Search Results (220)

Background/Objectives: Lysophosphatidylcholine (LPC) is composed of various lipid species, some of which exert pro-inflammatory and others anti-inflammatory activities. However, most of the LPC species analyzed to date are reduced in the serum of patients with inflammatory bowel disease (IBD) compared to healthy controls. To our knowledge, the correlation between serum LPC species levels and measures of inflammation, as well as their potential as markers for monitoring IBD activity, has not yet been investigated. Methods: Thirteen LPC species, varying in acyl chain length and number of double bonds, were measured in the serum of 16 controls and the serum of 57 patients with IBD. Associations with C-reactive protein (CRP) and fecal calprotectin levels as markers of IBD severity were assessed. Results: Serum levels of LPC species did not differ between the healthy controls and the entire patient cohort. In patients with IBD, serum levels of LPC 16:1, 18:0, 18:3, 20:3, and 20:5, as well as total LPC concentrations, showed inverse correlations with both CRP and fecal calprotectin levels, indicating an association with inflammatory activity. Nine LPC species were significantly reduced in patients with high fecal calprotectin compared to those with low values. LPC species with 22 carbon atoms and 4 to 6 double bonds were not related to disease activity. Stool consistency and gastrointestinal symptoms did not influence serum LPC profiles. Corticosteroid treatment was associated with lower serum LPC 20:3 and 22:5 levels, while mesalazine, anti-TNF, and anti-IL-12/23 therapies had no significant impact on LPC concentrations. There was a strong positive correlation between LPC species containing 15 to 18 carbon atoms and serum cholesterol, triglycerides, and phosphatidylcholine levels. However, there was no correlation with markers of liver disease. Conclusions: Shorter-chain LPC species are reduced in patients with active IBD and reflect underlying hypolipidemia. While these lipid alterations provide insight into IBD-associated metabolic changes, they appear unsuitable as diagnostic or disease monitoring biomarkers. Full article

Background: Inflammatory bowel diseases with an early-onset form (EO-IBDs) make up a special disease group with certain clinical and phenotypic characteristics. This article discusses the features of such early onset in a group of children, based on five years of monitoring a registry of children with IBD from a specialized center. Methods: This retrospective single-center cohort study included pediatric patients diagnosed with EO-IBD between 2019 and 2024. Clinical, laboratory, and endoscopic data were collected from medical records, including fecal calprotectin, inflammatory markers, disease activity indices, and endoscopic severity scores. Localization was classified according to the Paris system, and histological activity was assessed using the IBD-DCA score. Results: There were 20 patients with ulcerative colitis (UC) and 17 with Crohn’s disease (CD). Clinical activity was moderate or high (p = 0.179). UC was more characterized by diarrhea and rectal bleeding. CD was more often accompanied by abdominal pain, weight loss, and fever. In total, 82.4% of patients with CD had an inflammatory form. UC-like intestinal lesion was typical of both nosologies—L3 64.7% and E4 60% forms in CD and UC, respectively. Morphological activity was moderate for both nosologies (p = 0.54). IBD-U was present in 43.2% of patients. The median time after which it was possible to diagnose UC was 24 weeks (IQR 20–48) and 40 weeks (IQR 30–45.5) for CD (p = 0.56). Conclusions: Our study confirms the presence of characteristic signs of EO-IBD development, such as a frequent family history of IBD, high or moderate clinical activity during diagnosis verification, colon damage, and a high frequency of extraintestinal manifestations. Full article

