ADAMTS12 promotes fibrosis by restructuring extracellular matrix to enable activation of injury-responsive fibroblasts.

Fibrosis represents the uncontrolled replacement of parenchymal tissue with extracellular matrix (ECM) produced by myofibroblasts. While genetic fate-tracing and single-cell RNA-Seq technologies have helped elucidate fibroblast heterogeneity and ontogeny beyond fibroblast to myofibroblast differentiation, newly identified fibroblast populations remain ill defined, with respect to both the molecular cues driving their differentiation and their subsequent role in fibrosis. Using an unbiased approach, we identified the metalloprotease ADAMTS12 as a fibroblast-specific gene that is strongly upregulated during active fibrogenesis in humans and mice. Functional in vivo KO studies in mice confirmed that Adamts12 was critical during fibrogenesis in both heart and kidney. Mechanistically, using a combination of spatial transcriptomics and expression of catalytically active or inactive ADAMTS12, we demonstrated that the active protease of ADAMTS12 shaped ECM composition and cleaved hemicentin 1 (HMCN1) to enable the activation and migration of a distinct injury-responsive fibroblast subset defined by aberrant high JAK/STAT signaling.

What Is the Link between Attention-Deficit/Hyperactivity Disorder (ADHD) and Dyslipidemia in Adults? A German Retrospective Cohort Study.

Background: Alterations in the serum lipid profile have been suspected in many psychiatric disorders, such as schizophrenia and depression. However, studies on lipid status in attention-deficit/hyperactivity disorder (ADHD) are sparse and inconsistent. Methods: Using the nationwide, population-based IQVIA Disease Analyzer database, this retrospective cohort study included 5367 outpatients from general practices in Germany aged ≥18 years with a documented first diagnosis of ADHD between January 2005 and December 2021 and 26,835 propensity score-matched individuals without ADHD. Study outcomes were the first diagnosis of lipid metabolism disorders as a function of ADHD within up to 10 years of the index date. The cumulative 10-year incidence was analyzed using Kaplan-Meier curves and compared using the log-rank test. In addition, univariate Cox regression analyses were performed. Results: In the regression analysis, there was no significant association between ADHD and subsequent lipid metabolism disorders in the total population (HR: 0.94; 95% CI: 0.83-1.08), among women (HR: 1.04; 95% CI: 0.84-1.28), and among men (HR: 0.89; 95% CI: 0.74-1.06). In addition, no significant association was observed in the disease-stratified analyses. Conclusions: The findings of this study indicate that ADHD does not exert an influence on lipid metabolism. However, further investigation is warranted, particularly with respect to pharmacological interventions.

Association between Helicobacter pylori and its eradication and the development of cancer.

BACKGROUND: Helicobacter pylori (H. pylori) is a gram-negative gastrointestinal pathogen that colonises the human stomach and is considered a major risk factor for gastric cancer and mucosa-associated lymphoid tissue lymphoma. Furthermore, H. pylori is a potential trigger of a wide spectrum of extragastric cancer entities, extraintestinal chronic inflammatory processes and autoimmune diseases. In the present study, we evaluated the association between H. pylori infection and its eradication with the development of subsequent gastrointestinal and non-gastrointestinal cancer. METHODS: We identified 25 317 individuals with and 25 317 matched individuals without a diagnosis of H. pylori from the Disease Analyzer database (IQVIA). A subsequent cancer diagnosis was analysed using Kaplan-Meier and conditional Cox-regression analysis as a function of H. pylori and its eradication. RESULTS: After 10 years of follow-up, 12.8% of the H. pylori cohort and 11.8% of the non-H. pylori cohort were diagnosed with cancer (p=0.002). Results were confirmed in regression analysis (HR: 1.11; 95% CI 1.04 to 1.18). Moreover, a non-eradicated H. pylori status (HR: 1.18; 95% CI 1.07 to 1.30) but not an eradicated H. pylori status (HR: 1.06; 95% CI 0.97 to 1.15) was associated with a subsequent diagnosis of cancer. In subgroup analyses, H. pylori eradication was negatively associated with bronchus and lung cancer (HR: 0.60; 95% CI 0.44 to 0.83). CONCLUSION: Our data from a large outpatient cohort in Germany reveal a distinct association between H. pylori infection and the subsequent development of cancer. These data might help to identify patients at risk and support eradication strategies in the future.

