Response and Resistance to Trametinib in MAP2K1-Mutant Triple-Negative Melanoma.

The development of targeted therapies for non-BRAF p.Val600-mutant melanomas remains a challenge. Triple wildtype (TWT) melanomas that lack mutations in BRAF, NRAS, or NF1 form 10% of human melanomas and are heterogeneous in their genomic drivers. MAP2K1 mutations are enriched in BRAF-mutant melanoma and function as an innate or adaptive resistance mechanism to BRAF inhibition. Here we report the case of a patient with TWT melanoma with a bona fide MAP2K1 mutation without any BRAF mutations. We performed a structural analysis to validate that the MEK inhibitor trametinib could block this mutation. Although the patient initially responded to trametinib, he eventually progressed. The presence of a CDKN2A deletion prompted us to combine a CDK4/6 inhibitor, palbociclib, with trametinib but without clinical benefit. Genomic analysis at progression showed multiple novel copy number alterations. Our case illustrates the challenges of combining MEK1 and CDK4/6 inhibitors in case of resistance to MEK inhibitor monotherapy.

Occupational accidents involving pesticides notified by SINAN.

Introduction: The present article analyzed the number of pesticide accidents registered in Tocantins. In the case of occupational exposure to pesticides, the impact of pesticides on farmers is particularly great during direct handling or improper storage. This paper aims, through notifications of industrial accidents involving pesticides, to provide its target audience with information on notifications of accidents. Objectives: To analyze notifications of occupational accidents with pesticides via SINAN in the state of Tocantins, northern Brazil, from 2012 to 2017. Methods: The research deals with an explanatory literature that provides greater familiarity with the problem, making it clear or structured. Results: We can emphasize that pesticide poisoning is a serious public health problem. Among notifications of this event, 178 involved three types of pesticides, accounting for 12.35% of pesticide notifications. Furthermore, the most marketed pesticides are those whose formulation is based on the following active ingredients: glyphosate, 2,4-D, and mancozeb. Conclusions: After analyzing the data, we observed that the challenges brought by pesticide poisoning are related to the eligibility of the database of occupational accidents involving exogenous intoxications, being necessary to replace the use of agricultural pesticides, use pesticides safely for workers and the population, and seriously combat underreporting.

Introdução: O presente artigo analisou o número de acidentes de agrotóxicos registrados no Tocantins. No caso de exposição ocupacional a pesticidas, o impacto dos pesticidas sobre os agricultores é particularmente grande durante o manuseio direto ou armazenamento inadequado. Este trabalho propõe, por meio das notificações de acidentes industriais envolvendo agrotóxicos, fornecer ao seu público-alvo informações sobre notificações de acidentes. Objetivos: Analisar as notificações de acidente de trabalho com agrotóxicos via SINAN no estado do Tocantins entre os anos de 2012 e 2017. Métodos: A pesquisa trata de uma literatura explicativa que proporciona uma maior familiaridade com o problema, tornando-o claro ou estruturado. Resultados: Podemos enfatizar que a intoxicação por agrotóxicos é um sério problema de saúde pública. Dentre as notificações desse evento, 178 envolveram três tipos de agrotóxicos, representando 12,35% das notificações de agrotóxicos. Os agrotóxicos mais comercializados foram aqueles com formulação à base dos seguintes ingredientes ativos: glifosato, 2,4-D e mancozebe. Conclusões: Após a análise dos dados, observamos que os desafios colocados pela intoxicação por agrotóxicos estão relacionados à elegibilidade do banco de dados de acidentes de trabalho envolvendo intoxicações exógenas, sendo necessário substituir o uso de defensivos agrícolas, usar agrotóxicos com segurança para o trabalhador e para a população, e combater seriamente as subnotificações.

Safety and Efficacy of Ipilimumab plus Nivolumab and Sequential Selective Internal Radiation Therapy in Hepatic and Extrahepatic Metastatic Uveal Melanoma.

