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Heliyon Mar 2024Ulcerative colitis is a common type of inflammatory bowel disease that affects millions of individuals around the world. Traditional UC treatment has focused on...
Ulcerative colitis is a common type of inflammatory bowel disease that affects millions of individuals around the world. Traditional UC treatment has focused on suppressing immune responses rather than treating the underlying causes of UC, which include oxidative stress, inflammation, and microbiota dysbiosis. Diosmin (DIO), a naturally occurring flavonoid, possesses antioxidant and anti-inflammatory properties. This study aimed to assess the efficacy of DIO in treating dextran-sulfate sodium (DSS)-induced colitis, and to investigate some of its underlying mechanisms, with an emphasis on abundance, inflammatory markers, and intestinal barrier function. C57BL/6 mice were given 4% (w/v) DSS to induce colitis. DSS-induced mice were administered DIO (100 and 200 mg/kg) or sulfasalazine orally for 7 days. Every day, the disease activity index (DAI) was determined by recording body weight, diarrhea, and bloody stool. Changes in fecal abundance, colonic MUC1 and MUC2 expression, as well as oxidative stress and inflammatory markers were all assessed. Histopathological changes, colonic PIK3PR3 and ZO-1 levels, and immunohistochemical examinations of occludin and claudin-1, were investigated. DIO administration resulted in a dose-dependent decrease in DAI, as well as increase in abundance and MUC2 expression while decreasing MUC1 expression. DIO also dramatically reduced colonic oxidative stress and inflammation by regulating the NF-κB and Nrf2 cascades, restored intestinal barrier integrity by inhibiting PIK3R3 and inducing ZO-1, and improved occludin/claudin-1 gene expression and immunostaining. This study provides the first evidence that DIO preserves intestinal barrier integrity and increases abundance in DSS-induced colitis. However, more research is required to explore the impact of DIO on the overall composition and diversity of the gut microbiota. Likewise, it will be important to fully understand the molecular mechanisms by which maintains intestinal barrier function and its potential use as an adjuvant in the treatment of UC.
PubMed: 38500992
DOI: 10.1016/j.heliyon.2024.e27527 -
Rheumatology and Therapy Jun 2024Short-term placebo (PBO)- or active-controlled clinical studies have demonstrated that etanercept (ETN) is effective and well tolerated in patients with radiographic...
INTRODUCTION
Short-term placebo (PBO)- or active-controlled clinical studies have demonstrated that etanercept (ETN) is effective and well tolerated in patients with radiographic axial spondyloarthritis (r-axSpA) with long-term efficacy and safety continuing for up to 7 years after treatment start. Short-term randomized controlled trials (RCTs) have shown the efficacy of ETN after 12-24 weeks, with statistically significant improvements as early as week 2. This post hoc analysis investigated the timeframe (i.e., temporal responses) in which patients with r-axSpA achieved their first clinical response with ETN and how patients responded over a longer period according to different temporal responses in index studies.
METHODS
Data were analyzed from three phase 3/4 PBO- or sulfasalazine-controlled RCTs of ETN for the treatment of r-axSpA (index studies). Long-term open-label extension (OLE) studies assessed how patients responded over a longer period according to different temporal responses ("Early," "Intermediate," "Late," or "Non-response") in their corresponding index studies.
RESULTS
Within each index study, patient responses differed significantly between ETN and control arms for achievement of Assessment in SpondyloArthritis international Society (ASAS) 20 and other measures of treatment response. In general, the proportion of responders in the OLE studies was high for those with "Early" and "Intermediate" responses as defined in the index studies. Despite patients being considered non-responders in the index studies, a large proportion achieved response on continued treatment in the OLE studies over the longer term, including through 48 weeks.
CONCLUSIONS
Response in the index studies was maintained in the long term, and continued treatment was warranted in a large proportion of patients despite initial non-response. Absence of an early response in index studies did not predict non-response over the long term, and early response to treatment was not always a predictor for later response.
TRIAL REGISTRATION
NCT00421915; NCT00247962; NCT00356356; NCT00421980; NCT00410046.
