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Additionally, in most cases patients' basal autoantibody levels are not available, making it difficult to give a clear statement regarding the coherence of autoimmune phenomena and antibodies with a SARS-CoV-2 infection. The novel Coronavirus SARS-CoV-2 is suspected of acting as a trigger for autoimmune diseases and the production of autoantibodies. These aggregates activate transcription factor NF- B, which in turn stimulates the production of Type I IFN, interleukin-6 (IL-6) and further pro-inflammatory cytokines.15 Activation of plasmacytoid dendritic cells (pDC) follows Type I IFN-mediated activation of B cells which can lead to autoantibody production, e.g, anti-MDA5 antibodies. gl 1 TableOverview of reported autoantibodies in articles included in meta-analysis. [Extracted from the article]

Dear Editor, Netherton syndrome (NS) is a rare autosomal recessive ichthyosis syndrome, which manifests at birth or shortly thereafter, and is characterized by erythroderma, ichthyosis linearis circumflexa, trichorrhexis invaginata, immunodeficiency, failure to thrive and high serum IgE level.[1] Approximately 80 different mutations in exonic and intronic regions of the I SPINK5 i gene have been reported, resulting in deficiency of lymphoepithelial Kazal-type-related inhibitor (LEKTI) protein, a serine protease inhibitor in epithelia, thymus, tonsils, parathyroid glands and trachea. Treatment of NS has always been challenging,[2] but evidence is accumulating that (i) an interleukin (IL)17-dominant inflammatory response is found in orphan ichthyoses[3] and (ii) the inflammation may be targeted efficiently by anti-tumour necrosis factor (TNF) and anti-IL12/23 antibodies.[4] A 15-year-old girl with erythroderma was admitted to our ward. Recently, it has been shown to be effective in pityriasis rubra pilaris and other inflammatory skin diseases.[5] Paller I et al i . found an IL-17 dominant immune profile and increased levels of TNF in patients with NS and other ichthyoses. [Extracted from the article]

Local anaesthetics are an integral part of modern surgery since diluted solutions of cocaine were described nearly 150 years before. Tumescent local anaesthesia (TLA) utilizes a mixture of highly diluted local anaesthetics in a carrier solution and is used for skin biopsies, excision of skin tumours and vein surgery.[1] Also, wide excisions for hidradenitis suppurativa, serial excisions of giant congenital nevi (Fig.), Rhinophyma surgery or lymph node dissections are feasible using TLA.[[2]]. [Extracted from the article]

The author comments on the article "Therapeutic drug monitoring of patients with psoriasis during tumour necrosis factor (TNF)-α antagonist treatment using a novel interleukin-8 reporter cell line," by Y. Kimura and colleagues. Topics discussed include the link of tumour necrosis factor (TNF) with psoriasis, the importance of biopharmaceuticals for dermatology, and the impact of antidrug antibodies (ADAs) development for biologic therapy.

