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1.
Dermatol Ther ; 35(6): e15489, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35385202

RESUMEN

Several new biologic agents targeting IL23/Th17 axis, such as risankizumab, have been developed for the treatment of psoriasis. The aim of the present study was to analyze the efficacy and safety of risankizumab in patients with moderate-to-severe psoriasis over a 52-week period. A multicentric retrospective study was conducted in patients who initiated risankizumab between July 2019 and December 2020. Psoriasis Area and Severity Index-PASI was measured at baseline and after 4, 16, 28 and 52 weeks. Clinical responses were evaluated by PASI75, PASI90 and PASI100 at the same timepoints. Potential safety issues and adverse events (AEs) were collected. Univariable and multivariable logistic regressions were performed for variables predicting clinical response. One hundred and twelve patients with psoriasis were included. PASI90 response was achieved by 17.86% of patients at week 4, 72.22% at week 16, 91.0% at week 28 and 95.24% at week 52 (as observed analysis). No associations between the considered variables and the efficacy endpoints were retrieved, influence of variables such as Body Mass Index (BMI), baseline PASI or previous biologics were not shown. No serious safety issues or discontinuations related to adverse events were reported. Risankizumab showed high efficacy and a favorable safety profile, regardless of patient- and disease-related factors.


Asunto(s)
Psoriasis , Anticuerpos Monoclonales , Humanos , Psoriasis/diagnóstico , Psoriasis/tratamiento farmacológico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
2.
Aesthetic Plast Surg ; 44(5): 1955, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32514639

RESUMEN

The authors of this article wish to make the following clarification: The FACE-Q is a trademarked patient reported outcome instrument. The "Satisfaction with Nose" scale described and reproduced in this article is similarly trademarked; the copyright is retained by the Q-Portfolio. If readers would like to use the FACE-Q in research or clinical practice, they are directed to www.qportfolio.org to obtain a license permission from the copyright holders. Reproduction of the FACE-Q in publications without prior permission is not permitted.

3.
Aesthetic Plast Surg ; 44(5): 1742-1750, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32410198

RESUMEN

INTRODUCTION: This randomized controlled study aimed to analyse the long-term results of thin-skinned patients who underwent rhinoplasty. MATERIALS AND METHODS: All the included study patients had the following characteristics: underwent primary rhinoplasty for functional and/or cosmetic problems, were thin-skinned, had been followed for almost 2 years, underwent both standard pre- and post-operative photography, had a good understanding of the Italian language, and had signed a consent form for inclusion in the study. The patients were randomly divided into 4 groups as follows: group 1, camouflage of the dorsum by diced cartilage; group 2, camouflage of the dorsum with lipofilling; group 3, camouflage of the dorsum by a temporal fascia graft; and group 4 (control group), without camouflage of the dorsum. Patients answered the Italian version of the FACE-Q rhinoplasty module. The Obagi skin pinch test was used to measure nasal skin thickness. We compared pre- and post-operative patient satisfaction with the appearance of their nose between the 4 patient groups by the Chi-squared test for unpaired data. Two plastic surgeons reviewed all the post-operative photographs of the study patients and rated the photographs on a scale of 1 to 5. RESULTS: A total of 101 patients who underwent primary rhinoplasty between January 2016 and March 2018 in our department of plastic surgery and satisfied the inclusion criteria were enrolled in this study. The mean patient age was 38.5 years. The mean follow-up time was 2.5 years. The differences between the preoperative and post-operative FACE-Q values for group 1 were significant (P < 0.01), whereas the differences between the preoperative and post-operative FACE-Q values for the other groups were not significant. The results for group 1 patients remained stable over the long-term follow-up compared with the results for other groups (P < 0.01). Groups 2 and 4 underwent more secondary procedures than groups 1 and 3 (P < 0.01). The 2 reviewers determined that patient groups 1 and 3 obtained more satisfactory outcomes than groups 1 and 4 (P < 0.01). CONCLUSIONS: This was the first randomized study to demonstrate that diced cartilage grafts used for thin-skinned patients was the best approach for obtaining a satisfactory long-term outcome and durable natural appearance. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Asunto(s)
Rinoplastia , Estética , Humanos , Italia , Satisfacción del Paciente , Resultado del Tratamiento
4.
J Neurophysiol ; 121(1): 38-49, 2019 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-30379630

