Adi Lahat

Curcumin in Combination With Mesalamine Induces Remission in Patients With Mild-to-Moderate Ulcerative Colitis in a Randomized Controlled Trial

BACKGROUND & AIMS The phytochemical compound curcumin was reported to be effective in maintaining remission in patients with ulcerative colitis (UC). We investigated curcumins efficacy in inducing remission in patients with active mild-to-moderate UC. METHODS We performed a multicenter randomized, placebo-controlled, double-blind study of 50 mesalamine-treated patients with active mild-to-moderate UC (defined by the Simple Clinical Colitis Activity Index [SCCAI]) who did not respond to an additional 2 weeks of the maximum dose of mesalamine oral and topical therapy. Patients were randomly assigned to groups who were given curcumin capsules (3 g/day, n = 26) or an identical placebo (n = 24) for 1 month, with continued mesalamine. The primary outcome was the rate of clinical remission (SCCAI ≤2) at week 4. Clinical and endoscopic responses were also recorded. RESULTS In the intention-to-treat analysis, 14 patients (53.8%) receiving curcumin achieved clinical remission at week 4, compared with none of the patients receiving placebo (P = .01; odds ratio [OR], 42; 95% confidence interval [CI], 2.3-760). Clinical response (reduction of ≥3 points in SCCAI) was achieved by 17 patients (65.3%) in the curcumin group vs. 3 patients (12.5%) in the placebo group (P < .001; OR, 13.2; 95% CI, 3.1-56.6). Endoscopic remission (partial Mayo score ≤1) was observed in 8 of the 22 patients evaluated in the curcumin group (38%), compared with none of 16 patients evaluated in the placebo group (P = .043; OR, 20.7; 95% CI, 1.1-393). Adverse events were rare and comparable between the 2 groups. CONCLUSIONS Addition of curcumin to mesalamine therapy was superior to the combination of placebo and mesalamine in inducing clinical and endoscopic remission in patients with mild-to-moderate active UC, producing no apparent adverse effects. Curcumin may be a safe and promising agent for treatment of UC. Clinicaltrials.gov number: NCT01320436.

Detection of Small Bowel Mucosal Healing and Deep Remission in Patients With Known Small Bowel Crohn’s Disease Using Biomarkers, Capsule Endoscopy, and Imaging

Objectives:Mucosal healing (MH) and deep remission (DR) are associated with improved outcomes in Crohn’s disease (CD). However, most of the current data pertain to colonic MH and DR, whereas the evidence regarding the prevalence and impact of small bowel (SB) MH is scarce. The aim of this study was to to evaluate the prevalence of SBMH and DR in quiescent SBCD.Methods:Patients with known SBCD in clinical remission (CDAI<150) or with mild symptoms (CDAI<220) were prospectively recruited and underwent video capsule endoscopy after verification of SB patency. Inflammation was quantified using the Lewis score (LS). SBMH was defined as LS<135, whereas a significant inflammation was defined as LS>790. Clinico-biomarker remission was defined as a combination of clinical remission and normal biomarkers. DR was defined as a combination of clinico-biomarker remission and MH.Results:Fifty-six patients with proven SB patency were enrolled; 52 (92.9%) patients were in clinical remission and 21 (40.4%) in clinico-biomarker remission. SBMH was demonstrated in 8/52 (15.4%) of patients in clinical remission. Moderate-to-severe SB inflammation was demonstrated in 11/52 (21.1%) of patients in clinical remission and in 1/21 (4.7%) of patients in clinical and biomarker remission. Only 7/52 (13.5%) patients were in DR.Conclusions:SB inflammation is detected in the majority of CD patients in clinical and biomarker remission. SBMH and DR were rare and were independent of treatment modality. Our findings represent the true inflammatory burden in quiescent patients with SBCD.

Risk Factors Regarding the Need for a Second Operation in Patients with Crohn’s Disease

Background/Aims: The majority of Crohn’s disease patients undergo surgery. However, the factors that predict post-operative recurrence remain controversial. The aim of the present study was to shed light on the potential predictors of such recurrence. Methods: 86 patients who underwent operative procedures for Crohn’s disease were retrospectively studied. Recurrence was defined as the need for a second operation. Life table and multivariate analysis were performed to find the predictors of recurrence. Results: In 26/86 (30%) of the patients, post-operative recurrence was diagnosed within a mean of 42 months of the follow-up. Logistic regression analysis revealed that smoking (OR 3.69, 95% CI 2.06–11.52) and perforating disease (OR 4.09, 95% CI 1.31–12.65) were associated with a risk of recurrence. However, survival analysis showed that only perforating disease was associated with an early post-operative recurrence (log-rank test, p < 0.001). Neither resected surgical specimen characteristics, nor the duration and the location of the disease were found to predict the need for a second operation. Conclusion: The risk for Crohn’s disease patients who undergo surgery is related to the presence of perforating disease and smoking, which predict the need for a second operation. The former is associated with an even earlier recurrence.

