Introduction: Ulcerative colitis is chronic inflammatory condition affecting the colon, necessitating remission inducing therapeutic interventions. With the emergence of newer more advanced options, their relative effectiveness remains unclear. This network meta-analysis (NMA) will compare the effectiveness of presently available biologics and small molecules in achieving and maintaining remission among patients of moderate-to-severe ulcerative colitis as part of induction and maintenance therapy. Methods: A systematic search was conducted up to 21st February 2025, including only phase 2b/3 or 3 randomized controlled trials. The primary outcome was induction and maintenance of clinical remission (Full Mayo Score (FMS) ≤ 2, with no individual subscore > 1). Secondary outcomes assessed were clinical response, endoscopic improvement (Mayo Endoscopic Score (MES) ≤ 1 either with or without friability) and steroid free remission. Results: Across 22 studies (7,683 patients), upadacitinib had the highest likelihood of inducing clinical remission (99.08%), clinical response (97.44%) and endoscopic improvement (99.32%), followed by Infliximab and guselkumab following close by for specific outcomes. In maintenance of clinical remission and endoscopic improvement upadacitinib again ranked highest (95.60%) and (99.46%). Tofacitinib (92.43%) has the highest probability with upadacitinib (87.73%) following behind in achieving steroid free remission. Conclusion: Upadacitinib displayed high efficacy across multiple outcomes in both induction and maintenance therapy with Infliximab, guselkumab, and filgotinib following closely behind. For achieving steroid free remission tofacitinib has the highest probability of doing so. Overall small molecules and selective IL-23 inhibitors seems promising alternative to older biologics though additional head-to-head trial are warranted along with more real-world data.

Purpose: Colorectal carcinoma constitutes a predominant etiology of oncological mortality globally. This systematic review and meta-analysis elucidated the prognostic utility of circulating tumor DNA (ctDNA) as a predictive biomarker for postsurgical recurrence in colorectal cancer patients. Methods: Two independent investigators conducted systematic literature search across PubMed, Web of Science, Embase, Scopus, and clinical trial registries. Studies investigating ctDNA prognostic significance for colorectal cancer recurrence were incorporated. Random-effects models were implemented utilizing restricted maximum likelihood methodology. The study quality was assessed using Newcastle–Ottawa Scale. Results: Following screening of 2259 records, 11 studies were incorporated. ctDNA-positive patients exhibited significantly elevated recurrence risk as compared to ctDNA-negative counterparts (pooled HR: 2.34; 95% CI: 1.90–2.79; p < 0.001). Moderate heterogeneity was observed ( I ² = 66.40%), attributable to patient stage distribution, sampling timing, detection platforms, and mutational panel variations. Stage I-III patients demonstrated exceptional consistency (HR: 2.04, I ² = 0.00%). Detection platforms showed robust performance: droplet digital PCR (HR: 3.63), next-generation sequencing (HR: 2.67), and Safe-SeqS (HR: 2.16), with no significant differences ( p = 0.10). Adjuvant chemotherapy analysis revealed differential performance: treated patients (HR: 2.50; 95% CI: 2.08–2.93) versus untreated (HR: 1.70; 95% CI: 1.07–2.34; p = 0.04). Extended analysis confirmed prognostic utility for overall survival (HR: 2.24) and surveillance recurrence-free survival (HR: 3.54). Conclusions: ctDNA represents a robust prognostic biomarker for postsurgical colorectal cancer recurrence with consistent cross-platform performance. Enhanced prognostic value in adjuvant chemotherapy patients supports personalized surveillance implementation, though methodological standardization remains warranted.

Ulcerative colitis (UC) is a chronic inflammatory disease that affects the colon, triggering persistent inflammation and ulceration, resulting in a severe impact on patients’ quality of life. Currently, the standard diagnostic methods for UC include invasive procedures such as colonoscopy and the use of non-specific inflammatory markers like C-reactive protein, which can be inconvenient or painful and lack specificity. This underscores the need for non-invasive and highly specific biomarkers for UC. MicroRNAs (miRNAs) are small non-coding RNAs, typically 22 nucleotides in length, which are well described as gene expression regulators. Several studies have reported their differential expression in various pathological conditions, including UC. Due to their role in gene regulation and stability in biological fluids, miRNAs present a promising opportunity as biomarkers. This systematic review explores the potential use of miRNAs as diagnostic biomarkers to distinguish between active and inactive ulcerative colitis. Following PRISMA guidelines and based on inclusion and exclusion criteria, seven studies, encompassing a total of 514 participants (181 with active UC and 116 with inactive UC), were included. Multiple miRNAs exhibiting differential expression between active and inactive UC were identified. Most notably, miR-21, miR-126, miR-146b-5p, and miR-223 exhibited consistent upregulation in active UC, suggesting their potential as diagnostic biomarkers. Supporting these findings is the fact that these miRNAs are involved in inflammatory pathways, further highlighting their relevance to the pathogenesis of UC. This review emphasizes the need for further validation studies with larger cohorts to confirm the utility of miRNAs as diagnostic tools for UC disease activity differentiation, which could enhance non-invasive disease monitoring and inform therapeutic decision-making. Future research should also evaluate the prognostic potential of these miRNAs for predicting treatment responses and long-term disease outcomes.

Background and Objective Colorectal cancer remains a major global health challenge, necessitating the development of accurate non-invasive diagnostic tools. Circulating and excretory microRNAs (miRNAs) are promising biomarkers owing to their stability and regulatory roles in tumorigenic pathways. While single miRNA assays often lack sufficient diagnostic accuracy, panels combining multiple miRNAs have shown enhanced performance. This systematic review and meta-analysis evaluated the diagnostic accuracy of multi-miRNA panels and explored their mechanistic relevance to colorectal cancer pathogenesis. Methods A comprehensive search of PubMed, Embase, Web of Science, and Scopus was conducted through March 2025 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The study protocol was registered with PROSPERO (CRD420251060655). Eligible studies assessed the diagnostic accuracy of multi-miRNA panels for colorectal cancer using extractable data on sensitivity, specificity, and area under the curve. Data were extracted independently by two reviewers. A bivariate random-effects model was used to calculate pooled diagnostic estimates. Study quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool, and heterogeneity was evaluated using I² statistics. Subgroup analyses were conducted by sample type (e.g., plasma, serum, stool) and panel size. Target genes of recurrent miRNAs were mapped to canonical colorectal cancer-related pathways. Results Twenty-nine studies comprising 5497 participants (3070 colorectal cancer cases and 2427 controls) and 35 multi-miRNA panels were included. Pooled sensitivity was 0.85 (95% confidence interval 0.80–0.88), specificity was 0.84 (95% confidence interval 0.80–0.88), and the area under the curve was 0.90, despite substantial heterogeneity (I² > 77%). Panels derived from plasma samples showed the highest balanced performance (sensitivity 0.88; specificity 0.87), while three-miRNA panels exhibited the best diagnostic trade-offs. Mechanistic analysis of 42 recurrent miRNAs revealed consistent involvement in key colorectal cancer pathways, including PI3K/AKT, Wnt/β-catenin, epithelial-mesenchymal transition, angiogenesis, and immune regulation. Conclusions Multi-miRNA panels derived from diverse biospecimen sources demonstrate high diagnostic accuracy for colorectal cancer and are mechanistically linked to fundamental oncogenic pathways. Future efforts should focus on panel standardization, biospecimen-specific validation, and integration into clinical workflows to advance precision oncology.