Brazilian Medical Survey on Telemedicine since the onset of COVID-19

ABSTRACT Objective The primary aim of this study was to understand the difference in the use of Telemedicine by Brazilian physicians before and after the onset of COVID-19 pandemic and their intention to continue using it post the pandemic period. The secondary objective was to analyze the differences of opinion between physicians in the private and public sectors. Methods We conducted an online medical survey through the SurveyMonkey platform in a large hospital in São Paulo, Brazil, from May to July 2022. Results Three-hundred-and -two physicians responded to the survey. We found that there was a significant increase in the number of physicians who started using Telemedicine in both the public and private sectors (p<0.0001) since the onset of COVID-19 pandemic and that >50% of them intend to continue using Telemedicine in their daily practice. Most responders consider that Telemedicine is useful in screening, diagnosis and management of patients; that it facilitates the physician's daily practice; that it can maintain or even add financial gains through reducing office expenses; and that is another medium for dispensing medical care. They also believe that Telemedicine should be regulated by the Brazilian Federal Council of Medicine. There were no significant differences between the responses from private and public sector physicians. Conclusion Telemedicine has played a major role in healthcare since the onset of COVID-19 pandemic and most of the physicians approve its use and intend to continue using Telemedicine in their daily practice.

Diagnosis and treatment of systemic mastocytosis in Brazil: Recommendations of a multidisciplinary expert panel

ABSTRACT Introduction: Systemic Mastocytosis comprises a group of neoplastic diseases characterized by clonal expansion and infiltration of mast cells into several organs. The diagnosis and treatment of this disease may be challenging for non-specialists. Objective: Make suggestions or recommendations in Systemic Mastocytosis based in a panel of Brazilian specialists. Method and results: An online expert panel with 18 multidisciplinary specialists was convened to propose recommendations on the diagnosis and treatment of Systemic Mastocytosis in Brazil. Recommendations were based on discussions of topics and multiple-choice questions and were graded using the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Chart. Conclusion: Twenty-two recommendations or suggestions were proposed based on a literature review and graded according to the findings.

Efficacy and safety of dupilumab in two adolescents with severe atopic dermatitis / Eficácia e segurança do uso de dupilumabe em dois adolescentes com dermatite atópica grave

ABSTRACT We report the cases of two adolescent siblings with severe atopic dermatitis, who, despite weighing approximately 40kg, presented a good response to dupilumab with the off-label dose for individuals aged 12 years and weighing 60kg. Both had already used cyclosporine, azathioprine, methotrexate and oral corticosteroids for long periods, plus topical treatments with no adequate disease control. Skin lesions were constant and widespread, with frequent skin infections and very poor quality of life, with numerous physical and psychosocial consequences, such as dropping out of school activities due to severe itching, appearance and bullying. They also showed delayed growth and development. In 2018, dupilumab, an immunobiological agent, was approved for treatment of moderate to severe atopic dermatitis in adults and, in 2019, extended to the 12-17-year age group. Although it had already been approved by the Brazilian Health Surveillance Agency, the 200mg presentation (indicated for the weight of patients) was not available, with no expected arrival date. Therefore, weighing the risks and benefits of the situation of both, we chose to treat them with an adult dose (loading dose of 600mg subcutaneously, and 300mg subcutaneously every 2 weeks) despite the low weight. So far, they have received eight injections, showing significant improvement of disease and quality of life. There were no major adverse effects, only worsening of allergic conjunctivitis in one of them. The patients and their family are very satisfied, and we believe that the therapy has been successful.

