Prebiotics for Induction and Maintenance of Remission in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis.

BACKGROUND: Prebiotics are nondigestible carbohydrates fermented by gut bacteria into metabolites that confer health benefits. However, evidence on their role for inflammatory bowel disease (IBD) is unclear. This study systematically evaluated the research on prebiotics for treatment of IBD. METHODS: A search was performed in PubMed, Embase, Cochrane, and Web of Science. Eligible articles included randomized controlled trials or prospective observational studies that compared a prebiotic with a placebo or lower-dose control in patients with IBD. Meta-analyses were performed using random-effects models for the outcomes of clinical remission, clinical relapse, and adverse events. RESULTS: Seventeen studies were included. For induction of clinical remission in ulcerative colitis (UC), the fructooligosaccharide (FOS) kestose was effective (relative risk, 2.75, 95% confidence interval, 1.05-7.20; n = 40), but oligofructose-enriched inulin (OF-IN) and lactulose were not. For maintenance of remission in UC, germinated barley foodstuff trended toward preventing clinical relapse (relative risk, 0.40; 95% confidence interval, 0.15-1.03; n = 59), but OF-IN, oat bran, and Plantago ovata did not. For Crohn's disease, OF-IN and lactulose were no different than controls for induction of remission, and FOS was no different than controls for maintenance of remission. Flatulence and bloating were more common with OF-IN; reported adverse events were otherwise similar to controls for other prebiotics. CONCLUSION: Prebiotics, particularly FOS and germinated barley foodstuff, show potential as effective and safe dietary supplements for induction and maintenance of remission in UC, respectively. The overall certainty of evidence was very low. There would be benefit in further investigation on the role of prebiotics as treatment adjuncts for IBD.

Prebiotics are nutrients fermented by gut microbes into healthful metabolites. This systematic review and meta-analysis examined the available research on the efficacy and safety of prebiotics for the treatment of inflammatory bowel diseases.

Herbal Medicines for the Treatment of Active Ulcerative Colitis: A Systematic Review and Meta-Analysis.

Herbal medicines are used by patients with IBD despite limited evidence. We present a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating treatment with herbal medicines in active ulcerative colitis (UC). A search query designed by a library informationist was used to identify potential articles for inclusion. Articles were screened and data were extracted by at least two investigators. Outcomes of interest included clinical response, clinical remission, endoscopic response, endoscopic remission, and safety. We identified 28 RCTs for 18 herbs. In pooled analyses, when compared with placebo, clinical response rates were significantly higher for Indigo naturalis (IN) (RR 3.70, 95% CI 1.97-6.95), but not for Curcuma longa (CL) (RR 1.60, 95% CI 0.99-2.58) or Andrographis paniculata (AP) (RR 0.95, 95% CI 0.71-1.26). There was a significantly higher rate of clinical remission for CL (RR 2.58, 95% CI 1.18-5.63), but not for AP (RR 1.31, 95% CI 0.86-2.01). Higher rates of endoscopic response (RR 1.56, 95% CI 1.08-2.26) and remission (RR 19.37, 95% CI 2.71-138.42) were significant for CL. CL has evidence supporting its use as an adjuvant therapy in active UC. Research with larger scale and well-designed RCTs, manufacturing regulations, and education are needed.

Perianal fistulizing Crohn's disease: Current perspectives on diagnosis, monitoring and management with a focus on emerging therapies.

Crohn's disease (CD), a chronic inflammatory bowel disorder, manifests in various phenotypes, with fistulizing perianal CD (CD-PAF) being one of its most severe phenotypes. Characterized by fistula formation and abscesses, CD-PAF impacts 17% to 34% of all CD cases and with a significantly deleterious impact on patient's quality of life, while increasing the risk for anorectal cancers. The pathogenesis involves a complex interplay of genetic, immunological and environmental factors, with cytokines such as tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-ß) playing pivotal roles. Diagnostic protocols require a multi-disciplinary approach including colonoscopy, examination under anesthesia and magnetic resonance imaging. In terms of treatment, biologics alone often prove inadequate, making surgical interventions such as setons and fistula surgeries essential. Emerging therapies such as mesenchymal stem cells are under study. The South Asian context adds layers of complexity, including diagnostic ambiguities related to high tuberculosis prevalence, healthcare access limitations and cultural stigma toward perianal Crohn's disease and ostomy surgery. Effective management necessitates an integrated, multi-disciplinary approach, especially in resource-constrained settings. Despite advances, there remain significant gaps in understanding the disease's pathophysiology and a dearth of standardized outcome measures, underscoring the urgent need for comprehensive research.

Use of Biologics for the Treatment of Inflammatory Conditions of the Pouch: A Systematic Review.

