Complete Mucosal Healing Research Articles

Effect of the Specific Carbohydrate Diet on Inflammatory Bowel Disease: A 5-Year Longitudinal Study

Introduction: We previously reported the effects of the Specific Carbohydrate Diet (SCD), a low-complex carbohydrate diet that excludes grains, sugars and starches, in improving extraintestinal and intestinal manifestations of IBD in 12 patients who followed the diet for an average of 19 months. This study assesses the longitudinal effectiveness of the SCD in 8 patients who followed the diet for 66 months. Methods: We collected and analyzed data from 8 patients who followed the SCD for an average of 5.5 years (range 3-10 years). Patient characteristics are shown in Table 1. We used a modified version of the IBDQ, a validated, disease-specific questionnaire, to assess clinical manifestations of disease before and after SCD to determine the diet's impact on disease activity. We also evaluated the effects of the diet on ability to discontinue biologics and immunosuppressive medications. All 8 patients underwent endoscopic evaluation to assess mucosal healing.Table: Table. Patient CharacteristicsResults: The average improvement in modified IBDQ score after implementation of SCD was 62%. The average time to see improvement after starting the diet was 30 days (range 3 days to 4 months). 75% of the patients were compliant with the diet 80-100% of the time, while 25% of patients reported 60-80% compliance. 4 out of 8 patients were able to discontinue biologics or immunosuppressive therapy as a result of the diet. Colonoscopy showed complete mucosal healing in 3 out of 8 patients, and active inflammation but with improvement from pre-SCD colonoscopy in 5 out of 8 patients. Conclusion: Our data confirms that the Specific Carbohydrate Diet is an effective long-term treatment for IBD that can result in improvement of symptoms, mucosal healing, and discontinuation of biologic and immunosuppressive medications.

Sepsis Markers Soluble IL-2 Receptor and Soluble CD14 Subtype as Potential Biomarkers for Complete Mucosal Healing in Patients With Inflammatory Bowel Disease

Novel noninvasive biomarkers with high diagnostic accuracy are required to assess mucosal healing, which is associated with sustained clinical remission, in inflammatory bowel disease. This study aimed to explore sepsis markers as potential biomarkers for mucosal healing. Patients with ulcerative colitis [UC] or Crohn's disease [CD], who underwent blood tests for C-reactive protein [CRP], serum procalcitonin [PCT], soluble interleukin-2 receptor [sIL-2R], and plasma soluble CD14 subtype [sCD14-ST] within 2 weeks of endoscopy, were retrospectively recruited; and we assessed the relationship between marker levels and clinical features. Complete mucosal healing [cMH] was defined as a Mayo endoscopic subscore [MES] of 0 for UC and a simple endoscopic score for Crohn's disease [SES-CD] of 0 for CD. In all, 68 UC patients and 33 CD patients were included in this study. In patients with UC, the sIL-2R level was significantly higher in patients without cMH than in those with cMH. The sIL-2R level had the highest diagnostic value for identifying cMH in UC. In patients with CD, CRP and sCD14-ST levels were significantly higher in patients without cMH than in those with cMH, and both CRP and sCD14-ST had good diagnostic values for identifying cMH. The sCD14-ST level had a high diagnostic value for identifying cMH even among CD patients with complete clinical remission, defined as a Harvey-Bradshaw index of 0. The sIL-2R and sCD14-ST levels in patients with UC and CD, respectively, can be useful surrogate markers for identifying mucosal healing in inflammatory bowel disease.

Lack of Mucosal Healing From Modified Specific Carbohydrate Diet in Pediatric Patients With Crohn Disease.

