Comparison of The Toronto IBD Global Endoscopic Reporting (TIGER) score, Mayo endoscopic score (MES), and ulcerative colitis endoscopic index of severity (UCEIS) in predicting the need for ileal pouch-anal anastomosis in patients with ulcerative colitis.

BACKGROUND: Total proctocolectomy (TPC) with ileal pouch-anal anastomosis (IPAA) has been accepted as a radical surgery for refractory ulcerative colitis (UC). We aimed to assess the predictive value of several novel and widely used endoscopic core systems, The Toronto IBD Global Endoscopic Reporting (TIGER) score, Mayo endoscopic score (MES), and ulcerative colitis endoscopic index of severity (UCEIS) in guiding the need for IPAA. METHODS: Data on patients with UC from June 1986 and June 2022 at our institute were collected. The endoscopic evaluation was recorded according to the first colonoscopy after hospitalization. Primary outcome was the need for IPAA during admission and follow-up. RESULTS: A total of 313 patients with a median follow-up time and a median TIGER score of 12.0 years (interquartile range (IQR): 6.0-17.0) and 212.0 (IQR: 7.0-327.0) were enrolled. IPAA was conducted in 110 (35.1%) patients, which significantly improved the long-term quality of life. TIGER score had the biggest area under the receiver-operating characteristic curve of 0.810 with a sensitivity of 75.0% and specificity of 87.1% at the cut-off value of 315 (p < 0.001). TIGER score ≥ 315 was an independent risk factor with the highest odds ratio for the need for IPAA and associated with the shortest IPAA-free survival time compared with UCEIS and MES. CONCLUSION: TIGER score was superior to UCEIS and MES in predicting the need for IPAA. For colorectal surgeons, three or more segments with moderate-to-severe endoscopic activity should be considered as a threshold value for decision-making for IPAA.

Intraoperative crystalloid-colloid infusion ratio associated with the development of early surgical complications after ileal pouch-anal anastomosis in ulcerative colitis: a multicenter long-term follow-up study.

BACKGROUND: Intraoperative intravenous fluid administration proves to be associated with surgical patients' postoperative outcomes. Few studies reported the relationship between intraoperative crystalloid-colloid infusion ratio and early surgical complications after ileal pouch-anal anastomosis (IPAA) in ulcerative colitis (UC). METHODS: Data on patients with underwent IPAA from January 2008 to March 2022 at our three inflammatory bowel disease (IBD) surgery centers were retrospectively collected. Intraoperative anesthetic data were recorded and later evaluated by our team anesthesiologist. RESULTS: A total of 140 eligible patients with a median follow-up time of 6.0 years [interquartile range (IQR): 2.0-8.0] were enrolled. Among all enrolled patients, 34 (24.3%) developed early surgical complications after IPAA. Greater blood loss and lower crystalloid-colloid infusion ratio were observed in patients with early surgical complications. Crystalloid-colloid infusion ratio < 2 and blood loss ≥ 200 ml had the most significant area under the receiver-operating characteristic curve (AUC) of 0.664 and 0.674 in predicting early surgical complications. Crystalloid-colloid infusion ratio < 2 [odds ratio (OR), 2.571; 95% confidence intervals (CI), 1.067-6.195, p = 0.035] and blood loss ≥ 200 ml (OR, 3.165; 95% CI, 1.288-7.777, p = 0.012) were independent risk factors for the development of early post-IPAA complications. CONCLUSION: Intraoperative crystalloid-colloid infusion ratio < 2 and blood loss volume over 200 ml during IPAA contribute to the occurrence of early surgical complications. Early attentions and necessary interventions are warranted to avoid these risk factors during the IPAA surgery in order to prevent the development of early surgical complications.

Effects of ginkgolic acid(C15:1)on biofilm formation, pathogenic factor production and quorum sensing of Pseudomonas aeruginosa.

To complete the investigation of the bacterial inhibitory activity of ginkgolic acid (GA), the quorum sensing activity of GA was investigated to assess the potential of ginkgo biloba exocarp for the production of quorum sensing inhibitor. The effect of GA (C15:1) on the growth and secondary metabolism of p. aeruginosa PAO1 were tested. The results showed that GA (C15:1) had no effect on the growth of p. aeruginosa PAO1, and that GA (C15:1) was able to inhibit the formation of quorum sensing dependent virulence factors, but promoted the formation of biofilms. Finally, the above experimental results were verified by LasR-GFP, RhlR-GFP system and fluorescence quantitative PCR. These results suggested that GA (C15:1) was capable of modulating the quorum sensing system of p. aeruginosa PAO1 and possessed potential as an anti-virulence factor drug, but is not suitable for development as a broad-spectrum biofilm inhibitor.

The antibacterial activity and mechanism of ginkgolic acid C15:1.