RESUMEN

Recent studies have shown that sympathetic nervous system (SNS) activity can be heavily impacted not only by basic threats to survival but also by threats to social bonds. In this study we explored the behavioral and physiological consequences of social exclusion/inclusion in patients with psoriasis, a disease frequently associated with the experience of being ostracized and with deficient emotion regulation skills. We employed a virtual ball-tossing game (Cyberball) to induce the experience of social exclusion/inclusion. We then used a Trust Game to measure the effects of this social modulation on trust. During Cyberball, infrared thermal imaging was used to record participants' facial temperature and thus obtain an online measure of SNS activation. Behavioral data showed that social exclusion shifted participants' trust toward unfamiliar players who had not previously excluded them. Physiological data indicated that in control participants, social exclusion triggered higher SNS activation than inclusion. No such effect was found in patients with psoriasis, whose SNS activity was the same during inclusion as it was during exclusion, suggesting that they benefit less from inclusive experiences than control participants. In addition, in patients but not in controls, higher SNS activation during social exclusion was linked to higher monetary investment toward unfamiliar players, a result in keeping with the social reconnection hypothesis, according to which emotions triggered by social rejection can be regulated by investing in new social interactions. We also found that an increase in periorbital temperature is accompanied by a decrease in happiness ratings after social exclusion was experienced during the Cyberball game. NEW & NOTEWORTHY Previous research on emotional processes in psoriasis has mainly employed self-report measures. In this study we used thermal imaging to obtain an online measure of the sympathetic nervous system (SNS) activity during social exclusion and tested how this experience influenced subsequent trust. We found that being included was a less positive experience for patients compared with controls and that SNS activity during exclusion had a stronger influence on subsequent trust in patients than in controls.


Asunto(s)
Emociones , Psoriasis/fisiopatología , Psoriasis/psicología , Aislamiento Social/psicología , Sistema Nervioso Simpático/fisiopatología , Confianza/psicología , Adulto , Anciano , Temperatura Corporal , Emociones/fisiología , Cara , Femenino , Humanos , Masculino , Persona de Mediana Edad , Termografía , Realidad Virtual , Adulto Joven
5.
Exp Brain Res ; 237(1): 211-222, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30374785

RESUMEN

Psoriasis is a chronic dermatologic disease which is frequently associated with psychological distress. Although studies suggest a relationship between this condition and difficulties in emotion regulation, behavioral and physiological evidence about this link is scarce. We measured implicit emotion regulation abilities of psoriasis patients and a healthy control group by examining the impact of distracting emotional (positive, negative or neutral) images on a working memory task ("Emotional N-Back") which could present high (2-back) or low (1-back) cognitive workload. Moreover, we used Functional Infrared Thermal Imaging to record participants' facial temperature and obtain a measure of the activation of the autonomic system. Rising of temperature over the peri-orbital areas and the nose tip are believed to reflect the activation and the de-activation of the sympathetic system, respectively. Patients scored higher than controls on the "Lack of emotional clarity" sub-scale of the Difficulties in Emotion Regulation Scale. Compared to controls, who performed much better in the low vs. high cognitive load condition, patients showed a smaller accuracy difference between the two conditions. Moreover, patients showed less sympathetic (lower peri-orbital and higher nasal tip temperature) activity (especially in the negative and neutral blocks) during the high vs. low cognitive load condition, suggesting that the former condition might be less emotionally demanding for them. Patients benefit more than controls from the load-dependent interference effect when dealing with emotional information; thus, therapeutic techniques aiming at teaching how to use cognitive strategies to downregulate emotions might be particularly appropriated for them.


Asunto(s)
Cognición/fisiología , Emociones/fisiología , Psoriasis/fisiopatología , Termografía/métodos , Adulto , Anciano , Femenino , Humanos , Modelos Lineales , Masculino , Memoria a Corto Plazo/fisiología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Estimulación Luminosa , Encuestas y Cuestionarios , Adulto Joven
6.
Aesthetic Plast Surg ; 43(4): 1014-1020, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30937477

