Creation of a Case-Finding Definition for Identifying Patients With Acute Pouchitis in Administrative Claims Data.

Acute pouchitis is the most common complication after a restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis, affecting 40% of patients within the first year after surgery.1 Although up to 80% of patients can develop pouchitis symptoms,2,3 substantial gaps remain in our understanding of the epidemiology and burden of pouchitis. Administrative claims have been used to advance the knowledge of other areas of inflammatory bowel disease4-6; however, a prerequisite to conducting such studies in pouchitis is a valid, reliable case-finding algorithm. Given concerns that the International Classification of Diseases (ICD) code for pouchitis may not be reliably used by clinicians (resulting in a low sensitivity), the objectives of the study were to (1) develop a series of case-finding definitions for acute pouchitis and (2) compare the performance of these case-finding definitions to that of a single ICD code for pouchitis.

Predictive value of individual serum neurofilament light chain levels in short-term disease activity in relapsing multiple sclerosis.

Background: The assessment of serum neurofilament light chain (sNFL) has emerged as a diagnostic and prognostic tool in monitoring multiple sclerosis (MS). However, the application of periodic measurement in daily practice remains unclear. Objective: To evaluate the predictive value of individual sNFL levels in determining disease activity in patients with relapsing MS (RMS). Methods: In this two-year prospective study, 129 RMS patients underwent quarterly sNFL assessments and annual MRI scans. The study analyzed the correlation between individual NFL levels and past, current, and future disease activity. Group-level Z-scores were employed as a comparative measure. Results: Among the 37 participants, a total of 61 episodes of disease activity were observed. sNFL levels proved valuable in distinct ways; they were confirmatory of previous and current clinical and/or radiological activity and demonstrated a high negative predictive value for future 90 days activity. Interestingly, Z-scores marginally outperformed sNFL levels in terms of predictive accuracy, indicating the potential for alternative approaches in disease activity assessment. In our cohort, sNFL cut-offs of 10.8 pg./mL (sensitivity 27%, specificity 90%) and 14.3 pg./mL (sensitivity 15%, specificity 95%) correctly identified 7 and 4 out of 26 cases of radiological activity within 90 days, respectively, with 14 and 15% false negatives. When using lower cut-off values, individuals with sNFL levels below 5 pg/mL (with a sensitivity of 92%, specificity of 25%, and negative predictive value of 94%) were less likely to experience radiological activity within the next 3 months. Conclusion: Individual sNFL levels may potentially confirm prior or current disease activity and predict short-term future radiological activity in RMS. These findings underscore its periodic measurement as a valuable tool in RMS management and decision-making, enhancing the precision of clinical evaluation in routine practice.

Metabolic analyses reveal dysregulated NAD+ metabolism and altered mitochondrial state in ulcerative colitis.

Ulcerative colitis (UC) is a complex, multifactorial disease driven by a dysregulated immune response against host commensal microbes. Despite rapid advances in our understanding of host genomics and transcriptomics, the metabolic changes in UC remain poorly understood. We thus sought to investigate distinguishing metabolic features of the UC colon (14 controls and 19 patients). Metabolomics analyses revealed inflammation state as the primary driver of metabolic variation rather than diagnosis, with multiple metabolites differentially regulated between inflamed and uninflamed tissues. Specifically, inflamed tissues were characterized by reduced levels of nicotinamide adenine dinucleotide (NAD+) and enhanced levels of nicotinamide (NAM) and adenosine diphosphate ribose (ADPr). The NAD+/NAM ratio, which was reduced in inflamed patients, served as an effective classifier for inflammation in UC. Mitochondria were also structurally altered in UC, with UC patient colonocytes displaying reduced mitochondrial density and number. Together, these findings suggest a link between mitochondrial dysfunction, inflammation, and NAD+ metabolism in UC.