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Background The forced vital capacity (FVC) of healthy individuals depends on their age, sex, ethnicity and height. Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is characterised by loss of FVC. We compared FVC values in the subjects with SSc-ILD in the SENSCIS trial of nintedanib versus placebo with values from hypothetical matched healthy references. Methods The SENSCIS trial enrolled subjects with SSc with first non-Raynaud symptom in the prior ≤ 7 years, extent of fibrotic ILD on HRCT ≥ 10%, and FVC ≥ 40% predicted. FVC at baseline and decline in FVC over 52 weeks were compared with FVC values in hypothetical healthy reference subjects matched 1:1 to the subjects in the trial for age, sex, ethnicity and height, determined using equations published by the European Respiratory Society Global Lung Function Initiative. Results At baseline, mean (SD) FVC was 2460 (737) mL in the nintedanib group (n = 287) compared with 3403 (787) mL in the hypothetical matched healthy references. Mean (SD) FVC was 2544 (817) mL in the placebo group (n = 286) compared with 3516 (887) mL in the hypothetical matched healthy references. Mean (SE) changes in FVC at week 52, i.e., age-related loss of lung function, in the hypothetical healthy references matched to the nintedanib and placebo groups, respectively, were − 26.3 (0.5) mL and − 25.8 (0.5) mL. The difference in the change in FVC at week 52 between the nintedanib group and the hypothetical healthy references was 26.6 mL (95% CI: 1.2, 52.0; p = 0.04). The difference in the change in FVC at week 52 between the placebo group and the hypothetical healthy references was 77.5 mL (95% CI: 51.4, 103.7; p Conclusions Subjects with SSc-ILD in the SENSCIS trial had impaired lung function at baseline and experienced further deterioration over 52 weeks. The decline in FVC in the placebo group was four-fold greater than in a hypothetical group of matched healthy references, whereas the decline in FVC in patients who received nintedanib was two-fold greater than in hypothetical healthy references. These data highlight the clinical relevance of the slowing of FVC decline provided by nintedanib. Trial registration Registered 5 November 2015, https://clinicaltrials.gov/ct2/show/NCT02597933.

Additional file 2: Table S1. Baseline FVC (mL) in subjects in the SENSCIS trial versus healthy reference subjects in subgroups by baseline characteristics.

Additional file 1: Supplementary Methods S1. Estimated model coefficients for the joint model of FVC% predicted and time to first hospitalisation or death over 52 weeks. Supplementary Methods S2. Estimated model coefficients for the joint model of FVC% predicted and time to first SSc-related hospitalisation or death over 52 weeks. Supplementary Methods S3. Estimated model coefficients for the joint model of FVC% predicted and time to first ER or hospital admission followed by ICU or death over 52 weeks. Supplementary Methods S4. Estimated model coefficients for the joint model of FVC% predicted and time to first hospitalisation or death over the whole trial. Supplementary Methods S5. Estimated model coefficients for the joint model of FVC% predicted and time to first SSc-related hospitalisation or death over the whole trial. Supplementary Methods S6. Estimated model coefficients for the joint model of FVC% predicted and time to first ER or hospital admission followed by ICU or death over the whole trial. Supplementary Results S7. Summary of SSc-related medical conditions with an incidence of > 5%. Supplementary Results S8. Summary of baseline comorbidities with an incidence of > 5%. Supplementary Results S9. Summary of patient discontinuations during trial period. Supplementary Results S10. Association between current value of FVC% predicted and risk of first hospitalisation endpoints over 52 weeks.

Additional file 1: Appendix S1. Calculation of FVC (mL) in reference subjects.

