[Practice and challenges of delegating medical tasks in the interprofessional everyday work of inpatient healthcare in Germany - An exploratory survey]. / Praxis und Herausforderungen der Delegation ärztlicher Tätigkeiten im interprofessionellen Arbeitsalltag der stationären Krankenversorgung in Deutschland: eine explorative Befragung.

BACKGROUND: The delegation of medical tasks (DMT) plays a significant role in the everyday practice of inpatient care but also presents a potential challenge in interprofessional collaboration. Assessing the conditions of DMT in everyday work is crucial to identify areas for optimization. METHODS: In a nationwide exploratory study, physicians, nursing and allied health professionals working for inpatient care facilities were surveyed regarding various aspects of DMT using a standardized online questionnaire. RESULTS: The majority of the 757 participants (64.9% physicians), perceived DMT to be both economically and time-efficient (88.5% agreement) and in the best interest of patients (74%). For 78.7% of the respondents, DMT represents a potential conflict in their daily work, depending on the quality of interprofessional communication. Inadequate staffing was identified as a barrier to a broader implementation of DMT by 83.8% of participants. 63.2% of the participants considered their knowledge of legal aspects related to DMT to be at least good (participants with less than 5 years of professional experience: 52.6%). Physicians primarily acquire relevant knowledge through professional practice (71.3% vs. non-physicians 39.5%). CONCLUSION: Across the different professional groups DMT was considered beneficial and serving the interests of patients. Targeted promotion of safe and cost-effective DMT should be incorporated into medical education. Achieving greater benefits from DMT requires explicit legal frameworks, effective communication within the team and, in particular, adequate staffing among the professional groups responsible for delegated tasks.

Quantitative Metabolomics and Lipoprotein Analysis of PDAC Patients Suggests Serum Marker Categories for Pancreatic Function, Pancreatectomy, Cancer Metabolism, and Systemic Disturbances.

Pancreatic ductal adenocarcinoma (PDAC) is difficult to diagnose in the early stages and lacks reliable biomarkers. The scope of this project was to establish quantitative nuclear magnetic resonance (NMR) spectroscopy to comprehensively study blood serum alterations in PDAC patients. Serum samples from 34 PDAC patients obtained before and after pancreatectomy as well as 83 age- and sex-matched control samples from healthy donors were analyzed with in vitro diagnostics research (IVDr) proton NMR spectroscopy at 600 MHz. Uni- and multivariate statistics were applied to identify significant biofluid alterations. We identified 29 significantly changed metabolites and 98 lipoproteins when comparing serum from healthy controls with those of PDAC patients. The most prominent features were assigned to (i) markers of pancreatic function (e.g., glucose and blood triglycerides), (ii) markers related to surgery (e.g., ketone bodies and blood cholesterols), (iii) PDAC-associated markers (e.g., amino acids and creatine), and (iv) markers for systemic disturbances in PDAC (e.g., gut metabolites DMG, TMAO, DMSO2, and liver lipoproteins). Quantitative serum NMR spectroscopy is suited as a diagnostic tool to investigate PDAC. Remarkably, 2-hydroxybutyrate (2-HB) as a previously suggested marker for insulin resistance was found in extraordinarily high levels only after pancreatectomy, suggesting this metabolite is the strongest marker for pancreatic loss of function.

Durvalumab Plus Gemcitabine and Cisplatin in Patients with Advanced Biliary Tract Cancer: An Exploratory Analysis of Real-World Data.

