المؤلفون: William, William N, Zhang, Jianjun, Zhao, Xin, Parra, Edwin R, Uraoka, Naohiro, Lin, Heather Y, Peng, S Andrew, El‐Naggar, Adel K, Rodriguez‐Canales, Jaime, Song, Jaejoon, Gillenwater, Ann M, Wistuba, Ignacio I, Myers, Jeffrey N, Gold, Kathryn A, Ferrarotto, Renata, Hwu, Patrick, Davoli, Teresa, Lee, J Jack, Heymach, John V, Papadimitrakopoulou, Vassiliki A, Lippman, Scott M

المصدر: Cancer. 129(5)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Dental/Oral and Craniofacial Disease, Cancer, Rare Diseases, Clinical Research, Humans, B7-H1 Antigen, Biomarkers, Tumor, Genomics, Head and Neck Neoplasms, Lymphocytes, Tumor-Infiltrating, Mouth Neoplasms, Neoplasm Recurrence, Local, Prospective Studies, Squamous Cell Carcinoma of Head and Neck, Tumor Microenvironment, copy-number alterations, genomics, head and neck cancer, HPV, immune profiling, PD-L1, precancer, T-cells, tumor microenvironment, Public Health and Health Services, Oncology & Carcinogenesis, Oncology and carcinogenesis, Public health

الوصف: BackgroundStudies of the immune landscape led to breakthrough trials of programmed death-1 (PD-1) inhibitors for recurrent/metastatic head and neck squamous cell carcinoma therapy. This study investigated the timing, influence of somatic copy-number alterations (SCNAs), and clinical implications of PD-L1 and immune-cell patterns in oral precancer (OPC).MethodsThe authors evaluated spatial CD3, CD3/8, and CD68 density (cells/mm2 ) and PD-L1 (membranous expression in cytokeratin-positive intraepithelial neoplastic cells and CD68) patterns by multiplex immunofluorescence in a 188-patient prospective OPC cohort, characterized by clinical, histologic, and SCNA risk factors and protocol-specified primary end point of invasive cancer. The authors used Wilcoxon rank-sum and Fisher exact tests, linear mixed effect models, mediation, and Cox regression and recursive-partitioning analyses.ResultsEpithelial, but not CD68 immune-cell, PD-L1 expression was detected in 28% of OPCs, correlated with immune-cell infiltration, 9p21.3 loss of heterozygosity (LOH), and inferior oral cancer-free survival (OCFS), notably in OPCs with low CD3/8 cell density, dysplasia, and/or 9p21.3 LOH. High CD3/8 cell density in dysplastic lesions predicted better OCFS and eliminated the excess risk associated with prior oral cancer and dysplasia. PD-L1 and CD3/8 patterns revealed inferior OCFS in PD-L1 high intrinsic induction and dysplastic immune-cold subgroups.ConclusionThis report provides spatial insight into the immune landscape and drivers of OPCs, and a publicly available immunogenomic data set for future precancer interrogation. The data suggest that 9p21.3 LOH triggers an immune-hot inflammatory phenotype; whereas increased 9p deletion size encompassing CD274 at 9p24.1 may contribute to CD3/8 and PD-L1 depletion during invasive transition. The inferior OCFS in PD-L1-high, immune-cold OPCs support the development of T-cell recruitment strategies.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/70x617xtTest

المؤلفون: Wang, Tracy Y, Vora, Amit N, Peng, S Andrew, Fonarow, Gregg C, Das, Sandeep, de Lemos, James A, Peterson, Eric D

المصدر: Journal of the American Heart Association. 5(1)