BACKGROUND: Patients with medically-refractory ulcerative colitis or advanced neoplasia are often offered an ileal-pouch-anal anastomosis to restore bowel continuity. However, up to 50% of patients can suffer from inflammatory conditions of the pouch, some of which require biological therapy to treat. The aim of this study was to determine the efficacy of each biological agent for the treatment of inflammatory conditions of the pouch. MATERIALS AND METHODS: A comprehensive literature search was performed in the major databases from inception through February 11, 2020, for studies assessing the efficacy of biologics in chronic antibiotic-refractory pouchitis (CARP) and Crohn's disease (CD) of the pouch. Both prospective and retrospective studies were included. The primary outcomes of interest were complete and partial responses were defined within each study. χ 2 test was used to compare variables. RESULTS: Thirty-four studies were included in the systematic review and meta-analysis. Sixteen studies (N=247) evaluated the use of infliximab (IFX), showing complete response in 50.7% and partial response in 28.1% for CARP, and complete response in 66.7% and partial response in 20% for CD of the pouch. Seven studies (n=107) assessed the efficacy of adalimumab. For CARP, 33.3% of patients had a complete response, and 38.1% had a partial response, whereas for CD of the pouch, 47.7% experienced a complete response, and 24.6% had a partial response. Three studies (n=78) reported outcomes with the use of ustekinumab, showing 50% complete response and 3.8% partial response for CARP. For the CD of the pouch, 5.8% had a complete response and 78.8% had a partial response. Seven studies (n=151) reported the efficacy of vedolizumab, showing 28.4% complete response and 43.2% partial response in patients with CARP, whereas 63% of patients experienced partial response in CD of the pouch. IFX had higher rates of complete response in CARP compared with adalimumab ( P =0.04) and compared with vedolizumab ( P =0.005), but not compared with ustekinumab ( P =0.95). There were no new safety signals reported in any of the studies. CONCLUSIONS: Biologics are safe and efficacious in the treatment of chronic, refractory inflammatory conditions of the pouch. IFX seems to be more efficacious than adalimumab and vedolizumab for CARP. Further prospective, head-to-head evaluations are needed to compare biological therapies in the treatment of CARP and CD of the pouch.

Longitudinal Trends in Pregnancy Outcomes Among Women With Inflammatory Bowel Disease in the Era of Biologics: A 20-Year Nationwide Analysis.

BACKGROUND: Many women with inflammatory bowel disease (IBD) are diagnosed by their reproductive years. Prior literature suggests that women with IBD may be at increased risk of adverse pregnancy outcomes. Biologics have revolutionized IBD treatment, and current evidence favors continuation during pregnancy. We sought to examine trends in pregnancy outcomes over 20 years with the evolution of IBD treatment. METHODS: Using the National Inpatient Sample, IBD and non-IBD obstetric hospitalizations were identified between 1998 and 2018 using International Classification of Diseases 9 and 10 codes. Outcomes of interest included cesarean delivery, gestational diabetes, preeclampsia/eclampsia, premature rupture of membranes (PROM), preterm delivery, fetal growth restriction (FGR), fetal distress, and stillbirth. Stratified by Crohn's disease (CD), ulcerative colitis (UC), and non-IBD deliveries, temporal trends and multivariable logistic regression were analyzed. RESULTS: There were 48 986 CD patients, 30 998 UC patients, and 69 963,805 non-IBD patients. Between 1998 and 2018, CD deliveries increased from 3.3 to 12.9 per 10 000 deliveries (P < 0.001) and UC deliveries increased from 2.3 to 8.6 per 10 000 deliveries (P < 0.001). Cesarean deliveries, gestational diabetes, preeclampsia/eclampsia, PROM, FGR, and fetal distress increased over time for IBD and non-IBD women, while preterm deliveries decreased (P < 0.001). Multivariable analyses demonstrated that IBD patients had higher risk of cesarean delivery, preeclampsia/eclampsia, PROM, and preterm delivery compared with non-IBD patients. CONCLUSION: Over a 20-year period, live deliveries amongst women with IBD have increased. Trends in pregnancy outcomes have followed a similar trajectory in patients with and without IBD. However, there is still demonstrable risk of adverse pregnancy outcomes in patients with IBD.

In this study examining pregnancy trends over 20 years, the proportion of live deliveries amongst women with IBD increased steadily. Despite advances in treatment, we found that IBD still confers a higher risk for many adverse pregnancy outcomes.

Antibody Kinetics after Three Doses of SARS-CoV-2 mRNA Vaccination in Patients with Inflammatory Bowel Disease.