BACKGROUND: The present study investigated the antibacterial activity and underlying mechanisms of ginkgolic acid (GA) C15:1 monomer using green fluorescent protein (GFP)-labeled bacteria strains. RESULTS: GA presented significant antibacterial activity against Gram-positive bacteria but generally did not affect the growth of Gram-negative bacteria. The studies of the antibacterial mechanism indicated that large amounts of GA (C15:1) could penetrate GFP-labeled Bacillus amyloliquefaciens in a short period of time, and as a result, led to the quenching of GFP in bacteria. In vitro results demonstrated that GA (C15:1) could inhibit the activity of multiple proteins including DNA polymerase. In vivo results showed that GA (C15:1) could significantly inhibit the biosynthesis of DNA, RNA and B. amyloliquefaciens proteins. CONCLUSION: We speculated that GA (C15:1) achieved its antibacterial effect through inhibiting the protein activity of B. amyloliquefaciens. GA (C15:1) could not penetrate Gram-negative bacteria in large amounts, and the lipid soluble components in the bacterial cell wall could intercept GA (C15:1), which was one of the primary reasons that GA (C15:1) did not have a significant antibacterial effect on Gram-negative bacteria.

Surface-enhanced Raman spectroscopy analysis reveals biochemical difference in urine of patients with perianal fistula.

BACKGROUND & AIMS: Perianal fistulising Crohn's disease (PFCD) is different from the characteristics and outcomes of traditional non-inflammatory bowel disease (IBD) anal fistulas. The presence of perianal disease was a poor prognostic indicator for Crohn's disease (CD) patients and PFCD patients were more likely to bear an increased risk of recurrence. However, the effective and accurate diagnosis methods to early distinguish PFCD from simple perianal fistula were still scarce. The purpose of this study is to develop a non-invasive detecting approach to predict CD in patients with perianal fistulas. METHODS: Data on patients with anal fistulizing disease were collected from July 2020 to September 2020 in two IBD centers. Urine samples from PFCD and simple perianal fistula patients were investigated by surface-enhanced Raman spectroscopy (SERS). Principal component analysis (PCA)-support vector machine (SVM) was utilized to establish classification models to distinguish PFCD from simple perianal fistula. RESULTS: After a case-matched 1:1 selection by age and gender, 110 patients were included in the study. By analyzing the average SERS spectra of PFCD and simple perianal fistula patients, it revealed that there were significant differences in intensities at 11 Raman peaks. The established PCA-SVM model distinguished PFCD from simple perianal fistula with a sensitivity of 71.43%, specificity 80.00% and accuracy 75.71% in the leave-one-patient-out cross-validation. The accuracy of the model in validation cohort was 77.5%. CONCLUSIONS: Investigation of urine samples by SERS helps clinicians to predict Crohn's disease from perianal fistulas, which make patients achieve benefit from a more individualized treatment strategy.

Surgical Options for Appropriate Length of J-Pouch Construction for Better Outcomes and Long-term Quality of Life in Patients with Ulcerative Colitis after Ileal Pouch-Anal Anastomosis.

Background/Aims: Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is widely accepted as a radical surgery for refractory ulcerative colitis (UC). Definite results on the appropriate pouch length for an evaluation of the risk-to-benefit ratio regarding technical complications and long-term quality of life (QOL) are still scarce. Methods: Data on UC patients who underwent IPAA from 2008 to 2022 in four well-established pouch centers affiliated to China UC Pouch Center Union were collected. Results: A total of 208 patients with a median follow-up time of 6.0 years (interquartile range, 2.3 to 9.0 years) were enrolled. The median lengths of the patients' short and long pouches were 14.0 cm (interquartile range, 14.0 to 15.0 cm) and 22.0 cm (interquartile range, 20.0 to 24.0 cm), respectively. Patients with a short J pouch configuration were less likely to achieve significantly improved long-term QOL (p=0.015) and were prone to develop late postoperative complications (p=0.042), such as increased defecation frequency (p=0.003) and pouchitis (p=0.035). A short ileal pouch was an independent risk factor for the development of late postoperative complications (odds ratio, 3.100; 95% confidence interval, 1.519 to 6.329; p=0.002) and impaired longterm QOL improvement (odds ratio, 2.221; 95% confidence interval, 1.218 to 4.050, p=0.009). Conclusions: The length of the J pouch was associated with the improvement in long-term QOL and the development of late post-IPAA complications. A long J pouch configuration could be a considerable surgical option for pouch construction.

AMBRA1 promotes intestinal inflammation by antagonizing PP4R1/PP4c mediated IKK dephosphorylation in an autophagy-independent manner.

