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Zusammenfassung Hintergrund Die getroffenen Maßnahmen zur Eindämmung der Ausbreitung der Coronavirus-2019-Erkrankung (COVID-19) schränken die sozialen Teilhabemöglichkeiten vieler Menschen ein. Insbesondere Menschen mit chronischen Erkrankungen waren hiervon betroffen. Ziel dieser Beobachtungsstudie war die Untersuchung der sozialen Teilhabe bei Patient:innen mit fortgeschrittenem malignem Melanom mit Immuntherapie unter Pandemiebedingungen. Damit wurde erstmalig soziale Teilhabe als Endpunkt in einer sehr spezifischen Gruppe untersucht. Dies kann als Basis für folgende Studien im wachsenden Kollektiv von Tumorlangzeitüberlebenden in Pandemiezeiten verstanden werden. Methodik Querschnittuntersuchung von Melanompatient:innen mit Erhebung des Index zur Messung von Einschränkungen der Teilhabe (IMET). Ergebnisse werden mit publizierten Normdaten verglichen. Ergebnisse Es wurden 47 Patient:innen mit malignem Melanom in der Auswertung berücksichtigt. Sie waren im Mittel 58,5 Jahre (SD 13,2) alt, 18 Patient:innen befanden sich im Stadium III und erhielten eine adjuvante Immuntherapie; 29 Patient:innen wurden wegen eines metastasierten Melanoms (Stadium IV) behandelt. Die Ergebnisse des IMET ergaben im Gesamtscore keine signifikanten Einschränkungen der sozialen Teilhabe im Vergleich zu den publizierten vorpandemischen Normdaten. Teilnehmerinnen hatten jedoch eine signifikant eingeschränktere Teilhabe. Diskussion Der Endpunkte soziale Teilhabe rückt bei Langzeitüberlebenden mit malignem Melanom in den Vordergrund. Unter Pandemiebedingungen sind insbesondere Patientinnen von Einschränkungen der sozialen Teilhabe gefährdet. Eine Differenzierung zwischen Pandemieeinflüssen und erkrankungsspezifischen Faktoren geht aus unseren Daten nicht hervor. Ausgehend von dieser Studie können und sollten weitere Erhebungen zur sozialen Teilhabe in Zeiten von pandemischen Infektionserkrankungen, insbesondere im wachsenden Kollektiv onkologischer Langzeitüberlebender erfolgen. Graphic abstract

Immunocompromised people are less likely to be vaccinated, despite an increased benefit of many vaccinations in terms of benefit-risk assessment, including the vaccines against SARS CoV-2 (COVID-19). Attitudes, expectations, and experiences with previous vaccinations influence the decision to get vaccinated.To explore the attitudes of immunocompromised people towards vaccinations in general and COVID-19 vaccination in particular and their experiences with COVID-19 vaccinations.As part of the CoCo Immune study, immunocompromised participants were surveyed in the spring and summer of 2021 (1 November 2021-7 September 2021) using questionnaires. Initially, they were asked about their expectations concerning a COVID-19 vaccination and followed up about their experience after COVID-19 vaccination. In addition, sociodemographic data, general attitudes toward vaccinations and experiences with previous vaccinations were collected. Analysis was performed using descriptive and bivariate statistics.The 243 participants mostly approved vaccinations and expected the COVID-19 vaccination to be effective and well-tolerated. Women were more concerned about the safety of vaccinations and were more often worried about side effects. Older persons felt better informed than younger persons. Participants who reported subjective side effects of previous vaccinations were more skeptical about vaccinations as well as the government institutions that recommend vaccinations. They less often agreed with the statement "in retrospect, the COVID-19 vaccination has been harmless for me so far".The participants mostly expressed a positive attitude and anticipation towards COVID-19 vaccinations; however, the age and sex differences found suggest that there are different information needs which should be addressed when educating individuals about vaccinations or designing vaccination campaigns.HINTERGRUND: Immunsupprimierte sind seltener geimpft, gleichzeitig profitieren sie im Hinblick auf die Nutzen-Risiko-Abschätzung deutlich von vielen Impfungen – auch bei den neuen Impfstoffen gegen SARS-CoV-2 (COVID-19). Bei der Entscheidung für eine Impfung sind Einstellungen, Erwartungen und Erfahrungen in Bezug auf bisherige Impfungen maßgeblich.Welche Einstellungen haben immunsupprimierte Menschen gegenüber Impfungen allgemein und einer COVID-19 Impfung im Speziellen? Wie haben sie ihre COVID-19-Impfung erlebt?Im Rahmen der CoCo-Immun-Studie wurden im Frühjahr und Sommer 2021 (11.01.2021–07.11.2021) immunsupprimierte Teilnehmende zu 2 Zeitpunkten zu ihren Erwartungen an eine COVID-19-Impfung und zum Erleben der COVID-19-Impfung mit Fragebögen befragt. Zusätzlich wurden soziodemografische Daten, allgemeine Einstellungen gegenüber Impfungen sowie Erfahrungen mit bisherigen Impfungen erhoben. Die Auswertung erfolgte mittels deskriptiver und bivariater Statistik.Die 243 Befragten standen Impfungen überwiegend positiv und befürwortend gegenüber und erwarteten eine gute Verträglichkeit und Wirksamkeit. Frauen hatten weniger Vertrauen in die Sicherheit von Impfungen und häufiger Sorgen vor Impfreaktionen und -nebenwirkungen. Ältere Personen fühlten sich zum Zeitpunkt der Impfung besser informiert als jüngere. Personen, die über subjektive Nebenwirkungen bzw. Impfreaktionen bei vorangegangenen Impfungen berichteten, standen Impfungen und staatlichen Institutionen, die sie empfehlen, skeptischer gegenüber. Sie stimmten auch der Aussage „Rückblickend war die COVID-19-Impfung bisher harmlos für mich“ seltener zu.Die COVID-19-Impfungen wurden von den befragten Personen überwiegend positiv antizipiert. Die Alters- und Geschlechtsunterschiede in den Zustimmungswerten deuten jedoch darauf hin, dass es unterschiedliche Informationsbedürfnisse gibt, auf die es in Aufklärungsgesprächen und Impfkampagnen einzugehen gilt.

