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Yulan Liu,1 Yang Meng,2 Lu Wang,1 Zhou Liu,1 Jiao Li,3 Weiguo Dong3 1Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, China; 2Department of Gastroenterology Surgery, Renmin Hospital of Wuhan University, Wuhan, China; 3Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China Background and aim: Despite several studies being conducted to examine the associations between the NUDT15 R139C polymorphism and thiopurine-induced leukopenia in the Asian population, the results remain inconsistent. This meta-analysis determined the risk of thiopurine-induced leukopenia conferred by the NUDT15 R139C polymorphism. Materials and methods: All eligible studies published in English up to May 2018 were identified by searching PubMed, Web of Science, Embase, and the Cochrane Library. Pooled OR and 95% CI were calculated using fixed- or random-effect model. Results: In all, total of 14 studies containing 918 patients and 2,341 controls were included; of these, 8 studies concerned inflammatory bowel disease (IBD) and 4 concerned acute lymphoblastic leukemia (ALL). Overall, the results indicated that the NUDT15 R139C polymorphism was associated with leukopenia induced by thiopurines (OR =9.04, 95% CI 6.05–13.50, P

Yichen Meng,* Heng Jiang,* Chenglin Zhang,* Jianquan Zhao, Ce Wang, Rui Gao, Xuhui Zhou Department of Orthopedics, Changzheng Hospital, Second Affiliated Hospital of Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Postoperative analgesia remains a challenge for orthopedic surgeons. The aim of this meta-analysis is to compare the efficacy of epidural analgesia (EA) and intravenous patient-controlled analgesia (IV-PCA) following major spine surgery. We searched electronic databases, including the PubMed, EMBASE, Ovid and Cochrane databases, for randomized controlled trials (RCTs) published before June 2016. The quality of the included trials was assessed using the Cochrane risk-of-bias tool. Random effects models were used to estimate the standardized mean differences (SMDs) and relative risks (RRs), with the corresponding 95% confidence intervals (CI). Subgroup analyses stratified by the type of epidural-infused medication and epidural delivery were also performed. A total of 17 trials matched the inclusion criteria and were chosen for the following meta-analysis. Overall, EA provided significantly superior analgesia, higher patient satisfaction and decreased overall opioid consumption compared with IV-PCA following major spine surgery. Additionally, no differences were found in the side effects associated with these two methods of analgesia. Egger’s and Begg’s tests showed no significant publication bias. We suggest that EA is superior to IV-PCA for pain management after major spine surgery. More large-scale, high-quality trials are needed to verify these findings. Keywords: adolescent idiopathic scoliosis, lumbar fusion, epidural analgesia, intravenous application, perioperative pain

ERCC1 rs11615 and ERCC2 rs238406 single nuclear polymorphism (SNPs) are known for their association with treatment outcome, likely related to radiosensitivity of both tumor and normal tissue in patients with non-small-cell lung cancer. This study aimed to review the effect of 1) these ERCC1/2 SNPs and 2) other SNPs of DNA repair genes on radiation pneumonitis (RP) in patients with lung cancer. SNPs of our interest included ERCC1 rs11615 and ERCC2 rs238406 and other genes of DNA repair pathways that are functional and biologically active. DNA repair SNPs reported by at least two independent studies were pooled for meta-analysis. The study endpoint was radiation pneumonitis (RP) after radiotherapy. Recessive, dominant, homozygous, heterozygous, and allelic genotype models were used where appropriate. A total of 16 studies (3080 patients) were identified from the systematic review and 12 studies (2090 patients) on 11 SNPs were included in the meta-analysis. The SNPs were ATM rs189037, ATM rs373759, NEIL1 rs4462560, NEIL1 rs7402844, APE1 rs1130409, XRCC3 rs861539, ERCC1 rs11615, ERCC1 rs3212986, ERCC2 rs238406, ERCC2 rs13181, and XRCC1 rs25487. ERCC1 rs11615 (236 patients) and ERCC2 rs238406 (254 patients) were not significantly associated with RP. Using the allelic model, the G allele for NEIL1 gene was significantly associated with a reduced odds of developing symptomatic (grade ≥2) RP compared to the C allele for rs7402844 (OR 0.70, 95% CI: 0.49, 0.99, P = 0.04). Similarly, the T allele for APE1 gene was significantly associated with a reduced odds of developing symptomatic (grade ≥2) RP compared to the G allele for rs1130409 (OR 0.59, 95% CI: 0.43, 0.81, P = 0.001). Genetic variation in the DNA repair pathway genes may play a significant role in the risk of developing radiation pneumonitis in patients with lung cancer. Further studies are needed on genotypic features of DNA repair pathway genes and their association with treatment sensitivity, as such knowledge may guide personalized radiation dose prescription. • A total of 16 studies (3080 patients) were identified from the systematic review. • Genetic variation in NEIL1 rs7402844 and APE1 rs1130409 may predict RP. • Need to further elucidate relationship between ERCC1 rs11615, ERCC2 rs238406 with RP. [ABSTRACT FROM AUTHOR]