مصطلحات موضوعية: Humans, Myocardial Infarction, Hyperkalemia, Spironolactone, Stroke Volume, Treatment Outcome, Registries, Risk Assessment, Risk Factors, Age Factors, Time Factors, Databases, Factual, Aged, Aged, 80 and over, Medicare, Drug Utilization Review, United States, Female, Male, Heart Failure, Drug Prescriptions, Acute Kidney Injury, Mineralocorticoid Receptor Antagonists, Practice Patterns, Physicians', aldosterone antagonist therapy, heart failure, mortality, older population, Cardiovascular, Heart Disease, Clinical Research, 6.1 Pharmaceuticals, Cardiorespiratory Medicine and Haematology

الوصف: BackgroundWhile aldosterone antagonists have proven benefit among post-myocardial infarction (MI) patients with low ejection fraction (EF), how this treatment is used among older MI patients in routine practice is not well described.Methods and resultsUsing ACTION Registry-GWTG linked to Medicare data, we examined 12 080 MI patients ≥65 years with EF ≤40% who were indicated for aldosterone antagonist therapy per current guidelines and without documented contraindications. Of these, 11% (n=1310) were prescribed aldosterone antagonists at discharge. Notably, 10% of patients prescribed an aldosterone antagonist were eligible for, but not concurrently treated with, an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. Spironolactone was the predominantly prescribed aldosterone antagonist. At 2-year follow-up, aldosterone antagonist use was not associated with lower mortality (unadjusted 39% versus 38%; HR 0.99, 95% CI 0.88-1.33 using inverse probability-weighted propensity adjustment) except in symptomatic HF patients (HR 0.84, 95% CI 0.72-0.99, Pinteraction=0.009). Risks of hyperkalemia were low at 30 days, but significantly higher among patients prescribed aldosterone antagonists (unadjusted 2.3% versus 1.5%; adjusted HR 2.04, 95% CI 1.16-3.60), as was 2-year risk of acute renal failure (unadjusted 6.7% versus 4.8%; adjusted HR 1.39, 95% CI 1.01-1.92) compared with patients not prescribed aldosterone antagonists.ConclusionsAldosterone antagonist use among eligible older MI patients in routine clinical practice was not associated with lower mortality except in patients with HF symptoms, but was associated with increased risks of hyperkalemia and acute renal failure. These results underscore the importance of close post-discharge monitoring of this patient population.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9sk64721Test

المؤلفون: Mumma, Bryn E, Kontos, Michael C, Peng, S Andrew, Diercks, Deborah B

المصدر: American Heart Journal. 167(6)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Atherosclerosis, Heart Disease, Heart Disease - Coronary Heart Disease, Cardiovascular, Clinical Research, Aged, Ambulances, Angioplasty, Balloon, Coronary, Cohort Studies, Electrocardiography, Emergency Medical Services, Female, Geography, Humans, Linear Models, Male, Middle Aged, Myocardial Infarction, Retrospective Studies, Time-to-Treatment, Treatment Outcome, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology

الوصف: BackgroundCurrent guidelines recommend ≤90 minutes from first medical contact to percutaneous coronary intervention (FMC2B) for ST-segment-elevation myocardial infarction (STEMI) patients. We evaluated the relationship between patient home distance from a percutaneous coronary intervention (PCI) center, prehospital electrocardiogram (ECG) use, and FMC2B time among patients with STEMI.MethodsWe performed a retrospective cohort study including all STEMI patients in the ACTION-Get With The Guidelines registry from July 1, 2008, to September 30, 2012, who were transported by ambulance to a PCI center. Patient home distance was defined as the driving distance from the patient's home zip code to the PCI center address. Distance was classified into tertiles, and linear regression was used to characterize the interaction between prehospital ECG use and patient home distance with respect to FMC2B time.ResultsOf the 29,506 STEMI patients, 19,690 (67%) received a prehospital ECG. The median patient home distance to the PCI center was 11.0 miles among patients with and 9.9 miles among those without a prehospital ECG. Prehospital ECGs were associated with a 10-minute reduction in the FMC2B time (P < .0001), which was consistent across distance tertiles (11 vs 11 vs 10 minutes). The association between prehospital ECGs and shorter FMC2B was attenuated by 0.8 minute for every 10-mile increase in distance (interaction P = .0002).ConclusionsPrehospital ECGs are associated with a 10-minute reduction in the FMC2B time. However, patient home distance from a PCI center does not substantially change this association.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4dj0m2x4Test

