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A Bibliometric Analysis of Alopecia Areata Literature over the Past 50 Years. 过去 50 年脱发症文献的文献计量分析。
Sapir Itzhaki Gabay, Barak Zlakishvili, Amir Horev

Background: An extensive body of literature has been published regarding alopecia areata (AA) in the past 50 years. The current paper used a bibliometric analysis (BA) to identify high-quality research articles using criteria such as annual citations (ACs) and journal impact factor.

Objectives: To identify and analyze the top 100 most cited articles in AA scientific literature over the past 50 years using BA methods.

Methods: Web of Science (webOS) citation indexing database was used, on April 4th, 2023, to identify the most cited articles on AA. Articles were ranked by their ACs. Data sets were then subdivided into corresponding and senior authors, year of publication, journal and impact factor, total citations according to webOS database, ACs, affiliation, country of origin, manuscript type, design, focus, and usage count since 2013.

Results: The extracted articles were published between 1975-2019. Mean total citations ranged between 67 and 578. The most cited paper was: "Tofacitinib for the treatment of severe alopecia areata and variants: A study of 90 patients" by Liu et al. with an AC of 26.5. Most publications were published between 1990 and 1999 (n=28). The Journal of the American Academy of Dermatology was the most published journal (25 articles). The research focus of original papers was treatment (36%), epidemiology (22%), pathogenesis (20%), basic science (16%), and diagnosis (6%).

Conclusion: This analysis is the first to provide detailed bibliometric characteristics, highlighting the worldwide burden and research trends in.

背景:在过去的 50 年中,发表了大量有关斑秃(AA)的文献。本文采用文献计量分析法(BA),以年度引文(AC)和期刊影响因子等标准来识别高质量的研究文章:采用文献计量学分析方法,确定并分析过去 50 年 AA 科学文献中被引用次数最多的前 100 篇文章:方法:使用 Web of Science(webOS)引文索引数据库(2023 年 4 月 4 日)来确定有关 AA 的被引用次数最多的文章。文章按其 AC 排序。然后将数据集细分为通讯作者和资深作者、发表年份、期刊和影响因子、webOS数据库的总引用次数、ACs、所属单位、原籍国、稿件类型、设计、重点以及自2013年以来的使用次数:提取的文章发表于 1975-2019 年间。平均总被引次数介于 67 与 578 之间。被引用次数最多的论文是"托法替尼治疗重度斑秃及其变异型:90名患者的研究",AC值为26.5。大多数论文发表于 1990 年至 1999 年(n=28)。美国皮肤病学会杂志》是发表文章最多的杂志(25 篇)。原创论文的研究重点是治疗(36%)、流行病学(22%)、发病机制(20%)、基础科学(16%)和诊断(6%):这项分析首次提供了详细的文献计量学特征,突出了该领域的全球负担和研究趋势。
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引用次数: 0
Plasma Cell Mucositis: A Clinical Conundrum. 浆细胞粘膜炎:临床难题。
Mahnaz Fatahzadeh, Joseph Rinaggio, Robert A Schwartz

Plasma cell mucositis (PCM) is an unusual disorder most evident in the accessible mucosa and usually reported in the upper aerodigestive tract, although it is named according to its specific anatomical site of involvement such as plasma cell cheilitis, plasma cell gingivitis, plasma cell vulvitis, and Zoon's balanitis. PCM reflects a dense polyclonal rather than a monoclonal plasma cell proliferation of unclear and unknown etiology. This perplexing disorder tends to be treated by avoiding possible triggers and intralesional and/or systemic steroids. In this work, we provide a review and update on PCM, which often represents a clinical conundrum.

