INTRODUCTION: Most patients with irritable bowel syndrome (IBS) and dual-diagnosis IBS and inflammatory bowel disease (IBD) report that symptoms originate from or are exacerbated by trigger foods. Despite patient interest and need, there... more
INTRODUCTION: Most patients with irritable bowel syndrome (IBS) and dual-diagnosis IBS and inflammatory bowel disease (IBD) report that symptoms originate from or are exacerbated by trigger foods. Despite patient interest and need, there is no consensus on what diet is optimal. Popular diets have notable limitations including cost, length, implementation complexity, and lack of personalization. METHODS: This pilot study evaluated the feasibility, desirability, and effect on gastrointestinal symptoms of a digitally delivered personalized elimination diet for patients with IBS and comorbid IBS/IBD, powered by machine learning. Participants were recruited online and were provided access to a digital personalized nutrition tool for 9 weeks (N = 37; IBS only = 16, Crohn's disease and IBS = 9, and ulcerative colitis and IBS = 12). RESULTS: Significant symptom improvement was seen for 81% of participants at study midpoint and persisted for 70% at end point, measured by the relevant sym...
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Lay Summary Patients with MS and IBD were as likely to have stricturing, fistulizing, and extensive IBD as IBD controls. Although MS-IBD patients were less likely to initiate anti-TNF therapy, they did not have worsened risk of... more
Lay Summary Patients with MS and IBD were as likely to have stricturing, fistulizing, and extensive IBD as IBD controls. Although MS-IBD patients were less likely to initiate anti-TNF therapy, they did not have worsened risk of progression to surgery on follow-up.
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Aim The aim of this study was to determine the immunologic effects and safety of oral anti-CD3 in patients with ulcerative colitis (UC). Methods An open-label pilot study of orally delivered anti-CD3 was performed in patients with... more
Aim The aim of this study was to determine the immunologic effects and safety of oral anti-CD3 in patients with ulcerative colitis (UC). Methods An open-label pilot study of orally delivered anti-CD3 was performed in patients with moderate-to-severe UC. The primary end points were changes in immunologic parameters and evaluation for safety. Results Six subjects received oral OKT3. Biologic effects of oral anti-CD3 included significantly increased proliferation in response to anti-CD3 and anti-inflammatory gene expression profile in peripheral blood mononuclear cells. No serious treatment-related adverse events occurred. Conclusion Orally delivered anti-CD3 resulted in immunologic changes in patients with UC.
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Acute lower gastrointestinal bleeding is an uncommon but potentially life-threatening complication of Crohn's disease. Because of the relative infrequency of severe bleeding due to CD, reports of larger numbers of cases are few,... more
Acute lower gastrointestinal bleeding is an uncommon but potentially life-threatening complication of Crohn's disease. Because of the relative infrequency of severe bleeding due to CD, reports of larger numbers of cases are few, and the medical literature provides insufficient information to direct management. Nevertheless, certain clear guidelines can be offered once other causes for GI blood loss have been excluded and the diagnosis of a Crohn's-related bleed is likely. While the initial episode may abate spontaneously, the primary treatment is determined by the severity and persistence of bleeding as well as the risk for recurrence. Localization of the site of bleeding is essential whether endoscopic therapy, surgery, or medical management is attempted. Endoscopic evaluation is preferable, if feasible, as it will provide a broader assessment of extent of disease as well as having a reasonable likelihood of identifying the site of bleeding with possible therapeutic intervention. An angiogram can be a useful alternative, but therapeutic intervention with embolization should be avoided because of the risk for intestinal infarction. Surgery remains the standard of care for persistent severe acute bleeds. If the acute bleeding ceases, an interval to attempt pharmacologic therapy may be available, permitting treatment of the underlying Crohn's disease. Newer therapies such as infliximab, which may produce relatively rapid mucosal healing, may be beneficial; while they offer hopeful treatment alternatives, they have not been demonstrated to be of use for these cases.
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ConclusionHeparin’s promise has begun to be confirmed as a useful therapy in IBD. The counterintuitive nature of the therapy may reveal under-appreciated elements of the pathophysiology of UC and Crohn’s disease as central to the... more
ConclusionHeparin’s promise has begun to be confirmed as a useful therapy in IBD. The counterintuitive nature of the therapy may reveal under-appreciated elements of the pathophysiology of UC and Crohn’s disease as central to the pathophysiology of these diseases. The possible therapeutic benefit of heparin likely extends beyond its action as an anticoagulant, and includes anti-inflammatory mechanisms as well as promotion of endothelial and mucosal healing. The full potential of heparin remains to be defined with further ongoing and planned studies.
