Melanoma in children: A systematic review and individual patient meta-analysis.

The current evidence on paediatric melanoma is heterogeneous, especially regarding the prognosis of different histological subtypes. We sought to systematically review the evidence on paediatric melanoma, highlighting the major sources of heterogeneity and focusing on available data on single patients. A systematic search was performed from 1948 to 25 January 2021. Only studies reporting at least one case of cutaneous melanoma in patients aged ≤18 years were included. Unknown primary and uncertain malignant melanomas were excluded. Three couples of authors independently performed title/abstract screening and two different authors reviewed all the relevant full texts. The selected articles were manually cross-checked for overlapping data for qualitative synthesis. Subsequently data on single patients were extracted to perform a patient-level meta-analysis. PROSPERO registration number: CRD42021233248. The main outcomes were melanoma-specific survival (MSS) and progression-free survival (PFS) outcomes. Separate analyses were done of cases with complete information on histologic subtype, focusing on superficial spreading (SSM), nodular (NM) and spitzoid melanomas, as well as of those classified as de-novo (DNM) and acquired or congenital nevus-associated melanomas (NAM). The qualitative synthesis covered 266 studies; however, data on single patients were available from 213 studies including 1002 patients. Among histologic subtypes, NM had a lower MSS than both SSM and spitzoid melanoma, and a lower PFS than SSM. Spitzoid melanoma had a significantly higher progression risk than SSM and trended toward lower mortality. Focusing on nevus-associated status, DNM demonstrated better MSS after progression than congenital NAM, and no differences were highlighted in PFS. Our findings describe the existence of different biological patterns in paediatric melanoma. Specifically, spitzoid melanomas demonstrated intermediate behaviour between SSM and NM and showed a high risk of nodal progression but low mortality. This raises the question of whether spitzoid lesions are being over-diagnosed as melanoma in childhood.

Dermatoscopy of nodular/plaque-type primary cutaneous T- and B-cell lymphomas: A retrospective comparative study with pseudolymphomas and tumoral/inflammatory mimickers by the International Dermoscopy Society.

BACKGROUND: Limited data on dermatoscopy of nodular/plaque-type T-/B-cell primary cutaneous lymphomas (PCLs) is available. OBJECTIVE: To describe dermatoscopic features of nodular/plaque-type PCLs, comparing them with those of clinical mimickers (pseudolymphomas, tumors, and inflammatory lesions) and investigating possible differences according to histologic subtypes. METHODS: Participants were invited to join this retrospective, multicenter case-control study by submitting histologically/immunohistochemically confirmed instances of nodular/plaque-type PCLs and controls. Standardized assessments of the dermatoscopic images and comparative analyses were performed. RESULTS: A total of 261 lesions were included (121 PCLs and 140 controls). Orange structureless areas were the strongest PCL dermatoscopic predictor on multivariate analysis compared with tumors and noninfiltrative inflammatory dermatoses. On the other hand, a positive association was found between PCLs and either unfocused linear vessels with branches or focal white structureless areas compared with infiltrative inflammatory dermatoses, whereas white lines were predictive of PCLs over pseudolymphomas. Differences in the vascular pattern were also seen between B- and T-cell PCLs and among B-cell PCL subtypes. LIMITATIONS: Retrospective design and the lack of a dermatoscopic-pathologic correlation analysis. CONCLUSION: Nodular/plaque-type PCLs display dermatoscopic clues, which may partially vary according to histologic subtype and whose diagnostic relevance depends on the considered clinical differential diagnoses.

Development of Two-Layer Hybrid Scaffolds Based on Oxidized Polyvinyl Alcohol and Bioactivated Chitosan Sponges for Tissue Engineering Purposes.