Trends and outcomes in colorectal cancer surgery: a multicenter cross-sectional study of minimally invasive versus open techniques in Germany.

BACKGROUND: The objective of this study was to assess the trend from open to modern minimally invasive (laparoscopic and robot-assisted) surgical techniques for colorectal cancer (CRC) in Germany, with a particular focus on hospital mortality, postoperative complications, and length of hospital stay. METHODS: A multicenter cross-sectional study was conducted using data from 36 German hospitals, encompassing 1,250,029 cases from January 2019 to December 2023. The study included all hospitalized patients aged ≥ 18 with CRC who underwent surgery. Surgical cases were categorized as open or minimally invasive. Outcomes assessed included in-hospital mortality, morbidity, and hospital length of stay. Statistical analyses involved multivariable logistic and linear regression models adjusted for main diagnosis, metastasis presence, age, sex, and comorbidities. RESULTS: The study included 4525 CRC cases: 2767 underwent open surgery and 1758 underwent minimally invasive surgery (173 robotic). In-hospital mortality was significantly higher in open surgery (6.1% vs. 1.7%). Open surgery was also significantly associated with higher rates of acute post-hemorrhagic anemia (OR: 2.38; 95% CI: 1.87-3.02), respiratory failure (OR: 1.71; 95% CI: 1.34-2.18), and intraoperative and postprocedural complications (OR: 3.64; 95% CI: 2.83-4.70). Average hospital stay was longer for open surgery (19.5 days vs. 11.0 days). CONCLUSION: Despite the advantages of minimally invasive surgery, including reduced mortality, morbidity, and shorter hospital stays, open surgery remains the predominant approach for CRC in Germany. These findings underscore the need for increased adoption of minimally invasive techniques and highlight the potential benefits of shifting toward minimally invasive methods to enhance the overall quality of CRC care.

Temporal Trends in Mental Disorder Rates among Patients with Colorectal Cancer: A Comprehensive Analysis.

Background: Colorectal cancer (CRC) stands as one of the most prevalent and burdensome malignancies worldwide. Similar to other cancers, CRC has been associated with the development of psychiatric diseases, including anxiety and depression. However, temporal trends in psychiatric disorders rates within CRC patients have not been investigated so far. Methods: The present study included 15,619 individuals with colorectal cancer and 78,095 propensity score-matched individuals without cancer, who were identified within the Disease Analyzer (IQVIA) database in Germany between 2005 and 2022. Cox regression analysis was conducted to assess the association between CHC and subsequent psychiatric diseases, including depression, anxiety disorders, and adjustment disorder, by period (2005-2010, 2011-2016, 2017-2022). Results: The 12-month cumulative incidence of any psychiatric disorder diagnosis in the CRC cohort increased from 6.3% in 2005-2010 to 8.2% in 2017-2022. The strongest increase was observed for reaction to severe stress and adjustment disorder (1.0% in 2005-2010 to 2.6% in 2017-2022). Notably, the strong increase in psychiatric disorders was not specific for cancer patients since a slight increase in psychiatric disorders was also observed in the non-cancer cohort. Regression analyses revealed that CRC was strongly and significantly associated with an increased risk of depression, anxiety disorders, reaction to severe stress and adjustment disorders, as well as any psychiatric disorder. Of note, the extent of the association was stronger in 2017-2022 compared to 2005-2010, clearly proving a "real" increase in the rates of psychiatric disorders over time. Conclusions: This study presents novel data from a large cohort of outpatients in Germany, providing strong evidence for an increase in psychiatric disorders in the recent years. These findings contribute to the existing body of literature and should trigger the recognition of psychiatric problems in cancer survivors.

