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Diseases of the Colon and Rectum Jun 2024Chronic antibiotic refractory pouchitis after restorative proctocolectomy with IPAA, characterized by at least 4 weeks of pouchitis symptoms that have not responded to... (Review)
Review
BACKGROUND
Chronic antibiotic refractory pouchitis after restorative proctocolectomy with IPAA, characterized by at least 4 weeks of pouchitis symptoms that have not responded to standard antibiotic therapy, presents a therapeutic challenge for patients and health care providers.
OBJECTIVE
The aim of this narrative review was to summarize the current evidence regarding the management of chronic antibiotic refractory pouchitis.
DATA SOURCES
Studies were identified through a search of the PubMed database from the National Library of Medicine.
STUDY SELECTION
We included case series, cohort studies, randomized controlled trials, and systematic reviews with meta-analyses that addressed chronic antibiotic refractory pouchitis management, with prioritization of data published within the past 3 to 5 years.
INTERVENTION
Studies examining pharmacologic and select nonpharmacologic interventions were included.
MAIN OUTCOME MEASURE
Outcomes measures included clinical, endoscopic, and histologic end points.
RESULTS
Mesalamine has demonstrated efficacy in symptom improvement but no improvement in quality of life. Budesonide has demonstrated high rates of clinical remission that have mostly been sustained in a small number of patients. Anti-tumor necrosis factor therapies have demonstrated efficacy in reaching clinical and even endoscopic end points, although rates of treatment discontinuation were not insignificant. Limited evidence is encouraging for the use of ustekinumab in achieving clinical response. Data for vedolizumab are favorable across clinical, endoscopic, and histologic end points, including one of the only randomized, placebo-controlled trials. Nonmedication therapies, including hyperbaric oxygen therapy and fecal microbiota transplant, have undergone limited evaluation, and concerns about the ultimate accessibility of these therapies remain.
LIMITATIONS
Overall, studies assessing therapeutic options for chronic antibiotic refractory pouchitis are mostly limited to case series and retrospective studies with small sample sizes.
CONCLUSIONS
Biologic therapies have demonstrated efficacy in the management of chronic antibiotic refractory pouchitis and offer a steroid-sparing option for refractory disease. Nonpharmacologic therapies, including hyperbaric oxygen and fecal microbiota transplant, require further exploration. See video from symposium .
Topics: Pouchitis; Humans; Anti-Bacterial Agents; Proctocolectomy, Restorative; Chronic Disease; Fecal Microbiota Transplantation; Evidence-Based Medicine
PubMed: 38363696
DOI: 10.1097/DCR.0000000000003207 -
Cureus Aug 2023Diarrhoea is a common presentation in acute emergency with potentially multifactorial causes. Hence, the chances of misdiagnosis can be high. Among these causes are...
Diarrhoea is a common presentation in acute emergency with potentially multifactorial causes. Hence, the chances of misdiagnosis can be high. Among these causes are listed diseases which are primarily inflammatory in nature. Presented here is a rare case of Behcet's colitis with valuable clinical lessons, in a patient who is known to have Behcet's disease and was admitted with acute onset bloody diarrhoea. This was a gastrointestinal manifestation of the patient's multisystemic inflammatory disorder as proven by investigations via computed tomography (CT) scan, sigmoidoscopy, and histology. He was treated with steroids and mesalazine, and later switched to infliximab and made a quick recovery.
PubMed: 37750152
DOI: 10.7759/cureus.44101 -
The American Journal of Case Reports Nov 2023BACKGROUND Ulcerative colitis (UC) is a chronic immune-mediated disease of the colon. The mainstay of treatment to achieve and maintain remission is 5-aminosalicylic... (Review)
Review
BACKGROUND Ulcerative colitis (UC) is a chronic immune-mediated disease of the colon. The mainstay of treatment to achieve and maintain remission is 5-aminosalicylic acid (5-ASA). At least 20% of patients with UC experience an acute severe ulcerative colitis (ASUC) flare, requiring aggressive early intervention to prevent complications. The first-line treatment of ASUC is intravenous steroids followed by infliximab or cyclosporin in patients for whom steroids fail. Refractory disease failing medical therapy and warranting surgery is common. Lately, Janus kinase (JAK) inhibitors, such as tofacitinib, filgotinib, and upadacitinib, have been licensed for moderate-to-severe UC in adults. Nevertheless, the safety and efficacy of upadacitinib in ASUC has not yet been established. CASE REPORT We report a case of an 18-year-old woman with 4-year history of severe UC. Both infliximab and adalimumab treatments failed, despite the concurrent use of azathioprine, and she was reliant on steroids. Moreover, tofacitinib failed after 1 year of therapy. She was admitted as a case of ASUC. Flexible sigmoidoscopy confirmed severe pancolitis. Finally, she was treated effectively with oral upadacitinib 45 mg given once daily. She went into full clinical, biochemical, and steroid-free remission in 60 days and endoscopic remission at 180 days. CONCLUSIONS This case report features the potential safety and efficacy of upadacitinib in adults with ASUC. Larger trials are required to confirm the efficacy and safety in patients admitted with ASUC.
