Research Spotlight

Shutze, W., R. Shutze, P. Dhot and G. O. Ogola (2018). “Patient-reported outcomes of endovenous superficial venous ablation for lower extremity swelling.” Phlebology Nov 22. [Epub ahead of print].

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OBJECTIVE: To evaluate the effect of endovenous ablation in patients presenting with leg swelling. METHODS: We identified Clinical, Etiology, Anatomy, Pathophysiology (CEAP) clinical class 3 (C3) patients undergoing endovenous ablation from 21 January 2005 to 19 March 2015 with an 810-nm or 1470-nm laser. Patients were surveyed regarding the degree of edema, use of compression stockings, and satisfaction with the procedure. RESULTS: A total of 1634 limbs were treated by endovenous ablation for incompetent saphenous veins with or without adjunctive segmental varicose vein microphlebectomy. Of these, 528 limbs were treated for CEAP C3. The average time period from the procedure date until the survey date was 1494 days (range, 562-2795 days). Ninety-two respondents accounted for 130 ablations in 128 limbs with an average venous segmental disease score of 2.7. Ninety-seven limbs (75.8%) had reduced or resolved swelling, 29 limbs (22.6%) were unchanged, and 2 limbs (1.6%) had increased swelling. The vast majority (81%) were satisfied with their decision to have the procedure. CONCLUSIONS: Endovenous ablation for edema secondary to superficial venous insufficiency is effective and has high patient satisfaction. Further investigation is needed regarding risk factors for immediate failure and delayed recurrence of edema.

Ross, R. D., R. C. Shah, S. Leurgans, T. Bottiglieri, R. S. Wilson and D. R. Sumner (2018). “Circulating Dkk1 and TRAIL Are Associated With Cognitive Decline in Community-Dwelling, Older Adults With Cognitive Concerns.” J Gerontol A Biol Sci Med Sci 73(12): 1688-1694.

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Background: Osteoporosis and Alzheimer’s disease are common diseases of aging that would seem to be unrelated, but may be linked through the influence of bone-derived signals on brain function. The aim of the current study is to investigate the relationship between circulating levels of bone-related biomarkers and cognition. Methods: The population included 103 community-dwelling older individuals with memory concerns but without cognitive impairment. A global cognition summary measure was collected at baseline and 6, 12, and 18 months post-enrollment by converting raw scores from 19 cognitive function tests to z-scores and averaging. Baseline plasma concentrations of bone-related biomarkers, including undercarboxylated, carboxylated, and total osteocalcin, parathyroid hormone, C-terminal telopeptide of collagen 1 (CTX-1), procollagen type 1 amino-terminal propeptide, osteoprotegrin, osteopontin, Dickkopf WNT signaling pathway inhibitor 1 (Dkk1), sclerostin, and amyloid beta peptides (Abeta40 and Abeta42), were measured. Results: Using sex, age, and education-adjusted mixed-effects models, we found that baseline levels of TNF-related apoptosis-inducing ligand (TRAIL; p < .001), Dkk1 (p = .014), and CTX-1 (p = .046) were related to the annual rate of change of global cognition over the 18 month follow-up. In cognitive domain-specific analysis, baseline TRAIL was found to be positively related to the annual rate of change in episodic (p < .001) and working memory (p = .016), and baseline Dkk1 was positively related to semantic memory (p = .027) and negatively related to working memory (p = .016). Conclusions: These results further confirm the link between bone and brain health and suggest that circulating levels of bone-related biomarkers may have diagnostic potential to predict worsening cognition.

Shang, M., J. R. Chung, M. L. Jackson, L. A. Jackson, A. S. Monto, E. T. Martin, E. A. Belongia, H. Q. McLean, M. Gaglani, K. Murthy, R. K. Zimmerman, M. P. Nowalk, A. M. Fry and B. Flannery (2018). “Influenza vaccine effectiveness among patients with high-risk medical conditions in the United States, 2012-2016.” Vaccine 36(52): 8047-8053.

