Characteristics and feeding intolerance in critically ill adult patients receiving peptide-based enteral nutrition: A retrospective cross-sectional study.

BACKGROUND & AIMS: Patients who experience gastrointestinal (GI) intolerance and hyperglycemia (or glucose intolerance) may not achieve appropriate caloric requirements and experience poor outcomes. The aim was to examine patient characteristics, disease severity, and enteral nutrition (EN) formula use in relation to feeding intolerance and healthcare resource utilization. METHODS: A retrospective, cross-sectional design using real-world data from PINC AI™ Healthcare Database, 2015-2019 was used. Critically ill hospitalized adults who required ≥3 days of 100% whey peptide-based EN, other peptide-based diets, or intact-protein standard and diabetic EN formulas were included. Primary outcomes were enteral feeding intolerance, including GI intolerance and hyperglycemia. Pairwise comparisons of other peptide-based and standard intact-protein groups with 100% whey-peptide were completed. Associations between EN group with GI intolerance and hyperglycemia, respectively, were evaluated via multivariable logistic regressions. RESULTS: Across 67 US hospitals, 19,679 inpatients (3242,100% whey-peptide, 3121 other peptide-based, and 13,316 standard intact-protein) were included. The 100% whey-peptide group had higher severity of illness and frequencies of comorbidities compared with other peptide-based and standard intact-protein groups. Hospital length of stay, intensive care unit stay, and 30-day readmission were similar across peptide-based cohorts. After controlling for demographic, visit, and severity characteristics, odds of GI intolerance were 18% higher for the other peptide-based group and 15% higher for the standard intact-protein group compared with the 100% whey-peptide group (each P < 0.03). In secondary analysis, odds of hyperglycemia were 81% higher for the other peptide-based group compared with the subgroup of very high-protein/low carbohydrate 100% whey-peptide (P < 0.001). CONCLUSIONS: Lower GI intolerance and greater glycemic control were associated with the use of 100% whey-peptide formulas relative to other formulas. Appropriate and optimal delivery of EN using specialized peptide-based formulas is a strategy to minimize feeding intolerance and benefit critically ill patients.

Systematic Review and Meta-Analysis: Preoperative Vedolizumab and Postoperative Complications in Patients with IBD.

OBJECTIVES: The effect of vedolizumab on postoperative outcomes in patients with inflammatory bowel disease (IBD) remains unclear. We aimed to determine the relation between preoperative vedolizumab and early postoperative complications in patients with IBD undergoing abdominal surgery. METHODS: A search of databases and abstracts from gastroenterology conferences was performed. Primary outcomes included overall and infectious postoperative complication rates as well as surgical site infections. Studies that compared Crohn disease, ulcerative colitis, or patients with IBD-undefined with preoperative vedolizumab treatment undergoing abdominal surgery with controls with preoperative antitumor necrosis factor-α (anti-TNF-α) treatment or no preoperative biologic treatment were included. A meta-analysis was completed using the Mantel-Haenszel and DerSimonian and Laird models. RESULTS: Six studies totaling 1201 patients were included; 281 patients were treated preoperatively with vedolizumab, 327 patients were treated preoperatively with anti-TNF-α agents, and 593 patients were not treated preoperatively with any biologics. There was no significant difference in overall complications (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.48-2.24, P = 0.92, I2 =77%) between the vedolizumab and no-biologic groups. There also was no significant difference in infectious complications (OR 1.00, 95% CI 0.37-2.69, P = 1.00, I2 = 78%), which persisted after sensitivity analysis (OR 0.71, 95% CI 0.31-1.60, P = 0.41, I2 = 46%). Furthermore, there was no significant difference in overall complications (OR 0.77, 95% CI 0.24-2.46, P = 0.66, I2 = 85%) and infectious complications (OR 0.89, 95% CI 0.20-3.94, P = 0.87, I2 = 86%) between the vedolizumab and anti-TNF-α groups. After sensitivity analysis, differences in overall and infectious complications remained insignificant (OR 0.54 and 0.50, 95% CI 0.24-1.17 and 0.22-1.15, P = 0.12 and 0.10, I2 = 39% and 18%, respectively). Vedolizumab was also not associated with a significant increase in surgical site infections compared with the no-biologic (OR 1.45, 95% CI 0.33-6.32, P = 0.62, I2 = 75%) and anti-TNF (OR 1.30, 95% CI 0.22-7.60, P = 0.77, I2 = 81%) groups. CONCLUSIONS: Preoperative treatment with vedolizumab in patients with IBD undergoing abdominal surgery is not associated with increases in overall or infectious postoperative complications compared with preoperative anti-TNF-α treatment and no preoperative biologic treatment. Large, prospective studies are needed to further assess the impact of preoperative vedolizumab treatment on postoperative complications, particularly with respect to IBD subtype.