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In India, approximately 20 percent of children under the age of four suffer from severe malnutrition, while half of all the children suffer from undernutrition. The contributions of knowledge and attitudes of nutrition-conscious behaviors... more
In India, approximately 20 percent of children under the age of four suffer from severe malnutrition, while half of all the children suffer from undernutrition. The contributions of knowledge and attitudes of nutrition-conscious behaviors of the mothers to childhood malnutrition has been unclear. The purpose of this study was to explore maternal knowledge of the causes of malnutrition, health-care-seeking attitudes and socioeconomic risk factors in relation to children's nutritional status in rural south India. A case-controlled study was conducted in a rural area in Tamil Nadu, India. Thirty-four cases and 34 controls were selected from the population of approximately 97,000 by using the local hospital's list of young children. A case was defined as a mother of a severely malnourished child under four years of age. Severe malnutrition was defined as having less than 60 percent of expected median weight-for-age. A control had a well-nourished child and was matched by the loc...
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Research Interests: Probiotics, Medical Microbiology, Treatment Outcome, Clostridium difficile, Medicine, and 14 moreClinical Microbiology, Biological Sciences, Humans, Female, Disease, Lactobacillus, Male, Aged, Anti-Bacterial Agents, Combination drug therapy, Pilot Projects, SECONDARY PREVENTION, Medical, and Medical and Health Sciences
A major advance in understanding diverticular disease occurred decades ago with the epidemiologic association between fiber intake and the development of diverticular disease. This association has been well documented with investigations... more
A major advance in understanding diverticular disease occurred decades ago with the epidemiologic association between fiber intake and the development of diverticular disease. This association has been well documented with investigations into the emergence of diverticular disease in underdeveloped countries where the disease had been virtually unknown before the adoption of a westernized diet, low in fiber. The high frequency of right-sided diverticular disease in Asian countries diverges from what is seen in the West. The physiologic effects of insoluble fiber has been well examined as well, increasing bulk and decreasing transit time, with a deficiency contributing to the high pressures implicated in the physiology which leads to diverticular disease. However, at most, 10% to 25% of individuals with diverticular disease will develop diverticulitis. Risk factors for symptomatic diverticular have been increasingly described in recent years with obesity and red meat intake being of particular importance, in addition to age. However, the known factors poorly identify those at increased risk and the predisposing pathophysiology is incompletely understood as well. Insoluble fiber, but not soluble fiber, has been viewed as the principal component which has been deficient in western diets and is the culprit which leads to the establishment of diverticular disease and in turn, diverticulitis. Soluble fiber and its effect on the intestinal flora is proposed as having significant influence on the development of diverticulitis. This understanding, if demonstrated, would have important implications for the primary and secondary prevention of diverticulitis.
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The understanding of diverticulitis has advanced little beyond the initial postulates of Burkitt and Painter who proposed that diverticular disease results from a deficiency of dietary fiber. Diverticular disease and diverticulitis are... more
The understanding of diverticulitis has advanced little beyond the initial postulates of Burkitt and Painter who proposed that diverticular disease results from a deficiency of dietary fiber. Diverticular disease and diverticulitis are viewed simply as a consequence of a diet, which takes in relatively little fiber. Our understanding of diverticulitis has not advanced beyond these basic concepts. As many as two-thirds of individuals in the West have diverticular disease by the age of 85 years, but only 10% to 25% will manifest any related clinical symptoms. Other than age, several risk factors have been identified for the development of diverticular disease and diverticulitis. In particular, obesity and red meat intake are risk factors. Smoking is more controversial and alcohol, coffee, and caffeine have not shown to be risk factors. Vegetable intake, a strict vegetable diet, and increased fiber intake decreases the risk of development of diverticular disease, as well as diverticulitis. Physical activity also seems protective. Despite these evidences, the risk factors and pathophysiology progression from asymptomatic diverticular disease to diverticulitis have been inadequately studied. This subject is reviewed in more detail in this manuscript.
