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Background: Paediatric thoracolumbar spine injuries are rare, and meaningful epidemiological data are lacking., Objectives: The aim of this study was to provide epidemiological data for paediatric patients with thoracolumbar spinal trauma in Germany with a view to enhancing future decision-making in relation to the diagnostics and treatment of these patients., Materials and Methods: A retrospective multicentre study includes patients up to 16 years of age who were suffering from thoracolumbar spine injuries who had been treated in six German spine centres between 01/2010 and 12/2016. The clinical database was analysed for patient-specific data, trauma mechanisms, level of injury, and any accompanying injuries. Diagnostic imaging and subsequent treatment were investigated. Patients were divided into three age groups for further evaluation: age group I (0-6 years), age group II (7-9 years) and age group III (10-16 years)., Results: A total of 153 children with 345 thoracolumbar spine injuries met the inclusion criteria. The mean age at the time of hospitalization due to the injury was 12.9 (± 3.1) years. Boys were likelier to be affected (1:1.3). In all age groups, falls and traffic accidents were the most common causes of thoracolumbar spine injuries. A total of 95 patients (62.1%) were treated conservatively, while 58 (37.9%) of the children underwent surgical treatment. Minimally invasive procedures were the most chosen procedures. Older children and adolescents were likelier to suffer from higher-grade injuries according to the AOSpine classification. The thoracolumbar junction (T11 to L2) was the most affected level along the thoracolumbar spine (n = 90). Neurological deficits were rarely seen in all age groups. Besides extremity injuries (n = 52, 30.2%), head injuries represented the most common accompanying injuries (n = 53, 30.8%). Regarding spinal injuries, most of the patients showed no evidence of complications during their hospital stay (96.7%)., Conclusions: The thoracolumbar junction was more frequently affected in older children and adolescents. The majority of thoracolumbar spinal column injuries were treated conservatively. Nevertheless, 37.9% of hospitalized children had to be treated surgically, and there was an acceptable complication rate for the surgeries that were performed., (© 2023. The Author(s).)

Introduction: Two next-generation pneumococcal conjugate vaccines (PCVs), a 15- and a 20-valent PCV (PCV15 and PCV20), have recently been licensed for use in adults, and PCV15 has also been licensed in children. We developed a dynamic transmission model specific for Germany, with the aim to predict carriage prevalence and invasive pneumococcal disease (IPD) burden for serotypes included in these vaccines., Methods: The model allows to follow serotype distributions longitudinally both in the absence and presence of PCV vaccinations. We considered eight age cohorts and seven serotype groups according to the composition of different pneumococcal vaccines. This comprises the additional serotypes contained in PCV15 and PCV20 but not in PCV13., Results: The model predicted that by continuing the current vaccine policy (standard vaccination with PCV13 in children and with PPSV23 in adults) until 2031, IPD case counts due to any serotype in children <2 years of age will remain unchanged. There will be a continuous decrease of IPD cases in adults aged 16-59y, but a 20% increase in adults ≥60y. Furthermore, there will be a steady decrease of the proportion of carriage and IPD due to serotypes included in PCV7 and PCV13 over the model horizon and a steady rise of non-PCV13 serotypes in carriage and IPD. The highest increase for both pneumococcal carriage and absolute IPD case counts was predicted for serotypes 22F and 33F (included in both PCV15 and PCV20) and serotypes 8, 10A, 11A, 12F, and 15B (included in PCV20 only), particularly in older adults. Between 2022 and 2031, serotypes included in PCV20 only are expected to cause 19.7-25.3% of IPD cases in adults ≥60y., Conclusions: We conclude that introduction of next-generation PCVs for adults may prevent a substantial and increasing proportion of adult IPDs, with PCV20 having the potential to provide the broadest protection against pneumococcal disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Horn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Clinical trials, epidemiological studies, clinical registries, and other prospective research projects, together with patient care services, are main sources of data in the medical research domain. They serve often as a basis for secondary research in evidence-based medicine, prediction models for disease, and its progression. This data are often neither sufficiently described nor accessible. Related models are often not accessible as a functional program tool for interested users from the health care and biomedical domains., Objective: The interdisciplinary project Leipzig Health Atlas (LHA) was developed to close this gap. LHA is an online platform that serves as a sustainable archive providing medical data, metadata, models, and novel phenotypes from clinical trials, epidemiological studies, and other medical research projects., Methods: Data, models, and phenotypes are described by semantically rich metadata. The platform prefers to share data and models presented in original publications but is also open for nonpublished data. LHA provides and associates unique permanent identifiers for each dataset and model. Hence, the platform can be used to share prepared, quality-assured datasets and models while they are referenced in publications. All managed data, models, and phenotypes in LHA follow the FAIR principles, with public availability or restricted access for specific user groups., Results: The LHA platform is in productive mode (https://www.health-atlas.de/). It is already used by a variety of clinical trial and research groups and is becoming increasingly popular also in the biomedical community. LHA is an integral part of the forthcoming initiative building a national research data infrastructure for health in Germany., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Disease modelling has had considerable policy impact during the ongoing COVID-19 pandemic, and it is increasingly acknowledged that combining multiple models can improve the reliability of outputs. Here we report insights from ten weeks of collaborative short-term forecasting of COVID-19 in Germany and Poland (12 October-19 December 2020). The study period covers the onset of the second wave in both countries, with tightening non-pharmaceutical interventions (NPIs) and subsequently a decay (Poland) or plateau and renewed increase (Germany) in reported cases. Thirteen independent teams provided probabilistic real-time forecasts of COVID-19 cases and deaths. These were reported for lead times of one to four weeks, with evaluation focused on one- and two-week horizons, which are less affected by changing NPIs. Heterogeneity between forecasts was considerable both in terms of point predictions and forecast spread. Ensemble forecasts showed good relative performance, in particular in terms of coverage, but did not clearly dominate single-model predictions. The study was preregistered and will be followed up in future phases of the pandemic., (© 2021. The Author(s).)

