Keratolytics can replace curettage in daylight photodynamic therapy for actinic keratosis on the face/scalp: A randomized clinical trial.

BACKGROUND: Methyl aminolevulinate (MAL) photodynamic therapy (PDT) is commonly used for field treatment of actinic keratoses (AKs). In standard natural daylight PDT (n-DL-PDT) the first step, after the application of chemical solar filter, is removal of crusts and scales by curettage, followed by the application of MAL cream. Some patients experience intense pain during curettage and stinging after application of the photosensitizer to just curettaged skin. OBJECTIVES: To evaluate whether n-DL-PDT without curettage, but preceded by application of keratolytics, would maintain a similar efficacy, based on clinical, dermoscopic, reflectance confocal microscopy (RCM) assessments, safety and patient satisfaction as standard n-DL-PDT with curettage. METHODS: Forty patients with multiple AKs on the face and/or scalp were enrolled in this study. Patients were randomized into two groups of treatment as follows: (i) MAL n-DL-PDT without previous curettage, preceded by skin preparation at home with keratolytics (30% urea cream, twice a day for 7 days; -Cur group) and (ii) MAL n-DL-PDT preceded by skin preparation at the hospital with curettage (+Cur group). RESULTS: Thirty-nine participants completed the study. Four hundred and twenty-one AKs in -Cur group and 337 AKs in +Cur group were treated. The mean reduction in the number of AK lesions 3 months after the treatment was 10.7 (-54.7%) in the -Cur and 10.4 (-58.7%) in the +Cur group. We found that the differences in terms of efficacy and patient satisfaction comparing the two treatment regimens were not statistically significant. The pain score reported during and after daylight exposure was similar and low in both groups. Moreover, no unexpected adverse events occurred during the trial period. CONCLUSIONS: According to our results, curettage is not necessary to obtain the full treatment effect of n-DL-PDT. We experienced in a real-life setting that n-DL-PDT protocol could be changed by replacing curettage with keratolytics.

Infliximab therapy decreases the expression of serum and faecal miR-126 and miR-20a in paediatric Crohn's disease: A pilot study.

AIM: We aimed to evaluate the serum and faecal expression of miR-126 and miR-20a in children with Crohn's disease (CD) during infliximab (IFX) therapy. METHODS: In this prospective observational study, serum and faeces from CD patients were collected before IFX therapy (T0), after induction (T1) and after 6 months from IFX (T2). IFX levels were determined by Enzyme-linked immunosorbent assay at T1 and T2. miRNAs were profiled through Real-Time RT-PCR. The activity of disease was evaluated through the Paediatric Crohn's disease activity index (PCDAI), serum C-reactive protein (CRP) and faecal calprotectin. RESULTS: Nine CD children were enrolled. Serum and faecal miR-126 and miR-20a levels were higher at T0 and showed a time-dependent decrease, being significantly down-regulated after IFX treatment at T2. Specifically, IFX levels recorded at T1 and T2 negatively correlated with the serum and faecal expression of miR-126 and miR-20a. Serum and faecal changes of miR-126 and miR20-a were positively associated with the decrease of the inflammatory marker CRP and PDCAI at all time points. CONCLUSION: In children with CD, IFX therapy decreases the expression of serum and faecal miR-126 and miR-20a, suggesting an involvement of these two miRNAs in the action of the drug.

Primary Cutaneous B-Cell Lymphomas with Large Cell Morphology: A Practical Review.

