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Background: Health benefits of the Mediterranean Diet (MD) have been shown in different at-risk populations. A German translation of the Mediterranean Diet Adherence Screener (MEDAS) from the PREvención con DIeta MEDiterránea (PREDIMED) consortium was used in the LIBRE study, investigating effects of lifestyle-intervention on women with BRCA1/2 mutations. The purpose of the present study is to validate the MEDAS German version.Methods: LIBRE is a multicentre (three university hospitals during this pilot phase), unblinded, randomized, controlled clinical trial. Women with a BRCA1/2 mutation of age 18 or over who provided written consent were eligible for the trial. As part of the assessment, all were given a full-length Food Frequency Questionnaire (FFQ) and MEDAS at baseline and after 3 months. Data derived from FFQ was compared to MEDAS in order to evaluate agreement or concordance between the two questionnaires. Additionally, the association of dietary intake biomarkers in the blood (β-carotene, omega-3, omega-6 and omega-9 fatty acids and high-sensitivity C-reactive protein (hsCRP)) with some MEDAS items was analyzed using t-Tests and a multivariate regression.Results: The participants of the LIBRE pilot study were 68 in total (33 Intervention, 35 Control). Only participants who completed both questionnaires were included in this analysis (baseline: 66, month three: 54). The concordance between these two questionnaires varied between the items (Intraclass correlation coefficient of 0.91 for pulses at the highest and -0.33 for sugar-sweetened drinks). Mean MEDAS scores (sum of all items) were 9% higher than their FFQ counter-parts at baseline and 15% after 3 months. Higher fish consumption (at least 3 portions) was associated with lower omega-6 fatty acid levels (p = 0.026) and higher omega-3 fatty acid levels (p = 0.037), both results being statistically significant.Conclusions: We conclude that the German MEDAS in its current version could be a useful tool in clinical trials and in practice to assess adherence to MD.Trial Registration: ClinicalTrials.gov , registered on March 12, 2014, identifier: NCT02087592 . World Health Organization Trial Registration, registered on 3 August 2015, identifier: NCT02087592 . [ABSTRACT FROM AUTHOR]

Background: Obesity and associated metabolic disorders are related to impairments of the intestinal barrier. Objective: We examined lactulose:mannitol (Lac:Man) permeability in obese individuals with and without liver steatosis undergoing a weight-reduction program to test whether an effective weight-loss program improves gut barrier function and whether obese patients with or without liver steatosis differ in this function. Design: Twenty-seven adult, nondiabetic individuals [mean ± SD body mass index (BMI; in kg/m²): 43.7 ± 5.2; 78% with moderate or severe liver steatosis] were included in the follow-up intervention study (n =13 by month 12). All patients reduced their weight to a mean ± SD BMI of 36.4 ± 5.1 within 12 mo. We assessed barrier functions by the oral Lac:Man and the fecal zonulin tests. Insulin resistance was assessed by the homeostatic model assessment index (HOMA), and liver steatosis by sonography and the fatty liver index (FLI). Results: The Lac:Man ratio and circulating interleukin (IL) 6 concentration decreased during intervention from 0.080 (95% CI: 0.073, 0.093) to 0.027 (95% CI: 0.024, 0.034; P < 0.001) and from 4.2 ± 1.4 to 2.8 ± 1.6 pg/mL (P < 0.01), respectively. At study start, the Lac:Man ratio was higher in patients with moderate or severe steatosis than in those without any steatosis (P < 0.001). The Lac:Man ratio tended to correlate with HOMA (p = 0.55, P = 0.052), which correlated with FLI (p = 0.75, P < 0.01). A multiple-regression analysis led to a final model explaining FLI best through BMI, waist circumference, and the Lac:Man ratio. Conclusions: Intestinal permeability is increased in obese patients with steatosis compared with obese patients without. The increased permeability fell to within the previously reported normal range after weight reduction. The data suggest that a leaky gut barrier is linked with liver steatosis and could be a new target for future steatosis therapies. [ABSTRACT FROM AUTHOR]

The intestinal microbiota is involved in many physiological processes and it is increasingly recognized that differences in community composition can influence the outcome of a variety of murine models used in biomedical research. In an effort to describe and account for the variation in intestinal microbiota composition across the animal facilities of participating members of the DFG Priority Program 1656 “Intestinal Microbiota”, we performed a survey of C57BL/6J mice from 21 different mouse rooms/facilities located at 13 different institutions across Germany. Fresh feces was sampled from five mice per room/facility using standardized procedures, followed by extraction and 16S rRNA gene profiling (V1–V2 region, Illumina MiSeq) at both the DNA and RNA (reverse transcribed to cDNA) level. In order to determine the variables contributing to bacterial community differences, we collected detailed questionnaires of animal husbandry practices and incorporated this information into our analyses. We identified considerable variation in a number of descriptive aspects including the proportions of major phyla, alpha- and beta diversity, all of which displayed significant associations to specific aspects of husbandry. Salient findings include a reduction in alpha diversity with the use of irradiated chow, an increase in inter-individual variability (beta diversity) with respect to barrier access and open cages and an increase in bacterial community divergence with time since importing from a vendor. We further observe a high degree of facility-level individuality, which is likely due to each facility harboring its own unique combination of multiple varying attributes of animal husbandry. While it is important to account and control for such differences between facilities, the documentation of such diversity may also serve as a valuable future resource for investigating the origins of microbial-driven host phenotypes. [ABSTRACT FROM AUTHOR]

Objectives PEPDar compared the tolerability and safety of ritonavir-boosted darunavir ( DRV/r)-based post-exposure prophylaxis ( PEP) with the tolerability and safety of standard of care ( SOC). The primary endpoint was the early discontinuation rate among the per-protocol population. Methods PEPDar was an open-label, randomized, multicentre, prospective, noninferiority safety study. Subjects were stratified by type of event (occupational vs. nonoccupational, i.e. sexual) and were randomized to receive DRV/r plus two nucleoside reverse transcriptase inhibitors ( NRTIs) or SOC PEP. Twenty-two private or university HIV clinics in Germany participated. Subjects were ≥ 18 years old and had documented or potential HIV exposure and indication for HIV PEP. They initiated PEP not later than 72 h after the event and were HIV negative. Results A total of 324 subjects were screened, the per-protocol population was 305, and 273 subjects completed the study. One hundred and fifty-five subjects received DRV/r-based PEP and 150 subjects received ritonavir-boosted lopinavir ( LPV/r)-based PEP for 28-30 days; 298 subjects also received tenofovir/emtricitabine. The early discontinuation rate in the DRV/r arm was 6.5% compared with 10.0% in the SOC arm ( P = 0.243). Adverse drug reactions ( ADRs) were reported in 68% of DRV/r subjects and 75% of SOC subjects ( P = 0.169). Fewer DRV/r subjects (16.1%) had at least one grade 2 or 3 ADR compared with SOC subjects (29.3%) ( P = 0.006). All grades of diarrhoea, nausea, and sleep disorders were significantly less frequent with DRV/r, while headache was significantly more frequent. No HIV seroconversion was reported during follow-up. Conclusions Noninferiority of DRV/r to SOC was demonstrated. DRV/r should be included as a standard component of recommended regimens in PEP guidelines. [ABSTRACT FROM AUTHOR]

Evidence suggests a correlation between the gut microbiota composition and weight loss caused by caloric restriction. Laparoscopic sleeve gastrectomy (LSG), a surgical intervention for obesity, is classified as predominantly restrictive procedure. In this study we investigated functional weight loss mechanisms with regard to gut microbial changes and energy harvest induced by LSG and a very low calorie diet in ten obese subjects (n=5 per group) demonstrating identical weight loss during a follow-up period of six months. For gut microbiome analysis next generation sequencing was performed and faeces were analyzed for targeted metabolomics. The energy-reabsorbing potential of the gut microbiota decreased following LSG, indicated by the Bacteroidetes/Firmicutes ratio, but increased during diet. Changes in butyrate-producing bacterial species were responsible for the Firmicutes changes in both groups. No alteration of faecal butyrate was observed, but the microbial capacity for butyrate fermentation decreased following LSG and increased following dietetic intervention. LSG resulted in enhanced faecal excretion of nonesterified fatty acids and bile acids. LSG, but not dietetic restriction, improved the obesity-associated gut microbiota composition towards a lean microbiome phenotype. Moreover, LSG increased malabsorption due to loss in energy-rich faecal substrates and impairment of bile acid circulation. This trial is registered with ClinicalTrials.gov NCT01344525. [ABSTRACT FROM AUTHOR]

