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Epstein-Barr virus (EBV)-associated lymphomas cover a range of histological B- and T-cell non-Hodgkin and Hodgkin lymphoma subtypes. The role of EBV on B-cell malignant pathogenesis and its impact on the tumour microenvironment are intriguing but incompletely understood. Both the International Consensus Classification (ICC) and 5th Edition of the World Health Organization (WHO-HAEM5) proposals give prominence to the distinct clinical, prognostic, genetic and tumour microenvironmental features of EBV in lymphoproliferative disorders. There have been major advances in our biological understanding, in how to harness features of EBV and its host immune response for targeted therapy, and in using EBV as a method to monitor disease response. In this article, we showcase the latest developments and how they may be integrated to stimulate new and innovative approaches for further lines of investigation and therapy.
Assuntos
Infecções por Vírus Epstein-Barr , Doença de Hodgkin , Linfoma não Hodgkin , Linfoma , Transtornos Linfoproliferativos , Humanos , Herpesvirus Humano 4/genética , Doença de Hodgkin/patologia , Microambiente TumoralRESUMO
BACKGROUND: We recently introduced a policy to use O positive red cells in emergency transfusions for males >16 years of age and females >50 years of age. Here, we investigate changes in emergency transfusion practice and rates of red cell alloimmunization with the use of O positive blood for emergency transfusion. STUDY DESIGN AND METHODS: State-wide retrospective review of emergency transfusions between June 2020 and June 2021. The laboratory information system and patient medical records were used to collect demographic details, indications for transfusion, usage of O positive and O negative blood and rates of alloimmunization. RESULTS: There were 2354 red cell units transfused to 1013 patients (male = 59%, average age = 53 years) during the 12-month period. O positive units accounted for 46.9% (1103 units) of emergency transfusions. However, 726 (30.8%) O negative units were transfused to patients without a mandatory indication for O negative blood. Twenty-eight patients (2.9%) had a red cell alloantibody prior to transfusion including anti-E (n = 10), anti-D (n = 4), and anti-K (n = 4). One patient with prior anti-D had mild delayed hemolysis. There were 19 patients (4.3%, median follow-up 22 days) who developed a red cell alloantibody after emergency transfusion and include anti-E (n = 10), anti-D (n = 7), and anti-C (n = 5). DISCUSSION: The use of O positive blood for emergency transfusion has saved 1103 O negative red cell units with no detriment to patient outcome. There remains potential to optimize use of O positive blood in emergency transfusion and to understand red cell alloimmunization rates in a prospective fashion.
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Classical Hodgkin lymphoma (cHL) accounts for 0.4% of all new cancer cases globally. Despite high cure rates with standard treatment, approximately 15% of patients still experience relapsed or refractory (RR) disease, and many of these eventually die from lymphoma-related causes. Exciting new targeted agents such as anti-PD-1 agents and brentuximab vedotin have changed the therapeutic paradigm beyond chemotherapy and radiotherapy alone. Advances in understanding of the molecular biology are providing insights in the context of novel therapies. The signature histology of cHL requires the presence of scant malignant Hodgkin Reed-Sternberg cells (HRSCs) surrounded by a complex immune-rich tumour microenvironment (TME). The TME cellular composition strongly influences outcomes, yet knowledge of the precise characteristics of TME cells and their interactions with HRSCs is evolving. Novel high-throughput technologies and single-cell sequencing allow deeper analyses of the TME and mechanisms elicited by HRSCs to propagate growth and avoid immune response. In this review, we explore the evolution of knowledge on the prognostic role of immune cells within the TME and provide an up-to-date overview of emerging prognostic data on cHL from new technologies that are starting to unwind the complexity of the cHL TME and provide translational insights into how to improve therapy in the clinic.
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OBJECTIVE: Frailty is associated with increased vulnerability to poor health. There is growing interest in understanding the association between frailty and chronic kidney disease (CKD). This systematic review explored how frailty is measured in patients with CKD and the association between frailty and adverse outcomes across different stages of renal impairment. STUDY DESIGN: Systematic analysis of peer reviewed articles. DATA SOURCES: Pubmed, Medline, Web of Science and Cochrane were used to identify the articles. DATA SYNTHESIS: Articles published before the 17th of September 2016, that measured frailty in patients with CKD was eligible for the systematic review. Two independent researchers assessed the eligibility of the articles. Quality of the articles was assessed using the Epidemiological Appraisal Instrument. RESULTS: The literature search yielded 540 articles, of which 32 met the study criteria and were included in the review (n=36,076, age range: 50-83 years). Twenty-three (72%) studies used or adapted the Fried phenotype to measure frailty. The prevalence of frailty ranged from 7% in community-dwellers (CKD Stages 1-4) to 73% in a cohort of patients on haemodialysis. The incidence of frailty increased with reduced glomerular filtration rate. Frailty was associated with an increased risk of mortality and hospitalization. CONCLUSION: Frailty is prevalent in patients with CKD and it is associated with an increased risk of adverse health outcomes. There are differences in the methods used to assess frailty and this hinders comparisons between studies.