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Research Interests: Magnetic Resonance Imaging, Adolescent, Medicine, Humans, Intestinal Mucosa, and 14 moreFemale, Feasibility Studies, Male, Three Dimensional Imaging, Clinical Sciences, Middle Aged, Gastrointestinal Endoscopy, Adult, Sensitivity and Specificity, Crohn Disease, Contrast Media, Small Intestine, Inflammatory Bowel Diseases, and Severity of Illness Index
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Research Interests: Gastroenterology, Treatment, Medicine, Inflammatory Bowel Disease, Humans, and 12 moreDisease, Therapy, Monoclonal Antibodies, Clinical Sciences, Tumor necrosis factor-alpha, Crohn Disease, Thalidomide, immunoglobulin G, Pentoxifylline, Immunosuppressive Agents, Infliximab, and Tumor necrosis factor
Some environmental factors have been established firmly as influences on the development of IBD, such as smoking and appendectomy. Other behaviors, such as oral contraceptive use and sugar intake, have been suggested as risk factors, but... more
Some environmental factors have been established firmly as influences on the development of IBD, such as smoking and appendectomy. Other behaviors, such as oral contraceptive use and sugar intake, have been suggested as risk factors, but he data conflict sharply. The importance of other behaviors, such as breast-feeding, is even murkier with sharply divergent data. Some issues studied may not be factors in themselves but rather markers for other unidentified influences. The conflicting evidence in many of these studies may be clarified as specific genes are identified and the interplay between these environmental factors and genetic subtypes is investigated.
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Inflammatory bowel disease (IBD) results from intermittent and severe activation of the mucosal immune system in the gastrointestinal tract to promote a chronic state of inflammation. Crohn9s disease (CD) and ulcerative colitis (UC) are... more
Inflammatory bowel disease (IBD) results from intermittent and severe activation of the mucosal immune system in the gastrointestinal tract to promote a chronic state of inflammation. Crohn9s disease (CD) and ulcerative colitis (UC) are the two major forms of IBD. Infiltration of gut tissue by lymphocytes, neutrophils, and macrophages results in prolonged exposure to chemical agents such as pro-inflammatory cytokines and reactive oxygen/nitrogen species. Chronic exposure to these inflammation products leads to mis-regulated cell signaling, altered protein expression, and chemical damage to lipids, protein, and nucleic acids. IBD is a significant risk factor for colon cancer. IBD exhibits phases of active disease (active inflammation) and remission, which complicate therapeutic intervention. Clinical biomarkers currently in use are not predictive of the transition from remission to active disease. Our laboratory has conducted an unbiased, four-pronged approach to IBD biomarker identification in human serum utilizing proteomic discovery of acute phase proteins, cytokine profiling, quantification of oxidative tyrosine modifications (chlorotyrosine (Cl-Tyr), bromotyrosine (Br-Tyr), and nitrotyrosine (NO-Tyr)–markers of neutrophil activity), and measurement of carbonylated proteins. One hundred and ten human serum samples were analyzed. This network of data was analyzed by orthogonormalized partial least squares (OPLS) analysis to identify covariance in the data set. Variable importance in projection (VIP) scores were determined to identify which variables were most predictive of clinically diagnosed disease score (VIP >1). Using data available from the cytokine and oxidative tyrosine analysis, the data set was stratified to clinically diagnosed active and inactive disease, with the intent of identifying serum markers that were predictive of this transition. Several variables for UC and CD demonstrated strong covariance with disease score. The top VIP scores identified for UC were: Interleukin-8 (IL-8), granulocyte-colony stimulating factor (G-CSF), IL-6, and Cl-Tyr. The top VIP scores identified for CD were: Cl-Tyr, macrophage inflammatory protein-1β (MIP-1β), inflammatory chemokine-10 (IP-10), IL-6, and IL-1 receptor antagonist (IL-1ra). A Total Score was generated for each UC and CD serum sample by normalizing the raw data to a base-10 spread, scaling by the VIP factor, and summing the total. Based on the Total Score the calculated specificity and sensitivity for identifying active UC was 81.8% and 84.2%, respectively, while the specificity and sensitivity for identifying active CD was 87.5% and 75%, respectively. We anticipate that the addition of acute phase and cabonylated protein analysis will improve the Total Score assessment. Results from this study strongly suggest that a cassette of in vivo serum markers may be predictive of the transition from remission to active disease in IBD. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5113. doi:10.1158/1538-7445.AM2011-5113