Oxidized polyvinyl alcohol (OxPVA) is a new polymer for the fabrication of nerve conduits (NCs). Looking for OxPVA device optimization and coupling it with a natural sheath may boost bioactivity. Thus, OxPVA/chitosan sponges (ChS) as hybrid scaffolds were investigated to predict in the vivo behaviour of two-layered NCs. To encourage interaction with cells, ChS were functionalized with the self-assembling-peptide (SAP) EAK, without/with the laminin-derived sequences -IKVAV/-YIGSR. Thus, ChS and the hybrid scaffolds were characterized for mechanical properties, ultrastructure (Scanning Electron Microscopy, SEM), bioactivity, and biocompatibility. Regarding mechanical analysis, the peptide-free ChS showed the highest values of compressive modulus and maximum stress. However, among +EAK groups, ChS+EAK showed a significantly higher maximum stress than that found for ChS+EAK-IKVAV and ChS+EAK-YIGSR. Considering ultrastructure, microporous interconnections were tighter in both the OxPVA/ChS and +EAK groups than in the others; all the scaffolds induced SH-SY5Y cells' adhesion/proliferation, with significant differences from day 7 and a higher total cell number for OxPVA/ChS+EAK scaffolds, in accordance with SEM. The scaffolds elicited only a slight inflammation after 14 days of subcutaneous implantation in Balb/c mice, proving biocompatibility. ChS porosity, EAK 3D features and neuro-friendly attitude (shared with IKVAV/YIGSR motifs) may confer to OxPVA certain bioactivity, laying the basis for future appealing NCs.

Impact of Magnetic Stimulation on Periodontal Ligament Stem Cells.

The aim of this study was to evaluate the effect of a time-dependent magnetic field on the biological performance of periodontal ligament stem cells (PDLSCs). A Western blot analysis and Alamar Blue assay were performed to investigate the proliferative capacity of magnetically stimulated PDLSCs (PDLSCs MAG) through the study of the MAPK cascade (p-ERK1/2). The observation of ALP levels allowed the evaluation of the effect of the magnetic field on osteogenic differentiation. Metabolomics data, such as oxygen consumption rate (OCR), extracellular acidification rate (ECAR) and ATP production provided an overview of the PDLSCs MAG metabolic state. Moreover, the mitochondrial state was investigated through confocal laser scanning microscopy. Results showed a good viability for PDLSCs MAG. Magnetic stimulation can activate the ERK phosphorylation more than the FGF factor alone by promoting a better cell proliferation. Osteogenic differentiation was more effectively induced by magnetic stimulation. The metabolic panel indicated significant changes in the mitochondrial cellular respiration of PDLSCs MAG. The results suggested that periodontal ligament stem cells (PDLSCs) can respond to biophysical stimuli such as a time-dependent magnetic field, which is able to induce changes in cell proliferation and differentiation. Moreover, the magnetic stimulation also produced an effect on the cell metabolic profile. Therefore, the current study demonstrated that a time-dependent magnetic stimulation may improve the regenerative properties of PDLSCs.

Pattern of response of unresectable and metastatic cutaneous squamous cell carcinoma to programmed death-1 inhibitors: A review of the literature.

Cutaneous squamous cell carcinoma (cSCC) is the second most frequent nonmelanoma skin cancer (NMSC). The majority of in situ cSCC [cSCC (Tis)] can be cured surgically, while local advanced and metastatic ones require other treatments, but there are no therapies approved by U.S. Food and Drug Administration (FDA). Available treatments for these stages included radiotherapy, chemotherapy as cisplatin, but responses to these treatments are usually of short duration. Programmed death-1 (PD-1) inhibitors (pembrolizumab, nivolumab, and cemiplimab) are an innovative immunologic treatment that now has been shown to be useful for the treatment of advanced cSCC. Nowadays, data about the response rate with the use of PD-1 inhibitors in cSCC are still few and, especially, the duration of the response after the start of treatment is short. Moreover, the number of cases is too small to express the beneficial effects of these treatments, although most data reported in the literature show quite good response rates. This review focused on some of the studies and associated results through an interesting research on search engines of all the cases about these systemic drugs, analyzing effects and side effects, and the research has been conducted considering published cases since March 2016 to October 2019.

NMR Structure of the FIV gp36 C-Terminal Heptad Repeat and Membrane-Proximal External Region.