Needlestick injuries (NSI) pose a significant health hazard among healthcare personnel (HCP). The aim of our prospective observational study was to evaluate the psychological impact of NSI and assess measures to prevent NSI. The target group was the medical staff and students of Frankfurt University Hospital who had experienced a NSI ( n = 370) during the 12-month study period. Data were retrieved from accident insurance reports, occupational follow-up examinations and a standardized anonymous questionnaire sent to the affected HCP. Analysis of the completed questionnaires (232/370) revealed that stress (48.3 %) and tiredness (36.6 %) were common factors contributing to the NSI and that >80 % of the respondents were concerned about the consequences of the NSI. Higher levels of anxiety were reported when the patient was known to have a chronic virus infection. Stressful working conditions, lack of adequate protective medical/technical equipment and poor work routines were suggested as factors contributing to NSI. [ABSTRACT FROM AUTHOR]

Aim To determine the prevalence of metabolic abnormalities, and differences between the sexes, in prepubertal overweight and normal weight children aged from 5 to 8 years, without any signs of health impairments or metabolic disturbances at the time of recruitment. Methods General health status and inflammatory markers were assessed in 100 overweight and 51 normal weight children, who were living in Germany and had undergone mandatory medical examinations. The study comprised of 81 girls and 70 boys. Results Despite being recruited as healthy, 73% of the overweight children and 16% of the normal weight children were found to suffer from one or more metabolic abnormalities, such as hypertension or insulin resistance. Girls with a body mass index ( BMI) percentile of ≥80th showed an increased susceptibility to metabolic disorders, and a similar effect was found for boys with a BMI percentile of ≥95th. Plasma levels of pro-inflammatory markers, such as plasminogen activator inhibitor-1 and leptin, were also significantly higher in overweight than normal weight children. Conclusion Metabolic and cardiovascular abnormalities and pro-inflammatory markers were prevalent in overweight prepubertal children. The prevalence rates appeared to differ between the sexes. [ABSTRACT FROM AUTHOR]

Background: Several studies indicate that dietary pattern and leisure time activities of adults not only differ between sexes but also between overweight and normal weight individuals. The aim of the present study was to determine if sex-specific differences in dietary pattern and leisure time activity already exist and are associated with weight status in young childhood. Methods: Nutritional intake, anthropometric parameters, leisure time activities and socio- demographical factors were assessed in 100 overweight and 51 normal weight children (81 girls and 70 boys), aged 5-8 years. Results: In general, independent of body weight, boys ate more cheese while girls consumed more vegetables and spent more time with sedentary activities. Moreover, regardless of sex, total energy and macronutrient intake did not differ between normal weight and overweight children. Also, time spent with sportive activities did not differ between groups; however, overweight boys spent significantly more leisure time with sedentary activities than normal weight boys. Furthermore, BMI of mothers and time spent with sedentary activities were identified as independent risk factors for the development of overweight when performing multiple regression analyses. Conclusions: Taken together, results of our study suggest that already at young age sex influences dietary pattern independent of body weight. Furthermore, an increased time spent with sedentary activities and an elevated maternal BMI were found to be associated with an elevated body weight in children. (Trial registration: NCT01306396) [ABSTRACT FROM AUTHOR]

Objectives Renal disease is a common and serious complication in HIV-infected patients. Methods A retrospective cohort analysis for the period 1989-2010 was carried out to determine the prevalence, incidence and risk factors for end-stage renal disease ( ESRD). ESRD was defined as initiation of renal replacement therapy. Three time periods were defined: 1989-1996 [pre-highly active antiretroviral therapy ( HAART)], 1997-2003 (early HAART) and 2004-2010 (late HAART). Results Data for 9198 patients [78.2% male; 88.9% Caucasian; cumulative observation time 68 084 patient-years ( PY)] were analysed. ESRD was newly diagnosed in 35 patients (0.38%). Risk factors for ESRD were Black ethnicity [relative risk ( RR) 5.1; 95% confidence interval ( CI) 2.3-10.3; P < 0.0001], injecting drug use ( IDU) ( RR 2.3; 95% CI 1.1-4.6; P = 0.02) and hepatitis C virus ( HCV) coinfection ( RR 2.2; 95% CI 1.1-4.2; P = 0.03). The incidence of ESRD decreased in Black patients over the three time periods [from 788.8 to 130.5 and 164.1 per 100 000 PY of follow-up ( PYFU), respectively], but increased in Caucasian patients (from 29.9 to 41.0 and 43.4 per 100 000 PYFU, respectively). The prevalence of ESRD increased over time and reached 1.9 per 1000 patients in 2010. Mortality for patients with ESRD decreased nonsignificantly from period 1 to 2 ( RR 0.72; P = 0.52), but significantly from period 1 to 3 ( RR 0.24; P = 0.006), whereas for patients without ESRD mortality decreased significantly for all comparisons. ESRD was associated with a high overall mortality ( RR 9.9; 95% CI 6.3-14.5; P < 0.0001). Conclusion As a result of longer survival, the prevalence of ESRD is increasing but remains associated with a high mortality. The incidence of ESRD declined in Black but not in Caucasian patients. IDU and HCV were identified as additional risk factors for the development of ESRD. [ABSTRACT FROM AUTHOR]

Background: Over the last three decades the prevalence of overweight and obesity has increased dramatically among children and adolescents worldwide. As the results of animal and human studies suggest that a diet rich in fructose may be a risk factor for the development of overweight, the aim of the pilot study was to evaluate if a dietary counseling aimed at a moderate reduction of dietary fructose intake (-50% in comparison to intake at baseline) has a positive effect on the body mass index (BMI) of overweight and obese children. Methods: Fifteen overweight or obese children aged 5-8 years were included into the 3 month dietary intervention study. At baseline and after 4 and 8 weeks children and their parents were trained to reduce fructose in the children's diet. Anthropometric parameters for calculating BMI and BMI standard deviation scores (BMI-SDS) as well as nutritional intake were assessed at baseline, after the 12-week intervention and after 12 week of follow up. Results: After the 12-week intervention children had significantly reduced their total energy, fructose, sucrose and glucose intake. BMI and BMI-SDS were significantly reduced by 0.68 kg/m2 and 0.21, respectively, at the end of the intervention. At follow up, the BMI-SDS was significantly lower in comparison to baseline while the BMI was only decreased by trend (P = 0.08). Conclusions: The results of our pilot study indicate that counseling aimed towards a moderate reduction of dietary fructose and/or general sugar intake may have a positive effect on BMI in overweight and obese children. [ABSTRACT FROM AUTHOR]

In this study, we employ the concept of political market orientation to better understand how the main political parties in the United Kingdom and Germany relate to other stakeholders in the political sphere through an exploratory content analysis of their core election offering, the manifesto. This study has two aims: first, we will discuss the different facets of the market orientation of the main U.K. and German parties in their respective 2005 general elections through an exploratory content analysis, and second, we will compare characteristics of market orientation between the two countries. While the U.K. parties generally exhibited similar levels of market orientation on each of the relevant construct dimensions, the German parties had more distinct profiles; thus, the applied dimensions of political market orientation show discriminatory power within and across electoral systems. In the United Kingdom, it was found that there was a marketplace-determined “gravitational center effect” that limited the political market orientation of the manifesto, while this was less pronounced in Germany. This leads to the hypothesis that certain aspects of political market orientation may be mediated by structural variables such as the electoral system. [ABSTRACT FROM AUTHOR]

