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Purpose: Annual cervical cancer screening is recommended in Germany as a part of the statutory preventive care. Abnormal results can provoke psychological distress and anxiety, compromising women's adherence. Little is known about how a cervical dysplasia impacts adherence follow-up visits and prevention habits over time. To optimize care strategies, this study aims to identify women at risk for nonadherence to follow-up visits after a screening event.Methods: Between November 2015 and May 2017, participants with an abnormal Pap smear at the Heidelberg and Leipzig University Hospitals received a four-part questionnaire (sociodemographic data, PHQ-D, self-designed fear and prevention habit questions) at the first consultation (T1) and subsequently after 3 (T2) and 6 (T3) months; healthy controls completed the questionnaire at T1.Results: 132 women with an abnormal Pap smear [with conization: S1 (n = 68, 51.5%), without intervention: S2 (n = 64, 48.5%)] and healthy controls (K, n = 101) generally adhered to gynecological checkups, except S1 6 months after the first diagnosis (S1/T3 - 0.47, signed rank p < 0.0005). Knowledge of primary prevention information, i.e., HPV vaccination, was significantly higher among K (K 58%, S1 29%, S2 44%, Chi-squared p = 0.01) as was vaccine uptake (K 39% versus S1/S2 7% and 17%, respectively, Chi-squared p = 0.0004). Fear of upcoming Pap smears rose significantly over time (S1/T1-S1/T2-S1/T3, Wilcoxon signed-rank test p < 0.001) and was higher among those with conization at T2 (Chi-square test, p = 0.01) and partially accompanied by panic disorders at T1 (Chi-square test p = 0.035). Realization of general preventive habits rose significantly among women without an operative procedure (S2) over the study.Conclusion: This study advances the understanding of non-participation in follow-up visits after a dysplasia diagnosis, identifying post-conization women as a special risk group for decreased adherence. [ABSTRACT FROM AUTHOR]

Study Question: Is there a difference in mental development of children conceived by IVM in comparison to IVF or ICSI, independently, at the age of 2 years?Summary Answer: No differences could be found in mental development of IVM children compared to IVF and IVM children compared to ICSI as well.What Is Known Already: Only few retrospective or non-controlled studies addressed the health of IVM children and did not show a negative impact of the IVM procedure.Study Design, Size, Duration: Prospective controlled single-blinded study including 63 pregnancies (21 per IVM, IVF and ICSI groups) with 70 children expected. Examinations of 62 embryos at first trimester screening, of 57 fetuses at 21st week of pregnancy, of 60 children at birth and of 37 children at their second birthday were performed during the study period from January 2009 until October 2016. Bayley score at the age of 2 was the primary outcome parameter. Data of 40 children after spontaneous conception from a previous prospective unrelated study were further used as control at 2 years examination and compared to the pooled ART group (IVM, IVF and ICSI).Participants/materials, Setting, Methods: Twenty-one IVM pregnancies achieved in the study period were included. For each of them, the following IVF- and ICSI pregnancies were recruited as controls. Ultrasound examinations during pregnancy, examinations of newborns and of children around their second birthday were done by blinded prenatal specialists, pediatricians and neuropediatricians, respectively.Main Results and the Role Of Chance: Children conceived after IVM did not show differences during embryonic development, at birth nor in their neuropediatric development at the age of 2 compared to their counterparts after IVF and after ICSI (Bayley score 91.3 ± 21.0 for IVM, 96.8 ± 13.2 for IVF and 103.9 ± 13.1 for ICSI) and of the pooled ART group compared to children after spontaneous conception (96.6 ± 16.4 ART and 103.2 ± 9.4 spontaneous conception). When analyzing singleton pregnancies only, again no differences during pregnancy, at birth and at their 2-year evaluation were detected between IVM versus IVF and IVM versus ICSI.Limitations, Reasons For Caution: Due to the small sample size data must be interpreted with caution. To allow a confirmative answer that there are no health risks for children conceived by IVM, large multicenter cohort or registry-based studies are urgently needed.Wider Implications Of the Findings: The study adds further information to previous uncontrolled or retrospective studies, which were unable to detect risks for the health of IVM children.Study Funding/competing Interest(s): The study was supported by the 'Deutsche Forschungsgemeinschaft' (DFG): STR 387/4-1. G.R. receives royalties from Pearson Assessment Germany (editor fee for Bayley-III). The other authors have no conflicts of interest to declare.Trial Registration Number: Not applicable. [ABSTRACT FROM AUTHOR]

What is known and objective Patients' drug administration errors are often promoted by poor drug knowledge resulting from inadequate oral or written information. It has previously been shown that a medication plan enhanced with graphical and textual information on drug handling (enhanced medication plan) proved to immediately increase patients' drug knowledge. This study aimed to evaluate the effect of the enhanced medication plan on drug knowledge in outpatients after 2 months (intervention group) compared to patients with a simple medication plan with standard information (control group). Methods We recruited patients using ≥5 drugs in four family practices in Germany. After inclusion, patients' knowledge on handling of their drugs was assessed using three questions from a standardized catalog. Thereafter, patients were randomized to the intervention or control group. After 2 months, drug knowledge was reassessed with three different questions from the same standardized catalog. Results and discussion Of 120 enrolled patients, 75% of participants in the control group (42/60 patients) and 78% of participants in the intervention group (46/60; P = 0·71) completed the study. Baseline drug knowledge was similar in both groups (43·7% vs. 40·6% correct answers). After 2 months, patients' drug knowledge showed an absolute increase of 23·2% in the intervention group ( P < 0·01) and was unchanged in the control group (46·0%; P = 0·70). What is new and conclusion The enhanced medication plan outperformed the effect of a simple medication plan and persistently increased the fraction of correct answers of polypharmacy patients. This demonstrates that the enhanced medication plan may be a useful tool in promoting drug knowledge. [ABSTRACT FROM AUTHOR]

Study design:Serum levels of interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α) were measured over a 12-week period in 23 patients with spinal cord injury (SCI) with and without neurological improvement.Objectives:To determine the course of IL-1β and TNF-α in patients with SCI and observe a possible relationship between improvements in neurological functioning and cytokine levels.Setting:All patients were treated at the BG Trauma Centre, Ludwigshafen, Germany. All lab work was done at the University Hospital, Heidelberg.Methods:Spinal cord injury was classified according to the American Spinal Injury Association (ASIA) impairment scale (AIS) in 23 patients. TNF-α and IL-1β levels were measured upon arrival at the hospital, after 4 h, 9 h and 12 h, on days 1 and 3 and at the end of weeks 1, 2, 4, 8 and 12.Results:Temporal changes in TNF-α and IL-1β in SCI patients were seen. Patients with AIS improvement (Group 1) had significantly lower TNF-α levels at 9 h compared with patients without AIS improvement (Group 2; P<0.01). The course of IL-1β fluctuated greatly between 4 h and week 1 in the groups; however, between 2 and 12 weeks post trauma, there was an overall decline in both groups.Conclusion:Measuring serum levels of TNF-α and IL-1β over time could be useful in tracking the course of SCI. Our data show differences in measured cytokines over a 12-week period for SCI patients with and without neurological improvement. [ABSTRACT FROM AUTHOR]

Summary: Vitamin D deficiency is associated with increased fracture risk. The observational study aimed to investigate vitamin D status and supplementation in ambulatory patients. Only 20% of patients had optimal serum 25-hydroxyvitamin D [25(OH)D] levels. Commonly recommended dosages were insufficient to achieve clinically relevant increase of 25(OH)D levels. Higher dosages were safe and effective under clinical practice conditions. Introduction: Vitamin D deficiency is associated with adverse health outcome. The study aimed to investigate vitamin D status and supplementation in ambulatory patients. Methods: Nine hundred seventy-five women and 188 men were evaluated for bone status from January 2008 to August 2008 within an observational study; 104 patients ( n = 70 osteoporosis) received follow-up after 3 months. Dosage of vitamin D supplementation was documented and serum 25(OH)D and parathyroid hormone (PTH) determined. Results: In all patients (age, 60.4 ± 14.1 years), distribution of 25(OH)D was 56.3 ± 22.3 nmol/L (normal range, 52-182 nmol/L) and PTH 53.8 ± 67.5 ng/L (normal range, 11-43 ng/L). The proportion of patients with 25(OH)D < 25, 25 to <50, 50 to <75, ≥75 nmol/L was 7.5%, 33.3%, 38.9% and 20.2% in the total group and 20.1%, 38.5%, 30.8%, 10.6% at baseline in the follow-up group, respectively. After 3 months, 3.9% had still 25(OH)D < 25 nmol/L; only 12.5% achieved 25(OH)D ≥ 75 nmol/L. In osteoporosis patients, 25(OH)D increased more in those taking ≥1,500 (median, 3,000) IU vitamin D per day (33.1 ± 14.7 nmol/L) compared with ≤1,000 (median, 800) IU/day (10.6 ± 20.0 nmol/L) ( p < 0.0008). PTH decreased more in patients taking ≥1,500 IU/day (−13.2 ± 15.2 ng/L) compared with ≤1,000 IU/day (−7.6 ± 19.2 ng/L; p = 0.29). 25(OH)D was negatively correlated to PTH ( r = −0.49, p < 0.0001). An increase of 25(OH)D ≥ 75 nmol/L resulted in normalised PTH. Conclusion: Supplementation with higher vitamin D dosages (2,000-3,000 IU/day) is required to achieve a relevant increase of 25(OH)D and normalisation of PTH. [ABSTRACT FROM AUTHOR]

