Dawn M. Wiese

A randomized, double-blind, placebo-controlled pilot study of Lactobacillus reuteri ATCC 55730 for the prevention of antibiotic-associated diarrhea in hospitalized adults.

Goals The purpose of the study was to evaluate Lactobacillus reuteri for the prevention of antibiotic-associated diarrhea (AAD) in hospitalized adults. Background AAD is a problem in hospitalized adults, contributing to increased length of stay, cost, and mortality. Probiotics have been proposed as a way to prevent AAD. L. reuteri decreases acute infectious diarrhea in children; however, L. reuteri has never been evaluated for the prevention of AAD. Study In a randomized, double-blind, placebo-controlled pilot study, in-patients receiving antibiotics were given L. reuteri 1×108 colony-forming units twice daily or an identical placebo for 4 weeks. Stool frequency, consistency, and gastrointestinal symptoms were monitored during the 4-week treatment period and during a 2-week follow-up period. Results A total of 31 patients were enrolled. Eight patients were excluded in the data analysis because of length of study participation less than 14 days. Mean age was 51±18 years; 63% were female and 37% male. Most frequent primary diagnosis was pneumonia (20%), followed by abscess (10%), chronic obstructive pulmonary disease (6.7%), and bronchitis (6.7%). Thirteen patients received L. reuteri and 10 received placebo. Patients treated with L. reuteri had a significantly lower frequency of diarrhea compared with placebo (50% in the placebo group vs. 7.7% in the probiotic group, P=0.02). There were no differences in the frequency or severity of gastrointestinal symptoms. Conclusions In this placebo-controlled, pilot study, L. reuteri twice daily for 4 weeks significantly decreased AAD among hospitalized adults. L. reuteri was safe and well tolerated.

Measurement of Nutrition Status in Crohn's Disease Patients Receiving Infliximab Therapy

AIM There is limited information on the nutrition impact of antitumor necrosis factor-alpha treatment in adult Crohns disease (CD). This study was performed to examine the effect of a 6-month course of infliximab on enterocyte function, nutrient status, metabolism, and body composition in these patients. METHODS Seven CD patients were assessed for disease activity, enterocyte function, and body composition prior to, after 6 weeks, and after 6 months of infliximab treatment. Measurements included (1) disease activity: Inflammatory Bowel Disease Questionnaire, Harvey Bradshaw Index, and C-reactive protein; (2) enterocyte function: folate, homocysteine, vitamin B(12), citrulline, vitamin D, beta-carotene, d-xylose absorption; (3) Prognostic Inflammatory and Nutritional Index (PINI); and (4) body composition and metabolism: body mass index (BMI), fat and lean body mass, resting energy expenditure (RRE), and respiratory quotient. RESULTS Most patients had improvement in disease activity with infliximab. PINI decreased in all patients (-3.35, P = .04). Plasma folate concentration significantly increased. There was an increase in BMI, fat mass, and lean body mass. The respiratory quotient increased in most patients. Changes in citrulline level and REE were inconsistent. CONCLUSIONS Crohns disease patients have improvements in an index that measures both inflammation and nutrition (PINI) with infliximab therapy. Increases in plasma folate suggest improvement in enterocyte function and/or increased oral intake. The increase in respiratory quotient suggests decreased lipolysis and the lack of a starvation state. It was unclear whether weight gain was predominantly fat or lean muscle mass. These finding also support the use of PINI in Crohns patients as an overall marker of inflammation and nutrition, and as a measure of response to infliximab therapy.

Managing Perianal Crohn’s Disease

Perianal Crohn’s Disease (CD) is a significant cause of morbidity in CD patients. Accurate identification of perianal involvement requires advanced imaging techniques in addition to physical exam. Treatment of the disease is aimed at improving both the perianal and intestinal manifestations. Proper treatment depends upon the severity of the disease and combines current medical and surgical therapies to maximize response. The ability to improve perianal disease has grown significantly since the introduction of anti-TNF agents which are now a mainstay of treatment along with antibiotics and immunomodulators. New experimental therapies are limited by lack of research to support their use.