Background: The emergence of new SARS-CoV-2 variants calls for more data on SARS-CoV-2 mRNA vaccine response. Aims: We aimed to assess the response to a third mRNA vaccine dose against SARS-CoV-2 in inflammatory bowel disease (IBD) patients. Methods: This was a single-center, observational prospective study of IBD patients who received a third mRNA vaccine dose against SARS-CoV-2. Antibody titers were taken post-third-dose at one and three months using the Roche Elecsys anti-SARS-CoV-2-S enzyme immunoassay. Titers less than 0.8 units/mL were considered negative according to the manufactures. Titers between 0.8 units/mL and 250 units/mL were considered non-neutralizing. Titers greater than 250 units/mL were considered neutralizing. Results: Eighty-three patients were included, all of whom had detectable antibodies at 3 months post-third dose. A total of 89% showed neutralizing and 11% non-neutralizing titers. Participants with non-neutralizing titers were more likely to be on systemic corticosteroids (p = 0.04). Two participants seroconverted from negative to positive, whereas 86% with non-neutralizing titers boosted to neutralizing levels. Only one participant with neutralizing titers after a third dose had a decrease to a non-neutralizing level within 3 months. Conclusions: Our findings support the ongoing recommendations for additional doses in immunocompromised individuals. However, longitudinal studies with a greater-sized patient population are needed.

Superior Efficacy of Infliximab Versus Adalimumab for First-Line Treatment of Crohn's Perianal Fistulae.

BACKGROUND: Crohn's disease perianal fistulae (CD-PAF) occur in 25% of patients and are notoriously challenging to manage. Tumor necrosis factor inhibitors are first line agents. AIMS: The aim of this study was to compare infliximab (IFX) versus adalimumab (ADA) efficacy in CD-PAF healing over time. METHODS: A retrospective study at two large-tertiary medical centers was performed. Inclusion criteria were actively draining CD-PAF and initial treatment with IFX or ADA following CD-PAF diagnosis. The primary endpoints were perianal fistula response and remission at 6 and 12 months. Secondary endpoints included biologic persistence over time and dose escalation at 6 and 12 months. RESULTS: Among 151 patients included in the study, 92 received IFX and 59 received ADA as first line agents after CD-PAF diagnosis. At 6 months, the 64.9% of the IFX group and 34.8% of the ADA group demonstrated CD-PAF clinical improvement (p < 0.01). Univariate and multivariate analyses demonstrated significant differences among the IFX and ADA groups for clinical response at 6-months and 12-months (p = 0.002 and p = 0.042, respectively). There were no factors that predicted response, with the exception of concomitant immunomodulator affecting the 6-month clinical response (p = 0.021). Biologic persistence, characterized by Kaplan Meier methods, was significantly longer in the IFX group compared to the ADA group (Log-rank p = 0.01). CONCLUSION: IFX induction and maintenance is associated with higher rates of response and remission in CD-PAF healing as well as higher treatment persistence compared to ADA. Additionally, our study supports the use of concomitant immunomodulator therapy for CD-PAF healing and remission.

Machine Learning-based Characterization of Longitudinal Health Care Utilization Among Patients With Inflammatory Bowel Diseases.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with increased health care utilization. Forecasting of high resource utilizers could improve resource allocation. In this study, we aimed to develop machine learning models (1) to cluster patients according to clinical utilization patterns and (2) to predict longitudinal utilization patterns based on readily available baseline clinical characteristics. METHODS: We conducted a retrospective study of adults with IBD at 2 academic centers between 2015 and 2021. Outcomes included different clinical encounters, new prescriptions of corticosteroids, and initiation of biologic therapy. Machine learning models were developed to characterize health care utilization. Poisson regression compared frequencies of clinical encounters. RESULTS: A total of 1174 IBD patients were followed for more than 5673 12-month observational windows. The clustering method separated patients according to low, medium, and high resource utilizers. In Poisson regression models, compared with low resource utilizers, moderate and high resource utilizers had significantly higher rates of each encounter type. Comparing moderate and high resource utilizers, the latter had greater utilization of each encounter type, except for telephone encounters and biologic therapy initiation. Machine learning models predicted longitudinal health care utilization with 81% to 85% accuracy (area under the receiver operating characteristic curve 0.84-0.90); these were superior to ordinal regression and random choice methods. CONCLUSION: Machine learning models were able to cluster individuals according to relative health care resource utilization and to accurately predict longitudinal resource utilization using baseline clinical factors. Integration of such models into the electronic medical records could provide a powerful semiautomated tool to guide patient risk assessment, targeted care coordination, and more efficient resource allocation.

Management of Perianal Crohn's Disease.

