Research Spotlight

Kim, E. S., A. M. Sharma, R. Scissons, D. Dawson, R. T. Eberhardt, M. Gerhard-Herman, J. P. Hughes, S. Knight, A. Marie Kupinski, G. Mahe, M. Neumyer, P. Poe, R. Shugart, P. Wennberg, D. M. Williams and R. Eugene Zierler (2020). “Interpretation of peripheral arterial and venous Doppler waveforms: A Consensus Statement from the Society for Vascular Medicine and Society for Vascular Ultrasound.” Vasc Med Jul 15;1358863X20937665. [Epub ahead of print.].

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This expert consensus statement on the interpretation of peripheral arterial and venous spectral Doppler waveforms was jointly commissioned by the Society for Vascular Medicine (SVM) and the Society for Vascular Ultrasound (SVU). The consensus statement proposes a standardized nomenclature for arterial and venous spectral Doppler waveforms using a framework of key major descriptors and additional modifier terms. These key major descriptors and additional modifier terms are presented alongside representative Doppler waveforms, and nomenclature tables provide context by listing previous alternate terms to be replaced by the new major descriptors and modifiers. Finally, the document reviews Doppler waveform alterations with physiologic changes and disease states, provides optimization techniques for waveform acquisition and display, and provides practical guidance for incorporating the proposed nomenclature into the final interpretation report.

Karakkattil, P. S., E. Trudelle-Jackson, A. Medley and C. Swank (2020). “Effects of two different types of ankle-foot orthoses on gait outcomes in patients with subacute stroke: a randomized crossover trial.” Clin Rehabil 34(8): 1094-1102.

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OBJECTIVE: To identify whether patients in the subacute stage of stroke, with foot drop, would have better gait outcomes when using a double-adjustable AFO (DA AFO) or a posterior leaf spring AFO (PLS AFO) at baseline without practice and to determine whether one week of practice would significantly change gait outcomes with either of the AFOs. DESIGN: Within-subject 2 × 2 repeated measures design. SETTING: Postacute and outpatient rehabilitation center. PARTICIPANTS: Twenty individuals with mean age of 57 years (SD: 12.0 years) with subacute stroke. INTERVENTIONS: Participants were measured using DA AFO and PLS AFO at baseline. Follow-up measurements were taken after one week of practice with each type of AFO in randomly assigned order. OUTCOME MEASURES: Gait endurance (6-Minute Walk Test (6MWT)), gait symmetry, and gait velocity at self-selected and fast-paced velocity measured using GAITRite gait analysis system and patient report of AFO preference. RESULTS: At baseline, no significant differences were found between the 2 AFOs (P > 0.05). There was no significant interaction (P > 0.05) of AFO and practice for gait endurance, symmetry, and velocity. Main effect of practice was significant for gait endurance (P < 0.001), self-selected velocity (P = 0.001), and fast-paced velocity (P < 0.001). In all, 16 participants preferred using DA AFO for walking. CONCLUSIONS: No difference between DA AFO and PLS AFO was found on measures of gait endurance, symmetry, and velocity at baseline or after practice. With practice over time, participants improved in gait endurance and velocity regardless of AFO type.

Kandimalla, R., H. Tomihara, J. K. Banwait, K. Yamamura, G. Singh, H. Baba and A. Goel (2020). “A 15-Gene Immune, Stromal, and Proliferation Gene Signature that Significantly Associates with Poor Survival in Patients with Pancreatic Ductal Adenocarcinoma.” Clin Cancer Res 26(14): 3641-3648.