Topics: Adult; Female; Humans; Adolescent; Colitis, Ulcerative; Infliximab; Heterocyclic Compounds, 3-Ring; Mesalamine; Steroids; Treatment Outcome
PubMed: 37926993
DOI: 10.12659/AJCR.940966 -
Journal of Controlled Release :... May 2024Successful treatment of ulcerative colitis (UC) is highly dependent on several parameters, including dosing regimen and the ability to deliver drugs to the disease site....
Successful treatment of ulcerative colitis (UC) is highly dependent on several parameters, including dosing regimen and the ability to deliver drugs to the disease site. In this study two strategies for delivering mesalazine (5-aminosalicylic acid, 5-ASA) to the colon were compared in an advanced in vitro model of the human gastrointestinal (GI) tract, the SHIME® system. Herein, a prodrug strategy employing bacteria-mediated drug release (sulfasalazine, Azulfidine®) was evaluated alongside a formulation strategy that utilised pH and bacteria-mediated release (5-ASA, Octasa® 1600 mg). SHIME® experiments were performed simulating both the GI physiology and colonic microbiota under healthy and inflammatory bowel disease (IBD) conditions, to study the impact of the disease state and ileal pH variability on colonic 5-ASA delivery. In addition, the effects of the products on the colonic microbiome were investigated by monitoring bacterial growth and metabolites. Results demonstrated that both the prodrug and formulation approaches resulted in a similar percentage of 5-ASA recovery under healthy conditions. On the contrary, during experiments simulating the GI physiology and microbiome of IBD patients (the target population) the formulation strategy resulted in a higher proportion of 5-ASA delivery to the colonic region as compared to the prodrug approach (P < 0.0001). Interestingly, the two products had distinct effects on the synthesis of key bacterial metabolites, such as lactate and short chain fatty acids, which varied according to disease state and ileal pH variability. Further, both 5-ASA and sulfasalazine significantly reduced the growth of the faecal microbiota sourced from six healthy humans. The findings support that the approach selected for colonic drug delivery could significantly influence the effectiveness of UC treatment, and highlight that drugs licensed for UC may differentially impact the growth and functioning of the colonic microbiota.
Topics: Mesalamine; Humans; Colon; Gastrointestinal Microbiome; Anti-Inflammatory Agents, Non-Steroidal; Sulfasalazine; Prodrugs; Drug Delivery Systems; Colitis, Ulcerative; Hydrogen-Ion Concentration; Inflammatory Bowel Diseases; Drug Liberation
PubMed: 38599548
DOI: 10.1016/j.jconrel.2024.04.016 -
Free Radical Biology & Medicine Mar 2024Ulcerative colitis (UC) is a chronic gastrointestinal disease that can be managed with 5-aminosalicylic acid (5-ASA), the standard treatment for UC. However, the...
Ulcerative colitis (UC) is a chronic gastrointestinal disease that can be managed with 5-aminosalicylic acid (5-ASA), the standard treatment for UC. However, the effectiveness of 5-ASA is not always optimal. Our study revealed that despite 5-ASA treatment, cells continued to experience excessive ferroptosis, which may hinder mucosal healing in UC and limit the success of this treatment approach in achieving disease remission. We found that combining 5-ASA with the ferroptosis inhibitor Fer-1 led to a significant inhibition of ferroptosis in macrophages present in the colon tissue, along with an increase in the proportion of M2 macrophages, suggesting that targeting ferroptosis in M2 macrophages could be a potential therapeutic strategy for alleviating UC. Our study also demonstrated that M2 macrophages are more susceptible to ferroptosis compared to M1 macrophages, and this susceptibility is associated with the activated arachidonic acid (AA) metabolism pathway mediated by ERK-cPLA2-ACSL4. Additionally, we found that the expression of cPLA2 gene pla2g4a was increased in the colon of UC patients compared to healthy controls. Furthermore, targeted metabolomics analysis revealed that the combination treatment group, as opposed to the 5-ASA treatment group, exhibited the ability to modulate AA metabolism. Overall, our findings emphasize the importance of addressing macrophage ferroptosis in order to enhance macrophage anti-inflammation, improve mucosal healing, and achieve better therapeutic outcomes for patients with UC.
