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Background: Second victim phenomena (SVP) are critical to workplace and patient safety, and epidemiological data are limited to investigate the causes and impact on German health care. We investigated SVP in German nurses regarding prevalence, causes, and predisposition compared to a preceding study on German physicians (Second Victims in Deutschland/SeViD-I)., Methods: We conducted a nationwide anonymous cross-sectional online study in 2020 using a modified SeViD questionnaire including the BFI-10 (personality traits). Statistical analysis was conducted using chi² tests and binary logistic regression models., Results: Of 332 nurses, 60% reported to experience SVP at least once a working lifetime, with a 12-month prevalence among SVP of 49%. Of the nurses, 24% reported recovery times of more than 1 year. In contrast to physicians from SeViD-I, a main cause for becoming a second victim was aggressive behavior by patients. High neuroticism values, higher age, and medium work life experience, but neither gender nor workplace position, were predisposing for SVP. Like SeViD-I, nurses reported demand for an institutional response in cases of SVP., Conclusions: SVP is common among German nurses and comprises other causes and a different course than in physicians. Further research should concentrate on specific prevention strategies, e.g., profession- and workplace-based educational programs.

Background:  Demographic changes in the society and among doctors, as well as changing attitudes towards and norms of how living should be structured are creating challenges regarding the organization of work environment in the hospital. In addition, organization of medical training is increasingly being influenced by economic considerations as well as a high level of medical specialization. We asked young respiratory physicians how they assessed their current situation with respect to quality of medical training and organization of their work environment., Methods:  From September to November 2019, we performed an online survey adressing young respiratory physicians in Germany. Participants were recruited via three emails (baseline and reminders after 2 and 6 weeks) sent by the German Respiratory Society (DGP) and the German Union of Pulmonologists (BdP). The questionnaire consisted of a maximum of 62 questions. Apart from own questions that had been aligned with other questionnaires from similar surveys in other medical specialties, we also assessed the effort-reward ratio (ER ratio) based on the short version of the effort-reward imbalance questionnaire (16 questions)., Results:  We recuited n = 224 participants (33.8 ± 4.5 years, 5.4 ± 2.9 years of medical training, 54.4 % female , 86.8 % with German nationality). A little under half of the interviewees (n = 103, 46 %) reported to be very or generally satisfied with their working conditions, while n = 60 (27 %) were unsure. The main reasons for not being satisfied were long working hours and high work-load, as well as a lack of streamlining the work environment in the hospital to the specific needs of doctors. Despite the fact that many participants were satisfied, a large majority (n = 166, 88.2 %) depicted an unfavorable effort-reward ratio imbalance (adjusted mean 1.89 ± 2.18)., Conclusion:  Compared to many other European countries and internationally, the German healthcare system offers high-quality patient care and a well-equipped work environment. Increasing demands in the health care sector, however, are leading to a gratification crisis that not only harms the health and work performance of doctors but is also leading to reduced attractiveness of the job that might possibly lead to the search for new fields of activity or migration. Respiratory medicine is a discipline of growing interest and motivating young doctors to secure the promotion of this discipline is increasingly important. Factors harming the growth of this discipline should be immediately addressed. The results of this survey might help leaders in the field to restructure the work environment and medical education according to the actual needs., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

The coronavirus disease 2019 (COVID-19) pandemic has caused and is still causing tremendous morbidity, mortality, and damage to our societies. The disease course of COVID-19 can be unpredictable ranging from asymptomatic infections to multi-organ failure and death. Transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from an asymptomatic infected individual to others has been observed early in the pandemic. Asymptomatic individuals have been shown to have quantitative SARS-CoV-2 viral loads, there may or may not be radiological and/or laboratory abnormalities. No antiviral therapy has been approved for the treatment of asymptomatic SARS-CoV2- infection. The management of asymptomatic individuals at home requires that the person can be monitored for any signs and symptoms of deterioration and that the requirements for infection prevention and control measures can be fulfilled. It is crucial to properly diagnose and manage asymptomatic COVID-19 cases with effective testing, contact tracing, quarantine, and isolation strategies. Preventing asymptomatic SARS-CoV-2 infections that have a major role in the unhindered transmission of the virus is a milestone to take control of the pandemic. Vaccination has been proven to be the crucial pillar for preventing asymptomatic infections and real-life data will continue to exhibit the effects of community vaccination in breaking the transmission chain of SARS-CoV-2 infections., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Introduction: Pembrolizumab is a highly effective standard of care in PD-L1 overexpressing (≥ 50%) non-small-cell lung cancer. However, a substantial share of patients from everyday clinical practice is treated without clear evidence from clinical trials., Patients and Methods: We performed a retrospective multicentric study including all consecutive patients from 6 certified lung cancer centers in Berlin, Germany, having received pembrolizumab as first-line palliative therapy from January 1 until December 31, 2017. Aims were to validate published clinical trials with a special focus on efficacy and outcome in patients with reduced performance status (PS), brain metastases, and steroids., Results: A total of 153 patients were included (median age 69 years, 58% men, 69% adenocarcinoma). Rates for PS ≥ 2, brain metastases, and steroids were 24.8%, 20.9%, and 24.2%, respectively. Median objective response rate, progression-free and overall survival were 48.5%, 8.2 and 22.0 months for all patients and 52.4%, 8.8 and 29.2 months in patients fulfilling the inclusion criteria for the KEYNOTE-024 trial. Patients with a comorbidity-defined PS ≥ 2, symptomatic brain metastases requiring upfront radiotherapy, or baseline steroids had significantly reduced survival. In contrast, durable responses occurred with a tumor-related PS ≥ 2 or asymptomatic brain metastases. Grade 3/4 and 5 immune-related adverse events affected 13.7% and 2.0% of patients., Conclusion: Real-world and clinical trial efficacy with upfront pembrolizumab correspond well. Pembrolizumab may sufficiently control asymptomatic brain metastases and may improve a cancer-related reduced PS. However, the frail share of patients with a comorbidity-defined PS ≥ 2, symptomatic brain metastases, or baseline steroids derives no relevant benefit., (Copyright © 2021. Published by Elsevier Inc.)