BACKGROUND: The combination of gemcitabine and cisplatin (gem/cis) with the anti-PD-L1-antibody durvalumab was recently approved as first line therapy for biliary tract cancer (BTC) based on the results of the TOPAZ-1 trial. OBJECTIVE: We aim to analyse the feasibility and efficacy of the triple combination therapy in patients with BTC in a real-world setting and in correspondence with the genetic alterations of the cancer. METHODS: In this single-centre retrospective analysis, all patients with BTC and treated with durvalumab plus gem/cis from April 2022 to September 2023 were included. Survival and treatment response were investigated, within the context of the inclusion and exclusion criteria of TOPAZ-1 and in correspondence with genetic alterations of the cancer. RESULTS: In total, 35 patients, of which 51% met the inclusion criteria of the TOPAZ-1 trial, were analysed. Patients treated within TOPAZ-1 criteria did not have a significantly different median overall survival and progression free survival than the rest of the patients (10.3 versus 9.7 months and 5.3 versus 5 months, respectively). The disease control rate of patients within the TOPAZ-1 criteria was 61.1%, in comparison to 58.8% in the rest of patients. A total of 51 grade 3 and 4 adverse events were observed without significant differences in the subgroups. No specific correlating patterns of genetic alterations with survival and response were observed. CONCLUSIONS: The treatment of advanced patients with BTC with durvalumab and gem/cis, even beyond the inclusion criteria of the TOPAZ-1 trial, shows promising safety.

Serum Amyloid A as a Potential Biomarker in Inflammatory Bowel Diseases, Especially in Patients with Low C-Reactive Protein.

The acute phase protein Serum Amyloid A (SAA) is synthesised by the liver in response to inflammatory stimuli. Previous studies have revealed that SAA may be a better biomarker of disease activity in inflammatory bowel disease (IBD) compared to C-reactive protein (CRP). This retrospective monocentric study evaluated whether SAA correlates with biomarkers like faecal calprotectin (FC), CRP, the Neutrophil to Lymphocyte ratio (NLR), the platelet count and clinical disease activity of IBD patients. Serum samples from the IBD outpatient clinic of the University Hospital Heidelberg were analysed for SAA concentrations if an FC concentration measurement was available from ±14 days to collection of the serum sample. Three hundred and six serum samples from 265 patients (166 with Crohn's disease, 91 with ulcerative colitis and 8 with IBD unclassified) met the inclusion criteria. There was a significant positive correlation between SAA and FC, CRP, NLR, platelet count and the Simple Clinical Colitis Activity Index (SCCAI). The cut-off for SAA serum concentration at 4.55 mg/L achieved a sensitivity of 57.5% and a specificity of 69.7% for the detection of active inflammation in IBD. SAA may be used as an additional biomarker in the disease monitoring strategy of IBD patients, especially in patients with low CRP concentrations.

Endoscopic papillectomy for ampullary lesions of minor papilla.

BACKGROUND AND AIMS: Ampullary lesions (ALs) of the minor duodenal papilla are extremely rare. Endoscopic papillectomy (EP) is a routinely used treatment for AL of the major duodenal papilla, but the role of EP for minor AL has not been accurately studied. METHODS: We identified 20 patients with ALs of minor duodenal papilla in the multicentric database from the Endoscopic Papillectomy vs Surgical Ampullectomy vs Pancreatitcoduodenectomy for Ampullary Neoplasm study, which included 1422 EPs. We used propensity score matching (nearest-neighbor method) to match these cases with ALs of the major duodenal papilla based on age, sex, histologic subtype, and size of the lesion in a 1:2 ratio. Cohorts were compared by means of chi-square or Fisher exact test as well as Mann-Whitney U test. RESULTS: Propensity score-based matching identified a cohort of 60 (minor papilla 20, major papilla 40) patients with similar baseline characteristics. The most common histologic subtype of lesions of minor papilla was an ampullary adenoma in 12 patients (3 low-grade dysplasia and 9 high-grade dysplasia). Five patients revealed nonneoplastic lesions. Invasive cancer (T1a), adenomyoma, and neuroendocrine neoplasia were each found in 1 case. The rate of complete resection, en-bloc resection, and recurrences were similar between the groups. There were no severe adverse events after EP of lesions of minor papilla. One patient had delayed bleeding that could be treated by endoscopic hemostasis, and 2 patients showed a recurrence in surveillance endoscopy after a median follow-up of 21 months (interquartile range, 12-50 months). CONCLUSIONS: EP is safe and effective in ALs of the minor duodenal papilla. Such lesions could be managed according to guidelines for EP of major duodenal papilla.