Coronary heart disease, an inflammatory disease, is the leading cause of death globally. White blood cell counts (including monocytes) are easily available biomarkers of systemic inflammation. Monocyte subtypes can be measured by flow cytometry and classified into classical (CD14high, CD16neg), intermediate (CD14high, CD16+) and non-classical (CD14+, CD16high) with distinct functional properties. The goal of this study was to investigate the association of monocyte total count and its subtypes with cardiovascular risk groups defined by the Framingham Risk Score, which is used to estimate the 10-year risk of developing myocardial infarction or predict mortality following coronary heart disease. We also aimed to investigate whether monocyte counts are associated with relevant cardiovascular risk factors not included in the Framingham Risk Score, such as carotid atherosclerotic plaque and intima-media thickness. Our data came from the LIFE-Adult study, a population-based cohort study of 10,000 randomly selected participants in Leipzig, Germany. Data was gathered using self-administered questionnaires and physical examinations. Carotid plaques and intima-media thickness were measured using carotid artery sonography. Monocyte subtypes in blood were determined by 10-color flow cytometry for a total of 690 individuals. In a multivariate regression analysis adjusting for the risk factors BMI, intima-media thickness, presence of carotid plaques and diabetes mellitus, monocyte subtypes and total count were found to be significantly associated with the dichotomized Framingham Risk Score (≥10% versus <10%): Odds ratios [95% confidence interval] for monocyte subtypes: classical: 11.19 [3.79-34.26]; intermediate: 2.27 [1.11-4.71]; non-classical: 4.18 [1.75-10.20]; total: 14.59 [4.61-47.95]. In absence of prospective data, the FRS was used as a surrogate for CHD. Our results indicate that monocyte counts could provide useful predictive value for cardiovascular disease risk., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Markus Scholz receives funding from Pfizer Inc. for a project not related to this research. The remaining authors have nothing to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Coronary artery disease (CAD) is a significant risk factor for atrial fibrillation (AF). Experimental studies demonstrated that atrial ischemia induced by right coronary artery (RCA) stenosis promote AF triggers and development of electro-anatomical substrate for AF., Aim: To analyze the association between AF prevalence and coronary arteries status in the LIFE-Heart Study., Methods: This analysis included patients with available coronary catheterization data recruited between 2006 and 2014. Patients with acute myocardial infarction were excluded. CAD was defined as stenosis ≥75%, while coronary artery sclerosis (CAS) was defined as non-critical plaque(s) <75%., Results: In total, 3.458 patients (median age 63 years, 34% women) were included into analysis. AF was diagnosed in 238 (6.7%) patients. There were 681 (19.7%) patients with CAS and 1.411 (40.8%) with CAD (27.5% with single, 32.4% with double, and 40.1% with triple vessel CAD). In multivariable analysis, there was a significant association between prevalent AF and coronary artery status (OR 0.64, 95% CI 0.53-0.78, P trend  < .001). Similarly, AF risk was lower in patients with higher CAD extent (OR 0.54, 95%CI 0.35-0.83, P trend = .005). Compared to single vessel CAD, the risk of AF was lower in double (OR 0.42, 95%CI 0.19-0.95, P = .037) and triple CAD (OR 0.31, 95%CI 0.13-0.71, P = .006). Finally, no association was found between AF prevalence and CAD origin among patients with single vessel CAD., Conclusion: In the LIFE-Heart Study, CAS but not CAD was associated with increased risk of AF., (© 2020 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background and Aims: Current epidemiologic data suggest beneficial cardiovascular effects of fermented dairy products (FDP). However, the relationship between FDP consumption and angiographic coronary status has not been previously studied. Furthermore, the role of novel metabolomic biomarkers of cardiovascular risk in this context is unclear. We hypothesize that short-chain acylcarnitines (SCA) reflect the link between FDP intake and angiographic extent of stable coronary artery disease (CAD)., Methods and Results: We recruited 1185 patients admitted for suspected CAD [median age 62 years (interquartile range: 54-69); 714 men (60.3%)]. Prior to coronary angiography, each patient completed a validated Food Frequency Questionnaire. In addition, venous blood was collected from each patient for whole blood metabolomic analysis, using targeted mass-spectrometry. CAD was defined by the presence of ≥1 coronary stenosis ≥50%. Patients with CAD (n = 441) reported lower median FDP intake [86.8 g/day (IQR: 53.4-127.6)] than patients without CAD [n = 744; 103.9 g/day (IQR: 62.9-152.7); p < 0.001]. Upon adjustment for relevant confounders, increased circulating SCA, particularly level of acetylcarnitine (C2) associated with both higher CAD probability [SCA:β(SE) = 0.584 (0.235), p = 0.013; C2:β(SE) = 0.575 (0.242), p = 0.017] and decreased FDP consumption [SCA:β/100 g FDP-increment/day (SE) = -0.785 (0.242), p = 0.001; C2:β(SE) = -0.560 (0.230), p = 0.015]. By mediation analysis, neither SCA nor C2 showed relevant mediator effect linking FDP consumption to the risk of CAD., Conclusion: Increased consumption of fermented milk was associated with lower prevalence of CAD and correlated inversely with circulating SCA, in particular with acetylcarnitine. No substantial mediator effect of SCA linking fermented milk intake with risk of CAD was found., Clinical Trial Registry: NCT00497887., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

As the frequency and intensity of extreme events such as droughts, heatwaves and floods have increased over recent decades, more extreme biological responses are being reported, and there is widespread interest in attributing such responses to anthropogenic climate change. However, the formal detection and attribution of biological responses to climate change is associated with many challenges. We illustrate these challenges with data from the Elbe River floodplain, Germany. Using community turnover and stability indices, we show that responses in plant, carabid and mollusc communities are detectable following extreme events. Community composition and species dominance changed following the extreme flood and summer heatwave of 2002/2003 (all taxa); the 2006 flood and heatwave (molluscs); and after the recurring floods and heatwave of 2010 and the 2013 flood (plants). Nevertheless, our ability to attribute these responses to anthropogenic climate change is limited by high natural variability in climate and biological data; lack of long-term data and replication, and the effects of multiple events. Without better understanding of the mechanisms behind change and the interactions, feedbacks and potentially lagged responses, multiple-driver attribution is unlikely. We discuss whether formal detection and/or attribution is necessary and suggest ways in which understanding of biological responses to extreme events could progress.

Background: In general, pediatric spinal injuries are rare. No reliable data on the epidemiology of spinal injuries in pediatric patients in Germany are available. Especially in pediatric patients, for whom the medical history, clinical examination and the performance of imaging diagnostics are difficult to obtain, all available information on a spinal injury must be taken into account., Objective: The aim of this study was to provide epidemiological data for pediatric patients with spinal trauma in Germany in order to enhance future decision-making for the diagnostics and treatment of these patients., Material and Methods: Within the framework of a national multicenter study, data were retrospectively obtained from 6 German spine centers for 7 years between January 2010 and December 2016. In addition to the demographic data, the clinical databases were screened for specific trauma mechanisms, level of injury as well as accompanying injuries. Furthermore, diagnostic imaging and the treatment selected were also analyzed., Results: A total of 367 children (female: male = 1:1.2) with a total of 610 spinal injuries were included in this study. The mean age was 12 years (±3.5 years). The most frequent trauma mechanisms were falls from <3 m and traffic accidents. The imaging diagnostics were only rarely carried out with the child under anesthesia. Younger children (0-9 years old) suffered more injuries to the cervical spine, whereas injuries to the thoracic and lumbar spine were more frequently found in older children (>10 years old). The children frequently showed accompanying injuries to the head and the extremities. Accompanying spinal injuries mostly occurred in adjacent regions and only rarely in other regions. Around 75% of the children were treated conservatively., Conclusion: The results were different from the knowledge obtained from adult patients with spinal trauma and describe the special circumstances for pediatric patients with spinal trauma. Despite certain limitations these facts may help to enhance future decision-making for the diagnostics and treatment of these patients.

