[Evidence of positive care effects by digital health apps-methodological challenges and approaches]. / Nachweis positiver Versorgungseffekte von digitalen Gesundheitsanwendungen ­ methodische Herausforderungen und Lösungsansätze.

Since 2020, digital health applications (DiGA) can be prescribed at the expense of the German statutory health insurance (SHI) system after undergoing an approval procedure by the Federal Institute for Drugs and Medical Devices (BfArM). DiGA can be approved provisionally for 1 year (with the option of extension) or permanently. The latter is dependent on scientific evidence of a positive effect on care, which can be a medical benefit or a patient-relevant structural and procedural improvement in care. However, it is apparent that the investigation of DiGA in scientific studies is challenging, as they are often complex interventions whose success also includes user and prescriber factors. In addition, health services research data underpinning the benefits of DiGA are lacking to date. In the current article, methodological considerations for DiGA research are presented, and a selection of internal medicine DiGAs is used to critically discuss current research practice.

Outcomes in patients receiving palliative chemotherapy for advanced biliary tract cancer.

BACKGROUND & AIMS: Advanced biliary tract cancer (ABTC) is associated with a poor prognosis. Real-world data on the outcome of patients with ABTC undergoing sequential chemotherapies remain scarce, and little is known about treatment options beyond the established first- and second-line treatments with gemcitabine + cisplatin and FOLFOX. This study aimed to evaluate the outcome of patients with regard to different oncological therapies and to identify prognostic factors. METHODS: From January 2010 until December 2019, 142 patients started palliative chemotherapy at our tertiary care liver center. Overall survival (OS) was calculated using Kaplan-Meier plots. Prognostic factors were evaluated using cox proportional-hazards. RESULTS: Patients received a median number of 2 lines of chemotherapy. Median OS was 6.7, 15.2 and 18.2 months for patients who received 1, 2 and 3 lines of chemotherapy, respectively. Patients treated with FOLFIRINOX had a significantly extended OS of 23.8 months (log-rank test: p = 0.018). The univariate cox regression analysis identified several clinical parameters associated with survival (e.g. albumin, bilirubin, carcinoembryonic antigen, carbohydrate antigen 19-9 levels). CONCLUSIONS: Our study provides real-world data on the prognosis of ABTC including survival times for patients receiving third and later lines of chemotherapy. LAY SUMMARY: Real-world data depicting the outcome of patients with advanced biliary tract cancer outside the framework of controlled trials remain rare despite being extremely important for clinical decision-making. This study therefore provides important real-world data on the established first- and second-line treatments with gemcitabine + cisplatin and FOLFOX, as well as on other chemotherapy regimens or later lines of chemotherapy. It further demonstrates that the use of FOLFIRINOX is associated with promising survival and that there is an association between various clinical parameters such as pre-therapeutic albumin, bilirubin or carbohydrate antigen 19-9 levels and survival.

[Recommendations for Drug Treatment in Patients with Multimorbidity]. / Entwicklung von Empfehlungen zum Management von Arzneimitteltherapie bei Multimorbidität.

Applying guidelines in patients with multimorbidity can result in dangerous or contraindicated drug-drug and drug-disease-interactions. A representative working group of medical scientific associations identifies such therapeutic conflicts and develops management strategies that will be published as a formally consensus based (S2K) guideline. Rational, aims and methods used are described, as well as evaluation and updating of recommendations.

[Perspectives 2025 - Positions of the German Society of Internal Medicine]. / Perspektiven 2025 ­ ein Positionspapier der Deutschen Gesellschaft für Innere Medizin.

Celebrating the 200th anniversary of its founder, Friedrich Theodor von Frerichs, the German Society of Internal Medicine (DGIM) publishes perspectives for its work in the coming years, which will be shaped by challenges for medicine and science. Based on ten critically analyzed topics - namely physicians as researchers, "choosing wisely", digital medicine, the economization of medicine, medical education, demographic changes and multimorbidity, systems medicine, infectious diseases and hygiene, intensive care and emergency departments, and nursing and medical assistance jobs - this paper outlines the fundamental positions of the society.

Leaving colorectal polyps in place can be achieved with high accuracy using blue light imaging (BLI).

