Ulcerative Patients Research Articles

Draft genome sequences of multi-drug-resistant Escherichia coli strains isolated from ulcerative colitis patients.

The whole-genome sequences of four multi-drug-resistant Escherichia coli strains, namely, DAK02, DAK03, DAK05, and DAK10, are reported here. The E. coli strains were isolated from fecal samples of ulcerative colitis patients from Northern India. The size of the draft genome sequence ranged from 4,809 to 5,000 kb.

Broadening perspectives in the treatment of chronic pouchitis.

We present the case of a 64-year-old male diagnosed with corticosteroid-dependent ulcerative colitis in 1999, who underwent total proctocolectomy with a J-pouch in 2005. Three years later, he developed recurrent histologically confirmed pouchitis, with clinical worsening. Several therapies were tried, including Infliximab, which provided stability for six years, until the development of antibodies led to moderate pouchitis in the rectal stump. Attempts with Adalimumab, Vedolizumab, and Ustekinumab failed, leading to worsening cuffitis, pouchitis, and anastomotic stenosis. Tofacitinib was started at 10 mg/12h, leading to a >50% reduction in fecal calprotectin and a PDAI drop from 4 to 0 within four weeks. After reducing the dose to 5 mg/12h, disease control was maintained, and the patient remains asymptomatic after two years and seven months, with normal colonoscopy findings showing complete mucosal healing. Despite advances in treatment, around 15% of ulcerative colitis patients require surgery, and 30-50% of those develop acute or chronic cuffitis or pouchitis. Tofacitinib, a JAK inhibitor, is approved for ulcerative colitis but has shown inconsistent results in treating pouchitis and cuffitis. While some studies report a lack of efficacy, others show potential responses in refractory cases. More research with larger patient cohorts is needed to better understand the role of JAK inhibitors in this context.

Anti PR3 ANCA as a Marker of Diagnosis and Assessing the Severity in Ulcerative Colitis Patients

Anti PR3 ANCA as a Marker of Diagnosis and Assessing the Severity in Ulcerative Colitis Patients

Fine-mapping and molecular characterisation of primary sclerosing cholangitis genetic risk loci

Genome-wide association studies of primary sclerosing cholangitis have identified 23 susceptibility loci. The majority of these loci reside in non-coding regions of the genome and are thought to exert their effect by perturbing the regulation of nearby genes. Here, we aim to identify these genes to improve the biological understanding of primary sclerosing cholangitis, and nominate potential drug targets. We first build an eQTL map for six primary sclerosing cholangitis-relevant T-cell subsets obtained from the peripheral blood of primary sclerosing cholangitis and ulcerative colitis patients. These maps identify 10,459 unique eGenes, 87% of which are shared across all six primary sclerosing cholangitis T-cell types. We then search for colocalisations between primary sclerosing cholangitis loci and eQTLs and undertake Bayesian fine-mapping to identify disease-causing variants. In this work, colocalisation analyses nominate likely primary sclerosing cholangitis effector genes and biological mechanisms at five non-coding (UBASH3A, PRKD2, ETS2 and AP003774.1/CCDC88B) and one coding (SH2B3) primary sclerosing cholangitis loci. Through fine-mapping we identify likely causal variants for a third of all primary sclerosing cholangitis-associated loci, including two to single variant resolution.

Ulcerative Colitis Patients are at Increased Risk for Adverse Events Following Total Hip Arthroplasty

