The strange connection between epidermal growth factor receptor tyrosine kinase inhibitors and dapsone: from rash mitigation to the increase in anti-tumor activity

The presence of an aberrantly activated epidermal growth factor receptor (EGFR) in many epithelial tumors, due to its overexpression, activating mutations, gene amplification and/or overexpression of receptor ligands, represent the fundamental basis underlying the use of EGFR tyrosine kinase inhibitors (EGFR-TKIs). Drugs inhibiting the EGFR have different mechanisms of action; while erlotinib and gefitinib inhibit the intracellular tyrosine kinase, monoclonal antibodies like cetuximab and panitumumab bind the extracellular domain of the EGFR both activating immunomediated anti-cancer effect and inhibiting receptor function. On the other hand, interleukin-8 has tumor promoting as well as neo-angiogenesis enhancing effects and several attempts have been made to inhibit its activity. One of these is based on the use of the old sulfone antibiotic dapsone that has demonstrated several interleukin-8 system inhibiting actions. Erlotinib typically gives a rash that has recently been proven to come out via up-regulated keratinocyte interleukin-8 synthesis with histological features reminiscent of typical neutrophilic dermatoses. In this review, we report experimental evidence that shows the use of dapsone to improve quality of life in erlotinib-treated patients by ameliorating rash as well as short-circuiting a growth-enhancing aspect of erlotinib based on increased interleukin-8 secretion.     

中医辩证治疗小儿手足口病的临床疗效

目的观察分析中医辩证治疗小儿手足口病的临床疗效。方法选取我院2011年3月~2014年11月收治的56例手足口综合症患儿为研究对象,随机分为对照组与观察组,比较两组患儿的临床疗效。结果观察组患儿的治疗总有效率高于对照组,P0.05,差异具有统计学意义。结论中医辩证治疗小儿手足口病的临床疗效显著。     

EGFR-TKIs相关重度皮疹的治疗和护理

目的探讨应用米诺环素、甘油止痒洗剂结合护理干预措施,对表皮受体酪氨酸激酶抑制剂（EGFR-TKIs）致晚期非小细胞肺癌（NSCLC）患者重度皮疹的疗效。方法吉非替尼或厄洛替尼治疗相关重度皮疹的NSCLC患者28例,严重程度分级均为3级,给予米诺环素200mg口服2/d,甘油止痒洗剂适量抹患处3/d,结合护理干预措施。结果 10例患者皮疹完全消退,14例降为1级、3例降为2级,1例经处理无效且主观症状加重而终止EGFR-TKIs治疗,总体有效率96.4%。干预前后HAMA（P〈0.001）和HAMD评分（P〈0.001）改善有显著差异。结论局部应用甘油止痒洗剂,口服米诺环素,结合护理干预措施,可作为一个较好的方案用于EGFR-TKIs致重度皮疹的处理。     

399例手足口病临床分析

目的 分析399例手足口病患儿的临床特征、实验室检查及流行特点,加强对手足口病的认识及提高救治水平.方法 收集2009济宁医学院附属济宁市第一人民医院感染科收治的399例手足口病住院患儿临床资料.分析其流行特征、临床表现、实验室检查、治疗、转归情况.结果 在该样本中,男性患儿人数为274例,占总数的68.67％.女性患...     

手足口病525例发病情况及临床分析

目的了解手足口病的发病情况及临床特征,提高对本病的认识,防止爆发流行。方法采用回顾性方法对2008年1月至2008年10月平谷区医院就诊的525例手足口病患者进行分析。结果5～7月份为该病的高发季节,发病人群主要为1～5岁的散居儿童和幼托儿童,特别是1～3岁儿童。临床表现主要为发热和皮疹,皮疹部位以手、足、口、臀、膝等为主。结论除对患儿进行积极的隔离治疗和疫点处理外,有效的健康教育对该病的预防能起到事半功倍的效果。     

When it is not an infection: metal allergy after the Nuss procedure for repair of pectus excavatum

Purpose

Increasing use of implantable bars for minimally invasive pectus excavatum repair has introduced metal allergy (nickel and chromium) to pediatric surgeons. Metal allergy is a well-recognized entity in neurologic, orthopedic, and craniofacial surgery. This study was performed to evaluate metal allergy and its effects on treatment with the Nuss procedure in 862 patients.