Exclusive enteral nutrition is effective in pediatric Crohn disease but challenging as maintenance therapy. There is interest in food-based therapies such as the specific carbohydrate diet (SCD) but paucity of data on efficacy and effect on mucosal healing, an evolving target of IBD therapy. We conducted a retrospective review of the mucosal healing effect of the SCD in pediatric Crohn disease (CD). The endoscopic findings for children younger than 18 years with CD treated exclusively with the SCD or modified SCD (mSCD; SCD + addition of "illegal foods") were reviewed before and after the diet. Ileocolonoscopic examinations were scored according to the Simple Endoscopic Score for CD and findings on upper endoscopy were described. Seven subjects were identified, all on mSCD. The average age at starting the SCD was 11 ± 3.4 years and median duration of SCD/mSCD therapy was 26 months. All subjects reported no active symptoms before repeat endoscopic evaluation on mSCD, the majority had consistently normal C-reactive protein, albumin and hematocrit assessments, and mildly elevated fecal calprotectin (>50 μg/g, median 201, range 65-312) at any point within 3 months before the repeat endoscopy. One patient showed complete ileocolonic healing but persistent upper gastrointestinal tract ulceration. Complete macroscopic mucosal healing of both the ileocolon and upper gastrointestinal tract was not seen in any patient.

Complete mucosal healing of distal lesions induced by twice-daily budesonide 2-mg foam promoted clinical remission of mild-to-moderate ulcerative colitis with distal active inflammation: double-blind, randomized study

BackgroundBudesonide foam is used for the topical treatment of distal ulcerative colitis. This phase III study was performed to confirm mucosal healing and other therapeutic effects of twice-daily budesonide 2-mg foam in patients with mild-to-moderate ulcerative colitis including left-sided colitis and pancolitis.MethodsThis was a multicenter, randomized, placebo-controlled, double-blind trial. A total of 126 patients with mild-to-moderate ulcerative colitis with active inflammation in the distal colon were randomized to two groups receiving twice-daily budesonide 2 mg/25 ml foam or placebo foam. The primary endpoint was the percentage of complete mucosal healing of distal lesions (endoscopic subscore of 0) at week 6. Some patients continued the treatment through week 12. Drug efficacy and safety were evaluated.ResultsThe percentages of both complete mucosal healing of distal lesions and clinical remission were significantly improved in the budesonide as compared with the placebo group (p = 0.0003 and p = 0.0035). Subgroup analysis showed similar efficacy of budesonide foam for complete mucosal healing of distal lesions and clinical remission regardless of disease type. The clinical remission percentage tended to be higher in patients achieving complete mucosal healing of distal lesions than in other patients. There were no safety concerns with budesonide foam.ConclusionsThis study confirmed for the first time complete mucosal healing with twice-daily budesonide 2-mg foam in mild-to-moderate ulcerative colitis with distal active inflammation. The results also indicated that complete mucosal healing of distal lesions by budesonide foam promotes clinical remission of ulcerative colitis. Clinical trial registration no.: Japic CTI-142704.

Anti–Tumor Necrosis Factor With a Glyco-Engineered Fc-Region Has Increased Efficacy in Mice With Colitis

