Background & Aims Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have revolutionized the treatment of type 2 diabetes mellitus and obesity in recent years. While gastrointestinal adverse events are common, their association with nutritional deficiencies, including thiamine, has not been comprehensively investigated. This study aimed to evaluate whether treatment with GLP-1 RAs is associated with the occurrence of Wernicke encephalopathy (WE). Methods We conducted a pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS) and a narrative literature review. Disproportionality analysis assessed WE reporting following GLP-1 RA treatment using the reporting odds ratio (ROR) and the lower bound of the information component (IC) 95% credibility interval. Results We identified 15 cases of GLP-1 RA-associated WE: 13 from FAERS, 1 from published literature, and 1 from our medical center. Most cases occurred with semaglutide (n=8/15) or tirzepatide (6/15), and were reported in 2023-2024 (14/15). Most patients (13/15) reported gastrointestinal manifestations of either weight loss, vomiting, loss of appetite, or malnutrition. Classic WE symptoms were reported in 11 patients, and the full clinical triad in 2 patients. Long-term neurological sequelae were noted in 7 of 11 patients with follow-up data. Disproportionality analysis showed increased reporting of WE with GLP-1 RAs compared with other medications (ROR=2.35 [95%CI, 1.38-4.01]; IC025=0.29). Conclusions WE is a potentially rare but severe adverse event of GLP-1 RA treatment, mainly with semaglutide or tirzepatide. As early detection may prevent neurological sequelae, increased clinical awareness is warranted, especially in individuals experiencing severe gastrointestinal symptoms.

Background:Dietary interventions and multiple food-item restrictions are challenging for patients with irritable bowel syndrome (IBS), and associated with inadequate adherence. We aimed to examine the efficacy of an individualized-selective dietary intervention, based on Leukocyte activation to food-components (i.e. Alcat-guided diet) in IBS. Methods:A randomized, double-blind, sham-controlled trial allocated IBS patients at Sheba Medical Center (Ramat Gan, Israel) between 5 August 2020 and 11 April 2022 to either an Alcat-guided or a sham-balanced diet for 8-week treatment. The primary outcome was a 50-point reduction on the IBS-symptom severity scale (IBS-SSS). The rates of improvement in the IBS Global Improvement Scale (IBS-GIS) and positive response (yes/no) were defined as secondary and exploratory outcomes, respectively. Results:A total of 68 patients with IBS-D/M (44/24) were enrolled. Baseline characteristics were comparable between groups except for a higher median IBS-SSS score in the Alcat group compared with controls [390 (305-435) vs 330 (240-390), P = 0.013]. At week 8, 30 of 35 (85.7%) patients in the Alcat group met the primary outcome, compared with 18 of 33 (54.5%) of controls (P = 0.005). Alcat patients had higher rates of IBS-GIS improvement (74.3% vs 42.4%, P = 0.008) and positive response (85.7% vs 57.6%, P = 0.010) compared with controls at week 8. Among a balanced sub-cohort of patients (n = 49) with IBS-SSS score of 250-450 [median: 380 (305-410) vs 355 (310-400) for the Alcat and control groups, respectively, P = 0.487], the primary outcome was still more commonly achieved among Alcat patients compared with controls (90% vs 59%, P = 0.022). No serious adverse events were reported. Conclusion:Immune-based personalized-diet was more efficient than sham-based diet for reducing symptoms in IBS patients, and may serve as a safe treatment option in this population.