Body composition parameters predict survival in pancreatic cancer-A retrospective multicenter analysis.

BACKGROUND: Parameters to adapt individual treatment strategies for patients with pancreatic ductal adenocarcinoma (PDAC) are urgently needed. The present study aimed to evaluate body composition parameters as predictors of overall survival (OS) in PDAC patients. METHODS: Measurements of body composition parameters were performed on computed tomography scans at diagnosis. Height-standardized and Body Mass Index- and sex-adjusted regression formulas deriving cut-offs from a healthy population were used. The Kaplan-Meier method with the log-rank test was performed for survival analysis. Independent prognostic factors were identified with uni- and multivariable Cox regression analyses. RESULTS: In total, 354 patients were analyzed. In a multivariable Cox model, besides tumor stage and resection status, only myosteatosis (HR 1.53; 95% CI 1.10-2.14, p = 0.01) was an independent prognostic factor of OS among body composition parameters. Subgroup analyses revealed that the prognostic impact of myosteatosis was higher in patients ≤68 years of age, with advanced tumor stages and patients without curative intended resection. CONCLUSIONS: The analysis of one of the largest Caucasian cohorts to date, demonstrated myosteatosis to be an independent prognostic factor of OS in PDAC. To improve outcomes, prospective trials aiming to investigate the utility of an early assessment of myosteatosis with subsequent intervention by dieticians, sports medicine physicians, and physiotherapists are warranted.

Treatment of esophageal leakages with the Microtech®-VAC-Stent: a monocentric early experience of three cases.

Background: Endoscopic approaches in the treatment of transmural esophageal defects, either after esophageal resection or due to perforation, have demonstrated convincing feasibility. Surgical options are limited and associated with high morbidity and mortality rates. Currently, internal endoscopic drainage with pigtail stents, self-expanding metal stent (SEMS), or endoscopic vacuum therapy (EVT) are options for first-line treatment. Here, we report the outcome of the recently developed combination of SEMS and EVT using the endoscopic Microtech®-VAC-Stent (EVS). Methods: Between June and July 2022, three consecutive patients (one female and two males) with esophageal transmural defects were treated with the Microtech®-VAC-Stent. Two patients suffered from an anastomotic leak after oncologic gastroesophageal surgery, and one patient presented with esophageal perforation due to Boerhaave syndrome. Results: Three consecutive patients were successfully treated with EVS. In one patient, one EVS treatment was sufficient, whereas the other two patients needed two and six EVS exchanges. Exchanges were scheduled every 7 days and no procedural adverse events were observed. Conclusion: In line with the former case series, EVS therapy is a promising new approach for the treatment of esophageal leaks. Exchange of the EVS seems feasible every 7 days reducing interventions for the individual patient. Prospective studies comparing EVS with other endoscopic therapies are needed to define the best therapeutic approach.

Anti-angiogenic therapy using the multi-tyrosine kinase inhibitor Regorafenib enhances tumor progression in a transgenic mouse model of ß-cell carcinogenesis.

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) represent a distinct hypervascularized tumor entity, often diagnosed at metastatic stage. Therapeutic efficacy of anti-angiogenic multi-kinase inhibitors is frequently limited by primary or acquired resistance in vivo. This study aimed to characterize the molecular mode of action as well as resistance mechanisms to the anti-angiogenic multi-tyrosine kinase inhibitor (TKI) Regorafenib in vitro and in vivo. METHODS: In vitro, human and murine pancreatic neuroendocrine cell lines were comparatively treated with Regorafenib and other TKIs clinically used in PNETs. Effects on cell viability and proliferation were analyzed. In vivo, transgenic RIP1Tag2 mice were treated with Regorafenib at two different time periods during carcinogenesis and its impact on angiogenesis and tumor progression was evaluated. RESULTS: Compared to the established TKI therapies with Sunitinib and Everolimus, Regorafenib showed the strongest effects on cell viability and proliferation in vitro, but was unable to induce apoptosis. Unexpectedly and in contrast to these in vitro findings, Regorafenib enhanced proliferation during early tumor development in RIP1Tag2 mice and had no significant effect in late tumor progression. In addition, invasiveness was increased at both time points. Mechanistically, we could identify an upregulation of the pro-survival protein Bcl-2, the induction of the COX2-PGE2-pathway as well as the infiltration of CSF1R positive immune cells into the tumors as potential resistance mechanisms following Regorafenib treatment. DISCUSSION: Our data identify important tumor cell-autonomous and stroma-dependent mechanisms of resistance to antiangiogenic therapies.