Summary: Our network meta-analysis analyzed the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on fracture risk. By combining data from randomized controlled trials, we found that GLP-1 RAs were associated with a decreased bone fracture risk, and exenatide is the best option agent with regard to the risk of fracture. This study is registered with PROSPERO (CRD42018094433).Introduction: Data on the effects of GLP-1 RAs on fracture risk are conflicted. This study aimed to analyze the available evidence on the effects of GLP-1 RAs on fracture risk in type 2 diabetes mellitus patients.Methods: Electronic databases were searched for relevant published articles, and unpublished studies presented at ClinicalTrials.gov were searched for relevant clinical data. All analyses were performed with STATA 12.0 and R software (Version 3.4.4). We estimated the risk ratio (RR) and 95% confidence interval (CI) by combining RRs for fracture effects of included trials.Results: There were 54 eligible random control trials (RCTs) with 49,602 participants, including 28,353 patients treated with GLP-1 RAs. Relative to placebo, exenatide (RR, 0.17; 95% CI 0.03-0.67) was associated with lowest risk of fracture among other GLP-1 RAs. Exenatide had the highest probability to be the safest option with regard to the risk of fracture (0.07 ‰), followed by dulaglutide (1.04%), liraglutide (1.39%), albiglutide (5.61%), lixisenatide (8.07%), and semaglutide (18.72%). A statistically significant inconsistency was observed in some comparisons.Conclusion: The Bayesian network meta-analysis suggests that GLP-1 RAs were associated with a decreased bone fracture risk compared to users of placebo or other anti-hyperglycemic drugs in type 2 diabetes mellitus patients, and exenatide is the best option agent with regard to the risk of fracture. [ABSTRACT FROM AUTHOR]

The effects of resistant starch (RS) on serum cholesterol levels have been previously investigated. However, the results of those studies are inconsistent. The purpose of our meta-analysis was to determine if RS affects blood lipids based on the current literature. The methods included searching databases (PubMed, Embase, Scopus, and Cochrane Library) up to September 2017, as well as hand-searching reference lists of articles published in English. The initial search yielded 1228 articles. Of these, 14 articles (20 trials) were included in our investigation focusing on the effects of RS on total cholesterol (TC; 19 trials), triglycerides (TG; 19 trials), low-density lipoprotein cholesterol (LDL-C; 16 trials), and high-density lipoprotein cholesterol (17 trials). Methodological quality was assessed using TC, LDL-C, TGs, and high-density lipoprotein cholesterol. Pooled effects were calculated using a random-effects model. The meta-analysis of these data showed that RS supplementation has an effect on lowering TC and LDL-C (TC: mean difference, −7.33 mg/dL [95% confidence interval −12.15 to −2.52 mg/dL]; LDL-C: mean difference: −3.40 mg/dL [95% confidence interval, −6.74 to −0.07 mg/dL]). Subgroup meta-analysis revealed that a longer time (>4 weeks) of RS supplementation can generate more obvious effects on TC and LDL-C levels, and higher dose (>20 g/d) of RS also had a lowering effect on TG level. Future research should focus on the relationship between RS type and cholesterol-lowering effects, and the effects on subjects of different health status or those with different baseline levels of serum lipids. Moreover, the mechanism for the cholesterol-lowering effects of RS should be further explored. In conclusion, RS can reduce serum TC and LDL-C levels, particularly when administered for a duration longer than 4 weeks. [ABSTRACT FROM AUTHOR]