Systematic review and meta-analysis: risks of postoperative complications with preoperative use of anti-tumor necrosis factor-alpha biologics in inflammatory bowel disease patients.

OBJECTIVE: The preoperative use of anti-tumor necrosis factor-alpha (anti-TNF) in inflammatory bowel disease (IBD) patients undergoing surgery has been controversial due to concern for increased risks of postoperative complications. We aimed to determine the effect of preoperative anti-TNF therapy on postoperative complications in IBD patients undergoing abdominal surgery. METHODS: A literature search of Google Scholar, PubMed, The Cochrane Library, EMBASE, and CINAHL was performed through October 2019. Studies reporting postoperative complication rates of Crohn's disease (CD), ulcerative colitis (UC), and IBD-unspecified patients with preoperative anti-TNF treatment undergoing abdominal surgery compared to controls without preoperative anti-TNF treatment were included. The main outcomes measured were overall, infectious, and noninfectious postoperative complications. RESULTS: Forty-one studies totaling 20 274 patients were included. There was a significant increase in overall complications in all patients treated with anti-TNF vs. controls [odds ratio (OR) = 1.13, 95% confidence interval (CI), 1.01-1.25, P = 0.03, I2 = 6%] with an absolute risk increase (ARI) of 5.5% and a number needed to harm (NNH) of 18. There was also a significant increase in infectious complications in CD patients (OR = 1.44; 95% CI 1.02-2.03, P = 0.04, I2 = 49%, ARI = 5.5%, NNH = 20) only. Contrastingly, there was a significant increase in noninfectious complications in all patients (OR = 1.44, 95% CI 1.13-1.85, P = 0.003, I2 = 8%, ARI = 6.4%, NNH = 16) and UC patients (OR = 1.57, 95% CI 1.15-2.14, P = 0.005, I2 = 25%, ARI = 8.5%, NNH = 12) only. CONCLUSION: Preoperative use of anti-TNF agents in IBD patients undergoing abdominal surgery is associated with increases in overall postoperative complications in all patients, infectious postoperative complications in CD patients, and noninfectious postoperative complications in UC patients.

Decreased risk of hepatocellular carcinoma recurrence with direct-acting antivirals compared with no treatment for hepatitis C: a meta-analysis.

BACKGROUND: Studies investigating the association between direct-acting antivirals (DAAs) and the recurrence of hepatocellular carcinoma (HCC) related to hepatitis C (HCV) have yielded conflicting results. The objective of this meta-analysis was to define the short- and long-term recurrence rates of HCC after DAA treatment. METHODS: A search of multiple databases was performed, including Scopus, Cochrane, MEDLINE/PubMed and abstracts from gastroenterology meetings. Only studies reporting the recurrence of HCC in patients receiving DAA treatment, compared to HCV controls without DAA treatment, were evaluated. A meta-analysis was completed using the Mantel-Haenszel model. RESULTS: A comprehensive literature search resulted in 32 abstracts and papers. Six papers met our inclusion criteria and were included in the analysis. Follow up ranged from 1.25-4 years. Analysis of these 6 studies found a >60% lower risk of HCC recurrence in patients exposed to DAA compared to controls (odds ratio [OR] 0.36, 95% confidence interval [CI] 0.27-0.47; P<0.001; I 2=88%). A sensitivity analysis, which excluded studies showing the lowest recurrence rate to reduce heterogeneity, showed that patients receiving DAA still had a 60% lower risk of developing HCC (OR 0.4, 95%CI 0.26-0.61; P<0.0001; I 2=39%) and a 66% lower risk of developing HCC beyond 1 year (OR 0.34, 95%CI 0.22-0.54; P<0.00001; I 2=0%) compared to controls. CONCLUSIONS: The use of DAA is associated with a significantly lower risk of HCC development compared to DAA-untreated patients, both overall and beyond 1 year of treatment. Further studies are needed to assess the impact of DAAs on early recurrence.