Background: Longer cecal withdrawal time has been linked to a higher adenoma detection rate (ADR), with a minimum duration of 6 min recommended. Therefore, we developed the cecal withdrawal vocal timer (CWVT), a novel software tool that is command-activated at cecal intubation and vocally informs the endoscopist of the withdrawal duration every minute. Objectives: Evaluating the efficacy of the CWVT in enhancing adenoma detection. Design: A retrospective, single-center study of screening colonoscopies with adequate preparation and documented cecal intubation. Methods: The primary endpoint was the change in the department’s ADR before (2022) and after the CWVT introduction (January 2023–February 2024). Secondary endpoints included the ADR change between procedures with and without CWVT after its introduction and the ADR change among individual endoscopists. Results: The study included 1098 and 1330 eligible colonoscopies pre- and post-CWVT introduction, respectively. Following CWVT introduction, 67.3% of colonoscopies were performed with activated CWVT, with a median withdrawal time of 8.7 (interquartile range: 6.9–11.8) min. The department ADR was 25.5% following CWVT introduction, without a significant difference compared to the year before (26.2%, p = 0.71). During the post-CWVT implementation period, colonoscopies with activated CWVT had higher ADR than those without (28.4% vs 19.5%, respectively, p < 0.001). The improvement was mainly driven by the detection of adenomas smaller than 10 mm and was consistent across 11 out of 12 months in this period and among most endoscopists. Conclusion: While an overall ADR improvement was not achieved with the CWVT, the ADR was higher in post-CWVT procedures that utilized the CWVT than those that did not, warranting further prospective studies to evaluate CWVT’s contribution to screening colonoscopy performance.

AbstractAims and BackgroundMatrix metalloproteinase‐7 (MMP‐7) and Syndecan‐1 (SDC1) are involved in multiple functions during tumorigenesis. We aimed to evaluate the diagnostic and prognostic performance of these serum proteins, as potential biomarkers, in patients with pancreatic ductal adenocarcinoma (PDAC) and benign pancreatic cysts.MethodsIn this case–control study, patients with newly diagnosed PDAC (N = 121) were compared with the benign cyst (N = 66) and healthy control (N = 48) groups. Serum MMP‐7 and SDC1 were measured by ELISA. The diagnostic accuracy of their levels for diagnosing PDAC and pancreatic cysts was computed, and their association with survival outcomes was evaluated.ResultsMMP‐7 median serum levels were significantly elevated in the PDAC (7.3 ng/mL) and cyst groups (3.7 ng/mL) compared with controls (2.9 ng/mL) (p < 0.001 and 0.02, respectively), and also between the PDAC and cyst groups (p < 0.001), while SDC1 median serum levels were significantly elevated in PDAC (43.3 ng/mL) compared with either cysts (30.1 ng/mL, p < 0.001) or controls (31.2 ng/mL, p < 0.001). The receiver operating characteristic curve analysis area under the curve in PDAC versus controls was 0.90 and 0.78 for MMP‐7 and SDC1, respectively, while it was 1.0 for the combination of the two and CA 19‐9 (p < 0.001). The combination of the three biomarkers had a perfect sensitivity (100%).ConclusionsDue to its high sensitivity, this biomarker panel has the potential to rule out PDAC in suspected cases.

BackgroundSedation increases colonoscopy risks and prolongs recovery time. We examined whether virtual reality (VR) can substitute for sedation. The primary outcome was the overall satisfaction of patients who underwent colonoscopy with VR headset compared with patients who underwent standard sedation. Pain during the procedure, polyp detection rate (PDR), colonoscopy duration, post-colonoscopy adverse events, post-colonoscopy recovery, time-to-return to daily functions, and turnaround time at the endoscopy unit were secondary outcomes.MethodsThe study was approved by Sheba Medical Center's ethics committee IRB number 21-8177-SMC. Sixty patients were sequentially enrolled in a 1:1 ratio to either standard sedated colonoscopy or VR-unsedated procedure, and all patients signed a written informed consent. 28/30 patients successfully completed the colonoscopy using VR headset. Overall satisfaction score was comparable between the groups.ResultsThere was no difference between VR and controls in colonoscopy duration, or PDR. VR patients had numerically lower rate of post-colonoscopy adverse events than controls. The proportion of VR patients who reported resuming daily activities on the day of the procedure was significantly higher than in the control group. The VR group patients spent significantly less time in the hospital compared to the control group.ConclusionsVR technology can provide adequate substitution for sedation for most patients undergoing colonoscopy and offers comparable patient satisfaction and faster return to daily activities.

