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81.
Weiyu Ye Anna Olsson-Brown Robert A. Watson Vincent T. F. Cheung Robert D. Morgan Isar Nassiri Rosalin Cooper Chelsea A. Taylor Umair Akbani Oliver Brain Rubeta N. Matin Nicholas Coupe Mark R. Middleton Mark Coles Joseph J. Sacco Miranda J. Payne Benjamin P. Fairfax 《British journal of cancer》2021,124(10):1661
Background Immune checkpoint blockers (ICBs) activate CD8+ T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear.Methods Retrospective evaluation of irAEs on survival was performed across primary (N = 144) and secondary (N = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab—sICB) or combination (nivolumab and ipilimumab—cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8+ T cells was sequenced and differential gene expression according to irAE development assessed.Results 58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P < 0.0001). Median survival for patients without irAEs was 16.6 months (95% CI: 10.9–33.4) versus not-reached (P = 2.8 × 10−6). Pre-treatment monocyte and neutrophil counts, but not BMI, were additional predictors of clinical outcome. Differential expression of numerous gene pathway members was observed in CD8+ T cells according to irAE development, and patients not developing irAEs demonstrating upregulated CXCR1 pre- and post-treatment.Conclusions Early irAE development post-ICB is associated with favourable survival in MM. Development of irAEs is coupled to expression of numerous gene pathways, suggesting irAE development in-part reflects baseline immune activation.Subject terms: Immunotherapy, Melanoma 相似文献
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R.D. Olmos R.C. de Figueiredo E.M. Aquino P.A. Lotufo I.M. Bensenor 《Brazilian journal of medical and biological research》2015,48(8):751-758
Thyroid diseases are common, and use of levothyroxine is increasing worldwide. We
investigated the influence of gender, race and socioeconomic status on the diagnosis
and treatment of thyroid disorders using data from the Brazilian Longitudinal Study
of Adult Health (ELSA-Brasil), a multicenter cohort study of civil servants (35-74
years of age) from six Brazilian cities. Diagnosis of thyroid dysfunction was by
thyrotropin (TSH), and free thyroxine (FT4) if TSH was altered, and the use of
specific medications. Multivariate logistic regression models were constructed using
overt hyperthyroidism/hypothyroidism and levothyroxine use as dependent variables and
sociodemographic characteristics as independent variables. The frequencies of overt
hyper- and hypothyroidism were 0.7 and 7.4%, respectively. Using whites as the
reference ethnicity, brown, and black race were protective for overt hypothyroidism
(OR=0.76, 95%CI=0.64-0.89, and OR=0.53, 95%CI=0.43-0.67, respectively, and black race
was associated with overt hyperthyroidism (OR=1.82, 95%CI=1.06-3.11). Frequency of
hypothyroidism treatment was higher in women, browns, highly educated participants
and those with high net family incomes. After multivariate adjustment, levothyroxine
use was associated with female gender (OR=6.06, 95%CI=3.19-11.49) and high net family
income (OR=3.23, 95%CI=1.02-10.23). Frequency of hyperthyroidism treatment was higher
in older than in younger individuals. Sociodemographic factors strongly influenced
the diagnosis and treatment of thyroid disorders, including the use of
levothyroxine. 相似文献
90.
Fudaba M. Tachibana D. Misugi T. Nakano A. Koyama M. 《Journal of thrombosis and thrombolysis》2021,51(3):818-820
Journal of Thrombosis and Thrombolysis - Amniotic fluid embolism (AFE) is a catastrophic condition in the peripartum period and still remains as a leading cause of maternal death. Although over 80%... 相似文献