Background: Sedation prior to performance of diagnostic esophagogastroduodenoscopy (EGDE) is widespread and increases patient comfort. But 98% of all serious adverse events during EGDEs are ascribed to sedation. The S3 guideline for sedation procedures in gastrointestinal endoscopy published in 2008 in Germany increases patient safety by standardization. These new regulations increase costs because of the need for more personnel and a prolonged discharge procedure after examinations with sedation. Many patients have difficulties to meet the discharge criteria regulated by the S3 guideline, e.g. the call for a second person to escort them home, to resign from driving and working for the rest of the day, resulting in a refusal of sedation. Therefore, we would like to examine if an acupuncture during elective, diagnostic EGDEs could increase the comfort of patients refusing systemic sedation. Methods/Design: A single-center, double blinded, placebo controlled superiority trial to compare the success rates of elective, diagnostic EGDEs with real and placebo acupuncture. All patients aged 18 years or older scheduled for elective, diagnostic EGDE who refuse a systemic sedation are eligible. 354 patients will be randomized. The primary endpoint is the rate of successful EGDEs with the randomized technique. Intervention: Real or placebo acupuncture before and during EGDE. Duration of study: Approximately 24 months. Discussion: Organisation/Responsibility The ACUPEND - Trial will be conducted in accordance with the protocol and in compliance with the moral, ethical, and scientific principles governing clinical research as set out in the Declaration of Helsinki (1989) and Good Clinical Practice (GCP). The Interdisciplinary Endoscopy Center (IEZ) of the University Hospital Heidelberg is responsible for design and conduct of the trial, including randomization and documentation of patients' data. Data management and statistical analysis will be performed by the independent Institute for Medical Biometry and Informatics (IMBI) and the Center of Clinical Trials (KSC) at the Department of General, Visceral and Transplantation Surgery, University of Heidelberg. [ABSTRACT FROM AUTHOR]

Objective: To analyse time trends in overweight and obesity from 1991 to 2000 in samples of German children and to test the hypothesis of a trend difference between the samples from East and West Germany during this time period. Design: Repeated cross-sectional studies using data of 35 434 five to seven-year-old children from school entry examinations in several rural and urban areas in East and West Germany (between 1991 and 2000). The main outcome measures were overweight and obesity. Weight and height were measured and body mass index was calculated. International cut-off points were used to classify overweight and obesity. Results: From 1991 to 2000, the prevalence of overweight increased from 10.0% to 17.5% in the East and from 14.8% to 22.2% in the West. The prevalence of obesity increased from 2.1% to 5.7% in the East and from 3.6% to 7.6% in the West. All increases were significant. There was no evidence of a trend difference between the East and the West German samples. Conclusions: Unlike in other countries in transition, prevalences of childhood overweight and obesity were increasing in samples of East German children after reunification in 1990, possibly as a result of the rapid adoption of a western lifestyle in the East. Although prevalences were generally higher in the West German samples, there was no evidence that the increase was levelling off in the West. Overall, trends were similar in the East and West German samples. [ABSTRACT FROM AUTHOR]

Background Pruritus is the most frequent and distressing symptom associated with dermatoses and various internal and neurological diseases. Objectives To investigate two different populations of patients with pruritus, one in Germany and one in Uganda, with a particular focus on clinical characteristics, aetiology and quality of life. Methods We investigated by questionnaire 132 patients (59 men, 73 women, mean age 54·5 years) who were referred to the Department of Dermatology at the University Hospital of Magdeburg, Germany, with the diagnosis of pruritus as a leading symptom. The questionnaire was also applied in 84 patients who consulted the Dermatology Clinic at Mbarara, Uganda for pruritus. The questions referred to personal data and disease history of the individual, history and present occurrence of concomitant diseases, present and past therapy, quality, frequency and triggers of itching and scratching, other disorders and complaints, quality of life and impact on work and disability. Results Seventy-five (57%) of the German patients had pruritus due to dermatoses, 47 patients (36%) had pruritus due to a systemic disease and in 10 patients (8%) pruritus was of unknown origin. Most had a history of pruritus of several months up to years. Pruritus associated with dermatoses mostly affected the whole body and was permanent with an undulatory character. Affective reactions such as aggression and depression occurred more frequently in dermatological patients compared with those with systemic pruritus. The former group felt that pruritus had a greater impact on their lives. Almost all Ugandan patients had pruritus due to dermatoses except for three patients with pruritus of unknown origin. Eczema and prurigo were the most frequently observed dermatoses in both German and Ugandan patients. Patients with pruritus in both populations showed an impaired quality of life. There was no pronounced difference between the populations with regard to feelings of depression and suicidal thoughts. Conclusions A great deal of helpful information in this complex group of patients can be obtained using this questionnaire. Pruritus has a major impact on quality of life and especially impairs those patients with pruritus associated with dermatoses and pruritus of unknown origin. [ABSTRACT FROM AUTHOR]

Construction workers have a substantial risk of developing irritant and/or allergic contact dermatitis. Unfortunately, however, there is little population-based epidemiological data relating to occupational skin diseases (OSD) in the European construction industry that allow assessment of preventive measures. In this investigation, the yearly incidence rates and causes of OSD in the construction industry were analysed on the basis of our register in Northern Bavaria. From 1990 until 1999, all incidences of OSD in the construction industry were recorded prospectively. This enables the calculation of incidence rates of OSD in relation to the employed population in Northern Bavaria as recorded by the German Federal Employment Office. In the construction industry, a total of 335 OSD were registered. These comprise 9·0% of all OSD in the register. We classified them into four relevant groups: (A) tile setters and terrazzo workers (incidence per 10 000 employees = 19·9); (B) painters (7·8); (C) construction and cement workers (5·2); and (D) wood processors (2·6). The overall incidence was 5·1 per 10 000 employees over 10 years, which is a little below average for the entire register (6·7). Of these, 43·6% were at least 40 years old. Allergic contact dermatitis (61·5%) occurred more often than irritant contact dermatitis (44·5%). Potassium dichromate caused roughly half of all cases of sensitization found to be occupationally relevant in the construction industry (152 cases) followed by epoxy resin (40) and cobalt chloride (32). The results indicate that potassium dichromate is still the most important allergen in the construction industry of Northern Bavaria; there has been no significant decline during the 1990s. This contrasts with the Scandinavian countries, where the prevalence of potassium dichromate sensitization declined following the reduction of chromium VI levels resulting from the addition of ferrous sulphate to cement. Within the construction industry, tile setters and terrazzo workers have a strikingly high incidence of OSD. [ABSTRACT FROM AUTHOR]

Objectives: Several studies concerning the prevalence of hand eczema in certain occupations have been performed during the last years, but few data exist from population-based surveys. The following study investigates the 1-year prevalence and point prevalence of hand eczema in the population of Heidelberg, Germany. Methods: 2500 randomly selected inhabitants of Heidelberg between 20 and 60 years of age were asked to fill in a questionnaire on hand eczema consisting of both symptom-based and diagnose-related questions. The questionnaire was developed according to the one validated and published in 1992 by Smit et al. Furthermore, the study population was asked about a possible correlation between skin changes and occupation. Results: With 192 persons having already moved out of the study area and a remaining sample size of 2308, the response rate was 73%. For yet another 5% of the study population, reasons for non-response could be assessed. Of the 1690 responders, 22% had experienced at least one of the following symptoms on their hands during the last 12 months: redness and swelling, redness and fissures, vesicles, scaling and fissures, itching and fissures. 41% of affected persons reported their symptoms persisting for longer than 3 weeks, and in 77% of affected persons the symptoms occurred more than once. However, a self-reported diagnosis of hand eczema during the last 12 months was given by only 6% of study participants, and only 3,5% reported a present hand eczema. 6% of study participants (26% of persons with skin changes on their hands) established a relationship between their symptoms and occupation, a further 4% was not sure how to answer. Conclusions: Symptoms possibly pointing to hand eczema are often to be found in our study population, but only a fraction of the persons affected seems to be aware of the diagnosis. If symptom-related questions are used in questionnaire surveys, the prevalence of hand eczema could be overestimated, but asking only for a self-reported diagnosis could lead to an underestimation of the true values for prevalence. Validated criteria for the diagnosis of hand eczema should be defined in order to facilitate questionnaire studies. [ABSTRACT FROM AUTHOR]

Context: Long-term data are scarce on large cohorts with sporadic (sMTC) and hereditary medullary thyroid carcinoma (hMTC)., Objectives: To compare long-term disease-specific survival (DSS) and outcomes between sMTC and hMTC groups., Design: Retrospective analysis., Setting: German tertiary referral center., Patients: A total of 673 patients with MTC that underwent surgery from January 1974 to July 2019., Intervention: None (observational study)., Main Outcome Measure: Differences between sMTC and hMTC in long-term, stage-dependent survival and outcomes., Results: Surgery was performed at median ages of 49 years for sMTC (n = 477, 44% male) and 29 years for hMTC (n = 196, 43% male; P < 0.0001). The mean follow-up times were 9.2 ± 8.0 (sMTC) and 14.6 ± 10.3 years (hMTC). Age and tumor stage at diagnosis were significantly different between the 2 groups (P < 0.0001). The sMTC and hMTC groups had different overall DSS (log rank, P = 0.0183), but similar stage-dependent DSS (log rank, P = 0.1242-0.8981). In a multivariate analysis, sMTC and hMTC did not differ in DSS (hazard ratio [HR] = 1.56; 95% CI, 0.94-2.57), but in both groups, a worse DSS was significantly associated with age at diagnosis (HR = 1.04; 95% CI, 1.02-1.05), male sex (HR = 0.49; 95% CI, 0.32-0.76), and stages III and IV at diagnosis (HR = 20.00; 95% CI, 2.74-145.91 and HR = 97.47; 95% CI, 13.07-726.67, respectively). The groups had significantly different (P < 0.0001) outcomes (i.e., cured, minimal residual disease, structural detectable disease, and death), but similar stage-dependent outcomes (P = 0.9449-0.0511), except for stage III (P = 0.0489)., Conclusion: Patients with sMTC and hMTC had different ages of onset, but similar stage-dependent DSS and outcomes after the MTC diagnosis. This finding suggested that tumor behavior was similar in sMTC and hMTC., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Psychosocial and biological factors influence the perception of physical changes during pregnancy. Some pregnant women present to the obstetric emergency department (ED) with diverse symptoms not requiring urgent medical action. These visits result in over-consultation, tying up resources and inflating health care expenses. This study outlines factors associated with multiple ED visits during pregnancy, measures the prevalence of anxiety and depression, and explores the choice of maternity clinic for delivery aiming to elucidate options for care strategies., Methods: This prospective, cross-sectional, questionnaire-based bicentric study was performed in the obstetric outpatient departments of two university hospitals in Germany and recruited pregnant women between 12/2016 and 11/2017. The questionnaire included socio-demographics, obstetric history, anxiety (GAD-7), depression (PHQ-9), and health status (WHO-5, SF-12)., Results: This analysis included 496 women and showed that women with numerous ED visits were significantly younger (p < 0.0001), less educated (p = 0.0002), and more likely to be unemployed and single. Different prevalences for anxiety and depression were detected correlating with the number of ED visits although each showing only low effect sizes (0.024 resp. 0.015)., Conclusions: Pregnant women attending the ED more often might benefit from health education, psychosomatic interventions, and social support to overcome their depression and anxiety to avoid non-urgent ED consultations. Further prospective studies are needed to support these findings.

