Faculty Bibliography

Background/Purpose: The relationship between gout and cancer remains unclear. Whereas some studies have reported possible anti-cancer benefits of uric acid and monosodium urate crystals, others have found an increased risk of cancer in gout patients. Our study aimed to clarify the relationship between gout and colon metaplasia, including cancer and polyps. Methods: We conducted a retrospective study of patients in a VA hospital system using two distinct approaches. To obtain a historical, cross-sectional view of colon cancer prevalence, we assessed the presence of physiciancoded diagnoses of colon cancer and/or polyps in gout patients, versus patients with osteoarthritis (OA) but no gout, with active records in our computerized patient record system (CPRS) between 2007 and 2008. Lung and prostate cancer prevalence were recorded for comparison. In the second approach, we included only patients with documented colonoscopy reports in CPRS, and performed a retrospective cohort study of colon cancer and polyp incidences in gout versus OA patients over a ten-year period (2001-2010). In addition, colon cancer and polyp incidences were compared between patients who had undergone screening versus diagnostic colonoscopy, those who used aspirin or NSAIDs and those who did not, and between gout patients who used allopurinol and/or colchicine and those who did not. Results: 1287 gout patients and 1287 OA patients were included. Gout and OA patients were similar in age, ethnicity, BMI and smoking history. Gout patients had a lower physician-coded prevalence of all colonic lesions (cancer or polyp: 1.8 versus 9.6%, p<0.001), and a lower prevalence of colon cancer (1.0 versus 1.9%, p<0.001), than OA patients (Figure A). Lung and prostate cancer were similar between the two groups. Among 581 gout patients and 598 OA subjects with documented colonoscopies, the ten-year incidence of colon cancer was lower in gout patients than in patients with OA (0.8 versus 3.7%, p=0.0008) (Figure B). This difference in colon cancer incidence remained significant after accounting for NSAID and/or aspirin use. Among gout patients, the use of colchicine and/or allopurinol, as well as the presence or absence of concomitant of OA, did not appear to influence colon cancer prevalence. Differences in colon cancer incidence were significant between gout and OA patients undergoing diagnostic colonoscopy (0.5% in gout patients versus 4.6% in OA patients, p<0.001) but not those undergoing screening colonoscopy (0.9% in gout patients versus 1% in OA patients, p=1.0). No protective effect of gout was observed for prostate or lung cancer. Conclusion: Patients with gout had decreased physician-reported prevalence, and colonoscopy-documented incidence of colon cancer compared to patients with OA, suggesting a possible protective effect of gout or a goutassociated clinical, epidemiological or genetic factor. (Figure Presented)

Background/Purpose: To date, most studies of gout and cardiovascular disease have been cross-sectional or retrospective, and have addressed the outcome of acute coronary syndromes. Less is known regarding the impact of gout on basic vascular health, including arterial endothelial function. We asked whether initiating gout treatment with colchicine and urate-lowering therapy (ULT) reduces inflammation (CRP), and improves endothelial function as measured by brachial artery flow-mediated dilation (FMD). Methods: Gout patients initiating treatment with their physicians were enrolled. Physicians agreed to follow a care strategy that sequenced colchicine and ULT (allopurinol or febuxostat) initiation. Demographics and cardiovascular risk factors were recorded, and CRP and FMD were measured at baseline, after 6 weeks of colchicine (0.6 mgs daily), and again 4 weeks after ULT had been titrated to clinical target (<6.0 mg/dL; <5.0 mg/dL for patients with tophi) in the presence of continuing colchicine. Results: 34 untreated male gout patients (mean age 57.9 years) were enrolled. To date, 32 have completed postcolchicine, and 22 have completed post-ULT assessments. CRP decline was observed from baseline to post-colchicine and further to post-ULT (total change from baseline, 0.207 mg/dL) (Figure). Overall we observed no net FMD improvement post-colchicine, but patients who experienced CRP reduction post-colchicine had higher rates of FMD improvement than CRP non-responders (58.8% versus 25.0% FMD response). We stratified the overall cohort based on smoking status, and observed greater rates of post-colchicine improvement in both FMD and CRP in the non-smoker, compared with the smoker group. FMD improvement occurred in 60.0% of non-smokers versus 38.1% of smokers; CRP improved in 75% of non-smokers versus 52.4% of smokers. Non-smokers with CRP improvement were also more likely than non-smoker CRP non-responders to demonstrate FMD improvement (66.7% versus 50% response rate). Baseline to post-ULT trends in CRP improvement were also more pronounced in the non-smoker group, with 75% of non-smokers versus 56% of smokers experiencing a CRP decrease. Analysis of FMD outcomes in patients post-ULT is ongoing. Conclusion: This prospective observational pilot study suggests that treatment with colchicine and ULT is associated with an overall reduction in CRP. Among patients whose CRP declined, FMD also tended to improve, suggesting a common beneficial effect. Smoking appears to hinder improvement in inflammation and vascular function in response to colchicine and ULT. Data from the third and final (ULT) stage of the study are still being collected with analyses ongoing. Larger and longer studies may be warranted to confirm the anti-inflammatory and pro-vascular benefits of colchicine and ULT in patients undergoing gout treatment initiation. (Figure presented)