Background/Objectives: Calprotectin and intestinal fatty acid-binding protein (IFABP) may reflect the intestinal maturation process of very preterm infants (VPI) but have also been associated with gut inflammation. To establish normative values for fecal calprotectin (FC) and urinary intestinal fatty acid-binding protein (uIFABP) in VPI and to study their correlations with demographic and clinical factors. Methods: A cohort of VPI (born before or at 32.0 weeks of gestation) was recruited in two neonatal intensive care units. Urine and fecal samples were collected at 1, 4 and 8 weeks of life to measure urinary IFABP (normalized to creatinine as uIFABP/Cr) and FC, respectively. UIFABP was determined by ELISA and FC by fluoroenzyme immunoassay. Results: 194 newborns had at least one valid biomarker measurement. The study cohort mean gestational age was 28.9 ± 2.3 weeks and mean birth weight 1178 ± 365 g. Although uIFABP/Cr concentrations differed between the two centres, they were negatively correlated with gestational age, with a statistically significant correlation observed in both centres at week 4 (Hospital Clínic: Spearman’s rho −0.500; p = 0.000 and Hospital Sant Joan de Déu: Spearman’s rho −0.474; p = 0.000). Conversely, FC showed a positive significant correlation at the same time point (Spearman’s rho 0.302; p = 0.006). At week one, FC increased with antibiotic exposure (28 mcg/g of stool per antibiotic day, 95%CI 3–57; p = 0.028). FC at week 4 was inversely correlated with mother’s own milk (MOM) exposure during the first month (Spearman’s rho −0.253; p = 0.023). Conclusions: uIFABP/Cr and FC are associated with gestational age at 4 weeks and FC is also influenced by antibiotic treatment and MOM exposure. Full article

Background/Objectives: The prevalence of inflammatory bowel disease (IBD) in spondyloarthritis (SpA) patients is unknown. Our objective was to assess the prevalence of undiagnosed IBD in SpA patients, including those with axial spondylarthritis (axSpA) or psoriatic arthritis (PsA). Additionally, we examined fecal calprotectin (FC) levels in relation to the accuracy of IBD diagnosis. Methods: EISER was a cross-sectional, multicenter, observational, rheumatologist–gastroenterologist collaborative study. Patients with SpA naïve to biologics were recruited. Demographic and clinical characteristics, disease activity, and treatment information were collected. Patients with FC ≥ 80 µg/g or IBD-related symptoms underwent a colonoscopy or video capsule endoscopy. Receiver operating characteristic analysis assessed the predictive value of FC for IBD diagnosis. Results: Of the 570 patients recruited, 494 were evaluable for the main outcome, 248 (50.2%) had axSpA, and 246 (49.8%) had PsA. Overall, 28/494 patients were diagnosed with IBD (5.7%, 95%CI 3.6–7.7). Sorted by clinical entity, 22 (8.9%, 95%CI 5.3–12.4) axSpA and 6 (2.4%, 95%CI 0.5–4.4) PsA patients had a diagnosis of IBD: 24 (86%, 95%CI 79.4–92.6) had ileal/ileocolonic Crohn’s disease (CD), 3 (11%, 95%CI 5.1–16.9) unclassified IBD, and 1 (3.5%, 95%CI 0.0–6.9) ulcerative colitis. The ROC curve for FC and IBD diagnosis (AUC: 0.870, p < 0.001, 95%CI 83.7–89.8) showed that an FC ≥ 147 µg/g had a positive predictive value of 17.4% (95%CI 14.5–20.8) Conclusions: In SpA, the prevalence of undiagnosed IBD was 5.7%, higher in axSpA (8.9%) than in PsA (2.4%) patients, with CD being the most common. SpA patients with FC levels < 147 µg/g had a very low probability of IBD. Full article