Feline immunodeficiency virus (FIV), a lentivirus causing an immunodeficiency syndrome in cats, represents a relevant model of pre-screening therapies for human immunodeficiency virus (HIV). The envelope glycoproteins gp36 in FIV and gp41 in HIV mediate the fusion of the virus with the host cell membrane. They have a common structural framework in the C-terminal region that includes a Trp-rich membrane-proximal external region (MPER) and a C-terminal heptad repeat (CHR). MPER is essential for the correct positioning of gp36 on the lipid membrane, whereas CHR is essential for the stabilization of the low-energy six-helical bundle (6HB) that is necessary for the fusion of the virus envelope with the cell membrane. Conformational data for gp36 are missing, and several aspects of the MPER structure of different lentiviruses are still debated. In the present work, we report the structural investigation of a gp36 construct that includes the MPER and part of the CHR domain (737-786gp36 CHR-MPER). Using 2D and 3D homo and heteronuclear NMR spectra on 15N and 13C double-labelled samples, we solved the NMR structure in micelles composed of dodecyl phosphocholine (DPC) and sodium dodecyl sulfate (SDS) 90/10 M: M. The structure of 737-786gp36 CHR-MPER is characterized by a helix-turn-helix motif, with a regular α-helix and a moderately flexible 310 helix, characterizing the CHR and the MPER domains, respectively. The two helices are linked by a flexible loop regulating their orientation at a ~43° angle. We investigated the positioning of 737-786gp36 CHR-MPER on the lipid membrane using spin label-enhanced NMR and ESR spectroscopies. On a different scale, using confocal microscopy imaging, we studied the effect of 737-786gp36 CHR-MPER on 1,2-dioleoyl-sn-glycero-3-phosphocholine/1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DOPC/DOPG) multilamellar vesicles (MLVs). This effect results in membrane budding and tubulation that is reminiscent of a membrane-plasticizing role that is typical of MPER domains during the event in which the virus envelope merges with the host cell membrane.

Erosive Pustular Dermatosis of the Scalp: Why Do We Miss It?

Erosive pustular dermatosis of the scalp (EPDS) is an uncommon disease and primarily affects older men who have photo-damaged bald scalp, as was confirmed by our case series. EPDS is probably an overlooked disease, whose diagnosis is often missed because of a higher incidence of other cutaneous diseases affecting the same area and usually secondary to chronic actinic damage, such as actinic keratosis, basal cell carcinoma, and squamous cell carcinoma. For the first time, we report a case series of misdiagnosed EPDS with the aim of understanding why a diagnosis of EPDS was initially missed and try to give some tips to avoid future diagnostic delay.

Plasma radiofrequency ablation for treatment of benign skin lesions: Clinical and reflectance confocal microscopy outcomes.

BACKGROUND: In the latest few years, plasma radiofrequency ablation has turned out a good option for treatment of several benign skin lesions. The technique can be easily performed to treat skin lesions with limited tissue invasion and no residual scars or hypo/hyperpigmentation areas. OBJECTIVE: The aim of this study was to assess the effects of plasma radiofrequency ablation in treatment of benign skin lesions, through clinical and reflectance confocal microscopy outcomes. METHODS: Six patients who presented benign skin lesions underwent long-wave plasma radiofrequency ablation treatment with DAS medical device (Technolux, Italia). Reflectance confocal microscopy analysis was performed at baseline and after 1 month. RESULTS: The treatment was well tolerated; only a slight erythema and a thin crust on the treated area were referred for 3-7 days after treatment. After one month from treatments, we observed the complete disappearance of the lesions and no significant signs of inflammation, redness, hypo/hyperpigmentation, or scars on the site of the treated areas; these clinical data were also confirmed by reflectance confocal microscopy analysis. CONCLUSIONS: Long-wave plasma radiofrequency ablation actually can be considered a well-tolerated, painless, safe, effective, and low-cost procedure for skin treatments.

Dermoscopy of Cutaneous Lymphoproliferative Disorders: Where Are We Now?

The prompt identification of cutaneous lymphoproliferative disorders (CLD) has always been a challenge in dermatological practice, due to the rarity of this group of diseases, the heterogeneity in clinical presentation, and plenty of variants described in the literature so far. The strict cooperation between dermatologist and pathologist is the key element for the correct diagnosis of CLD deriving from the perfect integration of clinical and histopathological features. In this complex context, dermoscopy could play an adjuvant role in the achievement of the diagnosis, as it fits itself as the third diagnostic tool in the paraphernalia of the dermatologist between the clinical and histopathological examination. This review provides the state of art of dermoscopy of CLD.

Dermoscopy of Malignant Skin Tumours: What's New?

