Diagnostic and prognostic significance of circulating secreted frizzled-related protein 5 in colorectal cancer.

BACKGROUND: Secreted Frizzled-Related Protein 5 (SFRP5) modulates Wnt signalling pathways, affecting diverse biological processes. We assessed the diagnostic and prognostic value of circulating SFRP5 (cSFRP5) in colorectal cancer (CRC) METHODS: Plasma cSFRP5 concentrations were measured using enzyme-linked immunosorbent assay (ELISA) in healthy donors (n = 133), individuals diagnosed with CRC (n = 449), colorectal polyps (n = 85), and medical conditions in other organs including cancer, inflammation, and benign states (n = 64). RESULTS: Patients with CRC, polyps, and other conditions showed higher cSFRP5 levels than healthy individuals (p < 0.0001). Receiver operating characteristic curves comparing healthy donors with medical conditions, polyps and CRC were 0.814 (p < 0.0001), 0.763 (p < 0.0001) and 0.762 (p < 0.0001), respectively. In CRC, cSFRP5 correlated with patient age (p < 0.0001), tumour stage (p < 0.0001), and histological differentiation (p = 0.0273). Levels, adjusted for patient age, sex, plasma age and collection institution, peaked in stage II versus I (p < 0.0001), III (p = 0.0002) and IV (p < 0.0001), were lowest in stage I versus III (p = 0.0002) and IV (p = 0.0413), with no difference between stage III and IV. Elevated cSFRP5 levels predicted longer overall survival in stages II-III CRC (univariate: HR 1.82, 95% CI: 1.02-3.26, p = 0.024; multivariable: HR 2.34, 95% CI: 1.12-4.88, p = 0.015). CONCLUSION: This study confirms cSFRP5 levels are elevated in CRC compared to healthy control and reveals a correlation between elevated cSFRP5 and overall survival in stages II-III disease.

Bowel Stiffness Assessed by Shear-Wave Ultrasound Elastography Predicts Disease Behavior Progression in Patients With Crohn's Disease.

INTRODUCTION: There is a lack of reliable predictors of disease behavior progression in patients with Crohn's disease (CD). Real-time shear-wave elastography (SWE) is a novel method for evaluating tissue stiffness. However, its value for assessing CD has not yet been investigated. We aimed to explore the value of SWE and other ultrasound parameters at diagnosis in predicting CD behavior progression. METHODS: We retrospectively collected data from patients with CD with the nonstenotic nonpenetrating disease (B1 phenotype based on the Montreal classification). All patients underwent intestinal ultrasound at baseline and were followed up. The end point was defined as disease behavior progression to stricturing (B2) or penetrating (B3) disease. Cox regression analysis was performed for the association between baseline characteristics and subsequent end points. In addition, a multivariate nomogram was established to predict the risk of disease behavior progression quantitatively. RESULTS: A total of 130 patients with CD with B1 phenotype were enrolled. Twenty-seven patients (20.8%) developed B2 or B3 disease, with a median follow-up of 33 months. Multivariate analysis identified that SWE was the only independent predictor of disease behavior progression (hazard ratio 1.08, 95% confidence interval 1.03-1.12, P = 0.001). A reverse of the HR appeared at the cutoff 12.75 kPa. The nomogram incorporating SWE and other clinical characteristics showed a good prediction performance (area under the curve = 0.792). DISCUSSION: Intestinal stiffness assessed using SWE is an independent predictor of disease behavior progression in patients with CD. Patients with CD with SWE >12.75 kPa at diagnosis are prone to progress toward stricturing or penetrating diseases.

Systematic review and meta-analysis: Association of a pre-illness Western dietary pattern with the risk of developing inflammatory bowel disease.