Context: Common genetic susceptibility may underlie the frequently observed co-occurrence of type 1 and type 2 diabetes in families. Given the role of HLA class II genes in the pathophysiology of type 1 diabetes, the aim of the present study was to test the association of high density imputed human leukocyte antigen (HLA) genotypes with type 2 diabetes., Objectives and Design: Three cohorts (Ntotal = 10 413) from Leipzig, Germany were included in this study: LIFE-Adult (N = 4649), LIFE-Heart (N = 4815) and the Sorbs (N = 949) cohort. Detailed metabolic phenotyping and genome-wide single nucleotide polymorphism (SNP) data were available for all subjects. Using 1000 Genome imputation data, HLA genotypes were imputed on 4-digit level and association tests for type 2 diabetes, and related metabolic traits were conducted., Results: In a meta-analysis including all 3 cohorts, the absence of HLA-DRB5 was associated with increased risk of type 2 diabetes (P = 0.001). In contrast, HLA-DQB*06:02 and HLA-DQA*01:02 had a protective effect on type 2 diabetes (P = 0.005 and 0.003, respectively). Both alleles are part of the well-established type 1 diabetes protective haplotype DRB1*15:01~DQA1*01:02~DQB1*06:02, which was also associated with reduced risk of type 2 diabetes (OR 0.84; P = 0.005). On the contrary, the DRB1*07:01~DQA1*02:01~DQB1*03:03 was identified as a risk haplotype in non-insulin-treated diabetes (OR 1.37; P = 0.002)., Conclusions: Genetic variation in the HLA class II locus exerts risk and protective effects on non-insulin-treated type 2 diabetes. Our data suggest that the genetic architecture of type 1 diabetes and type 2 diabetes might share common components on the HLA class II locus., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: CAP (Community acquired pneumonia) is frequent, with a high mortality rate and a high burden on health care systems. Development of predictive biomarkers, new therapeutic concepts, and epidemiologic research require a valid, reproducible, and quantitative measure describing CAP severity., Methods: Using time series data of 1532 patients enrolled in the PROGRESS study, we compared putative measures of CAP severity for their utility as an operationalization. Comparison was based on ability to correctly identify patients with an objectively severe state of disease (death or need for intensive care with at least one of the following: substantial respiratory support, treatment with catecholamines, or dialysis). We considered IDSA/ATS minor criteria, CRB-65, CURB-65, Halm criteria, qSOFA, PSI, SCAP, SIRS-Score, SMART-COP, and SOFA., Results: SOFA significantly outperformed other scores in correctly identifying a severe state of disease at the day of enrollment (AUC = 0.948), mainly caused by higher discriminative power at higher score values. Runners-up were the sum of IDSA/ATS minor criteria (AUC = 0.916) and SCAP (AUC = 0.868). SOFA performed similarly well on subsequent study days (all AUC > 0.9) and across age groups. In univariate and multivariate analysis, age, sex, and pack-years significantly contributed to higher SOFA values whereas antibiosis before hospitalization predicted lower SOFA., Conclusions: SOFA score can serve as an excellent operationalization of CAP severity and is proposed as endpoint for biomarker and therapeutic studies., Trial Registration: clinicaltrials.gov NCT02782013 , May 25, 2016, retrospectively registered.

Background: To date, no evidence-based treatment algorithm is available for fractures of the subaxial spine. The aim of the present study was to assess and compare the management strategy for traumatic subaxial fractures among German and Dutch spine surgeons., Methods: In our web-based multicenter study, German and Dutch spine surgeons evaluated the computed tomography data of traumatic subaxial fractures (C3-C7). Supplementary case-specific information was provided. The fractures were classified using the AO spine classification. Next, 9 questions concerning the treatment algorithm were evaluated. Data were analyzed using SPSS. Statistical significance was defined as P < 0.05., Results: Ten surgeons (5/country) evaluated 31 cases (310 votes). The fractures were classified as AO type A in 37% (114 votes), type B in 50% (155 votes), and type C in 13% (41 votes). German spine surgeons had a lower threshold concerning the indication for surgical treatment (German, 94.2% vs. Netherlands, 58.1%; P < 0.05). A consensus was present for operative stabilization for type B and C injuries, but a discrepancy was found in the therapeutic algorithm for type A fractures. The most significant difference was seen in the treatment of type A2 and A3 fractures (surgery for type A2/A3 fracture: German, 92.9% vs. Netherlands, 5.3%; P < 0.05)., Conclusion: We found a consensus for the stabilization of AO type B and C fractures but country-specific differences in the treatment of type A fractures, especially for A2 and A3 fractures. Further evidence is necessary to ensure more consistent international treatment strategies., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and Aims: Dyslipidemia is a major risk factor for atherosclerotic cardiovascular disease (ASCVD). As key regulators of lipoprotein metabolism, apolipoproteins (apos) are discussed as vascular risk factors. This study aimed to analyze associations of major plasma apos with coronary artery disease (CAD), peripheral artery disease (PAD) and carotid artery plaque (CAP) to elucidate their diagnostic potential in risk assessment., Methods: ApoA-I, apoA-II, apoA-IV, apoB-100, apoC-I, apoC-III, apoE, and apoJ were simultaneously quantified in 3 μL EDTA-plasma by LC-MS/MS in a case-control subgroup of the Leipziger LIFE-Heart Study (N = 911). Confounder analysis with demographic, clinical covariates and serum lipids, cardiac, inflammatory, and hepatic markers were performed. Apos were associated with CAD, CAP, and PAD in a multivariate regression model., Results: Fasting and statin therapy showed strongest effects on apo concentrations. Inverse correlations of HDL-related apos A-I, A-II, A-IV, and C-I were observed for troponin T and interleukin 6. Concentrations of apos A-II, B-100, C-I, and E were decreased under statin therapy. After adjustment for influencing factors and related lipids, only apoB-100 (odds ratio per one SD [OR], 1.39; 95% confidence interval [CI], 1.05-1.84) was independently associated with CAD while apoA-IV (OR, 0.74; 95% CI 0.58-0.95) indicated PAD. ApoB-100 (OR, 1.55; 95% CI, 1.18-2.04), apoC-III (OR, 1.30; 95% CI, 1.06-1.58), and apoE (OR, 1.34; 95% CI, 1.13-1.58) were associated with CAP., Conclusions: Triglyceride rich lipoproteins (TRLs) associated apos A-IV, B-100, C-III, and E are independently associated with stable ASCVD, providing further evidence for a potential role of TRLs in atherogenesis., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Extra Corporeal Membrane Oxygenation (ECMO) has become an accepted treatment option for severely ill patients. Due to a limited availability of ECMO support therapy, patients must often be transported to a specialised centre before or after cannulation. According to the ELSO guidelines, an ECMO specialist should be present for such interventions. Here we describe the safety and efficacy of a reduced team approach involving one anaesthesiologist, experienced in specialised intensive care medicine, and a specialised critical care nurse., Methods: This study is a 10 years retrospective, single institution analysis of all data collected between January 2007 and December 2016 from the medical records at the University Hospital Bonn, Germany., Results: The Bonner mobile ECMO team was deployed in 170 cases for on-site evaluation for ECMO support therapy. 4 (2.4%) patients died prior to arrival or during the implementation of ECMO support. Of the remaining 166 patients, 126 were cannulated at the referring site, 40 were transported without ECMO. Of those, 21 were subsequently cannulated out our centre. 19 patients never received ECMO treatment. The primary indication for ECMO treatment was ARDS (159/166 patients). Veno-venous ECMO was initiated in 137, whilst 10 patients received veno-arterial ECMO treatment. Mean transportation time was 75 ± 36 min, and mean transport distance was 56 ± 57 km. In total, 26 complications were observed, three being directly transport-related. The overall survival was 55%., Conclusions: Initiation of extracorporeal membrane oxygenation and subsequent transport can be safely and efficiently performed by a two-man team with good outcome.

Aims and Background: Parameters of arterial stiffness such as pulse wave velocity (PWV) were recently proposed as independent risk factors of cardiovascular events. We analyse three PWV parameters in the large population-based study LIFE-Adult to identify risk factors, normal and reference values., Methods and Results: Brachial-ankle (ba), brachial-femoral (bf) and carotid-femoral (cf) PWV assessment was performed using Vicorder device. 8509 participants aged 19-80 were analysed. PWV parameters were moderately correlated (r(ba/bf) = 0.6, r(ba/cf) = 0.46, r(bf/cf) = 0.59). Age and blood pressure are the dominant determinants of PWV parameters explaining > 18% of variability. Sex was only relevant for bfPWV and cfPWV. All further analysed cardiovascular and other risk factors are of minor importance. We provide age-dependent percentiles for the population (reference values) and for the subgroup of normotonic individuals. All percentiles show a strong increase with age. The difference between normotonic and all individuals is small for younger age groups but increases up to 1 m/s for elderly subjects., Conclusion: Our study confirms and further underpins the strong impact of age and blood pressure on arterial stiffness and the relatively weak contribution of other factors, supporting an independent role of arterial stiffness in cardiovascular disease development. Age-dependent reference and normal values were provided on the basis of the so far largest study sample facilitating the implementation of PWV assessment in clinical practice. Due to better compliance, handling and stronger association with age and blood pressure, baPWV could serve as an alternative to cfPWV. Follow-up data are required to estimate the clinical significance of specified PWV cut-offs.

