Normal Ileal Mucus Is Inadequate for Epithelial Protection in Ileal Pouch Mucosa.

BACKGROUND: Clinical, nonspecific pouchitis is common after restorative proctocolectomy for ulcerative colitis, but its cause is unknown. A possible lack of protection for the ileal mucosa in its role as a reservoir for colonic-type bacteria may be the missing piece in defining the causes of pouchitis. OBJECTIVE: The study aimed to review the causes of pouchitis and introduce the hypothesis that inadequate mucus protection in the pouch, combined with a predisposition to abnormal inflammation, is the most common cause of nonspecific pouchitis. DATA SOURCES: Review of PubMed and MEDLINE for articles discussing pouchitis and intestinal mucus. STUDY SELECTION: Studies published from 1960 to 2023. The main search terms were "pouchitis," and "intestinal mucus," whereas Boolean operators were used with multiple other terms to refine the search. Duplicates and case reports were excluded. MAIN OUTCOME MEASURES: Current theories about the cause of pouchitis, descriptions of the role of mucus in the physiology of intestinal protection, and evidence of the effects of lack of mucus on mucosal inflammation. RESULTS: The crossreference of "intestinal mucus" with "pouchitis" produced 9 references, none of which discussed the role of mucus in the development of pouchitis. Crossing "intestinal mucus" with "pouch" resulted in 32 articles, combining "pouchitis" with "barrier function" yielded 37 articles, and "pouchitis" with "permeability" yielded only 8 articles. No article discussed the mucus coat as a barrier to bacterial invasion of the epithelium or mentioned inadequate mucus as a factor in pouchitis. However, an ileal pouch produces a colonic environment in the small bowel, and the ileum lacks the mucus protection needed for this sort of environment. This predisposes pouch mucosa to bacterial invasion and chronic microscopic inflammation that may promote clinical pouchitis in patients prone to an autoimmune response. LIMITATIONS: No prior studies address inadequate mucus protection and the origin of proctitis. There is no objective way of measuring the autoimmune tendency in patients with ulcerative colitis. CONCLUSIONS: Studies of intestinal mucus in the ileal pouch and its association with pouchitis are warranted.

Is Vaccination Against COVID-19 Associated With Inflammatory Bowel Disease Flare? Self-Controlled Case Series Analysis Using the UK CPRD.

INTRODUCTION: To investigate the association between vaccination against coronavirus disease 2019 (COVID-19) and inflammatory bowel disease (IBD) flare. METHODS: Patients with IBD vaccinated against COVID-19 who consulted for disease flare between December 1, 2020, and December 31, 2021, were ascertained from the Clinical Practice Research Datalink. IBD flares were identified using consultation and corticosteroid prescription records. Vaccinations were identified using product codes and vaccination dates. The study period was partitioned into vaccine-exposed (vaccination date and 21 days immediately after), prevaccination (7 days immediately before vaccination), and the remaining vaccine-unexposed periods. Participants contributed data with multiple vaccinations and IBD flares. Season-adjusted incidence rate ratios (aIRR) and 95% confidence intervals (CI) were calculated using self-controlled case series analysis. RESULTS: Data for 1911 cases with IBD were included; 52% of them were female, and their mean age was 49 years. Approximately 63% of participants had ulcerative colitis (UC). COVID-19 vaccination was not associated with increased IBD flares in the vaccine-exposed period when all vaccinations were considered (aIRR [95% CI] 0.89 [0.77-1.02], 0.79 [0.66-0.95], and 1.00 [0.79-1.27] in IBD overall, UC, and Crohn's disease, respectively). Analyses stratified to include only first, second, or third COVID-19 vaccinations found no significant association between vaccination and IBD flares in the vaccine-exposed period (aIRR [95% CI] 0.87 [0.71-1.06], 0.93 [0.75-1.15], and 0.86 [0.63-1.17], respectively). Similarly, stratification by COVID-19 before vaccination and by vaccination with vectored DNA or messenger RNA vaccine did not reveal an increased risk of flare in any of these subgroups. DISCUSSION: Vaccination against COVID-19 was not associated with IBD flares regardless of prior COVID-19 infection and whether messenger RNA or DNA vaccines were used.