Background: The Communication and Tracing App HIV (COMTRAC-HIV) project is developing a mobile health (mHealth) app for integrated care of HIV patients in Germany. The complexity of HIV treatment and continuous care necessitates the need for tailored mHealth solutions. This qualitative study explores design solutions and a prototype to enhance the app's functionality and effectiveness., Methods: A total of eight HIV patients and pre-exposure prophylaxis (PrEP) users, recruited at the HIV Center Frankfurt, participated in focus groups and thinking-aloud tests (TA test). In the focus groups, design solutions were discussed for user-interface clarity, leading to the development of an interactive prototype, the usability of which was evaluated with a TA test. Data collection involved video/audio recordings. Qualitative analysis was conducted using a deductive category system, and focused on app design and usage in focus groups, and layout, navigation, interaction, terminology, comprehension, feedback, and level of satisfaction in TA tests., Results: The app was commended for its simple, clear design, especially its medication reminders and health tracking features. Opinions on the symptom diary varied however, respondents noting it more suitable for HIV users than PrEP users. Privacy concerns suggest avoiding display of HIV-specific information. Suggested improvements include e.g. image uploads, drug interaction checks and prescription tracking. A total of 25 usability issues were identified in the TA test, with most found in the layout (n = 6), navigation (n = 5), interaction (n = 5), and terminology (n = 5) categories. Two examples are non-intuitive controls and illogical button placement. Despite these disadvantages, participants noted positive impressions (n = 5) in the satisfaction category., Conclusion: The study emphasizes the need for patient-centered design in mobile HIV care solutions, highlighting to the app's user-friendliness and potential to enhance care. Further research is necessary to refine the app's functionality and to align it with clinical and patients' privacy needs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Cryptococcosis is the most prevalent fungal infection of the central nervous system worldwide. We performed a retrospective multicenter cohort study to gain insights into the epidemiology of cryptococcosis in Germany. We describe the use of diagnostic tests, clinical management and patient outcome. We included 64 patients with underlying HIV infection (55%) or other predispositions. Molecular typing by MLST documented 20 individual sequence types among 42 typed isolates. A fatal outcome was documented in 14% of patients in the first two months after diagnosis., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Delayed HIV diagnosis at advanced stages of disease remains common (33%-64%). This analysis of the multi-center FindHIV study including newly diagnosed HIV-infected adults in Germany, focused on the potential role of socio-demographic and psychological factors on late diagnosis (formerly "late presentation", AIDS diagnosis or CD4 cells <350/µL). These data were collected from patient profiles, physician-patient interviews and questionnaires. Participating centers ( n  = 40) represented the diverse health care settings in HIV care and geographic regions. Of 706 newly diagnosed adults (92% male, median age 39 years) between 2019 and 2020, 55% (388/706) were diagnosed late with a median CD4 cell count of 147/µL; 20% (142/706) presented with AIDS. From the physicians' perspective, earlier diagnosis would have been possible in 45% of participants (late versus non-late presentation 58% versus 29%). The most common physician-perceived reason was an underestimated risk for HIV infection by the patient (37%). In multivariable logistic regression analysis, older age, sexual contacts with both sexes as possible route of HIV transmission, being married, and a poor level of knowledge about HIV treatment were found to be associated with a significantly elevated risk for late presentation. Education, employment status, sexual relations, migration background and personality traits were not. Trial registration : German Clinical Trials Register (DRKS00016351).

Objectives: This study examined the incidence rates and predictive utility of established prognostic factors for the progression to AIDS among people living with HIV under clinical care., Methods: We used data from two observational cohorts of people living with HIV in Germany between 1999 and 2018. The outcome measure was the first AIDS-defining event that occurred during follow-up. Incidence rates (IRs) per 1000 person-years (PY) were calculated by years of follow-up and calendar periods. We used Cox models in our prediction analyses, including CD4 count, viral load, and age at baseline to estimate the predictive performance. Additionally, we included transmission mode to examine its predictive utility., Results: A total of 23 299 people living with HIV were included in the analyses. Of these, 1832 developed a first AIDS event during follow-up, constituting an overall rate of 14.6/1000 PY (95% confidence interval [CI] 13.9-15.2). IRs were highest in the first year of follow-up (45.6/1000 PY, 95% CI 42.6-48.8) and then declined continuously. IRs were highest among people living with HIV who enrolled between 1999 and 2003 (36.1/1000 PY, 95% CI 32.6-40.0). A low CD4 count, high viral load, and older age at baseline increased the likelihood of progressing to AIDS. Adding transmission mode to the models did not improve the predictive performance., Conclusions: The rates of a first AIDS event among people living with HIV have continuously declined in Germany. Health outcomes depend on a person's CD4 count, viral load, and age but not on transmission mode. To further reduce the number of AIDS cases, the focus should be on groups more likely to present in progressed stages of their HIV infection., (© 2023 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: Information on testing units in health care is scarce, particularly the group of late-presenters among the HIV-first diagnoses is still a challenge in Germany., Aim: Analysis of the impact of testing units on and reasons for the prevalence of HIV-first diagnoses and late presentation, taking 2014 for illustrative purposes., Material and Methods: Cross-sectional analysis of all individuals, treated in the Network HIV-Regional who were first diagnosed with HIV in 2014; patient characteristics, demographic and clinical data, including information on HIV testing were collected retrospectively and in a decentralised manner, pseudonymized and statistically evaluated., Results: A total of 971 individuals with HIV-first diagnosis from 31 specialised care centres throughout Germany (15 hospitals, 16 private practices) represented 27.5% of all National HIV-first diagnoses -registrations from Robert Koch Institute for 2014, with similar results for CD4-cell count and HIV-transmission risk. The most common test site was a hospital (34.8%), followed by the office of a family doctor (19.6%) and medical specialist (16.1%). If the first diagnosis was established in hospital, then the patients were on average older than those tested on an ambulant care basis (42 vs. 37 years, p=0.001); moreover, the HI-viral load was higher (585 vs. 270 thousand copies/mL, p<0.001) and the CD4-cell count lower (265 vs. 414/µL, p<0.001). In 208/971 individuals with first diagnosis, at least one AIDS-defining disease was found, most frequently pneumocystis-pneumonia (43.8%), candidiasis (36.5%) and Kaposi sarcoma (10.6%). A regional comparison revealed that in eastern Germany, for first diagnosed HIV-patients were younger, had a higher HIV-RNA viral load and also more often clinical AIDS., Conclusion: This analysis of HIV-Regional for 2014 enables a deeper insight into HIV first diagnoses, on the eve of the introduction of important prevention tools in Germany, e. g., HIV home testing and pre-exposure prophylaxis. This cross-sectional analysis was representative for Germany and underscores the importance of specialised hospitals, in particular for eastern Germany, and furthermore the involvement of late-presenters into HIV health care., Competing Interests: B.T. Schleenvoigt erhielt Honorare und finanzielle Unterstützung von Gilead, MSD, Janssen-Cilag, Pfizer, ViiV, AIDS-Hilfe Potsdam, AIDS-Hilfe Dresden, RG Ges. f. Information und Organisation mbH, CRM und Merck außerhalb der vorliegenden Arbeit. H. Stocker erhielt Honorare von Gilead, Janssen, MSD und ViiV außerhalb der vorliegenden Arbeit. A. Stoehr erhielt Honorare und finanzielle Unterstützung von Abbvie, Gilead, Janssen, MSD und VIIV außerhalb der vorliegenden Arbeit. C. Schulz erhielt öffentliche Förderungen von DZIF, Bayresq.net und der Else Kröner Stiftung außerhalb der vorliegenden Arbeit.H. Wesselmann erhielt Honorare von MSD, ViiV und BMS außerhalb der vorliegenden Arbeit.O. Degen erhielt Honorare und finanzielle Unterstützung von ViiV Healthcare, Janssen, MSD Gilead Sciences und Theratechnologies außerhalb der vorliegenden Arbeit.U. Seybold erhielt Honorare und finanzielle Unterstützung von Gilead Sciences GmbH, ViiV Healthcare GmbH, RG Ges. f. Information und Organisation mbH, and more Media GmbH, Bristol Myers Squibb GmbH, MSD Sharp & Dohme GmbH, Janssen Cilag GmbH, FomF GmbH, Springer Medizin Verlag, med update GmbH, promedicis GmbH, Sanofi-Aventis GmbH, Falk Foundation e.V., BAGNÄ e.V. außerhalb der vorliegenden Arbeit. C. Stephan und A. Haberl erhielten Honorare und finanzielle Unterstützung von Gilead, Janssen-Cilag, MSD, Merck, Roche, Shionogi, ViiV, Astellas und TAD außerhalb der vorliegenden Arbeit. J. Ankert, M. Bickel, C. Lehmann und M.W. Pletz geben an, dass keine Interessenkonflikte in Zusammenhang mit der vorliegenden Studie bestehen., (Thieme. All rights reserved.)