Introduction: Dietary intervention is a common treatment among patients with irritable bowel syndrome (IBS). However, insufficient patient adherence, and essential need for ingredient restrictions limiting its use in this population. Immune assay guided diet may provide an individualized intervention, which may increase its effectiveness compared with non-personalized dietary strategies. We aimed to test the effectiveness of an individualized dietary intervention, based on Leukocyte activation to dietary components (Alcat, Germany), to improve patient compliance to diet modifications. Methods: A randomized, double-blind, 2-arm trial, comparing the efficacy of Alcat-diet versus a “Sham” balanced diet for 8-week treatment of IBS. The primary outcome was defined as a reduction of ≥50 points on the IBS-severity scoring system (IBS-SSS). Secondary outcomes included the raw scores of IBS-SSS, Irritable Bowel Syndrome Quality of Life Questionnaire (IBS-QoL) and the Visual Analogue Scale for Irritable Bowel Syndrome (VAS-IBS). IBS-Adequate Response rate and the rates of moderate / substantial improvement on the IBS Global assessment of improvement (IBS-GAI) and the IBS Global Improvement Scale (IBS-GIS) were documented. Results: Sixty-eight patients with IBS-D (44) and IBS-M (24) were enrolled. At baseline, patients in the Alcat-group had a higher median IBS-SSS score compared with the controls (390 [305-435] vs 330 [240-390], respectively, P=0.013). At week 8 of dietary intervention, 30/35 (85.7%) patients in the Alcat-group met the primary outcome, compared with 18/33 (54.5%) of the controls (P=0.005). After 8 weeks, there were higher rates of patients in the Alcat-group who reported a symptomatic improvement (i.e., positive response: 85.7% vs 57.6%, P=0.010 and IBS-GIS: 74.3% vs 42.4%, P=0.008, Δ VAS-IBS abdominal pain score: 49.7±29.8 vs 31.6±28.8, P=0.020) compared with the controls. Alcat-diet was more beneficial for patients who were naïve to dietary-intervention (ΔIBS-SSS≥50 rate: 100% vs 57%, respectively, P=0.010), than patients who had previously tried any dietary-intervention (ΔIBS-SSS≥50 rate: 77% vs 50%, respectively, P=0.148) compared with the Sham-diet. No serious adverse events were reported during follow-up. Conclusion: Immune-based personalized diet was more efficient than Sham-diet for reducing symptoms in IBS patients, and may serve as a safe treatment option in this population (Figure 1).Figure 1.: Study outcome rates at the end of follow-up (8-week time point) divided to the Alcat-based diet group and the Sham-based diet group. Abbreviations: Irritable bowel syndrome, IBS; IBS Symptom Severity Scale, IBS-SSS; IBS global assessment of improvement, IBS-GAI; IBS global improvement scale, IBS-GIS.

INTRODUCTION: Although Crohn's disease (CD) is a known risk factor of small bowel adenocarcinoma (SBA), early diagnosis remains a significant clinical challenge. Identification of biomarkers for SBA may lead to early detection. METHODS: This is a retrospective study comparing albumin levels and neutrophil-to-lymphocyte ratio (NLR) of patients with long-standing CD who underwent small bowel resection with and without malignancy. RESULTS: Forty-two patients with CD were included in this study (11 with SBA). Median NLR before surgery was 8.5 (interquartile range 6.2–31.3) in patients with SBA and 3.8 (interquartile range 2.8–5.3) for patients without SBA (P < 0.05). Mean albumin levels before surgery were significantly lower among patients with SBA compared with patients without SBA (2.6 ± 0.6 g/dL vs 3.5 ± 0.6 g/dL, respectively, P < 0.05), despite patients with SBA being under longer total parenteral nutrition treatment duration. DISCUSSION: CD patients with SBA diagnosis have increased NLR and lower albumin before surgery compared with CD patients without detection of SBA.