Current perspectives on pediatric inflammatory bowel disease focusing on transitional care management. What should we consider?

The prevalence of inflammatory bowel disease (IBD) continues to rise around the globe. Although the percentage of pediatric IBD patients seems to be increasing, rates are surprisingly heterogeneous among different populations. Although the pathogenesis of IBD is believed to be multifactorial, a genetic predisposition may be especially relevant in pediatric-onset IBD. Phenotypic characteristics can also be significantly different when comparing pediatric and adult-onset IBD. Patients that develop the disease at a younger age usually present with more extensive and more aggressive disease and develop complications faster when compared to those that develop it during adulthood. Children with IBD are found to have frequent mood disorders and have a higher risk of developing socio-economic hardship, failing to meet development milestones. Therefore, IBD management should always involve a multidisciplinary team that is not limited to medical providers. Most institutions do not have an established transition protocol and lack the resources and training for transition care. Although there is no consensus on an optimal timing to transition the patient's care to an adult team, it is usually accepted they should be eligible for adult care when most of the key transition points have been met. Management strategies should be tailored to each patient's developmental level and environment. A successful transition can improve the long-term outcomes such as sustained remission, medication adherence, mental health and social and academic performance, while decreasing healthcare utilization. Every institution that manages pediatric IBD patients should have a well-established transition protocol in order to make sure to maintain continuity of care.

ONSET OF NONSPECIFIC ULCERATIVE COLITIS POST COVID-19 (CASE STUDY).

The patient suffered from a mild form of COVID-19 and was treated on an outpatient basis. According to the family doctor's prescription, she took Azithromycin 500 mg a day per os for 6 days, and then Ceftriaxone 1.0 g twice a day i.m. for another 6 days. Diarrhea appeared on the 10th day of treatment up to 10-15 times a day, a month later - blood admixtures in the stool appeared. The result was negative. Data from colonoscopy and histological examination of the intestinal mucosa and the clinical picture showed nonspecific ulcerative colitis, moderately severe. The patient started treatment with Salofalk first at a dose of 2 mg and then 4 mg per day. Due to the insufficient clinical effect, the patient was additionally prescribed Budenofalk in a daily dose of 9 mg with a positive clinical effect.

Nuances of Ileal Pouch-Anal Anastomosis in Familial Adenomatous Polyposis.

BACKGROUND: Patients with familial adenomatous polyposis are sometimes treated with prophylactic or therapeutic proctocolectomy to either prevent or treat the almost inevitable colorectal cancer that develops in the numerous, early onset tubular adenomas to which they are prone. These patients are potential candidates for a restorative IPAA. OBJECTIVE: This study aimed to highlight the particular nuances of ileal pouch-anal surgery faced by patients with familial adenomatous polyposis and point out the implications of the syndrome for patients who are candidates for an IPAA and the surgeons operating on them. STUDY SELECTION: A literature search was performed on PubMed and MEDLINE using the terms "ulcerative colitis," "familial adenomatous polyposis," "surgery," and "ileal pouch-anal anastomosis." CONCLUSIONS: As a result of a fundamental difference in pathophysiology, there are significant differences in demographics, presentation, surgical strategy, and sequelae of proctocolectomy and IPAA between familial adenomatous polyposis and ulcerative colitis. Proctocolectomy with IPAA in selected familial adenomatous polyposis patients can be performed in 1 stage, but their lack of symptoms means that any complications assume a greater significance. In polyposis patients, postoperative endoscopic surveillance of residual large intestine begins immediately, whereas surveillance of the pouch itself becomes increasingly important. Symptoms leading to a diagnosis of pouchitis are instead often due to structural and functional issues.

Ileal pouch-anal anastomosis; 18 years of experience and outcomes across two generations of surgeons at a tertiary center in Sweden.