Prostate specific membrane antigen (PSMA) is an emerging diagnostic and therapeutic target in prostate cancer.

Background: Immunogenicity of SARS-CoV-2 vaccines is modestly impaired in cancer patients due to a generally weakened immune system. Immune checkpoint inhibitors (ICI) are expected to enhance immune response. This has already been described to be the case in influenza vaccines, and first data about COVID-19 vaccines show a trend in this direction. Aim: We aimed to investigate the immune response of patients with melanoma under ICI therapy after COVID-19 vaccination. Patients and Methods: In the Skin Cancer Center Hanover (Germany), we recruited 60 patients with advanced melanoma who either received ICI therapy during or before the vaccination period. Serological blood analysis was performed using quantitative ELISA for Anti-SARS-CoV-2 spike protein 1 IgG antibodies. Results: We did not observe an enhanced humoral immune response in patients under active or past ICI therapy after COVID-19 vaccination. Nevertheless, there is a tendency of higher antibody levels when ICI therapy was received within the last 6 months before vaccination. Subgroup analysis revealed that patients in our study population under ongoing targeted therapy during vaccination period had significantly higher median antibody levels than patients without any active antitumor treatment. Conclusion: Melanoma patients under ICI therapy show comparable antibody response after SARS-CoV-2 vaccination to healthy health care professionals. This finding is independent of the timing of ICI therapy.

The prognostic value of Claudin-6 (CLDN6) in non clear cell renal cell carcinoma (RCC) is still unclear.To evaluate the prognostic impact of CLDN6 expression in a large cohort of chromophobe RCC (chRCC).Patients who underwent renal surgery due to chRCC were recruited. Clinical data were retrospectively evaluated. Tumor specimens were analyzed for CLDN6 expression by immunohistochemistry.81 chRCC patients were eligible for analysis, thereof 10 (12.3%) patients were positive for CLDN6. No significant associations were found for CLDN6 expression and clinical attributes in patients with chRCC. Kaplan-Meier analysis revealed no differences in overall survival (OS) for patients with CLDN6⁻ compared to CLDN6⁺ tumors (87.0% versus 62.5%; p=0.174).In chRCC CLDN6 expression is not associated with parameters of aggressiveness or survival. Due to the rare incidence of chRCC further studies with larger cohorts are warranted.

Background: Overexpression of tumor-associated growth arrest-specific protein 6 (Gas6) is found in many tumor entities. The prognostic value of Gas6 in renal cell carcinoma (RCC), especially in non-clear cell RCC, is still unclear. Aim: The aim of the study was to evaluate the prognostic impact of Gas6 expression in a large cohort of patients with chromophobe RCC (chRCC). Material and Methods: Patients who underwent renal surgery due to chRCC were retrospectively evaluated. Tumor specimens were analyzed for Gas6 expression by immunohistochemistry. Results: Eighty-one chRCC patients were eligible for analysis; of these, 24 (29.6%) patients were positive for Gas6. No significant associations were found for Gas6 expression and clinical attributes in patients with chRCC. The Kaplan-Meier analysis revealed no differences in 5-year overall survival for Gas6− compared to Gas6+ (89.6% vs. 100.0%; p = 0.288) tumors. Conclusion: In chRCC, Gas6 expression is not associated with survival and other parameters of aggressiveness. Due to the rare incidence of chRCC, further studies with larger cohorts are warranted.

