Research Spotlight

Rendon, R., K. Mannoia, S. Reiman, L. Hitchman and W. Shutze (2019). “Rotational vertebral artery occlusion secondary to completely extraosseous vertebral artery.” J Vasc Surg Cases Innov Tech 5(1): 14-17.

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Rotational vertebral artery (VA) occlusion is a possible cause of reduced blood flow through the posterior circulation of the brain due to compression of the VA on head turning when blood flow from the contralateral VA is compromised. When compression occurs in the V2 segment of the VA, it is usually due to compression from the longus colli muscle or cervical osteophytes. We present a unique case of a patient with a completely extraosseous course of the V2 segment of her dominant right VA that resulted in symptomatic rotational VA occlusion.

Reich, K., P. Rich, C. Maari, R. Bissonnette, C. Leonardi, A. Menter, A. Igarashi, P. Klekotka, D. Patel, J. Li, J. Tuttle, M. Morgan-Cox, E. Edson-Heredia, S. Friedrich and K. Papp (2019). “Efficacy and Safety of Mirikizumab (LY3074828) in the Treatment of Moderate-to-Severe Plaque Psoriasis: Results from a Randomised Phase 2 Study.” Br J Dermatol Feb 7. [Epub ahead of print].

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BACKGROUND AND OBJECTIVES: Inhibiting the interleukin (IL)-23 cytokine in patients with psoriasis has demonstrated high levels of skin clearance. In this Phase 2 (AMAF, NCT02899988), multicentre, double-blind trial, we investigated the efficacy and safety of three dose groups of mirikizumab (LY3074828), a p19-directed IL-23 antibody, compared to placebo in patients with moderate-to-severe plaque psoriasis. METHODS: Adult patients were randomised 1:1:1:1 to receive placebo (N=52), mirikizumab 30 mg (N=51), 100 mg (N=51), or 300 mg (N=51) subcutaneously at Weeks 0 and 8. The primary objective was to evaluate superiority of mirikizumab to placebo in achieving a 90% improvement in the Psoriasis Area and Severity Index (PASI 90) response at Week 16. Comparisons were done using logistic regression analysis with treatment, geographic region and previous biologic therapy in the model. Missing data were imputed as nonresponse. RESULTS: Ninety-seven percent of patients completed the first 16 weeks of Study AMAF. The primary endpoint was met for all mirikizumab dose groups versus placebo, with PASI 90 response rates at Week 16 of 0%, 29.4% (p=0.009), 58.8% (p<0.001) and 66.7% (p<0.001) for patients receiving placebo, mirikizumab 30 mg, 100 mg and 300 mg, respectively. There were 2 (1.3%) serious AEs in mirikizumab-treated patients compared to 1 (1.9%) placebo-group patient. CONCLUSIONS: At Week 16, 66.7% of patients treated with mirikizumab 300 mg at 8-week intervals achieved PASI 90. The percentage of patients reporting at least one treatment-emergent adverse event was similar among patients treated with placebo or mirikizumab.

Packer, M. (2019). “When Cardiovascular Trials Collide.” Eur Heart J 40(6): 501-504.

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In the modern era of clinical trials, we do not expect large-scale, definitively designed and executed studies to yield misleading results if they are meticulously analysed in an unbiased manner. Fortunately, the discordant results of the MITRA-FR and COAPT trials do not undermine this conventional wisdom. Instead, the reporting of discordant results from the two studies has led us to rediscover a conceptual framework in which the results of both trials are valid. With respect to MITRA-FR and COAPT, the combined results of the trials tell us that patients with functional MR do not have a homogenous disorder. By providing complementary information, the trials (when considered together) indicate that we must now make a clear distinction between MR that is proportionate or disproportionate to the degree of LV enlargement. Optimal medical therapy seems to be the best choice for patients with proportionate MR, whereas mitral valve repair is highly desirable in those with disproportionate MR. Such a coherent understanding could not have been achieved if the MITRA-FR and COAPT trials had studied the same patients and yielded the same results. Integration of the results of MITRA-FR and COAPT allows us to optimally individualize the management of the heterogeneous group of patients who present with functional MR, heart failure, and LV dysfunction. (Excerpt from text, p. 503; no abstract available.)

Osoegawa, K., T. A. Vayntrub, S. Wenda, D. De Santis, K. Barsakis, M. Ivanova, S. Hsu, J. Barone, R. Holdsworth, M. Diviney, M. Askar, A. Willis . . . and M. A. Fernandez-Vina (2019). “Quality control project of NGS HLA genotyping for the 17th International HLA and Immunogenetics Workshop.” Hum Immunol Feb 6. [Epub ahead of print].

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The 17th International HLA and Immunogenetics Workshop (IHIW) organizers conducted a Pilot Study (PS) in which 13 laboratories (15 groups) participated to assess the performance of the various sequencing library preparation protocols, NGS platforms and software in use prior to the workshop. The organizers sent 50 cell lines to each of the 15 groups, scored the 15 independently generated sets of NGS HLA genotyping data, and generated “consensus” HLA genotypes for each of the 50 cell lines. Proficiency Testing (PT) was subsequently organized using four sets of 24 cell lines, selected from 48 of 50 PS cell lines, to validate the quality of NGS HLA typing data from the 34 participating IHIW laboratories. Completion of the PT program with a minimum score of 95% concordance at the HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 loci satisfied the requirements to submit NGS HLA typing data for the 17th IHIW projects. Together, these PS and PT efforts constituted the 17th IHIW Quality Control project. Overall PT concordance rates for HLA-A, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, HLA-DRB4 and HLA-DRB5 were 98.1%, 97.0% and 98.1%, 99.0%, 98.6%, 98.8%, 97.6%, 96.0%, 99.1%, 90.0% and 91.7%, respectively. Across all loci, the majority of the discordance was due to allele dropout. The high cost of NGS HLA genotyping per experiment likely prevented the retyping of initially failed HLA loci. Despite the high HLA genotype concordance rates of the software, there remains room for improvement in the assembly of more accurate consensus DNA sequences by NGS HLA genotyping software.

Menter, A. and R. Warren (2019). “A Summary of 2018 and What Lies Ahead for Dermatology and Therapy in 2019.” Dermatol Ther (Heidelb) 9(1): 1-3.

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[A review of the year 2018 by the editors of the journal Dermatology and Therapy; no abstract available.]