Timing of first abdominal operation in Crohn's disease based on a diagnostic model.

This study aims to develop a clinical diagnostic model for assessing the need for initial abdominal surgery in patients diagnosed with Crohn's disease (CD) and create a nomogram to facilitate clinical decision-making. A total of 164 surgical CD patients and 230 control CD patients were included in this retrospective analysis. Least Absolute Shrinkage and Selection Operator (Lasso) regression and binomial logistic regression were employed to select clinical variables. The 394 CD patients were randomly allocated to a training set and a validation set in a 7:3 ratio. The filtered variables were used to establish a diagnostic model and nomogram in the training set, subsequently validated in the testing set. Decision Curve Analysis (DCA) and clinical impact curve were constructed to validate the clinical applicability of the model. Binomial logistic regression analysis identified seven clinical variables with a p-value less than 0.01, including Biomarker (B), Waist-to-Height Ratio (WHtR), Intestinal obstruction, Albumin (ALB), Crohn's Disease Activity Index (CDAI), Myocardial Flow Index (MFI), and C-reactive protein (CRP). These variables were utilized to establish the diagnostic model. Calibration curves showed good alignment, with a C-index of 0.996 in the training set and 0.990 in the testing set. DCA and clinical impact curve demonstrated that the diagnostic model had good clinical efficiency and could provide clinical benefits. A validated diagnostic model for determining the timing of the first abdominal operation in CD patients was established and evaluated, showing high discriminative ability, calibration, and clinical efficiency. It can be utilized by clinicians to assess the optimal timing for transitioning CD patients from medical treatment to surgical intervention, providing valuable references for individualized treatment decisions for CD patients.

Surgical management of duodenal Crohn's disease.

BACKGROUND: The case of Crohn's disease involving the duodenum is rare, and its surgical management requires a thorough understanding. AIM: To investigate the surgical management of duodenal Crohn's disease. METHODS: We systematically reviewed patients diagnosed with duodenal Crohn's disease who underwent surgery in the Department of Geriatrics Surgery of the Second Xiangya Hospital of Central South University from January 1, 2004, to August 31, 2022. The general information, surgical procedures, prognosis, and other information of these patients were collected and summarized. RESULTS: A total of 16 patients were diagnosed with duodenal Crohn's disease, where 6 cases had primary duodenal Crohn's disease, and 10 had secondary duodenal Crohn's disease. Among patients with primary disease, 5 underwent duodenal bypass and gastrojejunostomy, and 1 received pancreaticoduodenectomy. Among those with a secondary disease, 6 underwent closure of duodenal defect and colectomy, 3 received duodenal lesion exclusion and right hemicolectomy, and 1 underwent duodenal lesion exclusion and double-lumen ileostomy. CONCLUSION: Crohn's disease involving the duodenum is a rare condition. Different surgical management should be applied for patients with Crohn's disease presenting with different clinical manifestations.

Quantitative analysis of adipose tissue for predicting Crohn's disease postoperative endoscopic recurrence and anastomotic ulcer.

