Germline mutations in cancer predisposition genes among pediatric patients with cancer and congenital anomalies.

BACKGROUND: Childhood cancer has a poorly known etiology, and investigating the underlying genetic background may provide novel insights. A recognized association exists between non-chromosomal birth defects and childhood cancer susceptibility. METHODS: We performed whole-exome sequencing and chromosomal microarray analysis in a cohort of childhood cancer (22 individuals, 50% with congenital anomalies) to unravel deleterious germline variants. RESULTS: A diagnostic yield of 14% was found, encompassing heterozygous variants in bona fide dominant Cancer Predisposition Genes (CPGs). Considering candidate and recessive CPGs harboring monoallelic variants, which were also deemed to play a role in the phenotype, the yield escalated to 45%. Most of the deleterious variants were mapped in genes not conventionally linked to the patient's tumor type. Relevant findings were detected in 55% of the syndromic individuals, mostly variants potentially underlying both phenotypes. CONCLUSION: We uncovered a remarkable prevalence of germline deleterious CPG variants, highlighting the significance of a comprehensive genetic analysis in pediatric cancer, especially when coupled with additional clinical signs. Moreover, our findings emphasized the potential for oligogenic inheritance, wherein multiple genes synergistically increase cancer risk. Lastly, our investigation unveiled potentially novel genotype-phenotype associations, such as SETD5 in neuroblastoma, KAT6A in gliomas, JAG1 in hepatoblastomas, and TNFRSF13B in Langerhans cell histiocytosis. IMPACT: Novel gene-phenotype associations and candidate genes for pediatric cancer were unraveled, such as KAT6A in gliomas, SETD5 in neuroblastoma, JAG1 in hepatoblastomas, and TNFRSF13B in Langerhans cell histiocytosis. Our analysis revealed a high frequency of deleterious germline variants, particularly in cases accompanied by additional clinical signs, highlighting the importance of a comprehensive genetic evaluation in childhood cancer. Our findings also underscored the potential for oligogenic inheritance in pediatric cancer risk. Understanding the cancer etiology is crucial for genetic counseling, often influencing therapeutic decisions and offering valuable insights into molecular targets for the development of oncological therapies.

SARS-CoV-2 in children with cancer in Brazil: Results of a multicenter national registry.

BACKGROUND: Strategies to mitigate the impact of COVID-19 in special populations are complex and challenging. Few studies have addressed the impact of COVID-19 on pediatric patients with cancer in low- and middle-income countries. METHODS: Multicenter observational cohort study with prospective records and retrospective analyses starting in April 2020 in 21 pediatric oncology centers distributed throughout Brazil. PARTICIPANTS: Patients under 18 years of age who are infected by the SARS-CoV-2 virus (confirmed diagnosis through reverse transcriptase-polymerase chain reaction [RT-PCR]) while under treatment at pediatric oncology centers. The variables of interest included clinical symptoms, diagnostic and therapeutic measures. The repercussions of SARS-CoV-2 infection on cancer treatment and general prognosis were monitored. RESULTS: One hundred seventy-nine patients were included (median age 6 [4-13] years, 58% male). Of these, 55.9% had acute leukemia and 34.1% had solid tumors. The presence of SARS-CoV-2 was diagnosed by RT-PCR. Various laboratory markers were analyzed, but showed no correlation with outcome. Children with low or high BMI for age had lower overall survival (71.4% and 82.6%, respectively) than those with age-appropriate BMI (92.7%) (p = .007). The severity of presentation at diagnosis was significantly associated with outcome (p < .001). Overall mortality in the presence of infection was 12.3% (n = 22). CONCLUSION: In children with cancer and COVID-19, lower BMI was associated with worse prognosis. The mortality in this group of patients (12.3%) was significantly higher than that described in the pediatric population overall (∼1%).

Atenção precoce e educação em saúde na atividade laboral: uma abordagem da infecção pelo HIV/Aids na odontologia do trabalho / Early attention and health education in work activity: an approach to HIV/Aids Iinfection in dental work

Introdução: a equipe de saúde ocupacional possui a responsabilidade de exercer o cuidado e a atenção integral de indivíduos infectados pelo HIV, noque diz respeito à saúde bucal, que perpassa desde a assistência até a realização de campanhas informativas e preventivas nas empresas em que prestam serviço. Objetivo: descrever os aspectos preventivos e educativos relacionados à infecção pelo HIV/aids por meio de uma visão da atuação prática da Odontologia do Trabalho através de uma revisão da literatura. Métodos: foi realizado um levantamento bibliográfico que utilizou periódicos científicos,livros técnicos, notas técnicas, publicações de organismos nacionais e internacionais (Medline, SciELO e Lilacs no período de 1988 até 2010). Resultados:as atribuições do cirurgião-dentista na odontologia do trabalho perpassam desde a observação e o controle de infecções da cavidade oral, bem como depossíveis manifestações orais provenientes da infecção pelo HIV, além do trabalho de promoção da saúde bucal, até a realização de campanhas informativase preventivas nas empresas em que prestam serviços. Conclusão: a busca pela atualização dos conhecimentos técnico-científicos é prevista por norma regulamentadora e dará ao profissional a segurança necessária para não agir de forma preconceituosa e discriminatória, capacitando-o para a realização deum trabalho educativo junto aos demais componentes do seu ambiente laboral e social, incluindo indivíduos infectados pelo HIV.

Introduction: the occupational health team has the responsibility of taking comprehensive care of individuals infected by HIV in relation to oral health care since that comprehends the informative campaigns and preventive actions in companies that provide service. Objective: to describe the preventive and educational aspects related to HIV/aids through an over view of the performance practice of dentistry labour through the literature review. Methods:we conducted a literature review that used scientific journals, technical books, technical notes, publications, national and international (Medline, SciELO and Lilacs in the period between 1988 to 2010). Results: the tasks of the dentist in dental work permeate the observation and control of infections of theoral cavity, as well as oral manifestations of HIV infection, in addition to efforts to promote oral health, the informative and preventive campaigns in the companies they serve. Conclusion: the search for the updating of technical and scientific knowledge is provided by regulation and professional will secureenough acting not to prejudicial and discriminatory way, enabling him to carry out educational work with the other components of their work environmentand social, including individuals infected by HIV.

Infecção pelo HIV e a atividade laboral do portador: uma relação ética e legal na visão da odontologia do trabalho / HIV infection and working patient activity: a ethical and legal relation in the vision of the work dentistry

Introdução: o controle da infecção pelo vírus da imunodeficiência humana (HIV) na vida do trabalhador infectado é de responsabilidade da equipe de saúde ocupacional, na qual o dentista do trabalho está inserido. Objetivo: realizar uma revisão bibliográfica a fim de trazer ao conhecimento dos cirurgiões-dentistas, principalmente os profissionais que exercem sua função monitorando a saúde do trabalhador, os aspectos éticos e legais relacionados com os indivíduos infectados pelo HIV. Métodos: para isto foi realizado um levantamento bibliográfico que utilizou periódicos científicos, livros técnicos, notas técnicas, publicações de organismos nacionais e internacionais (Medline e Lilacs dos últimos 10 anos). Resultados: as atribuições do dentista do trabalho perpassam desde a observação e o controle das manifestações orais provenientes da aids, a promoção da saúde bucal, até a realização de campanhas informativas e preventivas nas empresas em que prestam serviço. Conclusão: a busca pela atualização dos conhecimentos técnico-científicos é prevista por norma regulamentadora e dará ao profissional a segurança necessária para não agir de forma preconceituosa e discriminátoria, capacitando-o para a realização de um trabalho educativo junto aos demais componentes do seu ambiente laboral e social.