AIM: Reconstructive surgery with ileal pouch-anal anastomosis (IPAA) is the standard procedure after colectomy in patients with Ulcerative Colitis (UC) and Familial Adenomatous Polyposis (FAP). It is of interest to understand how a generation shift of the surgeons performing IPAA has affected patients' outcomes. METHOD: All consecutive patients who underwent IPAA in the period 1999-2016 at Sahlgrenska University Hospital/Östra, Gothenburg, Sweden, were included. Surgeons representing two different generations performed the surgeries during this period. The following 6-year time periods were assigned for surgeries performed by: experienced surgeons (1999-2004; Period 1); the new generation of surgeons undergoing training (2005-2010; Period 2); and the new generation of experienced surgeons (2011-2016; Period 3). The primary endpoint was post-operative complications (Clavien-Dindo ≥3b), and the secondary endpoints were the functional outcome, failure of the pouch, and mortality. Logistic analyses of the results were performed. RESULTS: Overall, 281 patients were included in the study. The rate of post-operative severe complications was lower in Period 1 [Odds Ratio (OR) 0.137; p = .01]. There was no difference in functional outcome between the groups. CONCLUSION: This study implicates that the risk of post-operative complications after IPAA is lower when the surgery is performed by a generation of more-experienced surgeons. This might support literature that concludes that surgical units that have a high throughput of patients and are staffed by surgeons who perform many procedures provide better outcomes.

Effects of ethnicity and socioeconomic status on surgical outcomes from inflammatory bowel disease.

PURPOSE: Evidence suggests that ethnicity and socioeconomic status of patients with chronic diseases influence their healthcare outcomes. The aim of this study was to assess the impact of these factors on the surgical outcome of patients with inflammatory bowel disease (IBD) over a 15-year period. METHODS: A retrospective observational study investigated IBD patients operated on at an NHS Trust between 2000-2015, with follow-up data until 2020. Logistic regression models were used to determine the relationship between ethnic minority background and Index of Multiple Deprivation (IMD) on outcomes including requirement for intra-abdominal surgery, permanent stoma, re-do surgery and surgical complications, accounting for age, gender, smoking history and biologic treatment. RESULTS: There were 1,620 patients (56.7% ulcerative colitis (UC) and 43.3% Crohn's disease (CD)). Median age was 32 years, and 49.6% were female. Patients with an ethnic minority background accounted for 20.6%. Within 5 years of first presentation, 369 patients required intra-abdominal surgery, 95 permanent stomas and 107 re-do surgery. For CD patients, younger age at diagnosis, female patients, those with an ethnic minority background, higher IMD quintile, smoking history and biologic treatment were more likely to have intra-abdominal surgery. Ethnic minority background and higher IMD score were further associated with surgical complications for CD but not UC patients. CONCLUSION: Ethnic minority status and socioeconomic deprivation were associated with worse surgical outcomes within our cohort of IBD patients. These findings may stimulate discourse regarding the strategic planning of equitable healthcare services.

Postoperative complications, bowel function, and prognosis in restorative proctocolectomy for ulcerative colitis-a single-center observational study of 320 patients.

PURPOSE: To determine the selection criteria, postoperative complications, bowel function, and prognosis of stapled ileal pouch-anal anastomosis (IPAA) and hand-sewn IPAA for ulcerative colitis (UC). METHODS: We defined our surgical indications and strategy, and compared the postoperative complications, bowel function, and prognoses between patients who underwent stapled and hand-sewn IPAA for UC at the Yokohama City University Medical Center between 2004 and 2017. RESULTS: Among 320 patients enrolled, 298 patients underwent stapled IPAA while 22 underwent hand-sewn IPAA. There was no significant difference in the postoperative complications between the two groups. Regarding postoperative bowel function, stapled IPAA caused significantly less soiling (stapled vs hand-sewn: 9.1% vs 41.0%, odds ratio (OR) = 0.14, p < 0.0002), spotting (stapled vs hand-sewn: 23.2% vs 63.6%, OR = 0.17, p < 0.0001), and difficulty in distinguishing feces from flatus (stapled vs hand-sewn: 39.9% vs 63.6%, OR = 0.36, p < 0.026). No postoperative neoplasia was observed at the final follow-up in all patients. CONCLUSION: In this study, there was no clear difference in the postoperative complications between stapled and hand-sewn IPAA, but stapled IPAA resulted in better postoperative bowel function. Postoperative oncogenesis from the residual mucosa is rare. However, future cancer risk remains; thus, careful follow-up is required.

