Women with fair phenotypes seem to confer a survival advantage in a low UV milieu. A nested matched case control study.
- 作者列表："Lindqvist PG","Epstein E","Landin-Olsson M","Åkerlund M","Olsson H
BACKGROUND:Sun exposure in combination with skin pigmentation is the main determinant for vitamin D status. Human skin color seems to be adapted and optimized for regional sun ultraviolet (UV) intensity. However, we do not know if fair, UV-sensitive skin is a survival advantage in regions with low UV radiation. METHODS:A population-based nested case-control study of 29,518 Caucasian women, ages 25 to 64 years from Southern Sweden who responded to a questionnaire regarding risk-factors for malignant melanoma in 1990 and followed for 25 years. For each fair woman, defined as having red hair or freckles (n = 11,993), a control was randomly selected from all non-fair women from within the cohort of similar age, smoking habits, education, marital status, income, and comorbidity, i.e., 11,993 pairs. The main outcome was the difference in all-cause mortality between fair and non-fair women in a low UV milieu, defined as living in Sweden and having low-to-moderate sun exposure habits. Secondary outcomes were mortality by sun exposure, and among those non-overweight. RESULTS:In a low UV milieu, fair women were at a significantly lower all-cause mortality risk as compared to non-fair women (log rank test p = 0.04) with an 8% lower all-cause mortality rate (hazard ratio [HR] = 0.92, 95% CI 0.84‒1.0), including a 59% greater risk of dying from skin cancer among fair women (HR 1.59, 95% CI 1.26‒2.0). Thus, it seem that the beneficial health effect from low skin coloration outweigh the risk of skin cancer at high latitudes. CONCLUSION:In a region with low UV milieu, evolution seems to improve all-cause survival by selecting a fair skin phenotype, i.e., comprising fair women with a survival advantage.
背景: 日晒结合皮肤色素沉着是维生素d状态的主要决定因素。人类的肤色似乎是适应和优化的区域太阳紫外线 (UV) 强度。然而，我们不知道是否公平，紫外线敏感的皮肤是低紫外线辐射地区的生存优势。 方法: 一项基于 29,518 名高加索妇女的人群巢式病例对照研究，年龄 25 ~ 64 岁，来自瑞典南部，1990 年回答了一份关于恶性黑色素瘤危险因素的问卷，并随访了 25 年。对于每个漂亮的女性，定义为有红色头发或雀斑 (n = 11,993)，从年龄相似、吸烟习惯、教育、婚姻状况、收入和共病，即，11,993 双。主要结果是低紫外线环境中公平和非公平女性的全因死亡率差异，定义为生活在瑞典，有低至中度的阳光暴露习惯。次要结局是阳光照射的死亡率，以及那些非超重的死亡率。 结果: 在低紫外线环境下，公平女性的全因死亡风险显著低于非公平女性 (log rank检验p = 0.04) 全因死亡率降低 8% (风险比 [HR] = 0.92，95% CI 0.84-1.0)，包括公平女性死于皮肤癌的风险增加 59% (HR 1.59，95% CI 1.26-2.0)。因此，它似乎是有益的健康效果从低皮肤着色超过风险的皮肤癌在高纬度地区。 结论: 在低UV环境的地区，进化似乎通过选择公平的皮肤表型来提高全因生存率，即包括具有生存优势的公平女性。
METHODS::Blue rubber bleb naevus syndrome (BRBNS) is an extremely rare venous malformation that often manifests as multiple haemangioma-like lesions in the skin and gastrointestinal tract. The drug sirolimus plays a key role in the signalling pathway of angiogenesis and subsequent development of BRBNS and its use has been described in several case reports. We present a case series of four patients with BRBNS who exhibited good treatment response to sirolimus. All four patients were administered oral sirolimus at doses of 1.0-1.5 mg/m2 /day with a target drug level of 5-10 ng/mL and median treatment duration of 20 months. All patients had a reduction in the size of the lesions and a normalization of coagulopathy with tolerable drug adverse reactions at follow-up. Sirolimus may be effective and safe in paediatric patients with BRBNS. Further prospective studies are suggested to evaluate the long-term effectiveness of this drug.
METHODS:BACKGROUND:Human papillomavirus (HPV) infections are associated with common dermatologic and nondermatologic diseases. Although HPV vaccines are well established as preventive measures for genital warts and cervical neoplasia, their use as therapeutic agents deserves greater attention. OBJECTIVE:To evaluate the use of HPV vaccine(s) as a treatment modality for cutaneous and/or mucosal disease. METHODS:A primary literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in January 2019 by using the PubMed and Cochrane databases. RESULTS:A total of 63 articles with 4439 patients were included. The majority of patients with cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas were successfully treated with HPV vaccination. Preliminary data on patients with pre-existing anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia is promising. LIMITATIONS:This review was limited by the lack of controls, patients' previous HPV vaccination status, and publication bias. CONCLUSION:The commercially available three-dose, quadrivalent HPV vaccine is a potential therapeutic option for the treatment of cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas. Noncommercially available HPV vaccines demonstrate therapeutic response for treating anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia. The vaccine's efficacy as an adjunct therapy for HPV-associated cutaneous and/or mucosal disease warrants further exploration.
METHODS::Our understanding of melanoma precursors and progression to melanoma has developed as a result of advances in the field of molecular diagnostics. We now better understand the potential for genetic heterogeneity within a single lesion. Combined tumors can pose a diagnostic challenge when deciding the line between benign and malignant, which in turn has direct implications for patient management. Primary cilia (PC) are ubiquitous sensory organelles that have essential functions in cellular proliferation, differentiation, and development. The ciliation index (percentage of ciliated melanocytes) has been shown to reliably differentiate melanoma, which fail to ciliate, from melanocytic nevi, which retain PC. We therefore analyzed the potential for using the ciliation index to differentiate benign and malignant components in combined melanocytic lesions. We collected patient samples (n = 10) of unequivocal combined lesions with both melanoma and associated nevus components. Melanocytes were highlighted with SOX10 and costained with gamma-Tubulin and acetylated alpha-Tubulin to highlight the basal body and cilium, respectively. The number of melanocytes retaining cilia under high-power microscopy was examined. The melanoma component had average of 4% ciliation (SD: 7%), whereas the associated nevus component was significantly higher with 59% ciliation (SD: 17%). These data show that PC may be a reliable means of distinguishing benign from malignant components within a single tumor. The ciliation index may be a helpful tool in distinguishing challenging cases of combined lesions of melanoma in situ with a dermal nevus component from invasive melanoma, thus promoting improved staging and clinical management.