المؤلفون: Granger, Christopher B., Bates, Eric R., Jollis, James G., Antman, Elliott M., Nichol, Graham, O'Connor, Robert E., Gregory, Tammy, Roettig, Mayme L., Peng, S. Andrew, Ellrodt, Gray, Henry, Timothy D., French, William J., Jacobs, Alice K.

المصدر: Journal of the American Heart Association ; volume 8, issue 1 ; ISSN 2047-9980

الوصف: Background We aimed to determine the change in treatment strategies and times to treatment over the first 5 years of the Mission: Lifeline program. Methods and Results We assessed pre‐ and in‐hospital care and outcomes from 2008 to 2012 for patients with ST ‐segment–elevation myocardial infarction at US hospitals, using data from the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry—Get With The Guidelines Registry. In‐hospital adjusted mortality was calculated including and excluding cardiac arrest as a reason for primary percutaneous coronary intervention delay. A total of 147 466 patients from 485 hospitals were analyzed. There was a decrease in the proportion of eligible patients not treated with reperfusion (6.2% versus 3.3%) and treated with fibrinolytic therapy (13.4% versus 7.0%). Median time from symptom onset to first medical contact was unchanged (≈50 minutes). Use of prehospital ECGs increased (45% versus 71%). All major reperfusion times improved: median first medical contact‐to‐device for emergency medical systems transport to percutaneous coronary intervention–capable hospitals (93 to 84 minutes), first door‐to‐device for transfers for primary percutaneous coronary intervention (130 to 112 minutes), and door‐in–door‐out at non–percutaneous coronary intervention–capable hospitals (76 to 62 minutes) (all P <0.001 over 5 years). Rates of cardiogenic shock and cardiac arrest, and overall in‐hospital mortality increased (5.7% to 6.3%). Adjusted mortality excluding patients with known cardiac arrest decreased by 14% at 3 years and 25% at 5 years ( P <0.001). Conclusions Quality of care for patients with ST ‐segment–elevation myocardial infarction improved over time in Mission: Lifeline, including increased use of reperfusion therapy and faster times‐to‐treatment. In‐hospital mortality improved for patients without cardiac arrest but did not appear to improve overall as the number of these high‐risk patients increased.

الإتاحة: https://doi.org/10.1161/jaha.118.008096Test

المؤلفون: Vial, Macarena R., Khan, Kashif A., O’Connell, Oisin, Peng, S. Andrew, Gomez, Daniel R., Chang, Joe Y., Rice, David C., Mehran, Reza, Jimenez, Carlos J., Grosu, Horiana B., Ost, David E., Eapen, George A.

المساهمون: National Institutes of Health National Cancer Institute

المصدر: The Annals of Thoracic Surgery ; volume 103, issue 5, page 1600-1605 ; ISSN 0003-4975

مصطلحات موضوعية: Cardiology and Cardiovascular Medicine, Pulmonary and Respiratory Medicine, Surgery

الإتاحة: https://doi.org/10.1016/j.athoracsur.2016.09.106Test
https://api.elsevier.com/content/article/PII:S0003497516313753?httpAccept=text/plainTest
https://api.elsevier.com/content/article/PII:S0003497516313753?httpAccept=text/xmlTest

المؤلفون: Hess, Connie N., Hellkamp, Anne S., Roe, Matthew T., Thomas, Laine, Scirica, Benjamin M., Peng, S. Andrew, Peterson, Eric D., Wang, Tracy Y.