RESUMO Relatamos os casos de dois irmãos adolescentes com dermatite atópica grave e que, apesar de pesarem cerca de 40kg, apresentaram boa resposta ao dupilumabe com a dose off-label para indivíduos com 12 anos e peso de 60kg. Ambos já tinham usado ciclosporina, azatioprina, metotrexato e corticoide oral por longos períodos, acrescidos de tratamentos tópicos sem controle adequado da doença. As lesões cutâneas eram constantes e disseminadas, e os irmãos apresentavam infeções de pele frequentes e qualidade de vida muito ruim, com inúmeras consequências físicas e psicossociais, como o abandono da atividade escolar pelo prurido intenso, pela aparência e pelo bullying sofrido. Apresentavam também retardo de crescimento e de desenvolvimento. Em 2018, o dupilumabe, um agente imunobiológico, foi aprovado para o tratamento de dermatite atópica moderada a severa para adultos e, em 2019, ampliado para faixa etária de 12 a 17 anos. Embora já tivesse a aprovação da Agência Nacional de Vigilância Sanitária no Brasil, a apresentação de 200mg (indicada para o peso dos pacientes) não estava disponível, sem previsão de chegada. Assim, pesando os riscos e benefícios da situação de ambos, optamos por tratá-los com dose de adulto (ataque de 600mg por via subcutânea e 300mg por via subcutânea a cada 2 semanas) apesar do baixo peso. Até o momento, eles realizaram oito aplicações, apresentando importante melhora da doença e da qualidade de vida. Não houve efeitos adversos importantes - apenas a piora da conjuntivite alérgica em um deles. Os pacientes e sua família estão muito satisfeitos, e nós avaliamos que a terapia está sendo bem-sucedida.

Escabiose mascarada por mastocitose sistêmica / Scabies masked by systemic mastocytosis

Paciente do sexo feminino, com 59 anos de idade, portadora de mastocitose sistêmica há 20 anos. A mastocitose é doença rara, caracterizada pela proliferação excessiva e o subsequente acúmulo de mastócitos em órgãos e tecidos, principalmente na medula óssea, pele e no trato gastrointestinal. Há 1 mês, relatava história de novas lesões cutâneas caracterizadas por pápulas e placas eritemato-edematosas com escoriação e intenso prurido. Feito o raspado da pele com confirmação diagnóstica de escabiose.

A 59-year-old female patient had a diagnosis of systemic mastocytosis for 20 years. Mastocytosis is a rare disease characterized by excessive proliferation and accumulation of mast cells in organs and tissues, especially in the bone marrow, skin and gastrointestinal tract. She reported new skin lesions characterized by erythematous papules and plaques with excoriation and intense itching for one month. Skin scraping confirmed the diagnosis of scabies.

Abordagem da conjuntivite em paciente com dermatite atópica em uso de dupilumabe / Management of conjunctivitis in patients with atopic dermatitis using dupilumab

O dupilumabe foi aprovado para o tratamento de dermatite atópica moderada a grave em adultos e adolescentes no Brasil. Ensaios clínicos e estudos de vida real mostraram alta eficácia e segurança deste imunobiológico, porém a frequência de conjuntivite no grupo de pacientes com dermatite atópica tratado com esse medicamento foi mais alta do que no grupo controle. A conjuntivite é mais frequente em pacientes com dermatite atópica do que na população geral, e foi o efeito adverso mais frequente nos pacientes com dermatite atópica em uso do dupilumabe. A maioria dos casos apresentou quadro leve, sem necessidade de suspender a medicação. Apresentamos uma sugestão de algoritmo para a abordagem da conjuntivite nos pacientes em uso do dupilumabe para tratamento da dermatite atópica.

Dupilumab has been approved for the treatment of moderate to severe atopic dermatitis in adults and adolescents in Brazil. Clinical trials and real-life studies have demonstrated the high efficacy and safety of this immunobiological agent, but the frequency of conjunctivitis in the group of patients treated with this drug for atopic dermatitis has been higher than that in the control group. Conjunctivitis is more common in patients with atopic dermatitis than in the general population, and it has been reported as the most common adverse effect in patients with atopic dermatitis using dupilumab. Most cases are of mild severity, without the need to discontinue medication. We suggest an algorithm for the management of conjunctivitis in patients treated with dupilumab for atopic dermatitis.

Dupilumab in the treatment of severe atopic dermatitis refractory to systemic immunosuppression: case report / Dupilumabe no tratamento da dermatite atópica grave refratária à imunossupressão sistêmica: relato de caso