To assess the safety and efficacy of ipilimumab plus nivolumab around selective internal radiation therapy (SIRT) in patients with metastatic uveal melanoma (mUM). We present a retrospective, single center study of 32 patients with mUM divided into two groups based on the treatment received between April 2013 and April 2021. The SIRT_IpiNivo cohort was treated with Yttrium-90 microspheres and ipilimumab plus nivolumab before or after the SIRT (n = 18). The SIRT cohort underwent SIRT but did not receive combined immunotherapy with ipilimumab plus nivolumab (n = 14). Twelve patients (66.7%) of the SIRT_IpiNivo arm received SIRT as first-line treatment and six patients (33.3%) received ipilimumab plus nivolumab prior to SIRT. In the SIRT group, seven patients (50.0%) received single-agent immunotherapy. One patient treated with combined immunotherapy 68 months after the SIRT was included in this group. At the start of ipilimumab plus nivolumab, 94.4% (n = 17) presented hepatic metastases and 72.2% (n = 13) had extra liver disease. Eight patients (44.4%) of the SIRT_IpiNivo group experienced grade 3 or 4 immune related adverse events, mainly colitis and hepatitis. Median overall survival from the diagnosis of metastases was 49.6 months (95% confidence interval (CI); 24.1-not available (NA)) in the SIRT_IpiNivo group compared with 13.6 months (95% CI; 11.5-NA) in the SIRT group (log-rank p-value 0.027). The presence of extra liver metastases at the time of SIRT, largest liver lesion more than 8 cm (M1c) and liver tumor volume negatively impacted the survival. This real-world cohort suggests that a sequential treatment of ipilimumab plus nivolumab and SIRT is a well-tolerated therapeutic approach with promising survival rates.

Inferior Turbinate Reduction during Rhinoplasty: Is There Any Effect on Rhinitis Symptoms?

Abstract Introduction Inferior turbinate surgery is often performed concomitantly with rhinoseptoplasty. As inferior turbinates play a major role in allergic rhinitis, it seems reasonable to suggest that inferior turbinate surgery reduces allergy. Objective To assess the impact of nasal turbinate surgery on non-obstructive allergic symptoms (nasal discharge, sneezing, pruritus, and allergic conjunctivitis) and on the use of allergic medication in patients with allergic rhinitis undergoing rhinoseptoplasty. Methods Secondary analysis of aggregated data from two randomized controlled trials. Participants with allergic rhinitis aged 2: 16 years were recruited. Data from two groups were analyzed: patients with rhinoseptoplasty and concomitant turbinate reduction (intervention group) and patients with rhinoseptoplasty only (control group). The 90-day postoperative frequency of non-obstructive allergic symptoms and of nasal steroid and oral antihistamine use were analyzed. Results A total of 100 patients were studied. The groups were similar in terms of allergic symptom intensity and mean age. The frequency of non-obstructive allergic symptoms decreased 90 days postoperative in both groups (p < 0.01). There was no difference between the groups in the frequency of non-obstructive allergic symptoms at 90 days (p = 0.835). Topical nasal steroid and oral histamine antagonist use decreased in the intervention group at 90 days (p < 0.05). Conclusions Ninety days after the surgery, turbinate reduction performed in association with rhinoseptoplasty did not reduce the frequency of non-obstructive allergic symptoms more than rhinoplasty alone. However, the observed decrease in nasal steroid and oral antihistamine use suggests an impact of turbinate reduction on medication use in patients with allergic rhinitis undergoing rhinoseptoplasty. Trial Registration ClinicalTrials.gov database (NCT01457638 and NCT02231216).

Inferior Turbinate Reduction during Rhinoplasty: Is There Any Effect on Rhinitis Symptoms?