The use of artificial intelligence (AI) continues to establish itself in the most diverse areas of medicine at an increasingly fast pace. Nevertheless, many healthcare professionals lack the basic technical understanding of how this technology works, which severely limits its application in clinical settings and research. Thus, we would like to discuss the functioning and classification of AI using melanoma as an example in this review to build an understanding of the technology behind AI. For this purpose, elaborate illustrations are used that quickly reveal the technology involved. Previous reviews tend to focus on the potential applications of AI, thereby missing the opportunity to develop a deeper understanding of the subject matter that is so important for clinical application. Malignant melanoma has become a significant burden for healthcare systems. If discovered early, a better prognosis can be expected, which is why skin cancer screening has become increasingly popular and is supported by health insurance. The number of experts remains finite, reducing their availability and leading to longer waiting times. Therefore, innovative ideas need to be implemented to provide the necessary care. Thus, machine learning offers the ability to recognize melanomas from images at a level comparable to experienced dermatologists under optimized conditions., (© 2024 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Background: Polyethylene glycol (PEG) may elicit anaphylaxis to COVID-19 mRNA vaccines, and guidance for patients at risk is needed., Methods: In retrospective patients with PEG allergy collected from 2006 till 2019, clinical, skin, and basophil activation test (BAT) characteristics discriminative for PEG allergy were analyzed and compared with the literature. In 421 prospective real-life patients asking for allergy workup for COVID-19 vaccine hypersensitivity in 2020/2021, risk assessment was performed and tolerance of the recommended vaccination approach was assessed., Results: Ten patients with PEG allergy were found in the retrospective cohort. Patients reacted with immediate anaphylaxis (100%) not only to PEG-based laxatives/bowel preparations or injections, but also to cold medication, antiseptics, analgetics, or antibiotics. Skin tests ± BAT with PEG ± elicitors were positive in 10/10. Provocation tests were positive in 7/9 patients. From the prospective cohort, 370/421 patients self-reporting increased risk for vaccine allergy lacked criteria necessitating allergy workup and were recommended for routine vaccination. A total of 51/421 patients were tested, and three (6%) with PEG allergy were identified, whereas 48 patients remained negative in skin tests. Vaccination was recommended in all those patients. No hypersensitivity reactions were reported to vaccination including six PEG-allergic patients tolerating COVID-19 vaccination., Conclusions: Taking a detailed history excluded PEG allergy in most referred patients and enabled direct safe vaccination. Immediate urticaria/anaphylaxis to typical elicitors identified patients requiring PEG allergy workup. Skin tests ± BAT identified PEG allergy and helped to select the vaccine and the vaccination approach. Even PEG-allergic patients can tolerate COVID-19 vaccines., (© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Hintergrund: Die Dermatomyositis gehört zur Gruppe der seltenen, idiopathischen, inflammatorischen Myositiden. Für die paraneoplastische Form der Dermatomyositis wurde in der Vergangenheit ein Zusammenhang mit Malignomen erkannt. Faktoren, die für eine Malignom-Assoziation sprechen, werden bis heute untersucht., Patienten Und Methodik: Es wurden retrospektiv über einen Zeitraum von 15 Jahren die Daten von 63 Patienten mit Dermatomyositis analysiert., Ergebnisse: Folgende Faktoren gaben einen Hinweis für eine Dermatomyositis mit Malignom-Assoziation: ein höheres Patientenalter (> 52 Jahre [P = 0,001], > 65 Jahre [P = 0,002], ≥ 75 Jahre [P = 0,002]), eine kürzere Zeit zwischen Erstmanifestation und Erstdiagnose (Malignom-Gruppe: 59 Tage vs. Nicht-Malignom-Gruppe: 137 Tage [P = 0,022]), eine Hautbeteiligung in Form von Gottron-Zeichen (P = 0,045), zentrofazialen Erythemen (P = 0,036) oder typischen Erythemen an den Ober-/Unterarmen (P = 0,019), eine oropharyngeale Beteiligung (P = 0,015) und eine GPT-Erhöhung (P = 0,031). Folgende Faktoren sprachen eher gegen eine Malignom-Assoziation: ein jüngeres Patientenalter (≤ 52 Jahre [P = 0,001], 40-65 Jahre [P = 0,045]) und Juckreiz (P = 0,026)., Schlussfolgerungen: In der Literatur finden sich heterogene Ergebnisse zu den genannten Faktoren hinsichtlich ihrer Eignung als Marker für eine Malignom-Assoziation. Erschwert ist die Faktorenfindung aufgrund kleiner Studienpopulationen, wenigen prospektiven und kontrollierten Studien, die Einordnung von Populationen als Myositis-Patienten ohne Differenzierung und eine inkonsistente Verwendung der Nomenklatur. Mit unserer Studie wollen wir einen wichtigen Beitrag zur Identifizierung von Risikofaktoren bei Dermatomyositis mit Malignom-Assoziation leisten., (© 2021 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Background: Dermatomyositis belongs to the rare idiopathic, inflammatory myositis group. A previously postulated link between some cases of dermatomyositis and malignancy has been established in recent years. Criteria suggestive of a malignancy association are still being explored., Patients and