INTRODUCTION: Syndecan-1 (SDC1) has multiple functions in tumorigenesis in general and specifically in pancreatic cancer. We aimed to evaluate SDC1 as a diagnostic and prognostic biomarker in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: In this case-control study, patients newly diagnosed with a biopsy-proven PDAC were enrolled alongside healthy individuals in a derivation-validation cohort design. Serum SDC1 was measured by enzyme-linked immunoassay. The diagnostic accuracy of SDC1 levels for diagnosing PDAC was computed. A unified cohort enriched with additional early-stage patients with PDAC was used to evaluate the association of SDC1 with survival outcomes and patient characteristics. RESULTS: In the derivation cohort, serum SDC1 levels were significantly higher in patients with PDAC (n = 39) compared with healthy controls (n = 20) (40.1 ng/mL, interquartile range 29.8–95.3 vs 25.6 ng/mL, interquartile range 17.1–29.8, respectively; P < 0.001). The receiver operating characteristic analysis area under the curve was 0.847 (95% confidence interval 0.747–0.947, P < 0.001). These results were replicated in a separate age-matched validation cohort (n = 38 PDAC, n = 38 controls; area under the curve 0.844, 95% confidence interval 0.757–0.932, P < 0.001). In the combined-enriched PDAC cohort (n = 110), using a cutoff of 35 ng/mL, the median overall 5-year survival between patients below and above this cutoff was not significantly different, although a trend for better survival after 1 year was found in the lower level group (P = 0.06). There were 12 of the 110 patients with PDAC (11%) who had normal CA 19-9 in the presence of elevated SDC1. DISCUSSION: These findings suggest serum SDC1 as a promising novel biomarker for early blood-based diagnosis of pancreatic cancer.

Question: A 59-year-old man presented to the emergency room with severe neck pain that started 3 days before presentation and was accompanied by odynophagia and progressive dysphagia to solids and fluids. He was otherwise healthy, without any previous neck surgeries. He denied having any fever, chills, trauma, or weight loss. No neurologic complains were reported. He did not recall any previous episodes resembling this presentation. He had normal vital signs with a temperature of 36.7°C.

I1 World Congress for Integrative Medicine & Health 2017 - A global forum for exploring the future of comprehensive patient care Benno Brinkhaus1, Torkel Falkenberg2,3, Aviad Haramati4,5, and Stefan N. Willich1 1Institute for Social Medicine, Epidemiology and Health Economics, Charite – Universitatsmedizin Berlin, Berlin, Germany; 2Department of Neurobiology Care Sciences and Society, Division of Nursing, Research Group Integrative Care, Karolinska Institutet, Stockholm, Sweden; 3I C – The Integrative Care Science Center, Jarna, Sweden; 4Department of Biochemistry, Molecular and Cellular Biology, Georgetown University, Medical Center, Washington, DC, USA; 5Department of Medicine, Georgetown University Medical Center, Washington, DC, USA We are excited to present the abstracts of the keynote speakers, parallel sessions and oral and poster presentations of the World Congress on Integrative Medicine & Health (WCIMH 2017; http://www.ecim-iccmr.org/2017/) to be held in Berlin on May 3-5, 2017, which will be jointly convened by the European Society of Integrative Medicine (ESIM) and the International Society for Complementary Medicine Research (ISCMR). The Congress will take place in association with a number of national and international organizations from North America and other continents. Consequently, the congress will provide the most comprehensive global forum and perspective in the field of Complementary and Integrative Medicine in 2017. The congress goal is reflected in its tag line: The Future of Comprehensive Patient Care - Strengthening the Alliance of Researchers, Educators and Providers. We believe that by bringing together researchers, educators and providers, who are addressing various aspects of Integrative Medicine and health, we can build on the evidence obtained through research to inform clinical education and practice and thereby create a better platform for comprehensive patient care. The main themes of the Congress are: Clinical care: The practice of Integrative Medicine should be based on distinct definitions, should be informed by evidence and evolve from guidelines that are developed by experts from conventional and complementary medicine. Education: Academic leaders and health officials have called for future clinicians to possess the knowledge and skills to understand how Integrative Medicine can be incorporated into conventional care to improve the health of the public. Therefore, it is essential to share best practices in how to create robust curricular opportunities for medical students to experience systematic teaching of the principles, strengths and limitations of Integrative Medicine. Research: Within this Congress scientists will showcase the highest quality research worldwide in this field and will provide the state-of-the-science evidence base through plenary lectures, symposia and abstract presentations. Traditional healing systems (THS): Traditional healing practices and practitioners are an important and often underestimated part of health care. THS is found in almost every country in the world and the demand for its services is increasing. Research contributing