Background: Second victims, defined as healthcare team members being traumatised by an unanticipated clinical event or outcome, are frequent in healthcare. Evidence of this phenomenon in Germany, however, is sparse. Recently, we reported the first construction and validation of a German questionnaire. This study aimed to understand this phenomenon better in a sample of young (<= 35 years) German physicians., Methods: The electronic questionnaire (SeViD-I survey) was administered for 6 weeks to a sample of young physicians in training for internal medicine or a subspecialty. All physicians were members of the German Society of Internal Medicine. The questionnaire had three domains - general experience, symptoms, and support strategies - comprising 46 items. Binary logistic regression models were applied to study the influence of various independent factors on the risk of becoming a second victim, the magnitude of symptoms and the time to self-perceived recovery., Results: The response rate was 18% (555/3047). 65% of the participants were female, the mean age was 32 years. 59% experienced second victim incidents in their career so far and 35% during the past 12 months. Events with patient harm and unexpected patient deaths or suicides were the most frequent key incidents. 12% of the participants reported that their self-perceived time to full recovery was more than 1 year or have never recovered. Being female was a risk factor for being a second victim (odds ratio (OR) 2.5) and experiencing a high symptom load (OR 2). Working in acute care was promoting a shorter duration to self-perceived recovery (OR 0.5). Support measures with an exceptionally high approval among second victims were the possibility to discuss emotional and ethical issues, prompt debriefing/crisis intervention after the incident and a safe opportunity to contribute insights to prevent similar events in the future., Conclusion: The second victim phenomenon is frequent among young German physicians in internal medicine. In general, these traumatic events have a potentially high impact on physician health and the care they deliver. A better understanding of second victim traumatisations in Germany and broad implementation of effective support programs are warranted.

Background: Pembrolizumab is a standard of care as first line palliative therapy in PD-L1 overexpressing (≥50%) non-small cell lung cancer (NSCLC). This study aimed at the identification of KRAS and TP53-defined mutational subgroups in the PD-L1 high population to distinguish long-term responders from those with limited benefit., Methods: In this retrospective, observational study, patients from 4 certified lung cancer centers in Berlin, Germany, having received pembrolizumab monotherapy as first line palliative treatment for lung adenocarcinoma (LuAD) from 2017 to 2018, with PD-L1 expression status and targeted NGS data available, were evaluated., Results: A total of 119 patients were included. Rates for KRAS, TP53 and combined mutations were 52.1%, 47.1% and 21.9%, respectively, with no association given between KRAS and TP53 mutations (P=0.24). By trend, PD-L1 expression was higher in KRAS-positive patients (75% vs. 65%, P=0.13). Objective response rate (ORR), median progression-free survival (PFS) and overall survival (OS) in the KRAS G12C group (n=32, 51.6%) were 63.3%, 19.8 months (mo.) and not estimable (NE), respectively. Results in KRAS other and wild type patients were similar and by far lower (42.7%, P=0.06; 6.2 mo., P<0.001; 23.4 mo., P=0.08). TP53 mutations alone had no impact on response and survival. However, KRAS G12C /TP53 co-mutations (n=12) defined a subset of long-term responders (ORR 100.0%, PFS 33.3 mo., OS NE). In contrast, patients with KRAS other /TP53 mutations showed a dismal prognosis (ORR 27.3%, P=0.002; PFS 3.9 mo., P=0.001, OS 9.7 mo., P=0.02)., Conclusions: A comprehensive assessment of KRAS subtypes and TP53 mutations allows a highly relevant prognostic differentiation of patients with metastatic, PD-L1 high LuAD treated upfront with pembrolizumab., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-958). NF reports personal fees and other from AstraZeneca, personal fees and other from Bristol Myers Squibb, personal fees and other from AbbVie, personal fees and other from Boehringer Ingelheim, personal fees from Pfizer, personal fees from Roche Pharma, personal fees from Merck Sharp & Dohme, personal fees from Takeda, all outside the submitted work. JK reports being an advisory Board member without receiving any personal fees for: Roche Pharma, Boehringer Ingelheim, Bristol Myers Squibb, Merck Sharp & Dohme, Takeda and Lilly Oncology, all outside the submitted work. The other authors have no conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