In this article, we explore to what extent sex and gender differences may be reproduced in the 3D bioprinting of kidneys. Sex and gender differences have been observed in kidney function, anatomy, and physiology, and play arole in kidney donation and transplantation through differences in kidney size (sex aspect) and altruism (gender aspect). As a form of personalized medicine, 3D bioprinting might be expected to eliminate sex and gender bias.On the basis of an analysis of recent literature, we conclude that personalized techniques such as 3D bioprinting of kidneys alone do not mean that sex and gender bias does not happen. Therefore, sex and gender considerations should be included into every step of developing and using 3D-bioprinted kidneys: in the choice of design, cells, biomaterials, and X-chromosome-activated cells.

Claudins are promising biomarkers for diagnosis and prognosis or targets for treatment. They play a major role in signal transduction and are important in nearly all aspects of tumorigenesis. Claudin 6 is a member of the claudin family and is part of the tight junction molecule. It is reactivated in several cancer types and serves as prognostic marker in, for example, gastric, breast or non small cell lung cancer. The prognostic role of Claudin 6 in renal cell carcinoma (RCC), especially in papillary RCC (pRCC), is still unclear.The patients' sample collection was a joint collaboration of the PANZAR consortium. Patients' medical history and tumor specimens were collected from n = 240 and n = 128 patients with type 1 and 2 pRCC, respectively. Expression of Claudin 6 was determined by immunohistochemistry.In total, Claudin 6 staining was positive in 55 of 240 type 1 and 30 of 128 type 2 pRCC cases. Kaplan-Meier analysis disclosed an overall survival of 84% for Claudin 6- compared to 78% for Claudin 6 + in pRCC type 1 tumors (p = 0.449, log-rank) and 68% for Claudin 6- compared to 65.4% for Claudin 6 + in pRCC type 2 tumors (p = 0.364, log-rank).In this study, claudin 6 expression showed no significant association regarding overall survival (OS) and therefore did not qualify as a prognostic marker in pRCC. Future studies will have to determine, whether Claudin 6 plays a prognostic role in other RCC entities. In addition, the function of Claudin 6 as a predictive marker for therapeutic approaches has to be evaluated in future studies.

Background:Restrictions to contain the COVID-19 pandemic affect the social participation of people worldwide. Especially those at high risk for a severe disease tend to abstain from social gatherings. While there are a few questionnaires to measure social participation in elderly or chronic patients, a valid survey instrument that includes pandemic-related social participation is needed.MethodsWe developed a social participation questionnaire that aims to assess pandemic-related restrictions in social participation. Items were developed using a theory and literature-based approach and then compiled in a discursive process involving experts and lay people. This was followed by the validation of the questionnaire through a cross-sectional survey on 431 individuals. Items with low item-total correlations and low factor loadings using exploratory factor analysis [EFA] were excluded. Using EFA on the remaining items, the factor structure was retrieved and tested with a confirmatory factor analysis [CFA]. Internal consistency was assessed with Chronbachs α.ResultsInitially, 27 items were developed which were used for validation. 13 items were excluded due to low item-total correlations and factors loadings. EFA of the remaining 14 items revealed three factors which were identified as domains “active social participation,” “wellbeing,” and “restrictions”. CFA showed an acceptable model fit using the three-dimensional structure. Chronbachs α of 0.81 and McDonalds Ω of 0.87 indicate good internal consistency. Correlation analysis showed an association between the developed questionnaire and previously-established participation and mental health scales.ConclusionThis study suggests that our 14 item questionnaire is of high reliability and validity and can be used to measure social participation during a pandemic.

