Iron therapy supplementation in inflammatory bowel disease patients with iron deficiency anemia: findings from a real-world analysis in Italy.

BACKGROUND: This real-world analysis evaluated iron therapy supplementation in inflammatory bowel disease patients with iron-deficiency anemia, considering disease progression and healthcare resource consumption. METHODS: A retrospective observational study was conducted using administrative databases of a pool of Italian healthcare entities, covering about 9.3 million beneficiaries. Between January 2010 and September 2017, adult patients were enrolled in the presence of either hospitalization or active exemption code for ulcerative colitis/Crohn's disease, or one vedolizumab prescription. Iron-deficiency anemia was identified by at least one prescription for iron and/or hospitalization for iron-deficiency anemia and/or blood transfusion (proxy of diagnosis). Patients were divided in untreated and iron-treated during 12-month follow-up and analyzed before and after propensity score matching. Disease progression, was evaluated through inflammatory bowel disease-related hospitalizations and surgeries, and healthcare resource utilization was assessed. RESULTS: Overall, 1753 patients were included, 1077 (61.4%) treated with iron therapy and 676 (38.6%) untreated. After propensity score matching, 655 patients were included in each group. In unbalanced cohorts, disease progression was significantly reduced in patients receiving iron therapy compared to the untreated (11.0% vs. 15.7%, P  < 0.01), and this trend was maintained also after applying propensity score matching. The overall mean cost/patient was significantly lower in iron-treated than untreated (4643€ vs. 6391€, P  < 0.01). CONCLUSION: The findings of this real-world analysis suggest that iron therapy was associated with significant benefits in inflammatory bowel disease patients with iron-deficiency anemia, in terms of both disease progression and healthcare resource utilization.

Dysbiosis and Associated Stool Features Improve Prediction of Response to Biological Therapy in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Dysbiosis of the gut microbiota is considered a key contributor to inflammatory bowel disease (IBD) etiology. Here, we investigated potential associations between microbiota composition and the outcomes to biological therapies. METHODS: The study prospectively recruited 296 patients with active IBD (203 with Crohn's disease, 93 with ulcerative colitis) initiating biological therapy. Quantitative microbiome profiles of pretreatment and posttreatment fecal samples were obtained combining flow cytometry with 16S amplicon sequencing. Therapeutic response was assessed by endoscopy, patient-reported outcomes, and changes in fecal calprotectin. The effect of therapy on microbiome variation was evaluated using constrained ordination methods. Prediction of therapy outcome was performed using logistic regression with 5-fold cross-validation. RESULTS: At baseline, 65.9% of patients carried the dysbiotic Bacteroides2 (Bact2) enterotype, with a significantly higher prevalence among patients with ileal involvement (76.8%). Microbiome variation was associated with the choice of biological therapy rather than with therapeutic outcome. Only anti-tumor necrosis factor-α treatment resulted in a microbiome shift away from Bact2, concomitant with an increase in microbial load and butyrogen abundances and a decrease in potentially opportunistic Veillonella. Remission rates for patients hosting Bact2 at baseline were significantly higher with anti-tumor necrosis factor-α than with vedolizumab (65.1% vs 35.2%). A prediction model, based on anthropometrics and clinical data, stool features (microbial load, moisture, and calprotectin), and Bact2 detection predicted treatment outcome with 73.9% accuracy for specific biological therapies. CONCLUSION: Fecal characterization based on microbial load, moisture content, calprotectin concentration, and enterotyping may aid in the therapeutic choice of biological therapy in IBD.

International clinical practice guideline on the use of traditional Chinese medicine for ulcerative colitis by Board of Specialty Committee of Digestive System Disease of World Federation of Chinese Medicine Societies (2023).

Ulcerative colitis (UC), a chronic and nonspecific inflammatory disease of the intestine, has become a prevalent global health concern. This guideline aims to equip clinicians and caregivers with effective strategies for the treatment and management of adult UC patients using traditional Chinese medicine (TCM). The guideline systematically evaluated contemporary evidence through the Grading of Recommendations Assessment, Development, and Evaluation framework. Additionally, it incorporated insights from ancient Chinese medical sources, employing the evidence grading method found in traditional TCM literature. The development process involved collaboration with multidisciplinary experts and included input from patients with UC. The guideline, based on a comprehensive review of available evidence, present 40 recommendations. They offer a condensed overview of TCM's role in understanding the pathogenesis, diagnosis, and treatment of UC, along with an assessment of the efficacy of various TCM-based treatments. TCM exhibits promising outcomes in the treatment of UC. However, to establish its efficacy conclusively, further high-quality clinical studies on TCM for UC are essential.