Most primary cutaneous lymphomas consist of T-cell lymphomas or small cell lymphomas; however, the skin may also be affected by lymphomas with large cell morphology, as a primary or secondary localization. A minority of cases consist of primary cutaneous B-cell lymphomas (PCBCLs). PCBCLs are a heterogeneous group of rare neoplasms with an overlapping morphological and immunohistochemical picture of the different subtypes. Nevertheless, differential diagnosis in the setting of this group of neoplasms is mandatory to identify the correct therapy and prognosis, but it may be challenging since, due to the rarity of these neoplasms, they may not always be familiar to pathologists. Indeed, immunohistochemistry may not be enough to distinguish the different histotypes, which overlap in immunohistochemical features. Furthermore, the ever-increasing knowledge of the molecular features of systemic B-cell lymphomas, such as gene rearrangements with clinical significance, has led in recent years to further investigation into the molecular landscape of PCBCLs with large cell morphology. This work aimed to provide a practical diagnostic guide for pathologists dealing with primary cutaneous large B-cell lymphomas.

Cellular and Molecular Mechanism of Pulmonary Fibrosis Post-COVID-19: Focus on Galectin-1, -3, -8, -9.

Pulmonary fibrosis is a consequence of the pathological accumulation of extracellular matrix (ECM), which finally leads to lung scarring. Although the pulmonary fibrogenesis is almost known, the last two years of the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its post effects added new particularities which need to be explored. Many questions remain about how pulmonary fibrotic changes occur within the lungs of COVID-19 patients, and whether the changes will persist long term or are capable of resolving. This review brings together existing knowledge on both COVID-19 and pulmonary fibrosis, starting with the main key players in promoting pulmonary fibrosis, such as alveolar and endothelial cells, fibroblasts, lipofibroblasts, and macrophages. Further, we provide an overview of the main molecular mechanisms driving the fibrotic process in connection with Galactin-1, -3, -8, and -9, together with the currently approved and newly proposed clinical therapeutic solutions given for the treatment of fibrosis, based on their inhibition. The work underlines the particular pathways and processes that may be implicated in pulmonary fibrosis pathogenesis post-SARS-CoV-2 viral infection. The recent data suggest that galectin-1, -3, -8, and -9 could become valuable biomarkers for the diagnosis and prognosis of lung fibrosis post-COVID-19 and promising molecular targets for the development of new and original therapeutic tools to treat the disease.

A Proteomic Approach Reveals That miR-423-5p Modulates Glucidic and Amino Acid Metabolism in Prostate Cancer Cells.

Recently, we have demonstrated that miR-423-5p modulates the growth and metastases of prostate cancer (PCa) cells both in vitro and in vivo. Here, we have studied the effects of miR-423-5p on the proteomic profile in order to identify its intracellular targets and the affected pathways. Applying a quantitative proteomic approach, we analyzed the effects on the protein expression profile of miR-423-5p-transduced PCa cells. Moreover, a computational analysis of predicted targets of miR-423-5p was carried out by using several target prediction tools. Proteomic analysis showed that 63 proteins were differentially expressed in miR-423-5-p-transfected LNCaP cells if compared to controls. Pathway enrichment analysis revealed that stable overexpression of miR-423-5p in LNCaP PCa cells induced inhibition of glycolysis and the metabolism of several amino acids and a parallel downregulation of proteins involved in transcription and hypoxia, the immune response through Th17-derived cytokines, inflammation via amphorin signaling, and ion transport. Moreover, upregulated proteins were related to the S phase of cell cycle, chromatin modifications, apoptosis, blood coagulation, and calcium transport. We identified seven proteins commonly represented in miR-423-5p targets and differentially expressed proteins (DEPs) and analyzed their expression and influence on the survival of PCa patients from publicly accessible datasets. Overall, our findings suggest that miR-423-5p induces alterations in glucose and amino acid metabolism in PCa cells paralleled by modulation of several tumor-associated processes.

Melanoma diagnosed on digital dermoscopy monitoring: A side-by-side image comparison is needed to improve early detection.

