Nomogram to predict primary non-response to infliximab in patients with Crohn's disease: a multicenter study.

BACKGROUND: Infliximab (IFX) is effective at inducing and maintaining clinical remission and mucosal healing in patients with Crohn's disease (CD); however, 9%-40% of patients do not respond to primary IFX treatment. This study aimed to construct and validate nomograms to predict IFX response in CD patients. METHODS: A total of 343 patients diagnosed with CD who had received IFX induction from four tertiary centers between September 2008 and September 2019 were enrolled in this study and randomly classified into a training cohort (n = 240) and a validation cohort (n = 103). The primary outcome was primary non-response (PNR) and the secondary outcome was mucosal healing (MH). Nomograms were constructed from the training cohort using multivariate logistic regression. Performance of nomograms was evaluated by area under the receiver-operating characteristic curve (AUC) and calibration curve. The clinical usefulness of nomograms was evaluated by decision-curve analysis. RESULTS: The nomogram for PNR was developed based on four independent predictors: age, C-reactive protein (CRP) at week 2, body mass index, and non-stricturing, non-penetrating behavior (B1). AUC was 0.77 in the training cohort and 0.76 in the validation cohort. The nomogram for MH included four independent factors: baseline Crohn's Disease Endoscopic Index of Severity, CRP at week 2, B1, and disease duration. AUC was 0.79 and 0.72 in the training and validation cohorts, respectively. The two nomograms showed good calibration in both cohorts and were superior to single factors and an existing matrix model. The decision curve indicated the clinical usefulness of the PNR nomogram. CONCLUSIONS: We established and validated nomograms for the prediction of PNR to IFX and MH in CD patients. This graphical tool is easy to use and will assist physicians in therapeutic decision-making.

The clinical value of multimodal ultrasound for the evaluation of disease activity and complications in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) has the characteristics of chronic relapse and remission, which makes early diagnosis and effective evaluation of disease activity especially crucial. With the development of ultrasound technology, its role in the diagnosis and treatment of IBD is increasing. This study aimed to explore the value of multimodal ultrasound in the assessment of disease activity and complications in IBD. METHODS: Patients with clinically confirmed IBD were selected and examined with two-dimensional ultrasound, Doppler ultrasound, contrast-enhanced ultrasound (CEUS), elastography, endoscopy with biopsies, and whole-abdominal enhanced computed tomography (CT). Collect relevant laboratory data, including C-reactive protein, erythrocyte sedimentation rate, etc. Endoscopy is used as the gold standard for disease activity assessment, and the diagnostic value of each ultrasound parameter is compared separately, and correlation analysis is made. RESULTS: Intestinal maximum wall thickness in patients in the disease activity group (active group) was significantly thicker than that in patients in remission group (7.93±2.65 vs. 4.16±1.08 mm, P<0.001). The mean values of Peak Enhancement (PE) and the area under the receiver operating characteristic (ROC) curve (AUC) were higher in the active stage than in remission, with a significant difference (-40.66±4.81 vs. -50.47±5.03 db, 356.44±170.67 vs. 194.42±92.09 dBsec, both P<0.05). Time To Peak (TTP) showed no significant difference between the active stage and remission (20.04±8.74 vs. 20.09±11.13 s, P>0.05). Twenty cases of intestinal stricture were detected by ultrasound, and no fistula or abscesses were detected. CEUS and elastography could distinguish inflammatory bowel stenosis and fibrous bowel stenosis in patients with IBD. In the fibrosis group and inflammation group, the mean shear wave velocity, Young's modulus, TTP, PE, and AUC were statistically significantly different (P<0.05). The mean maximum wall thickness and disease extent assessed by ultrasound and CT were strongly correlated (r=0.799, 0.831). Wall thickness showed a moderate positive correlation with CRP and ESR and a strong positive correlation with Mayo score (P<0.05), but no significant correlation with CDAI (P>0.05). CONCLUSIONS: Multimodal ultrasound provides more detailed clinical reference values for the comprehensive evaluation of IBD.

Bicyclol Attenuates Acute Liver Injury by Activating Autophagy, Anti-Oxidative and Anti-Inflammatory Capabilities in Mice.

