RESUMEN
Extramammary Paget disease (EMPD) is an intraepithelial adenocarcinoma that primarily affects the genital and axillary areas in older individuals. A limited number of paired patients with familial EMPD (i.e. parent-offspring, siblings) have been reported but the genetics have not yet been adequately studied. We report, to the best of our knowledge, the first familial cases of patients with EMPD involving three affected siblings. The tumour-only multigene panel testing using surgical specimens revealed a heterozygous c.2997A>C (p.Glu999Asp) nonsynonymous variant in the proto-oncogene MET (NM_000245.4) in the three affected siblings. The germline multigene panel testing using peripheral blood lymphocytes revealed the same missense MET variant in all five family members who were tested, including two asymptomatic offspring (51 and 37â years of age). The MET variant we identified could be involved in EMPD carcinogenesis. Further genomic analyses of patients with familial EMPD are warranted to validate the pathogenic relevance of MET variants in EMPD development.
Asunto(s)
Enfermedad de Paget Extramamaria , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas c-met , Hermanos , Humanos , Masculino , Enfermedad de Paget Extramamaria/genética , Enfermedad de Paget Extramamaria/patología , Persona de Mediana Edad , Femenino , Proteínas Proto-Oncogénicas c-met/genética , Adulto , Mutación Missense , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Anciano , LinajeAsunto(s)
Toxinas Bacterianas , Infecciones Comunitarias Adquiridas , Fascitis Necrotizante , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Fascitis Necrotizante/diagnóstico , Fascitis Necrotizante/tratamiento farmacológico , Japón , Exotoxinas/genética , Leucocidinas/genética , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológico , Antibacterianos/uso terapéuticoRESUMEN
BACKGROUND: Adrenaline is the first-line medication for managing anaphylaxis. A better understanding of prescription trends for adrenaline auto-injectors (AAIs) is important to improving patient care as well as information on health education interventions and medical guidelines. However, it has been difficult to gather comprehensive data in a sustainable manner. Thus, we aimed to investigate trends in AAI prescriptions in Japan. METHODS: We searched the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), a unique and comprehensive database of health insurance claims, and investigated prescriptions for AAIs for all ages (April 2017 to March 2018). We assessed the annual number of prescriptions per person as well as prescription rates per 100,000 population per year by age, sex, and geographic region. RESULTS: A total of 88,039 subjects (56,109 males, 31,930 female) and 116,758 devices (1.33 AAIs per patient per year) were prescribed AAIs at least once a year for all ages. The prescription rate for AAIs was 69.5 per 100,000 population-years. Patients aged 0-9 years were prescribed AAIs at the rate of 278.9 per 100,000 population-years. Patients aged 0-19 years were 6.4 times more likely to be prescribed AAIs than those over 20 years of age. Males were more frequently prescribed AAIs than females in all age groups, except for those aged 20-24 years. We also evaluated differences in prescription rates by geographic region. CONCLUSIONS: This comprehensive evaluation revealed trends in AAI prescriptions, thus helping develop preventive strategies with respect to anaphylaxis in Japan.