Perianal Crohn's disease affects 25%-35% of patients with Crohn's disease and has proven to be one of the most difficult complications of the disease to treat. Patients with perianal Crohn's disease have lower health-related quality of life scores typically related to pain and fecal incontinence. In addition, patients with perianal Crohn's disease have higher rates of hospitalizations, surgeries, and overall healthcare costs. A multidisciplinary approach is necessary for the successful management of Crohn's disease with perianal fistula. Medical management is required to treat the underlying immune dysregulation to heal the luminal inflammation and the inflammation within the fistula tracts. Current options for medical therapy include biologics, dual therapy with thiopurines, therapeutic drug monitoring, and a close follow-up. Surgical management is critical to drain abscesses before immunosuppressive therapy and place setons when appropriate. Once the patient's inflammatory burden is well managed, definitive surgical therapies including fistulotomies, advancement flaps, and ligation of intersphincteric fistula tract procedures can be considered. Most recently, the use of stem cell therapy in the treatment of perianal fistula has given new hope to the cure of perianal fistula in Crohn's disease. This review will outline the most current data in the medical and surgical management of perianal Crohn's disease.

A nanofiber-hydrogel composite improves tissue repair in a rat model of Crohn's disease perianal fistulas.

Perianal fistulas (PAFs) represent a severe complication of Crohn's disease (CD). Despite the advent of biologic and small-molecule therapeutics for luminal disease, PAFs in CD (CD-PAF) are relatively resistant to treatment, with less than 50% responding to any therapy. We report an injectable, biodegradable, mechanically fragmented nanofiber-hydrogel composite (mfNHC) loaded with adipose-derived stem cells (ADSCs) for the treatment of fistulas in a rat model of CD-PAF. The ADSC-loaded mfNHC results in a higher degree of healing when compared to surgical treatment of fistulas, which is a standard treatment. The volume of fistulas treated with mfNHC is decreased sixfold compared to the surgical treatment control. Molecular studies reveal that utilization of mfNHC reduced local inflammation and improved tissue regeneration. This study demonstrates that ADSC-loaded mfNHC is a promising therapy for CD-PAF, and warrants further studies to advance mfNHC toward clinical translation.

Initial Clinical Outcomes Using Umbilical Cord-Derived Tissue Grafts to Repair Anovaginal Fistula.

BACKGROUND: Perianal fistula is a debilitating disease and challenging condition to treat. Recently, the use of stem cells has been shown to improve healing of fistulas. OBJECTIVE: The aim was to examine the use of an umbilical cord-derived stem cell graft in a pilot study as a novel scaffold/stem inlay implanted into fistula repairs for anovaginal fistula to examine healing rates. DESIGN: This was a pilot study. SETTINGS: This study took place in a colorectal surgery practice. PATIENTS: Patients with anovaginal fistula consented to participate. Cryopreserved umbilical cord tissue graft with viable cells was incorporated as an inlay using a previously reported technique by the authors. Demographic data including history of previous repairs and IBD were included. All patients were followed for a minimum of 6 weeks. MAIN OUTCOME MEASURES: The primary measures were safety and efficacy of novel stem cell graft in the treatment of anovaginal fistula. RESULTS: From September 2017 to September 2019, 15 patients underwent anovaginal fistula repair. Three of these patients underwent a second repair, for a total of 18 repairs. No patient was intentionally diverted, but 3 patients presented for repair with a preexisting stoma. The majority of repairs were previous repair failures (12; 67%), and 7 repairs were performed on 5 patients with IBD. Median follow-up was 30 (6-104) weeks. The safety profile for cryopreserved umbilical cord tissue graft was excellent as no adverse events occurred. Overall complete healing rate was 39%, and 12 (67%) repairs resulted in improvement of symptoms. LIMITATIONS: This was a small pilot study. CONCLUSIONS: This is the largest series using cryopreserved umbilical cord graft for anovaginal fistula repair. The use of umbilical cord was safe and effective at closing defects. Randomized studies are necessary to determine added benefits over current standard of care. See Video Abstract at http://links.lww.com/DCR/B896 . RESULTADOS CLNICOS INICIALES DEL USO DE INJERTOS DE TEJIDO DERIVADO DE PLACENTA PARA REPARACIN DE FSTULAS ANOVAGINALES: ANTECEDENTES:La fístula perianal es una enfermedad debilitante y una afección difícil de tratar. Recientemente, se ha demostrado que el uso de células madre mejora la curación de las fístulas.OBJETIVO:Deseamos examinar el uso de un injerto de células madre derivadas de cordón umbilical en un estudio piloto como una nueva matriz/injerto de células madre implantado en reparaciones de fístula para fístula anovaginal para examinar las tasas de curación.DISEÑO:Este fue un estudio piloto.ESCENARIO:Este estudio se llevó a cabo en una clínica de cirugía colorrectal.PACIENTES:Se obtuvo consentimiento informado de pacientes con fístula anovaginal. El injerto de tejido de cordón umbilical criopreservado con células viables se incorporó como incrustación utilizando una técnica previamente informada por los autores. Se incluyeron datos demográficos que incluían antecedentes de reparaciones previas y enfermedad inflamatoria intestinal. Todos los pacientes fueron seguidos durante un mínimo de 6 semanas.PRINCIPALES MEDIDAS DE RESULTADO:Las principales medidas fueron la seguridad y la eficacia del nuevo injerto de células madre en el tratamiento de la fístula anovaginal.RESULTADOS:Desde 9/2017-9/2019, 15 pacientes fueron sometidas a reparación de fístula anovaginal. Tres de estos pacientes fueron sometidos a una segunda reparación, para un total de 18 reparaciones. Ningún paciente fue derivado intencionalmente mientras que 3 pacientes se presentaron para reparación con un estoma preexistente. La mayoría de las reparaciones fueron fallas de reparaciones previas (12, 67%) y se realizaron siete reparaciones en 5 pacientes con enfermedad inflamatoria intestinal (EII). La mediana de seguimiento fue de 30 semanas (6-104). El perfil de seguridad del injerto de tejido de cordón umbilical criopreservado fue excelente ya que no se produjeron efectos adversos. La tasa general de curación completa fue del 39% y 12 (67%) reparaciones dieron como resultado una mejoría de los síntomas.LIMITACIONES:Este fue un pequeño estudio piloto.CONCLUSIÓNES:Ésta es la serie más grande de utilización de injerto de cordón umbilical criopreservado para la reparación de una fístula anovaginal. La utilización del cordón umbilical resultó segura y eficaz para cerrar defectos. Se necesitan estudios aleatorizados para determinar los beneficios adicionales sobre el estándar de atención actual. Consulte Video Resumen en http://links.lww.com/DCR/B896 . (Traducción-Dr. Jorge Silva Velazco ).