Background Screening programmes for tuberculosis (TB) among immigrants rarely consider the heterogeneity of risk related to migrants’ country of origin. We assess the performance of a large screening programme in asylum seekers by analysing (i) the difference in yield and numbers needed to screen (NNS) by country and WHO-reported TB burden, (ii) the possible impact of screening thresholds on sensitivity, and (iii) the value of WHO-estimated TB burden to improve the prediction accuracy of screening yield. Methods We combined individual data of 119,037 asylum seekers screened for TB in Germany (2002–2015) with TB estimates of the World Health Organization (WHO) (1990–2014) for their 81 countries of origin. Adjusted rate ratios (aRR) and 95% credible intervals (CrI) of the observed yield of screening were calculated in Bayesian Poisson regression models by categories of WHO-estimated TB incidence. We assessed changes in sensitivity depending on screening thresholds, used WHO TB estimates as prior information to predict TB in asylum seekers, and modelled country-specific probabilities of numbers needed to screen (NNS) conditional on different screening thresholds. Results The overall yield was 82 per 100,000 and the annual yield ranged from 44.1 to 279.7 per 100,000. Country-specific yields ranged from 10 (95%- CrI: 1–47) to 683 (95%-CrI: 306–1336) per 100,000 in Iraqi and Somali asylum seekers, respectively. The observed yield was higher in asylum seekers from countries with a WHO-estimated TB incidence > 50 relative to those from countries ≤50 per 100,000 (aRR: 4.17, 95%-CrI: 2.86–6.59). Introducing a threshold in the range of a WHO-estimated TB incidence of 50 and 100 per 100,000 resulted in the lowest “loss” in sensitivity. WHO’s TB prevalence estimates improved prediction accuracy for eight of the 11 countries, and allowed modelling country-specific probabilities of NNS. Conclusions WHO’s TB data can inform the estimation of screening yield and thus be used to improve screening efficiency in asylum seekers. This may help to develop more targeted screening strategies by reducing uncertainty in estimates of expected country-specific yield, and identify thresholds with lowest loss in sensitivity. Further modelling studies are needed which combine clinical, diagnostic and country-specific parameters. Electronic supplementary material The online version of this article (10.1186/s12879-019-3902-x) contains supplementary material, which is available to authorized users.

Supplementary Files: The Vacuolar H+ ATPase α3 Subunit Negatively Regulates Migration and Invasion of Human Pancreatic Ductal Adenocarcinoma Cells

Additional file 1.

In the original version of this Article the values in the rightmost column of Table 1 were inadvertently shifted relative to the other columns. This has now been corrected in the PDF and HTML versions of the Article.

Yield of screening and number needed to screen. Yield of screening for active TB per 1000 screened individuals and number needed to screen to detect 1 case of TB with 95% credible intervals, stratified by age group, sex, year of screening, and asylum seekersâ country of origin. (PDF 77 kb)

Technical appendix. Technical appendix containing additional details related to methods, data sources, and analysis. (PDF 542 kb)

Period averaged incidence of tuberculosis (per 100,000) and 95% confidence intervals reported by WHO, 1990–2014. Overview of period averaged incidence of tuberculosis (per 100,000) and 95% confidence intervals reported by WHO (1990–2014) based on own calculations for countries used in this study. (PDF 113 kb)

Hintergrund: Geographische Unterschiede wie auch zeitabhängige Veränderungen der Häufigkeit von Infektionskrankheiten spielen eine wesentliche Rolle für die Entwicklung und Bewertung von präventiven Versorgungsleistungen. Internationale Studien zeigen, dass regionale Deprivation[zum vollständigen Text gelangen Sie über die oben angegebene URL], 17. Deutscher Kongress für Versorgungsforschung (DKVF)

Introduction Based on data from the Baden-Wuerttemberg stroke registry, we aimed to explore the diurnal variation of acute ischemic stroke (IS) care delivery. Materials and methods 92,530 IS patients were included, of whom 37,471 (40%) presented within an onset-to-door time ≤4.5 h. Daytime was stratified in 3-h time intervals and working vs. non-working hours. Stroke onset and hospital admission time, rate of door-to-neurological examination time ≤30 min, onset-/door-to-imaging time IV thrombolysis (IVT) rates, and onset-/door-to-needle time were determined. Multivariable regression models were used stratified by stroke onset and hospital admission time to assess the relationship between IVT rates, quality performance parameters, and daytime. The time interval 0:00 h to 3:00 h and working hours, respectively, were taken as reference. Results The IVT rate of the whole study population was strongly associated with the sleep–wake cycle. In patients presenting within the 4.5-h time window and potentially eligible for IVT stratification by hospital admission time identified two time intervals with lower IVT rates. First, between 3:01 h and 6:00 h (IVT rate 18%) and likely attributed to in-hospital delays with the lowest diurnal rate of door-to-neurological examination time ≤30 min and the longest door-to-needle time Second, between 6:01 h and 15:00 h (IVT rate 23–25%) compared to the late afternoon and evening hours (IVT rate 27–29%) due to a longer onset-to-imaging time and door-to-imaging time. No evidence for a compromised stroke service during non-working hours was observed. Conclusion The analysis provides evidence that acute IS care is subject to diurnal variation which may affect stroke outcome. An optimization of IS care aiming at constantly high IVT rates over the course of the day therefore appears desirable.

