• 文章类型: Review
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  • 文章类型: Journal Article
    分化差与皮肤鳞状细胞癌(CSCC)的不良预后密切相关。此外,国家综合癌症网络(NCCN)指南将低分化肿瘤指定为“非常高风险”。尽管有明确的预后意义,目前普遍使用的CSCC分化没有标准化的分级系统。皮肤病理学家和Mohs外科医生的CSCC分化分级不一致,可靠性研究表明,这两组的评分者间和评分者内可靠性都不理想。缺乏标准化和可靠的分级系统阻碍了在CSCC分期中区分的使用,尽管它与疾病结局明显相关。我们对总结历史CSCC差异化分级系统的文献进行了全面回顾,以及非皮肤性头颈部SCC的分级系统作为参考点。相关文章是通过搜索Embase和PubMed确定的,以及通过查看其他文章和组织学教科书摘录的参考列表。识别和总结的CSCC分级系统包括历史Broders系统,世界卫生组织系统,美国病理学家学院系统,和2023年Delphi皮肤病理学家共识小组描述的系统。
    Poor differentiation is strongly associated with poor outcomes in cutaneous squamous cell carcinoma (CSCC). In addition, the National Comprehensive Cancer Network (NCCN) guidelines designate poorly differentiated tumors as \"very high risk\". Despite its clear prognostic implications, there is no standardized grading system for CSCC differentiation in common use today. CSCC differentiation is graded inconsistently by both dermatopathologists and Mohs surgeons, and reliability studies have demonstrated suboptimal inter- and intra-rater reliability in both of these groups. The absence of a standardized and reliable grading system has impeded the use of differentiation in CSCC staging, despite its apparent correlation with disease outcomes. We performed a comprehensive review of the literature summarizing historical CSCC differentiation grading systems, as well as grading systems in non-cutaneous head and neck SCC as a point of reference. Relevant articles were identified by searching Embase and PubMed, as well as by reviewing reference lists for additional articles and histology textbook excerpts. CSCC grading systems that were identified and summarized include the historical Broders system, the World Health Organization system, the College of American Pathologists\' system, and a system described by a 2023 Delphi consensus panel of dermatopathologists.
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  • 文章类型: Journal Article
    来自皮肤活检的生物库代表了生物多样性保护的有趣策略。然而,真皮的形态和细胞模式可受个体的年龄和性别的影响。因此,评估这些因素对于形成安的列尔海牛的生物库很有趣。这些动物,海洋动物的代表,他们的人口减少了,生物银行对它们的保护至关重要。然后,我们评估了年龄的影响(3.5岁与3.6-16年vs.23.6岁)和性别(男性vs.雌性)使用组织学和体外培养技术对形态和细胞参数进行研究。不管年龄,真皮厚度没有观察到差异,胶原纤维,组织增殖活性和活细胞恢复。尽管如此,与其他动物相比,在23.6岁的组中观察到成纤维细胞减少(p<0.05)。此外,来自3.6-16岁动物细胞的线粒体损伤比其他组更明显(p<0.05)。不管性别,真皮厚度没有观察到差异,胶原纤维,组织增殖活性和活细胞恢复;然而,女性的成纤维细胞少于男性(p<0.05)。与雄性细胞相比,雌性细胞的线粒体损伤较低。总之,虽然年龄和性别不影响皮肤厚度和细胞恢复,各组间观察到成纤维细胞数量和线粒体特征的变化.这些差异对于理解与生物库系统相关的真皮方面可能是重要的。
    The biobanks from dermal biopsies represent an interesting strategy for biodiversity conservation. Nevertheless, the morphological and cellular patterns of the dermis can be influenced by the age and sex of the individual. Therefore, evaluating these factors is interesting for forming biobanks of Antillean manatees. These animals, representatives of marine fauna, have had their population reduced, and biobanks are essential for their conservation. Then, we evaluated the effects of age (3.5 years vs. 3.6-16 years vs. 23.6 years) and sex (males vs. females) on morphological and cellular parameters using histological and in vitro culture techniques. Regardless of age, no differences were observed for dermal thickness, collagen fibres, tissue proliferative activity and viable cell recovery. Nonetheless, fibroblast reduction was observed in groups aged 23.6 years compared to other animals (p < 0.05). Additionally, cells from animals aged 3.6-16 years showed more significant mitochondrial damage than the other groups (p < 0.05). Regardless of sex, no differences were observed for dermal thickness, collagen fibres, tissue proliferative activity and viable cell recovery; however, females had fewer fibroblasts than males (p < 0.05). Cells from females showed lower mitochondrial damage when compared to cells from males. In summary, although age and sex do not influence dermal thickness and cell recovery, variations in the number of fibroblasts and mitochondrial characteristics were observed among the groups. These differences may be significant for understanding the dermis aspects to be correlated to biobank systems.
