Recurrent Clostridioides difficile Infection and Outcome of Fecal Microbiota Transplantation Use: A Population-Based Assessment.

Background: Fecal microbiota transplantation (FMT) is recommended for the treatment of recurrent Clostridioides difficile infection (rCDI). In the current study, we evaluated rates of rCDI and subsequent FMT in a large metropolitan area. We compared demographic and clinical differences in FMT recipients and nonrecipients and quantified differences in outcomes based on treatment modality. Methods: A retrospective community-wide cohort study was conducted using surveillance data from the Georgia Emerging Infections Program, the Georgia Discharge Data System, and locally maintained lists of FMTs completed across multiple institutions to evaluate all episodes of C. difficile infection (CDI) in this region between 2016 and 2019. Cases were limited to patients with rCDI and ≥1 documented hospitalization. A propensity-matched cohort was created to compare rates of recurrence and mortality among matched patients based on FMT receipt. Results: A total of 3038 (22%) of 13 852 patients with CDI had rCDI during this period. In a propensity-matched cohort, patients who received an FMT had lower rates of rCDI (odds ratio, 0.6 [95% confidence interval, .38-.96) and a lower mortality rate (0.26 [.08-.82]). Of patients with rCDI, only 6% had received FMT. Recipients were more likely to be young, white, and female and less likely to have renal disease, diabetes, or liver disease, though these chronic illnesses were associated with higher rates of rCDI. Conclusions: These data suggest FMT has been underused in a population-based assessment and that FMT substantially reduced risk of recurrence and death.

Nonalcoholic fatty liver disease and gastric bypass surgery regulate serum and hepatic levels of pyruvate kinase isoenzyme M2.

Treatment of nonalcoholic fatty liver disease (NAFLD) focuses on the underlying metabolic syndrome, and Roux-en-Y gastric bypass surgery (RYGB) remains one of the most effective options. In rodents and human patients, RYGB induces an increase in the gene and protein expression levels of the M2 isoenzyme of pyruvate kinase (PKM2) in the jejunum. Since PKM2 can be secreted in the circulation, our hypothesis was that the circulating levels of PKM2 increase after RYGB. Our data, however, revealed an unexpected finding and a potential new role of PKM2 for the natural history of metabolic syndrome and NAFLD. Contrary to our initial hypothesis, RYGB-treated patients had decreased PKM2 blood levels compared with a well-matched group of patients with severe obesity before RYGB. Interestingly, PKM2 serum concentration correlated with body mass index before but not after the surgery. This prompted us to evaluate other potential mechanisms and sites of PKM2 regulation by the metabolic syndrome and RYGB. We found that in patients with NAFLD and nonalcoholic steatohepatitis (NASH), the liver had increased PKM2 expression levels, and the enzyme appears to be specifically localized in Kupffer cells. The study of murine models of metabolic syndrome and NASH replicated this pattern of expression, further suggesting a metabolic link between hepatic PKM2 and NAFLD. Therefore, we conclude that PKM2 serum and hepatic levels increase in both metabolic syndrome and NAFLD and decrease after RYGB. Thus, PKM2 may represent a new target for monitoring and treatment of NAFLD.

Predictors of vitamin D deficiency in inflammatory bowel disease and health: A Mississippi perspective.

