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Cureus May 2024Crohn's disease is a type of inflammatory bowel disease (IBD) that typically presents in the second or third decade of life. There are various pharmaceutical therapies...
Crohn's disease is a type of inflammatory bowel disease (IBD) that typically presents in the second or third decade of life. There are various pharmaceutical therapies that have been developed to treat the disease's symptoms. However, some patients still do not find relief with these medications and turn to other therapies such as diet modification. The underlying cause of Crohn's disease involves multiple factors such as uncontrolled inflammation and several genetic variants. While most current medication therapies control the symptoms that occur due to this uncontrolled level of inflammation, an anti-inflammatory diet (AID) may actually lower the level of inflammation in the gut and therefore reduce the amount of disease symptoms in Crohn's disease. Some such diets include the IBD-AID, Crohn's disease exclusion diet, and the Groningen AID (GrAID). This report describes a case of treatment-resistant Crohn's disease in a patient who was given all categories of pharmaceutical therapies including prednisone, budesonide, sulfasalazine, olsalazine, 6-mercaptopurine, methotrexate, mesalamine, and adalimumab. These only gave temporary relief of symptoms and eventually failed for various reasons including allergic reaction, insufficient symptom control, and antibody formation against the medication. This prompted the patient to independently research AIDs instead. In conclusion, for patients whose disease is refractory to different treatments, or who develop antibodies to the medication, AIDs may offer a solution to reduce disease symptoms and progression. Education of healthcare professionals and patients alike is vital in order for Crohn's patients to gain the benefits from dietary therapy.
PubMed: 38939280
DOI: 10.7759/cureus.61262 -
Przeglad Gastroenterologiczny 2024Inflammatory bowel disease (IBD) patients use a wide variety of immunosuppressive drugs, including biologics, but their effect on SARS-CoV-2 vaccine antibody levels...
INTRODUCTION
Inflammatory bowel disease (IBD) patients use a wide variety of immunosuppressive drugs, including biologics, but their effect on SARS-CoV-2 vaccine antibody levels remains a mystery.
AIM
We analysed whether the drugs used in the treatment of IBD patients could affect the concentration of SARS-CoV-2 antibodies.
MATERIAL AND METHODS
This is a prospective, single-centre evaluation of the persistence of SARS-CoV-2 antibodies after vaccination at various time points: every 2 months throughout the 6 month after the first dose.
RESULTS
We included a total of 346 vaccinated IBD patients in the study. A negative correlation between antibody level and time from full vaccination was confirmed for the following types of therapy: infliximab (rho = -0.32, < 0.001), adalimumab (rho = -0.35, = 0.025), and vedolizumab (rho = -0.50, < 0.001). In the case of other, long-term drug administration, a negative correlation between antibody level and time from full vaccination was confirmed for mesalazine (rho = -0.35, < 0.001), budesonide (rho = -0.58, = 0.004), systemic glucocorticoids (rho = -0.58, < 0.001), and azathioprine (rho = -0.44, < 0.001).
CONCLUSIONS
Due to the immunosuppressive and biological treatment, IBD patients are exposed to a shorter persistence of SARS-CoV-2 antibodies and require booster doses. The role of gastroenterologists in educating patients about the need to continue SARS-CoV-2 vaccination remains crucial.
PubMed: 38939061
DOI: 10.5114/pg.2023.130126 -
Clinical Nutrition ESPEN Jun 2024Inflammatory bowel disease (IBD) is characterized by recurrent inflammation of the gastrointestinal tract and has been linked to an imbalance in gut bacteria....
Multispecies synbiotics alleviate dextran sulfate sodium (DSS)-induced colitis: Effects on clinical scores, intestinal pathology, and plasma biomarkers in male and female mice.
BACKGROUND
Inflammatory bowel disease (IBD) is characterized by recurrent inflammation of the gastrointestinal tract and has been linked to an imbalance in gut bacteria. Synbiotics, which combine probiotics and prebiotics, are emerging as potential IBD treatments.
AIM
To examine the effects of four synbiotic formulations on intestinal inflammation and peripheral biomarkers in a rodent IBD model of both sexes.
METHODS
Colitis was induced in male and female C57BL/6 mice using 1% dextran sulfate sodium (DSS). Concurrently, a non-exposed control group was maintained. Starting on day 4 post-induction, DSS-exposed mice received one of four synbiotic preparations (Synbio1-4 composed of lactic acid bacteria, Bifidobacterium and dietary fibres), an anti-inflammatory drug used to treat IBD (mesalazine), or placebo (water) until day 14. Clinical symptoms and body weight were monitored daily. Blood samples (taken on days -3, 4, and 14, relative to DSS introduction), were used to analyze plasma biomarkers. At the end of the study, intestinal tissues underwent histological and morphological evaluation.