Early introduction of a semi-elemental formula may be cost saving compared to a polymeric formula among critically ill patients requiring enteral nutrition: a cohort cost-consequence model.

OBJECTIVES: Gastrointestinal (GI) intolerance is associated with adverse outcomes in critically ill patients receiving enteral nutrition (EN). The objective of this analysis is to quantify the cost of GI intolerance and the cost implications of starting with semi-elemental EN in intensive care units (ICUs). STUDY DESIGN: A US-based cost-consequence model was developed to compare the costs for patients with and without GI intolerance and the costs with semi-elemental or standard EN while varying the proportion of GI intolerance cases avoided. MATERIALS AND METHODS: ICU data on GI intolerance prevalence and outcomes in patients receiving EN were derived from an observational study. ICU stay costs were obtained from literature and the costs of EN from US customers' price lists. The model was used to conduct a threshold analysis, which calculated the minimum number of cases of GI intolerance that would have to be avoided to make the initial use of semi-elemental formula cost saving for the cohort. RESULTS: Out of 100 patients receiving EN, 31 had GI intolerance requiring a median ICU stay of 14.4 days versus 11.3 days for each patient without GI intolerance. The model calculated that semi-elemental formula was cost saving versus standard formula when only three cases of GI intolerance were prevented per 100 patients (7% of GI intolerance cases avoided). CONCLUSION: In the US setting, the model predicts that initial use of semi-elemental instead of standard EN can result in cost savings through the reduction in length of ICU stay if >7% of GI intolerance cases are avoided.

Does preoperative enteral or parenteral nutrition reduce postoperative complications in Crohn's disease patients: a meta-analysis.

OBJECTIVES: Crohn's disease (CD) patients frequently develop complications that require surgery for management. The high prevalence of malnutrition in CD patients presents a challenge because poor preoperative nutritional status has been shown to increase postoperative complications. In this study, we assessed whether preoperative enteral nutrition (EN) or total parenteral nutrition (TPN) decreases postoperative complications in CD patients. MATERIALS AND METHODS: A three-point systematic and comprehensive literature search was carried out on multiple databases followed by a meta-analysis with results presented as odds ratio (OR) using two models, the Mantel-Haenszel model and the DerSimonian and Laird model. The I measure of inconsistency was utilized to assess heterogeneity. If statistically significant heterogeneity was identified, the results underwent a separate sensitivity analysis. RESULTS: Five studies met inclusion criteria totaling 1111 CD patients. The rate of postoperative complications in the group receiving preoperative nutrition (EN or TPN) support was 20.0% compared with 61.3% in the group who had standard care without nutrition support [OR=0.26, 95% confidence interval (CI): 0.07-0.99, P<0.001]. Postoperative complications occurred in 15.0% of patients in the group who received preoperative TPN compared with 24.4% in the group who did not (OR=0.65, 95% CI: 0.23-1.88, P=0.43). Postoperative complications occurred in 21.9% in the group who received preoperative EN compared with 73.2% in the group that did not received preoperative EN (OR=0.09, 95% CI: 0.06-0.13, P<0.001). CONCLUSION: Preoperative nutrition supplementation reduces postoperative complications in CD patients. In particular, EN in CD patients before undergoing surgery is superior to standard of care without nutrition support with a number needed to treat of 2. There is a trend toward TPN being superior to standard of care without nutrition support, but this trend did not reach statistical significance. Further studies are necessary to evaluate specific components in EN or TPN that may be most beneficial for CD patients requiring surgical intervention.

Cap-assisted colonoscopy versus standard colonoscopy: is the cap beneficial? A meta-analysis of randomized controlled trials.