Although tumor necrosis factor (TNF) antagonists reduce many clinical features of inflammatory bowel disease, complete mucosal healing occurs in fewer than 50% of patients. The Fc-region of monoclonal antibodies against TNF has immunosuppressive properties via effects on macrophage polarization. We examined the interaction between the anti-TNF Fc-region and Fcγ receptors (FcγR), and whether the absence of the Fc core fucose (which increases binding to FcγRIIIa) increases the efficacy of anti-TNF in mice with colitis. We generated Rag1-/- mice that lackall activating FcγRs (FcγRI, FcγRIII, and FcγRIV; called FcγR-/-Rag1-/- mice). We produced hypo-fucosylated antibodies against mouse and human TNF (adalimumab). Colitis was induced in mice by transfer of CD4+CD45RBhi to FcγR-/-Rag1-/- or Rag1-/- littermates; mice were given different antibodies against TNF or isotype (control) antibodies and disease activity index scores were determined. Colon tissues were collected and analyzed by histology. Human peripheral blood mononuclear cells (PBMCs) were isolated from blood of healthy donors. T-cell proliferation and proportions of CD206+ (immune regulatory) macrophages were measured in mixed lymphocyte reactions. Human PBMCs were genotyped for FCGR3A158 (the FcγRIIIa-158F allotype displays a lower Fc binding affinity) using the TaqMan single nucleotide polymorphism genotype assay. Rag1-/- mice with colitis given anti-TNF had near complete mucosal healing and Rag1-/- mice given an isotype control antibody developed severe colitis. In contrast, FcγR-/-Rag1-/- mice were refractory to the effects of anti-TNF: their histological colitis scores were as severe as those from FcγR-/-Rag1-/- mice given a control antibody. Colons from Rag1-/- mice that received anti-TNF had an increased number of CD206+ macrophages compared with Rag1-/- mice given control antibody; in FcγR-/-Rag1-/- mice given anti-TNF these numbers were as low as FcγR-/-Rag1-/- given the control antibody. In human PBMCs, anti-TNF increased the number of CD206+ macrophages: this required expression of FcγRIIIa; numbers of these cells were reduced in PBMCs with the low-affinity FcγRIIIa-158F genotype. A hypo-fucosylated form of adalimumab bound human FcγRIIIa with a higher affinity than control adalimumab. When hypo-fucosylated adalimumab was added to PBMCs, a larger number of CD206+ macrophages formed and T-cell proliferation was reduced, compared with addition of a control adalimumab. Hypo-fucosylated adalimumab increased the number of CD206+ macrophages in PMBCs that expressed the low-affinity FcγRIIIa. In mice with colitis, hypo-fucosylated anti-TNF significantly increased the number of CD206+ macrophages in the colon compared with control anti-TNF and was more effective in reducing colitis severity as measured by histology. In a study of the invitro and invivo mechanisms of anti-TNF, we found FcγR engagement by anti-TNF to be required for reduction of colitis in mice and development of CD206+ macrophages. A hypo-fucosylated form of anti-TNF binds FcγRIIIa with higher affinity and induces development of CD206+ macrophages in human PBMCs, especially PBMCs that express low-affinity FcγRIIIa. Hypo-fucosylated anti-TNF might be more effective in patients with inflammatory bowel disease.

When to remove the urethral catheter after endoscopic realignment of traumatic disruption of the posterior urethra?

To detect the optimal time for urethral stent removal after endoscopic urethral realignment and its effect on the incidence of development of urethral stricture. Eighteen patients underwent endoscopic urethral realignment after traumatic disruption of the posterior urethra. Post-operative urethroscopy was done using the flexible cystoscope to assess progress of urethral healing. The urethral Foley catheter that served as a stent and for urine drainage was removed only when complete mucosal healing was observed by flexible urethroscopy. There was a post-operative follow-up period of 12-36months. Uroflowmetry was performed at the end of the follow-up period. Endoscopy 6weeks after realignment showed 50-75% mucosal epithelialization at the site of urethral disruption in all patients. Epithelialization was complete at 9weeks in 15/18 patients (83%) and at 12weeks in the remaining 3 patients (17%). One patient (5.6%) developed a mild symptomatic stricture 5months post stent removal that was successfully treated by a single session of visual urethrotomy. All 18 patients had normal uroflowmetry readings at 12-36months after realignment. Urethral stenting should be continued till mucosal healing at the site of urethral disruption became complete. Removal of the stent at this optimal time decreases the incidence of post-operative urethral stricture. Flexible urethroscopy was a safe procedure for post-operative follow-up of endoscopic urethral realignment to assess the progress and completion of mucosal healing at the site of realignment. 4.