RESUMEN

INTRODUCTION: The goal of this study report is to define the "gender angle," a new angle which represents the masculine or feminine nasal shape, for performing a gender-oriented rhinoplasty. The use of the "gender angle" in Caucasian patients will help the plastic surgeon in the search for a suitable nose for the patient's face and above all for the search for maximum patient satisfaction. MATERIALS AND METHODS: The study population was obtained from Caucasian patients who had undergone rhinoplasty between January 1986 and September 2016 at our department. Patients answered the Italian version of the FACE-Q outcome instrument on post-rhinoplasty satisfaction with their nose. Anthropometric measurements were taken retrospectively by AutoCAD for MAC on a photograph of the profile view taken postoperatively at the last follow-up. RESULTS: A total of 1774 (706 male and 1068 female) patients satisfied the inclusion criteria and were finally enrolled in this study. We identified a gender-specific angle ranging from 168° to 182° for the male nose and from 160° to 178° for the female nose. We subdivided all study patients into 3 ranges of angles as follows: male nose, range 1 = 168°-172°, range 2 = 173°-177°, range 3 = 178°-182°; female nose, range 1 = 160°-166°, range 2 = 167°-171°, range 3 = 172°-178°. All study patients completed the FACE-Q rhinoplasty postoperative module. Analysis was performed of the FACE-Q results and the angle obtained for each nose. The most satisfactory angle range for male patients was range 3 (P = 0.01) and for the female patients was range 2 (P = 0.01). CONCLUSIONS: The "gender angle" might be a parameter that effectively provides the optimal cosmetic result for male and female patients who undergo rhinoplasty. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors - www.springer.com/00266 .


Asunto(s)
Estética , Tabique Nasal/cirugía , Nariz/cirugía , Rinoplastia/métodos , Encuestas y Cuestionarios , Población Blanca/genética , Adulto , Antropometría , Estudios de Cohortes , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Nariz/anatomía & histología , Satisfacción del Paciente/estadística & datos numéricos , Cuidados Preoperatorios/métodos , Estudios Retrospectivos , Caracteres Sexuales , Resultado del Tratamiento , Adulto Joven
7.
Mol Carcinog ; 56(2): 681-693, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27377812

RESUMEN

In previous works, we have shown that insulin-like growth factor-binding protein-3 (IGFBP-3), a tissue and circulating protein able to bind to IGFs, decreases drastically in the blood serum of patients with diffuse metastatic melanoma. In agreement with the clinical data, recombinant IGFBP-3 was found to inhibit the motility and invasiveness of cultured metastatic melanoma cells and to prevent growth of grafted melanomas in mice. The present work was aimed at identifying the signal transduction pathways underlying the anti-tumoral effects of IGFBP-3. We show that the anti-tumoral effect of IGFBP-3 is due to inhibition of the Wnt pathway and depends upon the presence of CD44, a receptor protein known to modulate Wnt signaling. Once it has entered the cell, IGFBP-3 binds the Wnt signalosome interacting specifically with its component GSK-3ß. As a consequence, the ß-catenin destruction complex dissociates from the LRP6 Wnt receptor and GSK-3ß is activated through dephosphorylation, becoming free to target cytoplasmic ß-catenin which is degraded by the proteasomal pathway. Altogether, the results suggest that IGFBP-3 is a novel and effective inhibitor of Wnt signaling. As IGFBP-3 is a physiological protein which has no detectable toxic effects either on cultured cells or live mice, it might qualify as an interesting new therapeutic agent in melanoma, and potentially many other cancers with a hyperactive Wnt signaling. © 2016 The Authors. Molecular Carcinogenesis Published by Wiley Periodicals, Inc.


Asunto(s)
Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Melanoma/metabolismo , Neoplasias Cutáneas/metabolismo , Vía de Señalización Wnt , Animales , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Humanos , Receptores de Hialuranos/metabolismo , Melanoma/patología , Metástasis de la Neoplasia/patología , Complejo de la Endopetidasa Proteasomal/metabolismo , Mapas de Interacción de Proteínas , Proteolisis , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Wistar , Piel/patología , Neoplasias Cutáneas/patología , Células Tumorales Cultivadas , Proteínas Wnt/metabolismo , beta Catenina/metabolismo
8.
Aesthetic Plast Surg ; 41(3): 661-666, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28127660