OBJECTIVE: Previous studies have presented conflicting results on Western diets and the risk of inflammatory bowel disease (IBD). This study aimed to evaluate the role of a pre-illness Western dietary pattern in the development of IBD. METHODS: The Western dietary pattern was defined as that met at least two of the following, either a high intake of refined grains, red and processed meat, animal protein, animal fats or high-fat dairy products, or with a low consumption of fruit and vegetables. Four medical databases (PubMed, EMBASE, the Cochrane Library and the China National Knowledge Infrastructure) were searched to identify all relevant references. Risk estimate and corresponding 95% confidence interval (CI) were pooled using a random-effects model. RESULTS: Nine studies (seven case-control studies and two prospective cohorts) were included, with a total of 1491 IBD cases and 53 089 controls. A Western dietary pattern was associated with a risk of all IBD (relative risk [RR] 1.92, 95% CI 1.37-2.68) and separately with Crohn's disease (CD) (RR 1.72, 95% CI 1.01-2.93) and ulcerative colitis (UC) (RR 2.15, 95% CI 1.38-3.34). Subgroup analysis by region showed that a Western dietary pattern was associated with the risk of CD and UC for studies performed in Europe (RR 2.25, 95% CI 1.44-3.50 for CD; RR 2.65, 95% CI 1.61-4.36 for UC). The pooled RR was 2.26 (95% CI 1.42-3.59) in the pediatric CD subgroup. CONCLUSION: This meta-analysis indicates that a pre-illness Western dietary pattern may increase the risk of developing CD and UC.

Relationship between carotid intima-media thickness and carotid artery stiffness assessed by ultrafast ultrasound imaging in patients with type 2 diabetes.

OBJECTIVES: To evaluate the relationship between carotid stiffness and carotid intima-media thickness (CIMT) in patients with type 2 diabetes (T2DM). MATERIALS AND METHODS: Carotid properties were evaluated in 317 consecutive subjects (98 volunteers for controls, 105 patients with normal CIMT for T2DM group 1, and 114 patients with thickened CIMT for T2DM group 2). The CIMT and carotid pulse wave velocity at the beginning (PWV-BS) and at the end of systole (PWV-ES) were measured. RESULTS: Apart from PWV-BS in T2DM group 1, CIMT and PWV-ES were significant higher in patients groups than those of in controls. In multiple regression analysis, diabetes was independently associated with PWV-ES and not with PWV-BS. Moreover, when adjusting for baseline covariates, only PWV-ES (odds ratio = 4.27, P < 0.001) distinguished carotid in T2DM group 1 from that of controls. Concerning the relationship between log(CIMT) and PWV-ES, when adjusting for baseline covariates, the association were still significant in controls and T2DM group 1, whereas it was no longer present in T2DM group 2 (P = 0.091). Additionally, the slope (ß) after adjustment for the PWV-ES to log(CIMT) was significantly steeper in T2DM group 1 than that of in controls (ß= 8.35 vs. 3.31, P < 0.01). CONCLUSIONS: The PWV-ES seem to be a better biomarker candidate than PWV-BS to assess the carotid stiffness in diabetic patients. Compared with controls, diabetic patients showed more advanced functional changes than morphological changes despite normal CIMT, whereas the relationship trend was not present when thickened CIMT emerged.

Systematic review with meta-analysis: the efficacy and safety of stem cell therapy for Crohn's disease.

BACKGROUND AND AIMS: Stem cell therapy (SCT) for the treatment of Crohn's disease (CD) is still in its infancy, and whether SCT is associated with improved outcomes is unclear. We performed a meta-analysis to evaluate the efficacy and safety of patients receiving SCT. METHODS: Electronic databases were searched for studies that reported the use of stem cells for the treatment of patients with CD. Raw data from included studies were pooled for effect estimates. Subgroup analyses were performed for exploration of heterogeneity regarding all outcomes. RESULTS: We analyzed 21 studies comprising 514 patients with active CD. A random-effects meta-analysis of studies of SCT as systemic infusion showed 56% (95% confidence interval (CI) 33-76, n = 150) of patients achieved clinical response. Similarly, random-effects pooled rates of clinical or endoscopic remission were 46% (95% CI 25-69, n = 116) and 15% (95% CI 0-50, n = 48), respectively. A random-effects meta-analysis of all perianal CD studies showed that 57% (95% CI 44-69%, n = 251) of patients had healed fistula with SCT, with an odds ratio of 3.83 (95% CI 1.06-13.86, n = 121, P = 0.04) versus control. The pooled rate of clinical recurrence was high at 16% (95% CI 4-34, n = 101) with follow-up >12 months. The pooled rates of severe adverse events (SAEs) and SAEs related to SCT were 12% (95% CI 6-23, n = 378) and 8% (95% CI 3-18, n = 378), respectively. The Egger test suggests no publication bias existed for fistula healing (P = 0.36), but did for clinical response (P = 0.003). CONCLUSIONS: SCT seems potentially effective and may serve as an alternative treatment for refractory active CD. Toxicity will remain the most significant barrier to systemic SCT in patients with CD.

