RESUMO
MONITORING OF ANALGESIA, SEDATION AND DELIRIUM: The prerequisite for monitoring goal-oriented analgesia and screening for the presence of delirium is the use of validated measuring instruments such as the Richmond Agitation and Sedation Scale as well as an adequate medical and intensive care staffing ratio. IMPLEMENTATION OF ANALGESIA AND SEDATION: The goal, if possible, is an awake, oriented, cooperative patient who is free of pain. In this regard, multimodal analgesic treatment is of great importance. The lowest possible sedation should also be aimed for in COVID-19 patients, although deep sedation is recommended for invasively ventilated COVID-19 patients in the prone position.
Assuntos
Analgesia , COVID-19 , Delírio , COVID-19/terapia , Delírio/terapia , Humanos , Dor , Manejo da DorAssuntos
Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Supressora de Tumor p53/genética , Antineoplásicos Alquilantes/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Humanos , Estimativa de Kaplan-Meier , Melfalan/uso terapêutico , Mieloma Múltiplo/terapia , Prognóstico , Transplante Autólogo , Resultado do TratamentoAssuntos
Antineoplásicos Alquilantes/administração & dosagem , Genes ras , Transplante de Células-Tronco Hematopoéticas , Melfalan/administração & dosagem , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , Mutação , Condicionamento Pré-Transplante , Transplante Autólogo , Humanos , Estimativa de Kaplan-Meier , Mieloma Múltiplo/mortalidade , Prognóstico , Resultado do TratamentoRESUMO
Epstein-Barr virus (EBV)-associated diffuse large B-cell lymphoma (DLBCL) of the elderly constitutes a provisional clinicopathological entity in the current World Health Organization (WHO) classification and its genomic features remain sparsely characterized. We investigated a cohort of 26 cases of untreated de novo EBV-positive DLBCL of the elderly by high-resolution array-based comparative genomic profiling and fluorescence in situ hybridization (FISH). Moreover, we screened for activating mutations affecting nuclear factor (NF)-κB pathway signaling and chromatin remodeling (EZH2, CD79B, CARD11 and MYD88) due to their impact of gene expression signatures and postulated upcoming therapeutic targetability. We identified an overlap between genomic aberrations previously described to be exclusive features of plasmablastic lymphoma (PL), post-transplant lymphoproliferative disorder (PTLD) and DLBCL, respectively, indicating a close cytogenetic relationship between these entities. Few mutations affecting CD79B and CARD11 and no MYD88 mutations were detectable, hinting at EBV-mediated activation of NF-κB as an alternative to pathologically enforced B-cell receptor signaling in this rare entity.
Assuntos
Aberrações Cromossômicas , Infecções por Vírus Epstein-Barr/complicações , Linfoma Difuso de Grandes Células B/genética , Mutação , Proteínas Oncogênicas/genética , Idoso , Idoso de 80 Anos ou mais , Proteínas Adaptadoras de Sinalização CARD/genética , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Antígenos CD79/genética , Antígenos CD79/metabolismo , Hibridização Genômica Comparativa , Variações do Número de Cópias de DNA , Feminino , Guanilato Ciclase/genética , Guanilato Ciclase/metabolismo , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/epidemiologia , Masculino , Pessoa de Meia-Idade , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Proteínas Oncogênicas/metabolismo , Prevalência , Análise Serial de TecidosRESUMO
BACKGROUND: Primary mediastinal large B-cell lymphoma (PMBL) is a distinct subtype of diffuse large B-cell lymphoma (DLBCL) frequently observed in young patients. High-dose immunochemotherapy constitutes the current therapeutic gold-standard, despite significant toxicity and serious late effects. Several hotspots harboring oncogenic gain-of-function mutations were recently shown to pose vital hallmarks in activated B-cell like (ABC-) (CD79B, CARD11 and MYD88) and germinal center like (GCB-) DLBCL (EZH2), respectively. Several promising targeted-therapy approaches, derived from these findings, are currently under development. MATERIALS AND METHODS: We thoroughly characterized a cohort of 25 untreated patients with de novo PMBL by immunohistochemical and cytogenetic means and assessed the prevalence of activating mutations affecting EZH2, CD79B and CARD11 utilizing a polymerase chain reaction (PCR)-based capillary sequencing approach. Moreover, the MYD88 p. L265P status was assessed by employing a pyrosequencing approach. RESULTS: PMBLs included in this study did not harbor any of the reported hotspot mutations activating the nuclear factor (NF)-kappa B signaling cascade or the EZH2-mediated epigenetic deregulation of gene expression. Immunohistochemical characterization revealed an ABC phenotype in 44% (n=11) of cases. CONCLUSION: We report that genetic alterations of these genes are rare events in PMBL unlike other subtypes of DLBCL. Our findings suggest that a substantial subset of PMBL patients may benefit from treatment approaches targeting BCR-mediated activation of NF-kappa B.
