Research Spotlight

Posted July 15th 2021

Aesthetic Surgery in Plastic Surgery Academia.

Michel H. Saint-Cyr, M.D.

Michel H. Saint-Cyr, M.D.

Perdikis, G., Eaves, F.F., Glassman, G.E., Walker, S., Huang, L.C., Mast, B., Damitz, L., Rubin, J.P., Serletti, J.M., Hansen, J., Potochny, J., Kenkel, J., Taub, P.J., Sobczyk, S., Gilman, R.H., Saint-Cyr, M.H. and Cederna, P. (2021). “Aesthetic Surgery in Plastic Surgery Academia.” Aesthet Surg J 41(7): 829-841.

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BACKGROUND: Aesthetic surgery is a critical component of academic plastic surgery. As institutions are placing increased focus on aesthetic surgery, there is an opportunity to identify factors that facilitate the creation and maintenance of successful aesthetic plastic surgery programs. OBJECTIVES: The aim of this study was to conduct a national survey to evaluate the current state of academic aesthetic surgery and to identify factors that contribute to success. METHODS: A REDCap 122-question survey was developed and validated by members of the Academic Aesthetic Surgery Roundtable (AASR). The national survey was distributed to department chairs and division chiefs with active ACGME-approved plastic surgery programs (n = 92). Responses underwent Pearson’s chi-squared, Wilcoxon rank-sum, and postselection inference analyses. AASR members convened to interpret data and identify best practices. RESULTS: Responses were received from 64 of 92 queries (69.6%). The multivariate analysis concluded traits associated with successful academic aesthetic surgery practices included the presence of aesthetic surgery-focused, full-time faculty whose overall practice includes >50% aesthetic surgery (P = 0.040) and nonphysician aesthetic practitioners who provide injection services (P = 0.025). In the univariate analysis, factors associated with strong aesthetic surgery training programs included resident participation in faculty aesthetic clinics (P = 0.034), aesthetic research (P = 0.006), and discounted resident aesthetic clinics (P < 0.001). CONCLUSIONS: The growth of academic aesthetic surgery practices represents a significant opportunity for advancement of resident training, departmental financial success, and diversification of faculty practices. By identifying and sharing best practices and strategies, academic aesthetic surgery practices can be further enhanced.


Posted July 15th 2021

Phosphate Control: The Next Frontier in Dialysis Cardiovascular Mortality.

Peter McCullough, M.D.

Peter McCullough, M.D.

McCullough, P.A. (2021). “Phosphate Control: The Next Frontier in Dialysis Cardiovascular Mortality.” Cardiorenal Med 11(3): 123-132.

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BACKGROUND: Cardiovascular disease (CVD) is a major cause of death in patients with chronic kidney disease (CKD) on dialysis. Mortality rates are still unacceptably high even though they have fallen in the past 2 decades. Hyperphosphatemia (elevated serum phosphate levels) is seen in almost all patients with advanced CKD and is by far the largest remaining modifiable contributor to CKD mortality. SUMMARY: Phosphate retention drives multiple physiological mechanisms linked to increased risk of CVD. Fibroblast growth factor 23 and parathyroid hormone (PTH) levels, both of which have been suggested to have direct pathogenic CV effects, increase in response to phosphate retention. Phosphate, calcium, and PTH levels are linked in a progressively worsening cycle. Maladaptive upregulation of phosphate absorption is also likely to occur further exacerbating hyperphosphatemia. Even higher phosphate levels within the normal range may be a risk factor for vascular calcification and, thus, CV morbidity and mortality. A greater degree of phosphate control is important to reduce the risk of CV morbidity and mortality. Improved phosphate control and regular monitoring of phosphate levels are guideline-recommended, established clinical practices. There are several challenges with the current phosphate management approaches in patients with CKD on dialysis. Dietary restriction of phosphate and thrice-weekly dialysis alone are insufficient/unreliable to reduce phosphate to <5.5 mg/dL. Even with the addition of phosphate binders, the only pharmacological treatment currently indicated for hyperphosphatemia, the majority of patients are unable to achieve and maintain phosphate levels <5.5 mg/dL (or more normal levels) [PhosLo® gelcaps (calcium acetate): 667 mg (prescribing information), 2011, VELPHORO®: (Sucroferric oxyhydroxide) (prescribing information), 2013, FOSRENAL®: (Lanthanum carbonate) (prescribing information), 2016, AURYXIA®: (Ferric citrate) tablets (prescribing information), 2017, RENVELA®: (Sevelamer carbonate) (prescribing information), 2020, RealWorld dynamix. Dialysis US: Spherix Global Insights, 2019]. Phosphate binders do not target the primary pathway of phosphate absorption (paracellular), have limited binding capacity, and bind nonspecifically [PhosLo® gelcaps (calcium acetate): 667 mg (prescribing information). 2013, VELPHORO®: (Sucroferric oxyhydroxide) (prescribing information), 2013, FOSRENAL®: (Lanthanum carbonate) (prescribing information), 2016, AURYXIA®: (Ferric citrate) tablets (prescribing information), 2017, RENVELA®: (Sevelamer carbonate) (prescribing information) 2020]. Key Messages: Despite current phosphate management strategies, most patients on dialysis are unable to consistently achieve target phosphate levels, indicating a need for therapeutic innovations [RealWorld dynamix. Dialysis US: Spherix Global Insights, 2019]. Given a growing evidence base that the dominant mechanism of phosphate absorption is the intestinal paracellular pathway, new therapies are investigating ways to reduce phosphate levels by blocking absorption through the paracellular pathway.


Posted July 15th 2021

Low Influenza Vaccine Effectiveness Against A(H3N2)-Associated Hospitalizations in 2016-2017 and 2017-2018 of the Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN).