BACKGROUND: Digital dermoscopy monitoring (DDM) helps to recognize melanomas lacking specific dermoscopic features at baseline, but the number of melanomas eventually developing specific features is still unknown. OBJECTIVE: To assess how many melanomas are identified because they develop melanoma-specific criteria over time compared with melanomas recognized by side-by-side image comparison. METHODS: A case-control study was conducted collecting 206 melanomas: 103 melanomas diagnosed during DDM follow-up and 103 melanomas diagnosed at baseline. The control group was composed of 309 benign lesions consisting of 103 nevi excised for diagnostic reasons, 103 not excised nevi, and 103 not excised seborrheic keratoses. Dermoscopic images of all 515 lesions were randomly presented to 2 blinded experts to give a diagnosis and to score the criteria of the 7-point checklist. RESULTS: Of the 103 melanomas diagnosed at baseline, 78.6% (n = 81) were correctly identified compared with only 40.8% (n = 42) of melanomas diagnosed after DDM (P < .001). Of the 103 melanomas excised after DDM, 59.2% (n = 61), did not develop melanoma-specific criteria and were identified only because of the side-by-side image comparison. LIMITATIONS: The type of morphologic changes considered as suspicious on DDM was not assessed. CONCLUSIONS: Most melanomas are diagnosed with DDM by side-by-side image comparison.

Cutaneous Melanoma Arising in Congenital Melanocytic Nevus: A Retrospective Observational Study.

BACKGROUND: Congenital melanocytic nevi (CMN) are benign proliferations of melanocytes usually present at birth. The magnitude of the melanoma risk for CMN is controversial, generating an ongoing debate on the best approach to manage these lesions. OBJECTIVE: To perform a retrospective, observational study with the aim to evaluate the prevalence of CMN-associated melanomas in tertiary referral centers, as well as the eventual correlation between clinical, dermoscopic, and histological features of CMN-associated melanomas. METHODS: A single-center retrospective observational study was performed on all clinical and dermoscopic images of histologically confirmed melanomas arising on CMN over a 14-year period (January 2005 to March 2019). RESULTS: Our database included 2,159 melanomas in the considered period. Of those, 27 (1.3%) were CMN-associated melanomas. The mean age of patients with CMN-associated melanoma was 33 years (range, 11-70 years). The mean diameter of CMN-associated melanoma was 18 mm (range, 6 mm to 20 cm), and 56% were located on the back. Twenty-one (77.8%) of CMN-associated melanomas arose on small CMN (<1.5 cm), 5 (18.5%) on medium-sized CMN (1.5-19.9 cm), and 1 (3.7%) on a large/giant type (≥20 cm). The majority of CMN-associated melanomas (63%) exhibited a globular dermoscopic pattern in their benign part, while a blue-white veil and irregular blotches were the most frequent dermoscopic features in the malignant part. About three quarters of melanomas occupied 10-50% of the nevus surface. Breslow thickness was higher in melanomas involving less than 10% of nevus surface (mean thickness, 1 mm) than in those affecting 10-50 and >50% of the nevus surface (0.8 and 0.7 mm, respectively). CONCLUSIONS: In our series, small CMN was the most frequent type of CMN-associated melanoma. Although the risk of melanoma is increasing by the increasing size of CMN, our finding is definitely related to the much higher prevalence of small CMN in the general population as compared to the prevalence of intermediate-sized and large CMN. LIMITATIONS: Small sample size, single-center experience, retrospective design.

Sex and Age-Related Differences in Neuroinflammation and Apoptosis in Balb/c Mice Retina Involve Resolvin D1.

(1) Background: The pro-resolving lipid mediator Resolvin D1 (RvD1) has already shown protective effects in animal models of diabetic retinopathy. This study aimed to investigate the retinal levels of RvD1 in aged (24 months) and younger (3 months) Balb/c mice, along with the activation of macro- and microglia, apoptosis, and neuroinflammation. (2) Methods: Retinas from male and female mice were used for immunohistochemistry, immunofluorescence, transmission electron microscopy, Western blotting, and enzyme-linked immunosorbent assays. (3) Results: Endogenous retinal levels of RvD1 were reduced in aged mice. While RvD1 levels were similar in younger males and females, they were markedly decreased in aged males but less reduced in aged females. Both aged males and females showed a significant increase in retinal microglia activation compared to younger mice, with a more marked reactivity in aged males than in aged females. The same trend was shown by astrocyte activation, neuroinflammation, apoptosis, and nitrosative stress, in line with the microglia and Müller cell hypertrophy evidenced in aged retinas by electron microscopy. (4) Conclusions: Aged mice had sex-related differences in neuroinflammation and apoptosis and low retinal levels of endogenous RvD1.