Introduction Inferior turbinate surgery is often performed concomitantly with rhinoseptoplasty. As inferior turbinates play a major role in allergic rhinitis, it seems reasonable to suggest that inferior turbinate surgery reduces allergy. Objective To assess the impact of nasal turbinate surgery on non-obstructive allergic symptoms (nasal discharge, sneezing, pruritus, and allergic conjunctivitis) and on the use of allergic medication in patients with allergic rhinitis undergoing rhinoseptoplasty. Methods Secondary analysis of aggregated data from two randomized controlled trials. Participants with allergic rhinitis aged ≥ 16 years were recruited. Data from two groups were analyzed: patients with rhinoseptoplasty and concomitant turbinate reduction (intervention group) and patients with rhinoseptoplasty only (control group). The 90-day postoperative frequency of non-obstructive allergic symptoms and of nasal steroid and oral antihistamine use were analyzed. Results A total of 100 patients were studied. The groups were similar in terms of allergic symptom intensity and mean age. The frequency of non-obstructive allergic symptoms decreased 90 days postoperative in both groups ( p < 0.01). There was no difference between the groups in the frequency of non-obstructive allergic symptoms at 90 days ( p = 0.835). Topical nasal steroid and oral histamine antagonist use decreased in the intervention group at 90 days ( p < 0.05). Conclusions Ninety days after the surgery, turbinate reduction performed in association with rhinoseptoplasty did not reduce the frequency of non-obstructive allergic symptoms more than rhinoplasty alone. However, the observed decrease in nasal steroid and oral antihistamine use suggests an impact of turbinate reduction on medication use in patients with allergic rhinitis undergoing rhinoseptoplasty. Trial Registration ClinicalTrials.gov database (NCT01457638 and NCT02231216).

Estimated Costs of the Ipilimumab-Nivolumab Therapy and Related Adverse Events in Metastatic Melanoma.

Combined ipilimumab and nivolumab significantly improve outcomes in metastatic melanoma patients but bear an important financial impact on the healthcare system. Here, we analyze the treatment costs, focusing on irAE. We conducted a retrospective analysis of 62 melanoma patients treated with ipilimumab-nivolumab at the Lausanne University Hospital between 1 June 2016 and 31 August 2019. The frequency of irAEs and outcomes were evaluated. All melanoma-specific costs were analyzed from the first ipilimumab-nivolumab dose until the therapy given subsequently or death. A total of 54/62 (87%) patients presented at least one irAE, and 31/62 (50%) presented a grade 3-4 irAE. The majority of patients who had a complete response 12/14 (86%) and 21/28 (75%) of overall responders presented a grade 3-4 toxicity, and there were no responses in patients without toxicity. Toxicity costs represented only 3% of the total expenses per patient. The most significant contributions were medication costs (44%) and disease costs (39%), mainly disease-related hospitalization costs, not toxicity-related. Patients with a complete response had the lowest global median cost per week of follow up (EUR 2425) and patients who had progressive disease (PD), the highest one (EUR 8325). Except for one patient who had a Grade 5 toxicity (EUR 6043/week), we observe that less severe toxicity grades (EUR 9383/week for Grade 1), or even the absence of toxicity (EUR 9922/week), are associated with higher median costs per week (vs. EUR 3266/week for Grade 4 and EUR 2850/week for Grade 3). The cost of toxicities was unexpectedly low compared to the total costs, especially medication costs. Patients with higher toxicity grades had better outcomes and lower total costs due to treatment discontinuation.

The combination of stereotactic radiosurgery with immune checkpoint inhibition or targeted therapy in melanoma patients with brain metastases: a retrospective study.

BACKGROUND: Evidence pointing to a synergistic effect of stereotactic radiosurgery (SRS) with concurrent immunotherapy or targeted therapy in patients with melanoma brain metastases (BM) is increasing. We aimed to analyze the effect on overall survival (OS) of immune checkpoint inhibitors (ICI) or BRAF/MEK inhibitors initiated during the 9 weeks before or after SRS. We also evaluated the prognostic value of patients' and disease characteristics as predictors of OS in patients treated with SRS. METHODS: We identified patients with BM from cutaneous or unknown primary origin melanoma treated with SRS between 2011 and 2018. RESULTS: We included 84 patients. The median OS was 12 months (95% CI 9-20 months). The median follow-up was 30 months (95% CI 28-49). Twenty-eight patients with newly diagnosed BM initiated anti-PD-1 +/-CTLA-4 therapy (n = 18), ipilimumab monotherapy (n = 10) or BRAF+/- MEK inhibitors (n = 11), during the 9 weeks before or after SRS. Patients who received anti-PD-1 +/-CTLA-4 mAb showed an improved survival in comparison to ipilimumab monotherapy (OS 24 vs. 7.5 months; HR 0.32, 95% 0.12-0.83, p = 0.02) and BRAF +/-MEK inhibitors (OS 24 vs. 7 months, respectively; HR 0.11, 95% 0.04-0.34, p = 0.0001). This benefit remained significant when compared to the subgroup of patients treated with dual BRAF/MEK inhibition (BMi) (n = 5). In a multivariate Cox regression analysis an age > 65, synchronous BM, > 2 metastatic sites, > 4 BM, and an ECOG > 1 were correlated with poorer prognosis. A treatment with anti-PD-1+/-CTLA-4 mAbs within 9 weeks of SRS was associated with better outcomes. The presence of serum lactate dehydrogenase (LDH) levels ≥ 2xULN at BM diagnosis was associated with lower OS (HR 1.60, 95% CI 1.03-2.50; p = 0.04). CONCLUSIONS: The concurrent administration of anti-PD-1+/-CTLA-4 mAbs with SRS was associated with improved survival in melanoma patients with newly diagnosed BM. In addition to CNS tumor burden, the extension of systemic disease retains its prognostic value in patients treated with SRS. Elevated serum LDH levels are predictors of poor outcome in these patients.