The IBD-FITT study - moderate-intensity exercise for patients with inflammatory bowel disease with moderate disease activity: an open-label randomized controlled trial.

BACKGROUND: Inflammatory bowel disease (IBD), Crohn's disease, and ulcerative colitis are chronic autoimmune lifelong diseases with fluctuating activity over time. The treatment includes medical therapy and surgery, however, there is no definite cure. Therefore, the quest for new and supplementary treatment options is imperative to improve patients' general health and quality of life. Physical activity and exercise have been suggested to be elements in both the prevention and supplementary treatment of IBD; however, this is based on limited underpowered trials. Thus, the role of exercise as a treatment option still has to be settled. We aim to investigate the effect of a 12-week exercise intervention in adult patients with moderately active IBD on three categories of outcomes (1) disease-specific health-related quality of life (IBDQ); (2) general health status of the patients, i.e., waist circumference, disease activity by clinical scorings systems (Harvey Bradshaw Index, Simple Clinical Colitis Activity Index), blood pressure, blood lipids, and non-disease specific quality of life (EQ5D) scores; and (3) explorative outcomes on biomarkers (C-reactive protein and fecal calprotectin) plus different biomarkers of immunology (cytokine panel). METHODS: We will apply a superiority design in this open-label randomized clinical trial including 150 patients equally allocated to intervention and usual care. The intervention will be based on a 12-week aerobic exercise program and will include two supervised exercise sessions of 60 min per week, combined with one weekly home training session. We have defined a moderate exercise level as 60-80% of patients' maximum heart rate. The patients in the intervention group will also be offered an online video lesson of 15-25 min on lifestyle guidance, and the same online video lesson will be offered in the comparator group. Questionnaires on quality of life will be forwarded electronically both at inclusion and at the end of the study, and the patients will have blood samples, and fecal samples for calprotectin at baseline, weeks 4 and 8, as well as after 12 weeks (study end). DISCUSSION: This will be a clinical trial investigating the effect of exercise on patients with Crohn's disease and ulcerative colitis. This trial will add to the evidence on the possible effect of exercise and might clarify whether exercise can benefit as a supplementary treatment addendum. Thus, the trial may provide a new patient-active disease management approach. TRIAL REGISTRATION: ClinicalTrials.gov NCT04816812. Date of first registration: March 23, 2021.

Higher Intra-Abdominal Visceral Adipose Tissue Mass Is Associated With Lower Rates of Clinical and Endoscopic Remission in Patients With Inflammatory Bowel Diseases Initiating Biologic Therapy: Results of the Constellation Study.

BACKGROUND & AIMS: We sought to assess the association between intra-abdominal visceral adipose tissue (IA-VAT) and response to 3 different biologic drugs in patients with inflammatory bowel disease (IBD) and to investigate its effects on inflammatory cytokine expression, pharmacokinetics, and intestinal microbiota. METHODS: We prospectively enrolled subjects with active IBD initiating infliximab, vedolizumab, or ustekinumab and a healthy control group. Baseline body composition (including IA-VAT as percent of total body mass [IA-VAT%]) was measured using GE iDXA scan. Primary outcome was corticosteroid- free deep remission at weeks 14-16, defined as Harvey Bradshaw Index <5 for Crohn's disease and partial Mayo score <2 for ulcerative colitis, with a normal C-reactive protein and fecal calprotectin. Secondary outcomes were corticosteroid-free deep remission and endoscopic remission (Endoscopic Mayo Score ≤1 in ulcerative colitis or Simple Endoscopic Score for Crohn's disease ≤2) at weeks 30-46. RESULTS: A total of 141 patients with IBD and 51 healthy controls were included. No differences in body composition parameters were seen between the IBD and healthy control cohorts. Patients with higher IA-VAT% were less likely to achieve corticosteroid-free deep remission (P < .001) or endoscopic remission (P = .02) vs those with lower IA-VAT%. Furthermore, nonresponders with high IA-VAT% had significantly higher serum interleukin-6 and tumor necrosis factor at baseline compared with responders and patients with low IA-VAT%. Drug pharmacokinetic properties and microbiota diversity were similar when comparing high and low IA-VAT% groups. CONCLUSIONS: Higher IA-VAT% was independently associated with worse outcomes. This association could be driven at least partially by discrete differences in inflammatory cytokine expression.