to evidence informed decision making is imperative to develop a cohesive and integrative approach to health care that allows governments, health care practitioners and, most importantly, those who use health care services, to access THS in a safe, respectful, cost-efficient and effective manner. Arts and medicine: For the first time at a research congress, this theme will explore the important contributions of the arts (music, visual arts, dancing, etc,) for integrative therapeutic interventions to achieve optimal health and healing. Given the ambitious scope of this worldwide international congress, the four authors of the present editorial serve as co-presidents and they are guided by the International Organizing Committee consisting of many experts from around the world including Myeong S. Lee, Jianping Liu, Kenji Watanabe (from Far East Asia), Renee Street (Africa), Amie. Steel (Australia), Paulo Arturo Caceres Guido, Chin An Lin (South America), Heather Boon, Josephine Briggs, John Weeks (North America) and Abdullah Al-Bedah, Mohamed Khalil, Elad Schiff (Middle East and Israel). The programming for each of the five themes is directed by WCIMH 2017 theme subcommittees involving some of the most highly regarded clinicians, educators and researchers in the world in this field (in alphabetic order): Linda Balneaves, Lesley Braun, Eva Bojner Horwitz, Gustav Dobos, Jeffery Dusik, David Eisenberg, Iva Fattorini, Eckhart G. Hahn, Suzanne B. Hanser, Frederick Hecht, George Lewith, Harald Matthes, Andreas Michalsen, Judy Rollins, Volker Scheid, Michael Teut, Robert Saper, Claudia M. Witt, Merlin Wilcox and Darong Wu. The Local Organizing Board is coordinated by M. Cree. We are very grateful to all organisations and individuals working diligently to making this first World Congress for Integrative Medicine & Health in 2017 a great success. We are also pleased to announce that the opening welcome will include the Director General for the World Health Organization, Dr Margaret Chan (on video). All plenary speakers are internationally recognized experts in the field of Complementary and Integrative Medicine such as Josephine B Briggs (US) and Merlin Willcox (UK) as keynote speakers for the theme traditional healing systems; Klaus Linde (Ger) and Michael Moore (UK) for the research theme; Lisa M Wong (US) and Tores Theorell (Sweden) will address the theme of arts and medicine; Darong Wu (China) and Jeffery A Dusek (US) are presenting on the theme of clinical care; and Aviad Haramati and David Eisenberg (both US) will close the Congress with presentations on education. In addition, more than 100 oral presentations in over 40 parallel sessions will be in the program to provide newly emerging data from recent research projects, experiences from new treatment aspects in clinical care, descriptions of new models of education in medicine, information about integration of traditional healing systems in health care systems and new aspects on the integration of arts in medicine. In addition, more than 400 posters will be presented in guided poster sessions during the three days of the Congress. To translate the congress goals and objectives into a tangible action for the field, a Berlin Agreement is being developed. With the title ‘Social and Self-responsibility in practicing and fostering Integrate Health and Medicine Globally,’ this document is meant to help shape the future of comprehensive patient care in Integrative Medicine, and addresses the responsibilities of all participants, including patients and citizens, physicians and all colleagues working in the healthcare system. The Berlin Agreement has been developed by the WCIMH 2017 congress presidents and the International Organizing Committee to create a document for further distribution to the scientific and clinical community and to health care stakeholders, decision makers, and politicians. We anticipate having the final version of the Berlin Agreement endorsed by a number of organizations prior to the Congress and also soliciting the support of congress at the WCIMH 2017 in Berlin. Our hope is that this document will provide an important impetus for further engagement world-wide after the Congress has concluded. Immediately before the start of WCIMH 2017 on Wednesday May 3rd 2017 there will be several high-quality pre-conference workshops covering all congress topics. Reflecting the political situation in recent years, especially in Europe, we have arranged for a unique half-day workshop on the topic: “Refugees with Chronic Diseases between the Middle-East and Europe: The Role of Traditional and Integrative Medicine in Bridging Gaps”, The speakers are all from the Middle East and Europe and will address how Integrative Medicine may serve as an important element to overcome the problematic health situation of refugees around the world. We are convinced that the field of Complementary and Integrative Medicine, including traditional healing systems and medicine and the arts, will benefit from The 2017 World Congress on Integrative Medicine & Health—a preeminent scientific international forum that is focused on highlighting advances in these thematic areas. We invite all practitioners, educators and researchers in the field of Integrative Medicine to come together, participate and engage together to make this Congress an exciting meeting for the successful advancement of Integrative Medicine across the globe.

