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Update on Immunotherapeutics in the Management of Metastatic Melanoma 转移性黑色素瘤的免疫治疗进展
Q1 Medicine Pub Date : 2019-01-01
David Bulir, Steven Liang, Maureen O’Malley, Elaine McWhirter

Today, a number of treatment options are now available for metastatic melanoma. Within the last decade, the development of novel immunotherapies for cancer has significantly altered the course of the disease in patients with melanoma. With more patients receiving these potentially life-saving treatments, not only have we learned more about the interplay between the immune system and melanoma, but more importantly, which treatment options are most appropriate given the clinical picture.

如今,对于转移性黑色素瘤有许多治疗选择。在过去的十年里,新型癌症免疫疗法的发展显著地改变了黑色素瘤患者的病程。随着越来越多的患者接受这些可能挽救生命的治疗,我们不仅更多地了解了免疫系统和黑色素瘤之间的相互作用,更重要的是,根据临床情况,哪种治疗方案是最合适的。
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引用次数: 0
The Treatment of Primary Focal Hyperhidrosis 原发性局灶性多汗症的治疗
Q1 Medicine Pub Date : 2019-01-01
Todd Wechter, Steven R Feldman, Sarah L Taylor

Primary focal hyperhidrosis is a relatively common disease that has a significant impact on afflicted patient’s quality of life. The pathogenesis of the disease is thought to stem from increased cholinergic activity on eccrine sweat glands. Topical aluminum chloride based antiperspirants are good first-line agents for all affected body sites. Anticholinergic agents are emerging as effective topical alternatives. Iontophoresis passes an electrical current through the skin and is an excellent treatment option for palmoplantar disease. Botulinum toxin type A injections remain a mainstay second-line treatment. Local procedural advances including microwave thermolysis, laser therapy and focused ultrasound are emerging as safe and effective alternatives for refractory disease. Oral anticholinergics are generally well tolerated and can also be used for intractable disease. Last-line interventions include local surgical options and sympathectomy, though some patients may prefer permanent treatment. Further investigation of novel treatments as well as ways to optimize existing therapeutic options are needed.

原发性局灶性多汗症是一种相对常见的疾病,对患者的生活质量有重大影响。该病的发病机制被认为是源于内分泌汗腺胆碱能活性的增加。局部氯化铝止汗剂对所有受影响的身体部位都是很好的一线药物。抗胆碱能药物正在成为有效的局部替代药物。离子导入是一种通过皮肤的电流,是掌足底疾病的一种极好的治疗选择。注射A型肉毒杆菌毒素仍然是主要的二线治疗方法。局部手术的进步包括微波热解、激光治疗和聚焦超声正在成为难治性疾病安全有效的替代方法。口服抗胆碱能药通常耐受性良好,也可用于顽固性疾病。最后一线干预包括局部手术选择和交感神经切除术,尽管一些患者可能更喜欢永久性治疗。需要进一步研究新的治疗方法以及优化现有治疗方案的方法。
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引用次数: 0
Afamelanotide in the Treatment of Dermatologic Disease 阿麦兰肽在皮肤病治疗中的应用
Q1 Medicine Pub Date : 2018-11-01
Morgan M McNeil, Amanda F Nahhas, Taylor L Braunberger, Iltefat H Hamzavi

Afamelanotide, an α-melanocyte stimulating hormone analogue, has become an emerging therapeutic option for a variety of skin conditions previously refractory to other treatments. Its efficacy has been demonstrated in several dermatologic conditions, including erythropoietic protoporphyria (EPP), solar urticaria, polymorphic light eruption (PMLE), vitiligo, acne, and Hailey-Hailey disease. Its relatively low risk side effect profile makes it an attractive treatment option and also paves the way for innovative use in other disorders.

Afamelanotide是一种α-黑素细胞刺激激素类似物,已经成为一种新兴的治疗选择,用于治疗以前难以用其他治疗方法治疗的各种皮肤状况。其疗效已被证明在几种皮肤病,包括红细胞生成性原生卟啉症(EPP),日光性荨麻疹,多态光疹(PMLE),白癜风,痤疮,和黑利-黑利病。其相对较低的风险副作用使其成为一种有吸引力的治疗选择,也为其他疾病的创新应用铺平了道路。
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引用次数: 0
The Therapeutic Potential of Cannabinoids in Dermatology 大麻素在皮肤病学中的治疗潜力
Q1 Medicine Pub Date : 2018-11-01
Dustin H. Marks, Adam Friedman