Unmet Needs in Real-World Advanced Therapy-Naïve and -Experienced Patients with Moderately to Severely Active Ulcerative Colitis in the United States.

INTRODUCTION: Despite availability of advanced therapies (ATs) for ulcerative colitis (UC), many patients fail to respond to treatment. This study examined real-world clinical and humanistic outcomes associated with current treatments in patients with UC. METHODS: This cross-sectional study used US data from the Adelphi Real World Disease Specific Programme for inflammatory bowel disease from before (2017-2018) and during the COVID-19 pandemic (2020-2021). Physicians (gastroenterologists) seeing > 5 patients/month reported patients' disease characteristics, current symptoms and treatments, and reasons for treatment choices for their next seven consecutive patients aged ≥ 18 years with moderately to severely active UC before current treatment. Patients were asked to complete the EQ-5D-5L health-related quality of life (HRQoL) measure. ATs included tumor necrosis factor inhibitors (TNFis), integrin receptor antagonists, interleukin-12/23 antagonists, and Janus kinase inhibitors. Patients were classified as AT-naïve or AT-experienced based on current treatment received for ≥ 8 weeks and further classified as responders or non-responders based on symptoms, disease flare status, and remission. Descriptive analyses are presented. RESULTS: The 2017-2018 cohort included 92 physicians and 539 patients (208 [38.6%] AT-experienced). The 2020-2021 cohort included 73 physicians and 448 patients (349 [77.9%] AT-experienced). TNFis were the most common ATs. In 2017-2018, 195 (58.9%) AT-naïve and 113 (54.3%) AT-experienced patients were non-responders; in 2020-2021 this was 57 (57.6%) and 182 (52.1%). Efficacy and induction of remission were physicians' most common reasons for AT choice. Dislike of injections/infusions was the most common reason for eligible patients not receiving biologic therapy. Numerically, non-responders (both AT-naïve and AT-experienced) had more symptoms, overall pain and fatigue, and lower HRQoL scores than responders. CONCLUSIONS: Before (2017-2018) and during the pandemic (2020-2021), over half of patients with UC did not respond to AT. Non-responders carried a high burden of disease. Alternative therapies are urgently needed to treat UC.

Impact of biologic therapies and small molecules on the risk of major adverse cardiovascular events in patients with inflammatory bowel diseases: systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: The aim of this study is to estimate the risk of major adverse cardiovascular events (MACEs) in adult patients with inflammatory bowel disease (IBD) treated with biologic therapies and small molecules. METHODS: Databases were searched up to July 2022 to identify eligible studies that assessed the risk of MACEs in patients (age≥18 years) with IBD treated with biologic therapies and small molecules. Primary outcome was the rate of MACEs observed in patients receiving biologic or small molecules therapies during induction and maintenance phases of RCTs. RESULTS: In total 64 studies were included in the analysis. 22 RCTs involving 12,196 patients with Crohn's disease (CD) were included and 32 RCTs involving 22,007 patients with ulcerative colitis (UC). In patients with CD, risk of MACE was not higher than placebo during induction or maintenance phases, infliximab (OR 0.63, 95% CI 0.07-6.14) and ustekinumab (OR 0.50, 95% CI 0.03-8.04). In patients with UC, risk of MACE was not higher than placebo, tofacitinib (OR 1.30, 95% CI 0.15-11.21) and upadcitinib (OR 0.50, 95% CI 0.03-7.97) during induction or maintenance. CONCLUSION: The use of biologic therapies and small molecules among adult patients with IBD had no significant impact on the risk of MACEs during induction and maintenance period of RCTs. Real world data is warranted to assess long-term risks.

Biologic and new small molecule therapies have been shown to be effective in treating patients with moderate to severe inflammatory bowel disease (IBD), both Crohn's disease and ulcerative colitis. The risk of major adverse cardiovascular events (MACE), such as heart attack or heart failure, due to taking these medications in patients with IBD is not well established. The aim of this systematic review and meta-analysis is to estimate the risk of MACE in patients with IBD on biologic or small molecule therapies during induction and maintenance phases of randomized controlled trials. [Figure: see text].

Efficacy of 1-kestose supplementation in patients with mild to moderate ulcerative colitis: A randomised, double-blind, placebo-controlled pilot study.

