RESUMO
In 2015, an outbreak involving a highly virulent zoonotic outbreak strain of Streptococcus agalactiae serotype III, multilocus sequence type 283 occurred in Singapore with increased neurologic complications, septic arthritis, and spinal infections in healthier patients. We report a case of a successful dual kidney transplant from a deceased donor with infective endocarditis and disseminated infection with the same strain of S agalactiae and we review the current literature.
Assuntos
Antibioticoprofilaxia/métodos , Endocardite Bacteriana/prevenção & controle , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Infecções Estreptocócicas/prevenção & controle , Streptococcus agalactiae/genética , Idoso , Antibacterianos/uso terapêutico , Surtos de Doenças , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/transmissão , Feminino , Humanos , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Complicações Pós-Operatórias/microbiologia , Sorogrupo , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/transmissão , Doadores de Tecidos , Resultado do TratamentoAssuntos
Ascite Quilosa/etiologia , Soluções para Diálise/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Falência Renal Crônica/terapia , Diálise Peritoneal Ambulatorial Contínua/métodos , Antibacterianos/uso terapêutico , Ascite Quilosa/dietoterapia , Ascite Quilosa/fisiopatologia , Clostridioides difficile/isolamento & purificação , Dieta com Restrição de Gorduras , Enterocolite Pseudomembranosa/complicações , Enterocolite Pseudomembranosa/tratamento farmacológico , Seguimentos , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Medição de RiscoRESUMO
Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.