Introduction: Thyroid transcription factor 1 (TTF-1) is a prognostic biomarker in lung adenocarcinoma; however, TTF-1-positive patients also display more favorable factors like actionable target mutations. In contrast, TTF-1-negative cancer is a poorly described entity. We performed a retrospective study to characterize a TTF-1-negative phenotype and to evaluate outcome depending on the chemotherapy regimen applied in the EGFR/ALK-negative population., Patients and Methods: Phenotypic traits were analyzed in 741 patients with evaluable TTF-1 expression status, among them 529 patients with platinum-based first-line chemotherapy, with disease diagnosed between 2009 and 2016 at a tertiary referral university hospital. The influence of TTF-1 and several cofactors on progression-free survival and overall survival (OS) were analyzed using a 1:1 propensity score matching model, depending on the platinum doublet chemotherapy's incorporating pemetrexed or not, with subsequent Cox regression., Results: TTF-1 negativity implied a distinct cancer phenotype with the predominance of male sex, worse Eastern Cooperative Oncology Group performance status, greater metastatic burden at primary diagnosis, and more adrenal gland metastases. These patients had improved progression-free survival (hazard ratio, 0.42; P = .001) and OS (hazard ratio, 0.40; P < .001) when gemcitabine-, taxane-, or vinorelbine-based regimens were provided instead of pemetrexed. None of the regimens was superior in TTF-1-positive patients with regard to OS. Overall, TTF-1 expression was strongly prognostic with a substantial increase in progression-free survival (hazard ratio, 0.54; P < .001) and OS (hazard ratio, 0.53; P < .001)., Conclusion: TTF-1 negativity is associated with a distinct cancer phenotype. Incorporation of this biomarker may be helpful when choosing an appropriate therapy regimen., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: General conditions in the health-care system in Germany have changed dramatically in recent years. Factors affecting this include above all demographic change, rapid developments in diagnostic and therapeutic options, and the application of economic criteria to the health-care sector. This study aimed to establish the current status quo regarding conditions of work and training for young doctors in gynecology and obstetrics, analyze stress factors, and suggest potential improvements., Methods: Between October 2015 and March 2016, a web-based survey was carried out among residents and members of the German Society for Gynecology and Obstetrics. The electronic questionnaire comprised 65 items on seven topics. Part of the survey included the short version of a validated model of professional gratification crises for analyzing psychosocial work-related stress., Results: The analysis included a total of 391 complete datasets. Considerable negative findings in relation to psychosocial work pressure, time and organizational factors, quality of specialty training, and compatibility between work and family life and work and academic tasks were detected. A high level of psychosocial work pressure is associated with more frequent job changes, reduced working hours, poorer health among physicians, and a lower subjectively assessed quality of care., Conclusions: Greater efforts are needed from all the participants involved in patient care to achieve high-quality training and working conditions that allow physicians to work in a healthy and effective way. These aspects are all prerequisites for sustainably maximizing the resource "physician" and for ensuring high-quality patient care.

Introduction: An increased psychosocial workload can have an negative impact on health. An effective way to record this is the effort reward imbalance model postulated by Siegrist. Values on this topic from ENT residents are missing, which is why the concept and corresponding questions were included in the survey on the current situation in further education., Material and Methods: An online survey on the current situation of the ENT residency including the recording of psychosocial workload was developed by ENT physicians on the basis of a well-known questionnaire of colleagues of the Alliance of Young Physicians. The short version of the validated questionnaire on the effort reward imbalance model according to Siegrist with 16 items was used. An online survey was carried out addressing all ENT residents in Germany known to the German society of Oto-Rhino-Laryngology, Head and Neck surgery. The survey was sent by e-mail and was available from April 1 st to July 31 st in 2019., Results: 92,3 % of the participants had an effort-reward imbalance. The mean value of effort reward imbalance was 1.57 ± 0.43, adjusted 2.16 ± 1.36. The effort scale was 10.71 ± 1.40 (3-12), adjusted 85.72 ± 15.52, reward scale 16.58 ± 2.86 (7-28), adjusted 45.61 ± 13.63, over commitment 17 ± 3.37, adjusted 61.14 ± 18.73. A high effort reward imbalance had positive significant correlations with regard to the duration of residency, the number of working hours per week and the number of duty hours per month., Conclusion: The effort and reward imbalance is comparable to other specialty physicians in residency. It is related to working hours, services and the progress of training. It can be improved through personal initiative and could be supplemented with the support of the hospital's internal stakeholders., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose:  Good training is the basis for high job satisfaction and high-quality patient care in radiology. The aim of this survey was to record the current state of working conditions for residents in radiology training in Germany and to focus on the aspects of training and psychosocial workload. The description of the actual state should help to identify possible problem areas and to develop improvement approaches., Materials and Methods:  At the beginning of 2018, we sent an electronic questionnaire to the German Roentgen Society (DRG), the German Association of Chairmen in Academic Radiology (KLR), the Chief Physician Forum of the DRG (CAFRAD) and the Forum of Registered Radiologists (FUNRAD) with the request to forward it to radiology residents. With 63 questions, the questionnaire covered seven essential areas of medical working and training conditions. In order to ensure interdisciplinary comparability, most questions were identical to previous surveys among residents of other disciplines., Results:  643 residents started the survey. 501 (78 %) questionnaires were fully processed and included in the final analysis. 65 % of respondents were satisfied with their current job situation. At the same time, shortcomings, especially with regard to the reconciliation of family and work as well as scientific and clinical work, became clear. Only 36 % of participants with children were satisfied with the compatibility of family and work at their workplace. Only 31 % of the researchers were satisfied with their research conditions. In addition, residents experienced a high psychosocial workload., Conclusion:  Job satisfaction is high among radiology residents in direct comparison to other disciplines. However, based on this survey, adjustments to working conditions and training in radiology seem necessary to maintain the health of the physicians concerned, to encourage motivation for scientific work and to enhance development opportunities, especially for women, through a better compatibility of work and family life. The present survey identifies strategies and leadership tools that can help to achieve this., Key Points:  Residents in radiology training ... · have a relatively high job satisfaction.. · experience a high psychosocial workload.. · evaluate the compatibility of family and work as in need of improvement.. · are interested in research, but evaluate research conditions as insufficient., Citation Format: · Oechtering TH, Panagiotopoulos N, Völker M et al. Work and Training Conditions of German Residents in Radiology - Results from a Nationwide Survey Conducted by the Young Radiology Forum in the German Roentgen Society. Fortschr Röntgenstr 2020; 192: 458 - 469., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