浆细胞粘膜炎(PCM)是一种不常见的疾病,在可触及的粘膜上最为明显,通常报告发生在上消化道,但也会根据具体的受累解剖部位来命名,如浆细胞颊炎,浆细胞牙龈炎,浆细胞外阴炎和祖恩氏包茎炎。浆细胞性阴茎炎反映的是病因不明的致密多克隆而非单克隆浆细胞增生。对于这种令人困惑的疾病,治疗方法往往是避免可能的诱发因素,以及使用局部和/或全身性类固醇激素。在本论文中,我们对 PCM 进行了综述和更新,PCM 通常是一种临床难题。
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引用次数: 0
Leukomelanoderma Resembling Hyperpigmented Mycosis Fungoides. 类似色素沉着性真菌病的白斑病
Natsuko Aoki, Hozumi Sano, Kimiko Nakajima, Shigetoshi Sano, Kozo Nakai

Acquired circumscribed hyperpigmented patches and plaques have various differential diagnoses, including post-inflammatory hyperpigmentation and mycosis fungoides (MF). Leukomelanoderma is an uncommon cutaneous condition in which the pathogenesis is not fully elucidated. It has been reported that leukomelanoderma occurs after allergic contact dermatitis from hydroquinone or acute cutaneous graft-versus-host disease (1,2). Hyperpigmented MF is a cutaneous T-cell lymphoma with a frequent CD8+ phenotype (3). Herein, we report a case of leukomelanoderma clinically and histologically resembling hyperpigmented MF. A 55-year-old Japanese woman was referred to our department for evaluation of reticulate pigmentation with pruritic erythema on the face. She had used commercially available depigmenting cosmetic reagents for 20 years and ointment containing 10% hydroquinone for 3 months. Physical examination revealed diffuse hyperpigmentation and demarcated hypopigmented macules on the face and neck (Figure 1, a). Dermoscopy showed depigmented spots and reticulated plus dotted hyperpigmentation; it presented a pseudo-pigment network (Figure 1, b). Histological examination of a tissue specimen biopsied from the lesion showed superficial band-like lymphocytic infiltration in dermis accompanying single cells or small clusters in epidermis (Figure 1, c). Interface changes were observed together with melanophages in the dermis. Melan-A-positive melanocytes were absent. Immunohistochemical analysis demonstrated that the epidermotropic lymphocytes were CD3+CD7-, and they had predominance of CD8+ cells (Figure 1, d). These immunohistochemical results mimicked MF. However, PCR analysis of the T-cell receptor g-gene rearrangement was negative. Closed patch test result with hydroquinone (5% pet.) was graded D2 (+?) and D3 (+). Ten months after discontinuing cosmetic reagents and hydroquinone, the pigmentary changes showed improvement. The pathomechanism of leukomelanoderma is unclear. Although post-inflammatory pigmentation due to allergic or contact dermatitis together with direct depigmenting effects from hydroquinone use has been suggested (1), the immunophenotype of T-cells has not been examined. As observed in our patient, interface changes with melanophages, in addition to frequent CD8+ phenotype of the epidermotropism and dermal infiltrate of lymphocytes, were characteristic for hyperpigmented MF (3). Moreover, minimal CD7 expression was a specific finding for MF (4). T-cell receptor clonality was negative in our patient, but the clonality appears to be detected by PCR in up to 50% of the patients with early MF (3). In contrast, the closed patch test was positive for hydroquinone in our patient, and it is reported that CD8+ T-cells are recruited to the interphase between the epidermis and the dermis of the patients with allergic contact dermatitis (5). CD8+ T-cells might contribute to acute cutaneous graft-versus-host disease-like interface changes and des

