Silk fibroin/chitosan-based anal fistula scaffolds loaded with curcumin and 5-aminosalicylic acid.

The present work describes the development of silk fibroin (SF)/chitosan (CS)-based porous composite anal fistula scaffold (SCAFS) with anti-inflammatory and healing functions. The SCAFS comprises an inner layer made from degummed silk fiber using a vertical braiding machine, and an outer layer created by freeze-drying a mixture of short SF fibers and curcumin (CUR)/5-aminosalicylic acid (5-ASA) loaded SF/CS solution. Results revealed that the SCAFS has high porosity of 42.4 %, remarkable water absorption rate of 370.5 %, robust dry/wet compression resistance of 12.28 ± 2.61 N/3.08 ± 0.43 N. The in vitro & in vivo biocompatibility and anti-inflammatory effect of SCAFS were further examined. The expression of pro-inflammatory cytokine TNF-α, anti-inflammatory cytokine IL-10, CD31 and CD68 was determined by immunohistochemistry (IHC) staining, H&E staining, Immunofluorescence (IF) staining and Masson assay. The results showed that the scaffolds possess a sustainable drug release above 400 h, better biocompatibility and anti-inflammatory effect than the control groups (p < 0.05). Thus, the SCAFS has potential application in the treatment of Crohn's disease.

CT-based radiomics signature of visceral adipose tissue and bowel lesions for identifying patients with Crohn's disease resistant to infliximab.

PURPOSE: To develop a CT-based radiomics model combining with VAT and bowel features to improve the predictive efficacy of IFX therapy on the basis of bowel model. METHODS: This retrospective study included 231 CD patients (training cohort, n = 112; internal validation cohort, n = 48; external validation cohort, n = 71) from two tertiary centers. Machine-learning VAT model and bowel model were developed separately to identify CD patients with primary nonresponse to IFX. A comprehensive model incorporating VAT and bowel radiomics features was further established to verify whether CT features extracted from VAT would improve the predictive efficacy of bowel model. Area under the curve (AUC) and decision curve analysis were used to compare the prediction performance. Clinical utility was assessed by integrated differentiation improvement (IDI). RESULTS: VAT model and bowel model exhibited comparable performance for identifying patients with primary nonresponse in both internal (AUC: VAT model vs bowel model, 0.737 (95% CI, 0.590-0.854) vs. 0.832 (95% CI, 0.750-0.896)) and external validation cohort [AUC: VAT model vs. bowel model, 0.714 (95% CI, 0.595-0.815) vs. 0.799 (95% CI, 0.687-0.885)), exhibiting a relatively good net benefit. The comprehensive model incorporating VAT into bowel model yielded a satisfactory predictive efficacy in both internal (AUC, 0.840 (95% CI, 0.706-0.930)) and external validation cohort (AUC, 0.833 (95% CI, 0.726-0.911)), significantly better than bowel alone (IDI = 4.2% and 3.7% in internal and external validation cohorts, both p < 0.05). CONCLUSION: VAT has an effect on IFX treatment response. It improves the performance for identification of CD patients at high risk of primary nonresponse to IFX therapy with selected features from RM. CRITICAL RELEVANCE STATEMENT: Our radiomics model (RM) for VAT-bowel analysis captured the pathophysiological changes occurring in VAT and whole bowel lesion, which could help to identify CD patients who would not response to infliximab at the beginning of therapy. KEY POINTS: • Radiomics signatures with VAT and bowel alone or in combination predicting infliximab efficacy. • VAT features contribute to the prediction of IFX treatment efficacy. • Comprehensive model improved the performance compared with the bowel model alone.

Computed tomography-based radiomics nomogram using machine learning for predicting 1-year surgical risk after diagnosis of Crohn's disease.