Background: Patients who are post-COVID-19 will require more treatment soon. Therefore, it is important to understand the root cause of their psychological and somatic conditions. Previous studies showed contradictory results on the influence of pre-existing mental conditions. The present study examines the influence of these pre-existing conditions and their pre-treatment on the severity of post-COVID-19 symptoms. Methods: This analysis employs questionnaire data from a large study sample in Germany. Overall, 801 participants were included. All participants rated their health status on a scale from 0 to 100. Fatigue, depression, and anxiety were measured using the FAS, PHQ-9, and GAD-7 scales. Results: All pre-pandemic values showed no significant differences between the groups. The current health status was rated similarly by the recovered patients (μ = 80.5 ± 17.0) and the control group (μ = 81.2 ± 18.0) but significantly worse by acutely infected (μ = 59.0 ± 21.5) and post-COVID-19 patients (μ = 54.2 ± 21.1). Fatigue, depression, and anxiety were similar for recovered patients and the control group. By contrast, there were significant differences between the control and the post-COVID-19 groups concerning fatigue (45.9% vs. 93.1%), depression (19.3% vs. 53.8%), and anxiety (19.3% vs. 22.3%). Conclusion: Fatigue and psychological conditions of post-COVID-19 patients are not associated with pre-existing conditions.

The increasing digitalization of medicine stressed the importance of teaching digital competencies in undergraduate medical education. However, in many medical curricula in Germany, medical informatics is underrepresented. Due the upcoming reorganization of medical undergraduate education in Germany, topics previously assigned to medical informatics represent curricular challenges for all medical disciplines. Against this background, experiences from the project DigiWissMed show how medical informatics can support the teaching of digital competencies in all disciplines of medical education. Therefore, interdisciplinary teaching teams of medical informatics professionals and physicians were formed. In different academic years, this teaching teams jointly designed and implemented new seminars to convey digital competencies. The seminars covers topics such as technology acceptance, telemedicine and assistive health care related to the medical specialty. So, in the project DigiWissMed, the practicability and usefulness of interdisciplinary teaching teams to convey digital competencies could be demonstrate. In the digitalization process of medicine, medical informatics plays a key role. For future-proof medical education, experts of this field should be involved in teaching digital competencies, too.

The increasing digitalization of medicine stressed the importance of teaching digital competencies in undergraduate medical education. However, in many medical curricula in Germany, medical informatics is underrepresented. Due the upcoming reorganization of medical undergraduate education in Germany, topics previously assigned to medical informatics represent curricular challenges for all medical disciplines. Against this background, experiences from the project DigiWissMed show how medical informatics can support the teaching of digital competencies in all disciplines of medical education. Therefore, interdisciplinary teaching teams of medical informatics professionals and physicians were formed. In different academic years, this teaching teams jointly designed and implemented new seminars to convey digital competencies. The seminars covers topics such as technology acceptance, telemedicine and assistive health care related to the medical specialty. So, in the project DigiWissMed, the practicability and usefulness of interdisciplinary teaching teams to convey digital competencies could be demonstrate. In the digitalization process of medicine, medical informatics plays a key role. For future-proof medical education, experts of this field should be involved in teaching digital competencies, too.

The COVID‐19 pandemic has reinforced Germany's role as global health player, but the education system is lagging behind and does not adequately prepare health professionals for the new challenges. This study aims to strengthen global health in undergraduate medical education in Germany. Major objectives include: to review the current situation, explore changing demand for global health and introduce innovative teaching models and the drivers for change. Mixed methods and an explorative approach were applied, comprising a scoping review, online surveys carried out at Hanover Medical School, March/April 2020. Target groups were undergraduate medical students (n = 384) and additionally lecturers (n = 172), and finally new multiprofessional teaching courses initiated by students and developed collaboratively. The results reveal only slow pace of change on the level of the education system, while demand for global health education has increased markedly in all actor groups, but strongest in the group of students in the preclinical phase. Implementation of global health programmes illustrates how students can become change agents and enhance institutional innovation bottom‐up. However, in order to achieve wider transformative potential, these efforts must be flanked by macro‐level policy changes and integrated in future pandemic preparedness strategies.

Background Data is available on sexual discrimination and subjective perceptions of equal opportunity in medical education for many countries. Surveys focussing on sexual harassment have not yet been conducted at German medical schools. Methods A student initiative surveyed all medical students at the Hannover Medical School (MHH) using an anonymous online questionnaire on equal opportunity and sexual discrimination to identify potential problems in education. Results A total of 343 students (15%) participated in the survey. Over 50% reported having either witnessed sexual harassment or experienced it themselves. Female students indicated having experienced sexual harassment three times more often than their male peers; verbal forms of sexual discrimination predominate. These observations and experiences of sexual harassment demonstrated significant influences on many perceptions regarding equal opportunity and equal treatment in the MHH undergraduate medical education at MHH. Conclusion This blind spot in medical education in the German-speaking countries should be scrutinized more closely. The experience of sexism in the context of undergraduate medical education, which has negative effects on students, should no longer be ignored in empirical education research.

