Research Spotlight

Xenogiannis, I., F. Gkargkoulas, D. Karmpaliotis, K. Alaswad, O. Krestyaninov, D. Khelimskii, J. W. Choi [ . . . ] 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 (2019). “The Impact of Peripheral Artery Disease in Chronic Total Occlusion Percutaneous Coronary Intervention (Insights From PROGRESS-CTO Registry).” Angiology Dec 17. [Epub ahead of print].

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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.

Su, Q. and B. Z. Igyarto (2019). “One-step artificial antigen presenting cell-based vaccines induce potent effector CD8 T cell responses.” Sci Rep 9(1): 18949.

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The production and wide use of artificial antigen presenting cells (aAPCs) in the clinic as cancer immunotherapeutics are hindered by the need of identifying immunogenic cancer antigens and production of recombinant patient-specific major histocompatibility complexes (MHC) loaded with these peptides. To overcome these limitations, in this study, we tested the idea of whether peptide-MHCs can directly be captured from cell lysates, including cancer cells using affinity beads, and used to initiate T cell responses. In theory, these affinity beads covered with the unknown peptide-MHC repertoire captured from the cancer cells could interact with a wide range of antigen-specific T cells and promote anti-cancer responses. Indeed, we found that we can successfully pull-down peptide-MHCs from cell lysates and the aAPCs generated using this technique were able to induce antigen-specific cytotoxic effector T cell responses that led to in vitro and in vivo tumor cell killing. In summary, we present here a novel technique to generate patient-specific aAPCs, that might have the potential to revolutionize the field of cancer vaccines, and provide patients with a vaccine in matters of days at minimal costs.

Steward, A. M., E. Wiggs, T. Lindstrom, S. Ukwuani, E. Ryan, N. Tayebi, T. Roshan Lal, G. Lopez, R. Schiffmann and E. Sidransky (2019). “Variation in cognitive function over time in Gaucher disease type 3.” Neurology 93(24): e2272-e2283.

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OBJECTIVE: To identify relevant efficacy parameters essential in designing clinical trials for brain-penetrant therapies for Gaucher disease, we evaluated cognitive function longitudinally in 34 patients with Gaucher disease type 3 seen at the NIH Clinical Center. METHODS: Individuals were tested with age-appropriate Wechsler Intelligence Scales administered between 1 and 18 times over 29 years. Variation in all IQ domains was not linear with time and was best characterized with the coefficient of variation (SD/mean) for each individual. Mixed-effects regressions were used to determine whether IQ was associated with clinical features. Models were controlled for variation in test version, participant identification, and test administrator. RESULTS: Mean verbal, performance, and full-scale IQs were 81.77, 75.98, and 82.02, respectively, with a consistent discrepancy between verbal and performance IQs. Mean (SD) verbal, performance, and full-scale coefficient of variations were 0.07 (0.04), 0.09 (0.05), and 0.06 (0.02), respectively. IQ varied about a mean, with no clear trajectory, indicating no clear patterns of improvement or decline over time. EEG lateralization and behavioral issues were consistently associated with IQ. CONCLUSIONS: The observed variation in IQ in Gaucher disease type 3 across the cohort and within single individuals over time may be characteristic of other neuronopathic diseases. Therefore, to reliably use IQ as an efficacy measure in any clinical trial of neurotherapeutics, a normal variation range must be established to assess the clinical relevance of any IQ change.

Sheehy, A. M., A. L. Masica and S. S. Shah (2020). “Next Steps for Next Steps: The Intersection of Health Policy with Clinical Decision-Making.” J Hosp Med 15(1): 5.

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The Journal of Hospital Medicine introduced the Choosing Wisely: Next Steps in Improving Healthcare Value series in 2015 as a companion to the popular Choosing Wisely: Things We Do for No Reason series that was introduced in October in the same year. Both series were created in partnership with the American Board of Internal Medicine Foundation and were designed in the spirit of the Choosing Wisely campaign’s mission to “promote conversations between clinicians and patients” in choosing care supported by evidence that minimizes harm, including avoidance of unnecessary treatments and tests. The Choosing Wisely: Next Steps in Improving Healthcare Value series extends these principles as a forum for manuscripts that focus on translating value-based concepts into daily operations, including systems-level care delivery redesign initiatives, payment model innovations, and analyses of relevant policies or practice trends. Since its inception, Choosing Wisely: Next Steps in Improving Healthcare Value manuscripts have been published, encompassing a wide range of topics such as post-acute care transitions,4 the role of hospital medicine practice within accountable care organizations (ACOs),5 and quality and value at end-of-life. Few physicians receive health policy training. Hospital medicine practitioners are a core component of the workforce, driving change and value-based improvements at almost every inpatient facility across the country. Regardless of their background or experience, hospital medicine practitioners must interface with legislation, regulation, and other policies every day while providing patient care. Intentional, value-based improvements are more likely to succeed if those providing direct patient care understand health policies, particularly the effects of those policies on transactional, point-of-care decisions. We are pleased to expand the Choosing Wisely: Next Steps in Improving Healthcare Value series to include articles exploring health policy implications at the bedside. (Excerpt from text, p. 5; no abstract available.)

Shahbazov, R., B. Naziruddin, O. Salam, G. Saracino, M. F. Levy, E. Beecherl and N. Onaca (2020). “The impact of surgical complications on the outcome of total pancreatectomy with islet autotransplantation.” Am J Surg 219(1): 99-105.

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Total pancreatectomy with islet autotransplantation is a promising treatment for refractory chronic pancreatitis. We analyzed postoperative complications in 83 TPIAT patients and their impact on islet graft function. We examined patient demographics, preoperative risk factors, intraoperative variables, and 30- and 90-day postoperative morbidity and mortality. Daily insulin requirement, HbA1c, C-peptide levels, and narcotic requirements were analyzed before and after surgery. Adverse events were recorded, with postoperative complications graded according to the Clavien-Dindo classification. There was no mortality in this patient group. Postoperative complications occurred in 38 patients (45.7%). Patients with postoperative complications were readmitted significantly more often within 30 days (p=0.01) and 90 days posttransplant (p<0.0003) and had a significantly longer hospital stay (p=0.004) and intensive care unit stay (p=0.001). Insulin dependence and graft function assessed by HbA1c, C-Peptide and insulin requirements did not differ significantly by these complications. Postoperative complications after TPIAT are associated with longer hospital and intensive care unit stay and with readmission; however, the surgical complications do not affect islet graft function.