Research Spotlight

Testa, G. and L. Johannesson (2018). “Correspondence: Future direction of uterine transplantation.” Curr Opin Organ Transplant Dec 3. [Epub ahead of print].

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We would like to direct your attention to a statement written in the article “Current status and future direction of uterus transplantation” authored by Dr. Mats Brannstrom and published in Current Opinion in Organ Transplantation, October 2018. In the Section, “Live Donor Uterus Transplantation: Results”, it is stated that “Although the case proved to be successful, it has to be pointed out that bilateral use of utero-ovarian veins will necessitate donor oophorectomy and this will lead to premature menopause, with may lead to increase morbidity in this 32-year-old altruistic donor.” This statement is incorrect. In the publication announcing the first live birth after uterus transplantation in the United States, G. Testa et al. American Journal of Transplantion, May 2018, we clearly specified that “The utero ovarian veins were identified as they run closely to the fallopian and dissected free from the ovary. The ovaries were left in situ.” This donor surgical technique has been used routinely by us. In fact, the second mother to give birth in our programme also received a uterus transplant in which the venous outflow was based exclusively on the utero-ovarian vein segment and who donor did not require and oophorectomy. We thank you for the attention given to reporting the correct information. (Excerpt from text of this correspondence; no abstract available.)

Strober, B., J. Crowley, R. G. Langley, K. Gordon, A. Menter, C. Leonardi, D. Arikan and W. C. Valdecantos (2018). “Systematic review of the real-world evidence of adalimumab safety in psoriasis registries.” J Eur Acad Dermatol Venereol 32(12): 2126-2133.

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Long-term safety of adalimumab in psoriasis clinical studies has been established. The objective of this research was to review real-world evidence of adalimumab safety from registries of adult patients with psoriasis treated in clinical practice. Databases (BIOSIS Previews, Current Contents Search, Derwent Drug File, EMBASE, EMBASE Alert, EMCare, MEDLINE, SciSearch) were searched for psoriasis registries with adalimumab safety data. Eligible papers were English language manuscripts (conference abstracts excluded) from psoriasis registries presenting safety data for adult patients with psoriasis receiving adalimumab. The incidence and rate (events/100 patient-years [PY]) of adverse events (AEs), serious AEs (SAEs) and AEs of special interest are reported. Abstracts of 425 publications were screened, and 401 publications excluded (208 conference abstracts; 193 papers). Remaining manuscripts were fully screened; 14 were excluded (no adalimumab data, n = 10; no safety data, n = 2; no on-treatment data, n = 1; not English, n = 1), and 10 selected. Overall rates of AEs (4273 [22.2/100PY]) and SAEs (827 [4.3/100PY]) were reported in the ESPRIT registry (N = 6059). Rates of infections (7.7-14.7/100PY) and serious infections (<0.6-2.0/100PY) were reported in four studies. Cardiovascular-related events were reported in three studies:

Silfvast-Kaiser, A., S. Y. Paek and A. Menter (2018). “Anti-IL17 therapies for psoriasis.” Expert Opin Biol Ther Nov 30. [Epub ahead of print].

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INTRODUCTION: Interleukin-17 (IL-17) is a proinflammatory cytokine considered to play a significant role in the immunopathogenesis of plaque psoriasis. As a result, focus in clinical trials has undergone a shift towards disease specific targets, with the goals of more effective treatment and reduction in the incidence of serious adverse events. Areas Covered: Two monoclonal antibodies targeting IL-17A (secukinumab, ixekizumab) and one against the IL-17 receptor (brodalumab) are approved for the treatment of moderate-to-severe plaque psoriasis. Herein, the clinical efficacy, safety and tolerability of each is reviewed by summarizing the existing literature (found via PubMed database). Expert Commentary: The development and approval of the IL-17 inhibitor agents secukinumab, ixekizumab, and brodalumab has expanded psoriatic treatment with effective options, validating the importance of the pro-inflammatory role of IL-17 psoriatic pathophysiology. Biologic treatment options for psoriasis will continue to grow, especially IL-17 and IL-23 related agents, with an increasing specificity of agents to be available in the future.

Shutze, W. P., Sr., R. Shutze, P. Dhot, M. Forge, A. Salazar and G. O. Ogola (2018). “Sex as an independent risk factor for long-term survival after endovascular aneurysm repair.” J Vasc Surg Nov 26. [Epub ahead of print].

