Jiaming Qian

Risk factors and outcome of PCR-detected clostridium difficile infection in ileal pouch patients

Background:The clinical implication of Clostridium difficile infection (CDI) in patients with ileal pouch–anal anastomosis (IPAA) for underlying inflammatory bowel disease (IBD) has not been well studied. This study was designed to investigate the cumulative incidence, risk factors, and outcome of CDI in patients with ileal pouches. Methods:Consecutive IPAA patients (n = 196) from the subspecialty Pouchitis Clinic with an increase of at least three stools per day more from the postoperative baseline for more than 4 weeks were enrolled from October 2010 to December 2011. CDI was diagnosed based on the presence of symptoms and positive polymerase chain reaction (PCR)-based stool test for C. difficile toxin B. Risk factors for CDI were assessed with univariate and multivariate analyses. All patients with CDI (n = 21) were treated with oral vancomycin (500 - 1000mg/day) for 2–4 weeks. The treatment outcome of these patients was documented. Results:Twenty-one patients (10.7%) were diagnosed with CDI. On univariate analysis, patients with CDI had more stool frequency (P = 0.014) and significant current weight loss (P = 0.003) than patients with no CDI. In logistic regression analysis, there was a trend that recent hospitalization (odds ratio [OR] = 4.00, 95% confidence interval [CI], 0.95–16.84) might be associated with CDI. Of the 14 CDI patients with follow-up data, eight (57.1%) had either recurrent (n = 5) or refractory (n = 3) CDI after oral vancomycin therapy. Conclusions:A high index of suspicion for CDI in pouch patients should be given to those with recent hospitalization or constitutional symptoms, such as weight loss. Recurrent or refractory CDI is common, even with standard oral vancomycin therapy.

Consensus on the management of inflammatory bowel disease in China in 2007.

Blackwell Publishing Asia Melbourne, Australia CDD hines Journal of Digestive Diseases 1443-9611

Intrathecal cytokine and chemokine profiling in neuropsychiatric lupus or lupus complicated with central nervous system infection.

The aims of this study are to investigate the cytokine, chemokine and adhesion molecule profiles in cerebrospinal fluid from patients with neuropsychiatric systemic lupus erythematosus and systemic lupus erythematosus with central nervous system infection. Experimental sets were established which included 108 patients and 132 cerebrospinal fluid samples. The patients were grouped as neuropsychiatric systemic lupus erythematosus (n = 54), systemic lupus erythematosus with central nervous system infection (n = 16), systemic lupus erythematosus controls (n=20), and non-inflammatory neurological disease (n=18). The dynamic changes of 21 patients in the neuropsychiatric systemic lupus erythematosus group before and after induction therapy were further analyzed. IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, TNFα, IFNγ, IP-10, MCP-1, RANTES, VCAM-1, and P-selectin were measured in cerebrospinal fluid samples by using a fluorescent bead-based assay. Cerebrospinal fluid levels of IL-8, MCP-1, P-selectin and VCAM-1 were significantly increased in neuropsychiatric systemic lupus erythematosus compared with systemic lupus erythematosus controls. IL-6, IL-17, IL-8 and VCAM-1 were higher in systemic lupus erythematosus with central nervous system infection than in systemic lupus erythematosus controls. Among systemic lupus erythematosus with central nervous system infection, the IL-6, IL-17, IL-8 and IP-10 levels were higher than those in neuropsychiatric systemic lupus erythematosus. After sufficient induction therapy, IL-8, MCP-1, P-selectin, VCAM-1 and IL-6 in patients with neuropsychiatric systemic lupus erythematosus decreased significantly. Levels of all molecules tested in non-inflammatory central nervous system disease were not different from those of systemic lupus erythematosus controls. From our data, the intrathecal cytokine/chemokine profile is different among patients with neuropsychiatric systemic lupus erythematosus, systemic lupus erythematosus complicated with central nervous system infection and systemic lupus erythematosus controls. IL-8, MCP-1, VCAM-1, P-selectin and IL-6 in cerebrospinal fluid are effective parameters to monitor neuropsychiatric systemic lupus erythematosus disease activity and response to treatment. Significantly elevated IL-17, IL-6, and to a lesser extent, IL-8, favors central nervous system infection in systemic lupus erythematosus. Lupus (2010) 19, 689—695.