Context: Recent data on long-term outcomes and aggressiveness of medullary thyroid carcinoma (MTC) are lacking for patients with multiple endocrine neoplasia type 2 (MEN2)., Objectives: To analyze the long-term outcomes in MEN2 and compare MTC aggressiveness in three defined RET mutation-risk categories: moderate risk (MOD), high risk (H), and highest risk (HST)., Design, Setting: Retrospective study of 263 operated patients with MEN2 from one German tertiary referral center from 1979 to 2017 comparing demographic, biochemical, genetic, and outcome parameters., Intervention: None (observational study)., Main Outcome Measure: Long-term survival and outcomes in three risk groups., Results: Surgery was performed at a mean age of 35.3 ± 18.8 (MOD, n = 122), 23.0 ± 15.7 years (H, n = 120), and 14.9 ± 9.3 (HST, n = 21) years (P < 0.05). The mean follow-up was 12.9 ± 9.8 years. Age and tumor stage at diagnosis differed among the three risk groups (P < 0.0001). Multivariate analysis of disease-specific survival (DSS) showed that increasing age [hazard ratio (HR), 1.06; 95% CI, 1.02 to 1.09], stage III/IV at diagnosis (HR, 7.39; 95% CI, 2.39 to 22.8), and HST group (HR, 14.4; 95% CI, 3.32 to 62.6) were significantly associated with worse DSS; the H group was not (P = 0.175). The DSS rates and outcomes were not different between the MOD and H groups (P = 0.179 and P = 0.893, respectively) but were significantly inferior in the HST group (P < 0.0008 and P < 0.0001, respectively)., Conclusion: MTC in patients with MEN2 showed a clearly different age of onset in the different risk groups. DSS and outcomes after MTC diagnosis were similar in the MOD and H groups, suggesting similar tumor behavior. The HST group had inferior outcomes and survival vs the MOD and or H groups., (Copyright © 2019 Endocrine Society.)

Background: The placement of prophylactic intra-abdominal drains has been common practice in abdominal operations including pancreatic surgery. The PANDRA trial showed that the omission of drains following pancreatic head resection was non-inferior to intra-abdominal drainage in terms of postoperative reinterventions and superior in terms of clinically relevant pancreatic fistula rate and fistula-associated complications. The aim of the present PANDRA II trial is to evaluate the clinical outcome with versus without prophylactic drain placement after distal pancreatectomy., Methods: The PANDRA II trial is a mono-center, randomized controlled, non-inferiority trial with two parallel study groups. In the control group at least one passive intra-abdominal drain is placed at the pancreatic resection margin. In the experimental group no drains are placed. The primary endpoint of this trial will be the Comprehensive Complication Index (CCI) measuring all postoperative complications within 90 days. Secondary endpoints are in-hospital mortality and morbidity, including the rates of postoperative pancreatic fistula, chyle leak, postpancreatectomy hemorrhage, delayed gastric emptying, reinterventions and reoperations, surgical site infection, and abdominal fascia dehiscence. Moreover, length of hospital stay, duration of intensive care unit stay, and the rate of readmission after discharge from hospital (up to day 90 after surgery) are assessed. We will need to analyze 252 patients to test the hypothesis that no drainage is non-inferior to drain placement in terms of the CCI (δ 7.5 points) in a one-sided t test with a one-sided level of significance of 2.5% and a power of 80%., Discussion: The results of the PANDRA II trial will help to evaluate the effect of an omission of prophylactic intraperitoneal drainage on the rate of complications after open or minimally invasive distal pancreatectomy., Trial Registration: German Clinical Trials Register (DRKS), DRKS00013763 . Registered on 6 March 2018.

Purpose: Despite antifungal prophylaxis following liver transplantation (LTX), patients are at risk for the development of subsequent opportunistic infections, such as an invasive fungal disease (IFD). However, culture-based diagnostic procedures are associated with relevant weaknesses., Methods: Culture and next-generation sequencing (NGS)-based fungal findings as well as corresponding plasma levels of ß-D-glucan (BDG), galactomannan (GM), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-2, -4, -6, -10, -17A and mid-regional proadrenomedullin (MR-proADM) were evaluated in 93 patients at 6 consecutive time points within 28 days following LTX., Results: A NGS-based diagnostic approach was shown to be suitable for the early identification of fungal pathogens in patients following LTX. Moreover, MR-proADM and IL-17A in plasma proved suitable for the identification of patients with an IFD., Conclusion: Plasma measurements of MR-proADM and IL-17A as well as a NGS-based diagnostic approach were shown to be attractive methodologies to attenuate the weaknesses of routinely used culture-based diagnostic procedures for the determination of an IFD in patients following LTX. However, an additional confirmation within a larger multicenter trial needs to be recommended., Trial Registration: German Clinical Trials Register: DRKS00005480 .

Objective: The introduction of a stemless prosthesis in shoulder arthroplasty represents a novel design whereby the proximal humerus is restored anatomically, while leaving the diaphysis of the humerus untouched. The aim of this study was to present the mid-term results of total evolutive shoulder system (TESS; Biomet ® ), a stemless shoulder prosthesis., Methods: The study included 38 consecutive patients (18 men and 20 women; mean age: 66 years; range: 55-81 years) treated with shoulder arthroplasty between 2009 and 2011 with TESS for primary glenohumeral arthritis. Total shoulder arthroplasty (TSA) was performed in 28 cases (74%), hemi-shoulder arthroplasty (HSA) in 10 (26%). Constant score, active range of motion, patient satisfaction rate, and radiological assessment were analyzed. Mean time of follow-up was 37 months., Results: Constant score improved from 21.8 points (28.6 adjusted for age) preoperatively to 74.1 points (86.6 adjusted for age) postoperatively. Active range of motion increased significantly from the pre- to postoperative status. Eighty-nine percent were very satisfied or satisfied with shoulder replacement surgery. One cemented glenoid was revised due to aseptic loosening. None of the components were found to be loose at the final follow-up. No signs of stress shielding were seen., Conclusions: This study shows promising results of this implant concept in the short- to mid-term. These results are comparable with the results achieved with long-established arthroplasty designs., Level of Evidence: Level IV, Therapeutic Study., (Copyright © 2019 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Use of the arm above shoulder level has been described as a risk factor for developing rotator cuff tears (RCT). There is a lack of information regarding the frequency and distribution of RCT in a population using their arms above shoulder level during daily work. The aim of this study was to analyze clinical and radiographic findings in a population of painters working more than 10 years and to compare the results with a control group (CG)., Materials and Methods: 100 individuals working more than 10 years as a painter were compared to 100 matched controls without using their arms above shoulder level. MRI scans were performed in all participants. Clinically, the Constant score, DASH score and range of motion (ROM) of the shoulders were analyzed., Results: In the painter group (PG) a tear of the supraspinatus tendon was detected in 45% (10%full-thickness; 35% partial) compared to 8% in the (CG) (3% full-thickness; 5%partial; p<0.001). Impingement test was painful in 52% of PG and 7% of CG (p<0.001). The Constant score in the PG was significantly lower compared to the CG (62 vs. 93 points; p<0.001). PG had significantly worse DASH scores and inferior active and passive ROM of the dominant shoulders. In the multivariable logistic regression analysis, three risk factors (smoking, sports activity, and handedness) showed no effect. However, group membership (PG/CG) and age revealed a significant effect., Conclusion: Long-term occupational load on the shoulders in painters seems to be associated with an increased risk for developing RCT. Our findings may provide support for developing preventive strategies for this unique cohort. Level of evidence: III., Competing Interests: The authors have declared that no competing interests exist.

Background: Eye-drop administration errors occur in the majority of patients and increase the risk for treatment failure or systemic adverse events. While lacking knowledge is the principal error cause, most patients overestimate their skills and are unaware of often substantial knowledge gaps. Therefore, the impact of including motivational patient education on long-term eye-drop administration skills of patients was investigated., Methods: This is a cluster-randomized controlled trial in German community pharmacies. Patient education in both groups comprised observation of the patient during eye-drop administration to identify individual errors, pharmaceutical counseling, and teach-back evaluation of the training. In the intervention group, motivational communication techniques were included to increase error awareness and readiness for patient education. In addition, intervention patients were trained on repeated errors until administration was performed correctly. In contrast, patients in the control group only received feedback on erroneous administration steps without another assessment and reinforced training., Results: In total, 152 adult patients were eligible to the study and 91 patients (intervention group N = 46) agreed to participate in a 1-month, 6-month, and 12-month follow-up. Patient education significantly increased the proportion of patients correctly administering eye-drops from 6% (7 out of 56 intervention patients, 1 out of 82 control patients) at baseline to 35% (12 out of 30 intervention patients, 12 out of 39 control patients, p ≤ 0.001) at the 1-month follow-up, and 64% (11 out of 15 intervention patients, 17 out of 29 control patients, p ≤ 0.001) at the 6-month follow-up irrespective of group allocation. In some patients previously resolved errors recurred during follow-up visits. This emphasizes the need for periodical reevaluation of patient administration skills and the provision of prevention strategies besides education., Conclusion: Patient education that included demonstration of administration skills and verbal and written counseling on observed errors improved eye-drop administration skills irrespective of the communication technique applied. Whereof, high drop-out rates limited the power to detect a difference between groups. In particular, periodic demonstration of administration skills seemed important for sustainable improvement of administration skills. However, further error prevention strategies such as additional education materials or support by a caregiver may be necessary in some patients., Competing Interests: The authors have declared that no competing interests exist.

