INTRODUCTION: Intravenous corticosteroids are the mainstay of treatment of patients hospitalized with acute severe ulcerative colitis (ASUC). However, 30%–40% of the patients are refractory to corticosteroids. We investigated whether addition of tofacitinib to corticosteroids improved the treatment responsiveness in patients with ASUC. METHODS: This single-center, double-blind, placebo-controlled trial randomized adult patients with ASUC (defined by the Truelove Witts severity criteria) to receive either tofacitinib (10 mg thrice daily) or a matching placebo for 7 days while continuing intravenous corticosteroids (hydrocortisone 100 mg every 6 hours). The primary end point was response to treatment (decline in the Lichtiger index by >3 points and an absolute score <10 for 2 consecutive days without the need for rescue therapy) by day 7. The key secondary outcome was the cumulative probability of requiring initiation of infliximab or undergoing colectomy within 90 days following randomization. All analyses were performed in the intention-to-treat population. RESULTS: A total of 104 patients were randomly assigned to a treatment group (53 to tofacitinib and 51 to placebo). At day 7, response to treatment was achieved in 44/53 (83.01%) patients receiving tofacitinib vs 30/51 (58.82%) patients receiving placebo (odds ratio 3.42, 95% confidence interval 1.37–8.48, P = 0.007). The need for rescue therapy by day 7 was lower in the tofacitinib arm (odds ratio 0.27, 95% confidence interval 0.09–0.78, P = 0.01). The cumulative probability of need for rescue therapy at day 90 was 0.13 in patients who received tofacitinib vs 0.38 in patients receiving placebo (log-rank P = 0.003). Most of the treatment-related adverse effects were mild. One patient, receiving tofacitinib, developed dural venous sinus thrombosis. DISCUSSION: In patients with ASUC, combination of tofacitinib and corticosteroids improved treatment responsiveness and decreased the need for rescue therapy.

Background/Aims: Primary sclerosing cholangitis (PSC) represents the most common hepatobiliary extraintestinal manifestation of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD). Limited data exist on PSC in patients with IBD from India. We aimed to assess the prevalence and disease spectrum of PSC in Indian patients with IBD. Methods: Database of IBD patients at 5 tertiary care IBD centers in India were analyzed retrospectively. Data were extracted and the prevalence of PSC-IBD was calculated. Results: Forty-eight patients out of 12,216 patients with IBD (9,231 UC, 2,939 CD, and 46 IBD unclassified) were identified to have PSC, resulting in a prevalence of 0.39%. The UC to CD ratio was 7:1. Male sex and pancolitis (UC) or colonic CD were more commonly associated with PSC-IBD. The diagnosis of IBD preceded the diagnosis of PSC in most of the patients. Majority of the patients were symptomatic for liver disease at diagnosis. Eight patients (16.66%) developed cirrhosis, 5 patients (10.41%), all UC, developed malignancies (3 colorectal cancer [6.25%] and 2 cholangiocarcinoma [4.16%]), and 3 patients died (2 decompensated liver disease [4.16%] and 1 cholangiocarcinoma [2.08%]) on follow-up. None of the patients mandated surgical therapy for IBD. Conclusions: Concomitant PSC in patients with IBD is uncommon in India and is associated with lower rates of development of malignancies.

Neurological manifestations in inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis, are increasingly recognized as significant contributors to both disease burden and patient morbidity. This comprehensive review delves into the spectrum of neurological complications linked with IBD, highlighting the involvement of both the central and peripheral nervous systems. The neurological impairments range from more common conditions such as peripheral neuropathy, characterized by nerve damage leading to pain and numbness, and cerebrovascular diseases, which include strokes and transient ischemic attacks, to less frequent but intensely severe conditions such as multiple sclerosis and myasthenia gravis, which involve the immune system attacking components of the nervous system. The complex pathophysiology underlying these manifestations integrates various factors including immune-mediated responses, vascular abnormalities such as thromboembolism, nutritional deficiencies often exacerbated by malabsorption and chronic inflammation, and the adverse effects elicited by IBD medications such as corticosteroids and immunomodulators. This review underscores the importance of adopting a multidisciplinary management approach. By integrating the expertise of gastroenterologists with that of neurologists, rheumatologists, and other specialists, patient outcomes can be significantly optimized. Further emphasis is placed on the necessity for heightened clinical awareness and the implementation of early diagnostic interventions to effectively identify and mitigate the neurological complications associated with IBD. In conclusion, ongoing research aimed at elucidating the underlying mechanisms that connect IBD with neurological disorders is imperative to facilitate the development of more effective preventative and therapeutic strategies for these challenging complications.

INTRODUCTION: Multitarget stool DNA (MT-sDNA) tests (i.e., Cologuard) serve as screening tests for colorectal cancer (CRC) and are recommended by the US Preventive Services Task Force every 1–3 years. In this study, in a primary care setting, our aim was to evaluate the diagnostic performance of MT-sDNA testing and colonoscopy findings after a positive MT-sDNA testing result. METHODS: This was a retrospective cohort study of electronic health record data including all patients who underwent MT-sDNA tests (Cologuard; Exact Sciences, Madison, WI) at 35 network primary care facilities from Winter of 2019 to Spring of 2023. Patients who were at high risk and had a prior colonoscopy or prior negative MT-sDNA test result were excluded. Assessment of pathology was as previously described, including for advanced adenomas and CRC. RESULTS: Among the 5,827 patients for whom MT-sDNA testing was ordered, 3,119 patients completed the test; 482 (15%) had a positive MT-sDNA test, most of whom were women, had an average age of 65 years, and were predominantly White (Supplemental Figure 1, Table 1). Among these 482 patients, 277 (57%) had a follow-up screening colonoscopy, with 253 patients having complete colonoscopy data. Ten patients (4%) had CRC, 61 (24%) had advanced adenomas, and 184 patients (73%) had neither. The sigmoid colon was the most common site for CRC, with 8 of 10 patients having tumor, node, metastasis stage ≥1 CRC. DISCUSSION: The rate of colon cancer detection (10/5,827 [0.2%] patients for whom it was ordered and 10/3,119 [0.3%] who completed the test) was lower than expected in a screening cohort. Most patients who completed MT-sDNA testing had a false-positive result for advanced adenomas or CRC (73%). Together, these findings raise questions about the effectiveness of screening based on MT-sDNA testing in an average risk population.

Introduction: Patients with inflammatory bowel disease (IBD) are at increased risk of developing other autoimmune disorders due to possible shared genetic, environmental, and immunological mechanisms. While autoimmune diseases are frequently observed in patients with IBD, data quantifying their inpatient prevalence and their association with outcomes such as mortality remain limited. Methods: National Inpatient Sample (NIS) 2016–2020 and International Classification of Diseases 10th Version, Clinical Modification (ICD-10-CM) diagnosis codes were used to identify patients with IBD and autoimmune conditions. A multivariate logistic regression analysis to identify an association between various autoimmune diseases and various IBDs was performed. Results: The study population included 141,478,025 patients. An association was found between 24 autoimmune conditions and IBD. Conclusions: Our study identified autoimmune comorbidities that are more prevalent in IBD patients. We found that polymyositis, AIHA, ITP, and thrombotic microangiopathy are associated with a higher risk of in-hospital mortality. Psoriasis and hypothyroidism are associated with a lower risk of in-hospital mortality. Further studies are needed to explore the mechanisms responsible.