BACKGROUND: In an effort to improve visualization during colonoscopy, a transparent plastic cap or hood may be placed on the end of the colonoscope. Cap-assisted colonoscopy (CAC) has been studied and is thought to improve polyp detection. Numerous studies have been conducted comparing pertinent clinical outcomes between CAC and standard colonoscopy (SC) with inconsistent results. METHODS: Numerous databases were searched in November 2016. Only randomized controlled trials (RCTs) involving adult subjects that compared CAC to SC were included. Outcomes of total colonoscopy time, time to cecum, cecal intubation rate, terminal ileum intubation rate, polyp detection rate (PDR), and adenoma detection rate (ADR) were analyzed in terms of odds ratio (OR) or mean difference (MD) with fixed effect and random effects models. RESULTS: Five hundred eighty-nine articles and abstracts were discovered. Of these, 23 RCTs (n=12,947) were included in the analysis. CAC showed statistically significant superiority in total colonoscopy time (MD -1.51 min; 95% confidence interval [CI] -2.67 to -0.34; P<0.01) and time to cecum (MD -0.82 min; 95%CI -1.20 to -0.44; P<0.01) compared to SC. CAC also showed better PDR (OR 1.17; 95%CI 1.06-1.29; P<0.01) but not ADR (OR 1.11; 95%CI 0.95-1.30; P=0.20). In contrast, on sensitivity analysis, ADR was better with CAC. Terminal ileum intubation and cecal intubation rates demonstrated no significant difference between the two groups (P=0.11 and P=0.73, respectively). CONCLUSIONS: The use of a transparent cap during colonoscopy improves PDR while reducing procedure times. ADR may improve in cap-assisted colonoscopy but further studies are required to confirm this.

Strategies for overcoming anti-tumor necrosis factor drug antibodies in inflammatory bowel disease: Case series and review of literature.

Anti-tumor necrosis factor (TNF) biologics are currently amongst the most widely used and efficacious therapies for inflammatory bowel disease (IBD). The development of therapeutic drug monitoring for infliximab and adalimumab has allowed for measurement of drug levels and antidrug antibodies. This information can allow for manipulation of drug therapy and prediction of response. It has been shown that therapeutic anti-TNF drug levels are associated with maintenance of remission, and development of antidrug antibodies is predictive of loss of response. Studies suggest that a low level of drug antibodies, however, can at times be overcome by dose escalation of anti-TNF therapy or addition of an immunomodulator. We describe a retrospective case series of twelve IBD patients treated at the University of California-Irvine, who were on infliximab or adalimumab therapy and were found to have detectable but low-level antidrug antibodies. These patients underwent dose escalation of the drug or addition of an immunomodulator, with subsequent follow-up drug levels obtained. Eight of the twelve patients (75%) demonstrated resolution of antidrug antibodies, and were noted to have improvement in disease activity. Though data regarding overcoming low-level anti-TNF drug antibodies remains somewhat limited, cases described in the literature as well as our own experience suggest that this may be a viable strategy for preserving the use of an anti-TNF drug. Low-level anti-TNF drug antibodies may be overcome by dose escalation and/or addition of an immunomodulator, and can allow for clinical improvement in disease status. Therapeutic drug monitoring is an important tool to guide this strategy.

Guidance for supplemental enteral nutrition across patient populations.

Enteral nutrition is preferred over parenteral nutrition as a result of the greater safety of enteral nutrition therapy and comparative convenience. A wide variety of enteral nutrition products have been developed, including disease-specific products to help manage the nutritional needs of patients with kidney failure, liver failure, lung disease, diabetes, and other conditions. An assessment of each patient's nutritional needs and digestive function should be conducted prior to initiation of enteral nutrition therapy. Other considerations in determining the appropriate route and method of enteral nutrition administration include the time and nursing involvement required for administration, potential complications of medication administration, and concerns related to pancreatic dysfunction in certain groups. Tailored guidelines and treatment considerations are reviewed in this manuscript the application of enteral nutrition in various patient populations.

Exposure to oral contraceptives increases the risk for development of inflammatory bowel disease: a meta-analysis of case-controlled and cohort studies.

BACKGROUND: The oral contraceptive pill (OCP) is a widely used method of contraception. There have been conflicting studies linking the use of OCPs to the development of inflammatory bowel disease (IBD). The intent of this meta-analysis is to better define the association between OCP exposure and the risk for development of IBD. METHODS: A thorough search of multiple databases, including Scopus, Cochrane, MEDLINE/PubMed, and CINAHL, and abstracts from major gastroenterology meetings was performed (October, 2016). Studies reporting the development of IBD in patients with or without previous exposure to OCP, compared with healthy controls, were included. A meta-analysis was completed using the Mantel-Haenszel model to evaluate the risk of developing IBD in the setting of previous OCP exposure. RESULTS: In a complete analysis of 20 studies, there appeared to be over a 30% increased risk for the development of IBD in patients exposed to OCP compared with patients not exposed to OCP [odds ratio (OR): 1.32, 95% confidence interval (CI): 1.17-1.49, P<0.001, I=14%]. More specifically, there was a 24% higher risk for developing Crohn's disease (OR: 1.24, 95% CI: 1.09-1.40, P<0.001; I=38%) and a 30% higher risk for developing ulcerative colitis (OR: 1.30, 95% CI: 1.13-1.49, I=26%) in patients exposed to OCP compared with those not exposed to the medication. CONCLUSION: The use of OCP is associated with an increased risk for development of Crohn's disease and ulcerative colitis in the genetically susceptible host. The total duration, dose of OCP exposure, and the risk for development of IBD need to be better characterized.

