Publications by authors named "Jeffrey P Carpenter"

99 Publications

How and why are educators using Instagram?

Teach Teach Educ 2020 Nov 24;96:103149. Epub 2020 Jul 24.

Elon University, Campus Box 2105, Elon, NC, 27244, USA.

Social media are commonplace in many educators' lives, but their Instagram activities have received no prior attention in the empirical literature. We therefore created and disseminated a survey regarding educators' Instagram use. Analyses of 841 responses suggested participants were generally intensive users of Instagram who engaged in the exchange of both professional knowledge and wisdom, as well as affective support. In addition to identifying benefits to Instagram use, some participants offered critiques of Instagram's professional utility. We discuss the implications of these findings for educators' work in a digital era and the future of research on educators' social media activities.
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http://dx.doi.org/10.1016/j.tate.2020.103149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380928PMC
November 2020

Transformative instruction or old wine in new skins? Exploring how and why educators use HyperDocs.

Comput Educ 2020 Nov 21;157:103979. Epub 2020 Jul 21.

California State University Fullerton, 800 N. State College Blvd, Fullerton, CA, 92834, USA.

HyperDocs are interactive, digital teaching and learning materials created, disseminated, and remixed by educators. To date, HyperDocs have not been the subject of published, peer-reviewed research. To address this research gap, we engaged in exploratory, primarily qualitative research to systematically examine how and why teachers use HyperDocs. We used an online survey to gather data on educators' ( 261) uses of and perceptions regarding HyperDocs. Analysis suggested a wide range of definitions of, purposes for, and approaches to HyperDoc use, indicating that educators are adapting HyperDocs to their practice in myriad ways. Consistent with the openness and flexibility in finding, remixing, and using HyperDocs, educators identified a number of benefits of using these tools in their practice, including changes in student engagement and learning, shifts in instructional design and delivery, and changes in their own support and dispositions. Analysis of examples of HyperDocs shared by a subset of participants suggested some mismatch between rhetoric about HyperDocs and what was actually incorporated into them. We discuss these findings in relation to the work of educators and the future of research on HyperDocs and other crowdsourced teaching and learning initiatives.
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http://dx.doi.org/10.1016/j.compedu.2020.103979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373012PMC
November 2020

Poly-Specialty Application Practices of Medical Students Applying to Integrated Vascular Surgery Residency.

Ann Vasc Surg 2020 Nov 15;69:125-132. Epub 2020 Jun 15.

Division of Vascular Surgery, Cooper University Hospital, Camden, NJ. Electronic address:

Background: It is not uncommon for medical students seeking surgical residencies to apply to and rank two or more surgical specialties. Level of interest in a specialty is consistently cited as one of the most important factors for program directors when evaluating applicants for 0 + 5 integrated vascular surgery (IVS) programs. The purpose of this study was to examine trends in poly-specialty application submission to IVS and poly-specialty ranking of IVS to determine the percentage of applicants to IVS residencies with vascular surgery as their true preference.

Methods: Electronic Residency Application Service (ERAS) statistics for noninternational medical graduates from 2011 to 2017 were mined for trends in poly-specialty applications between IVS and other surgical disciplines. The poly-specialty application percentage, range, and standard deviation were determined. The National Resident Match Program (NRMP) results and data from 2011 to 2018 were also used to identify those U.S. seniors who ranked IVS programs as their preferred choice, defined as ranking vascular as the only choice or the first-choice specialty. This was compared with those who ranked a specialty other than vascular surgery first but had vascular surgery listed on their rank list. These data were also collected for applicants to orthopedic surgery, neurosurgery, otolaryngology, obstetrics and gynecology, integrated cardiothoracic surgery, and integrated plastic surgery.