The effect of chronic dental inflammation on development of Stage 0 medication-related osteonecrosis of the jaw

ObjectiveThe pathogenesis of medication-related osteonecrosis of jaw (MRONJ) is poorly understood. The aim of this prospective study was to determine the effect of chronic dental inflammation on the development of Stage 0 MRONJ based on histopathological findings. MethodsThe study involved patients with a history of bisphosphonate use and an indication for tooth extraction. Before surgery, C-terminal telopeptide test (CTX) values were collected from all patients. All tooth extractions were performed according to a determined protocol. To detect whether any medication-related osteonecrotic changes were present in the non-exposed bone, biopsy samples were taken from the alveolar bone. ResultsA total of 50 patients were included in the study (39 women and 11 men). The patients were mean age of 57.4 ± 12.1 years. In total, 74 teeth were extracted (29 maxillary and 45 mandibular). Histologic examination of three patients (6%) revealed Stage 0 MRONJ. Postoperatively, the complete mucosal healing success rate was 96%. MRONJ risk was not significantly correlated with low CTX value (p = 0.285). ConclusionsChronic inflammation may contribute to Stage 0 MRONJ; however, its role may not be sufficient alone for its development. Application of a predetermined protocol for dentoalveolar processes will help to prevent MRONJ development.

PD29-08 WHEN TO REMOVE THE FOLEY CATHETER AFTER ENDOSCOPIC REALIGNMENT OF TRAUMATIC DISRUPTION OF THE POSTERIOR URETHRA?

You have accessJournal of UrologyTrauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) II1 Apr 2017PD29-08 WHEN TO REMOVE THE FOLEY CATHETER AFTER ENDOSCOPIC REALIGNMENT OF TRAUMATIC DISRUPTION OF THE POSTERIOR URETHRA? Hamed El Darawani Hamed El DarawaniHamed El Darawani More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1360AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To verify a correlation between the period of urethral stenting after endoscopic urethral realignment and the incidence of post-operative urethral stricture. This study was designed to evaluate the outcome of continuing urethral stenting till the gap between the 2 realigned urethral segments has been completely epithelialized. METHODS Eighteen patients underwent endoscopic urethral realignment after traumatic disruption of the posterior urethra. Post-operative urethroscopy was done using the flexible cystoscope to assess the progress of urethral healing. The urethral Foley catheter that acted as a stent and also for urine drainage was removed when complete mucosal healing was observed by urethroscopy. Post-operative development of urethral stricture was noted and uroflowmetry was done at 12–36 months. RESULTS Endoscopy 6 weeks after realignment showed 50%-75% epithelialization in all patients (figure 1). At 9 weeks, epithelialization was 100% in 15/18 patients (83%) and complete epithelialization at 12 weeks in all patients (figure 2). After stent removal, 1 patient (5.6%) developed a mild symptomatic stricture that was successfully treated by a single session of visual urethrotomy. All 18 patients had normal uroflowmetry readings at 12-36 months after realignment. CONCLUSIONS Following endoscopic urethral realignment, urethral stenting till mucosal healing was complete reduced the incidence of subsequent urethral stricture. Urethroscopy showed complete mucosal healing in 9–12 weeks after realignment. During a follow-up period of 12-36 month, 94.4% of the patients were symptom-free. Presence of asymptomatic large-caliber strictures or possibility of development of symptomatic strictures during longer follow-up periods can’t be ruled out. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e575 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Hamed El Darawani More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Mo1776 - Serum Sepsis Markers Soluble CD14 Subtype and Soluble IL2 Receptor as Potential Biomarkers for Complete Mucosal Healing in Patients with Inflammatory Bowel Disease

Mo1776 - Serum Sepsis Markers Soluble CD14 Subtype and Soluble IL2 Receptor as Potential Biomarkers for Complete Mucosal Healing in Patients with Inflammatory Bowel Disease

Mucosal Recovery and Mucosal Healing in Biopsy-Defined Adult Celiac Disease

Celiac disease (gluten-sensitive enteropathy) is an immune mediated disorder with characteristic histopathological small bowel mucosal changes that respond to a strict gluten-free diet. Recent studies have suggested that complete (rather than partial) mucosal recovery and healing is possible, but in some this may require a more prolonged period than is currently appreciated. In this study, 182 patients (60 males, 122 females) referred for evaluation of symptoms, including diarrhea and weight loss, were selected only if initial biopsies showed characteristic inflammatory changes with severe architectural disturbance. All patients were treated with a strict gluten diet alone and diet compliance regularly monitored. Up to 90% or more of patients showed a complete mucosal response or healing. A time-dependent rate of response was noted with most patients requiring more than 1 year, and even 2 years or more, to respond, however, complete mucosal healing was still possible within 6 months. In this evaluation, females in each of 4 different age ranges had mucosal response and healing rates superior to males, while elderly celiacs had lower rates. Such factors should be considered before labeling a patient with “non-responsive” disease. However, inflammatory changes with persistent architectural disturbance, especially in celiacs with a late diagnosis and resultant late initiation of a gluten-free diet treatment, may be at increased risk for a later small bowel complication, including lymphoma.