获得性环状色素沉着斑和斑块有多种鉴别诊断,包括炎症后色素沉着和真菌病(MF)。白斑病是一种不常见的皮肤病,其发病机制尚未完全阐明。有报道称,白斑病发生于对苯二酚过敏性接触性皮炎或急性皮肤移植物抗宿主病之后(1,2)。色素沉着性白皮病是一种皮肤 T 细胞淋巴瘤,多为 CD8+ 表型(3)。在此,我们报告了一例在临床和组织学上与色素沉着病相似的白斑病病例。一名 55 岁的日本妇女因网状色素沉着伴面部瘙痒性红斑转诊至我科。她使用市售脱色化妆品试剂已有 20 年,使用含 10% 氢醌的软膏已有 3 个月。体检发现面部和颈部有弥漫性色素沉着和分界不清的色素减退斑(图 1,a)。皮肤镜检查显示有色素减退斑和网状加点状色素沉着,呈现假性色素网络(图 1,b)。对病变组织标本的组织学检查显示,真皮层有浅表带状淋巴细胞浸润,表皮层有单细胞或小细胞群(图 1,c)。在真皮层观察到界面变化和噬黑色素细胞。Melan-A阳性黑素细胞缺失。免疫组化分析表明,表皮淋巴细胞为 CD3+CD7-,其中以 CD8+细胞为主(图 1,d)。这些免疫组化结果与 MF 相似。但 T 细胞受体 g 基因重排的 PCR 分析结果为阴性。氢醌(5%)封闭斑贴试验结果分为 D2(+?)和 D3(+)级。停用化妆品试剂和氢醌 10 个月后,色素变化有所改善。白斑病的病理机制尚不清楚。虽然有人认为过敏性或接触性皮炎导致的炎症后色素沉着,以及使用氢醌产生的直接脱色作用(1),但尚未对 T 细胞的免疫表型进行研究。正如在我们的患者身上观察到的那样,除了频繁出现的 CD8+ 表型表皮细胞和真皮浸润的淋巴细胞外,噬黑色素细胞的界面变化也是色素沉着性中耳炎的特征(3)。此外,CD7 表达极少也是 MF 的特异性发现(4)。在我们的患者中,T 细胞受体克隆呈阴性,但在多达 50% 的早期 MF 患者中,PCR 似乎可以检测到克隆(3)。与此相反,我们的患者在封闭斑贴试验中对苯二酚呈阳性,有报道称 CD8+ T 细胞被招募到过敏性接触性皮炎患者的表皮和真皮之间(5)。CD8+ T 细胞可能导致急性皮肤移植物抗宿主病样界面变化,并破坏白斑病皮损中的黑色素细胞。因此,我们的患者被认为是过敏性接触性皮炎表现为白斑病。然而,还需要更多的报告和研究来支持这一观点。因此,我们认为有必要对患者进行随访,因为 MF 并没有绝对消除。
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引用次数: 0
Solitary Basaloid Follicular Hamartoma: A Report of Two Cases. 单发基底样毛囊性 Hamartoma:两个病例的报告。
Danica Tiodorović, Andrija Jović, Slađana Cekić, Nataša Vidović, Tatjana Radević, Željko Mijušković

Basaloid follicular hamartoma (BFH) is rare benign follicular malformation that is often clinically misdiagnosed. Patients with BFH demonstrate a variety of clinical manifestations and associated abnormalities. BFH may be a familial, congenital, or acquired condition with localized or generalized distribution. Several clinical variants of generalized BFH are known, and they can be associated with a diverse spectrum of abnormalities. Herein, we report two cases of solitary BFH in pediatric patients, both documented dermoscopically.

基底样滤泡束状瘤(BFH)是一种罕见的良性滤泡畸形,临床上经常被误诊。BFH 患者有多种临床表现和相关异常。BFH 可能是家族性、先天性或后天性疾病,分布于局部或全身。目前已知全身性 BFH 有几种临床变异,可伴有多种异常。在此,我们报告了两例儿童患者的单发 BFH 病例,两例病例均有皮肤镜检查记录。
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引用次数: 0
Is There a Need to Educate Patients with Atopic Dermatitis in Baseline Therapy? 是否有必要对特应性皮炎患者进行基础治疗教育?
Mikołaj Cichoń, Mariusz Baran, Magdalena Trzeciak

Introduction: The baseline therapy of atopic dermatitis (AD) includes emollient therapy, prevention of triggering factors and proper patients' education. Appropriate level of education about AD among patients is crucial for successful treatment of the disease.

Aims: To compare and evaluate the level of knowledge about baseline therapy in atopic dermatitis (AD) between the adults with AD and the parents of children with AD.

Materials and methods: Adult patients with AD (n=180) and parents of children with AD (n=106) completed an original questionnaire covering issues of emollient therapy and bathing. For statistical comparison a chi - square test was used with significance level of 0,05.

Results: With significance level of 0,05, the chi - square test showed a statistically significant difference comparing both groups. 52,38% adults and 68,73% parents proved to know the principles of basic therapy (p<0,05). 55,00% adults and 50,00% parents have not been informed how to apply emollients appropriately (p>=0,05). 75,56% and 74,53%, respectively, seek additional education about it (p>=0,05). 63,89% adults and 49,06% parents have not been informed about the principles of bathing (p<0,05). 70,00% and 74,54%, respectively, expect more comprehensive explanation of bathing rules (p>=0,05).