IκB kinase (IKK) complex is central regulators of the NF-κB pathway, and dysregulation of IKK phosphorylation leads to hyperactivation of proinflammatory response in various chronic inflammatory diseases, including inflammatory bowel disease (IBD). However, the dynamic modulation of IKK phosphorylation and dephosphorylation in intestinal inflammation remains uncharacterized. Here, we found that autophagy/beclin-1 regulator 1 (AMBRA1) was highly expressed in inflamed colons in a colitis mouse model and in clinical IBD samples. Importantly, AMBRA1 deletion significantly decreased proinflammatory cytokine expression and enhanced the therapeutic effect of infliximab on intestinal inflammation. Mechanistically, the N-term F1 domain of AMBRA1 was required for AMBRA1 to competitively interact with protein phosphatase 4 regulatory subunit 1 (PP4R1) and catalytic protein phosphatase 4 (PP4c) to suppress their interactions with IKK, promote the dissociation of the PP4R1/PP4c complex, and antagonize the dephosphorylation activity of this complex towards the IKK complex. In response to TNF-α stimulation, IKKα phosphorylates AMBRA1 at S1043 to stabilize AMBRA1 expression by impairing its binding to Cullin4A (CUL4A) to decrease its CUL4A-mediated K48-linked ubiquitination. Overall, our study identifies an autophagy-independent function of AMBRA1 as a positive modulator of IKK phosphorylation to promote intestinal inflammation, thus providing a new targeted therapeutic strategy for patients with refractory IBD.

Risk Factors and Quality of Life in Patients with Diffuse Pouchitis After Ileal Pouch Anal Anastomosis According to the Chicago Classification for J Pouch: a Retrospective Multicenter Cohort Study in China.

BACKGROUND: Pouchitis is a common late complication in patients with ulcerative colitis (UC) who undergo ileal pouch-anal anastomosis (IPAA). The heterogeneous nature of the clinical and endoscopic presentations could affect the evaluation of therapeutic interventions for pouchitis. Thus, identifying the risk factors and clinical outcomes of pouch inflammation at different sites and severity is becoming increasingly important for colorectal surgeons. METHODS: Data on patients who underwent IPAA January from 2008 to June 2022 in our three pouch centers affiliated with the China UC Pouch Center Union were retrospectively collected. Pouchitis was categorized as a different phenotype according to the Chicago Classification. J pouches were classified into short (14 ± 2 cm) and long pouches (22 ± 2 cm) according to the distribution of ileal pouch length in our institute. RESULTS: Altogether, 143 patients with a median follow-up time of 5.0 years (interquartile range: 2.0-8.0) were enrolled. Among them, 41 patients (28.7%) developed pouchitis and 32 patients (78%) had diffuse inflammation of the pouch. Patients with diffuse pouchitis had a higher pouchitis disease activity index and more seriously impaired improvement of long-term quality of life than those with pouch phenotypes. A short J pouch, recurrent UC, and preoperative high white blood cell count were independent risk factors for diffuse pouchitis. Furthermore, a short J pouch could effectively predict the occurrence of diffuse pouchitis with an area under the receiver-operating characteristic curve of 0.614, a sensitivity of 62.5%, and a specificity of 60.4% (p = 0.049) and significantly decreased the overall diffuse pouchitis-free survival compared to a long J pouch (p = 0.0002). CONCLUSION: Diffuse pouchitis is a common phenotype of pouchitis that seriously impairs long-term prognosis. For colorectal surgeons, decision-making regarding pouch construction with an appropriate length should be considered to prevent the development of diffuse pouchitis.

The endoscopic prediction model of simple endoscopic score for Crohn's disease (SES-CD) as an effective predictor of intestinal obstruction in Crohn's disease: A multicenter long-term follow-up study.

Background: The simple endoscopic score for Crohn's disease (SES-CD) is a widely used index to evaluate clinical and endoscopic activity. However, the association and predictive value of SES-CD for intestinal obstruction in Crohn's disease (CD) remains unclear. We aimed to establish the best cut-off indicators of SES-CD for early clinical intervention and subsequent prevention of intestinal obstruction in CD. Methods: Data on patients with CD evaluated at our institute from January 2016 to January 2022 were retrospectively collected. The SES-CD and Crohn's Disease Activity Index scores used in the analysis indicated the results of the first clinical and colonoscopy evaluations after hospitalization. The primary outcome was the occurrence of intestinal obstruction during admission and follow-up. Results: A total of 248 patients with a median follow-up time of 2 years [interquartile range: 1.0-4.0] were enrolled, of which 28.2% developed intestinal obstruction. An SES-CD score of 8 was the most significant threshold evaluation, and SES-CD ≥8 had the largest area under the receiver operating characteristic curve (0.705), with a sensitivity of 52.9% and specificity of 88.2% in predicting intestinal obstruction. Furthermore, SES-CD ≥8 had the greatest risk factor for intestinal obstruction (odds ratio: 7.731; 95% confidence interval: 3.901-15.322; p < 0.001) and significantly decreased the overall intestinal obstruction-free survival (p < 0.001). Conclusion: The SES-CD endoscopic prediction model could be an effective predictor of intestinal obstruction in patients with CD. More frequent follow-up and colonoscopic surveillance should be considered in patients with SES-CD score ≥8 to prevent the development of intestinal obstruction.