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Activated Platelets Induce Endothelial Cell Inflammatory Response in Psoriasis Via COX-1 (Cyclooxygenase-2)
Garshick, Michael S; Tawil, Michael; Barrett, Tessa J; Salud-Gnilo, Charissa M; Eppler, Michael; Lee, Angela; Scher, Jose U; Neimann, Andrea L; Jelic, Sanja; Mehta, Nehal N; Fisher, Edward A; Krueger, James G; Berger, Jeffrey S
OBJECTIVE:=0.02). CONCLUSIONS:In patients with psoriasis, platelets are activated and induce endothelial cell inflammation. Low-dose aspirin improved endothelial cell health in psoriasis via platelet COX-1 inhibition. These data demonstrate a previously unappreciated role of platelets in psoriasis and endothelial cell inflammation, which suggests that aspirin may be effective in improving vascular health in patients with psoriasis. Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03228017.
PMID: 32131611
ISSN: 1524-4636
CID: 4339722
Chronic kidney disease and outcomes of lower extremity revascularization for peripheral artery disease
Smilowitz, Nathaniel R; Bhandari, Nipun; Berger, Jeffrey S
BACKGROUND & AIMS/OBJECTIVE:Renal disease is a risk factor for peripheral artery disease (PAD), yet its impact on outcomes after lower extremity (LE) revascularization is not well established. We aimed to characterize the association between chronic kidney disease (CKD) and/or end stage renal disease (ESRD) and post-procedural outcomes in PAD patients undergoing LE revascularization in the United States. METHODS:Adults age ≥18 years undergoing surgical or endovascular LE revascularization for PAD with and without CKD or ESRD were identified from the 2014 Nationwide Readmissions Database. Major adverse cardiovascular events (MACE), defined as a composite of death, myocardial infarction or ischemic stroke, were identified for patients with and without renal disease. All-cause hospital readmissions within 6 months of discharge were determined for all survivors. RESULTS:Among 39,441 patients with PAD hospitalized for LE revascularization, 10,530 had renal disease (26.7%), of whom 69% had CKD without ESRD and 31% had ESRD. Patients with renal disease were more likely to have MACE after LE revascularization (5.2% vs. 2.5%; adjusted OR [aOR] 1.74, 95% CI 1.40-2.16), require LE amputation (26.1% vs. 12.2%; aOR 1.33, 95% CI 1.19-1.50), and require hospital readmission within 6 months (61.0% vs. 43.6%; adjusted HR [aHR] 1.38, 95% CI 1.28-1.48) compared to those without renal disease. CONCLUSIONS:Renal disease is common among patients undergoing LE revascularization for PAD and was independently associated with in-hospital MACE, LE amputation, and hospital readmission within 6 months. Additional efforts to improve outcomes of patients with renal disease and PAD requiring LE revascularization are necessary.
PMID: 31948675
ISSN: 1879-1484
CID: 4264552
Evaluation of machine learning methodology for the prediction of healthcare resource utilization and healthcare costs in patients with critical limb ischemia-is preventive and personalized approach on the horizon?