Background Psoriasis is a chronic, recurrent skin disease that affects approximately 2-3% of the world's population, and can significantly impair patients' wellbeing and their physical and mental functioning. Aim To systematically evaluate the efficacy and safety of ustekinumab versus placebo for psoriasis. Methods We performed a systematic review of all the relevant published literature relating to randomized controlled trials ( RCTs) of ustekinumab from 1990 to August 2013. Relative ratios ( RRs) and 95% confidence intervals ( CIs) were calculated, and meta-analysis was conducted with Revman5.2.6 software, while GRADE Profile 3.6 was used to evaluate the quality of the evidence. Results In total, 9 RCTs involving 11 381 patients were included. The meta-analysis results were as follows. (i) At the end of 12 weeks, the ustekinumab group had a larger number of patients with improvement in Psoriasis Area and Severity Index ( PASI) of at least 50% ( PASI50), at least 75% ( PASI75) and at least 90% ( PASI90); a larger number with improvement in Physician's Global Assessment ( PGA), and a larger number with improvement in Dermatology Life Quality Index ( DLQI) to a score of 0 or 1 (no effect at all on patient's life). (ii) There was no significant difference in efficacy between 45 mg and 90 mg ustekinumab at the end of 12 weeks. (iii) There was no obvious difference between the ustekinumab and placebo groups in the incidence of adverse events over 5 years. There was also no obvious difference between the two doses of ustekinumab after 5 years. Conclusion Our results indicate that ustekinumab is safe for patients with moderate to severe plaque psoriasis over a period of 5 years, and it is effective after 12 weeks. There was no significant superiority in efficacy between the 45 mg and 90 mg doses for short-term therapy. Results of the long-term safety evaluation are consistent with short-term reports of ustekinumab safety. More long-term studies and RCTs are needed to validate these results. [ABSTRACT FROM AUTHOR]

Background: A systematic review and network meta-analysis was undertaken to consider the evidence for the efficacy and tolerability of placebo, cilostazol, naftidrofuryl oxalate and pentoxifylline in patients with intermittent claudication due to peripheral arterial disease (PAD). Methods: MEDLINE, Embase, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Conference Proceedings, BIOSIS, National Research Register and MetaRegister databases were searched. Eligible studies were randomized controlled trials (RCTs) and published systematic reviews of patients with intermittent claudication due to PAD and whose symptoms persisted despite a period of conservative management. Study selection was conducted by one reviewer with involvement from a clinician. Data were extracted by one reviewer with no blinding to authors or journal, and checked by a second reviewer. Outcome measures were maximum walking distance (MWD) and pain-free walking distance (PFWD). Results: The review identified 1876 citations; 26 RCTs met the inclusion criteria for the systematic review. Eleven trials provided data relevant for the meta-analysis. Naftidrofuryl oxalate was ranked first for both MWD and PFWD (probability of 0·947 and 0·987, respectively, of being the best treatment) followed by cilostazol and pentoxifylline. For naftidrofuryl oxalate, cilostazol and pentoxifylline, MWD increased by 60 (95 per cent credible interval 20 to 114) per cent, 25 (11 to 40) per cent and 11 (−1 to 24) per cent respectively relative to placebo, and PFWD increased by 49, 13 and 9 per cent. Conclusion: Naftidrofuryl oxalate and cilostazol are both effective treatments for claudication; naftidrofuryl oxalate is likely to be the most effective, with minimal serious adverse events. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Current methods of identifying axillary node metastases in breast cancer patients are highly accurate, but are associated with several adverse events. This review evaluates the diagnostic accuracy of magnetic resonance imaging (MRI) techniques for identification of axillary metastases in early stage newly diagnosed breast cancer patients. Methods: Comprehensive searches were conducted in April 2009. Study quality was assessed. Sensitivity and specificity were meta-analysed using a bivariate random effects approach, utilising pathological diagnosis via node biopsy as the comparative gold standard. Results: Based on the highest sensitivity and specificity reported in each of the nine studies evaluating MRI (n = 307 patients), mean sensitivity was 90% (95% CI: 78–96%; range 65–100%) and mean specificity 90% (95% CI: 75–96%; range 54–100%). Across five studies evaluating ultrasmall super-paramagnetic iron oxide (USPIO)-enhanced MRI (n = 93), mean sensitivity was 98% (95% CI: 61–100%) and mean specificity 96% (95% CI: 72–100%). Across three studies of gadolinium-enhanced MRI (n = 187), mean sensitivity was 88% (95% CI: 78–94%) and mean specificity 73% (95% CI: 63–81%). In the single study of in-vivo proton MR spectroscopy (n = 27), sensitivity was 65% (95% CI: 38–86%) and specificity 100% (95% CI: 69–100%). Conclusions: USPIO-enhanced MRI showed a trend towards higher sensitivity and specificity and may make a useful addition to the current diagnostic pathway. Additional larger studies with standardised methods and standardised criteria for classifying a node as positive are needed. Current estimates of sensitivity and specificity do not support replacement of SLNB with any current MRI technology in this patient group. [Copyright &y& Elsevier]