Bicyclol, a novel synthetic antihepatitis drug, has been shown to protect against liver injury via various pharmacological activities. The purpose of the current study was to further investigate the protective effect of bicyclol against carbon tetrachloride (CCl4)-induced acute liver injury (ALI) and its underlying molecular mechanism, particularly autophagic machinery, anti-oxidative, and anti-inflammatory potentials. Our results found that treatment with bicyclol significantly reduced CCl4-induced hepatotoxicity by alleviating histopathological liver changes, decreasing the alanine transaminase levels, promoting autophagic flux, attenuating the expression of inflammatory cytokines, and modulating oxidative markers. Furthermore, bicyclol efficiently induced the conversion of LC3 and enhanced the liver expressions of ATG7 and Beclin-1. Meanwhile, bicyclol induced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and p62. These protective effects may be mediated by activation of AMP-activated protein kinase and inhibition of mTOR or MAPK signaling pathways. Taken together, our study firstly suggests that bicyclol has protective potential against CCl4-induced hepatotoxicity, which might be closely associated with induction of autophagy, concomitant anti-oxidative stress, and anti-inflammatory response.

[Clinical characteristics of Cronkhite-Canada syndrome in Chinese: meta-analysis of 35 cases].

OBJECTIVE: To investigate the clinical characteristics of Chinese patients with Cronkhite-Canada syndrome (CCS). METHODS: Relevant data of Chinese CCS patients from 1985 to 2006 were retrieved from Medline and Chinese biomedical database and a meta-analysis was conducted. RESULTS: A total of 35 CCS cases had been reported by Chinese hospitals with the clinical characteristics of gastrointestinal polyposis with ectodermal trilogy, mainly manifested as diarrhea, bellyache, weight loss, anemia, and edema. Canceration was reported in 2 patients. Some patients had symptomatic response to combination therapy. There might be racial or regional differences in CCS susceptibility; however, such information was often neglected in the medical records at home and abroad. New techniques, such as (99)Tc(m)-HSA scan, double-balloon enteroscopy and wireless capsule endoscopy provided new information on CCS. CONCLUSION: The clinical features of Chinese CCS patients are similar to those of the European or Japanese patients. Novel appliance, case report standardization and sharing database may promote the understanding of this rare syndrome.

[A study of interleukin-10 gene polymorphism in irritable bowel syndrome].

OBJECTIVE: To investigate whether three diallelic polymorphisms at the position -1082, -819 and -592 in the promoter region of the IL-10 gene were associated with diarrhea-predominant irritable bowel syndrome (D-IBS). METHODS: The IL-10 gene -1082, -819 and -592 position polymorphisms were genotyped by amplification refractory mutation systems-polymerase chain reaction (ARMS-PCR) methods in 43 patients with D-IBS and 41 healthy subjects (HS). RESULTS: Compared with HS, D-IBS patients had a greater frequency of T/T genotype at IL-10 gene promoter -819 position (67.4% vs 39.0%, P < 0.05), the frequencies of -819 C/T and C/C genotype were not significantly different (23.3% vs 43.9% and 9.3% vs 17.1%, P > 0.05). D-IBS patients also had a greater frequency of -592 A/A genotype compared with HS (67.4% vs 39.0%, P < 0.05), the frequencies of -592 C/A and C/C genotype were not significantly different (23.3% vs 43.9% and 9.3% vs 17.1%, P > 0.05). No significant difference was found in genotype at IL-10 gene promoter -1082 position. The -819 T allele frequency in D-IBS was significantly higher than that in control (79.1% vs 61.0%, P < 0.05), whereas -819 C allele frequency in D-IBS was lower (20.9% vs 39.0%, P < 0.05). D-IBS patients also had a greater frequency of -592 A allele compared with HS (79.1% vs 61.0%, P < 0.05), -592 C allele frequency in D-IBS was lower (20.9% vs 39.0%, P < 0.05). No significant difference was found in -1082 G or A allele frequency. CONCLUSIONS: The presence of -819 T/T and -592 A/A genotype may be related to development of D-IBS.