Interaction of mental comorbidity and physical multimorbidity predicts length-of-stay in medical inpatients.

BACKGROUND: Mental comorbidities of physically ill patients lead to higher morbidity, mortality, health-care utilization and costs. OBJECTIVE: The aim of the study was to investigate the impact of mental comorbidity and physical multimorbidity on the length-of-stay in medical inpatients at a maximum-care university hospital. DESIGN: The study follows a retrospective, quantitative cross-sectional analysis approach to investigate mental comorbidity and physical multimorbidity in internal medicine patients. PATIENTS: The study comprised a total of n = 28.553 inpatients treated in 2017, 2018 and 2019 at a German Medical University Hospital. MAIN MEASURES: Inpatients with a mental comorbidity showed a median length-of-stay of eight days that was two days longer compared to inpatients without a mental comorbidity. Neurotic and somatoform disorders (ICD-10 F4), behavioral syndromes (F5) and organic disorders (F0) were leading with respect to length-of-stay, followed by affective disorders (F3), schizophrenia and delusional disorders (F2), and substance use (F1), all above the sample mean length-of-stay. The impact of mental comorbidity on length-of-stay was greatest for middle-aged patients. Mental comorbidity and Elixhauser score as a measure for physical multimorbidity showed a significant interaction effect indicating that the impact of mental comorbidity on length-of-stay was greater in patients with higher Elixhauser scores. CONCLUSIONS: The findings provide new insights in medical inpatients how mental comorbidity and physical multimorbidity interact with respect to length-of-stay. Mental comorbidity had a large effect on length-of-stay, especially in patients with high levels of physical multimorbidity. Thus, there is an urgent need for new service models to especially care for multimorbid inpatients with mental comorbidity.

Gender-specific changes of the gut microbiome correlate with tumor development in murine models of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a dismal outcome. To improve understanding of sequential microbiome changes during PDAC development we analyzed mouse models of pancreatic carcinogenesis (KC mice recapitulating pre-invasive PanIN formation, as well as KPC mice recapitulating invasive PDAC) during early tumor development and subsequent tumor progression. Diversity and community composition were analyzed depending on genotype, age, and gender. Both mouse models demonstrated concordant abundance changes of several genera influenced by one or more of the investigated factors. Abundance was significantly impacted by gender, highlighting the need to further elucidate the impact of gender differences. The findings underline the importance of the microbiome in PDAC development and indicate that microbiological screening of patients at risk and targeting the microbiome in PDAC development may be feasible in future.

[Climate Crisis: What Gastrointestinal Complications of this Medical Emergency Should We Be Aware Of?] / Klimakrise: Welche gastroenterologischen Folgeerkrankungen dieses medizinischen Notfalls sollten wir kennen?