Methods

After institutional review board approval, we undertook a retrospective review of a prospectively gathered database of patients undergoing the Nuss procedure. Metal allergy was diagnosed either with the use of dermal patch or clinically, based on rash, fever, elevated erythrocyte sedimentation rate, cultures, and pathology specimens. Data collection included demographics, an allergy to jewelry, and history of atopy. Clinical outcomes including need for reoperation, removal of stainless steel bar, and replacement with titanium bar were evaluated.

Results

Over an 18-year period (1987-2005), 862 patients underwent the Nuss procedure. Nineteen (2.2%) were diagnosed with metal allergy, with an average age of 14.7 years (9-23 years). Eighteen (95%) were males. A history of atopy was present in 9 (56%) patients. Ten (63%) patients presented with rash and erythema, 1 (6%) with granuloma, 5 (32%) with pleural effusion, and 3 (15%) were diagnosed on preoperative screening. Stainless steel bars were removed because of allergic skin breakdown in 3 patients, with 2 patients requiring replacement titanium bars. In all 3 of these patients, symptoms resolved after removal of stainless steel bars. Titanium bars were placed in the 3 patients who were diagnosed preoperatively with metal allergy, without event.

Conclusions

Allergy symptoms often are misdiagnosed as infection, but require different treatment. If a history of metal allergy or atopy is suggested preoperatively, the patient should be tested for metal allergy, and if positive, a titanium bar used. Because the consequences of metal allergy may include the need to replace the bar, pediatric surgeons should be aware of this occurrence.     

Adverse Event Management of mTOR Inhibitors During Treatment of Hormone Receptor–Positive Advanced Breast Cancer: Considerations for Oncologists

Breast cancer (BC) is diagnosed in nearly 1 in 3 women with cancer in the United States; one third of these patients have regional lymph node metastases at the time of diagnosis. The 5-year survival rate of patients with metastatic BC is very low, and approximately 40,000 women were expected to die of the disease in 2013. About 75% of patients with BC have hormone receptor–positive (HR⁺) disease, which is often managed with endocrine therapy; however, most patients eventually have resistance to these therapies. Recently, the mammalian target of rapamycin (mTOR) inhibitor everolimus, in combination with exemestane, improved progression-free survival (PFS) of patients with advanced BC, leading to its approval by the US Food and Drug Administration. Because adverse events (AEs) associated with everolimus might differ from AEs that oncologists who treat patients with BC are more familiar with, everolimus AEs and their effective management are reviewed in this article. Possible dose adjustments of everolimus for patients with renal or hepatic impairment and strategies for minimizing potential interactions of everolimus with other drugs and food are also discussed.     

第25例:临床表现发热、皮疹、胸痛

<正>患者男性,39岁,因"发热、皮疹4 d,胸痛3 h"于2007年9月25日入院。患者入院前4 d连续工作劳累后突发高热,体温在39～40℃,同时出现上下肢紫红色斑、丘疹,次日出现针尖大小血疱,伴明显疼痛,皮肤科以"带状疱疹,血栓性脉管炎"收住院。3 h后突发胸前区闷痛,伴憋气、出汗,胸痛持续不缓解,急查心电图示Ⅰ、aVL、V2～V6导联抬高0.1～0.5 mV,     

山东省麻疹监测系统敏感性评价

为评价山东省与美国疾病控制与预防中心 /世界卫生组织开展麻疹监测合作项目以来麻疹监测系统 (MSS)的敏感性 ,结合山东省法定传染病报告系统 (NNDRS)、MSS以及居民和医疗机构发热出疹性疾病 (RFIs)漏报调查等 ,对MSS各环节进行分析。结果显示 ,尽管MSS报告RFIs显著多于NNDRS ,但仍存在漏报现象 ,本次调查居民漏报率为 94 12 % ,各级各类医疗机构漏报率为 4 4 4 4 % ,虽较 1998年有所好转 ,但在现阶段采用敏感病例定义的情况下 ,MSS仍欠敏感。改进和提高MSS工作质量 ,将是今后麻疹控制的一项长期和艰巨的任务。