Risk of Lymphoma and Leukemia in Thyroid Cancer Patients: A Retrospective Cohort Study in Germany.

Thyroid cancer is the ninth most common cancer worldwide. While differentiated thyroid cancer (DTC) has a high survival rate, concerns arise regarding optimal treatment strategies and potential long-term risks, including second primary malignancies (SPMs), associated with therapies such as radioiodine (RAI). The aim of the present study was to investigate the association between thyroid cancer and the incidence of subsequent lymphoma and leukemia in Germany. This retrospective cohort study used the IQVIA TM Disease Analyzer database and included adults with a first documented diagnosis of thyroid cancer between January 2005 and December 2021 as well as propensity score matched individuals without thyroid cancer in 1284 general practices. Univariate Cox regression models were performed to examine the association between thyroid cancer and the incidence of subsequent lymphoma and leukemia. A total of 4232 thyroid cancer patients (mean age: 54.2 years; 73.6% female) and 21 160 controls (mean age: 54.2 years; 72.6% female) were available for analyses. Thyroid cancer was significantly associated with a higher lymphoma incidence (HR: 3.35, 95% CI: 2.04-5.52), especially in men (HR: 5.37) and those aged 61-70 years. Leukemia incidence was not significantly associated with thyroid cancer (HR: 1.79, 95% CI: 0.91-3.53), although associations were notable in younger age groups. Thyroid cancer is positively associated with a risk of subsequent lymphoma, highlighting the need for vigilant surveillance and tailored treatment strategies. While the association with leukemia is less pronounced, close surveillance remains critical, especially in younger patients.

Trends in hypertension and hypertension treatment in primary care in general practices in Germany between 2013 and 2022.

Background: There is a scarcity of data on the epidemiology of hypertension and its treatment in Germany in recent years. Objectives: The present study aimed to investigate trends in the number of adults diagnosed with hypertension and those being prescribed antihypertensive drugs each year in general practices from this country between 2013 and 2022. Methods: This retrospective cohort study used data of adults aged ≥18 years continuously collected from 336 general practices in Germany (IQVIA) during 2013-2022. The diagnosis of hypertension and the prescription of antihypertensive drugs were coded using the ICD-10 and the EphMRA classification, respectively. Covariates included the total number of patients, mean (SD) age of patients, and proportion of women per practice. Trends in hypertension diagnosis and treatment were studied using linear regression models. Results: The mean (SD) total number of patients per practice ranged from 2,235 (1,055) in 2013-2,845 (2,090) in 2021 (p-value < 0.001). The mean (SD) age of patients per practice was between 48.4 (21.5) and 50.5 (21.4) years, while the proportion of women was 52.1%-53.9% (p-values < 0.001). After adjusting for covariates, there was a significant decrease in the number of patients diagnosed with hypertension (beta coefficient = -7.91, p-value < 0.001) and treated with any antihypertensive drug per practice per year between 2013 and 2022 (beta coefficient = -5.40, p-value < 0.001). Conclusion: This study identified decreasing trends in the diagnosis and treatment of hypertension in general practices in Germany in the last decade. These data may suggest that the prevention of hypertension has improved in this country in recent years.

Hemorrhoids are associated with an increased risk of depression in Germany: A retrospective cohort study in primary care outpatients.