Young-onset stroke complicating ulcerative colitis.

A 16-year-old girl developed a proximal occlusion of the right middle cerebral artery during a flare-up of acute ulcerative colitis. Although mechanical thrombectomy led to successful middle cerebral artery recanalisation, she required an immediate second thrombectomy due to reocclusion of the same arterial segment. She developed a second ischaemic event 7 days later despite intravenous heparin infusion, later switched to low-molecular-weight heparin, and a third event after 3 days despite the addition of aspirin. We discuss stroke risks in people with inflammatory bowel disease and the uncertainties around anticoagulation and antiplatelet regimens in such cases.

Inflammatory Bowel Disease: Clinical Diagnosis and Surgical Treatment-Overview.

This article is an overview of guidelines for the clinical diagnosis and surgical treatment of predominantly colonic inflammatory bowel diseases (IBD). This overview describes the systematically and comprehensively multidisciplinary recommendations based on the updated principles of evidence-based literature to promote the adoption of best surgical practices and research as well as patient and specialized healthcare provider education. Colonic IBD represents idiopathic, chronic, inflammatory disorders encompassing Crohn's colitis (CC) and ulcerative colitis (UC), the two unsolved medical subtypes of this condition, which present similarity in their clinical and histopathological characteristics. The standard state-of-the-art classification diagnostic steps are disease evaluation and assessment according to the Montreal classification to enable explicit communication with professionals. The signs and symptoms on first presentation are mainly connected with the anatomical localization and severity of the disease and less with the resulting diagnosis "CC" or "UC". This can clinically and histologically be non-definitive to interpret to establish criteria and is classified as indeterminate colitis (IC). Conservative surgical intervention varies depending on the disease phenotype and accessible avenues. The World Gastroenterology Organizations has, for this reason, recommended guidelines for clinical diagnosis and management. Surgical intervention is indicated when conservative treatment is ineffective (refractory), during intractable gastrointestinal hemorrhage, in obstructive gastrointestinal luminal stenosis (due to fibrotic scar tissue), or in the case of abscesses, peritonitis, or complicated fistula formation. The risk of colitis-associated colorectal cancer is realizable in IBD patients before and after restorative proctocolectomy with ileal pouch-anal anastomosis. Therefore, endoscopic surveillance strategies, aimed at the early detection of dysplasia, are recommended. During the COVID-19 pandemic, IBD patients continued to be admitted for IBD-related surgical interventions. Virtual and phone call follow-ups reinforcing the continuity of care are recommended. There is a need for special guidelines that explore solutions to the groundwork gap in terms of access limitations to IBD care in developing countries, and the irregular representation of socioeconomic stratification needs a strategic plan for how to address this serious emerging challenge in the global pandemic.

An endoscopic treatment strategy for superficial tumors in patients with ulcerative colitis.