In order to get admission to study medicine at a German university, the most important criterion is the proof of an excellent final college prep school examination (Abitur) in order to get an adequate study place without time loss. For the purpose of a suitable selection for admission of candidates, however, the best qualified and suitable applicants should be found to be distributed to the limited available university places for medicine. The final examination mark alone can represent such a suitability - if at all - only to a very limited extent. In order to figure out which skills and competences characterize a potential medical student and after studies a well-practicing and resilient later physician, we sought for initial steps to apply competence profiling as a predictor matching suitable prerequisites to a subsequent successful outcome. In order to meet these demands, we founded a project called ComMedMent at the Friedrich Alexander University of Erlangen-Nürnberg (FAU), where we defined competences for successfully becoming a medical expert while studying the medical curriculum. Here we present a comprehensive catalogue of 16 standards and meaningful key competencies for potentially successful medical students at the FAU. In collaboration with the Center for Competence Balancing - CeKom SÜD - (Pforzheim; Germany) and a local competence team comprising institute management, lecturers and students of different educational backgrounds, a target profile for the "ideally equipped students and later successful practitioners" was established. The identification of a site-specific and/or general requirement profile for medical students could open up new perspectives for the selection process and show the opportunities for helping students along the path to becoming medical experts., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Background & Aims: Organ allocation for liver transplantation is based on prognosis, using the model for end-stage liver disease (MELD) or MELD including serum sodium (MELD-Na) score. These scores do not consider systemic inflammation and septic complications. Blood level of C-reactive protein (CRP), in addition to the MELD score, associates with mortality in patients with end-stage liver disease, whereas levels of interleukin 6 (IL6) have not been systematically studied., Methods: We performed a retrospective observational cohort study of 474 patients with end-stage liver disease (63.5% male; median age, 56.9 years), evaluated for liver transplantation in Germany, with at least 1 year of follow up. Data were collected on blood levels of CRP, IL6, and white blood cell count (WBC). Findings were analyzed in relation to mortality and compared with patients' MELD scores and MELD-Na scores. For survival analysis, the cohort was divided into quartiles of IL6, CRP, and WBC levels, as well as MELD scores. Log-rank test and the Cox proportional hazards regression model were used to compare the groups, and area under the receiver operating characteristic (AUROC) values were calculated., Results: Blood levels of IL6 and MELD scores associated with mortality: none of the patients with levels of IL6 below the first quartile (below 5.3 pg/mL) died within 1 year. In contrast, 67.7% of the patients in the highest quartile of IL6 level (37.0 pg/mL or more) died within 1 year. MELD score also correlated with mortality: among patients with MELD scores below 8.7, 0.9% died within 1 year, whereas in patients with MELD scores of 18.0 or more, 67.4% died within 1 year. The predictive value of level of IL6 (AUROC, 0.940) was higher than level of CRP (AUROC, 0.866) (P = .009) or WBC (AUROC, 0.773) (P < .001) for 90-day mortality. MELD scores associated with 90-day mortality (AUROC, 0.933) (P = .756) as did MELD-Na score (AUROC, 0.946) (P = .771). Level of IL6 associated with 1-year mortality (AUROC, 0.916) to a greater extent than liver synthesis or detoxification markers international normalized ratio (AUROC, 0.839) (P = .007) or bilirubin (AUROC 0.846) (P = .007). Level of IL6 was an independent, significant risk factor for mortality after adjustment for MELD score, MELD-Na score, level of CRP, or WBC., Conclusions: In a retrospective analysis, we found high blood levels of IL6 to associate with 90-day and 1-year mortality in patients with end-stage liver disease; its predictive value was comparable to that of MELD or MELD-Na score, and was higher than that of level of CRP or WBC. Further studies should be performed to confirm the results in different cohorts., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: Adipose tissue-derived signals potentially link obesity and adipose tissue dysfunction with metabolic and cardiovascular diseases. Although some adipocytokines have been closely related to metabolic and cardiovascular traits, it is unknown which adipocytokine or adipocytokine clusters serve as meaningful markers of metabolic syndrome (MS) components. Therefore, this study investigated the associations of 12 adipocytokines with components of the MS to identify the most relevant cytokines potentially related to specific metabolic profiles., Research Design and Methods: Twelve cytokines [adiponectin, adipocyte fatty acid-binding protein (AFABP), angiopoietin-related growth factor, chemerin, fibroblast growth factor (FGF) 19, FGF21, FGF23, insulin-like growth factor-1, interleukin 10, irisin, progranulin, and vaspin] were quantified in a cross-sectional cohort of 1046 subjects. Hypothesis-free cluster analysis, multivariate regression analyses with parameters of the MS, and discriminant analysis were performed to assess associations and the relative importance of each cytokine for reflecting MS and its components., Results: Among the studied adipocytokines, adiponectin, AFABP, chemerin, and FGF21 showed the strongest associations with MS and several MS components in discriminant analyses and multiple regression models. For certain metabolic components, these adipocytokines were better discriminators than routine metabolic markers. Other cytokines investigated in the present cohort are less able to distinguish between metabolically healthy and unhealthy subjects., Conclusions: Adiponectin, AFABP, chemerin, and FGF21 showed the strongest associations with MS components in a general population, suggesting that adverse adipose tissue function is a major contributor to these metabolic abnormalities. Future prospective studies should address the question whether these adipocytokines can predict the development of metabolic disease states.

Identifying microbial strains and characterizing their functional potential is essential for pathogen discovery, epidemiology and population genomics. We present pangenome-based phylogenomic analysis (PanPhlAn; http://segatalab.cibio.unitn.it/tools/panphlan), a tool that uses metagenomic data to achieve strain-level microbial profiling resolution. PanPhlAn recognized outbreak strains, produced the largest strain-level population genomic study of human-associated bacteria and, in combination with metatranscriptomics, profiled the transcriptional activity of strains in complex communities.