Topics: Humans; Colitis, Ulcerative; Ferroptosis; Lipid Metabolism; Macrophages; Mesalamine
PubMed: 38367927
DOI: 10.1016/j.freeradbiomed.2024.02.016 -
Surgical Case Reports Sep 2023Postoperative recurrence is frequently encountered in the management of patients with Crohn's disease and is most often found at the anastomotic site. A novel technique,...
BACKGROUND
Postoperative recurrence is frequently encountered in the management of patients with Crohn's disease and is most often found at the anastomotic site. A novel technique, the Sasaki-W anastomosis, is an antimesenteric cutback end-to-end isoperistaltic anastomosis. We report a patient with Crohn's disease who underwent partial intestinal resection for postoperative anastomotic stenosis, reconstructed with the Sasaki-W anastomosis, after initial intestinal resection reconstructed with a Kono-S anastomosis.
CASE PRESENTATION
A 30-year-old male was diagnosed with Crohn's disease and treated with mesalamine and adalimumab, and he underwent ileocecal resection using the Kono-S anastomosis at the time of diagnosis. He was treated with infliximab without any symptoms or recurrence for 7 years. He was admitted presenting with upper abdominal pain. Physical examination showed mild tenderness and distension in the upper abdomen. Laboratory data showed no remarkable findings. Computed tomography scan showed wall thickening in the ileum with proximal dilation and fluid retention. Non-operative management with antibiotics and fasting did not improve the symptoms within 7 days. Ten days after admission, ileocecal resection reconstructed with the Sasaki-W anastomosis was performed. At operation, there was a 15-cm intestinal stenosis at the site of the previous Kono-S anastomosis. The transverse colon and ileum were reconstructed with the Sasaki-W anastomosis. The postoperative course was uneventful, and the patient was discharged 17 days postoperatively. The patient had no obstructive symptoms and no findings consistent with bowel obstruction were observed on computed tomography scan one year postoperatively.
CONCLUSIONS
The Sasaki-W anastomosis is a viable option for intestinal reconstruction in patients with postoperative recurrence after a Kono-S anastomosis.
PubMed: 37773306
DOI: 10.1186/s40792-023-01747-z -
Inflammatory Bowel Diseases Nov 2023The knowledge of patients' perceptions of factors contributing to ulcerative colitis (UC) flares is limited; however, online patient communications could offer insight....
BACKGROUND
The knowledge of patients' perceptions of factors contributing to ulcerative colitis (UC) flares is limited; however, online patient communications could offer insight. This analysis aimed to identify the most frequent patient-reported triggers and symptoms of UC flares, which could highlight potential interventions for outcome improvement.
METHODS
Online posts written pre- and postflare by patients with UC on 8 public forums in 6 countries between January 1, 2019, and February 14, 2021, were identified using flare-related keywords. Flare-related posts were captured and Netbase Quid™ artificial intelligence text analytics and natural language processing software were used to semantically map and identify commonly discussed themes and topics (subsets of themes).
RESULTS
Of >27 000 patient posts, 12 900 were identified as flare related. The most frequent themes were treatment experiences and side effects (28.5% of posts), followed by flare symptoms (22.9% of posts). The most frequent topic was emotional/peer support (9.4% of posts), followed by experiences with mesalamine (and other oral/rectal formulations; 8.0% of posts), and dietary recommendations (6.0% of posts). Stress and anxiety were the most frequently reported flare triggers (37.9% of posts), followed by diet (28.4% of posts). Stress and anxiety were frequently identified as both triggers for, and general symptoms of, flare. Blood in the stool was the most discussed flare indicator (57.8% of posts).
CONCLUSIONS
Frequently discussed patient-perceived triggers of UC flares included diet, stress, and anxiety. These results suggest that physicians could incorporate a broader and more holistic approach to UC monitoring and management than is currently practiced.
PubMed: 37934789
DOI: 10.1093/ibd/izad247 -
Toxics Jun 2024Drug-induced liver disease (DILI) represents one of the main problems in the therapeutic field. There are several non-modifiable risk factors, such as age and sex, and... (Review)
Review
Drug-induced liver disease (DILI) represents one of the main problems in the therapeutic field. There are several non-modifiable risk factors, such as age and sex, and all drugs can cause hepatotoxicity of varying degrees, including those for the treatment of inflammatory bowel diseases (IBD). The aim of this review is to illustrate the adverse effects on the liver of the various drugs used in the treatment of IBD, highlighting which drugs are safest to use based on current knowledge. The mechanism by which drugs cause hepatotoxicity is not fully understood. A possible cause is represented by the formation of toxic metabolites, which in some patients may be increased due to alterations in the enzymatic apparatus involved in drug metabolism. Various studies have shown that the drugs that can most frequently cause hepatotoxicity are immunosuppressants, while mesalazine and biological drugs are, for the most part, less associated with such complications. Therefore, it is possible to assume that in the future, biological therapies could become the first line for the treatment of IBD.
