Faculty Bibliography

Background/Purpose : Gout is a very prevalent condition associated with many metabolic and cardiorenal comorbidities. A few studies have investigated the comorbidity subtypes of gout patients by cluster analyses; however, such analyses have not yet been performed among Blacks nor confirmed in a general population cohort. As such the generalizability of these findings remains unknown. Thus, our objective was to identify gout subtypes based on comorbidities using cluster analysis among Black adults with gout in the US general population. Furthermore, we sought to compare these findings to that of White adults with gout. Methods : We used data from 371 Black and 656 White participants in the 2007-2016 cycle of the National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of adults in the US with detailed clinical and physical examination data. Diagnosis of gout was based on survey of physician-or health professionaldiagnosed gout. We employed Ward's minimum variance method of clustering to group patients with gout into clusters (i.e., subtypes) based on distinct comorbidity patterns according to 8 variables: obesity, hypertension, diabetes, dyslipidemia (i.e., hypercholesterolemia and/or hypertriglyceridemia), coronary heart disease (CHD), heart failure (HF), chronic kidney disease (CKD), and non-alcoholic fatty liver disease (NAFLD). Results : Metabolic and cardiorenal comorbidities were prevalent among both Black and White participants with gout ( Table 1 ). Cluster analysis identified 5 comorbidity subgroups among Black patients with gout ( Table 2 ). All patients in Group 1 had dyslipidemia and hypertension. Group 2 had the highest proportion of patients with diabetes (95%), and nearly all patients with NAFLD belonged to this group. Group 3 consisted of patients with gout but few other comorbidities. All patients in Group 4 had CKD. Group 5 had the highest proportion of patients with CHD and HF. Cluster analysis among Whites also identified subgroups with isolated gout (Group 2) and dyslipidemia and hypertension (Group 1) ( Table 3 ). It also identified a subgroup that combined cardiac and renal disease (Group 5). Key differences among Whites was the presence of obese (Group 3) and hypertension only (Group 4) clusters, and the lack of a diabetes group. The higher prevalence of obesity in Blacks and the smaller number of Black participants likely contributed to these differences. Conclusion : These findings from a nationally representative sample of Black US adults identified 5 subgroups of gout based on comorbidities: dyslipidemia/HTN, diabetes, isolated gout, CKD, and heart disease. Notable differences from the European population and American White cohorts included the separation of CKD and cardiac disease and the absence of a group defined by obesity among US Blacks. Overall, these subgroups could be broadly classified as i) isolated gout, ii) dyslipidemia/hypertension, iii) obese or diabetes, and iv) cardiorenal disease (separately or together). These subgroups may shed light on pathophysiologic mechanisms that contribute to gout and have implications for personalized interventions to reduce the burden of gout and its comorbidities

BACKGROUND/OBJECTIVE/OBJECTIVE:The connection between gout and various cancers remains unclear. We assessed the relationship between gout and colorectal cancer in a population of veterans. METHODS:We reviewed the Computerized Patient Record System of the VA New York Harbor Health Care System to assess the 10-year occurrence of colorectal cancer in patients with gout undergoing colonoscopy, versus patients with osteoarthritis but no gout. RESULTS:Gout and osteoarthritis subjects were similar in age, ethnicity, body mass index, and smoking history. Among 581 gout and 598 osteoarthritis subjects with documented colonoscopies, the 10-year prevalence of colorectal cancer was significantly lower in gout (0.8%) versus osteoarthritis (3.7%) (p = 0.0008) patients. Differences in colorectal cancer rates remained significant after stratifying for nonsteroidal anti-inflammatory drug use. Among gout subjects, use of colchicine and/or allopurinol, as well as the presence/absence of concomitant osteoarthritis, did not influence colorectal cancer occurrence. On subanalysis, differences in colorectal cancer occurrence between gout and osteoarthritis subjects persisted among those who underwent diagnostic (0.5% in gout vs 4.6% in osteoarthritis subjects, p < 0.001) but not screening (0.9% in gout subjects vs 1% in osteoarthritis subjects, p = 1.0) colonoscopy. There was no significant difference in nonmalignant colorectal polyp occurrence between gout and osteoarthritis subjects. CONCLUSIONS:Subjects with gout had decreased colonoscopy-documented occurrence of colorectal cancer compared with osteoarthritis subjects, suggesting a possible protective effect.