RESUMEN

BACKGROUND: A multitude of options are traditionally used for the treatment of acne scars; however, newer treatment modalities are emerging to decrease the propensity for post-inflammatory hyperpigmentation and upregulate new collagen production. The aim of this study was to evaluate the efficacy of nanofat and platelet-rich plasma (PRP) infiltration alone and combined with fractional CO2 laser resurfacing to improve atrophic scars of the face. METHODS: From March 2014 to June 2015, 30 patients with atrophic acne scars on the cheeks were selected for this study. Patients were evaluated pre- and postoperatively by physical examination, photographs and ultrasound with a 22-MHz probe to measure subcutaneous tissue thickness. All patients were treated with infiltration of nanofat plus PRP. The production of PRP was achieved using the RegenLab THT tube® method. In 15 randomly chosen patients, a fractional CO2 laser resurfacing at 15 W was also performed right after the infiltration. An Italian version of the FACE-Q postoperative module was administered to analyze each patient's satisfaction and aesthetic perception of the result. RESULTS: The average preoperative thickness of subcutaneous tissue of patients from group A was 0.532 cm, while the average preoperative thickness of subcutaneous tissue of patients from group B was 0.737 cm. The average postoperative thickness of subcutaneous tissue was 1.201 cm in group A and 1.367 cm in group B. The improvement of thickness of subcutaneous tissue was 0.668 cm in group A and 0.63 cm in group B. We applied a t test on unpaired data, comparing the difference in thickness obtained with the treatment in both group A and in group B, with a p value =0.7289 (not significant). All patients in both groups had a treatment benefit, confirmed with FACE-Q postoperative module, but without a significant difference between the two groups. CONCLUSIONS: Subcutaneous infiltration with nanofat and PRP seems to be effective to improve atrophic scars, either alone or combined with fractional CO2 laser resurfacing. The FACE-Q module confirmed the impact of treatment of facial acne scars in social life and relationships. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Asunto(s)
Acné Vulgar/complicaciones , Cicatriz/terapia , Terapia por Luz de Baja Intensidad/métodos , Plasma Rico en Plaquetas , Acné Vulgar/diagnóstico , Tejido Adiposo/trasplante , Adulto , Cicatriz/etiología , Estudios de Cohortes , Terapia Combinada , Estética , Femenino , Estudios de Seguimiento , Humanos , Italia , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Proyectos Piloto , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Trasplante Autólogo , Resultado del Tratamiento , Adulto Joven
9.
Drugs Context ; 122023.
Artículo en Inglés | MEDLINE | ID: mdl-37077769

RESUMEN

Background: Data on the treatment of palmoplantar psoriasis (PP) are scarce, representing a therapeutic challenge. This study aims to assess the efficacy and safety of risankizumab in a population of patients with psoriasis with a palmoplantar involvement, over a 52-week treatment period. Methods: We performed a retrospective analysis in a cohort of patients with PP, with or without involvement of other skin sites. Palmoplantar Psoriasis Area and Severity Index (ppPASI) was assessed at baseline and after 4, 16, 28 and 52 weeks, to evaluate the PP severity. Results: Sixteen patients were enrolled. The rates of ppPASI90 responses constantly increased during the period of observation and were 18.7%, 62.2%, 75.0% and 81.2% at weeks 4, 16, 28 and 52, respectively. Only two patients suspended treatment because of ineffectiveness at week 16. Conclusion: Our data from a series of 16 patients reveal that risankizumab could represent an effective and safe therapeutic choice in patients with PP.

10.
Cancers (Basel) ; 15(4)2023 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-36831472

RESUMEN

Sequential digital dermoscopy (SDD) enables the diagnosis of a subgroup of slow-growing melanomas that lack suspicious features at baseline examination but exhibit detectable change on follow-up. The combined use of total-body photography and SDD is recommended in high-risk subjects by current guidelines. To establish the usefulness of SDD for low-risk individuals, we conducted a retrospective study using electronic medical records of low-risk patients with a histopathological diagnosis of cutaneous melanoma between 1 January 2016 and 31 December 2019, who had been referred and monitored for long-term follow-up of clinically suspicious melanocytic nevi. We sought to compare the distribution of "early" cutaneous melanoma, defined as melanoma in situ and pT1a melanoma, between SDD and periodical handheld dermoscopy in low-risk patients. A total of 621 melanomas were diagnosed in a four-year timespan; 471 melanomas were diagnosed by handheld dermoscopy and 150 by digital dermoscopy. Breslow tumor thickness was significantly higher for melanomas diagnosed by handheld compared to digital dermoscopy (0.56 ± 1.53 vs. 0.26 ± 0.84, p = 0.030, with a significantly different distribution of pT stages between the two dermoscopic techniques. However, no significant difference was found with respect to the distribution of pT stages, mean Breslow tumor thickness, ulceration, and prevalence of associated melanocytic nevus in tumors diagnosed on periodical handheld dermoscopy compared to SDD. Our results confirm that periodical dermoscopic examination enables the diagnosis of cutaneous melanoma at an earlier stage compared to first-time examination as this was associated in our patients with better prognostic features. However, in our long-term monitoring of low-risk subjects, Breslow tumor thickness and pT stage distribution did not differ between handheld periodical dermoscopy and SDD.