Background: Pregnancy can be distressing, particularly if expectant mothers are worried about the well-being of their fetus. Consequently, the desire for reassurance and frequent fetal monitoring is often pronounced. Smart wearable devices and telemedicine are promising tools that could assist women in self-monitoring their pregnancy at home, hence disburdening emergency departments (EDs). They present the possibility to clarify the need for urgent care remotely and offer tighter pregnancy monitoring. However, patients' acceptance of such new technologies for fetal monitoring has not yet been explored extensively., Objective: This survey aimed to elucidate the attitudes of women toward self-monitoring of their pregnancy using noninvasive electronic devices. The technical details of the proposed devices were not specified., Methods: A cross-sectional multicenter study was conducted at the departments of obstetrics of the University Hospitals of Heidelberg and Leipzig, Germany. All patients seen in the obstetrics clinic who were above 18 years were offered participation. We designed a survey questionnaire including validated instruments covering population characteristics, issues in current and past pregnancies, as well as attitudes toward self-monitoring of pregnancy with smart devices., Results: A total of 509 pregnant women with no previous experience in telemedicine participated. Only a small minority of 5.9% (29/493) regarded self-monitoring with wearable devices as an alternative to consulting their physicians. Along these lines, only 7.7% (38/496) strongly believed they would visit the ED less often if such devices were readily available. However, if the procedure were combined with a Web-based telemetric physician consult, 13.5% (66/487) would be highly motivated to use the devices. Furthermore, significantly more women regarded it as an alternative prior to seeing a doctor when they perceived a decline in fetal movements (P<.001). Interestingly, women with university degrees had a higher propensity to engage in pregnancy self-monitoring compared with women without one (37% vs 23%; P=.001). Of the participants, 77.9% (381/489) would like smart wearable devices to measure fetal heart sounds, and 62.6% (306/489) wished to use the devices on their own. Feedback from a doctor or midwife was also very important in their choice of such devices (61.8%, 301/487 wished feedback). The intended frequency of use differed vastly among women, ranging from 13.8% (65/471) who would like to use such a device several times per day to 31.6% (149/471) who favored once per week at most., Conclusions: Our results point to a skeptical attitude toward pregnancy self-monitoring among pregnant women. Nevertheless, many women are open to using devices for pregnancy monitoring in parallel to consulting their physician. The intention to use such devices several times daily or weekly, expressed by more than half of the participants, highlights the potential of such technologies., (©Katharina Schramm, Niklas Grassl, Juliane Nees, Janine Hoffmann, Holger Stepan, Thomas Bruckner, Markus W Haun, Imad Maatouk, Markus Haist, Timm C Schott, Christof Sohn, Sarah Schott. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 07.01.2019.)

Background: Dental and cervical controls are two established screening programs in Germany. Compliance to orthodontic treatment in childhood is essential for dental health and one of the first health interventions that requires adherent behavior; therefore, it may be associated with participation in further screening programs in adulthood. However, it is not yet known whether early orthodontic treatment influences long-term screening adherence., Methods: Using a questionnaire administered during a visit to a special dysplasia outpatient service, this case-control study evaluated women's personal history of orthodontic care, long-term satisfaction, and dental and gynecological screening adherence. Oral health status and dental anxiety were assessed with validated instruments. Cases were categorized as cervical dysplasia only (S2) or cervical dysplasia with conization (S1) and compared to healthy controls with a normal PAP smear., Results: A study population of 233 participants included 132 cases and 101 controls. The control group had had orthodontic treatment during childhood more often than our study population with abnormal PAP smears (68.3% controls versus 56.1% subjects; p < 0.005). Orthodontic treatment was not associated with attending dental appointment or gynecological check-ups. However, women with an orthodontic treatment in childhood were significantly more often vaccinated against human papillomavirus than women without orthodontic treatment (p < 0.03)., Conclusion: Data suggest that women with orthodontic treatment in childhood are more conscious about prevention strategies in adulthood; therefore, compliant behavior might be established in childhood.

Background: Chest tube insertion is a standard intervention for management of various injuries of the thorax. Efficient clinical training of this and similar bed-side procedures is equally demanded and improvable. Here, we propose a nouveau means of assessment and feedback using an Objective Structured Assessment of Technical Skills (OSATS) tool. The modified OSATS for chest drain insertion is evaluated in a pilot trial focusing on chest drain insertion. Methods: Participants in the pilot trial were medical students (3 rd -6 th year of studies, n=9), junior residents (1 st -3 rd post-graduate year, n=12), senior residents (4 th -6 th post-graduate year, n=14), and attending surgeons (n=6) from Heidelberg University. Chest drain insertions on a cadaveric porcine model were rated by experts with the modified OSATS score. Participants' performances were videotaped and subsequently rated by two remote experts (video rating). Primary aim was to assess criterion validity of the OSATS to distinguish experience levels. Results: Kruskal-Wallis test showed significant differences between means of scores between four groups stratified by previous experience in chest tube insertion (level 0: 22.1±3.2 vs. level 1: 26.8±2.8 vs. level 2: 35.4±2.2 vs. level 3: 41.0±2.0; p=0.002; p 1,3 =0.049, p 0,3 =0.005). However, if groups were stratified by formal professional level, no statistically significant distinction could be made using OSATS. Hence, the OSATS tool showed criterion validity for differentiation between experience levels. Conclusion: In the pilot study, the modified OSATS for chest tube insertion was apt to standardize expert rating and could be used to measure skill and to depict different experience levels. The OSATS will help facilitate training and assessment of chest drain insertion and could therefore improve surgical training for trauma situations. According to our data, the OSATS might be integrated into modern curricula.

Aim: To study liver stiffness (LS) during pregnancy and its association with complications during pregnancy., Methods: In this observational, diagnostic study, 537 pregnant women were prospectively enrolled at the Department of Obstetrics and Gynecology, University hospital Heidelberg and Salem Medical Center. LS was measured using the Fibroscan device (Echosens, Paris) in all women and in 41 cases 24 h after delivery. Clinical and morphological data were recorded and abdominal ultrasound and standard laboratory tests were performed. No complications were observed in 475 women (controls) while preeclampsia and intrahepatic cholestasis of pregnancy (ICP) developed in 22 and 40 women, respectively., Results: In controls, LS increased significantly from initially 4.5 ± 1.2 kPa in the second trimester to 6.0 ± 2.3 kPa ( P < 0.001) in the third trimester. In the third trimester, 41% of women had a LS higher than 6 kPa. Elevated LS in controls was significantly correlated with alkaline phosphatase, leukocytes, gestational age and an increase in body weight and body mass index (BMI). In women with pregnancy complications, LS was significantly higher as compared to controls ( P < 0.0001). Moreover, in multivariate analysis, LS was an independent predictor for preeclampsia with an odds ratio of 2.05 (1.27-3.31) and a cut-off value of 7.6 kPa. In contrast, ICP could not be predicted by LS. Finally, LS rapidly decreased in all women within 24 h after delivery from 7.2 ± 3.3 kPa down to 4.9 ± 2.2 kPa ( P < 0.001)., Conclusion: During pregnancy, LS significantly and reversibly increases in the final trimester of pregnant women without complications. In women with preeclampsia, LS is significantly elevated and an independent non-invasive predictor., Competing Interests: Conflict-of-interest statement: The authors have declared no conflicts of interest.

Background: Stereotactic body radiation therapy (SBRT) using intensity-modulated radiotherapy (IMRT) with dose escalation by simultaneous integrated boost (SIB) can be a safe modality for treating spinal bone metastases with enhanced targeting accuracy and improve local tumor control., Methods/design: This is a single-center, prospective, randomized, controlled trial. One hundred and twenty patients with spinal bone metastases will receive palliative radiation therapy at the Heidelberg University Hospital. SBRT will be given in five or ten fractions with or without SIB. Four treatment arms are planned: IMRT with 30 Gy in ten fractions, IMRT with 30 Gy in ten fractions and SIB to 40 Gy, IMRT with 20 Gy in five fractions, and IMRT with 20 Gy in five fractions and SIB to 30Gy in five fractions will be compared. The target parameters will be measured at baseline level and at three and six months after radiation., Discussion: The primary endpoint of this study was to assess and compare the local tumor control (by means of different fractionation schedules and biological doses to the tumor area). Secondary endpoints are acute and chronic adverse events, pain relief, quality of life, and fatigue., Trial Registration: ClinicalTrials.gov, NCT02832765 . Registered on 27 July 2016.