Berger, Jeffrey S; Haskell, Lloyd; Ting, Windsor; Lurie, Fedor; Chang, Shun-Chiao; Mueller, Luke A; Elder, Kenneth; Rich, Kelly; Crivera, Concetta; Schein, Jeffrey R; Alas, Veronica
Background/UNASSIGNED:Critical limb ischemia (CLI) is a severe stage of peripheral arterial disease and has a substantial disease and economic burden not only to patients and families, but also to the society and healthcare systems. We aim to develop a personalized prediction model that utilizes baseline patient characteristics prior to CLI diagnosis to predict subsequent 1-year all-cause hospitalizations and total annual healthcare cost, using a novel Bayesian machine learning platform, Reverse Engineering Forward Simulation™ (REFS™), to support a paradigm shift from reactive healthcare to Predictive Preventive and Personalized Medicine (PPPM)-driven healthcare. Methods/UNASSIGNED:Patients ≥ 50 years with CLI plus clinical activity for a 6-month pre-index and a 12-month post-index period or death during the post-index period were included in this retrospective cohort of the linked Optum-Humedica databases. REFS™ built an ensemble of 256 predictive models to identify predictors of all-cause hospitalizations and total annual all-cause healthcare costs during the 12-month post-index interval. Results/UNASSIGNED:The mean age of 3189 eligible patients was 71.9 years. The most common CLI-related comorbidities were hypertension (79.5%), dyslipidemia (61.4%), coronary atherosclerosis and other heart disease (42.3%), and type 2 diabetes (39.2%). Post-index CLI-related healthcare utilization included inpatient services (14.6%) and ≥ 1 outpatient visits (32.1%). Median annual all-cause and CLI-related costs per patient were $30,514 and $2196, respectively. REFS™ identified diagnosis of skin and subcutaneous tissue infections, cellulitis and abscess, use of nonselective beta-blockers, other aftercare, and osteoarthritis as high confidence predictors of all-cause hospitalizations. The leading predictors for total all-cause costs included region of residence and comorbid health conditions including other diseases of kidney and ureters, blindness of vision defects, chronic ulcer of skin, and chronic ulcer of leg or foot. Conclusions/UNASSIGNED:REFS™ identified baseline predictors of subsequent healthcare resource utilization and costs in CLI patients. Machine learning and model-based, data-driven medicine may complement physicians' evidence-based medical services. These findings also support the PPPM framework that a paradigm shift from post-diagnosis disease care to early management of comorbidities and targeted prevention is warranted to deliver a cost-effective medical services and desirable healthcare economy.
PMCID:7028871
PMID: 32140185
ISSN: 1878-5077
CID: 4340842
Sex-Specific Risks of Major Cardiovascular and Limb Events in Patients With Symptomatic Peripheral Artery Disease
Haine, Axel; Kavanagh, Sarah; Berger, Jeffrey S; Hess, Connie N; Norgren, Lars; Fowkes, F Gerry R; Katona, Brian G; Mahaffey, Kenneth W; Blomster, Juuso I; Patel, Manesh R; Jones, W Schuyler; Rockhold, Frank W; Hiatt, William R; Baumgartner, Iris
BACKGROUND:Patients with peripheral artery disease (PAD) have a higher risk of major adverse cardiovascular events (MACE) compared with those without PAD. OBJECTIVES/OBJECTIVE:The aim of this post hoc analysis was to evaluate sex-specific differences in MACE and limb events in the EUCLID (Examining Use of Ticagrelor in PAD) trial. METHODS:Cox proportional hazards models were used to compare time-to-event outcomes stratified by sex. Covariates were introduced after adjusted model selection. RESULTS:EUCLID enrolled 13,885 patients with PAD (28% women [n = 3,888]). PAD severity and medical treatment were comparable between sexes, whereas prior lower extremity revascularization was reported less frequently in women (54.8% vs. 57.3%; p = 0.006). Women were older (mean ± SD age: 67.8 ± 8.9 vs. 66.1 ± 8.2 years; p < 0.001) and more likely to have diabetes mellitus (p = 0.004), hypertension, hyperlipidemia, and chronic kidney disease (all p < 0.001). Over a mean follow-up of 30 months, women had a lower risk of MACE (9.5% vs. 11.2%; adjusted hazard ratio: 0.77; 95% confidence interval: 0.68 to 0.88; p < 0.001) and all-cause-mortality (7.6% vs. 9.7%; adjusted hazard ratio: 0.61; 95% confidence interval: 0.53 to 0.71; p < 0.001). In contrast, risk for major adverse limb events (2.6% vs. 3.0%) and hospitalization for acute limb ischemia (1.6% vs. 1.7%) were not different by sex. CONCLUSIONS:Although women with PAD are at lower risk for MACE and all-cause mortality, risk for limb events was similar between sexes over a mean follow-up of 30 months. Understanding sex-specific differences and dissociation between baseline cardiovascular risk and subsequent cardiovascular events requires further investigation. (A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease [EUCLID]; NCT01732822).