Brinquedos e jogos tradicionais da Trifronteira / Traditional tri border toys and games

O presente estudo tem como objetivo apresentar os resultados de uma investigação acerca dos brinquedos e jogos tradicionais da Trifronteira (Dionísio Cerqueira-SC, Barracão-PR e Bernardo de Irigoyen-AR) no período da fundação das três cidades, entre os anos 1950 e 1960. A pesquisa foi desenvolvida através de entrevistas semiestruturadas realizadas com 33 pessoas (10 do sexo masculino e 23 do sexo feminino) com idade igual ou superior a 55 anos, que viveram a infância no referido período e local. Como resultado, os brinquedos mais citados foram a boneca de pano e o carrinho de descida. Com relação à produção, constatou-se que 86% dos brinquedos eram produzidos artesanalmente com as ferramentas disponíveis e com resíduos das atividades realizadas nos espaços de trabalho em casa. Com relação aos jogos, destacaram-se a peteca, esconde-esconde e caçador, muito praticados no turno inverso a escola, ao ar livre.

This study aims to present the results of an investigation about to traditional toys and games at Tri Border (Dionísio Cerqueira-SC, Barracão-PR and Bernardo de Irigoyen-AR) during the foundation of the three cities, between the 1950s and 1960s. Research was conducted through an interview with 33 people (10 males and 23 females) aged 55 years or over who lived their childhood in that period and place. As a result, the most cited toys were the cloth doll and the cart. Regarding production, it was found that 86% of the toys were produced by hand with the tools available and with residues of the activities carried out in the work spaces at home. Regarding the games, the peteca, hide-and-seek and hunter stood out, much practiced in the inverse shift to school, in the open air.

Microleakage analysis of dental caries lesions sealed with flow resin and compared to microhybrid resin restorations in dentin / Avaliação da microinfiltração de lesões de cárie dentinárias seladas com resina flow e restauradas com resina microhíbrida

ABSTRACT Objective: To evaluate the sealing of cavities of dentinal occlusal caries lesions, reproduced in vitro, with flow resin compared to cavity restorations presenting healthy dentin using microhybrid composite resin. Methods: The sample consisted of 27 healthy deciduous molars where cavities of approximately 2 mm in the fossa region were performed and occlusal cleft of each tooth were sealed, impermeabilization was performed and the sample was randomly divided into 2 groups: group I underwent cariogenic challenge and occlusal sealing with resin flow. The teeth of group II were restored with microhybrid composite resin. The teeth were immersed in 5% methylene blue for 8 hours at 37° C and washed until all the dye was removed from the surface. The teeth were sectioned in the mesio-distal direction. The penetration of the dye was evaluated: 0- no penetration; 1- dye penetration up to 1/3 of the restoration; 2- dye penetration up to 2/3 of the restoration depth; 3 - penetration of dye into the pulp wall. The results were analyzed by the Biostat 4.0 program. Descriptive analysis and the mode among the examiners submitted to the Mann-Whitney test. Results: There was no significant difference in microleakage between restoration performed in healthy dentin with microhybrid composite resin or maintenance of infected dentin in primary teeth sealed with resin flow (p = 0.6035). Conclusion: It was concluded that the marginal infiltration of primary molars sealed with microhybrid composite resin and resin flow was not influenced by the removal -or not -of the carious tissue or the material used.