BACKGROUND: Ulcerative colitis involves an excessive immune response to intestinal bacteria. Whether administering prebiotic 1-kestose is effective for active ulcerative colitis remains controversial. AIMS: This randomised, double-blind, placebo-controlled pilot trial investigated the efficacy of 1-kestose against active ulcerative colitis. METHODS: Forty patients with mild to moderate active ulcerative colitis were randomly treated with 1-kestose (N = 20) or placebo (maltose, N = 20) orally for 8 weeks in addition to the standard treatment. The Lichtiger clinical activity index and Ulcerative Colitis Endoscopic Index of Severity were determined. Faecal samples were analysed to evaluate the gut microbiome and metabolites. RESULTS: The clinical activity index at week 8 was significantly lower in the 1-kestose group than in the placebo group (3.8 ± 2.7 vs. 5.6 ± 2.1, p = 0.026). Clinical remission and response rates were higher in the 1-kestose group than in the placebo group (remission: 55% vs. 20%, p = 0.048; response: 60% vs. 25%, p = 0.054). The Ulcerative Colitis Endoscopic Index of Severity at week 8 was not significantly different (2.8 ± 1.6 vs. 3.5 ± 1.6, p = 0.145). Faecal analysis showed significantly reduced alpha-diversity in the 1-kestose group, with a decreased relative abundance of several bacteria, including Ruminococcus gnavus group. The short-chain fatty acid levels were not significantly different between the groups. The incidence of adverse events was comparable between the groups. DISCUSSION: Oral 1-kestose is well tolerated and provides clinical improvement for patients with mild to moderate ulcerative colitis through modulation of the gut microbiome.

Amino acids-targeted metabolomics reveals novel diagnostic biomarkers for ulcerative colitis and Crohn's disease.

Inflammatory bowel disease (IBD), which mainly comprises ulcerative colitis (UC) and Crohn's disease (CD), is a common chronic intestinal inflammatory disease that affects the ileum, rectum, and colon. Currently, the diagnosis of IBD is based on clinical history, physical examination and complementary diagnostic tests. It is challenging for physicians to make a definitive diagnosis. This study aimed to analyze the variation in amino acid metabolites in IBD serum and to identify potential predictive biomarkers of IBD diagnosis and progression. Serum samples were collected from 158 UC patients, 130 CD patients and 138 healthy controls (HCs). The 37 amino acids in serum were determined by ultra-high-pressure liquid chromatography coupled to a mass spectrometer. A panel of three-amino-acid metabolites (taurine, homocitrulline and kynurenine) was identified as a specific biomarker panel of IBD. Receiver operating characteristic analysis (ROC) showed that the panel had a sensitivity of 88.4% with a specificity of 84.6% for discriminating CD patients from UC patients. The biomarkers identified are increased in CD compared to UC. Our approach demonstrated a strong relationship between serum amino acid levels and IBD. We successfully identified serum amino acid biomarkers associated with CD and UC. The biomarker panel has potential in clinical practice for IBD diagnosis and will provide new insights into IBD pathogenesis.

Leaks From the Tip of the J-pouch: Diagnosis, Management, and Long-term Pouch Survival.

