EGFR mutation types and abundance were associated with the overall survival of advanced lung adenocarcinoma patients receiving first-line tyrosine kinase inhibitors

BackgroundEpidermal growth factor receptor tyrosine kinases inhibitors (EGFR-TKIs) are currently recognized as the standard treatment for advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations. Clinically found patients with different EGFR mutational status have different prognosis.MethodsA retrospective cohort study was performed to explore the relationship between EGFR mutations and abundance with patient survival by using patient data from the Affiliated Cancer Hospital of Zhengzhou University between January 2013 and November 2016. All patients involved in the present study had sensitive EGFR mutations [either exon 19 deletion (DEL) or exon 21 L858R] and treated by EGFR-TKIs. They were followed up every three months until lost or dead. Mutation abundance was calculated as the copies of EGFR mutation divided by copies of EGFR locus, and the cut-off values for 19DEL and L858R were 4.9% and 9.5%, respectively.ResultsTotal of 236 patients were included, comprising 116 (49.2%) patients with 19DEL mutation and 120 (50.8%) patients with L858R mutation. The median follow-up duration was 23.2 months (95% CI: 14.9–26.7 months). Overall survival (OS) was significantly longer in patients with 19DEL mutation (20.9 months, 95% CI: 17.7–24.1 months versus 17.0 months, 95% CI: 14.4–19.6 months in patients with L858R; P=0.008) and in patients with high mutation abundance (20.9 months, 95% CI: 18.3–23.5 months versus 13.0 months, 95% CI: 10.3–15.7 months in patients with low mutation abundance; P<0.001). Multivariate Cox regression including age, performance status and tumor stage revealed that longer OS was independently associated with 19DEL mutation (HR: 0.48, 95% CI: 0.39–0.67, P=0.033) and high mutation abundance (HR: 0.62, 95% CI: 0.50–0.79, P=0.027).ConclusionsEGFR mutation types and abundance was associated with the patients’ survival which might be used to predict the efficacy of targeted therapy by EGFR-TKIs.     

Prior statin and short‐term outcomes of primary intracerebral hemorrhage: From a large‐scale nationwide longitudinal registry

IntroductionThe relationship between statins and intracerebral hemorrhage outcomes is unclear.AimWe aimed to compare the in‐hospital mortality and evacuation of intracranial hematoma rates in patients with primary intracerebral hemorrhage between prior statin users and nonusers.ResultsThe final study population included 66,263 patients. Multivariable logistics analyses showed that prior statin use was not associated with in‐hospital mortality for primary intracerebral hemorrhage (adjusted odd ratio 0.78, 95% CI 0.61–1.01), but reduced the proportion of patients undergoing evacuation of intracranial hematoma (adjusted odd ratio 0.70, 95% CI 0.61–0.82). Propensity score matching analyses yielded similar results.ConclusionPrior statin use was not associated with in‐hospital mortality but did reduce evacuation of intracranial hematoma rates.     

P2Y12 inhibitor pretreatment in patients with nonST-segment elevation acute coronary syndrome: A meta-analysis

Background:The 2020 European Society of Cardiology guidelines do not recommend pretreatment for nonST-segment elevation myocardial infarction (NSTEMI) patients with unclear coronary anatomy, which is inconsistent with our routine preoperative approach to loading P2Y12 receptor inhibitors (e.g., preoperative loading of 300 mg of clopidogrel).Objectives:The purpose of our study was to compare the safety and effectiveness of P2Y12 inhibitors administered before coronary angiography or at least before percutaneous coronary intervention (PCI) with during or after PCI.Methods:Cochrane, PubMed, and Embase databases were searched. The primary effect endpoint and safety endpoint were any-cause death and major bleeding, respectively. Major adverse cardiovascular events, myocardial infarction and revascularization were also analyzed.Results:Our search identified 9 trials. P2Y12 inhibitor pretreatment was associated with lower death from any cause (OR 0.62, 95% CI 0.53–0.72, P < 0.00001) without increasing the risk of bleeding (OR 1.02, 95% CI 0.80–1.30, P = 0.89). However, prasugrel or ticagrelor pretreatment was not associated with a lower risk of mortality (OR 0.70, 95% CI 0.31–1.59, P = 0.40) and increased the risk of bleeding (OR 1.67, 95% CI 1.10–2.54, P = 0.02).Conclusions:In summary, clopidogrel pretreatment was associated with significantly lower mortality, major adverse cardiovascular events, myocardial infarction and revascularization with no increase in major bleeding. However, these advantages were not observed with prasugrel or ticagrelor pretreatment.     