German hospitals are now confronted with major challenges from both shortages and fluctuations in the numbers of physicians and nurses. This makes it even more important that physicians and nurses do not prematurely leave patient care. The objective of the present study was to improve our understanding of the factors that trigger intentions to leave the profession. For this purpose, data from 1060 young physicians and nurses in hospital care were analysed. Intentions to leave the profession was assessed with the Copenhagen Psychosocial Questionnaire (COPSOQ). In the first step, the association was determined between intention to leave the profession and the factors of perceived quality of care and job satisfaction. In a second step, a mediation analysis was performed to determine the effect of perceived quality of care after correction for the possible mediator of job satisfaction. There were statistically significant negative associations between perceived quality of care and intention to leave the profession (beta: -2.9, 95% CI: -4.48--1.39) and job satisfaction and intention to leave the profession (beta: -0.5, 95% CI: -0.64--0.44). The effect of perceived quality of care on intention to leave the profession was partially mediated by job satisfaction. Thus, high perceived quality of care and high job satisfaction are both important factors that tend to prevent young physicians and nurses from leaving their professions.

Objective: The working and training conditions of young physicians in Germany have changed over the last few years, as a result of far-reaching changes in the healthcare system. Therefore, Germany-wide surveys among young physicians of several disciplines were evaluated in a pooled analysis, in order to obtain a current interdisciplinary impression of conflicts in their daily work., Material and Methods: Data from web-based surveys from residents training in six disciplines were analyzed together retrospectively. One focus was a gratification crises model for the assessment of psychosocial workload., Results: Data on 4041 participants were evaluated. In day-to-day work, young physicians were burdened with a high proportion of tasks that were not directly medical. Instruments of good subspecialty training, such as training contracts, curricula and regular feedback were associated with a lower psychosocial workload, which was generally significant among the participants. An economic influence on medical-professional decisions was subjectively clearly present among the participants., Conclusion: Many young doctors find the current work and training conditions in the medical work environment unsatisfactory. This might have consequences not only for the doctors themselves, but also for the patients they care for. A healthy work environment with health professionals in good health is therefore crucial and should be in everyone's interest., Competing Interests: S. C. Joachim, D. Bitzinger, H. Arnold, J. Lermann, T. H. Oechtering, S. Schott, K. Schulte und M. Raspe geben an, dass kein Interessenskonflikt besteht. Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Recurrent pleural effusion is a common cause of dyspnoea, cough and chest pain during the course of infectious pleurisy and non-malignant diseases like congestive heart failure (CHF) or liver cirrhosis with hepatic hydrothorax (HH). With regard to the chronic character of the underlying diseases, indwelling pleural catheters (IPC) are increasingly used, not only assuring immediate symptom relief but also potentially leading to pleurodesis without sclerosing agents., Patients and Methods: In this single-centre retrospective observational study, patient characteristics, procedural variables and outcome in patients with IPC in non-malignant pleural effusion (NMPE) were evaluated and prognostic factors for pleurodesis were identified., Results: From 2006 to 2017, 54 patients received 62 IPC, of whom 48.4% with CHF and 43.5% with HH. The median length of insertion was 1.5 months (IQR 0.6-2.9 months), the median survival time after insertion 3.2 months (IQR 1.1-16.0). An adequate symptom relief was achieved in 93.2% with no need for subsequent interventions. In patients surviving ≥30 days after IPC insertion, pleurodesis was observed in 45.9%, being associated to age (<55 years, p=0.02), the primary diagnosis (p=0.03) and interventions for the underlying disease (p<0.001). Complications occurred in 24.2% of all procedures (n=15), the majority concerning mechanical obstructions (n=10) and infections (n=4). Patients with HH had an excess risk for complications (37.3%)., Conclusion: Efficacy in symptom relief and a generally manageable safety profile recommend IPC as a first-line treatment option in NMPE, where disease-specific treatments are exhausted. Caution is warranted in patients with HH due to an excess risk for complications., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Profound transformations in the German healthcare system lead to intense working conditions for young employees in inpatient care. Published data suggest associated health risks., Objectives: This investigation aims to assess current stress factors, their consequences, and subjective measures for improvement., Methods: During September 2017, a cross-sectional survey was conducted among physicians and nurses ≤35 years of age and with work experience in inpatient care not exceeding six years. Field access was gained via seven scientific and professional societies. The electronic questionnaire consisted of mainly validated instruments. Regression models included confounders into the final data analysis., Results: Included in the final data analysis were 1060 complete cases. The overall response rate was 13%. Different stress factors (e.g. time-related or psychosocial) were found at high levels. These stress factors were connected to reduced health and higher risk of burnout. Furthermore, they were associated with inferior perceived quality of care. Young physicians claimed less documentation requirements and less intense working conditions. Young nurses demanded fair salary and an appropriate nurse-patient allocation., Conclusion: Today's working conditions in inpatient care are a threat to the health status of young employees. General conditions, which ensure a sustainable healthy and effective working environment, need to be ensured.