RESULTS
Compared to placebo, the Synbio1-, 2- and 3-treated groups had improved clinical scores by day 14. Synbio1 was the only preparation that led to clinical improvements to scores comparable to those of controls. The Synbio1-and 3-treated groups also demonstrated histological improvements in the colon. Plasma biomarker analyses revealed significant Synbio1-induced changes in plasma IL17A, VEGFD, and TNFRSF11B levels that correlated with improved clinical or histological scores. Sex-stratified analyses revealed that most therapeutic-like effects were more pronounced in females.
CONCLUSION
Our findings underscore the potential therapeutic benefits of specific synbiotics for IBD management. However, further research is needed to validate these outcomes in human subjects.
PubMed: 38923468
DOI: 10.1016/j.clnesp.2024.06.011 -
Toxics Jun 2024Drug-induced liver disease (DILI) represents one of the main problems in the therapeutic field. There are several non-modifiable risk factors, such as age and sex, and... (Review)
Review
Drug-induced liver disease (DILI) represents one of the main problems in the therapeutic field. There are several non-modifiable risk factors, such as age and sex, and all drugs can cause hepatotoxicity of varying degrees, including those for the treatment of inflammatory bowel diseases (IBD). The aim of this review is to illustrate the adverse effects on the liver of the various drugs used in the treatment of IBD, highlighting which drugs are safest to use based on current knowledge. The mechanism by which drugs cause hepatotoxicity is not fully understood. A possible cause is represented by the formation of toxic metabolites, which in some patients may be increased due to alterations in the enzymatic apparatus involved in drug metabolism. Various studies have shown that the drugs that can most frequently cause hepatotoxicity are immunosuppressants, while mesalazine and biological drugs are, for the most part, less associated with such complications. Therefore, it is possible to assume that in the future, biological therapies could become the first line for the treatment of IBD.
PubMed: 38922101
DOI: 10.3390/toxics12060421 -
International Immunopharmacology Jun 2024Ulcerative colitis (UC) is a type of inflammatory bowel disease associated with persistent inflammation. Animal studies proved the efficacy of metformin in UC.
BACKGROUND
Ulcerative colitis (UC) is a type of inflammatory bowel disease associated with persistent inflammation. Animal studies proved the efficacy of metformin in UC.
AIM
To investigate the potential role of metformin and its protective pathways in patients with UC.
METHODS
This is a randomized, controlled, and double-blinded clinical trial that included 60 participants with mild to moderate UC and was divided randomly into two groups (n = 30). For 6 months, the mesalamine group received 1 g of mesalamine three times daily (t.i.d.). For six months, the metformin group received mesalamine 1 g t.i.d. and metformin 500 mg twice daily. A gastroenterologist evaluated patients at baseline and 6 months after starting the treatment in order to measure serum levels of zonulin, sphingosine 1 phosphate (S1P), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Biopsies from the colon were used to measure gene expression of zonula occuldin-1 (ZO-1), signal transducer and activator of factor-3 (STAT-3), and intracellular adhesion molecule-1 (ICAM-1). The numeric pain rating scale (NRS) and partial Mayo score were also assessed for each patient.
RESULTS
When compared to the mesalamine group, the metformin group demonstrated a statistical decrease in serum IL-6, zonulin, TNF-α, SIP, gene expression of ICAM-1 and STAT-3, and a significant increase in colonic ZO-1 when compared to the mesalamine group. The metformin group also showed a significant decrease in NRS and partial Mayo score index in comparison with the mesalamine group.
CONCLUSION
Metformin may be a promising additional therapy for UC patients. Trial registration identifier: NCT05553704.
PubMed: 38917525
DOI: 10.1016/j.intimp.2024.112541 -
Inflammatory Bowel Diseases Jun 2024The efficacy data on treatment in older adults are scarce, while the greatest increase in ulcerative colitis (UC) prevalence is observed in age groups of individuals 40...
Similar Efficacy of Mesalazine in Adult and Older Adult Ulcerative Colitis Patients: Post Hoc Analysis of a Randomized Noninferiority Trial of 1600 mg vs 400 mg Tablets.
BACKGROUND
The efficacy data on treatment in older adults are scarce, while the greatest increase in ulcerative colitis (UC) prevalence is observed in age groups of individuals 40 to 65 years of age and ≥65 years of age.
AIM
We assessed the difference in rates of clinical and endoscopic response and remission in UC adults (≤60 years) and older adults (>60 years) treated with mesalazine.