Dermoscopy represents a new and effective tool that assists dermatologists in improving the accuracy of clinical diagnosis in onco-dermatology. The aim of this article is to provide an overview of the latest and important dermoscopic progress and observations in this ever-evolving field of dermatology.

Dermoscopy of Subungual Exostosis: A Retrospective Study of 10 Patients.

INTRODUCTION: Subungual exostosis (SE), the most common nail tumor of young adults, is a benign bony proliferation of the distal phalanx occurring beneath the nail. Misdiagnosis or late diagnosis frequently occurs and no dermoscopy features of this tumor were previously outlined. MATERIAL AND METHODS: To describe the dermoscopic appearance of SE, 10 patients with radiologically and histologically confirmed SE were retrospectively retrieved from our tertiary referral centers. Data regarding age, gender, time to diagnosis, clinical presentation, dermoscopic features, involved nail and history of trauma were recorded for each patient. RESULTS: In our patients, clinical findings were similar to previous reports. Among the dermoscopic features, vascular ectasia was the most common finding (70%), followed by hyperkeratosis (60%), onycholysis (40%), and ulceration (30%). CONCLUSION: Dermoscopy could be a useful technique aimed at creating diagnostic suspicion of this benign nail condition, although X-ray examination and histopathology are mandatory for the diagnosis.

3D fibre deposition and stereolithography techniques for the design of multifunctional nanocomposite magnetic scaffolds.

Magnetic nanocomposite scaffolds based on poly(ε-caprolactone) and poly(ethylene glycol) were fabricated by 3D fibre deposition modelling (FDM) and stereolithography techniques. In addition, hybrid coaxial and bilayer magnetic scaffolds were produced by combining such techniques. The aim of the current research was to analyse some structural and functional features of 3D magnetic scaffolds obtained by the 3D fibre deposition technique and by stereolithography as well as features of multimaterial scaffolds in the form of coaxial and bilayer structures obtained by the proper integration of such methods. The compressive mechanical behaviour of these scaffolds was investigated in a wet environment at 37 °C, and the morphological features were analysed through scanning electron microscopy (SEM) and X-ray micro-computed tomography. The capability of a magnetic scaffold to absorb magnetic nanoparticles (MNPs) in water solution was also assessed. confocal laser scanning microscopy was used to assess the in vitro biological behaviour of human mesenchymal stem cells (hMSCs) seeded on 3D structures. Results showed that a wide range of mechanical properties, covering those spanning hard and soft tissues, can be obtained by 3D FDM and stereolithography techniques. 3D virtual reconstruction and SEM showed the precision with which the scaffolds were fabricated, and a good-quality interface between poly(ε-caprolactone) and poly(ethylene glycol) based scaffolds was observed for bilayer and coaxial scaffolds. Magnetised scaffolds are capable of absorbing water solution of MNPs, and a preliminary information on cell adhesion and spreading of hMSCs was obtained without the application of an external magnetic field.

The Use of Traditional Chinese Medicine in Some Dermatologic Diseases: Part II--Autoimmune Bullous Disorders and Lichen Planus.

Over the centuries, traditional Chinese medicine (TCM) and Western medicine have traveled along parallel lines with no opportunity for collaboration. In recent decades, while an interest in TCM has been growing among Western clinicians, progress has been made in the comprehension of pathogenic mechanisms of skin disorders, and the communication between Western and Eastern medicines has become more and more intensive. In this paper, the authors discuss TCM remedies used in the treatment of autoimmune bullous disorders (pemphigus and bullous pemphigoid) and lichen planus. Future studies on the active components of the TCM will certainly shed new light on the still obscure aspects of some dermatologic diseases.

The use of traditional Chinese medicine in some dermatologic diseases: Part I--Acne, psoriasis, and atopic dermatitis.

Traditional Chinese medicine (TCM) is increasingly being used in the Western world particularly in specialty areas such as gynecology, pediatrics, nutrition, and dermatology. TCM is an alternative method of therapy that proposes to treat symptoms that Western medicine is unable to manage by treating the underlying causes of disease. The authors provide a general overview of TCM remedies used in the treatment of various dermatologic disorders (acne, psoriasis, atopic dermatitis) for dermatologists interested in this unconventional therapeutic approach.