BACKGROUND The incidence of Clostridium difficile infection (CDI) has increased among hospitalized patients and is a common complication of leukemia. We investigated the risks for and outcomes of CDI in hospitalized leukemia patients. METHODS Adults with a primary diagnosis of leukemia were extracted from the United States Nationwide Inpatient Sample database, 2005-2011. The primary outcomes of interest were CDI incidence, CDI-associated mortality, length of stay (LOS), and charges. In a secondary analysis, we sought to identify independent risk factors for CDI in leukemia patients. Logistic regression was used to derive odds ratios (ORs) adjusted for potential confounders. RESULTS A total of 1,243,107 leukemia hospitalizations were identified. Overall CDI incidence was 3.4% and increased from 3.0% to 3.5% during the 7-year study period. Leukemia patients had 2.6-fold higher risk for CDI than non-leukemia patients, adjusted for LOS. CDI was associated with a 20% increase in mortality of leukemia patients, as well as 2.6 times prolonged LOS and higher hospital charges. Multivariate analysis revealed that age >65 years (OR, 1.13), male gender (OR, 1.14), prolonged LOS, admission to teaching hospital (OR, 1.16), complications of sepsis (OR, 1.83), neutropenia (OR, 1.35), renal failure (OR, 1.18), and bone marrow or stem cell transplantation (OR, 1.27) were significantly associated with CDI occurrence. CONCLUSIONS Hospitalized leukemia patients have greater than twice the risk of CDI than non-leukemia patients. The incidence of CDI in this population increased 16.7% from 2005 to 2011. Development of CDI in leukemia patients was associated with increased mortality, longer LOS, and higher hospital charges.

Abstract Abstract AIM: To evaluate the risk factors for primary liver carcinoma (PLC) in Chinese population. METHODS:Chinese Biomedical Literature Database, China Hospital Knowledge Database and MEDLINE were searched. All the related literatures were screened, and the risk factors for PLC in Chinese population were studied. Heterogeneity was evaluated by odds ratio (OR) q test. Combined OR and its 95% confidence interval (95%CI) were calculated, the association between the investigated risk factors and PLC was determined. Validity and bias of the findings were evaluated by sensitivity analysis and funnel plot analysis respectively. RESULTS:Fifty-five of one hundred and ninety identified studies were accepted according to the inclusive criteria. Ten factors related to PLC were demonstrated by sensitive analysis and funnel plot analysis. They were cirrhosis (OR = 11.97, P = 0.000), HBV infection (OR = 11.34, P = 0.000), HCV infection (OR = 4.28, P = 0.000), family history of liver cancer (OR = 3.49, P = 0.000), unstable emotion (OR = 2.20, P = 0.000), depressed characters (OR = 3.07, P = 0.000), aflatoxin (OR = 1.80, P = 0.000), alcoholic (OR = 1.88, P = 0.000), intake of musty food (OR = 1.87, P = 0.000) and drinking contaminated water from pond (OR = 1.77, P = 0.003). CONCLUSION:The main risk factors for PLC in China are liver diseases, family history of liver carcinoma, poor psychic status, aflatoxin, and some unhealthy behaviors.

Background and Purpose Celastrol exhibits anti‐arthritic effects in rheumatoid arthritis (RA), but the role of celastrol‐mediated Ca 2+ mobilization in treatment of RA remains undefined. Here, we describe a regulatory role for celastrol‐induced Ca 2+ signalling in synovial fibroblasts of RA patients and adjuvant‐induced arthritis (AIA) in rats. Experimental Approach We used computational docking, Ca 2+ dynamics and functional assays to study the sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase pump (SERCA). In rheumatoid arthritis synovial fibroblasts (RASFs)/rheumatoid arthritis fibroblast‐like synoviocytes (RAFLS), mechanisms of Ca 2+ ‐mediated autophagy were analysed by histological, immunohistochemical and flow cytometric techniques. Anti‐arthritic effects of celastrol, autophagy induction, and growth rate of synovial fibroblasts in AIA rats were monitored by microCT and immunofluorescence staining. mRNA from joint tissues of AIA rats was isolated for transcriptional analysis of inflammatory genes, using siRNA methods to study calmodulin, calpains, and calcineurin. Key Results Celastrol inhibited SERCA to induce autophagy‐dependent cytotoxicity in RASFs/RAFLS via Ca 2+ /calmodulin‐dependent kinase kinase‐β–AMP‐activated protein kinase–mTOR pathway and repressed arthritis symptoms in AIA rats. BAPTA/AM hampered the in vitro and in vivo effectiveness of celastrol. Inflammatory‐ and autoimmunity‐associated genes down‐regulated by celastrol in joint tissues of AIA rat were restored by BAPTA/AM. Knockdown of calmodulin, calpains, and calcineurin in RAFLS confirmed the role of Ca 2+ in celastrol‐regulated gene expression. Conclusion and Implications Celastrol triggered Ca 2+ signalling to induce autophagic cell death in RASFs/RAFLS and ameliorated arthritis in AIA rats mediated by calcium‐dependent/‐binding proteins facilitating the exploitation of anti‐arthritic drugs based on manipulation of Ca 2+ signalling.

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