Effectiveness and safety of a third-line rescue treatment for acute severe ulcerative colitis refractory to infliximab or ciclosporin (REASUC study).

BACKGROUND: The advent of new therapeutic agents and the improvement of supporting care might change the management of acute severe ulcerative colitis (ASUC) and avoid colectomy. AIMS: To evaluate the colectomy-free survival and safety of a third-line treatment in patients with ASUC refractory to intravenous steroids and who failed either infliximab or ciclosporin. METHODS: Multicentre retrospective cohort study of patients with ASUC refractory to intravenous steroids who had failed infliximab or ciclosporin and received a third-line treatment during the same hospitalisation. Patients who stopped second-line treatment due to disease activity or adverse events (AEs) were eligible. We assessed short-term colectomy-free survival by logistic regression analysis. Kaplan-Meier curves and Cox regression models were used for long-term assessment. RESULTS: Among 78 patients, 32 received infliximab and 46 ciclosporin as second-line rescue treatment. Third-line treatment was infliximab in 45 (58%), ciclosporin in 17 (22%), tofacitinib in 13 (17%) and ustekinumab in 3 (3.8%). Colectomy was performed in 29 patients (37%) during follow-up (median 21 weeks). Of the 78 patients, 32 and 18 were in clinical remission at, respectively, 12 and 52 weeks. At the last visit, 25 patients were still on third-line rescue treatment, while 12 had stopped it due to clinical remission. AEs were reported in 26 (33%) patients. Two patients died (2.6%), including one following colectomy. CONCLUSION: Third-line rescue treatment avoided colectomy in over half of the patients with ASUC and may be considered a therapeutic strategy.

Effectiveness and safety of darvadstrocel in patients with complex perianal fistulizing Crohn's disease: a systematic review.

Background: Managing complex perianal fistulizing Crohn's disease (CD) remains challenging, despite current medical and surgical treatment approaches. Darvadstrocel, a therapy utilizing adipose-derived stem cells, shows promise in promoting tissue regeneration and healing, offering a novel and effective treatment for fistula management. Method: A systematic literature search was conducted on PubMed and Scopus to identify studies involving patients with complex perianal fistulizing CD treated with darvadstrocel. Results: In total, 2 randomized controlled trials (RCT), 5 observational studies with retrospective data collection and 2 observational studies with prospective design were included in the final review. Data from the European ADMIRE-CD RCT demonstrated that darvadstrocel is superior to placebo in terms of clinical and imaging improvement over both the short and long term. These findings align with the prospective studies analyzed in this systematic review. The rate of treatment-emergent adverse events in the ADMIRE-CD trial's RCTs was similar in both the darvadstrocel and control groups, with perianal abscess being the most common adverse event up to 52 weeks after drug administration. Retrospective studies indicated no side-effects beyond 52 weeks. Conclusions: Darvadstrocel appears to be a new, potentially effective and safe treatment option for the management of complex perianal fistulas. However, more randomized clinical trials are needed to evaluate the efficacy and safety profile of the drug.

An overview of recent treatment options for primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic hepatic dysfunction characterized by inflammatory and tissue-degenerative strictures of the biliary tree, leading to cirrhosis and cholangiocarcinoma. The pathophysiological mechanisms involve immune-mediated responses. Numerous treatment modalities targeting the inflammatory aspects have been suggested, but a consensus on the best treatment option is lacking. This study aims to review the most up-to-date treatment options for PSC.

The current role of Tofacitinib in acute severe ulcerative colitis in adult patients: A systematic review.

BACKGROUND: Despite rescue therapy, acute severe ulcerative colitis (ASUC) is associated with a high risk of colectomy, while treatment options remain limited. Tofacitinib, a rapidly acting Janus Kinase (JAK) inhibitor, is gaining ground as an effective alternative treatment option for the management of acute severe ulcerative colitis, which may prevent emergency colectomy. METHODS: A systematic literature search of PubMed and Embase was undertaken for studies of adult patients with ASUC treated with tofacitinib. RESULTS: In total, two observational studies, seven case series and five case reports incorporating 134 patients who received tofacitinib in ASUC were identified with a follow-up period ranging from 30 days to 14 months. Overall, the pooled colectomy rate was 23.9% (95% CI 16.6-31.2). The pooled 90-day and 6-month colectomy free rate were 79.9% (95% CI 73.1-86.7) and 71.6% (95% CI 64-79.2) respectively. The most frequent adverse event was C. Difficile infection. CONCLUSIONS: Tofacitinib appears to be a promising option for the treatment of ASUC. Randomized clinical trials are required to further access the efficacy, safety and optimal dose of tofacitinib in cases of ASUC.

Inflammatory bowel disease and atrial fibrillation: a contemporary overview.