المصدر: Journal of the American Heart Association ; volume 5, issue 3 ; ISSN 2047-9980

الوصف: Background While use of P2Y12 receptor inhibitor is recommended by guidelines, few studies have examined its effectiveness among older non– ST ‐segment elevation myocardial infarction patients who did not undergo coronary revascularization. Methods and Results We included unrevascularized non– ST ‐segment elevation myocardial infarction patients ≥65 years discharged home from 463 ACTION Registry‐ GWTG hospitals from 2007 to 2010. Rates of discharge clopidogrel use were described for patients with no angiography, angiography without obstructive coronary artery disease ( CAD ; ≥50% stenosis in ≥1 vessel), and angiography with obstructive CAD . Two‐year outcomes were ascertained from linked Medicare data and included composite major adverse cardiac events (defined as all‐cause death, myocardial infarction readmission, or revascularization), and individual components. Outcomes associated with clopidogrel use were adjusted using inverse probability‐weighted propensity modeling. Of 14 154 unrevascularized patients, 54.7% (n=7745) did not undergo angiography, 10.6% (n=1494) had angiography without CAD , and 34.7% (n=4915) had angiography with CAD . Discharge clopidogrel was prescribed for 42.2% of all unrevascularized patients: 37.8% without angiography, 34.1% without obstructive CAD at angiography, and 51.6% with obstructive CAD at angiography. Discharge clopidogrel use was not associated with major adverse cardiac events in any group: without angiography (adjusted hazard ratio [95% CI ]: 0.99 [0.93–1.06]), angiography without CAD (1.04 [0.74–1.47]), and angiography with CAD (1.12 [1.00–1.25], P interaction =0.20). Conclusions We found no association between discharge clopidogrel use and long‐term risk of major adverse cardiac events among older, unrevascularized non– ST ‐segment elevation myocardial infarction patients. Clopidogrel use in this population requires further prospective evaluation.

الإتاحة: https://doi.org/10.1161/jaha.115.002784Test

المؤلفون: Goyal, Abhinav, de Lemos, James A., Peng, S. Andrew, Thomas, Laine, Amsterdam, Ezra A., Hockenberry, Jason M., Peterson, Eric D., Wang, Tracy Y.

المصدر: Circulation: Cardiovascular Quality and Outcomes ; volume 8, issue 6, page 567-575 ; ISSN 1941-7713 1941-7705

الوصف: Background— Little is known about whether enrollment versus nonenrollment in Medicare’s prescription drug plan (Part D) is associated with better outcomes after acute myocardial infarction (AMI). Methods and Results— Using Medicare records linked to Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With The Guidelines, we identified 59 149 Medicare beneficiaries (age ≥65 years) discharged after AMI between January 2007 and December 2010. We described trends in Medicare Part D enrollment, and compared the following 30-day and 1-year outcomes: all-cause death, all-cause readmissions, and major adverse cardiac events (a composite of all-cause death or readmission for AMI or stroke) between Part D enrollees and nonenrollees, after adjustment for patient and hospital factors. From 2007 to 2010, 29 264 (49.5%) patients with AMI enrolled in Medicare were also participating in Part D by hospital discharge. All-cause 30-day death was more common among enrollees versus nonenrollees (4.0% versus 3.3%), but this difference was not statistically significant after multivariable adjustment (adjusted hazard ratio, 1.06 [95% confidence interval, 0.97–1.17]). Enrollees also had higher unadjusted risks of 30-day all-cause readmissions or major adverse cardiac events, and 1-year mortality, all-cause readmissions, or major adverse cardiac events, but these were attenuated after multivariable adjustment. Adherence to key secondary prevention medications (statins, β-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and P2Y 12 antagonists) remained low (range, 55%–64%) at 1 year post discharge among Part D enrollees. Conclusions— Only half of Medicare-insured patients with AMI were enrolled in Part D by hospital discharge, and their 30-day and 1-year adjusted outcomes did not differ substantially from nonenrollees. There remain opportunities for improvement in medication adherence among patients with prescription drug coverage.