Background: In 2013 RheinMain University launched its bachelor's degree program Health Care Economics requiring each student to participate in a mandatory two-month nursing internship. A preliminary risk assessment revealed serious risks for both students and patients and had to be addressed by appropriate measures such as mandatory systematic safety training for each student., Methods: A short-term educational intervention named "Survival-Day" was designed to minimize risks related to nursing internships of students. This intervention consists of six 45-min-units with theoretical input (2 units) and hands-on training (4 units) imparting basic knowledge and skills in CPR, hand hygiene and handling of masks and protective gowns, prevention of needle stick injuries, fire protection and firefighting. Performance of CPR was assessed using computerized manikins. Acceptance, necessity and usability were assessed anonymously by standardized written questionnaires after completion of nursing internships., Results: 462 students have completed the Survival-Day until January 2019. CPR performance showed acceptable adherence rates to guideline recommendations (mean 78.8%, SD ±22.6%). The majority of students performed aseptic health care activities (66%), treated patients with multi-resistant pathogens (62%) and disposed sharp instruments such as blood-contaminated needles (76%). According to students' self-reports about these hazardous activities, less than 50% of these students received adequate safety training at nursing facilities. However, no sentinel events such as needle stick injuries or students becoming second victim have been reported., Conclusion: Our study reveals severe discrepancies between legal obligation of nursing facilities to ensure safety instructions for nursing interns and initial training as perceived by this group. Mandatory initial training before conduction of hazardous tasks was mainly covered by our short-term educational intervention (Survival-Day). Regarding responsibility for their students a preliminary safety instruction program like the Survival-Day should be considered for all educational institutions sending students to nursing internships unless mandatory and sufficient safety trainings for nursing interns can be guaranteed by nursing facilities., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2019.)

Introduction: Recurrent pleural effusion is a common cause of dyspnoea, cough and chest pain during the course of malignant diseases. Chemical pleurodesis had been the only definitive treatment option until two decades ago. Indwelling pleural catheters (IPC) emerged as an alternative, not only assuring immediate symptom relief but also potentially leading to pleurodesis in the absence of sclerosing agents., Methods: In this single-centre retrospective observational study patient characteristics, procedural variables and outcome in a large population of patients with IPC in malignancy were evaluated and prognostic factors for pleurodesis were identified., Results: From 2006 to 2016, 395 patients received 448 IPC, of whom 121 (30.6%) had ovarian, 91 (23.0%) lung and 45 (11.4%) breast cancer. The median length of IPC remaining in place was 1.2 months (IQR, 0.5-2.6), the median survival time after insertion 2.0 months (IQR, 0.6-6.4). An adequate symptom relief was achieved in 94.9% of all patients, with no need for subsequent interventions until last visit or death. In patients surviving ≥30 days after IPC insertion, pleurodesis was observed in 44.5% and was more common in patients < 60 years (HR, 1.72; 95% CI, 1.05-2.78; p = 0.03). The use of an additional talc slurry via the IPC was highly predictive for pleurodesis (HR 6.68; 95% CI, 1.44-31.08; p = 0.02). Complications occurred in 13.4% of all procedures (n = 60), 41.8% concerning infections (local infections at the tunnel/exit site (n = 14) and empyema (n = 11)), and 98.3% being low or mild grade (n = 59). Complication rates were higher in men than women (18.6 vs. 12.4%, p = 0.023)., Conclusion: High efficacy in symptom relief and a favourable safety profile confirm IPC as suitable first line option in most malignant pleural effusions. The study presents the largest dataset on IPC in gynaecologic cancer to date. Gender-specific differences in complication rates warrant further study.

Competing Interests: TB, JW, CF, MK, SB, RK und MR geben keine Interessenskonflikte bezüglich des publizierten Inhalts an.OK ist in einem Angestelltenverhältnis mit der DGP.

Infectious Diseases are a cross-sectional area connected to various medical disciplines and offer interested physicians multiple working opportunities. The spectrum of infectious diseases covers both out- and inpatient care as well as basic, clinical and epidemiological research. The need for infectious diseases specialists is increasing, thus career prospects are promising. Working conditions in infectious diseases are comparatively family-friendly. With this article we intend to arouse interest for working in the fascinating fields of infectious diseases and provide information on career opportunities. Data from a recently conducted survey among members of the German Society of Infectious Diseases deliver insight, how infectious disease specialists work today., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: The influenza vaccination rate among older and chronically ill patients in Germany has declined in the past decade in spite of vaccination campaigns., Methods: The influenza vaccination rate among persons with chronic renal disease was studied with the aid of billing data from various Associations of Statutory Health Insurance Physicians (Kassenärztliche Vereinigungen, ASHIPs) in Germany. It was tested in a randomized controlled trial whether a written vaccination appeal, sent by physicians to patients, led to an increase in the vaccination rate. It was tested in a further such trial whether the vaccination rate among patients with renal disease could be improved by an appeal for vaccination that was sent by the ASHIPs to the treating nephrologists. Finally, it was also tested in a prospective interventional study whether the vaccination rate could be improved by an appeal for vaccination sent by a health- insurance carrier directly to the patients., Results: In 2012-2017, the vaccination rate among persons with chronically impaired renal function ranged from 41.1% to 46.9%; it ranged from 31.7% to 33.7% in kidney transplant recipients and from 42.7% to 44.7% in dialysis patients. An appeal for vaccination that was sent from physicians to patients raised the vaccination rate by 8.3% in the intervention group compared to the control group (p = 0.03; number needed to treat [NNT]: 13). On the other hand, an appeal for vaccination that was sent to the nephrologists lowered the vaccination rate by 0.8% in the intervention group compared to the control group. Finally, an appeal for vaccination that was sent by the health-insurance fund to the patients raised the vaccination rate by 3.2% (p<0.001; NNT: 32)., Conclusion: Fewer than half of all patients with chronic renal failure in Germany are vaccinated against influenza. The vaccination rate was found to be increased only after an appeal for vaccination that was sent directly to the patients. A letter sent to the treating physicians had no positive effect at all.