BackgroundPatients who have the autoinflammatory bowel disease ulcerative colitis (UC) may become candidates for total hip arthroplasty (THA). Having UC may predispose patients to postoperative adverse events, but it remains unclear if these events are related more to the disease process itself or perhaps related to the medications used to treat the condition. MethodsPatients undergoing THA were identified from a large administrative dataset. Those who did not have and those who had UC were matched 4:1 based on patient age, sex, and the Elixhauser Comorbidity Index (ECI). Matched THA patients who did not have UC (n = 19,482) and those who had UC (n = 4,874) were identified. The matched groups were compared regarding 90-day adverse and five-year survival. Further analyses were performed based on classes of medications. ResultsControlling for patient age, sex, and ECI, UC patients were at significantly higher odds of 90-day adverse events: any (odds ratio [OR] 1.59), severe (OR 1.72), and minor (OR 1.63) (all P < 0.001). Despite this, no differences in 5-year survival were identified. Relative to those who did not have UC, there were increasing odds of any adverse event based on the potency of related medications: no corticosteroids /immunomodulators/5-aminosalicylic acid (5-ASA) (OR 1.42), corticosteroids only (OR 1.58), 5-ASA ± corticosteroids OR (1.72), and immunomodulators ± corticosteroids (OR 1.74, all P < 0.001). ConclusionsTotal hip arthroplasty patients who have UC were at higher odds for 90-day postoperative adverse events relative to those who did not have UC, and this risk was even greater for those on defined classes of medications. Total hip arthroplasty patients who have UC bear specific considerations, and surgeons must carefully consider and manage the patient’s medication regimen in the perioperative period of the THA.

Clinical profiles of leucine-rich alpha-2 glycoprotein for indicating mucosal healing in ulcerative colitis patients under administration of molecular targeted drug.

Leucine-rich alpha-2 glycoprotein (LRG) is a useful serum biomarker for monitoring disease activity during remission in ulcerative colitis (UC). Because LRG levels differ among patients, it is necessary to assess them after profiling patients, especially in patients with refractory UC undergoing treatment with molecular targeted drugs. This study aimed to analyze LRG levels that indicate mucosal healing according to clinical characteristics and molecular targeted drugs. Among 214 patients with UC treated with biologics or Janus kinase (JAK) inhibitors, this study evaluated 111 patients (174 measurements) who achieved mucosal healing based on colonoscopy performed within 2 months before and after LRG measurement and experienced no changes in disease status or treatment during the same period. We analyzed the relationship of LRG with clinical characteristics (including sex, age, body mass index, and disease type and duration) and molecular targeted drugs. Compared with men, women had significantly higher LRG levels (9.5 μg/mL vs. 11.3 μg/mL, P&lt;0.001). In addition, LRG levels were significantly higher in older patients (12.0 μg/mL vs. 9.8 μg/mL, P&lt;0.01). LRG levels were the highest in patients treated with vedolizumab and lower in patients treated with JAK inhibitors (vedolizumab: 12.7 μg/mL; tofacitinib: 8.9 μg/mL; upadacitinib: 8.5 μg/mL; and filgotinib: 9.1 μg/mL; P&lt;0.0001). Among the patients who achieved mucosal healing, LRG levels were significantly higher in women and older patients. LRG levels differed according to the molecular targeted drug used, and were higher with vedolizumab and lower with JAK inhibitors.

Association of oral manifestations with severity of the disease in ulcerative colitis patients

ObjectiveInflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), are chronic conditions primarily affecting the intestines. This study aims to identify the nature and frequency of oral symptoms and signs in patients with ulcerative colitis and to explore the connection between these complications and the activity of the disease.MethodsThis descriptive-analytical study involved ulcerative colitis patients who visited the gastroenterology clinic at Shahid Sayad Shirazi Hospital in Gorgan, along with an equal number of healthy companions as a control group in 2019. A gastroenterology internist assessed the disease severity through clinical examination and a simple clinical disease activity index for colitis patients. The collected data were then analyzed statistically using SPSS version 19.ResultsThe average age of patients in the case group was 41.84 ± 11.66 years, while in the control group it was 40.43 ± 12.67 years. There was a significant correlation between difficulty swallowing, burning sensation in the mouth, vomiting, acidic taste, the presence of oral ulcers, and a coated tongue with the severity of disease activity (p < 0.05). However, no significant relationship was found between other variables and the severity of disease activity (p > 0.05).ConclusionThe results of this study confirm that as the severity of ulcerative colitis increases, the occurrence of oral lesions also rises, particularly during severe disease activity. Among oral symptoms, dry mouth had the highest incidence, followed by bad breath and changes in taste. The most common oral lesions observed were a coated tongue, grooved tongue, and oral ulcers, respectively.