Use of Endoscopic Ultrasound to Guide Adalimumab Treatment in Perianal Crohn's Disease Results in Faster Fistula Healing

Background:Perianal disease is a manifestation of Crohns disease (CD) that has poor long-term treatment outcomes. The aim was to determine if rectal endoscopic ultrasound (EUS)–guided therapy with adalimumab (ADA) can improve outcomes for patients with perianal fistulizing CD. Methods:This is a randomized prospective study comparing serial EUS guidance of fistula treatment versus standard of care in fistulizing perianal CD. At enrollment, all patients underwent a rectal EUS and an EUA with seton placement and/or I&D. Treatment was maximized with immunomodulators, antibiotics, and ADA induction. Surgical interventions were determined by the surgeons discretion in the control group and assisted by every 12th week EUS in the intervention group. Primary and secondary endpoints where complete drainage cessation at week 48 was fistula status per EUS, respectively. Results:Twenty patients were enrolled: 11 control and 9 EUS guidance. At 24 weeks, 7/9 (78%) in EUS group and 3/11 (27%) in control group had drainage cessation (P = 0.04). This significant difference was lost at week 48 (P = 0.44). Three patients in the EUS and 1 in the control group had additional surgical intervention. Those in the EUS group had more rapid escalation of ADA dosing (P = 0.003). There was no difference in the change in PDAI at week 48 versus baseline (P = 0.81). Conclusions:Rectal EUS-guided ADA therapy for CD perianal fistulas showed an initial benefit at 24 weeks, which was lost at week 48. This is likely due to small sample size and higher fistula closure in the controls. However, the faster rate of fistula resolution is a clinically significant finding.

Serum Fatty Acids Are Correlated with Inflammatory Cytokines in Ulcerative Colitis

Background and Aims Ulcerative colitis (UC) is associated with increased dietary intake of fat and n-6 polyunsaturated fatty acids (PUFA). Modification of fat metabolism may alter inflammation and disease severity. Our aim was to assess differences in dietary and serum fatty acid levels between control and UC subjects and associations with disease activity and inflammatory cytokines. Methods Dietary histories, serum, and colonic tissue samples were prospectively collected from 137 UC subjects and 38 controls. Both histologic injury and the Mayo Disease Activity Index were assessed. Serum and tissue cytokines were measured by Luminex assay. Serum fatty acids were obtained by gas chromatography. Results UC subjects had increased total fat and oleic acid (OA) intake, but decreased arachidonic acid (AA) intake vs controls. In serum, there was less percent saturated fatty acid (SFA) and AA, with higher monounsaturated fatty acids (MUFA), linoleic acid, OA, eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA) in UC. Tissue cytokine levels were directly correlated with SFA and inversely correlated with PUFA, EPA, and DPA in UC subjects, but not controls. 5-aminosalicylic acid therapy blunted these associations. Conclusions In summary, we found differences in serum fatty acids in UC subjects that correlated with pro-inflammatory tissue cytokines. We propose that fatty acids may affect cytokine production and thus be immunomodulatory in UC.

The Effects of an Oral Supplement Enriched With Fish Oil, Prebiotics, and Antioxidants on Nutrition Status in Crohn’s Disease Patients

BACKGROUND Research in the treatment of Crohns disease (CD) supports anti-inflammatory benefits of n-3 fatty acids from fish oil, prebiotics, and antioxidants. A nutritionally balanced inflammatory bowel disease nutrition formula (IBDNF) enriched with these compounds has the potential to improve nutrition status and disease activity in CD. METHODS This is an open-label pilot study investigating the effects of IBDNF on nutrition status in CD patients. Twenty-eight patients with active CD on stable medication were asked to consume 16 oz of IBDNF/d for 4 months. Nutrition status was assessed with dual-energy X-ray absorptiometry scans and serum micronutrient levels. Disease activity and quality of life were measured using the Crohns Disease Activity Index (CDAI) and the Inflammatory Bowel Disease Questionnaire (IBDQ). RESULTS Twenty patients completed the final visit. After 4 months, there was a significant decrease in plasma phospholipid levels of arachidonic acid with increases in eicosapentaenoic acid (EPA) and docosahexaenoic acid. Ten patients had a final EPA concentration of >2%. There was improvement in fat-free and fat mass in patients with final EPA >2% (P = .014 and P = .05). Vitamin D (25-OH) levels improved in all patients (18.5-25.9 ng/mL, P < .001). Those with EPA >2% had significantly lower CDAI (116 ± 94.5 vs 261.8 ± 86.5; P = .005) and higher IBDQ (179.1 ± 26.6 vs 114.6 ± 35.9, P < .001) compared to those with EPA <2%. CONCLUSIONS IBDNF has the potential to deposit fat-free and fat mass, improve vitamin D status, and improve quality of life in CD patients.