Results: Between 2011 and 2017, applicants who submitted ERAS applications to IVS most often poly-specialty applied to IVS and general surgery (87%) followed by IVS and the following: preliminary surgery (71%), plastic surgery (22%), orthopedic surgery (19%), neurosurgery (17%), otolaryngology (16%), obstetrics and gynecology (12%), and urology (3%). The percentage of the applicant pool submitting rank lists with multiple specialties fell over the study period from 94% in 2011 to 67% in 2018. Between 2011 and 2018, an average of 14% of IVS applicants (n = 463), who submitted rank lists to the NRMP, ranked a specialty other than vascular as their true preference (range 7-23 SD 5). Only integrated cardiothoracic surgery had a higher percentage of applicants listing a different specialty as their true preference at 25% (range 18-36 SD 7). Nearly all (97-99%) applicants to orthopedic surgery, neurosurgery, otolaryngology, obstetrics and gynecology, and plastic surgery applied to that specialty as their true preference.

Conclusions: IVS residency applicants were most likely to apply for poly-specialty via the ERAS to general surgery and IVS. Compared to the other surgical specialties, those who submitted rank lists to the NRMP listing integrated cardiothoracic and IVS had the highest likelihood of ranking another specialty higher. Care must be taken when evaluating applications to IVS residencies to determine the applicant's level of interest in vascular surgery as a career.
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http://dx.doi.org/10.1016/j.avsg.2020.06.011DOI Listing
November 2020

Locally Transplanted Adipose Stem Cells Reduce Anastomotic Leaks in Ischemic Colorectal Anastomoses: A Rat Model.

Dis Colon Rectum 2020 07;63(7):955-964

Department of Surgery, Cooper University Hospital, Camden, New Jersey.

Background: Anastomotic leakage remains a dreaded complication after colorectal surgery. Stem-cell-based therapies have been shown to increase angiogenesis and cell proliferation.

Objective: The purpose of this research was to investigate the use of adipose-derived stem cells on the healing of ischemic colonic anastomoses in a rat model.

Design: This is an animal research study using xenotransplantation.

Settings: Male Wistar rats (300-400 g, n = 48) were purchased from a licensed breeder.

Patients: Adipose stem cells were isolated from the subcutaneous fat of healthy human donors.

Interventions: The rats underwent laparotomy with creation of an ischemic colorectal anastomosis created by ligation of mesenteric vessels. The animals were divided into 3 groups: control group with an ischemic anastomosis, vehicle-only group in which the ischemic anastomosis was treated with an absorbable gelatin sponge, and a treatment group in which the ischemic anastomosis was treated with an absorbable gelatin sponge plus adipose stem cells. Animals were killed at postoperative days 3 and 7.

Main Outcome Measures: Anastomotic leakage was defined as the finding of feculent peritonitis or perianastomotic abscess on necropsy. Rat mRNA expression was measured using real-time polymerase chain reaction.

Results: Adipose-derived stem cells significantly decreased anastomotic leakage when compared with control at both postoperative days 3 (25.0% vs 87.5%; p = 0.02) and 7 (25.0% vs 87.5%; p = 0.02). The use of an absorbable gelatin sponge alone had no effect on anastomotic leakage when compared with control and postoperative days 3 or 7. We found that stem cell-treated animals had a 5.9-fold and 7.4-fold increase in the expression of vascular endothelial growth factor when compared with control at 3 and 7 days; however, this difference was not statistically significant when compared with the absorbable gelatin sponge group.

Limitations: This is a preclinical animal research study using xenotransplantation of cultured stem cells.