Abstract: Purpose: Sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) are used to assess axillary nodal status in breast cancer, but are invasive procedures associated with morbidity, including lymphoedema. This systematic review evaluates the diagnostic accuracy of positron emission tomography (PET), with or without computed tomography (CT), for assessment of axillary nodes in early breast cancer. Methods: Eleven databases including MEDLINE, EMBASE and the Cochrane Library, plus research registers and conference proceedings, were searched in April 2009. Study quality was assessed using the QUality Assessment of Diagnostic Accuracy Studies (QUADAS) checklist. Sensitivity and specificity were meta-analysed using a bivariate random effects approach. Results: Across 26 studies evaluating PET or PET/CT (n = 2591 patients), mean sensitivity was 63% (95% CI: 52–74%; range 20–100%) and mean specificity 94% (95% CI: 91–96%; range 75–100%). Across 7 studies of PET/CT (n = 862), mean sensitivity was 56% (95% CI: 44–67%) and mean specificity 96% (90–99%). Across 19 studies of PET-only (n = 1729), mean sensitivity was 66% (50–79%) and mean specificity 93% (89–96%). Mean sensitivity was 11% (5–22%) for micrometastases (≤2 mm; five studies; n = 63), and 57% (47–66%) for macrometastases (>2 mm; four studies; n = 111). Conclusions: PET had lower sensitivity and specificity than SLNB. Therefore, replacing SLNB with PET would avoid the adverse effects of SLNB, but lead to more false negative patients at risk of recurrence and more false positive patients undergoing unnecessary ALND. The present evidence does not support the routine use of PET or PET-CT for the assessment of the clinically negative axilla. [Copyright &y& Elsevier]

A response from the authors of the article "Systematic review and economic evaluation of cilostazol, naftidrofuryl oxalate, pentoxifylline and inositol nicotinate for the treatment of intermittent claudication in people with peripheral arterial disease" in a 2011 issue is presented.

Objectives p16, a tumour suppressor, is unable to express its suppressive effects following interaction with E7-retinoblastoma protein. Previous reports have suggested that p16 immunostaining allows precise identification of cervical intra-epithelial neoplasia and cervical cancer lesions in biopsies. The prognostic value of p16 expression in cervical cancers has been evaluated for several years, but the results remain controversial. As such, the authors undertook a systematic review and meta-analysis of studies assessing the impact of p16 expression on overall survival and disease-free survival. Study design Medline, Embase and China National Knowledge Infrastructures were searched to identify studies on the prognostic impact of p16 expression in patients with cervical cancer. In total, 1070 patients from 10 eligible studies were included in the analysis. Pooled risk ratios (RRs) with 95% confidence intervals (95% CI) were calculated. Results A significant association was found between p16 expression and increased disease-free survival (RR 0.60; 95% CI 0.44–0.82; p = 0.001). However, no significant association was found between p16 and overall survival. Conclusion p16 expression may be predictive of a favourable prognosis in patients with cervical cancer. However, large-scale, multicentre and well-matched cohort studies are warranted to confirm this finding. [ABSTRACT FROM AUTHOR]