The decline of anti-drug antibody titres after discontinuation of anti-TNFs: implications for predicting re-induction outcome in IBD

Anti‐drug antibodies can be elicited by infliximab and adalimumab, but the rate of their decay after therapy is stopped is unknown.

Impact of Cannabis Treatment on the Quality of Life, Weight and Clinical Disease Activity in Inflammatory Bowel Disease Patients: A Pilot Prospective Study

Background and Aims: Inflammatory bowel disease (IBD) patients suffer from significant morbidity and diminished life quality. The plant cannabis is beneficial in various gastrointestinal diseases, stimulating appetite and causing weight gain. Our aims were to assess whether treatment with inhaled cannabis improves quality of life, disease activity and promotes weight gain in these patients. Methods: Patients with long-standing IBD who were prescribed cannabis treatment were included. Two quality of life questionnaires and disease activity indexes were performed, and patient’s body weight was measured before cannabis initiation and after 3 months’ treatment. Results: Thirteen patients were included. After 3 months’ treatment, patients reported improvement in general health perception (p = 0.001), social functioning (p = 0.0002), ability to work (p = 0.0005), physical pain (p = 0.004) and depression (p = 0.007). A schematic scale of health perception showed an improved score from 4.1 ± 1.43 to 7 ± 1.42 (p = 0.0002). Patients had a weight gain of 4.3 ± 2 kg during treatment (range 2–8; p = 0.0002) and an average rise in BMI of 1.4 ± 0.61 (range 0.8–2.7; p = 0.002). The average Harvey-Bradshaw index was reduced from 11.36 ± 3.17 to 5.72 ± 2.68 (p = 0.001). Conclusions: Three months’ treatment with inhaled cannabis improves quality of life measurements, disease activity index, and causes weight gain and rise in BMI in long-standing IBD patients.

Lidocaine down-regulates nuclear factor-κB signalling and inhibits cytokine production and T cell proliferation

Lidocaine is a commonly used local anaesthetic agent which has also been found to possess anti‐inflammatory activity in several disorders. However, the mechanism of this effect has been little explored. The aim of this study was to investigate the effect of lidocaine on stimulated human T cells. The effect of lidocaine on Jurkat T cells was examined by enzyme‐linked immunosorbent assay (ELISA) to determine secretion of interleukin (IL)‐2, and by the [3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide] viability assay. Tumour necrosis factor (TNF)‐α and IL‐2 mRNA expression was determined by reverse transcription–polymerase chain reaction. In addition, the effect of lidocaine on the proliferation of freshly isolated peripheral blood (PB) CD3+ T cells was examined by carboxyfluorescein succinimidyl ester dilution. Apoptosis induction and cytokine production and secretion were determined by annexin V/PI assay, intracellular immunostaining and ELISA respectively. The results showed that lidocaine exerts a dose‐dependent inhibition of IL‐2 and TNF‐α secretion by Jurkat T cells at the protein and mRNA levels. Moreover, lidocaine reduced nuclear factor‐κB (NF‐κB) signalling in clinically relevant concentrations. Similarly, proliferation of anti‐CD3 stimulated PB T cells was abrogated significantly by lidocaine, and the percentage of interferon‐γ‐ and TNF‐α‐producing T cells was diminished after culture with this agent. In both experimental systems, lidocaines effect was not mediated by cytotoxic mechanism, as no significant apoptosis or necrosis was demonstrated following co‐culture of T cells with this drug. In conclusion, lidocaines anti‐inflammatory effect may be mediated by a drug‐induced abrogation of T cell proliferation and cytokine secretion independent of cell death. These effects are mediated at least partly by inhibition of NF‐κB signalling.