Conclusions: Adults with AD have lesser knowledge about baseline therapy than parents of children with AD. Both groups express a very strong need for education about baseline therapy in AD.

简介:特应性皮炎(AD)的基础治疗包括润肤疗法、预防诱发因素和适当的患者教育。目的:比较并评估成人特应性皮炎患者和儿童特应性皮炎患者家长对特应性皮炎基础治疗的了解程度:成人特应性皮炎患者(180 人)和儿童特应性皮炎患者的父母(106 人)填写了一份原始问卷,内容涉及润肤疗法和沐浴问题。统计比较采用卡方检验,显著性水平为 0.05:结果:在显著性水平为 0.05 的情况下,卡方检验结果显示,两组数据在统计学上存在显著差异。事实证明,52.38% 的成人和 68.73% 的家长了解基本治疗原则(P=0.05)。分别有 75.56% 和 74.53% 的家长寻求更多的相关教育(P>=0.05)。63.89%的成人和49.06%的家长未被告知沐浴原则(P=0.05):与 AD 儿童的父母相比,AD 成人对基线疗法的了解较少。两个群体都表示非常需要进行有关 AD 基线疗法的教育。
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引用次数: 0
COVID-19-associated Telogen Effluvium After Hospital Discharge: A Prospective Cohort Study. 与 COVID-19 相关的出院后脱发:一项前瞻性队列研究
Katerina Damevska, Tomica Sotirovski, Bojana Batkoska, Marija Djambazova, Vaska Radeski, Jorde Simonoska, Dimitri Bachevski, Kujtime Rushiti Mehmeti, Tomche Popovski, Ermira Labenishta, Aleksandar Ristovski, Anita Najdova

Introduction Telogen effluvium (TE) is a common sequela of SARS-CoV-2 infection. Existing studies are highly heterogeneous. We aimed to assess the prevalence of TE in a cohort of patients with severe disease hospitalized for acute COVID-19. Methods This prospective cohort study was conducted at the University Clinic of Dermatology, part of the COVID-19 University Hospital Network throughout the pandemic. The acute phase data were extracted from electronic hospital records. Details about hair loss were obtained at two follow-up points, 3 and 6 months after hospital discharge, using telephone interviews. Results A total of 77 patients were successfully followed up, and 40 (48.8%) were male. The mean age was 55.91, SD=10,588. Overall, 68.8% of patients reported TE. Among these, 52.8% reported early onset, and 50.9% reported moderate hair loss. 11 (20.7%) reported complete hair regrowth within three months, and an additional 32 (60.3%) reported complete regrowth within six months. 4 (7.5%) patients have chronic TE. Female sex (p<0.0001), anemia (p=0.019), hypoproteinemia (p=0.037), and severe pneumonia (p=0.004) were associated with TE. Age, fever, SpO2, CRP levels, in-hospital complications, and raised D-dimers were not associated with TE. Discussion Our study confirmed a high prevalence of COVID-19-associated TE in hospitalized patients. Anemia and hypoalbuminemia were associated with TE, shedding new light on the possible pathogenesis. COVID-19-associated TE occurs earlier than classic TE and has a good prognosis in most patients. However, chronic ТЕ was reported by 7.5%. Even a small incidence of long-term sequelae during a pandemic could have substantial health consequences.

引言 毛发脱落症(TE)是感染 SARS-CoV-2 后常见的后遗症。现有的研究差异很大。我们的目的是评估因急性 COVID-19 而住院的重症患者中 TE 的发病率。方法 这项前瞻性队列研究在整个大流行期间在 COVID-19 大学医院网络下属的大学皮肤病诊所进行。急性期的数据来自医院的电子病历。在出院后 3 个月和 6 个月的两次随访中,通过电话采访获得了脱发的详细情况。结果 共有 77 名患者成功接受了随访,其中 40 名(48.8%)为男性。平均年龄为 55.91 岁,SD=10,588。总体而言,68.8%的患者报告了 TE。其中,52.8%的患者早期发病,50.9%的患者中度脱发。11名患者(20.7%)在三个月内头发完全再生,另有32名患者(60.3%)在六个月内头发完全再生。4(7.5%)名患者患有慢性 TE。女性(p
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引用次数: 0
A Case of Noonan Syndrome and Kyrle's Disease: Coincidence or Causality? 一例努南综合征和柯尔氏症:巧合还是因果关系?
Marco Brusasco, Arlind Kalaja, Francesca Satolli, Claudio Feliciani, Maria Beatrice De Felici Del Giudice