Objectives: To assess pancreatic fistula rate and secondary endpoints after pancreatogastrostomy (PG) versus pancreatojejunostomy (PJ) for reconstruction in pancreatoduodenectomy in the setting of a multicenter randomized controlled trial., Background: PJ and PG are established methods for reconstruction in pancreatoduodenectomy. Recent prospective trials suggest superiority of the PG regarding perioperative complications., Methods: A multicenter prospective randomized controlled trial comparing PG with PJ was conducted involving 14 German high-volume academic centers for pancreatic surgery. The primary endpoint was clinically relevant postoperative pancreatic fistula. Secondary endpoints comprised perioperative outcome and pancreatic function and quality of life measured at 6 and 12 months of follow-up., Results: From May 2011 to December 2012, 440 patients were randomized, and 320 were included in the intention-to-treat analysis. There was no significant difference in the rate of grade B/C fistula after PG versus PJ (20% vs 22%, P = 0.617). The overall incidence of grade B/C fistula was 21%, and the in-hospital mortality was 6%. Multivariate analysis of the primary endpoint disclosed soft pancreatic texture (odds ratio: 2.1, P = 0.016) as the only independent risk factor. Compared with PJ, PG was associated with an increased rate of grade A/B bleeding events, perioperative stroke, less enzyme supplementation at 6 months, and improved results in some quality of life parameters., Conclusions: The rate of grade B/C fistula after PG versus PJ was not different. There were more postoperative bleeding events with PG. Perioperative morbidity and mortality of pancreatoduodenectomy seem to be underestimated, even in the high-volume center setting.

Children with sickle cell disease (SCD) benefit from newborn screening, because life-threatening complications can be prevented by pre-symptomatic diagnosis. In Germany, the immigration of people from endemic countries is steadily growing. Comprehensive data about the epidemiology and prevalence of SCD in Germany are however lacking, and SCD is not included in the national newborn screening program. We provide data on the prevalence of SCD in a population from both urban and rural areas in Southwest Germany. Anonymized dried blood spots from 37,838 unselected newborns were analyzed by allele-specific PCR for the HbS mutation. Samples tested positive were subjected to Sanger sequencing of the entire β-globin coding sequence firstly to validate the screening and secondly to identify compound heterozygous SCD patients with other mutations of the β-globin gene. We identified 83 carriers of the sickle cell trait, three compound heterozygous SCD patients (two with sickle cell-β-thalassemia, one with sickle cell-Hb Tianshui) but no homozygous SCD patients. The novel molecular method and strategy for newborn screening for SCD presented here compares favorably in terms of sensitivity (1.0 for homozygous HbS, 0.996 for heterozygous HbS), specificity (0.996), practicability, and costs with conventional biochemical screening. Our results demonstrate a significant prevalence of SCD of approximately 1:12,000 in an unselected urban and rural population in Southwest Germany. Together with previously published even higher results from exclusively urban populations in Berlin and Hamburg, our data provide the basis for the decision on a newborn screening program for SCD in Germany.

Background: The former 'EU Nickel Directive' and, since 2009, the REACH Regulation (item 27 of Annex XVII) do not include all metallic objects. The nickel content of tools is not regulated by the REACH Regulation, even if they may come into in prolonged contact with the skin. Tools might be possible sources of nickel and cobalt sensitization, and may contribute to elicitation and maintenance of hand eczema., Objectives: To perform a current analysis of the frequency of nickel or cobalt release from new handheld tools purchased in Germany., Methods: Six hundred unused handheld tools from the German market were investigated with the dimethylglyoxime test for nickel release and with disodium-1-nitroso-2-naphthol-3,6-disulfonate solution for cobalt release., Results: Nickel release was detected in 195 of 600 (32.5%) items, and cobalt in only six (1%) of them. Positive nickel results were nearly twice as frequent in tools 'made in Germany' than in tools without a mark of origin. Tools made in other European countries did not release nickel. Cobalt release was only found in pliers and a saw. A correlation was found between price level and nickel release. Among toolkits, 34.2% were inhomogeneous concerning nickel release., Conclusion: The German market currently provides a large number of handheld tools that release nickel, especially tools 'made in Germany'. For consumer protection, it seems appropriate to include handheld tools in the REACH Regulation on nickel., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: From 2000 to 2012, the annual incidence of inpatient treatment for distal radius fracture in Germany rose from 65 to 86 per 100 000 persons. It is unclear whether open reduction and volar angle-stable plate osteosynthesis (ORIF), a currently advocated treatment, yields a better functional outcome or quality of life than closed reposition and casting., Methods: In the ORCHID multi-center trial, 185 patients aged 65 and older with an AO type C distal radial fracture were randomly assigned to ORIF or closed reposition and casting. Their health-related quality of life and hand/arm function were assessed 3 and 12 months afterward with the Short Form 36 (SF-36) questionnaire and the Disability of the Arm, Shoulder and Hand (DASH) questionnaire. The radiological findings, range of movement of the wrist, and EuroQol-5D (EQ-5D) scores were documented as well., Results: Among the 149 patients in the intention-to-treat-analysis, there was no significant difference in SF-36 scores between the two treatment groups at one year (mean difference, 3.3 points in favor of ORIF; 95% confidence interval, -0.2 +6.8 points; p = 0.058). The DASH scores showed moderately strong, but clinically unimportant effects in favor of ORIF, and there was no difference in EQ-5D scores. ORIF led to better radiological results and wrist mobility at 3 months, with comparable results at 12 months. 37 of the patients initially allotted to nonsurgical treatment underwent secondary surgery due to significant loss of reduction., Conclusion: The findings with respect to mobility, functionality, and quality of life at 12 months provide marginal and inconsistent evidence for the superiority of volar angle-stable plate osteosynthesis over closed reduction and casting in the treatment of intra-articular distal radius fractures. Primary nonsurgical management is also effective in suitable patients.

Background: Some Rofil Medical breast implants are relabelled Poly Implant Prothèse (PIP) implants, and it is recommended that Rofil implants be managed in the same way as PIP implants. We report the results of a systematic recall of patients who had received Rofil implants., Method: All patients who received Rofil implants at our centre were identified and invited for specialist consultation. In patients who opted for explantation, preoperative and intraoperative work-up was performed in accordance with national guidelines and analysed. In cases suspicious for rupture, an MRI scan was performed., Results: Two-hundred and twenty-five patients (average age 56; range 28-80) received a total of 321 Rofil implants an average of 5.8 (range 1-11) years previously, 225/321 (70%) implants were used for reconstruction after breast cancer. A total of 43 implants were removed prior to 2011, mainly due to capsular contracture (CC). A total of 188 patients were still affected at the time of recall. Of the 188 patients, 115 (61%) attended for specialist consultation, of which 50 (44%) requested immediate implant removal. To date, 72 of 115 (63%) women attending consultation (38% of all affected) have chosen explantation, 66 of 72 (92%) opting for new implants. Of the 108 explanted implants, 25 (23%) had capsular rupture and 57 (53%) had implant bleeding. Preoperative clinical assessment was unreliable for predicting CC or rupture., Conclusion: The majority of patients attended for consultation and requested explantation. The quality of the explanted Rofil implants was comparable to PIP implants, with a higher rupture prevalence compared with other, non-affected implants. Nevertheless, the acceptance of breast implants for reimplantation remained high., (Copyright © 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: The effect of bariatric surgery on weight loss and improvement of co-morbidities is no longer doubted. However, little attention has been given to the treatment goals from the patient's point of view (patient expectations). The objective of this study was to examine patients' expectations of bariatric surgery and identify gender differences., Methods: Bariatric patients were asked to complete a questionnaire. Statistical analysis was performed using chi-square, Pearson correlation coefficient, and Wilcoxon rank sum test., Results: Overall, 248 patients participated in this study (69.4% females). The male patients (45.2 yr, SD±11.1) were significantly older than the female (41.8 yr, SD±12.0; P = .04) and suffered significantly more often from diabetes, hypertension, hypercholesterolemia, and sleep apnea. One hundred thirty patients (52.4%) expected to lose at least 45 kg and 39 patients (15.7%)>70 kg. The mean expected excess weight loss was 71.8%. Females expected significantly more often that surgery alone would induce weight loss (P = .03). "Improved co-morbidity" was by far the highest ranked parameter., Conclusion: The male bariatric surgery patients were older and suffered from more co-morbidities. Most of the patients had unrealistic weight loss goals and overestimated the effect of the surgical intervention. However, for both female and male patients, "improved co-morbidity" was the most important issue., (Copyright © 2014 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: It is estimated that approximately 1 million adults in Germany suffer from grade III obesity. The aim of this article is to describe the challenges faced when constructing an operative obesity center., Methods: The inflow of patients as well as personnel and infrastructure of the interdisciplinary Diabetes and Obesity Center in Heidelberg were analyzed. The distribution of continuous data was described by mean values and standard deviation and analyzed using variance analysis., Results: The interdisciplinary Diabetes and Obesity Center in Heidelberg was founded in 2006 and offers conservative therapeutic treatment and all currently available operative procedures. For every operative intervention carried out an average of 1.7 expert reports and 0.3 counter expertises were necessary. The time period from the initial presentation of patients in the department of surgery to an operation was on average 12.8 months (standard deviation SD ± 4.5 months). The 47 patients for whom remuneration for treatment was initially refused had an average body mass index (BMI) of 49.2 kg/m(2) and of these 39 had at least the necessity for treatment of a comorbidity. Of the 45 patients for whom the reason for the refusal of treatment costs was given as a lack of conservative treatment, 30 had undertaken a medically supervised attempt at losing weight over at least 6 months. Additionally, 19 of these patients could document participation in a course at a rehabilitation center, a Xenical® or Reduktil® therapy or had undertaken the Optifast® program. For the 20 patients who supposedly lacked a psychosomatic evaluation, an adequate psychosomatic evaluation was carried out in all cases., Conclusions: The establishment of an operative obesity center can last for several years. A essential prerequisite for success seems to be the constructive and targeted cooperation with the health insurance companies.