BACKGROUND: The aim of the present study was to analyze the cumulative incidence of depression diagnosis in patients with hemorrhoids and to evaluate the association between hemorrhoids and subsequent depression diagnosis. METHODS: This retrospective cohort study was based on electronic medical records from the Disease Analyzer database (IQVIA) and included 87,264 individuals with hemorrhoids (mean age: 54.2 years; 42% women) and 87,264 propensity score-matched individuals without hemorrhoids in 1284 general practices in Germany between January 2005 and December 2021. Univariable Cox regression analysis was conducted to assess the association between hemorrhoids and depression. RESULTS: After up to 10 years of follow-up, 21.4% of patients with hemorrhoids versus 16.3% of the matched cohort (p < 0.001) were diagnosed with depression. There was a significant association between hemorrhoids and a subsequent diagnosis of depression (HR: 1.32; 95% CI: 1.28-1.37), which was confirmed in age- and sex-stratified analyses. The association was stronger with increasing degree of hemorrhoids, from HR: 1.29 (95% CI: 1.15-1.45) for Grade 1 to HR: 1.73 (95% CI: 1.11-2.69) for Grade 4 compared to no hemorrhoids. CONCLUSIONS: The present study provides compelling evidence of an association between hemorrhoids and subsequent depression. Addressing the mental health of individuals with hemorrhoids may not only improve their overall well-being but could also lead to better treatment outcomes for the primary condition.

Metabolic Signaling in Cancer Metastasis.

Metastases, which are the leading cause of death in patients with cancer, have metabolic vulnerabilities. Alterations in metabolism fuel the energy and biosynthetic needs of metastases but are also needed to activate cell state switches in cells leading to invasion, migration, colonization, and outgrowth in distant organs. Specifically, metabolites can activate protein kinases as well as receptors and they are crucial substrates for posttranslational modifications on histone and nonhistone proteins. Moreover, metabolic enzymes can have moonlighting functions by acting catalytically, mainly as protein kinases, or noncatalytically through protein-protein interactions. Here, we summarize the current knowledge on metabolic signaling in cancer metastasis. SIGNIFICANCE: Effective drugs for the prevention and treatment of metastases will have an immediate impact on patient survival. To overcome the current lack of such drugs, a better understanding of the molecular processes that are an Achilles heel in metastasizing cancer cells is needed. One emerging opportunity is the metabolic changes cancer cells need to undergo to successfully metastasize and grow in distant organs. Mechanistically, these metabolic changes not only fulfill energy and biomass demands, which are often in common between cancer and normal but fast proliferating cells, but also metabolic signaling which enables the cell state changes that are particularly important for the metastasizing cancer cells.

Is there a link between appendicitis and the risk of diverticular disease?: a large German cohort study.

PURPOSE: Appendicitis, characterized by inflammation of the vermiform appendix, is a common abdominal emergency necessitating appendectomy. Recent evidence suggests a potential link between appendicitis and subsequent diverticular disease, yet population-based studies investigating this association are limited. METHODS: Utilizing the Disease Analyzer database encompassing data from over 1000 primary care practices in Germany, we conducted a retrospective cohort study. We included 25,379 adults diagnosed with appendicitis and an equal number of matched controls without appendicitis. The incidence of diverticular disease over a 10-year follow-up period was compared between the two cohorts. Cox regression analysis was performed to assess the association between appendicitis and diverticular disease, adjusting for potential confounders. RESULTS: Our findings revealed a significant association between appendicitis and subsequent diverticular disease (HR: 1.76; 95% CI: 1.57-1.97), with an increased risk observed across all age groups. Notably, this association was stronger in men (HR: 2.00; 95% CI: 1.68-2.37) than in women (HR: 1.58; 95% CI: 1.36-1.84). The cumulative 10-year incidence of diverticular disease was higher in patients with appendicitis (6.5%) compared to those without (3.6%). Additionally, we observed a clear age-dependent increase in the incidence of diverticular disease. CONCLUSION: This large-scale population-based study provides valuable insights into the interaction between appendicitis and diverticular disease. The study underscores the need for further research elucidating the underlying mechanisms linking appendicitis to diverticular disease. Probiotics emerge as a potential therapeutic avenue warranting exploration in the management of both conditions. These findings have important implications for clinical practice, highlighting the importance of considering appendicitis as a potential risk factor for diverticular disease, particularly in men. Further investigation is warranted to validate these findings and explore potential therapeutic interventions targeting the shared pathophysiological pathways underlying both conditions.

Associating Appendicitis with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Novel Insight into an Unexpected Connection.