A Novel Patient-like Swine Model of Perianal Crohn's Disease.

BACKGROUND: Perianal Crohn's disease is associated with poor outcomes and high medical costs. It is notoriously difficult to treat despite therapeutic advancements for luminal disease. A large animal model that mimics human perianal disease is needed to test innovative therapies. OBJECTIVE: This study aimed to create a swine model that replicates the inflammatory component and therapeutic challenges found in patients with perianal Crohn's disease. DESIGN: This was an animal preclinical study. SETTINGS: The experiments were performed at the animal laboratory at the Johns Hopkins University. PATIENTS: Four sus scrufus female pigs were included in the study. INTERVENTIONS: Four female pigs underwent creation of 3 surgical perianal fistulas each, 1 rectovaginal and 2 perianal. Size 24 French setons were placed to maintain patency of the fistula tracts for 4 weeks. After removal of the setons, trinitrobenzene sulfonic acid was administered into the fistula tract to create and maintain local inflammation mimicking perianal Crohn's disease. MAIN OUTCOMES MEASURES: An MRI was obtained to assess the fistulas and the pigs were euthanized to review histopathology. RESULTS: Three inflammatory chronic fistula tracts were successfully created in each pig as confirmed by MRI and examination under anesthesia. This is the first report of maintaining patent fistulas in swine 2 weeks after removal of setons. For the first time, we reported that 2 pigs developed branching fistulas and small abscesses reminiscent of human perianal Crohn's disease. The corresponding histopathologic examination found significant chronic active inflammation on standard hematoxylin and eosin staining. LIMITATIONS: The fistulas were surgically induced and did not occur naturally. CONCLUSIONS: A chronic perianal fistula model in pigs that strongly resembles human perianal Crohn's disease was successfully created. This model can be used to test novel therapeutics and techniques to pave the path for human trials. See Video Abstract at http://links.lww.com/DCR/B969 . UN NUEVO MODELO PORCINO SIMILAR A UN PACIENTE DE LA ENFERMEDAD DE CROHN PERIANAL ANTECEDENTES: La enfermedad de Crohn perianal se asocia con malos resultados y altos costos médicos. Es notoriamente difícil de tratar a pesar de los avances terapéuticos para la enfermedad luminal. Se precisa de un modelo animal grande que imite la enfermedad perianal humana para probar terapias innovadoras.OBJETIVO:Nuestro objetivo de este estudio fue crear un modelo porcino que replique el componente inflamatorio y los desafíos terapéuticos que se encuentran en los pacientes con enfermedad de Crohn perianal.DISEÑO:Este fue un estudio preclínico en animales.AJUSTES:Los experimentos se realizaron en el laboratorio de animales de la Universidad Johns Hopkins.PACIENTES:Se incluyeron en el estudio cuatro cerdas sus scrofa.INTERVENCIONES:Cuatro cerdas fueron sometidas a la creación de 3 fístulas perianales quirúrgicas cada una: 1 recto vaginal y 2 perianales. Se colocaron sedales de 24 French para mantener la permeabilidad de los trayectos fistulosos durante 4 semanas. Tras el retiro de los sedales, se administró ácido trinitrobenceno sulfónico en el trayecto de la fístula para crear y mantener la inflamación local simulando la enfermedad de Crohn perianal.PRINCIPALES MEDIDAS DE RESULTADOS:Se obtuvo una resonancia magnética para evaluar las fístulas y los cerdos fueron sacrificados para revisar la histopatología.RESULTADOS:Se crearon de manera exitosa tres trayectos fistulosos inflamatorios crónicos en cada cerdo, confirmados por imágenes de resonancia magnética y examen bajo anestesia. Este es el primer informe de preservación de fístulas permeables en cerdos 2 semanas tras el retiro de los setones. Por primera vez, informamos que dos cerdos desarrollaron fístulas ramificadas y pequeños abscesos que recuerdan a la enfermedad de Crohn perianal humana. El examen histopatológico correspondiente encontró una significativa inflamación crónica activa en la tinción estándar de hematoxilina y eosina.LIMITACIONES:Las fístulas se indujeron quirúrgicamente y no se produjeron de forma natural.CONCLUSIONES:Se logro recrear con éxito un modelo de fístula perianal crónica en cerdos que se asemeja mucho a la enfermedad de Crohn perianal humana. Este modelo se puede utilizar para probar nuevas terapias y técnicas para allanar el camino para los ensayos en humanos. Consulte Video Resumen en http://links.lww.com/DCR/B969 . (Traducción-Dr Osvaldo Gauto).