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  • 文章类型: Case Reports
    黑色素瘤是第九最普遍和第二最致命的肿瘤。病因和发病机制仍不确定。它发生在老年人身上,在第五个十年里,在男性中占主导地位。临床上,它们表现为无症状的黄斑或结节状生长。预后受肿瘤大小和远处转移的影响。远处转移患者的5年生存率低于30%,构成转移是黑色素瘤相关死亡的主要原因。目前,由于无法手术的状态,转移性黑色素瘤的主要治疗方法是免疫疗法,肿瘤的放射抗性性质和化疗中细胞毒性的高机会。一个老年男性病人,他被诊断出患有口腔恶性黑色素瘤的上颌颊部牙龈,并向肝脏和前列腺远处转移,在这里报告。尽管向肝脏转移在恶性黑色素瘤中很常见,在这种情况下,转移到前列腺突出的稀有性。
    UNASSIGNED: Melanoma is the ninth most prevalent and the second most lethal tumour. The aetiology and pathogenesis remain uncertain. It occurs in elderly people, over the fifth decade, and is predominant in males. Clinically, they present as an asymptomatic macular or nodular growth. The prognosis is impacted by the size of the tumour and distant metastases. Patients with distant metastases have a 5-year survival rate of less than 30%, constituting metastasis as the major cause of melanoma-related fatality. Currently, the mainstay of treatment for metastatic melanoma is immunotherapy due to the inoperable state, radioresistant nature of the tumour and high chances of cytotoxicity in chemotherapy. A senile male patient, who was diagnosed with oral malignant melanoma of the maxillary buccopalatal gingiva with distant metastasis to the liver and the prostate, is reported here. Although metastasis to the liver is common among malignant melanomas, in this case metastasis to the prostate gland highlights the rarity.
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  • 文章类型: Journal Article
    转运扩增(TA)细胞是经历扩增阶段然后转变为消光阶段的祖细胞。尚未在体内实验观察到具有双相行为的长期假定的表皮TA祖细胞。这里,我们使用小鼠Aspm-CreER遗传细胞标记的克隆分析来鉴定这样的TA群体,揭示了对成人皮肤稳态和损伤修复的贡献。该TA群体比Dlx1-CreER标记的长期自我更新(例如干细胞)群体更频繁地分裂。新开发的长期谱系追踪数据的广义出生-死亡模型表明,TA祖细胞和干细胞均表现出中性竞争,但只有干细胞显示中性漂移。新生TA细胞及其直接后代的定量进化表明,TA祖细胞确实在过渡前放大了基底层,并且稳态TA种群大多处于灭绝阶段。该模型将广泛用于分析行为随克隆年龄变化的祖细胞。这项工作确定了一类长期缺失的非自我更新双相表皮TA祖细胞,并对理解组织更新机制具有广泛意义。
    Transit-amplifying (TA) cells are progenitors that undergo an amplification phase followed by transition into an extinction phase. A long postulated epidermal TA progenitor with biphasic behavior has not yet been experimentally observed in vivo. Here, we identify such a TA population using clonal analysis of Aspm-CreER genetic cell-marking in mice, which uncovers contribution to both homeostasis and injury repair of adult skin. This TA population is more frequently dividing than a Dlx1-CreER-marked long-term self-renewing (e.g. stem cell) population. Newly developed generalized birth-death modeling of long-term lineage tracing data shows that both TA progenitors and stem cells display neutral competition, but only the stem cells display neutral drift. The quantitative evolution of a nascent TA cell and its direct descendants shows that TA progenitors indeed amplify the basal layer before transition and that the homeostatic TA population is mostly in extinction phase. This model will be broadly useful for analyzing progenitors whose behavior changes with their clone age. This work identifies a long-missing class of non-self-renewing biphasic epidermal TA progenitors and has broad implications for understanding tissue renewal mechanisms.
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  • 文章类型: Journal Article
    目的:探讨抗黑色素瘤分化相关基因5(MDA5)阳性的临床肌病性皮肌炎(CADM)和间质性肺病(ILD)患者的预后因素。
    方法:回顾性分析2014年12月至2022年12月华东地区10个分支的125例抗MDA5+CADM-ILD患者的临床资料。预后因素分析采用χ2检验,Log-ranktest,COX和logistic回归分析。
    结果:在此队列中,125名抗MDA5+CADM-ILD患者表现出37.6%的快速进展性间质性肺病(RPILD)发病率,总死亡率为24.8%。一名患者失去了随访。诊断为RPILD后,在3个月内死亡的患者死亡率为53.2%,5.6%出现在存活3个月以上的人中。多因素分析显示,C反应蛋白(CRP)≥10mg/L(p=0.01)和含21(Ro52)(+)(p=0.003)的重组人三方基序与抗MDA5+CADM-ILD患者发生RPILD的风险较高相关;CRP≥10mg/L(p=0.018)和是否存在RPILD(p=0.003)是患者生存时间的影响因素。而关节炎是保护因素(p=0.016)。
    结论:抗MDA5+CADM-ILD患者的死亡率更高,诊断为RPILD后的最初3个月被认为是预后不良的风险窗。CRP≥10mg/L的患者,Ro52(+)和RPILD可能与较短的生存时间有关,而患有关节炎的患者可能会出现相对温和的情况。
    OBJECTIVE: To investigate the prognostic factors of patients with anti-melanoma differentiation-associated gene 5 (MDA5) positive clinically amyopathic dermatomyositis (CADM) and interstitial lung disease (ILD).