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BACKGROUND: Several vascular surgical procedures, including repair of abdominal aortic aneurysms (AAAs), show poorer outcomes for women than for men. We evaluated the impact of sex-based demographic differences on survival after endovascular aneurysm repair (EVAR). METHODS: We reviewed EVARs performed at our institution between 2003 and 2009 and assessed aortic neck variables (length, diameter, angulation, and calcification), iliac artery variables (length, tortuosity, angulation, and calcification), and AAA diameter. Cox proportional hazards models were used to examine the association between sex and 5-year mortality while adjusting for patients’ demographics, comorbidities, anatomic variables, and AAA parameters. The final model adjusted for sex, age, body mass index, hypertension, iliac artery length, and aortic neck length. RESULTS: Of 336 patients, 278 were male (mean age, 73 years) and 58 were female (mean age, 77 years; P = .0005). Men had more coronary artery bypass grafts (79 vs 8; P = .02) and percutaneous coronary interventions (52 vs 4; P = .03) than women did. Significant differences between the sexes was seen for aortic neck angle, diameter, and length and for iliac artery diameter and length. Men (44%) were more likely than women (22%; P = .0002) to have EVAR performed within the device guidelines. Five-year survival was 73% in men and 49% in women. Multivariable analysis showed that female sex, increase in age, low body mass index (<25 kg/m(2)), and aortic neck length were significantly associated with risk of 5-year mortality. CONCLUSIONS: Women presented at an older age and with a more hostile anatomy. They had reduced survival compared with men after EVAR. After controlling for comorbidities and aortic neck and iliac artery anatomy, sex remained an independent predictor for survival.

Shutze, W., V. Suominen, W. Jordan, P. Cao, S. Oweida and R. Milner (2018). “The incidence and effect of noncylindrical neck morphology on outcomes after endovascular aortic aneurysm repair in the Global Registry for Endovascular Aortic Treatment.” J Vasc Surg 68(6): 1714-1724.

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BACKGROUND: The Gore Global Registry for Endovascular Aortic Treatment (GREAT) was designed to evaluate real-world outcomes after treatment with Gore aortic endografts used in a real-world, global setting. We retrospectively analyzed the GREAT data to evaluate the incidence and effects of noncylindrical neck anatomy in patients undergoing endovascular aortic aneurysm repair. METHODS: The present analysis included patients with data in the GREAT who had been treated with the EXCLUDER endograft from August 2010 to October 2016. A noncylindrical neck was defined when the proximal aortic landing zone diameter had changed >/=2 mm over the first 15 mm of the proximal landing zone, indicating a tapered, conical, or hourglass morphology. Cox multivariate regression analyses were performed for any reintervention (including reinterventions on aortic branch vessels), device-related reinterventions, and reintervention specifically for endoleak. Independent binary (cylindrical vs noncylindrical necks) and continuous (percentage of neck diameter change) variables were assessed. The abdominal aortic aneurysm (AAA) diameter, proximal neck length, maximal infrarenal neck angle, gender, and use of aortic extender cuffs were also assessed. RESULTS: Of 3077 GREAT patients with available proximal aortic landing zone diameter measurements available, 1765 were found to have cylindrical necks and 1312 had noncylindrical necks. The noncylindrical neck cohort had a significantly greater proportion of women (17.4% vs 12.6%; P < .001) and more severe infrarenal angulation (33.8 degrees vs 28.4 degrees; P < .001). A total 14.7% of noncylindrical neck patients and 11.2% cylindrical neck patients underwent implantation outside of the EXCLUDER instructions for use regarding the anatomic inclusion criteria (P = .004). The procedural characteristics were similar between the two cohorts; however, noncylindrical neck patients required significantly more aortic extender cuffs (P = .004). The average follow-up was 21.2 +/- 17.5 months and 17.8 +/- 15.8 months for the cylindrical and noncylindrical cohorts, respectively (P < .001). The Cox multivariate regression models demonstrated female gender and maximum AAA diameter were significant risk factors for subsequent reintervention (overall, device-related, and endoleak-specific). Women were 2.2 times as likely to require device-related intervention during the follow-up period compared with men (P < .001). Neck shape morphology was not a significant predictor, except for device-related intervention, for which cylindrical necks (binary definition) resulted in a slightly elevated risk (1.5 times; P = .03). CONCLUSIONS: Noncylindrical neck morphology was more common in women and was associated with an increased use of aortic extender cuffs but did not increase the risk of intervention. Female gender and AAA diameter were associated with an increased need for reintervention.