Breastfeeding (BF) in mothers living with HIV (MLWH) is still discussed controversially in resource-rich settings. In Germany, where formula feeding is recommended for MLWH single BF cases have been reported, but no systematic data collection and analysis are available so far. This study, titled HELENE, aims to fill this data gap. A questionnaire covering the course of BF was distributed by a graduate student visiting each study site. Information was collected from patient files and by personal communication with the health care provider. Primary study objectives were the duration of BF and the maternal antiretroviral treatment (ART). Fifteen treatment centers across Germany contributed a total of 42 BF cases, observed from May 2009 to July 2020. There was an increasing number of BF cases over time. The median duration of BF was 20 weeks varying from single BF of colostrum to 104 weeks. All BF women except one elite controller received ART: 39% non-nucleoside reverse transcriptase inhibitor-, 37% INSTI-, 29% protease inhibitor-based regimens; one woman was on maraviroc. Thirty-nine percent of the ART regimens included drugs that were not recommended by the German-Austrian pregnancy guidelines. Our findings highlight the diversity of BF cases in Germany in terms of duration, maternal ART, and monitoring. Since the number of BF cases is increasing, guidelines are obliged to implement more detailed recommendations on BF, the monitoring of BF mothers, and the follow-up of the infants. There is an urgent need for prospective national and European data collections to further improve HIV prevention of mother-to-child transmission (PMTCT) in the setting of BF.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused a pandemic with tens of millions of cases and hundreds of thousands of deaths. The infection causes coronavirus disease 2019 (COVID-19), a disease of the respiratory system of divergent severity. In the current study, humoral immune responses were characterized in a cohort of 143 patients with COVID-19 from the University Hospital Frankfurt am Main, Germany., Methods: SARS-CoV-2-specific-antibodies were detected by enzyme-linked immunosorbent assay (ELISA). SARS-CoV-2 and human coronavirus NL63 neutralization activity was analyzed with pseudotyped lentiviral vectors., Results: The severity of COVID-19 increased with age, and male patients encountered more serious symptoms than female patients. Disease severity was correlated with the amount of SARS-CoV-2-specific immunoglobulin (Ig) G and IgA and the neutralization activity of the antibodies. The amount of SARS-CoV-2-specific IgG antibodies decreased with time after polymerase chain reaction conformation of the infection, and antibodies directed against the nucleoprotein waned faster than spike protein-directed antibodies. In contrast, for the common flu coronavirus NL63, COVID-19 disease severity seemed to be correlated with low NL63-neutralizing activities, suggesting the possibility of cross-reactive protection., Conclusion: The results describe the humoral immune responses against SARS-CoV-2 and might aid the identification of correlates of protection needed for vaccine development., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Tenofovir disoxoproxil fumarate (TDF) is recommended for antiretroviral treatment for pregnant women living with HIV. As a comparative method to study bone density, we investigated the influence of in utero tenofovir exposure on the prevalence and distribution of developmental defects of enamel (DDE) in the primary dentition, as the mineralization process in teeth is higher and more complex and thus more vulnerable. HIV-exposed children with in utero exposition to tenofovir were included in this prospective observational single-center study. Dental status and enamel defects were assessed by an experienced dentist following a standardized protocol. Further information was collected using a standardized questionnaire, available in German and English. The prevalence of developmental defects in children with intrauterine tenofovir exposure was compared with literature data from a recent study of 377 healthy children in Germany and literature data from a study of 1221 healthy African children. Thirty-one children (mean age 2.1 ± 0.3 years; 41.9% female) were included. Median tenofovir exposure in utero was 28 weeks (mean ± 10.52 SD). Prevalence of developmental defects in the primary dentition in tenofovir-exposed children was similar compared to data of unexposed children (16.1% vs. 5.3%, p = 0.051 (compared to German cohort); 16.1% vs. 33.3%, p = 0.068 (compared to African cohort)).Conclusion: HIV-uninfected infants with in utero exposure to TDF showed no significant differences in the prevalence of DDE in comparison to cross-sectional data of HIV- and TDF-unexposed children; thus, the in utero exposure to TDF did not negatively influence the prevalence or distribution of DDE. What is Known: • There are no data available on the prevalence of developmental defects of enamel (DDE) in the primary dentition in intrauterine HIV- and tenofovir-exposed children. • Conclusions can be drawn from intrauterine milk tooth development to bone development and mineralization. What is New: • Prevalence of developmental defects in the primary dentition in tenofovir-exposed children was similar compared to data of unexposed children. • Preterm birth and hospitalization did not show a significant association on the prevalence of developmental defects in the primary dentition.

We analyzed 1,397 HIV-1 pol sequences of antiretroviral therapy-naive patients in a total of 7 university hospitals in Bonn, Cologne, Frankfurt, Hamburg, Hannover, and Munich, Germany. Phylogenetic and network analysis elucidated numerous cases of shared drug resistance mutations among genetically linked patients; K103N was the most frequently shared mutation.

Objective: Combination antiretroviral therapy (cART) has markedly increased survival and quality of life in people living with HIV. With the advent of new treatment options, including single-tablet regimens, durability and efficacy of first-line cART regimens are evolving., Methods: We analyzed data from the prospective multicenter German Clinical Surveillance of HIV Disease (ClinSurv) cohort of the Robert-Koch Institute. Kaplan-Meier and Cox proportional hazards models were run to examine the factors associated with treatment modification. Recovery after treatment initiation was analyzed comparing pre-cART viral load and CD4+ T-cell counts with follow-up data., Results: We included 8788 patients who initiated cART between 2005 and 2017. The sample population was predominantly male (n = 7040; 80.1%), of whom 4470 (63.5%) were reporting sex with men as the transmission risk factor. Overall, 4210 (47.9%) patients modified their first-line cART after a median time of 63 months (IQR 59-66). Regimens containing integrase strand transfer inhibitors (INSTI) were associated with significantly lower rates of treatment modification (adjusted hazard ratio 0.44; 95% CI 0.39-0.50) compared to protease inhibitor (PI)-based regimens. We found a decreased durability of first-line cART significantly associated with being female, a low CD4+ T-cell count, cART initiation in the later period (2011-2017), being on a multi-tablet regimen (MTR)., Conclusions: Drug class and MTRs are significantly associated with treatment modification. INSTI-based regimens showed to be superior compared to PI-based regimens in terms of durability.

Most official food composition tables and food questionnaires do not provide enough data to assess fermentable dietary fibers (DF) that can exert a health effect through their interaction with the gut microbiota. The aim of this study was to develop a database and a food frequency questionnaire (FFQ) allowing detailed DF intake estimation including prebiotic (oligo)saccharides. A repertoire of DF detailing total, soluble DF, insoluble DF and prebiotic (oligo)saccharides (inulin-type fructans, fructo-oligosaccharides and galacto-oligosaccharides) in food products consumed in Europe has been established. A 12 month FFQ was developed and submitted to 15 healthy volunteers from the FiberTAG study. Our data report a total DF intake of 38 g/day in the tested population. Fructan and fructo-oligosaccharides intake, linked notably to condiments (garlic and onions) ingestion, reached 5 and 2 g/day, respectively, galacto-oligosaccharides intake level being lower (1 g/day). We conclude that the FiberTAG repertoire and FFQ are major tools for the evaluation of the total amount of DF including prebiotics. Their use can be helpful in intervention or observational studies devoted to analyze microbiota-nutrient interactions in different pathological contexts, as well as to revisit DF intake recommendations as part of healthy lifestyles considering specific DF.

