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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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A typical time series in functional magnetic resonance imaging (fMRI) exhibits autocorrelation, that is, the samples of the time series are dependent. In addition, temporal filtering, one of the crucial steps in preprocessing of functional magnetic resonance images, induces its own autocorrelation. While performing connectivity analysis in fMRI, the impact of the autocorrelation is largely ignored. Recently, autocorrelation has been addressed by variance correction approaches, which are sensitive to the sampling rate. In this article, we aim to investigate the impact of the sampling rate on the variance correction approaches. Toward this end, we first derived a generalized expression for the variance of the sample Pearson correlation coefficient (SPCC) in terms of the sampling rate and the filter cutoff frequency, in addition to the autocorrelation and cross‐covariance functions of the time series. Through simulations, we illustrated the importance of the variance correction for a fixed sampling rate. Using the real resting state fMRI data sets, we demonstrated that the data sets with higher sampling rates were more prone to false positives, in agreement with the existing empirical reports. We further demonstrated with single subject results that for the data sets with higher sampling rates, the variance correction strategy restored the integrity of true connectivity. 相似文献
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Walid K. Abu Saleh Phillip Mason Odeaa Al Jabbari Hany Samir Brian A. Bruckner 《Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital》2015,42(6):569-571
The Impella 5.0, a percutaneously inserted left ventricular assist device, has been used to support patients who have severe heart failure or who are undergoing high-risk percutaneous coronary intervention. We report our surgical placement of the Impella 5.0, through a graft sewn to the aorta, to unload the left ventricle of a 59-year-old man who was undergoing venoarterial extracorporeal membrane oxygenation for postcardiotomy shock. The patient underwent successful placement of a long-term left ventricular assist device before his discharge from the hospital. The versatility of the Impella 5.0 is exemplified in this patient who was successfully bridged to long-term support. 相似文献
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Anna Grace Tribble Phillip Summers Haiying Chen Sara A. Quandt 《Archives of environmental & occupational health》2016,71(6):309-316
The jobs of Latino manual laborers place their mental and physical health at risk. This study evaluates the associations among musculoskeletal pain, mental health, and work organization in Latino manual laborers. Farmworkers and nonfarmworkers (n = 189) in North Carolina were interviewed for self-reported musculoskeletal pain, depressive symptoms, stress, work safety climate, and precarious job status. More nonfarmworkers than farmworkers had neck and shoulder pain, but they did not differ in other areas of musculoskeletal pain. Depressive symptoms had a significant association with neck and shoulder pain (p < .05). Precariousness had a significant association with back pain (p < .05). Farmworker participants had H-2A visas and were afforded some protection compared to nonfarmworker manual workers. Research is needed to improve policy that relieves pain and improves mental health for all Latino manual workers. 相似文献
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Bimal Bhindi Christine M. Lohse Phillip J. Schulte Ross J. Mason John C. Cheville Stephen A. Boorjian Bradley C. Leibovich R. Houston Thompson 《European urology》2019,75(5):766-772