Dietary Interventions for the Treatment of Inflammatory Bowel Diseases: An Updated Systematic Review and Meta-analysis.

BACKGROUND & AIMS: This study aimed (1) to systematically review controlled trials of solid food diets for the treatment of inflammatory bowel disease (IBD); and (2) to grade the overall quality of evidence. METHODS: Systematic review of prospective controlled trials of solid food diets for the induction or maintenance of remission in IBD. Two authors independently performed study selection, data extraction, and assessment of certainty of evidence. Meta-analyses were performed on studies with quantitative data on response, remission, and relapse. RESULTS: There were 27 studies for meta-analysis. For induction of remission in Crohn's disease (CD), low refined carbohydrate diet and symptoms-guided diet outperformed controls, but studies had serious imprecision and very low certainty of evidence. The Mediterranean diet was similar to the Specific Carbohydrate Diet (low certainty of evidence), and partial enteral nutrition (PEN) was similar to exclusive enteral nutrition (very low certainty of evidence). PEN reduced risk of relapse (very low certainty of evidence), whereas reduction of red meat or refined carbohydrates did not (low certainty of evidence). For ulcerative colitis, diets were similar to controls (very low and low certainty of evidence). CONCLUSIONS: Among the most robust dietary trials in IBD currently available, certainty of evidence remains very low or low. Nonetheless, emerging data suggest potential benefit with PEN for induction and maintenance of remission in CD. Reduction of red meat and refined carbohydrates might not reduce risk of CD relapse. As more dietary studies become available, the certainty of evidence could improve, thus allowing for more meaningful recommendations for patients.

Ironing It All Out: A Comprehensive Review of Iron Deficiency Anemia in Inflammatory Bowel Disease Patients.

Iron deficiency anemia affects approximately 45% of patients with inflammatory bowel disease (IBD), negatively impacts the quality of life in this patient population, and significantly burdens our healthcare system. The pathogenesis of iron deficiency in IBD patients is multifactorial, including intestinal bleeding, malabsorption, and inadequate oral intake. Regular screening and diagnosis in these patients are imperative, and often patients have mixed iron deficiency anemia and anemia of chronic disease, especially in those with active inflammation. Iron may be replenished either orally or intravenously. While oral iron is safe, affordable, and easy to administer, patients often suffer from intolerable gastrointestinal side effects, and particularly in IBD patients, oral iron may increase inflammation and contribute to flares. Therefore, although it is substantially underused, intravenous (IV) iron is considered first-line treatment for patients with active disease, severe anemia, oral iron intolerance, and erythropoietin requirements. Several IV iron formulations are available, and iron sucrose and ferric carboxymaltose are the most frequently used and well studied in patients with IBD. However, iron isomaltoside could potentially become a popular choice among providers given its safety, efficacy, and convenience. Overall, screening, diagnosis, and treatment of iron deficiency anemia are important in patients with IBD. Individual patient characteristics, risks, and benefits, and advantages and disadvantages, should be considered when determining the best route and formulation for iron repletion.

Advanced endoscopic resection for colorectal dysplasia in inflammatory bowel disease: a meta-analysis.