AIM: To identify the predictors of vitamin D deficiency in patients with and without inflammatory bowel disease (IBD). METHODS: Patients with ulcerative colitis (UC) or Crohn's disease (CD) related diagnostic codes who received medical care at University of Mississippi Medical Center between July 2012 and 2015 were identified. After thorough chart review, we identified patients with biopsy proven IBD who had also been tested for serum 25-hydroxyvitamin D [25(OH)D] concentration. We compared these patients to a previously studied cohort of healthy controls who also had vitamin D concentration checked. Logistic regression analysis was performed to determine the association between vitamin d deficiency and UC, CD, race, age, gender and body mass index (BMI). RESULTS: We identified 237 patients with confirmed IBD. Of these, only 211 had a serum 25(OH)D concentrations available in the medical record. The group of healthy controls consisted of 98 individuals with available serum 25(OH)D concentration. 43% of IBD patients were African American (AA). Patients with CD were more likely to have vitamin D concentration checked. Bivariate analysis showed that AA (51% vs 21%, P = 0.00001), subjects with BMI >30 kg/m2 (39% vs 23% P = 0.01) and CD (40% vs 26%, P = 0.04) were more likely to be vitamin D deficient than vitamin D sufficient. Those with Age > 65 were more likely to be vitamin D sufficient (46% vs 15%, P = 0.04). Multiple regression showed that only BMI > 30 kg/m2 and AA race are associated with vitamin D deficiency. CONCLUSION: BMI > 30 kg/m2 and AA race are predictive of vitamin D deficiency. Gender, age and diagnosis of IBD are not predictive of vitamin D deficiency.

Bioelectrical Stimulation for the Reduction of Inflammation in Inflammatory Bowel Disease.

Crohn's disease and ulcerative colitis are the primary inflammatory bowel diseases (IBDs) affecting the gastrointestinal tract. The current therapy aims at decreasing inflammation and reducing symptoms. This typically requires immune suppression by steroids, thiopurines, methotrexate, or tumor necrosis factor inhibitors. Patients may be unreceptive to medical therapy, and some may discontinue the treatment due to adverse effects. Noninvasive, transcutaneous vagus nerve stimulation (VNS) is currently used as a treatment for depression and epilepsy, and it is being investigated for the treatment of conditions such as multiple sclerosis, migraines, and Alzheimer's disease. Recent studies have demonstrated the importance of splenic and vagus nerve functions in the inflammatory process through the production of certain cytokines. We hypothesize that using transcutaneous VNS via the auricular afferent branch could achieve a selective anti-inflammatory effect on the intestinal wall. This review examines the possibility of using vagal stimulators as a therapy for IBD. This could open the door to novel treatments for numerous vagally mediated diseases characterized by poor responses to current therapies.

The current state of stem cell therapy for peripheral artery disease.

Patients with advanced peripheral arterial disease may develop critical limb ischemia with rest pain, non-healing ulcerations, and eventually may require major amputation despite currently available revascularization technologies. Stem cell therapies hold promise as novel therapeutics to promote vasculogenesis and improve tissue perfusion in these patients. This article reviews the current state of stem cell therapy for patients with peripheral arterial disease, with a focus on the cell types that have been studied, barriers to clinical development, and development of new endpoints for clinical trials.

Abatacept: a new treatment option for refractory adult autoimmune enteropathy.

Autoimmune enteropathy (AIE) is a rare disease that has been observed in both children and adults. It typically manifests with symptoms of diarrhea, requiring long-term immunosuppression. Endoscopically, the duodenum typically exhibits villous blunting with partial or complete villous blunting, deep crypt lymphocytosis, increased apoptotic bodies, and minimal intraepithelial lymphocytosis on histologic analysis. The pathophysiology of AIE likely involves a hyperactive immune state in the setting of a T-cell regulatory defect, resulting in destruction of the enterocyte. We report a case of a 49-year-old woman who presented with refractory diarrhea, diagnosed as AIE. After failing multiple conventional therapies, she demonstrated clinical and histologic response to abatacept, a selective modulator of T-cell activation. We aim to increase awareness of this rare inflammatory disorder and new treatment options for this debilitating condition.

Reprogramming of intestinal glucose metabolism and glycemic control in rats after gastric bypass.