METHODS
We performed a post hoc analysis of data from a phase 3 noninferiority trial of 817 UC patients treated with mesalazine for 8 and additional 26 weeks in a double-blind and open-label study, respectively. We used Wilcoxon rank sum or chi-square test to analyze differences between groups and multivariable logistic regression to determine the associations between endoscopic remission as outcome (Mayo endoscopic subscore [MES] = 0 or ≤1) and independent variables including disease duration, baseline MES, age, sex, comedications, and comorbidities.
RESULTS
Older adults had a longer disease duration, a higher number of comorbidities, concomitant medications, and higher baseline MES (2.38 ± 0.486 in older adults vs 2.26 ± 0.439 in adults; P = .008) compared with adults. We observed no difference in rates of combined clinical and endoscopic remission, clinical remission and response, and endoscopic remission and response at week 8 and 38 post-treatment. In addition to other well-known predictors of worse outcome, patients with ≥3 comedications were less likely to achieve an MES = 0 at week 8 and 38 and an MES ≤1 at week 38.
CONCLUSIONS
We observed similar efficacy of mesalazine in adult and older adult UC patients. The increased comedication number rather than age may decrease effectiveness of UC medications, highlighting the importance of healthy aging.
PubMed: 38902993
DOI: 10.1093/ibd/izae123 -
Frontiers in Pharmacology 2024Current pharmacological treatments for Ulcerative Colitis (UC) have limitations. Therefore, it is important to elucidate any available alternative or complementary...
Current pharmacological treatments for Ulcerative Colitis (UC) have limitations. Therefore, it is important to elucidate any available alternative or complementary treatment, and Chinese herbal medicine shows the potential for such treatment. As a traditional Chinese herbal medicine, Danshen-related preparations have been reported to be beneficial for UC by improving coagulation function and inhibiting inflammatory responses. In spite of this, the credibility and safety of this practice are incomplete. Therefore, in order to investigate whether Danshen preparation (DSP) is effective and safe in the treatment of UC, we conducted a systematic review and meta-analysis. PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database and CQVIP Database were searched for this review.The main observation indexes were the effect of DSP combined with mesalazine or DSP on the effective rate, platelet count (PLT), mean platelet volume (MPV) and C-reactive protein (CRP) of UC. The Cochrane risk of bias tool was used to assess the risk of bias. The selected studies were evaluated for quality and data processing using RevMan5.4 and Stata17.0 software. A total of 37 studies were included. Among them, 26 clinical trials with 2426 patients were included and 11 animal experimental studies involving 208 animals were included. Meta-analysis results showed that compared with mesalazine alone, combined use of DSP can clearly improve the clinical effective rate (RR 0.86%, 95% CI:0.83-0.88, < 0.00001) of UC. Furthermore it improved blood coagulation function by decreasing serum PLT and increasing MPV levels, and controlled inflammatory responses by reducing serum CRP, TNF-α, IL-6, and IL-8 levels in patients. Combining DSP with mesalazine for UC can enhance clinical efficacy. However, caution should be exercised in interpreting the results of this review due to its flaws, such as allocation concealment and uncertainty resulting from the blinding of the study. : http://www.crd.york.ac.uk/PROSPERO/myprospero.php, identifier PROSPERO: CRD42022293287.
PubMed: 38881869
DOI: 10.3389/fphar.2024.1334474 -
ACS Nano Jun 2024While mesalamine, a 5-aminosalicylic acid (5-ASA), is pivotal in the management of inflammatory bowel disease (IBD) through both step-up and top-down approaches in...
While mesalamine, a 5-aminosalicylic acid (5-ASA), is pivotal in the management of inflammatory bowel disease (IBD) through both step-up and top-down approaches in clinical settings, its widespread utilization is limited by low bioavailability at the desired site of action due to rapid and extensive absorption in the upper gastrointestinal (GI) tract. Addressing mesalamine's pharmacokinetic challenges, here, we introduce nanoassemblies composed exclusively of a mesalamine prodrug that pairs 5-ASA with a mucoadhesive and cathepsin B-cleavable peptide. In an IBD model, orally administered nanoassemblies demonstrate enhanced accumulation and sustained retention in the GI tract due to their mucoadhesive properties and the epithelial enhanced permeability and retention (eEPR) effect. This retention enables the efficient uptake by intestinal pro-inflammatory macrophages expressing high cathepsin B, triggering a burst release of the 5-ASA. This cascade fosters the polarization toward an M2 macrophage phenotype, diminishes inflammatory responses, and simultaneously facilitates the delivery of active agents to adjacent epithelial cells. Therefore, the nanoassemblies show outstanding therapeutic efficacy in inhibiting local inflammation and contribute to suppressing systemic inflammation by restoring damaged intestinal barriers. Collectively, this study highlights the promising role of the prodrug nanoassemblies in enhancing targeted drug delivery, potentially broadening the use of mesalamine in managing IBD.
