Research Spotlight

Kotliarov, Y., R. Sparks, A. J. Martins, M. P. Mule, Y. Lu, M. Goswami, L. Kardava, R. Banchereau, V. Pascual, A. Biancotto, J. Chen, P. L. Schwartzberg, N. Bansal, C. C. Liu, F. Cheung, S. Moir and J. S. Tsang (2020). “Broad immune activation underlies shared set point signatures for vaccine responsiveness in healthy individuals and disease activity in patients with lupus.” Nature Medicine Feb 24. [Epub ahead of print].

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Responses to vaccination and to diseases vary widely across individuals, which may be partly due to baseline immune variations. Identifying such baseline predictors of immune responses and their biological basis is of broad interest, given their potential importance for cancer immunotherapy, disease outcomes, vaccination and infection responses. Here we uncover baseline blood transcriptional signatures predictive of antibody responses to both influenza and yellow fever vaccinations in healthy subjects. These same signatures evaluated at clinical quiescence are correlated with disease activity in patients with systemic lupus erythematosus with plasmablast-associated flares. CITE-seq profiling of 82 surface proteins and transcriptomes of 53,201 single cells from healthy high and low influenza vaccination responders revealed that our signatures reflect the extent of activation in a plasmacytoid dendritic cell-type I IFN-T/B lymphocyte network. Our findings raise the prospect that modulating such immune baseline states may improve vaccine responsiveness and mitigate undesirable autoimmune disease activity.

Zeitzer, J. M., F. Hon, J. Whyte, K. R. Monden, J. Bogner, M. Dahdah, L. Wittine, K. R. Bell and R. Nakase-Richardson (2020). “Coherence between sleep detection by actigraphy and polysomnography in a multi-center, in-patient cohort of individuals with traumatic brain injury.” PM & R Mar 3. [Epub ahead of print].

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INTRODUCTION: Sleep is increasingly recognizes as a crucial component to rapid and successful rehabilitation, especially from traumatic brain injuries (TBI). Assessment of longitudinal patterns of sleep in a hospital setting, however, are difficult and often the expertise or equipment to conduct such studies are not available. Actigraphy (wrist worn accelerometry) has been used for many years as a simple proxy measurement of sleep patterns, but its use has not been thoroughly validated in individuals with TBI. OBJECTIVE: To determine the validity of different sensitivity settings of actigraphy analysis to optimize its use as a proxy for recording sleep patterns in individuals with a traumatic brain injury (TBI). DESIGN: Comparison of actigraphy to criterion standard polysomnographic (PSG)-determination of sleep on a single overnight study. SETTING: Six rehabilitation hospitals in the TBI Model System. PARTICIPANTS: 227 consecutive, medically stable individuals with a TBI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Concordance between PSG- and actigraphy-determined sleep using different sensitivity threshold settings (low, medium, high, automated). RESULTS: Bland-Altman plots revealed increasing error with increasing amounts of wake during the sleep episode. Precision-recall statistics indicate that with less sensitive actigraphy thresholds, episodes identified as “wake” are usually ‘wake’, but many true episodes of ‘wake’ are missed. With more sensitive actigraphy thresholds, more episodes of ‘wake’ are identified, but only some of these are true episodes of ‘wake’. CONCLUSIONS: In hospitalized patients with TBI and poor sleep, actigraphy underestimates the level of sleep disruption and has poor concordance with PSG-determined sleep. Alternate methods of scoring sleep from actigraphy data are necessary in this population.

Xenogiannis, I., F. Gkargkoulas, D. Karmpaliotis, O. Krestyaninov, D. Khelimskii, F. A. Jaffer, J. J. Khatri, D. E. Kandzari, R. M. Wyman, A. H. Doing, P. Dattilo, C. Toma, R. W. Yeh, H. Tamez, J. W. Choi, W. Jaber, H. Samady, A. M. Sheikh, S. Potluri, M. Patel, E. Mahmud, B. Elbaruni, M. P. Love, M. Koutouzis, I. Tsiafoutis, B. K. Jefferson, T. Patel, B. Uretsky, J. W. Moses, N. J. Lembo, M. Parikh, A. J. Kirtane, Z. A. Ali, A. B. Hall, M. S. Megaly, E. Vemmou, I. Nikolakopoulos, B. V. Rangan, P. W. Morley, B. Bou Dargham, S. Abdullah, S. Garcia, S. Banerjee, M. N. Burke, E. S. Brilakis and K. Alaswad (2020). “Retrograde Chronic Total Occlusion Percutaneous Coronary Intervention via Saphenous Vein Graft.” JACC Cardiovasc Interv 13(4): 517-526.