We read with great interest the article by Lang et al1Lang A. et al.Clin Gastroenterol Hepatol. 2015; 13: 1444-1449Google Scholar on curcumin in combination with mesalamine in inducing remission of ulcerative colitis (UC). In this randomized, double-blind, placebo-controlled trial, Lang et al1Lang A. et al.Clin Gastroenterol Hepatol. 2015; 13: 1444-1449Google Scholar added curcumin to mesalamine in patients with mild to moderate UC. They reported impressive improvement in induction of remission in the curcumin-treated group when compared with placebo. This important study has the potential to improve care of patients with UC. The authors appropriately call attention to concerns regarding how effectively the subjects were blinded, as does the accompanying editorial by Bernstein.2Bernstein C.N. Clin Gastroenterol Hepatol. 2015; 13: 1450-1452Google Scholar Another unaddressed concern is the inclusion of patients on concomitant immunomodulator medications (azathioprine and 6-mercaptopurine) in addition to mesalamine. Lang et al1Lang A. et al.Clin Gastroenterol Hepatol. 2015; 13: 1444-1449Google Scholar took several steps to ensure that these patients could be reasonably compared with subjects on mesalamine alone. To be included, patients needed to be on a stable dose of an immunomodulator for at least 12 weeks. The patients also were randomized after stratification according to use of immunomodulators to ensure that they were distributed evenly between the treatment and placebo groups. However, the randomization strategy was not described, and no statistical analyses were performed to assess the impact of immunomodulators on the primary end point of clinical remission. Of concern, the study protocol included with the Curcumin Study Protocol and filed with ClinicalTrials.gov explicitly excludes “Patients receiving immunomodulator therapy like azathioprine, 6-mercaptopurine.” The inclusion of such patients is a significant deviation from the protocol. The rationale for including these patients was unaddressed by the authors. This protocol violation raises uncertainty about the conduct of the study and calls into question the study’s results and interpretation. Why were patients on immunomodulators included after specific exclusion in the initial protocol? How were they recruited, and was this performed in a systematic way? Lang et al1Lang A. et al.Clin Gastroenterol Hepatol. 2015; 13: 1444-1449Google Scholar stated that patients treated with concomitant immunomodulator therapy “did not demonstrate any difference in outcomes, but statistical analysis is precluded by the small size of this subgroup,” but this does not sufficiently address the problem. These 9 patients represent nearly 1 in 5 patients in the study. If included, they should be analyzed as an important subgroup. A conservative approach to the data interpretation and analysis would be to suggest that the data as currently analyzed do not support the conclusions. However, there still may be important evidence gleaned from this study. A casual analysis of the data available suggests response among patients who took curcumin compared with placebo. However, neither the per-protocol nor the intention-to-treat (ITT) analyses were performed in a manner to support this conclusion. ITT analysis demands strictly adhering to protocol and randomization, regardless of actual treatment taken by the patient. At minimum, ITT analyses should be conducted with the exclusion of the patients on concomitant immunomodulator therapy who were included contrary to protocol. Analyzing the results of a study including the patients only as treated, regardless of initial randomization, often is referred to as per-protocol. However, per protocol analysis should refer only to curcumin treatment or lack thereof, with the exclusion of other potentially confounding variables such as immunomodulators. Although the 9 patients on immunomodulator medications were randomized as such, they were included contrary to protocol. If per-protocol analyses were conducted appropriately, these patients should have been excluded from this analysis. Exclusion of the patients on immunomodulators results in a smaller sample size, which may not meet statistical significance. Thus, it is misleading to refer to the results as analyzed by either ITT or per-protocol. At best, the data analysis should be considered a post hoc analysis, acknowledging that patients were included who should not have been included by study design. These limitations aside, there still may be evidence, albeit of lower quality, suggesting a benefit of the use of curcumin in UC. The analysis of patients in this study remains noteworthy. However, we should consider it more akin to an observational cohort study than the high quality of a randomized controlled study. That said, we agree with Bernstein2Bernstein C.N. Clin Gastroenterol Hepatol. 