With the increase of ageing population, rates of chronic diseases and complex medical conditions, the management of high-risk surgical patients is likely to become a great concern in most countries. Considering all these factors, it is certainly rational and intuitive that internists should be included into a collaborative model of medical and surgical co-management, where their multi-potentiality and synthesis capacity require them to coordinate the multidisciplinary team and to be the leading agent of change. In this regard, our aim was to present the official position and approach of the Working Group on Professional Issues and Quality of Care of the European Federation of Internal Medicine (EFIM), for implementation of this strategy of care, encouraging internists to assume an important role and to provide continuity of multidisciplinary care, from the decision to operate through to rehabilitation and recovery. Moving from the traditional model of medical care of the surgical patients to the co-management model, from a reactive simple consultation to a new pro-active continued service, may optimize the quality and perioperative care, improving the survival, shortening hospital stays, replacing the old strategy of late and complication treatment to an early and preventive one., (Copyright © 2018. Published by Elsevier B.V.)

Introduction: Local ablative treatment (LAT) improves outcome in lung cancer with oligometastatic disease (OMD) and potentially leads to long term survival. The aim of this retrospective study was to evaluate and quantify the additional benefit of LAT in synchronous OMD and to further identify prognostic factors for survival., Patients and Methods: A propensity score-matched pairs analysis was performed on a set of patient and disease variables in 180 patients, treated for synchronous single organ OMD including non small-cell and neuroendocrine lung cancer with ≤4 metastases between 2000 and 2016 in 3 lung cancer centers in Berlin, Germany. Patients either received LAT for all sites of disease (intervention group) by means of surgery or stereotactic radiotherapy, or standard chemotherapy, if necessary combined with a local treatment with palliative intent (control group)., Results: Median follow-up time was 32.2 and 18.8 months for the intervention and control group, respectively. Substantial benefits in median progression-free survival (PFS, 25.1 vs. 8.2 months; HR, 0.30; 95% CI, 0.21-0.43; p < 0.001) and overall survival (OS, 60.4 vs. 22.5 months; HR, 0.42; 95% CI, 0.28-0.62; p < 0.001) were associated with LAT. Histology of adenocarcinoma and T1a primaries also predicted a favorable prognosis concerning PFS and OS. More favorable nodal stage (N0-2 vs. 3) and solitary metastases were associated with an extended PFS, whereas initial ECOG-PS (0-1 vs. 2) predicted OS., Conclusions: LAT was the strongest predictor for PFS and OS in OMD with ≤4 metastases. Survival in the control group identifies OMD as a subset of lung cancer with a generally more favorable prognosis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Addressing the current collision course between growing healthcare demands, rising costs and limited resources is an extremely complex challenge for most healthcare systems worldwide. Given the consensus that this critical reality is unsustainable from staff, consumer, and financial perspectives, our aim was to describe the official position and approach of the Working Group on Professional Issues and Quality of Care of the European Federation of Internal Medicine (EFIM), for encouraging internists to lead a thorough reengineering of hospital operational procedures by the implementation of innovative hospital ambulatory care strategies. Among these, we include outpatient and ambulatory care strategies, quick diagnostic units, hospital-at-home, observation units and daycare hospitals. Moving from traditional 'bed-based' inpatient care to hospital ambulatory medicine may optimize patient flow, relieve pressure on hospital bed availability by avoiding hospital admissions and shortening unnecessary hospital stays, reduce hospital-acquired complications, increase the capacity of hospitals with minor structural investments, increase efficiency, and offer patients a broader, more appropriate and more satisfactory spectrum of delivery options., (Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background:  Medical specialty training is the basis for career development of young internists and it is vital for the delivery of high-quality medical care. In 2014 the young internists of two professional bodies in Germany conducted a survey among their young members and described major factors influencing training and working conditions. We present the results of a follow-up survey to describe changes of these factors over time. An additional focus is set on the difficulties of balancing medical career and family., Methods:  In the end of 2016 we conducted an online-based survey of all members in training of the German Society of Internal Medicine (DGIM) and the Professional Association of German Internists (BDI). The questionnaire used in the 2014 survey was modified and items investigating the balance between career and family were added., Results:  A total of 1587 questionnaires were returned and analysed. Mayor findings did not change over time. Psychosocial strain remains very high among medical trainees in internal medicine. A structured training curriculum and meaningful feedback are associated with lower psychosocial strain and higher work satisfaction. Internists - and here especially women - with children experience the daily balance of medical career and family as extremely challenging., Conclusion:  These results demonstrate that there is still a serious need for adjusting training and working conditions of young internists in Germany. Especially the role and increasing importance of female physicians has to be recognized by enabling a successful integration of medical career and family., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

We developed single-image fluorescence lifetime imaging microscopy (siFLIM), a method for acquiring quantitative lifetime images from a single exposure. siFLIM takes advantage of a new generation of dedicated cameras that simultaneously record two 180°-phase-shifted images, and it allows for video-rate lifetime imaging with minimal phototoxicity and bleaching. siFLIM is also inherently immune to artifacts stemming from rapid cellular movements and signal transients.