Introduction: Owing to increasing numbers of decompressive craniectomies in patients with malignant middle cerebral artery infarction, cranioplastic surgery becomes more relevant. However, the current literature mainly consists of retrospective single-centre (evidence class III) studies. This leads to a wide variability of technical approaches and clinical outcomes. To improve our knowledge about the key elements of cranioplasty, which may help optimising clinical treatment and long-term outcome, a prospective multicentre registry across Germany, Austria and Switzerland will be established., Methods: All patients undergoing cranioplastic surgery in participating centres will be invited to join the registry. Technical methods, materials, medical history, adverse events and clinical outcome measures, including modified Rankin scale and EQ-5D, will be assessed at several time points. Patients will be accessible to inclusion either at initial decompressive surgery or when cranioplasty is planned. Scheduled monitoring will be carried out at time of inclusion and subsequently at time of discharge, if any readmission is necessary, and at follow-up presentation. Cosmetic results and patient satisfaction will also be assessed. Collected data will be managed and statistically analysed by an independent biometric institute. The primary endpoint will be mortality, need for operative revision and neurological status at 3 months following cranioplasty., Ethics and Dissemination: Ethics approval was obtained at all participating centres. The registry will provide reliable prospective evidence on surgical techniques, used materials, adverse events and functional outcome, to optimise patient treatment. We expect this study to give new insights in the treatment of skull defects and to provide a basis for future evidence-based therapy regarding cranioplastic surgery., Trial Registration Number: This trial is indexed in the German Clinical Trials Register (DRKS-ID: DRKS00007931). The Universal Trial Number (UTN) is U1111-1168-7425., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Based on level I evidence, postoperative platinum-based radiochemotherapy (PORCT) is the recommended standard of care in defined risk situations after resection of squamous cell carcinomas of the larynx and hypopharynx (LHSCC). The value of the addition of chemotherapy to adjuvant radiation in intermediate and high risk situations other than extracapsular spread or R1-/R2 resection is still debated. From 1993 to 2009, 555 patients (median follow-up: 24.4 months) with advanced LHSCC (UICC stages III-IVB) were treated in a curative intent. Patient data were continuously documented in the county of Leipzig cancer registry and were retrospectively analyzed as mono institutional survey. PORCT was introduced into the standard procedures in 2004, but also applied before in selected cases. Based on this paradigm shift, the patient population was divided into two comparative groups treated before and after 2004. 361 patients were treated before 2004. 43.8 % received primary surgery (OP) + postoperative radiotherapy (PORT) and 20.2 % OP + PORCT. 194 patients were treated after 2004: 21.1 % received OP + PORT and 35.6 % OP + PORCT. Regarding the PORCT groups, 20.6 % received cisplatin plus 5FU before 2004 which shifted to 59.4 % after 2004. The 3-year tumor-specific-survival rate of the whole cohort was improved from 47 to 60 % (p = 0.006). The subgroup treated with OP + PORT or PORCT improved from 56.1 to 68.5 % (p = 0.028). Localization proved to be a significant and independent factor. Only patients with advanced laryngeal cancer had significant improved survival (p < 0.01), while the improvement for hypopharyngeal cancer patients was not significant (p < 0.2). After 2004, there was a slight increase (+10.2 %) of primary radiochemotherapy (pRCT) due to stronger selection if R0 > 5 mm-resectability is unlikely. Standardised use of PORCT and pRCT considering clear indications showed to be significantly involved in improved survival in advanced LHSCC.

Background: Although a relationship between elevated triglycerides (TG) and cardiovascular diseases is generally accepted, its extent is still discussed. This retrospective study analyzed the incidence of cardiovascular events (CVE) and pancreatitis as well as the therapeutic regimen in patients being treated for hypertriglyceridemia (HTG) at an outpatient department., Methods: The cohort included 183 patients with mild and 49 patients with severe HTG; subgroups were formed and compared according to gender, presence of metabolic vascular syndrome (MVS) and lipid values., Results: Patients in this study seem to have had CVE at younger age than reported event rates in the general population. TG levels, rates of CVE and pancreatitis were reduced in all groups during therapy, which could be linked to use of omega-3 fatty acids and fibrates. Patients with persisting severe HTG as a result of incompliance showed massive risk for pancreatitis., Conclusion: Although no significant association between TG levels and CVE could be established, the combination of HTG and other cardiovascular risk factors such as MVS seems to be especially dangerous. The lipid-lowering drug therapy appeared to be effective with respect to CVE and pancreatitis incidence., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Cetuximab and bevacizumab have both been shown to improve outcomes in patients with metastatic colorectal cancer when added to chemotherapy regimens; however, their comparative effectiveness when partnered with first-line fluorouracil, folinic acid, and irinotecan (FOLFIRI) is unknown. We aimed to compare these agents in patients with KRAS (exon 2) codon 12/13 wild-type metastatic colorectal cancer., Methods: In this open-label, randomised, phase 3 trial, we recruited patients aged 18-75 years with stage IV, histologically confirmed colorectal cancer, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, an estimated life expectancy of greater than 3 months, and adequate organ function, from centres in Germany and Austria. Patients were centrally randomised by fax (1:1) to FOLFIRI plus cetuximab or FOLFIRI plus bevacizumab (using permuted blocks of randomly varying size), stratified according to ECOG performance status, number of metastatic sites, white blood cell count, and alkaline phosphatase concentration. The primary endpoint was objective response analysed by intention to treat. The study has completed recruitment, but follow-up of participants is ongoing. The trial is registered with ClinicalTrials.gov, number NCT00433927., Findings: Between Jan 23, 2007, and Sept 19, 2012, 592 patients with KRAS exon 2 wild-type tumours were randomly assigned and received treatment (297 in the FOLFIRI plus cetuximab group and 295 in the FOLFIRI plus bevacizumab group). 184 (62·0%, 95% CI 56·2-67·5) patients in the cetuximab group achieved an objective response compared with 171 (58·0%, 52·1-63·7) in the bevacizumab group (odds ratio 1·18, 95% CI 0·85-1·64; p=0·18). Median progression-free survival was 10·0 months (95% CI 8·8-10·8) in the cetuximab group and 10·3 months (9·8-11·3) in the bevacizumab group (hazard ratio [HR] 1·06, 95% CI 0·88-1·26; p=0·55); however, median overall survival was 28·7 months (95% CI 24·0-36·6) in the cetuximab group compared with 25·0 months (22·7-27·6) in the bevacizumab group (HR 0·77, 95% CI 0·62-0·96; p=0·017). Safety profiles were consistent with the known side-effects of the study drugs. The most common grade 3 or worse adverse events in both treatment groups were haematotoxicity (73 [25%] of 297 patients in the cetuximab group vs 62 [21%] of 295 patients in the bevacizumab group), skin reactions (77 [26%] vs six [2%]), and diarrhoea (34 [11%] vs 40 [14%])., Interpretation: Although the proportion of patients who achieved an objective response did not significantly differ between the FOLFIRI plus cetuximab and FOLFIRI plus bevacizumab groups, the association with longer overall survival suggests that FOLFIRI plus cetuximab could be the preferred first-line regimen for patients with KRAS exon 2 wild-type metastatic colorectal cancer., Funding: Merck KGaA., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Psychiatric disorders (Burnout, depression, anxiety disorders) are common among medical students with a distinctly higher prevalence compared to the general public. Although medi-cal students show a normal health status at the beginning of their university study period, a deterioration of these aspects in higher semesters is evident and continues when they become residents. In our study ESTRELLAS we examined 530 medical students in the preclinical semesters (1st-4th) before their first "Staatsexamen" with validated psychological questionnaires for depression, anxiety, quality of life and sense of coherence. Students in their 1st semester show normal values like the general public. During the 4 semesters a slow and continuous rise of depressive symptoms and anxiety was detected. Quality of life and sense of coherence constantly deteriorated. An increase of physical symptoms was not detected. In the 4th semester the number of depressive students had already doubled. The development of worsening psychological problems and resulting psychiatric disorders seems to be a continuous process, starting with the beginning of the medical studies and growing continuously during the preclinical semesters. Effect-ive strategies for coping with distress should be integrated in the medical curriculum at universities from the very first semester on. Relaxation techniques could thus be an opportunity., (© Georg Thieme Verlag KG Stuttgart · New York.)

