Citations

Objective The portable Freedom Drive (SynCardia Inc, Tucson, AZ USA) for total artificial heart (TAH-t) support was approved for an investigational device exemption study in March 2010. We review our center's experience with the portable driver. Methods A retrospective review was conducted of patients who underwent TAH-t implantation and transfer to portable driver from September 2008 to June 2012, with follow-up through December 2012. Results A total of 30 patients underwent TAH-t implantation during this time period, with 11 patients successfully transferred to the Freedom Driver. Transfer to Freedom Driver after TAH-t implant was a median of 46 days (range, 225–86 days). Ninety-one percent (10) of 11 patients transferred to Freedom Driver were bridged to transplantation. One patient died on support. Five (45.5%) of 11 patients were discharged home and 5 (45.5%) remained in-patient on the portable driver before transplantation. Four patients (80%) successfully discharged home required at least 1 hospital readmission (range, 1–5 admissions per patient). Six patients (55%) transferred to the portable driver required a return to a main driver console. Two patients were temporarily maintained on the main driver then returned to the Freedom Driver for bridge to transplantation. Conclusions Patients with TAH-t can be considered for transfer to the portable Freedom Driver while awaiting transplantation. Issues that complicated this patient population included inadequate social support, hemodynamic instability, and concurrent morbidities. The potential benefits of the portable driver are currently undergoing assessment. These may include increased mobility and improved quality of life, opportunity for discharge home, and decreased overall medical costs.

Abstract Recent thymic emigrants are newly generated T cells that need to undergo postthymic maturation to gain functional competency and enter the long-lived naive T cell pool. The mechanism of T cell maturation remains incompletely understood. Previously, we demonstrated that the transcriptional repressor NKAP is required for T cell maturation. Because NKAP associates with histone deacetylase 3 (HDAC3), we examined whether HDAC3 is also required for T cell maturation. Although thymic populations are similar in CD4-cre HDAC3 conditional knockout mice compared with wild-type mice, the peripheral numbers of CD4+ and CD8+ T cells are dramatically decreased. In the periphery, the majority of HDAC3-deficient naive T cells are recent thymic emigrants, indicating a block in T cell maturation. CD55 upregulation during T cell maturation is substantially decreased in HDAC3-deficient T cells. Consistent with a block in functional maturation, HDAC3-deficient peripheral T cells have a defect in TNF licensing after TCR/CD28 stimulation. CD4-cre HDAC3 conditional knockout mice do not have a defect in intrathymic migration, thymic egress, T cell survival, or homeostasis. In the periphery, similar to immature NKAP-deficient peripheral T cells, HDAC3-deficient peripheral T cells were bound by IgM and complement proteins, leading to the elimination of these cells. In addition, HDAC3-deficient T cells display decreases in the sialic acid modifications on the cell surface that recruit natural IgM to initiate the classical complement pathway. Therefore, HDAC3 is required for T cell maturation.

Based on our experience in treating peripheral non‐neural sheath derived pathology, we have identified a novel pattern of lesion progression along the anatomic course of nerves. This report highlights the existence of a subparaneurial compartment around peripheral nerves. We first applied an anatomic framework to review MR images and intraoperative photographs of patients treated by the senior author in the last 10 years. After identifying a pattern that was consistent with subparaneurial lesion progression, we searched for other examples of cases that might exhibit this pattern. Four examples of subparaneurial pathology were identified, a hemangioma of the ulnar nerve, a ganglion cyst of the common fibular nerve, a lymphoma of the sciatic nerve and a lipoma of the ulnar nerve. All four patients were operated on and had intraoperative photographs; three had high resolution MR imaging. This report highlights the existence of pathology contained within a subparaneurial compartment, outside of the epineurium, that follows the course of the nerve and surrounds it circumferentially. The subparaneurial localization of peripheral nerve lesions has hitherto received little attention. Identification of this new pattern on preoperative MRI may have implications for surgical management. Clin. Anat. 28:925–930, 2015. © 2015 Wiley Periodicals, Inc.