BACKGROUND: The gut microbiome modulates the liver immune microenvironment and is deeply integrated into the pathophysiology of metabolic dysfunction-associated steatotic liver disease (MASLD). Appendectomies, which are performed in almost all patients diagnosed with appendicitis, cause long-term alterations to the gut microbiome, providing a potential link with the development of MASLD. We therefore investigated a potential link between appendicitis and the presence of MASLD in a large cohort of outpatients in Germany. METHODS: The present study included 26,717 individuals with and 26,717 without appendicitis. Univariable Cox-regression analyses were conducted to assess the association between appendicitis and MASLD. RESULTS: During the long-term follow-up, 4.8% of patients with appendicitis and 3.4% of those in the non-appendicitis group were diagnosed with MASLD (p < 0.001), corresponding to an incidence of 5.4 (appendicitis cohort) versus 3.5 (non-appendicitis cohort) cases per 1000 patient years. These findings were confirmed in regression analysis, revealing a strong and statistically significant association between appendicitis and the development of MASLD (HR: 1.57; 95% CI: 1.39-1.78). This link was observed for all age groups and was independent of patients' sex. CONCLUSION: We provide evidence from a large cohort of outpatients in Germany suggesting a link between appendicitis and MASLD. This might help to better stratify patients according to their individual risk for the development of chronic liver diseases.

Cancer Risk in Patients with Down Syndrome-A Retrospective Cohort Study from Germany.

BACKGROUND: Individuals with Down syndrome are thought to have a unique tumor profile. METHODS: Using the IQVIA Disease Analyzer database, patients aged ≥18 years diagnosed with Down syndrome in German general practices between 2005 and 2021 were compared with patients without Down syndrome for cancer incidence, adjusting for age, sex, average annual visit frequency, and comorbidity. The 5-year cumulative incidence of cancer overall and specific cancers was analyzed using Kaplan-Meier curves and compared using the log-rank test. In addition, univariable Cox regression analysis was performed. RESULTS: A total of 2438 patients with Down syndrome and 12,190 patients without Down syndrome were included; 3.9% of patients without Down syndrome and 3.1% of patients with Down syndrome were diagnosed with cancer (p = 0.143). Regression analysis showed no significant association between Down syndrome and subsequent cancer in the total population (HR: 0.79; 95% CI: 0.57-1.09), in women (HR: 0.89; 95% CI: 0.56-1.37), or in men (HR: 0.69; 95% CI: 0.43-1.11). Analyses by cancer type and sex showed a strong but not significant negative association between Down syndrome and breast cancer in women (HR: 0.33; 95% CI: 0.12-0.93). CONCLUSIONS: Our results could form the basis for future studies to clarify whether and to what extent an adapted screening program needs to be modified for individuals with Down syndrome due to the particular cancer distribution pattern.

In-Hospital Mortality and Associated Factors among Colorectal Cancer Patients in Germany.

BACKGROUND: In the present study, we used the data from 14 hospitals to systematically evaluate the in-hospital mortality of patients with colorectal cancer as well as its influencing factors in Germany. METHODS: This multicenter cross-sectional study included hospitalized patients with a main diagnosis of colorectal cancers in the period between January 2019 and July 2023. The outcome of the study was the prevalence of in-hospital mortality. To access the associations between demographic and clinical variables and in-hospital mortality, univariable and multivariable logistic regression analyses were conducted. RESULTS: A total of 4146 colorectal cancer patients (mean age: 70.9 years; 45.3% female) were included. The in-hospital mortality rate was 8.7%. In a multivariable regression, seven variables were significantly associated with an increased in-hospital mortality, including ages of 71-80 years (OR: 2.08; 95% CI: 1.01-4.29), an age group >80 years (OR: 2.44; 95% CI: 1.18-5.05) as compared to an age group ≤ 50 years, patient clinical-complexity level (PCCL) 3 (OR: 3.01 95% CI: 1.81-4.99) and PCCL 4 (OR: 3.76; 95% CI: 2.22-6.38) as compared to PCCL 0, the presence of distant metastases (OR: 4.95; 95% CI: 3.79-6.48), renal failure (OR: 2.38; 95% CI: 1.80-3.14), peritonitis (OR: 1.87; 95% CI: 1.23-2.85), acute posthemorrhagic anemia (OR: 1.55; 95% CI: 1.11-2.15), and respiratory failure (OR: 3.28; 95% CI: 2.44-4.41). CONCLUSIONS: Our findings underscore the critical role of renal failure, peritonitis, acute posthemorrhagic anemia, and respiratory failure in influencing the mortality outcomes of colorectal cancer patients during hospitalization. The awareness and management of these risk factors may guide clinicians in formulating targeted interventions to improve patient outcomes and enhance the quality of care for individuals with colorectal cancer.

