Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2.

PURPOSE: Preclinical studies indicate that gefitinib (Iressa, ZD1839; AstraZeneca, Wilmington, DE), an orally active epidermal growth factor receptor tyrosine kinase inhibitor, may enhance antitumor efficacy of cytotoxics, and combination with paclitaxel and carboplatin had acceptable tolerability in a phase I trial. Gefitinib monotherapy demonstrated unparalleled antitumor activity for a biologic agent, with less toxicity than docetaxel, in phase II trials in refractory, advanced non-small-cell lung cancer (NSCLC). This phase III, randomized, placebo-controlled, double-blind trial evaluated gefitinib plus paclitaxel and carboplatin in chemotherapy-naive patients with advanced NSCLC. PATIENTS AND METHODS: Patients received paclitaxel 225 mg/m(2) and carboplatin area under concentration/time curve of 6 mg/min/mL (day 1 every 3 weeks) plus gefitinib 500 mg/d, gefitinib 250 mg/d, or placebo. After a maximum of six cycles, daily gefitinib or placebo continued until disease progression. End points included overall survival, time to progression (TTP), response rate (RR), and safety evaluation. Results A total of 1,037 patients were recruited. Baseline demographic characteristics were well balanced. There was no difference in overall survival (median, 8.7, 9.8, and 9.9 months for gefitinib 500 mg/d, 250 mg/d, and placebo, respectively; P =.64), TTP, or RR between arms. Expected dose-related diarrhea and skin toxicity were observed in gefitinib-treated patients, with no new significant/unexpected safety findings from combination with chemotherapy. Subset analysis of patients with adenocarcinoma who received > or = 90 days' chemotherapy demonstrated statistically significant prolonged survival, suggesting a gefitinib maintenance effect. CONCLUSION: Gefitinib showed no added benefit in survival, TTP, or RR compared with standard chemotherapy alone. This large, placebo-controlled trial confirmed the favorable gefitinib safety profile observed in phase I and II monotherapy trials.     

Terapia con estimulación del nervio vago en pacientes con epilepsia fármaco-resistente y callosotomía previa

ObjectiveTo analyse the results of vagus nerve stimulation in patients with drug-resistant epilepsy and previous corpus callosotomy.Materials and methodsWe prospectively reviewed data from patients with drug-resistant epilepsy who showed persistence of disabling seizures after undergoing corpus callosotomy, in whom it was not possible to identify an epileptogenic focus and who were subsequently treated with vagus nerve stimulation.Variables analysed included: age, gender, aetiology of epilepsy, frequency and characteristics of the crises and Engel scale classification, before and after vagal stimulator implant. Furthermore, the percentage differences in seizure frequency changes were also calculated.ResultsFour patients were identified: two male and two female. The total seizure frequency had decreased between 20% and 81% after corpus callosotomy in three patients and one of them did not show any favourable response (Engel IVB). Following implantation of the stimulator they became reduced to between 57% and 100% after a mean follow-up period of 8.3 months (range: 3 to 12 months). Generalised seizures decreased between 71.4% and 100%, and focal seizures between 57.7% and 100%.ConclusionsVagus nerve stimulation therapy proved to be an alternative for the reduction of seizure frequency in patients with drug-resistant epilepsy who suffered disabling seizures despite undergoing corpus callosotomy as primary surgery.     

Choroidal thickening in a case of carotid cavernous fistula

A 47-year-old woman was diagnosed with dural carotid cavernous fistula (CCF) in her right eye (RE). Scans of the choroid using Spectralis optic coherence tomography (OCT) demonstrated significant asymmetry in subfoveal choroidal thickness (RE 451 μm, left eye (LE) 367 μm). This asymmetry disappeared after the fistula was embolizated through the ophthalmic artery (RE 341 μm; LE 340 μm). This case suggests that OCT should be considered as an ancillary test in the diagnosis of CCF.     

重症颅脑损伤患者急救中应用急诊护理路径

目的探讨重症颅脑损伤患者急救中应用急诊护理路径的临床效果。方法选取2017年2月—2018年10月期间本院急诊收治的72例重症颅脑损伤患者,根据急诊护理模式分为常规组和急诊护理路径组,各36例。常规组患者按重症颅脑损伤进行常规急诊护理,急诊护理路径组则采取急诊护理路径,对比两组救治效果与效率,并观察两组死亡率。结果急救后,急诊护理路径组APACHEⅡ评分(10.01±2.69)分显著低于常规组(15.02±8.06)分,差异有统计学意义(P<0.05)。急诊护理路径组急诊救治时间(21.06±3.05)min和住院时间(20.36±5.69)d均显著少于常规组(30.69±10.96)min、(28.67±8.06)d,差异具有统计学意义(P<0.05)。急诊护理路径组死亡率(0)显著低于常规组(16.67%),差异具有统计学意义(P<0.05)。结论急诊护理路径有助于提升重症颅脑损伤急诊救治效果,并显著提高了急救效率,降低了死亡风险,有利于患者预后的改善。     

