Assuntos
Antineoplásicos/efeitos adversos , Melanoma/tratamento farmacológico , Doenças da Unha/induzido quimicamente , Segunda Neoplasia Primária/induzido quimicamente , Neoplasias Cutâneas/tratamento farmacológico , Idoso , Feminino , Humanos , Melanoma/secundário , Doenças da Unha/diagnóstico , Doenças da Unha/patologia , Unhas/patologia , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/patologia , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Neoplasias Cutâneas/patologiaRESUMO
OBJECTIVE: The purpose of this study is to evaluate the clinical determinants of complete response in locally advanced basal cell carcinoma (laBCC) patients receiving Sonidegib in a real-life, retrospective, observational study. Hedgehog pathway inhibitors (Vismodegib and Sonidegib) are approved for the systemic treatment of locally advanced basal cell carcinoma (laBCC). The objective response rate was the primary endpoint of the trials for both drugs. PATIENTS AND METHODS: Adult patients with laBCC treated with Sonidegib at the Dermato-Oncology Unit of IFO San Gallicano between June 2020 and September 2022 were included in the study. Patient, tumor, and treatment characteristics were recorded. The complete response rate was the primary outcome. The median time to the best response and complete response were the secondary outcomes. Treatment-related adverse events (TRAEs) and dose adjustments were recorded. RESULTS: Of the 19 patients included in the study, eight (42.1%) achieved a complete response, seven (36.8%) had a partial response, and four experienced progressive disease (21%). The median time to the best response was 3 months in the group of patients with partial response (range 2.0-4.0, with three patients not evaluable) and 3.5 months in the group of patients with complete response (range 2-5). TRAEs occurred in 14 (73.6%) patients, with 8 (57.1%) reporting ≤2 TRAE categories and 6 (42.8%) >2. A total of 78.9% of patients received a modified treatment schedule; 12.5% of patients who achieved a complete response received full dosage from the beginning to the end of treatment, compared with 27.3% of those with a partial response. CONCLUSIONS: The associations between the clinical outcome of interest (objective response rate) and the clinicopathological and treatment characteristics were evaluated. No statistically significant association was observed. Our analysis confirms the observation that no statistically significant correlation exists between clinical response and Sonidegib alternate dose regimen.
Assuntos
Antineoplásicos , Compostos de Bifenilo , Carcinoma Basocelular , Piridinas , Neoplasias Cutâneas , Adulto , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Compostos de Bifenilo/farmacologia , Compostos de Bifenilo/uso terapêutico , Carcinoma Basocelular/tratamento farmacológico , Carcinoma Basocelular/patologia , Proteínas Hedgehog , Piridinas/farmacologia , Piridinas/uso terapêutico , Estudos Retrospectivos , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: Our understanding of the genetic basis of predisposition to psoriasis is increasing exponentially due to the progress of genetic studies. However, so far little is known about genetic predisposition in relation to the response to psoriasis treatments. Recent data identified genetic predictors for the clinical outcome of conventional treatments such as methotrexate, acitretin and vitamin D derivatives, but few studies are available on genetic predictors of response to biologics. We hypothesized that genetic variations associated with increased risk of developing psoriasis may also act as predictors for the outcome of biologic therapy. OBJECTIVES: The aim of our study was to analyse the presence of three different psoriasis susceptibility genetic variations (HLA-Cw6; TNFAIP3 rs610604 polymorphism; LCE3B/3C gene deletions) in a cohort of patients affected by moderate to severe psoriasis under ustekinumab treatment. Our primary endpoint was to evaluate the association between Psoriasis Area and Severity Index (PASI) 75 response at week 12 and HLA-Cw6 status. METHODS: Fifty-one patients were genotyped by standard methods and psoriasis severity (PASI score) was evaluated at day 0 and after 4, 12, 24 and 40 weeks of treatment. RESULTS: We observed increased response to ustekinumab in Cw6-positive (Cw6POS) patients [PASI 75 at week 12: 96·4% in Cw6POS vs. 65·2% in Cw6-negative (Cw6NEG) patients; P = 0·008]. In addition, we show that HLA-Cw6POS patients responded faster to ustekinumab, 89·3% of them reaching PASI 50 at week 4, after a single injection (vs. 60·9% of HLA-Cw6NEG patients). The superior response of HLA-Cw6POS patients was maintained throughout the study period, reaching the highest statistical significance for PASI 75 at week 28 (96·35% Cw6POS vs. 72·7% Cw6NEG; odds ratio 9·8). Analysis of TNFAIP3 rs610604 polymorphism and LCE3B/3C gene deletions did not show any significant association with response to ustekinumab. CONCLUSIONS: Our observations underline the role of HLA-Cw6 not only as a psoriasis susceptibility gene, but also as a pharmacogenetic marker of response to ustekinumab in psoriasis.