Objective: The aim of this study was to examine the safety and tolerance of Bifidobacterium longum subsp. infantis YLGB-1496 (B. infantis YLGB-1496) in toddlers with respiratory illness. Methods: In this randomized controlled trial, 120 toddlers with respiratory illness were randomly assigned to the probiotic (YLGB-1496) or control group for a 12-week intervention. Follow-up examinations were conducted at baseline (week 0) and at weeks 6 and 12 of the intervention. Toddlers’ height and weight were measured by trained personnel, and defecation characteristics and gastrointestinal symptoms were recorded by parents or guardians. Stool samples were collected to determine the fecal pH, fecal calprotectin (FC) concentration, and fecal α1-antitrypsin (AAT) concentration. Results: A total of 115 toddlers completed the 12-week intervention (58 in the YLGB-1496 group and 57 in the control group). The height-for-age Z score (HAZ) in the YLGB-1496 group was significantly greater than that in the control group (p = 0.006). The weight-for-age Z score (WAZ) in the YLGB-1496 group increased between weeks 6 and 12, whereas the WAZ in the control group continuously decreased during the intervention. No differences in the frequency or consistency of defecation between the groups were observed. Toddlers in the YLGB-1496 group had lower incidences of poor appetite, nausea, vomiting, stomachache, lower abdominal pain, diarrhea, and dehydration (p < 0.05) but higher fecal AAT concentrations (p = 0.008) than did those in the control group. No differences in the fecal pH or FC concentration were observed between the groups. Conclusions: B. infantis YLGB-1496 demonstrated excellent safety and tolerability in toddlers and effectively reduced the gastrointestinal discomfort associated with respiratory illnesses. Full article

Objectives: This study aimed to evaluate the potential of salivary calprotectin (SCP) as a novel biomarker in the management of Early Onset Inflammatory Bowel Disease (EOIBD), comparing EOIBD and healthy controls and differentiating patients based on their history of oral manifestations (OM). We correlated SCP and fecal calprotectin (FCP) in EOIBD and assessed the prognostic accuracy of SCP in predicting disease relapses. Methods: A sample of stimulated saliva was collected at baseline by 27 EOIBD and 9 healthy controls and then processed by ELISA for SCP determination. At sampling, a stool specimen was also provided by each patient for routine FCP assessment. Clinical disease activity was measured through Pediatric Ulcerative Colitis Activity Index (PUCAI) or Pediatric Crohn’s Disease Activity Index (PCDAI) at baseline and during follow-up at 4, 8 and 12 weeks. Results: A history of OM was described by 13 EOIBD. EOIBD with OM reported significantly higher SCP than EOIBD without OM (p < 0.01**) and controls (p < 0.05*). When evaluating the correlation between SCP and FCP in EOIBD with OM, positive FCP values (>120 mg/kg) were found to be associated with higher SCP concentrations (p < 0.05*), while in EOIBD without OM, a negative correlation was described (p < 0.05*). Lastly, EOIBD with OM who reported higher SCP were found to have significantly increased risk of relapse (p < 0.05*). Conclusions: In EOIBD with OM SCP was significantly more elevated and was correlated to intestinal inflammation and flare-up risk. Our results suggest the potential use of SCP as prognostic biomarker in children with intestinal and oral disease. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common cause of chronic liver disease and is closely associated with metabolic abnormalities and cardiovascular risks. Butyrate, a short-chain fatty acid produced by gut microbiota, has the potential to enhance liver health by modulating inflammation and supporting gut barrier integrity. This study aimed to investigate and compare the effects of sodium butyrate and calcium butyrate in patients with MASLD. In this single-center, randomized clinical trial, 181 patients with MASLD were enrolled and assigned to receive either sodium butyrate (n = 121) or calcium butyrate (n = 60) supplementation at a daily dose of 1000 mg. The primary endpoint was the change in liver steatosis, measured using the Controlled Attenuation Parameter (CAP) via FibroScan^®. Secondary endpoints included liver stiffness, biochemical parameters, hepatic steatosis and fatty liver indices, fecal calprotectin levels, stool short-chain fatty acid levels, and microbiome composition. A subgroup analysis compared responders (a ≥ 5% reduction in CAP) to non-responders. There were no significant changes in CAP values for either group (ΔCAP: sodium butyrate, 0.84; calcium butyrate, −0.23; p = 0.70). Sodium butyrate significantly reduced serum trimethylamine N-oxide and fatty liver index, while calcium butyrate led to a decrease in fecal calprotectin levels. Responders demonstrated a lower body mass index, higher levels of high-sensitivity C-reactive protein and HbA1c, and distinct microbiome profiles, characterized by lower abundance of Subdoligranulum and higher abundance of Catenibacterium. Although butyrate supplementation did not significantly improve liver steatosis as measured by CAP, the differing effects on metabolic and inflammatory markers suggest that there may be potential benefits for specific subgroups of patients with MASLD. Full article

