Low vitamin D levels are common in IBD patients and are associated with higher morbidity and disease severity, signifying the potential importance of vitamin D monitoring and treatment.

Obesity in IBD is not associated with increased health care utilization and IBD-related surgeries. Optimal regimens for drug dosing in obese patients with IBD have yet to be defined.

Geriatric patients diagnosed with CD earlier in life had greater small bowel involvement compared with new onset geriatric CD. There is low utilization of immunomodulator and biologic agents in geriatric IBD patients. Duration of CD correlates with nutrient deficiency. Prospective studies are warranted in this respect.

Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers.

Apoliprotein J (apoJ)/clusterin has attracted considerable interest based on its inducibility in multiple injury processes and accumulation at sites of remodeling, regression, and degeneration. We therefore sought to investigate apoJ/clusterin's role in kidney aging, as this may reveal the accumulated effects of diminished protection. Aging mice deficient in apoJ/clusterin developed a progressive glomerulopathy characterized by the deposition of immune complexes in the mesangium. Up to 75% of glomeruli in apoJ/clusterin-deficient mice exhibited moderate to severe mesangial lesions by 21 months of age. Wild-type and hemizygous mice exhibited little or no glomerular pathology. In the apoJ/clusterin-deficient mice, immune complexes of immunoglobulin G (IgG), IgM, IgA, and in some cases C1q, C3, and C9 were detectable as early as 4 weeks of age. Electron microscopy revealed the accumulation of electron-dense material in the mesangial matrix and age-dependent formation of intramesangial tubulo-fibrillary structures. Even the most extensively damaged glomeruli showed no evidence of inflammation or necrosis. In young apoJ/clusterin-deficient animals, the development of immune complex lesions was accelerated by unilateral nephrectomy-induced hyperfiltration. Injected immune complexes localized to the mesangium of apoJ/clusterin-deficient but not wild-type mice. These results establish a protective role of apoJ/clusterin against chronic glomerular kidney disease and support the hypothesis that apoJ/clusterin modifies immune complex metabolism and disposal.Apolipoprotein J (apoJ)/clusterin is a circulating glycoprotein constitutively expressed by diverse epithelial cells. The protein is induced in injured organs in various disease states, such as Alzheimer's disease, atherosclerosis, myocardial infarction, and multiple forms of acute and chronic renal disease (20,25). Proposed functions for apoJ/clusterin include lipid transport, complement defense, regulation of apoptosis, membrane protection, and promotion of cell-cell interactions (25). ApoJ/ clusterin can bind a large number of macromolecules implicated in disease initiation and progression, including immunoglobulins and complement components. Recently clusterin has been demonstrated to function as a molecular chaperone, preventing denatured protein precipitation through binding to exposed hydrophobic regions and improving high-molecularweight complex solubility (6).The structure of apoJ/clusterin has not provided much insight into function. Mammalian apoJ/clusterins are approximately 80-kDa heterodimers (9, 16) consisting of two 40-kDa chains joined by a unique five-disulfide-bond motif (10). The protein has limited homology to other proteins and lacks clear functional motifs (9). It does contain three putative amphipathic ␣-helical regions, which could allow it to interact with lipids and hydrophobic regions of other proteins (6).We have recently shown that apoJ/clusterin-deficient mice exhibit enhanced inflammatory severity and sequelae in an autoimmune myocarditis...