The resolution of type 2 diabetes after Roux-en-Y gastric bypass (RYGB) attests to the important role of the gastrointestinal tract in glucose homeostasis. Previous studies in RYGB-treated rats have shown that the Roux limb displays hyperplasia and hypertrophy. Here, we report that the Roux limb of RYGB-treated rats exhibits reprogramming of intestinal glucose metabolism to meet its increased bioenergetic demands; glucose transporter-1 is up-regulated, basolateral glucose uptake is enhanced, aerobic glycolysis is augmented, and glucose is directed toward metabolic pathways that support tissue growth. We show that reprogramming of intestinal glucose metabolism is triggered by the exposure of the Roux limb to undigested nutrients. We demonstrate by positron emission tomography-computed tomography scanning and biodistribution analysis using 2-deoxy-2-[18F]fluoro-D-glucose that reprogramming of intestinal glucose metabolism renders the intestine a major tissue for glucose disposal, contributing to the improvement in glycemic control after RYGB.

Cord colitis syndrome: a cause of granulomatous inflammation in the upper and lower gastrointestinal tract.

Cord colitis syndrome (CCS) is a recently described diarrheal illness of uncertain pathogenesis that affects recipients of umbilical cord blood transplant and is associated with negative cultures. CCS exhibits a peculiar histopathologic appearance, as it commonly manifests as granulomatous inflammation involving the upper and lower gastrointestinal tract, with features of chronicity in the colon. Importantly, the treatment for CCS differs from that for acute graft-versus-host disease, which is commonly in the clinical differential diagnosis: CCS responds to antibiotic treatment, whereas acute graft-versus-host disease responds to immunosuppression. We describe here the case of a 36-year-old woman with a history of acute myeloid leukemia who developed refractory diarrhea after cord blood transplant. Endoscopic biopsies of the stomach and colon revealed granulomatous inflammation, consisting of scattered ill-defined aggregates of epithelioid histiocytes, with associated mild neutrophilic inflammation and mildly increased epithelial cell apoptosis. In the colon, the granulomatous inflammation was associated with surface epithelial injury (including surface erosions) and contained occasional multinucleated epithelioid giant cells. Paneth cell metaplasia was present in the distal colon, but crypt architecture was preserved, and there was no basal lymphoplasmacytosis. Special stains and immunohistochemical stains for infectious organisms were negative. A diagnosis of CCS was made, and the patient promptly responded to treatment with ciprofloxacin and metronidazole. We present this case to raise awareness among pathologists of this newly described entity, in order to facilitate its timely diagnosis and treatment.

The relationship between C-reactive protein and atherosclerosis differs on the basis of body mass index: the Dallas Heart Study.

OBJECTIVES: This study sought to evaluate whether the relationship between C-reactive protein (CRP) and atherosclerosis is modified by body mass index (BMI). BACKGROUND: CRP levels are affected by obesity, and it is unknown whether the associations between CRP and cardiovascular (CV) disease differ between obese and nonobese individuals. METHODS: We measured CRP and multiple atherosclerosis phenotypes, including coronary artery calcification (CAC) (n = 2,685), aortic wall thickness (AWT) (n = 2,238), and aortic plaque burden (APB) (n = 2,224), in subjects ages 30 to 65 years from the Dallas Heart Study. The associations of CRP with CAC, AWT, and APB were compared across categories of BMI (normal, 18.5 to <25 kg/m(2); overweight, 25 to <30 kg/m(2); obese, ≥30 kg/m(2)) in sex-stratified analyses. RESULTS: The overall prevalence of obesity was 38% in men and 53% in women. Increasing CRP levels (<1 mg/l, 1 to 3 mg/l, >3 mg/l) were associated with increased CAC prevalence in normal and overweight men and in normal weight women (p < 0.01), but not in obese subjects of either sex. Likewise, the correlations between CRP and AWT and APB diminished with increasing BMI and were nonsignificant in obese individuals (p < 0.05 in nonobese, p > 0.1 in obese). Interaction tests between CRP and obesity were significant for all atherosclerosis measures in men and for AWT and ABP in women (p interaction <0.05 each). In both sexes, the c-statistics of CRP for all 3 atherosclerosis measures were greater for normal weight than obese individuals. CONCLUSIONS: In a large, population-based study, the association between CRP and multiple measures of atherosclerosis is diminished in obese individuals. The role of CRP for predicting CV outcomes in obese subjects requires further evaluation.