Prevalence of and Variables Associated with Syncope-Related Injuries and Fractures in Germany: A Cross-Sectional Study in General Practices.

Background: There is a lack of studies investigating the prevalence of syncope-related injuries in a large representative cohort. The aim of this cross-sectional study is to investigate the prevalence of, and variables associated with syncope-related injuries and fractures in a large outpatient population in Germany. Methods: The present study used data from the Disease Analyzer database (IQVIA) and included adults with first-time diagnoses of syncope in 1 of 1284 general practices in Germany between 2005 and 2022 (index date). The prevalence of injuries and separate fractures documented on the index date was examined, and the association of demographic and clinical variables with the risk of syncope-related injuries and fractures was studied using multivariable logistic regression. Results: A total of 143,226 patients (mean age: 57.1 years, 56.9% female) were included in this study. The proportion of injuries was 10.4% and increased from 6.4% in the age group 18-30 to 15.0% in the age group >80 years. Female sex was associated with a slightly higher risk of injury (OR: 1.09; 95% CI: 1.05-1.13) and fractures (OR: 1.17; 95% CI: 1.07-1.28). Osteoporosis was associated with a higher risk of injury (OR: 1.25; 95% CI: 1.16-1.34) and fracture (OR: 1.53; 95% CI: 1.33-1.76), while obesity was only associated with a slightly increased risk of injury. Conclusions: Syncope-related injuries are common among syncope patients. Factors associated with a higher risk of syncope-related injuries, such as female sex, older age, and osteoporosis, can be incorporated into an effective risk stratification and help to improve the outcome of syncope patients.

Association between iron deficiency anemia and subsequent stomach and colorectal cancer diagnosis in Germany.

PURPOSE: Iron deficiency anemia (IDA) is the most common form of anemia worldwide, resulting in a high burden of disease. Accumulating evidence suggests that IDA is associated with the development of gastrointestinal (GI) cancers. METHODS: Data from the IDA database (IQVIA) of primary care practices in Germany of adult patients first diagnosed with IDA between January 2005 and December 2021 were retrospectively analyzed and compared with a 1:1 propensity score-adjusted cohort without IDA. Study outcomes were first stomach cancer or colorectal cancer (CRC) diagnosis up to 10 years after the index date as a function of IDA. RESULTS: A total of 122,502 individuals with IDA and 122,502 individuals without IDA were included. The 10-year cumulative incidence of CRC was 1.4% in the IDA patients compared to 0.8% in the cohort without IDA (p < 0.001). Regression analysis revealed a significant association between IDA and subsequent CRC (HR 2.05; 95% CI 1.83-2.30). Stomach cancer was diagnosed in 0.3% of IDA patients compared to 0.2% in the non-IDA cohort during the 10-year follow-up period (p = 0.002). However, this was significant only in the age group > 80 years (HR 2.73; 95% CI 1.60-4.67) and in men (HR 1.90; 95% CI 1.38-2.61). CONCLUSION: These findings add to the literature and suggest an association between IDA and GI cancers. The extent to which this association is due to GI bleeding or other pathophysiological processes that may be caused by IDA requires further investigation, particularly experimental studies.

