Endovascular and Hybrid Repair in Patients with Heritable Thoracic Aortic Disease.

BACKGROUND: In individuals with heritable thoracic aortic disease (HTAD), endovascular repair for treatment of aortic aneurysm and dissection may be lifesaving, but is associated with increased risk of failure of endovascular repair and adverse outcomes. This study reports our experience with early and late outcomes of endovascular aortic and branch vessel repair in patients with HTAD. METHODS: A retrospective case series was performed by chart review of individuals with HTAD followed at Washington University School of Medicine/Barnes-Jewish Hospital who underwent endovascular aortic and/or branch vessel repair. Clinical features, imaging characteristics, and short- and long-term outcomes were collected. RESULTS: Twenty-nine patients with HTAD (20 male; mean age 45 ± 13 years) underwent 37 endovascular procedures between 2006 and 2020 with mean follow up of 54 ± 41 months. Seven patients underwent two or more separate endovascular procedures. Each procedure was considered separate for data collection and analysis. Underlying conditions included Marfan syndrome (n = 16 procedures), Loeys-Dietz syndrome (n = 14 procedures), vascular Ehlers-Danlos syndrome (n = 3 procedures), and nonsyndromic HTAD (n = 4 procedures). Twenty patients (69%) had prior open surgical aortic repair. Indications for endovascular aortic repair (n = 31) included urgent repairs of acute complications of aortic dissection (n = 10) or aneurysm rupture (n = 3), and elective aortic repair (n = 18; 10 chronic dissections and eight chronic aneurysms). Six patients underwent elective endovascular repair of six branch vessel aneurysms or dissections. Six patients underwent hybrid open surgical and endovascular repair. Of the 37 procedures, 25 (68%) proximal landing zones were in the native aorta or branch vessel, 11 (30%) were in a surgical graft or elephant trunk and one was in a previously placed endograft. Thirty-six (97%) procedures were technically successful, and none required emergency surgical conversion. Two patients died: one from sepsis and one from presumed late pseudoaneurysm rupture, for a 5% per-procedure mortality rate. Two procedures were complicated by stroke and one patient developed paraparesis. Of the 31 aortic procedures, seven aortic endografts (23%) developed a stent-induced new entry (SINE) discovered with imaging at 20 ± 15 days post-procedure. Seven endografts (23%) developed a Type I endoleak and eight (26%) developed a Type II endoleak. No Type III endoleaks were seen. Within 30 days, two endografts (of 37, 5%) required reintervention. After 30 days, fifteen additional endografts (of 37, 41%) required reintervention. Two patients (of 6, 33%) who underwent hybrid repair required reintervention. CONCLUSIONS: This study is the largest single-center case series examining outcomes of HTAD patients following endovascular repair. Urgent and elective endovascular repairs in patients with HTAD can manage acute and chronic complications of aortic aneurysm and dissection with relatively low risk. However, risk of early and late endoleaks and SINE is high. Close post-procedural surveillance is required, and many individuals will require additional interventions. Hybrid repair shows promise and requires further investigation.

Engagement of SLAMF3 enhances CD4+ T-cell sensitivity to IL-2 and favors regulatory T-cell polarization in systemic lupus erythematosus.

Signaling lymphocytic activation molecule family 3 (SLAMF3/Ly9) is a coregulatory molecule implicated in T-cell activation and differentiation. Systemic lupus erythematosus (SLE) is characterized by aberrant T-cell activation and compromised IL-2 production, leading to abnormal regulatory T-cell (Treg) development/function. Here we show that SLAMF3 functions as a costimulator on CD4(+) T cells and influences IL-2 response and T helper cell differentiation. SLAMF3 ligation promotes T-cell responses to IL-2 via up-regulation of CD25 in a small mothers against decapentaplegic homolog 3 (Smad3)-dependent mechanism. This augments the activation of the IL-2/IL-2R/STAT5 pathway and enhances cell proliferation in response to exogenous IL-2. SLAMF3 costimulation promotes Treg differentiation from naïve CD4(+) T cells. Ligation of SLAMF3 receptors on SLE CD4(+) T cells restores IL-2 responses to levels comparable to those seen in healthy controls and promotes functional Treg generation. Taken together, our results suggest that SLAMF3 acts as potential therapeutic target in SLE patients by augmenting sensitivity to IL-2.

How Effective Was the 2014 AUA Cryptorchidism Guideline? A Multi-institutional Evaluation.

INTRODUCTION: In 2014, the AUA published guidelines regarding the evaluation of cryptorchidism. This multi-institutional study aims to determine if these guidelines reduced the age of referral and the utilization of ultrasound in boys with cryptorchidism. We hypothesize that delayed referral continues, and utilization of ultrasound remains unchanged. METHODS: A retrospective review of boys referred for the evaluation of cryptorchidism was performed at 4 academic institutions, collecting data for 1 year prior (2013) and 2 nonconsecutive years following guideline creation (2015 and 2019). Across these time frames, we compared median ages at evaluation and surgery, and rates of patient comorbidities, orchiopexy, and preevaluation ultrasound. RESULTS: A total of 3,293 patients were included. The median age at initial pediatric urology evaluation in all cohorts was 39 months (IQR: 14-92 months). Following publication of the AUA Guidelines, there was no difference (P = .08) in the median age at first evaluation by a pediatric urologist between 2013 and 2015, and an increase (P = .03) between 2013 and 2019. Overall, 21.2% of patients received an ultrasound evaluation prior to referral, with no significant difference between 2013 and 2015 (P = .9) or 2019 (P = .5) cohorts. CONCLUSIONS: Our data suggest that, despite publication of the AUA Guidelines on evaluation and treatment of cryptorchidism, there has been no reduction in the age of urological evaluation or the utilization of imaging in boys with undescended testis. Finding alternative avenues to disseminate these evidence-based recommendations to referring providers and exploring barriers to guideline adherence is necessary to improve care for patients with cryptorchidism.