BACKGROUND AND AIM: Endoscopic resection is feasible for superficial tumors in patients with ulcerative colitis; however, endoscopic resection options have not been evaluated comprehensively. We evaluated the efficacy and safety of endoscopic submucosal dissection and endoscopic mucosal resection, and decision making regarding endoscopic resection options for patients with ulcerative colitis. METHODS: Endoscopically treated tumors from patients with ulcerative colitis were analyzed retrospectively. We evaluated en bloc and R0 resection, adverse events, local tumor recurrence, and metachronous lesion occurrence rates. RESULTS: We examined 102 tumors (mean size, 12 mm; non-polypoid, 55 tumors) from 74 patients with ulcerative colitis, of whom, 39 and 63 underwent endoscopic submucosal dissection and endoscopic mucosal resection, respectively. The R0 resection rate was significantly higher for endoscopic submucosal dissection (97%) than for endoscopic mucosal resection (80%) (P = 0.0015). For 11-20-mm tumors, the R0 resection rate was significantly higher for endoscopic submucosal dissection (94%) than for endoscopic mucosal resection (55%) (P = 0.0027); the endoscopic submucosal dissection and endoscopic mucosal resection R0 rates did not differ for ≤ 10-mm tumors. The non-polypoid tumor R0 resection rates were significantly higher for endoscopic submucosal dissection (100%) than for endoscopic mucosal resection (65%) (P < 0.001) and did not differ regarding the polypoid tumor R0 resection rates (75% vs 86%, P = 0.49). Four patients experienced intraoperative perforation during endoscopic submucosal dissection. No local recurrences occurred. Metachronous high-grade dysplasia occurred in three patients during surveillance. CONCLUSIONS: In patients with ulcerative colitis, endoscopic submucosal dissection is suitable for ≥ 11-mm and non-polypoid tumors, whereas endoscopic mucosal resection is acceptable for ≤ 10-mm tumors.

Growth Delay in Inflammatory Bowel Diseases: Significance, Causes, and Management.

Growth delay with height and weight impairment is a common feature of pediatric inflammatory bowel diseases (PIBD). Up to 2/3 of Crohn Disease patients have impaired weight at diagnosis, and up to 1/3 have impaired height. Ulcerative colitis usually manifests earlier with less impaired growth, though patients can be affected. Ultimately, growth delay, if not corrected, can reduce final adult height. Weight loss, reduced bone mass, and pubertal delay are also concerns associated with growth delay in newly diagnosed PIBD patients. The mechanisms for growth delay in IBD are multifactorial and include reduced nutrient intake, poor absorption, increased fecal losses, as well as direct effects from inflammation and treatment modalities. Management of growth delay requires optimal disease control. Exclusive enteral nutrition (EEN), biologic therapy, and corticosteroids are the primary induction strategies used in PIBD, and both EEN and biologics positively impact growth and bone development. Beyond adequate disease control, growth delay and pubertal delay require a multidisciplinary approach, dependent on diligent monitoring and identification, nutritional rehabilitation, and involvement of endocrinology and psychiatry services as needed. Pitfalls that clinicians may encounter when managing growth delay include refeeding syndrome, obesity (even in the setting of malnutrition), and restrictive diets. Although treatment of PIBD has improved substantially in the last several decades with the era of biologic therapies and EEN, there is still much to be learned about growth delay in PIBD in order to improve outcomes.

Effectiveness of Ursodeoxycholic Acid in the Treatment of Primary Sclerosing Cholangitis with Ulcerative Colitis: A Pediatric Case.

Primary sclerosing cholangitis is a rare disease with poor prognosis that potentially leads to liver cirrhosis and is often complicated by inflammatory bowel disease. Although ursodeoxycholic acid is the most commonly used drug to treat primary sclerosing cholangitis, its effectiveness in treating primary sclerosing cholangitis has not yet been established. An 11-year-old girl had a fever, upper and lower abdominal pain, and bloody stools. Colonoscopy revealed ulcerative colitis. She also had elevated hepatobiliary enzyme levels and C-reactive protein levels, indicating cholangitis after starting food intake, and primary sclerosing cholangitis was diagnosed with endoscopic retrograde cholangiography. Her hepatobiliary enzyme levels gradually improved after ursodeoxycholic acid was started, and symptoms did not recur after food intake. Primary sclerosing cholangitis should be considered if patients, even children, with inflammatory bowel disease, have upper abdominal pain with elevated biliary enzyme levels. The clinical guidelines for primary sclerosing cholangitis treatment have recommended that ursodeoxycholic acid should not be actively used. However, there are some recent reports stating its effectiveness for primary sclerosing cholangitis. In this patient, ursodeoxycholic acid may have been effective for the normalization of the hepatobiliary enzymes. However, it is unknown whether ursodeoxycholic acid improves long-term prognosis. Hence, further evidence regarding the effectiveness of ursodeoxycholic acid in the treatment of primary sclerosing cholangitis needs to be established.

