Faculty Bibliography

OBJECTIVE: Osteoarthritis (OA) and gout have each been associated with increased cardiovascular disease (CVD), but their relative impact is unknown. We compared CVD rates among patients with gout versus patients with OA and no gout (OA-only). METHODS: We identified male patients at the VA New York Harbor Healthcare System with gout (with or without concur - rent OA) and with OA-only between August 2007 and August 2008. For each group, we collected baseline demographic data and CVD risk factors. The primary outcome was a composite index (CV4) of any diagnosis of coronary artery disease (CAD), angina, myocardial infarction (MI), or coro- nary bypass surgery (CABG). Secondary outcomes included individual diagnoses within the CV4, CHF, and death. We subsequently divided the gout patients into those who did versus did not have concurrent diagnoses of OA (gout-only; gout+OA). Logistic regression was used to compare the associations of OA-only, gout-only, and gout+OA with CV outcomes. RESULTS: 1,280 gout subjects met inclusion criteria (983 gout- only and 297 gout+OA), along with 1,231 OA-only subjects. Gout subjects overall had more CVD risk factors at baseline, including hypertension, hyperlipidemia, and chronic kidney disease, versus OA-only. Compared with OA-only, gout subjects overall had increased rates of all outcomes except MI. Both the gout-only and gout+OA subgroups also had increased risk for all outcomes except MI, and CABG in the case of gout+OA subjects. After adjusting for traditional CVD risk factors, both gout-only and gout+OA subjects continued to have increased risk for multiple CVD outcomes. Gout+OA did not impart ad- ditional risk over gout-only for any outcome studied. CONCLUSION: Our data suggest that gout is associated with higher risk of CVD compared with OA, and that OA does not impart any additive CVD risk to patients who also have gout. Significance and Innovations: * In our dataset, gout subjects both with and without con- comitant OA had more cardiovascular disease (CVD) risk factors at baseline, and higher prevalence of CVD outcomes, than patients with OA only. * After adjusting for traditional CVD risk factors, gout-only and gout+OA subjects continued to have increased rates of multiple CVD outcomes, suggesting an intrinsic CVD risk to the diagnosis of gout, compared with OA. * These observations underline that gout patients represent a group at increased CVD risk, for whom both rheumatic disease management and CVD prevention need to be addressed.

Background: Unlike for coronary artery disease, the association between neutrophil-lymphocyte ratio (NLR) and peripheral artery disease (PAD) has not been well established. The aim of this study was to determine the association between neutrophil-lymphocyte ratio and the severity of lower extremity peripheral artery disease. Methods: A retrospective chart review analysis identified 928 patients referred for peripheral angiography at a tertiary care center between December 2012 and June 2015. NLR was assessed from routine pre-procedural hemograms with automated differentials and available in 733 (79%) patients. Outcomes of interest included extent of disease on peripheral angiography and target vessel revascularization. Median follow-up was 10.4 months. Odds ratio (OR) [95% confidence intervals] was assessed using a logistic regression model. Results: There was a significant association between elevated NLR and the presence of severe multi-level PAD versus isolated suprapopliteal or isolated infrapopliteal disease (OR 1.42 [1.18-1.70], p=<0.001). This association between NLR and severe multi-level PAD remained significant even after adjustment for age (OR 1.31 [1.09-1.58], p=0.004); age, sex, race, and body mass index (OR 1.27 [1.05-1.5], p=0.015); and age, sex, race, body mass index, hypertension, diabetes, coronary artery disease, and creatinine (OR 1.25 [1.03-1.53], p=0.024). In patients who underwent endovascular intervention (n=523), there was no significant difference in the rate of target vessel revascularization on follow-up across tertiles of NLR (1st tertile 14.8%, 2nd tertile 14.1%, 3rd tertile 20.1%; p= 0.32). Conclusion: In a contemporary cohort of patients undergoing peripheral angiography with possible endovascular intervention, elevated NLR was independently associated with severe multi-level PAD