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Adalimumab is a subcutaneously administered, recombinant, human IgG1 monoclonal antibody specific for human tumor necrosis factor (TNF). The clinical efficacy and safety of adalimumab in patients with moderate to severe Crohn's... more
Adalimumab is a subcutaneously administered, recombinant, human IgG1 monoclonal antibody specific for human tumor necrosis factor (TNF). The clinical efficacy and safety of adalimumab in patients with moderate to severe Crohn's disease has been demonstrated in four pivotal, randomized, double-blind trials (CLASSIC-I, GAIN, CHARM, and CLASSIC-II) that included a total of >1400 patients. In the CLASSIC-I trial, adalimumab was significantly more effective than placebo for induction of remission in patients who had not previously received anti-TNF therapy. Adalimumab was also more effective than placebo for induction of remission in the GAIN study in patients who had either lost responsiveness or developed intolerance to infliximab. The CHARM trial showed that, among patients who responded to open-label adalimumab induction, maintenance therapy with adalimumab 40 mg weekly or every other week for up to 1 year was associated with significantly greater remission rates than placebo at weeks 26 and 56. In addition, significantly more adalimumab than placebo recipients achieved corticosteroid-free remission and had complete fistula closure. In CLASSIC-II, an extension of the CLASSIC-I trial, patients who were in remission after a short course of adalimumab and were randomized to receive up to 1 year's treatment with adalimumab 40 mg weekly or every other week were significantly more likely to remain in remission than those randomized to receive placebo. In general, the tolerability profile of adalimumab in patients with Crohn's disease was similar to that in patients with rheumatoid arthritis or other approved indications.
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Nutritional issues in inflammatory bowel disease (IBD) often receive inadequate attention both in regard to therapy and nutritionally related complications of IBD. This article reviews much of the research that has evaluated the role of... more
Nutritional issues in inflammatory bowel disease (IBD) often receive inadequate attention both in regard to therapy and nutritionally related complications of IBD. This article reviews much of the research that has evaluated the role of diet in the causation, primary treatment, and adjunctive therapy of both ulcerative colitis (UC) and Crohn's disease (CD). Benefits have been demonstrated in the use of elemental diets or polymeric diets in CD in both acute flare up or maintenance of IBD. A careful team approach can overcome problems in implementing nutritional therapy. Nutrition also has a critical benefit in postoperative CD and perioperative UC. Numerous easily corrected, nutritional abnormalities are often overlooked in patients with IBD, which may have significant consequences. Nutritional therapy may have a central place in the hierarchy of treatment in IBD and further research is critical in this area to better define the benefits of nutrition in IBD.
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On the basis of several studies that have been completed to date, some growth factors appear promising for the treatment of inflammatory bowel disease: keratinocyte-like growth factor-2 (KGF-2), epidermal growth factor (EGF) enemas used... more
On the basis of several studies that have been completed to date, some growth factors appear promising for the treatment of inflammatory bowel disease: keratinocyte-like growth factor-2 (KGF-2), epidermal growth factor (EGF) enemas used in combination with oral mesalamine, somatropin (human growth hormone), and sargramostim (recombinant human GM-CSF). The results of these studies are highlighted and suggest that new insights into the regulation of intestinal immunity may provide effective synergistic or single-agent treatment alternatives to immunosuppression for inflammatory bowel disease. These data focus on the reparative components of mucosal homeostasis.
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... Reprints: Joshua R. Korzenik, MD, Department of Internal Medicine, Massachusetts General Hospital, MGH Crohn's and Colitis Center, 165 Cambridge Street, 9th floor ... and Duthie 47 found that supplementing patient's diets... more
... Reprints: Joshua R. Korzenik, MD, Department of Internal Medicine, Massachusetts General Hospital, MGH Crohn's and Colitis Center, 165 Cambridge Street, 9th floor ... and Duthie 47 found that supplementing patient's diets with 18 g of fiber in the form of bran tablets increased ...