Effects of caregiver burden on quality of life and coping strategies utilized by caregivers of adult patients with inflammatory bowel disease.

BACKGROUND: While previous studies have evaluated caregivers' quality of life (QOL), burnout, and stress amongst across a variety of chronic illnesses, few such studies have been related to inflammatory bowel disease (IBD). METHODS: Caregivers accompanying adult patients with IBD at 6 tertiary centers were enrolled. They completed self-administered surveys related to QOL and burden, including the QOL scale, Zarit Burden Interview (ZBI), and Brief COPE. RESULTS: Of the 200 consecutive caregivers asked to participate, 162 (81.0%) enrolled and completed the survey. A total of 43.8% caregivers reported having a high level of burden as measured by the ZBI. Factors predictive of a high burden included female gender, younger age of caregiver, household income <$30,000, having more than one dependent in the household, caring for a patient with active disease and higher disease severity, and a personal history of psychiatric illness. Over one third of the caregivers reported a maladaptive coping pattern. The caregiver factors predictive of maladaptive coping skills included male gender, lack of involvement in a support group, a personal history of psychiatric illness, and living in a different household from the patient. CONCLUSIONS: A large proportion of caregivers of IBD patients experience a high level of caregiver burden and reduced QOL. Participation in religious/spiritual activities and support groups appeared to reduce perceived caregiver burden and improve QOL. This study suggests there is an unmet need to address the caregiver burden of adult IBD patients.

Use of the Endocuff during routine colonoscopy examination improves adenoma detection: A meta-analysis.

AIM: To perform meta-analysis of the use of Endocuff during average risk screening colonoscopy. METHODS: Scopus, Cochrane databases, MEDLINE/PubMed, and CINAHL were searched in April 2016. Abstracts from Digestive Disease Week, United European Gastroenterology, and the American College of Gastroenterology meeting were also searched from 2004-2015. Studies comparing EC-assisted colonoscopy (EAC) to standard colonoscopy, for any indication, were included in the analysis. The analysis was conducted by using the Mantel-Haenszel or DerSimonian and Laird models with the odds ratio (OR) to assess adenoma detection, cecal intubation rate, and complications performed. RESULTS: Nine studies (n = 5624 patients) were included in the analysis. Compared to standard colonoscopy, procedures performed with EC had higher frequencies for adenoma (OR = 1.49, 95%CI: 1.23-1.80; P = 0.03), and sessile serrated adenomas detection (OR = 2.34 95%CI: 1.63-3.36; P < 0.001). There was no significant difference in cecal intubation rates between the EAC group and standard colonoscopy (OR = 1.26, 95%CI: 0.70-2.27, I2 = 0%; P = 0.44). EAC was associated with a higher risk of complications, most commonly being superficial mucosal injury without higher frequency for perforation. CONCLUSION: The use of an EC on colonoscopy appears to improve pre-cancerous polyp detection without any difference in cecal intubation rates compared to standard colonoscopy.

Prophylactic clipping and post-polypectomy bleeding: a meta-analysis and systematic review.