A 39-year-old Caucasian woman affected by Noonan Syndrome (NS) mutated in RAF1 was referred to us with itchy lesions on her limbs that had appeared two months earlier. Clinically, there were multiple umbilicated papules with a hyperkeratotic central plug, localized on the upper and lower limbs (Figure 1, a-b). The patient had no personal history of diabetes mellitus and no chronic renal failure, but suffered from hypertrophic cardiomyopathy. Blood tests showed no abnormalities. On histological examination of a skin lesion, an ectatic hair follicle with hyperkeratotic ostium was observed with fragments of hair, inflammatory cells, and epidermal perforation. A final diagnosis of Kyrle's disease (KD) was established. The patient underwent narrowband UVB (NB-UVB) phototherapy with residual atrophic scars (Figure 1, c-d) but with complete and long-lasting resolution of symptoms as well. KD belongs to perforating dermatoses (PD), a heterogeneous group of skin diseases characterized by the transepidermal elimination of dermal components. Despite the classification of PD being debated, four primary forms are traditionally recognized: reactive perforating collagenosis, elastosis perforans serpiginosum, perforating folliculitis, and KD (1). The typical skin manifestation of KD is an eruption of dome-shaped papules and nodules with a whitish central keratotic plug, mainly localized on the extremities and the buttocks. Described by Kyrle in 1916, KD is frequently associated with systemic diseases, especially chronic renal failure and diabetes mellitus. Other associated conditions include chronic hepatic disease, internal malignancies, and congestive heart disease (1). Despite the absence of a consensus, the control of the underlying disease remains the first therapeutic target. Both topical (keratolytics, retinoids, and corticosteroids) and systemic treatments (corticosteroid, retinoids, antibiotics, and phototherapy) have been reported to control skin manifestations (2). In our experience, NB-UVB is an effective option as first-line therapy in case of diffuse lesions, both in KD and in other PDs (3). NS is a relatively common RASopathy, an heterogenous group of genetic disease characterized by a defect of the Ras-mitogen-activated protein kinase (Ras-MAPK) pathway, with an estimated prevalence of 1/1000-2500. PTPN11 is the most frequent mutated gene, accounting for 50% of cases, but more than ten genes were identified as causing NS (4). Classical features include a distinctive facial dysmorphism, short stature, pulmonic stenosis, and other anomalies of different organs. The skin is commonly involved. Keratinization disorders and hair abnormalities such as keratosis pilaris, ulerythema ophryogenes, wavy or curly hair, and scarce scalp hair are often described. Other cutaneous signs include easy bruising, skin hyperlaxity, multiple lentigines, and café-au-lait spots (5). To the best of our knowledge, no cases of KD in patients with NS have been previous

