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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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Stress Testing Versus CT Angiography in Patients With Diabetes and Suspected Coronary Artery Disease
Abhinav Sharma Adrian Coles Nishant K. Sekaran Neha J. Pagidipati Michael T. Lu Daniel B. Mark Kerry L. Lee Hussein R. Al-Khalidi Udo Hoffmann Pamela S. Douglas 《Journal of the American College of Cardiology》2019,73(8):893-902
Background
The optimal noninvasive test (NIT) for patients with diabetes and stable symptoms of coronary artery disease (CAD) is unknown.Objectives
The purpose of this study was to assess whether a diagnostic strategy based on coronary computed tomographic angiography (CTA) is superior to functional stress testing in reducing adverse cardiovascular (CV) outcomes (CV death or myocardial infarction [MI]) among symptomatic patients with diabetes.Methods
PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) was a randomized trial evaluating an initial strategy of CTA versus functional testing in stable outpatients with symptoms suggestive of CAD. The study compared CV outcomes in patients with diabetes (n = 1,908 [21%]) and without diabetes (n = 7,058 [79%]) based on their randomization to CTA or functional testing.Results
Patients with diabetes (vs. without) were similar in age (median 61 years vs. 60 years) and sex (female 54% vs. 52%) but had a greater burden of CV comorbidities. Patients with diabetes who underwent CTA had a lower risk of CV death/MI compared with functional stress testing (CTA: 1.1% [10 of 936] vs. stress testing: 2.6% [25 of 972]; adjusted hazard ratio: 0.38; 95% confidence interval: 0.18 to 0.79; p = 0.01). There was no significant difference in nondiabetic patients (CTA: 1.4% [50 of 3,564] vs. stress testing: 1.3% [45 of 3,494]; adjusted hazard ratio: 1.03; 95% confidence interval: 0.69 to 1.54; p = 0.887; interaction term for diabetes p value = 0.02).Conclusions
In diabetic patients presenting with stable chest pain, a CTA strategy resulted in fewer adverse CV outcomes than a functional testing strategy. CTA may be considered as the initial diagnostic strategy in this subgroup. (PROspective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]; NCT01174550) 相似文献3.
Evaluation of training nurses to perform semi‐automated three‐dimensional left ventricular ejection fraction using a customised workstation‐based training protocol 下载免费PDF全文
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Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT1 ) receptors in rabbit aorta and human recombinant AT1 receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'2 = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [125 I]AII binding to rabbit aortic membranes (AT, receptors) and [125 I][Sar1 , Ile8 ]AII binding to human recombinant AT1 receptors in a concentration-dependent manner with IC50 values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [125 I)AII binding to bovine cerebellum membranes (ÀT2 receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT1 receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT1 selective angiotensin receptor antagonist which exerts a competitive antagonism in the [125 I]AII binding assay and insurmountable AT1 receptor antagonism in the functional study. 相似文献
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R Hunter J A Williams D W Thomas M E Coles R Walsh A S Leong J G Copland 《The Australian and New Zealand journal of surgery》1988,58(10):791-794
The results of a screening programme for colorectal neoplasia in a high risk group using an immunochemical test for blood has been reported recently. This test is known as the faecal human haemoglobin (FHH) test. This paper reports the results of rescreening this group after an interval of 1-2 years. The FHH test was compared with a paper disc method. All individuals with positive tests were investigated and those with negative tests were offered investigation. The results confirm the value of the FHH test in screening a high risk group: 19 individuals in 1,153 participants were found to have a significant neoplasm (1.6%). The predictive value of the test for a significant neoplasm was 42%. A false negative rate of 2.6% was found, all lesions being benign. It appears to be more reliable than the paper disc method but the differences do not reach statistical significance. The FHH test is recommended for screening the general population over the age of 40 years, with rescreening annually. 相似文献
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Coles A. J. Cox A. Le Page E. 《世界核心医学期刊文摘》2006,2(5):39-40
1991—2002年间采用可长期消耗T淋巴细胞的人单克隆抗体(Cam path-1H)治疗58例多发性硬化症(M S)患者,患者的临床症状和炎性替代标记物得到抑制。在M S的复发-缓解(R R)和继发进展(SP)期,Cam path-1H可降低患者的年复发率(分别由2.2降至0.19和由0.7降至0.001,P<0.001)。7年前使 相似文献
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SUMMARY Elevated plasma levels of Lp(a) do seem to influence the progression of atherosclerosis. Evidence is emerging that certain apo(a) isoforms may be more atherogenic than others, and in transgenic mice free apo(a) has been shown to be associated with accelerated atherosclerosis. Currently it is not known whether treating elevated Lp(a) levels will reduce progression of atherosclerosis and, as therapeutic options are limited, mass screening of Lp(a) levels in populations is not indicated. The presence of raised Lp(a) levels, however, warrants aggressive treatment to reduce other cardiovascular risk factors. Continuing research to investigate the relationship of the apo(a) gene to other genes, including the plasminogen gene and apo(a)-related genes, will add further information pertaining to the evolution, function, regulation and clinical implications of Lp(a). 相似文献