Vascular Endothelial Growth Factor and Ischemic Heart Disease Risk: A Mendelian Randomization Study

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Evaluating the impact of AMPK activation, a target of metformin, on risk of cardiovascular diseases and cancer in the UK Biobank: A Mendelian randomization study

Aims/hypothesis: Whether metformin reduces cardiovascular or cancer risk is unclear owing to concerns over immortal time bias and confounding in observational studies. This study evaluated the effect of AMP-activated protein kinase (AMPK), the target of metformin, on risk of cardiovascular disease and cancer. Methods: This is a Mendelian randomisation design, using AMPK, the pharmacological target of metformin, to infer the AMPK pathway-dependent effects of metformin on risk of cardiovascular disease and cancer in participants of white British ancestry in the UK Biobank. Results: A total of 391,199 participants were included (mean age 56.9 years; 54.1% women), including 26,690 cases of type 2 diabetes, 38,098 cases of coronary artery disease and 80,941 cases of overall cancer. Genetically predicted reduction in HbA1c (%) instrumented by AMPK variants was associated with a 61% reduction in risk of type 2 diabetes (OR 0.39; 95% CI 0.20, 0.78; p = 7.69 × 10−3), a 53% decrease in the risk of coronary artery disease (OR 0.47; 95% CI 0.26, 0.84; p = 0.01) and a 44% decrease in the risk of overall cancer (OR 0.56; 95% CI 0.36, 0.85; p = 7.23 × 10−3). Results were similar using median or quartiles of AMPK score, with dose–response effects (p for trend = 4.18 × 10−3 for type 2 diabetes, 4.37 × 10−3 for coronary artery disease and 4.04 × 10−3 for overall cancer). Conclusions/interpretation: This study provides some genetic evidence that AMPK activation by metformin may protect against cardiovascular disease and cancer, which needs to be confirmed by randomised controlled trials

The effect of statins on testosterone in men and women, a systematic review and meta-analysis of randomized controlled trials

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Birth weight and risk of ischemic heart disease: A Mendelian randomization study

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Intravenous bolus somatostatin after diagnostic cholangiopancreatography reduces the incidence of pancreatitis associated with therapeutic endoscopic retrograde cholangiopancreatography procedures: A randomised controlled trial

Background: Previous studies suggested that somatostatin given before endoscopic retrograde cholangiopancreatography (ERCP) may reduce the incidence of post-ERCP pancreatitis. However, the routine use of somatostatin in all patients undergoing ERCP is not likely to be cost effective. This study evaluated whether intravenous bolus somatostatin given after diagnostic cholangiopancreatography could reduce the incidence of pancreatitis in a group of patients undergoing therapeutic ERCP procedures. Methods: In a randomised, double blind, controlled trial, the effect of intravenous bolus somatostatin 250 μg given immediately after diagnostic cholangiopancreatography was compared with that of placebo in patients who required endoscopic sphincterotomy or other therapeutic procedures. The primary end point was the incidence of post-ERCP clinical pancreatitis, and a secondary end point was the incidence of hyperamylasemia. Results: A total of 270 patients were randomised. The somatostatin group (n = 135) and the placebo group (n = 135) were comparable in age, sex, indications for treatment, and types of procedure. The frequencies of clinical pancreatitis (4.4% v 13.3%; p = 0.010) and hyperamylasemia (26.0% v 38.5%; p = 0.036) were both significantly lower in the somatostatin group compared with the placebo group. Conclusions: A single dose of intravenous bolus somatostatin, given immediately after diagnostic cholangiopancreatography, is effective in reducing the incidence of pancreatitis after therapeutic ERCP. This novel approach of administering prophylactic somatostatin may offer a cost effective prophylaxis for post-ERCP pancreatitis.published_or_final_versio

Liver Enzymes and Risk of Ischemic Heart Disease and Type 2 Diabetes Mellitus: A Mendelian Randomization Study

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香港結核病患者的特徵與治療結果

OBJECTIVES: To identify the general characteristics of patients with tuberculosis, and to evaluate their treatment outcomes. DESIGN: Retrospective study. SETTING: Tuberculosis and Chest Service, Department of Health, Hong Kong. SUBJECTS AND METHODS: All patients with tuberculosis registered for treatment from 1 January 1996 to 31 December 1996 were included in the study. Information was extracted from their medical records at treatment commencement and at 12 and 24 months after treatment was instigated. Data gathered included demographic data, past treatment, site of disease, case category, treatment regimen, bacteriological status, and treatment outcome. RESULTS: There were 5757 patients for analysis. Approximately one third of patients were aged 60 years or older, and 69.1% were male. Pulmonary disease alone occurred in 77.7% of patients, while both pulmonary and extrapulmonary diseases occurred in 8.6%. New patients comprised 84.6% of cases, and 16.3% had concomitant illnesses. There was excess risk of disease among patients who were male, elderly, or who had silicosis. Only 0.1% of patients were co-infected with human immunodeficiency virus infection. Among the 5757 cases evaluated, 1324 (23.0%) were new patients with a positive sputum smear, 299 (5.2%) were patients who were retreated with a positive sputum smear, and 4134 (71.8%) were new or retreatment patients with a negative sputum smear. The overall treatment completion rates at 12 and 24 months were 80.4% and 84.8%, respectively. Males and patients aged 60 years or older had lower treatment completion rates. Non-adherence, transfer to other services, and mortality among the elderly were key factors influencing treatment outcomes. Co-morbidity was associated with better case-holding, and this more than compensated for its effect on prolongation of treatment and mortality. CONCLUSIONS: There was an excess risk of tuberculosis among male and elderly patients, who also had a less favourable outcome. Active screening of clearly identified risk groups may be appropriate but requires the completion of more in-depth studies and careful cost-effectiveness analyses. Further efforts with respect to case-holding are indicated to address treatment defaulting and transfer rates.published_or_final_versio