PubMed: 38488976
DOI: 10.1007/s40744-024-00656-3 -
International Journal of Rheumatic... Mar 2024
Topics: Humans; Sulfasalazine; Drug Hypersensitivity; Syndrome; Sulfonamides
PubMed: 38488376
DOI: 10.1111/1756-185X.15108 -
Oral and Maxillofacial Surgery Mar 2024Pyodermatitis-pyostomatitis vegetans (PPV) is a rare mucocutaneous disease characterized by multiple pustules and it is considered a marker for inflammatory bowel...
BACKGROUND
Pyodermatitis-pyostomatitis vegetans (PPV) is a rare mucocutaneous disease characterized by multiple pustules and it is considered a marker for inflammatory bowel disease (IBD). The oral manifestations of this condition are referred to as pyostomatitis vegetans (PSV).
PURPOSE
To investigate which features could help in establishing the diagnosis of PSV, with or without cutaneous lesions, based on information retrieved from all cases of PSV described in the literature. A case of PV from the authors was also included in the analysis.
METHODS
An electronic search was undertaken, last updated in August 2022. Inclusion criteria included publications reporting cases of PSV, with the diagnosis confirmed by the pathological examination of oral or skin lesions, and presence of IBD.
RESULTS/CONCLUSIONS
Sixty-two publications with 77 cases of PSV and an associated IBD were included. Features that are helpful in establishing the diagnosis of PSV are snail track appearance of oral lesions, an associated IBD (which is not always symptomatic), evidence of intraepithelial clefting on microscopic examination of oral lesions, and peripheral blood eosinophilia. A gold standard for the management of PSV does not exist and high-level evidence is limited. There is no established therapeutic protocol for PSV and management primarily consists of topical and/or systemic corticosteroids, antirheumatic drugs (sulfasalazine, mesalazine), monoclonal antibody (infliximab, adalimumab) immunosuppressives (azathioprine, methotrexate), antibiotics (dapsone), or a combination of these. The risk of recurrence of oral lesions is considerable when the medication dose is decreased or fully interrupted.
PubMed: 38467949
DOI: 10.1007/s10006-024-01234-1 -
Journal of Cutaneous Medicine and... 2024
Topics: Humans; Pyoderma Gangrenosum; Sulfasalazine; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 38462891
DOI: 10.1177/12034754241238713 -
Transplantation and Cellular Therapy May 2024Inborn errors of immunity (IEI) are often associated with inflammatory bowel disease (IBD). IEI can be corrected by allogeneic hematopoietic stem cell transplantation...
Inborn errors of immunity (IEI) are often associated with inflammatory bowel disease (IBD). IEI can be corrected by allogeneic hematopoietic stem cell transplantation (HSCT); however, peritransplantation intestinal inflammation may increase the risk of gut graft-versus-host disease (GVHD). Vedolizumab inhibits the homing of lymphocytes to the intestine and may attenuate gut GVHD, yet its role in preventing GVHD in pediatric patients with IEI-associated IBD has not been studied. Here we describe a cohort of pediatric patients with IEI-associated IBD treated with vedolizumab before and during allogeneic HSCT. The study involved a retrospective chart review of pediatric patients with IEI-associated IBD treated with vedolizumab at 6 weeks, 4 weeks, and 1 week before undergoing HSCT. The conditioning regimen consisted of treosulfan, fludarabine, and cyclophosphamide with rabbit antithymocyte globulin, and GVHD prophylaxis included tacrolimus and steroids. Eleven patients (6 females) with a median age of 5 years (range, 0.4 to 14 years) with diverse IEI were included. IBD symptoms were characterized by abdominal pain, loose stools, and blood in stools. Four patients had developed a perianal fistula, and 1 patient had a rectal prolapse. One patient had both a gastrostomy tube and a jejunal tube in situ. Treatment of IBD before HSCT included steroids in 11 patients, anakinra in 2, infliximab in 4, sulfasalazine in 2, mesalazine in 2, and vedolizumab. IBD symptoms were considered controlled in the absence of abdominal pain, loose stools, or blood in stools. Graft sources for HSCT were unrelated donor cord in 5 patients (2 with a 5/8 HLA match, 2 with a 7/8 match, and 1 with a 6/8 match), peripheral blood stem cells in 5 patients (2 haploidentical, 1 with a 9/10 HLA match, and 2 with a 10/10 match), and bone marrow in 1 patient (10/10 matched sibling donor). The median number of vedolizumab infusions was 4 (range, 3 to 12) before HSCT and 1 (range, 1 to 3) after HSCT, and all were reported to be uneventful. All patients had engrafted. Acute GVHD occurred in 4 patients and was limited to grade I skin GVHD only. Chronic GVHD occurred in 1 patient and again was limited to the skin. There was no gut GVHD. Three patients experienced cytomegalovirus viremia, and 2 patients had Epstein-Barr virus viremia. At the time of this report, all patients were alive with no evidence of IBD at a median follow-up of 15 months (range, 3 to 39 months). Administration of vedolizumab pre- and post-HSCT in pediatric patients with IEI-associated IBD is well tolerated and associated with a low rate of gut GVHD. These findings provide a platform for the prospective study and use of vedolizumab for GVHD prophylaxis in pediatric patients with known intestinal inflammation as a pre-HSCT comorbidity.