Background: Spinal bone metastases are commonly diagnosed in cancer patients. The consequences are pain both at rest and under exercise, impairment of activities of daily life (ADL), reduced clinical performance, the risk of pathological fractures, and neurological deficits. The aim of this randomized, controlled pilot trial was to investigate the feasibility of muscle-training exercises in patients with spinal bone metastases under radiotherapy. Secondary endpoints were local control, pain response and survival., Methods: This study was a prospective, randomized, monocentre, controlled explorative intervention trial to determine the multidimensional effects of exercises for strengthening the paravertebral muscles. On the days of radiation treatment, patients in the control group were physically treated in form of respiratory therapy. Sixty patients were randomized between September 2011 and March 2013 into one of the two groups: differentiated resistance training or physical measure with thirty patients in each group., Results: The resistance training of the paravertebral muscles was feasible in 83.3% of patients (n = 25). Five patients died during the first three months. The exercise group experienced no measurable side effects. "Chair stand test" in the intervention group was significant enhanced with additionally improved analgesic efficiency. Patients in intervention group improved in pain score (VAS, 0-10) over the course (p < .001), and was significant better between groups (p = .003) after 3 months. The overall pain response showed no significant difference between groups (p = .158) There was no significant difference in overall and bone survival (survival from first diagnosed bone metastases to death)., Conclusions: Our trial demonstrated safety and feasibility of an isometric resistance training in patients with spinal bone metastases. The results offer a rationale for future large controlled investigations to confirm these findings.

Background: Methylentetrahydrofolate reductase (MTHFR) plays a major role in folate metabolism and consequently could be an important factor for the efficacy of a treatment with 5-fluorouracil. Our aim was to evaluate the prognostic and predictive value of two well characterized constitutional MTHFR gene polymorphisms for primarily resected and neoadjuvantly treated esophagogastric adenocarcinomas., Methods: 569 patients from two centers were analyzed (gastric cancer: 218, carcinoma of the esophagogastric junction (AEG II, III): 208 and esophagus (AEG I): 143). 369 patients received neoadjuvant chemotherapy followed by surgery, 200 patients were resected without preoperative treatment. The MTHFR C677T and A1298C polymorphisms were determined in DNA from peripheral blood lymphozytes. Associations with prognosis, response and clinicopathological factors were analyzed retrospectively within a prospective database (chi-square, log-rank, cox regression)., Results: Only the MTHFR A1298C polymorphisms had prognostic relevance in neoadjuvantly treated patients but it was not a predictor for response to neoadjuvant chemotherapy. The AC genotype of the MTHFR A1298C polymorphisms was significantly associated with worse outcome (p = 0.02, HR 1.47 (1.06-2.04). If neoadjuvantly treated patients were analyzed based on their tumor localization, the AC genotype of the MTHFR A1298C polymorphisms was a significant negative prognostic factor in patients with gastric cancer according to UICC 6th edition (gastric cancer including AEG type II, III: HR 2.0, 95% CI 1.3-2.0, p = 0.001) and 7th edition (gastric cancer without AEG II, III: HR 2.8, 95% CI 1.5-5.7, p = 0.003), not for AEG I. For both definitions of gastric cancer the AC genotype was confirmed as an independent negative prognostic factor in cox regression analysis. In primarily resected patients neither the MTHFR A1298C nor the MTHFR C677T polymorphisms had prognostic impact., Conclusions: The MTHFR A1298C polymorphisms was an independent prognostic factor in patients with neoadjuvantly treated gastric adenocarcinomas (according to both UICC 6th or 7th definitions for gastric cancer) but not in AEG I nor in primarily resected patients, which confirms the impact of this enzyme on chemotherapy associated outcome.

We compared functional and structural changes in the hands, in particular the prevalence of carpal tunnel syndrome, in 56 paraplegic patients who had been wheelchair dependent for over 25 years with a group of able-bodied volunteers (with matching criteria for gender and age). The hands were assessed by clinical examination, electrophysiology, disabilities of the arm shoulder and hand score and magnetic resonance imaging. Hand function was worse and wrist pain was experienced more often in the paraplegic patients, and they also had a significantly higher prevalence of carpal tunnel syndrome both clinically and electrophysiologically. The prevalence of wrist and trapeziometacarpal osteoarthritis was significantly higher in the right hand.

Background and Purpose: For palliative care of spinal bone metastases, stability assessment is of crucial importance. Pathological fractures, instability-related patient immobility and the extent of bone metastasis have been reported to affect patient outcome and these parameters have therefore been used for treatment stratification. We report on stability-dependent fracture and survival rates in over 300 non-small cell lung cancer (NSCLC) patients., Materials and Methods: Data from 303 patients with 868 osteolytic metastases treated with radiotherapy (RT) between 2000 and 2012 were evaluated retrospectively., Results: In NSCLC patients with bone metastases only, the retrospective 6- and 12-month overall survival (OS) rates were 76.7 and 47.2%, respectively. In patients with additional non-bone distant metastases, these values were 60.0 and 34.0%, respectively. Survival rates were significantly lower in patients with multiple bone metastases and in those suffering pathological fractures (p=0.017). No significant impact of histological type, location of spinal lesions or treatment regime was detected. Furthermore, stability assessment revealed no influence of vertebral column stability on patient outcome (p=0.739)., Conclusion: Our analysis demonstrated a correlation between the pathological fractures of bone lesions, the number of bone metastases, additional distant metastases and survival. The results offer a rationale for future prospective investigations.

Background: In line with the growing number of surgical procedures being performed worldwide, postoperative complications are also increasing proportionately. Prevention of these postoperative complications is a high medical priority. Preoperative education of patients, including provision of preparatory information about the correct behavior after surgery, could improve the postoperative outcome, but the evidence for this is inconclusive. The aim of the PEDUCAT trial is to evaluate the feasibility and the impact of preoperative patient education on postoperative morbidity, mortality and quality of life in patients scheduled for elective major visceral surgery., Methods/design: PEDUCAT is designed as a cluster-randomized controlled pilot study. The experimental group will visit a standardized preoperative seminar to learn how best to behave after surgery in addition to being given a standard information brochure, whereas the control group will only receive the information brochure. Outcome measures such as postoperative morbidity, postoperative pain, postoperative anxiety and depression, patient satisfaction, quality of life, length of hospital stay and postoperative mortality will be evaluated. Statistical analysis will be based on the intention-to-treat population. Analysis of covariance will be applied for the intervention group comparison, adjusting for age, center and quality of life before surgery. This is a pilot study to show the feasibility of the concept. Nevertheless, the planned sample size of n = 204 is large enough to show an effect with power of 90% and a significance level of 5%., Trial Registration: German Clinical Trial Register number: DRKS00004226.

The objective of the present cross-sectional study was to determine in vivo titanium ion levels following cementless total hip arthroplasty (THA) using a modular stem system with different shapes for femoral canal fit and multiple neck options. A consecutive series of 173 patients (190 hips) who underwent cementless modular neck THA and a ceramic on polyethylene bearing with a median follow-up of 9 (7-13) years was evaluated retrospectively. According to a standardized protocol, titanium ion measurements were performed on 67 patients using high-resolution inductively coupled plasma-mass spectrometry. Ion levels were compared to a control group comprising patients with non-modular titanium implants (n=11) and to individuals without implants (n=23). Modular neck THA did not result in elevated titanium ion levels compared to non-modular THA. Compared to individuals without implants, both modular THA and non-modular THA showed elevated titanium ion levels. Absolute titanium ion levels, however, were comparatively low for both implants. The data suggest that the present modular stem system does not result in elevated systemic titanium ion levels in the medium term when compared to non-modular stems. Further longitudinal studies are needed to evaluate the use of systemic titanium ion levels as an objective diagnostic tool to identify THA failure and to monitor patients following revision surgery., (Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: Patients undergoing cardiac surgery are at risk for postoperative cognitive dysfunction (POCD). Evaluating preoperative risk factors represents 1 possible way to minimize the postoperative risk of cognitive dysfunction. We investigated marked deterioration in cholinergic neurotransmission as 1 such potential risk factor for transient and long-lasting POCD. Serum anticholinergic activity (SAA) has already been described as a risk factor for developing delirium in an elderly study population. However, the role of SAA for long-lasting POCD is unknown., Methods: Following local ethics board approval and written informed consent, we recruited a cohort of patients aged ≥ 55 years undergoing cardiac surgery. Before surgery, levels of SAA were measured and a battery of neuropsychologic tests (NPTs) was applied. S100 calcium binding protein ß concentration was measured intraoperatively. Pre-, intra-, and postoperative patient-specific characteristics were recorded. The NPTs were repeated 3 months after hospital discharge to evaluate 3-month POCD. A group of nonsurgical patients (n = 34) was recruited as control subjects to adjust NPT scores, using reliable methods for the change index. Logistic multivariate regression was used to evaluate independent predictors of POCD., Results: One hundred fifty-four patients were screened before surgery, and 117 completed the second NPT. POCD was identified in 25.6% of patients. In contrast to intraoperatively increased S100 calcium binding protein ß, preoperative SAA was not associated with POCD following adjustment for covariates., Conclusions: Preoperatively increased SAA did not predict POCD 3 months after cardiac surgery., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Partial pancreatico-duodenectomy (PD) is the standard treatment for tumors of the pancreatic head. Today, preservation of the pylorus has been widely accepted as the surgical standard in this procedure. A common postoperative complication is the occurrence of delayed gastric emptying (DGE), which causes impairment of oral intake andpatients' quality of life, prolongation of hospital stay and delay of further treatment (for example adjuvant chemotherapy). In a small number of two retrospective and one randomized studies, a modification by resection of the pylorus with preservation of the stomach has shown to reduce DGE incidence. The aim of the present study is to investigate the effect of pylorus resection on postoperative DGE in PD., Methods/design: Patients undergoing elective PD for any indication equal or older than 18 years and who have given informed consent will be included. Patients will be randomized to either PD with pylorus preservation or PD with pylorus resection and complete stomach preservation. Sample size (n = 89 patients per group) is calculated on an assumed difference in DGE incidence of 20%. Primary study endpoint is DGE within 30 days; secondary endpoints are operation time, blood loss, morbidity, mortality, hospital stay and quality of life (QoL)., Discussion: DGE is a relevant clinical problem following PD with a great impact on patients' recovery, length of hospital stay, QoL and consecutive adjuvant therapies. As there is no causal therapy, prevention of DGE is essential to improve outcome. The technical modification of pylorus resection may offer a simple and effective method for this purpose. The present study is designed to increase the existing body of evidence and potentially change the future standard surgical procedure of PD., Trial Registration: German Clinical Trials Register DRKS00004191.