This study aimed at confirmatory testing the factorial structure of the established assessment instruments ODI, SF-12 and HADS-D by means of structural equation modeling in a sample of n=184 rehabilitation patients with musculo-skeletal diseases. According to local and global fit indices for each instrument an acceptable to good fit to the underlying theoretical model could be verified. For the ODI as well as for the HADS-D only single weak item-construct associations indicated shortcomings in the assumed model structure. For the SF-12 the constructs "physical health" and "mental health" could be validated after defining the additional first order factors "role - physical", "role - emotional" and "well-being", respectively. In general, the study findings proved the factorial validity of the instruments. Additionally, specific measurement properties on item and structural level could be identified which might enhance the understanding of construct definitions in rehabilitation patients with musculoskeletal diseases., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: A method was developed to convert clinically prescribed RBE (Relative Biological Effectiveness)-weighted doses from the approach used at the Heavy-Ion Medical Accelerator (HIMAC) at the National Institute of Radiological Science, Chiba, Japan, to the LEM (Local Effect Model)-based TReatment planning for Particles (TRiP98) approach used in the pilot project at the GSI Helmholtzzentrum, Darmstadt, and the Heidelberg Ion-Beam Therapy Center (HIT)., Methods and Materials: The proposed conversion method is based on a simulation of the fixed spread-out Bragg peak (SOBP) depth dose profiles as used for the irradiation at HIMAC by LEM/TRiP98 and a recalculation of the resulting RBE-weighted dose distribution. We present data according to the clinical studies conducted at GSI in the past decade (LEM I), as well as data used in current studies (refined LEM version: LEM IV)., Results: We found conversion factors (RBE-weighted dose LEM/RBE-weighted dose HIMAC) reaching from 0.4 to 2.0 for prescribed carbon ion doses from 1 to 60 Gy (RBE) for SOBP extensions ranging from 20 to 120 mm according to the HIMAC approach. A conversion factor of 1.0 was found for approximately 5 Gy (RBE). The conversion factor decreases with increasing prescribed dose. Slightly smaller values for the LEM IV-based data set compared with LEM I were found. A significant dependence of the conversion factor from the SOBP width could be observed in particular for LEM IV, whereas the depth dependence was found to be small., Conclusions: For the interpretation and comparison of clinical trials performed at HIMAC and GSI/HIT, it is of extreme importance to consider these conversion factors because according to the various methods to determine the RBE-weighted dose, similar dose values might not necessarily be related to similar clinical outcomes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Population isolates have long been of interest to genetic epidemiologists because of their potential to increase power to detect disease-causing genetic variants. The Sorbs of Germany are considered as cultural and linguistic isolates and have recently been the focus of disease association mapping efforts. They are thought to have settled in their present location in eastern Germany after a westward migration from a largely Slavic-speaking territory during the Middle Ages. To examine Sorbian genetic diversity within the context of other European populations, we analyzed genotype data for over 30 000 autosomal single-nucleotide polymorphisms from over 200 Sorbs individuals. We compare the Sorbs with other European individuals, including samples from population isolates. Despite their geographical proximity to German speakers, the Sorbs showed greatest genetic similarity to Polish and Czech individuals, consistent with the linguistic proximity of Sorbian to other West Slavic languages. The Sorbs also showed evidence of subtle levels of genetic isolation in comparison with samples from non-isolated European populations. The level of genetic isolation was less than that observed for the Sardinians and French Basque, who were clear outliers on multiple measures of isolation. The finding of the Sorbs as only a minor genetic isolate demonstrates the need to genetically characterize putative population isolates, as they possess a wide range of levels of isolation because of their different demographic histories.

Background: The Sorbs are an ethnic minority in Germany with putative genetic isolation, making the population interesting for disease mapping. A sample of N = 977 Sorbs is currently analysed in several genome-wide meta-analyses. Since genetic differences between populations are a major confounding factor in genetic meta-analyses, we compare the Sorbs with the German outbred population of the KORA F3 study (N = 1644) and other publically available European HapMap populations by population genetic means. We also aim to separate effects of over-sampling of families in the Sorbs sample from effects of genetic isolation and compare the power of genetic association studies between the samples., Results: The degree of relatedness was significantly higher in the Sorbs. Principal components analysis revealed a west to east clustering of KORA individuals born in Germany, KORA individuals born in Poland or Czech Republic, Half-Sorbs (less than four Sorbian grandparents) and Full-Sorbs. The Sorbs cluster is nearest to the cluster of KORA individuals born in Poland. The number of rare SNPs is significantly higher in the Sorbs sample. FST between KORA and Sorbs is an order of magnitude higher than between different regions in Germany. Compared to the other populations, Sorbs show a higher proportion of individuals with runs of homozygosity between 2.5 Mb and 5 Mb. Linkage disequilibrium (LD) at longer range is also slightly increased but this has no effect on the power of association studies. Oversampling of families in the Sorbs sample causes detectable bias regarding higher FST values and higher LD but the effect is an order of magnitude smaller than the observed differences between KORA and Sorbs. Relatedness in the Sorbs also influenced the power of uncorrected association analyses., Conclusions: Sorbs show signs of genetic isolation which cannot be explained by over-sampling of relatives, but the effects are moderate in size. The Slavonic origin of the Sorbs is still genetically detectable. Regarding LD structure, a clear advantage for genome-wide association studies cannot be deduced. The significant amount of cryptic relatedness in the Sorbs sample results in inflated variances of Beta-estimators which should be considered in genetic association analyses.

Purpose: To identify predictors for the development of temporal lobe reactions (TLR) after carbon ion radiation therapy (RT) for radiation-resistant tumors in the central nervous system and to evaluate the predictions of the local effect model (LEM) used for calculation of the biologically effective dose., Methods and Materials: This retrospective study reports the TLR rates in patients with skull base chordomas and chondrosarcomas irradiated with carbon ions at GSI, Darmstadt, Germany, in the years 2002 and 2003. Calculation of the relative biological effectiveness and dose optimization of treatment plans were performed on the basis of the LEM. Clinical examinations and magnetic resonance imaging (MRI) were performed at 3, 6, and 12 months after RT and annually thereafter. Local contrast medium enhancement in temporal lobes, as detected on MRI, was regarded as radiation-induced TLR. Dose-volume histograms of 118 temporal lobes in 59 patients were analyzed, and 16 therapy-associated and 2 patient-associated factors were statistically evaluated for their predictive value for the occurrence of TLR., Results: Median follow-up was 2.5 years (range, 0.3-6.6 years). Age and maximum dose applied to at least 1 cm(3) of the temporal lobe (D(max,V - 1 cm)3, maximum dose in the remaining temporal lobe volume, excluding the volume 1 cm(3) with the highest dose) were found to be the most important predictors for TLR. Dose response curves of D(max,V - 1 cm)3 were calculated. The biologically equivalent tolerance doses for the 5% and 50% probabilities to develop TLR were 68.8 ± 3.3 Gy equivalents (GyE) and 87.3 ± 2.8 GyE, respectively., Conclusions: D(max,V - 1 cm)3 is predictive for radiation-induced TLR. The tolerance doses obtained seem to be consistent with published data for highly conformal photon and proton irradiations. We could not detect any clinically relevant deviations between clinical findings and expectations based on predictions of the LEM., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate the diagnostic value of monitoring CD64 antigen upregulation on polymorphonuclear neutrophils (PMN) for the identification of infectious complications in the postoperative course of solid organ transplanted patients. Twenty-five kidney, 13 liver, and four pancreas-kidney transplanted patients were included. Beginning with preoperative values up to postoperative values after 3 months for each patient, the PMN CD64 Index, HLA-DR on monocytes, NKp44+ NK and NK/T cells, CXCR3+ NK cells, CXCR3+ T helper cells, CXCR3+ NK/T cells, and CD4/CD8 ratio were measured by flow cytometry. Subsequently they were correlated with confirmed postoperative complications. Measuring the PMN CD64 Index reached a sensitivity of 89% and a specificity of 65% in the detection of infectious complications. Concerning this matter, it was a significantly better marker than all other included parameters except CXCR3+ NK/T cells. In contrast, according to our results the PMN CD64 Index has no diagnostic relevance in detection of rejections. The combination of included parameters showed no improved diagnostic value. Due to its high sensitivity and specificity for infectious complications CD64 on PMN could be proven a very good indicator in evaluating suspected infectious complications in the postoperative course of transplanted patients., (Copyright © 2011 International Society for Advancement of Cytometry.)