Circulating MiRNA-195-5p and -451a in Diabetic Patients with Transient and Acute Ischemic Stroke in the Emergency Department.

(1) Background: Circulating micro-RNAs (miRNAs) modulate the expression of molecules in diabetes. We evaluated the expression of serum miRNA-195-5p and -451a in diabetic patients with ischemic stroke and correlated them with two markers of brain tissue integrity. (2) Methods: Seventy-eight subjects with acute ischemic stroke (AIS) or transient ischemic attack (TIA) (40 with diabetes) were enrolled. Serum miRNA levels, brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor A (VEGF-A) were assessed at admission and 24 and 72 h after a post-ischemic stroke, and were compared to 20 controls. (3) Results: Both circulating miRNAs were two-fold up-regulated in diabetic AIS and TIA patients compared to non-diabetics. Their levels progressively decreased at 24 and 72 h in both AIS and TIA patients. Interestingly, in the non-diabetic TIA group, both circulating miRNAs, although higher than the controls, tended to achieve a complete decay after 72 h. Furthermore, miRNA-195-5p and miRNA-451a levels inversely correlated with both BDNF and VEGF-A serum levels. (4) Conclusions: These data show a different profile of both micro-RNAs in diabetic versus non-diabetic patients after acute ischemic stroke, suggesting their pivotal role in cerebrovascular ischemic attack.

Dermoscopic similarity is an independent predictor of BRAF mutational concordance in multiple melanomas.

BACKGROUND: The association of clinical and dermoscopic features with BRAF mutational status has been poorly analysed in multiple primary melanomas (MPM). OBJECTIVE: To investigate whether concordance of BRAF mutational status is associated with dermoscopic similarity in multiple melanomas of the same patient. METHODS: Dermoscopic images and corresponding tissue sections of 124 melanomas from 62 patients with MPM were selected at four Italian Dermatology Departments. Similarity of dermoscopic appearance between multiple melanomas was evaluated according to the presence of the same prevalent dermoscopic feature. The BRAFV600 mutational status was analysed with allele-specific TaqManTM assays or pyrosequencing. Spearman's correlation and univariate and multivariate regression analysis were used for statistical analysis. RESULTS: A similar dermoscopic appearance was identified in 38.7% (24/62) of patients with MPM and was correlated with older age at first diagnosis (rho: 0.26; P: 0.042) and occurrence on sun-damaged skin (rho: 0.27; P: 0.037). The BRAFV600 mutation was detected in 39.5% (49/124) of the tumors and a concordant BRAF mutational status between melanomas in 33/62 (53.2%) MPM patients. Dermoscopically similar melanomas showed 5.7-fold higher odds to be concordant for BRAF mutational status compared to dissimilar lesions (OR: 5.7; 95% CI 1.7-19.5; P: 0.005). CONCLUSION: Dermoscopic similarity of multiple melanomas represents an independent clinical predictor of a concordant BRAF mutational status in MPM patients.

Efficacy and safety of secukinumab in a psoriatic patient affected by comorbid metabolic disorders.

Psoriasis is a common, chronic, immune-mediated disease occurring more frequently in association with comorbid metabolic disorders. The management of patients with multiple organ dysfunction is challenging since the use of all conventional systemic agents is limited or contraindicated. In the last two decades, the introduction of biological drugs has revolutionized treatment paradigms of psoriasis and enabled numerous patients to achieve disease control with an acceptable safety profile. We reported for the first time the case of a 66-year-old female psoriatic patient affected by myocardial infarction, hypertension, chronic renal failure, hyperthyroidsm and morbid obesity, who experienced remarkable improvement in skin and joint synthoms and metabolic parameters after 48 weeks of secukinumab monotherapy. In our patient, secukinumab was well tolerated and no side effects have been observed. Our observation suggests that secukinumab could be a safe therapeutic option in patients with organ impairment or failure in which the majority of conventional systemic agents are contraindicated.