Atrial fibrillation is the most common arrhythmia in clinical practice and it is associated with increased morbidity and mortality. Atrial fibrillation is linked with inflammatory signaling while inflammation and oxidative stress promote atrial remodeling promoting the development and perpetuation of the arrhythmia. On the other hand, inflammatory bowel disease (IBD) is considered a chronic inflammatory condition with flares and remissions. IBD has been associated with an increased risk of atherosclerotic cardiovascular disease but its relationship with atrial fibrillation has not been studied well. Recent epidemiological evidence indicates an association between IBD and atrial fibrillation, especially during flares/hospitalizations. This brief review provides a concise overview of all available data regarding the association between IBD and atrial fibrillation including the predictive role of electrocardiographic and echocardiographic markers. Several unresolved issues including the thromboembolic risk in this setting and the potential role of antiinflammatory interventions are also discussed.

Detection of Helicobacter Pylori in Nasal Polyps: An Epidemiological Study.

Many studies have described the detection of Helicobacter pylori (HP) in the nasal polyps; however, although gastroesophageal reflux has been associated with chronic rhinosinusitis and nasal polyps development, the role of HP remains unclear. Our aim was to describe the prevalence of HP detection in nasal polyps and its association with gastric HP infection and gastroesophageal reflux dsease (GERD). The prospective study involved 36 patients with nasal polyps, who underwent to endoscopic surgery removal of nasal polyps. Before surgical procedure all patients were tested for gastric HP infection by 13 C-urea breath test, while tissue samples from nasal polyps were tested for HP detection, using rapid urease test (CLO test) and histological examination with Giemsa stain. All patients were asked about GERD-related symptoms. HP in nasal polyps was detected in 9 out of 36 patients (25%) using histological examination with Giemsa stain, while the detection rate of HP was 30.5% (11/36) using CLO test. Furthermore, 28 out of 36 patients (77.7%) had gastric HP infection. All patients with HP colonization in nasal polyps had gastric HP infection and all patients with HP in nasal polyps reported symptoms related to GERD. HP was detected in approximately one out of three patients in nasal polyps, while all patients with HP detection in nasal polyps had concurrently gastric HP infection and reported GERD-related symptoms, suggesting a gastro-nasal route of HP.

Post-inflammatory Polyp Burden as a Prognostic Marker of Disease-outcome in Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Post-inflammatory polyps [PIPs] are considered as indicators of previous episodes of severe inflammation and mucosal ulceration. Inflammatory bowel disease [IBD], namely Crohn's disease [CD] and ulcerative colitis [UC], exhibit a perpetuating, relapsing and remitting pattern, and PIPs are a frequent sequela of chronicity. The aim of this study was to determine whether a high PIP burden is associated with a more severe disease course in patients with IBD. METHODS: This was a multinational, multicentre, retrospective study. IBD patients previously diagnosed with PIPs were retrieved from the endoscopic database of each centre. PIP burden was evaluated and associated with demographic and clinical data as well as factors indicating a more unfavourable disease course. RESULTS: A total of 504 IBD patients with PIPs were recruited [male: 61.9%]. The mean age at IBD diagnosis was 36.9 [±16.8] years. Most patients [74.8%] were diagnosed with UC. A high PIP burden was present in 53.4% of patients. On multivariable Cox regression analysis, a high PIP burden was independently associated with treatment escalation (hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.04-1.75; p = 0.024), hospitalization [HR 1.90; 95% CI 1.24-2.90; p = 0.003], need for surgery [HR 2.28; 95% CI 1.17-4.44, p = 0.02] and younger age at diagnosis [HR 0.99, 95% CI 0.98-0.99; p = 0.003]. CONCLUSION: PIP burden was associated with a more severe outcome. Future prospective studies should focus on the characterization of PIP burden as to further risk stratify this patient cohort.

Medical, Endoscopic and Surgical Management of Stricturing Crohn's Disease: Current Clinical Practice.

The development of fibrostenotic intestinal disease occurs in approximately one-third of patients with Crohn's disease and is associated with increased morbidity. Despite introducing new biologic agents, stricturing Crohn's disease remains a significant clinical challenge. Medical treatment is considered the first-line treatment for inflammatory strictures, and anti-TNF agents appear to provide the most considerable benefit among the available medical treatments. However, medical therapy is ineffective on strictures with a mainly fibrotic component, and a high proportion of patients under anti-TNF will require surgery. In fibrotic strictures or cases refractory to medical treatment, an endoscopic or surgical approach should be considered depending on the location, length, and severity of the stricture. Both endoscopic balloon dilatation and endoscopic stricturoplasty are minimally invasive and safe, associated with a small risk of complications. On the other hand, the surgical approach is indicated in patients not suitable for endoscopic therapy. This review aimed to present and analyze the currently available medical, endoscopic, and surgical management of stricturing Crohn's disease.