Review article: moving towards common therapeutic goals in Crohn's disease and rheumatoid arthritis.

Crohn's disease (CD) and rheumatoid arthritis are chronic, progressive and disabling conditions that frequently lead to structural tissue damage. Based on strategies originally developed for rheumatoid arthritis, the treatment goal for CD has recently moved from exclusively controlling symptoms to both clinical remission and complete mucosal healing (deep remission), with the final aim of preventing bowel damage and disability. To review the similarities and differences in treatment goals between CD and rheumatoid arthritis. This review examined manuscripts from 1982 to 2016 that discussed and/or proposed therapeutic goals with their supportive evidence in CD and rheumatoid arthritis. Proposed therapeutic strategies to improve outcomes in both rheumatoid arthritis and CD include: (i) evaluation of musculoskeletal or organ damage and disability, (ii) tight control, (iii) treat-to-target, (iv) early intervention and (v) disease modification. In contrast to rheumatoid arthritis, there is a paucity of disease-modification trials in CD. Novel therapeutic strategies in CD based on tight control of objective signs of inflammation are expected to change disease course and patients' lives by halting progression or, ideally, preventing the occurrence of bowel damage. Most of these strategies require validation in prospective studies, whereas several disease-modification trials have addressed these issues in rheumatoid arthritis over the last decade. The recent approval of new drugs in CD such as vedolizumab and ustekinumab should facilitate initiation of disease-modification trials in CD in the near future.

Higher infliximab trough levels are associated with perianal fistula healing in patients with Crohn's disease.

Infliximab has been found to be efficacious in the treatment of fistulas in the setting of Crohn's disease, even though some patients do not benefit from therapy. To assess the correlation between perianal fistula healing and trough levels of infliximab. In this cross-sectional study, we identified patients with Crohn's disease who had perianal fistulas and were treated with infliximab for at least 24weeks. We excluded patients who underwent a faecal diversion procedure or proctectomy. Predictive variables included demographics, disease phenotype, disease activity, infliximab levels, anti-infliximab antibodies. The primary outcome was fistula healing defined as the absence of drainage. The secondary outcome was complete fistula closure and mucosal healing. 117 patients were included. Patients with fistula healing had significantly higher median serum infliximab levels when compared to those with active fistulas [15.8 vs. 4.4μg/mL, respectively (P<0.0001)]. There was an incremental gain in fistula healing with higher infliximab levels. The AUC for the association between fistula healing and infliximab levels was 0.82 (P<0.0001), while the AUC for the association of infliximab levels and fistula closure was 0.69 (P=0.014). Patients with anti-infliximab antibodies had a lower chance of achieving fistula healing (OR: 0.04 [95%CI: 0.005-0.3], P<0.001). There is a significant association between serum infliximab levels and rates of fistula healing. Achieving infliximab levels ≥10.1mcg/mL in patients with Crohn's disease and perianal fistulas may improve outcomes as part of a treat-to-target strategy.