Methods: We retrospectively analyzed data from 63 patients with dermatomyositis over a period of 15 years., Results: The following criteria argue for cancer-associated dermatomyositis: older age (> 52 years [P = 0.001], > 65 years [P = 0.002], ≥ 75 years [P = 0.002]), shorter time between manifestation and diagnosis of dermatomyositis (malignancy group: 59 days vs. non-malignancy group: 137 days [P = 0.022]), typical skin involvement such as Gottron sign (P = 0.045), centrofacial erythema (P = 0.036) and typical erythema on the upper arms and forearms (P = 0.019), oropharyngeal involvement (P = 0.015) and increased ALT (P = 0.031). The following criteria argue for non-cancer-associated dermatomyositis: younger age (≤ 52 years [P = 0.001], 40-65 years [P = 0.045]) and pruritus (P = 0.026)., Conclusions: The aforementioned criteria have been documented in the literature, but reported findings are heterogenous concerning the suitability of their markers for malignancy association. Small study populations, few prospective controlled studies, summarization of different forms of myositis and inconsistent use nomenclature contribute to biased results. Our study aims to make an important contribution toward the identification of risk factors in cancer-associated dermatomyositis., (© 2021 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Purpose: The T-box transcription factor brachyury has been demonstrated as a prognostic factor in a variety of cancer types and considered a novel oncotarget in solid tumors. Brachyury acts as a regulator of the epithelial-mesenchymal transition (EMT) process, leading to more aggressive behavior and poorer prognosis. However, recent literature evidence suggests a tumor suppressor role in other neoplasms. In the present study, we aimed to study brachyury expression and its prognostic impact in Ewing sarcoma, an aggressive neoplasm of young individuals., Methods: We analyzed the expression of brachyury by immunohistochemistry in a series of 96 Ewing sarcomas in a tissue microarray and investigated the association of the protein expression with the clinical parameters and overall survival., Results: More than half of the cases (51%, n ​= ​49) depicted positive nuclear brachyury expression, while a lack of expression was observed in 49% (n ​= ​47) of cases. Nuclear brachyury staining was significantly associated with non-white ethnicity (p ​= ​0.04) and axial localization (p ​= ​0.025). Importantly, lack of brachyury expression was significantly associated with lower overall survival in multivariate analyses (hazard ratio - HR: 2.227, p ​= ​0.008)., Conclusions: Our findings indicate, that brachyury is an independent prognostic biomarker in Ewing sarcoma, which might suggest a tumor suppressor role and which yet to be fully elucidated., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Cancer risk is highly variable in carriers of the common TP53- R337H founder allele, possibly due to the influence of modifier genes. Whole-genome sequencing identified a variant in the tumor suppressor XAF1 (E134*/Glu134Ter/rs146752602) in a subset of R337H carriers. Haplotype-defining variants were verified in 203 patients with cancer, 582 relatives, and 42,438 newborns. The compound mutant haplotype was enriched in patients with cancer, conferring risk for sarcoma ( P = 0.003) and subsequent malignancies ( P = 0.006). Functional analyses demonstrated that wild-type XAF1 enhances transactivation of wild-type and hypomorphic TP53 variants, whereas XAF1 -E134* is markedly attenuated in this activity. We propose that cosegregation of XAF1- E134* and TP53- R337H mutations leads to a more aggressive cancer phenotype than TP53- R337H alone, with implications for genetic counseling and clinical management of hypomorphic TP53 mutant carriers., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Background: Venom immunotherapy (VIT) is an established and effective treatment for patients with Hymenoptera venom allergies. Especially during the build-up of VIT, systemic allergic reactions are a key issue., Objective: To investigate the safety and effectiveness of a 3-day rush insect VIT protocol and a strategy for the management of individuals with VIT-induced anaphylaxis., Methods: In this retrospective monocentric study, 11-year data regarding build-up cycles of VIT were retrieved from institutional records. The following parameters of VIT-induced anaphylaxis were analyzed: frequency, severity, time of occurrence within the build-up cycle, and impact on the success of VIT. The effectiveness of VIT was assessed by the results of sting challenges (SCs) by the culprit insect., Results: In total, 1,317 initial build-up cycles of VIT were evaluated in this study, and the frequency of VIT-induced anaphylaxis was 6.6%. Anaphylaxis occurred most frequently when the daily cumulative venom dose was ≥100 µg. A group (n = 65) of patients with VIT-induced anaphylaxis in this dose range temporarily received a reduced maintenance dose, and without additional co-medications or complications, the target dose was reached after a second build-up in 91% of the cycles. After completing the VIT build-up, SCs were performed in 76.9% of the cohort, and the effectiveness of VIT was confirmed by 98.5% of the tests., Conclusions: In this study, we report a 3-day VIT rush protocol with a reasonable rate of VIT-induced anaphylaxis and excellent effectiveness of VIT., (© 2019 S. Karger AG, Basel.)