Safety Profile of Thiopurines in Crohn Disease: Analysis of 893 Patient-Years Follow-Up in a Southern China Cohort.

Thiopurines have been associated with both clinical improvement and mucosal healing in treating Crohn disease (CD). Unfortunately, the high rate of adverse events (AEs) leading to drug withdrawal represents a major limitation in the use of these drugs.To evaluate the safety of thiopurines in patients with CD. To identify predictive factors associated with the development of thiopurine-induced AEs and withdrawal.This longitudinal cohort study examined patients from a university-based IBD referral center. Time-to-event analysis was performed with the Kaplan-Meier curve. Cox regression analysis was performed to identify potential predictive factors of AEs.Two hundred sixty-seven CD patients on thiopurines were included. A total of 143 AEs occurred at a median of 7.4 months (interquartile range, 3.7-15.3 months) after starting treatment. The cumulative incidence of AEs was 26%, with an annual risk of 4.3% per patient-year of treatment. The most frequent was leucopenia (41/267, 15.36%), followed by infections (29/267, 10.86%). Independent factors predictive of leucopenia were lower baseline hemoglobin (hazard ratio (HR), 0.34; 95% confidence interval (CI) 0.18-0.67) and the concomitant use of 5-aminosalicylic acid (HR, 3.05; 95% CI 1.44-8.76). Of the 28.44% (76/267) CD patients discontinued therapy, 14.61% due to AEs. A lower body mass index, the presence of extraintestinal manifestation, and the incidence of leucopenia independently predicted thiopurine withdrawal. In total, 37.5% of these patients restarted thiopurines and 52.3% of them had AEs again.About a quarter of patients on thiopurine therapy had AEs during follow-up and 1 of 7 patients had to discontinue thiopurines due to AEs.

Chinese psychiatrists views on global features of CCMD-III, ICD-10 and DSM-IV.

OBJECTIVE: To survey psychiatrists' opinions about psychiatric classification in China, and provide information and suggestions for developing a new version of classificatory system. METHOD: The questionnaire about psychiatry classification written by Professor Graham Mellsop, New Zealand, was translated and modified into Chinese. An anonymous field survey of 380 psychiatry professionals was undertaken in Beijing. RESULTS: A total of 181 questionnaires were eligible for analysis. The Chinese Classification of Mental Disorders version 3 (CCMD-III) is the most commonly used in China (63.8%), then ICD-10 (28.5%) and DSM-IV (7.7%). Half of the respondents (53.0%) agreed that the most important diagnostic classification is for communication among physicians, and then for communication between physician and patient (21.0%). Most professionals (90.0%) agree that classification should include less than 100 diagnostic options. Disagreement presents on cross-culture application of the ICD-10 and DSM-III: 75.1% professionals agreed that they are "useful and reliable regardless of patient ethnicity and culture", while 46.8% found "sometimes difficult to apply across cultures", and 35.8% thought classification is "over-embedded in European cultural concepts and values". CONCLUSION: There is a strong trend of convergence and unification of China's diagnostic standards with international standards inevitable. A classification that is less complicated and confused, easy-to-communicate and understand and cross-cultural/nation applicable is expected by most Chinese psychiatrists. Such classification should also be reflective of the advances in understanding of aetiology of disorders and helpful in clinical management.