BACKGROUND: Bleeding after polypectomy is a common issue associated with colonoscopy. To help prevent post-polypectomy bleeding, many endoscopists place clips at the site. However, this practice remains controversial. Therefore, we performed a meta-analysis of the efficacy of clip placement in the prevention of post-polypectomy bleeding. METHODS: Multiple databases, including Embase, Scopus, MEDLINE/PubMed, CINAHL, Cochrane databases, and recent abstracts from major American meetings were searched in April 2016. Using the DerSimonian and Laird (random effects) model with odds ratio (OR), a meta-analysis was performed of post-polypectomy bleeding with prophylactic clip versus no prophylactic clip. RESULTS: Five hundred and thirty potential articles and abstracts were discovered. Thirty-five articles were reviewed, with 12 studies satisfying the inclusion criteria. No statistically significant difference in prophylactic clipping versus no prophylactic clipping for post-polypectomy bleeding in all polyps was found when all studies (OR 1.49; 95% CI: 0.56-4.00; P=0.42), only peer-reviewed studies where abstracts were excluded (OR 0.84; 95% CI: 0.42-1.69; P=0.63), and only randomized controlled trials (OR 1.24; 95% CI: 0.69-2.24; P=0.47) were analyzed. CONCLUSIONS: The use of prophylactic clipping for all polypectomies does not seem to prevent post-polypectomy bleeding and should not be a routine practice. However, for large polyps (>2 cm), prophylactic clipping may or may not be beneficial in preventing post-polypectomy bleeding. Further studies are required to fully evaluate this subgroup.

Long-Term Nutrition: A Clinician's Guide to Successful Long-Term Enteral Access in Adults [Formula: see text].

Long-term nutrition support requires long-term enteral access. To ensure the success of long-term enteral access, many factors need to be taken into consideration. This article represents a guide to placing and maintaining access in patients requiring long-term nutrition and addresses many of the common questions regarding long-term enteral access, such as indications, types of access, feeding after access placed, and recognition and treatment of potential complications. This guide will help the clinician establish and maintain access to maximize nutrition in patients requiring long-term nutrition.

Bleeding risk with clopidogrel and percutaneous endoscopic gastrostomy.

AIM: To compare bleeding within 48 h in patients undergoing percutaneous endoscopic gastrostomy (PEG) with or without clopidogrel. METHODS: After institutional review board approval, a retrospective study involving a single center was conducted on adult patients having PEG (1/08-1/14). Patients were divided into two groups: Clopidogrel group consisting of those patients taking clopidogrel within 5 d of PEG and the non-clopidogrel group including those patients not taking clopidogrel within 5 d of the PEG. RESULTS: Three hundred and nineteen PEG patients were found. One hundred and sixty-eight males and 151 females with mean body mass index 28.47 ± 9.75 kg/m(2) and mean age 65.03 ± 16.11 years were identified. Thirty-three patients were on clopidogrel prior to PEG with 286 patients not on clopidogrel. No patients in either group developed hematochezia, melena, or hematemesis within 48 h of percutaneous endoscopic gastrostomy (PEG). No statistical differences were observed between the two groups with 48 h for hemoglobin decrease of > 2 g/dL (2 vs 5 patients; P = 0.16), blood transfusions (2 vs 7 patients; P = 0.24), and repeat endoscopy for possible gastrointestinal bleeding (no patients in either group). CONCLUSION: Based on the results, no significant post-procedure bleeding was observed in patients undergoing PEG with recent use of clopidogrel.

Nutritional Strategies in the Management of Adult Patients with Inflammatory Bowel Disease: Dietary Considerations from Active Disease to Disease Remission.

Inflammatory bowel disease (IBD) is a group of chronic, lifelong, and relapsing illnesses, such as ulcerative colitis and Crohn's disease, which involve the gastrointestinal tract. There is no cure for these diseases, but combined pharmacological and nutritional therapy can induce remission and maintain clinical remission. Malnutrition and nutritional deficiencies among IBD patients result in poor clinical outcomes such as growth failure, reduced response to pharmacotherapy, increased risk for sepsis, and mortality. The aim of this review is to highlight the consequences of malnutrition in the management of IBD and describe nutritional interventions to facilitate induction of remission as well as maintenance; we will also discuss alternative delivery methods to improve nutritional status preoperatively.

Vitamin D and the Pathogenesis of Inflammatory Bowel Disease.

Vitamin D has traditionally been known for its role in bone metabolism, but emerging evidence has suggested a broader role for vitamin D in immune regulation. Vitamin D deficiency has been associated with the pathogenesis of diverse autoimmune disorders and has similarly been implicated as a contributor to inflammatory bowel disease. In this review, we discuss animal, in vitro, genetic, and epidemiologic studies that have linked vitamin D deficiency with inflammatory bowel disease pathogenesis or severity. Nonetheless, we present the caveat in interpreting these studies in the context of reverse causation: Does vitamin D deficiency lead to gastrointestinal disease, or does gastrointestinal disease (with related changes in dietary choices, intestinal absorption, nutritional status, lifestyle) lead to vitamin D deficiency?