Background: Major transformations within the German healthcare system (e. g. implementation of the G-DRG system, growing focus on economic aspects, demographic changes) led to changes of work and training conditions of young internists and to criticism and dissatisfaction. So far, there is a lack of up-to-date and nationwide data analyzing these issues with focus on economic pressure and psychosocial strain., Methods: The young internists of the two professional bodies conducted an online-based survey addressing all their members in training. The questionnaire covers five central areas of conflict. Furthermore, the model of effort-reward-imbalance (ERI) was applied to measure psychosocial strain at work., Results: 1696 internists in training participated in the survey. Workdays characterized by high pace and workload do not leave much room for professional training as well as for family and research friendly working conditions. A relevant part of the affected physicians draws or at least considers personal consequences. Economical pressure is clearly noticeable. Psychosocial strain among the questioned internists is very high and conveys a risk for physicians' health and patients' quality of care., Conclusion: Adjustments of working and training conditions in internal medicine are necessary to preserve physicians health, high-quality medical treatment and to ensure an attractive working environment., (© Georg Thieme Verlag KG Stuttgart · New York.)

Optical (molecular) imaging can benefit from a combination of the high signal-to-background ratio of activatable fluorescence imaging with the high specificity of luminescence lifetime imaging. To allow for this combination, both imaging techniques were integrated in a single imaging agent, a so-called activatable lifetime imaging agent. Important in the design of this imaging agent is the use of two luminophores that are tethered by a specific peptide with a hairpin-motive that ensured close proximity of the two while also having a specific amino acid sequence available for enzymatic cleavage by tumor-related MMP-2/9. Ir(ppy)3 and Cy5 were used because in close proximity the emission intensities of both luminophores were quenched and the influence of Cy5 shortens the Ir(ppy)3 luminescence lifetime from 98 ns to 30 ns. Upon cleavage in vitro, both effects are undone, yielding an increase in Ir(ppy)3 and Cy5 luminescence and a restoration of Ir(ppy)3 luminescence lifetime to 94 ns. As a reference for the luminescence activation, a similar imaging agent with the more common Cy3-Cy5 fluorophore pair was used. Our findings underline that the combination of enzymatic signal activation with lifetime imaging is possible and that it provides a promising method in the design of future disease specific imaging agents.

Eukaryotic cells use second messengers such as Ca(2+), IP3, cGMP, and cAMP to transduce extracellular signals like hormones, via membrane receptors to downstream cellular effectors. FRET-based sensors are ideal to visualize and measure these rapid changes of second messenger concentrations in time and place. Here, we describe the use of EPAC-based FRET sensors to measure cAMP with spatiotemporal resolution in cells by fluorescence lifetime imaging (FLIM).

In this proof-of-concept study, a new activatable imaging agent based on two luminophores and two different quenching mechanisms is reported. Both partial and total activation of the luminescence signal can be achieved, either in solution or in vitro. Bond cleavage makes the compound suitable for luminescence lifetime imaging.

Bayesian spiking neurons (BSNs) provide a probabilistic interpretation of how neurons perform inference and learning. Online learning in BSNs typically involves parameter estimation based on maximum-likelihood expectation-maximization (ML-EM) which is computationally slow and limits the potential of studying networks of BSNs. An online learning algorithm, fast learning (FL), is presented that is more computationally efficient than the benchmark ML-EM for a fixed number of time steps as the number of inputs to a BSN increases (e.g., 16.5 times faster run times for 20 inputs). Although ML-EM appears to converge 2.0 to 3.6 times faster than FL, the computational cost of ML-EM means that ML-EM takes longer to simulate to convergence than FL. FL also provides reasonable convergence performance that is robust to initialization of parameter estimates that are far from the true parameter values. However, parameter estimation depends on the range of true parameter values. Nevertheless, for a physiologically meaningful range of parameter values, FL gives very good average estimation accuracy, despite its approximate nature. The FL algorithm therefore provides an efficient tool, complementary to ML-EM, for exploring BSN networks in more detail in order to better understand their biological relevance. Moreover, the simplicity of the FL algorithm means it can be easily implemented in neuromorphic VLSI such that one can take advantage of the energy-efficient spike coding of BSNs.

Vascular diseases are the most challenging health problems in developed countries. The vascular segmentation as well as registration techniques are the topics of past and ongoing research activities. In this work we target an abdominal aorta registration technique. The developed methodology is useful in the assessment of abdominal aortic aneurysm treatment by visualizing the correspondence between pre- and postoperative Computed Tomography (CT) data. The presented approach makes it possible to match all voxels belonging to the aorta from different CT series. It is based on aorta lumen segmentation and graph matching method. To segment the lumen area a hybrid level-set active contour approach is used. The matching step is performed based on a path similarity skeleton graph matching procedure. The registration results have been tested on the database of 8 patients, for which two different contrast-enhanced CT series were acquired. All registration results achieved with our system and verified by an expert prove the efficiency of the approach and encourage to further develop this method.