Serum analysis of tryptophan catabolism pathway: correlation with Crohn's disease activity.

BACKGROUND: Indoleamine 2,3 dioxygenase-1 (IDO1) is a tryptophan catabolizing enzyme with immunotolerance-promoting functions. We sought to determine if increased gut expression of IDO1 in Crohn's disease (CD) would result in detectable changes in serum levels of tryptophan and the initial IDO1 pathway catabolite, kynurenine. METHODS: Individuals were prospectively enrolled through the Washington University Digestive Diseases Research Center. The Montreal Classification was used for disease phenotyping. Disease severity was categorized by the Physician's Global Assessment. Serum tryptophan and kynurenine were measured by high-pressure liquid chromatography. IDO1 immunohistochemical staining was performed on formalin-fixed tissue blocks. RESULTS: In all, 25 CD patients and 11 controls were enrolled. Eight CD patients had serum collected at two different timepoints and levels of disease activity compared. Strong IDO1 expression exists in both the lamina propria and epithelium during active CD compared to controls. Suppressed serum tryptophan levels and an elevated kynurenine/tryptophan (K/T) ratio were found in individuals with active CD as compared to those in remission or the control population. K/T ratios correlated positively with disease activity as well as with C-reactive protein and erythrocyte sedimentation rate. In the subgroup of CD patients with two serum measurements, tryptophan levels were elevated while kynurenine levels and the K/T ratio lowered as the disease activity lessened. CONCLUSIONS: IDO1 expression in CD is associated with lower serum tryptophan and an elevated K/T ratio. These levels may serve as a reasonable objective marker of gut mucosal immune activation and as a surrogate for CD activity.

Impact of obesity on bowel preparation for colonoscopy.

BACKGROUND & AIMS: An inadequately cleansed colon can lead to missed lesions, repeat procedures, increased cost, and complications from colonoscopy. Because obesity, with its known link to colorectal neoplasia, might be associated with inadequate bowel cleansing, we investigated the impact of increased body mass index (BMI) on quality of bowel preparation at colonoscopy. METHODS: All colonoscopy procedures performed at a tertiary referral center during a 4-month period were evaluated. Bowel preparation was assigned a unique composite outcome score that took into account a subjective bowel preparation score, earlier recommendation for follow-up colonoscopy as a result of inadequate bowel preparation, and the endoscopist's confidence in adequate evaluation of the colon. Univariate and multivariate logistic regression analyses were performed to identify the role of BMI in predicting an inadequate bowel preparation. RESULTS: During the study period, 1588 patients (59.1% female; mean age, 57.4 +/- 0.34 years) fulfilled inclusion criteria. An abnormal BMI (> or =25) was associated with an inadequate composite outcome score (P = .002). In multivariate logistic regression analyses, both BMI > or =25 (P = .04) and > or =30 (P = .006) were retained as independent predictors of inadequate bowel preparation. Each unit increase in BMI increased the likelihood of an inadequate composite outcome score by 2.1%. Additional independent predictors of inadequate preparation exponentially increased the likelihood of an inadequate composite outcome score; 7 additional risk factors identified 97.5% of overweight patients with an inadequate composite outcome score. CONCLUSIONS: Obesity is an independent predictor of inadequate bowel preparation at colonoscopy. The presence of additional risk factors further increases the likelihood of a poorly cleansed colon.

Vitamin B12 deficiency and severe weight loss in an elderly patient.

Elderly individuals who have gastric surgery are at increased risk of developing vitamin B12 (cobalamin) deficiency, which often goes unrecognized by the provider. In conjunction with social risk factors and physiologic changes that occur naturally with aging, this population is also at risk for developing protein malnutrition. By intervening early with parenteral vitamin B12 and nutritional assessment prior to onset of weight loss in at risk individuals, clinicians will be able to improve their patients' quality of life. We present a 73-year-old individual with weight loss and anemia. This case presentation serves as a reminder about the prevalence of vitamin B12 deficiency and malnutrition in elderly individuals in our community.