Conclusions: Locally transplanted adipose stem cells enhance the healing of ischemic colorectal anastomoses and may be a novel strategy for reducing the risk of anastomotic leakage in colorectal surgery. See Video Abstract at http://links.lww.com/DCR/B203. EL TRANSPLANTE LOCAL DE CÉLULAS MADRE ADIPOSAS REDUCE LA FUGA ANASTOMÓTICA EN LAS SUTURAS COLORRECTALES ISQUÉMICAS: MODELO EN RATAS: Las fugas anastomóticas son una complicación pusilánime después de toda cirugía colorrectal. Se ha demostrado que el tratamiento con células madre aumenta la angiogénesis y la proliferación celular.Investigar el uso de células madre derivadas de tejido adiposo en la cicatrización de una anastomosis colónica isquémica basada en ratas como modelo.Estudio de investigación en animales utilizando xenotrasplantes.Adquisición de típicas ratas de laboratorio raza Wistar, todas machos (300-400 g, n = 48) de un criadero autorizado.Aislamiento de células madre de tipo adiposo del tejido celular subcutáneo en donantes humanos sanos.Las ratas se sometieron a laparotomía con la creación de una anastomosis colorrectal isquémica obtenida mediante ligadura controlada de los vasos mesentéricos correspondientes. Los animales se dividieron en tres grupos: grupo de control con anastomosis isquémica, grupo de vehículo único en el que la anastomosis isquémica se trató con una esponja de gelatina absorbible, y un grupo de tratamiento en el que la anastomosis isquémica se trató con una esponja de gelatina absorbible asociada a un vástago adiposo de células madre. Los animales fueron sacrificados el POD3 y el POD7.La fuga anastomótica fué definida como el hallazgo de peritonitis fecaloidea o absceso perianastomótico a la necropsia. La expresión de RNAm de las ratas se midió usando PCR en tiempo real.Las células madre derivadas de tejido adiposo disminuyeron significativamente la fuga anastomótica en comparación con el grupo control tanto en el POD3 (25% frente a 87.5%, p = 0.02) como en el POD7 (25% frente a 87.5%, p = 0.02). El uso de una esponja de gelatina absorbible sola, no tuvo efecto sobre la fuga anastomótica en comparación con los controles el POD3 o el POD7. Descubrimos que los animales tratados con células madre adiposas tenían un aumento de 5,9 y 7,4 veces en la expresión de VEGF en comparación con el control a los 3 y 7 días, respectivamente; sin embargo, esta diferencia no fue estadísticamente significativa en comparación con el grupo de esponja de gelatina absorbible.Este es un estudio preclínico de investigación en animales que utiliza xenotrasplantes de células madre adiposas cultivadas.Las células madre de tipo adiposo trasplantadas localmente mejoran la cicatrisación en casos de anastomosis colorrectales isquémicas, y podrían convertirse en una nueva estrategia para reducir el riesgo de fugas anastomóticas en casos de cirugía colorrectal. Consulte Video Resumen en http://links.lww.com/DCR/B203. (Traducción-Dr Xavier Delgadillo).
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http://dx.doi.org/10.1097/DCR.0000000000001667DOI Listing
July 2020

Trends in the 10-year history of the vascular integrated residency match: More work, higher cost, same result.

J Vasc Surg 2020 07 7;72(1):298-303. Epub 2020 Feb 7.

Division of Vascular Surgery, Cooper University Hospital, Camden, Camden, NJ. Electronic address:

Objective: The purpose of this study was to examine trends in application submission, rank lists, and applicant quality for vascular surgery integrated residency.

Methods: The National Resident Matching Program Results and Data reports and the Electronic Residency Application Service Statistics from 2007 to 2017 were compiled and mined for trends in terms of application submission and the number of applicants a program needed to rank to fill all residency positions. Applicant pool depth and percentage of programs applied to were calculated. Outcome data from the National Resident Matching Program were reviewed for 2014 and 2016 for United States Medical Licensing Examination Step scores and experiences.

Results: During the last 10 years, the number of vascular surgery integrated residency spots rose from 9 to 60 per year. Most programs offer one spot per year; none offer more than two. The average number of applications received by programs rose from 17 applications in 2008 to 63.8 in 2017. The average rank list depth needed by programs to fill the spots has not increased (range, 2.5-5.1; standard deviation, 0.73). The proportional depth of the applicant pool decreased from 4.6 U.S. and Canadian applicants for every one residency spot in 2008 to 1.7 applicants for every one residency spot in 2017. Applicant quality metrics were available for 2 years (2014 and 2016). Step 1 scores (237/239), Step 2 scores (250/250), research experiences (3.7/4.2), and volunteer experiences (5.9/5.5) remained nearly unchanged. The number of contiguous ranks for matched applicants remained stable (12.3/12.8).