Background: Although there have been discussions about traditional lecturing, lectures are still largely a widespread concept of knowledge transfer. Therefore, it is important to constantly review and evaluate this format. The aims of this study were to analyze which effect a criteria-based written feedback has on the lecture course in geriatrics as an alternative to the conventional student evaluation. Furthermore, we wanted to investigate what kind of impact structured feedback has on lecturers in terms of content, organization and quality. Methods: The study was a prospective longitudinal analysis. The 34 lectures on the subject of geriatrics were analyzed over two cohorts using a standardized evaluation sheet. The assessment was carried out on a 5-point-scale using a 22-item feedback instrument. After the first evaluation, each lecturer received an individual evaluation with strengths and suggestions for improvement. In the second cohort the lecture series was evaluated again, and individual feedback was sent. Results: In six of 22 sub-categories the improvement was significant. The most significant improvement was made in terms of content/structure with an increase from 3.4 to 4.3 points. Conclusion: This study shows that significant improvement in teaching is possible by means of individualized written feedback for the lecturers and that students perceive the resulting improvements positively. Our results suggest that the implementation of these feedback instruments in other modules might improve their teaching as well.

Internationally, scientific and research-related competencies need to be sufficiently targeted as core outcomes in many undergraduate medical curricula. Since 2015, standards have been recommended for Germany in the National Competency-based Learning Objective Catalogue in Medicine (NKLM). The aim of this study is to develop a multi-center mapping approach for curricular benchmarking against national standards and against other medical faculties.A total of 277 faculty members from four German medical faculties have mapped the local curriculum against the scientific and research-related NKLM objectives, using consented procedures, metrics, and tools. The amount of mapping citations of each objective is used as indicator for its weighting in the local curriculum. Achieved competency levels after five-year education are compared.All four programs fulfill the NKLM standards, with each emphasizing different sub-competencies explicitly in writing (Scholar: 17-41% of all courses; Medical Scientific Skills: 14-37% of all courses). Faculties show major or full agreement in objective weighting: Scholar 44%, scientific skills 79%. The given NKLM competency level is met or even outperformed in 78-100% of the courses.The multi-center mapping approach provides an informative dataset allowing curricular diagnosis by external benchmarking and guidance for optimization of local curricula.

// Yvonne Maertens 1 , Verena Humberg 1 , Franziska Erlmeier 2 , Sandra Steffens 1 , Julie Steinestel 1 , Martin Bogemann 1 , Andres Jan Schrader 1 and Christof Bernemann 1 1 Clinic for Urology, University Hospital Muenster, Muenster, Germany 2 Institute for Pathology and Pathological Anatomy, Technical University Munich, Munich, Germany Correspondence to: Christof Bernemann, email: christof.bernemann@ukmuenster.de Keywords: clear cell renal cell carcinoma, circulating tumor cells, biomarker, liquid biopsy, genitourinary cancer Received: June 15, 2017 Accepted: August 25, 2017 Published: September 23, 2017 ABSTRACT Background: Analysis of circulating tumor cells (CTCs) has progressed in several tumor entities. However, little is known about CTCs in clear cell renal cell carcinoma (ccRCC) patients. Aim of our studies was to build a stable in vitro fundament for isolation of CTCs in ccRCC. Methods: We compared the analytical performance of different CTC isolation methods with regard to yield and purity: EpCAM based enrichment, leukocyte depletion and size based enrichment. EpCAM and cytokeratin 8 (KRT8) as biomarker for CTCs expression were evaluated in ccRCC cell lines as well as clinical samples. Results: While the EpCAM based approach failed to successfully isolate tumor cells, CD45 based approaches showed intermediate recovery rates. The cell-size based Parsortix system showed highest recovery rates. EpCAM expression was low or absent in most cell lines as well as in clinical samples, whereas KRT8 was detected as a potential biomarker in ccRCC. Conclusion: EpCAM based approaches might miss a high number of CTCs due to low or absent expression of EpCAM in ccRCC, as shown in cell lines as well as in patient samples. We identified the cell-sized based, label independent Parsortix system to be the most effective recovery system for ccRCC CTCs.