Background and study aims Little is known about outcomes of advanced endoscopic resection (ER) for patients with inflammatory bowel disease (IBD) with dysplasia. The aim of our meta-analysis was to estimate the safety and efficacy of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for dysplastic lesions in patients with IBD. Methods We performed a systematic review through Jan 2021 to identify studies of IBD with dysplasia that was treated by EMR or ESD. We estimated the pooled rates of complete ER, adverse events, post-ER surgery, and recurrence. Proportions were pooled by random effect models. Results Eleven studies including 506 patients and 610 lesions were included. Mean lesion size was 23 mm. The pooled rate of complete ER was 97.9 % (95 % confidence interval [CI]: 95.3 % to 99.7 %). The pooled rate of endoscopic perforation was 0.8 % (95 % CI:0.1 % to 2.2 %) while bleeding occurred in 1.6 % of patients (95 %CI:0.4 % to 3.3 %). Overall, 6.6 % of patients (95 %CI:3.6 % to 10.2 %) underwent surgery after an ER. Among 471 patients who underwent surveillance, local recurrence occurred in 4.9 % patients (95 % CI:1.0 % to 10.7 %) and metachronous lesions occurred in 7.4 % patients (95 %CI:1.5 % to 16 %) over a median follow-up of 33 months. Metachronous colorectal cancer (CRC) was detected in 0.2 % of patients (95 %CI:0 % to 2.2 %) during the surveillance period. Conclusions Advanced ER is safe and effective in the management of large dysplastic lesions in IBD and warrants consideration as first-line therapy. Although the risk of developing CRC after ER is low, meticulous endoscopic surveillance is crucial to monitor for local or metachronous recurrence of dysplasia.

Endoscopic submucosal dissection for colorectal dysplasia in inflammatory bowel disease: a US multicenter study.

Background and study aims In patients with inflammatory bowel disease (IBD), endoscopically visible lesions with distinct borders can be considered for endoscopic resection. The role of endoscopic submucosal dissection (ESD) for these lesions is not well defined because of a paucity of data. We aimed to evaluate the outcomes of colorectal ESD of dysplastic lesions in patients with IBD across centers in the United States. Patients and methods This was a retrospective analysis of consecutive patients with IBD who were referred for ESD of dysplastic colorectal lesions at nine centers. The primary endpoints were the rates of en bloc resection and complete (R0) resection. The secondary endpoints were the rates of adverse events and lesion recurrence. Results A total of 45 dysplastic lesions (median size 30mm, interquartile range [IQR] 23 to 42 mm) in 41 patients were included. Submucosal fibrosis was observed in 73 %. En bloc resection was achieved in 43 of 45 lesions (96 %) and R0 resection in 34 of 45 lesions (76 %). Intraprocedural perforation occurred in one patient (2.4 %) and was treated successfully with clip placement. Delayed bleeding occurred in four patients (9.8 %). No severe intraprocedural bleeding or delayed perforation occurred. During a median follow-up of 18 months (IQR 13 to 37 months), local recurrence occurred in one case (2.6 %). Metachronous lesions were identified in 11 patients (31 %). Conclusions ESD, when performed by experts, is safe and effective for large, dysplastic colorectal lesions in patients with IBD. Despite the high prevalence of submucosal fibrosis, en bloc resection was achieved in nearly all patients with IBD undergoing ESD. Careful endoscopic surveillance is necessary to monitor for local recurrence and metachronous lesions after ESD.

Antibody Response 3 Months After 2-Dose SARS-CoV-2 mRNA Vaccination in Patients With Inflammatory Bowel Disease.

INTRODUCTION: The response to SARS-CoV-2 vaccination of patients with inflammatory bowel disease (IBD) on immune-modifying therapies requires further investigation because previous studies indicate that patients on immune therapy might have decreased antibody concentrations. METHODS: We present the antireceptor binding domain antibody response over a period of 3 months in 217 patients with IBD who completed standard 2-dose SARS-CoV-2 mRNA vaccine series. RESULTS: Almost all (98.6%) IBD vaccine recipients had a positive antireceptor binding domain antibody response at least 3 months after vaccination. Decreased antibody titers at 3 months were seen in a subset of patients on antitumor necrosis factor-alpha. Approximately 10% of the participants with high-titer antibodies at 1 month had a decrease to low-positive titers at 3 months, which was mostly observed in those on combination therapy and antitumor necrosis factor-alpha monotherapy. DISCUSSION: Larger longitudinal studies are required to define the response in IBD population and its clinical impact.

Antibody Response Six Months after SARS-CoV-2 mRNA Vaccination in Patients with Inflammatory Bowel Disease.