    METHODS: A retrospective analysis was conducted on clinical data of 125 patients with anti-MDA5 + CADM-ILD collected from 10 branches in eastern China between December 2014 and December 2022. Prognostic factors were analyzed using χ2 test, Log-rank test, COX and logistic regression analysis.
    RESULTS: In this cohort, 125 anti-MDA5 + CADM-ILD patients exhibited a rapidly progressive interstitial lung disease (RPILD) incidence of 37.6%, and an overall mortality rate of 24.8%. One patient was lost to follow-up. After diagnosis of RPILD, a mortality rate of 53.2% occurred in patients died within 3 months, and that of 5.6% appeared in those who survived for more than 3 months. Multiple factor analysis revealed that C-reactive protein (CRP) ≥ 10 mg/L (p = 0.01) and recombinant human tripartite motif containing 21 (Ro52) (+) (p = 0.003) were associated with a higher risk of RPILD in anti-MDA5 + CADM-ILD patients; CRP ≥ 10 mg/L (p = 0.018) and the presence of RPILD (p = 0.003) were identified as the factors influencing survival time in these patients, while arthritis was the protective factor (p = 0.016).
    CONCLUSIONS: Patients with anti-MDA5 + CADM-ILD will have a higher mortality rate, and the initial 3 months after diagnosis of RPILD is considered the risk window for the dismal prognosis. Patients with CRP ≥ 10 mg/L, Ro52 (+) and RPILD may be related to a shorter survival time, while patients complicated with arthritis may present with relatively mild conditions.
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  • 文章类型: Journal Article
    鲸目动物的外表面上有多个外生生物,这些附着在特定的微生境上。了解是什么驱动了附件站点的选择,这与完善epibiont作为宿主指标的使用有关。我们报告了约100只雌性中寄生co足类Pennellabalaenoptera的雌性,它们附着在突尼斯(地中海西部)的死去的Cuvier喙鲸Ziphiuscavirostris上;该国的首例报告。co足类仅附着于许多尖锐的,可能是人为的,在宿主皮肤上发现伤口。这一发现表明,新招募的雌性可能会积极寻找促进身体渗透的皮肤区域;一个可能有助于解释Pennellaspp微生境选择模式的因素。,也许还有其他pennellids,在他们的主机上。巴氏疟原虫寄生的估计年龄(由同时发生的表生藤壶球藻的年龄估计支持)也表明鲸目动物宿主可能在这些伤害中幸存下来,至少在最初,推测的死亡原因是由于被渔网缠住而导致的饥饿。
    Cetaceans harbor multiple epibionts on their external surface, and these attach to particular microhabitats. Understanding what drives the selection of attachment sites is relevant for refining the use of epibionts as indicators of their hosts. We report on about 100 females of the mesoparasitic copepod Pennella balaenoptera attached to a dead Cuvier\'s beaked whale Ziphius cavirostris stranded in Tunisia (western Mediterranean); the first report of P. balaenoptera in this country. The copepods were exclusively attached to numerous incisive, likely anthropogenic, wounds found on the host\'s skin. This finding suggests that newly recruited females may actively seek skin areas where physical penetration is facilitated; a factor that may help explain patterns of microhabitat selection by Pennella spp., and perhaps other pennellids, on their hosts. The estimated age of parasitization by P. balaenoptera (supported by age estimations of the co-occurring epibiotic barnacle Conchoderma virgatum) also suggests that the cetacean host likely survived these injuries, at least initially, and the presumed cause of death was starvation due to entanglement in a fishing net.