Background: To evaluate clinical outcomes after either immediate or deferred initiation of antiretroviral therapy in HIV-1-infected patients, presenting late with pneumocystis pneumonia (PCP) or toxoplasma encephalitis (TE)., Methods: Phase IV, multicenter, prospective, randomized open-label clinical trial. Patients were randomized into an immediate therapy arm (starting antiretroviral therapy (ART) within 7 days after initiation of OI treatment) versus a deferred arm (starting ART after completing the OI-therapy). All patients were followed for 24 weeks. The rates of clinical progression (death, new or relapsing opportunistic infections (OI) and other grade 4 clinical endpoints) were compared, using a combined primary endpoint. Secondary endpoints were hospitalization rates after completion of OI treatment, incidence of immune reconstitution inflammatory syndrome (IRIS), virologic and immunological outcome, adherence to proteinase-inhibitor based antiretroviral therapy (ART) protocol and quality of life., Results: 61 patients (11 patients suffering TE, 50 with PCP) were enrolled. No differences between the two therapy groups in all examined primary and secondary endpoints could be identified: immunological and virologic outcome was similar in both groups, there was no significant difference in the incidence of IRIS (11 and 10 cases), furthermore 9 events (combined endpoint of death, new/relapsing OI and grade 4 events) occurred in each group., Conclusions: In summary, this study supports the notion that immediate initiation of ART with a ritonavir-boosted proteinase-inhibitor and two nucleoside reverse transcriptase inhibitors is safe and has no negative effects on incidence of disease progression or IRIS, nor on immunological and virologic outcomes or on quality of life.

Purpose: Enteral and parenteral nutrition of adult critically ill patients varies in terms of the route of nutrient delivery, the amount and composition of macro- and micronutrients, and the choice of specific, immune-modulating substrates. Variations of clinical nutrition may affect clinical outcomes. The present guideline provides clinicians with updated consensus-based recommendations for clinical nutrition in adult critically ill patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g., mechanical ventilation) to maintain organ function., Methods: The former guidelines of the German Society for Nutritional Medicine (DGEM) were updated according to the current instructions of the Association of the Scientific Medical Societies in Germany (AWMF) valid for a S2k-guideline. According to the S2k-guideline classification, no systematic review of the available evidence was required to make recommendations, which, therefore, do not state evidence- or recommendation grades. Nevertheless, we considered and commented the evidence from randomized-controlled trials, meta-analyses and observational studies with adequate sample size and high methodological quality (until May 2018) as well as from currently valid guidelines of other societies. The liability of each recommendation was described linguistically. Each recommendation was finally validated and consented through a Delphi process., Results: In the introduction the guideline describes a) the pathophysiological consequences of critical illness possibly affecting metabolism and nutrition of critically ill patients, b) potential definitions for different disease phases during the course of illness, and c) methodological shortcomings of clinical trials on nutrition. Then, we make 69 consented recommendations for essential, practice-relevant elements of clinical nutrition in critically ill patients. Among others, recommendations include the assessment of nutrition status, the indication for clinical nutrition, the timing and route of nutrient delivery, and the amount and composition of substrates (macro- and micronutrients); furthermore, we discuss distinctive aspects of nutrition therapy in obese critically ill patients and those treated with extracorporeal support devices., Conclusion: The current guideline provides clinicians with up-to-date recommendations for enteral and parenteral nutrition of adult critically ill patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g., mechanical ventilation) to maintain organ function. The period of validity of the guideline is approximately fixed at five years (2018-2023)., (Copyright © 2019 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Purpose: NTM are ubiquitous bacteria that can cause colonisation and infection in immunocompetent and compromised hosts. The aim of this study was to elucidate the epidemiology of infection or colonisation with NTM for the metropolitan region of Frankfurt, Germany., Methods: All patients from whom NTM were isolated within the period from 2006 to 2016 were included in this retrospective analysis. Patient data were retrieved using the local patient data management system. Different groups were formed according to clinical manifestations, underlying diseases and mycobacterial species. They were compared in regard to mortality, duration of infection/colonisation and their geographical origins., Results: A total of 297 patients with a median of 28 new patients each year were included. Most patients suffered from lung infection or colonisation (72.7%, n = 216), followed by disseminated mycobacteriosis (12.5%, n = 37). The majority were HIV-positive, suffering from malignoma or cystic fibrosis (29.3%, n = 87, 16.2%, n = 48, and 13.8%, n = 41, respectively). 17.2% of patients showed no predisposing condition (n = 51). Mycobacterium avium complex (MAC) species were most frequently isolated (40.7%, n = 121). Infection/colonisation was longest in CF patients (median of 1094 days). The mortality was highest in malignoma patients (52.4%), while CF patients had the lowest overall mortality rate (5.3%). But mortality analysis showed non-significant results within different mycobacterial species and clinical manifestations., Conclusion: NTM remain rare but underestimated pathogens in lung and disseminated disease. MAC were the species most frequently isolated. Depending on species and underlying predispositions, the duration of infection/colonisation can be unexpectedly long.

Purpose: Variations of clinical nutrition may affect outcome of critically ill patients. Here we present the short version of the updated consenus-based guideline (S2k classification) "Clinical nutrition in critical care medicine" of the German Society for Nutritional Medicine (DGEM) in cooperation with 7 other national societies. The target population of the guideline was defined as critically ill adult patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g. mechanical ventilation) to maintain organ function., Methods: The former guidelines of the German Society for Nutritional Medicine (DGEM) were updated according to the current instructions of the Association of the Scientific Medical Societies in Germany (AWMF) valid for a S2k-guideline. We considered and commented the evidence from randomized-controlled trials, meta-analyses and observational studies with adequate sample size and high methodological quality (until May 2018) as well as from currently valid guidelines of international societies. The liability of each recommendation was indicated using linguistic terms. Each recommendation was finally validated and consented by a Delphi process., Results: The short version presents a summary of all 69 consented recommendations for essential, practice-relevant elements of clinical nutrition in the target population. A specific focus is the adjustment of nutrition according to the phases of critical illness, and to the individual tolerance to exogenous substrates. Among others, recommendations include the assessment of nutritional status, the indication for clinical nutrition, the timing, route, magnitude and composition of nutrition (macro- and micronutrients) as well as distinctive aspects of nutrition therapy in obese critically ill patients and those with extracorporeal support devices., Conclusion: The current short version of the guideline provides a concise summary of the updated recommendations for enteral and parenteral nutrition of adult critically ill patients who suffer from at least one acute organ dysfunction requiring pharmacological and/or mechanical support. The validity of the guideline is approximately fixed at five years (2018 - 2023)., Competing Interests: Die Interessenkonflikte der Autoren sind in Tab. 2 aufgelistet., (Georg Thieme Verlag KG Stuttgart · New York.)

Objective: While Rilpivirine has shown high overall response rates in treatment-naïve patients without sex and gender specific differences in clinical trials, Sex and gender specific data in treatment experienced patients receiving rilpivirine are still limited. We conducted a 48 week efficacy and safety analysis in naïve and treatment experienced men and women using retrospective data from the HIVCENTER Frankfurt., Materials and Methods: In this retrospective observational study data of all patients who received a rilpivirine based regimen at the HIVCENTER between March 2011 and December 2015 were analyzed. Primary endpoint was the proportion of patients with any discontinuation until week 48. Virologic response rates (FDA snapshot analysis; HIV-1 RNA <50 copies/mL) were assessed at week 48., Results: 194 patients (34% female) were included in the analysis. 74% were treatment-experienced and 26% naïve, respectively. Discontinuations were observed in 31 (15.9%) patients. Regarding sex differences, the proportion of discontinuations was significantly higher in women than in men (24.2% vs. 11.7%; p=0.024; ODDS-Ratio = 2.41; CI 1.12 - 5.18). Virologic failure occurred in 8 PLWHIV (4.1%)., Conclusion: While virologic overall response rates to rilpivirine based ART were high for both treatment-experienced and -naïve patients the proportion of discontinuations was significantly higher in women (24.2% vs. 11.7%; p = 0.024; ODDS-Ratio = 2.41; CI 1.12 - 5.18). Although the total number of patients with virologic failure was low (4.1%), the higher rate of ART discontinuations in female patients receiving RPV require close monitoring in the first months of treatment addressing special needs of women living with HIV., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The consumption of high amounts of fructose is associated with metabolic diseases. However, the underlying mechanisms are largely unknown., Objective: To determine the effects of high fructose intake on plasma metabolomics., Study Design: We enrolled 12 healthy volunteers (six lean and six obese women, age 24⁻35 years) in a crossover intervention study. All participants carried out three diets: (1) low fructose (<10 g/day); (2) high fructose (100 g/day) from natural food sources (fruit); and (3) high fructose (100 g/day) from high fructose syrup (HFS)., Outcome Measures: The primary outcome was changes in plasma metabolites measured by targeted metabolomics., Results: High compared to low fructose diets caused a marked metabolite class separation, especially because of changes in acylcarnitine and lysophosphatidylcholine levels. Both high fructose diets resulted in a decrease in mean acylcarnitine levels in all subjects, and an increase in mean lysophosphatidylcholine and diacyl-phosphatidylcholine levels in obese individuals. Medium chain acylcarnitines were negatively correlated with serum levels of liver enzymes and with the fatty liver index., Discussion: The metabolic shifts induced by high fructose consumption suggest an inhibition of mitochondrial β-oxidation and an increase in lipid peroxidation. The effects tended to be more pronounced following the HFS than the fruit diet.

