RESUMO
BACKGROUND: Moderate-to-severe atopic dermatitis (AD) can be difficult to manage in paediatric patients, with few licensed treatments in this age group. Dupilumab is approved for AD in children older than 6 months. OBJECTIVES: To assess the effectiveness and safety of dupilumab in a real-life cohort of paediatric AD patients in Spain. METHODS: A multicentre, retrospective real-life study on the effectiveness and safety of dupilumab in patients aged 2 to 18 years old with moderate-to-severe AD was conducted. Demographic and clinical characteristics were analysed, and effectiveness (EASI, IGA, DLQI, NRS itch), safety, and drug survival measures were assessed. A comparison of our results with other real-world outcomes and with clinical trials was made. RESULTS: Data from 243 patients from 19 centres was collected, with a mean follow-up of 85 weeks. Dupilumab exhibited significant effectiveness, with marked reductions in severity scores from week 4. By week 16, 79.4% of patients reached EASI75 and 40.5% reached EASI90. Mean percentage reduction in EASI was 79.7%. Increasing improvements were observed until week 52, with 85.8% and 49.6% achieving EASI75 and EASI90, respectively. Forty-three patients developed adverse events (AE) (43/243, 17.7%), being the most frequent ocular surface diseases (20/243, 8.2%), injection site reactions (8/243, 3.3%) and facial redness (7/243, 2.9%). Drug survival was high (96.9% and 93.1% after 1 and 2 years of follow-up, respectively), with only 19 (19/243, 7.8%) patients interrupting treatment: 7 (7/243, 2.9%) due to AE, 2 (2/243, 0.82%) due to secondary failure, 5 (5/243, 2.1%) were lost to follow-up and 5 (5/243, 2.1%) entered remission and stopped treatment. CONCLUSION: Real-life use of dupilumab in paediatric AD showcased sustained effectiveness, high drug survival, and acceptable safety profiles. Longer-term studies are crucial for AE surveillance and how to manage disease remission.
RESUMO
BRAF/V600E mutation and other cell growth/growth-control mechanisms are involved in naevogenesis and melanomagenesis. Immunoexpression of BRAF/V600E and other molecules (p16, phosphatase and tensin homologue (PTEN), Ki67, hTERT and Cav3.1 and 3.2 calcium channels) were investigated in 80 histopatho-logically and dermoscopically classified acquired naevi. Regarding BRAF/V600E, dysplastic naevi showed lower immunostaining than common naevi, which was significant in comparison with intradermal naevi, which showed the highest BRAF/V600E histoscore. Junctional naevi showed the lowest BRAF/V600E levels. Globular/cobblestone and reticular dermoscopic patterns were consistently associated with high and low BRAF/V600E immunoexpression, respectively, but Zalaudek's peripheral globule pattern (CR/PG) showed the highest BRAF/V600E immunoexpression. Among global patterns, the previously not investigated multicomponent pattern showed the lowest BRAF/V600E immunoexpression. Regarding the remaining biomarkers, new immunohistochemical features were found, in particular p16 and PTEN low expression in multicomponent pattern; and Ki67, hTERT and Cav.3.1 high expression in CR/PG. In conclusion, histopathology and dermoscopy provide complementary information regarding the biology of melanocytic naevi.
Assuntos
Canais de Cálcio Tipo T , Nevo Pigmentado , Neoplasias Cutâneas , Biomarcadores , Dermoscopia , Humanos , PTEN Fosfo-Hidrolase , Proteínas Proto-Oncogênicas B-raf/genéticaRESUMO
Multi-spectral RGB-NIR sensors have become ubiquitous in recent years. These sensors allow the visible and near-infrared spectral bands of a given scene to be captured at the same time. With such cameras, the acquired imagery has a compromised RGB color representation due to near-infrared bands (700â»1100 nm) cross-talking with the visible bands (400â»700 nm). This paper proposes two deep learning-based architectures to recover the full RGB color images, thus removing the NIR information from the visible bands. The proposed approaches directly restore the high-resolution RGB image by means of convolutional neural networks. They are evaluated with several outdoor images; both architectures reach a similar performance when evaluated in different scenarios and using different similarity metrics. Both of them improve the state of the art approaches.