PubMed: 38922101
DOI: 10.3390/toxics12060421 -
Scientific Reports Jul 2023Although many therapeutic options are available for inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA) is still the key medication, particularly for...
Although many therapeutic options are available for inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA) is still the key medication, particularly for ulcerative colitis (UC). However, the mechanism of action of 5-ASA remains unclear. The intestinal microbiota plays an important role in the pathophysiology of IBD, and we hypothesized that 5-ASA alters the intestinal microbiota, which promotes the anti-inflammatory effect of 5-ASA. Because intestinal inflammation affects the gut microbiota and 5-ASA can change the severity of inflammation, assessing the impact of inflammation and 5-ASA on the gut microbiota is not feasible in a clinical study of patients with UC. Therefore, we undertook a translational study to demonstrate a causal link between 5-ASA administration and alterations of the intestinal microbiota. Furthermore, by rigorously controlling environmental confounders and excluding the effect of 5-ASA itself with a vertical transmission model, we observed that the gut microbiota altered by 5-ASA affected host mucosal immunity and decreased susceptibility to dextran sulfate sodium-induce colitis. Although the potential intergenerational transmission of epigenetic changes needs to be considered in this study, these findings suggested that alterations in the intestinal microbiota induced by 5-ASA directed the host immune system towards an anti-inflammatory state, which underlies the mechanism of 5-ASA efficacy.
Topics: Humans; Animals; Mice; Mesalamine; Gastrointestinal Microbiome; Colitis; Colitis, Ulcerative; Inflammation; Inflammatory Bowel Diseases; Anti-Inflammatory Agents; Dextran Sulfate; Disease Models, Animal; Colon; Mice, Inbred C57BL
PubMed: 37507482
DOI: 10.1038/s41598-023-39491-x -
International Journal of Biological... Jan 2024Microalgae polysaccharides (MAPS) have emerged as novel prebiotics, but their direct effects on intestinal epithelial barrier are largely unknown. Here, MAPS isolated...
Microalgae polysaccharides exert antioxidant and anti-inflammatory protective effects on human intestinal epithelial cells in vitro and dextran sodium sulfate-induced mouse colitis in vivo.
Microalgae polysaccharides (MAPS) have emerged as novel prebiotics, but their direct effects on intestinal epithelial barrier are largely unknown. Here, MAPS isolated from Chlorella pyrenoidosa, Spirulina platensis, and Synechococcus sp. PCC 7002 were characterized as mainly branched heteropolysaccharides, and were bioavailable to Caco-2 cells based on fluorescein isothiocyanate labeling and flow cytometry analysis. These MAPS were equally effective to scavenge hydroxyl and superoxide radicals in vitro and to attenuate the HO-, dextran sodium sulfate-, tumor necrosis factor α-, and interleukin 1β-induced burst of intracellular reactive oxygen species and mitochondrial superoxide radicals, interleukin-8 production, cyclooxygenase-2 and inducible nitric oxide synthase expression, and/or tight junction disruption in polarized Caco-2 cells. MAPS and a positive drug Mesalazine were intragastrically administered to C57BL/6 mice daily for 7 d during and after 4-d dextran sodium sulfate exposure. Clinical signs and colon histopathology revealed equivalent anti-colitis efficacies of MAPS and Mesalazine, and based on biochemical analysis of colonic tight junction proteins, goblet cells, mucin 2 and trefoil factor 3 transcription, and colonic and peripheral pro-inflammatory cytokines, MAPS alleviated dextran sodium sulfate-induced intestinal epithelial barrier dysfunction, and their activities were even superior than Mesalazine. Overall, MAPS confer direct antioxidant and anti-inflammatory protection to intestinal epithelial barrier function.
Topics: Humans; Animals; Mice; Antioxidants; Microalgae; Dextrans; Caco-2 Cells; Mesalamine; Chlorella; Hydrogen Peroxide; Superoxides; Mice, Inbred C57BL; Colitis; Epithelial Cells; Anti-Inflammatory Agents; Dextran Sulfate; Intestinal Mucosa; Disease Models, Animal
PubMed: 37923042
DOI: 10.1016/j.ijbiomac.2023.127811