The fungal pathogen Cryptococcus gattii was considered to be restricted to tropic and sub- tropic regions. A recent outbreak in North America due to isolates belonging to molecular type VG II, affecting mostly non-immunocompromised hosts, documented the potential public health impact of this fungal pathogen also in temperate regions. Surveillance of these infections in Germany is challenging, as cryptococcosis is not notifiable and often C. gattii is diagnostically not distinguished from the more prevalent Cryptococcus neoformans. We used hospital discharge data and identified cryptococcal isolates received by the German cryptococcosis reference laboratory at the species level to gain insights into the epidemiology of C. gattii-infections in Germany between 2004 and 2013. Between 49 and 60 (Median 57) hospitalizations for cryptococcosis are documented per year. Between 5 and 28 (Median 14) isolates were received at the reference laboratory per year. Among 155 single patient isolates, four C. gattii (3%) of the molecular types VGI and VG III were identified from patients with meningoencephalitis, including one interspecies hybrid. Patient histories and molecular typing suggest that half of the infections were acquired abroad. Only one patient survived the infection. C. gattii remains rarely identified as agent of cryptococcosis in Germany but underestimation is likely. Definition of environmental niches occupied by C. gattii in Germany may help to assess the associated risk of infection and prevent this deadly fungal infection., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Occupational transmission of HIV among healthcare personnel is rare but has repeatedly been published in the literature. Early initiation of postexposure HIV prophylaxis (HIV-PEP) is crucial to prevent virus transmission. For this reason the need for HIV-PEP has to be evaluated immediately and if necessary, started as soon as possible. This article presents an early intervention program in a university hospital which enables healthcare personnel immediate 24/7/365 access to a HIV-PEP prophylaxis kit following occupational HIV exposure.

Objectives: The renal elimination of tenofovir (TFV) may be subject to renal drug-drug interactions that may increase the risk of kidney injury. Case reports indicated that diclofenac might increase TFV-associated nephrotoxicity via a drug-drug interaction, leading to an increased intracellular TFV concentration in proximal tubular cells., Methods: A retrospective analysis of data for all patients from the Frankfurt HIV Cohort (FHC) who had diclofenac prescriptions between January 2008 and June 2012 was carried out., Results: Among 89 patients with diclofenac use, 61 patients (68.5%) were treated with tenofovir disoproxil fumarate (TDF) and 28 patients (31.5%) were treated with TDF-sparing combination antiretroviral therapy (cART). Thirteen patients (14.6%) developed acute kidney injury (AKI) shortly after initiating diclofenac treatment. AKI occurred exclusively in TDF-treated patients, although all had previously stable renal function. All cases were accompanied by new onset of at least two parameters indicating proximal tubular damage, such as normoglycaemic-glucosuria and hypophosphataemia. TFV-associated nephrotoxicity was demonstrated by renal biopsy in four cases. Additionally, 11.5% of patients on TDF treatment developed new-onset proximal tubular damage, while having a preserved glomerular filtration rate. In contrast, diclofenac did not affect renal function in patients with TDF-sparing cART, as only one case of isolated hypophataemia was observed in these patients. In univariate analysis, risk factors for AKI were TDF-containing cART (P = 0.0076) and pre-existing hypophosphataemia (P = 0.0086)., Conclusions: Drug-drug interaction caused by diclofenac could exacerbate TFV-associated nephrotoxicity. Diclofenac should be used with caution in patients on TDF therapy, especially in those with hypophosphataemia. Our findings need to be confirmed in larger studies., (© 2013 British HIV Association.)

Background: Lung cancer is one of the most common non-AIDS-defining malignancies in HIV-infected patients. However, data on clinical outcome and prognostic factors are scarce., Methods: This was a national German multicentre, retrospective cohort analysis of all cases of lung cancer seen in HIV-infected individuals from 2000 through 2010. Survival was analyzed with respect to the use of antiretroviral therapy (ART), specific lung cancer therapies, and other potential prognostic factors., Results: A total of 72 patients (mean age 55.5 y, CD4 T-cells 383/μl) were evaluated in this analysis. At time of lung cancer diagnosis, 86% were on ART. Of these, 79% had undetectable HIV-1 RNA (< 50 copies/ml) for a mean duration of 4.0 y. All but 1 patient were current or former heavy smokers (mean 42 package y). The median estimated overall survival was 1.08 y, with a 2-y overall survival of 24%. The prognosis did not improve during the observation time. A limited lung cancer stage of I-IIIA was associated with better overall survival when compared with the advanced stages IIIb/IV (p = 0.0003). Other factors predictive of improved overall survival were better performance status, CD4 T-cells > 200/μl, and a non-intravenous drug use transmission risk for HIV., Conclusions: Currently, most cases of lung cancer occur in the setting of limited immune deficiency and a long-lasting viral suppression. As in HIV-negative cases, the clinical stage of lung cancer is highly predictive of survival, and long-term overall survival can only be achieved at the limited stages. The still high mortality underscores the importance of smoking cessation strategies in HIV-infected patients.

Background: An estimated 1 million needlestick injuries (NSIs) occur in Europe each year. The Council Directive 2010/32/EU on the prevention of NSIs describes minimum requirements for prevention and calls for the implementation of local, national and Europe-wide reporting systems. The Directive is to be implemented by all EU member states by 11 May 2013. The purpose of this study was to assess (and improve) the procedures for the reporting and treatment of needlestick injuries in a German tertiary-care hospital., Methods: We carried out a prospective observational study of the NSI reporting system in the hospital over a period of 18 months and determined the incidence of NSIs, the prevalence of blood-borne pathogens among index patients, the rate of initiation of post-exposure prophylaxis, and the rate of serological testing of the affected health care personnel., Results: 519 instances of NSI were reported to the accident insurance doctor over the period of the study, which consisted of 547 working days. 86.5% of the index patients underwent serological study for hepatitis B and C (HBV and HCV) and for the human immune deficiency virus (HIV); this resulted in two initial diagnoses (one each of active hepatitis B and hepatitis C) in the index patient. 92 of 449 index patients, or one in five, was infected with at least one blood-borne pathogen. HIV post-exposure prophylaxis was initiated in 41 health care workers. One case of hepatitis C virus transmission arose and was successfully treated. Other than that, no infection was transmitted., Conclusion: Complete reporting of NSIs is a prerequisite for the identification of risky procedures and to ensure optimal treatment of the affected health care personnel. The accident insurance doctor must possess a high degree of interdisciplinary competence in order to treat NSI effectively.

Unlabelled: Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Over the past decade, minimally invasive laparoscopic radical prostatectomy and more recently robot-assisted laparoscopic prostatectomy have been introduced and have proven equally effective compared with open surgery in terms of mid-term cancer control and complication rates. Because long-term data is lacking, open prostatectomy is still considered the 'gold standard' by some authors, who argue that minimally invasive approaches have to measure up to the excellent long-term results of open surgery. This study represents one of the largest series (1845 patients) of minimally invasive radical prostatectomy with extended follow-up (11.3 years) and detailed data on oncological outcome and postoperative incontinence. It therefore supplies previously lacking information on these details for minimally invasive prostate surgery and provides important information for patient counselling., Objective: • To investigate biochemical recurrence (BCR) rates and data on postoperative incontinence in a large laparoscopic radical prostatectomy (LRP) cohort with extended follow-up., Materials and Methods: • BCR and independent predictors of BCR were identified using Kaplan-Meier and Cox regression analysis of 1845 patients who underwent LRP from 1999 to 2007. • Urinary incontinence was evaluated by pads per day and stratified as follows: 0-1 pad: no incontinence; 2-3 pads: mild incontinence; and ≥ 3 pads: severe incontinence., Results: • Organ-confined disease, extraprostatic extension, seminal vesicle invasion and lymph node metastasis were present in 71.3%, 20.5%, 6.7% and 3.2% of patients, respectively. The positive surgical margin rate was 29.2%. • Postoperatively, 74.9% of the patients were continent, while 9.2% had mild and 15.9% severe incontinence. • The mean follow-up was 5 years with a maximum follow-up of 11.3 years. • There were 51 overall deaths and six deaths from prostate cancer. The 5-year, 8-year and 10-year BCR-free survival rates were 83.9%, 78.6% and 75.6%, respectively. • On univariate analyses preoperative D'Amico risk classification, pathological tumour stage, postoperative Gleason sum and surgical margin status were predictors of BCR (P < 0.001). • On multivariable analysis, D'Amico classification, Gleason sum (P < 0.001), postoperative tumour stage (P < 0.001), nodal status (P < 0.001) and surgical margin status (P = 0.002) were independent predictors of BCR., Conclusions: • LRP offers excellent long-term functional and oncological results with a low incidence of BCR for patients with localized disease. • These results could be used for patient counselling before robot-assisted laparascopic prostatectomy (RALP) until long-term follow-up data for RALP is available., (© 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.)