Conclusions: The current system promotes multiple inefficiencies, resulting in application glut. Fewer applicants are flooding programs with an increasing number of applications. More money is being spent on Electronic Residency Application Service applications without changes in the number needed to rank by applicants or programs to achieve a match. There is no improvement in the quality of the applicant. Should these trends continue, they represent an unsustainable model for resident selection.
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http://dx.doi.org/10.1016/j.jvs.2019.10.066DOI Listing
July 2020

Proper technical procedures improved outcomes in a retrospective analysis of EVAS FORWARD IDE trial 3-year results.

J Vasc Surg 2020 09 5;72(3):918-930.e2. Epub 2020 Feb 5.

Department of Surgery, Spectrum Health, Grand Rapids, Mich.

Objective: Adverse outcomes observed late in the Nellix EndoVascular Aneurysm Sealing (EVAS) System (Endologix, Inc, Irvine, Calif) investigational device exemption trial prompted refinement of the anatomic instructions for use (IFU). This study aimed to investigate the association of procedural factors during Nellix endograft deployment and patient outcomes.

Methods: We retrospectively reviewed 1-month imaging of 333 patients enrolled in the prospective, multicenter EVAS investigational device exemption trial between January 2014 and September 2016. Initial observations of those patients who met revised anatomic IFU yet still experienced late adverse events suggested that inadequate seal and low graft placement were common among these patients. Key procedural variables identified from a univariate analysis were applied to construct four cohorts stratified by procedural technical performance (technically adequate [P+] or technically inadequate [P-]) and the revised anatomic indications for use (anatomically within IFU [A+] or anatomically outside of IFU [A-]) and to compare them for aneurysm-related outcomes. A logistic regression analysis was performed to identify significant predictors of sac expansion or migration.

Results: Proximal and distal seal zones and low graft placement were identified by logistic regression analysis as significant predictors of sac expansion or migration. Accordingly, acquisition of ≥10-mm proximal and distal seal zones and the position of the lowest stent within 10 mm of the lowest renal artery were clinically justified as thresholds for a technically adequate procedure. Patients who did not achieve these parameters were deemed to have a technically inadequate procedure. By use of the proposed procedural adequacy criteria and established anatomic criteria, patients were stratified into four cohorts: A+/P+ (n = 77), A+/P- (n = 54), A-/P+ (n = 71), and A-/P- (n = 131). Three-year estimates of freedom from migration of 10 mm were 98.6% in A+/P+, 95.9% in A+/P-, 85.8% in A-/P+, and 80.1% in A-/P-; freedom from type IA endoleak estimates were 98.6% in A+/P+, 100% in A+/P-, 96.4% in A-/ P+, and 90.3% in A-/P- cohorts. Freedom from sac expansion and secondary intervention were 96.9% and 90.6% in A+/P+, 86.0% and 93.6% in A+/P-, 87.1% and 83.1% in A-/P+, and 80.5% and 79.8% in A-/P- groups, respectively. Two early deaths (aneurysm-related mortality) on days 4 and 12 postoperatively were reported within the A+/P- group. Kaplan-Meier estimates of freedom from all-cause mortality and aneurysm-related mortality at 3 years were similar between cohorts.

Conclusions: This post hoc analysis suggests that achieving a 10-mm proximal and distal seal with adequate positioning of the endograft with respect to the renal arteries is associated with improved patient outcomes.
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http://dx.doi.org/10.1016/j.jvs.2019.11.039DOI Listing
September 2020

Endovascular Aneurysm Sealing is Associated with Higher Medium-Term Survival than Traditional EVAR.

Ann Vasc Surg 2020 Feb 16;63:145-154. Epub 2019 Oct 16.

Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, MA. Electronic address:

Background: Endovascular aneurysm repair (EVAR) is the dominant treatment modality for abdominal aortic aneurysm (AAA). Periprocedural risks are low, and cardiovascular events are the principle determinants of long-term survival. Recently, the concept of endovascular aneurysm sealing (EVAS) has been introduced into clinical investigation. In previous cohort studies, EVAS has been associated with a lower all-cause mortality than expected despite device issues. We used a propensity weighted approach to investigate whether EVAS was associated with lower all-cause mortality after aneurysm repair.

