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.

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.

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.

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.

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.

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.

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.

A New Nomogram-Based Prediction Model for Postoperative Outcome after Sigmoid Resection for Diverticular Disease.

Background and Objectives: Sigmoid resection still bears a considerable risk of complications. The primary aim was to evaluate and incorporate influencing factors of adverse perioperative outcomes following sigmoid resection into a nomogram-based prediction model. Materials and Methods: Patients from a prospectively maintained database (2004-2022) who underwent either elective or emergency sigmoidectomy for diverticular disease were enrolled. A multivariate logistic regression model was constructed to identify patient-specific, disease-related, or surgical factors and preoperative laboratory results that may predict postoperative outcome. Results: Overall morbidity and mortality rates were 41.3% and 3.55%, respectively, in 282 included patients. Logistic regression analysis revealed preoperative hemoglobin levels (p = 0.042), ASA classification (p = 0.040), type of surgical access (p = 0.014), and operative time (p = 0.049) as significant predictors of an eventful postoperative course and enabled the establishment of a dynamic nomogram. Postoperative length of hospital stay was influenced by low preoperative hemoglobin (p = 0.018), ASA class 4 (p = 0.002), immunosuppression (p = 0.010), emergency intervention (p = 0.024), and operative time (p = 0.010). Conclusions: A nomogram-based scoring tool will help stratify risk and reduce preventable complications.

Are sleep disorders associated with the risk of gastrointestinal cancer?-A case-control study.

PURPOSE: Sleep disorders are among the most common health problems worldwide and are linked to a variety of physical and mental health problems. Recently, there has been increasing evidence of an association between sleep disorders and cancer risk. We aimed to investigate this association specifically for cancers of the gastrointestinal (GI) tract. METHODS: Using the DA database (IQVIA), adult patients diagnosed with GI cancer between January 2010 and December 2022 were retrospectively compared to a 1:1 propensity score-matched cohort of patients without cancer. The outcome of the study was the association between sleep disorders and subsequent diagnosis of GI cancer. To determine whether sleep disorders were more common in patients with GI cancer than in patients without GI cancer, logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI). RESULTS: After matching, 37,161 cases with GI cancer and 37,161 controls without cancer were available for analysis. No association with cancer was found for sleep disorders in the overall history before the index date (OR 1.04; 95% CI 0.96-1.12), but considering sleep disorders documented within 1 year before the index date showed a positive association with GI cancer overall (OR 1.20; 95% CI 1.08-1.34). Stratified analyses by cancer site revealed higher odds of sleep disorders prior to diagnosis of gastric, pancreatic, and colorectal cancer. CONCLUSION: Our findings suggest that sleep disorders might be indicative of short-term health outcomes, including GI cancer, suggesting a role for sleep disorder screening in the context of cancer prevention efforts.

The Postoperative Effect of Sugammadex versus Acetylcholinesterase Inhibitors in Colorectal Surgery: An Updated Meta-Analysis.

BACKGROUND: the aim of this meta-analysis was to evaluate the postoperative effects of neuromuscular blockade reversal with sugammadex compared with acetylcholinesterase inhibitors in colorectal surgery. METHODS: A systematic literature search was performed for studies comparing the postoperative course of patients receiving neuromuscular blockade reversal with either sugammadex or acetylcholinesterase inhibitors (control) after colorectal surgery. Data from eligible studies were extracted, qualitatively assessed, and included in a meta-analysis. Odds ratios and standardized mean differences with 95% confidence intervals (CIs) were calculated. RESULTS: Five studies with a total of 1969 patients were included (sugammadex n = 1137, control n = 832). Sugammadex reversal resulted in a significantly faster return of defecation or flatus after surgery compared to acetylcholinesterase inhibitors (SMD 13.01, 95% CI 6.55-19.46, p = < 0.0001). There were no significant differences between the two groups in other clinical outcomes such as surgical morbidity and length of hospital stay. CONCLUSION: The present data support the beneficial impact of sugammadex on gastrointestinal motility after colorectal surgery. However, the effect of sugammadex on the prevention of surgical complications and a prolonged hospital stay is diminishing. Larger randomized controlled trials with standardized study protocols are needed to validate the results presented here.

