Prognostic factors for postoperative survival in melanoma patients with bone metastasis

Melanoma can spread to the bone by metastasis and is relevant to a poor outcome. However, because of the rarity of melanoma patients with bone metastasis, the prognostic postoperative survival factors of them have not been elucidated. The aim of this special population-based cohort was to elucidate the prognostic factors associated with postoperative survival. The Surveillance, Epidemiology, and End Results database was used to extract postoperative survival data relating to patients with melanoma and bone metastasis at diagnosis between 2010 and 2016, along with data on a range of potential postoperative prognostic factors. We then investigated the potential postoperative prognostic roles of these factors using a Cox regression model and the Kaplan-Meier analysis. In all, the Surveillance, Epidemiology, and End Results database included 186 cases. Regarding overall survival, the 1-, 3-, and 5-year overall survival rates for the entire cohort were 36.2%, 15.4%, and 9.5%, respectively. Regarding cancer-specific survival, the 1-, 3-, and 5-year cancer-specific survival rates were 42.0%, 23.2%, and 16.6%, respectively. Within a cohort of melanoma patients with bone metastasis after surgery, our analysis showed that a smaller tumor size and the lack of metastases at other sites were predictors of survival.     

Colorectal cancer in patients under close colonoscopic surveillance

BACKGROUND & AIMS: Colonoscopic polypectomy is considered effective for preventing colorectal cancer (CRC), but the incidence of cancer in patients under colonoscopic surveillance has rarely been investigated. We determined the incidence of CRC in patients under colonoscopic surveillance and examined the circumstances and risk factors for CRC and adenoma with high-grade dysplasia. METHODS: Patients were drawn from 3 adenoma chemoprevention trials. All underwent baseline colonoscopy with removal of at least one adenoma and were deemed free of remaining lesions. We identified patients subsequently diagnosed with invasive cancer or adenoma with high-grade dysplasia. The timing, location, and outcome of all cases of cancer and high-grade dysplasia identified are described and risks associated with their development explored. RESULTS: CRC was diagnosed in 19 of the 2915 patients over a mean follow-up of 3.7 years (incidence, 1.74 cancers/1000 person-years). The cancers were located in all regions of the colon; 10 were at or proximal to the hepatic flexure. Although most of the cancers (84%) were of early stage, 2 participants died of CRC. Seven patients were diagnosed with adenoma with high-grade dysplasia during follow-up. Older patients and those with a history of more adenomas were at higher risk of being diagnosed with invasive cancer or adenoma with high-grade dysplasia. CONCLUSIONS: CRC is diagnosed in a clinically important proportion of patients following complete colonoscopy and polypectomy. More precise and representative estimates of CRC incidence and death among patients undergoing surveillance examinations are needed.     

The ARVD/C Genetic Variants Database: 2014 Update

Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac disease characterized by myocardial atrophy, fibro‐fatty replacement, and a high risk of ventricular arrhythmias that lead to sudden death. In 2009, genetic data from 57 publications were collected in the arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) Genetic Variants Database (freeware available at http://www.arvcdatabase.info ), which comprised 481 variants in eight ACM‐associated genes. In recent years, deep genetic sequencing has increased our knowledge of the genetics of ACM, revealing a large spectrum of nucleotide variations for which pathogenicity needs to be assessed. As of April 20, 2014, we have updated the ARVD/C database into the ARVD/C database to contain more than 1,400 variants in 12 ACM‐related genes (PKP2, DSP, DSC2, DSG2, JUP, TGFB3, TMEM43, LMNA, DES, TTN, PLN, CTNNA3) as reported in more than 160 references. Of these, only 411 nucleotide variants have been reported as pathogenic, whereas the significance of the other approximately 1,000 variants is still unknown. This comprehensive collection of ACM genetic data represents a valuable source of information on the spectrum of ACM‐associated genes and aims to facilitate the interpretation of genetic data and genetic counseling.     

ProKinO: A Unified Resource for Mining the Cancer Kinome

Protein kinases represent a large and diverse family of evolutionarily related proteins that are abnormally regulated in human cancers. Although genome sequencing studies have revealed thousands of variants in protein kinases, translating “big” genomic data into biological knowledge remains a challenge. Here, we describe an ontological framework for integrating and conceptualizing diverse forms of information related to kinase activation and regulatory mechanisms in a machine readable, human understandable form. We demonstrate the utility of this framework in analyzing the cancer kinome, and in generating testable hypotheses for experimental studies. Through the iterative process of aggregate ontology querying, hypothesis generation and experimental validation, we identify a novel mutational hotspot in the αC‐β4 loop of the kinase domain and demonstrate the functional impact of the identified variants in epidermal growth factor receptor (EGFR) constitutive activity and inhibitor sensitivity. We provide a unified resource for the kinase and cancer community, ProKinO, housed at http://vulcan.cs.uga.edu/prokino .     