Hintergrund: Seit Oktober 2002 sind Versicherte der gesetzlichen Krankenkassen ab ihrem 50. bzw. 55. Geburtstag berechtigt, Darmkrebsfrüherkennung bzw. -vorsorge als Kassenleistung in Anspruch zu nehmen. Ab dem Alter von 50 Jahren wird jedem Versicherten der jährliche Test auf Blut im Stuhl[zum vollständigen Text gelangen Sie über die oben angegebene URL], HEC 2016: Health – Exploring Complexity; Joint Conference of GMDS, DGEpi, IEA-EEF, EFMI

Background: Medical imaging is essential for the diagnosis and therapy of patients across a broad spectrum of medical disciplines. Imaging data is required at the patient’s bedside, but is usually accessed at desktop workstations. Advances in mobile technology make real-time, point-of-care medical[for full text, please go to the a.m. URL], 133. Kongress der Deutschen Gesellschaft für Chirurgie

Hintergrund: Multivariable Regressionsmodelle dienen zur Ermittlung des Zusammenhanges zwischen mehreren erklärenden Variablen und einer bestimmten Zielgröße. Im Gegensatz zur parametrischen Modellierung (z. B. einfache lineare Regression) wird bei der nicht-parametrischen Modellierung[zum vollständigen Text gelangen Sie über die oben angegebene URL], 14. Deutscher Kongress für Versorgungsforschung

Background: Current research emphasizes the high prevalence and costs of low back pain (LBP). The STarT Back Tool was designed to support primary care decision making for treatment by helping to determine the treatment prognosis of patients with non-specific low back pain. The German version is the STarT-G. The cross-cultural translation of the tool followed a structured and widely accepted process but to date it was only partially validated with a small sample. The aim of the study was to test the psychometric properties construct validity, discriminative ability, internal consistency and test-retest-reliability of the STarT-G and to compare them with values given for the original English version. Methods: A consecutive cohort study with a two-week retest was conducted among patients with non-specific LBP, aged 18 to 60 years, from primary care practices. Questionnaires were collected before the first consultation, and two weeks later by post, using the following reference standards: the Roland and Morris disability questionnaire, the Tampa Scale of Kinesiophobia, the Pain Catastrophizing Scale and the Hospital Anxiety and Depression Scale. Psychometric properties examined included the tool’s discriminative abilities, whether the psychosocial subscale was one factor, internal consistency, item redundancy, test-retest reliability and floor and ceiling effects. Results: There were 228 patients recruited with a mean age of 42.2 (SD 11.0) years, and 53 % were female. The areas under the curve (AUC) for discriminative ability ranged from 0.70 (STarT-G Subscale - Pain Catastrophizing Scale; CI95 0.63, 0.78) to 0.77 (STarT-G Total - Composite reference standard, CI95 0.60, 0.94). Factor loadings ranged from 0.49 to 0.74. Cronbach’s alpha testing the internal consistency and redundancy for the total/subscale scores were α = 0.52/0.55 respectively. The STarT-G test-retest reliability Kappa values for the total/subscale scores were 0.67/0.68 respectively. No floor or ceiling effects were present. Conclusions: The STarT-G shows acceptable psychometric properties although not in exact agreement with the original English version. The items previously regarded as a psychosocial subscale may be better seen as an index of different individual psychosocial constructs. The relevance of using the tool at the point of consultation should be further examined.

BDSP (Public Health Databank) is a network of institutions initiated 20 years ago by the French ministry of health. Its aim is to collect and provide access to documents on public health topics, with specific attention to grey literature published in French. 40 organizations participate in this open and collaborative network, including the stakeholders of the French health system and from other French-speaking countries. It is managed by a team of 4 members of the EHESP School of Public Health. The network produces a multiservice portal which includes a bibliographic database with more than 470,000 records and 64,000 fulltext documents online. It also offers a multilingual glossary and a thesaurus in public health. The website receives about 3000 visits per day. BDSP is a unique product by its “construction”, its contents and its scope. Its flexible organization has allowed for many adaptations and extensions over the past 20 years, aiming to cover all fields on public health. The bibliographic database offers access to an important number of grey documents published by the main French organizations involved in public health, research units or government agencies, at both a national and regional level. The documents include expert’s reports, summary reports, policies, theses and dissertations. Participation in the BDSP network allows its members to archive their grey publications and data, to increase their visibility, to share current awareness tasks and exchange bibliographic records or documents as well as best practices. Working in a network further helps to deal with obstacles in managing grey literature such as insufficient recognition of the documents compared to journal articles, difficulties to obtain authorizations for the dissemination (in particular for government agencies) and to keep up with the rapid evolution of knowledge. At present the network explores ways to extend its cooperation with other French speaking countries and to share grey literature in French.