BACKGROUND: The standard of care for surgical treatment of ulcerative colitis is restorative proctocolectomy with ileal J-pouch. Leaks from the tip of the J-pouch are a known complication, but there is a paucity of literature regarding this type of leak. OBJECTIVE: We aimed to describe the diagnosis, management, and long-term clinical outcomes of leaks from the tip of the J-pouch at our institution. DESIGN: This was a retrospective study of a prospectively maintained pouch registry. SETTING: This study was conducted at a quaternary IBD referral center. PATIENTS: Patients included those with ileal J-pouches diagnosed with leaks from the tip of the J-pouch. MAIN OUTCOME MEASURES: The main measures of outcomes were pouch salvage rate, type of salvage procedures, and long-term Kaplan-Meier pouch survival. RESULTS: We identified 74 patients with leaks from the tip of the J-pouch. Pain (68.9%) and pelvic abscess (40.9%) were the most common presentations, whereas 10.8% of patients presented with an acute abdomen. The leak was diagnosed by imaging and/or endoscopy in 74.3% of patients but only discovered during surgical exploration in 25.6% of patients. Some 63.5% of patients were diagnosed only after loop ileostomy closure, whereas 32.4% of patients were diagnosed before ileostomy closure. The most common methods used for diagnosis were pouchoscopy (31.1%) and gastrograffin enema (28.4%). A definitive nonoperative approach was attempted in 48.6% of patients but was successful in only 10.8% of patients overall. Surgical repair was attempted in 89.2% of patients, whereas 4.5% of patients had pouch excision. Salvage operations (n = 63) included sutured or stapled repair of the tip of the J (65%), pouch excision with neo-pouch (25.4%), and pouch disconnection, repair, and reanastomosis (9.5%). Ultimately' 10 patients (13.5%) required pouch excision, yielding an overall 5-year pouch survival rate of 86.3%. LIMITATIONS: This was a retrospective review; referral bias may limit the generalizability. CONCLUSIONS: Leaks from the tip of the J-pouch have variable clinical presentations and require a high index of suspicion. Pouch salvage surgery is required in the majority of patients and is associated with a high pouch salvage rate. See Video Abstract at http://links.lww.com/DCR/C50 . FUGAS DEL EXTREMO DE LA BOLSA EN J DIAGNSTICO, MANEJO Y SUPERVIVENCIA A LARGO PLAZO DE LA BOLSA: ANTECEDENTES:El estándar de atención para el tratamiento quirúrgico de la colitis ulcerosa es la proctocolectomía restauradora con bolsa ileal en J. Las fugas del extremo de la bolsa en J son una complicación conocida, pero hay escasez de literatura sobre este tipo de fuga.OBJETIVO:Describir el diagnóstico, manejo y resultados clínicos a largo plazo de las fugas del extremo de la bolsa en J en nuestra institución.DISEÑO:Estudio retrospectivo de registro de bolsa mantenido prospectivamente.ENTORNO CLINICO:Centro de referencia de enfermedad inflamatoria intestinal cuaternaria.PACIENTES:Pacientes con bolsas ileales en J diagnosticadas con fugas del extremo de la J.PRINCIPALES MEDIDAS DE VALORACIÓN:Tasa de rescate de la bolsa, tipo de procedimientos de rescate y supervivencia a largo plazo de la bolsa Kaplan-Meier.RESULTADOS:Identificamos 74 pacientes con fugas del extremo de la bolsa en J. El dolor (68,9%) y el absceso pélvico (40,9%) fueron las presentaciones más comunes, mientras que el 10,8% de los pacientes presentaron abdomen agudo. La fuga se diagnosticó por imagen y/o endoscopia en el 74,3%, pero solo se descubrió durante la exploración quirúrgica en el 25,6%. El 63,5% fueron diagnosticados solo después del cierre de la ileostomía en asa, mientras que el 32,4% lo fueron antes del cierre de la ileostomía. Los métodos más comunes utilizados para el diagnóstico fueron la endoscopia (31,1%) y el enema de gastrografín (28,4%). Se intentó un abordaje no quirúrgico definitivo en el 48,6%, pero tuvo éxito en solo el 10,8% de los pacientes en general. Se intentó la reparación quirúrgica en el 89,2% de los pacientes, mientras que en el 4,5% se realizó la escisión del reservorio. Las operaciones de rescate (n = 63) incluyeron la reparación con sutura o grapas del extremo de la J (65%), la escisión del reservorio con neo-reservorio (25,4%) y la desconexión, reparación y reanastomosis del reservorio (9,5%). Finalmente, 10 (13,5%) pacientes requirieron la escisión de la bolsa, lo que se asocio con una alta tasa de supervivencia general de la bolsa a los 5 años del 86,3%.LIMITACIONES:Revisión retrospectiva; el sesgo de referencia puede limitar la generalización.CONCLUSIONES:Las fugas del extremo de la bolsa en J tienen presentaciones clínicas variables y requieren un alto índice de sospecha. La cirugía de rescate de la bolsa se requiere en la mayoría y se asocia con una alta tasa de rescate de la bolsa. Consulte Video Resumen en http://links.lww.com/DCR/C50 . (Traducción- Dr. Ingrid Melo ).

Sodium Butyrate Effectiveness in Children and Adolescents with Newly Diagnosed Inflammatory Bowel Diseases-Randomized Placebo-Controlled Multicenter Trial.