Prevalence and predictors of default from tuberculosis treatment in Hong Kong

OBJECTIVE: To determine the prevalence and risk factors of default from tuberculosis treatment in Hong Kong. DESIGN: Retrospective study. SETTING: Data were obtained from programme forms completed by physicians in the Hong Kong Government Tuberculosis and Chest Service and from medical records from Hong Kong chest clinics. PATIENTS: In all, 5917 patients registered for antituberculous drug therapy in 1996; medical records of 5757 patients were reviewed. MAIN OUTCOME MEASURES: Patients who defaulted treatment were defined as those who had failed to collect medication for more than 2 consecutive months after the date of the last attendance during the course of treatment. Demographic and clinical characteristics, including history, treatment, and outcome, were compared between defaulters and non-defaulters, both among the whole group and among those with pulmonary disease. RESULTS: There were 442 (8%) patients who defaulted from treatment. Forty-five percent of those who defaulted did so in the first 2 months of treatment. Key risk factors associated with non-compliance were a history of default, male sex, and a history of concomitant liver disease or lung cancer. Among patients with pulmonary tuberculosis (381 defaulters and 1537 non-defaulters), multiple drug resistance was also associated with default from treatment. Among defaulters with pulmonary disease, 39% were still bacteriologically positive at the time of default. CONCLUSION: Default from treatment may be partially responsible for the persistent high rates of tuberculosis in Hong Kong in the past decade. Health professionals should ensure that all barriers to treatment be removed and that incentives be used to encourage treatment compliance.published_or_final_versio

Profiles of cytokine and chemokine gene expression in human pulmonary epithelial cells induced by human and avian influenza viruses

Influenza pandemic remains a serious threat to human health. In this study, the repertoire of host cellular cytokine and chemokine responses to infections with highly pathogenic avian influenza H5N1, low pathogenicity avian influenza H9N2 and seasonal human influenza H1N1 were compared using an in vitro system based on human pulmonary epithelial cells. The results showed that H5N1 was more potent than H9N2 and H1N1 in inducing CXCL-10/IP-10, TNF-alpha and CCL-5/RANTES. The cytokine/chemokine profiles for H9N2, in general, resembled those of H1N1. Of interest, only H1N1, but none of the avian subtypes examined could induce a persistent elevation of the immune-regulatory cytokine - TGF-β2. The differential expression of cytokines/chemokines following infection with different influenza viruses could be a key determinant for clinical outcome. The potential of using these cytokines/chemokines as prognostic markers or targets of therapy is worth exploring

Protective effects of lycium barbarum polysaccharides on cerebral edema and blood-brain barrier disruption after ischemic stroke

Young Investigators Symposium I (Y3) - Di YangBACKGROUND: Ischemic stroke is a destructive cerebrovascular disease and one of the leading causes of death worldwide. The long term disability after stroke induces heavy burden both to the patients and the society. Yet, no effective neuroprotective agents are available. The polysaccharides extracted from the fruits of wolfberry, Lycium barbarum (LBP), showed neuroprotective and immune-modulative functions. We aim to evaluate the protective effects of LBP in experimental stroke using a focal cerebral ischemia/reperfusion (I/R) model. METHODS: C57BL/6N mice were subjected to 2 h of middle cerebral artery occlusion (MCAO) followed by 22 h of reperfusion. Prior to ischemia induction, animals were treated with either vehicle (PBS) or LBP daily for 7 days. Mice were evaluated for neurological deficits just before sacrifice. Brains were harvested for infarct size estimation, water content measurement and immunohistochemical analysis as well as Western blot experiments. Evans blue (EB) extravasation experiment was performed to determine blood-brain barrier (BBB) disruption after MCAO. RESULTS: LBP treatment significantly improved neurological scores and decreased infarct size, hemispheric swelling and water content as well as reduced EB extravasation. In addition, fewer apoptotic cells were identified in the LBP-treated brains by TUNEL assay. Immunoreactivity for aquaporin-4 and glial fibrillary acidic protein were also significantly decreased in LBP-treated brains. We further observed a reduction of nuclear factor-κB translocation and IκB expression after LBP treatment. CONCLUSION: Seven-day LBP pre-treatment effectively improved neurological deficits, decreased infarct size and cerebral edema as well as protected the brain from BBB disruption, aquaporin water channel up-regulation and glial activation. The protective effects of LBP might partially act through its anti-inflammatory effects. The present study suggests that LBP may be used as a preventive neuroprotectant for ischemic stroke.postprin