OBJECTIVE:In vitro and clinical studies suggest that urate may contribute to osteoarthritis (OA) risk. We tested the associations between hyperuricemia and knee OA, and examined the role of obesity, using a cross-sectional, nationally representative dataset. METHOD/METHODS:National Health and Nutrition Examination Survey (NHANES) III used a multistage, stratified probability cluster design to select USA civilians from 1988 to 1994. Using NHANES III we studied adults >60 years, with or without hyperuricemia (serum urate > 6.8 mg/dL), excluding individuals with gout (i.e., limiting to asymptomatic hyperuricemia (AH)). Radiographic knee OA (RKOA) was defined as Kellgren-Lawrence grade ≥ 2 in any knee, and symptomatic radiographic knee osteoarthritis (RKOA) (sRKOA) was defined as RKOA plus knee pain (most days for 6 weeks) in the same knee. RESULTS:AH prevalence was 17.9% (confidence interval (CI) 15.3-20.5). RKOA prevalence was 37.7% overall (CI 35.0-40.3), and was 44.0% for AH vs 36.3% for normouricemic adults (p = 0.056). symptomatic radiographic knee osteoarthritis (sRKOA) was more prevalent in AH vs normouricemic adults (17.4% vs 10.9%, p = 0.046). In multivariate models adjusting for obesity, model-based associations between AH and knee OA were attenuated (for RKOA, prevalence ratio (PR) = 1.14, 95% CI 0.95, 1.36; for sRKOA, PR = 1.40, 95% CI 0.98, 2.01). In stratified multivariate analyses, AH was associated with sRKOA in adults without obesity (PR = 1.66, 95% CI 1.02, 2.71) but not adults with obesity (PR = 1.21, 95% CI 0.66, 2.23). CONCLUSIONS:Among adults aged 60 or older, AH is associated with knee OA risk that is more apparent in adults without obesity.

OBJECTIVE:There is a lack of standardisation in the terminology used to describe gout. The aim of this project was to develop a consensus statement describing the recommended nomenclature for disease states of gout. METHODS:A content analysis of gout-related articles from rheumatology and general internal medicine journals published over a 5-year period identified potential disease states and the labels commonly assigned to them. Based on these findings, experts in gout were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach agreement on disease state labels and definitions. RESULTS:The content analysis identified 13 unique disease states and a total of 63 unique labels. The Delphi exercise (n=76 respondents) and face-to-face meeting (n=35 attendees) established consensus agreement for eight disease state labels and definitions. The agreed labels were as follows: 'asymptomatic hyperuricaemia', 'asymptomatic monosodium urate crystal deposition', 'asymptomatic hyperuricaemia with monosodium urate crystal deposition', 'gout', 'tophaceous gout', 'erosive gout', 'first gout flare' and 'recurrent gout flares'. There was consensus agreement that the label 'gout' should be restricted to current or prior clinically evident disease caused by monosodium urate crystal deposition (gout flare, chronic gouty arthritis or subcutaneous tophus). CONCLUSION/CONCLUSIONS:Consensus agreement has been established for the labels and definitions of eight gout disease states, including 'gout' itself. The Gout, Hyperuricaemia and Crystal-Associated Disease Network recommends the use of these labels when describing disease states of gout in research and clinical practice.