RESUMO Objetivo: Avaliar o selamento de cavidades de lesões de cárie oclusais em dentina, reproduzidas in vitro, com resina flow comparando com restaurações em cavidades com dentina hígida utilizando resina composta microhíbrida. Métodos: Foram selecionados 27 molares decíduos hígidos, realizadas cavidades de aproximadamente 2 mm na região de fossa e fissura da face oclusal de cada dente, impermeabilização e divisão em 2 grupos aleatoriamente: grupo I foram submetidos ao desafio cariogênico e selamento oclusal com resina flow. Os dentes do grupo II foram restaurados com resina composta microhíbrida. Os dentes foram imersos em azul de metileno a 5% durante 8 horas a 37 ° C e lavados até que todo o corante fosse removido da superfície. Os dentes foram seccionados no sentido mesio-distal. A penetração do corante foi avaliada: 0- nenhuma penetração; 1- a penetração de corante até 1/3 da restauração; 2- a penetração de corante até 2/3 da restauração profundidade; 3- penetração de corante para a parede pulpar. Os resultados foram analisados pelo programa Biostat 4.0. Foi feita análise descritiva e a moda entre os examinadores submetidas ao teste de Mann-Whitney. Resultados: Não houve diferença significante na microinfiltração entre restauração realizada em dentina hígida com resina composta microhíbrida ou a manutenção da dentina infectada em dentes decíduos selados com resina flow (p=0.6035). Conclusão: A remoção ou não do tecido cariado, assim como o material utilizado, não influenciou na infiltração marginal de molares decíduos selados com resina composta microhíbrida e resina flow.

Neurological Adverse Events Associated with Immune Checkpoint Inhibitors: Diagnosis and Management.

PURPOSE OF REVIEW: Immune checkpoint inhibitors represent a major step forward in the field of oncologic immunotherapy these last years and have significantly increased survival of cancer patients in an ever-growing number of indications. These agents block specific immune checkpoint molecules (programmed cell death protein 1 and its ligand as well as cytotoxic T-lymphocyte-associated antigen 4) that normally downregulate the immune response. These new agents show a specific range of adverse effects induced by abnormal immunologic activation. RECENT FINDINGS: Many different neurologic adverse events have been described, including encephalitis, myelopathy, aseptic meningitis, meningoradiculitis, Guillain-Barré-like syndrome, peripheral neuropathy (including mononeuropathy, mononeuritis multiplex, and polyneuropathy) as well as myasthenic syndrome. Immune checkpoint inhibitors have shown promising results in cancer but can possibly induce autoimmune disorders. Although rare, neurological adverse events require prompt recognition and treatment to avoid substantial morbidity.

Partial inferior turbinectomy in rhinoseptoplasty has no effect in quality-of-life outcomes: A randomized clinical trial.

OBJECTIVE: Evaluate the impact of endoscopic partial inferior turbinectomy (EPIT) associated with primary rhinoseptoplasty on quality-of-life outcomes (QOL), complications, and surgical duration. STUDY DESIGN: Randomized clinical trial. METHODS: Individuals with nasal obstruction aged ≥ 16 years who were candidates for functional and aesthetics primary rhinoseptoplasty were evaluated from March 2014 through May 2015. Eligible participants were randomly allocated to rhinoseptoplasty with or without EPIT (excision of one-third of the inferior turbinates). RESULTS: Fifty patients were studied. Most were Caucasian and had moderate/severe allergic rhinitis symptoms. Mean age was 36 ( ± 14.5) years. Rhinoseptoplasty was associated with improvement in all QOL scores irrespective of turbinate intervention (P < 0.001). Analysis of covariance was conducted to control for potential confounders. There was no difference between the groups in absolute score changes for Nasal Obstruction Symptom Evaluation-Portuguese (NOSE-p) (-50.5 vs. -47.6; P = 0.723), Rhinoplasty Outcome Evaluation (ROE) (47 vs. 44.8; P = 0.742), and all World Health Organization Quality of Life Scale-Abbreviated (WHOQOL-bref) score domains (P > 0.05). There were no differences between the groups regarding presence of the complications. Surgical duration was higher in the EPIT group (212 minutes ± 7.8 vs. 159.1 ± 5.6; P ? 0.001). CONCLUSIONS: Turbinate reduction through EPIT during primary rhinoseptoplasty did not improve short-term general and specific QOL outcomes. The use of EPIT increases surgical time considerably without improving QOL scores. There was no difference in postoperative incidence of complications, suggesting that EPIT is a safe technique. LEVEL OF EVIDENCE: 1b. Laryngoscope, 128:57-63, 2018.

