Background: 25-hydroxy vitamin D (Vit D)-deficiency is common among patients with chronic kidney disease (CKD) and contributes to cardiovascular disease (CVD). African Americans (AAs) suffer disproportionately from CKD and CVD, and 80% of AAs are Vit D-deficient. The impact of Vit D repletion on cardio-renal biomarkers in AAs is unknown. We examined Vit D repletion on full-length osteopontin (flOPN), c-terminal fibroblast growth factor-23 (FGF-23), and plasminogen activator inhibitor-1 (PAI-1), which are implicated in vascular and kidney pathology. Methods: We performed a randomized, placebo-controlled study of high-risk AAs with Vit D deficiency, treated with 100,000 IU Vit D3 (cholecalciferol; n = 65) or placebo (n = 65) every 4 weeks for 12 weeks. We measured kidney function (CKD-EPI eGFR), protein-to-creatinine ratio, vascular function (pulse wave velocity; PWV), augmentation index, waist circumference, sitting, and 24-h-ambulatory blood pressure (BP), intact parathyroid hormone (iPTH) and serum calcium at baseline and study end, and compared Vit D levels with laboratory variables. We quantified plasma FGF-23, PAI-1, and flOPN by enzyme-linked immunosorbent assay. Multiple regression analyzed the relationship between log flOPN, FGF-23, and PAI-1 with vascular and renal risk factors. Results: Compared to placebo, Vit D3 repletion increased Vit D3 2-fold (p < 0.0001), decreased iPTH by 12% (p < 0.01) and was significantly correlated with PWV (p < 0.009). Log flOPN decreased (p = 0.03), log FGF-23 increased (p = 0.04), but log PAI-1 did not change. Multiple regression indicated association between log flOPN and PWV (p = 0.04) and diastolic BP (p = 0.02), while log FGF-23 was associated with diastolic BP (p = 0.05), and a trend with eGFR (p = 0.06). Conclusion: Vit D3 repletion may reduce flOPN and improve vascular function in high risk AAs with Vit D deficiency.

Individuals diagnosed with colorectal adenomas with high-risk features during screening colonoscopy have increased risk for the development of subsequent adenomas and colorectal cancer. While US guidelines recommend surveillance colonoscopy at 3 years in this high-risk population, surveillance uptake is suboptimal. To inform future interventions to improve surveillance uptake, we sought to assess surveillance rates and identify facilitators of uptake in a large integrated health system. We utilized a cohort of patients with a diagnosis of ≥ 1 tubular adenoma (TA) with high-risk features (TA ≥ 1 cm, TA with villous features, TA with high-grade dysplasia, or ≥ 3 TA of any size) on colonoscopy between 2013 and 2016. Surveillance colonoscopy completion within 3.5 years of diagnosis of an adenoma with high-risk features was our primary outcome. We evaluated surveillance uptake over time and utilized logistic regression to detect factors associated with completion of surveillance colonoscopy. The final cohort was comprised of 405 patients. 172 (42.5%) patients successfully completed surveillance colonoscopy by 3.5 years. Use of a patient reminder (telephone, electronic message, or letter) for due surveillance (adjusted odds = 1.9; 95%CI = 1.2–2.8) and having ≥ 1 gastroenterology (GI) visit after diagnosis of an adenoma with high-risk features (adjusted odds = 2.6; 95%CI = 1.6–4.2) significantly predicted surveillance colonoscopy completion at 3.5 years. For patients diagnosed with adenomas with high-risk features, surveillance colonoscopy uptake is suboptimal and frequently occurs after the 3-year surveillance recommendation. Patient reminders and visitation with GI after index colonoscopy are associated with timely surveillance completion. Our findings highlight potential health system interventions to increase timely surveillance uptake for patients diagnosed with adenomas with high-risk features.