BACKGROUND: While strong associations are seen between serum uric acid levels and gout and cardiovascular disease (CVD), few studies have assessed differences between gout patients (pts) with and without CVD.
OBJECTIVE(S): To compare disease and comorbidity characteristics among gout pts with and without CVD, identifying differences in treatment patterns and healthcare utilization in a real-world cohort.
METHOD(S): Data were assessed from a survey of U.S. physicians and in-depth patient chart audits. Severity of gout was measured by physician global assessment, flares, organ/joint damage, and tophi. Type/dose of xanthine oxidase inhibitor, length of current treatment, sociodemographic factors, and physician type were identified. Multivariate and descriptive statistics described differences among pts with and without CVD and assessed urate-lowering therapy (ULT) use and gout disease control.
RESULT(S): 1159 patient charts were abstracted (738, CVD; 421, no CVD; 81% male; 38% >= 61 y; 71% white). Pts with CVD had longer duration of gout (52 vs. 34 mo; P < 0.001) and were more likely to have clinician-reported tophi (28% vs. 15%; P < 0.001), organ/joint damage (19% vs. 9%; P < 0.001), severe gout (19% vs. 11%; P < 0.001), and more flares in the past 12 mo. (2.1% vs. 1.8%; P = 0.017). Time from gout diagnosis to start of ULT was delayed for those with CVD (24 vs. 16 mo.; P = 0.02), but these pts were more likely to be on ULT (83% vs. 59%; P < 0.001). Gout pts with CVD were more likely to have obesity (28% vs. 18%; P < 0.001), diabetes (26% vs. 12%; P < 0.001), osteoarthritis (25% vs. 11%; P < 0.001), chronic kidney disease (17% vs. 5%; P < 0.001), and prostate disease (males, n = 933; 10% vs. 2%; P < 0.001). Gout pts with CVD were more likely to have an emergency department visit for gout in the past 12 mo. (12% vs. 7%; P = 0.003). Overall, ULT use was associated with better gout control. In a backward, stepwise logistic model in pts with CVD, those more likely be treated with ULT had organ/joint damage (odds ratio [OR] = 13.3), severe gout (OR = 1.5), or prostate disease (OR = 4.2), but these were not significant predictors for pts without CVD.
CONCLUSION(S): In this study, pts treated with ULT were more likely to have better gout control. Gout pts with CVD were more likely to be on ULT, despite delayed initiation of therapy. Given that gout pts with CVD were more likely to have additional comorbidities and more severe gout, the delay in treatment may be associated with the severity of disease in these pts. These data suggest that gout pts with CVD constitute a less healthy group in need of earlier, more aggressive therapy

The cardioprotective mechanisms of colchicine in patients with stable ischemic heart disease remain uncertain. We tested varying concentrations of colchicine on platelet activity in vitro and a clinically relevant 1.8-mg oral loading dose administered over 1 h in 10 healthy subjects. Data are shown as median [interquartile range]. Colchicine addition in vitro decreased light transmission platelet aggregation only at supratherapeutic concentrations but decreased monocyte- (MPA) and neutrophil-platelet aggregation (NPA) at therapeutic concentrations. Administration of 1.8 mg colchicine to healthy subjects had no significant effect on light transmission platelet aggregation but decreased the extent of MPA (28 % [22-57] to 22 % [19-31], p = 0.05) and NPA (19 % [16-59] to 15 % [11-30], p = 0.01), platelet surface expression of PAC-1 (370 mean fluorescence intensity (MFI) [328-555] to 333 MFI [232-407], p = 0.02) and P-selectin (351 MFI [269-492] to 279 [226-364], p = 0.03), and platelet adhesion to collagen (10.2 % [2.5-32.6] to 2.0 % [0.2-9.5], p = 0.09) 2 h post-administration. Thus, in clinically relevant concentrations, colchicine decreases expression of surface markers of platelet activity and inhibits leukocyte-platelet aggregation but does not inhibit homotypic platelet aggregation.

Kikuchi-Fujimoto's disease (KFD) and adult-onset Still's disease (AOSD) are rare inflammatory conditions with some overlapping features. We encountered a 22-year-old male patient who presented with daily fevers, neck discomfort, and sore throat and subsequently developed rash, arthritis, and cervical lymphadenopathy. Biopsy of the skin rash was consistent with KFD skin involvement. Given that the patient also met criteria for AOSD, a final diagnosis of KFD/AOSD co-occurrence was made. Anti-IL-1beta therapy with anakinra resulted in rapid resolution of all symptoms. A literature search identified eight more cases of KFD/AOSD. Fever, rash, arthritis, and lymphadenopathy were present in all patients. No case report demonstrated an association of rash eruption clearly associated with fever spikes. Duration of symptoms ranged from 3 weeks to 10 years. Seven patients had leukocytosis, six had anemia, and five demonstrated elevated ferritin and/or decreased glycosylated ferritin. Seven patients had elevated erythrocyte sedimentation rate (ESR), and seven had transaminitis. Eight of nine patients had no evidence of infectious disease. Autoantibodies were absent from all patients. KFD and AOSD are very rare diseases, yet they may overlap. The two conditions not only share several clinical and laboratory characteristics but also differ in characteristic ways. Given the rapid response observed with anakinra in the index patient, IL-1beta likely plays a role in both diseases.