Nova convenção internacional sobre o mercúrio expõe desafios para saúde global / New international convention on mercury presents challenges for gobal health

A questão sobre as contaminações, ocasionadas pelo mercúrio em escalamundial, produziu iniciativas políticas em diversos níveis (global,regional e nacional). Para buscar uma solução aos impactos à saúde eao meio ambiente, a comunidade internacional assinou a Convençãode Minamata sobre o Mercúrio, em outubro de 2013. O objetivo daConvenção de Minamata sobre o Mercúrio é o de proteger a saúdehumana e o meio ambiente das emissões antropogênicas de mercúrioCom 35 artigos, que abordam temas tecnico-científicos, políticose transversais, a Convenção aborda todo o ciclo de vida do produtoquímico. Os países latino-americanos, liderados pelo Brasil, tinhamposições firmes sobre a necessidade de se estabelecerem disposiçõessobre a saúde humana, no âmbito da convenção multilateral ambiental.Em seu artigo 16º, sobre os aspectos de saúde, há incentivo aos EstadosPartes para desenvolver e implementar estratégias e programas paraidentificar e proteger as populações vulneráveis. A Convenção aindadispõe sobre a substituição de produtos adicionados de mercúrio eutilizados nos serviços de saúde (termômetros e esfigmomanômetros)até 2020. Em relação às amálgamas dentárias, as disposições incluírammedidas para a redução de seu uso. Sobre o conservante de vacinatimerosal/tiomersal, este foi retirado das disposições da Convenção,sendo ainda permitido seu uso. Os profissionais e os ministérios desaúde dos Estados Partes podem contribuir com ações que visam àpromoção da saúde, durante o processo de ratificação e implementaçãoda Convenção.Descritores: Mercúrio; Intoxicação por Mercúrio; SaúdeAmbiental.

The question about the contaminations produced by the mercury ona global scale produced different initiatives on several levels (global,regional and national) and to find a solution for the impacts on healthand environment, the international community assign a Minamata´sConvention on mercury in October 2013. The objective of Minamata´sMercury Convention is to protect the human health and the environmentfrom the anthropogenic emissions of mercury beyond technical-scientist,political and transverse joins, addressing the entire product life cycle.The Latin-American countries, led by Brazil, had strong views on theneed for provisions on health in the field of environmental multilateralconvention. On the 16th article, about health issues, has incentives forMember States to develop and implement strategies and programsto identify and protect vulnerable populations. The Convention alsoprovides for the replacement of products containing added mercuryused in health services (thermometers, sphygmomanometers) to bereplaced by 2020. Regarding dental amalgams, the provisions includedmeasures to reduce their use. About preservative thimerosal/thiomersalvaccine, it was withdrawn from the provisions of the Convention, whilestill allowing use. Professionals and health ministries can contribute toactions aimed at health promotion, ratification and implementation ofthe Convention.

[Multidisciplinar approach to the management of gliomas]. / Prise en charge des tumeurs cérébrales primaires: une approche multidisciplinaire.

Gliomas represent two thirds of all primary brain tumors. Their prognosis depends directly upon their level of differentiation. On MRI, tumoral aggressivity is highlighted by contrast uptake and the infiltrative nature of the lesion. Clinical suspicion must however be confirmed by histology and molecular markers become essential to refine the diagnosis and tailor the treatment. Isocytrate dehydrogenase (IDH) mutations, codeletion of 1p and 19q and the presence of methylation of the MGMT promoter identify a subgroup of gliomas with better prognosis and may help predict response to treatment. Management of patients with primary brain tumors should always be defined in multidisciplinar tumor boards involving neurosurgeons, oncologists, radiation oncologists, neuropathologists and neuroradiologists.