一名 39 岁的白种女性因患 RAF1 突变的努南综合征(NS)而转诊至我院,她的四肢在两个月前出现了瘙痒性皮损。临床表现为上肢和下肢多发脐状丘疹,中央有角化过度的栓塞(图 1,a-b)。患者没有糖尿病病史,也没有慢性肾功能衰竭,但患有肥厚型心肌病。血液检查未发现异常。在对皮肤病变进行组织学检查时,发现了一个角化过度的异位毛囊,其表面有毛发碎片、炎症细胞和表皮穿孔。最终确诊为柯尔氏症(KD)。患者接受了窄带紫外线(NB-UVB)光疗,虽然有残留的萎缩性疤痕(图 1,c-d),但症状也得到了完全、持久的缓解。KD 属于穿孔性皮肤病(PD),这是一组异质性皮肤病,其特点是真皮成分经表皮脱落。尽管对穿孔性皮肤病的分类还存在争议,但传统上公认有四种主要形式:反应性穿孔性胶原病、浆膜穿孔性弹性纤维病、穿孔性毛囊炎和 KD (1)。KD 的典型皮肤表现是圆顶形丘疹和结节的糜烂,中央有白色角化栓,主要发生在四肢和臀部。KD 由 Kyrle 于 1916 年描述,常伴有全身性疾病,尤其是慢性肾功能衰竭和糖尿病。其他相关疾病包括慢性肝病、内脏恶性肿瘤和充血性心脏病(1)。尽管尚未达成共识,但控制潜在疾病仍是首要治疗目标。据报道,局部治疗(角质溶解剂、维甲酸和皮质类固醇)和全身治疗(皮质类固醇、维甲酸、抗生素和光疗)都能控制皮肤表现(2)。根据我们的经验,NB-UVB 是一种有效的一线疗法,可用于 KD 和其他 PD 的弥漫性病变(3)。NS 是一种相对常见的 RAS 病,是一组以 Ras-介质活化蛋白激酶(Ras-MAPK)通路缺陷为特征的异质性遗传病,估计发病率为 1/1000-2500。PTPN11 是最常见的突变基因,占病例的 50%,但有十多个基因被确定为导致 NS 的基因(4)。典型特征包括明显的面部畸形、身材矮小、肺动脉狭窄以及其他不同器官的异常。皮肤是常见的受累部位。角质化障碍和毛发异常,如毛囊角化症、毛囊溃疡、波浪状或卷曲的毛发以及头皮毛发稀少,都是常有的描述。其他皮肤症状还包括容易瘀伤、皮肤过度松弛、多发性色素沉着和咖啡斑(5)。据我们所知,迄今为止还没有关于 NS 患者出现 KD 病例的报道。KD 的确切发病机制尚不清楚,但有一种假设认为,糖尿病和慢性肾功能衰竭等全身性疾病可导致物质沉积或真皮改变,从而引发炎症过程,随后经表皮挤出(1)。在我们的病人身上,我们排除了与 KD 常见的所有病因。不过,这种表现有可能是患者疾病的直接结果。我们的患者患有弥漫性毛囊角化症,据推测,毛囊角化症的可能致病机制之一是表皮角化异常和继发性真皮炎症反应(1)。另一方面,NS典型的皮肤过度松弛和脆弱表明存在结缔组织的改变,这可能引发异常角质化,继而引发经表皮挤压和穿孔性弹性增生,并与遗传性结缔组织疾病有关(1)。此外,我们的患者患有心脏病,这也是与 KD 相关的另一种疾病(5)。尽管这些解释有其吸引力,但目前还没有足够的证据证明 KD 与 NS 之间存在联系,因此有必要收集更多的数据来证实这一假设。
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引用次数: 0
Spectrum and Frequency of BRAF Mutations in Skin Melanomas in the Dalmatian Region of Croatia. 克罗地亚达尔马提亚地区皮肤黑色素瘤中 BRAF 基因突变的范围和频率。
Joško Bezić, Ivana Tomić, Maja Pavić