Obesity, Metabolic Syndrome and the Risk of Development of Colonic Diverticulosis

Introduction: Colonic diverticulosis is a common condition with obscure pathogenesis. Obesity, hyperlipidemia and hypertension have been demonstrated to increase the risk of complicated diverticular disease, but the impact of metabolic risk factors on the prevalence of uncomplicated diverticulosis has not been clearly determined. Aims: The aim of the study was to examine the impact of obesity and metabolic syndrome on the prevalence of colonic diverticulosis. Methods: This retrospective case-control study included patients aged 40–85 years who were followed up by the Institute of Medical Screening in Israel and underwent colonoscopy in 2006–2011 for indication of colorectal cancer screening. Patients with diverticulosis as detected by colonoscopy were compared to patients without diverticulosis. The comparison parameters included medical history, biometric parameters, biochemical and lipid profile. Results: The study included 3,175 patients. Diverticulosis was diagnosed in 17.4% of the cohort. On univariate analysis, age, male gender, BMI (continuous variable), obesity, systolic blood pressure, low-density lipoprotein cholesterol level, history of hypertension, ischemic heart disease, hypothyroidism, and absence of diabetes mellitus were associated with an increased risk of colonic diverticulosis. On multivariate analysis, advanced age, male gender, obesity (BMI >30), history of hypothyroidism and absence of diabetes mellitus were associated with an increased risk of diverticulosis. Prevalence of colonic polyps was similar in patients with and without diverticulosis. Conclusion: Colonic diverticulosis was associated with age, male gender, obesity and hypothyroidism. Diabetes mellitus was associated with a decreased risk of colonic diverticulosis.

The utility of capsule endoscopy in the diagnosis of Crohn's disease based on patient's symptoms.

Background and Goals Video capsule endoscopy (VCE) enables visualization of the entire small bowel and can identify lesions that may go undetected by conventional endoscopy and radiography. In this study, we assessed whether patients selection based on symptoms may increase the yield of VCE in the diagnosis of Crohns disease (CD). Study Findings of 125 consecutive patients referred for VCE in whom CD may be suspected, were analyzed. Indications for VCE included iron-deficiency anemia, abdominal pain, diarrhea, or a combination of symptoms. Capsule endoscopy (CE) results were defined positive if 4 or more obvious clear ulcers, erosions, or a region with clear exudate and mucosal hyperemia and edema were identified. Results One hundred twelve patients were included in the final analysis. Mean age of patients was 44±22 years and median follow-up 36±15 months. Findings on CE were considered compatible with a diagnosis of CD in 7 patients (6%). In general, CE yielded a diagnosis of CD in a very small portion of the patients (0% to 4%), except in patients undergoing the test for a combination of abdominal pain and diarrhea. In this group, findings suggestive of inflammatory bowel disease were encountered in one-third of the patients (P=0.002). Conclusions The greatest yield of CE in diagnosing CD is achieved in young patients who present with symptoms of abdominal pain plus diarrhea.

Diverticulitis in the young is not more aggressive than in the elderly, but it tends to recur more often: systematic review and meta-analysis.

For years, the natural course of diverticulitis in the young has been debatable in terms of its severity and recurrence rate, and no consensus has been reached regarding its treatment and timing of surgery. Thus, the study aims to evaluate by meta‐analysis the natural course of acute diverticulitis in the young.

Tumour Necrosis Factor Mediates Bacterial Translocation After Haemorrhagic Shock and Endotoxaemia

OBJECTIVE To assess the extent of bacterial translocation after haemorrhagic shock and reperfusion, and the involvement of tumour necrosis factor (TNF) in its mediation. DESIGN Controlled, randomised prospective experiment. SUBJECTS 87 rats in 7 groups. INTERVENTIONS Haemorrhagic shock was induced in rats for 1 hour. Endotoxaemia was induced in a second group by the injection of lipopolysaccharide. A third group was injected with exogenous TNF. Some of the animals were further treated with anti-TNF. MEASUREMENTS After 24 hours, bacterial translocation in blood and in several remote organs, and serum TNF concentrations were measured. RESULTS High bacterial counts were found in all remote organs of rats with haemorrhagic shock or endotoxaemia. Their serum TNF concentrations were significantly higher than in the corresponding sham-operated controls. Anti-TNF significantly reduced the extent of bacterial translocation. Rats, the only treatment of which was exogenous TNF, developed substantial bacterial translocation. CONCLUSION Bacterial translocation is associated with increased serum TNF, and can be minimised by anti-TNF. This, and the triggering of translocation in unprovoked animals by TNF alone, suggest that TNF may be the stimulator, and not the consequence, of bacterial translocation.