Methods: We compared 333 patients in the Nellix United States Investigational Device Exemption trial to 15,431 controls from the Vascular Quality Initiative between 2014 and 2016 after applying the exclusion criteria from the investigational device exemption (hemodialysis, creatinine > 2.0 mg/dL, or rupture). We calculated propensity scores and applied inverse probability weighting to compare risk adjusted medium-term survival using Kaplan-Meier and Cox regression.

Results: After weighting, patients treated with the Nellix EVAS system experienced higher 3-year survival than controls from the Vascular Quality Initiative (93% vs. 88%, respectively). This corresponded to a 41% lower risk of mortality for EVAS compared with EVAR (HR 0.59 [0.38-0.92], P = 0.02). Subgroup analysis demonstrated that the association between EVAS and higher survival was strongest in the subgroup of patients with aneurysms over 5.5 cm (P for interaction < 0.001). In this subgroup, EVAS patients experienced half the rate of mortality as those patients treated with EVAR, with 3-year survival of 92% compared with 86% (HR 0.5 [0.3-0.9], P = 0.02).

Conclusions: In this select group of patients, EVAS was associated with higher medium-term survival than traditional EVAR. Although issues with the device have recently surfaced, this exploratory analysis shows that the concept of sac sealing may hold promise. Further study is needed to confirm this finding and determine whether EVAS is associated with lower rates of cardiovascular events.
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http://dx.doi.org/10.1016/j.avsg.2019.08.094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012730PMC
February 2020

Assessing trends, morbidity, and mortality in ruptured abdominal aortic aneurysm repair with 9 years of data from the National Surgical Quality Improvement Program.

J Vasc Surg 2020 02 18;71(2):423-431. Epub 2019 Jun 18.

Department of Vascular Surgery, Cooper University Hospital, Camden, NJ.

Background: The American College of Surgeons' National Quality Improvement Program (NSQIP) database can be used to assess trends and outcomes of ruptured abdominal aortic aneurysm (rAAA) repair. The purpose of this study is to examine the morbidity and mortality for ruptured endovascular (rEVAR) and ruptured open (rOPEN) aneurysm repair compared with elective endovascular (EVAR) and elective open (OPEN) aneurysm repair.

Methods: Ruptured and nonruptured abdominal aortic aneurysms were identified from the NSQIP database between 2008 and 2016. Data regarding demographics and comorbidities, 30-day mortality, and postoperative complications were collected for rEVAR, rOPEN, EVAR, and OPEN cases.

Results: There were 43,105 AAAs, 34,177 (79.28%) EVARs, and 8928 (20.71%) OPENs. There were 3806 rAAAs, 1843 (48.42%) rEVARs, and 1963 (51.58%) rOPENs. The incidence of rEVAR repair lagged behind EVAR considerably. Mortality for rOPEN was 575 (29.29%) and 344 (18.66%) for rEVAR. No difference between the ratio of men to women in rOPEN vs rEVAR was noted. There was a significant increase in mortality for women vs men undergoing rEVAR (P = .0362). No difference in mortality existed between women vs men undergoing rOPEN (P = .0639). There was no difference in the percentage of hypotensive cases undergoing rEVAR vs rOPEN (P =.1873). For all rAAAs with hypotension, rOPEN had an increased mortality compared to rEVAR (P = .0004). There were 20 (3.11%) rEVAR and 40 (8.00%) rOPEN cases with lower extremity ischemia. rOPEN conferred a significant increase in lower extremity ischemia (P = .0002). There were 46 (7.15%) rEVAR and 60 (12.00%) rOPEN cases of ischemic colitis. rOPEN had a significant increase in ischemic colitis (P = .0052).

