Evaluation des Therapieeffektes und dessen Nachhaltigkeit bei Patienten mit Anorexia und Bulimia nervosa nach stationärer Therapie in den Heiligenfeld Kliniken

Die vorliegende Studie an 96 essgestörten Patientinnen und Patienten intendierte den Behandlungserfolg der Heiligenfeld Kliniken in Bad Kissingen zu evaluieren. Hierfür wurden Patienten herangezogen, die sich im Zeitraum vom 01.02.2010 - 01.03.2015 stationär in oben genannter Klinik befanden und nach dem dort angewandten multimodalen Therapiekonzept behandelt wurden. Einschlusskriterien für die Aufnahme in unsere Studie war die Diagnosestellung einer Essstörung nach ICD-10 (International Statistical Classification of Diseases, 10. Revision) und die Kodierung des Behandlungspfad „Essstörung“. Von 34 der initial 96 Patientinnen der Erhebungsstichprobe konnten mittels Fragebogen Katamnesedaten erhoben werden. Zum Zeitpunkt der Aufnahme lag der BMI bei 15,9 kg/ m² und konnte innerhalb einer mittleren Verweildauer von 56,4 Tagen auf einen Entlass-BMI von 16,2 kg/ m² angehoben werden. In der durchschnittlichen Katamnesedauer von 2,8 Jahre konnte der BMI weiter stabilisiert werden und betrug bei Follow-up 17,7 kg/ m². Insgesamt ist es damit über 70% der Katamnesestichprobe gelungen seit Aufnahme an Gewicht zuzunehmen. Nach den Kriterien von Morgan & Russel zeigten 21% ein gutes, 53% ein mittleres und 26% ein schlechtes Outcome. Neben den „somatischen Erfolgen“ (signifikante Veränderung der BMI-Werte) konnten auch positive Ergebnisse auf der kognitiven Ebene der Essstörungspathologie erreicht werden. So können wir anhand der signifikant höheren Zufriedenheit mit dem aktuellen Gesundheitszustand unter den Patientinnen mit einem BMI ≥ 17,5 kg/ m² mutmaßen, dass es in der Therapie gelungen war die körperlichen Folgen des Hungerns und deren negativen Auswirkungen herauszuarbeiten und bewusstzumachen. Eine regressive Krankheitssymptomatik ließe sich auch aus der signifikant höheren Unzufriedenheit mit dem Gewicht in der Gruppe „BMI < 17,5“ ableiten. Sieht man die retrospektive Evaluation der Therapie in der Gesamtschau, so kann im Durchschnitt ein positives Fazit gezogen werden. Die deutliche Mehrheit der Patientinnen gab an, zufrieden mit dem Ergebnis ihrer Therapie zu sein und würde die Heiligenfeld Kliniken weiterempfehlen. Insgesamt betrachtet dokumentieren die gezeigten Ergebnisse, dass das Behandlungskonzept der Heiligenfeld Kliniken gute Erfolge in der Essstörungstherapie verzeichnet und in dieser Form weitergeführt werden sollte

Regional differences of physical activity and sedentary behaviour in Swiss children are not explained by socio-demographics or the built environment

Objective We evaluated whether regional differences in physical activity (PA) and sedentary behaviour (SB) existed along language boundaries within Switzerland and whether potential differences would be explained by sociodemographics or environmental characteristics. Methods We combined data of 611 children aged 4 to 7 years from four regional studies. PA and SB were assessed by accelerometers. Information about the socio-demographic background was obtained by questionnaires. Objective neighbourhood attributes could be linked to home addresses. Multivariate regression models were used to test associations between PA and SB and socio-demographic characteristics and neighbourhood attributes. Results Children from the German compared to the French-speaking region were more physically active and less sedentary (by 10–15 %, p\0.01). Although Germanspeaking children lived in a more favourable environment and a higher socioeconomic neighbourhood (differences p\0.001), these characteristics did not explain the differences in PA behaviour between French and German speaking. Conclusions Factors related to the language region, which might be culturally rooted were among the strongest correlates of PA and SB among Swiss children, independent of individual, social and environmental factors

Carcinoma of Unknown Primary and the 8th Edition TNM Classification for Head and Neck Cancer

