ABSTRACT
Background: Essential thrombocythemia (ET), a myeloproliferative neoplasm (MPN), has a substantial risk of evolving into post-essential thrombocythemia myelofibrosis (post-ET MF). This study aims to establish a prediction nomogram for early prediction of post-ET MF in ET patients. Methods: The training cohort comprised 558 patients from 8 haematology centres between January 1, 2010, and May 1, 2023, while the external validation cohort consisted of 165 patients from 6 additional haematology centres between January 1, 2010, and May 1, 2023. Univariable and multivariable Cox regression analysis was performed to identified independent risk factors and establish a nomogram to predict the post-ET MF free survival. Both bias-corrected area under the curve (AUC), calibration curves and concordance index (C-index) were employed to assess the predictive accuracy of the nomogram. Findings: Multivariate Cox regression demonstrated that elevated red blood cell distribution width (RDW), elevated levels of lactate dehydrogenase (LDH) and the level of haemoglobin (Hb), a history of smoking and the presence of splenomegaly were independent risk factors for post-ET MF. The C-index displayed of the training and validation cohorts were 0.877 and 0.853. The 5 years, 10 years AUC values in training and external validation cohorts were 0.948, 0.769 and 0.978, 0.804 respectively. Bias-corrected curve is close to the ideal curve and revealed a strong consistency between actual observation and prediction. Interpretation: We developed a nomogram capable of predicting the post-ET MF free survival probability at 5 years and 10 years in ET patients. This tool helps doctors identify patients who need close monitoring and appropriate counselling. Funding: This research was funded by the Key R&D Program of Zhejiang (No. 2022C03137); the Public Technology Application Research Program of Zhejiang, China (No. LGF21H080003); and the Zhejiang Medical Association Clinical Medical Research special fund project (No. 2022ZYC-D09).
ABSTRACT
In recent years, the traditional cognition of immunological memory being specific to adaptive immunity has been challenged. Innate immunity can mount enhanced responsiveness upon secondary stimulation, and a phenomenon is termed trained innate immunity. Trained innate immunity is orchestrated by distinct metabolic and epigenetic reprogramming in both circulating myeloid cells and myeloid progenitor cells in bone marrow, leading to long-term resistance to related and non-related pathogens infections. The induction of trained innate immunity can also polarize innate immune cells towards a hyperresponsive phenotype in the tumor microenvironment to exert antitumor effects. This review will discuss the current understanding of innate immune memory and the mechanisms during the induction of innate immunity, including signaling pathways, metabolic changes, and epigenetic rewriting. We also provide an overview of cross-protection against infectious diseases and cancers based on trained innate immunity.
Subject(s)
Trained ImmunityABSTRACT
BACKGROUND AND PURPOSE: Cancer has become one of the major killers of humanity due to the number of people over the age of 75 increasing with population ageing. The aim of this study was to analyse the incidence and mortality rates in people over 75 of 29 cancer types in 204 countries and regions, as well as the trends from 1990 to 2019. METHODS: Twenty-nine cancer types were collected from the Global Burden of Disease (GBD) 2019 database( https://vizhub.healthdata.org/gbd-results/ ). We collected global cancer data for 2019 in terms of sex, age, sociodemographic index (SDI), region, etc. The estimated annual percentage change (EAPC) was calculated to assess the trend of the cancer incidence and mortality rate from 1990 to 2019. RESULTS: In 2019, the number of new cancer cases and deaths among people 75 and older was almost 3 and 4.5 times that of 1990, respectively. From 1990 to 2019, there was a slow rise in incidence and a slight decline in mortality. There were significant differences in the cancer burden based on sex, age, region, and SDI. The cancer burden in men was higher than in women. In addition, the cancer burden varied from region to region. The highest cancer burden occurred in high-income North America. In addition, the higher the SDI was, the greater the burden of cancer. The incidence of cancer in high SDI was approximately seven times that of low SDI, and the trend of increase in high SDI was obvious. However, the trend of mortality in high SDI was decreasing, while it was increasing in low SDI. CONCLUSIONS: The present study focused on the cancer burden in adults over 75 years old. The findings in the study could serve as the basis for an analysis of the types of cancers that are most prevalent in different regions. This is beneficial for strategies of prevention and treatment according to the characteristics of different countries and regions to reduce the burden of cancer in older adults.
