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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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ABSTRACTCommunication between health professionals and patients is an intergroup phenomenon where the health professional has the most power and status. Over the past few decades, there has been a steady increase in the availability to patients of information about healthcare and specific diseases on the Internet. In this paper, we ask whether the use of Internet health information assists patients to manage their consultations with health professionals better and whether it alters the intergroup dynamic by providing a more equal status for patients. In this study 370 participants from Australia and Canada completed a survey that included a ‘willingness to communicate with health professionals’ scale. They also commented on their use and trust of Internet health information. Thematic analysis suggests that patients’ use of Internet health information serves as a broker between patients and their health provider in health consultations. We discuss the implications of these findings for health practitioners as they address how easier Internet access influences patient interactions with health professionals. We consider future research directions these finding provide in explaining communication behaviour in this context. 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
Background
Partial nephrectomy (PN) is generally favored for cT1 tumors over radical nephrectomy (RN) when technically feasible. However, it can be unclear whether the additional risks of PN are worth the magnitude of renal function benefit.Objective
To develop preoperative tools to predict long-term estimated glomerular filtration rate (eGFR) beyond 30 d following PN and RN, separately.Design, setting, and participants
In this retrospective cohort study, patients who underwent RN or PN for a single nonmetastatic renal tumor between 1997 and 2014 at our institution were identified. Exclusion criteria were venous tumor thrombus and preoperative eGFR <15 ml/min/1.73 m2.Intervention
RN and PN.Outcome measurements and statistical analysis
Hierarchical generalized linear mixed-effect models with backward selection of candidate preoperative features were used to predict long-term eGFR following RN and PN, separately. Predictive ability was summarized using marginal , which ranges from 0 to 1, with higher values indicating increased predictive ability.Results and limitations
The analysis included 1152 patients (13 206 eGFR observations) who underwent RN and 1920 patients (18 652 eGFR observations) who underwent PN, with mean preoperative eGFRs of 66 ml/min/1.73 m2 (standard deviation [SD] = 18) and 72 ml/min/1.73 m2 (SD = 20), respectively. The model to predict eGFR after RN included age, diabetes, preoperative eGFR, preoperative proteinuria, tumor size, time from surgery, and an interaction between time from surgery and age (marginal ). The model to predict eGFR after PN included age, presence of a solitary kidney, diabetes, hypertension, preoperative eGFR, preoperative proteinuria, surgical approach, time from surgery, and interaction terms between time from surgery and age, diabetes, preoperative eGFR, and preoperative proteinuria (marginal ). Limitations include the lack of data on renal tumor complexity and the single-center design; generalizability needs to be confirmed in external cohorts.Conclusions
We developed preoperative tools to predict renal function outcomes following RN and PN. Pending validation, these tools should be helpful for patient counseling and clinical decision-making.Patient summary
We developed models to predict kidney function outcomes after partial and radical nephrectomy based on preoperative features. This should help clinicians during patient counseling and decision-making in the management of kidney tumors. 相似文献8.
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Quantitative chemical exchange saturation transfer (qCEST) MRI – omega plot analysis of RF‐spillover‐corrected inverse CEST ratio asymmetry for simultaneous determination of labile proton ratio and exchange rate 下载免费PDF全文
Renhua Wu Gang Xiao Iris Yuwen Zhou Chongzhao Ran Phillip Zhe Sun 《NMR in biomedicine》2015,28(3):376-383
Chemical exchange saturation transfer (CEST) MRI is sensitive to labile proton concentration and exchange rate, thus allowing measurement of dilute CEST agent and microenvironmental properties. However, CEST measurement depends not only on the CEST agent properties but also on the experimental conditions. Quantitative CEST (qCEST) analysis has been proposed to address the limitation of the commonly used simplistic CEST‐weighted calculation. Recent research has shown that the concomitant direct RF saturation (spillover) effect can be corrected using an inverse CEST ratio calculation. We postulated that a simplified qCEST analysis is feasible with omega plot analysis of the inverse CEST asymmetry calculation. Specifically, simulations showed that the numerically derived labile proton ratio and exchange rate were in good agreement with input values. In addition, the qCEST analysis was confirmed experimentally in a phantom with concurrent variation in CEST agent concentration and pH. Also, we demonstrated that the derived labile proton ratio increased linearly with creatine concentration (P < 0.01) while the pH‐dependent exchange rate followed a dominantly base‐catalyzed exchange relationship (P < 0.01). In summary, our study verified that a simplified qCEST analysis can simultaneously determine labile proton ratio and exchange rate in a relatively complex in vitro CEST system. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
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