Background: Few studies have evaluated the efficacy of butyric acid in treating children with inflammatory bowel disease (IBD). In children and adolescents with recently diagnosed IBD, the purpose of this research was to assess the efficacy of oral sodium butyrate (the product-patented, sustained and targeted-release form of butyrate MSB^®) as an adjunct to conventional treatment. Methods: This trial was unicentric, prospective, randomized, and placebo-controlled. An amount of 150 mg sodium butyrate once a day (Group A), or a placebo (Group B) were randomly assigned to patients with ulcerative colitis or Crohn’s disease, aged 7–18 years, who were receiving conventional medication based on the severity of their conditions. Disease activity, C-reactive protein (CRP), and fecal calprotectin concentration differences between the two study groups at 12 weeks of the trial were the main outcomes. Results: With 44 patients in Group A and 44 in Group B, 88 individuals with initially active illness finished the research. Most patients experienced remission by week 12 of the study (36 patients in Group A with sodium butyrate, 81.82%; 21 patients in Group B with placebo, 47.73%). Between the two groups, a significant difference in disease activity was seen (p < 0.001). The sodium butyrate group appeared to have less systemic inflammation than the other group, as evidenced by the significantly lower CRP levels in Group A (18.14 ± 11.19 mg/L) compared to Group B (57.00 ± 33.28 mg/L) at 12 weeks (T2) (p < 0.001). No negative effects were recorded by any of the patients. Fecal calprotectin in Group A dropped much more after 12 weeks (T2) (p < 0.001), suggesting that the sodium butyrate group was better able to regulate intestinal inflammation. Conclusions: In newly diagnosed children and adolescents with IBD, a 12-week sodium butyrate supplementation did demonstrate effectiveness as an additional treatment. Full article

Background/Objectives: The consumption of highly processed foods (HPFs) is increasing on a global scale, and these foods have been associated with non-communicable diseases (NCDs). In particular, the consumption of HPFs has been associated with the intensification of inflammatory responses, with these foods being implicated in the exacerbation of chronic inflammatory conditions. Conversely, ultra-processed foods (UPFs) have been indicated as a possible factor in the pathogenesis of inflammatory bowel disease (IBD), particularly Crohn’s disease (CD). Methods: From October 2023 to October 2024, 275 patients with IBD were screened at a tertiary referral center. This study’s control cohort comprises 101 individuals from the local population. All study participants answered a questionnaire asking about the participants’ sex, body type and weight, height, age, marital status, employment, and other sociodemographic information. All subjects had to complete a food frequency questionnaire (FFQ) and the German version of the Screening Questionnaire of Highly Processed Food Consumption (sQ-HPF). IBD patients answered questions about their disease course and history as well as objective parameters of inflammation have been collected. Results: The sQ-HPF (%) showed significant differences (p < 0.001; g = −0.5) between the IBD cohort and the control group, suggesting higher HPF consumption within the IBD cohort. A subsequent analysis of the IBD cohort found no significant difference by disease type (Crohn’s disease: p = 0.441; g = −0.1; ulcerative colitis: p = 0.170; g = −0.3) or sex (women: p = 0.219; g = 0.2; men: p = 0.522; g = 0.1), but men with colitis did show higher HPF% compared to women with the same diagnosis. Spearman’s rho revealed no significant correlation between fecal calprotectin and HPF% in men with CD (p = 0.155, r = 0.191) or women with CD (p = 0.836, r = 0.026), and no correlation in men with UC (p = 0.707, r = 0.057) or women with UC (p = 0.560, r = −0.099). IBD health-related quality of life showed a significant positive correlation with HPF consumption in CD men (p = 0.026, r = 0.278), but not in CD women (p = 0.539, r = 0.075). No significant correlations between HPF consumption and health-related quality of life have been found in UC (men: p = 0.663, r = −0.064; women: p = 0.445, r = 0.121). Conclusions: The German version of the sQ-HPF is a reliable tool for rapid screening of habitual HPF% consumption in IBD patients. The findings of this analysis indicate a clear deviation from the recommended nutritional regimens for IBD, emphasizing the imperative for further investigation and the potential development of interventions to address these dietary discrepancies, with the ultimate goal of optimizing health outcomes for these patients. Full article