11.
Ital J Dermatol Venerol ; 158(6): 437-444, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38015482

RESUMEN

BACKGROUND: Cutaneous adverse events (CAEs) related to oncological therapies are a common scenario in daily clinical practice. METHODS: This is a retrospective observational study collecting the data regarding CAEs of patients treated with immune checkpoints inhibitors (ICIs) in four different Italian centers. RESULTS: Of 323 patients included, 305 were evaluable for this analysis; 182 patients (59.7%) had metastatic cutaneous melanoma (CM), 99 (32.5%) non-small cell lung cancer (NSCLC) and 24 (7.8%) renal cell carcinoma (RCC). The most frequent CAEs that we found, considering all the 305 patients, were pruriginous maculopapular rash (10.2% of the patients), vitiligo-like areas (7.2% of the patients), psoriasiform rash (6.2% of the patients), asymptomatic maculopapular rash (4.6% of the patients), and lichenoid rash (4.3% of the patients). Vitiligo-like areas occurred more frequently in patients with CM, while a lichenoid rash was more frequently observed in patients with RCC. Treatment interruption was related to drug-induced CAEs in 15.4% of melanoma patients and 0.0% of lung and kidney patients. Patients developing a cutaneous adverse event had better overall response rate and higher progression free survival and overall survival than the patients without CAEs. CONCLUSIONS: Our study brings new information on the characteristics of CAEs related to ICIs treatment in three different types of cancers, CM, NSCLC and RCC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Renales , Exantema , Hipopigmentación , Neoplasias Renales , Neoplasias Pulmonares , Melanoma , Neoplasias Cutáneas , Vitíligo , Humanos , Melanoma/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Exantema/inducido químicamente
12.
J Dermatolog Treat ; 34(1): 2230685, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37400981

RESUMEN

OBJECTIVES: The purpose of this study was to analyze the drug survival rate of dupilumab up to 2 years in a large real-world cohort of adult patients affected by moderate/severe atopic dermatitis (AD), and to investigate the clinical, demographic and predictive factors influencing the patients' treatment persistence. MATERIAL AND METHODS: This study included adult patients affected by moderate-to-severe AD treated with dupilumab for at least 16 weeks who visited 7 dermatologic outpatient clinics in Lazio, Italy, from January 2019 until August 2021. RESULTS: A total of 659 adult patients (345 male [52.3%], mean age: 42.8 years) with an average treatment duration of 23.3 months were enrolled in the study. Overall, 88.6% and 76.1% of patients were still on treatment after 12 and 24 months, respectively. The drug survival rate for discontinuation due to AEs and dupilumab ineffectiveness was 95.0% at 12 months and 90.0% at 24 months. The main reasons for drug discontinuation included inefficacy (29.6%), failed compliance (17.4%), persistent efficacy (20.4%) and adverse events (7.8%). Adult AD onset (≥18 years) and EASI score severity measured at the last follow-up visit were the only factors significantly associated with lower drug survival. CONCLUSION: This study revealed an increased cumulative probability of dupilumab survival at 2 years, reflected by a sustained effectiveness and a favorable safety profile of the drug.


Asunto(s)
Dermatitis Atópica , Humanos , Adulto , Masculino , Dermatitis Atópica/tratamiento farmacológico , Resultado del Tratamiento , Índice de Severidad de la Enfermedad , Anticuerpos Monoclonales Humanizados/efectos adversos , Método Doble Ciego
13.
J Am Acad Dermatol ; 64(5): 865-72, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21429618