To develop the next generation of translational investigators, New York University School of Medicine (NYUSOM) and the NYU-NYC Health and Hospitals Corporation Clinical and Translational Science Institute (NYU-HHC CTSI) developed the Master's of Science in Clinical Investigation dual-degree (MD/MSCI) program. This 5-year program dedicates 1 year to coursework and biomedical research, followed by a medical school/research overlap year, to prepare students for academic research careers. This paper details the MD/MSCI program's curriculum and approach to mentorship, describes the research/professional interests of students, and reports student productivity. In the first 4 years of the program (2010-2014) 20 students were matriculated; 7 (35%) were women, and 12 (60%) research projects were in surgical specialties. To date, 14 students have applied to residency, and half pursued surgical residency programs. Our students have produced 68 accepted abstracts, 15 abstracts in submission, 38 accepted papers, and 24 papers in submission. Despite the time-limited nature of this program, additional training in research design and implementation has promoted a high level of productivity. We conclude that dual-degree training in medicine and translational research is feasible for medical students and allows for meaningful participation in valuable projects. Follow-up is warranted to evaluate the academic trajectory of these students. Clin Trans Sci 2015; Volume #: 1-6.

Gout is characterized by the deposition of monosodium urate crystals and by acute and chronic inflammation in response to crystals so deposited. Multiple case reports and series describe the deposition of monosodium urate in the spine as a rare manifestation of gout, but the actual prevalence of spinal involvement is unknown and likely to be higher than generally anticipated. Here we review the characteristics of 131 previously reported cases of spinal involvement in gout. We focus in particular on the use of imaging modalities and the extent to which they correlate with presenting symptoms and tissue diagnoses. The recent innovation of using dual-energy computerized tomography to identify urate crystal deposition holds promise for reducing the need for surgical intervention and for establishing a true prevalence rate for spinal gout.

Background/Purpose: Osteoarthritis (OA) and gout are each associated with increased cardiovascular disease (CVD), but their relative impacts on CV risk are not known. We compared rates of CVD among patients with OA (OA-only), gout (gout-only), or both (gout+OA). Methods: We used ICD-9 codes to identify male patients from within our VA health care system with OA-only, goutonly, or gout+OA, and an active medical record between August 2007 and August 2008. For each group, we collected baseline demographics and CVD risk factors. The primary outcome was a composite index (CV4) consisting of any diagnosis of myocardial infarction (MI), angina, coronary bypass surgery (CABG), and/or coronary artery disease (CAD). Secondary outcomes included individual diagnoses within the CV4, congestive heart failure (CHF) and death. Logistic regression was used to compare the associations of OA-only, gout-only, and gout+OA with CV outcomes, adjusting for traditional CV risk factors: age, race, hypertension (HTN), diabetes mellitus, hyperlipidemia (HLD), chronic kidney disease (CKD), and smoking. Results: 1280 gout subjects met inclusion criteria (983 gout-only, 297 gout+OA), along with 1231 OA-only subjects. Gout subjects, with or without OA, had more CVD risk factors at baseline, including HTN, HLD and CKD vs. OA-only. In an unadjusted model, a diagnosis of gout increased the risk for CV4, CAD, angina, CABG, CHF, and death compared to a diagnosis of OA-only. In a fully adjusted model, gout-only subjects continued to have increased risk for all outcomes except MI and death compared to OA-only subjects, while gout+OA subjects exhibited increased risk for angina and CHF (Table 1). Gout+OA did not impart additional risk over gout-only for any outcome except CABG. Conclusion: Our data suggest that gout is associated with higher risk of CVD compared with OA, that at least some of this increased risk may be independent of traditional risk factors, and that OA does not impart additive CVD risk to patients who also have gout. (Table Presented)