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.

Triple-Negative Breast Cancers: Systematic Review of the Literature on Molecular and Clinical Features with a Focus on Treatment with Innovative Drugs.

PURPOSE OF REVIEW: Triple-negative breast cancer (TNBC) accounts for 15-20% of diagnosed breast tumours, with higher incidence in young and African-American women, and it is frequently associated with BRCA germline mutations. Chemotherapy is the only well-established therapeutic option in both early- and advanced-stages of the disease. TNBC tumours relapse earlier after standard anthracycline- and/or taxane-based chemotherapy treatments, generally within 1-3 years after the diagnosis, and often develop visceral metastases, representing the subtype with a worse prognosis among all breast cancers. In the present review, we will provide an updated overview of the available results of recent clinical trials for this disease and we will describe the implications of the known molecular pathways representing novel targets for development of future therapies for TNBC patients. RECENT FINDINGS: Over the past decade, the advent of gene expression micro-array technology has led to the identification of different actionable targets including various genomic alterations, androgen receptor, PARP, PI3K, VEGF and other proteins of the angiogenic pathway. Thus, novel targeted drugs have been tested in clinical trials reporting promising results in specific TNBC molecular subgroups. Although cytotoxic chemotherapy remains the mainstay of treatment for TNBC patients, the identification of novel 'drugable' targets and pathways for developing personalized treatments represents a promising investigational approach in the management of the TNBC subtype.

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.

Seven Non-melanoma Features to Rule Out Facial Melanoma.

Facial melanoma is difficult to diagnose and dermatoscopic features are often subtle. Dermatoscopic non-melanoma patterns may have a comparable diagnostic value. In this pilot study, facial lesions were collected retrospectively, resulting in a case set of 339 melanomas and 308 non-melanomas. Lesions were evaluated for the prevalence (> 50% of lesional surface) of 7 dermatoscopic non-melanoma features: scales, white follicles, erythema/reticular vessels, reticular and/or curved lines/fingerprints, structureless brown colour, sharp demarcation, and classic criteria of seborrhoeic keratosis. Melanomas had a lower number of non-melanoma patterns (p< 0.001). Scoring a lesion suspicious when no prevalent non-melanoma pattern is found resulted in a sensitivity of 88.5% and a specificity of 66.9% for the diagnosis of melanoma. Specificity was higher for solar lentigo (78.8%) and seborrhoeic keratosis (74.3%) and lower for actinic keratosis (61.4%) and lichenoid keratosis (25.6%). Evaluation of prevalent non-melanoma patterns can provide slightly lower sensitivity and higher specificity in detecting facial melanoma compared with already known malignant features.

Translational Research and Plasma Proteomic in Cancer.

Proteomics is a recent field of research in molecular biology that can help in the fight against cancer through the search for biomarkers that can detect this disease in the early stages of its development. Proteomic is a speedily growing technology, also thanks to the development of even more sensitive and fast mass spectrometry analysis. Although this technique is the most widespread for the discovery of new cancer biomarkers, it still suffers of a poor sensitivity and insufficient reproducibility, essentially due to the tumor heterogeneity. Common technical shortcomings include limitations in the sensitivity of detecting low abundant biomarkers and possible systematic biases in the observed data. Current research attempts are trying to develop high-resolution proteomic instrumentation for high-throughput monitoring of protein changes that occur in cancer. In this review, we describe the basic features of the proteomic tools which have proven to be useful in cancer research, showing their advantages and disadvantages. The application of these proteomic tools could provide early biomarkers detection in various cancer types and could improve the understanding the mechanisms of tumor growth and dissemination.