Carotid artery dissections from TCAR as reported by the Food and Drug Administration

BACKGROUND: Transcarotid artery revascularization (TCAR) is hybrid procedure that allows carotid stenting using direct surgical access of the carotid artery to restore blood flow through the carotid artery. It has shown the lowest perioperative stroke rate when compared with any prospective trial of transfemoral carotid artery stenting. However, intraoperative injuries related to the procedure and its management are not well characterized. We anticipate that this analysis will add qualitative insight in further characterizing adverse outcomes of this novel technology. METHODS: The FDA maintains a database called the MAUDE (Manufacturer and User Facility Device Experience) for surveillance of all medical devices approved for use. This database was queried for all cases associated with Silk Road Medical’s ENROUTE Transcarotid Neuroprotection System from September 2016 to October 2020.. Case narratives related to patient injuries were individually analyzed to determine type (carotid artery dissection) and time of injury (intraoperative, recovery, post-discharge follow- up). Carotid artery dissection (CD) reporting was further analyzed for associated procedural event at the time of injury, number of access attempts to CD repair, and type of CD repair. RESUTS: Of the 115 unique incidents in the database, there were 58 CDs. Most were identified intraoperatively (n=55), while 3 were incidentally identified postoperatively. Overall, sheath placement was the most common procedural event attributed to CD (n=34). There was adequate narrative information about CD repair in 54 patients where 52 of them were performed intraoperatively. There were total of 28 endovascular repair and 24 open surgical repairs of CDs from TCAR procedure. There was no significant difference in rate of endovascular and open surgical repair of CDs that did not need additional access attempts. However, rate of open surgical repair was significantly higher in CDs with persistent failure to engage the true lumen in 2 or more additional access attempts. Total of 4 strokes were associated with CD. Two occurred during recovery from TCAR admission where one was not intervened per physician’s discretion despite evidence of dissection during the procedure. The other was associated with a fall from a hypotensive event 7 hours after an endovascular CD repair. One incident of stroke occurred intraoperatively during a conversion to CEA as a result of CD. One incident of stroke occurred 4 days after TCAR procedure in which a CD was identified during the stroke evaluation Conclusion: Carotid artery dissection is the most common injury related to TCAR as reported on MAUDE database. Most common procedural event associated CD was sheath placement. Rate of open surgical repair was significantly higher than endovascular repair in dissections with persistent failure to engage true lumen despite additional access attempts. This should add to qualitative insight among vascular surgery community regarding intraoperative management of carotid artery dissections from a TCAR procedure.https://scholarscompass.vcu.edu/gradposters/1144/thumbnail.jp

Aurora-A and Polo-Like Kinases are Important Diagnostic and Therapeutic Markers in Hodgkin Lymphoma and Mimics

Background: Aurora-A (AA) and Polo-like kinases (PLK) are mitotic kinases that regulate the G2/M phase of the cell cycle. It has been demonstrated that AA acts as an upstream regulator of PLK, mediating its phosphorylation in the presence of a cofactor named Bora. PLK is activated by AA to promote checkpoint recovery in mitosis. AA and PLK are implicated in the tumorigenesis of solid tumors, and, recently, in B- and T-cell non Hodgkin lymphomas (NHL). They play a key role in tumor proliferation and disease progression in highly aggressive B-cell NHL. They also serve as indicators of disease activity and are thus attractive potential therapeutic targets. Expression of AA and/or PLK has not yet been assessed in Classic Hodgkin Lymphoma (CHL) and its mimics. This study assesses AA and PLK expression in different CHL types, such as nodular sclerosis type, mixed cellularity type, and lymphocyte rich type, and their mimics: nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and primary mediastinal B-cell lymphoma (PMBL).Design:We assessed 27 CHL cases, 16 NLPHL cases, and 8 PMBL cases for AA and PLK expression by immunohistochemistry. CHL cases included the following: 8 mixed cellularity CHL, 1 lymphocyte rich CHL, and 18 nodular sclerosis CHL. A mouse monoclonal AA-antibody (1:1000 dilution, Abcam, UK) and a PLK-antibody (1:500 dilution, Cell Signaling Technologies, USA) were used. Each case was semi-quantitatively graded for percentage of positive cells (\u3c50% vs. \u3e50%), for staining intensity (1-3+), and for localization (nuclear vs. cytoplasmic). Immunohistochemical analysis was performed independently by 2 pathologists (KMH and KVI). Statistical analysis was performed using Fisher\u27s exact test.Results:AA was expressed in 100% of CHL and NLPHL cases. AA stained predominantly cytoplasm of tumor cells in both NLPHL and CHL. PLK was expressed in 100% of NLPHL and 96% of CHL cases (1 mixed cellularity type CHL did not stain for PLK). PLK showed both nuclear and cytoplasmic staining for both NLPHL and CHL. In contrast, only 37% of PMBL cases were positive for AA and PLK (Table 1). In the CHL group, cases with more than 50% of tumor cells expressing PLK tended to present with higher stage and extranodal disease. In the NLPHL group, PLK correlated with higher stage (III-IV) disease at presentation (p=0.044). No statistically significant differences were found in either intensity or localization of AA or PLK within or between NLPHL and CHL cohorts.Aurora-A PositiveAurora-A NegativePLK PositivePLK NegativeClassic Hodgkin Lymphoma270261Nodular Lymphocyte Predominant Hodgkin Lymphoma160160Primary Mediastinal B-cell Lymphoma3535Table 1. AA and PLK positivity in CHL, NLPHL, and PMBL.AA was expressed in CHL but not PMBL (p=0.0002)PLK was expressed in CHL but not PMBL (p=0.0009)AA was expressed in NLPHL but not PMBL (p=0.0013)PLK was expressed in NLPHL but not PMBL (p=0.0013). Conclusion: AA and PLK are commonly expressed in CHL and NLPHL but not in PMBL. Thus, they are useful markers in the distinction of CHL or NLPHL from PMBL. PLK is a useful marker for the prognostication of NLPHL. AA and PLK are attractive potential therapeutic targets in the treatment of CHL and NLPHL. Additional studies are underway to characterize an array of hematopoietic lesions known to overlap with CHL.https://scholarlycommons.henryford.com/merf2019clinres/1027/thumbnail.jp