Mutation of the BRAF oncogene is one of the most common mutations detected in human neoplasia, occurring in 40-60% of all cutaneous melanoma. BRAF is a serine/threonine protein kinase which is an essential part of the mitogen-activated protein kinase (MAPK) pathway. It is physiologically activated by RAS, but in mutated form, due to molecular conformational change, BRAF becomes constitutively active with subsequent persistent activation of downstream cytoplasmic and nuclear proteins (MEK, ERK, ETS), which finally leads to gene expression that promotes cell growth and survival. Inhibition of the altered MAPK pathway by BRAF inhibitors and combined BRAF/MEK inhibitors in BRAF mutated melanoma has become a standard therapeutic approach (1,2). We recently reported the frequency and clinicopathological features of BRAF V600E mutated melanomas in the Dalmatian region of Croatia. This report included 80 cutaneous melanomas with BRAF analyses performed at our institution until the second half of 2017, using a kit which detected only BRAF V600E mutation (3). From the second half of 2017, we started using a kit which detects several types of BRAF mutations along with NRAS mutation. The aim of this report was to determine the spectrum and frequency of different BRAF mutations in a group of skin melanomas in the Dalmatian region of Croatia and to comment on the relationship between type of BRAF mutation and therapeutic response to MAPK pathway inhibition. The analysis included 179 patients with stage 3 and stage 4 cutaneous melanoma with known BRAF/NRAS mutational status. The paraffin blocks were forwarded from four Dalmatian hospitals (Split: 139 cases, Zadar: 17 cases, Šibenik: 13 cases, Dubrovnik: 10 cases). BRAF/NRAS mutation analysis was performed at the Institute of Pathology, Clinical Hospital Center Split, Croatia, in the period from the second half of 2017 to the end of 2022. For DNA extraction analysis, hematoxylin and eosin stained slides from each submitted sample were reviewed by a pathologist, and tumor tissue was identified for analysis. For all tissue specimens, DNA was extracted from sections (10 mm thick) using the cobas® DNA Sample Preparation Kit (Roche Molecular Diagnostics), following the manufacturer's protocol. The amount of genomic DNA was quantified using the Qubit® 2.0 Fluorometer (Life Technologies) and adjusted to a fixed concentration to be added to the amplification/detection mixture. For mutation analysis, the target DNA was amplified and detected on the cobas z 480 analyzer using the amplification and detection reagents provided in the Roche BRAF/NRAS mutation test (LSR) kit, according to the manufacturer's protocol. The test results were reported as follows: BRAF exon 11 mutation detected, BRAF V600E/E2/D mutation detected, BRAF V600K mutation detected, BRAF V600R mutation detected, BRAF K601E mutation detected, NRAS (G12X, G13X, A18T, Q61X, other NRAS Ex3/4) mutation detected, mutation not detected, or invalid result

然而,不同的I类BRAF突变对靶向治疗的敏感性是不同的。关于 BRAF/MEK 联合抑制的大型随机对照试验显示,对于最常见的 V600E 和 V600K 突变的黑色素瘤,总体反应良好(63%-68%),无进展生存期(PFS)和总生存期(OS)也有所改善,而 Menzer 等人的研究则显示,在 BRAF V600 突变(V600E/K 除外)的转移性黑色素瘤组中,MAPK 通路抑制的反应率较低(45%)。同一组 BRAF 非 V600 突变(II 类和 III 类突变)的黑色素瘤对 MAPK 通路抑制的总体反应率仅为 18%(7)。在我们这组BRAF突变的皮肤转移性黑色素瘤中,我们发现只有6例(6.9%)对MAPK通路抑制剂的反应率预期较低:2例为V600R突变(I类非V600E/K突变),1例为K601E突变(II类突变),3例为外显子11突变(II类和III类突变)。
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引用次数: 0
The Safety Profiles of Adalimumab, Infliximab, Etanercept, Secukinumab and Ustekinumab in Psoriasis - A 30-month Observational Cohort Prospective Study of Adverse Events in Biologic Therapy. 阿达木单抗(Adalimumab)、英夫利昔单抗(Infliximab)、依那西普(Etanercept)、塞库单抗(Secukinumab)和优思库单抗(Ustekinumab)治疗银屑病的安全性概况--一项为期 30 个月的生物疗法不良事件观察性队列前瞻性研究。
Zoltán Paluch, Emanuel Marques, Petr Boháč, Kateřina Zemková, Jana Hercogová

Background: Although biologic agents are very effective, long-term comparative studies demonstrating their safety relative to one another are still lacking.

Methods: A total of 124 patients with psoriasis were followed up for 30 months; 74 received anti-TNF-alpha inhibitors (adalimumab, etanercept, infliximab), 33 were on ustekinumab, and 17 were treated with secukinumab. The rates of adverse events in these groups were recorded and statistically analyzed.

Results: Infliximab-treated patients showed a high occurrence of asymptomatic, but increased liver enzymes, fatigue, and respiratory as well as dermatologic infections. Adalimumab-treated patients were more often affected by musculoskeletal disorders and infections of all types. Patients treated with secukinumab presented with higher rates of cardiovascular disorders as well as respiratory and dermatologic infections. The group receiving etanercept was more often diagnosed with musculoskeletal and reproductive disorders, specifically menstrual disorders. The rates of therapy discontinuation and serious adverse events did not reach statistically significant values.