Intracorporeal Versus Extracorporeal Colo-colic Anastomosis in Minimally-invasive Left Colectomy: a Systematic Review and Meta-analysis.

PURPOSE: The primary aim was to investigate the operative outcomes of intracorporeal (IA) and extracorporeal (EA) anastomosis in left-sided minimally-invasive colectomy. METHODS: A comprehensive literature search was conducted for studies comparing operative outcomes and follow-up data of IA versus EA in minimally-invasive left colectomy. Studies that investigated recto-sigmoid resections using transanal circular staplers were excluded. Data from eligible studies were extracted, qualitatively assessed, and included in a meta-analysis. Odds ratios (ORs) and mean differences with 95 per cent confidence intervals were calculated. RESULTS: Eight studies with a total of 750 patients were included (IA n = 335 versus EA n = 415). IA was associated with significantly lower overall morbidity (OR 0.40, 95% CI 0.26-0.61, p < 0.0001) and less frequent surgical site infection (SSI) (OR 0.27, 95% CI 0.12-0.61, p = 0.002) as primary outcomes compared to EA. Of the secondary outcomes, length of incision (SMD -2.51, 95% CI -4.21 to -0.81, p = 0.004), time to first oral diet intake (SMD -0.49, 95% CI -0.76 to -0.22, p = 0. 0004) and time to first bowel movement (SMD -0.40, 95% CI -0.71 to -0.09, p = 0.01) were significantly in favor of IA, while operative time was significantly shorter in the EA group (SMD 0.36, 95% CI 0.14-0.59, p = 0.001). CONCLUSIONS: IA proves to be a safe and feasible option as it demonstrates benefits in terms of lower overall morbidity, fewer rates of SSI, smaller incision length, and faster postoperative gastrointestinal recovery despite a longer operative time compared to EA.

Drug landscape in patients receiving general outpatient palliative care in Germany: results from a retrospective analysis of 10,464 patients.

BACKGROUND: According to § 27 and § 87 1b of the German Social Code, Book V, general outpatient palliative care (GOPC) aims to promote, maintain, and improve the quality of life and self-determination of seriously ill people. It should enable them to live in dignity until death in their preferred environment. Instead of a curative approach GOPC treatment focuses on the multiprofessional objective of alleviating symptoms and suffering on a case-by-case basis using medication or other measures, as well as the management of an individual treatment plan. The aim of this study was therefore to investigate to what extent medication differs from 12 months prior GOPC treatment within 12 months following GOPC treatment. METHODS: A retrospective database cross sectional study based on the IQVIA Disease Analyzer (DA) was performed, including adult patients with cancer diagnosis and at least one documentation of palliative support between January 1st, 2018 and December 31st, 2021, in 805 general practices (GP). RESULTS: The results of this study show, that in the context of general general outpatient palliative care, there is a significant increase in the prescription of opioids (18.3% vs. 37.7%), sedatives (7.8% vs. 16.2%) and antiemetics (5.3% vs. 9.7%), as well as a significant reduction in other medications such as statins (21.4% vs. 11.5%), proton pump inhibitors (PPI) (41.2% vs. 35.3%), or antihypertensives (57.5% vs. 46.6%). CONCLUSIONS: Our results support the role of GOPC as an important element in improving pharmacological symptom control and deprescription to improve quality of life of patients at the end of their life.

The Role of Alternative Lymph Node Classification Systems in Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NEN): Superiority of a LODDS Scheme Over N Category in Pancreatic NEN (pNEN).