Efficacy of adalimumab for Crohn's disease in real clinical practice

To evaluate the efficacy and safety of adalimumab (ADA) in patients with Crohn's disease (CD) treated at the Department of Inflammatory Bowel Diseases, Moscow Clinical Research and Practical Center, and to determine the predictors of a therapy response. All the patients with CD treated with ADA were followed up for at least 6 months or until the drug was discontinued. Therapeutic effectiveness was evaluated at 4 weeks and 6 months after the initiation of treatment and at the end of a follow-up. Complete intestinal mucosal healing was assessed at 3 and 12 months following treatment initiation. Univariate and multivariate analyses were used to determine the predictors of treatment response. A clinical analysis covered 70 patients (57.1% male); the follow-up period averaged 112 weeks. Perianal fistulas were at baseline established in 22 (31.4%) patients with CD. 12 (17.4%) patients had been previously treated with infliximab (INF), 7 of them discontinued the drug for secondary loss of response and 5 for adverse reactions. 68 (97.1%) patients responded to an induction course of ADA. At 4 weeks, 6 months, and at the end of the follow-up, clinical remission occurred in 66.7, 80.4 and 67.4 % of patients with luminal CD and in 45.4, 36.5, and 36.4% of those with perianal CD, respectively. At 3 and 12 months and at the end of the follow-up, there was complete healing of the intestinal mucosa in 23.5, and 41.2 and 29.5% of cases, respectively. Six (8.8%) patients responding to the induction course needed to be optimized with ADA to 40 mg weekly. The time interval between treatment initiation and dose optimization averaged 30 weeks (range 12-120 months). There were 15 (21,4%) adverse events that were responsible for ADA discontinuation in 3 (4,2%) patients. The findings demonstrate the efficacy and safety of ADA used in clinical practice.

DOP031 Subtherapeutic serum infliximab trough levels and complete mucosal healing are associated with sustained clinical remission after infliximab discontinuation in paediatric Crohn's disease patients

DOP031 Subtherapeutic serum infliximab trough levels and complete mucosal healing are associated with sustained clinical remission after infliximab discontinuation in paediatric Crohn's disease patients

Mucosal Healing in Ulcerative Colitis: A Comprehensive Review.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by periods of remission and periods of relapse. Patients often present with symptoms such as rectal bleeding, diarrhea and weight loss, and may require hospitalization and even colectomy. Long-term complications of UC include decreased quality of life and productivity and an increased risk of colorectal cancer. Mucosal healing (MH) has gained progressive importance in the management of UC patients. In this article, we review the endoscopic findings that define both mucosal injury and MH, and the strengths and limitations of the scoring systems currently available in clinical practice. The basic mechanisms behind colonic injury and MH are covered, highlighting the pathways through which different drugs exert their effect towards reducing inflammation and promoting epithelial repair. A comprehensive review of the evidence for approved drugs for UC to achieve and maintain MH is provided, including a section on the pharmacokinetics of anti-tumor necrosis factor (TNF)-α drugs. Currently approved drugs with proven efficacy in achieving MH in UC include salicylates, corticosteroids (induction only), calcineurin inhibitors (induction only), thiopurines, vedolizumab and anti-TNFα drugs (infliximab, adalimumab, and golimumab). MH is of crucial relevance in the outcomes of UC, resulting in lower incidences of clinical relapse, the need for hospitalization and surgery, as well as reduced rates of dysplasia and colorectal cancer. Finally, we present recent evidence towards the need for a more strict definition of complete MH as the preferred endpoint for UC patients, using a combination of both endoscopic and histological findings.

Management Challenges in Adolescents with Crohn?s Disease-Current Practice

The incidence and prevalence of Crohn's disease (CD) in adolescents is rising. The clinical course differs in several aspects from that of adults. Pediatric-onset disease is more extensive and its course is somewhat more aggressive. In addition to the common manifestation of CD, adolescents with CD may present with pubertal delay, growth retardation and osteopenia. These unique aspects of adolescence CD should impact the treatment paradigm. In cases of growth impairment and osteopenia, treatment should be intensive aiming at promoting complete mucosal healing and, in turn, improved growth and bone formation. The use of enteral nutrition should be thus encouraged both for induction and maintenance of remission. However, adolescent CD carries implications that go beyond the physical manifestations of the disease. Children diagnosed with IBD are at increased risk of emotional distress and decreased social functioning. The use of support groups and other psychosocial interventions is advocated as a mean to enhance coping skills and improve quality of life. As many as half of adolescents are non-compliant with the recommended treatment hence, a particular emphasis should be placed on engaging the adolescent in the treatment plan, using several intervention strategies. Adolescence is a time of dynamic physical changes and growth along with emotional maturation. This review highlights some of the unique aspects that should come into play while managing CD during this sensitive period of life.