Megacolon in inflammatory bowel disease: response to infliximab.

Megacolon is a serious complication of inflammatory bowel disease that often requires a colectomy. Infliximab is a therapeutic alternative when conventional treatment fails, before resorting to surgery. Its use is currently based on the publication of isolated cases. We present a series of 12 patients with megacolon treated with infliximab, five with signs of systemic toxicity. Seventy-five percent of the patients avoided a colectomy during their acute episode after early infliximab treatment, 2.45 days after the megacolon diagnosis. There was a greater risk of surgery among patients with ulcerative colitis and toxicity criteria. Two more patients required follow-up surgery despite long-term infliximab treatment. No patient suffered significant treatment-related adverse effects or significant post-surgery complications.

Tracheobronchitis in ulcerative colitis: a case report of therapeutic response with infliximab and review of the literature.

BACKGROUND: The extra-intestinal manifestation of tracheobronchitis is a rare complication of ulcerative colitis (UC). Here, we present a case of UC-related tracheobronchitis wherein the positive clinical effects of infliximab are demonstrated. CASE PRESENTATION: We report the case of a 39-year old woman who presented with a chronic productive cough on a distant background of surgically managed ulcerative colitis (UC). Our patient failed to achieve a satisfactory clinical improvement despite treatment with high dose inhaled corticosteroids, oral corticosteroids and azathioprine. Infliximab therapy was commenced and was demonstrated to achieve macroscopic and symptomatic remission of disease. CONCLUSIONS: We present the first case report documenting the benefits of infliximab in UC-related tracheobronchitis.

Thrombotic complications in inflammatory bowel diseases.

Inflammatory bowel disease (IBD), Crohn's Disease (CD) and Ulcerative Colitis (UC) are associated with an increased risk of arterial and venous thromboembolism. A 2 to 3 time fold increased risk of developing thromboembolic complications was reported for IBD patients compared to general population. A systematic literature search was conducted using PubMed, Medline, Scopus, Cochrane database. The key words were: "Inflammatory Bowell Disease", "Crohn's Disease and Thrombosis", "Ulcerative Colitis and Thrombosis", "Thrombosis" and "Inflammatory Bowel Diseases and Thrombosis". Full articles and abstracts were included. Studies such as case reports, letters and commentaries were excluded from the analysis if appropriate data could not be extracted. Although no randomized controlled trials (RCTs) have been established to evaluate the efficacy of thromboprophylaxis in patients with IBD due to the incidence of VTE and PE in such patients, it is highly recommended the adoption of thromboprophylactic measures. Available prophylaxis and treatment options include pharmacological anticoagulant therapy (LMWH-Low Molecular Weight Heparin, Fondaparinux and UH-Unfractionated Heparin) and mechanical prophylaxis. In case of acute VTE patient must be treated with fibrinolytic agents and in selected non-responsive cases vascular surgery. IBD patients have an increased risk of VTE complications. Prophylaxis for VTE should be recommended in all patients who do not show contraindications to treatment.

Celiac disease associated with ulcerative colitis.

The article provides clinical observation of a patient who was diagnosed with celiac disease when he was 52 years (Marsh stage IIIB). Following gluten-free diet (GFD) clinical remission and restoration of small intestinal mucosa (SIM) structure occurred, however in 6 years ulcerative colitis developed and an impairment of SIM morphological structure was identified (Marsh stage IIIA). Ulcerative colitis and celiac disease remission is supported by GFD, anti-cytokine therapy (adalimumab) in combination with mesalazine.