Child's anxiety preceding the dental appointment: evaluation through a playful tool as a conditioning feature / Ansiedade infantil prévia à consulta odontológica: avaliação mediante instrumento lúdico como condicionamento

Objective: The aim of this study was to evaluate the emotional reactions before and after the application of a child audiovisual book that illustrates the trigger fear and anxiety points in the dental appointment. Moreover, the educational effect of this book as preconditioning to dental care was also verified. Methods: The study is a prospective pilot study conducted at the University of Western Santa Catarina with a convenience sample of 20 children aged 4-6 years old, with and without previous dental experience. All these children received the book and they were assessed before and after the presentation by responsible attendants. The projective test FIS (Facial Image Scale) was applied in 2 stages on the same day of assistance. Both tests were applied at the reception waiting room: before the child came into contact with the book in the dental clinic room and after the child came into contact with the playful instrument. Anamnesis and clinical examination were performed in the dental office by the dentist to start or continue the treatment. Results: The children were able to answer the projective test with self -analysis. The idealized audiovisual book was successfully constructed and used in the research. The comparison between FIS 1 and FIS 2 made with paired t-test showed significant improvements by comparing the results before the presentation of the playful instrument and after the use of it (p <0.0001), with no differences in childhood anxiety between genders and ages. Conclusion: The result of the conditioning technique using the book before the dental treatment was highly significant in reducing anxiety.

Objetivos: Avaliar as reações emocionais antes e após a aplicação de um livro audiovisual infantil que ilustra os pontos desencadeadores de medo e ansiedade na consulta odontológica. Além disso, verificou-se o efeito educativo desse livro como condicionamento prévio ao atendimento dental. Métodos: A pesquisa é um estudo piloto prospectivo conduzido na Universidade Comunitária da Região de Chapecó, com amostra de conveniência de 20 crianças entre 4 a 6 anos de idade, com e sem experiência odontológica anterior. Todas essas crianças receberam o livro e foram avaliadas antes e após a apresentação desse pelos seus responsáveis. Aplicou-se o teste projetivo de FIS (Facial Image Scale), em 2 etapas no mesmo dia do atendimento. Os dois testes foram aplicados na recepção: antes da criança entrar em contato com o livro na sala anexa à clínica odontológica e após a criança entrar em contato com o instrumento lúdico. Foi realizada a anamnese e exame clínico no consultório odontológico pela odontopediatra para iniciar ou dar continuidade ao tratamento. Resultados: As crianças foram capazes de responder o teste projetivo com auto-análise. O livro audiovisual idealizado foi construído com sucesso e utilizado na pesquisa. A comparação entre FIS 1 e FIS 2 feito com teste-t pareado apresentou melhoras significativas comparando-se o resultado antes da apresentação do instrumento lúdico e após o uso do instrumento (p<0,0001), sendo que não houve diferença na ansiedade infantil entre os gêneros e as idades. Conclusão: O resultado da técnica de condicionamento utilizando o livro, antes do atendimento odontológico, foi altamente significativo na redução da ansiedade.

[New therapeutic weapons in stage IV melanoma]. / Nouvelles armes thérapeutiques contre le mélanome de stade IV.

The treatment of stage IV melanoma has been revolutionized over the last years with the development of immunotherapies that, for the first time, have shown a significant benefit in overall survival, as well as with extremely effective targeted therapies, that also led to improved survival. These results are the fruits of an important translational research effort that allowed a rational approach with a very fast clinical development. The treatment of metastatic melanoma is, therefore, an illustration of the new paradigms of modern molecular research in oncology. In this review, we will present the various agents that have made the proof of their clinical benefit, as well as the scientific discoveries that allowed their development. Some of the remaining questions will be touched upon with the ongoing clinical trials. Inclusion of patients in these studies remains the top priority to improve on the clinical care.