with gradually increasing energy content over nine weeks) over 15 weeks. All subjects underwent a standardized MRI protocol including a confounder-adjusted chemical-shift-encoded MR sequence with water/fat separation before the program as well at the end of the six weeks of formula diet and at the end of the program at 15 weeks. Fat fractions of abdominal organs and vertebral bone marrow as well as volumes of visceral and subcutaneous fat were determined. Furthermore, muscle area was evaluated using the L4/L5 method. Data were compared using the Wilcoxon signed-rank test for paired samples. Results Median BMI decreased significantly from 34.0 kg/m2 to 29.9 kg/m2 (p < 0.001) at 15 weeks. Liver fat content was normalized (14.2% to 4.1%, p < 0.001) and vertebral bone marrow fat (57.5% to 53.6%, p = 0.018) decreased significantly throughout the program, while fat content of pancreas (9.0%), spleen (0.0%), and psoas muscle (0.0%) did not (p > 0.15). Visceral fat volume (3.2 L to 1.6 L, p < 0.001) and subcutaneous fat diameter (3.0 cm to 2.2 cm, p < 0.001) also decreased significantly. Muscle area declined by 6.8% from 243.9 cm2 to 226.8 cm2. Conclusion MRI allows noninvasive monitoring of changes in abdominal compartments during weight loss. In overweight diabetics, weight loss leads to fat reduction in abdominal compartments, such as visceral fat, as well as liver fat and vertebral bone marrow fat while pancreas fat remains unchanged.

Early Parenteral Nutrition in Patients with Biliopancreatic Mass Lesions, a Prospective, Randomized Intervention Trial.

Purpose Patients with biliopancreatic tumors frequently suffer from weight loss and cachexia. The in-hospital work-up to differentiate between benign and malignant biliopancreatic lesions requires repeated pre-interventional fasting periods that can aggravate this problem. We conducted a randomized intervention study to test whether routine in-hospital peripheral intravenous nutrition on fasting days (1000 ml/24 h, 700 kcal) has a beneficial effect on body weight and body composition. Material and Methods 168 patients were screened and 100 enrolled in the trial, all undergoing in-hospital work-up for biliopancreatic mass lesions and randomized to either intravenous nutrition or control. Primary endpoint was weight loss at time of hospital discharge; secondary endpoints were parameters determined by bioelectric impedance analysis and quality of life recorded by the EORTC questionnaire. Results Within three months prior to hospital admission patients had a median self-reported loss of 4.0 kg (25*th: -10.0 kg and 75*th* percentile: 0.0kg) of body weight. On a multivariate analysis nutritional intervention increased body weight by 1.7 kg (95% CI: 0.204; 3.210, p = 0.027), particularly in patients with malignant lesions (2.7 kg (95% CI: 0.71; 4.76, p < 0.01). Conclusions In a hospital setting, patients with suspected biliopancreatic mass lesions stabilized their body weight when receiving parenteral nutrition in fasting periods even when no total parenteral nutrition was required. Analysis showed that this effect was greatest in patients with malignant tumors. Further studies will be necessary to see whether patient outcome is affected as well. Trial Registration ClinicalTrials.gov NCT02670265

Risk Factor Prevalence and Their Relative Influence on Fatty Liver and Gallstone Disease: A Cross-Ethnic Study Comparing Two High-Risk Populations from Chile and Northeast Germany

Objective: Fatty Liver Disease (FLD) and Gallstone disease (GSD) are among the most common gastrointestinal disorders worldwide. Based on data of two ethnically distant populations from Santiago de Chile and Northeast Germany sharing remarkably high prevalence for both diseases, we aimed to estimate (1) the standardised prevalence of FLD and GSD, (2) the population-specific prevalence of known risk factors and (3) the relative influence of each risk factor for the occurrence of the respective outcome. Design: We used data from two population-based studies from Chile (n=742) and Germany (n=3632). Regression methods were applied to assess the prevalence of risk factors at a specific age. To quantify the relative contribution of the risk factors to the occurrence of FLD and GSD, we used hierarchical variation partitioning. Results: The standardised prevalence of FLD ranged from 20.7% in Chilean men to 37.9% in German men and the standardised prevalence of GSD from 14.5% in German men to 40.5% in Chilean women. Risk profiles differed considerably between populations and sexes. Overall, the contributions of the risk factors to the occurrence of FLD and GSD coincided widely. For FLD, age and BMI were the predominant factors, followed by serum triglyceride levels and the Single-Nucleotide Polymorphism (SNP) rs738409 C>G of the PNPLA3 gene. In GSD age was the predominant determinant, in women additionally BMI. Alcohol consumption played a marked role in Chilean men, being positively associated with GSD, similarly the use of contraceptives in Chilean women. The relative contribution of the lithogenic SNP rs11887543 was low in both populations, with marginal effect in Chileans. Conclusion: Despite marked differences in risk profiles, relative influences of risk factors coincided widely between study populations. Knowledge about importance of risk factors for fatty liver and gallstone disease may guide therapy and advises for lifestyle changes.

Nest-boxes for Common Swifts Apus apus as compensatory measures in the context of building renovation: efficacy and predictors of occupancy

Currently, renovation and thermal insulation of buildings is happening at a high rate in many European countries, driven in part by the political aim to reduce greenhouse gas emissions. Unfortunately, building renovations often lead to a loss of structures, such as accessible cavities, on which synanthropic species, for example house-nesting birds, depend. In Germany, due to legislative regulations, it is a common practice to install nest-boxes as compensation for destroyed nest sites of birds. However, studies on the efficacy of such measures remain sparse. We monitored the occupancy of 477 compensatory nest-boxes for Common Swifts Apus apus , predominantly placed on renovated prefabricated buildings in a city in Germany. We found 24.3% of the boxes occupied by Swifts. On most buildings, the number of occupied boxes was as high as or even higher than the assumed number of breeding sites prior to renovation. Furthermore, in a district where nearly all buildings had been renovated in the past 10 years, we recorded a remarkably high density of Swifts breeding in nest-boxes. Using boosted regression trees, we analysed whether eight different nest-box properties influenced box occupation probability. The number of neighbouring boxes was the most important. Additionally, box age, facade orientation, city district, relative and absolute height, and manner of installation (external/internal) also played a role. Between different nest-box types, we found only negligible differences in occupation probability. Our findings suggest that installing nest-boxes is likely to be an appropriate measure to compensate for nesting sites of Swifts lost during building renovations. Based on our results, we recommend mounting the boxes a few metres apart from each other and close to the roof edge to maximise success. Further studies should be carried out to assess whether our results and conclusions can be confirmed in other situations.