地方高校图书馆特色资源建设分析*

本文以广西中医药大学图书馆近几年来建设特色资源库情况为例,分析建库内容、建库层次,指出存在的问题及应对对策,提出深化建库内容、深化层次建设是特色资源建设的发展趋势。     

基于基因表达综合数据库筛选调控急性T淋巴细胞白血病超高剂量率放疗敏感性的枢纽基因

目的 通过生物信息学方法对基因表达综合(GEO)数据库中超高剂量率(FLASH)放疗的数据进行分析,寻找参与调控急性T淋巴细胞白血病FLASH放疗敏感性的枢纽(Hub)基因。方法 从GEO数据库中下载和提取接受FLASH放疗恶性肿瘤基因表达谱芯片数据,采用R软件进行差异基因的筛选,并对这些基因进行生物学功能、信号传导通路等分析。通过STRING在线软件分析差异基因的蛋白质相互作用(PPI) 网络,Cytoscape插件筛选Hub基因。最后,应用肿瘤基因组图谱(TCGA)和GTEx数据库验证Hub基因在急性T淋巴细胞白血病中的表达情况。结果 自GEO数据库中获得GSE100718芯片数据,共有12 800个基因与急性T淋巴细胞白血病放疗敏感性相关。选择表达量显著改变的61个基因进行进一步分析,这些基因参与代谢、应激反应、免疫应答等生物学过程。主要涉及氧化磷酸化、未折叠蛋白应答、脂质代谢等信号转导通路。通过PPI分析筛选出的Hub基因及后续验证表明HSPA5及SCD参与调控FLASH放疗敏感性,且在合并TRD/LMO2融合基因的急性T淋巴细胞白血病中显著高表达。结论 通过生物信息学分析可以有效筛选出调控FLASH放疗敏感性的Hub基因,基因表达谱可用于指导肿瘤患者分层以实现精准放疗。     

原发性人脑胶质瘤的预后影响因素:基于SEER数据库的分析

目的 探讨原发性人脑胶质瘤病人预后影响因素。方法 通过SEER*Stat（8.3.8版本）软件搜集SEER数据库2004~2015年原发性人脑胶质瘤病人的临床资料,采用R（4.0.2版本）软件进行单因素与多因素Cox回归分析,通过Kaplan-Meier生存曲线分析不同治疗方式和婚姻状态与病人预后的关系。结果 共纳入符合标准的原发性人脑胶质瘤18 523例。多因素Cox回归分析结果显示,年龄≥30岁、肿瘤直径≥2 cm、病理级别高、肿瘤位于额叶以外部位、离婚、丧偶为原发性胶质瘤预后不良的独立危险因素（P<0.05）,手术治疗、术后放疗、化疗是原发性胶质瘤预后的独立保护因素（P<0.05）。生存曲线分析结果显示,手术治疗（全切除或部分切除肿瘤）、术后放疗、化疗均明显延长原发性胶质瘤病人的生存期（P<0.05）,婚姻状态为结婚的病人预后明显好于丧偶的病人（P<0.05）。结论 对原发性人脑胶质瘤,尽可能手术全切除肿瘤,同时术后辅助放化疗,能够延长病人的生存时间。同时,临床应加强病人心理干预。     

Adverse events recorded in English primary care: observational study using the General Practice Research Database

Background

More accurate and recent estimates of adverse events in primary care are necessary to assign resources for improvement of patient safety, while predictors must be identified to ameliorate patient risk.

Aim

To determine the incidence of recorded iatrogenic harm in general practice and identify risk factors for these adverse events.

Design and setting

Cross-sectional sample of 74 763 patients at 457 English general practices between 1 January 1999 and 31 December 2008, obtained from the General Practice Research Database.

Method

Patient age at study entry, sex, ethnicity, deprivation, practice region, duration registered at practice, continuity of care, comorbidities, and health service use were extracted from the data. Adverse events were defined by Read Codes for complications of care (Chapters S, T, and U). Crude and adjusted analyses were performed by Poisson regression, using generalised estimating equations.

Results

The incidence was 6.0 adverse events per 1000 person-years (95% confidence interval [CI] = 5.74 to 6.27), equivalent to eight adverse events per 10 000 consultations (n = 2 540 877). After adjustment, patients aged 65–84 years (risk ratio [RR] = 5.62, 95% CI = 4.58 to 6.91; P<0.001), with the most consultations (RR = 2.14, 95% CI = 1.60 to 2.86; P<0.001), five or more emergency admissions (RR = 2.08, 95% CI = 1.66 to 2.60; P<0.001), or the most diseases according to expanded diagnosis clusters (RR = 8.46, 95% CI = 5.68 to 12.6; P<0.001) were at greater risk of adverse events. Patients registered at their practice for the longest periods of time were less at risk of an adverse event (RR = 0.40, 95% CI = 0.35 to 0.47; P<0.001).

Conclusion

The low incidence of recorded adverse events is comparable with other studies. Temporal sequencing of risk factors and case ascertainment would benefit from data triangulation. Future studies may explore whether first adverse events predict future incidents.