Types, behaviour and therapeutic requirements of inflammatory pouch disorders: Results from the RESERVO study of GETECCU

Background and AimsInflammatory pouch disorders exhibit a heterogeneous clinical spectrum and therapeutic requirements have not been properly studied. MethodsThis retrospective, multicentre study included ulcerative colitis patients with ileal pouch construction and were later diagnosed with an inflammatory pouch disorder between 1995 and 2020. Classifications, behaviour and therapies applied were recorded and compared in the long-term. ResultsOverall, 338 patients were recruited. The most common disorders were pouchitis (n = 258, 76%), Crohn's disease of the pouch (n = 55, 16%) and cuffitis (n = 25, 7%). Pouchitis presented mainly as chronic (65.2%) and recurrent (87%) forms. Crohn's disease manifested as stricturing/penetrating in 53% of cases and perianal disease in 42%. Patients received multiple therapies: 86% antibiotics, 42% steroids, 27% immunosuppressants, 43% biologics and 27% surgery. Compared with pouchitis, Crohn's disease of the pouch was characterised by a later diagnosis (99 vs. 55 months, p < 0.001) and greater needs for immunosuppressants (OR 3.53, 1.79–6.94, p < 0.0001), biologics (OR 5.45, 2.78–10.6, p < 0.0001) and surgeries (OR 2.65, 1.43–4.89, p < 0.001). ConclusionsChronic pouchitis is the most common pouch disorder presentation. These entities have diverse therapeutics requirements, particularly for Crohn's disease of the pouch.

Safety and Potential Efficacy of Expanded Umbilical Cord-Derived Mesenchymal Stromal Cells in Luminal Ulcerative Colitis Patients.

Inflammatory bowel disease (IBD) is characterized by periods of flare-ups and remission. It is likely to be an autoimmune in origin, presenting persistent therapeutic challenges despite current therapies. This study aims to investigate the potential of umbilical cord mesenchymal stromal cells (UCMSCs) in treating ulcerative colitis (UC). This study is a prospective phase 1 pilot, open-label, single-arm, and single-center study. UCMSCs were cultured under current Good Manufacturing Practice (cGMP) conditions and intravenously administered to six patients with UC. Safety and efficacy were evaluated using the Mayo Score/Disease Activity Index. Among the six enrolled adult patients, five completed long-term follow-ups. All exhibited at diagnosis active UC confirmed through comprehensive assessment methods. Each patient received three injections intravenously 2 weeks apart with a dose of 100 million UCMSC each. No significant short-term or intermediate-term adverse events were detected post-UCMSC administration. Long-term follow-up at 12 and 24 months showed sustained safety and no adverse events. Notably, three out of five patients achieved a Mayo score of 0 for UC, maintained at both 12 and 24 months, indicating a highly significant response (P < 0.001). This study demonstrates the safety and potential efficacy of UCMSCs in active UC. However, larger trials are warranted to validate these preliminary findings and to establish the role of UCMSC therapy as an option for managing UC.

Tryptophan Metabolites Improve Intestinal Mucosal Barrier via the Aryl Hydrocarbon Receptor-Interleukin-22 Pathway in Murine Dextran Sulfate Sodium-Induced Pouchitis.

