Effects of 5-aminosalicylates or thiopurines on the progression of low-grade dysplasia in patients with inflammatory bowel disease: a systematic review and meta-analysis.

PURPOSE: Although 5-aminosalicylates and thiopurines may have an antineoplastic effect on colorectal neoplasia in patients with inflammatory bowel disease (IBD), their impact on the progression of low-grade dysplasia (LGD) in IBD is uncertain. Therefore, we performed a systematic review and meta-analysis to evaluate whether 5-aminosalicylates or thiopurines can protect against the progression of LGD in patients with IBD. METHODS: Systematic searches of PubMed, EMBASE, Cochrane Library databases, and major conference proceedings were conducted to identify all eligible studies through March 2020. Data were pooled using a random effects model. Study quality was assessed using the Newcastle-Ottawa Scale. RESULTS: Five studies comprising 776 IBD patients with LGD were included. Overall, 5-aminosalicylates (Hazard ratio (HR) = 0.91, 95% confidence interval (CI) 0.55-1.51) and thiopurines (HR = 0.64, 95% CI 0.23-1.79) did not significantly reduce the risk of advanced colorectal neoplasia (high-grade dysplasia/cancer) in IBD patients with LGD. Moreover, the effects of 5-aminosalicylates or thiopurines on risk of advanced colorectal neoplasia in IBD patients with LGD were not significant by different primary sclerosing cholangitis status, study quality, sample size, and IBD type. CONCLUSIONS: In this study, we did not find a significant protective effect of 5-aminosalicylates or thiopurines on the progression of LGD in patients with IBD.

Opportunistic Infection in Hospitalised Patients with Inflammatory Bowel Disease.

OBJECTIVE: To investigate the incidence, clinical features, and risk factors of opportunistic infections in elderly patients with inflammatory bowel disease (IBD). STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of Digestive and Geriatrics Center, Sichuan University West China Hospital, China between January 2012 and January 2019. METHODOLOGY: Patients (≥18 years) with IBD were enrolled in this study. Clinical data from the infected elderly group (age ≥60 years), non-infected elderly group (age ≥60 years) and infected adult group (age: 18-59 years) were compared. Logistic regression analysis was used for risk factors associated with opportunistic infection. RESULTS:  A total of 8.9% (307/3,456) of patients with IBD had opportunistic infection. The opportunistic infection rate of elderly group was 16.5% (80/485), which was significantly higher than that of adult group (7.6%, 227/2,971, p <0.05). Compared with infected adult group or non-infected elderly group, infected elderly group had less fever and leukocytosis, but more hypoproteinemia and several activities (p <0.05). Cytomegalovirus and Epstein-Barr virus were the most common agents in elderly group and adult group, respectively. Multiple episodes (three or more) were more common in infected elderly group; the time of opportunistic infections was associated with systemic inflammatory reaction syndrome (SIRS, p <0.05). Logistic regression analysis showed that age ≥60 years, corticosteroids, immunosuppressive and biological agents were risk factors for opportunistic infections in patients with IBD. CONCLUSION: Hospitalised elderly IBD patients, receiving corticosteroids, immunosuppressive, and biological agents, are at higher risk for infection. The symptoms of opportunistic infections in elderly patients are atypical, but they are prone to multiple infections with poor prognosis. Key Words: Elderly patients, Inflammatory bowel disease, Opportunistic infection, Systemic inflammation reaction syndrome.

Glial-derived neurotrophic factor regulates enteric mast cells and ameliorates dextran sulfate sodium-induced experimental colitis.

