Inflammatory bowel disease is associated with an increase in the incidence of multiple sclerosis: a retrospective cohort study of 24,934 patients.

BACKGROUND: Recent data suggest a potential pathophysiological link between inflammatory bowel disease (IBD) and multiple sclerosis (MS), two immune-mediated diseases both of which can have a significant impact on patients' quality of life. In the present manuscript, we investigate the association between IBD and MS in a German cohort of general practice patients. These results may have important implications for the screening and management of patients with IBD, as well as for further research into the pathophysiological mechanisms underlying both disorders. METHODS: 4,934 individuals with IBD (11,140 with Crohn's disease (CD) and 13,794 with ulcerative colitis (UC)) as well as 24,934 propensity score matched individuals without IBD were identified from the Disease Analyzer database (IQVIA). A subsequent diagnosis of MS was analyzed as a function of IBD using Cox regression models. RESULTS: After 10 years of follow-up, 0.9% and 0.7% of CD and UC patients but only 0.5% and 0.3% of matched non-IBD pairs were diagnosed with MS, respectively (pCD = 0.002 and pUC < 0.001). Both CD (HR: 2.09; 95% CI 1.28-3.39) and UC (HR: 2.35; 95% CI 1.47-3.78) were significantly associated with a subsequent MS diagnosis. Subgroup analysis revealed that the association between both CD and UC and MS was more pronounced among male patients. CONCLUSION: The results of our analysis suggest a notable association between IBD and a subsequent MS diagnosis. These findings warrant further pathophysiological investigation and may have clinical implications for the screening of IBD patients in the future.

Association between inflammatory bowel disease and subsequent depression or anxiety disorders - A retrospective cohort study of 31,728 outpatients.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are characterized by chronic intestinal and systemic inflammation. The extraintestinal sequelae of inflammatory bowel disease (IBD) are major contributors to disease morbidity and significantly affect patients' quality of life. Here, we evaluated the association between IBD and subsequent depression or anxiety disorder in a large outpatient collective from Germany. METHODS: 15,864 individual IBD patients (CD: n = 6,791, UC: n = 9073) and 15,864 nearest neighbor propensity score matched patients without IBD were included from the Disease Analyzer database (IQVIA). Diagnoses of depression and anxiety disorders were compared between IBD and non-IBD patients during a five-year follow-up period using Kaplan-Meier estimators and Cox-regression models. RESULTS: After 5 years of follow-up, depression was diagnosed in 14.4% of CD patients versus 10.2% of matched pairs (p < 0.001) and in 13.1% of UC patients versus 10.1% of matched pairs (p < 0.001). In line, the incidence of anxiety order was significantly higher among CD (4.7% vs. 4.4%, p = 0.009) and UC patients (4.3% vs. 3.5%, p = 0.005). Regression analysis confirmed a significant association between IBD and both mental conditions (Hazard Ratio (HR)CD/depression: 1.40, HRUC/depression: 1.32, HRCD/anxiety disorder: 1.21, HRUC/anxiety disorder: 1.28). Subgroup analyses revealed a stronger association for CD and depression (HR: 1.51) and UC and depression (HR:1.49) among male patients as well as UC and anxiety disorders (HR: 1.51) among female patients. CONCLUSION: Our data argue for a significant association between IBD and mental diseases including depression and anxiety disorders. Although further pathophysiological research is warranted, we hypothesize that specific psychological screening measures in IBD patients could improve quality of life and outcome.

Association between Inflammatory Bowel Disease and Subsequent Development of Restless Legs Syndrome and Parkinson's Disease: A Retrospective Cohort Study of 35,988 Primary Care Patients in Germany.