ABSTRACT Case report of a patient with severe atopic dermatitis who showed a good response to dupilumab. She had already used two immunosuppressive agents, cyclosporine A and mycophenolate mofetil, for the treatment of atopic dermatitis with no proper control of the disease. She had also been taking all measures to control severe cases of the disease: bath and environmental controls, topical potent corticosteroids and emollients. She presented constant pruritus and skin lesions, frequent skin infections e poor quality of life. She also developed depression due to her disease. Recently, dupilumab, a new biological agent, was approved for the treatment of moderate/severe atopic dermatitis in many countries, including Brazil. Dupilumab is a monoclonal antibody with a common alpha chain of interleukin (IL) 4 and IL-13 receptors, two cytokines involved in the Th2 profile immune response that promote atopic inflammation. In a pioneer way in Brazil, the patient initiated the treatment with an attack dose of 600mg subcutaneous of dupilumab and 300mg subcutaneous every other week. Up to now, she has taken four applications, presenting a great improvement of the disease and her quality of life. There were no adverse effects, nor in the injection site nor of other kind. Patient and her family are very satisfied, and the medical team evaluates that the treatment is being well succeed. The case report described here subsidizes the use of dupilumab in the treatment of severe atopic dermatitis refractory to use of immunosuppressive agents.

RESUMO Relatamos o caso de uma paciente com dermatite atópica grave, que mostrou boa resposta ao dupilumabe. Ela já tinha usado dois agentes imunossupressores, a ciclosporina A e o micofenolato de mofetila, para o tratamento da dermatite atópica, sem obter o controle adequado da doença. Ela também vinha fazendo uso de todas as medidas de controle para casos graves da doença: cuidados com o banho, controle ambiental, corticosteroides potentes tópicos e emolientes. Apresentava prurido e lesões cutâneas constantes, infeções de pele frequentes e qualidade de vida ruim. Passou a apresentar depressão devido à sua doença. Recentemente, o dupilumabe, um agente biológico novo, foi aprovado para o tratamento de dermatite atópica moderada a severa em muitos países, incluindo o Brasil. Dupilumabe é um anticorpo monoclonal cujo alvo é a cadeia alfa comum aos receptores da interleucina (IL) 4 e IL-13, duas citocinas envolvidas no perfil de resposta imune Th2, que promove inflamação atópica. De modo pioneiro no Brasil, a paciente iniciou o tratamento, com dose de ataque de 600mg por via subcutânea de dupilumabe e 300mg também por via subcutânea a cada 2 semanas. Até o momento deste relato, ela realizou quatro aplicações, apresentando grande melhora da doença e da qualidade de vida. Não houve efeitos adversos, nem no local da injeção e nem de outro tipo. A paciente e sua família estão muito satisfeitas, e os médicos que a tratam avaliam que a terapia está sendo bem-sucedida. Este relato de caso subsidia o uso de dupilumabe no tratamento da dermatite atópica grave refratária ao uso de imunossupressores.

Efetividade e segurança do dupilumabe na dermatite atópica / Efficacy and safety of dupilumab in atopic dermatitis

Relato de caso que ilustra a eficácia e a segurança do uso do dupilumabe na dermatite atópica. O uso de anticorpos monoclonais também possibilita o maior conhecimento sobre a fisiopatogenia da doença.

This case report shows the efficacy and safety of dupilumab in atopic dermatitis. The use of monoclonal antibodies provides further knowledge on the pathophysiology of the disease.

Melanoma: tumor microenvironment and new treatments

Abstract: In the recent past years, many discoveries in the tumor microenvironment have led to changes in the management of melanoma and it is rising up hopes, specially, to those in advanced stages. FDA approved seven new drugs from 2011 to 2014. They are: Vemurafenib, Dabrafenib and Trametinib, kinases inhibitors used for patients that have BRAFV600E mutation; Ipilimumab (anti-CTLA4), Pembrolizumab (anti-PD-1) and Nivolumab (anti-PD-1), monoclonal antibodies that stimulate the immune system; and Peginterferon alfa-2b, an anti-proliferative cytokine used as adjuvant therapy. In this article, we will review the molecular bases for these new metastatic melanoma therapeutic agents cited above and also analyze new molecular discoveries in melanoma study, as Cancer-Testis antigens (CT). They are capable of induce humoral and cellular immune responses in cancer patients and because of this immunogenicity and their restrict expression in normal tissues, they are considered an ideal candidate for vaccine development against cancer. Among CT antigens, NY-ESO-1 is the best characterized in terms of expression patterns and immunogenicity. It is expressed in 20-40% of all melanomas, more in metastatic lesions than in primary ones, and it is very heterogeneous inter and intratumoral. Breslow index is associate with NY-ESO-1 expression in primary cutaneous melanomas, but its relation to patient survival remains controversial.