BACKGROUND: Identifying patients with aggressive Crohn's disease (CD) threatened by a high risk of early onset surgery is challenging. PURPOSE: We aimed to establish and validate a radiomics nomogram to predict 1-year surgical risk after the diagnosis of CD, thereby facilitating therapeutic strategies making. METHODS: Patients with CD who had undergone baseline computed tomography enterography (CTE) examination at diagnosis were recruited and randomly divided into training and test cohorts at a ratio of 7:3. Enteric phase CTE images were obtained. Inflamed segments and mesenteric fat were semiautomatically segmented, followed by feature selection and signature building. A nomogram of radiomics was constructed and validated using a multivariate logistic regression algorithm. RESULTS: A total of 268 eligible patients were retrospectively included, 69 of whom underwent surgery 1-year after diagnosis. A total of 1218 features from inflamed segments and 1218 features from peripheral mesenteric fat were extracted, and reduced to 10 and 15 potential predictors, respectively, to construct two radiomic signatures. By incorporating the radiomics signatures and clinical factors, the radiomics-clinical nomogram showed favorable calibration and discrimination in the training cohort, with an area under the curve (AUC) of 0.957, which was confirmed in the test set (AUC, 0.898). Decision curve analysis and net reclassification improvement index demonstrated the clinical usefulness of the nomogram. CONCLUSIONS: We successfully established and validated a CTE-based radiomic nomogram with both inflamed segment and mesenteric fat simultaneously evaluated to predict 1-year surgical risk in CD patients, which assisted in clinical decision-making and individualized management.

Extra intravenous Ustekinumab reinduction is an effective optimization strategy for patients with refractory Crohn's disease.

Objectives: Ustekinumab (UST) optimization strategies, including shortening intervals and intravenous reinduction, should be administered to patients with partial or loss of respond. Evidence comparing these types of optimization treatments is limited. We evaluated the efficacy and safety of weight-based UST intravenous reinduction in patients with refractory Crohn's disease (CD). Methods: This was a single-center retrospective observational study. Optimization strategies were designed for patients showing partial or loss of response to standardized UST therapy. Clinical, biochemical, and endoscopic response and remission rate were determined by Crohn's disease activity index (CDAI), C-reactive protein (CRP) levels, and SES-CD evaluation. UST trough concentrations were detected and adverse events were recorded. Results: A total of 128 patients receiving UST optimization therapies were included, with 105 patients administered shortening intervals of q8w or q4w, and 23 receiving intravenous reinduction followed by subcutaneous q8w or q4w. The follow-up duration for the shortening interval and reinduction cohorts were 15.0 (10.0, 31.0) and 23.0 (13.0, 70.0) weeks, respectively. A significant CDAI delta variation pre-and post-treatment could be found between groups [17.0 (-4.4, 65.9) vs. 69.0(10.7, 151.0), p = 0.013]. the trough concentration of UST increased [2.5 (1.3, 5.3) vs. 1.1 (0.5, 2.3), p = 0.001] after intravenous reinduction. Clinical and endoscopic remission were achieved in 69.6 and 31.8% of patients in the intravenous reinduction cohort, and 62.9 and 22.2% of patients in the shortening interval cohort, respectively. No significant difference was found between groups regarding safety. Conclusion: Intravenous reinduction brought about favorable recapture of clinical and endoscopic remission, and should have significant priority over the strategy of merely shortening drug intervals, which should be launched before switching to other biologics targeting different inflammatory pathways.Clinical Trial Registration: identifier NCT04923100. https://classic.clinicaltrials.gov/ct2/show/NCT04923100?id=04923100&draw=2&rank=1.

Preoperative computed tomography enterography-based radiomics signature: A potential predictor of postoperative anastomotic recurrence in patients with Crohn's disease.