Effect of tissue inhibitor of metalloproteinases-3 genetics polymorphism on clinicopathological characteristics of uterine cervical cancer patients in Taiwan

Single nucleotide polymorphisms (SNPs) of tissue inhibitor of metalloproteinases-3 (TIMP-3) have been revealed to be related to various cancers. To date, no study explores the relationships between TIMP-3 polymorphisms and uterine cervical cancer. The purposes of this research were to investigate the associations among genetic variants of TIMP-3 and development and clinicopathological factors of uterine cervical cancer, and patient 5 years survival in Taiwanese women. The study included 123 patients with invasive cancer and 97 with precancerous lesions of uterine cervix, and 300 control women. TIMP-3 polymorphisms rs9619311, rs9862 and rs11547635 were checked and their genotypic distributions were determined by real-time polymerase chain reaction. It showed that women with genotypes CT/TT in rs9862 were found to display a higher risk of developing cervical cancer with moderate and poor cell differentiation. Moreover, it revealed that cervical cancer patients carrying genotypes CC in rs9619311 exhibited a poorer 5 years survival, as compared to those with TT/TC in Taiwanese women, using univariate analysis. In addition, pelvic lymph node metastasis was determined to independently predict 5 years survival in cervical cancer patients using multivariate analysis. Conclusively, TIMP-3 SNPs polymorphisms rs9619311 are related to cervical patient survival in Taiwanese women.     

Characteristics and immune checkpoint inhibitor effects on non-smoking non-small cell lung cancer with KRAS mutation: A single center cohort (STROBE-compliant)

Kirsten rat sarcoma (KRAS) mutation (KRASm) is associated with poor prognosis in non-small cell lung cancer (NSCLC) patients. We have aimed to survey NSCLC patients harboring KRASm in Taiwan, where never-smoking lung adenocarcinoma predominates, and analyze the immune checkpoint inhibitor effect on NSCLC harboring KRASm.NSCLC patients with KRASm were enrolled and tested on programmed death-ligand 1 (PD-L1) expression using available tissue. We analyzed their clinical features, PD-L1 status, responses to ICIs, and overall survival (OS).We studied 93 patients with a median age 66.0 years, 23.7% of whom were women, and 22.6% were never-smokers. The results showed that G12C (36.6%) was the most common KRASm. In 47 patients with available tissue for PD-L1 testing, PD-L1 expression was positive in 66.0% of patients, while PD-L1 ≥50% was higher in ever-smokers (P = .038). Among 23 patients receiving ICI treatment, those with PD-L1 ≥50% experience a 45.5% response rate to ICI. There were benefits from ICI treatment on OS compared with no ICI treatment (median OS 35.6 vs 9.8 months, P = .002) for all of our patients, and for patients with PD-L1 ≥50% (median OS not-reached vs 8.4 months, P = .008). There were no differences in survival across different KRAS subtypes (P = .666).Never-smokers composed more than one-fifth of KRASm in NSCLC in Taiwan. A high PD-L1 expression was related to smoking history and responded well to ICI. ICI treatment improved the OS in NSCLC patients with KRASm, particularly those with PD-L1 ≥50%.     

Combination therapy of tacrolimus,high doses of glucocorticosteroids,and cyclophosphamide against existing historical treatment for patients in severe conditions of interstitial lung diseases complicated with dermatomyositis: A retrospective analysis

The high-dose glucocorticosteroid (GC) treatment is the first choice for dermatomyositis complicated with interstitial lung disease (DM-ILD) but patients are resistant to the high-dose GC monotherapy. Besides, the high dose of GC, the secondary immunosuppressive agent(s) is necessary but there is controversy for the selection of immunosuppressive agent(s). The objectives of the study were to analyze the efficacy of different therapeutic options for DM-ILD to identify the optimal therapy. A total of 60 patients had received intravenous 1.0–2.0 mg/ kg/day prednisolone for DM-ILD. In severe conditions, patients had received oral 1 to 3 mg/day tacrolimus (TAC), 500 mg/ m²/month cyclophosphamide (CY), and/or 1 g/ day methylprednisolone pulse (TI cohort, n = 24). In severe conditions, patients had received 1 g/day methylprednisolone pulse and 2–3 mg/ kg/day cyclosporine A (CsA) and/or 500 mg/ m²/month CY (existing historical treatment; CT cohort, n = 36). Patients of the TI cohort did not receive CsA. Patients in the CT cohort were received CY in significantly fewer numbers than those of the TI cohort during treatment (P = .0112). A total of 11 (46%) patients from the TI cohort and 14 (39%) patients from the CT cohort were developed relapsed. At the end of the 30-months, higher numbers of patients of the TI cohort had an event(s) free survival than those of the CT cohort (7 (29%) vs 2 (6%), P = .0229). Also, higher numbers of patients of the TI cohort had survived irrespective of an event(s) than those of the CT cohort (21 (87%) vs 22 (61%), P = .0399). Patients of the TI cohort had developed herpes zoster (2 (8%)) and cytomegalovirus (4 (17%)) infections. Patients of the CT cohort developed renal dysfunction (10 (28%)). Hyperglycemia, hyperlipidemia, and fracture (GC-related toxicities) were also reported in both cohorts and these toxicities were fever in the TI cohort. The addition of TAC to high doses GC with CY is an ideal treatment for severe conditions of DM-ILD (Level of Evidence: III; Technical Efficacy Stage: 4).     