OBJECTIVE: Inflammation and ulcers at the anastomotic site are frequently observed after intestinal resection surgery for Crohn's disease (CD), which often signify postoperative recurrence. Crohn's disease causes abnormalities in whole-body fat metabolism, and alterations in subcutaneous and visceral fat are potential indicators of disease development. This study aimed to quantify the areas of subcutaneous (SFA) and visceral fat (VFA) and investigate the relationship between fat tissue and endoscopic recurrence and anastomotic ulceration after Crohn's disease surgery. METHODS: We conducted a retrospective analysis of clinical data from 279 patients diagnosed with Crohn's disease. Using abdominal CT (Computed Tomography) scans at the level of the umbilicus, we measured the area of subcutaneous and visceral fat, and calculated the Mesenteric Fat Index (MFI), which is defined as the ratio of the area of visceral fat to subcutaneous fat. We compared the changes in fat tissue between surgical Crohn's disease patients and non-surgical patients in remission, as well as changes in fat tissue before and after surgery, and between patients with and without endoscopic recurrence after surgery. RESULTS: The MFI value of the surgical group was higher than that of the non-surgical group(0.88(1.27 ± 1.26) VS 0.39(0.44 ± 0.21), P < 0.001), while the SFA value was lower(70.16(92.97 ± 78.23) VS 157.64(175.96 ± 101.58), P < 0.001). Of the 134 surgical patients who underwent abdominal CT examination after surgery, the SFA value was significantly higher after surgery(143.61 ± 81.86 VS 90.87 ± 71.93, P < 0.001), and the MFI value decreased accordingly(0.57 ± 0.36 VS 1.30 ± 1.35, P < 0.001). Multivariate Cox analysis indicated that high VFA and MFI values, smoking history, and preoperative biologic therapy were all risk factors for postoperative endoscopic recurrence(p < 0.05), while high MFI values and preoperative biologic therapy were also risk factors for anastomotic ulcers(p < 0.05). The Kaplan-Meier analysis showed that these factors increased the risk of reaching the endpoint with time(p < 0.05). The ROC curve results showed that MFI value had high diagnostic value for postoperative endoscopic recurrence [AUC:0.831, 95% CI: 0.75-0.91, p < 0.001] and anastomotic ulcers [AUC:0.801, 95% CI: 0.71-0.89, p < 0.001]. CONCLUSIONS: Surgical CD patients have significantly higher MFI values but the values decline after surgery. When the preoperative MFI value is > 0.82, the risk of postoperative endoscopic recurrence increases significantly, and when the MFI value is ≥ 1.10, the risk of anastomotic ulceration after surgery increases significantly. Meanwhile, biologic therapy preoperatively also is a high-risk factor for early postoperative endoscopic recurrence or anastomotic ulcers after intestinal resection surgery.

METTL3 overexpression aggravates LPS-induced cellular inflammation in mouse intestinal epithelial cells and DSS-induced IBD in mice.

The inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory disorders of the intestine. Dysregulated cytokine secretion and signal transduction mechanisms via intestinal epithelial cells are involved in IBD pathogenesis, in which the transcription factor NF-κB plays a critical role. In this study, METTL3, which plays a key role in inflammation regulation, has been recognized significantly up-regulated in IBD samples, DSS-induced IBD mice, and LPS-treated MODE-K cells. Within LPS-treated MODE-K cells, METTL3 knockdown promoted cell viability, inhibited cell apoptosis, decreased apoptotic caspase3/9 cleavage, and decreased the levels of proinflammatory cytokines (IL-1ß, TNF-α, IL-6, and IL-18) and inflammatory enzymes (COX-2 and iNOS). Under the same conditions, METTL3 knockdown inhibited, whereas METTL3 overexpression promoted p65 phosphorylation in MODE-K cells; NF-κB inhibitor JSH-23 partially abolished the promotive effects of METTL3 overexpression upon p65 phosphorylation. Consistently, the effects of METTL3 overexpression upon LPS-stimulated MODE-K cells were partially abolished by JSH-23. Lastly, METTL3 knockdown in DSS-induced IBD mice significantly ameliorated DSS-induced IBD and inhibited DSS-induced p65 phosphorylation. In conclusion, METTL3 overexpression aggravates LPS-induced cellular inflammation in mouse intestinal epithelial cells and DSS-induced IBD in mice. The NF-κB signaling might be involved, and the regulatory mechanism remains to be investigated in our future study.

Cutting Edge: Probiotics and Fecal Microbiota Transplantation in Immunomodulation.

Probiotics are commensal or nonpathogenic microbes that confer beneficial effects on the host through several mechanisms such as competitive exclusion, antibacterial effects, and modulation of immune responses. Some probiotics have been found to regulate immune responses via immune regulatory mechanisms. T regulatory (Treg) cells, T helper cell balances, dendritic cells, macrophages, B cells, and natural killer (NK) cells can be considered as the most determinant dysregulated mediators in immunomodulatory status. Recently, fecal microbiota transplantation (FMT) has been defined as the transfer of distal gut microbial communities from a healthy individual to a patient's intestinal tract to cure some immune disorders (mainly inflammatory bowel diseases). The aim of this review was followed through the recent literature survey on immunomodulatory effects and mechanisms of probiotics and FMT and also efficacy and safety of probiotics and FMT in clinical trials and applications.