Topics: Mesalamine; Prodrugs; Macrophages; Inflammatory Bowel Diseases; Animals; Mice; Humans; Nanoparticles; Intestinal Mucosa; Mice, Inbred C57BL; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 38867457
DOI: 10.1021/acsnano.4c05544 -
Immunity, Inflammation and Disease Jun 2024Banxia Xiexin decoction (BXD) can control irinotecan (CPT-11)-caused delayed diarrhea, but the corresponding mechanism remains undefined.
BACKGROUND
Banxia Xiexin decoction (BXD) can control irinotecan (CPT-11)-caused delayed diarrhea, but the corresponding mechanism remains undefined.
AIMS
This paper aimed to uncover the mechanism of BXD in regulating CPT-11-caused delayed diarrhea.
MATERIALS & METHODS
Sprague-Dawley (SD) rats were assigned into the control, model, BXD low-dose (BXD-L, 5 g/kg), BXD medium-dose (BXD-M, 10 g/kg), BXD high-dose (BXD-H, 15 g/kg), 5-aminosalicylic acid (5-ASA, 10 mL/kg), and BXD-M + 5-ASA groups. Rats were injected intraperitoneally with 150 mg/kg CPT-11 at Day 4 and Day 5 to induce delayed diarrhea, and later treated with various doses (low, medium, and high) of BXD and 5-ASA for 9 days, except for rats in control group. The body weight of rats was measured. The rat colon tissue injury, inflammatory cytokine levels, and the activation of toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signaling pathway were detected.
RESULTS
BXD (5, 10, or 15 g/kg) or 5-ASA (10 mL/kg) alleviated body weight loss and colon tissue injury, decreased levels of inflammatory cytokines, and inactivated TLR4/NF-κB signaling pathway in CPT-11-induced model rats. BXD at 10 g/kg (the optimal concentration) could better treat CPT-11-induced intestinal dysfunction, as evidenced by the resulting approximately 50% reduction on injury score of model rats. Moreover, BXD-M (10 g/kg) synergistic with 5-ASA (10 mL/kg) further strengthened the inhibition on rat body weight loss, colon tissue injury, inflammatory cytokine levels, and TLR4/NF-κB signaling pathway.
CONCLUSION
To sum up, BXD has a protective effect against CPT-11-induced intestinal dysfunction by inhibiting inflammation through inactivation TLR4/NF-κB signaling pathway. In particular, the combined use of BXD and 5-ASA holds great promise for treating CPT-11-induced delayed diarrhea.
Topics: Animals; Toll-Like Receptor 4; NF-kappa B; Rats; Signal Transduction; Irinotecan; Drugs, Chinese Herbal; Rats, Sprague-Dawley; Diarrhea; Male; Mesalamine; Disease Models, Animal; Drug Therapy, Combination
PubMed: 38860759
DOI: 10.1002/iid3.1208 -
Clinical Gastroenterology and... Jun 2024Management of inflammatory bowel diseases (IBD) is complex and variation in care has been well-documented. However, the drivers of practice variation remain unexplored....
BACKGROUND
Management of inflammatory bowel diseases (IBD) is complex and variation in care has been well-documented. However, the drivers of practice variation remain unexplored. We examined variation based on the treating gastroenterologist's IBD focus (proportion of outpatient visits for IBD).
METHODS
We conducted a retrospective cohort of newly diagnosed patients with IBD using data from Optum's de-identified Clinformatics® Data Mart Database (2000-2020). The exposure variable was whether the treating gastroenterologist had an IBD-focus (>90 percentile of IBD visits/total outpatient visits). We used adjusted regression models to evaluate associations between provider IBD focus and process measures (use of meslamine, corticosteroid, biologic and narcotic medications and endoscopic or radiographic imaging) and clinical outcomes (time to IBD-related hospitalization and bowel resection surgery). We tested for change in treatment patterns over time by including an interaction term for study era (2004-2012 versus 2013-2020).
RESULTS
The study included 772 children treated by 493 providers and 2864 adults treated by 2076 providers. In children, none of the associations between provider focus and process or outcome measures were significant. In adults, care from an IBD-focused provider was associated with more use of biologics, combination therapy, and imaging and endoscopy, and less mesalamine use for Crohn's disease (P<.05 for all comparisons) but not with other process measures. Biologics were prescribed more frequently and narcotics less frequently during the later era (P<.05 for both). Hospitalization and surgery rates were not associated with IBD-focus or era.
CONCLUSIONS
IBD care for adults varies by provider specialization. Given the evolving complexity, novel methods may be needed to standardize care.
PubMed: 38844254
DOI: 10.1016/j.cgh.2024.05.024