Gastric metastasis from breast cancer presenting as dysphagia.

Gastric metastasis from breast cancer occurs infrequently and causes non-specific symptoms, usually attributed to the underlying disease. Furthermore, endoscopic findings are almost identical to primary gastric cancer, making the immunohistochemical examination of biopsies necessary for diagnosis. We present the case of a 64-year-old woman who was diagnosed with lobular breast cancer 3 years ago and received chemotherapy with evidence of remission. The patient presented with dyspepsia and progressive dysphagia for the last 6 months, not responsive to PPI treatment. Upper endoscopy revealed partial occlusion of the cardio-esophageal junction and thickened gastric folds resembling linitis plastica. However, immunohistochemical analysis of endoscopic biopsies showed infiltration of gastric mucosa by lobular breast cancer cells, making the diagnosis of gastric metastasis. Therefore, clinicians' awareness of possible gastric metastasis is warranted in patients with a history of advanced breast cancer and severe gastric symptoms.

Mental Health, Work Presenteeism, and Exercise in Inflammatory Bowel Disease.

BACKGROUND: Chronic diseases, such as IBD, can lead to anxiety and depression which can have a significant impact on productivity at work [presenteeism]. The aim of this study was to assess the prevalence of depression/anxiety, presenteeism and exercise levels among IBD patients. METHODS: This was a multicentre study whereby adult IBD patients, in clinical remission, were asked to answer a questionnaire anonymously. Hospital Anxiety and Depression Score [HADS], Stanford Presenteeism Scale [SPS-6] and Godin Exercise Score were also collected. RESULTS: A total of 585 patients were recruited. The majority had Crohn's disease [CD, 62.2%] and were male [53.0%], with a median age of 39 years [IQR 30-49]. A psychiatric diagnosis was present in 10.8% of patients prior to their IBD diagnosis. A further 14.2% of patients were psychiatrically diagnosed after IBD diagnosis, this being commoner in CD patients [41.6% of CD, p <0.01]. A raised HADS-Anxiety or a HADS-Depression score ≥8 was present in 46.1% of patients, with 27.4% having a score ≥11. Low presenteeism at work was present in 34.0%. Patients diagnosed with depression/anxiety had a more sedentary lifestyle [p <0.01], lower presenteeism at work [p <0.01] and a higher rate of unemployment [p <0.01]. CONCLUSIONS: A significant percentage of IBD patients in remission suffer from anxiety and/or depression. Risk factors for these are CD, female gender, use of biologic medications, long-standing and/or perianal disease. Depression/anxiety was associated with a sedentary lifestyle, lower presenteeism at work and unemployment. Validated screening tools and appropriate referrals to psychologists and/or psychiatrists should be employed within IBD clinics.

The efficacy of immunomodulators in the prevention and suppression of anti-drug antibodies to anti-tumor necrosis factor therapy in inflammatory bowel disease.

The development of biological agents against tumor necrosis factor (TNF) has revolutionized the management of inflammatory bowel disease (IBD), frequently achieving induction and maintenance of remission in both ulcerative colitis and Crohn's disease. However, a loss of response due to the development of anti-drug antibodies (ADA) is seen annually in approximately 20% of IBD patients receiving anti-TNF therapy. Current evidence suggests that the use of immunomodulators (IMM), such as thiopurines (azathioprine and 6-mercaptopurine) or methotrexate, may prevent or suppress ADA formation. In this article, we present a comprehensive review of the available literature regarding the efficacy of IMM in the prevention and suppression of ADA development to anti-TNF therapy in patients with IBD.

Current noninvasive modalities in Crohn's disease monitoring.

Crohn's disease (CD) is characterized by a remitting and relapsing course. Longstanding active CD may result in accumulating intestinal damage and disease-related complications. In contrast, mucosal healing is associated with significant improvement in the health-related quality of life, longer periods of disease remission and lower risk of disease progression, complications, hospitalizations, intestinal surgeries, as well as a lower risk of developing colorectal cancer. Mucosal healing, the new treatment endpoint in CD, made necessary the development of noninvasive, accurate, objective and reliable tools for the evaluation of CD activity. Ileocolonoscopy with biopsies remains the reference standard method for the evaluation of the colonic and terminal ileal mucosa. However, it is an invasive procedure with a low risk of complications, allowing the investigation of only a small part of the small bowel mucosa without being able to assess transmural inflammation. These disadvantages limit its role in the frequent follow up of CD patients. In this review, we present the currently available biomarkers and imaging modalities for the noninvasive assessment of CD activity.

Inflammatory Bowel Disease and Patients With Mental Disorders: What Do We Know?