INTRODUCTION: There have been a myriad of efforts to address suboptimal colorectal cancer (CRC) screening rates in the United States (US). Individuals with high-risk colon polyps detected during screening colonoscopy have 2- to 5-fold increased risk for the future development of CRC; however, there are few efforts directed towards optimizing risk reduction in this group. We examined surveillance uptake for patients with high-risk polyps in a large, academic healthcare system. METHODS: \We identified a cohort of patients: 1) age 50–75; 2) with a colonoscopic diagnosis of high-risk adenoma (HRA; 1 adenoma >1 cm, adenoma with villous histology, adenoma with high-grade dysplasia, or 3 or more adenomas) between January 2013 and January 2016; and 3) regular primary care (PC) at UCLA Health. We collected information from the electronic health record (EHR) on demographics, polyp histology, colonoscopy completion, and office visits. We determined the proportion of patients that completed surveillance colonoscopy each year and used Student's t-tests and chi-square tests to evaluate univariate associations between patient characteristics and colonoscopy completion. RESULTS: Our cohort included 203 individuals with HRA. Mean age was 62.5 (SD = 7.6), 62.6% were male, and 75.3% were White (Table 1). There were 153 (75.4%) patients who did not complete surveillance within 3 years. Surveillance completion increased from 24.6% to 40.4% by 3.5 years. 110 (54.2%) completed surveillance by the end of 5 years (Table 2). In all, 202 (99.5%) patients had documentation of a PC visit and 165 (81.3%) had documentation of a GI visit before surveillance was due. There were 121 (59.6%) patients with a documented history of adenoma in the EHR problem list. Patients with ≥1 GI visit after HRA diagnosis (165, 81.3%) were more likely to complete surveillance than patients without a GI visit after HRA diagnosis (38, 18.7%) (P < 0.001). CONCLUSION: Overall uptake of surveillance colonoscopy was low at 3 years for patients with HRA. There was notable improvement in follow-up by 3.5 years; however, adherence remained suboptimal at 40%. Clinical implications of this delay are unknown. Documentation of adenoma history was low. Individuals with HRA represent a group that has been largely neglected in CRC prevention/control research and that warrants evidence-based strategies to ensure appropriate follow-up to reduce CRC burden.

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INTRODUCTION: National guidelines recommend that patients with colorectal adenomas ≥1cm undergo surveillance colonoscopy to prevent colorectal cancer. Polyp size is often assessed twice, once during colonoscopy and again during pathology examination. It remains unclear whether these measurements vary and which should govern surveillance intervals. METHODS: We retrospectively analyzed a random sample of primary care patients who underwent polypectomy between January 1, 2013 and January 1, 2016 in a large academic healthcare center. Chart abstractors reviewed electronic health record data for colonoscopic polyp descriptors and measurements, corresponding pathology measurements, and histology. We excluded cases with normal histology, missing pathology, fragments, unreliable polyp matches between reports, and >5 polypectomies. We performed a paired t-test to assess polyp size discordance between reports and calculated Cohen's kappa coefficient to assess agreement whether the size was ≥1 cm. RESULTS: We reviewed 1,528 patient charts, and 831 (54.4%) met inclusion criteria, representing 1,532 polyps. Sizes ranged from 0.1-3.0cm on colonoscopy and 0.1-2.7cm on pathology reports. On colonoscopy report, the majority (881, 57.5%) used only a descriptive term rather than a numeric value to describe size (Table 1). Descriptive size terms were diminutive (513), tiny (39), small (328), and large (1). Only 2.8% of polyps described as diminutive, small, or tiny on the colonoscopy report were ≥1cm on the corresponding pathology report. Among the 367 (24.0%) polyps with discrete numeric sizes on both reports, size discordance varied by >0.2 cm for 50% of polyps (Figure 1). More of these polyps were ≥1 cm on colonoscopy (70) than on pathology (51) report, and there was remarkable clustering at 1 cm by colonoscopy report estimation (Figure 2). There was moderate agreement (kappa = 0.52) on size ≥1 cm. Among tubular adenomas (TA) ≥1 cm on colonoscopy or pathology report (36), 10 (27.8%) were ≥1 cm on both, 18 (50.0%) were ≥1 cm on colonoscopy only, and 8 (22.2%) were ≥1 cm on pathology only. CONCLUSION: There is considerable discordance between colonoscopic and pathology polyp size measurements, with more polyps sized as ≥1 cm by colonoscopic estimation compared to pathology, which has implications for surveillance frequency. Future studies should investigate the implications of discordant measurements on clinical outcomes and inform guidelines on surveillance intervals.