BACKGROUND: In addition to the gastrointestinal symptoms, inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is associated with extraintestinal manifestations, including neurological disorders, which are gaining increasing attention due to a recently increased focus on the gut-brain axis. Here we aim to evaluate the association between IBD and restless legs syndrome (RLS) as well as Parkinson's disease (PD) in a cohort of primary care patients in Germany. METHODS: The study included 17,994 individuals with a diagnosis of IBD (7544 with CD and 10,450 with UC) and 17,994 propensity-score-matched individuals without IBD from the Disease Analyzer database (IQVIA). An initial diagnosis of RLS or PD was assessed as a function of IBD. Associations between CD and UC with RLS and PD were analyzed using Cox regression models. RESULTS: During the 10-year observation period, 3.6% of CD patients vs. 1.9% of matched non-IBD pairs (p < 0.001) and 3.2% of UC patients vs. 2.7% of matched pairs (p < 0.001) were diagnosed with RLS. The results were confirmed by Cox regression analysis, which showed a significant association between UC (HR: 1.26; 95% CI: 1.02-1.55) and CD (HR: 1.60; 95% CI: 1.23-2.09) and subsequent RLS. The incidence of PD in IBD patients was not significantly increased. However, we observed a non-significant trend towards a higher incidence of PD in male patients with CD but not UC (HR: 1.55; 95%CI: 0.98-2.45, p = 0.064). CONCLUSIONS: The present analysis suggests a significant association between IBD and the subsequent development of RLS. These findings should stimulate further pathophysiological research and may eventually lead to specific screening measures in patients with IBD.

Acyl-CoA-Binding Protein Drives Glioblastoma Tumorigenesis by Sustaining Fatty Acid Oxidation.

Glioblastoma multiforme (GBM) undergoes metabolic reprogramming to meet the high ATP and anabolic demands of the tumor cells. However, the role of fatty acid oxidation (FAO) and its regulators in the GBM context has been largely unknown. Here, we show that the neural stem cell pro-proliferative factor acyl-CoA-binding protein (ACBP, also known as DBI) is highly expressed in GBM, and by binding to acyl-CoAs, it cell-autonomously maintains high proliferation rates, promoting tumor growth and poor survival in several preclinical models. Mechanistic experiments using ACBP-acyl-CoA binding affinity variants and pharmacological FAO modulators suggest that ACBP supports tumor growth by controlling the availability of long-chain fatty acyl-CoAs to mitochondria, promoting FAO in GBM. Thus, our findings uncover a critical link between lipid metabolism and GBM progression established by ACBP and offer a potential therapeutic strategy for an effective anti-proliferative metabolic management of GBM.

Radiomic Machine Learning for Characterization of Prostate Lesions with MRI: Comparison to ADC Values.

Purpose To compare biparametric contrast-free radiomic machine learning (RML), mean apparent diffusion coefficient (ADC), and radiologist assessment for characterization of prostate lesions detected during prospective MRI interpretation. Materials and Methods This single-institution study included 316 men (mean age ± standard deviation, 64.0 years ± 7.8) with an indication for MRI-transrectal US fusion biopsy between May 2015 and September 2016 (training cohort, 183 patients; test cohort, 133 patients). Lesions identified by prospective clinical readings were manually segmented for mean ADC and radiomics analysis. Global and zone-specific random forest RML and mean ADC models for classification of clinically significant prostate cancer (Gleason grade group ≥ 2) were developed on the training set and the fixed models tested on an independent test set. Clinical readings, mean ADC, and radiomics were compared by using the McNemar test and receiver operating characteristic (ROC) analysis. Results In the test set, radiologist interpretation had a per-lesion sensitivity of 88% (53 of 60) and specificity of 50% (79 of 159). Quantitative measurement of the mean ADC (cut-off 732 mm2/sec) significantly reduced false-positive (FP) lesions from 80 to 60 (specificity 62% [99 of 159]) and false-negative (FN) lesions from seven to six (sensitivity 90% [54 of 60]) (P = .048). Radiologist interpretation had a per-patient sensitivity of 89% (40 of 45) and specificity of 43% (38 of 88). Quantitative measurement of the mean ADC reduced the number of patients with FP lesions from 50 to 43 (specificity 51% [45 of 88]) and the number of patients with FN lesions from five to three (sensitivity 93% [42 of 45]) (P = .496). Comparison of the area under the ROC curve (AUC) for the mean ADC (AUCglobal = 0.84; AUCzone-specific ≤ 0.87) vs the RML (AUCglobal = 0.88, P = .176; AUCzone-specific ≤ 0.89, P ≥ .493) showed no significantly different performance. Conclusion Quantitative measurement of the mean apparent diffusion coefficient (ADC) improved differentiation of benign versus malignant prostate lesions, compared with clinical assessment. Radiomic machine learning had comparable but not better performance than mean ADC assessment. © RSNA, 2018 Online supplemental material is available for this article.