Pouchitis is the commonest complication after ileal pouch-anal anastomosis for ulcerative colitis. The protective effect of tryptophan metabolites on the mucosal barrier may be an effective method for treating pouchitis. The role of tryptophan metabolites on pouchitis remained unclear. We aimed to establish a murine model of dextran sulfate sodium-induced pouchitis to examine the roles of tryptophan metabolites in its pathogenesis. This is a study combined clinical patient data and animal research. A total of 22 patients were enrolled: 5 with familial adenomatous polyposis after ileal pouch-anal anastomosis, eight ulcerative colitis patients after ileal pouch-anal anastomosis patients with pouchitis, and 9 ulcerative colitis patients after ileal pouch-anal anastomosis with normal pouch. The demographic data and fecal samples of patients were collected. Male C57BL/6 mice were purchased from a licensed breeder and underwent ileal pouch-anal anastomosis to establish murine model of pouch. The bloods, feces, tissues of mice were collected. This study was performed in an academic medical center in China. The demographic data of patients were observational collected. The mice underwent ileal pouch-anal anastomosis were divided into six groups: control group with chow diet, dextran sulfate sodium, 6-formylindolo[3,2-b] carbazole + dextran sulfate sodium, high tryptophan diet + dextran sulfate sodium, CH-223191 + dextran sulfate sodium, indole-3-carboxaldehyde + dextran sulfate sodium. Animals were sacrificed after dextran sulfate sodium for 7 days. Fecal tryptophan metabolite level and microbiome composition, the severity of pouchitis, intestinal mucosal barrier function, and activation of the aryl hydrocarbon receptor-interleukin 22 pathway were assessed. Patients with pouchitis had lower fecal microbial diversity and indole-3-acetic acid levels. In murine pouchitis model, high-tryptophan diet increased fecal levels of 3-indoleglyoxylic acid, indole-3-aldehyde, and indole. A high-tryptophan diet and intraperitoneal aryl hydrocarbon receptor ligand 6-formylindolo[3,2-b] carbazole injection alleviated pouchitis. Tryptophan metabolites improved pouch mucosal barriers. aryl hydrocarbon receptor inhibitors exacerbated experimental pouchitis and disrupted the mucosal barrier; however, the aryl hydrocarbon receptor ligand indole-3-carboxaldehyde reversed this effect. This study was limited by small human sample size and lacking an Aryl hydrocarbon receptor knockout mouse model. A high-tryptophan diet and aryl hydrocarbon receptor ligand alleviated dextran sulfate sodium-induced pouchitis in murine ileal pouch-anal anastomosis model, which might be through regulating epithelial tight junctions and promoting goblet-cell differentiation, as well as maintaining the integrity and function of the mucosal barrier. This study provides a rationale for the clinical application of Aryl hydrocarbon receptor ligands in the treatment of pouchitis. See Video Abstract.

Efficacy of Second-Line Biological Therapies in Moderate to Severe Ulcerative Colitis Patients with Prior Failure of Anti-Tumor Necrosis Factor Therapy: A Multi-Center Study.

Few studies have compared the efficacy and safety of second-line biological therapies in ulcerative colitis (UC) patients with prior exposure to anti-tumor necrosis factor (TNF) therapy. We aim to compare the efficacy and safety between ustekinumab, vedolizumab, and tofacitinib, a current option as second-line biological therapy with different mechanisms in those patients. This retrospective multi-center study was conducted across five institutions from 2011 to 2022. We enrolled patients with moderate to severe UC who failed anti-TNF therapy and subsequently received ustekinumab, vedolizumab, or tofacitinib as second-line biological therapy. The outcomes were analyzed for clinical response/remission and endoscopic improvement/remission rates after induction therapy, drug persistency, and adverse events. A total of 70 UC patients were included and grouped into ustekinumab (11 patients), vedolizumab (40 patients), and tofacitinib (19 patients) treatments. The clinical response/remission rates after induction therapy were similar between ustekinumab (90.9/81.8%), vedolizumab (92.5/65.0%), and tofacitinib (94.7/73.7%). There were no significant differences in the endoscopic improvement/remission rates between the three groups: 90.9/18.2% for ustekinumab, 72.5/12.5% for vedolizumab, and 84.2/26.3% for tofacitinib. Drug persistence was similar across the three agents (p = 0.130). Three patients of the tofacitinib group experienced adverse events (herpes zoster and hypertriglyceridemia). Based on real-world data, second-line biological therapy with ustekinumab, vedolizumab, and tofacitinib showed comparable efficacy in patients with moderate to severe UC with prior exposure to anti-TNF therapy.

Cost-effectiveness and cost-utility of optimized mercaptopurine treatment versus placebo in ulcerative colitis patients: The randomized controlled OPTIC trial.