Manjusha Gaglani M.D.

Manjusha Gaglani M.D.

Martin, E.T., Cheng, C., Petrie, J.G., Alyanak, E., Gaglani, M., Middleton, D.B., Ghamande, S., Silveira, F.P., Murthy, K., Zimmerman, R.K., Monto, A.S., Trabue, C., Talbot, H.K. and Ferdinands, J.M. (2021). “Low Influenza Vaccine Effectiveness Against A(H3N2)-Associated Hospitalizations in 2016-2017 and 2017-2018 of the Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN).” J Infect Dis 223(12): 2062-2071.

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BACKGROUND: The 2016-2017 and 2017-2018 influenza seasons were notable for the high number of hospitalizations for influenza A(H3N2) despite vaccine and circulating strain match. METHODS: We evaluated vaccine effectiveness (VE) against hospitalization in the test-negative HAIVEN study. Nasal-throat swabs were tested by quantitative reverse transcription polymerase chain reaction (RT-PCR) for influenza and VE was determined based on odds of vaccination by generalized estimating equations. Vaccine-specific antibody was measured in a subset of enrollees. RESULTS: A total of 6129 adults were enrolled from 10 hospitals. Adjusted VE against A(H3N2) was 22.8% (95% confidence interval [CI], 8.3% to 35.0%), pooled across both years and 49.4% (95% CI, 34.3% to 61.1%) against B/Yamagata. In 2017-2018, the A(H3N2) VE point estimate for the cell-based vaccine was 43.0% (95% CI, -36.3% to 76.1%; 56 vaccine recipients) compared to 24.0% (95% CI, 3.9% to 39.9%) for egg-based vaccines. Among 643 with serology data, hemagglutinin antibodies against the egg-based A(H3N2) vaccine strain were increased in influenza-negative individuals. CONCLUSIONS: Low VE for the A/Hong Kong/4801/2014 vaccine virus in both A(H3N2) seasons emphasizes concerns for continued changes in H3N2 antigenic epitopes, including changes that may impact glycosylation and ultimately reduce VE.


Posted July 15th 2021

Trailblazing perspectives on targeting breast cancer stem cells.

Erxi Wu, Ph.D.

Erxi Wu, Ph.D.

Li, J., Qi, D., Hsieh, T.C., Huang, J.H., Wu, J.M. and Wu, E. (2021). “Trailblazing perspectives on targeting breast cancer stem cells.” Pharmacol Ther 223: 107800.

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Breast cancer (BCa) is one of the most prevalent malignant tumors affecting women’s health worldwide. The recurrence and metastasis of BCa have made it a long-standing challenge to achieve remission-persistent or disease-undetectable clinical outcomes. Cancer stem cells (CSCs) possess the ability to self-renew and generate heterogeneous tumor bulk. The existence of CSCs has been found to be vital in the initiation, metastasis, therapy resistance, and recurrence of tumors across cancer types. Because CSCs grow slowly in their dormant state, they are insensitive to conventional chemotherapies; however, when CSCs emerge from their dormant state and become clinically evident, they usually acquire genetic traits that make them resistant to existing therapies. Moreover, CSCs also show evidence of acquired drug resistance in synchrony with tumor relapses. The concept of CSCs provides a new treatment strategy for BCa. In this review, we highlight the recent advances in research on breast CSCs and their association with epithelial-mesenchymal transition (EMT), circulating tumor cells (CTCs), plasticity of tumor cells, tumor microenvironment (TME), T-cell modulatory protein PD-L1, and non-coding RNAs. On the basis that CSCs are associated with multiple dysregulated biological processes, we envisage that increased understanding of disease sub-classification, selected combination of conventional treatment, molecular aberration directed therapy, immunotherapy, and CSC targeting/sensitizing strategy might improve the treatment outcome of patients with advanced BCa. We also discuss novel perspectives on new drugs and therapeutics purposing the potent and selective expunging of CSCs.


Posted July 15th 2021

Comparison of incidence/occurrence of cardiovascular events between ponatinib vs bosutinib among patients with at least one prior line of tyrosine kinase inhibitors in chronic myeloid leukemia in a community setting in the United States.

Moshe Y. Levy M.D.

Moshe Y. Levy M.D.

Levy, M., Xie, L., Wang, Y., Neumann, F., Srivastava, S., Naranjo, D., Xu, J., Zhang, Q. and Dalal, M. (2021). “Comparison of incidence/occurrence of cardiovascular events between ponatinib vs bosutinib among patients with at least one prior line of tyrosine kinase inhibitors in chronic myeloid leukemia in a community setting in the United States.” Cancer Treat Res Commun 28: 100424.

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INTRODUCTION: In this real-world study, the incidence of cardiovascular events (CV) including major adverse cardiac events (MACE), arterial occlusive events (AOE), and venous occlusive events (VOE) was evaluated in chronic myeloid leukemia (CML) patients treated with ponatinib or bosutinib in a US commercial database population. MATERIALS AND METHODS: CML patients aged ≥18 years with use of 1 or 2 prior tyrosine kinase inhibitors prescribed bosutinib or ponatinib were selected from the IBM® MarketScan® Research database. Cox proportional hazard model analyses were conducted to examine any difference in CV event risk. RESULTS: Ponatinib and bosutinib was associated with similar incidence and risk of CV events, including MACEs (HR: 1.02; 95% CI: 0.35, 3.01), AOEs (HR: 0.90; 95% CI: 0.43, 1.85) and VOEs (HR: 0.92; 95% CI: 0.44, 1.94). CONCLUSION: Treatment with ponatinib or bosutinib was not associated with significant differences in the incidence of CV events in CML patients.