Hyperbaric Oxygen Therapy Achieved Fistula Healing in a Young Patient With Severe Refractory Perianal Crohn's Disease.

The presence of perianal fistulae constitutes a more severe phenotype of Crohn's disease (CD) that often requires intensive medical therapy, wound care, and surgical intervention. Despite therapeutic advances in inflammatory bowel disease, the treatment of perianal fistulae remains challenging. Hyperbaric oxygen therapy (HBOT) has been proposed as an adjunctive treatment modality for induction of fistula healing. We illustrate a case in which HBOT achieved fistula healing in a young patient with severe refractory perianal Crohn's disease (pCD). We also review the current literature and discuss the role of HBOT in the treatment armamentarium of pCD.

Clinical utility of thiopurine metabolite monitoring in inflammatory bowel disease and its impact on healthcare utilization in Singapore.

Background and Aim: Thiopurines are recommended for maintenance of steroid-free remission (SFR) in inflammatory bowel disease (IBD). Thiopurine metabolite monitoring (MM) is increasingly used in the West but remains novel in Singapore, with limited information on its therapeutic and economic benefits. Hence, this study aims to investigate MM's clinical utility and its impact on healthcare resource utilization in Singaporean IBD patients. Methods: A retrospective observational study was conducted at Singapore General Hospital outpatient IBD Centre. Patients with IBD, baseline MM during 2014-2017, and weight-based thiopurine doses for ≥4 weeks were followed up for 1 year. Actions were taken to optimize therapy, and metabolite levels before and after the first action were documented. Outcomes assessed included SFR, no therapy escalation or surgery, healthcare resource utilization, and direct healthcare costs. Results: Ninety IBD patients (50 Crohn's disease, 40 ulcerative colitis) were included. Among them, 40% had baseline metabolite levels within therapeutic range, 31.1% sub-therapeutic, 21.1% supra-therapeutic, and 7.8% shunters. Repeated MM with subsequent dose optimization helped 67.2% of patients achieve therapeutic levels after 1 year. Overall, 87.8% of patients achieved SFR and 90% had no therapy escalation or surgery. Despite greater outpatient visits and laboratory investigations with MM, the median total healthcare costs at 1 year only increased marginally (S$6407.66 [shunters] vs S$5215.20 [supra-therapeutic] vs S$4970.80 [sub-therapeutic] vs S$4370.48 [control (within therapeutic range)], P = 0.592). Conclusion: MM guided timely therapy escalation for non-responders, identification of non-adherence, and reversal of shunting. Therefore, it is a useful clinical tool to optimize thiopurines without significantly increasing healthcare costs.

Oral Supplementation of Tocotrienol-Rich Fraction Alleviates Severity of Ulcerative Colitis in Mice.

Ulcerative colitis (UC) is characterized by damaged colonic mucosa and submucosa layers that are caused by excessive inflammatory reactions and oxidative stress. This study aimed to examine the use of tocotrienol-rich fraction (TRF) in mitigating damages caused by UC on the colon epithelium. Dextran sulfate sodium (DSS)-induced UC mice were treated with vehicle control, TRF, alpha-tocopherol (αTP) and 5-aminosalicylic acid (5-ASA). Observable clinical signs, quality of stool, histopathological scoring, inflammatory and oxidative markers were assessed. Vitamin E levels of colons and plasma were quantified. Oral supplementation of TRF significantly reduced the severity of DSS-induced UC by lowering the disease activity index (DAI) and histopathological inflammatory scoring. TRF also attenuated the DSS-induced enlargement of spleen and shortening of the colon. TRF has demonstrated marked anti-inflammatory and antioxidative properties indicated by the attenuation of DSS-induced upregulation of inflammation and oxidative stress markers including interleukin (IL)-6, IL-17, tumor necrosis factor (TNF)-α, myeloperoxidase (MPO), cyclooxygenase-2 (COX-2), nitric oxide (NO), malondialdehyde (MDA) and pNF-κB. These improvements were similar to that of 5-aminosalicylic acid (5-ASA) treatment. In contrast, αTP did not demonstrate evident clinical and histopathological improvements. The superior protective effect of TRF may be ascribed to the preferential absorption of TRF by the gut mucosa. TRF alleviated the signs and symptoms of acute UC in murine model via the reduction of local inflammatory reactions and oxidative stress. These effects suggested that TRF could serve as a gut health supplement for preventive measures for UC condition in patients.