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Introduction: Infliximab, adalimumab, and certolizumab pegol (CZP) are approved for use in inducing andmaintaining remission inmoderate-to-severe Crohn's disease (CD). However, a significant proportion of patients either fail to... more
Introduction: Infliximab, adalimumab, and certolizumab pegol (CZP) are approved for use in inducing andmaintaining remission inmoderate-to-severe Crohn's disease (CD). However, a significant proportion of patients either fail to respond to these agents or lose response over time. Prior failure is associated with lower rates of response to subsequent anti-TNF therapy. In patients who fail two anti-TNF agents, a choice exists between using a thirdanti TNF therapy vs. initiating natalizumab (NAT), an integrin inhibitor that acts through a distinct biologic mechanism. The cost-effectiveness of these two competing strategies in patients with loss of response to two prior anti-TNF therapies has not been examined. Methods: A decision analysis model was constructed to compare the performance of CZP as the third-line anti-TNF therapy vs. NAT in patients withmoderate-to-severe CD. Previously published estimates of efficacy of third-line anti-TNF therapy (Allez M, APT 2010) and NAT (Sandborn WJ, NEJM 2005) were used to inform the model. Costs were expressed in 2010 US dollars. A 1 year time frame was used for the analysis. The incremental cost-effectiveness ratio (ICER) was calculated and sensitivity analyses were performed by varying cost and efficacy estimates. Results: For the base case scenario, we assumed a response rate at 2 months of 61% for CZP among whom 54% were able to maintain response or remission at the end of the year (Allez M, APT 2010). From the ENACT trials, a 2 month response rate of 58% was estimated for NAT; 39% of these patients maintained remission at 12 months with 15% achieving clinical response. At the base case estimate, use of NAT was more effective (0.72 vs. 0.71 QALYs) but was associated with an incremental cost of $1,502 yielding an ICER of $120,976/QALY. For 2 month response rate with CZP of 50% or lower, NAT had an acceptable ICER at a willingness-to-pay threshold of $80,000/QALY or lower(Figure). Reduction in CZP costs by 25% yielded high ICER for NAT at all CZP response rates > 10%. In a hypothetical cohort of 100,000 patients, both strategies resulted in similar proportion of patients achieving clinical remission or response (61,051 with CZP compared to 60,111 with NAT) at the end of 1 year. Conclusion: In patients with moderateto-severe CD failing two-anti TNF therapies, using a third-anti TNF (CZP) appears to be a cost-effective strategy if response rates of at least 50% can be achieved at 2 months.
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Background: Given the significant costs associated with hospitalization for patients with inflammatory bowel disease (IBD), increased focus has been placed on the prevention of hospital readmission among patients with IBD. Prior... more
Background: Given the significant costs associated with hospitalization for patients with inflammatory bowel disease (IBD), increased focus has been placed on the prevention of hospital readmission among patients with IBD. Prior literature has suggested that pediatric patients with IBD are at greater risk for readmission than adult patients. There is a paucity of literature from nationally representative databases regarding the factors associated with hospital readmissions in pediatric patients with IBD, and thus we aimed to evaluate the burden of hospital readmissions among pediatric patients with IBD using the Nationwide Readmissions Database (NRD). Methods: We performed a retrospective cohort study using 2013 data from the NRD, a nationally representative database from the Healthcare Cost and Utilization Project. With data from 21 states, the NRD can be used to create national estimates of readmission rates for all payers and the uninsured. International Classification of Disease...
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Background Clinical and molecular subcategories of inflammatory bowel disease (IBD) are needed to discover mechanisms of disease and predictors of response and disease relapse. We aimed to develop a study of a prospective adult research... more
Background Clinical and molecular subcategories of inflammatory bowel disease (IBD) are needed to discover mechanisms of disease and predictors of response and disease relapse. We aimed to develop a study of a prospective adult research cohort with IBD (SPARC IBD) including longitudinal clinical and patient-reported data and biosamples. Methods We established a cohort of adults with IBD from a geographically diverse sample of patients across the United States with standardized data and biosample collection methods and sample processing techniques. At enrollment and at time of lower endoscopy, patient-reported outcomes (PRO), clinical data, and endoscopy scoring indices are captured. Patient-reported outcomes are collected quarterly. The quality of clinical data entry after the first year of the study was assessed. Results Through January 2020, 3029 patients were enrolled in SPARC, of whom 66.1% have Crohn’s disease (CD), 32.2% have ulcerative colitis (UC), and 1.7% have IBD-unclassi...