Alzheimer's disease (AD) is hallmarked by amyloid-β (Aβ) peptides accumulation and aggregation in extracellular plaques, preceded by intracellular accumulation. We examined whether intracellular Aβ can be cleared by cytosolic peptidases and whether this capacity is affected during progression of sporadic AD (sAD) in humans and in the commonly used APPswePS1dE9 and 3xTg-AD mouse models. A quenched Aβ peptide that becomes fluorescent upon degradation was used to screen for Aβ-degrading cytoplasmic peptidases cleaving the aggregation-prone KLVFF region of the peptide. In addition, this quenched peptide was used to analyze Aβ-degrading capacity in the hippocampus of sAD patients with different Braak stages as well as APPswePS1dE9 and 3xTg-AD mice. Insulin-degrading enzyme (IDE) was found to be the main peptidase that degrades cytoplasmic, monomeric Aβ. Oligomerization of Aβ prevents its clearance by IDE. Intriguingly, the Aβ-degrading capacity decreases already during the earliest Braak stages of sAD, and this decline correlates with IDE protein levels, but not with mRNA levels. This suggests that decreased IDE levels could contribute to early sAD. In contrast to the human data, the commonly used APPswePS1dE9 and 3xTg-AD mouse models do not show altered Aβ degradation and IDE levels with AD progression, raising doubts whether mouse models that overproduce Aβ peptides are representative for human sAD., (© 2013 John Wiley & Sons Ltd and the Anatomical Society.)

We have built an all-solid-state camera that is directly modulated at the pixel level for frequency-domain fluorescence lifetime imaging microscopy (FLIM) measurements. This novel camera eliminates the need for an image intensifier through the use of an application-specific charge coupled device design in a frequency-domain FLIM system. The first stage of evaluation for the camera has been carried out. Camera characteristics such as noise distribution, dark current influence, camera gain, sampling density, sensitivity, linearity of photometric response, and optical transfer function have been studied through experiments. We are able to do lifetime measurement using our modulated, electron-multiplied fluorescence lifetime imaging microscope (MEM-FLIM) camera for various objects, e.g., fluorescein solution, fixed green fluorescent protein (GFP) cells, and GFP-actin stained live cells. A detailed comparison of a conventional microchannel plate (MCP)-based FLIM system and the MEM-FLIM system is presented. The MEM-FLIM camera shows higher resolution and a better image quality. The MEM-FLIM camera provides a new opportunity for performing frequency-domain FLIM.

During wound healing, hemidesmome disassembly enables keratinocyte migration and proliferation. Hemidesmosome dynamics are altered downstream of epidermal growth factor (EGF) receptor activation, following the phosphorylation of integrin β4 residues S1356 and S1364, which reduces the interaction with plectin; however, this event is insufficient to drive complete hemidesmome disassembly. In the studies reported here, we used a fluorescence resonance energy transfer-based assay to demonstrate that the connecting segment and carboxy-terminal tail of the β4 cytoplasmic domain interact, which facilitates the formation of a binding platform for plectin. In addition, analysis of a β4 mutant containing a phosphomimicking aspartic acid residue at T1736 in the C-tail suggests that phosphorylation of this residue regulates the interaction with the plectin plakin domain. The aspartic acid mutation of β4 T1736 impaired hemidesmosome formation in junctional epidermolysis associated with pyloric atresia/β4 keratinocytes. Furthermore, we show that T1736 is phosphorylated downstream of protein kinase C and EGF receptor activation and is a substrate for protein kinase D1 in vitro and in cells, which requires its translocation to the plasma membrane and subsequent activation. In conclusion, we identify T1736 as a novel phosphorylation site that contributes to the regulation of hemidesmome disassembly, a dynamically regulated process involving the concerted phosphorylation of multiple β4 residues.

A major function of proteasomes and macroautophagy is to eliminate misfolded potentially toxic proteins. Mammalian proteasomes, however, cannot cleave polyglutamine (polyQ) sequences and seem to release polyQ-rich peptides. Puromycin-sensitive aminopeptidase (PSA) is the only cytosolic enzyme able to digest polyQ sequences. We tested whether PSA can protect against accumulation of polyQ fragments. In cultured cells, Drosophila and mouse muscles, PSA inhibition or knockdown increased aggregate content and toxicity of polyQ-expanded huntingtin exon 1. Conversely, PSA overexpression decreased aggregate content and toxicity. PSA inhibition also increased the levels of polyQ-expanded ataxin-3 as well as mutant α-synuclein and superoxide dismutase 1. These protective effects result from an unexpected ability of PSA to enhance macroautophagy. PSA overexpression increased, and PSA knockdown or inhibition reduced microtubule-associated protein 1 light chain 3-II (LC3-II) levels and the amount of protein degradation sensitive to inhibitors of lysosomal function and autophagy. Thus, by promoting autophagic protein clearance, PSA helps protect against accumulation of aggregation-prone proteins and proteotoxicity.

Several neurodegenerative disorders, including Huntington's disease, are caused by expansion of the polyglutamine (polyQ) tract over 40 glutamines in the disease-related protein. Fragments of these proteins containing the expanded polyQ tract are thought to initiate aggregation and represent the toxic species. Although it is not clear how these toxic fragments are generated, in vitro data suggest that proteasomes are unable to digest polyQ tracts. To examine whether the resulting polyQ peptides could initiate aggregation in living cells, we mimicked proteasomal release of monomeric polyQ peptides. These peptides lack the commonly used starting methionine residue or any additional tag. Only expanded polyQ peptides seem to be peptidase resistant, and their accumulation initiated the aggregation process. As observed in polyQ disorders, these aggregates subsequently sequestered proteasomes, ubiquitin and polyQ proteins, and recruited Hsp70. The generated expanded polyQ peptides were toxic to neuronal cells. Our approach mimics proteasomal release of pure polyQ peptides in living cells, and represents a valuable tool to screen for proteins and compounds that affect aggregation and toxicity.