High-Dose Dual Therapy Versus Bismuth-Containing Quadruple Therapy for the Treatment of Helicobacter pylori Infection: A Systematic Review with Meta-Analysis

Background:This study aimed to evaluate the efficacy and safety of high-dose dual therapy for Helicobacter pylori (H. pylori) eradication compared to bismuth-containing quadruple therapy.Methods:The electronic database of PubMed, Embase, and Cochrane Library were searched from inception to March 18, 2021. Randomized, controlled trials that evaluated high-dose dual therapy versus bismuth-containing quadruple therapy for H. pylori infection were included.Results:We included 6 studies containing 1677 patients with H. pylori infection. This meta-analysis demonstrated that high-dose dual therapy achieved similar eradication rate compared with bismuth-containing quadruple therapy (intention-to-treat: 84.6% vs 83.7%, relative risk (RR) = 1.01, 95% CI: 0.97-1.06, P = .49; per-protocol = 88.4% vs 89.0%, RR = 1.00, 95% CI: 0.97-1.04, P = .99). However, high-dose dual therapy showed fewer side effects (13.1% vs 32.0%, RR = 0.51, 95% CI: 0.34-0.78, P = .002) and better compliance (96.1% vs 93.3%, RR = 1.03, 95% CI: 1.00-1.05, P = .03) compared to bismuth-containing quadruple therapy.Conclusion:This meta-analysis demonstrated that high-dose dual therapy is equally effective with bismuth-containing quadruple therapy in eradicating H. pylori, with fewer side effects and better compliance.     

男性高尿酸血症患者血尿酸与PAI-1和内皮素的关系

目的：探讨中老年男性高尿酸血症患者血浆纤溶酶原激活物抑制剂-1（PAI-1）与内皮素（ET）水平变化，观察高尿酸对血管内皮细胞功能的影响。方法：随机选择35岁以上的男性高尿酸血症患者138例（高尿酸血症，UA组），年龄、地域相匹配的健康者80例为正常对照组。采用酶联免疫吸附双抗体夹心法测定PAI-1，采用放射免疫法测定ET。胰岛素抵抗指数采用稳态模型评估（HOMA—IR）。采用尿酸氧化酶法测定血尿酸。结果：（1）UA组PAI-1、ET水平高于正常对照（均P〈0．01）。（2）UA组收缩压、舒张压、腰围与臀围比值、体质量指数与正常对照组相比差异有统计学意义（P〈0．05或P〈0．01）。（3）uA组胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-c）、空腹血糖、糖负荷后2h血糖、空腹胰岛素、HOMA—IR均显著高于正常对照组（P〈0．05或P〈0．01）。（4）UA组高密度脂蛋白胆固醇（HDL-c）低于正常对照组（P〈0．05）。（5）在以PAI-1为因变量的逐步回归分析中血尿酸、腰围与臀围比值、HOMA—IR进入回归方程（调整后R2=0．77，P〈0．01）。（6）在以ET为因变量的逐步回归分析中，血尿酸、血肌酐、腰围与臀围比值、HOMA—IR进入回归方程（调整后R2=0．70，P〈0．01）。结论：高尿酸是血管内皮细胞功能障碍独立的危险因素，降低血尿酸水平有望改善血管内皮细胞功能，减少动脉粥样硬化的发生和发展。     

射频导管消融术对凝血激活程度的影响

目的观察射频导管消融术（RFCA）对患者血中凝血激活程度的影响,以及术后恢复时间。方法对56例接受RFCA术的患者,在RFCA术前,心内电生理检查后,成功消融后即刻、术后第2天和第7天,抽取静脉血,测定D-二聚体（D-Dimer）、血管内血友病因子（Vonwillebrandfactor,vWF）,血浆组织纤溶酶原（Tissue Plasminogen Activator,t-pa）和组织纤溶酶原抑制剂（Plas-minogen Activator Inhibitor,PAI-1）含量。结果与术前比较,血清D-二聚体、vWF浓度以及血浆PAI-1含量在心内电生理检查后、消融成功后即刻和术后第2天均显著上升（P〈0.01）,并于第7天降至术前水平,而t-PA含量在心内电生理检查后,消融成功后即刻和术后第2天显著下降（P〈0.01）,并于第7天降至术前水平。结论 RFCA术可引起血中凝血物质水平的显著增加。术后、术后对其监测有利于指导抗凝药物应用和预防血栓栓塞的发生。