INTRODUCTION: The climate crisis has serious consequences for many areas of life. This applies in particular to human health - also in Europe. While cardiovascular, pneumological and dermatological diseases related to the climate crisis are often discussed, the crisis' significant gastroenterological consequences for health must also be considered. METHODS: A literature search (Pubmed, Cochrane Library) was used to identify papers with relevance particularly to the field of gastroenterology in (Central) Europe. Findings were supplemented and discussed by an interdisciplinary team. RESULTS: The climate crisis impacts the frequency and severity of gastrointestinal diseases in Europe due to more frequent and severe heat waves, flooding and air pollution. While patients with intestinal diseases are particularly vulnerable to acute weather events, the main long-term consequences of climate change are gastrointestinal cancer and liver disease. In addition to gastroenteritis, other infectious diseases such as vector-borne diseases and parasites are important in the context of global warming, heat waves and floods. DISCUSSION: Adaptation strategies must be consistently developed and implemented for vulnerable groups. Patients at risk should be informed about measures that can be implemented individually, such as avoiding heat, ensuring appropriate hydration and following hygiene instructions. Recommendations for physical activity and a healthy and sustainable diet are essential for the prevention of liver diseases and carcinomas. Measures for prevention and the promotion of resilience can be supported by the physicians at various levels. In addition to efforts fostering sustainability in the immediate working environment, a system-oriented commitment to climate protection is important.

Mental health in Germany in the first weeks of the Russo-Ukrainian war.

BACKGROUND: In the connected world, although societies are not directly involved in a military conflict, they are exposed to media reports of violence. AIMS: We assessed the effects of such exposures on mental health in Germany during the military conflict in Ukraine. METHOD: We used the German population-based cohort for digital health research, DigiHero, launching a survey on the eighth day of the Russo-Ukrainian war. Of the 27 509 cohort participants from the general population, 19 444 (70.7%) responded within 17 days. We measured mental health and fear of the impact of war compared with other fears (natural disasters or health-related). RESULTS: In a subsample of 4441 participants assessed twice, anxiety in the population (measured by the Generalised Anxiety Disorder-7 screener) was higher in the first weeks of war than during the strongest COVID-19 restrictions. Anxiety was elevated across the whole age spectrum, and the mean was above the cut-off for mild anxiety. Over 95% of participants expressed various degrees of fear of the impact of war, whereas the percentage for other investigated fears was 0.47-0.82. A one-point difference in the fear of the impact of war was associated with a 2.5 point (95% CI 2.42-2.58) increase in anxiety (11.9% of the maximum anxiety score). For emotional distress, the increase was 0.67 points (0.66-0.68) (16.75% of the maximum score). CONCLUSIONS: The population in Germany reacted to the Russo-Ukrainian war with substantial distress, exceeding reactions during the strongest restrictions in the COVID-19 pandemic. Fear of the impact of war was associated with worse mental health.

[Sex-specific differences in gastroenterological diseases]. / Geschlechtsspezifische Unterschiede in gastroenterologischen Erkrankungen.

Diseases of the gastrointestinal tract present with substantial sex differences that have a potential impact on patient outcome. This fact is not sufficiently addressed either in basic research or in clinical studies. For example, most animal studies utilize male animals. Despite differences in incidence, sex may affect complication rates, prognosis, or therapeutic response. The incidence of gastrointestinal cancers is frequently higher in males, but this observation cannot solely rely on a distinct risk behaviour. Here, differences in immune response and p53 signalling may be factors responsible for this finding. Nevertheless, taking sex differences into account and improving our understanding of relevant mechanisms is crucial and will most likely have a substantial impact on disease outcome. This overview aims to highlight sex differences in the context of various gastroenterological diseases, primarily to enhance awareness. Attention to sex-specific differences is essential to improve individualized treatment.

Mental burden and moral distress among oncologists and oncology nurses in Germany during the third wave of the COVID-19 pandemic: a cross-sectional survey.

