Mucosal vitamin D signaling in inflammatory bowel disease.

Epidemiological studies have identified vitamin D (25(OH)D) deficiency to be highly prevalent among patients with inflammatory bowel disease (IBD), and low serum levels correlate with a higher disease activity and a more complicated disease course. The link to IBD pathogenesis has been subject of investigations, primarily due to the distinct immunological functions of vitamin D signaling, including anti-inflammatory and anti-fibrotic actions. Vitamin D is a pleiotropic hormone that executes its actions on cells through the vitamin D receptor (VDR). A leaky gut, i.e. an insufficient intestinal epithelial barrier, is thought to be central for the pathogenesis of IBD, and emerging data support the concept that vitamin D/VDR signaling in intestinal epithelial cells (IECs) has an important role in controlling barrier integrity. Here we review the latest evidence on how vitamin D promotes the interplay between IECs, the gut microbiome, and immune cells and thereby regulate the intestinal immune response. On the cellular level, vitamin D signaling regulates tight junctional complexes, apoptosis, and autophagy, leading to increased epithelial barrier integrity, and promotes expression of antimicrobial peptides as part of its immunomodulating functions. Further, intestinal VDR expression is inversely correlated with the severity of inflammation in patients with IBD, which might compromise the positive effects of vitamin D signaling in patients with flaring disease. Efforts to reveal the role of vitamin D in the pathophysiology of IBD will pave the road for the invention of more rational treatment strategies of this debilitating disease in the future.

Systematic review with meta-analysis: association of vitamin D status with clinical outcomes in adult patients with inflammatory bowel disease.

BACKGROUND: Vitamin D deficiency is highly prevalent among patients with IBD, however, data on its association with clinical outcomes are conflicting. AIM: To perform a systematic review and meta-analysis to explore the association of low vitamin D status with clinical outcomes in patients with IBD. METHODS: We searched PubMed, Embase, Scopus and Web of Science from inception to February 2018 for observational studies evaluating the association of low 25(OH)D status on IBD disease activity, mucosal inflammation, clinical relapse and quality of life. Odds ratios (ORs) were pooled and analysed using a random effects model. RESULTS: Twenty-seven studies were eligible for inclusion comprising 8316 IBD patients (3115 ulcerative colitis, 5201 Crohn's disease). Among IBD patients, low 25(OH)D status was associated with increased odds of disease activity (OR 1.53, 95% CI 1.32-1.77, I2  = 0%), mucosal inflammation (OR 1.25, 95% CI 1.06-1.47, I2  = 0%), low quality of life (QOL) scores (OR 1.30, 95% CI 1.06-1.60, I2  = 0%) and future clinical relapse (OR 1.23, 95% CI 1.03-1.47, I2  = 0%). In subgroup analysis, low vitamin D status was associated with Crohn's disease activity (OR 1.66, 95% CI 1.36-2.03, I2  = 0%), mucosal inflammation (OR 1.39, 95% CI 1.03-1.85, I2  = 0%), clinical relapse (OR 1.35, 95% CI 1.14-1.59, I2  = 0%), and low QOL scores (OR 1.25, 95% CI 1.04-1.50, I2  = 0%) and ulcerative colitis disease activity (OR 1.47, 95% CI 1.03-2.09, I2  = 0%) and clinical relapse (OR 1.20, 95% 1.01-1.43, I2  = 0%). CONCLUSIONS: Low 25(OH)D status is a biomarker for disease activity and predictor of poor clinical outcomes in IBD patients.

Cortical stimulation mapping for localization of visual and auditory language in pediatric epilepsy patients.

OBJECTIVE: To determine resection margins near eloquent tissue, electrical cortical stimulation (ECS) mapping is often used with visual naming tasks. In recent years, auditory naming tasks have been found to provide a more comprehensive map. Differences in modality-specific language sites have been found in adult patients, but there is a paucity of research on ECS language studies in pediatric patients. The goals of this study were to evaluate word-finding distinctions between visual and auditory modalities and identify which cortical subregions most often contain critical language function in a pediatric population. METHODS: Twenty-one pediatric patients with epilepsy or temporal lobe pathology underwent ECS mapping using visual (n = 21) and auditory (n = 14) tasks. Fisher's exact test was used to determine whether the frequency of errors in the stimulated trials was greater than the patient's baseline error rate for each tested modality and subregion. RESULTS: While the medial superior temporal gyrus was a common language site for both visual and auditory language (43.8% and 46.2% of patients, respectively), other subregions showed significant differences between modalities, and there was significant variability between patients. Visual language was more likely to be located in the anterior temporal lobe than was auditory language. The pediatric patients exhibited fewer parietal language sites and a larger range of sites overall than did adult patients in previously published studies. CONCLUSIONS: There was no single area critical for language in more than 50% of patients tested in either modality for which more than 1 patient was tested (n > 1), affirming that language function is plastic in the setting of dominant-hemisphere pathology. The high rates of language function throughout the left frontal, temporal, and anterior parietal regions with few areas of overlap between modalities suggest that ECS mapping with both visual and auditory testing is necessary to obtain a comprehensive language map prior to epileptic focus or tumor resection.