Clinical Activity of Afatinib in Patients With Non–Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Spanish Retrospective Multicenter Study

IntroductionUncommon epidermal growth factor receptor (EGFR) mutations (u-EGFRm) are a heterogeneous group of molecular alterations and have also been reported as comutations with other EGFR mutations (complex mutations) in non–small-cell lung cancer (NSCLC). Afatinib has shown activity against some u-EGFRm, and we examined its efficacy in Spanish clinical practice.Patients and MethodsData of 67 patients with advanced NSCLC with u-EGFRm treated with afatinib between 2012 and 2017 at 23 Spanish institutions were reviewed. u-EGFRm were analyzed as complex mutations (group A), EGFR exon 20 insertions (ins20; group B), or single mutations (group C). Efficacy was evaluated in terms of overall survival (OS) and tumor response.ResultsGroup A complex u-EGFRm consisted of double mutations of G719X+E709F, G719X+S768I, G719X+L861Q, L858R+T790M, L858R+S768I, L858R+S765I, del19+S768I, del19+L747S, or R776C+L861Q. No differences in clinical characteristics were found between groups A (n = 20), B (n = 23), and C (n = 24). Afatinib was administered as first-line therapy in 80% of patients. Median time of receipt of therapy was 4.2 months (range, 2.0–12.9 months). Median OS for the entire cohort was 19.9 months (95% confidence interval, 9.7, 30.1). Hazard ratios for OS were 0.26 (95% confidence interval, 0.10, 0.71; P = .008) and 0.40 (95% confidence interval, 0.17, 0.95; P = .037) for groups A and C compared to B, respectively. Response was significantly higher in groups A (70%) and C (54%) compared to B (13%; pairwise comparison P < .001 and .008, respectively).ConclusionIn clinical practice, afatinib was active in patients with u-EGFRm NSCLC, particularly in complex and single mutations. Further strategies are needed for patients with ins20, a subgroup u-EGFRm with a lower clinical benefit with afatinib.     

A benchmark dose study of prenatal exposure to di(2-ethylhexyl) phthalate and behavioral problems in children

IntroductionPrenatal exposure to di(2-ethylhexyl) phthalate (DEHP) has been reported to be associated with adverse effects on neurodevelopment that yield behavior syndromes in young children with an estimated median exposure lower than the currently recommended tolerable daily intake (TDI) and reference dose (RfD).ObjectivesOur aim was to derive the benchmark dose for prenatal exposure to DEHP for the neurodevelopmental health in children.MethodsA total of 122 mother-child pairs from the Taiwan Maternal and Infant Cohort Study were analyzed for the dose-response relationship between maternal exposure to DEHP and children's behavioral syndromes evaluated at 8 years (n = 122, 2009), 11 years (n = 96, 2012), and 14 years (n = 78, 2015) of age. We employed a multivariate regression model to assess the statistical associations between the estimated maternal average daily intake of DEHP and child's individual CBCL scores for boys and girls at each separate age, followed by a mixed model for all the children across three ages accounting for individual variations. We then employed structural equation models by combining the children's specific behavioral problem scores at different ages and obtained a simulated overall latent score in relation to maternal exposure. Based on the established dose-response relationship, we derived the benchmark dose (BMD) and the lower limit (BMDL).ResultsAssociations of maternal DEHP exposure (median 4.54$\mu g/kg\_bw/day$) with the Child Behavior Checklist (CBCL) scores were all significant, except for somatic complaints, adjusting for child's age, gender, IQ, and family income. The BMDL, given a benchmark response of 0.10 (0.05) and a background response of 0.05, was 6.01 (2.16) $\mu g/kg\_bw/day$for an integrated CBCL score.ConclusionsThe current TDI (RfD) of 50 (20) $\mu g/kg\_bw/day$ for DEHP might not protect pregnant women for their children from behavioral problems. There remains the lack of comparable toxicological data. Further investigations are needed.     

体质指数与糖尿病交互作用对肛周脓肿术后复发的影响

目的:探讨体质指数与糖尿病交互作用对肛周脓肿术后复发的影响。方法:选取2015年1月至2016年3月贵州中医药大学第一附属医院收治的肛周脓肿住院患者790例的临床资料作为研究对象,进行回顾性分析,通过Cox比例风险模型及似然比检验分析体质量指数(BMI)和糖尿病对术后复发的交互作用。结果:合并有糖尿病的脓肿患者,每增加1个1 kg/m~2的BMI,将会增加28%的术后脓肿复发的风险(HR=1.28,95%CI 1.05,1.56,P交互=0.03)。结论:脓肿术后复发风险在患有糖尿病且BMI高的人群中较高,从而有助于早期识别高危患者,改善预后。     