Preventing Collateral Damage in the Inflammatory Bowel Disease Patient: Using Disease Assessment and Prognostic Factors to Optimise Clinical Outcomes

Inflammatory bowel diseases (IBDs) are chronic disabling conditions. Despite the benefits of anti-tumour necrosis factor-α agents in improving quality of life and reducing the need for surgery in many patients, only one-third achieve clinical remission after 1 year of treatment. It is important that treatments go beyond just the alleviation of symptoms, and help to achieve mucosal healing and deep remission.1 The symposium reviewed the natural course of IBD and discussed how focussing management strategies away from simple symptomatic control towards maintaining mucosal healing can significantly improve the quality of life and wider clinical outcomes of patients with IBD. However, this shift in approach requires the redefining of disease severity to highlight the importance of inflammation control and mucosal healing in preventing long-term damage and disability. Dr Peyrin-Biroulet opened the sessions by reviewing how the Randomised Evaluation of an Algorithm for Crohn’s Treatment (REACT) study has enhanced the understanding of the natural history of IBD, and how complete mucosal healing provides the best outcomes in IBD.2 Dr Colombel highlighted that uncontrolled inflammation in IBD can lead to poor outcomes, and how simple demographic and clinical features can guide the clinician in identifying patients at higher risk for disease complications both at diagnosis and throughout the disease course. Dr Ghosh discussed the importance of defining disease severity in IBD and reinforced that while symptoms related to disease activity are a component of overall disease severity, many factors need to be considered to understand the total impact on a patient’s quality of life.

Acute Esophageal Necrosis in a Patient with Liver Kidney Transplant

This is a case of a 63 year old African American male being evaluated for severe sepsis from healthcare associated pneumonia. He has history of liver cirrhosis from hepatitis C, end stage renal disease, combined liver and kidney transplantation in 2007 and was on immunosuppressant (mycophenolate mofetil, and cyclosporine), prednisone, and trimethoprim-sulfamethoxazole. He was admitted to the MICU and commenced on broad spectrum antibiotics. Cyclosporine was held due to AKI. On day 8, he developed diffuse abdominal pain, diarrhea consisting of dark stools, and one episode of coffee ground emesis. On physical exam, abdomen was non-distended with diffuse tenderness but no peritoneal signs. Labs revealed serum creatinine of 1.65 mg/dl. Patient exhibited mild leukocytosis to 13,300/uL. CT abdomen-pelvis revealed non-specific thickening of the esophagus. Naso-gastric tube returned non-bloody bilious gastric contents. Upper endoscopy revealed circumferential esophageal necrosis extending to mid esophagus. There was luminal narrowing in the distal esophagus. Biopsies taken were notable for “extensive necrotic debris with ulcerative acute esophagitis”. Patient was kept NPO, commenced on IV pantoprazole and sucralfate. Patient was treated with bowel rest, two weeks of antibiotics and four weeks of antifungals. Abdominal pain, loose stools and melena resolved. Repeat upper endoscopy one month later revealed complete resolution of esophageal necrosis. Acute esophageal necrosis(AEN) also known as ‘black esophagus’ is a rare disease with incidence of 0.01% to 0.2% in endoscopic studies. Mortality specific to AEN is 6% and is related to complications such as perforation. It presents with acute upper GI bleed in 90% of cases. Diagnosis is by endoscopic visualization of the characteristic esophageal features and this can be confirmed by pathology result of biopsy specimen but not required. Treatment consists of treating the underlying condition, restoration of normal blood pressure, acid suppression therapy with IV PPI, H2 blocker with or without sucralfate, bowel rest for a few days with total parenteral nutrition (TPN). Complete mucosal healing can be seen as early as 1 week. Complications include stenosis, superinfection and perforation. AEN is a rare disease entity that can be diagnosed only endoscopically and requires a high index of suspicion for early diagnosis and prompt treatment. Further research is needed to understand how to prevent it.Figure 1Figure 2Figure 3

Therapeutic drug monitoring in inflammatory bowel disease.