Clinical features of upper gastrointestinal serrated lesions: An endoscopy database analysis of 98746 patients.

AIM: To analyse the clinical features of patients with the serrated lesions in the upper gastrointestinal tract (UPGI) tract. METHODS: Patients who underwent routine esophagogastroduodenoscopy (EGD) at the Digestive Endoscopy Centre of General Hospital, Tianjin Medical University between January 2011 and December 2015 were consecutively recruited. Patients with UPGI serrated lesions were consecutively identified. The patients' demographics and histopathology were recorded. The colorectal findings for patients who underwent colonoscopy simultaneously or within six months were also extracted from the colonoscopy database. In addition, we analysed differences in colorectal neoplasia detection between the study patients and randomly selected patients matched for age and gender who did not exhibit serrated lesions and who also underwent colonoscopy in the same period. RESULTS: A total of 21 patients out of 98746 patients (0.02%) who underwent EGD were confirmed to have serrated lesions with predominantly crenated, sawtooth-like configurations. The mean age of the 21 patients was (55.3 ± 17.2) years, and 11 patients were male (52.4%). In terms of the locations of the serrated lesions, 17 were found in the stomach (including 3 in the cardia, 9 in the corpus and 5 in the antrum), 3 were found in the duodenum, and 1 was found in the esophagus. Serrated lesions were found in different mucosal lesions, with 14 lesions were detected in polyps (8 hyperplastic polyps and 6 serrated adenomas with low grade dysplasia), 3 detected in Ménétrier gastropathy, 3 detected in an area of inflammation or ulcer, and 1 detected in the intramucosal carcinoma of the duodenum. In addition, colonoscopy data were available for 18 patients, and a significantly higher colorectal adenoma detection rate was observed in the UPGI serrated lesions group than in the randomly selected age- and gender-matched group without serrated lesions who also underwent colonoscopy in the same period (38.9% vs 11.1%, OR = 5.091, 95%CI: 1.534-16.890, P = 0.010). The detection rate of advanced adenoma was also higher in the UPGI serrated lesions group (22.2% vs 4.2%, OR = 6.571, 95%CI: 1.322-32.660, P = 0.028). CONCLUSION: Serrated lesions in the UPGI were detected in various mucosal lesions with different pathological morphologies. Moreover colonoscopy is recommended for the detection of concurrent colorectal adenoma for these patients.

Detection Rate, Distribution, Clinical and Pathological Features of Colorectal Serrated Polyps.

BACKGROUND: Colorectal serrated polyp is considered as histologically heterogeneous lesions with malignant potential in western countries. However, few Asian studies have investigated the comprehensive clinical features of serrated polyps in symptomatic populations. The aim of the study was to evaluate the features of colorectal serrated polyps in a Chinese symptomatic population. METHODS: Data from all consecutive symptomatic patients were documented from a large colonoscopy database and were analyzed. Chi-square test or Fisher's exact test and logistic regression analysis were used for the data processing. RESULTS: A total of 9191 (31.7%) patients were detected with at least one colorectal polyp. The prevalence of serrated polyps was 0.53% (153/28,981). The proportions of hyperplastic polyp (HP), sessile serrated adenoma/polyp (SSA/P), and traditional serrated adenoma (TSA) of all serrated polyps were 41.2%, 7.2%, and 51.6%, respectively, which showed a lower proportion of HP and SSA/P and a higher proportion of TSA. Serrated polyps appeared more in males and elder patients while there was no significant difference in the subtype distribution in gender and age. The proportions of large and proximal serrated polyps were 13.7% (21/153) and 46.4% (71/153), respectively. In total, 98.9% (89/90) serrated adenomas were found with dysplasia. Moreover, 14 patients with serrated polyps were found with synchronous advanced colorectal neoplasia, and large serrated polyps (LSPs) (odds ratio: 3.446, 95% confidence interval: 1.010-11.750, P < 0.05), especially large HPs, might have an association with synchronous advanced neoplasia (AN). CONCLUSIONS: The overall detection rate of colorectal serrated polyps in Chinese symptomatic patient population was low, and distribution pattern of three subtypes is different from previous reports. Moreover, LSPs, especially large HPs, might be associated with an increased risk of synchronous AN.