Background: The standard approach to monitor subjects with gout is to measure serum urate. The assumption is that the signs and symptoms of disease will improve if serum urate is maintained below the target level of 6 mg/dL. However, there has been little emphasis on whether lowering urate transiently would have a prolonged impact on the clinical manifestations of advanced gout.
Objective(s): Assess the clinical benefit in patients with advanced gout who had transient lowering of serum urate resulting from treatment with pegloticase, a pegylated recombinant uricase.
Method(s): A post hoc analysis was carried out using the results from two randomized controlled trials (RCTs) of 6 months duration to assess the efficacy of treatment with 8 mg of pegloticase every 2 weeks (q2w)1. Serum urate was measured before each infusion and the serum urate area under the curve (AUC) was calculated as described2 for the first and second three-month periods of time in the RCTs. The following clinical outcomes were assessed: gout flares, tophus reduction, patient global assessment (PtGA), tender and swollen joints (TJC and SJC), pain measured with a 100-mm visual analog scale (VAS) and a variety of patient reported outcomes (36-Item Short Form Health Survey [SF-36] Physical Component Score [PCS] and Arthritis-Specific Health Index Score [ASHIS]).
Result(s): The analysis included 85 subjects treated with q2w pegloticase and 43 patients who received placebo. Of the 85 pegloticase-treated subjects, 49 had only a transient decrease in serum urate owing to the development of anti-pegloticase antibodies. The mean length of time these subjects experienced a serum urate <6 mg/dL was approximately 6 weeks3. Despite the transient reduction in serum urate, the serum urate AUC for the first and second 3 months of the RCTs was significantly (p=0.008) decreased compared to placebo-treated subjects. However, it was significantly (p<0.0001) less reduced compared with those with persistent urate lowering throughout the 6 month RCTs (Table 1). Results for both the subjects with persistent and transient lowering of serum urate to <6 mg/dL indicated significant reduction in tophi and improvements from baseline in PtGA, TJC, SJC, pain, and ASHIS after 6 months of the RCT. No significant improvements were observed in the patients who received placebo.
Conclusion(s): A transient reduction in serum urate resulting from pegloticase therapy can result in significant clinical benefit lasting through the 6 months of the RCTs. These results suggest that transient lowering of urate can alter the trajectory of the clinical manifestations of advanced gout. Moreover, estimates of serum urate AUC may be more helpful in assessing the impact of urate lowering therapy than individual measurements of serum urate. (Table Presented)

Mini-sabbaticals are formal short-term training and educational experiences away from an investigator's home research unit. These may include rotations with other research units and externships at government research or regulatory agencies, industry and non-profit programs, and training and/or intensive educational programs. The National Institutes of Health have been encouraging training institutions to consider offering mini-sabbaticals, but given the newness of the concept, limited data are available to guide the implementation of mini-sabbatical programs. In this paper, we review the history of sabbaticals and mini-sabbaticals, report the results of surveys we performed to ascertain the use of mini-sabbaticals at Clinical and Translational Science Award hubs, and consider best practice recommendations for institutions seeking to establish formal mini-sabbatical programs.

OBJECTIVES/OBJECTIVE:Gout patients with chronic kidney disease (CKD) accumulate the active allopurinol metabolite oxypurinol, suggesting that allopurinol may promote greater serum urate (sU) lowering in CKD patients. METHODS:We identified all patientswith gout diagnoses on either 100 mg or 300 mg of allopurinol daily, with available pre- and on-treatment sU levels, in our system in a 1-year period. Mean sU decrement by dosing per CKD groups was determined by CKD stage. RESULTS:Of 1,288 subjects with gout, 180 met entry criteria, with 83 subjects receiving 100 mg and 97 receiving 300 mg allopurinol. Subjects with CKD stage 1 experienced less sU lowering with 100 mg than 300 mg of allopurinol. Subjects with stage 4 and 5 CKD had equivalent sU decreases across the 100 mg and 300 mg allopurinol groups. However, the 100 mg group started at a higher pre-treatment sU and ended at a higher final sU than the 300 mg group. CONCLUSIONS:The strategy of titrating allopurinol to sU in patients with kidney impairment may result in greater sU lowering at lower doses than in patients without CKD but may also pose a treatment challenge from a possible drug ceiling effect.