BACKGROUND: Butyric acid's effectiveness has not yet been assessed in the pediatric inflammatory bowel disease (IBD) population. This study aimed to evaluate the effectiveness of oral sodium butyrate as an add-on to standard therapy in children and adolescents with newly diagnosed IBD. METHODS: This was a prospective, randomized, placebo-controlled multicenter study. Patients aged 6-18 years with colonic Crohn's disease or ulcerative colitis, who received standard therapy depending on the disease's severity, were randomized to receive 150 mg sodium butyrate twice a day (group A) or placebo (group B). The primary outcome was the difference in disease activity and fecal calprotectin concentration between the two study groups measured at 12 weeks of the study. RESULTS: In total, 72 patients with initially active disease completed the study, 29 patients in group A and 43 in group B. At week 12 of the study, the majority of patients achieved remission. No difference in remission rate or median disease activity was found between the two groups (p = 0.37 and 0.31, respectively). None of the patients reported adverse events. CONCLUSIONS: A 12-week supplementation with sodium butyrate, as adjunctive therapy, did not show efficacy in newly diagnosed children and adolescents with IBD.

Endoscopic Disease Activity and Biologic Therapy Are Independent Predictors of Suboptimal Bowel Preparation in Patients with Inflammatory Bowel Disease Undergoing Colonoscopy.

BACKGROUND AND AIMS: Optimal bowel preparation (BP) is critical for endoscopic assessment of inflammation and dysplasia in patients with inflammatory bowel disease (IBD). Comorbidities and patient-related factors have been associated with suboptimal BP (SOBP) in the general population. We sought to identify disease-specific characteristics that may impact the quality of BP in patients with IBD. METHODS: We conducted a retrospective analysis of adult IBD patients who underwent outpatient colonoscopies between January 2014 and September 2020 at a large academic medical center. Quality of BP was documented using the Boston Bowel Preparation Scale (BBPS) or the Aronchick scale and dichotomized into "suboptimal" (BBPS 0-5 or Aronchick "fair," "poor," unsatisfactory") and "optimal" (BBPS 6-9 or Aronchick "excellent," "good"). IBD-specific and other factors associated with SOBP were evaluated using logistic regression analyses. RESULTS: Among a total of 395 IBD patients [54% males, mean age 40 years, 63% with Crohn's disease (CD), 35% with ulcerative colitis (UC)], 24.8% had SOBP. On multivariable analysis, moderate-to-severe endoscopic disease vs mild or inactive disease was associated with a higher odds of SOBP [adjusted OR 2.7(95% CI 1.52-4.94)], whereas baseline biologic use was associated with a lower odds of SOBP [aOR 0.24(0.09-0.65)] among the overall IBD cohort. Additionally, age > 65 years [aOR 2.99(1.19-7.54)] and single-dose vs split-dose BP [aOR 2.37(1.43-3.95)] were predictors of SOBP. In the subgroup analysis by IBD type, moderate-to-severe endoscopic disease predicted SOBP among both CD and UC cohorts. CONCLUSION: Endoscopic disease activity was predictive of SOBP, and biologic therapy was protective against SOBP among IBD patients.

Ulcerative Colitis: Rapid Evidence Review.

Ulcerative colitis is a relapsing and remitting inflammatory bowel disease of the large intestine. Risk factors include recent Salmonella or Campylobacter infection and a family history of ulcerative colitis. Diagnosis is suspected based on symptoms of urgency, tenesmus, and hematochezia and is confirmed with endoscopic findings of continuous inflammation from the rectum to more proximal colon, depending on the extent of disease. Fecal calprotectin may be used to assess disease activity and relapse. Medications available to treat the inflammation include 5-aminosalicylic acid, corticosteroids, tumor necrosis factor-alpha antibodies, anti-integrin antibodies, anti-interleukin-12 and -23 antibodies, and Janus kinase inhibitors. Choice of medication and method of delivery depend on the location and severity of mucosal inflammation. Other treatments such as fecal microbiota transplantation are considered experimental, and complementary therapies such as probiotics and curcumin have mixed data. Surgical treatment may be needed for fulminant or refractory disease. Increased risk of colorectal cancer and use of immunosuppressive therapies affect the preventive care needs for these patients.

Role of vitamin D in ulcerative colitis: an update on basic research and therapeutic applications.