الإتاحة: https://doi.org/10.1161/circoutcomes.115.001650Test

المؤلفون: Hess, Connie N., Peterson, Eric D., Peng, S. Andrew, de Lemos, James A., Fosbol, Emil L., Thomas, Laine, Bhatt, Deepak L., Saucedo, Jorge F., Wang, Tracy Y.

المساهمون: GlaxoSmithKline, Eli Lilly and Company, Merck, AstraZeneca, American College of Cardiology Foundation, Agency for Healthcare Research and Quality, Gilead Sciences, American Heart Association, Boehringer Ingelheim, Genentech, Janssen Pharmaceuticals

المصدر: Journal of the American College of Cardiology ; volume 66, issue 6, page 616-627 ; ISSN 0735-1097

مصطلحات موضوعية: Cardiology and Cardiovascular Medicine

الإتاحة: https://doi.org/10.1016/j.jacc.2015.05.062Test
https://api.elsevier.com/content/article/PII:S0735109715026765?httpAccept=text/plainTest
https://api.elsevier.com/content/article/PII:S0735109715026765?httpAccept=text/xmlTest

المؤلفون: Goyal, Abhinav, de Lemos, James, Peng, S. Andrew, Thomas, Laine, Amsterdam, Ezra, Hockenberry, Jason, Peterson, Eric, Wang, Tracy

المصدر: Journal of the American College of Cardiology ; volume 65, issue 10, page A50 ; ISSN 0735-1097

مصطلحات موضوعية: Cardiology and Cardiovascular Medicine

الإتاحة: https://doi.org/10.1016/s0735-1097Test(15)60050-x
https://api.elsevier.com/content/article/PII:S073510971560050X?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S073510971560050X?httpAccept=text/plainTest

المؤلفون: Sherwood, Matthew W., Wiviott, Stephen D., Peng, S. Andrew, Roe, Matthew T., DeLemos, James, Peterson, Eric D., Wang, Tracy Y.

المصدر: Journal of the American Heart Association ; volume 3, issue 2 ; ISSN 2047-9980

الوصف: Background P2Y12 antagonist therapy improves outcomes in acute myocardial infarction ( MI ) patients. Novel agents in this class are now available in the US . We studied the introduction of prasugrel into contemporary MI practice to understand the appropriateness of its use and assess for changes in antiplatelet management practices. Methods and Results Using ACTION Registry‐ GWTG (Get‐with‐the‐Guidelines), we evaluated patterns of P2Y12 antagonist use within 24 hours of admission in 100 228 ST elevation myocardial infarction (STEMI) and 158 492 Non‐ST elevation myocardial infarction (NSTEMI) patients at 548 hospitals between October 2009 and September 2012. Rates of early P2Y12 antagonist use were approximately 90% among STEMI and 57% among NSTEMI patients. From 2009 to 2012, prasugrel use increased significantly from 3% to 18% (5% to 30% in STEMI ; 2% to 10% in NSTEMI ; P for trend <0.001 for all). During the same period, we observed a decrease in use of early but not discharge P2Y12 antagonist among NSTEMI patients. Although contraindicated, 3.0% of patients with prior stroke received prasugrel. Prasugrel was used in 1.9% of patients ≥75 years and 4.5% of patients with weight <60 kg. In both STEMI and NSTEMI , prasugrel was most frequently used in patients at the lowest predicted risk for bleeding and mortality. Despite lack of supporting evidence, prasugrel was initiated before cardiac catheterization in 18% of NSTEMI patients. Conclusions With prasugrel as an antiplatelet treatment option, contemporary practice shows low uptake of prasugrel and delays in P2Y12 antagonist initiation among NSTEMI patients. We also note concerning evidence of inappropriate use of prasugrel, and inadequate targeting of this more potent therapy to maximize the benefit/risk ratio.

الإتاحة: https://doi.org/10.1161/jaha.114.000849Test