There are an expanding number of therapies available to treat pediatric inflammatory bowel disease (IBD). As pediatric gastroenterologists attempt to achieve complete intestinal mucosal healing for their patients, it has become more important to gain an understanding of how to maximize the efficacy of our medications while minimizing their toxicities. We aim to provide an overview of therapeutic drug monitoring in IBD with an emphasis on the biologic therapies (antitumor necrosis factor and anti-integrin monoclonal antibodies). Recent findings do support optimized drug dosing for infliximab based on early trough levels, but question the utility of checking these values in patients doing well in maintenance therapy. Patients with severe colonic inflammation may be at increased risk for needing optimization with dose escalation because of medication loss in the stool. Dose escalation can recapture response in some patients with a secondary loss of response, including those with low level antibody formation. The monitoring of nontrough drug levels to allow timelier dose adjustment as well as the role of drug monitoring with anti-integrin therapy are areas of active research. Therapeutic drug monitoring is an effective strategy in the management of pediatric IBD that can help patients achieve mucosal healing and aid the clinical decision-making of the pediatric gastroenterologist.

Single-Center Experience on the Use of Vedolizumab for the Treatment of Inflammatory Conditions of the Ileal Pouch: 2016 ACG Presidential Poster Award

Restorative proctocolectomy with ileal-pouch anal anastomosis (IPAA) is the surgical treatment of choice in patients with ulcerative colitis. Pouchitis is the most common complication after IPAA and its treatment has not been standardized. Vedolizumab has been used in the treatment of ulcerative colitis but its use in inflammatory conditions of the pouch has not been evaluated. Retrospective chart review was performed on patients with IPAA and pouchitis in our institution who had been exposed to vedolizumab. Pouchitis was confirmed by evaluation of clinical, endoscopic, and laboratory parameters. We identified 4 patients with ulcerative colitis who underwent restorative proctocolectomy with IPAA and were exposed to vedolizumab after IPAA. A Caucasian male with IPAA and pouch repair/reconstruction and a history of chronic untreated pouchitis developed moderate pouchitis mainly affecting the proximal pouch, refractory to antibiotics, adalimumab and infliximab. He achieved complete mucosal healing one month after four vedolizumab infusions (See Figures). A Caucasian male with recurrent pouchitis refractory to steroids, antibiotics, adalimumab and certolizumab pegol developed prepouch ileitis and pouch inflammation suggestive of Crohn's disease (CD) that responded to three vedolizumab infusions along with antibiotics with mucosal healing after one month. A Caucasian female intolerant to infliximab and adalimumab developed CD of the pouch requiring diverting loop ileostomy due to anal pain. Seven months later she developed pouchitis that responded to three vedolizumab infusions and steroids with repeat pouchoscopy after two weeks revealing scant/rare pouch ulcerations and anal-IPAA stricture. A Hispanic female developed proximal pouch and pouch inlet inflammation and cuffitis refractory to antibiotics and adalimumab. She received five vedolizumab infusions, and methotrexate was initiated four weeks after the first vedolizumab infusion. She did not respond to vedolizumab and repeat pouchoscopy one week after the last infusion revealed deep pouch ulcerations and cuffitis. ESR and CRP decreased after treatment in 3 out of 4 patients (See Table). Vedolizumab was successful in the treatment of inflammatory conditions of the pouch in three out of four IPAA patients. Inflammatory markers improved in three out of four patients. Further studies are needed to examine its potential role for treating refractory pouchitis.Table 1: Endoscopic and inflammatory marker response to vedolizumab treatment. Repeat endoscopic findings and laboratory values obtained 3-6 months after medication induction phase.Figure 1Figure 2