PMID: 32057375
ISSN: 1558-3597
CID: 4303842
Correction to: Real-World Predictors of Major Adverse Cardiovascular Events and Major Adverse Limb Events Among Patients with Chronic Coronary Artery Disease and/or Peripheral Arterial Disease
Berger, Ariel; Simpson, Alex; Leeper, Nicholas J; Murphy, Brian; Nordstrom, Beth; Ting, Windsor; Zhao, Qi; Berger, Jeffrey
In the original article. The third author name is incorrect. The correct name is Nicholas J. Leeper.
PMID: 31933050
ISSN: 1865-8652
CID: 4334832
Real-World Predictors of Major Adverse Cardiovascular Events and Major Adverse Limb Events Among Patients with Chronic Coronary Artery Disease and/or Peripheral Arterial Disease
Berger, Ariel; Simpson, Alex; Leeper, Nicholas; Murphy, Brian; Nordstrom, Beth; Ting, Windsor; Zhao, Qi; Berger, Jeffrey
INTRODUCTION/BACKGROUND:Collectively, coronary artery disease (CAD) and peripheral artery disease (PAD) are highly prevalent and are associated with increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Improved ability to identify those at highest risk of these events may help optimize secondary prevention efforts in this population. METHODS:Using the Optum Integrated Database, a healthcare claims database linked to electronic medical records (EMR), we identified patients with CAD and/or PAD between January 1, 2009, and September 30, 2016. Index date was the earliest date on which chronic and stable disease was established. Follow-up ran from index date until earliest of patient death, plan disenrollment, or end of study. We developed multivariate Cox proportional hazards models to identify predictors of MACE and/or MALE, limited to measures presumed available to clinicians during patient encounters (e.g., age, presence of selected comorbidities). RESULTS: = 0.98), ranging from 2.3 per 100 PYs among those without predictors (4.9% of patients) to 18.7 per 100 PYs among those with ≥ 6 (6.9%). Patients with ≥ 1 predictor experienced 7.4 MACE and/or MALE per 100 PYs. CONCLUSION/CONCLUSIONS:Readily identifiable predictors can be used to identify subgroups with chronic CAD and/or PAD at elevated risk of MACE and/or MALE. Further research is required to understand the degree to which these subgroups may benefit from early identification and treatment with secondary prevention therapies. FUNDING/BACKGROUND:Janssen Pharmaceuticals.
PMID: 31705434
ISSN: 1865-8652
CID: 4190632
Genome-wide Association Study of Peripheral Artery Disease and Critical Limb Ischemia Identifies Novel Genetic Loci and Coagulation Pathways [Meeting Abstract]
Krittanawong, Chayakrit; Narula, Jagat; Johnson, Kipp W.; Narula, Navneet; Berger, Jeffrey S.; Olin, Jeffrey W.; Al-Mulla, Fahd; Al-Ozairi, Ebaa; Do, Ron; Nadkarni, Girish
ISI:000607190402144
ISSN: 0009-7322
CID: 4916702
Cardiovascular Risk Assessment for Noncardiac Surgery - Reply [Letter]
Smilowitz, N R; Berger, J S
EMBASE:633585417
ISSN: 0098-7484
CID: 4713392
Cardiovascular Risk Assessment for Noncardiac Surgery Reply [Letter]
Smilowitz, Nathaniel R.; Berger, Jeffrey S.
ISI:000596035700032
ISSN: 0098-7484
CID: 4729732
Sex Differences in Myocardial Injury and Outcomes of Covid-19 Infection [Meeting Abstract]
Talmor, Nina; Mukhopadhyay, Amrita; Xia, Yuhe; Adhikari, Samrachana; Pulgarin, Claudia; Iturrate, Eduardo; Horwitz, Leora I.; Hochman, Judith S.; Berger, Jeffrey S.; Fishman, Glenn I.; Troxel, Andrea B.; Reynolds, Harmony
ISI:000607190404381
ISSN: 0009-7322
CID: 5263742