Research Spotlight

Brinkman, W.T. (2020). “DARTS Trial.” Ann Thorac Surg Aug 21;S0003-4975(20)31339-4. [Epub ahead of print.].

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The DARTS trial presented in this issue of The Annals was a prospective, nonrandomized, international trial of patients with acute DeBakey I dissections. During the period of deep hypothermic arrest, the Ascyrus Medical Dissection Stent (AMDS) was deployed antegrade across the aortic arch and into the descending aorta in the true lumen. It is important to note that the centers enrolled “all comers” in a consecutive manner with Debakey type 1 dissections with certain exclusion criteria (such as known connective tissue disorder, iatrogenic dissections, preoperative ongoing CPR, age 80, or an arch or ascending aneurysm greater than 45mm). The primary entry tear was present in the ascending aorta and was resected in all cases. Secondary entry tears in the aortic arch were not required to be resected and were treated per individual surgeon preference. Surprisingly, it’s important to also realize that this is perhaps the first prospective multicenter trial ever done for ATAAD in the medical literature.

Diamond, J.R., Becerra, C., Richards, D., Mita, A., Osborne, C., O’Shaughnessy, J., Zhang, C., Henner, R., Kapoun, A.M., Xu, L., Stagg, B., Uttamsingh, S., Brachmann, R.K., Farooki, A. and Mita, M. (2020). “Phase Ib clinical trial of the anti-frizzled antibody vantictumab (OMP-18R5) plus paclitaxel in patients with locally advanced or metastatic HER2-negative breast cancer.” Breast Cancer Res Treat Aug 14. [Epub ahead of print.].

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PURPOSE: Vantictumab is a monoclonal antibody that binds to frizzled (FZD) receptors and inhibits canonical WNT signaling. This phase Ib dose escalation study enrolled patients with locally recurrent or metastatic HER2-negative breast cancer who were treated with weekly paclitaxel in combination with escalating doses of vantictumab. METHODS: Patients were enrolled in dose escalation cohorts treated with weekly paclitaxel 90 mg/m(2) on days 1, 8 and 15 in combination with vantictumab 3.5-14 mg/kg days 1 and 15 or 3-8 mg/kg day 1 of every 28-day cycle. Primary endpoints were safety, dose-limiting toxicities (DLTs). Secondary endpoints included pharmacokinetics, efficacy and an exploratory biomarker analysis. RESULTS: Forty-eight female patients with a mean age of 54 were enrolled. The majority (66.6%) received prior chemotherapy for recurrent or metastatic disease; 45.8% were hormone receptor (HR)-positive, HER2-negative and 54.2% triple-negative. The most frequent adverse events related to any study treatment were nausea (54.2%), alopecia (52.1%), fatigue (47.9%), and peripheral neuropathy (43.8%). No DLTs occurred; however, 6 patients experienced fractures outside of the DLT window. The overall response rate was 31.3% and the clinical benefit rate was 68.8%. A 6-gene WNT pathway signature showed significant association with progression-free survival (PFS) and overall survival (OS) for the biomarker high versus biomarker low groups (PFS: p = 0.029 and OS: p = 0.00045, respectively). CONCLUSIONS: The combination of vantictumab and weekly paclitaxel was generally well tolerated with promising efficacy; however, the incidence of fractures limits future clinical development of this particular WNT inhibitor in metastatic breast cancer.

Maddur, H. and Asrani, S.K. (2020). “Alcohol-associated hepatitis and liver transplantation: Mind the (racial, sex, economic, geographic, center, waitlist, and posttransplant outcomes) gap.” Am J Transplant Aug 9. [Epub ahead of print.].

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Over the last decade, liver transplantation (LT) for alcohol‐associated hepatitis (AH) has increased. In addition, the true number of patients undergoing LT for AH is likely underestimated. Changes in public perception may also be contributing. Given the rapidly evolving landscape of transplantation for AH, continuous examination of the US experience and relevant outcomes is needed. In this issue of the American Journal of Transplantation, Cotter and colleagues describe recent trends in LT for AH. First, the overall rates of transplantation for AH increased 5‐fold during the study period, albeit stabilizing during the last 2 years of the study period. LT rates had an 8‐fold variation between regions in addition to significant center variation within regions. Moreover, as compared to other indications, there were notable differences by demographics beyond younger age. LT recipients were disproportionately white (93% in some regions), male, more educated, and the majority had private insurance. Finally, outcomes after LT for AH were lower for select patient groups: lower survival was seen among women and nonwhite LT recipients. [No abstract; excerpt from article.].

Shrank, W.H., Caveney, B., Miller, S., Medows, R.M., Arroliga, A., Doga, B., Ban, K., Muldoon, S., Seiden, J.M., Tong, I., Chaguturu, S. and Wohlgemuth, J.G. (2020). “A Simple Algorithm for Return to Workplace Employer Antibody Testing.” Popul Health Manag Aug 26. [Epub ahead of print.].

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The role of serological antibody testing to aid in the management of the COVID-19 pandemic has garnered considerable enthusiasm in the lay media and policy spheres. There is intuitive appeal in using Immunoglobin G (IgG) testing to better understand levels of immunity in individuals and population as we develop plans for resuming economic activity. [No abstract available; excerpt from article.].

Daoulah, A., Al-Faifi, S.M., Alhamid, S., Youssef, A.A., Alshehri, M., Al-Murayeh, M., Farghali, T., Maghrabi, M., Balghith, M., ElSayed, O., Alasmari, A., Arafat, A.A., Elmahrouk, A.F., Eldesoky, A., Refaat, W.A., Alshahrani, S.S., Ghazi, A.M., Al-Azizi, K.M., Dahdouh, Z. and Lotfi, A. (2020). “Spontaneous Coronary Artery Dissection in the Gulf: G-SCAD Registry.” Angiology Aug 13;3319720946974. [Epub ahead of print.].

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Data on spontaneous coronary artery dissection (SCAD) is based on European and North American registries. We assessed the prevalence, epidemiology, and outcomes of patients presenting with SCAD in Arab Gulf countries. Patients (n = 83) were diagnosed with SCAD based on angiographic and intravascular imaging whenever available. Thirty centers in 4 Arab Gulf countries (Kingdom of Saudi Arabia, United Arab Emirates, Kuwait, and Bahrain) were involved from January 2011 to December 2017. In-hospital (myocardial infarction [MI], percutaneous coronary intervention, ventricular tachycardia/fibrillation, cardiogenic shock, death, implantable cardioverter-defibrillator placement, dissection extension) and follow-up (MI, de novo SCAD, death, spontaneous superior mesenteric artery dissection) cardiac events were recorded. Median age was 44 (37-55) years, 42 (51%) were females and 28.5% were pregnancy-associated (21.4% were multiparous). Of the patients, 47% presented with non-ST-elevation acute coronary syndrome, 49% with acute ST-elevation myocardial infarction, 12% had left main involvement, 43% left anterior descending, 21.7% right coronary, 9.6% left circumflex, and 9.6% multivessel; 52% of the SCAD were type 1, 42% type 2, 3.6% type 3, and 2.4% multitype; 40% managed medically, 53% underwent percutaneous coronary intervention, 7% underwent coronary artery bypass grafting. Females were more likely than males to experience overall (in-hospital and follow-up) adverse cardiovascular events (P = .029).