Ocular fundus photography allows detection of both ocular and systemic diseases. This study investigated the efficacy of a broad screening in a department of internal medicine using nonmydriatic digital fundus photography. For 8 weeks a medical technician was trained in using the camera as well as interpreting the photographs. The medical technician and an ophthalmologist evaluated the fundus photographs separately by using a self-developed questionnaire. The fundus camera was user-friendly and after several weeks of adjustment and practical application the medical technician was able to detect the majority of pathological fundus photographs. Out of 218 patients examined 148 (68%) were identified as pathological by the medical technician and 163 (75%) by the ophthalmologist (p = 0.0003). The medical technician missed 15 (7%) patients. Furthermore the diagnoses made by the medical technician were faulty. In summary an ophthalmological screening by a medical technician is feasible but the diagnosis still remains the responsibility of ophthalmologists. Such a compromise could facilitate the examination of a large number of patients and disclose previously unrecognized diseases.

Objectives: The objective of the HASTA trial was to compare hand suture versus stapling loop ileostomy closure in a randomized controlled trial., Background: Bowel obstruction is one of the main and the clinically and economically most relevant complication following closure of loop ileostomy after low anterior resection. The best surgical technique for closure of loop ileostomy has not been defined yet., Methods: HASTA trial is a multicenter pragmatic randomized controlled surgical trial with 2 parallel groups to compare hand suture versus stapling for closure of loop ileostomy. The primary endpoint was the rate of bowel obstruction within 30 days after ileostomy closure., Results: A total of 337 randomized patients undergoing closure of loop ileostomy after low anterior resection because of rectal cancer in 27 centers were included. The overall rate of postoperative ileus after ileostomy closure was 13.4%. Seventeen of 165 (10.3%) patients in the stapler group and 27 of 163 (16.6%) in the hand suture group developed bowel obstruction within 30 days postoperatively [odds ratio (OR) = 1.72; 95% confidence interval (CI): 0.89-3.31 = 0.10]. Duration of surgical intervention was significantly shorter in the stapler group (15 minutes; P < 0.001). Multivariable analysis of potential risk factors did not reveal any significant correlation with development of postoperative ileus. Rate of anastomotic leakage (stapler: 3.0%, hand suture: 1.8%, P = 0.48) did not differ significantly as well as all other secondary endpoints., Conclusions: Hand-sewn anastomosis versus stapler ileo-ileostomy for ileostomy closure are equally effective in terms of postoperative bowel obstruction, with stapler anastomosis leading to a shorter operation time. Postoperative ileus after ileostomy reversal remains a relevant complication.

Background: New techniques using vascular clips or ultrasonically activated shears have been suggested to shorten operation time without compromising safety. The objective of the CLIVIT Trial was to compare ligatures with vascular clips for hemostasis in elective benign thyroid surgery., Methods: This multicenter, randomized, controlled, parallel group superiority trial was conducted in 13 German surgical centers. Patients scheduled for at least subtotal resection bilaterally were intraoperatively randomized. The primary endpoint was resection time. Secondary endpoints were the amount of postoperative bleeding, reoperation due to bleeding, wound infection, temporary (reversal within 12 months) and permanent (over 1 year) recurrent laryngeal nerve (RLN) paralysis, length of hospital stay, and safety., Registration: ISRCTN 96901396., Results: Two hundred fifty patients were treated with ligatures and 241 with vascular clips. No differences in patients' baseline and surgical characteristics were observed. No difference was detected for mean resection time (clip 63.5 min ± 29.6, ligature 66.1 min ± 29.3, P = 0.258). Postoperative bleeding (mean 86 ml ± 93), reoperation due to bleeding (clips 4, ligature 2), wound infections (clips 4, ligature 4), postoperative hospital stay (mean 3.0 ± 1.9), and safety data also did not vary significantly. The rates of temporary and permanent RLN paralysis were 6.9 % (34/491) and 2.9 % (14/491), respectively. Not using a surgical drain (123 patients) was not associated with a higher rate of complications., Conclusion: Vascular clips did not reduce the resection time. However, a 2.9 % rate of permanent RLN paralysis is of concern. Drains in elective surgery may be of no benefit.

Background: The optimal strategy for abdominal wall closure has been an issue of ongoing debate. Available studies do not specifically enroll patients who undergo emergency laparotomy and thus do not consider the distinct biological characteristics of these patients. The present randomized controlled trial evaluates the efficacy and safety of two commonly applied abdominal wall closure strategies in patients undergoing primary emergency midline laparotomy., Methods/design: The CONTINT trial is a multicenter, open label, randomized controlled trial with a two-group parallel design. Patients undergoing a primary emergency midline laparotomy are enrolled in the trial. The two most commonly applied strategies of abdominal wall closure after midline laparotomy are compared: the continuous, all-layer suture technique using slowly absorbable monofilament material (two Monoplus loops) and the interrupted suture technique using rapidly absorbable braided material (Vicryl sutures). The primary endpoint within the CONTINT trial is an incisional hernia within 12 months or a burst abdomen within 30 days after surgery. As reliable data on this primary endpoint is not available for patients undergoing emergency surgery, an adaptive interim analysis will be conducted after the inclusion of 80 patients, allowing early termination of the trial if necessary or modification of design characteristics such as recalculation of sample size., Discussion: This is a randomized controlled multicenter trial with a two-group parallel design to assess the efficacy and safety of two commonly applied abdominal wall closure strategies in patients undergoing primary emergency midline laparotomy., Trial Registration: NCT00544583.

Background: Pancreatoduodenectomy is one of the most complex abdominal operations, usually performed for tumors of the periampullary region and chronic pancreatitis. Leakage of pancreatic juice from the pancreatoenteric anastomosis, called postoperative pancreatic fistula, is the most prominent postoperative complication. Retrospective studies show a significant reduction of fistula rates with pancreatogastrostomy as compared to pancreatojejunostomy, the most frequently employed method of pancreatoenterostomy. Most single-center prospective trials, however, have not validated this finding. A large multicenter trial is needed for clarification., Methods/design: RECOPANC is a prospective, randomized, controlled multicenter trial with two treatment arms, pancreatogastrostomy versus pancreatojejunostomy. The trial hypothesis is that postoperative pancreatic fistula rate is lower after pancreatogastrostomy when compared to pancreatojejunostomy. Fourteen academic centers for pancreatic surgery will participate to allocate 360 patients to the trial. The duration of the entire trial is four years including prearrangement and analyses., Discussion: Postoperative pancreatic fistula is the main reason for clinically important postoperative morbidity after pancreatoduodenectomy. The primary goal of the chosen reconstruction technique for pancreatoenteric anastomosis is to minimize postoperative fistula rate. A randomized trial performed at multiple high-volume centers for pancreatic surgery is the best opportunity to investigate one of the most crucial issues in pancreatic surgery., Trial Registration: German Clinical Trials Register DRKS00000767 (2011/03/23), FSI 2011/05/31. Universal Trial Number U1111-1117-9588.

Background: Emergency treatment and resuscitation within hospitals are managed by so-called medical emergency teams (MET). The present study examined the circumstances, number, initial treatment and further hospital course of in-hospital emergency cases at a level 1 university hospital., Methods: A retrospective study of in-hospital emergencies on the surgical wards of a university hospital including all non-intensive care areas from January 2007 to June 2010 was carried out. A self-developed documentation protocol which was introduced in 2006 was used by the MET to document general patient characteristics and details of the emergency treatment. These data included the place where the emergency situation arose, the patient's assignment to a surgical discipline, a detailed description of the emergency situation, the effectiveness of basic life support measures as well as the further hospital course of the patient., Results: A total of 235 emergency cases were documented within the study period of 3.5 years. The frequency of in-hospital emergencies was 4/1,000 admitted patients per year. Cardiac arrest was encountered in 31,5%. Out of all patients 54,5% were admitted to an intensive care unit., Conclusion: The tasks of a MET at a surgical university hospital go beyond mere cardiopulmonary resuscitation. Emergency cases within the full spectrum of perioperative complications are encountered. Further multicenter studies with standardized protocols are required to analyze the management of German in-hospital emergencies.

Background: Colorectal cancer is the second most common tumor in developed countries, with a lifetime prevalence of 5%. About one third of these tumors are located in the rectum. Surgery in terms of low anterior resection with mesorectal excision is the central element in the treatment of rectal cancer being the only option for definite cure. Creating a protective diverting stoma prevents complications like anastomotic failure and meanwhile is the standard procedure. Bowel obstruction is one of the main and the clinically and economically most relevant complication following closure of loop ileostomy. The best surgical technique for closure of loop ileostomy has not been defined yet., Methods/design: A study protocol was developed on the basis of the only randomized controlled mono-center trial to solve clinical equipoise concerning the optimal surgical technique for closure of loop ileostomy after low anterior resection due to rectal cancer.The HASTA trial is a multi-center pragmatic randomized controlled surgical trial with two parallel groups to compare hand-suture versus stapling for closure of loop ileostomy. It will include 334 randomized patients undergoing closure of loop ileostomy after low anterior resection with protective ileostomy due to rectal cancer in approximately 20 centers consisting of German hospitals of all level of health care. The primary endpoint is the rate of bowel obstruction within 30 days after ileostomy closure. In addition, a set of surgical and general variables including quality of life will be analyzed with a follow-up of 12 months. An investigators meeting with a practical session will help to minimize performance bias and enforce protocol adherence. Centers are monitored centrally as well as on-site before and during recruitment phase to assure inclusion, treatment and follow up according to the protocol., Discussion: Aim of the HASTA trial is to evaluate the efficacy of hand-suture versus stapling for closure of loop ileostomy in patients with rectal cancer., Trial Registration: German Clinical Trial Register Number: DRKS00000040.