Inflammatory bowel disease (IBD) is a complex disorder influenced by genetic, environmental, and microbial factors, with emerging evidence highlighting the gut microbiome’s role in disease pathogenesis. This study investigates the impact of microbiome-targeted interventions in pediatric IBD by integrating multi-omics analysis, including metagenomics, metabolomics, transcriptomics, and clinical biomarkers, to identify microbial dysbiosis patterns and potential therapeutic targets. A cohort of pediatric IBD patients underwent a personalized intervention involving dietary modifications, probiotic supplementation, and selective antibiotic therapy. Microbiome composition, inflammatory markers (fecal calprotectin, CRP), and disease activity scores (PCDAI/PUCAI) were assessed before and after treatment. At the 3-month follow-up, patients showed significant clinical improvement, with reduced stool frequency (p = 0.004) and improved stool consistency (p < 0.001). Symptoms such as bloating and abdominal pain decreased, while energy levels increased (p < 0.001). Dietary changes included higher fruit, meat, and dairy intake, and lower fast-food and sweets consumption (p < 0.001). Physician assessments classified 90% as “improved”, reinforcing the effectiveness of personalized microbiome interventions. Microbiome-targeted interventions (diet, probiotics, and selective antibiotics) improved pediatric IBD outcomes by reducing pathogenic bacteria and increasing short-chain fatty acid (SCFA)-producing species, lowering inflammation and symptoms. Early-life factors (cesarean birth, and formula feeding) influence IBD risk. Personalized diets enhanced microbial balance. Integrating multi-omics supports precision medicine, offering microbiome-based biomarkers and reducing immunosuppressive reliance. Full article

Arachidonic acid levels are elevated in the colonic mucosa of patients with inflammatory bowel disease (IBD). Fecal metabolites are emerging as valuable diagnostic tools for IBD. This study aimed to investigate associations between 31 fecal fatty acids, including arachidonic acid, to identify potential correlations with disease severity. Among the 31 fatty acids analyzed in feces, dihomo-γ-linolenic acid, arachidonic acid, and adrenic acid were significantly increased in patients with IBD compared to controls. In contrast, levels of linoleic acid and γ-linolenic acid, the precursors of arachidonic acid, were similar between both groups. No significant differences in fatty acid levels were observed between patients with Crohn’s disease and ulcerative colitis. Arachidonic acid and adrenic acid levels positively correlated with fecal calprotectin, a clinically established marker of IBD severity, but showed no association with stool consistency or the Gastrointestinal Symptom Rating Scale. This suggests that these fatty acids are linked to disease severity rather than disease-related symptoms. Current IBD-specific medications had no significant impact on the fecal levels of any of the 31 fatty acids. In summary, this study demonstrates elevated fecal levels of dihomo-γ-linolenic acid, arachidonic acid, and adrenic acid in IBD patients. Normal levels of precursor fatty acids suggest that impaired downstream metabolism may contribute to the accumulation of these n-6 polyunsaturated fatty acids. Full article