Cannabinoids have demonstrated utility in the management of cancer, obesity, and neurologic disease. More recently, their immunosuppressive and anti-inflammatory properties have been identified for the treatment of several dermatologic conditions. This review thus assesses the therapeutic potential of phytocannabinoids, endoocannabinoids, and chemically synthetic cannabinoids in the management of cutaneous disease. The PubMed® and Scopus® databases were subsequently reviewed in December 2017 using MeSH and keywords, such as cannabinoid, THC, dermatitis, pruritus, and skin cancer. The search yielded reports on the therapeutic role of cannabinoids in the management of skin cancer, acne vulgaris, pruritus, atopic and allergic contact dermatitis, and systemic sclerosis. While cannabinoids have exhibited efficacy in the treatment of inflammatory and neoplastic skin conditions, several reports suggest pro-inflammatory and pro-neoplastic properties. Further investigation is necessary to understand the complexities of cannabinoids and their therapeutic potential in dermatology.

大麻素在治疗癌症、肥胖和神经系统疾病方面已被证明具有实用价值。最近,它们的免疫抑制和抗炎特性已被确定用于治疗几种皮肤病。因此,本综述评估了植物大麻素、内源性大麻素和化学合成大麻素在皮肤病治疗中的治疗潜力。随后于2017年12月使用MeSH和关键词(如大麻素、四氢大麻酚、皮炎、瘙痒和皮肤癌)对PubMed®和Scopus®数据库进行了审查。这项研究产生了关于大麻素在皮肤癌、寻常性痤疮、瘙痒症、特应性和过敏性接触性皮炎以及系统性硬化症的治疗作用的报告。虽然大麻素在治疗炎症性和肿瘤性皮肤状况方面表现出疗效,但一些报告表明其具有促炎和促肿瘤特性。进一步的研究是必要的,以了解大麻素的复杂性和他们的治疗潜力在皮肤病学。
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引用次数: 0
Chronic Pruritus: A Review of Neurophysiology and Associated Immune Neuromodulatory Treatments. 慢性瘙痒:神经生理学和相关免疫神经调节治疗的综述。
Q1 Medicine Pub Date : 2018-09-01
J M Patel, H Dao

Chronic pruritus remains a difficult condition to treat with many non-specific therapeutic options. Recent scientific discoveries have elucidated the physiology associated with pruritus. Combined with clinical and experimental trials with immune-modulatory agents, chronic pruritus now has novel treatment options with known mechanisms of action. This review goes over recent scientific progress in understanding the molecular mechanisms governing pruritus, the cross-talk between the immune and nervous systems that regulate itch, and central nervous pathways and projections affected by itch. In light of these recent discoveries, we briefly discuss a growing body of data from relevant clinical trials investigating immunomodulatory drugs targeting specific interleukin receptors (IL-4/13/31) and intracellular signaling (e.g., Janus kinase) pathways. We focus on the physiological processes that control this complex physical and emotional experience, as well as the role of newer drugs used to treat chronic itch.

慢性瘙痒症仍然是一个困难的条件,许多非特异性治疗方案治疗。最近的科学发现已经阐明了与瘙痒有关的生理学。结合免疫调节剂的临床和实验试验,慢性瘙痒现在有了新的治疗选择和已知的作用机制。本文综述了近年来在理解控制瘙痒的分子机制、调节瘙痒的免疫系统和神经系统之间的串扰以及受瘙痒影响的中枢神经通路和投射方面的科学进展。鉴于这些最近的发现,我们简要地讨论了相关临床试验中越来越多的数据,这些临床试验研究了针对特异性白细胞介素受体(IL-4/13/31)和细胞内信号传导(如Janus激酶)途径的免疫调节药物。我们专注于控制这种复杂的身体和情感体验的生理过程,以及用于治疗慢性瘙痒的新药的作用。
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引用次数: 0
Non-Invasive Gene Expression Testing to Rule Out Melanoma. 非侵入性基因表达测试排除黑色素瘤。
Q1 Medicine Pub Date : 2018-09-01
J K Rivers, M R Copley, R Svoboda, D S Rigel

The Pigmented Lesion Assay (PLA) is a gene expression test that helps rule out melanoma and has the potential to reduce the need for surgical biopsies of atypical pigmented skin lesions. Utilizing a new technological platform for the non-invasive profiling of skin, the assay analyzes samples collected from adhesive patches for expression of two key genes (PRAME and LINC00518) known to be overexpressed in melanoma. The test result is binary (positive/negative) based on the detection of one or both genes. PLA positive cases are generally biopsied to establish the histopathologic diagosis, while PLA negative cases are considered for ongoing monitoring. The combination of visual inspection with histopathology, the current gold standard for melanoma diagnosis, has a relatively low negative predictive value (NPV) of approximately 83%, meaning that 17% of melanomas will be interpreted as benign lesions. In contrast, the PLA has a very high NPV (>99%). Further, with its high specificity (69-91%), use of the PLA can reduce the number of false positive samples subjected to histopathology review. By adding the PLA to the current care pathway, the number of surgical biopsies needed to find a melanoma (number needed to biopsy) is markedly reduced from 20-25 biopsies for dermatologists and 39 biopsies for physician assistants, to an average of 2.7. To date, unnecessary surgical procedures of benign lesions have been reduced by 88% based on a sample of more than 20,000 analyzed cases. This has resulted in fewer missed melanomas and significant cost savings to health care systems.