Background: With patients living a decade or longer post-procedure, long-term data are needed to assess the durability of carotid artery stenting versus carotid endarterectomy. Identifying characteristics of those consenting or declining to continue in long-term follow-up may suggest strategies to improve retention in clinical trials. Purpose: This report describes differences between patients choosing or declining to continue follow-up for up to 10 years in the Carotid Revascularization Endarterectomy versus Stenting Trial. Methods: Following completion of the primary outcome, patients who were in active Carotid Revascularization Endarterectomy versus Stenting Trial follow-up were asked to continue beyond their original 4-year commitment for a maximum of 10 years. The characteristics of those who consented were compared with those who declined. Univariate and multivariable logistic regression were used for analysis, and backwards stepwise logistic regression (the most parsimonious model) was used to determine the factors associated with continuation. Results: Of the 1921 active Carotid Revascularization Endarterectomy versus Stenting Trial participants for whom consent to extend follow-up was requested, 1695 (88%; mean age: 68.4) consented; 226 (12%; mean age: 69.6) declined. Of those who did not consent versus those who consented, 66% versus 48% were symptomatic at baseline (p < 0.0001), at follow-up 28% versus 20% were smokers (p = 0.009), 85% versus 90% were hypertensive (p = 0.01), and 84% versus 94% were dyslipidemic (p < 0.0001). Additional factors that differed between those who did not consent and those who consented included the mean number of years in the study at time of consent (4.8 years vs 3.7 years (p = <0.0001)) and patients from sites that enrolled <30 patients compared to sites randomizing 30 or more (70% vs 52% (p < 0.0001)). Multivariable logistic regression indicated that those with lesser odds of consenting to the extended follow-up were older (odds ratio: 0.80; 95% confidence interval: 0.67, 0.96), more likely to be symptomatic (odds ratio: 0.58; 95% confidence interval: 0.42, 0.80), smokers (odds ratio: 0.48; 95% confidence interval: 0.34, 0.70), were in the study 5+ years versus <3 (odds ratio: 0.21; 95% confidence interval: 0.13, 0.34), and at a site that randomized <30 patients (odds ratio: 0.46; 95% confidence interval: 0.33, 0.63), while patients with dyslipidemia at follow-up had increased odds of consenting (odds ratio: 2.28 (1.47, 3.54)). Conclusion: Symptomatic status, increasing age, randomized at lower volume centers, and longer time in follow-up were associated with reduced odds of consenting to long-term follow-up. Identifying factors associated with reduced willingness to extend participation long-term can suggest targeted strategies to improve retention in future clinical trials.

Epigenetic drugs can overcome resistance to monoclonal antibodies in T-PLL and activate therapeutic targets for antibody-drug conjugates.

Background and Purpose— The majority of genome-wide association studies (GWAS) of stroke have focused on European-ancestry populations; however, none has been conducted in African Americans, despite the disproportionately high burden of stroke in this population. The Consortium of Minority Population Genome-Wide Association Studies of Stroke (COMPASS) was established to identify stroke susceptibility loci in minority populations. Methods— Using METAL, we conducted meta-analyses of GWAS in 14 746 African Americans (1365 ischemic and 1592 total stroke cases) from COMPASS, and tested genetic variants with P <10 −6 for validation in METASTROKE, a consortium of ischemic stroke genetic studies in European-ancestry populations. We also evaluated stroke loci previously identified in European-ancestry populations. Results— The 15q21.3 locus linked with lipid levels and hypertension was associated with total stroke (rs4471613; P =3.9×10 −8 ) in African Americans. Nominal associations ( P <10 −6 ) for total or ischemic stroke were observed for 18 variants in or near genes implicated in cell cycle/mRNA presplicing ( PTPRG , CDC5L ), platelet function ( HPS4 ), blood–brain barrier permeability ( CLDN17 ), immune response ( ELTD1, WDFY4 , and IL1F10-IL1RN ), and histone modification ( HDAC9 ). Two of these loci achieved nominal significance in METASTROKE: 5q35.2 ( P =0.03), and 1p31.1 ( P =0.018). Four of 7 previously reported ischemic stroke loci ( PITX2, HDAC9, CDKN2A/CDKN2B , and ZFHX3 ) were nominally associated ( P <0.05) with stroke in COMPASS. Conclusions— We identified a novel genetic variant associated with total stroke in African Americans and found that ischemic stroke loci identified in European-ancestry populations may also be relevant for African Americans. Our findings support investigation of diverse populations to identify and characterize genetic risk factors, and the importance of shared genetic risk across populations.