Assuntos
Proteínas Ricas em Prolina do Estrato Córneo/genética , Proteínas de Ligação a DNA/genética , Antígenos HLA-C/genética , Psoríase/genética , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Produtos Biológicos/uso terapêutico , Feminino , Deleção de Genes , Humanos , Interleucina-12/antagonistas & inibidores , Interleucina-23/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/genética , Ustekinumab , Adulto JovemRESUMO
BACKGROUND: In February 19, 2009, the European Medicines Agency (EMA) had recommended the suspension of the marketing authorization for efalizumab after the occurrence of cases of progressive multifocal leukoencephalopathy. OBJECTIVE: To explore the efficacy of alternative therapies for psoriasis and the health status of patients who discontinued efalizumab. METHODS: An observational study was performed on 101 patients. After the EMA communication, efalizumab was discontinued in the following 2-3 months. In agreement with the patients, we decided to either prescribe other treatments or none at all. RESULTS: After 1 year, 11 patients are still not treated, 63 patients are treated with biologics, and 9 patients are treated with systemic conventional therapies. CONCLUSION: In order to prevent rebound or relapse, various approaches are available, including cyclosporine, methotrexate and biologic therapies. Interestingly, in 11 out of 31 patients who did not receive any systemic drug, psoriasis is still under control, suggesting a long-term effect of efalizumab.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Psoríase/tratamento farmacológico , Retirada de Medicamento Baseada em Segurança , Suspensão de Tratamento , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Produtos Biológicos/uso terapêutico , Ciclosporina/uso terapêutico , Fármacos Dermatológicos/efeitos adversos , Feminino , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Biological therapy for moderate to severe psoriasis includes tumour necrosis factor (TNF) blockers (infliximab, etanercept and adalimumab) and T-cell-targeting agents (efalizumab, alefacept) that act in different steps of a common pathogenic pathway. Large amounts of data coming from clinical trials indicate each of these drugs as highly effective and safe. However, little is known about the efficacy of a second biological therapy after the failure of the first. OBJECTIVE: To evaluate whether the response to efalizumab in psoriasis patients was influenced by previous treatment with other biological agents. PATIENTS AND METHODS: We have retrospectively analyzed a group of 155 psoriasis patients treated with efalizumab during the last 5 years and determined its efficacy in patients previously treated with anti-TNF drugs comparing it with the efficacy and safety observed in patients previously treated with traditional systemic drugs instead. RESULTS: Efalizumab was shown to be as efficacious and safe in patients previously treated with biological agents as in those previously treated with traditional systemic drugs. Although not statistically significant, we observed a higher rate of response to efalizumab in patients previously treated with anti-TNF-alpha. PASI 75 was achieved at week 24 in 76.2% of the patients previously treated with biological agents versus 54.4% in patients previously treated with traditional drugs (OR = 2.9). CONCLUSIONS: These data suggest that efalizumab can be successfully used in psoriasis patients when TNF blockers cannot efficiently control the disease due to lack or loss of response, or when they have to be interrupted for intolerance or adverse events.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Psoríase/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Antígenos CD11 , Fármacos Dermatológicos/uso terapêutico , Etanercepte , Feminino , Humanos , Imunoglobulina G/uso terapêutico , Infliximab , Masculino , Pessoa de Meia-Idade , Receptores do Fator de Necrose Tumoral/uso terapêutico , Falha de Tratamento , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto JovemRESUMO
On the basis of a survey of the literature, an etiopathogenetic classification of biliary peritonitis is presented, with particular reference to forms without perforation. The variability of clinical picture and the difficulties of correct pre-operative diagnosis explain the mortality rate of 30-50%.
Assuntos
Bile , Peritonite/etiologia , Doenças Biliares/complicações , Diagnóstico Diferencial , Humanos , Peritonite/diagnóstico , Peritonite/fisiopatologia , Ruptura EspontâneaRESUMO
The Authors report their experience in the application of local anesthesia during breast prosthesis implantation.
Assuntos
Anestesia Local , Implantes de Mama , Mamoplastia , Adulto , Anestesia Local/métodos , Anestesia Local/normas , Feminino , HumanosRESUMO
The Authors report a case of Poland's syndrome formerly undergone reconstructive surgery with unsatisfactory results. Therefore, a new surgical reconstructive strategy having aesthetic purposes is illustrated.
Assuntos
Síndrome de Poland/cirurgia , Cirurgia Plástica/métodos , Adulto , Estética , Humanos , Masculino , Síndrome de Poland/etiologia , ReoperaçãoAssuntos
Bile , Peritonite/etiologia , Animais , Bile/análise , Bile/metabolismo , Cateterismo , Cães , Feminino , Vesícula Biliar/efeitos dos fármacos , Vesícula Biliar/patologia , Ligadura , Masculino , Ductos Pancreáticos/cirurgia , Suco Pancreático/análise , Suco Pancreático/metabolismo , Secretina/administração & dosagemRESUMO
Several cases of psoriasis associated with bullous disorders have been reported, and it is clearly recognized that bullous pemphigoid (BP) is the most common bullous disorder observed in association with psoriasis, especially after ultraviolet (UV)B and psoralen UVA therapy. Moreover, other medications have been repeatedly reported to induce bullous diseases, especially pemphigus vulgaris. We report for the first time a case of BP possibly induced by losartan, an angiotensin II antagonist, in a patient with a severe psoriatic background. Angiotensin II type 1 receptor antagonists belong to a new class of drug for hypertension or congestive heart failure with established efficacy and few side-effects. Coexistence of psoriasis vulgaris with bullous diseases represents also a difficult therapeutic challenge. This rare case of psoriasis and generalized BP triggered by a sartan drug was treated with rituximab and etanercept.