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Sex determines the presentation and outcomes in MPN and is related to sex-specific differences in the mutational burden.

ABSTRACT: The factors underlying the variable presentation and clinical course of myeloproliferative neoplasms (MPNs) remain unclear. The aim of this study was to evaluate the independent effect of sex on MPN presentation and outcomes. A total of 815 patients with essential thrombocytosis, polycythemia vera, or primary myelofibrosis were evaluated between 2005 and 2019, and the association of sex with presenting phenotype, JAK2 V617F burden, progression, and survival was examined. Men presented more often with primary myelofibrosis vs essential thrombocytosis (relative risk, 3.2; P < .001) and polycythemia vera (relative risk, 2.1; P < .001), had higher rates of transformation to secondary myelofibrosis (hazard ratio [HR], 1.55; P = .013) and acute myeloid leukemia (HR, 3.67; P < .001), and worse survival (HR, 1.63; P = .001) independent of age, phenotype at diagnosis, and MPN-specific mutation. Men had higher JAK2 V617F allele burdens in their CD34+ cells (P = .001), acquired more somatic mutations (P = .012) apart from the MPN-specific mutations, and had an increased frequency of 1 (odds ratio, 2.35; P = .017) and 2 (odds ratio, 20.20; P = .011) high-risk mutations independent of age, phenotype, and driver mutation. Male sex is an independent predictor of poor outcomes in MPNs. This seems to be due to an increased risk of non-MPN-specific somatic mutations, particularly high-risk mutations, rather than MPN-specific mutation allele frequency. Conversely, disease progression in female subjects is more dependent on JAK2 mutation allele burden than on acquisition of other somatic mutations. Sex should be considered in prognostic models and when evaluating therapeutic strategies in MPNs.

SUBMITTER: Karantanos T

PROVIDER: S-EPMC7322953 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Sex determines the presentation and outcomes in MPN and is related to sex-specific differences in the mutational burden.

Karantanos Theodoros T Chaturvedi Shruti S Braunstein Evan M EM Spivak Jerry J Resar Linda L Karanika Styliani S Williams Donna M DM Rogers Ophelia O Gocke Christopher D CD Moliterno Alison R AR

Blood advances 20200601 12

The factors underlying the variable presentation and clinical course of myeloproliferative neoplasms (MPNs) remain unclear. The aim of this study was to evaluate the independent effect of sex on MPN presentation and outcomes. A total of 815 patients with essential thrombocytosis, polycythemia vera, or primary myelofibrosis were evaluated between 2005 and 2019, and the association of sex with presenting phenotype, JAK2 V617F burden, progression, and survival was examined. Men presented more often ...[more]

PMID: 32542392

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Project description:Background Thoracic endovascular aortic repair (TEVAR) has been increasingly used for the treatment of descending thoracic aortic aneurysms and dissections. This study sought to evaluate the influence of sex on outcomes after TEVAR. Methods and Results This was an observational study from the Nationwide Readmissions Database analyzing all patients who underwent TEVAR from 2010 to 2018. Sampling weights were used to generate national estimates. International Classification of Diseases-Clinical Modification codes were used to identify patients with thoracic aortic aneurysms or dissections who underwent TEVAR. Patients were dichotomized according to sex, and 1:1 propensity score matching was applied. Mixed model regression for in-hospital mortality and weighted logistic regression with bootstrapping for 30-day readmissions were performed. A supplemental analysis was performed according to pathology (aneurysm or dissection). A weighted total of 27 118 patients were identified. Propensity-matching yielded 5026 risk-adjusted pairs. Men were more likely to undergo TEVAR for type B aortic dissection, whereas women were more likely to undergo TEVAR for aneurysm. In-hospital mortality was roughly 5% and was equivalent in the matched groups. Men were more likely to have paraplegia, acute kidney injury, and arrhythmias, while women were more likely to require transfusions after TEVAR. There were no significant differences in myocardial infarction, heart failure, respiratory failure, spinal cord ischemia, mesenteric ischemia, stroke, or 30-day readmission between the matched groups. On regression analysis, sex was not an independent risk factor for in-hospital mortality. Female sex was, however, significantly associated with a decreased odds of 30-day readmission (odds ratio, 0.90 [95% CI, 0.87-0.92]; P<0.001). Conclusions Women are more likely to undergo TEVAR for aneurysms, while men are more likely to undergo TEVAR for type B aortic dissection. In-hospital mortality after TEVAR is comparable among men and women irrespective of indication. Female sex is independently associated with a reduced odds of 30-day readmission after TEVAR.

Dataset Information

Sex determines the presentation and outcomes in MPN and is related to sex-specific differences in the mutational burden.

Publications

Sex determines the presentation and outcomes in MPN and is related to sex-specific differences in the mutational burden.

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