We assessed the cost-effectiveness and cost-utility of therapeutic drug monitoring (TDM)-guided mercaptopurine treatment compared with placebo in ulcerative colitis (UC) patients failing 5-aminosalicylates. Data were gathered alongside the randomized controlled OPTIC trial (EudraCT: 2015-005260-41). The evaluation was performed from a health care and societal perspective as cost-effectiveness and cost-utility analyses with a time horizon of one year. Volumes and costs of in-hospital care, out-of-hospital care, out-of-pocket expenses and productivity loss were assessed. The main outcomes were the extra costs per additional patient who achieved clinical remission and endoscopic improvement at 52weeks (responders) and extra costs per quality-adjusted life-year (QALY) gained. In total, 59 patients were randomized to the intervention (n=29) and control (n=30) group. Non-significant differences in costs were €63 (-€1267 to €1434; P=0.93) in favour of placebo from a health care perspective and -€742 (-€3683 to €2016; P=0.64) in favour of mercaptopurine from a societal perspective. The higher proportion of responders and a non-significant QALY difference of 0.0475 (-0.024-0.117) (P=0.184) favouring patients on mercaptopurine treatment resulted in €165 extra costs per additional responder and €1326 extra costs per QALY gained from a health care perspective. From a societal perspective, dominance over placebo was observed with cost savings of €1937 per additional responder and €15,621 per QALY gained. The probability of optimised mercaptopurine treatment being cost-effective was 0.80 at a willingness to pay per additional QALY of €20,000. TDM-based mercaptopurine treatment in UC patients failing 5-aminosalicylates is a cost-effective strategy from a societal perspective.

A Rare Cause of Severe Lower Gastrointestinal Bleeding in Ulcerative Colitis Patients in Remission: Giant Pseudopolyps

A Rare Cause of Severe Lower Gastrointestinal Bleeding in Ulcerative Colitis Patients in Remission: Giant Pseudopolyps

Prognostic Value of CRP/25 OH Vitamin D Ratio for Glucocorticoid Efficacy in Acute Severe Ulcerative Colitis Patients.

Introduction: Acute severe ulcerative colitis (ASUC) represents a life-threatening medical emergency. One-third of ASUC patients are steroid non-responders. Our study aimed to create a new ASUC algorithm to predict corticosteroid response in the early course of the disease. Materials and Methods: A cross-sectional study included 103 patients with ASUC (65 male, 38 female). We calculated the serum CRP to 25-hydroxy 25 OH vitamin D ratio at admission. Logistic regression determined patients' response to glucocorticoids, depending on the CRP/25 OH vitamin D ratio value. Results and Discussion: Significant differences were observed in the CRP/25 OH vitamin D ratio at admission between glucocorticoid responders and non-responders (p = 0.001). A negative correlation was found between glucocorticoid response and CRP/25 OH vitamin D levels (Spearman's rho = -0.338, p < 0.01). Logistic regression revealed a significant association (p = 0.003) with a model chi-square value of 11.131 (p = 0.001). ROC curve analysis showed an AUC of 0.696 (p = 0.001), indicating moderate discriminatory ability. To achieve 91% sensitivity, the CRP/25 OH vitamin D ratio must be less than 3.985 to predict a complete glucocorticoid response. Conclusions: The serum CRP to 25 OH vitamin D ratio on the first day of hospital admission can potentially determine the response to glucocorticoids in patients with ASUC and significantly affect the mortality of these patients.

S1336 Impact of Vitamin D Deficiency in Ulcerative Colitis Patients: A Nationwide Retrospective Cohort Study

S1336 Impact of Vitamin D Deficiency in Ulcerative Colitis Patients: A Nationwide Retrospective Cohort Study

S1281 Evaluating the Safety of JAK Inhibitors in Ulcerative Colitis Patients Undergoing Colectomy: A Propensity Score-Matched Analysis

S1281 Evaluating the Safety of JAK Inhibitors in Ulcerative Colitis Patients Undergoing Colectomy: A Propensity Score-Matched Analysis

Predicting mucosal inflammation in IBD patients using patient-reported symptom scores and a faecal calprotectin home test: protocol for a multicentre prospective validation study

IntroductionCrohn’s disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD) with a relapsing-remitting nature. With adequate non-invasive prediction of mucosal inflammation, endoscopies can be prevented and treatment optimised earlier...

