Objective: Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown. Methods:Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry. Results:In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78-0.87 (LAMP3, BST1, and MAPT) and susceptibility per-allele odds ratios of 1.14-1.43 (STK39, GAK, SNCA, LRRK2, SYT11, and HIP1R). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes (I 2 estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the BST1 (rs11724635) in Asian vs Caucasian populations and similar effects for SNCA, LRRK2, LAMP3, HIP1R, and STK39 in Asian and Caucasian populations, while MAPT rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD. Conclusion:Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity. Neurology ® 2012;79:659-667 GLOSSARY CI ϭ confidence interval; GEO-PD ϭ Genetic Epidemiology of Parkinson's Disease; GWAS ϭ genome-wide association studies; HWE ϭ Hardy-Weinberg equilibrium; MALDI-TOF ϭ matrix-assisted laser desorption/ionization time-of-flight; MSA ϭ multiple system atrophy; OR ϭ odds ratio; PD ϭ Parkinson disease; SNP ϭ single nucleotide polymorphism.

BackgroundTwo recent studies identified a mutation (p.Asp620Asn) in the vacuolar protein sorting 35 gene as a cause for an autosomal dominant form of Parkinson disease . Although additional missense variants were described, their pathogenic role yet remains inconclusive.Methods and resultsWe performed the largest multi-center study to ascertain the frequency and pathogenicity of the reported vacuolar protein sorting 35 gene variants in more than 15,000 individuals worldwide. p.Asp620Asn was detected in 5 familial and 2 sporadic PD cases and not in healthy controls, p.Leu774Met in 6 cases and 1 control, p.Gly51Ser in 3 cases and 2 controls. Overall analyses did not reveal any significant increased risk for p.Leu774Met and p.Gly51Ser in our cohort.ConclusionsOur study apart from identifying the p.Asp620Asn variant in familial cases also identified it in idiopathic Parkinson disease cases, and thus provides genetic evidence for a role of p.Asp620Asn in Parkinson disease in different populations worldwide.

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Key Points Question Can educational virtual reality videos for patients improve the quality of bowel preparation before colonoscopy? Finding This randomized clinical trial including 346 participants found that patients educated by virtual reality videos had a higher mean Boston Bowel Preparation Scale score, indicating better bowel preparation, than patients educated by conventional methods. Meaning Virtual reality videos can be used as an effective patient education tool for bowel preparation before colonoscopy.

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Background Photodynamic therapy (PDT) is a new option for oral lichen planus (OLP) management; however, there are different opinions on the efficacy of PDT for OLP. The aim of this study was to comprehensively assess the efficacy of PDT in the treatment of OLP and compare PDT with steroid therapy. Methods A systematic review and meta-analysis were conducted to assess the curative effect of PDT. Five electronic databases were searched, PubMed, Web of Science, the Cochrane Library, Embase, and EBSCO up to 1 December, 2019. Random and fixed effects models for pooled estimates calculation were used and the Meta package of R was applied. Results Pooled estimates revealed that, after PDT, the lesion size decreased by 1.53 cm2 (95% confidence interval (CI): 0.71–2.35) after PDT and the partial response (PR) was 0.77 (95% CI: 0.65–0.85). The visual analogue scale (VAS) score decreased by 3.82 (95% CI: 2.80–4.85) and the Thongprasom sign score decreased by 1.33 (95% CI: 0.56–2.10) after PDT. Subgroup analyses revealed that the 5-aminolevulinic acid (5-ALA) was more effective than methylene blue (MB), with a PR of 0.87 (95% CI: 0.80–0.91). The topical use of 5-ALA yielded a better response than gargling methylene blue. In terms of VAS, the diode laser showed a better clinical PR in the treatment of OLP. In terms of changes in lesion size, the efficacy of the semiconductor laser was higher than that of the diode laser. PDT had a similar efficacy to topical corticosteroids, as shown by pooled estimates of five randomised controlled trials with 139 lesions. Conclusion This systematic review indicates that PDT is an effective treatment modality for the management of OLP. PDT is as effective as topical corticosteroid in the treatment of OLP and could be used for cases resistant to steroids or when steroids are contraindicated.

The aim of the present network meta-analysis (NMA) was to explore the comparative effectiveness and safety of different Chinese herbal injections (CHIs) combined with the FOLFOX regimen versus FOLFOX alone for colorectal cancer (CRC). Methods: A comprehensive search for randomized controlled trials (RCTs) was performed with regard to different CHIs for treating CRC in several electronic databases up to July 2016. The quality assessment of the included RCTs was conducted according to the Cochrane risk of bias tool. Standard pair-wise and Bayesian NMA were designed to compare the effectiveness and safety of different CHIs combined with the FOLFOX regimen by utilizing WinBUGS 1.4.3 and Stata 13.1 software, simultaneously. Results: Initially, a total of 820 citations were retrieved through comprehensive searching, and 60 eligible articles involving 4849 participants and 14 CHIs were ultimately included. The results of the current evidence indicated that the FOLFOX regimen combined with Delisheng, Kanglaite, Shenqifuzheng, or Aidi injections were associated with the most favorable clinical efficacy compared with the FOLFOX regimen alone. Additionally, the FOLFOX regimen combined with Delisheng, Xiaoaiping, Lentinan, Kangai, Shenqifuzheng, or Aidi injections improved performance status among patients with CRC. Conclusions: The results of cluster analysis demonstrated that the combination of Compound matrine injection and FOLFOX regimen was associated with more preferable and beneficial outcomes than other CHIs groups. Nevertheless, the additional results from multicenter trials and high-quality studies will be pivotal for supporting our findings.

Current therapies for HER2-positive breast cancer have limited efficacy in patients with triple-positive breast cancer (TPBC). We conduct a multi-center single-arm phase 2 trial to test the efficacy and safety of an oral neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib (a CDK4/6 inhibitor) in patients with treatment-naïve, stage II–III TPBC with a Karnofsky score of ≥70 (NCT04486911). The primary endpoint is the proportion of patients with pathological complete response (pCR) in the breast and axilla. The secondary endpoints include residual cancer burden (RCB)−0 or RCB-I, objective response rate (ORR), breast pCR (bpCR), safety and changes in molecular targets (Ki67) from baseline to surgery. Following 5 cycles of 4-week treatment, the results meet the primary endpoint with a pCR rate of 30.4% (24 of 79; 95% confidence interval (CI), 21.3–41.3). RCB-0/I is 55.7% (95% CI, 44.7–66.1). ORR is 87.4%, (95% CI, 78.1–93.2) and bpCR is 35.4% (95% CI, 25.8–46.5). The mean Ki67 expression reduces from 40.4% at baseline to 17.9% (P < 0.001) at time of surgery. The most frequent grade 3 or 4 adverse events are neutropenia, leukopenia, and diarrhoea. There is no serious adverse event- or treatment-related death. This fully oral, chemotherapy-free, triplet combined therapy has the potential to be an alternative neoadjuvant regimen for patients with TPBC.