色素沉着病变测定(PLA)是一种基因表达测试,有助于排除黑色素瘤,并有可能减少非典型色素沉着皮肤病变的手术活检需求。利用一种非侵入性皮肤分析的新技术平台,该分析分析了从粘附斑块收集的样本中已知在黑色素瘤中过表达的两个关键基因(PRAME和LINC00518)的表达。基于一个或两个基因的检测,测试结果是二元的(阳性/阴性)。PLA阳性病例通常进行活检以确定组织病理学诊断,而PLA阴性病例则考虑持续监测。目视检查与组织病理学相结合是目前黑色素瘤诊断的金标准,其阴性预测值(NPV)相对较低,约为83%,这意味着17%的黑色素瘤将被解释为良性病变。相比之下,PLA具有非常高的净现值(>99%)。此外,PLA具有高特异性(69-91%),可以减少组织病理学检查的假阳性样本数量。通过将PLA添加到当前的护理路径中,发现黑色素瘤所需的手术活检次数(活检次数)显着减少,从皮肤科医生的20-25次活检和医师助理的39次活检,减少到平均2.7次。迄今为止,基于2万多例分析病例的样本,良性病变的不必要外科手术已经减少了88%。这减少了黑色素瘤的漏诊,大大节省了医疗保健系统的成本。
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引用次数: 0
Alitretinoin: An Update of Real-World Evidence in The Management of Chronic Hand Dermatitis. 阿利维甲酸:慢性手部皮炎治疗的真实世界证据的更新。
Q1 Medicine Pub Date : 2018-07-01
M J Gooderham

Chronic hand dermatitis is a debilitating inflammatory dermatosis that has a significant impact on the quality of life of those affected. Alitretinoin is an oral retinoid which has proven efficacy and safety in the treatment of chronic hand dermatitis through randomized controlled trials. Real-world evidence, information gathered in the clinic or community setting, as opposed to a research environment, can complement knowledge gained from clinical trials. Herein, real-world evidence supporting the safety and effectiveness of alitretinoin in the management of chronic hand dermatitis will be reviewed.

慢性手部皮炎是一种使人衰弱的炎症性皮肤病,对患者的生活质量有重大影响。阿利维甲酸是一种口服类维甲酸,通过随机对照试验证明其治疗慢性手部皮炎的有效性和安全性。与研究环境相反,在诊所或社区环境中收集的真实证据和信息可以补充从临床试验中获得的知识。本文将回顾支持阿利维甲酸治疗慢性手部皮炎的安全性和有效性的真实证据。
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引用次数: 0
The Evolution of Topical Formulations in Psoriasis. 银屑病局部配方的演变。
Q1 Medicine Pub Date : 2018-07-01
B Kuehl, N H Shear

Most people with mild-to-moderate psoriasis manage their disease with topical therapies. However, adherence to topical treatment remains a challenge, as the daily application creates a significant treatment burden. New topical therapeutic options need to offer higher efficacy and better patient acceptability, including easier application, to reduce treatment burden and enhance patient adherence. Topical foam vehicles are innovative alternatives to creams and ointments, addressing many patient challenges with traditional vehicles. Well-designed foam vehicles are easily spread over large areas of the skin, while importantly not leaving a greasy or oily film on the skin after application. Calcipotriol/betamethasone diproprionate aerosol foam is a new psoriasis treatment option that is rapidly effective, offers greater efficacy versus ointment and gel formulations, and has been shown to increase patient treatment satisfaction. Hence, by addressing the several crucial unmet clinical needs in patients with mild-to-moderate psoriasis, this optimized foam formulation is poised to improve treatment follow-through.