Profiles of Lamina Propria T Helper Cell Subsets Discriminate Between Ulcerative Colitis and Crohn's Disease.

Background:Distinction between 2 forms of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohns disease (CD), can be challenging. Aberrant mucosal immunity suggests that CD is a T helper type 1 cell (Th1)-driven disease, whereas UC as Th2-driven response. However, whether this paradigm truly distinguishes CD from UC is controversial. We aimed to clarify the discriminating potential of lamina propria Th subsets in patients with IBD. Methods:Biopsies from 79 patients with IBD and 20 healthy controls were collected for Th subsets analysis (Th1:interferon &ggr; [IFN-&ggr;], T-bet; Th2:interleukin 13 [IL-13], Gata3; Th17:IL-17, ROR&ggr;t; Treg:FoxP3). The receiver-operating characteristic curves were constructed to assess the discriminating ability by calculating the area under the receiver-operating characteristic curve. The equation with the highest area under the receiver-operating characteristic curve was applied to newly diagnosed patients to evaluate discriminating ability. Results:Patients with CD showed increased IFN-&ggr;+ or T-bet+ cells and decreased IL-13+ or Gata3+ cells compared with UC. A discriminant equation composed of 4 markers (IFN-&ggr;+, T-bet+, IL-13+, and Gata3+) yielded the highest area under the receiver-operating characteristic curve. In 36 established CD or UC, the sensitivity, specificity, positive and negative predictive probabilities were 92.6%, 55.6%, 86.2%, and 71.4% and in 14 newly diagnosed patients were 100.0%, 42.9%, 63.6%, and 100.0%. Furthermore, Gata3+ cells were increased in tumor necrosis factor inhibitor therapy nonresponders compared with responders in CD. IFN-&ggr;+ cells were directly and inversely proportional to disease activity in patients with CD and UC, respectively. Conclusions:The Th1/Th2 paradigm can distinguish CD from UC and may be further associated with response to tumor necrosis factor inhibitor in CD and disease activity in patients with IBD.

Haplotype‐based analysis of ulcerative colitis risk loci identifies both IL2 and IL21 as susceptibility genes in Han Chinese

Background: The incidence of ulcerative colitis (UC) varies between Western and Eastern ethnicities. A distinct genetic background may play a role in the differences. Until now, very little was known of the UC genetics in Asian populations. Here we performed a haplotype‐based analysis of six known UC susceptibility loci in Han Chinese patients. Methods: In all, 245 UC patients and 300 healthy controls of Han Chinese descent were genotyped for 27 single nucleotide polymorphisms (SNPs), which cover the major haplotypes of the chromosome regions containing IL10, IL2/IL21, MYO9B, ECM1, MST1, and IL23R in Han Chinese. Results: In contrast to the tight linkage disequilibrium (LD) block of the IL2/IL21 region in Caucasians, IL2 and IL21 reside in two independent LD blocks in Han Chinese. The IL2 SNP rs2069762 (P = 7.0 × 10−4, odds ratio [OR] = 1.54, 95% confidence interval [CI] 1.20–1.99) and the IL21 SNP rs2055979 (P = 1.2 × 10−4, OR = 1.50, 95% CI 1.17–1.92) were independently associated with UC. We identified one risk haplotype in IL2 and another independent risk haplotype in IL21. In addition to the IL2/IL21 locus, we observed association of the TT genotype of SNP rs1545620 in MYO9B with UC (P = 0.0169; OR = 0.29, 95% CI 0.11–0.78) and association of rs17375018 in IL23R with pancolitis in Chinese UC patients (P = 0.002; OR = 2.38, 95% CI 1.41–4.02). Conclusions: Our study confirmed the association of the IL2/IL21 region with UC in Han Chinese patients, and further implied both IL2 and IL21 as genetic risk factors for UC. Han Chinese UC patients share part of their genetic susceptibility with Caucasian patients.

