Care sequences leading to the diagnosis of Alzheimer's disease and related dementias: An analysis of electronic health records.

Background: We examined the sequences of clinical care leading to diagnoses of Alzheimer's disease and related dementias (ADRD) using electronic health records from a large academic medical center.

Methods: We included patients aged 65+ with their first ADRD diagnoses from January 1, 2014 to December 31, 2019. Using state sequence analysis, care sequences were defined by the ordering of healthcare utilizations occurred in the 2 years before ADRD diagnosis.

Lactase Non-persistence and Lactose Intolerance.

Purpose Of Review: To evaluate the clinical and nutritional significance of genetically determined lactase non-persistence and potential lactose and milk intolerance in 65-70% of the world's adult population.

Recent Findings: Milk consumption is decreasing in the USA and is the lowest in countries with a high prevalence of lactase non-persistence. The dairy industry and Minnesota investigators have made efforts to minimize the influence of lactose intolerance on milk consumption.

Characterization of Metabolic Status in Nonhuman Primates with the Intravenous Glucose Tolerance Test.

The intravenous glucose tolerance test (IVGTT) plays a key role in the characterization of glucose homeostasis. When taken together with serum biochemical profiles, inclusive of blood glucose levels in both the fed and fasted state, HbA1c, insulin levels, clinical history of diet, body composition, and body weight status, an assessment of normal and abnormal glycemic control can be made. Interpretation of an IVGTT is done through measurement of changes in glucose and insulin levels over time in relation to the dextrose challenge.

Association between serrated epithelial changes and colorectal dysplasia in inflammatory bowel disease.

Background And Aims: Serrated epithelial change (SEC) is a histologic finding in longstanding colitis that may be associated with dysplasia. Our primary aim was to determine the incidence of dysplasia and colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients with SEC. Secondary aims were to determine the rate of location concordance between SEC and dysplasia/CRC and to identify other risk factors associated with dysplasia in IBD patients with SEC.

Infections Requiring Hospitalization as Predictors of Pediatric-Onset Crohn's Disease and Ulcerative Colitis.

Objectives. To assess the relationship between infections and the risk of pediatric-onset inflammatory bowel disease (IBD). Methods.

Family history of inflammatory bowel disease among patients with ulcerative colitis: a systematic review and meta-analysis.

Background And Aims: Despite numerous shared susceptibility loci between Crohn's disease and ulcerative colitis, the prevalence of family history among ulcerative colitis patients is not well-established and considered to be less prevalent. A systemic review and meta-analysis were conducted to estimate the prevalence of family history of inflammatory bowel disease in ulcerative colitis patients, and its effect on disease outcomes.

Methods: PubMED was searched to identify studies reporting the prevalence of family history of inflammatory bowel disease among ulcerative colitis patients.

Lower regional and temporal ultraviolet exposure is associated with increased rates and severity of inflammatory bowel disease hospitalisation.

Background: In the northern hemisphere, the incidence of inflammatory bowel diseases (IBD) has a north-south gradient, suggesting a link between ultraviolet (UV) exposure or vitamin D status and the pathogenesis of IBD.

Aim: To test the association of UV exposure with the rates and severity of IBD hospitalisation.

Methods: We conducted a retrospective nationwide analysis of 649 932 Crohn's disease (CD), 384 267 ulcerative colitis (UC), and 288 894 297 non-IBD hospitalisations in the US between 1998 and 2010.

Genetic literacy and patient perceptions of IBD testing utility and disease control: a randomized vignette study of genetic testing.

Background: Findings from inflammatory bowel disease (IBD) genome-wide association studies are being translated clinically into prognostic and diagnostic indicators of disease. Yet, patient perception and understanding of these tests and their applicability to providing risk information is unclear. The goal of this study was to determine, using hypothetical scenarios, whether patients with IBD perceive genetic testing to be useful for risk assessment, whether genetic test results impact perceived control, and whether low genetic literacy may be a barrier to patient understanding of these tests.

Editorial: Can stenosis in ileal Crohn's disease be prevented by current therapy?

Diagnostic delay is common with Crohn's disease (CD), especially with ileitis. Recent data show that diagnostic delay is associated with an increased risk of bowel stenosis and intestinal surgery. It is nonetheless unclear whether early diagnosis and treatment can truly prevent CD stenosis.

MicroRNA-224 negatively regulates p21 expression during late neoplastic progression in inflammatory bowel disease.

Background: The development of colon cancer represents a major complication in patients with inflammatory bowel disease (IBD). The importance of microRNAs (miRs) in carcinogenesis is becoming clearer because miRs have been implicated in the regulation of cancer-related cellular processes to include apoptosis, differentiation, cell cycle progression, and immune function. In the current study, we sought to identify miR dysregulation specific to progression along the normal-inflammation-cancer axis in colonic specimens from patients with IBD.

Prenatal and perinatal characteristics associated with pediatric-onset inflammatory bowel disease.

Background: The majority of studies that report early life risk factors for pediatric-onset inflammatory bowel disease (IBD) do not account for potential confounding, which can lead to spurious associations and incorrect inferences.

Aims: To assess the relationship between prenatal and perinatal characteristics and the risk of pediatric-onset IBD accounting for potential confounding.

Methods: We conducted a nested case-control study of 189 cases aged ≤18 years and 3,080 age- and membership-matched controls born at a Kaiser Permanente Northern California facility between 1984 and 2006.

Serum anti-glycan antibody biomarkers for inflammatory bowel disease diagnosis and progression: a systematic review and meta-analysis.

Background: Anti-glycan antibody serologic markers may serve as a useful adjunct in the diagnosis/prognosis of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). This meta-analysis/systemic review aimed to evaluate the diagnostic value, as well as the association of anti-glycan biomarkers with IBD susceptible gene variants, disease complications, and the need for surgery in IBD.