RESUMO
The worldwide incidence of malignant melanoma is increasing. The number of pigmented naevi and amount of solar exposure are important risk factors. The aim of this study was to characterize a paediatric population (from Lleida, Catalonia, Spain) in terms of phenotype, sun behaviour and naevi prevalence. Data on the numbers and distributions of acquired naevi in 369 children, aged 4, 8 and 14 years, were collected and correlated with age, sex, skin phototype and environmental factors (annual/lifetime intermittent and chronic sun exposure, sunburns and sunscreen use). The density of naevi increased with age. Boys had more naevi on the trunk and girls had more naevi on the legs. Children with light skin phototype had more naevi. A higher level of accumulated sun exposure correlated with a higher number of naevi in children with non-adequate sunscreen use. In conclusion, several risk factors associated with naevi density and distribution were found, as previously reported by others. Multivariate analysis confirmed a protective role of sunscreen in the development of acquired melanocytic naevi.
Assuntos
Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias Induzidas por Radiação/prevenção & controle , Nevo Pigmentado/epidemiologia , Nevo Pigmentado/prevenção & controle , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/prevenção & controle , Luz Solar/efeitos adversos , Protetores Solares/uso terapêutico , Adolescente , Fatores Etários , Distribuição de Qui-Quadrado , Criança , Estudos Transversais , Relação Dose-Resposta à Radiação , Feminino , Humanos , Masculino , Análise Multivariada , Neoplasias Induzidas por Radiação/diagnóstico , Nevo Pigmentado/diagnóstico , Razão de Chances , Prevalência , Fatores de Proteção , Fatores de Risco , Fatores Sexuais , Neoplasias Cutâneas/diagnóstico , Pigmentação da Pele , Espanha/epidemiologia , Fatores de TempoRESUMO
Cutaneous mucinosis in infancy is rare. We report an infant with multiple congenital papules distributed over the trunk, neck, and extremities. These papules were mainly dispersed, but they also coalesced into plaques. Histopathologic findings showed features of cutaneous mucinosis of infancy (CMI). Over 2 years of follow-up, we observed that the preexisting lesions on the lower back and left trunk progressively increased in size, and a few new scattered papules continued to appear, mainly on the trunk; several lesions spontaneously resolved with no further complications. CMI is considered to be a persistent cutaneous disorder, even though spontaneously regressing cases have rarely been reported. This case demonstrates the broad clinical spectrum of CMI, with progressive, eruptive, and spontaneously involuting lesions all present in the same patient. This condition should be considered in the differential diagnosis of congenital or infantile-onset papules and plaques, especially those yellowish in color.
Assuntos
Mucinoses/diagnóstico , Dermatopatias/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Mucinoses/congênito , Pele/patologia , Dermatopatias/congênitoRESUMO
A 62-year-old woman with a past medical history of rheumatoid arthritis was referred to the Department of Dermatology because of an enlarging cutaneous lesion on the right thumb which resembled a soft tissue infection. She had received antibiotics without significant improvement. Clinical examination revealed an erythematous nodule involving almost the whole surface of the distal phalanx with spontaneous drainage of countless of small yellowish ovoid granules. Histopathologic study of these structures showed an inner core of amorphous acidophilic material with some interspersed chronic inflammatory cells and a surrounding thin fibrin layer. Special stains and cultures were negative for parasites, bacterium and mycobacterium. Magnetic resonance imaging (MRI) revealed distension of the first and fifth finger flexor sheaths and common finger flexor sheath. These areas were filled by fluid and multiple small nodular lesions. A diagnosis of non-infectious rice body tenosynovitis was rendered and surgical removal was performed. Total recovery was observed with no evidence of recurrence after 6 months of follow-up. To our knowledge, this is the first report of rice body tenosynovitis presenting as a pseudoinflammatory cutaneous lesion with evolution to a cutaneous fistula with drainage of rice grain-like structures. The description of this impressive and peculiar clinical and histopathologic picture is important to further recognize similar cases.