Topics: Humans; Antibodies, Monoclonal, Humanized; Hematopoietic Stem Cell Transplantation; Female; Child; Male; Adolescent; Child, Preschool; Inflammatory Bowel Diseases; Retrospective Studies; Graft vs Host Disease; Infant; Transplantation, Homologous; Immunomodulation; Transplantation Conditioning
PubMed: 38458476
DOI: 10.1016/j.jtct.2024.03.006 -
International Journal of Rheumatic... Mar 2024Acute anterior uveitis (AAU) is the most common extra-musculoskeletal manifestation in axial spondyloarthritis (axSpA). (Observational Study)
Observational Study
BACKGROUNDS
Acute anterior uveitis (AAU) is the most common extra-musculoskeletal manifestation in axial spondyloarthritis (axSpA).
OBJECTIVES
The aim of the study is to evaluate the factors associated with AAU attacks in patients with axSpA during a 36-month follow-up period.
METHODS
In total, 469 patients with axSpA were included in this observational study. Demographic data, clinical characteristics, disease activity measurements, and treatment patterns were compared between patients with and without a history of AAU. The development of AAU and its related factors were investigated using generalized estimating equations, which is a technique for longitudinal data analysis.
RESULTS
Overall, 99 (21%) out of 469 patients experienced at least one AAU attack, with 77 patients (78%) having a history of AAU and 53 patients (58% of whom had a history of AAU) experiencing AAU attacks during the follow-up period. At baseline, patients with a history of AAU were found to be older (p = .001), be more likely to have peripheral arthritis (p < .001), have higher serum CRP levels (p = .016), have a higher frequency of sulfasalazine (SLZ) and tumor necrosis factor inhibitors (TNFi) use (p < .001 and p < .001, respectively). In the longitudinal analysis, having a history of AAU was identified as the only independent determinant of the development of AAU.
CONCLUSIONS
AAU history might be a risk factor for the development of AAU attacks in patients with axSpA. Although TNFi and SLZ were prescribed more frequently to patients with a history of AAU, the effectiveness of these agents in preventing further AAU attacks was not demonstrated.
Topics: Humans; Longitudinal Studies; Spondylarthritis; Spondylitis, Ankylosing; Uveitis, Anterior; Axial Spondyloarthritis; Sulfasalazine; Acute Disease
PubMed: 38454194
DOI: 10.1111/1756-185X.15076 -
RMD Open Mar 2024Sulfasalazine-induced cytopenia, nephrotoxicity and hepatotoxicity is uncommon during long-term treatment. Some guidelines recommend 3 monthly monitoring blood tests...
BACKGROUND
Sulfasalazine-induced cytopenia, nephrotoxicity and hepatotoxicity is uncommon during long-term treatment. Some guidelines recommend 3 monthly monitoring blood tests indefinitely during long-term treatment while others recommend stopping monitoring after 1 year. To rationalise monitoring, we developed and validated a prognostic model for clinically significant blood, liver or kidney toxicity during established sulfasalazine treatment.