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OBJECTIVES: The aim of this study was to examine the use of saphenous vein grafts (SVGs) for retrograde crossing during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). BACKGROUND: The use of SVGs for retrograde crossing during CTO PCI has received limited study. METHODS: A total of 1,615 retrograde CTO PCIs performed between 2012 and 2019 at 25 centers were examined. Clinical, angiographic, and technical characteristics and procedural outcomes were compared among retrograde cases via SVGs (SVG group) versus other collateral vessels (non-SVG group). RESULTS: Retrograde CTO PCI via SVGs was performed in 189 cases (12%). Patients in the SVG group were older (mean age 70 +/- 9 years vs. 64 +/- 10 years; p < 0.01) and had higher rates of prior myocardial infarction (62% vs. 51%; p < 0.01) and prior PCI (81% vs. 70%; p < 0.01). They were more likely to have moderate or severe calcification (81% vs. 65%; p < 0.01) and moderate or severe tortuosity (53% vs. 44%; p = 0.02) and had similar J-CTO (Multicenter CTO Registry in Japan) scores (3.2 +/- 1.0 vs. 3.1 +/- 1.1; p = 0.13) but higher PROGRESS-CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) scores (4.7 +/- 1.7 vs. 3.1 +/- 1.1; p < 0.01). Technical (85% vs. 78%; p = 0.04) and procedural (81% vs. 74%; p = 0.04) success rates were higher in the SVG group, with no difference in in-hospital major adverse events (6.4% vs. 4.4%; p = 0.22). Contrast volume was lower in the SVG group (225 ml [173 to 325 ml] vs. 292 ml [202 to 400 ml]; p < 0.01). CONCLUSIONS: Use of SVGs for retrograde crossing is associated with higher rates of technical and procedural success and similar rates of in-hospital major adverse cardiac events compared with retrograde CTO PCI via other collateral vessels.

Xenogiannis, I., F. Gkargkoulas, D. Karmpaliotis, K. Alaswad, O. Krestyaninov, D. Khelimskii, J. W. Choi, F. A. Jaffer, M. Patel, E. Mahmud, J. J. Khatri, D. E. Kandzari, A. H. Doing, P. Dattilo, C. Toma, M. Koutouzis, I. Tsiafoutis, B. Uretsky, R. W. Yeh, H. Tamez, R. M. Wyman, B. K. Jefferson, T. Patel, W. Jaber, H. Samady, A. M. Sheikh, B. A. Malik, E. Holper, S. Potluri, J. W. Moses, N. J. Lembo, M. Parikh, A. J. Kirtane, Z. A. Ali, A. B. Hall, E. Vemmou, I. Nikolakopoulos, B. B. Dargham, B. V. Rangan, S. Abdullah, S. Garcia, S. Banerjee, M. N. Burke and E. S. Brilakis (2020). “The Impact of Peripheral Artery Disease in Chronic Total Occlusion Percutaneous Coronary Intervention (Insights From PROGRESS-CTO Registry).” Angiology 71(3): 274-280.

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The impact of peripheral artery disease (PAD) in patients undergoing chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. We reviewed 3999 CTO PCIs performed in 3914 patients between 2012 and 2018 at 25 centers, 14% of whom had a history of PAD. We compared the clinical and angiographic characteristics and procedural outcomes of patients with versus without history of PAD. Patients with PAD were older (67 +/- 9 vs 64 +/- 10 years, P < .001) and had a higher prevalence of cardiovascular risk factors. They also had more complex lesions as illustrated by higher Japanese CTO score (2.7 +/- 1.2 vs 2.4 +/- 1.3, P < .001). In patients with PAD, the final crossing technique was less often antegrade wire escalation (40% vs 51%, P < .001) and more often the retrograde approach (23 vs 20%, P < .001) and antegrade dissection/reentry (20% vs 16%, P < .001). Technical success was similar between the 2 study groups (84% vs 87%, P = .127), but procedural success was lower for patients with PAD (81% vs 85%, P = .015). The incidence of in-hospital major adverse cardiac events was higher among patients with PAD (3% vs 2%, P = .046). In conclusion, patients with PAD undergoing CTO PCI have more comorbidities, more complex lesions, and lower procedural success.

Wesson, D. E., H. Kitzman, A. Montgomery, A. Mamun, W. Parnell, B. Vilayvanh, K. M. Tecson and P. Allison (2020). “A population health dietary intervention for African American adults with chronic kidney disease: The Fruit and Veggies for Kidney Health randomized study.” Contemp Clin Trials Commun March 1. Volume 17, Article 100540.

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Background: Chronic kidney disease (CKD) is commonly asymptomatic until its late stages, reduces life quality and length, is costly to manage, and is disproportionately prevalent in low-income, African American (AA) communities. Traditional health system strategies that engage only patients with symptomatic CKD limit opportunities to prevent progression to end stage kidney disease (ESKD) with the need for expensive kidney replacement therapy and to reduce risk for their major mortality cause, cardiovascular disease (CVD). Published studies show that giving fruits and vegetables (F&V) to AA with early-stage CKD along with preparation instructions slowed CKD progression. This effective, evidenced-based, and potentially scalable dietary intervention might be a component of a community-based strategy to prevent CKD progression. Design: This study supported by NIH grant (R21DK113440) will test the feasibility of an innovative screening strategy conducted at community-based institutions in low-income AA communities and the ability to intervene in individuals identified to have CKD and increased CVD risk with F&V, with or without preparation instructions. Objectives: The study will prospectively compare changes in urine indices predictive of CKD progression and CVD in participants receiving, compared to those not receiving, preparation instructions along with F&V, six months after the intervention. Discussion: Addressing the challenge of increasing progression of early to more advanced stages of CKD with its increased CVD risk requires development of effective strategies to screen, identify, and intervene with individuals found to have CKD with effective, comparatively inexpensive, community-based, and scalable strategies to prevent CKD progression, particularly in low-income, AA communities.