Protein hydrolysates positively affect intestinal function in both humans and animals, but their impact on gut health and the gut microbial profile in cats has not been thoroughly investigated. In this study, a total of 30 adult cats were randomly assigned to one of three dietary treatments for a 60-day feeding trial. The three dietary treatments were as follows: (1) basal diet (CON), (2) diet containing 15% powdered chicken protein hydrolysate (HP15%), and (3) diet containing 15% liquid chicken protein hydrolysate (HL15%). Compared to the CON group, the HP15% group had a decreased calprotectin levels and fecal gases emissions (p < 0.05). A higher abundance of Bacteroidota, Veillonellaceae, and Bacteroidaceae, while a lower abundance of Firmicutes was showed in the HL15% group than that in the CON group (p < 0.05). At the genus level, compared with the CON group, an increased abundance of Bacteroides spp. and Bifidobacterium spp. was showed, whereas a reduced abundance of Alloprevotella spp. was presented in the HP15% and HL15% groups (p < 0.05). The metabolomic analysis revealed 1405 distinct metabolites between the HP15% and CON groups (p < 0.05, VIP-pred-OPLS-DA > 1), and the level of cholic acid decreased while the level of isodeoxycholic acid increased in the HP15% group (p < 0.05). The metabolomic analysis revealed 1910 distinct metabolites between the HL15% and CON groups (p < 0.05, VIP-pred-OPLS-DA > 1), and the levels of 4-coumaryl alcohol and enterolactone increased in the HL15% group (p < 0.05). In summary, this study suggested that partially replacing chicken meat with chicken protein hydrolysate in the diet of cats helps regulate the gut microbial community and metabolite profile and improves intestinal health. Full article

Background/Objectives: Fecal calprotectin (FC) is a biomarker of intestinal inflammation widely used in the assessment of gastrointestinal disorders. However, its role in chronic kidney disease (CKD) remains unclear. Given the growing recognition of the gut–kidney axis in CKD pathophysiology, this study aimed to investigate the association between FC levels, systemic inflammation, renal outcomes, and mortality in CKD patients. Methods: We enrolled a total of 515 CKD patients who underwent fecal calprotectin measurement between 2016 and 2023. After applying the exclusion criteria (inflammatory bowel disease, ongoing renal replacement therapy, or incomplete laboratory data), 260 patients were included in the final analysis and stratified into low-FC (<102 μg/g, n = 130) and high-FC (≥102 μg/g, n = 130) groups based on the median FC value. Factors associated with kidney disease progression and patient survival were analyzed. Results: Patients in the high-FC group (≥102 μg/g) were significantly older (72.8 ± 14.63 vs. 64.02 ± 18.15 years, p < 0.0001) and had a higher prevalence of diabetes mellitus (55.38% vs. 42.31%, p = 0.0349), heart failure (21.54% vs. 7.69%, p = 0.0016), and history of acute kidney injury (33.85% vs. 18.46%, p = 0.0048). Elevated FC was independently associated with increased mortality risk (hazards ratio [HR] 1.658, 95% confidence interval [CI] 1.034–2.658, p = 0.0357) with higher mortality rates (48.36 vs. 18.46 per 100,000 person-years). Subgroup analyses revealed stronger associations between FC and mortality in males (HR 2.160, 95% CI 1.046–4.463, p = 0.0375), elderly patients (≥75 years) (HR 2.122, 95% CI 1.209–3.725, p = 0.0088), and non-diabetic patients (HR 2.487, 95% CI 1.141–5.421, p = 0.0219). While FC was not significantly associated with end-stage kidney disease (ESKD) progression (odds ratio [OR] 1.289, 95% CI 0.455–3.650, p = 0.6323), higher FC levels paradoxically predicted slower estimated glomerular filtration rate (eGFR) decline (OR 2.763, 95% CI 1.139–6.699, p = 0.0245). Combined analysis revealed patients with both elevated FC and high-sensitivity C-reactive protein (hs-CRP) had the highest mortality risk (HR 3.504, 95% CI 1.163–10.554, p < 0.0001) compared to those with low levels of both markers. Conclusions: FC is a potential prognostic biomarker for mortality in CKD patients, independently of traditional inflammatory markers. Further research is warranted to elucidate the mechanisms underlying its paradoxical relationship with renal outcomes and its potential role in risk stratification and therapeutic targeting in CKD. Full article