2015; 13: 1450-1452Google Scholar that further well-designed, placebo-controlled studies should be conducted to ensure these findings are replicable. If curcumin is found to be effective in subsequent studies, it will be an attractive option for adjunct therapy in UC. As these studies are designed, it will be important to study the effect of curcumin when added to both immunomodulator and nonimmunomodulator medication and analyze these groups appropriately. Curcumin in Combination With Mesalamine Induces Remission in Patients With Mild-to-Moderate Ulcerative Colitis in a Randomized Controlled TrialClinical Gastroenterology and HepatologyVol. 13Issue 8PreviewThe phytochemical compound curcumin was reported to be effective in maintaining remission in patients with ulcerative colitis (UC). We investigated curcumin's efficacy in inducing remission in patients with active mild-to-moderate UC. Full-Text PDF ReplyClinical Gastroenterology and HepatologyVol. 14Issue 6PreviewWe thank Drs Singer and Adler for their interest and comments on the curcumin trial.1 In this trial we initially intended to exclude immunomodulator patients. This protocol version 1 was approved by the Sheba Medical Center Institutional Review Board (IRB) on May 23, 2011. However, very early on we realized that patients with background azathioprine/6-mercaptopurine treatment who have a mild-moderate flare often are treated similarly by optimization of concomitant mesalamine. Aiming to incorporate patients with this relevant clinical scenario, and to increase the rate of recruitment, we have amended the protocol, adding adequate measures, as acknowledged by Drs Singer and Adler, to ensure stratified separate randomization of patients with and without background immunomodulators, as well as including them only if they were on stable 12-week dosing of the immunomodulator. Full-Text PDF

The paper by Lang and coworkers1Lang A. et al.Clin Gastroenterol Hepatol. 2015; 13: 1444-1449Google Scholar reports on the success of an international multicenter prospective double-blind study of 3 g per day of a 95% pure curcumin compound added to 4 g of maintenance mesalamine to treat patients with mild to moderate ulcerative colitis. At the end of a 1-month study, a remarkable 53.8% of patients receiving curcumin achieved a clinical remission compared with none in the control group with parallel endoscopic improvement. This study, highlighted with an editorial2Bernstein C.N. Clin Gastroenterol Hepatol. 2015; 13: 1450-1452Google Scholar and frontispiece in Clinical Gastroenterology and Hepatology, and in the August issue of GI and Hepatology News, confirms the potential of curcumin as a therapeutic modality in inflammatory bowel disease shown in previous studies3Holt P.R. et al.Dig Dis Sci. 2005; 50: 2191-2193Google Scholar, 4Hanoi H. et al.Clin Gastroenterol Hepatol. 2006; 4: 1502-1506Google Scholar and larger therapeutic trials are urgently needed. One important caveat is that very pure curcumin compounds were used in these reported studies. Pharmacy and nutritional food store shelves are filled with a large number of products containing curcumin, but also containing numerous additives. This is the time to caution our patients with inflammatory bowel disease that many curcumin-containing compounds commercially available are very impure. Hype may cause harm. Curcumin in Combination With Mesalamine Induces Remission in Patients With Mild-to-Moderate Ulcerative Colitis in a Randomized Controlled TrialClinical Gastroenterology and HepatologyVol. 13Issue 8PreviewThe phytochemical compound curcumin was reported to be effective in maintaining remission in patients with ulcerative colitis (UC). We investigated curcumin's efficacy in inducing remission in patients with active mild-to-moderate UC. Full-Text PDF ReplyClinical Gastroenterology and HepatologyVol. 14Issue 1PreviewWe thank Holt et al for their interest in our recently published multicenter, randomized, placebo-controlled trial of curcumin as add-on therapy to mesalamine in active ulcerative colitis.1 We agree with the important issue of the divergent purity and possibly efficacy of various commercially available curcumin products. The food supplement market, including curcumin, offers numerous brands that are subject to lower-standard regulatory policies compared with pharmaceutical drugs. This has potentially serious implications. Full-Text PDF