A review of vedolizumab and ustekinumab for the treatment of inflammatory bowel diseases.

Recent advancement in the understanding of the pathophysiology of inflammatory bowel disease has seen an expansion in therapeutic options. Vedolizumab, a selective α4ß7 inhibitor, and ustekinumab, an IL 12/23 p40 inhibitor, have provided the much-awaited out-of-class alternatives for patients who have failed or who are intolerant to anti-Tumor Necrosis Factor (TNF) therapy. However, questions remain as to how we may best use these novel therapeutic agents. We evaluate the evidence available from randomized controlled trials and postmarketing cohort studies and discuss their safety, efficacy, and limitations, in relation to anti-TNF therapy, in optimizing the treatment outcomes.

Healing the mucosa in Crohn's disease: does it matter?

Clinical remission has been the therapeutic goal of Crohn's disease treatment for many years. While it has helped to ameliorate the symptoms, this treatment strategy has not brought about significant changes in the need for abdominal surgery in the natural history of Crohn's disease. The advent of biological agents (biologics) has shown that it is possible to induce and maintain mucosal healing in a significant proportion of treated patients. Data is also emerging to show that this has translated to fewer instances of hospitalisation and surgery for these patients. This is a paradigm shift in the therapeutic goal of Crohn's disease treatment.

Azathioprine is effective in corticosteroid-dependent Asian inflammatory bowel disease patients.

BACKGROUND: Azathioprine (AZA) is widely used to treat corticosteroid (CS)-dependent IBD patients but evidence supporting its use in Asian IBD patients is limited. We evaluated the efficacy of AZA in a single-center cohort of CS-dependent Asian IBD patients. METHODS: Patients treated with AZA were identified from our registry and the medical records were reviewed. Inclusion criterion was: first course of AZA and treatment duration ≥ 6 months. Clinical response was assessed at 6 months and classified as complete response, partial response, and nonresponse. Factors associated with response (age, gender, ulcerative colitis [UC] extent, Crohn's disease [CD] behavior, ethnicity, concomitant 5-aminosalicylates/sulfasalazine, baseline activity, disease duration, leukocyte count, mean corpuscular volume, and AZA dose) were analyzed using the chi-square or Mann-Whitney U-test. Probability of sustained remission was estimated using the Kaplan-Meier method. Differences in survival curves between factors were tested with log-rank tests. RESULTS: Sixty-four patients were included. At baseline the median age was 37.5 (range, 15-76) years, 50% male, 59.4% Chinese, 50% CD, 50% UC, and mean CS dose 20.2 (SD 10.9) mg. At month 6, complete response was 48.4% (95% confidence interval [CI], 36.7-61.3), partial response 45.1% (95% CI, 32.8-58.3), and nonresponse 7.8% (95% CI, 2.6-17.3). Partial responders had mean CS dose reductions of 11.7 mg (95% CI, 7.2-16.4, P < 0.001). The proportion of patients with sustained remission was 0.87 (95% CI, 0.73-1.0) at 2 years, 0.76 (95% CI, 0.57-0.95) at 3 years, and 0.61 (95% CI, 0.30-0.91) at 5 years of AZA treatment. Female gender was positively associated with sustained remission. CONCLUSIONS: Our study demonstrates the short- and long-term effectiveness of AZA therapy among CS-dependent Asian IBD patients.

The Incidence of self-prescribed oral complementary and alternative medicine use by patients with gastrointestinal diseases.

