Research Spotlight

Gaudino, M., D. J. Angiolillo, A. Di Franco, D. Capodanno, F. Bakaeen, M. E. Farkouh, S. E. Fremes, D. Holmes, L. N. Girardi, S. Nakamura, S. J. Head, S. J. Park, M. Mack, P. W. Serruys, M. Ruel, G. W. Stone, D. Y. Tam, M. Vallely and D. P. Taggart (2019). “Stroke After Coronary Artery Bypass Grafting and Percutaneous Coronary Intervention: Incidence, Pathogenesis, and Outcomes.” J Am Heart Assoc 8(13): e013032. Epub 2019 Jun 27.

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Stroke carries high short‐ and long‐term mortality and significantly adversely affects quality of life after both CABG and PCI. In an era in which practice guidelines endorse fully informing patients of the available treatment options and actively including them in the decision‐making process, defining the risk of stroke, both acute and long term, and its clinical implications is of paramount importance. CABG carries higher perioperative risk of stroke but provides greater long‐term freedom from recurrent ischemic coronary events and better survival, especially in the patients with most severe disease.2 Percutaneous revascularization is feasible in many patients and is associated with relatively low stroke rates, but this benefit needs to weighed against the higher rates of long‐term mortality and myocardial infarction, particularly in some categories of patients with diabetes mellitus and/or extensive multivessel disease. Indeed, better understanding the size of an injury deriving from a stroke with the 2 available revascularization approaches and the significance of silent brain lesions or neurocognitive changes that may occur would inform the decision‐making process. However, data on these measures (e.g., serial brain imaging) are lacking. A number of measures can be considered to reduce neurological risk in patients undergoing revascularization. For surgery, pre‐ and intraoperative screening of the ascending aorta and optimization of cerebral perfusion pressure based on continuous monitoring are important measures to minimize stroke risk. The use of the anaortic technique has the potential to minimize stroke risk during CABG. Given its technical complexity, specific training is required, ideally in the context of a new CABG subspecialty. Other technical advancements (e.g., embolic protection) warrant investigation to reduce the perioperative risk of stroke in patients undergoing CABG. For PCI, the reduction in mortality and bleeding—with some data also showing a reduction in peri-procedural stroke—associated with radial access potentially makes this approach the vascular access of choice. Regardless of vascular access, operator experience and competency play key roles in minimizing catheter‐induced trauma to the aortic wall and cerebral embolization. Other important measures include optimal anticoagulation and avoidance of air embolism with adequate flushing and connections to the manifold. Routine use of manual thrombectomy in ST‐segment–elevation myocardial infarction should be avoided; if required, adequate catheter engagement should be maintained to avoid embolization of thrombotic material. Finally, IABP and hemodynamic support devices in general should be used with caution, particularly in patients with diffuse atherosclerotic aortic disease. (Excerpt from text, p. e013032, 8-9; no abstract available.)

Garg, A., E. Neuren, D. Cha, . . . S. Y. Paek, B. Resnik, Q. Ju, L. Wang and A. Strunk (2019). “Evaluating Patients’ Unmet Needs in Hidradenitis Suppurativa: results from the Global VOICE project.” J Am Acad Dermatol Jul 3. [Epub ahead of print].

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BACKGROUND: A needs assessment for patients with hidradenitis suppurativa (HS) will support advancements in multidisciplinary care, treatment, research, advocacy, and philanthropy. OBJECTIVE: To evaluate unmet needs from the perspective of HS patients. METHODS: Prospective multinational survey of patients between October, 2017 and July, 2018. RESULTS: Majority (63.7%, n=827) visited a physician >/=5 times prior to receiving formal HS diagnosis. Mean delay in diagnosis was 10.2 years (+/- 8.9 years). Patients experienced flare daily, weekly, or monthly in 23.0%, 29.8%, and 31.1%, respectively. Most (61.4%, n=798) rated recent HS-related pain as moderate or higher, while 4.5% described recent pain to be worst possible. Access to dermatology was rated as difficult by 37.0% (n=481). Patients reported visiting the emergency department and hospital >/=5 times for symptoms in 18.3% and 12.5%, respectively. An extreme impact on life was reported by 43.3% (n=563), and 14.5% were disabled due to disease. Patients reported high frequency of comorbidities, most commonly mood disorders. Patients were dissatisfied with medical or procedural treatments in 45.9% and 34.5%, respectively. LIMITATIONS: Data was self-reported. Patients with more severe disease may have been selected. CONCLUSIONS: HS patients have identified several critical unmet needs that will require stakeholder collaboration to meaningfully address.

Fitzgerald, S., D. Dai, S. Wang, A. Douglas, R. Kadirvel, K. F. Layton, I. C. Thacker, M. J. Gounis, J. Y. Chueh, A. S. Puri, M. Almekhlafi, A. M. Demchuk, R. A. Hanel, E. Sauvageau, A. Aghaebrahim, A. J. Yoo, P. Kvamme, M. P. V, Y. Kayan, J. E. Delgado Almandoz, R. G. Nogueira, A. A. Rabinstein, D. F. Kallmes, K. M. Doyle and W. Brinjikji (2019). “Platelet-Rich Emboli in Cerebral Large Vessel Occlusion Are Associated With a Large Artery Atherosclerosis Source.” Stroke 50(7): 1907-1910.

