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1.
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
2.
A mixed‐method study of effects of a therapeutic play intervention for children on parental anxiety and parents' perceptions of the intervention
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3.
PNPLA3 gene polymorphism and response to lifestyle modification in patients with nonalcoholic fatty liver disease
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Prevalence of Potentially Inappropriate Prescribing Among Hong Kong Older Adults: A Comparison of the Beers 2003, Beers 2012, and Screening Tool of Older Person's Prescriptions and Screening Tool to Alert doctors to Right Treatment Criteria
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![点击此处可从《Journal of the American Geriatrics Society》网站下载免费的PDF全文](/ch/ext_images/free.gif)
8.
F Lofaso F Nicot M Lejaille L Falaize A Louis A Clement J-C Raphael D Orlikowski B Fauroux 《The European respiratory journal》2006,27(5):980-982
Sniff nasal inspiratory pressure (SNIP) measurement is a volitional noninvasive assessment of inspiratory muscle strength. A maximum of 10 sniffs is generally used. The purpose of the present study was to investigate whether the maximum SNIP improved after the tenth sniff. In total, 20 healthy volunteers and 305 patients with various neuromuscular and lung diseases were encouraged to perform 40 and 20 sniffs, respectively. The best SNIP among the first 10 sniffs was lower than the best SNIP among the next 10 sniffs in the healthy volunteers and patients. The SNIP improvement after the twentieth sniff was marginal. In conclusion, a learning effect persists after the tenth sniff. The current authors suggest using 10 additional sniffs when the best result of the first 10 sniffs is slightly below normal, or when sniff nasal inspiratory pressure is used to monitor a progressive decline in inspiratory muscle strength. 相似文献
9.
P F Plouin D L Clement H Boccalon J Dormandy I Durand-Zaleski G Fowkes L Norgren T Brown 《International angiology》2003,22(4):333-339
Atherosclerotic renal artery stenosis (ARAS) may cause hypertension, progressive renal failure, and recurrent pulmonary edema. It typically occurs in high risk patients with coexistent vascular disease elsewhere. Most patients with ARAS are likely to die from coronary heart disease or stroke before end-stage renal failure occurs. Recent controlled trials have shown that most patients undergoing angioplasty to treat renovascular hypertension still need antihypertensive agents 6 or 12 months after the procedure. Nevertheless, the number of antihypertensive agents required to control blood pressure adequately is lower following angioplasty than for medication alone. Trials assessing the value of revascularization for preserving renal function or preventing clinical events are only in the early recruitment phase. Revascularization should be undertaken in patients with ARAS and resistant hypertension or heart failure, and probably in those with rapidly deteriorating renal function or with an increase in plasma creatinine levels during angiotensin-converting enzyme inhibition. With or without revascularization, medical therapy using antihypertensive, hypolipidemic and antiplatelet agents is necessary in almost all cases. 相似文献
10.
J. M. Bourre M. Clement J. Chaudiere 《Molecular and chemical neuropathology / sponsored by the International Society for Neurochemistry and the World Federation of Neurology and research groups on neurochemistry and cerebrospinal fluid》1987,7(2):91-97
In the brain of quaking and shiverer mutants, vitamin E content was normal when related to both wet weight and dry weight. When related to lipid extract, phosphorus, and polyunsaturated fatty acids, vitamin E was slightly increased only in the quaking mutant. In the sciatic nerve from trembler mutants, vitamin E was 134% of control values in the dry material, but normal in relation to wet weight. It was 260% in the lipid extract and 716% based on phosphorus. In relation to total fatty acids, there was a threefold increase in trembler mutants. Interestingly, it was increased approximately three times when related to 18∶2 n?6, 20∶4 n?6, and 20∶5 n?3, and seven times when related to 22∶6 n?3. The fact that the amount of vitamin E in fresh weight was normal, suggests that vitamin E plays a role in some nonmembrane material, such as the extracellular matrix or the basal lamina. 相似文献