Combined Detection of NUDT15 Variants Could Highly Predict Thiopurine-induced Leukopenia in Chinese Patients with Inflammatory Bowel Disease: A Multicenter Analysis

Background: NUDT15 c.415C>T was a novel genetic marker confirmed in our center for thiopurine-induced leukopenia in Chinese inflammatory bowel disease (IBD). For validation, a large cohort study is needed. Meanwhile, the newly discovered NUDT15 coding variants (c.36_37insGGAGTC and c.52 G>A) have not been studied in patients with IBD. We aimed to further confirm the influence of 3 NUDT15 variants (c.415C>T, c.36_37insGGAGTC, and c.52G>A) on thiopurine-induced leukopenia in Chinese patients with IBD. Methods: Patients prescribed on thiopurines for at least 2 weeks were recruited from 4 tertiary hospitals. Clinical data were collected. NUDT15 genotypes were determined with polymerase chain reaction-RFLP and sequencing. The interactions between variants and leukopenia were analyzed. Results: A total of 732 patients were included, 177 (24.3%) of whom developed leukopenia. There were strong associations of NUDT15 c.415C>T, c.36_37insGGAGTC, and c.52G>A with thiopurine-induced leukopenia (P = 1.81 × 10−20, P = 4.74 × 10−8 and P = 0.04, respectively), whereas there was no relevance for thiopurine S-methyltransferase genotypes (P = 0.25). The predictive sensitivity of NUDT15 c.415C>T was 49.2%, whereas it increased to 55.4% when combined analysis with c.36_37insGGAGTC and c.52G>A. Notably, not only the homozygotes with NUDT15 c.415C>T but also the heterozygotes both carrying c.415C>T and c.52G>A developed early leukopenia. The median dosage for NUDT15 c.415C>T carriers was significantly lower than that for wild-type (P < 0.001). Conclusions: We confirmed that NUDT15 c.415C>T, c.36_37insGGAGTC, and c.52G>A variants were risk factors for thiopurine-induced leukopenia. Combined detection of the 3 variants could increase the predictive sensitivity of thiopurine-induced leukopenia and help to distinguish early leukopenia in heterozygote of c.415C>T in Chinese patients with IBD. Treatment monitoring by NUDT15 variants may be promising in individualized therapy.

Corticosteroid therapy in ulcerative colitis: Clinical response and predictors

AIM To evaluate clinical response to initial corticosteroid (CS) treatment in Chinese ulcerative colitis patients (UC) and identify predictors of clinical response. METHODS Four hundred and twenty-three UC patients who were initially treated with oral or intravenous CS from 2007 to 2011 were retrospectively reviewed at eight inflammatory bowel disease centers in China, and 101 consecutive cases with one-year follow-up were analyzed further for clinical response and predictors. Short-term outcomes within one month were classified as primary response and primary non-response. Long-term outcomes within one year were classified as prolonged CS response, CS dependence and secondary non-response. CS refractoriness included primary and secondary non-response. Multivariate analyses were performed to identify predictors associated with clinical response. RESULTS Within one month, 95.0% and 5.0% of the cases were classified into primary response and non-response, respectively. Within one year, 41.6% of cases were assessed as prolonged CS response, while 49.5% as CS dependence and 4.0% as secondary non-response. The rate of CS refractoriness was 8.9%, while the cumulative rate of surgery was 6.9% within one year. After multivariate analysis of all the variables, tenesmus was found to be a negative predictor of CS dependence (OR = 0.336; 95%CI: 0.147-0.768; P = 0.013) and weight loss as a predictor of CS refractoriness (OR = 5.662; 95%CI: 1.111-28.857; P = 0.040). After one-month treatment, sustained high Sutherland score (≥ 6) also predicted CS dependence (OR = 2.347; 95%CI: 0.935-5.890; P = 0.014). CONCLUSION Tenesmus was a negative predictor of CS dependence, while weight loss and sustained high Sutherland score were strongly associated with poor CS response.