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Background and Purpose- Nearly 30% of large vessel occlusion acute ischemic stroke clots are from an unknown source. We assessed histological clot composition in a series of patients with large vessel occlusion and investigated correlations between clot composition and stroke pathogenesis. Methods- As part of the multi-institutional STRIP registry (Stroke Thromboembolism Registry of Imaging and Pathology), consecutive emboli retrieved during mechanical thrombectomy were stained using Martius Scarlett Blue and analyzed using machine learning software. We assessed proportions of red blood cells, fibrin, platelets, and white blood cells. Correlations between clot components and stroke pathogenesis (large artery atherosclerosis, cardioembolism, and stroke of undetermined pathogenesis) were assessed using SPSS22. Results- One hundred five patients were included. The proportion of platelet-rich clots (55.0% versus 21.2%; P=0.005) and percentage of platelet content (22.1+/-4.2% versus 13.9+/-14.2%; P=0.03) was significantly higher in the large artery atherosclerosis group compared with the cardioembolic group. The proportion of platelet-rich clots (50.0% versus 21.2%; P=0.024) was also significantly higher in the cryptogenic group compared with cardioembolic cases. Large artery atherosclerosis and cryptogenic cases had a similar proportion of platelet-rich clots (55.0% versus 50.0%; P=0.636). There was no significant difference between stroke pathogenesis and the other major clot components. Conclusions- High platelet content of emboli is associated with a large artery atherosclerosis etiology of large vessel occlusion.

Fawaz, B., B. H. Chamseddin and J. R. Griffin (2019). “Defining the role of mirtazapine in the treatment of refractory pruritus.” J Dermatolog Treat Jun 27: 1-5. [Epub ahead of print]: 1-5.

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Background/Objective: Mirtazapine has traditionally been used for the treatment of major depressive disorder, with an added benefit in patients who have comorbid insomnia or anxiety. Recent studies describe its usefulness in treating refractory pruritus of various causes as well. Our goal is to better define the use of mirtazapine in the treatment of refractory pruritus. Method: Through a thorough literature review of PubMed, we identified all reports of the use of mirtazapine for pruritus. Results: Upon examination of 8 supporting articles, we found mirtazapine has quality evidence for the treatment of intra-thecal morphine-induced pruritus. Mirtazapine may also be effective in treating pruritus related to various other conditions, including psoriasis, atopic dermatitis, cutaneous malignancies (primary or metastatic), hematologic malignancies (lymphomas and leukemias), liver failure, renal failure, cholestasis, as well as pruritus of unknown origin. Conclusions: Mirtazapine plays a role in treatment for intra-thecel morphine-induced pruritis yet high-quality trials are needed to confirm its efficacy in other dermatologic conditions.

Elewski, B., A. Menter, J. Crowley, S. Tyring, Y. Zhao, S. Lowry, S. Rozzo, A. M. Mendelsohn, J. Parno and K. Gordon (2019). “Sustained and Continuously Improved Efficacy of Tildrakizumab in Patients with Moderate-to-Severe Plaque Psoriasis.” J Dermatolog Treat Jul 3: 1-19. [Epub ahead of print].

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Background: Tildrakizumab is a high-affinity, humanized, IgG1 kappa, anti-interleukin-23 monoclonal antibody approved for moderate-to-severe plaque psoriasis. Objectives: This analysis examined whether tildrakizumab’s week-28 efficacy can be sustained or improved to week 52. Methods: Psoriasis patients on the same-dose tildrakizumab (100 or 200 mg) in the first 52 weeks achieving week-28 PASI >/=50 were pooled from two phase-3 randomized controlled trials, and grouped into four mutually exclusive week-28 PASI response groups. Patients’ week-52 PASI responses were compared to their week-28 PASI responses. Results: Of 352 patients receiving 100-mg tildrakizumab, 10.5%, 25.3%, 38.4%, and 25.9% achieved PASI 50-74, 75-89, 90-99, and 100 at week 28, respectively. Among patients achieving PASI >/=90, >/=75, or >/=50 at week 28, 89.4%, 91.1%, or 97.4% maintained their week-28 PASI responses at week 52, respectively. Among patients achieving PASI 50-74, 75-89, or 90-99 at week 28, 64.8%, 33.7%, or 25.2% improved their week-28 PASI responses at week 52, respectively. Limitations: This post-hoc analysis may be less robust than an a priori analysis. Conclusions: Most tildrakizumab-treated patients with week-28 PASI >/=75 maintained their week-28 PASI improvement at week 52. More than half of week-28 partial responders (PASI 50-74) improved their PASI responses to PASI >/=75 at week 52. Clinicaltrials.gov Identifiers: NCT01722331, NCT01729754.