INTRODUCTION: Vitamin D deficiency is common in patients with ulcerative colitis (UC). Moreover, vitamin D supplementation seems to contribute to disease relief. Nevertheless, the exact etiological link between vitamin D deficiency and UC is far from clear, and an agreement has not been reached on the frequency and dosage of vitamin D supplementation required. AREAS COVERED: This review will outline the possible role of vitamin D in the pathogenesis of UC and summarize the current state of clinical research on vitamin D. Literature was searched on PUBMED, with 'Vitamin D,' 'Ulcerative colitis,' 'Vitamin D receptor,' and 'disease activity' as MeSH Terms. Relevant information is presented in figures or tables. EXPERT OPINION: The etiological relationship between vitamin D and the onset of UC is still being researched. More high-quality double-blind randomized clinical studies are needed to determine the efficacy of vitamin D supplementation in the treatment of UC, whether as the main treatment or as an adjuvant treatment. Importantly, determining the dosage and frequency of vitamin D supplementation should be the main research direction in the future, and regional factors should also be fully considered in this respect.

Influence of Corticosteroid Use on Short- and Long-Term Outcomes of Biologic Therapy for Inflammatory Bowel Diseases.

BACKGROUND: Corticosteroids (CS) are widely used to treat Crohn's disease (CD) and ulcerative colitis (UC), but are not recommended as maintenance therapy. Biologic drugs are widely used as an alternative to or in conjunction with CS to induce and maintain remission. This meta-analysis tested the hypothesis that CS use is associated with differential response to biologics. METHODS: We identified published placebo-controlled clinical trials of biologic drugs approved for the treatment of CD or UC. Pooled estimates of the risk difference (RD) and 95% confidence intervals were derived from random effects models for induction of response and remission and maintenance of remission comparing biologic with CS versus biologic alone. Heterogeneity of response was estimated using I2. RESULTS: Fifteen studies met the inclusion criteria. Pooled estimates of the RD and I2 comparing biologic plus CS versus biologic alone were as follows: induction of UC response 0.15 (0.05, 0.25), I2 = 57.29% and CD response 0.02 (- 0.03, 0.06), I2 = 0.01%; induction of UC remission 0.03 (- 0.01, 0.08), I2 = 0.00% and CD remission 0.08(0.02, 0.14), I2 = 7.81%; and maintenance of UC remission - 0.06 (- 0.13, 0.01), I2 = 0.00% and CD remission - 0.06 (- 0.14, 0.03), I2 = 11.24%. Patients in the placebo arm of CD trials who were receiving CS were less likely to achieve remission during the induction phase (pooled RD - 0.05 (- 0.09, - 0.00), I2 = 0.00%). CONCLUSIONS: In this meta-analysis of placebo-controlled trials, CS use was associated with higher biologic response rates for UC and remission rates for CD during the induction phase, but were not associated with improved maintenance of remission.

Paracentral acute middle maculopathy (PAMM) associated with ulcerative colitis and coexisting hyperhomocysteinemia: A case report.

INTRODUCTION: Paracentral acute middle maculopathy (PAMM) is a tomographic finding of a retinal occlusive vascular disorders with different aetiologies. Despite the well documented triple association among hyper-homocysteine, retinal vein occlusion and PAMM, up to date no reports exist on the development of PAMM in young patients affected by ulcerative colitis (UC). CASE DESCRIPTION: A multimodal imaging study, including fundus photographs, optical coherence tomography (OCT) B-scans, OCT angiography (OCT-A) and fluorescein and indocyanine green angiography, was performed in a 32-years-old male complaining of acute-onset paracentral scotoma in the right eye. Fundus images demonstrated the typical dark gray area of retinal capillary ischemia, corresponding on OCT B-scans to the hyper-reflective plaques in the INL, and consistent with PAMM lesions.The deep capillary plexus (DCP) was normal on OCT-A. Fluorescein angiography revealed a concurrent branch retinal vein preocclusion and showed capillary drop out parafoveally. Patient's anamnesis was negative except for a 15-years history of UC and use of acetylsalicylic acid (ASS). At the time of presentation, UC was quiescent, but new blood tests revealed concomitant high values of homocysteinemia requiring oral vitamin B12 and folate supplementation. Two months later PAMM lesions had disappeared on OCT B-scans and a retinal thinning at the level of the inner nuclear layer (INL) was visible. The DCP on OCT-A remained unchanged without any sign of capillary ischemia. CONCLUSIONS: Although no definitive evidence directly links UC with PAMM, the latter should be suspected in young patients affected by IBD with coexisting hyper-homocysteinemia and unexplained visual symptoms.

Is there higher percentage of undetected osteopenia and osteoporosis among patients with ulcerative colitis in Saudi Arabia?