早期肠内生态免疫营养对老年腹部术后病人的影响

目的探讨早期肠内生态免疫营养治疗对老年腹部术后病人全身营养状态、术后并发症发生率及免疫功能的影响。方法按纳入标准共选择 2016年 1月至 2017年 12月在西安交通大学第一附属医院老年外科行腹部手术的老年病人 85例,其中行胰十二指肠切除术 36例,胃空肠吻合术 25例,胃癌根治术 11例,结肠癌根治术 6例,其他手术 7例。通过 Excel自带程序随机分组法分为研究组和对照组。研究组 40例,对照组 45例。研究组于术后第 1天开始启动个性化肠内生态免疫营养治疗,对照组传统常规肠内营养处理。两组均查术前、术后 3、7、14 d血清白蛋白、前白蛋白、尿素、肌酐、血红蛋白及淋巴细胞计数(比例),观察术后通气时间、白蛋白使用量、住院时间、药占比。分析两组之间术后并发症、上述指标差异及治疗与术后并发症相关因素。结果研究组发生术后并发症 3例( 7.5%)对照组 14例( 31.1%),两者差异有统计学意义( χ2＝7.378,P＝0.007)logistic多因素相关分析提示术后并发症发生与治疗呈负相,关( OR＝0.212,95%CI:0.055~0.809,P＝0.023)。术后 3d研究组尿素,氮水平低于对照组(P＝0.016);研究组血清前白蛋白水平在术后 3d、7d、14 d均高于对照组(分别为 P＝0.023,0.019,＜0.001);术后 3d、14 d研究组淋巴细胞计数高于对照组(分别为 P＝0.026,P＜0.001),且14 d研究组淋巴细胞比例高于对照组(P＜0.001);术后 3d、14 d研究组血红蛋白水平高于对照组(分别为 P＝0.006;P＜0.001);研究组病人术后通气时间早于对照组(P＜0.001)白蛋白使用量少于对照组( P＝0.013),住院时间短于对照组( P＝0.027);药占比两组之间差异无统计学意义( P＝0.406)。结论,     

Deviations of the nasal septum and their relation to tubal physiopathology]

It is frequently shown by the specialist, the relation exists between an obstructive septal deviation and the bad function of the Eustachian tube. Nasal physiopathology, as regulator of the tubaric function has been established as a controversial subject during the past two decades. This research demonstrates the relation between the septal deviation and tubaric pathology.     

Studies on in vitro degradation of anhydroecgonine methyl ester (methylecgonidine) in human plasma

The presence of the cocaine pyrolysis product anhydroecgonine methyl ester (AEME, methylecgonidine) in plasma indicates the smoking of cocaine. The stability of this analyte in human plasma has not been studied. In the present investigation AEME and its hydrolysis product anhydroecgonine (AE, ecgonidine) were assayed in plasma and buffers using gas chromatography-mass spectrometry. It was found that 50% of AEME in human plasma was hydrolyzed to AE within 5 days at room temperature and within 13 days at 4 degrees C. Addition of esterase inhibitors such as sodium fluoride or echothiophate iodide reduced the hydrolysis significantly. Hydrolysis of AEME also occurred in buffers with pH values above 5, but the hydrolysis rate was significantly lower when compared with plasma and could be markedly increased by the addition of butyrylcholine esterase. The data suggest that AEME is degraded via two mechanisms: chemical hydrolysis at basic pH and enzymatic hydrolysis by butyrylcholine esterase. Therefore, proper storage conditions must be provided for the assay of AEME in plasma.     

Studies on hydrolytic and oxidative metabolic pathways of anhydroecgonine methyl ester (methylecgonidine) using microsomal preparations from rat organs

During smoking of cocaine-base (crack), anhydroecgonine methyl ester (AEME, methylecgonidine) is formed in large amounts as a pyrolysis product of cocaine and is absorbed in the lungs. The metabolism of AEME was studied in the present investigation using microsome preparations from rat liver, lung, kidney, and brain. Potential metabolites of AEME were synthesized and used as substrate to complement the experiments. Analysis of the incubation mixtures was performed using gas chromatography-mass spectrometry and nanoelectrospray multiple-stage mass spectrometry. Screening for metabolites was focused on postulated oxidative pathways, chemical and enzymatic hydrolysis, and ethanol dependent transesterification as known from cocaine metabolism. Enzymatic hydrolysis of AEME to anhydroecgonine (AE), which was inhibited by sodium fluoride, was found in all microsomal preparations. Liver microsomes exhibited the highest activity, brain microsomes the lowest. Anhydronorecgonine methyl ester (ANEME) and anhydroecgonine methyl ester N-oxide were identified as AEME metabolites of liver and lung microsomes only. In the presence of ethanol AEME was metabolized to anhydroecgonine ethyl ester and anhydronorecgonine ethyl ester. Further metabolism of AE or ANEME was not observed. No N-hydroxy-anhydronorecgonine derivatives were found which could represent precursors of cytotoxic metabolites as known to be formed from cocaine.