Intraoperative examination of sentinel axillary lymph nodes can be done by imprint cytology, frozen section, or, most recently, by PCR-based amplification of a cytokeratin signal. Using this technique, benign epithelial inclusions, representing mammary tissue displaced along the milk line, will likely generate a positive PCR signal and lead to a false-positive diagnosis of metastatic disease. To better appreciate the incidence of ectopic epithelial inclusions in axillary lymph nodes, we have performed an autopsy study, examining on 100 μm step sections 3,904 lymph nodes obtained from 160 axillary dissections in 80 patients. The median number of lymph nodes per axilla was 23 (15, 6, and 1 in levels 1, 2, and 3, respectively). A total of 30,450 hematoxylin-eosin stained slides were examined, as well as 8,825 slides immunostained with pan-cytokeratin antibodies. Despite this meticulous work-up, not a single epithelial inclusion was found in this study, suggesting that the incidence of such inclusions is much lower than the assumed 5% reported in the literature.

The introduction of prostate cancer treatment centers according to the criteria of the German Cancer Society ("Deutsche Krebsgesellschaft", DKG) aims at improving the quality of care for patients with prostate cancer. Systematic analyses of the effects and costs are lacking as yet. Three years after certification of the Interdisciplinary Prostate Cancer Center at the Charité Hospital Berlin we observed a decrease in the rate of positive surgical margins (tumor stage pT2), but other parameters of treatment quality including patient satisfaction remained unchanged. A survey among urologists of the region showed a high acceptance of prostate cancer centers in general. The majority of participating urologists appreciated the work of the Charité center, in particular the treatment recommendations given by the center were mostly followed and the majority of urologists regularly use educational activities of the center. However, only 30% of the participating urologists confirmed short-term improvements in the quality of patient care. Yearly additional costs for the Charité prostate cancer center are estimated at 205,000 euro (precertification phase and certification) and 138,000 euro (monitoring phase), despite the initial drop in mean treatment costs per case (radical prostatectomy). The introduction of prostate cancer treatment centers certified by the DKG is cost intensive, increases in treatment efficiency notwithstanding. Short-term improvements in quality of care cannot be unequivocally demonstrated. Prostate cancer centers serve an important role in counseling and medical education and may thus help disseminate evidence-based treatment strategies.

Objective: the RAINBOW survey is a multinational observational study assessing the tolerability and efficacy of ritonavir-boosted saquinavir (SQV/r), using the 500 mg film-coated SQV formulation, in routine clinical practice. This analysis presents data from the German subgroup of protease inhibitor (PI)-pretreated, but SQV-naive patients., Methods: multicenter, prospective, open-label, 48 week cohort study. Efficacy assessments included the proportion of patients with HIV-1 RNA <50 and <400 copies/mL and changes in CD4 cell count from baseline to week 48. Tolerability assessments included changes in liver enzymes and lipid levels from baseline to week 48., Results: a total of 426 patients were included in the analysis. The proportion of patients with HIV RNA levels <50 copies/mL at week 48 was 60.3 % (compared with 31.7% at switch to SQV/r) (intent-to-treat, last observation carried forward analysis). After 48 weeks, median CD4 count increased by +61 cells/mm3 from baseline (p<0.01) and 60.3% of patients achieved HIV-1 RNA <50 copies/mL. Median changes in fasting triglyceride levels (stratified according to baseline level) at week 48 were: +14 mg/dL (IQR -8; 57) for patients with baseline triglyceride <200 mg/dL; -50 mg/dL (IQR -139; 0) for baseline triglyceride 200-750 mg/dL, and -656 mg/dL (IQR -1024; 0) for baseline triglyceride >750 mg/dL (p<0.01 for all). Median changes in fasting total cholesterol (TC) levels (stratified according to baseline) were +16 mg/dL (IQR -3; 43) for patients with baseline TC <200 mg/dL (p<0.01), -3 mg/dL (IQR -25; 25) for baseline TC 200-300 mg/dL (p = 0.4), and -47 mg/dL (IQR -87; -4) for baseline TC >300 mg/dL (p<0.01). No significant changes in liver enzymes or bilirubin were observed. SQV treatment was discontinued in 22% of patients, 6% due to side effects., Conclusions: these data confirm the efficacy and tolerability of SQV/r in PI-experienced, SQV-naive patients treated in a real-life clinical setting. Of particular relevance are the improvements in triglycerides and TC levels observed in patients with baseline grade III-IV elevations.

Objective: To determine rates of seroconversion after single vaccination with a novel split virion, inactivated, adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in HIV-1-infected patients (ClinicalTrials.gov Identifier: NCT01017172)., Design: Single center diagnostic study., Setting: Institutional HIV outpatient department of an urban university clinic., Participants: Adult HIV-1-infected individuals., Intervention: Serum samples were taken before and 21 days after vaccination., Main Outcome Measures: Antibody titers determined by hemagglutination inhibition assay. Seroconversion to vaccination was defined by either an antibody titer of 1: 10 or less before and of at least 1: 40 after or at least 1: 10 before and at least four-fold increase in antibody titer 21 days after single vaccination., Results: One hundred and sixty patients (125 men/35 women) were analyzed. Before vaccination, 23 patients (14.4%) had a hemagglutination inhibition assay titer of at least 1: 40. A median of 22 +/- 3 days after vaccination, 110 (69%) patients seroconverted. Seroconverters were younger (45.1 +/- 10.0 vs. 48.8 +/- 11.3 years; P = 0.04), had a higher CD4 cell count (532 +/- 227 vs. 475 +/- 281 cells/microl; P = 0.03) and were more likely to have received a previous H5N1 vaccination in 2009 (25 vs. 8%; P = 0.02) when compared to nonresponders. No other significant differences were found comparing the two groups (prevaccination hemagglutination inhibition assay titer of > or =1: 40, AIDS, HAART, HIV RNA PCR <50 copies/ml or CD4 nadir, CD4 and CD8 percentage, sex, BMI, chronic hepatitis B or C)., Conclusion: Seroconversion after one dose of a split virion, inactivated, adjuvanted pandemic H1N1 influenza vaccine of HIV-infected patients was 69%. Studies to investigate whether a second dose of the vaccine will increase seroconversion rate are needed.

Selenium (Se) is essentially needed for the biosynthesis of selenoproteins. Low Se intake causes reduced selenoprotein biosynthesis and constitutes a risk factor for tumorigenesis. Accordingly, some Se supplementation trials have proven effective to reduce prostate cancer risk, especially in poorly supplied individuals. Because Se metabolism is controlled by selenoprotein P (SEPP), we have tested whether circulating SEPP concentrations correlate to prostate cancer stage and grade. A total of 190 men with prostate cancer (n = 90) and "no evidence of malignancy" (NEM; n = 100) histologically confirmed by prostate biopsy were retrospectively analyzed for established tumor markers and for their Se and SEPP status. Prostate specific antigen (PSA), free PSA, total Se, and SEPP concentrations were determined from serum samples and compared with clinicopathologic parameters. The diagnostic performance was analyzed with receiver operating characteristic curves. Median Se and SEPP concentrations differed significantly (P < 0.001) between the groups. Median serum Se concentrations in the 25th to 75th percentile were 95.9 microg/L (82-117.9) in NEM patients and 81.4 microg/L (67.9-98.4) in prostate cancer patients. Corresponding serum SEPP concentrations were 3.4 mg/L (1.9-5.6) in NEM and 2.9 mg/L (1.1-5.5) in prostate cancer patients. The area under the curve (AUC) of a marker combination with age, PSA, and percent free PSA (%fPSA) in combination with the SEPP concentration, yielded the highest diagnostic value (AUC 0.80) compared with the marker combination without SEPP (AUC 0.77) or %fPSA (AUC 0.76). We conclude that decreased SEPP concentration in serum might represent an additional valuable marker for prostate cancer diagnostics.