大多数患有轻度至中度牛皮癣的人用局部治疗来治疗他们的疾病。然而,坚持局部治疗仍然是一个挑战,因为每天的应用创造了显著的治疗负担。新的局部治疗方案需要提供更高的疗效和更好的患者可接受性,包括更容易应用,以减轻治疗负担并提高患者依从性。局部泡沫车辆是面霜和软膏的创新替代品,解决了传统车辆的许多患者挑战。精心设计的泡沫车很容易在皮肤上大面积涂抹,同时重要的是在使用后不会在皮肤上留下油腻或油性膜。钙化三醇/二本体酸倍他米松气溶胶泡沫是一种新的牛皮癣治疗选择,快速有效,提供比软膏和凝胶制剂更大的疗效,并已显示提高患者治疗满意度。因此,通过解决轻度至中度牛皮癣患者的几个关键未满足的临床需求,这种优化的泡沫配方有望改善治疗的后续效果。
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引用次数: 0
Janus Kinase Inhibitors: A Review of Their Emerging Applications in Dermatology Janus激酶抑制剂:在皮肤病学中的新应用综述
Q1 Medicine Pub Date : 2018-05-01
A Cinats, E Heck, L Robertson

The class of medications known as Janus kinase inhibitors block cytokine-mediated signaling via the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, which plays an important role in immunoregulation and normal cell growth. This class includes the drugs tofacitinib, approved for the treatment of rheumatoid arthritis, and ruxolitinib, approved for the treatment of myelofibrosis and polycythemia rubra vera. The most common adverse events (AEs) reported in patients taking tofacitinib are infections, whereas the most common AEs in patients taking ruxolitinib are anemia and thrombocytopenia. Both first and second generation Janus kinase inhibitors have become promising treatment modalities for dermatologic conditions such as psoriasis, atopic dermatitis, alopecia areata, vilitigo, dermatomyositis, and graft-versus-host disease. Future promising areas of investigation include treatment of cutaneous lupus, cutaneous T-cell lymphoma, melanoma, allergic contact dermatitis, and lichen planus.

一类被称为Janus激酶抑制剂的药物通过Janus激酶信号转导和转录激活因子(JAK-STAT)途径阻断细胞因子介导的信号传导,该途径在免疫调节和正常细胞生长中起重要作用。这类药物包括被批准用于治疗类风湿性关节炎的托法替尼(tofacitinib)和被批准用于治疗骨髓纤维化和真性红细胞增多症的ruxolitinib。服用托法替尼的患者报告的最常见不良事件(ae)是感染,而服用鲁索利替尼的患者最常见的ae是贫血和血小板减少症。第一代和第二代Janus激酶抑制剂已经成为皮肤病如牛皮癣、特应性皮炎、斑秃、白癜风、皮肌炎和移植物抗宿主病的有希望的治疗方式。未来有前景的研究领域包括皮肤狼疮、皮肤t细胞淋巴瘤、黑色素瘤、过敏性接触性皮炎和扁平苔藓的治疗。
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引用次数: 0
Chronic Urticaria: Following Practice Guidelines. 慢性荨麻疹:遵循实践指南。
Q1 Medicine Pub Date : 2018-05-01
E P Westby, C Lynde, G Sussman

Histamine is a key inflammatory player in the pathogenesis of urticaria, a mast-cell-driven disease characterized clinically by the development of wheals, angioedema, or both. Changes to the management of chronic spontaneous urticaria have recently been adopted due to increasing literature surrounding the efficacy and safety of up-dosing modern second-generation H1-antihistamines and the use of omalizamub, a biologic agent, as a third-line treatment. Given the prevalence of chronic urticaria and its impact on quality of life, this editorial aims to provide a summary of the proposed updated guidelines for the management of chronic urticaria as agreed upon at the 5th Consensus Conference on the Update and Revision of the EAACI/GA2LEN/EDF/WAO Guideline for Urticaria in Berlin in December 2016. The chronic urticaria treatment algorithm outlined here reflects the updates and revisions made by 43 international experts representing 40 societies from 25 countries. These guidelines have yet to be published and therefore will require approval by respective national and international boards before adoption.

组胺是荨麻疹发病机制中的关键炎症因子,荨麻疹是一种肥大细胞驱动的疾病,临床表现为荨麻疹、血管性水肿或两者兼而有之。由于越来越多的文献报道了增加剂量的现代第二代h1 -抗组胺药的有效性和安全性,以及使用生物制剂omalizamub作为三线治疗,慢性自发性荨麻疹的管理方法已经改变。鉴于慢性荨麻疹的流行及其对生活质量的影响,本社论旨在总结2016年12月在柏林举行的第五次EAACI/GA2LEN/EDF/WAO荨麻疹指南更新和修订共识会议上商定的拟议的慢性荨麻疹管理更新指南。这里概述的慢性荨麻疹治疗算法反映了代表25个国家40个学会的43名国际专家所做的更新和修订。这些准则尚未公布,因此在通过之前需要得到各自国家和国际委员会的批准。
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引用次数: 0
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Skin therapy letter
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