Trefoil Factor 3 in human serum as a predictor of disease activity in Egyptian ulcerative colitis patients and its role in colorectal cancer

Ulcerative colitis (UC), a chronic idiopathic inflammatory disease, is caused by abnormal immune response to intestinal microflora. Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality. The gold standard to establish diagnosis and assess disease activity remains endoscopy and histopathology. Non-invasive biomarkers are required for timely diagnosis of CRC and to assess disease activity as endoscopic assessment is not accepted by most patients. Enhanced trefoil factor 3 (TFF3) expression is seen following gastrointestinal tract injury. In the current study, the significance of serum TFF3 as a potential diagnostic biomarker of disease activity in naїve UC patients, and its diagnostic accuracy in CRC patients were investigated. We collected serum and fecal samples from 20 cases with active UC, 20 CRC patients, and 20 normal controls. TFF3 levels were higher in patients with active UC than in controls (p&lt;0.001). TFF3 cut-off value of 7.9 ng/ml could predict disease activity with sensitivity and specificity of 90% and 100%, respectively. However, the combination of TFF3, C-reactive protein (CRP), and fecal calprotectin (FC) was able to predict disease activity better than each biomarker alone by raising the sensitivity and specificity to 100%. There was no correlation between TFF3, FC, and endoscopic activity in UC assessed by ulcerative colitis endoscopic index of severity (UCEIS). In the CRC patient group, the serum level of TFF3 was significantly higher when compared to controls (p=0.012). TFF3 and the degree of dysplasia were significantly correlated (r=0.496, p=0.026). At a cut-off value of 5.9 ng/ml, serum TFF3 had a diagnostic sensitivity and specificity for CRC of 82% and 90%, respectively. In conclusion, serum TFF3 may be used as a non-invasive biomarker to predict disease activity in UC both alone and in combination with CRP and FC and it could have a potential role in diagnosis of CRC.

Occurrence of Entamoeba Histolytica infection in patients with Ulcerative colitis attending to the Al-Diwaniyah gastroenterology center/ Iraq

One Hundred Eighteen (118) Stool testers were composed from ulcerative colitis patients distress from intestinal sicknesses, abdominal discomfort, and cases of diarrhea which presence to gastroenterology center in Al-Diwaniyah Teaching Hospital and outpatient clinics from different age groups. for the period from August 2023 - March 2024. The samples were examined with a light microscope using The direct wet smear method from Human stool samples. Microscopic study revealed a important variance at (P ≤ 0.05) among ulcerative colitis patients and infection with E. histolytica was 81.35% (96 positive samples from 118). The results of showed that non-significant alterations at (p ≤ 0.05) between infection with the E. histolytica and age groups, Gender and Residency.

Effectiveness and safety of upadacitinib in acute severe ulcerative colitis patients from single Chinese IBD Center: a monocentric study

Upadacitinib is an oral new selective JAK1 inhibitor that has been approved for treating adult patients with moderately to severely active ulcerative colitis. However, a growing number of studies are needed on the effectiveness of upadacitinib in the treatment of acute severe ulcerative colitis. This study was mainly aimed to describe the clinical and endoscopic effectiveness of upadacitinib 45 mg in Chinese acute severe ulcerative colitis patients following eight weeks of treatment. In this study, we examined all patients with acute severe ulcerative colitis from Xijing IBD Center, Xi’an, China, with acute severe ulcerative colitis. All patients were initially given oral upadacitinib 45 mg. Clinical indicators, C-reactive protein, and erythrocyte sedimentation rates were collected. Clinical response and clinical remission were assessed using modified Mayo. Endoscopic evaluation was performed carried out using the Mayo Endoscopic Score and Ulcerative colitis endoscopic index of severity score. A total of 14 patients who received upadacitinib were included in the study period. All patients exhibited a clinical response to 45 mg upadacitinib initially. All patients completed the 8-week induction. The clinical remission rate was 28.6% after eight weeks. Two patients revealed endoscopic remission at 14.3%. The pathology improved in 50.0% of patients. The 8-week surgical resection rate was 7.1%, with the 16-week surgical resection rate being 14.3%. Adverse events included herpes simplex virus infection and increased thrombin time. The results of our study support the short-term effectiveness and safety of upadacitinib in acute severe ulcerative colitis, providing new choices for patients’ treatment. However, more extended investigation needs to be performed on the long-term effectiveness and safety.