Objective: In the 8th Edition TNM Classification for Head and Neck Cancer, the classification for carcinoma of unknown primary (CUP) changed in addition to oropharyngeal carcinomas. The current classification considers extranodal extension (ENE), determination of p16 (surrogate marker for human papillomavirus), and detection of Epstein-Barr virus (EBV). The aim of this study was to investigate the influence of the new classification on the prognosis of p16-positive and p16-negative CUP and the impact of EBV proof. Methods: Clinical and pathological data from patients with CUP of the head and neck between 2009 and 2018 were evaluated. The 7th (UICC7) and 8th (UICC8) edition of the Union for International Cancer Control staging system were applied and compared. Results: There were 97 patients treated, 26.8% women and 73.2% men. The average age at initial diagnosis was 64.6 years. Of which, 58.8% had a documented history of smoking, 37.1% were positive for p16, 4.1% were positive for EBV, and 66% had ENE. Most of the patients were at stage III/IVa (78.4% according to UICC7). According to UICC8, p16+ patients were mainly at stage I (86.1%), and p16- at stage IVb (56.1%). P16 status (P = .002), ENE (P = .001), nodal category (TNM7, P < .001), UICC stage (TNM7, P < .001) and UICC stage (TNM8, P < .001) had a significant impact on survival in the univariate analysis. The 8th TNM classification resulted in a downstaging of p16-positive CUP syndromes and an upstaging of p16-negative syndromes. Conclusion: The 8th TNM classification shows the lower UICC stage in p16-positive CUP syndromes. The prognostic significance for survival has improved from the 7th to the 8th TNM classification. LEVEL OF EVIDENCE USING THE 2011 OCEBM: Level 3

Back to WHAT?:The role of research ethics in pandemic times

Abstract The Covid-19 pandemic creates an unprecedented threatening situation worldwide with an urgent need for critical reflection and new knowledge production, but also a need for imminent action despite prevailing knowledge gaps and multilevel uncertainty. With regard to the role of research ethics in these pandemic times some argue in favor of exceptionalism, others, including the authors of this paper, emphasize the urgent need to remain committed to core ethical principles and fundamental human rights obligations all reflected in research regulations and guidelines carefully crafted over time. In this paper we disentangle some of the arguments put forward in the ongoing debate about Covid-19 human challenge studies (CHIs) and the concomitant role of health-related research ethics in pandemic times. We suggest it might be helpful to think through a lens differentiating between risk, strict uncertainty and ignorance. We provide some examples of lessons learned by harm done in the name of research in the past and discuss the relevance of this legacy in the current situation

Incidence and survival of HNSCC patients living with HIV compared with HIV-negative HNSCC patients

Purpose: The aim was to analyze the incidence and survival of patients living with HIV (PLWH) with head and neck squamous cell carcinoma (HNSCC) and to compare with a control group of HIV-negative HNSCC patients. Methods: Clinicopathological data and predictors for overall survival (OS) and disease-free survival (DFS) were investigated (2009-2019). Results: 50 of 5151 HNSCC patients (0.97%) were PLWH, and 76% were smokers. Age <= 60 years, HIV-PCR <= 50 copies, CD4 cells <= 200/mm(3), cART treatment, T and UICC classification, oral cavity and nasal/paranasal sinuses, and therapy were significantly associated with OS in univariate analysis. In the multivariate analysis, only age and HIV-PCR independently predicted OS. The OS of the 50 PLWH was not significantly altered compared with the 5101 HIV-negative controls. However, OS and DFS were significantly inferior in advanced tumor stages of PLWH compared with an age-matched control group of 150 HIV-negative patients. Conclusions: PLWH were diagnosed with HNSCC at a significantly younger age compared to HIV-negative patients. Taking into account patient age at initial diagnosis, both OS and DFS rates in PLWH are significantly worse compared with a matched control group of HIV-negative patients in advanced tumor stages UICC III/IV. The prognosis (OS) is improved when taking cART treatment, the HIV viral load is undetectable and CD4 count is high

The HTA Core Model: A novel method for producing and reporting health technology assessments