Assuntos
Abscesso/patologia , Dermatopatias/patologia , Pele/patologia , Tenossinovite/patologia , Abscesso/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Dermatopatias/cirurgia , Tenossinovite/cirurgiaRESUMO
BACKGROUND: Cutaneous melanoma shows high variability regarding clinicopathological presentation, evolution and prognosis. METHODS: Next generation sequencing was performed to analyze hotspot mutations in different areas of primary melanomas (MMp) and their paired metastases. Clinicopathological features were evaluated depending on the degree of variation of the BRAFV600E mutant allele frequency (MAF) in MMp. RESULTS: In our cohort of 14 superficial spreading, 10 nodular melanomas and 52 metastases, 17/24 (71%) melanomas had a BRAFV600E mutation and 5/24 (21%) had a NRASQ61 mutation. We observed a high variation of BRAFV600E MAF (H-BRAFV600E) in 7/17 (41%) MMp. The H-BRAFV600E MMp were all located on the trunk, had lower Breslow and mitotic indexes and predominantly, a first nodal metastasis. Regions with spindled tumor cells (Spin) and high lymphocytic infiltrate (HInf) were more frequent in the H-BRAFV600E patients (4/7; 57%), whereas regions with epithelial tumor cells (Epit) and low lymphocytic infiltrate (LInf) were predominant (6/10; 60%) and exclusive in the low BRAFV600E MAF variation tumors (L-BRAFV600E). The H-BRAFV600E/Spin/HInf MMp patients had better prognostic features and nodal first metastasis. CONCLUSIONS: The H-BRAFV600E MMp were located on the trunk, had better prognostic characteristics, such as lower Breslow and mitotic indexes as well as high lymphocytic infiltrate.
RESUMO
Safe and effective antiseptic use in neonatal intensive care units is mandatory. High efficacy and a low number of side-effects from chlorhexidine have permitted avoidance of the use of mercurials and iodine derivatives, but methanol use can be unsafe in extreme preterm newborns. We report two cases of chemical burn after skin cleansing, due to alcoholic chlorhexidine (0.5%) use in extremely premature infants used for umbilical catheter insertion. Although this formulation is less concerning for use in full-term newborns, nonalcoholic preparations are preferable for use in preterm newborns.
Assuntos
Queimaduras Químicas/etiologia , Clorexidina/efeitos adversos , Desinfetantes/efeitos adversos , Recém-Nascido Prematuro , Metanol/efeitos adversos , Cateterismo , Contraindicações , Humanos , Recém-Nascido , Solventes/efeitos adversos , Gêmeos , UmbigoRESUMO
Melanoma is a malignant neoplasia that is highly resistant to chemotherapy and radiotherapy and is associated with poor prognosis in advanced stage. Targeting melanoma that harbors the common BRAFV600E mutation with kinase inhibitors, such as vemurafenib, reduces tumor burden, but these tumors frequently acquire resistance to these drugs. We previously proposed that T-type calcium channel (TTCC) expression may serve as a biomarker for melanoma progression and prognosis, and we showed that TTCC blockers reduce migration and invasion rates because of autophagy blockade only in BRAFV600E-mutant melanoma cells. Here, we demonstrated that high expression of the TTCC Cav3.1 isoform is related to autophagic status in vemurafenib-resistant BRAFV600E-mutant melanoma cells and human biopsies, and in silico analysis revealed an enrichment of Cav3.1 expression in post-treatment melanomas. We also demonstrated that the TTCC blocker mibefradil induces apoptosis and impairs migration and invasion via inhibition of autophagy in resistant melanoma cells and mouse xenograft models. Moreover, we identified an association between PTEN status and Cav3.1 expression in these cells as a marker of sensitivity to combination therapy in resistant cells. Together, our results suggest that TTCC blockers offer a potential targeted therapy in resistant BRAFV600E-mutant melanoma and a therapeutic strategy to reduce progression toward BRAF inhibitor resistance.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo T/metabolismo , Melanoma/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Neoplasias Cutâneas/tratamento farmacológico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Melanoma/genética , Melanoma/patologia , Camundongos , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Vemurafenib/farmacologia , Vemurafenib/uso terapêutico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Primary acute cutaneous infections caused by Serratia marcescens are extremely unusual. Nevertheless, Serratia infections are especially frequent in chronic granulomatous disease, which is a primary immunodeficiency that affects phagocytic cells of the innate immune system. We report a young man without history of infections, who developed multiple dermal abscesses on a leg with chronic lymphoedema attributed to S marcescens. Laboratory investigations showed a delayed partial neutrophilic oxidative function. It is remarkable that the patient did not have any other infections during childhood, when most of the innate immune deficiencies are diagnosed, and he had no history of granulomatous lesions. We hypothesize that the delayed neutrophilic oxidative function could be explained by a partial neutrophilic oxidative function, which could be enough to maintain the patient asymptomatic until this infection.