首荟通便胶囊预防肝胆胰恶性肿瘤化疗后便秘的疗效观察

目的:探讨首荟通便胶囊预防肝胆胰恶性肿瘤化疗后便秘的临床疗效。方法:选取2016年8月至2018年8月河北医科大学第二医院肝胆外科收治的老年肝胆胰恶性肿瘤化疗患者80例作为研究对象,按照随机数字表法随机分为对照组和观察组,每组40例。对照组口服乳果糖口服液,观察组在对照组基础上加服首荟通便胶囊。治疗14 d后,比较2组的临床疗效。结果:中医病症临床疗效观察,对照组总有效率达到75%;观察组,总有效率达到90%,2组比较差异有统计学意义(P<0.05)。临床症状评分观察,对照组总有效率达到77.5%;观察组总有效率达到92.5%,2组比较差异有统计学意义(P<0.05)。排便评分(VAS评分)观察,治疗后对照组排便间隔时间和每次排便时间均长于观察组,2组VAS评分比较,差异均有统计学意义(P<0.05)。结论:首荟通便胶囊可以有效预防肝胆胰恶性肿瘤化疗后的便秘,有效缓解患者排便疼痛程度,减少排便时间,效果显著,值得临床推广。     

Upregulation of LAGE3 correlates with prognosis and immune infiltrates in colorectal cancer: A bioinformatic analysis

BackgroundColorectal cancer (CRC) is the primary cause of cancer-related deaths worldwide. Identification of new CRC biomarkers is imperative to improve the prognosis and development of therapies against the disease. LAGE3 (L Antigen Family Member 3) functions as a tRNA modifier, although its potential role in CRC has not been fully elucidated.MethodsRNA-seq matrix and corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, then subjected to survival, enrichment, and tumor microenvironment analyses using packages implemented in R.ResultsWe found that LAGE3 was upregulated and significantly correlating with poor prognosis in multiple CRC cohorts. Additionally, multivariate Cox regression analysis revealed that LAGE3 was an independent prognostic factor in patients with CRC, whereas functional enrichment analysis indicated that it could regulate protein targeting, tRNA processing, and the PD-1/PD-L1 checkpoint pathway. Furthermore, CIBERSORT analysis indicated a negative relationship between LAGE3 and levels of infiltration for multiple immune cells, especially CD8 + T cells in CRC. Particularly, LAGE3 expression was inversely correlated with the expression of immune checkpoints as well as that of various immune cell types of signature genes.ConclusionCollectively, our results indicate that high LAGE3 expression correlates with adverse prognosis and poor immune infiltration in CRC patients.     

Oral human papillomavirus prevalence and type distribution by country (Brazil,Mexico and the United States) and age among HPV infection in men study participants

Incidence of human papillomavirus (HPV) attributable oropharyngeal cancers (OPCs) has been increasing globally, especially among men in high-income countries. There is a lack of studies comparing oral HPV prevalence by age and country among healthy men. The purpose of our study was to assess oral HPV prevalence by country and age. Participants of the HPV Infection in Men Study (HIM), a cohort of 3,098 healthy men from São Paulo, Brazil, Cuernavaca, Mexico and Tampa, USA, were studied. Oral HPV prevalence and type distribution were assessed using the SPF₁₀ PCR-DEIA-LiPA₂₅ system. The prevalence of any HPV in Brazil, Mexico and the US was 8.7% (95% CI: 7.1%, 10.4%), 10.0% (95% CI: 8.3%, 12.1%) and 7.6% (95% CI: 5.9%, 9.5%), respectively, while the prevalence of high-risk HPV was 5.3% (95% CI: 4.1%, 6.7%), 7.3% (95% CI: 5.7%, 9.0%) and 5.4% (95% CI: 4.0%, 7.0%), respectively. No significant differences in prevalence of grouped HPV types were observed by country despite significant differences in sexual behaviors. However, the age-specific prevalence of oral HPV differed by country. Brazilian (6.0% [95% CI: 3.4%, 9.7%]) and Mexican (9.2% [95% CI: 5.6%, 14.0%]) participants had peak high-risk HPV prevalence among men aged 41–50 years whereas the US participants had peak prevalence at ages 31–40 years (11.0% [95% CI: 6.4%, 17.3%]). In conclusion, oral HPV prevalence was low with no difference in overall prevalence observed by country. Factors associated with the differences in oral HPV age-patterning by country and sexual orientation require further study.     