BACKGROUND: More than half of patients with Crohn's disease (CD) require at least one surgery for symptom management; however, approximately half of the patients may experience postoperative anastomotic recurrence (PAR). OBJECTIVES: This study aims to develop and validate a preoperative computed tomography enterography (CTE)-based radiomics signature to predict early PAR in CD. DESIGN: A total of 186 patients with CD (training cohort, n = 134; test cohort, n = 52) who underwent preoperative CTE and surgery between January 2014 and June 2020 were included in this retrospective multi-centre study. METHODS: 106 radiomic features were initially extracted from intestinal lesions and peri-intestinal mesenteric fat, respectively; significant radiomic features were selected from them and then used to develop intestinal or mesenteric radiomics signatures, using the least absolute shrinkage and selection operator and a Cox regression model. A radiomics-based nomogram incorporating these signatures with clinical-radiological factors was created for comparison with a model based on clinical-radiological features alone. RESULTS: 68 of 134 patients in training cohort and 16 of 52 patients in test cohort suffered from PAR. The intestinal radiomic signature (hazard ratio [HR]: 2.17; 95% confidence interval [CI]: 1.32-3.58; P = 0.002) and mesenteric radiomic signature (HR: 2.19; 95% CI: 1.14-4.19; P = 0.018) were independent risk factors for PAR in the training cohort as per a multivariate analysis. The radiomics-based nomogram (C-index: 0.710; 95% CI: 0.672-0.748) yielded superior predictive performance than the clinical-radiological model (C-index, 0.607; 95% CI: 0.582-0.632) in the test cohort. Decision curve analysis demonstrated that the radiomics-based nomogram outperformed the clinical-radiological model in terms of clinical usefulness. CONCLUSIONS: Preoperative mesenteric and intestinal CTE radiomics signatures are potential non-invasive predictors of PAR in postoperative patients with CD.

Magnetic resonance neuroimaging promotes the preservation of pelvic autonomic nerves in laparoscopic total mesorectal excision: a comparative study.

BACKGROUND: How to preserve pelvic autonomic nerves system (PANS) in total mesorectal excision (TME) is still a technical challenge for gastrointestinal surgeons, and nerve preservation according to preoperative magnetic resonance imaging (MRI) is a hot topic in pelvic surgery. The purpose of this study was to assess the postoperative urogenital function of patients with rectal cancer (RC) who underwent preoperative and postoperative neuroimaging of PANS vs. patients who did not. METHODS: Patients meeting the inclusion criteria were prospectively enrolled in a magnetic resonance neuroimaging (MRN) group from June 2018, while primary RC patients from January 2016 to May 2018 who met the inclusion criteria were enrolled in a non-MRN group. Patients in the MRN group underwent MRN examination before operation and 6 months after operation, while those in the non-MRN group were collected and analyzed retrospectively. RESULTS: Based on International Prostate Symptom Score (IPSS) and International Index of Erectile Function 5 (IIEF5) scores at 6 months, the postoperative urinary and sexual function of male patients in the MRN group were significantly better than that in the non-MRN group (P<0.05). In addition, based on International Consultation on Incontinence modular Questionnaire on Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) and Female Sexual Function Index (FSFI) scores at 6 months, the postoperative sexual function of female patients in the MRN group was significantly better than that in the non-MRN group (P<0.05). CONCLUSIONS: In the present study, we constructed a three-dimensional (3D) presentation of PANS based on preoperative MRN which showed in vivo pelvic autonomous innervation. This may promote the preservation of PANS during TME and reduce the postoperative urogenital dysfunction rate.

A self-sustaining advanced lignocellulosic biofuel production by integration of anaerobic digestion and aerobic fungal fermentation.

High energy demand hinders the development and application of aerobic microbial biofuel production from lignocellulosic materials. In order to address this issue, this study focused on developing an integrated system including anaerobic digestion and aerobic fungal fermentation to convert corn stover, animal manure and food wastes into microbial lipids for biodiesel production. Dairy manure and food waste were first anaerobically digested to produce energy and solid digestate (AD fiber). AD fiber and corn stover were then processed by a combined alkali and acid hydrolysis, followed by fungal lipid accumulation. The integrated process can generate 1L biodiesel and 1.9 kg methane from 12.8 kg dry dairy manure, 3.1 kg dry food wastes and 12.2 kg dry corn stover with a positive net energy of 57 MJ, which concludes a self-sustaining lignocellulosic biodiesel process and provides a new route to co-utilize corn stover and organic wastes for advanced biofuel production.