DESIGN
Retrospective cohort study.
SETTING
UK primary care. Data from Clinical Practice Research Datalink Gold and Aurum formed independent development and validation cohorts.
PARTICIPANTS
Age ≥18 years, new diagnosis of an inflammatory condition and sulfasalazine prescription.
STUDY PERIOD
1 January 2007 to 31 December 2019.
OUTCOME
Sulfasalazine discontinuation with abnormal monitoring blood-test result.
ANALYSIS
Patients were followed up from 6 months after first primary care prescription to the earliest of outcome, drug discontinuation, death, 5 years or 31 December 2019. Penalised Cox regression was performed to develop the risk equation. Multiple imputation handled missing predictor data. Model performance was assessed in terms of calibration and discrimination.
RESULTS
8936 participants were included in the development cohort (473 events, 23 299 person-years) and 5203 participants were included in the validation cohort (280 events, 12 867 person-years). Nine candidate predictors were included. The optimism adjusted R and Royston D statistic in the development data were 0.13 and 0.79, respectively. The calibration slope (95% CI) and Royston D statistic (95% CI) in validation cohort was 1.19 (0.96 to 1.43) and 0.87 (0.67 to 1.07), respectively.
CONCLUSION
This prognostic model for sulfasalazine toxicity uses readily available data and should be used to risk-stratify blood-test monitoring during established sulfasalazine treatment.
Topics: Humans; Adolescent; Sulfasalazine; Prognosis; Retrospective Studies
PubMed: 38453215
DOI: 10.1136/rmdopen-2023-003980 -
Heliyon Mar 2024Long noncoding RNA (lncRNAs) are involved in the pathogenesis of ulcerative colitis (UC). Moxibustion, a traditional Chinese medicine, can improve symptoms in patients...
Long noncoding RNA (lncRNAs) are involved in the pathogenesis of ulcerative colitis (UC). Moxibustion, a traditional Chinese medicine, can improve symptoms in patients with UC and reduce intestinal inflammation in rats with UC. However, it remains unclear whether the ameliorative effect of moxibustion on intestinal mucosal inflammation in UC is related to lncRNAs. Thirty-two rats were randomly assigned to four groups: normal control, UC, moxibustion (MOX), and sulfasalazine (SASP). The UC rat model was induced by administering 4% dextran sulfate sodium (DSS) in drinking water. Rats in the moxibustion group underwent bilateral Tianshu (ST25) moxibustion using the herbs-partition moxibustion method. Rats in the sulfasalazine group received SASP solution gavage twice daily for seven consecutive days. Our results revealed that, compared with the UC group [2.00 (1.00, 2.50)], the DAI score [0.25 (0.00, 0.50)] was significantly lower in the MOX group ( < 0.05). Compared with the UC group [13.00 (11.25, 14.00)], the histopathological score [5.50 (4.00, 7.75)] was significantly lower in the MOX group ( < 0.05). In addition, the CMDI and macroscopic scores were decreased in the MOX group ( < 0.05). Moxibustion significantly decreased the protein expression of inflammatory factors TNF-α, IFN-γ, and IL-1β in the colonic tissues of UC rats (0.05), thereby suppressing the inflammatory response. Moreover, moxibustion exerted a regulatory influence on colon lncRNA and mRNA expression profiles, upregulating LOC108352929 and downregulating Phf11 in rats with UC (0.05). Moxibustion also led to a reduction in the expression and colocalization of Phf11 and NF-κB in the colons of UC rats. Moreover, knockdown of LOC108352929 in rat enteric glial cells demonstrated a significant upregulation of TNF-α mRNA expression (0.05). In summary, these data illustrate that moxibustion effectively ameliorates DSS-induced colonic injury and inflammation while exerting regulatory control over the lncRNA-mRNA co-expression network in UC rats. Collectively, the and studies suggested that LOC108352929-Phf11 may serve as a potential biological marker for moxibustion in the treatment of UC.
PubMed: 38439851
DOI: 10.1016/j.heliyon.2024.e26898