Hintergrund: Im Rahmen des Bachelorstudiengangs Interprofessionelle Gesundheitsversorgung (IPG) wurde eine Lehrveranstaltung zum Thema Teamkommunikation entwickelt. Zur Erfassung studentischer Einstellungen wurde der Interprofessionelle Fragebogen der University of the West of England (UWE-IP) herangezogen.[for full text, please go to the a.m. URL], Jahrestagung der Gesellschaft für Medizinische Ausbildung (GMA)

The impact of open archives on the availability and selection of scientific and technical information is growing. Yet, there is little empirical evidence on the deposit and processing of grey literature in digital repositories. The purpose of this communication is to provide a survey on grey literature in French open archives, e.g. institutional and subject-based digital repositories. The survey is based on a selection of 56 representative French digital repositories. The different archives are selected through national and international registries of OAI repositories, following a defined set of criteria. The repositories are shortly described (type of repository, scientific domain, software, size, language, institution). Five aspects are analysed for each digital repository: 1. Typology of grey documents (in particular, theses and dissertations, reports, conference proceedings, working papers, courseware). 2. Part of grey literature in the whole archive (in %). 3. Specific metadata related to grey literature. 4. Quality control and policies (evaluation, validation). 5. Conditions of access to the full text. These information and data are linked to the characteristics of the repositories mentioned above, and specific features of grey literature are discussed. Furthermore, the question if the New York definition of grey literature applies to the content of digital repositories is discussed. The communication provides an overview of the preservation and dissemination of grey literature in French digital repositories, contributes to the discovery of French grey literature and open archives, and moves forward the debate on the future of grey literature in the environment of digital repositories., Issues du mouvement vers l'accès libre à l'information scientifique, les archives ouvertes constituent une formidable ressource documentaire pour la recherche scientifique. Malgré l'impact croissant de ces archives, il n'y a que peu de données sur le dépôt de la littérature grise. L'article présente les résultats d'une étude empirique sur le contenu de 56 archives ouvertes en France en 2008. Parmi les différents aspects abordés : typologie des sites et organismes, domaines scientifiques, nombre des dépôts, types de documents, qualité des contenus, avec une attention particulière pour les contenus non commerciaux (thèses, rapports, conférences...).

We will try to demonstrate that laparoscopic radical nephrectomy could be the new gold standard treatment for renal cell carcinoma with the aid of the current reports exploring the advantages and disadvantages of laparoscopic radical nephrectom overopen surgery.Reported perioperative outcomes like operating time, blood loss, postoperative analgesia requirement, and length of hospital stay and duration of convalescence had been found to be in favor of laparoscopic radical nephrectomy. Some technical issues like approach of laparoscopic technique (Transperitoneal versus retroperitoneal laparoscopic nephrectomy), removal of dissected specimen and need for lymph node dissection had been also discussed in detail in this review. Besides, oncological safety of laparoscopic radical nephrectomy had been explored. The overall five-year disease free survival rates of laparoscopic radical nephrectomy in recent series were found to be over 90%. All of the series including the present one at least confirmed the oncological efficacy of LRN as compared with open surgical approach.The contemporary review of the literature documents clearly demonstrated the perioperative benefits of laparoscopy compared to the open approach. Nevertheless, the development, however, more safe and reliable technique in laparoscopy is necessary for tumor extraction. Recent studies confirmed the long-term similar cancer control results of laparoscopic radical nephrectomy with open surgery. Despite some technical modifications by the different groups, it can be stated that laparoscopic radical nephrectomy is the new gold standard treatment modality for patients with localized renal cell carcinoma.