RESUMEN

BACKGROUND: Insulin-like growth factor (IGF) binding protein (IGFBP)-3 is the main carrier of circulating IGFs and the main modulator of their activity. IGFBP-3 controls cellular availability of IGFs, which cannot exert their pro-proliferative activity while bound to IGFBP-3. Proteolysis of IGFBP-3 is one mechanism to control IGF release. A reduction of serum IGFBP-3 levels and the associated increased availability of IGFs may represent a strategy whereby melanoma increases its metastatic potential. OBJECTIVE: The aim of our study was to evaluate the correlation between the IGFBP-3 serum level and melanoma stage. METHODS: The study included 41 patients, 24 male and 17 female, with median age of 60 years (range 24-80), affected by cutaneous melanoma. Blood samples were taken from each patient and IGFBP-3 serum levels were measured using Western blot analysis with commercial antibodies. Values were normalized using commercial IGFBP-3. RESULTS: The statistical analysis showed that full-size, glycosylated IGFBP-3 concentrations were significantly lower in the sera of patients with stage IV melanoma. Low serum levels of IGFBP-3 correlated with both disease progression and presence of disease at the time of sample collection. In patients who underwent follow-up visits with further collections of blood samples, the concentrations of glycosylated IGFBP-3 decreased only in those who showed progression of disease. LIMITATIONS: Our study shows only preliminary results on a limited number of patients. CONCLUSION: We demonstrate that there is a significant inverse correlation between the serum concentration of full-size, glycosylated IGFBP-3 and disease progression in patients with melanoma.


Asunto(s)
Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Melanoma/sangre , Neoplasias Cutáneas/sangre , Adulto , Anciano , Anciano de 80 o más Años , Western Blotting , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Melanoma/patología , Persona de Mediana Edad , Curva ROC , Neoplasias Cutáneas/patología , Adulto Joven
14.
Ital J Dermatol Venerol ; 156(5): 593-598, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-31804055

RESUMEN

BACKGROUND: Second primary melanomas (SPMs) are new developed primary melanomas occurring in a subset of patients affected by BRAF-mutated metastatic melanoma during treatment with BRAF-inhibitors. A drug-induced paradoxical activation of mitogen-activated protein kinase (MAPK) signaling pathway in BRAF-wild type/RAS-mutated cells have been proposed as a possible molecular mechanism but data on the mutational status of SPMs are lacking. In order to better understand genetic alterations affecting the biological mechanism of SPMs, we performed a personalized and targeted next-generation sequencing analysis of a patient affected by metastatic melanoma who developed multiple SPMs during treatment with encorafenib (LGX818). METHODS: Using a cancer panel of 50 genes for solid tumors enriched with a custom panel of 10 genes specifically involved in melanoma pathogenesis, we analyzed the primary melanoma, two SPMs, one benign compound nevus and the normal DNA extracted from blood lymphocytes of the patient. RESULTS: We identified HRAS Q61 somatic mutation in one SPM developed in a pre-existing nevus. In the primary melanoma, besides the BRAF mutation, we identified the clinically actionable IDH1 R132C somatic mutation. Both SPMs were BRAF wild type. The patient harbors the recently recognized pathogenetic germline variant KDR Q472. We observed that mutations detected in tumor samples involving genes related to melanoma pathogenesis (TP53, PIK3CA, FGFR3, ATF1, KIT, HRAS and MAP2K2) were present in heterozygosis in the germline status of the patient. CONCLUSIONS: Our results support the paradoxical mechanism of MAPK pathway for SPMs under BRAF inhibitors. Moreover, they suggest that targeted mutational assessment based on matching somatic and germline analysis represent a promising approach to detect the neoplastic landscape of the tumor and to identify most accurate treatment in metastatic melanoma patient.


Asunto(s)
Melanoma , Neoplasias Primarias Secundarias , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Neoplasias Cutáneas , Análisis Mutacional de ADN , Humanos , Melanoma/tratamiento farmacológico , Melanoma/genética , Neoplasias Primarias Secundarias/tratamiento farmacológico , Neoplasias Primarias Secundarias/genética , Nevo de Células Epitelioides y Fusiformes , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/genética
15.
Ital J Dermatol Venerol ; 156(3): 378-383, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-31355620