Background: Several studies suggest fusion rates are higher with anterior cervical discectomy and fusion procedures if supplemented with a plate. However, plates may be associated with higher postoperative morbidity and higher rates of dysphagia. This led to the development of a cervical stand-alone cage with integrated fixation for zero-profile segmental stabilization., Questions/purposes: We asked whether this new implant would be associated with a low rate of dysphagia and other short-term complications in patients having anterior cervical discectomy and fusion and would be able to achieve solid fusion and maintain postoperative reduction in pain., Methods: We prospectively followed 38 patients with radiculopathy/myelopathy undergoing anterior cervical discectomy and fusion using the new implant. Intraoperative parameters, clinical features (Neck Pain Disability Index, visual analog scale score for neck/arm pain, Odom's criteria), and dysphagia scores were recorded. Radiographs were taken to assess implant failure. Thirty-four patients had a minimum 6 months' followup (mean, 8 months; range, 6-11 months)., Results: Three patients at 6 weeks and one patient at 6 months complained about minor dysphagia-related symptoms. There was no hardware failure recordable and all patients had evidence of fusion. Compared to preoperatively, visual analog scale pain score and Neck Pain Disability Index were reduced at 6 weeks' followup without change during further followup., Conclusions: The new cervical stand-alone anterior fusion device allows decompression and fusion with low complication rates. The incidence of chronic postoperative dysphagia was infrequent in comparison to published data. Prospective randomized trials with more patients and longer followup are necessary to confirm these observations., Level of Evidence: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

This paper gives recommendations for treatment of thoracolumbar and lumbar spine injuries. The recommendations are based on the experience of the involved spine surgeons, who are part of a study group of the "Deutsche Gesellschaft für Unfallchirurgie" and a review of the current literature. Basics of diagnostic, conservative, and operative therapy are demonstrated. Fractures are evaluated by using morphologic criteria like destruction of the vertebral body, fragment dislocation, narrowing of the spinal canal, and deviation from the individual physiologic profile. Deviations from the individual sagittal profile are described by using the monosegmental or bisegmental end plate angle. The recommendations are developed for acute traumatic fractures in patients without severe osteoporotic disease.

Several small case-control studies have investigated whether factor V Leiden (FVL) is a risk factor for retinal vein occlusion (RVO) and generated conflicting data. To clarify this question we performed a large two-centre case-control study and a meta-analysis of published studies. Two hundred seven consecutive patients with RVO and a control group of 150 subjects were screened between 1996 and 2006. A systematic meta-analysis was done combining our study with further 17 published European case-control studies. APC resistance was detected in 16 out of 207 (7.7%) patients and eight out of 150 (5.3%) controls. The odds ratio (OR) estimated was 1.49 with a (non-significant) 95% confidence interval (CI) of 0.62-3.57. The meta-analysis including 18 studies with a total of 1,748 patients and 2,716 controls showed a significantly higher prevalence of FVL in patients with RVO compared to healthy controls (combined OR 1.66; 95% CI 1.19-2.32). All single studies combined in the meta-analysis were too small to reliably detect the effect individually. This explains the seemingly contradictory data in the literature. In conclusion, the prevalence of APC resistance (and FVL) is increased in patients with RVO compared to controls, but the effect is only moderate. Therefore, there is no indication for general screening of factor V mutation in all patients with RVO. We recommend this test to be performed in patients older than 50 years with an additional history of thromboembolic event and in younger patients without general risk factors like hypertension.

This article describes the practice of multi-family therapy in day care settings. Between six to eight families attend together for whole days and weeks and the principles and the methods of this approach are described and illustrated with examples of systemic work with children with severe behavioural and learning disorders, as well as with adolescents presenting with anorexia nervosa.

Purpose: The development of overall survival of a DOSAK (German-Austrian-Swiss Cooperative Group on tumours of the maxillofacial region) clinic's overall population comprising a time period of more than 20 years (1983-2004) should be assessed. At a cutoff date (January 1st, 1997), a change from a primarily surgically based to a consequent multi-modality treatment regimen was implemented. The periods of time before and after that change should be compared., Methods and Patients: The data of the DOSAK registry entries on 1038 patients suffering from primary untreated oral and oropharyngeal carcinomas were updated with respect to follow-up and mortality data to achieve a 100% quality of follow-up. The end point (death) was reached in 67% of the overall population. Statistical analysis was carried out by the Trium Analysis Online corporation, Munich., Results: The portion of female and older tumor patients increased, more than half of all tumor patients were clearly in stage IV of the disease at first referral. The portion of patients operated on persisted approximately (80%), the portion of additional treatment modalities could be increased considerably. The fact of a bony infiltration by the tumor and the operability remained highly significantly relevant for survival in multivariate analysis, despite of multi-modality treatment. The survival rate of the patients remained significantly dependent on the clinical stage of the disease in multivariate analysis but could be improved by 10% in the clinical stages II and III and in the patients who could not be operated on. All in all, the cutoff date was statistically relevant for survival in multivariate analysis, i.[Symbol: see text]e. the change in the treatment regimen had a verifiable positive effect on the survival of a unicentric overall population., Conclusion: Survival improvement in an overall population via change in treatment strategy is possible in relatively short time; the clinical stages II and III and the non-operable patients have the greatest benefit from a multi-modality treatment.

Background: Multiple sclerosis is a chronic disease of uncertain aetiology. Variations in its disease course make it difficult to impossible to accurately determine the prognosis of individual patients. The Sylvia Lawry Centre for Multiple Sclerosis Research (SLCMSR) developed an "online analytical processing (OLAP)" tool that takes advantage of extant clinical trials data and allows one to model the near term future course of this chronic disease for an individual patient., Results: For a given patient the most similar patients of the SLCMSR database are intelligently selected by a model-based matching algorithm integrated into an OLAP-tool to enable real time, web-based statistical analyses. The underlying database (last update April 2005) contains 1,059 patients derived from 30 placebo arms of controlled clinical trials. Demographic information on the entire database and the portion selected for comparison are displayed. The result of the statistical comparison is provided as a display of the course of Expanded Disability Status Scale (EDSS) for individuals in the database with regions of probable progression over time, along with their mean relapse rate. Kaplan-Meier curves for time to sustained progression in the EDSS and time to requirement of constant assistance to walk (EDSS 6) are also displayed. The software-application OLAP anticipates the input MS patient's course on the basis of baseline values and the known course of disease for similar patients who have been followed in clinical trials., Conclusion: This simulation could be useful for physicians, researchers and other professionals who counsel patients on therapeutic options. The application can be modified for studying the natural history of other chronic diseases, if and when similar datasets on which the OLAP operates exist.