Methods: The diagnostic odds ratio (DOR), 95% confidence interval (CI), and sensitivity/specificity were used to compare the diagnostic value of individual and combinations of anti-glycan markers and their association with disease course (complication and/or need for surgery).

Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.

Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10(-8)), increasing the number of ulcerative colitis-associated loci to 47.

Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.

We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP.

Dynamic changes in the expression of MicroRNA-31 during inflammatory bowel disease-associated neoplastic transformation.

Background: Patients with inflammatory bowel disease (IBD) are at increased risk of developing colorectal cancer. Aberrant microRNA (miR) expression has been linked to carcinogenesis; however, no reports document a relationship between IBD-related neoplasia (IBDN) and altered miR expression. In the current study we sought to identify specific miR dysregulation along the normal-inflammation-cancer axis.

Identification of microRNAs associated with ileal and colonic Crohn's disease.

Background: Crohn's disease (CD) and ulcerative colitis (UC) are associated with expression differences in genes involved in immune function, wound healing, and tissue remodeling. MicroRNAs (miRNAs) are small, noncoding RNAs that act as potent negative regulators of gene expression and are differentially expressed in chronic inflammatory diseases, including UC. We examined the expression of miRNAs in tissues from different intestinal regions and in patients with active ileal and colonic CD.

Peripheral blood microRNAs distinguish active ulcerative colitis and Crohn's disease.

Background: Crohn's disease (CD) and ulcerative colitis (UC) result from pathophysiologically distinct dysregulated immune responses, as evidenced by the preponderance of differing immune cell mediators and circulating cytokine expression profiles. MicroRNAs (miRNAs) are small, noncoding RNAs that act as negative regulators of gene expression and have an increasingly recognized role in immune regulation. We hypothesized that differences in circulating immune cells in CD and UC patients are reflected by altered miRNA expression and that miRNA expression patterns can distinguish CD and UC from normal healthy individuals.

Refractory lymphocytic enterocolitis and tumor necrosis factor antagonist therapy.

Background & Aims: Lymphocytic enterocolitis is a malabsorptive syndrome characterized by severe small-bowel villous abnormality and crypt hyperplasia and dense infiltrate of lymphocytes throughout the gastrointestinal tract.

Methods: We present 2 patients with lymphocytic enterocolitis refractory to usual medical therapy who were treated with tumor necrosis factor antagonists.

Results: Both patients had clinical improvement in diarrheal symptoms and intestinal histologic abnormalities.

Prediction of the need for surgical intervention in obstructive Crohn's disease by 18F-FDG PET/CT.

Unlabelled: We preoperatively determined the accuracy of (18)F-FDG PET/CT for differentiating fixed muscle hypertrophy and fibrotic stenoses from acute transmural inflammatory stenoses in patients with Crohn's disease (CD) scheduled to undergo surgical resection for obstructive symptoms.

Methods: Seventeen patients with known CD prospectively underwent (18)F-FDG PET/CT before already-planned surgery for obstructive symptoms. Image interpretation was by consensus of 2 readers with knowledge of patient participation in the study but not of other clinical history.

NOD2 mutations and anti-Saccharomyces cerevisiae antibodies are risk factors for Crohn's disease in African Americans.

Objectives: NOD2 mutations and anti-Saccharomyces cerevisiae antibodies (ASCAs) are established risk factors of Crohn's disease (CD) in whites but have not been assessed in African-American (AA) adults with CD.

Methods: AAs with CD and controls were recruited by the Mid-Atlantic African-American IBD Study as part of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) IBD Genetics Consortium. Genotyping for the three common CD NOD2 mutations (Leu1007fsinsC, G908R/2722g>c, and R702W/2104c>t) and ASCA enzyme-linked immunosorbent assays were performed in 183 AA CD patients and in 143 controls.

Identification of novel serological biomarkers for inflammatory bowel disease using Escherichia coli proteome chip.

Specific antimicrobial antibodies present in the sera of patients with inflammatory bowel disease (IBD) have been proven to be valuable serological biomarkers for diagnosis/prognosis of the disease. Herein we describe the use of a whole Escherichia coli proteome microarray as a novel high throughput proteomics approach to screen and identify new serological biomarkers for IBD. Each protein array, which contains 4,256 E.

Patient trust-in-physician and race are predictors of adherence to medical management in inflammatory bowel disease.

Background: Adherence plays an important role in the therapeutic effectiveness of medical therapy in inflammatory bowel disease (IBD). We assessed whether trust-in-physician and Black race were predictors of adherence.

Methods: We performed a cross-sectional study of Black (n = 120) and White (n = 115) IBD patients recruited from an outpatient IBD clinic.

Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study.

Ulcerative colitis is a chronic inflammatory disease of the colon that presents as diarrhea and gastrointestinal bleeding. We performed a genome-wide association study using DNA samples from 1,052 individuals with ulcerative colitis and preexisting data from 2,571 controls, all of European ancestry. In an analysis that controlled for gender and population structure, ulcerative colitis loci attaining genome-wide significance and subsequent replication in two independent populations were identified on chromosomes 1p36 (rs6426833, combined P = 5.

MicroRNAs are differentially expressed in ulcerative colitis and alter expression of macrophage inflammatory peptide-2 alpha.

Background & Aims: Chronic inflammatory bowel diseases such as ulcerative colitis (UC) are associated with differential expression of genes involved in inflammation and tissue remodeling. MicroRNAs (miRNAs), which direct mRNA degradation and translational inhibition, influence a number of disease processes. We examined whether miRNAs are differentially expressed in UC tissues and are associated with expression of genes that regulate inflammation.