In 2001, the German Federal Ministry of Education and Research (BMBF) initiated the National Genome Research Network (NGFN; www.ngfn.de) as a nation-wide multidisciplinary networking platform aiming at the analysis of common human diseases and aging. Within the NGFN the Human Brain Proteome Project (HBPP; www.smp-proteomics.de) focuses on the analysis of the human brain in health and disease. The concept is based on two consecutive steps: (i) Elaborating and establishing the necessary technology platforms. (ii) Application of the established technologies for research in Alzheimer's disease and Parkinson's disease. In the first funding period, HBPP1, running from 2001 to 2004, necessary technologies were established and optimized. In HBPP2, which started 2004 and will end in May 2008, the developed technologies are used for large-scale experiments, offering new links for disease related research and therapies. The following overview describes structure, aims and outcome of this unique German Brain Proteome Project.

Background & Aims: Malnutrition is frequently observed in chronic and severe diseases and associated with impaired outcome. In Germany general data on prevalence and impact of hospital malnutrition are missing., Methods: Nutritional state was assessed by subjective global assessment (SGA) and by anthropometric measurements in 1,886 consecutively admitted patients in 13 hospitals (n=1,073, university hospitals; n=813, community or teaching hospitals). Risk factors for malnutrition and the impact of nutritional status on length of hospital stay were analyzed., Results: Malnutrition was diagnosed in 27.4% of patients according to SGA. A low arm muscle area and arm fat area were observed in 11.3% and 17.1%, respectively. Forty-three % of patients 70 years old were malnourished compared to only 7.8% of patients <30 years. The highest prevalence of malnutrition was observed in geriatric (56.2%), oncology (37.6%), and gastroenterology (32.6%) departments. Multivariate analysis revealed three independent risk factors: higher age, polypharmacy, and malignant disease (all P<0.01). Malnutrition was associated with an 43% increase of hospital stay (P<0.001)., Conclusions: In German hospitals every fourth patient is malnourished. Malnutrition is associated with increased length of hospital stay. Higher age, malignant disease and major comorbidity were found to be the main contributors to malnutrition. Adequate nutritional support should be initiated in order to optimize the clinical outcome of these patients.

Purpose: Conception, implementation and evaluation of a risk-reducing and health-promoting brief intervention addressed to unemployed., Method: Control-group-study with repeated measurement. 131 unemployed took part in the intervention group and 95 persons were matched according to age and sex and served as a reference group. The intervention group were recruited via flyers, press articles and several institutions, the reference group via the journal of a health insurance company. The reference group received a questionnaire twice assessing the same health-related variables as the intervention group., Intervention: In the intervention group, life style-related variables - eating habits, exercising, smoking, alcohol consumption - were assessed via questionnaire. In a one-hour counselling session based on Motivational Interviewing, participants received an individual feedback on their results of the questionnaire, including a comparison against standards and a review of their personal risks and negative consequences as well as advice and recommendations, while the decision for or against a behaviour change was left to the participant., Results: 85.2 % of the participants of the intervention reported that the counselling met their expectations, and 86.2 % would recommend the intervention to a friend. Statistically significant effects for the intervention group compared to the control group from pre- to post-measurement could be shown for alcohol consumption, eating habits, and exercise (p

Unlabelled: For adult scoliosis patients with chronic pain bracing is indicated before spinal surgery is considered. The treatment with the "sagittal realignment brace" (physio-logic brace) has clearly improved chronic low back pain in a short test period. Thus we started a prospective study to estimate also medium term effects., Material and Methods: 29 Patients (Cobb angle 37 degrees ; age 41 years) have been treated with the physio-logic brace for an average of 7,5 Months (SD 5,6). Before brace prescription the brace action was simulated using the sagittal realignment test. Pain intensity was recorded before brace treatment, within the 1(st) week after brace adjustment and at follow-up using the Roland and Morris VRS. Period of daily wearing time as well as total wearing time / day was left up to the patients., Results: Pain intensity was high (3,38) before treatment (scale 0-5) and low (1,28) in the brace after adjustment. The differences where highly significant in the Wilcoxon test (z=-4,29; p < 0,0001). After follow-up the pain intensity was moderate to severe (2,69; ns). There was a clear reduction of pain severity, however in most of the cases the compliance has been lost during the follow-up period. Only 7 Patients continued to wear the brace for a considerable time (> 4 hrs.)., Conclusions: The brace action of the sagittal realignment brace leads to promising short-term effects. A better compliance might be achieved by prescribing the total wearing time / day and though a better efficiency of pain reduction in the long-term.

Background: Dengue fever is increasingly recognized in travelers returning from endemic areas with acute febrile illness; however, its true burden in nonendemic countries is unknown. Only few studies focus on clinical manifestations and serological findings in primarily nonimmune individuals., Patients and Methods: We analyzed the epidemiology, clinical manifestations and virological results in patients with imported acute dengue infection who presented at our travel clinic in Frankfurt am Main, Germany, between September 1998 and November 2000. An immunochromatographic test and an immunofluorescence assay were used for antibody testing., Results: Dengue fever was confirmed in 13 patients, thus being the second commonest tropical infection after malaria in patients with fever and a travel history to a tropical country (18 cases per 1,000 patient visits per year). Most patients had only spent a short time abroad, either in South Central or South East Asia or in the Caribbean., Conclusion: The clinical features considered typical for dengue were not always present. Antibody assays were typically negative early in the course of disease, with seroconversion occurring only after cessation of clinical symptoms. A high index of suspicion is needed in these patients who often present without typical features of dengue and whose early antibody tests may be negative.

History and Clinical Findings: Three male colleagues aged between 34 and 38 years were admitted at the same time to three different Rhein-Main area Hospitals. They presented with a variety of symptoms, including high fever (39.0 to 40.0 degrees C), chills, headache with meningismus or facial paralysis, mild hepatitis and renal involvement. About 18 days before they had been together on a boat rafting tour when the boat capsized when they had fallen into a river in high flood., Investigations: Laboratory tests showed elevated inflammatory parameters, signs of a mild hepatitis and renal involvement. All patients had leptospirosis antibodies, detected by immunofluorescence test. In two cases there was evidence of antibodies against Leptospira interrogans serovar bataviae in the microscopic agglutination test (MAT)., Treatment and Course: The history and clinical presentation indicated leptospirosis in all patients, in two cases confirmed by laboratory findings. Following therapy with doxycycline or ceftriaxone, symptoms resolved quickly and permanently., Conclusion: Leptospires of serogroup Bataviae is a known pathogen of anicteric non-Weil leptospirosis. The symptoms are non-specific and, moreover, in some cases the laboratory tests are negative, so that clinical diagnosis remains crucial. Typically there is a history of contact with contaminated water or urine. In our cases striking neurotropism was observed, which may be characteristic for this serovar.

Any medical procedure must be legally authorized by the patient, giving informed consent. This prerequisite is based on the right to self determination. Otherwise a medical procedure is considered as physical injury. Thus, the way, how a specific procedure is performed, predominantly depends on the patient's will. The attending physician's duty is to find out this will, which is especially important when old patients and patients incapable of giving valid consent are involved. Before the procedure the physician has to have a confidential talk with the patient. He has to point out the best treatment possible considering the individual circumstances of the patient's life. The physician has to find out, weather the patient is competent to refuse or consent to treatment. Furthermore the consultation is an opportunity to diminish the patient's fear and to increase his confidence. The main problem treating old patients is that they often lack the mental ability for appreciation of the nature of the situation. One has to differentiate between the physiological mental decay and dementia or psychiatric diseases. In these cases a third party consent is necessary.