Conclusions: NSQIP data, over 9 years, demonstrate an increased morbidity and mortality associated with open vs endovascular repair of rAAAs. A great disparity exists between the proportion of rEVAR and rOPEN to EVAR and OPEN. The lagging use of endovascular repair of rAAAs must be further explored.
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http://dx.doi.org/10.1016/j.jvs.2019.04.462DOI Listing
February 2020

The Effect of the Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid and Paclitaxel Treatment on Full-Thickness Wound Healing in Mice.

Ann Plast Surg 2018 10;81(4):482-486

Hematology and Oncology, Cooper University Hospital, Camden, NJ.

Introduction: Neoadjuvant chemotherapy prior to lumpectomy or mastectomy for breast cancer challenges wound healing. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, has been shown to work synergistically with paclitaxel in vitro and in preclinical studies. In addition, our laboratory has demonstrated that SAHA treatment decreases paclitaxel-associated stem cell toxicity, modulates inflammatory response, and promotes wound healing in injured fibroblast cells. Our goal was to determine if combined SAHA and paclitaxel treatment would improve wound healing in an in vivo full-thickness murine model, without altering antitumor effect.

Methods: Thirty-two nude athymic mice received intraperitoneal injections of paclitaxel (20 mg/kg), SAHA (25 mg/kg), paclitaxel + SAHA (20 mg/kg + 25 mg/kg), or no treatment for 2 weeks prior to surgery. Under general anesthesia, 8-mm full-thickness dorsal wounds were created in all animals, and a silicone splint was attached to minimize wound contraction. The wounds were measured twice a week with a surgical caliper until healing was complete. To evaluate the in vivo effect of drug treatment, 16 athymic nude mice with MDA-MB-231 xenografts received the treatments described previously, following which tumor volumes were compared between groups.

Results: Average wound healing time was prolonged in mice treated with paclitaxel (20 ± 1.9 days), and combination SAHA + paclitaxel therapy improved average wound healing time (17.0 ± 1.8 days). In the xenograft model, the antitumor effect of SAHA and paclitaxel (average tumor volume 43.9 ± 34.1 mm) was greater than paclitaxel alone (105.8 ± 73.8 mm).

Conclusions: The addition of SAHA to taxane chemotherapy improves the therapeutic effect on triple-negative breast cancer while decreasing the detrimental effect of paclitaxel on wound healing. This may have substantial implications on improving outcomes in breast reconstruction following chemotherapy.
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http://dx.doi.org/10.1097/SAP.0000000000001519DOI Listing
October 2018

Endothelial Differentiated Adipose-Derived Stem Cells Improvement of Survival and Neovascularization in Fat Transplantation.

Aesthet Surg J 2019 01;39(2):220-232

Department of Surgery, Cooper University Hospital, Camden, New Jersey.

Background: Adipose-derived stem cells (ASCs) assisted lipotransfer have been considered to facilitate the survival of fat grafts. However, emerging evidence of insufficient vascularization is another obstacle for fat graft survival in cell-assisted lipotransfer.

Objectives: This study evaluated if endothelial phenotype ASCs with fat lipoaspirate improves survival and neovascularization in fat transplantation.

Methods: ASCs were isolated from human periumbilical fat tissue and cultured in endothelial growth medium for 2 weeks. Fat lipoaspirate was mixed with fresh adipose stroma vascular fraction (SVF), endothelial differentiated ASCs (EC/ASCs), and fat lipoaspirate alone. Three fat mixtures were subcutaneously injected into the adult male Sprague-Dawley rat's dorsum at 3 locations. At 8 weeks after transplantation, the grafted fat lipoaspirates were harvested, and the extracted fat was evaluated using photographic, survival weights measurements and histological examination. Neo-vascularization was quantified by immunofluorescence and real-time RT-PCR.

Results: Grafts from the EC/ASC assisted group had a higher survival rate, morphologic integrity, and most uniform lipid droplets. They also revealed less inflammation and fibrosis with increased number of vessels by histological and immunofluorescence analysis. Quantitative RT-PCR analysis indicated that the expression levels of EC-specific markers of CD31 and vWF were higher in the EC/ASC group compared with in the control and fat with SVF transplants.