OBJECTIVES: A negative predictive value of more than 90% is proposed by the American Society of Gastrointestinal Endoscopy Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) statement for a new technology in order to leave distal diminutive colorectal polyps in place without resection. To our knowledge, no prior prospective study has yet evaluated the feasibility of the most recently introduced blue light imaging (BLI) system for real-time endoscopic prediction of polyp histology for the specific endpoint of leaving hyperplastic polyps in place. AIMS: Prospective assessment of real-time prediction of colorectal polyps by using BLI. MATERIAL AND METHODS: In total, 177 consecutive patients undergoing screening or surveillance colonoscopy were included. Colorectal polyps were evaluated in real-time by using high-definition endoscopy and the BLI technology without optical magnification. Before resection, the endoscopist described each polyp according to size, shape and surface characteristics (pit and vascular pattern, colour and depression), and histology was predicted with a level of confidence (high or low). RESULTS: Histology was predicted with high confidence in 92.5% of polyps. Sensitivity of BLI for prediction of adenomatous histology was 92.68%, with a specificity and accuracy of 94.87 and 93.75%, respectively. Following the recommendation of the PIVI statement, positive and negative predictive values were calculated with values of 95 and 92.5%, respectively. Prediction of surveillance based on both US and European guidelines was correctly predicted in 91% of patients. CONCLUSION: The most recently introduced BLI technology is accurate enough to leave distal colorectal polyps in place without resection. BLI also allowed for assignment of postpolypectomy surveillance intervals. This approach therefore has the potential to reduce costs and risks associated with the redundant removal of diminutive colorectal polyps.

The impact of patient and tumour baseline characteristics on the overall survival of patients with advanced hepatocellular carcinoma treated with sorafenib.

BACKGROUND: Impact of patient and tumour baseline characteristics on the overall survival is not well characterized in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. AIMS/METHODS: Univariate/multivariate analyses were conducted to identify retrospectively the impact of baseline characteristics on the survival of 110 patients with advanced HCC treated with sorafenib. RESULTS: Median survival of the whole cohort was 6.7 months, median survival in Child-Pugh A, B, C patients was 10.5, 6.1 and 3.0 months and median survival of patients with Barcelona Clinic Liver Cancer (BCLC) stage C/D was 6.8/2.6 months. Presence of ascites, presence of macrovascular invasion and BCLC stage D (mainly determined by Child-Pugh C status and Eastern Cooperative Oncology Group Performance Status>2) remained independent prognostic factors for the survival on multivariate analysis. Particularly, the presence of macrovascular invasion significantly influenced survival both in patients with liver cirrhosis Child-Pugh A and Child-Pugh B. CONCLUSION: Well maintained liver function and performance status are prerequisites for sorafenib treatment in patients with advanced HCC. Our findings do not support routine clinical use of sorafenib in Child-Pugh B patients. Evaluation of ascites and particularly macrovascular invasion might help to identify patients more likely to benefit from sorafenib treatment.

AFP measurement in monitoring treatment response of advanced hepatocellular carcinoma to sorafenib: case report and review of the literature.

BACKGROUND: The multi-targeted tyrosine kinase inhibitor sorafenib was the first agent to demonstrate a significant improvement in overall survival in patients with advanced hepatocellular carcinoma (HCC). However, survival under sorafenib treatment is still lower than 1 year in most patients in clinical practice. Sorafenib rarely produces radiological tumor regression, pointing out limitations in using conventional radiological assessment of response to targeted therapy. Serial alpha-fetoprotein (AFP) measurement may be useful in monitoring treatment response in patients with advanced HCC undergoing systemic therapy; however, this approach is poorly defined for the case of sorafenib. CASE REPORT: We herein report the case of a 48-year-old patient with advanced HCC presenting with normalization of highly elevated AFP levels after 5 months of reduced-dose sorafenib treatment, resulting in a sustained radiological and clinical response. CONCLUSIONS: Complete response to sorafenib may be possible in a small subgroup of patients with advanced HCC, strongly depending on one or more of the targets inhibited by sorafenib. Serial AFP measurement may provide additional information in monitoring treatment response to sorafenib and should be evaluated in future clinical trials in advanced HCC.

Interleukin-6 is essential for zwitterionic polysaccharide-mediated abscess formation.

Abscess formation associated with secondary peritonitis causes severe morbidity and can be fatal. Formation of abscesses requires the presence of CD4+ T-cells. Zwitterionic polysaccharides (ZPSs) represent a novel class of immunomodulatory bacterial antigens that stimulate CD4+ T-cells in a major histocompatibility complex (MHC) class II-dependent manner. The capsular polysaccharide Sp1 of Streptococcus pneumoniae serotype 1 possesses a zwitterionic charge with free amino groups and promotes T-cell-dependent abscess formation in an experimental mouse model. So far, nothing is known about the function of Interleukin (IL)-6 in intraperitoneal abscess formation. Here, we demonstrate that macrophages and dendritic cells (DCs), the most prevalent professional antigen-presenting cells involved in the formation of abscesses, secrete Interleukin (IL)-6 and are incorporated in the abscess capsule. Sp1 inhibits apoptosis of CD4+ T-cells and causes IL-17 expression by CD4+ T-cells in an IL-6-dependent manner. Abrogation of the Sp1-induced pleiotropic effects of IL-6 in IL-6-deficient mice and mice treated with an IL-6-specific neutralizing antibody results in significant inhibition of abscess formation. The data delineate the essential role of IL-6 in the linkage of innate and adaptive immunity in polysaccharide-mediated abscess formation.