ZusammenfassungImmuntherapeutika, wie beispielsweise die Programmed death 1-(PD-1-)Antikörper Pembrolizumab und Nivolumab, sind bei mehreren Tumorentitäten, wie z. B. dem malignen Melanom, in Europa bereits in der Erstlinientherapie zugelassen. Nach dem durchschlagenden Erfolg dieser Antikörper bei zahlreichen Tumorarten wird nun auch der mögliche Einsatz in der Uroonkologie erforscht. Die Zulassung des PD-1-Antikörpers Nivolumab für die Therapie des metastasierten Nierenzellkarzinoms setzte in der Uroonkologie einen neuen Meilenstein. Im Mai 2016 wurde dieser Erfolg durch die Zulassung des Programmed death ligand 1 (PD-L1)-Antikörpers Atezolizumab beim fortgeschrittenen Urothelkarzinom fortgeführt. Außerdem laufen derzeit zahlreiche klinische Studien mit anderen Checkpoint-Inhibitoren, welche ebenfalls eine vielversprechende Wirksamkeit beim fortgeschrittenen Urothelkarzinom zeigen.Die Grundlage für den Einsatz dieser Immuntherapeutika bildet unter anderem die immunhistochemische Auswertung des Tumors durch den Pathologen. Um eine einheitliche pathologische Bewertung zu erzielen, besteht aktuell jedoch noch ein erheblicher Standardisierungsbedarf. Bis dato werden sowohl unterschiedliche Bewertungssysteme als auch unterschiedliche Detektionssysteme für ein und denselben Antikörper angewandt. Dadurch wird die Vergleichbarkeit der Studien und damit die Beurteilung der Wirksamkeit der jeweiligen Antikörper erschwert.

Background Clostridium difficile infection (CDI) is a relevant healthcare burden worldwide and one of the leading causes for nosocomial diarrhea. Besides mild courses, the development of a severe infection can occur and has a relevant impact on healthcare costs and patient outcome.Methods We conducted a retrospective cohort study over a 4 year-long period to analyze the incidence of CDI and the contributing risk factors for a severe course at a tertiary care clinic. Independent risk factors were determined by a multivariable logistic regression analysis.Results A total of 761 CDI cases were identified in the study period, thereof 612 (80.4%) cases were nosocomially acquired. The mean incidence for a CDI was 0.42 cases per 1000 patient-days. A severe CDI occurred in 131 cases (17.2%). Independent risk factors for a severe course were pulmonary disease, a Charlson comorbidity index >3, and a preceding antibiotic therapy within three months with glycopeptides (vancomycin/teicoplanin) and/or aminoglycosides.Conclusions This study highlights the relevant burden of CDI in hospitals. Moreover, it underscores that specific knowledge of risk factors contributing to severe CDI is crucial to optimize treatment, infection prevention measures and to guide clinical monitoring and therapy strategy.

Background Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) play a decisive role as prognostic markers in clear-cell renal cell carcinoma (RCC). To date, the role of PD-1/PD-L1 as a prognostic marker in papillary RCC (pRCC) remains scarce. Patients and Methods Patients’ sample collection was a joint collaboration of the nationwide PANZAR consortium – a multicenter study. Medical history and tumor specimens were collected from 245 and 129 patients with pRCC types 1 and 2, respectively. Expression of PD-1 and PD-L1 was determined by immunohistochemistry in pRCC and tumor-infiltrating mononuclear cells. Results Of 374 pRCC specimens, 204 type 1 and 97 type 2 were evaluable for PD-1 and PD-L1 expression analysis. In total, PD-1 and PD-L1 expression were found in 8 (4.9%) of 162 and 12 (7.2%) of 166 evaluable pRCC type 1 specimens. Comparably, PD-1 and PD-L1 expression were found in 2 (2.4%) of 83 and 5 (6.2%) of 81 evaluable pRCC type 2 specimens. Hardly any clinically relevant associations between PD-1 and PD-L1 positivity and clinicopathologic or clinical courses were observed, neither in pRCC type 1 nor type 2. Conclusion The analysis of a large pRCC cohort from a multicenter consortium revealed no impact of PD-1/PD-L1 expression on prognosis in patients with pRCC with predominantly limited disease status, neither for type 1 nor type 2. However, the impact of PD-1 and PD-L1 in more advanced pRCC disease needs further elucidation.

Background: Worldwide educational programs face the challenge how to define and integrate digital competencies in medical education. This article describes the implementation of learning outcomes with respect to digital competencies in the compulsory curriculum at Hannover Medical School (MHH). Methods: An interdisciplinary MHH project group was constituted consisting of physicians and experts in medical informatics and in curriculum development. Over the course of 7 work sessions the group compared different international and national frameworks dealing with digital competencies for physicians. By a consensus driven approach the working group drew up a collection of learning outcomes which were regarded relevant to be incorporated in the curriculum at MHH. Results: The analysis of different frameworks indicated that data literacy is a central domain within all viewed preexisting catalogs. During the course of the project group analysis, 57 learning outcomes with respect to digital competencies were identified as necessary to be integrated in the compulsory curriculum. They were divided in 5 main categories: “handling of medical data,” “the digital infrastructure of the health system,” “scope of application: usage in patient care and in the field of preventive medicine,” “medico-legal and ethical basics,” and “transformation processes in medicine due to digitalization.” Conclusions: The MHH project group concluded that medical students should be taught digital competencies that enable an understanding of underlying functional principles of digital systems rather than their correct utilization. The presented project indicates that a close interdisciplinary collaboration of physicians and medical informaticians can be a promising approach to incorporate digital competencies in the undergraduate medical curriculum.