Conclusions: These results indicated that co-implantation of fat lipoaspirate with ASCs differentiated toward an endothelial phenotype improves both survival and neovascularization of the transplanted fat lipoaspirate, which might provide benefits and represents a promising strategy for clinical application in autologous fat transplantation.
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http://dx.doi.org/10.1093/asj/sjy130DOI Listing
January 2019

Refinement of anatomic indications for the Nellix System for endovascular aneurysm sealing based on 2-year outcomes from the EVAS FORWARD IDE trial.

J Vasc Surg 2018 09 31;68(3):720-730.e1. Epub 2018 Mar 31.

Division of Vascular Surgery, Department of Surgery, Spectrum Health, Grand Rapids, Mich.

Background: The Nellix System (Endologix, Inc, Irvine, Calif) for endovascular aneurysm sealing (EVAS) is a novel approach to abdominal aortic aneurysm treatment and conceptually different from endovascular aneurysm repair, whereby polymer is employed to fill and actively manage the abdominal aortic aneurysm sac. One-year safety and effectiveness results of the Nellix pivotal trial demonstrated encouraging outcomes with very low morbidity and mortality and high procedural and treatment success. Two-year imaging revealed a signal of migration, leading to a field safety notification issued by the manufacturer on October 21, 2016, and a dedicated root cause analysis, resulting in refinements to the instructions for use (IFU). We report the 2-year results of the investigational device exemption pivotal trial stratified according to the new and original criteria for selection of patients.

Methods: Comprehensive engineering evaluations, statistical analyses, and clinical assessments were conducted looking at patients enrolled in the pivotal trial (N = 150), roll-in cohort (N = 29), and continued access program (N = 154). All patients in all cohorts were treated on-IFU at the time of enrollment. Logistic regression models supported the mechanism that migration with Nellix is associated with a small aortic flow lumen relative to a large aneurysm thrombus burden and large aortic neck diameters. Based on these findings, refinements to the IFU criteria were applied, excluding patients with a thrombus index (maximum aneurysm sac/maximum flow lumen diameter) >1.4, aortic neck diameter >28 mm, and aortic neck conicity (>10% diameter change along the infrarenal neck) and requiring a 10-mm distal seal zone in the iliac artery.

Results: Freedom from all-cause mortality at 2 years was 94%. Patient outcomes were then stratified on the refined morphologic criteria and analyzed retrospectively. Two-year freedom from composite endoleak was high among both cohorts (95% on-IFU vs 92% off-IFU). Freedom from migration was 97.7% on-IFU vs 93.2% off-IFU (P = .0125). Freedom from aneurysm enlargement was 98.1% on-IFU vs 93.5% off-IFU (P value is not available because of failure of log-rank test assumptions). Composite freedom from migration, type IA endoleak, or aneurysm expansion was 95.9% among the on-IFU cohort vs 85.1% in the off-IFU cohort (P = .0017).

Conclusions: Consistent with the introduction of a novel therapy, the presentation of failure modes of EVAS over time was inevitable. Using detailed imaging as well as engineering and statistical analysis, we were able to understand risk factors for adverse events specific to EVAS and defined those patients best suited for Nellix. With this EVAS-specific approach to defining IFU, on-IFU patients were identified as those with large aneurysms with little thrombus that would be prone to type II endoleaks and sac expansion with traditional devices. When treated with Nellix, these patients were predicted to experience exceptional results, especially with regard to a low composite endoleak rate and low all-cause mortality.
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http://dx.doi.org/10.1016/j.jvs.2018.01.031DOI Listing
September 2018

Human adipose-derived stem cell treatment modulates cellular protection in both in vitro and in vivo traumatic brain injury models.

J Trauma Acute Care Surg 2018 05;84(5):745-751

From the Department of Surgery (N.S.K., S.C., W.M.H., M.P., T.O., P.Z., J.P.C., S.A.B.), Cooper University Hospital, Camden, NJ; and Division of Trauma (J.P.H.), Cooper University Hospital, Camden, NJ.