Objective: Associations between occupational styrene exposures and impairment of visual functions were investigated with a view to answering three questions: (1) are the published findings for colour vision deficiencies and impaired contrast sensitivity to reproduce in a new study approach, (2) if such effects exist, are they related to current or chronic exposures and (3) if effects exist, are there reductions in the effects during an exposure-free period?, Methods: Workers from a boat building plant were examined in groups of current low [n = 97, mean mandelic acid (MA) + phenylglyoxylic acid (PGA) = 51 mg/g creatinine], medium (n = 115, mean = 229 mg/g creatinine) and high (n = 30, mean = 977 mg/g creatinine) level exposure to styrene. Job tenure was about 6 years. In addition, subgroups chronically exposed to low-short (n = 34, lifetime weighted mean 200 mg/g creatinine for 6 years) and high-long (n = 17, mean = 660 mg/g creatinine, 15 years) styrene levels were analysed. The examinations were carried out during normal working days and during the company holidays. Colour vision was investigated with the Lanthony desaturated panel D-15d using the colour confusion index (CCI) as a relevant variable. Contrast sensitivity was investigated with the Vistech charts VCTS 6500 using frequency-related results as well as total scores as variables. Co-variance analyses with repeated measurements and multiple linear regressions were used for statistical analysis., Results: There was no evidence of significant associations between exposure parameters and CCI. This is true for the analyses with all participants as well as for those with the subgroups with high-long versus low-short exposure. Thus, no exposure related changes in the relevant variables were found during the exposure-free period. The analyses for contrast sensitivity show similar results. The largest portions of the variances in both tests were explained by age. German as mother tongue covered a considerable portion of the CCI variances. Education, long-term alcohol use and job tenure explain only partly significant portions of the test variances exhibited., Conclusion: Both acute styrene exposure levels of 40 ppm (range of standard deviation up to 54 ppm) and long term exposures to 27 ppm (range of standard deviation up to 44 ppm with higher exposure levels in the past) for a period of about 15 years were not identified as causing elevated risks for the investigated parameters of colour vision and contrast sensitivity. This statement contradicts the published results for styrene-related colour vision deficiencies but it seems to be compatible with published results for contrast sensitivity due to styrene exposure.

Objective: Associations between occupational styrene exposure and impairment of hearing function were investigated, guided by three questions: are there hearing losses concerning high frequency and standard audiometric test? Are there dose-response relationships and measurable thresholds of effects? Are there signs of reversibility of possible effects if the workers are examined during times of improvement from their work?, Methods: A group of workers from a boat building plant, some of whom were laminators, were examined in subgroups of current low (n = 99, mean mandelic acid MA + phenylglyoxylic acid PGA = 51 mg/g creatinine), medium (n = 118, mean 229 mg/g creat.) and high (n = 31, mean 970 mg/g creat.) exposure to styrene. In addition, subgroups chronically exposed to high-long (n = 17) and low-short (n = 34) styrene levels were analysed. The examinations were carried out during normal work days and during the company holidays. Hearing thresholds and transient evoked otoacoustic emissions (TEOAE) were measured. Statistics included multiple co-variance analyses with repeated measures, linear regressions, and logistic regressions., Results: The analyses of all participants demonstrated no clear exposure effects. Particularly no sufficient proof of dose-response relationship measured against parameters of current exposure (MA + PGA, styrene/blood) and of chronic exposure (cumulative and average life time exposure resp.) was found. The analyses of groups exposed to high levels show elevated thresholds at frequencies up to 1,500 Hz among the subgroup exposed to high styrene levels (e.g. 40-50 ppm as average) for a longer period of time (e.g. more than 10 years). These participants also demonstrated signs of "improvement" at frequencies above 2,000 Hz during work holidays, when they were not exposed to styrene. A significantly elevated odds ratio for cases of hearing loss (more than 25 dB (A) in one ear, 3,000-6,000 Hz) was found among the group exposed to high levels (above 30 ppm as average) for a longer period of time (more than 10-26 years). The measurements of TEOAE did not exhibit significant results related to exposure., Conclusion: This study found, that chronic and intensive styrene exposure increases the hearing thresholds. At levels of about 30-50 ppm as an average inhaled styrene per work day over a period of about 15 years with higher exposure levels above 50 ppm in the past, an elevated risk for impaired hearing thresholds can be expected. The formerly published results on ototoxic effects below 20 ppm could not be confirmed. With few exceptions (at frequencies of 1,000 and 1,500 Hz) no dose-response relationship between threshold and exposure data was found. Improvements of hearing thresholds during work- and exposure-free period are possible.

Introduction: Only a small part of the daily work in the field of surgery is based on high-level evidence. To improve the rate of evidence-based medicine (EBM) in surgery, more surgical, randomized controlled trials have been advocated. In addition, it has been recognized that educational issues that concern methods and techniques of clinical research are of similar importance. Therefore, a clinical investigator course focusing particularly on the issues of surgical trials was initiated in 2005. The structure of this course is demonstrated here as well as the results of its evaluation over the last 4 years., Material and Methods: All participants were invited to rate both the lecture and the teachers with the help of a standardized evaluation questionnaires (rating scale from 1 = excellent to 6 = insufficient). Lectures were evaluated via questions on content, comprehension, and learning effect. Teachers were evaluated in terms of rhetorical abilities, content, and presentation technique, respectively. Assessment of personal long-term learning effects was evaluated by an e-mail survey., Results: Seventy-three participants were trained in a total of 4 courses. Participants in each course completed the evaluation questionnaires. In 2005, 20 of 21 (95.2%) participants completed the questionnaire; in 2006, 11 of 11 participants completed it (100%); in 2007, 19 of 22 (86.4%) participants completed it; and in 2008, 16 of 19 (84.2%) participants completed it. The overall evaluation of the course was graded 1.52 for content and 1.72 for clarity, and the learning effect was assessed at 1.60. The 16 lecturers came from different institutions involved in clinical research and evidence-based surgery. Besides classic lecturing, the current assembly of the course consists of 6 lectures designed as hands-on sessions. A survey (48.5% response rate) with a mean follow-up of 1.72 years (range, 6 months to 3 years) revealed that the enduring learning effect was rated 2.09, and 70.4% of former participants actually participated in randomized controlled trials., Conclusions: The development of a clinical investigator course tailored to the needs of surgeons provides hospitals with a key tool for promoting surgical interest in clinical trials.

Introduction: Severe sepsis, septic shock, and resulting organ failure represent the most common cause of death in intensive care medicine, with mortality ranging from 40% to 70%. It is still unclear whether necrosis or apoptosis plays the predominant role in severe sepsis. Determining the prevalent mode of cell death would be valuable, as new therapeutic agents (eg, antiapoptotic drugs such as caspase inhibitors) may improve unsatisfactory outcomes in patients with severe sepsis. Furthermore, the prognostic value of newly developed cell death serum biomarkers is of great interest., Methods: In total, 147 patients (101 patients with severe sepsis, 28 postoperative patients after major abdominal surgery, 18 healthy volunteers) were enrolled. Baseline and clinical data were evaluated. Blood samples from patients with severe sepsis were collected at the time of sepsis diagnosis, and 48 and 120 hours later; samples from healthy volunteers were collected once, and from postoperative patients, once immediately after surgery. We measured caspase-cleaved and uncleaved cytokeratin-18 (CK-18, intermediate filament protein) as a marker of cell death, isolated CK-18 fragments as a marker of apoptosis, as well as IL-6, soluble vascular cell adhesion molecule, and soluble intercellular adhesion molecule., Results: Age and sex of patients with severe sepsis and postoperative patients were comparable, whereas healthy volunteers were significantly younger. In healthy volunteers, the mode of cellular turnover was primarily apoptotic cell death. Postoperative patients showed comparable levels of apoptotic activity, but necrotic cell death was markedly increased, probably due to surgical tissue injury. In contrast, patients with severe sepsis, and especially non-survivors of the septic group showed increased levels of markers for both apoptotic and necrotic cell death. In severe septic patients with liver dysfunction, necrosis is increased relative to severe septic patients with intact hepatic function. For severe septic patients with liver dysfunction, a cut-off value for caspase-cleaved and uncleaved cytokeratin-18 could be calculated, in order to identify patients at high risk for death due to severe sepsis., Conclusions: The measurement of caspase-cleaved and uncleaved cytokeratin-18 appears to be an early predictor for survival in severe septic patients with hepatic dysfunction. Furthermore, the loss of parenchymal cells due to necrosis may be the primary mode of cell death in these patients. This may limit possible therapeutic options.

The German Atopic Dermatitis Intervention Study (GADIS), which includes 823 children and adolescents, showed that age-related educational programmes are effective in the long-term management of atopic dermatitis. We investigated whether the itch severity obtained in the scoring of atopic dermatitis (SCORAD) correlates with quality of life and coping behaviour in children and parents. There were significant but low correlations between the severity of atopic dermatitis and the itch intensity. Itch and sleeplessness were significantly correlated. Significant correlations of itch with the coping behaviour and quality of life in parents of children with atopic dermatitis were measured. The coping and itching behaviour of children (8-12 years) and adolescents (13-18 years) had higher significant correlations with the itch compared with the parents' answers. Quality of life in children (8-12 years) and adolescents (13-18 years) showed a significant negative correlation with itch intensity. Quality of life, itch intensity and coping strategies should be considered when treating patients with atopic dermatitis.