Translational symmetry breaking in the superconducting state of the cuprates: Analysis of the quasiparticle density of states

Motivated by recent scanning tuneling microscopy STM experiments on Bi2Sr2CaCu2O8 J. E. Hoffman et al., Science 295, 466 2002 ; C. Howald et al., cond-mat/0201546 unpublished ; J. E. Hoffman et al., Science 297, 1149 2002 : K. McElroy et al. unpublished ; C. Howald et al., cond-mat/0208442 unpub- lished , we study the effects of weak translational symmetry breaking on the quasiparticle spectrum of a d-wave superconductor. We develop a general formalism to discuss periodic charge order, as well as quasipar- ticle scattering off localized defects. We argue that the STM experiments in Bi2 Sr2 CaCu2 O8 cannot be explained using a simple charge density wave order parameter, but are consistent with the presence of a periodic modulation in the electron hopping or pairing amplitude. We review the effects of randomness and pinning of the charge order and compare it to the impurity scattering of quasiparticles. We also discuss implications of weak translational symmetry breaking for angle resolved photoemission spectroscopy experi- ments.Physic

Transport Properties near the z=2 Insulator-Superconductor Transition

We consider here the fluctuation conductivity near the point of the insulator-superconductor transition in a system of regular Josephson junction arrays in the presence of particle-hole asymmetry or equivalently homogeneous charge frustration. The transition is characterised by the dynamic critical exponent $z=2$, opening the possibility of the perturbative renormalization-group (RG) treatment. The quartic interaction in the Ginzburg-Landau action and the coupling to the Ohmic heat bath, giving the finite quasiparticle life-time, lead to the non-monotonic behavior of the dc conductivity as a function of temperature in the leading logarithmic approximation.Comment: Revised version for publication. To appear in PR

Translational Symmetry Breaking in the Superconducting State of the Cuprates: Analysis of the Quasiparticle Density of States

Motivated by the recent STM experiments of J.E. Hoffman et.al. and C. Howald et.al., we study the effects of weak translational symmetry breaking on the quasiparticle spectrum of a d-wave superconductor. We develop a general formalism to discuss periodic charge order, as well as quasiparticle scattering off localized defects. We argue that the STM experiments in $Bi_2Sr_2CaCu_2O_{8+\delta}$ cannot be explained using a simple charge density wave order parameter, but are consistent with the presence of a periodic modulation in the electron hopping or pairing amplitude. We review the effects of randomness and pinning of the charge order and compare it to the impurity scattering of quasiparticles. We also discuss implications of weak translational symmetry breaking for ARPES experiments.Comment: 12 pages, 9 figs; (v2) minor corrections to formalism, discussions of dispersion, structure factors and sum rules added; (v3) discussion of space-dependent normalization added. To be published in PR

Rapid-Testing Technology and Systems Improvement for the Elimination of Congenital Syphilis in Haiti: Overcoming the "Technology to Systems Gap".

Background. Despite the availability of rapid diagnostic tests and inexpensive treatment for pregnant women, maternal-child syphilis transmission remains a leading cause of perinatal morbidity and mortality in developing countries. In Haiti, more than 3000 babies are born with congenital syphilis annually. Methods and Findings. From 2007 to 2011, we used a sequential time series, multi-intervention study design in fourteen clinics throughout Haiti to improve syphilis testing and treatment in pregnancy. The two primary interventions were the introduction of a rapid point-of-care syphilis test and systems strengthening based on quality improvement (QI) methods. Syphilis testing increased from 91.5% prediagnostic test to 95.9% after (P < 0.001) and further increased to 96.8% (P < 0.001) after the QI intervention. Despite high rates of testing across all time periods, syphilis treatment lagged behind and only increased from 70.3% to 74.7% after the introduction of rapid tests (P = 0.27), but it improved significantly from 70.2% to 84.3% (P < 0.001) after the systems strengthening QI intervention. Conclusion. Both point-of-care diagnostic testing and health systems-based quality improvement interventions can improve the delivery of specific evidence-based healthcare interventions to prevent congenital syphilis at scale in Haiti. Improved treatment rates for syphilis were seen only after the use of systems-based quality improvement approaches

Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression.

Recent developments in stem cell biology have enabled the study of cell fate decisions in early human development that are impossible to study in vivo. However, understanding how development varies across individuals and, in particular, the influence of common genetic variants during this process has not been characterised. Here, we exploit human iPS cell lines from 125 donors, a pooled experimental design, and single-cell RNA-sequencing to study population variation of endoderm differentiation. We identify molecular markers that are predictive of differentiation efficiency of individual lines, and utilise heterogeneity in the genetic background across individuals to map hundreds of expression quantitative trait loci that influence expression dynamically during differentiation and across cellular contexts