Patients with inflammatory bowel disease (IBD) are recommended to receive vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), regardless of their immunosuppression status. Immunosuppressive medications represent a mainstay of therapy in moderate to severe IBD; however, their impact on the SARS-CoV-2 vaccine response remains unclear. Studies thus far have shown that patients with IBD on various therapies had detectable antibody responses after standard vaccinations.1-5 To date, one study has examined the kinetics of antibody response at 3 months after vaccination in patients with IBD, but data beyond this time point are not yet available.6 The aim of this study was to assess anti-spike antibody response 6 months after completion of standard SARS-CoV-2 vaccination in patients with IBD. Secondarily, we observed antibody kinetics over 6 months in a subset of patients post-vaccination.

COVID-19 and Outcomes in Patients With Inflammatory Bowel Disease: Systematic Review and Meta-Analysis.

BACKGROUND: Our understanding of coronavirus disease 2019 (COVID-19) and its implications for patients with inflammatory bowel diseases (IBD) is rapidly evolving. We performed a systematic review and meta-analysis to investigate the epidemiology, clinical characteristics, and outcomes in IBD patients with COVID-19. METHODS: We searched PubMed, EMBASE, Cochrane Central, Clinicaltrials.gov, Web of Science, MedRxiv, and Google Scholar from inception through October 2020. We included studies with IBD patients and confirmed COVID-19. Data were collected on the prevalence, patient characteristics, pre-infection treatments for IBD, comorbidities, hospitalization, intensive care unit (ICU), admission, and death. RESULTS: Twenty-three studies with 51,643 IBD patients and 1449 with COVID-19 met our inclusion criteria. In 14 studies (n = 50,706) that included IBD patients with and without COVID-19, the prevalence of infection was 1.01% (95% confidence interval [CI], 0.92-1.10). Of IBD patients with COVID-19, 52.7% had Crohn's disease, 42.2% had ulcerative colitis, and 5.1% had indeterminate colitis. Nine studies (n = 687) reported outcomes according to IBD therapy received. Compared with patients on corticosteroids, those on antitumor necrosis factor (anti-TNF) therapy had a lower risk of hospitalization (risk ratio [RR], 0.24; 95% CI, 0.16-0.35; P < .01; I2 = 0%) and ICU admission (RR, 0.10; 95% CI, 0.03-0.37; P < .01) but not death (RR, 0.16; 95% CI, 0.02-1.71; P = .13; I2 = 39%). Compared with patients on mesalamine, those on antitumor necrosis factor therapy had a lower risk of hospitalizations (RR, 0.37; 95% CI, 0.25-0.54), ICU admissions (RR, 0.20; 95% CI, 0.07-0.58), and death (0.21; 95% CI, 0.04-1.00). Comparing patients on immunomodulators vs mesalamine or anti-TNF therapy, there was no difference in these outcomes. CONCLUSIONS: The prevalence of COVID-19 in IBD patients was low. Use of corticosteroids or mesalamine was significantly associated with worse outcomes, whereas use of anti-TNFs was associated with more favorable outcomes. Further investigation clarifying the mechanisms of these disparate observations could help identify risk and adverse outcome-mitigating strategies for patients with IBD.

Ustekinumab is effective for perianal fistulising Crohn's disease: a real-world experience and systematic review with meta-analysis.

BACKGROUND: Perianal Crohn's disease (pCD) is a debilitating complication affecting up to 30% of Crohn's disease (CD) population, leading to increased morbidity, mortality and decreased quality of life. Despite the growing armamentarium of medications for luminal CD, their efficacy in pCD remains poorly studied. AIM: To determine the efficacy of ustekinumab, a biologic approved for luminal CD, in pCD through a retrospective cohort study and systematic review. METHODS: A retrospective cohort study on patients with CD with active perianal fistulae treated with ustekinumab from September 2013 to August 2019 was performed to determine perianal fistula response and remission at 6 and 12 months after ustekinumab induction. A systematic review was performed to further establish rates of fistula response and remission with ustekinumab. RESULTS: At 6 months, 48.1% (13/27) patients achieved fistula response with none achieving fistula remission on provider exam, and 59.3% (16/27) achieved patient-reported symptomatic improvement with 3.7% (1/27) achieving symptomatic remission. At 1 year, on provider exam, 55.6% (5/9) had fistula response with none achieving fistula remission, and 100% (9/9) had symptomatic improvement with 22.2% (2/9) achieving symptomatic remission. There were no major safety signals during 1-year follow-up. The systematic review of 25 studies found 44% (92/209) of patients with active perianal fistulas had a clinical response within 6 months of follow-up, and 53.9% (85/152) of patients with 12 months of follow-up achieved clinical response. CONCLUSION: Ustekinumab presents a safe and effective therapy for treatment of pCD. Prospective, randomised trials are needed to further elucidate long-term efficacy of ustekinumab for pCD.