Análise da expressão da proteína NY-ESO-1 no melanoma cutâneo / NY-ESO-1 protein analysis in cutaneous melanoma

O câncer é a doença que mais mata pessoas com idade abaixo de 85 anos e é um problema de saúde pública. Os tumores podem expressar em determinada fase de seu desenvolvimento proteínas anômalas que podem ser alvo de métodos diagnósticos e de intervenções terapêuticas. A expressão de NY-ESO-1 é detectada em 20 a 40% dos melanomas. Há evidências que esta expressão é mais freqüente em tumores de estágios mais avançados e está associada a um pior prognóstico. OBJETIVOS: determinar a frequência de expressão da proteína NY-ESO-1 no melanoma cutâneo e tentar correlacioná-la com o índice de Breslow, aspectos histopatológicos do melanoma, incluindo o infiltrado linfocítico tumoral, e a morbi-mortalidade dos pacientes. MÉTODOS: o presente estudo é longitudinal de coorte retrospectiva e foi realizado de agosto de 2009 a outubro de 2015. Foram selecionados 89 melanomas de 87 pacientes do Ambulatório de Tumores do Departamento de Dermatologia da FMUSP, divididos em 3 grupos, sendo: grupo 1: 34 melanomas com índice de Breslow <= 1,0 mm; grupo 2: 29 melanomas com índice de Breslow entre 1,1 - 4,0 mm e grupo 3: 26 melanomas com índice de Breslow >= 4,0 mm. As lâminas dos exames anátomo-patológicos destes pacientes foram revisadas quanto ao diagnóstico de melanoma, seu índice de Breslow e a presença de infiltrado linfocítico tumoral. A seguir, realizou-se exame de imunohistoquímica para a determinação da presença do antígeno NY-ESO-1 em todos os 89 tumores coletados e em mais 20 nevos (11 displásicos e 9 intradérmicos) escolhidos ao acaso. Através da revisão dos dados do prontuário, foram obtidos os dados clínicos de: idade, sexo, raça, fototipo da pele, local de aparecimento do melanoma, status do linfonodo sentinela quando realizado, desenvolvimento de metástases e sobrevida dos pacientes. Os dados anátomo-patológicos do tumor analisados foram: tipo histológico, presença de ulceração, e tipo de infiltrado linfocítico tumoral. Nos melanomas que apresentavam...

Cancer is the disease that leads to the greatest number of deaths in people over 85 years old and it has become a major public health problem. Tumors may express aberrantly proteins during certain phases of their development, which can be target for diagnostic or treatment purposes. NY-ESO-1 is detected in 20 to 40% of melanomas. There is evidence that it is more frequent in advanced stages and that is associated with a worse prognosis. OBJECTIVES: to determine the frequency of NY-ESO-1 protein expression in cutaneous melanoma and to try to correlate it to Breslow index, melanoma histopathological aspects, including the tumor infiltrating lymphocytes, and patients morbi-mortality. METHODS: the present study is longitudinal of retrospective cohort. The research was carried on from August 2009 to October 2015. Eighty nine melanomas were selected from 87 patients in Oncology Outpatient Clinic, Dermatology Division, University of São Paulo and divided in 3 groups, such as: group 1: 34 melanomas with Breslow index <= 1,0 mm; group 2: 29 melanomas with Breslow index between 1,1 - 4,0 mm e group 3: 26 melanomas with Breslow index >= 4,0 mm. All specimens were reviewed for diagnostic, Breslow index and tumor infiltrating lymphocytes. After that, immunohistoquimical test for the presence of NY-ESO-1 antigen was performed in all 89 melanomas collected and in 20 nevi (11 dysplastic nevi and 9 dermal nevi) that were randomly chosen. By reviewing clinical charts, the following data was obtained: age, sex, skin phototype, site of the tumor, lymph node sentinel status, development of metastases and survival of the patients. The histological data analyzed was: histological melanoma type, presence of ulceration, grade of tumor infiltrating lymphocytes. In those melanomas that had tumor infiltrating lymphocytes, we performed immunohistoquimical tests for the presence of CD3+, CD8+, FoxP3+ and CD8+FoxP3+ (double positive) cells. RESULTS: antigen NY-ESO-1 was...