Background/Purpose: Osteoarthritis (OA) etiopathogenesis includes an inflammatory component. Published reports indicate that synovial fluid urate levels, even in patients without gout, associate with OA prevalence/severity. Whether serum urate (sUA), the precursor for gout and a biomarker for cardiovascular and kidney disease, may serve as a biomarker to convey or predict OA risk is not known. We investigated whether sUA levels associate with knee OA radiographic severity and contrast MRI-measured quantitative synovial volume (SV), and whether sUA levels predict radiographic progression, in a gout-free knee OA cohort. Methods: We assessed sUA in 88 gout-free subjects who completed a 24-month prospective, natural history knee OA study. Subjects had symptomatic medial knee OA, met ACR knee OA criteria and had BMI <33 at study entry. sUA was measured (enzyme-colorimetry) in serum frozen and banked at baseline. At baseline and 24 months, patients underwent standardized weight-bearing fixed-flexion posteroanterior knee radiographs (SynaFlexerTM). Twenty-seven subjects additionally had a dynamic gadolinium-enhanced 3.0T knee MRI that was read for quantitative synovial volume (SV). A musculoskeletal radiologist, blinded to subject data, determined joint space width (JSW) and Kellgren-Lawrence (KL) grades at each time point. Joint space narrowing (JSN) was determined as JSW change from baseline to 24 months. Pearson's correlations, student's t-tests, one-way ANOVA with post hoc Tukey-Kramer tests, ROC and AUC curves were used in statistical analyses, as appropriate. Results: sUA correlated with JSN in both univariate (r=0.40, p<0.01) and multivariate analyses (adjusting for age, gender and BMI, r=0.28, p=0.010). There was a significant difference in mean JSN after dichotomization of sUA at 6.8mg/dL, the solubility point for serum urate, even after adjustment for age, gender and BMI (JSN [+/-SEM] of 0.90mm+/-0.20mm for sUA>6.8; JSN [+/-SEM] of 0.31mm+/-0.09mm for sUA<6.8, p<0.01). Baseline sUA distinguished progressors (JSN>0.2mm), and fast progressors (JSN>0.5mm), from non-progressors (JSN<0.0mm) in multivariate analyses (area under the receiver operating characteristic curve [AUC] 0.626, p=0.027; AUC 0.620, p=0.045, respectively). sUA also correlated with SV (r=0.44, p=0.0040), a possible marker of JSN, though this correlation did not persist after controlling for age, gender and BMI (r=0.13, p=0.562). Conclusion: In non-gout patients with knee OA, sUA levels predict JSN and may serve as a biomarker for OA progression. (Figure presented)

The NYC Rheumatology Objective Structured Clinical Examination (NYC-ROSCE) is held annually to assess fellow competencies. We recently redesigned our OSCE to better assess subspecialty trainee communication skills and professionalism by developing scenarios in which the patients encountered were psychosocially or medically complex. The objective of this study is to identify which types of verbal and non-verbal skills are most important in the perception of professionalism in the patient-physician interaction. The 2012-2013 NYC-ROSCEs included a total of 53 fellows: 55 MD evaluators from 7 NYC rheumatology training programs (Hospital for Special Surgery-Weill Cornell (HSS), SUNY/Downstate, NYU, Einstein, Columbia, Mount Sinai, and North Shore/Long Island Jewish (NSLIJ)), and 55 professional actors/standardized patients participated in 5 stations. Quantitative fellow performance assessments were made on the following: maintaining composure; partnering with the patient; honesty; professionalism; empathy; and accountability. Free-text comments were solicited regarding specific strengths and weaknesses. A total of 53/53 eligible (100 %) fellows were evaluated. MD evaluators rated fellows lower for professionalism than did the standardized patients (6.8 +/- 0.6 vs. 7.4 +/- 0.8, p = 0.05), suggesting that physicians and patients view professionalism somewhat differently. Fellow self-evaluations for professionalism (6.6 +/- 1.2) were concordant with those of the MD evaluators. Ratings of empathy by fellows themselves (6.6 +/- 1.0), MD evaluators (6.6 +/- 0.7), and standardized patients (6.6 +/- 1.1) agreed closely. Jargon use, frequently cited by evaluators, showed a moderate association with lower professionalism ratings by both MD evaluators and patients. Psychosocially challenging patient encounters in the NYC-ROSCE permitted critical assessment of the patient-centered traits contributing to impressions of professionalism and indicate that limiting medical jargon is an important component of the competency of professionalism.

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.

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.

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.