Inflammatory bowel disease (IBD) is a multisystemic disease with a wide range of extraintestinal manifestations in both ulcerative colitis and Crohn's disease, while increasing evidence supports the interaction between gut and central nervous system, described as "gut-brain axis". According to epidemiological studies, it seems that patients with IBD present more frequently with impaired mental status compared to the general population, leading to diagnostic and management problems in this group of patients. The association between IBD and mental disorders, such as dementia and autism spectrum disorders, has not been fully clarified; genetic factors and the gut-brain axis seem to be involved. The purpose of this review is to present and analyze the epidemiological data about this issue, describe the possible pathogenetic mechanisms and discuss some considerations about the management of patients with IBD and impaired mental status.

Diagnosis, epidemiology and management of serrated polyposis syndrome: a comprehensive review of the literature.

Serrated polyp associated colorectal cancer (CRC) develops from an alternative mechanism of colorectal carcinogenesis and accounts for 10-15% of all CRC. Serrated polyposis syndrome (SPS) occurs infrequently and is characterized by the occurrence of multiple serrated polyps (hyperplastic polyps, sessile serrated lesions and traditional serrated adenomas) throughout the colon and/or rectum and has been strongly associated with development of CRC. However, SPS is frequently unrecognized, due to application failure of the WHO criteria regarding diagnosis and/or missed serrated polyps during endoscopy. The management of SPS requires surveillance at regular intervals and removal of large serrated polyps. Endoscopic resection suitability and technique depends on lesion size and the endoscopist's experience. In this manuscript, we present an update regarding SPS epidemiology, molecular characteristics, management, surveillance strategies and endoscopic resection techniques.

New insights into intestinal failure-associated liver disease in adults: A comprehensive review of the literature.

Intestinal failure-associated liver disease (IFALD) remains one of the most common and serious complications of parenteral nutrition (PN), causing a wide spectrum of hepatic manifestations from steatosis and mild cholestasis to portal hypertension and end-stage liver failure. The prevalence of IFALD depends on the diagnostic criteria and ranges from 4.3% to 65%. Moreover, many factors are shown to contribute to its development, including nutrient deficiencies, toxicity of PN, infections, and alterations of bile acid metabolism and gut microbiota. Prevention and management of IFALD aim at ameliorating or eliminating the risk factors associated with IFALD. The use of PN formulations with a lower ratio omega-6-to-omega-3 polyunsaturated fatty acids, cycle PN, optimization of enteral stimulation and prevention and early treatment of infections constitute the main therapeutic targets. However, failure of improvement and severe IFALD with end-stage liver failure should be considered as the indications of intestinal transplantation. The aim of this review is to provide an update of the epidemiology, pathophysiology, and diagnosis of IFALD in the adult population as well as to present a clinical approach of the therapeutic strategies of IFALD and present novel therapeutic targets.

Thromboembolic complications and cardiovascular events associated with celiac disease.

Celiac disease (CD) is a chronic intestinal immune-mediated disease occurring in genetically susceptible individuals who are exposed to gluten. Although it primarily affects the small intestine, CD has been associated with a wide spectrum of extraintestinal manifestations, including thromboembolism and cardiovascular events. The risk of ischemic stroke, myocardial infarction, and thromboembolism, such as deep vein thrombosis and pulmonary embolism, is higher in patients with CD, while there is accumulating evidence that gluten-free diet in CD patients decreases the risk of these complications. The pathogenetic mechanism of increasing hypercoagulability in CD is multifactorial and involves hyperhomocysteinemia due to malabsorption of vitamins B12, B6, and folic acid; endothelial dysfunction; acceleration of atherosclerosis; chronic inflammation; thrombocytosis; and thrombophilia. Therefore, in cases of thromboembolic complications and cardiovascular disease of obscure etiology, clinicians' awareness of possible celiac disease is warranted.

Correction to: Ocular manifestations in celiac disease: an overview.

In the original publication, first line of methods under the Abstract section was published incorrectly.

Ocular manifestations in celiac disease: an overview.

PURPOSE: To review and highlight the ocular manifestations associated with celiac disease (CD) and presentation of their pathogenetic mechanisms. METHODS: A thorough review of the literature was performed using PubMed to identify articles about serrated polyposis syndrome. The search was performed using the search string: ("celiac disease" OR "coeliac disease") AND ("ocular manifestations" OR "eye" OR "orbitopathy" OR "uveitis" OR "neuro-ophthalmic manifestations"). Only articles in English were reviewed. RESULTS: Several ocular symptoms and disorders have been associated with CD and are a result of defective intestinal absorption and immunological mechanisms. These include nyctalopia, dry eye, cataract, thyroid-associated orbitopathy, uveitis, central retinal vein occlusion and neuro-ophthalmic manifestations. In addition, CD-related ocular disease may represent the first manifestation of CD. CONCLUSION: CD may hold accountable for the development of ocular diseases of obscure etiology.