The Association Between CMV Viremia or Endoscopic Features and Histopathological Characteristics of CMV Colitis in Patients with Underlying Ulcerative Colitis

Background: Cytomegalovirus (CMV) infection has been shown to be related to severe or steroid-refractory ulcerative colitis (UC) flare-ups. The aim of this study was to evaluate the endoscopic and pathological characteristics of CMV colitis in patients with UC and to assess the predictive value of the endoscopic and pathological features of CMV colitis. Methods: A total of 50 consecutive UC patients with CMV infection who were admitted to Peking Union Medical College Hospital from 2010 to 2015 were enrolled in this study. Results: Twenty-five UC patients with CMV infection (50.0%) had concurrent CMV colitis. When the cutoff value was set at 1150 copies, the sensitivity and specificity of blood CMV DNAq polymerase chain reaction for predicting CMV colitis were 44.4% and 78.9%, respectively. A higher proportion of endoscopic punched-out ulcers, irregular ulcers, and cobblestone-like appearance were observed among the patients in the CMV colitis group than those in the non-CMV colitis group (52.0% versus 20.0%, 60.0% versus 16.0%, and 20.0% versus 0%, respectively, P < 0.05). The number of CMV inclusion bodies per high-power field was significantly higher in those with punch-out ulcerations (25.7% versus 60.0%, P < 0.05). A higher grade of pathological inflammation was observed in the CMV colitis group than in the control group (68.0% versus 44.0%). Conclusions: Characteristic endoscopic features with punch-out ulcers and high CMV viremia load may be useful for predicting the presence of CMV colitis in histology. Punch-out ulcers were found to be associated with a higher number of inclusion bodies on histology, suggesting a role of targeted biopsy for endoscopist.

Fluorescence In Situ Hybridization with the UroVysion Kit for the Detection of Biliary Cancer in Chinese Patients

BACKGROUND Conventional biliary brush via ERCP has low clinical detection for biliary malignancy. Therefore, new approaches are needed to facilitate diagnosis. We therefore explored the application of fluorescent in situ hybrization (FISH) using a UroVysion kit for the detection of malignancy in the bile duct. METHODS Genetic alterations of target chromosomes such as aneuploidy in Chinese biliary cancer cell lines and tissues were measured using a UroVysion kit. The diagnostic value of the FISH assay was assessed by probing 27 brush samples of biliary cytology and control routine cytology (RC) samples. The gold standard was established by the pathology or clinical outcomes at the 12-month follow-up. RESULTS Aneuploidy is commonly found in cell lines and tissues of biliary cancers, but not in normal cells or tissues. Here we probed for aneuploidy in clinical biliary brush specimens obtained by ERCP using FISH and a UroVysion kit. The sensitivity, specificity, and positive and negative predictive values for biliary malignancy were found to be 50%, 100%, 100% and 31.3%, respectively. The sensitivity, specificity, and positive and negative predictive values by RC were found to be 22.7%, 100%, 100% and 22.7%, respectively. In combination with RC, FISH increased the diagnostic sensitivity to 63.6% although this difference was not found to be statistically significant. CONCLUSIONS Aneuploidy is frequently present in bile duct carcinomas. Here we found that the FISH assay is useful for the detection of Chinese biliary cancers.

Cholestasis, ascites and pancytopenia in an immunocompetent adult with severe cytomegalovirus hepatitis.

Human cytomegalovirus (CMV) is a herpesvirus, which establishes lifelong latency after primary infection and leads to severe disease in immunocompromised patients. However, CMV infection in immunocompetent patients is usually asymptomatic and severe organ damage is rarely reported. We report a case of severe CMV hepatitis in an immunocompetent patient presenting with cholestasis, portal hypertension-related ascites and pancytopenia. The patient was asymptomatic with normal liver function and negative CMV DNA after two weeks of antiviral therapy. This case is an example of a common infection with an uncommon presentation, and suggests that testing for CMV should be carried out, even in patients with normal immune status, presenting with severe liver damage or cholestasis.