Assuntos
Abscesso/microbiologia , Infecções por Serratia/microbiologia , Serratia marcescens/isolamento & purificação , Abscesso/tratamento farmacológico , Doença Aguda , Adulto , Ciprofloxacina/uso terapêutico , Humanos , Masculino , Neutrófilos/fisiologia , Infecções por Serratia/tratamento farmacológicoAssuntos
Nevo , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/patologia , Nevo/patologia , DermoscopiaRESUMO
The incidence of lentigo maligna (LM), in situ (LM) or invasive (lentigo maligna melanoma, LMM), has increased during the last decades. Due to functional or cosmetic outcomes, optimal treatment with surgical excision may not be appropriate in some cases. We tried less invasive therapy, immunocryosurgery, as a single treatment for LM or combined with surgery for LMM, with better aesthetic results. Three patients with LM or LMM not amenable to complete surgical excision were selected. LMM patients underwent limited surgical resection of the invasive area. Subsequently, a combined treatment with topical imiquimod and cryosurgery was performed. The LM patient received immunocryosurgery directly. All of them were free of local and systemic disease at 48, 42 and 41 months after discontinuation of therapy. We consider that immunocryosurgery is an alternative option for LM or even for LMM (after removal of the invasive tissue with narrow margins) in poor surgical candidates, with good therapeutic, functional and cosmetic results.
Assuntos
Criocirurgia/métodos , Sarda Melanótica de Hutchinson/terapia , Imunoterapia/métodos , Melanoma/terapia , Neoplasias Cutâneas/terapia , Adjuvantes Imunológicos/uso terapêutico , Administração Cutânea , Idoso , Idoso de 80 Anos ou mais , Aminoquinolinas/uso terapêutico , Biópsia , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Criocirurgia/efeitos adversos , Procedimentos Cirúrgicos Dermatológicos/efeitos adversos , Procedimentos Cirúrgicos Dermatológicos/métodos , Feminino , Humanos , Sarda Melanótica de Hutchinson/patologia , Imiquimode , Imunoterapia/efeitos adversos , Melanoma/patologia , Pele/patologia , Creme para a Pele/uso terapêutico , Neoplasias Cutâneas/patologiaRESUMO
Lakes represent a considerable natural source of methane to the atmosphere compared to their small global surface area. Methanotrophs in sediments and in the water column largely control methane fluxes from these systems, yet the diversity, electron accepting capacity, and nutrient requirements of these microorganisms have only been partially identified. Here, we investigated the role of electron acceptors alternative to oxygen and sulfate in microbial methane oxidation at the oxycline and in anoxic waters of the ferruginous meromictic Lake La Cruz, Spain. Active methane turnover in a zone extending well below the oxycline was evidenced by stable carbon isotope-based rate measurements. We observed a strong methane oxidation potential throughout the anoxic water column, which did not vary substantially from that at the oxic/anoxic interface. Both in the redox-transition and anoxic zones, only aerobic methane-oxidizing bacteria (MOB) were detected by fluorescence in situ hybridization and sequencing techniques, suggesting a close coupling of cryptic photosynthetic oxygen production and aerobic methane turnover. Additions of nitrate, nitrite and to a lesser degree iron and manganese oxides also stimulated bacterial methane consumption. We could not confirm a direct link between the reduction of these compounds and methane oxidation and we cannot exclude the contribution of unknown anaerobic methanotrophs. Nevertheless, our findings from Lake La Cruz support recent laboratory evidence that aerobic methanotrophs may be able to utilize alternative terminal electron acceptors under oxygen limitation.