GOALS: To assess the incidence of oral complementary and alternative medicine (CAM) usage by gastroenterology patients at a single university center and compare against controls. BACKGROUND: The public awareness and usage of CAM have increased. The use of CAM has been described in patients with functional bowel disorders; however, their role in patients with gastrointestinal disease is less clear. STUDY: Patients attending luminal gastroenterology clinics and customers at local supermarkets completed a 30-point, structured questionnaire assessing their use of CAM. RESULTS: A total of 1,409 subjects were recruited. The incidence of CAM use was 49.5% for inflammatory bowel disease, 50.9% for irritable bowel syndrome, 20% for general gastrointestinal diseases, and 27% for controls. Pearson's chi(2) tests showed that patients with inflammatory bowel disease (IBD) or irritable bowel syndrome were more likely to use CAM than controls (P < 0.001). Binary logistic regression analysis showed that females were more likely to take CAM than men (P < 0.05). CONCLUSIONS: The percentage of CAM users among patients with IBD is similar to those with a functional diagnosis. Increasing numbers of IBD patients are using CAM in addition to conventional therapy. Awareness of this may prevent adverse CAM and conventional drug interactions.

Associations between diet and disease activity in ulcerative colitis patients using a novel method of data analysis.

BACKGROUND: The relapsing nature and varying geographical prevalence of ulcerative colitis (UC) implicates environmental factors such as diet in its aetiology. METHODS: In order to determine which foods might be related to disease activity in UC a new method of dietary analysis was developed and applied. Eighty-one UC patients were recruited at all stages of the disease process. Following completion of a 7 d diet diary, clinical assessment including a sigmoidoscopic examination (scale 0 (normal mucosa) to 6 (very active disease)) was conducted. Food weights for each person were adjusted (divided) by the person's calorific intake for the week. Each food consumed was given a food sigmoidoscopy score (FSS) calculated by summing the products of the (adjusted) weight of food consumed and sigmoidoscopy score for each patient and occurrence of food and dividing by the total (adjusted) weight of the food consumed by all 81 patients. Thus, foods eaten in large quantities by patients with very active disease have high FSSs and vice versa. Foods consumed by <10 people or weighing <1 kg for the whole group were excluded, leaving 75 foods. RESULTS: High FSS foods were characterized by high levels of the anti-thiamin additive sulfite (Mann-Whitney, p < 0.001), i.e. bitter, white wine, burgers, soft drinks from concentrates, sausages, lager and red wine. Caffeine also has anti-thiamin properties and decaffeinated coffee was associated with a better clinical state than the caffeine containing version. Beneficial foods (average intake per week) included pork (210 g), breakfast cereals (200 g), lettuce (110 g), apples and pears (390 g), milk (1250 ml), melon (350 g), bananas (350 g), bacon (120 g), beef and beef products (500 g), tomatoes (240 g), soup (700 g), citrus fruits (300 g), fish (290 g), yogurt (410 g), cheese (110 g), potatoes (710 g) and legumes (120 g). CONCLUSIONS: The dietary analysis method described provides a new tool for establishing relationships between diet and disease and indicates a potentially therapeutic diet for UC.

Probiotics, prebiotics and antibiotics in inflammatory bowel disease.

Probiotics and prebiotics are the sort of therapy that most patients with inflammatory bowel disease (IBD) wish for. They are without significant side effects, except possibly an increase in gas with prebiotics, and so far, appear to be entirely safe. However, are they effective? More than a dozen studies using probiotics in IBD have now been reported, and there is dear benefit in pouchitis and possibly also in Crohn's, although there are so many clinical types of this condition that a clear indication has yet to emerge. For ulcerative colitis (UC) more studies are needed. The use of prebiotics in IBD is only just starting, although significant effects on both the luminal and mucosa-associated flora have been demonstrated in healthy subjects. Antibiotics offer more certain hope in IBD treatment, although with a much greater risk of unwanted effects. Their efficacy in clinical studies varies, with Crohn's disease and pouchitis reporting more benefit than ulcerative colitis. However, the ideal combination of antibiotics, and rationale for their use has not been determined.