Purpose: Calculation of the average glandular dose for mammography on a full-field digital mammography system using a selenium flat-panel detector., Materials and Methods: Mammographic examinations were carried out using the Selenia digital mammographic system from Lorad/Hologic. 1992 mammographies of 500 patients in cranio-caudal and medio-lateral projections were evaluated. Based on the recorded exposure conditions (tube voltage, tube loading, filtration, compressed breast thickness), the entrance surface air kerma was calculated by multiplying the tube loading by the measured tube output and was corrected according to the inverse square law. The average glandular dose was determined for each exposure by multiplying the entrance surface air kerma value by the relevant conversion factor for a breast composition of 50 % adipose tissue and 50 % glandular tissue by weight., Results: The mean values for patient age and compressed breast thickness were 61 years and 58 mm, respectively. The average glandular dose was 1.57 mGy for a single view (1.46 mGy for cranio-caudal view images and 1.68 mGy for medio-lateral view images)., Conclusion: Full-field digital mammography with a selenium flat-panel detector requires a dose similar to that of units with a flat-panel detector based on amorphous silicon and a dose approximately 20 % lower than that of conventional screen/film mammography.

Aim: Surgery in cervical spine disease using titanium cages is a common procedure to reduce the pain and neurological deficits. This study was aimed to evaluate the results in pain reduction using the wing cage intraoperatively., Method: In this prospective study demographic data were noted, whereas special emphasis was placed on pain, which was noted using a visual pain scale and the prolo score, neurological deficits and the causing pathology. Furthermore, questions about the use of analgesics and the duration of pain were asked. After operation with insertion of a wing cage instead of the disk, a neurological investigation 6, 12 and 24 months later was done to evaluate the postoperative status., Results: 54 patients underwent a cervical discectomy in 64 segments as therapy for neck pain or a radiculopathy caused by osteochondrosis or disc disorder. Patients with brachialgia profited most from the operation. Less improvement was seen in cases of osteochondrosis or combined pathology., Conclusion: Patients with pain caused by discs in the cervical spine, have better improvement than patients with other pathologies. This should be taken into account when choosing the mode of therapy.

Applying the MIRA (German acronym for losing weight intelligently) concept, weight-losing programs were tested for guideline conformity and suitability in practice. The core of the concept comprises instruments for the analysis and evaluation of quality criteria for weight-reduction programs. A total of 116 men and women participated in the BCM program of PreCon GmbH & Co. KG, and the "Ich nehme ab" (l'm slimming) program (designed as a self-help aid) of the Deutsche Gesellschaft für Ernährung (German Society for Nutrition), and received counseling over a period of one year. Initial results of follow-up at 40 weeks showed a weight reduction of at least 5% in 66% of all participants, and at least 10% in 24%. The weight loss correlated with the number of counselings. On the basis of the 89 questionnaires evaluated to date, quality of life as measured by the IWQOL-Lite score showed an improvement in 80% of the subjects. These preliminary results indicate that the MIRA concept would appear to be a suitable quality control tool for obesity treatment programs.

Kinship determination is one of the major challenges for the anthropologist studying graveyard populations. Traditional techniques based on morphological comparisons of bone remains are limited. However, recent methods which generate and characterise DNA sequences derived from bones bear the possibility for a more accurate analysis. Extraction and characterisation of authentic nucleic acids was performed on a number of individuals from the early Medieval graveyard of Neresheim, South Germany. From this cemetery a total of 38 skeletal remains of individuals buried between 450 and 700 AD were examined using PCR-based methods. Comparisons were made using four human-specific short tandem repeat loci and the X/Y-specific amelogenin sex test. Twenty-eight of the approximately 1,500-year-old individuals yielded alleles in at least one of the polymorphic nuclear loci HumCD4, HumFES, HumTH01, HumVWA, and the sex test. These along with a 96 bp DNA variant previously unknown in recent CD4 contexts, and supporting evidence from anthropology and archaeology were used for defining one parental and one filial generation in each of three multiple burials (Ne 2, Ne 9 and Ne 78) in the cemetery.

The isolation and examination DNA segments from prehistoric and fossil bone samples has become one of the biggest challenges in anthropology within the past years. By using specially developed and/or adapted genetic methods, it is possible under laboratory conditions to amplify portions of DNA from bone remains in states of good preservation by the polymerase chain reaction (PCR). DNA sequence data can provide far more specific answers to palaeanthropological questions than one would expect solely by morphologic comparison. Here we introduce an alternative approach for the classification of total ancient DNA by means of Southern hybridisation techniques.

Southern blot hybridizations of genomic DNA were introduced as a relatively simple fossil-DNA-based approach to classify remains of Neanderthals. When hybridized with genomic DNA of either human or Neanderthal origin, DNA extracted from two Neanderthal finds-the Os parietale, from Warendorf-Neuwarendorf, Germany, and a clavicula, from Krapina, Croatia-was shown to yield hybridization signals that differ by at least a factor of two compared to the signals obtained with the use of fossil DNA of an early Homo sapiens from the Vogelherd cave (Stetten I), Germany. When labeled chimpanzee DNA was used as a probe, Neanderthal and human DNA, however, revealed hybridization signals of similar intensity. Thus, the genome of Neanderthals is expected to differ significantly from the genome of anatomically modern man, because of the contrasting composition of repetitive DNA. These data support the hypothesis that Neanderthals were not ancestors of anatomically modern man.

The most notable feature of DNA extracted from prehistoric material is that it is of poor quality. Amplification of PCR products from such DNA is consequently an exception. Here we present a simple method for the repair of degraded duplex DNA using the enzymes Escherichia coli DNA polymerase I and T4 DNA ligase. Adjacent sequences separated by nicks do not split up into intact strands during the denaturation step of PCR. Thus the target DNA is refractory to amplification. The proposed repair of nicked, fragmented ancient DNA results in an increase of amplification efficiency, such that the correct base order of the respective nuclear DNA segment can be obtained.

A total of 2,979 schoolboys and schoolgirls attending different types of German schools during their seventh year of school attendance (which begins at the age of six) were investigated by means of an anonymous questionnaire in two medium-sized German cities and their suburbs, in respect of smoking behaviour and consumption of drugs and alcoholic beverages. The proportion of schoolboys and schoolgirls smoking at least once or twice a week depended on the type of school: pupils of high schools (linguistic branch, known as "Gymnasium" in Germany) had a quota of 2.7%, whereas there were 14.3% smokers among those attending a category of public school termed "Hauptschule" (a kind of school with elementary and continuing education and a total of nine years' school attendance) and 5.6% smokers among the so-called "Realschüler" (a kind of grammar school stressing practical subjects with a total of 10 years of school attendance) and 8.2% among pupils attending a kind of integrated grammar-cum-"Hauptschule" with an alternative-choice 9-year or 10-year schedule (so-called "Gesamtschule"). A similar distribution was seen in respect of alcohol and drug consumption. Schoolboys and schoolgirls smoking at least once or twice a week will also be drinking a glass of beer per week six times as often as non-smoking pupils. In respect of wine the ratio is 4:1 and in respect of brandy 7:1. Smokers among the pupils have been trying out drugs at least once, six times as often as non-smokers. Results are statistically highly significant (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

The study was designed to examine the clinical applicability and use of computer-assisted EEG-analysis in comparison to visual EEG-analysis in patients with minor head injuries. For this in 31 patients the following examinations were performed within the first 24 hours, one, three and eight weeks after traumatization: EEG, neurological examination and standardized evaluation of subjective complaints. The EEG was analysed visually as well as computer-assisted. The results were compared to the neurological findings and subjective complaints. Reversible posttraumatic EEG-changes were observed in 50% of all patients. The results of computer-analysis and visual analysis were equivalent in respect to baseline-activity (as one of the main characteristic EEG-features). Furthermore, based on computer-assisted analysis a discriminant function is provided, which is of diagnostic and prognostic value in the single patient. We conclude that the computer-assisted EEG-analysis can be a useful alternative in EEG-routine diagnosis after minor head injuries.