Aim: The Ewing sarcoma family of tumors (ESFT) is a group of malignant small round cell neoplasms of bones and soft tissues closely histogenetically related. Methylthioadenosine phosphorylase (MTAP) deficiency has been recently associated with increased tumor aggressiveness and poor outcomes in different types of neoplasms. However, the expression of this biomarker and its biological role in ESFT remain largely unknown., Methods: Immunohistochemical expression of MTAP was accessed in 112 patients with ESFT in a tissue microarray platform and associated with clinicopathological parameters and overall survival (OS)., Results: Loss of MTAP expression was significantly associated with lower OS in both univariate and multivariate analyses., Conclusion: Loss of MTAP expression is an independent negative prognostic biomarker in ESFT.

Background: There are very few data about the mutational profile of families at-risk for hereditary breast and ovarian cancer (HBOC) from Latin America (LA) and especially from Brazil, the largest and most populated country in LA., Results: Of the 349 probands analyzed, 21.5% were BRCA1/BRCA2 mutated, 65.3% at BRCA1 and 34.7% at BRCA2 gene. The mutation c.5266dupC (former 5382insC) was the most frequent alteration, representing 36.7% of the BRCA1 mutations and 24.0% of all mutations identified. Together with the BRCA1 c.3331_3334delCAAG mutation, these mutations constitutes about 35% of the identified mutations and more than 50% of the BRCA1 pathogenic mutations. Interestingly, six new mutations were identified. Additionally, 39 out of the 44 pathogenic mutations identified were not previously reported in the Brazilian population. Besides, 36 different variants of unknown significance (VUS) were identified. Regarding ancestry, average ancestry proportions were 70.6% European, 14.5% African, 8.0% Native American and 6.8% East Asian., Materials and Methods: This study characterized 349 Brazilian families at-risk for HBOC regarding their germline BRCA1/BRCA2 status and genetic ancestry., Conclusions: This is the largest report of BRCA1/BRCA2 assessment in an at-risk HBOC Brazilian population. We identified 21.5% of patients harboring BRCA1/BRCA2 mutations and characterized the genetic ancestry of a sample group at-risk for hereditary breast cancer showing once again how admixed is the Brazilian population. No association was found between genetic ancestry and mutational status. The knowledge of the mutational profile in a population can contribute to the definition of more cost-effective strategies for the identification of HBOC families.

Over the past 15 years, the spectrum of systemic antipsoriatic treatments has dramatically expanded. Until the end of the last millennium, systemic therapy had been restricted to four oral agents: methotrexate, cyclosporine, acitretin, and fumaric acid esters. Today, there are additionally seven biologics and one new oral antipsoriatic drug, as well as the first available biosimilars. Six more biologics with novel target structures and at least four biosimilars are currently being developed (phase III). This progress has been based on new insights into the pathogenesis of psoriasis, in which tumor necrosis factor and especially Th17 immune responses with their associated cytokines interleukin 23 and 17 play a key role. The development of new-generation biologics as well as immunomodulatory small molecules can be attributed to these pathophysiological findings. Phosphodiesterase 4 inhibitors, dimethyl fumarate, and Janus kinase inhibitors all interact with Th17 immune responses. Some of these drugs are in advanced clinical development and are also beneficial in psoriatic arthritis. Today, psoriasis and psoriatic arthritis therefore rank among the most readily treatable inflammatory autoimmune disorders. Dermatology is increasingly becoming a specialty of modern targeted immunotherapies., (© 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

The identification of families at-risk for hereditary cancer is extremely important due to the prevention potential in those families. However, the number of Brazilian genetic services providing oncogenetic care is extremely low for the continental dimension of the country and its population. Therefore, at-risk patients do not receive appropriate assistance. This report describes the creation, structure and management of a cancer genetics service in a reference center for cancer prevention and treatment, the Barretos Cancer Hospital (BCH). The Oncogenetics Department (OD) of BCH offers, free of charge, to all patients/relatives with clinical criteria, the possibility to perform i) genetic counseling, ii) preventive examinations and iii) genetic testing with the best quality standards. The OD has a multidisciplinary team and is integrated with all specialties. The genetic counseling process consists (mostly) of two visits. In 2014, 614 individuals (371 families) were seen by the OD. To date, over 800 families were referred by the OD for genetic testing. The support provided by the Oncogenetics team is crucial to identify at-risk individuals and to develop preventive and personalized behaviors for each situation, not only to the upper-middle class population, but also to the people whose only possibility is the public health system.

Germline mutations in TP53 are the underlying defects in Li-Fraumeni syndrome (LFS) and its variant, Li-Fraumeni-like (LFL) Syndrome, autosomal dominant disorders that are characterized by predisposition to multiple early onset cancers. Here, we identified rs78378222 (A > C), a rare variant that is located in the 3' untranslated region (3' UTR) of TP53, in 7 probands (5.4%) of a cohort from LFS/LFL patients without TP53 germline mutations in the coding regions. To support its association with the LFS/LFL phenotype, we assessed p53 expression in tumor specimens and fibroblasts from rs78378222[C] carriers. Additionally, we investigated using in silico tools the evolutionary conservation and whether rs78378222[C] affects microRNA (miRNA) binding sites in the 3' UTR of TP53 mRNA. We found lower p53 protein levels in biological samples from rs78378222[C] carriers. Additionally, we showed that rs78378222[C] could interfere with a putative target site of miR-545-3p, a novel miRNA that is predicted to directly target the 3' UTR TP53. To our knowledge, this is the first description of rs78378222[C] in LFS/LFL patients. Moreover, these findings suggest that rs78378222[C] lead to haploinsufficiency of p53, a new mechanism of carcinogenesis in LFS/LFL., (Copyright © 2015 Elsevier Inc. All rights reserved.)