Background/Objectives: Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn’s disease, is characterized by chronic gut inflammation driven by microbial dysbiosis and immune dysfunction. Current therapies primarily involve anti-inflammatory and immunomodulatory strategies; however, many patients experience an inadequate response or a gradual loss of efficacy over time. This study evaluates the clinical efficacy of personalized microbiome modulation (PMM)—an AI-driven intervention designed to restore microbial balance and improve key treatment outcomes such as symptom control and remission rates. Methods: This was a single-arm, open-label validation trial involving 27 patients with moderate-to-severe IBD who had experienced prior treatment failure. Participants underwent three months of PMM, which included personalized dietary modifications, targeted probiotic supplementation, and antimicrobial interventions based on gut microbiome sequencing. Primary outcomes included stool frequency and consistency as well as inflammatory markers (C-reactive protein and fecal calprotectin), while secondary outcomes assessed nutritional status, metabolic function, and quality of life. Statistical analyses included paired t-tests and repeated measures ANOVA to determine significant changes over time. Results: PMM led to significant clinical improvements, including a 58% reduction in stool frequency (p < 0.001) and improved stool consistency. CRP and fecal calprotectin levels decreased markedly (p < 0.001), suggesting reduced systemic inflammation. Additionally, iron, vitamin B12, and vitamin D deficiencies improved (p < 0.001), alongside weight gain and increased energy levels. Notably, patients on anti-TNF biologics showed enhanced response rates, suggesting potential synergistic effects between microbiome modulation and biologic therapy. Conclusions: This study highlights PMM as a promising adjunctive therapy for IBD, demonstrating benefits across clinical, inflammatory, and metabolic parameters. While findings support the role of microbiome-targeted interventions in disease management, larger randomized controlled trials are required to confirm the long-term efficacy and applicability in broader patient populations. Full article

Background/Objectives: Evidence is needed on the real-world outcomes of upadacitinib in patients with ulcerative colitis. This systematic review and meta-analysis evaluated the real-world effectiveness of upadacitinib for active UC. Methods: The primary outcome was clinical remission evaluated at week 8. Secondary outcomes included response, steroid-free remission, biochemical remission, colectomy, and safety. A random-effects meta-analysis model was used to calculate the pooled effect sizes (percentages or incidence rates) of effectiveness and safety outcomes. Results: Twenty-four studies with 1388 patients were included. Ninety-four percent of patients had previously failed biologics or Janus kinase inhibitors (JAKi), including 53.2% with tofacitinib. Clinical remission at week 8 was achieved in 68.4% of patients (95% confidence interval 55.5–80.2). Clinical remission was achieved in 48.3%, 71.1%, and 64.6% of patients at weeks 2 to 6, 12 to 16, and 24 to 36, respectively. Response was achieved in 72.6%, 82.1%, and 78.7% of patients at weeks 2 to 6, week 8, and weeks 12 to 16, respectively. Steroid-free remission was achieved in 39% of patients at week 8. Upadacitinib results were unaffected by prior biologic or JAKi failure. Mean fecal calprotectin level decreased from 1485.0 µ/g at baseline to 454.8 µ/g post-treatment (p < 0.01). The mean CRP level decreased from 12.3 mg/L at baseline to 4.4 mg/L post-treatment (p = 0.02). The incidence rates of colectomy, serious adverse events, and herpes zoster were 13.3, 2.3, and 1.7 per 100 patient-years, respectively. Conclusions: This meta-analysis confirms the effectiveness and safety of upadacitinib in a highly treatment-refractory population of UC patients. Full article