PURPOSE: There is evidence for mental burden and moral distress among healthcare workers during the pandemic. However, there is scarcity of analyses regarding possible correlations of mental burden and moral distress in this context. This study provides data to quantify mental burden and possible associations with moral distress among physicians and nurses working in oncology in Germany. METHODS: We conducted a cross-sectional online survey with physicians and nurses working in oncology in Germany between March and July 2021. Next to sociodemographic characteristics and working conditions, mental burden and moral distress were assessed using standardized instruments. Binary multivariate logistic regression using the enter method was performed in order to explore the relationship between mental burden and moral distress. RESULTS: 121 physicians and 125 nurses were included in the study. Prevalence of clinically relevant depressive symptoms, anxiety, somatic symptoms, burnout symptoms and moral distress was 19.2, 14.5, 12.7, 46.0 and 34.7% in physicians and 41.4, 24.0, 46.8, 46.6 and 60.0% in nurses respectively. Mental burden was significantly associated with moral distress, being female/diverse, younger age < 40 and increase in workload. Nurses who felt sufficiently protected from COVID-19 reported significantly less moral distress. CONCLUSION: To improve pandemic resilience, there is a need to ensure safe working environment including psychosocial support. Further evidence on risk and protective factors for moral distress is needed to be able to develop and implement strategies to protect healthcare workers within and beyond the pandemic.

Postoperative Sigmoidoscopy and Biopsy After Elective Endovascular and Open Aortic Surgery for Preventing Mortality by Colonic Ischemia (PSB-Aorta-CI): Protocol for a Prospective Study.

BACKGROUND: Endovascular aortic repair is considered the standard procedure in treating patients diagnosed with pathologies of the abdominal aorta with suitable anatomy. Open surgery remains an option mostly for patients not suitable for endovascular surgery. Colonic ischemia is an important and life-threatening postoperative complication of these procedures. OBJECTIVE: The aim of this study is to evaluate the clinical value and safety of performing a planned sigmoidoscopy and biopsy for detection of colonic ischemia in patients undergoing elective aortic surgery. We also aim to develop prediction scores which could identify patients at risk for colonic ischemia and facilitate their timely treatment. METHODS: The trial is designed as a prospective study. The decision for aortic surgery and eligibility for these procedures will be ascertained according to current guidelines. Afterward, screening of the patient for the remaining inclusion and exclusion criteria will occur. If eligibility for study inclusion is confirmed, the patient will be informed about the aims of the study and all study-specific procedures (sigmoidoscopy and biopsy) and asked to provide informed consent. RESULTS: The primary end point is the proportion of patients diagnosed endoscopically with subclinical and clinically relevant colonic ischemia among all patients undergoing aortic surgery. Patient recruitment started on June 2021. The final patient is expected to be treated by the end of June 2023. Institutional Review Board review has been completed at the University of Halle (Saale; reference #052-2021). CONCLUSIONS: this shows that sigmoidoscopy can be performed safely and is effective for the timely diagnosis of colonic ischemia in these patients, this could result in its routine implementation in both elective and emergency settings. TRIAL REGISTRATION: German Clinical Trials Register DRKS00025587; https://www.drks.de/drks_web/navigate.do?navigationId =trial.HTML&TRIAL_ID=DRKS00025587. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39071.

Modeling Obesity-Driven Pancreatic Carcinogenesis-A Review of Current In Vivo and In Vitro Models of Obesity and Pancreatic Carcinogenesis.

Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic malignancy with a 5-year survival rate below 10%, thereby exhibiting the worst prognosis of all solid tumors. Increasing incidence together with a continued lack of targeted treatment options will cause PDAC to be the second leading cause of cancer-related deaths in the western world by 2030. Obesity belongs to the predominant risk factors for pancreatic cancer. To improve our understanding of the impact of obesity on pancreatic cancer development and progression, novel laboratory techniques have been developed. In this review, we summarize current in vitro and in vivo models of PDAC and obesity as well as an overview of a variety of models to investigate obesity-driven pancreatic carcinogenesis. We start by giving an overview on different methods to cultivate adipocytes in vitro as well as various in vivo mouse models of obesity. Moreover, established murine and human PDAC cell lines as well as organoids are summarized and the genetically engineered models of PCAC compared to xenograft models are introduced. Finally, we review published in vitro and in vivo models studying the impact of obesity on PDAC, enabling us to decipher the molecular basis of obesity-driven pancreatic carcinogenesis.