RESUMEN

BACKGROUND: Estrogens play a key role in the skin. They are associated with an increased production of melanin, proliferation of melanocytes, increased skin thickness and increased cutaneous vascularization. Spitz and Reed nevi are acquired melanocytic lesions that generally develop during childhood or adolescence, a period of changes in sex hormones background. Our study project aimed at investigating, through immunohistochemical analysis, the expression levels of ERß receptors and their expression patterns (cytoplasmic or nuclear) in Spitz and Reed nevi. METHODS: In our study, we collected a total of 86 melanocytic lesions of patients: of these, 16 were common nevi, 23 were Spitz nevi, 18 were Reed nevi and 29 were melanomas. Expression curves for estrogen receptors were constructed using the Kaplan-Meier method and compared using a log-rank test. Statistical analysis was performed using MedCalc® (MedCalc Software, Ostend, Belgium). Immunohistochemical analysis on all histological sections of nevi and melanomas was performed to evaluate the expression levels of of ERß and their expression patterns (cytoplasmic or nuclear). The agreement between the operators was calculated using Fleiss κ values. RESULTS: The correlation between immunoreactivity for the ß-estrogen receptor and the sex of patients with Spitz and Reed nevi showed that immunoreactivity was higher in male patients. The correlation between ß-estrogen receptor immunoreactivity and patient age for Spitz and Reed nevi showed no statistically significant correlation. Correlation between immunoreactivity for the ß-estrogen receptor and histotype: Spitz and Reed nevi showed a high intensity, while in common nevi and in melanomas the immunoreactive was low. The correlation between receptor immunoreactivity for ß estrogens and Breslow thickness in melanomas indicated that Breslow thickness of non-immunoreactive melanomas for ERß was much higher than those showing high immunoreactivity for this receptor. CONCLUSIONS: Spitz and Reed nevi express a higher immunoreactivity for estrogens than common nevi and melanomas, especially those with a high Breslow thickness; and immunoreactivity is higher in younger age groups.


Asunto(s)
Nevo , Neoplasias Cutáneas , Adolescente , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Masculino , Receptores de Estrógenos , Neoplasias Cutáneas/diagnóstico
16.
Ital J Dermatol Venerol ; 156(5): 610-615, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-32938160

RESUMEN

BACKGROUND: Basal cell carcinoma (BCC) is the most common skin cancer, and it can be easily treated by surgery or by various other physical modalities and topical chemotherapy. For metastatic, locally advanced BCC and for cancers that cannot be removed by surgery, systemic drugs known as hedgehog pathway blocker are used. High-frequency ultrasound (HFUS) is a non- invasive technique used in diagnosis of some skin cancers. It has proven potentially useful for BCC management. In this study we used high frequency ultrasounds to evaluate BCCs' thickness and the correlation with dermoscopic features. METHODS: We examined 86 basal cell carcinomas with dermoscopy and with high-frequency ultrasound. The main patterns identified by ultrasound were linear, ellipsoid and non-specific or undefined. Patients were divided by sex and age. The BCCs were grouped by anatomic location. Finally, we recorded specific dermoscopic features of BCCs noting their presence/absence in lesions overall and in each of four quadrants. Then the lesions were excised, and histological examination was made with definition of tumor thickness (in mm). RESULTS: In our study, two main echographic patterns were described: linear, associated with superficial BCC, and ellipsoid, found primarily in nodular variants. However, a small percentage of lesions have otherwise non-specific patterns. We observed a significant correlation between echographic tumor thickness and histotype. We observed high concordance between histological tumor thickness and ultrasounds. Also, dermoscopic criteria as large branching and blue ovoid nests were significantly associated with heightened histologic and echographic assessments of tumor thickness. CONCLUSIONS: Our study confirmed the utility of ultrasound in the diagnosis of BCCs and for the first time we have correlated ultrasounds' patterns with dermoscopy and tumor thickness.


Asunto(s)
Carcinoma Basocelular , Neoplasias Cutáneas , Carcinoma Basocelular/diagnóstico por imagen , Dermoscopía , Humanos , Neoplasias Cutáneas/diagnóstico por imagen , Ultrasonografía
17.
Expert Opin Biol Ther ; 21(9): 1291-1298, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34278889

RESUMEN

INTRODUCTION: Efficacy of anti-TNF-a agents seems inferior to IL-17 and IL-23 inhibitors. Nevertheless, after biosimilars approval, anti TNF-a agents are recommended as first-line for psoriatic patients, for economic reasons. METHODS: Predictive factors of response or non-response to adalimumab in bionaive patients who started adalimumab (originator or biosimilar) over 12 years in 9 dermatologic centers in Italy. Effectiveness was assessed with Psoriasis Area and Severity Index (PASI75 and PASI90) at weeks 12, 24 and 48. Multiple logistic regressions were used for variables predicting clinical response; Kaplan-Meier survival curves and Cox regression for drug survival. RESULTS: The drug survival analysis showed reduced hazard ratio of overall discontinuation with male gender and scalp localization. In contrast, baseline PASI and genital psoriasis were significantly associated with increased risk of overall discontinuation. Predictive factors of non-response seemed elevated in patients with baseline PASI, older age groups, previously treated patients with phototherapy, females or patients with palmo-plantar while scalp psoriasis, previous cyclosporine and acitretin appeared as a positive predictive factor. CONCLUSIONS: This real-life analysis might be useful for clinicians in case of bio-naive patients with moderate-to-severe psoriasis and various comorbidities.