Conclusion: A higher incidence of adverse events was observed among adalimumab-, and infliximab-treated patients, with ustekinumab found to have the safest profile. Our results demonstrate that a personalized approach, including evaluation of a patient's risk profile, is necessary before commencing a biologic. Further research is warranted to confirm the findings of our study.

背景:尽管生物制剂非常有效,但仍缺乏证明其安全性的长期比较研究:尽管生物制剂非常有效,但目前仍缺乏证明其安全性的长期比较研究:对124名银屑病患者进行了为期30个月的随访,其中74人接受了抗肿瘤坏死因子α抑制剂(阿达木单抗、依那西普、英夫利昔单抗)治疗,33人接受了乌斯特库单抗治疗,17人接受了赛库单抗治疗。对这些组别的不良反应发生率进行了记录和统计分析:结果:接受英夫利西单抗治疗的患者出现无症状但肝酶升高、疲劳、呼吸道感染和皮肤感染的比例较高。接受阿达木单抗治疗的患者更常见肌肉骨骼疾病和各类感染。接受secukinumab治疗的患者出现心血管疾病以及呼吸道和皮肤感染的比例较高。接受依那西普治疗的患者更常被诊断出患有肌肉骨骼和生殖系统疾病,尤其是月经失调。治疗中断率和严重不良事件发生率未达到统计学意义上的显著值:阿达木单抗和英夫利昔单抗治疗患者的不良反应发生率较高,而乌司替尼的安全性最高。我们的研究结果表明,在开始使用生物制剂之前,有必要采取个性化的方法,包括评估患者的风险状况。为了证实我们的研究结果,有必要开展进一步的研究。
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引用次数: 0
Resistin Gene Promoter -420C>G (rs1862513) and +299 G>A (rs3745367) Polymorphisms in Psoriasis. 银屑病中 Resistin 基因 Promoter -420C>G (rs1862513) 和 +299 G>A (rs3745367) 的多态性。
Nazli Dizen-Namdar, Raziye Akcilar, Fulya Yukcu, Selve Arslan-Utku, Zeynep Bayat-Sarioglu

Background: The pro-inflammatory adipokine resistin is known to be related to obesity, insulin resistance, and inflammation. Resistin's significance in the etiology of inflammatory illnesses, such as psoriasis, is explored herein. We examined the link between resistin gene polymorphisms (-420 C>G and +299 G>A) and psoriasis in the Turkish population.

Methods: In this study, we examined 107 patients with psoriasis and 103 healthy controls. Resistin -420 C>G (rs1862513) and +299 G>A (rs3745367) gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results: In patients with psoriasis, the frequency of the resistin -420 CG genotype was meaningfully lower than in the controls. In comparison with the controls, the resistin +299 GA genotype and A allele frequencies were significantly higher. The Resistin -420 CG genotype significantly reduced the risk of psoriasis incidence, while the resistin +299 GA genotype and A allele were found to be associated with a higher risk of psoriasis.

Conclusions: In the Turkish community, resistin gene polymorphisms at -420 C>G and +299 G>A may exert an important influence on psoriasis etiology and susceptibility.

背景:众所周知,促炎症脂肪因子抗脂素与肥胖、胰岛素抵抗和炎症有关。本文探讨了抵抗素在银屑病等炎症性疾病的病因学中的意义。我们研究了土耳其人群中抵抗素基因多态性(-420 C>G 和 +299 G>A)与银屑病之间的联系:在这项研究中,我们调查了 107 名银屑病患者和 103 名健康对照者。通过聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)测定了 Resistin -420 C>G (rs1862513) 和 +299 G>A (rs3745367)基因多态性:结果:在银屑病患者中,抵抗素-420 CG基因型的频率明显低于对照组。与对照组相比,抵抗素 +299 GA 基因型和 A 等位基因频率明显较高。抵抗素 -420 CG 基因型可显著降低银屑病发病风险,而抵抗素 +299 GA 基因型和 A 等位基因则与银屑病发病风险较高有关:结论:在土耳其社区,抵抗素基因的-420 C>G和+299 G>A多态性可能对银屑病的病因和易感性有重要影响。
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引用次数: 0
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Acta dermatovenerologica Croatica : ADC
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