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  • 文章类型: Journal Article
    特应性皮炎(AD)在临床实践中仍然是一个严峻的挑战。2型炎症是儿童和青少年AD患者中最常见的炎症通路。抗炎药,主要是皮质类固醇(CS)和免疫调节剂是抑制2型炎症的主要治疗方法。然而,AD患者可能需要长期高CS剂量或具有可能显著副作用的药物组合以实现和维持疾病控制。在这方面,生物制剂的出现构成了管理这种情况的突破。Dupilumab是一种针对IL-4受体α亚基(IL-4Rα)的单克隆抗体,拮抗IL-4和IL-13,并被批准用于儿科重度AD。这篇综述介绍并讨论了最近发表的关于dupilumab在儿童和青少年AD中的研究。有令人信服的证据表明dupilumab在治疗AD方面是安全有效的。它可以减少皮肤损伤和相关的瘙痒,减少对额外药物的需求,改善疾病控制和生活质量。然而,彻底的诊断途径是强制性的,特别是考虑到不同的AD表型。理想的合格候选人是患有AD的儿童或青少年,由于严重的临床表现和生活质量受损而需要全身治疗。
    Atopic dermatitis (AD) is still a demanding challenge in clinical practice. Type 2 inflammation is the most common inflammatory pathway in children and adolescents with AD. Anti-inflammatory drugs, mainly corticosteroids (CS) and immunomodulant agents are the primary therapeutic approach to dampening type 2 inflammation. However, AD patients may require long-term high CS doses or drug combinations with possibly significant adverse effects to achieve and maintain disease control. In this regard, the advent of biologics constituted a breakthrough in managing this condition. Dupilumab is a monoclonal antibody directed against the IL-4 receptor α-subunit (IL-4Rα), antagonizing both IL-4 and IL-13 and is approved for pediatric severe AD. This review presents and discusses the most recent published studies on dupilumab in children and adolescents with AD. There is convincing evidence that dupilumab is safe and effective in managing AD. It can reduce skin lesions and associated itching, reduce the need for additional medications, and improve disease control and quality of life. However, a thorough diagnostic pathway is mandatory, especially considering the different AD phenotypes. The ideal eligible candidate is a child or adolescent with AD requiring systemic treatment because of severe clinical manifestations and impaired quality of life.
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  • 文章类型: Letter
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  • 文章类型: Journal Article
    黑素瘤检测的标准度量是活检所需的数量(NNB)。该指标已用于评估执业皮肤科医生,皮肤科高级实践专业人员,和初级保健提供者。这个指标,然而,很少应用于住院医师诊所。我们旨在确定科罗拉多大学住院医师诊所的NNB。此外,我们试图确定2019年冠状病毒病(COVID-19)大流行对NNB的影响。这项研究是对2016年至2022年在丹佛健康医学中心和落基山地区退伍军人事务皮肤科诊所进行的活检的回顾性分析。活检时的鉴别诊断搜索关键词,包括黑色素瘤,原位黑色素瘤,还有恶性扁豆.排除包括再切除的皮肤活检。随后通过将活检的疑似黑素瘤病变的数量除以组织学证实的黑素瘤的数量来产生NNB。数据进一步按COVID-19之前的数据(2016-2020年2月)分开,COVID-19关闭期(2020年3月至2020年7月),和后COVID-19(2020年3月至今)。人口统计数据,包括年龄,性别,种族,和Fitzpatrick类型,被收集。从2016年到2022年,在两个临床地点的鉴别诊断中均有2230例疑似黑色素瘤的活检。其中,362例经组织学证实为黑色素瘤。NNB总数为6.16。前COVID-19NNB为5.86,后COVID-19NNB为6.91。住院医师诊所的NNB与执业皮肤科医生的公开值相似。此外,在这些诊所里,COVID-19大流行的影响得到了一位亲戚的赞赏,虽然统计上微不足道,NNB的增加。
    A standard metric for melanoma detection is the number needed to biopsy (NNB). This metric has been used to evaluate practicing dermatologists, dermatology advanced practice professionals, and primary care providers. This metric, however, has rarely been applied to residency clinics. We aimed to determine the NNB at the University of Colorado residency clinics. Moreover, we sought to determine the impact of the coronavirus disease 2019 (COVID-19) pandemic on NNB. This study is a retrospective analysis of biopsies performed from 2016 to 2022 at the Denver Health Medical Center and the Rocky Mountain Regional Veteran Affairs dermatology clinics. Differential diagnosis at the time of biopsy was searched for keywords including melanoma, melanoma in situ, and lentigo maligna. Skin biopsies that included re-excisions were excluded. The NNB was subsequently generated by dividing the number of biopsied lesions with suspected melanoma by the number of histologically confirmed melanomas. The data was further separated by pre-COVID-19 (2016-February 2020), COVID-19 shutdown period (March 2020-July 2020), and post-COVID-19 (March 2020-present). Demographic data, including age, sex, race, and Fitzpatrick type, were collected. There were 2230 biopsies with suspected melanoma in the differential diagnosis at both clinic sites from 2016 to 2022. Of these, 362 were histologically confirmed melanoma. Total NNB was 6.16. The pre-COVID-19 NNB was 5.86, and the post-COVID-19 NNB was 6.91. Residency clinics have NNB similar to published values of practicing dermatologists. Furthermore, within these clinics, the impact of the COVID-19 pandemic was appreciated by a relative, although statistically insignificant, increase in NNB.
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