Fecal microbiota transplantation broadening its application beyond intestinal disorders.

Intestinal dysbiosis is now known to be a complication in a myriad of diseases. Fecal microbiota transplantation (FMT), as a microbiota-target therapy, is arguably very effective for curing Clostridium difficile infection and has good outcomes in other intestinal diseases. New insights have raised an interest in FMT for the management of extra-intestinal disorders associated with gut microbiota. This review shows that it is an exciting time in the burgeoning science of FMT application in previously unexpected areas, including metabolic diseases, neuropsychiatric disorders, autoimmune diseases, allergic disorders, and tumors. A randomized controlled trial was conducted on FMT in metabolic syndrome by infusing microbiota from lean donors or from self-collected feces, with the resultant findings showing that the lean donor feces group displayed increased insulin sensitivity, along with increased levels of butyrate-producing intestinal microbiota. Case reports of FMT have also shown favorable outcomes in Parkinson's disease, multiple sclerosis, myoclonus dystonia, chronic fatigue syndrome, and idiopathic thrombocytopenic purpura. FMT is a promising approach in the manipulation of the intestinal microbiota and has potential applications in a variety of extra-intestinal conditions associated with intestinal dysbiosis.

CD106 identifies a subpopulation of mesenchymal stem cells with unique immunomodulatory properties.

Mesenchymal stem cells (MSCs) reside in almost all of the body tissues, where they undergo self-renewal and multi-lineage differentiation. MSCs derived from different tissues share many similarities but also show some differences in term of biological properties. We aim to search for significant differences among various sources of MSCs and to explore their implications in physiopathology and clinical translation. We compared the phenotype and biological properties among different MSCs isolated from human term placental chorionic villi (CV), umbilical cord (UC), adult bone marrow (BM) and adipose (AD). We found that CD106 (VCAM-1) was expressed highest on the CV-MSCs, moderately on BM-MSCs, lightly on UC-MSCs and absent on AD-MSCs. CV-MSCs also showed unique immune-associated gene expression and immunomodulation. We thus separated CD106(+)cells and CD106(-)cells from CV-MSCs and compared their biological activities. Both two subpopulations were capable of osteogenic and adipogenic differentiation while CD106(+)CV-MSCs were more effective to modulate T helper subsets but possessed decreased colony formation capacity. In addition, CD106(+)CV-MSCs expressed more cytokines than CD106(-)CV-MSCs. These data demonstrate that CD106 identifies a subpopulation of CV-MSCs with unique immunoregulatory activity and reveal a previously unrecognized mechanism underlying immunomodulation of MSCs.

Prevention of diabetic microangiopathy by prophylactic transplant of mobilized peripheral blood mononuclear cells.

AIM: To investigate whether the prophylactic local delivery of mobilized peripheral blood mononuclear cells (M-PBMNC) could prevent peripheral microangiopathy in diabetic nude mice. METHODS: Diabetic nude mice were induced with intraperitoneal injections of streptozotocin. With the time course of diabetes, we detected the capillary and arteriole density of mice adductor muscles by immunohistopathy. In situ apoptosis was detected by using TdT-mediated dUTP nick end labeling (TUNEL) methods. M-PBMNC were labeled and locally delivered to the adductor muscles. Mononuclear cells were also isolated and cultured in vitro for the detection and counting of endothelial progenitor cells(EPC). RESULTS: Rarefication of capillaries and arterioles, enhanced apoptosis in adductor muscles, and reduced circulating EPC in diabetic nude mice. Prophylactic local delivery of M-PBMNC halted the progression of microvascular rarefaction in hind-limb skeletal muscles by inhibiting apoptosis. We detected the survival, migration and incorporation of transplanted M-PBMNC into the murine vasculature in vivo. In addition, more EPC were available from M-PBMNC than non-mobilized cells. CONCLUSION: These results suggested that the prophylactic local delivery of M-PBMNC may represent a novel approach for the treatment of microvascular complications in diabetics.