Detection of prevalence and development of osteopenia or osteoporosis in patients with inflammatory bowel disease using only bone mineral density could be inappropriate to detect all individuals at risk for osteoporosis. Numerous patients could remain undetected by using only bone mineral density as a screening method, especially in patients with ulcerative colitis. Therefore, trabecular bone score should be used as a complementary method.

An Immunologic Compatibility Testing Was Not Useful for Donor Selection in Fecal Microbiota Transplantation for Ulcerative Colitis.

Fecal microbiota transplantation (FMT) is an effective procedure against Clostridioides difficile infection (CDI), with promising but still suboptimal performance in other diseases, such as ulcerative colitis (UC). The recipient's mucosal immune response against the donor's microbiota could be relevant factor in the effectiveness of FMT. Our aim was to design and validate an individualized immune-based test to optimize the fecal donor selection for FMT. First, we performed an in vitro validation of the test by co-culturing lymphocytes obtained from the small intestine mucosa of organ donor cadavers (n=7) and microbe-associated molecular patterns (MAMPs) obtained from the feces of 19 healthy donors. The inflammatory response was determined by interleukin supernatant quantification using the Cytometric Bead Array kit (B&D). We then conducted a clinical pilot study with 4 patients with UC using immunocompetent cells extracted from rectal biopsies and MAMPs from 3 donor candidates. We employed the test results to guide donor selection for FMT, which was performed by colonoscopy followed by 4 booster instillations by enema in the following month. The microbiome engraftment was assessed by 16S rDNA massive sequencing in feces, and the patients were clinically followed-up for 16 weeks. The results demonstrated that IL-6, IL-8, and IL-1ß were the most variable markers, although we observed a general tolerance to the microbial insults. Clinical and colonoscopy remission of the patients with UC was not achieved after 16 weeks, although FMT provoked enrichment of the Bacteroidota phylum and Prevotella genus, with a decrease in the Actinobacteriota phylum and Agathobacter genus. The most relevant result was the lack of Akkermansia engraftment in UC. In summary, the clinical success of FMT in patients with UC appears not to be influenced by donor selection based on the explored recipient's local immunological response to FMT, suggesting that this approach would not be valid for FMT fecal donor optimization in such patients.

Hyperbaric oxygen therapy in inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: Translational data suggest a potential role of hyperbaric oxygen therapy (HBOT) in a subset of patients with inflammatory bowel disease (IBD). We performed a systematic review and meta-analysis for the efficacy and safety of HBOT in IBD. METHODS: We searched Pubmed, Embase and CENTRAL to identify studies reporting the efficacy of HBOT in ulcerative colitis or Crohn's disease. We pooled the response rates for HBOT in ulcerative colitis and Crohn's disease separately. RESULTS: A total 18 studies were included in the systematic review and 16 in the analysis. The overall response rate of HBOT in ulcerative colitis was 83.24% (95% confidence interval: 61.90-93.82), while the response in Crohn's disease was 81.89 (76.72-86.11). The results of randomized trials for HBOT as adjuvant therapy in ulcerative colitis were conflicting. The complete healing of fistula in fistulizing Crohn's disease was noted 47.64% (22.05-74.54), while partial healing was noted in 34.29% (17.33-56.50%). Most of the adverse events were minor. CONCLUSION: Observational studies suggest benefit of use of HBOT in ulcerative colitis flares and Crohn's disease. However, adequately powered randomized trials are needed to draw a definite conclusion.

Use of granulocyte/monocytapheresis in ulcerative colitis: A practical review from a European perspective.

Half of the patients with ulcerative colitis require at least one course of systemic corticosteroids in their lifetime. Approximately 75% of these patients will also require immunosuppressive drugs (i.e., thiopurines or biological agents) in the mid-term to avoid colectomy. Immunosuppressive drugs raise some concerns due to an increased risk of serious and opportunistic infections and cancer, particularly in elderly and co-morbid patients, underlining the unmet need for safer alternative therapies. Granulocyte/monocytapheresis (GMA), a CE-marked, non-pharmacological procedure for the treatment of ulcerative colitis (among other immune-mediated diseases), remains the only therapy targeting neutrophils, the hallmark of pathology in ulcerative colitis. GMA has proven its efficacy in different clinical scenarios and shows an excellent and unique safety profile. In spite of being a first line therapy in Japan, GMA use is still limited to a small number of centres and countries in Europe. In this article, we aim to give an overview from a European perspective of the mechanism of action, recent clinical data on efficacy and practical aspects for the use of GMA in ulcerative colitis.