The National Competence Based Catalogue of Learning Objectives for Undergraduate Medical Education (NKLM) describes medical skills and attitudes without being ordered by subjects or organs. Thus, the NKLM enables systematic curriculum mapping and supports curricular transparency. In this paper we describe where learning objectives related to Medical Informatics (MI) in Hannover coincide with other subjects and where they are taught exclusively in MI.An instance of the web-based MERLIN-database was used for the mapping process.In total 52 learning objectives overlapping with 38 other subjects could be allocated to MI. No overlap exists for six learning objectives describing explicitly topics of information technology or data management for scientific research. Most of the overlap was found for learning objectives relating to documentation and aspects of data privacy.The identification of numerous shared learning objectives with other subjects does not mean that other subjects teach the same content as MI. Identifying common learning objectives rather opens up the possibility for teaching cooperations which could lead to an important exchange and hopefully an improvement in medical education.Mapping of a whole medical curriculum offers the opportunity to identify common ground between MI and other medical subjects. Furthermore, in regard to MI, the interaction with other medical subjects can strengthen its role in medical education.

Immunotherapy with programmed cell death protein-1 (PD-1) antibodies (pembrolizumab and nivolumab) has been approved in Europe for the first-line treatment of several tumour entities, e. g. malignant melanoma. Following the resounding therapeutic success of these antibodies in different types of tumours, their potential in urological tumours has been investigated in several studies. The approval of the PD-1 antibody nivolumab for the treatment of metastasised renal cell carcinoma has set a new milestone in urooncology. This success continued with the approval of the programmed cell death ligand 1 (PD-L1) atezolizumab for advanced urothelial carcinoma in 2016. In addition, several ongoing clinical trials of other checkpoint inhibitors have also shown promising efficacy in advanced urothelial carcinoma. The decision to treat a patient with immunotherapy is based, among other things, on the immunohistochemical staining and evaluation by a pathologist. However, due to the lack of standardised evaluation protocols and detection systems, it is difficult to compare different studies and evaluate the efficacy of the respective antibodies.Immuntherapeutika, wie beispielsweise die Programmed death 1-(PD-1-)Antikörper Pembrolizumab und Nivolumab, sind bei mehreren Tumorentitäten, wie z. B. dem malignen Melanom, in Europa bereits in der Erstlinientherapie zugelassen. Nach dem durchschlagenden Erfolg dieser Antikörper bei zahlreichen Tumorarten wird nun auch der mögliche Einsatz in der Uroonkologie erforscht. Die Zulassung des PD-1-Antikörpers Nivolumab für die Therapie des metastasierten Nierenzellkarzinoms setzte in der Uroonkologie einen neuen Meilenstein. Im Mai 2016 wurde dieser Erfolg durch die Zulassung des Programmed death ligand 1 (PD-L1)-Antikörpers Atezolizumab beim fortgeschrittenen Urothelkarzinom fortgeführt. Außerdem laufen derzeit zahlreiche klinische Studien mit anderen Checkpoint-Inhibitoren, welche ebenfalls eine vielversprechende Wirksamkeit beim fortgeschrittenen Urothelkarzinom zeigen.Die Grundlage für den Einsatz dieser Immuntherapeutika bildet unter anderem die immunhistochemische Auswertung des Tumors durch den Pathologen. Um eine einheitliche pathologische Bewertung zu erzielen, besteht aktuell jedoch noch ein erheblicher Standardisierungsbedarf. Bis dato werden sowohl unterschiedliche Bewertungssysteme als auch unterschiedliche Detektionssysteme für ein und denselben Antikörper angewandt. Dadurch wird die Vergleichbarkeit der Studien und damit die Beurteilung der Wirksamkeit der jeweiligen Antikörper erschwert.