Is There a Role for Bowel Rest in Nutrition Management of Crohn's Disease?

In 1988, Greenberg and colleagues published a large randomized controlled trial to address whether bowel rest could lead to improved disease activity in patients with active Crohns disease. The results of this study provide substantial evidence that bowel rest is not necessary to achieve remission in patients with active Crohns disease receiving nutrition support. Before this study, great controversy existed about the use of nutrition support and bowel rest in the treatment of active Crohns disease because of a limited number of conflicting studies providing evidence for and against its application. The results of the publication by Greenberg et al are fundamental because they helped to settle this important argument. Furthermore, this pivotal paper changed the clinical guidelines for the use of nutrition support in the management of active Crohns disease. Since the publication of this pivotal article, many developments in the field of nutrition and in the treatment of Crohns disease have helped validate and further its results. Subsequent studies and debate center on the use of enteral nutrition as primary treatment in patients with active Crohns disease. Data regarding the efficacy, composition, and overall role of adult enteral nutrition in the management of Crohns disease are presented. This article revisits the Greenberg paper and discusses some of these innovations in nutrition.

Calcium Intake and Ion Transporter Genetic Polymorphisms Interact in Human Colorectal Neoplasia Risk in a 2-Phase Study

BACKGROUND The kidney-specific sodium-potassium-chloride cotransporter (NKCC2) protein encoded by solute carrier family 12 member 1 (SLC12A1) is the direct downstream effector of the inward-rectifier potassium channel (ROMK) encoded by potassium inwardly-rectifying channel, subfamily J, member 1 (KCNJ1), both of which are critical for calcium reabsorption in the kidney. OBJECTIVE We hypothesized that polymorphisms in KCNJ1, SLC12A1, and 7 other genes may modify the association between calcium intake and colorectal neoplasia risk. METHODS We conducted a 2-phase study in 1336 cases and 2891 controls from the Tennessee Colorectal Polyp Study. RESULTS In phase I, we identified 5 single-nucleotide polymorphisms (SNPs) that significantly interacted with calcium intake in adenoma risk. In phase II, rs2855798 in KCNJ1 was replicated. In combined analysis of phases I and II, the P values for interactions between calcium intake and rs2855798 were 1 × 10(-4) for all adenoma and 5 × 10(-3) for multiple/advanced adenoma. The highest calcium intake was not associated with risk among those with no variant allele but was significantly associated with a 41% reduced adenoma risk among those who carried at least 1 variant allele in KCNJ1. The corresponding reduction in risk of multiple or advanced adenomas was 52% among those with at least 1 variant allele. The P values for interactions between calcium intake and combined SNPs from the KCNJ1 and SLC12A1 genes were 7.5 × 10(-5) for adenoma and 9.9 × 10(-5) for multiple/advanced adenoma. The highest calcium intake was not associated with risk among those with nonvariant alleles in 2 genes but was significantly associated with a 34% reduced adenoma risk among those who carried a variant allele in 1 of the genes. The corresponding reduction in risk of multiple or advanced adenomas was 64% among those with variant alleles in both genes. CONCLUSION These findings, if confirmed, will be critical for the development of personalized prevention strategies for colorectal cancer.