Objectives: The aim of this study was to develop and test a generic framework to enable international collaboration for producing and sharing results of health technology assessments (HTAs). Methods: Ten international teams constructed the HTA Core Model, dividing information contained in a comprehensive HTA into standardized pieces, the assessment elements. Each element contains a generic issue that is translated into practical research questions while performing an assessment. Elements were described in detail in element cards. Two pilot assessments, designated as Core HTAs were also produced. The Model and Core HTAs were both validated. Guidance on the use of the HTA Core Model was compiled into a Handbook. Results: The HTA Core Model considers health technologies through nine domains. Two applications of the Model were developed, one for medical and surgical interventions and another for diagnostic technologies. Two Core HTAs were produced in parallel with developing the model, providing the first real-life testing of the Model and input for further development. The results of formal validation and public feedback were primarily positive. Development needs were also identified and considered. An online Handbook is available. Conclusions: The HTA Core Model is a novel approach to HTA. It enables effective international production and sharing of HTA results in a structured format. The face validity of the Model was confirmed during the project, but further testing and refining are needed to ensure optimal usefulness and user-friendliness. Core HTAs are intended to serve as a basis for local HTA reports. Core HTAs do not contain recommendations on technology us

Direct evidence of nuclear Argonaute distribution during transcriptional silencing links the actin cytoskeleton to nuclear RNAi machinery in human cells

Mammalian RNAi machinery facilitating transcriptional gene silencing (TGS) is the RNA-induced transcriptional gene silencing-like (RITS-like) complex, comprising of Argonaute (Ago) and small interfering RNA (siRNA) components. We have previously demonstrated promoter-targeted siRNA induce TGS in human immunodeficiency virus type-1 (HIV-1) and simian immunodeficiency virus (SIV), which profoundly suppresses retrovirus replication via heterochromatin formation and histone methylation. Here, we examine subcellular co-localization of Ago proteins with promoter-targeted siRNAs during TGS of SIV and HIV-1 infection. Analysis of retrovirus-infected cells revealed Ago1 co-localized with siRNA in the nucleus, while Ago2 co-localized with siRNA in the inner nuclear envelope. Mismatched and scrambled siRNAs were observed in the cytoplasm, indicating sequence specificity. This is the first report directly visualizing nuclear compartment distribution of Ago-associated siRNA and further reveals a novel nuclear trafficking mechanism for RITS-like components involving the actin cytoskeleton. These results establish a model for elucidating mammalian TGS and suggest a fundamental mechanism underlying nuclear delivery of RITS-like components

APPL Proteins FRET at the BAR: Direct Observation of APPL1 and APPL2 BAR Domain-Mediated Interactions on Cell Membranes Using FRET Microscopy

Human APPL1 and APPL2 are homologous RAB5 effectors whose binding partners include a diverse set of transmembrane receptors, signaling proteins, and phosphoinositides. APPL proteins associate dynamically with endosomal membranes and are proposed to function in endosome-mediated signaling pathways linking the cell surface to the cell nucleus. APPL proteins contain an N-terminal Bin/Amphiphysin/Rvs (BAR) domain, a central pleckstrin homology (PH) domain, and a C-terminal phosphotyrosine binding (PTB) domain. Previous structural and biochemical studies have shown that the APPL BAR domains mediate homotypic and heterotypic APPL-APPL interactions and that the APPL1 BAR domain forms crescent-shaped dimers. Although previous studies have shown that APPL minimal BAR domains associate with curved cell membranes, direct interaction between APPL BAR domains on cell membranes in vivo has not been reported.Herein, we used a laser-scanning confocal microscope equipped with a spectral detector to carry out fluorescence resonance energy transfer (FRET) experiments with cyan fluorescent protein/yellow fluorescent protein (CFP/YFP) FRET donor/acceptor pairs to examine interactions between APPL minimal BAR domains at the subcellular level. This comprehensive approach enabled us to evaluate FRET levels in a single cell using three methods: sensitized emission, standard acceptor photobleaching, and sequential acceptor photobleaching. We also analyzed emission spectra to address an outstanding controversy regarding the use of CFP donor/YFP acceptor pairs in FRET acceptor photobleaching experiments, based on reports that photobleaching of YFP converts it into a CFP-like species.All three methods consistently showed significant FRET between APPL minimal BAR domain FRET pairs, indicating that they interact directly in a homotypic (i.e., APPL1-APPL1 and APPL2-APPL2) and heterotypic (i.e., APPL1-APPL2) manner on curved cell membranes. Furthermore, the results of our experiments did not show photoconversion of YFP into a CFP-like species following photobleaching, supporting the use of CFP donor/YFP acceptor FRET pairs in acceptor photobleaching studies