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PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with dismal survival rates. Tumor microenvironment (TME), comprising of immune cells and cancer-associated fibroblasts, plays a key role in driving poor prognosis and resistance to chemotherapy. Herein, we aimed to identify a TME-associated, risk-stratification gene biomarker signature in PDAC. EXPERIMENTAL DESIGN: The initial biomarker discovery was performed in The Cancer Genome Atlas (TCGA, n = 163) transcriptomic data. This was followed by independent validation of the gene signature in the International Cancer Genome Consortium (ICGC, n = 95), E-MTAB-6134 (n = 288), and GSE71729 (n = 123) datasets for predicting overall survival (OS), and for its ability to detect poor molecular subtypes. Clinical validation and nomogram establishment was undertaken by performing multivariate Cox regression analysis. RESULTS: Our biomarker discovery effort identified a 15-gene immune, stromal, and proliferation (ISP) gene signature that significantly associated with poor OS [HR, 3.90; 95% confidence interval (CI), 2.36-6.41; P < 0.0001]. This signature also robustly predicted survival in three independent validation cohorts ICGC [HR, 2.63 (1.56-4.41); P < 0.0001], E-MTAB-6134 [HR, 1.53 (1.14-2.04); P = 0.004], and GSE71729 [HR, 2.33 (1.49-3.63); P < 0.0001]. Interestingly, the ISP signature also permitted identification of poor molecular PDAC subtypes with excellent accuracy in all four cohorts; TCGA (AUC = 0.94), ICGC (AUC = 0.91), E-MTAB-6134 (AUC = 0.80), and GSE71729 (AUC = 0.83). The ISP-derived high-risk patients exhibited significantly poor OS in a clinical validation cohort [n = 119; HR, 2.62 (1.50-4.56); P = 0.0004]. A nomogram was established which included the ISP, CA19-9, and T- and N-stage for eventual clinical translation. CONCLUSIONS: We report a novel gene signature for risk-stratification and robust identification of patients with PDAC with poor molecular subtypes.

Johnson-Mann, C., M. Hassan and S. Johnson (2020). “COVID-19 pandemic highlights racial health inequities.” Lancet Diabetes Endocrinol 8(8): 663-664.

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The COVID-19 pandemic has substantially affected health care on a global scale, and has magnified the inequities in access to health care that existed before. This pandemic has highlighted the equity gap in outcomes for marginalised communities, specifically the Black community, as starkly shown by the disparate morbidity and mortality from COVID-19 in individuals from these communities compared with the majority white population.Furthermore, obesity and its associated comorbidities, which disproportionately affect racial or ethnic minorities, have played a central role in the severity of COVID-19 in marginalised communities. [No abstract; excerpt from article].

Jain, A., S. Yeramaneni, K. M. Kebaish, M. Raad, J. L. Gum, E. O. Klineberg, H. Hassanzadeh, M. P. Kelly, P. G. Passias, C. P. Ames, J. S. Smith, C. I. Shaffrey, S. Bess, V. Lafage, S. Glassman, L. Y. Carreon and R. A. Hostin (2020). “Cost-Utility Analysis of rhBMP-2 Use in Adult Spinal Deformity Surgery.” Spine (Phila Pa 1976) 45(14): 1009-1015.

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STUDY DESIGN: Economic modeling of data from a multicenter, prospective registry. OBJECTIVE: The aim of this study was to analyze the cost utility of recombinant human bone morphogenetic protein-2 (BMP) in adult spinal deformity (ASD) surgery. SUMMARY OF BACKGROUND DATA: ASD surgery is expensive and presents risk of major complications. BMP is frequently used off-label to reduce the risk of pseudarthrosis. METHODS: Of 522 ASD patients with fusion of five or more spinal levels, 367 (70%) had at least 2-year follow-up. Total direct cost was calculated by adding direct costs of the index surgery and any subsequent reoperations or readmissions. Cumulative quality-adjusted life years (QALYs) gained were calculated from the change in preoperative to final follow-up SF-6D health utility score. A decision-analysis model comparing BMP versus no-BMP was developed with pseudarthrosis as the primary outcome. Costs and benefits were discounted at 3%. Probabilistic sensitivity analysis was performed using mixed first-order and second-order Monte Carlo simulations. One-way sensitivity analyses were performed by varying cost, probability, and QALY estimates (Alpha = 0.05). RESULTS: BMP was used in the index surgery for 267 patients (73%). The mean (±standard deviation) direct cost of BMP for the index surgery was $14,000 ± $6400. Forty patients (11%) underwent revision surgery for symptomatic pseudarthrosis (BMP group, 8.6%; no-BMP group, 17%; P = 0.022). The mean 2-year direct cost was significantly higher for patients with pseudarthrosis ($138,000 ± $17,000) than for patients without pseudarthrosis ($61,000 ± $25,000) (P < 0.001). Simulation analysis revealed that BMP was associated with positive incremental utility in 67% of patients and considered favorable at a willingness-to-pay threshold of $150,000/QALY in >52% of patients. CONCLUSION: BMP use was associated with reduction in revisions for symptomatic pseudarthrosis in ASD surgery. Cost-utility analysis suggests that BMP use may be favored in ASD surgery; however, this determination requires further research. LEVEL OF EVIDENCE: 2.