Mo1734 Serum Fatty Acids Are Correlated With Tissue Cytokine Levels in Ulcerative Colitis

until used for cytokine determination. The concentration of intestine mucosa cytokines involved in the Th1 (IL-2, IL-12p70, IFN-γ), Th2 (IL-4), Th17 (IL-6, IL-17A, IL-23) and Treg (IL-10, TGF-β) cell commitment and IL-1 β and TNF-α (cytokines of the innate immune response) was assayed in duplicate by ELISA (Biosource, Camarillo, CA) and the results were expressed as picogram of cytokine per milligram of protein. Data were analyzed with SPSS. Comparisons between the groups were done by the two-tailed Mann-Whitney U-test. The ileal and colonic concentration of all proinflammatory cytokines was significantly higher in the patients with CD and also UC than in control group (p<0.001 for all). Otherwise, ileal IL-10 (369.7±47.9 vs. 1569.3±81.7) and TGF-β (10534.9±391.2 vs. 13045.8±1005.8) and colonic IL-10 (225.2±47.1 vs. 1563.3±81.7) and TGF-β (7224.0±306.7 vs. 12962.8±991.4) concentration was lower in UC than in controls. Also ileal IL-10 (224.9±23.9) and TGF-β (7073.6±54.4) and colonic IL-10 (310.7±55.3) and TGF-β (9089.1±1850.3) concentration was lower in CD patients than in controls. Significant differences between CD and UC were also observed. Thus, IL-2, IL-6, IL-17, IL-23 ileal and colonic concentration was higher in DC than in UC. Otherwise, IL-10 ileal concentration was lower in CD and IL-10 colonic concentration was lower in UC. The concentration of other cytokines including those of the innate immunity and Th1 response was higher in the ileum of CD and higher in the colon of UC when the diseases where compared. Next CD with and without complications were compared. Although no significant differences were observed between patients with stenosis (n=17) and fistula (n=7), the colonic concentration of Th17-associated cytokines and TNF-α was significantly higher (p<0.03), either in patients with stenosis or with fistula than in those without complications .In conclusion, in CD predominates a Th17 shift, and an insuficient Treg cell activation to suppress the overwhelming proinflammatory milieu was observed in both diseases.

Twenty Years Experience of Home TPN in Crohn's Disease: A Focus on Complications

conditions in patients with new onset of ulcerative colitis and compare the ANS activity with healthy controls (HC). The participants had nomedication ormedical condition affecting the heart rate or the ANS activity. The UC patients were assessed in remission, 3-6 months after the onset of the disease. The ANS function was assessed with HRV by analysis of 24hour Holter monitoring. These were started with controlled respirations in supine and standing position and then the patients were discharged for 24-hours of continuing Holter monitoring. The HRV analysis was performed in both time (RR-intervals, standard deviation of normal RR intervals (SDNN), the root-mean square of difference of successive normal RR intervals (RMSSD)) and frequency domains (low frequency (LF), high frequency (HF), LF/HF ratio). The RR intervals measure the heart rate and SDNN the total variability. RMSSD mainly reflect the parasympathetic tone and the LF/HF ratio in standing position mainly reflects the sympathetic tone. Subjects with UC were compared with HC using the nonparametric Mann Whitney U test. Differences were considered to be significant at the 5% level. Results: Forty-one UC patients and 31 HC were analyzed. There was no significant difference in age between UC patients and HC (34(26-45) vs. 35(28-44) years, NS). The UC patients had a lower LF/HF ratio in standing position compared with HC (3.52(1.60-5.28) vs. 5.51(3.74-8.47), p=0.03). Patients with left-sided colitis including proctitis had a lower LF/ HF ratio in standing position than patients with extensive colitis (2.49(0.86-4.45) vs. 4.59(2.29-7.70), p=0.03).There was no difference in LF/HF ratio in supine position. There was no difference in heart rate (RR intervals) (821(786-874) vs. 864(807-929) ms, NS), total variability (SDNN) 160(140-187) vs. 166(140-182) ms, NS) or parasympathetic tone (RMSSD) (40.5(32.6-61.8) vs. 44.8(34.4-62.1), NS) between the UC patients and the HC. Conclusion: The present study demonstrates an attenuated sympathetic ANS response in patients with new onset of UC and this was correlated to the extension of the disease. Whether this is a preexisting condition in the UC patients or an effect of the inflammation is unclear. An ongoing study will assess the role of ANS activity at onset for the disease course in UC patients.