RÉSUMÉ
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.
Sujet(s)
Antibioprophylaxie/méthodes , Endocardite bactérienne/prévention et contrôle , Transplantation rénale/effets indésirables , Complications postopératoires/prévention et contrôle , Infections à streptocoques/prévention et contrôle , Streptococcus agalactiae/génétique , Sujet âgé , Antibactériens/usage thérapeutique , Épidémies de maladies , Endocardite bactérienne/microbiologie , Endocardite bactérienne/transmission , Femelle , Humains , Transplantation rénale/méthodes , Mâle , Adulte d'âge moyen , Typage par séquençage multilocus , Complications postopératoires/microbiologie , Sérogroupe , Infections à streptocoques/microbiologie , Infections à streptocoques/transmission , Donneurs de tissus , Résultat thérapeutiqueSujet(s)
Ascite chyleuse/étiologie , Solutions de dialyse/effets indésirables , Compléments alimentaires/effets indésirables , Défaillance rénale chronique/thérapie , Dialyse péritonéale continue ambulatoire/méthodes , Antibactériens/usage thérapeutique , Ascite chyleuse/diétothérapie , Ascite chyleuse/physiopathologie , Clostridioides difficile/isolement et purification , Régime pauvre en graisses , Entérocolite pseudomembraneuse/complications , Entérocolite pseudomembraneuse/traitement médicamenteux , Études de suivi , Humains , Défaillance rénale chronique/complications , Défaillance rénale chronique/diagnostic , Mâle , Adulte d'âge moyen , Dialyse péritonéale continue ambulatoire/effets indésirables , Appréciation des risquesRÉSUMÉ
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.