BACKGROUND & AIMS: Although interactions between enteric glial cells (EGCs) and enteric mast cells have been demonstrated to play an important role in the pathogenesis of inflammatory bowel disease (IBD), the exact mechanisms by which EGCs regulate enteric mast cells are still unknown. The aims of this study were to investigate whether glial-derived neurotrophic factor (GDNF), which has been confirmed to be produced mostly by EGCs, might regulate enteric mast cells and ameliorate dextran sulfate sodium (DSS)-induced experimental colitis. METHODS: Recombinant adenoviral vectors encoding GDNF (Ad-GDNF) were administered intracolonically in experimental colitis induced by DSS. The disease activity index and histological score were measured. The expression of tumour necrosis factor-α (TNF-α), interleukin-6 and myeloperoxidase (MPO) activity were measured by ELISA assay. The expression of trypsin and ß-hexosaminidase were evaluated. GDNF specific receptor (GFR-α1/RET) was detected. The calcium reflux was tested by microplate reader. The expression p-JNK was analyzed by western blot assay. RESULTS: GDNF resulted in a significant inhibition of the activation of enteric mast cells by down-regulating JNK signal pathway, lessening intracellular calcium influx, and then reducing the degranulation as well as the expression of pro-inflammatory cytokines via combing with its receptor (GFR-α1/RET) in mast cells, and these inhibitory effects were abrogated by treatment with neutralizing antibody against GDNF. Moreover, the administration of GDNF led to an amelioration of experimental colitis. CONCLUSIONS: GDNF are able to regulate enteric mast cells and ameliorate experimental colitis. GDNF might be an important mediator of the cross-talk between EGCs and enteric mast cells, and GDNF might be a useful therapeutic drug for IBD.

Is comprehensive geriatric assessment recognized and applied in Southwest China? A survey from Sichuan Association of Geriatrics.

OBJECTIVES: To investigate how health care providers in Southwest China conducted comprehensive geriatric assessment (CGA) in their clinical practices. METHODS: One hundred twenty-two medical care providers who attended the 2012 Sichuan Association of Geriatrics (SAG) Continuing Medical Education participated in this cross-sectional survey. The instrument was divided into 2 parts, including respondents' demographics and information on their application of CGA. RESULTS: Of the total 122 participants, 120 (73 physicians and 47 nurses) responded. Three-quarters of the respondents reported that they evaluated at least 1 item of CGA separately. Among them, 30/32 respondents from university-affiliated hospitals reported having performed CGA compared with 18/22 from community hospitals or retirement/nursing facilities and 42/66 from provincial or county hospitals (P < .001), respectively. Respondents who attended the SAG Continuing Medical Education were more likely to complete the CGA (86.5% vs 66.2%, P = .011) and the integrated CGA (48.9% vs 20.0%, P < .001). Physicians were more likely to assess the instrument daily living capacity and communication capacity. Nurses were more focused on the basic activities of daily living, economic support, and caregiver. CONCLUSIONS: These findings showed that the application of CAG in the mainland of China is not adequate. The training program related to CGA held by the SAG was helpful in improving the proportion of effective use of CGA. More efforts should be made in the future to build the CGA work team.

[Effects of aging on the expressions of insulin receptor substrate-1, phosphate protein kinase B in rat liver and muscle].

OBJECTIVES: To investigate the effects of aging on the levels of free fatty acid (FFA), lipid profile, the expression of IRS-1 and its downstream signal Akt phosphorylation, so to explore the mechanisms of aging-associated glucose tolerance impairment. METHODS: Three different age groups (6, 12, 20-24 months) of SD rats were used. After being fasted for 12-14 h, the rats were anesthetized with sodium pentobarbital (30 mg/kg BW, i.p.), then the samples of blood, liver and muscle were collected. Blood samples were used for the detection of fasting blood glucose, lipid profile and FFA. The expressions of IRS-1 and p-Akt in liver and muscle were measured by immunohistochemical staining method. RESULTS: 1) The level of FFA in 20-24 months groups was significantly higher [(419.94 +/- 93.93) vs (256.22 +/- 73.93) mmol/L, P<0.05] than that of younger group (6 months); 2) IRS-1 was expressed in liver and muscle cell of all groups. The level of IRS-1 showed no significant change in both liver and muscle. 3) p-Akt expression in liver significantly decreased in old rat when comparing to younger counterparts [2911.06 +/- 268.13 vs 4683.72 +/- 582.29 (12 months) & 4903.06 +/- 688.44 (6 months), P<0.05], while no difference was found in muscle among three age groups. CONCLUSION: 1) FFA was the initial metabolic change in natural aging SD rat, which might play an important role in age-related insulin resistance. 2) There was no significant difference of IRS-1 expression among three rat age groups. 3) PI3K/Akt pathway in liver of old rat is a critical signal defect of insulin dysfunction with aging. Liver might be main component organ involved to age-related insulin resistance.