Non-alcoholic fatty liver disease (NAFLD) is associated with an increased incidence of chronic kidney disease (CKD).

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in the western world. The excess mortality in NAFLD patients is strongly related to extrahepatic comorbidities. Recently, an association between NAFLD and chronic kidney disease (CKD) has been reported in various populations. METHODS: Based on the IQVIA Disease Analyzer database, this retrospective study examined two cohorts from Germany matched for sex, age, index year, annual visit frequency, hypertension, and diabetes, including 92,225 patients with and without NAFLD. The incidence of CKD was assessed as a function of NAFLD using Cox regression models. RESULTS: A total of 92,225 NAFLD patients as well as 92,225 patients without NAFLD were included into analyses. CKD was diagnosed in 19.1% vs. 11.1% of patients with and without NAFLD within the 10 years observation period (p < 0.001). Cox regression confirmed a significant association between NAFLD and CKD with a hazard ratio (HR) of 1.80 (95%CI: 1.73-1.86, p < 0.001). Subgroup analyses revealed that this association was most pronounced in the age group of 18 to 50 years (HR: 2.13, 95%CI: 1.91-2.37, p < 0.001) and among female NAFLD patients (HR 1.85, 95%CI: 1.76-1.95, p < 0.001). CONCLUSIONS: The results of this study confirm a significantly increased risk of developing CKD in a large, real-world cohort of adult NAFLD patients in Germany. Interdisciplinary care of NAFLD patients, which is currently gaining importance worldwide, should be considered to include systematic measures for prevention and/or early detection of CKD with the aim of minimizing long-term renal complications.

Non-alcoholic fatty liver disease is associated with an increased risk of type 2 diabetes.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease worldwide and represents the leading cause of liver-related morbidity and mortality. Its all-cause mortality is often driven by co-existing metabolic diseases such as type 2 diabetes (T2DM), which share many pathophysiological characteristics. The risk of developing T2DM among NAFLD patients in Germany is only poorly described. METHODS: A cohort of 17 245 NAFLD patients and a propensity score-matched cohort of equal size were identified from the Disease Analyzer database (IQVIA) between 2005 and 2020. The incidence of T2DM was evaluated as a function of NAFLD during a 5-year study period using Cox-regression models. RESULTS: Within 5 years of the index date, 18.8% and 11.7% of individuals with and without NAFLD were diagnosed with T2DM ( P  < 0.001). Regression analysis revealed a hazard ratio of 1.77 [95% confidence interval (CI), 1.68-1.88] for the development of T2DM among NAFLD patients. Subgroup analyses confirmed this association for all age groups (18-50, 51-60, 61-70 and >70 years), male and female patients, as well as normal weight (BMI < 25 kg/m 2 ), overweighted (BMI 25-30 kg/m 2 ) and obese (BMI > 30 kg/m 2 ) patients. CONCLUSION: Our data revealed a significantly increased incidence of T2DM among NAFLD patients in Germany. Given the dramatically increasing global relevance of NAFLD, we believe that prevention and regular screening programs for T2DM in NAFLD patients could help to reduce its high mortality and morbidity in the future.

Adult Body Height Is Associated with the Risk of Type 2 but Not Type 1 Diabetes Mellitus: A Retrospective Cohort Study of 783,029 Individuals in Germany.

BACKGROUND: Diabetes mellitus is a major global health burden associated with high morbidity and mortality. Although a short adult body height has been associated with increased risk of type 2 diabetes (T2D), there are large inconsistencies between the studies. Therefore, we aimed to investigate the association between body height and T2D in a large cohort of adult outpatients in Germany. METHODS: A total of 783,029 adult outpatients with available body height data from the Disease Analyzer (IQVIA) database were included in Germany between 2010 and 2020. The incidence of diabetes mellitus (type 1 and type 2) was evaluated as a function of the patients' body height stratified by age, sex, and body-mass-index (BMI). RESULTS: In both women and men in all age groups, incidence of T2D decreased with the increasing body height (<50, 51-60, 61-70, and >70 years). There was no association between the body height and the individual HbA1c value. In multivariable Cox regression analyses adjusted for patient age and BMI, hazard ratios for the development of T2D were 1.15 (95% CI: 1.13-1.17) for each 10 cm decrease in body height in women and 1.10 (95% CI: 1.09-1.12) in men. No significant association was found between body height and the development of T1D. CONCLUSIONS: We present the first data from a large cohort of outpatients in Germany, providing strong evidence for an association between adult body height and T2D. These data add to the current literature and might help in implementing body height into existing diabetes risk stratification tools to further reduce morbidity and mortality worldwide.