Lymph node (LN) involvement in gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) has been reported to have prognostic and therapeutic implications. Numerous novel LN classifications exist; however, no comparison of their prognostic performance for GEP-NEN has been done yet. Using a nationwide cohort from the German Neuroendocrine Tumor (NET) Registry, the prognostic and discriminatory power of different LN ratio (LNR) and log odds of metastatic LN (LODDS) classifications were investigated using multivariate Cox regression and C-statistics in 671 patients with resected GEP-NEN. An increase in positive LN (pLN), LNR, and LODDS was associated with advanced tumor stages, distant metastases, and hormonal functionality. However, none of the alternative LN classifications studied showed discriminatory superiority in predicting prognosis over the currently used N category. Interestingly, in a subgroup analysis, one LODDS classification was identified that might be most appropriate for patients with pancreatic NEN (pNEN). On this basis, a nomogram was constructed to estimate the prognosis of pNEN patients after surgery. In conclusion, a more accurate classification of LN status may allow a more precise prediction of overall survival and provide the basis for individualized strategies for postoperative treatment and surveillance especially for patients with pNEN.

Non-Alcoholic Fatty Liver Disease (NAFLD) and risk of new-onset heart failure: a retrospective analysis of 173,966 patients.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) represents the leading cause of chronic liver disease. Its high mortality and morbidity are mainly caused by non-hepatic comorbidities and their clinical complications. Accumulating evidence suggests an association between NAFLD and heart failure (HF), but large-scale data analyses from Germany are scarce. METHODS: Using the Disease Analyzer database (IQVIA), this analysis retrospectively evaluated two cohorts of outpatients with and without NAFLD with respect to the cumulative incidence of HF as the primary outcome between January 2005 and December 2020. Cohorts were propensity score matched for sex, age, index year, yearly consultation frequency, and known risk factors for HF. RESULTS: A total of 173,966 patients were included in the analysis. Within 10 years of the index date, 13.2% vs. 10.0% of patients with and without NAFLD were newly diagnosed with HF (p < 0.001). This finding was supported by univariate Cox regression analysis in which NAFLD was found to be significantly associated with subsequent HF (Hazard Ratio (HR) 1.34, 95% Confidence Interval (CI) 1.28-1.39, p < 0.001). The association between NAFLD and HF was observed across all analysed age groups and as comparable between both men (HR 1.30, 95% CI 1.23-1.38; p < 0.001) and women (HR: 1.37, 95% CI 1.29-1.45; p < 0.001). CONCLUSION: NAFLD is significantly associated with an increased cumulative incidence of HF, which, given its rapidly increasing global prevalence, could be crucial to further reduce its high mortality and morbidity. We recommend risk stratification within a multidisciplinary approach for NAFLD patients, including systematic prevention or early detection strategies for HF.

Prediction of New-Onset Diabetes Mellitus within 12 Months after Liver Transplantation-A Machine Learning Approach.

BACKGROUND: Liver transplantation (LT) is a routine therapeutic approach for patients with acute liver failure, end-stage liver disease and/or early-stage liver cancer. While 5-year survival rates have increased to over 80%, long-term outcomes are critically influenced by extrahepatic sequelae of LT and immunosuppressive therapy, including diabetes mellitus (DM). In this study, we used machine learning (ML) to predict the probability of new-onset DM following LT. METHODS: A cohort of 216 LT patients was identified from the Disease Analyzer (DA) database (IQVIA) between 2005 and 2020. Three ML models comprising random forest (RF), logistic regression (LR), and eXtreme Gradient Boosting (XGBoost) were tested as predictors of new-onset DM within 12 months after LT. RESULTS: 18 out of 216 LT patients (8.3%) were diagnosed with DM within 12 months after the index date. The performance of the RF model in predicting the development of DM was the highest (accuracy = 79.5%, AUC 77.5%). It correctly identified 75.0% of the DM patients and 80.0% of the non-DM patients in the testing dataset. In terms of predictive variables, patients' age, frequency and time of proton pump inhibitor prescription as well as prescriptions of analgesics, immunosuppressants, vitamin D, and two antibiotic drugs (broad spectrum penicillins, fluocinolone) were identified. CONCLUSIONS: Pending external validation, our data suggest that ML models can be used to predict the occurrence of new-onset DM following LT. Such tools could help to identify LT patients at risk of unfavorable outcomes and to implement respective clinical strategies of prevention.