Programmed death-1 receptor (PD-1) and programmed death-1 receptor-ligand (PD-L1) have been suggested to play a role as prognostic markers in clear cell renal cell carcinoma (ccRCC). The association between PD-L1 and prognosis seems to be more robust than for PD-1. Further, preliminary analyses suggest that neither PD-1 nor its ligands play a role as prognostic markers in non-clear cell RCC, while the prognostic role of PD-L2 in ccRCC as well as in non-clear cell RCC remains unclear.

In the context of cancer immunotherapy, PD-1 as well as PD-L1 has been widely studied in renal cell carcinoma (RCC). PD-1 and PD-L1 play a significant role as prognostic markers in clear cell renal cell carcinoma. In contrast, little is known about PD-L2 expression patterns in RCC, especially in rarer subtypes. The aim of this study was to evaluate the prevalence, distribution and prognostic impact of PD-L2 expression in chromophobe (ch)RCC. Eighty-one patients who underwent renal surgery due to chRCC were retrospectively evaluated. Tumor specimens were analyzed for PD-L2 expression by immunohistochemistry. Expression data were associated with clinicopathological parameters and overall survival (OS). Twenty-three (28.4%) patients showed a PD-L2 > median (PD-L2 high) staining intensity. No significant association between clinicopathological parameters and PD-L2 expression was identified. A significant difference between 5- and 10-year OS in dependence of PD-L2 expression was found (PD-L2 low 96.4 and 87.7% vs. PD-L2 high 87.1 and 56%; log rank, p = 0.029). However, in multivariate analysis PD-L2 expression failed to be proofed as an independent prognostic factor. In conclusion, to our knowledge this is the first study evaluating the prognostic impact of PD-L2 in a considerably large cohort of chRCC. Our results showed a significant diminished OS in dependence of PD-L2 expression. This implicates that PD-L2 might play a role as prognostic marker in chRCC demanding further evaluation.

Chromophobe renal cell carcinoma (chRCC) is the third most common subtype of RCC, after clear cell (ccRCC) and papillary RCC. Its lower incidence and frequent exclusion from clinical trials might be why chRCC characteristics have not been extensively studied. The aim of our study was to examine tumor characteristics and long-term prognosis of chRCC compared to ccRCC. We collected 4,210 evaluable patients subjected to surgery for chRCC (n = 176) or ccRCC (n = 4,034) at five centers in Germany (University Hospitals of Hannover, Homburg/Saar, Mainz, Ulm, and Marburg) between 1990 and 2010. Patients with chRCC were significantly younger (mean, 60.1 vs. 62.1 years) and tended to be more frequently female (43.8 vs. 36.5 %). Although Fuhrman grade and median tumor diameter were not significantly different, significantly fewer patients with chRCC than with ccRCC presented with high tumor stage or metastasis at diagnosis (18.5 vs. 43.8 %). Moreover, significantly more chRCC patients were treated with partial nephrectomy (41.5 vs. 26.2 %). Accordingly, 5-year cancer-specific survival (CSS) rates were 83.2 % for chRCC against 75.8 % for ccRCC patients (p = 0.014, log rank). However, in multivariate analysis, chromophobe subtype was not confirmed as a significant positive prognostic factor for RCC (HR 0.88, 95 % CI 0.63-1.24; p = 0.48 Cox regression). This is one of the largest studies to date showing that chRCC is associated with a significantly lower risk of locally invasive tumor growth and metastatic disease than ccRCC. We conclude that the clinical behavior of chRCC is less aggressive than that of ccRCC, independent of Fuhrman grade or tumor size.

Objectives To evaluate whether low testosterone levels or obesity, or both, are directly associated with tumor stage/grade in patients with clinically localized prostate cancer. Methods Preoperative androgen serum levels (total and free testosterone), sex hormone-binding globulin, body mass index and waist circumference were assessed in 510 consecutive European Caucasian men treated with radical prostatectomy. Hormone levels and body mass index/waist circumference were correlated with patient- and tumor-specific characteristics using multivariable logistic regression analysis. Results Even though we confirmed an inverse correlation between bodyweight and testosterone levels, only overweight – but not low testosterone – was associated with advanced disease and poor differentiation of prostate cancer. Using multivariate analyses, both body mass index ≥30 kg/m2 and waist circumference >110 cm were associated with high-grade disease (Gleason score ≥8). A waist circumference >110 cm also correlated significantly with lymph node metastasis. Conclusions This is the first study showing that obesity, but not low serum testosterone levels, is significantly associated with high grade and metastatic disease in men diagnosed with clinically localized prostate cancer. The present findings suggest that low androgen levels at diagnosis, which used to be held responsible for the development of aggressive prostate cancer, is only an epiphenomenon of obesity rather than the cause of prostate cancer development and/or progression.