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BACKGROUND: Annual influenza vaccination has been recommended for persons with high-risk conditions since the 1960s. However, few estimates of influenza vaccine effectiveness (VE) for persons with high-risk conditions are available. METHODS: Data from the U.S. Influenza Vaccine Effectiveness Network from 2012 to 2016 were analyzed to compare VE of standard-dose inactivated vaccines against medically-attended influenza among patients aged >/=6months with and without high-risk medical conditions. Patients with acute respiratory illness were tested for influenza by RT-PCR. Presence of high-risk conditions and vaccination status were obtained from medical records. VE by influenza virus type/subtype and age group was calculated for patients with and without high-risk conditions using the test-negative design. Interaction terms were used to test for differences in VE by high-risk conditions. RESULTS: Overall, 9643 (38%) of 25,369 patients enrolled during four influenza seasons had high-risk conditions; 2213 (23%) tested positive for influenza infection. For all ages, VE against any influenza was lower among patients with high-risk conditions (41%, 95% CI: 35-47%) than those without (48%, 95% CI: 43-52%; P-for-interaction=0.02). For children aged <18years, VE against any influenza was 51% (95% CI: 39-61%) and 52% (95% CI: 39-61%) among those with and without high-risk conditions, respectively (P-for-interaction=0.54). For adults aged >/=18years, VE against any influenza was 38% (95% CI: 30-45%) and 44% (95% CI: 38-50%) among those with and without high-risk conditions, respectively (P-for-interaction=0.21). For both children aged <18 and adults aged >/=18years, VEs against illness related to influenza A(H3N2), A(H1N1)pdm09, and influenza B virus infection were similar among those with and without high-risk conditions. CONCLUSIONS: Influenza vaccination provided protection against medically-attended influenza among patients with high-risk conditions, at levels approaching those observed among patients without high-risk conditions. Results from our analysis support recommendations of annual vaccination for patients with high-risk conditions.

Raza, F. S., A. Y. Lee, A. K. Jamil, H. Qin, J. Felius, A. E. Rafael, G. V. Gonzalez-Stawinski, S. A. Hall, S. M. Joseph, B. Lima and A. S. Bindra (2018). “Relation of Vasoplegia in the Absence of Primary Graft Dysfunction to Mortality Following Cardiac Transplantation.” Am J Cardiol 122(11): 1902-1908.

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Vasoplegia following cardiac transplantation is associated with increased morbidity and mortality. Previous studies have not accounted for primary graft dysfunction (PGD). The definition of vasoplegia is based on pressor requirement at 48 hours, many PGD parameters may have normalized after the initial 24 hours on inotropes. We surmised that the purported negative effects of vasoplegia following transplantation may in part be driven by PGD. We reviewed 240 consecutive adult cardiac transplants at our center between 2012 and 2016. The severity of vasoplegia was evaluated as a risk factor for 1-year survival, and the analysis was repeated for the subgroup of 177 patients who did not develop PGD. Overall, 63 (26%) of patients developed mild, moderate, or severe PGD. In those without PGD, vasoplegia was associated with length of stay but not with short- or long-term mortality. Moderate and/or severe vasoplegia occurred in 35 (15%) patients and was associated with higher short-term mortality, length of stay, and PGD. Multivariate logistic regression identified body mass index >/=35 kg/m(2), left ventricular assist device before transplantation, and use of extracorporeal membrane oxygenation as joint risk factors for vasoplegia. In patients without PGD, only left ventricular assist device before transplantation was associated with vasoplegia. In conclusion, our results show that, in the sizeable subgroup of patients with no signs of PGD, vasoplegia had a much more modest impact on post-transplant morbidity and no significant effect on 1- and 3-year survival. This suggests that PGD may be a confounder when assessing vasoplegia as a risk factor for adverse outcomes.

Pollock, B. D., P. Stuchlik, E. W. Harville, K. T. Mills, W. Tang, W. Chen and L. A. Bazzano (2018). “Life course trajectories of cardiovascular risk: Impact on atherosclerotic and metabolic indicators.” Atherosclerosis 280: 21-27.

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BACKGROUND AND AIMS: In this analysis, we estimated population-level trajectory groups of life course cardiovascular risk to explore their impact on mid-life atherosclerotic and metabolic outcomes. METHODS: This prospective study followed n=1269 Bogalusa Heart participants, each with at least 4 study visits from childhood in 1973 through adulthood in 2016. We used discrete mixture modeling to determine trajectories of cardiovascular risk percentiles from childhood to adulthood. Outcomes included mid-life subclinical atherosclerotic measures [(carotid intima-media thickness (cIMT), pulse wave velocity (PWV)], metabolic indicators [(diabetes and body mass index (BMI)], and short physical performance battery (SPPB). RESULTS: Between the mean ages of 9.6-48.3 years, we estimated five distinct trajectory groups of life course cardiovascular risk (High-Low, High-High, Mid-Low, Low-Low, and Low-High). Adult metabolic and vascular outcomes were significantly determined by life course cardiovascular risk trajectory groups (all p<0.01). Those in the High-Low group had lower risks of diabetes (20% vs. 28%, respectively; p=.12) and lower BMIs (32.4kg/m(2)vs. 34.6kg/m(2); p=.06) than those who remained at high risk (High-High) throughout life. However, the High-Low group had better cIMT (0.89mm vs. 1.05mm; p<.0001) and PWV (7.8m/s vs. 8.2m/s; p=.03) than the High-High group. For all outcomes, those in the Low-Low group fared best. CONCLUSIONS: We found considerable movement between low- and high-relative cardiovascular risk strata over the life course. Children who improved their relative cardiovascular risk over the life course achieved better mid-life atherosclerotic health despite maintaining relatively poor metabolic health through adulthood.