Infliximab is an anti-tumor necrosis factor (TNF) used for treatment of inflammatory bowel disease (IBD) as well as rheumatoid arthritis, psoriasis, and other inflammatory conditions. Antibodies to infliximab (ATI) develop in 45% of infliximab-treated IBD patients and are correlated with loss of clinical response. Scarce data exist as to factors which predict infliximab immunogenicity.To investigate factors that may predict formation of antibodies to infliximab (ATI) and infliximab therapy failure.An observational study of consecutive IBD patients treated with infliximab between 2009 and 2013 was performed. Trough levels of ATI were measured. Patients were monitored for disease activity using clinical activity indexes and were classified according to ATI formation and clinical response. All clinical and demographic parameters were analyzed for association with the designated outcomes.One hundred fifty-nine patients were included and 1505 sera were tested. On multivariate analysis, Jewish Ashkenazi ethnicity was protective against both development of ATI (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.17-0.7, P = 0.005) and treatment failure (OR 0.29, 95% CI 0.13-0.66, P = 0.003). Concomitant immunomodulator therapy was also negatively associated with immunogenicity and infliximab therapy failure (OR 0.31, 95% CI 0.15-0.65, P = 0.002; OR 0.42, 95% CI 0.180.99, P Jewish Ashkenazi ethnicity is protective of ATI formation and infliximab therapy failure. These findings suggest a role for ethnicity, and implicitly for genetic predisposition, in modulating the risk of anti-TNF immunogenicity and treatment unresponsiveness.

Ulcerative Colitis (UC) is a chronic inflammatory disease of colon mucosa, which results from inappropriate inflammatory response. Pharmacological treatments that are used to manage UC are usually targeted to moderate the inflammatory response, however, they are associated with significant adverse effects, which call for finding additional treatment options. Curcumin is a polyphenol that is extracted from turmeric (Curcuma longa). This medicinal plant has been traditionally used in India and in China since ancient times. Recently curcumin has been demonstrated to possess anti-inflammatory, anti-proliferative and antibacterial properties. Based on these reports, our article describes a case report of a patient treated with curcumin in addition to 5-Aminosalicylic acid (5ASA) and presents an integrative approach for the treatment of ulcerative colitis.

Curcumin, a herbal-compound, may be efficacious in the treatment of ulcerative colitis (UC). In this study we investigated the efficacy of curcumin add-on therapy for inducing remission in patients with active mild-to moderate UC who failed maximal 5ASA treatment. In this multi-center randomized, placebo-controlled double-blind study, 50 patients with active mild-moderate UC (defined by score of 5 to12 in the Simple Clinical Colitis Activity Index (SCCAI)) who failed maximal (oral+topical) 5ASA treatment were allocated to receive 3gr daily of curcumin or placebo for one month on top of optimized (oral+topical) 5ASA treatment. Clinical index (SCCAI), endoscopic index (partial Mayo) and serological parameters were determined at entry and conclusion of study period. In the intention-to-treat analysis, 14/26 (54%) patients receiving curcumin and 0/24 patients receiving placebo achieved clinical remission (SCCAI ≤2) at week 4 (P=0.01, OR 42.2, 95CI 2.3 to 760). Clinical response (reduction of ≥3 points in SCCAI) was achieved in 17/26 patients receiving curcumin and in 3/24 patients receiving placebo (P<0.001, OR 13.2, 95CI 3.1 to 56.6). Endoscopic remission (partial Mayo score ≤ 1) was observed in 8/22 (36%) of patients receiving curcumin and in 0/16 (0%) of the patients receiving placebo (P=0.035, OR 23.5, 95CI 1.2 to 445). The mean change in partial Mayo score was +0,15±0.49 for the placebo arm compared to -0.55±0.79 in the curcumin arm (P=0.04). No serious adverse events were recorded. Curcumin as add-on therapy was superior to placebo for inducing clinical and endoscopic remission in mild-to-moderate active UC with no apparent adverse effects. Curcumin may be a safe and promising agent in the treatment of inflammatory bowel diseases.