Analyses of sex-based clinicopathological differences among patients with gastrointestinal neuroendocrine neoplasms in Europe.

BACKGROUND: Previous studies have found variations in cancer types, tumor progression, and disease outcomes between men and women. However, there is limited knowledge of the effect of sex on gastrointestinal neuroendocrine neoplasms (GI-NENs). METHODS: We identified 1354 patients with GI-NEN from the IQVIA's Oncology Dynamics database. Patients were derived from four European countries (Germany, France, the United Kingdom (UK), Spain). Clinical and tumor related characteristics including patients' age, tumor stage, tumor grading and differentiation, frequency and sites of metastases, as well as co-morbidities were analyzed as a function of patients´ sex. RESULTS: Among the 1354 included patients, 626 were female and 728 were male. The median age was similar between both groups (w: 65.6 years, SD: 12.1 vs. m: 64.7 years; SD: 11.9; p = 0.452). UK was the country with the most patients, however, there was no differences in the sex ratio between the different countries. Among documented co-morbidities, asthma was more often diagnosed in women (7.7% vs. 3.7%), while COPD was more prevalent in men (12.1% vs. 5.8%). The ECOG performance states was comparable between females and males. Of note, the patients´ sex was not associated with tumor origin (e.g., pNET or siNET). Females were overrepresented among G1 tumors (22.4% vs. 16.8%), however, median proliferation rates according to Ki-67 were similar between both groups. In line, no differences in tumor stages was found and rates of metastases as well as the specific sites of metastases were similar between males and females. Finally, no differences in the applied tumor specific treatments between the both sexes became apparent. CONCLUSION: Females were overrepresented among G1 tumors. No further sex-specific differences became apparent, highlighting that sex-related factors might play a rather subordinate role in the pathophysiology of GI-NENs. Such data may help to better understand the specific epidemiology of GI-NEN.

The Association between Antibiotic Use and the Incidence of Heart Failure: A Retrospective Case-Control Study of 162,188 Outpatients.

The pathogenesis of heart failure (HF) is multifactorial, and is characterized by structural, cellular, and molecular remodeling processes. Inflammatory signaling pathways may play a particularly understudied role in HF. Recent data suggest a possible impact of antibiotic use on HF risk. Therefore, the aim of this retrospective case-control study was to investigate the association between antibiotic use and the incidence of HF. Data from the Disease Analyzer (IQVIA) database for patients diagnosed with HF and matched non-HF controls from 983 general practices in Germany between 2000 and 2019 were analyzed. A multivariable conditional logistic regression model was performed. Regression models were calculated for all patients, as well as for data stratified for sex and four age groups. A total of 81,094 patients with HF and 81,094 patients without HF were included in the analyses. In the regression analysis, low, but not high, total antibiotic use was significantly associated with a slightly lower HF risk compared with non-antibiotic users (OR: 0.87; 95% CI: 0.85-0.90). A significantly lower HF incidence was observed for sulfonamides and trimethoprim (OR: 0.87, 95% CI: 0.81-0.93) and for macrolides (OR: 0.87, 95% CI: 0.84-0.91). High use of cephalosporins, however, was associated with an increased HF risk (OR: 1.16; 95% CI: 1.11-1.22). In conclusion, this study from a large real-world cohort from Germany provides evidence that the use of different antibiotics may be associated with HF risk in a dose-dependent manner, possibly due to involved inflammatory processes. Overall, this study should provide a basis for future research to offer new therapeutic strategies for HF patients to improve their limited prognosis.