Asunto(s)
Biosimilares Farmacéuticos , Psoriasis , Adalimumab/uso terapéutico , Anciano , Recolección de Datos , Femenino , Humanos , Masculino , Psoriasis/diagnóstico , Psoriasis/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Inhibidores del Factor de Necrosis Tumoral
18.
J Invest Dermatol ; 141(3): 484-495, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33162051

RESUMEN

Primary cutaneous lymphomas encompass a wide spectrum of rare lymphoproliferative disorders originating in the skin, among which, mycosis fungoides (MF) is the most common subtype. The treatment of this disease is based on skin-directed therapies eventually in association with biologic response modifiers in the early phases, whereas in patients with the advanced stages, several therapeutic strategies can be used including mono and/or polychemotherapy and bone marrow transplantation. In recent years, the identification of specific markers (phenotypical, immunological, and molecular) has led to the development of several studies (including two randomized phase III trials). The results of these studies are modifying our therapeutic strategy toward a personalized treatment approach in which the clinical characteristics of the patients and tumor-node-metastasis-blood stage are considered together with the expression of specific markers (i.e., a CD30-positive expression for the use of brentuximab vedotin). This review will provide a comprehensive scenario of the main phenotypical, molecular, and immunological markers related to MF pathogenesis and disease evolution, which could represent the target for the development of innovative effective treatments in this disease.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Biomarcadores de Tumor/antagonistas & inhibidores , Micosis Fungoide/tratamiento farmacológico , Síndrome de Sézary/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Antineoplásicos Inmunológicos/farmacología , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/inmunología , Ensayos Clínicos Fase III como Asunto , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Terapia Molecular Dirigida/métodos , Mutación , Micosis Fungoide/genética , Micosis Fungoide/inmunología , Micosis Fungoide/mortalidad , Supervivencia sin Progresión , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Síndrome de Sézary/genética , Síndrome de Sézary/inmunología , Síndrome de Sézary/mortalidad , Piel/efectos de los fármacos , Piel/inmunología , Piel/patología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/mortalidad , Resultado del Tratamiento , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología
20.
Dermatol Surg ; 36(10): 1521-8, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20698871

RESUMEN

BACKGROUND: Sentinel lymph node biopsy (SLNB) represents a useful tool for staging melanoma patients. However false-negative SLNB are reported in the literature. OBJECTIVE: The aim of our study is to identify predictive factors for false-negative SLNB in melanoma patients. MATERIALS AND METHODS: We conducted a retrospective analysis on 316 melanoma patients who underwent SLNB and were followed up at the Department of Dermatology and Plastic Surgery of University of Rome "Sapienza" from March 1994 to June 2008. RESULTS: In our patients, SLNB was positive in 35 cases (11.07%) whereas it was negative in 281 cases (88.93%); 12/316 patients (3.8%) had positive SLNB and positive therapeutic lymph node dissection (TLND); 23/316 (7.28%) patients had positive SLNB and negative TLND; 266/316 (84.18%) patients had negative SLNB but without subsequent metastases in the SLN site; 15/316 (4.74%) patients had negative SLNB, but with subsequent metastases in the same SLN site (false-negative patients). Among the different prognostic factors, only ulceration was the main predictive factor for false-negative SLNB, according to statistical analysis (p=.0420). CONCLUSION: Our data confirm that SLNB is a useful technique for staging melanoma patients. However, in patients with negative SLNB, a closer follow-up is recommended when ulceration is present. The authors have indicated no significant interest with commercial supporters.


Asunto(s)
Melanoma/secundario , Biopsia del Ganglio Linfático Centinela/normas , Neoplasias Cutáneas/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Reacciones Falso Negativas , Femenino , Estudios de Seguimiento , Humanos , Modelos Logísticos , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Neoplasias Cutáneas/mortalidad , Análisis de Supervivencia , Tasa de Supervivencia , Adulto Joven
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