Alimentary Pharmacology & Therapeutics最新文献

Background: Variant-adapted COVID-19 vaccines are recommended for patients with inflammatory bowel disease (IBD). However, many patients rely on pre-existing immunity by original vaccines or prior infections.

Aim: To assess whether such immunity sufficiently combats the highly immune-evasive SARS-CoV-2 JN.1 variant.

Methods: Utilising two longitudinal cohorts, we evaluated immunity against JN.1 induced by original vaccines (IBD: n = 98; healthy: n = 48), omicron breakthrough infection (IBD: n = 55; healthy: n = 57) or XBB.1.5-adapted vaccines (IBD: n = 18). Neutralisation and anti-receptor-binding domain (RBD) IgG levels against wild-type SARS-CoV-2 and JN.1 were assessed using multiplex immunoassays. Study outcomes were wild-type and JN.1 neutralisation following three doses of original mRNA vaccines, stratified by immunosuppressive therapy (primary outcome), and JN.1 neutralisation following third-dose breakthrough infection or a fourth dose of XBB.1.5-adapted mRNA vaccines (secondary outcomes).

Results: Following original vaccines, JN.1 neutralisation was lower than wild-type neutralisation in all study groups (healthy, anti-TNF and non-anti-TNF; each p < 0.001); most individuals lacked JN.1 neutralisation (healthy: 97.9%; anti-TNF: 98.3% and non-anti-TNF: 92.3%). Confounder-adjusted multivariable modelling strongly associated anti-TNF therapy with low levels of anti-JN.1-RBD IgG (fold-change 0.48 [95% CI 0.39-0.59]). JN.1 neutralisation was similar in patients with or without breakthrough infection (anti-TNF, non-anti-TNF; each p > 0.05); neutralisation failure was 100% despite breakthrough infection. XBB.1.5-adapted vaccines enhanced JN.1 neutralisation (p < 0.001) and reduced neutralisation failure rates in patients with IBD (94.4% pre-vaccination vs. 44.4% post-vaccination; p = 0.003).

Conclusions: Only variant-adapted vaccines protect against emerging SARS-CoV-2 variants. Patients with IBD and healthy individuals without recent vaccination may lack protection against the JN.1 subvariant KP.3 which causes current COVID-19 surges.

Background: The Rome IV criteria for irritable bowel syndrome (IBS) may be too restrictive for clinical practice and research.

Aims: To validate the Rome IV criteria and study the diagnostic performance of simple modifications to them.

Methods: We collected symptom data from consecutive adults with suspected IBS seen in a single clinic. We used a reference standard to confirm IBS (presence of lower abdominal pain associated with altered stool form or frequency; no evidence of organic gastrointestinal disease after limited investigation). We applied Rome IV criteria, but also two modifications. First, we re-incorporated abdominal discomfort but kept symptom frequency required for both abdominal pain and discomfort to at least 1 day per week. Second, we included only abdominal pain but relaxed symptom frequency back to 3 days per month. We calculated sensitivity, specificity and positive and negative likelihood ratios (LRs), with 95% confidence intervals (CIs), for each diagnostic criterion.

Results: We recruited 170 patients (76.5% female, mean age 37.9 years). Sensitivity and specificity of the Rome IV criteria were 82.1% and 85.1%, respectively; positive and negative LRs were 5.51 (95% CI 2.95-11.3) and 0.21 (95% CI 0.14-0.31), respectively. Modifying the criteria by relaxing the frequency of abdominal pain to 3 days per month led to the best performance [sensitivity 90.2%, specificity 85.1%, positive LR 6.06 (95% CI 3.25-12.2), and negative LR 0.11 (95% CI 0.07-0.19)].

Conclusions: The Rome IV criteria performed well in diagnosing IBS. A simple modification relaxing the required frequency of abdominal pain improved their performance.

Background: Perianal fistulas of Crohn's disease (CD) create a significant burden on patients' lives. However, the efficacy and safety of adipose-derived mesenchymal stem cell treatment are contradicting, and real-world evidence is lacking.

Aims: To examine the usability of darvadstrocel therapy in managing perianal CD.

Methods: We enrolled patients with CD and perianal fistulas in this retrospective multicenter study. The primary outcome was perianal clinical remission (defined as all treated fistulas closed) at weeks 26 and 52. Secondary outcomes were clinical response rates (≥ 1 fistulas closed), perianal activity (PDAI), patient satisfaction, and adverse events. Data were recorded at baseline and weeks 12, 26 and 52. Prediction of primary outcomes was performed by logistic regression.

Results: Overall, among 223 patients (male/female ratio: 0.48), perianal clinical remission was achieved in 78.2% and 62.3% until weeks 26 and 52. Baseline PDAI score (OR 0.75), number of fistulas (OR 0.28) and the number of weeks after preparation for surgery (OR 0.98) were associated with treatment failure. The clinical response rates were 84.8% and 79.8% at weeks 26 and 52. Improvement of subjective perianal symptoms was achieved in 77.8% and 78.4% of patients, respectively. Adverse events occurred in 13.5% of patients; perianal abscesses and proctalgia were the most frequently reported.

Conclusion: Effectiveness data were higher than in clinical trials. The safety profile was reassuring, and patients' satisfaction was high. Appropriate patient selection, fistula preparation and expertise may help to achieve treatment success.