祛寒逐风合剂联合西医常规疗法治疗膝骨关节炎风寒痹阻证临床研究

目的观察祛寒逐风合剂联合西医常规疗法对膝骨关节炎风寒痹阻证的临床疗效,以及对关节症状及相关实验室指标的影响。方法采用随机数字表法将94例膝骨关节炎风寒痹阻证患者分为观察组和对照组各47例。对照组采用常规药物疗法+康复训练,观察组在对照组基础上予祛寒逐风合剂,每次50m L,每日3次,口服。2组均连续治疗2周。比较2组临床疗效,观察2组治疗前后美国西大略湖和麦克马斯特大学骨关节炎指数(WOMAC)评分、视觉模拟评分法(VAS)评分、压痛指数、中医症状评分,白细胞介素(IL)-1β、IL-6、血管内皮生长因子(VEGF)、肿瘤坏死因子(TNF)-α、骨钙素、抗酒石酸盐酸性磷酸酶异构体(TRACP)-5b、骨特异性碱性磷酸酶(BALP)、纤维蛋白原、红细胞沉降率和红细胞聚集指数,对2组进行安全性评价。结果观察组总有效率为89.36%(42/47),对照组为74.47%(35/47),观察组明显优于对照组(P<0.05)。与本组治疗前比较,2组治疗后WOMAC评分、VAS评分、压痛指数、中医症状评分明显下降(P<0.05);2组治疗后比较,观察组WOMAC评分、VAS评分、压痛指数、中医症状评分明显低于对照组(P<0.05)。与本组治疗前比较,2组治疗后IL-1β、IL-6、TNF-α、VEGF、TRACP-5b水平明显下降,骨钙素、BALP水平明显升高(P<0.05);2组治疗后比较,观察组IL-1β、IL-6、TNF-α、VEGF、TRACP-5b水平明显低于对照组,骨钙素、BALP水平明显高于对照组(P<0.05)。与本组治疗前比较,观察组治疗后纤维蛋白原、红细胞沉降率、红细胞聚集指数明显下降(P<0.05);2组治疗后比较,观察组血液流变学各项指标明显低于对照组(P<0.05)。2组均未发生不良反应。结论祛寒逐风合剂联合西医常规疗法治疗膝骨关节炎风寒痹阻证患者疗效较好,可明显改善关节症状及相关实验室指标。     

气血同治法治疗胃息肉验案1则

胃息肉在消化道息肉中最常见,疾病早期多无明显症状,即使有临床症状也无特异性,主要表现为上腹疼痛和腹胀等症,极易造成漏治和误治,在很大程度上影响患者的生活质量。于春泉主任总结多年临床经验,在治疗胃息肉方面有独到的见解,以气血同治为治疗法则,通过补气、行气、活血和养血等治法扶正祛邪,恢复脏腑气血阴阳动态平衡,标本兼顾,临床效果可观。     

The risk of fractures,acute myocardial infarction,atrial fibrillation and ventricular arrhythmia in geriatric patients exposed to promethazine

ABSTRACT

Objectives: This study aimed to compare the risk of fractures, acute myocardial infarction, atrial fibrillation, and ventricular arrhythmia among Danish citizens aged ≥ 65 which were new users of promethazine or domperidone, triazolam, loratadine, and betahistine. Secondly, the study aimed to perform a risk stratification to identify the most relevant predictors for the study outcomes.

Methods: The study period was 01/01/2015 to 31/12/2016. The data sources were the Danish registers. Each patient was followed for 90 days. A logistic regression model was used to compute the unadjusted and adjusted odds ratios (OR), and a conditional inference tree was used to identify the most relevant predictors for the study outcomes.

Results: Promethazine had a higher risk of hospitalization for atrial fibrillation than loratadine and betahistine (OR 1.58; 95% CI 1.07–2.63 and OR 3.22; 95% CI 1.69–7.14, respectively). For fractures, acute myocardial infarction, and ventricular arrhythmia hospitalizations, no statistically significant differences were found among drugs under investigation. The medical history of cardiac arrhythmia (OR 4.14; 95% CI 2.94–5.78, p < 0.0001) was the most relevant predictor for atrial fibrillation hospitalizations.

Conclusion: This study found an increased risk of atrial fibrillation hospitalization among promethazine users, and the risk was higher among patients with prior cardiac arrhythmia.     

Analysis of Interventional Clinical Research Protocols Related to Coronavirus Disease 2019 and Future Expectations

Coronavirus disease 2019 (COVID?19) is a newly emerging infectious disease.After its outbreak, researchersstarted a large number of clinical interventional studies, using a variety of interventions to study the different types of COVID?19 cases. In this article, we searched the websites of Chinese Clinical Trial Registry, ClinicalTrials.gov, etc., to study the publicly registered research information. Through the classification and summary of interventional methods, evaluation indicators, research design, etc., this article provided readers with the outline of clinical research about COVID?19, and looked forward to the scientificity, feasibility, and future evidence of the clinical researches.