Their glycolytic metabolism imposes an increased acid load upon tumour cells. The surplus protons are extruded by the Na+/H+ exchanger (NHE) which causes an extracellular acidification. It is not yet known by what mechanism extracellular pH (pHe) and NHE activity affect tumour cell migration and thus metastasis. We studied the impact of pHe and NHE activity on the motility of human melanoma (MV3) cells. Cells were seeded on/in collagen I matrices. Migration was monitored employing time lapse video microscopy and then quantified as the movement of the cell centre. Intracellular pH (pHi) was measured fluorometrically. Cell-matrix interactions were tested in cell adhesion assays and by the displacement of microbeads inside a collagen matrix. Migration depended on the integrin alpha2beta1. Cells reached their maximum motility at pHe approximately 7.0. They hardly migrated at pHe 6.6 or 7.5, when NHE was inhibited, or when NHE activity was stimulated by loading cells with propionic acid. These procedures also caused characteristic changes in cell morphology and pHi. The changes in pHi, however, did not account for the changes in morphology and migratory behaviour. Migration and morphology more likely correlate with the strength of cell-matrix interactions. Adhesion was the strongest at pHe 6.6. It weakened at basic pHe, upon NHE inhibition, or upon blockage of the integrin alpha2beta1. We propose that pHe and NHE activity affect migration of human melanoma cells by modulating cell-matrix interactions. Migration is hindered when the interaction is too strong (acidic pHe) or too weak (alkaline pHe or NHE inhibition).

Background: Neoadjuvant treatment plays a crucial role in the therapy of advanced esophageal cancer. However, response to radiochemotherapy varies widely. Proton pump inhibitors (PPIs) have been demonstrated to impact on chemotherapy in a variety of other cancers. We analyzed the impact of PPI treatment on esophageal cancer cell lines, and investigated mechanisms that mediate the effect of PPI treatment in this tumour. Methods: We investigated the effect of esomeprazole treatment on cancer cell survival, adhesion, migration and chemotherapy in human adeno-(OE19) and squamous-cell-carcinoma (KYSE410) cell lines. Furthermore, we investigated the effect of PPI treatment on intra-/extracellular pH and on expression of resistance-relevant miRNAs. Results: Esomeprazole significantly inhibited tumour cell survival (in a dose-dependent manner), adhesion and migration in both tumour subtypes. Furthermore, esomeprazole augmented the cytotoxic effect of cisplatin and 5-FU in both tumour subtypes. Surprisingly, PPI treatment led to a significant increase of intracellular pH and a decrease of the extracellular pH. Finally, we found esomeprazole affected expression of resistance-relevant miRNAs. Specifically, miR-141 and miR-200b were upregulated, whereas miR-376a was downregulated after PPI treatment in both tumour types. Conclusion: Our study demonstrates for the first time that PPIs impact on tumour cell survival, metastatic potential and sensitivity towards chemotherapy in esophageal cancer cell lines. Furthermore, we observed that in this tumour entity, PPIs do not lead to intracellular acidification, but affect the expression of resistance-relevant miRNAs.

Autopsie nach Ex. der ULB Düsseldorf Vorlageform der Veröffentlichungsangabe: Iaenae, Apvd Ioh. Felicem Bielckium, M DCC XVII Paginierungsfehler: Seitenzählung springt von 546 auf 541 und von 979 auf 990. - Zwischen Seite 636/637 ist die Zählung 639/636 eingefügt. - S. 160 des zweiten Teils fälschlich als Seite 106 paginiert

Autopsie nach Ex. der ULB Düsseldorf Vorlageform der Veröffentlichungsangabe: Ienae, Apvd Ioh. Felicem Bielckivm, M DCC XXX

Solid tumors, including breast carcinomas, are heterogeneous but typically characterized by elevated cellular turnover and metabolism, diffusion limitations based on the complex tumor architecture, and abnormal intra- and extracellular ion compositions particularly as regards acid-base equivalents. Carcinogenesis-related alterations in expression and function of ion channels and transporters, cellular energy levels, and organellar H + sequestration further modify the acid-base composition within tumors and influence cancer cell functions, including cell proliferation, migration, and survival. Cancer cells defend their cytosolic pH and HCO 3 - concentrations better than normal cells when challenged with the marked deviations in extracellular H +, HCO 3 -, and lactate concentrations typical of the tumor microenvironment. Ionic gradients determine the driving forces for ion transporters and channels and influence the membrane potential. Cancer and stromal cells also sense abnormal ion concentrations via intra- and extracellular receptors that modify cancer progression and prognosis. With emphasis on breast cancer, the current review first addresses the altered ion composition and the changes in expression and functional activity of ion channels and transporters in solid cancer tissue. It then discusses how ion channels, transporters, and cellular sensors under influence of the acidic tumor microenvironment shape cancer development and progression and affect the potential of cancer therapies.

Major contributions of the 2nd annual meeting of the International Society of Cancer Metabolism, held in Venice, September 16–19, 2015, are here described and discussed. Among these, the impact of cancer metabolism on local and systemic aggressiveness was analyzed in the context of interactions between cancer and stroma, microenvironmental changes, epigenetic, and stemness modulation.