Background: Traumatic brain injury (TBI) is a common cause of morbidity and mortality in the civilian population. The purpose of this study was to examine the effect(s) of adipose-derived stem cell (ASC) treatment on cellular and functional recovery in TBI via both in vitro and in vivo methods.

Methods: Cultured neuroblastoma cells, SH-SY5Y, were scratched to mimic TBI in an in vitro model. The effect of ASC-conditioned medium (CM) on cell death, mitochondrial function, and expression of inflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin 1β [IL-1β], and IL-6), as well as apoptosis marker FAS, was measured. In our in vivo model, Sprague-Dawley rats underwent TBI via a frontal, closed-head injury model. Animals randomly received either intravenous human-derived ASCs or intravenous saline within 3 hours of injury and were compared with a sham group. Functional recovery was evaluated via accelerating Rotarod method. On post-TBI Day 3, brain tissue was harvested and assessed for cellular damage via enzyme-linked immunosorbent assay for TNF-α, as well as immunohistochemical staining for β-amyloid precursor protein (β-APP).

Results: Our in vitro data show that ASC treatment imparted reduced cell death (ratio to control: 1.21 ± 0.066 vs. 1.01 ± 0.056, p = 0.017), increased cell viability (ratio to control: 0.86 ± 0.009 vs. 1.09 ± 0.01, p = 0.0001), increased mitochondrial function (percentage of control: 78 ± 6% vs. 68 ± 3%), and significantly decreased levels of inflammatory cytokine IL-1β. In our in vivo study, compared with TBI alone, ASC-treated animals showed no difference in functional recovery, lower levels of expressed TNF-α (ratio to total protein, 0.47 ± 0.01 vs. 0.67 ± 0.04; p < 0.01), and lower levels of β-amyloid precursor protein (fluorescence ratio, 0.43 ± 0.05 vs. 0.69 ± 0.03; p < 0.01).

Conclusions: Adipose-derived stem cell treatment results in improved cell survival, decreased inflammatory marker release, and decreased evidence of neural injury. No difference in functional recovery was seen. These data suggest the potential for ASC treatment to aid in cellular protection and recovery in neural cells following TBI.
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http://dx.doi.org/10.1097/TA.0000000000001770DOI Listing
May 2018

The endothelial cell secretome as a novel treatment to prime adipose-derived stem cells for improved wound healing in diabetes.

J Vasc Surg 2018 07 29;68(1):234-244. Epub 2017 Jul 29.

Department of Surgery, Cooper University Hospital, Camden, NJ. Electronic address:

Background: Chronic wounds are a common surgical problem exacerbated by diabetes and ischemia. Although adipose-derived stem cells (ASCs) have shown promise as a wound healing therapy, their function and proliferation are hindered in diabetes. This study examines the ability of the human umbilical vein endothelial cell (HUVEC) secretome to reverse the deleterious effects of high glucose concentrations on ASCs through priming, thereby enhancing their ability to participate in angiogenesis and wound healing.

Methods: Institutional review board-approved human ASCs were cultured in M199 medium with or without glucose (30 mmol/L). HUVEC were grown in 30 mmol/L glucose-containing M199 medium; the resulting conditioned medium (HUVEC-CM) was collected every 3 days and used to prime ASCs. An aliquot of HUVEC-CM was heated (85°C for 30 minutes) to produce thermal denaturation of protein. Viability, proliferation, and endothelial differentiation were measured by MTT assays, growth curves, and quantitative polymerase chain reaction, respectively. A Matrigel assay was used to assess the ability of primed ASCs to participate in capillary-like tube formation. An Institutional Animal Care and Use Committee-approved in vivo murine model of diabetic and ischemic hindlimbs was used to evaluate the angiogenic potential of primed stem cells. Human ASCs were cultured with either control M199 or HUVEC-CM. Mice were randomized to a control group, an unprimed ASC group, or a HUVEC-primed ASC group. Cellular therapies were injected into the ischemic muscle. Thirty days later, slides were made. Microvessels were counted by three blinded observers.

Results: MTT assays revealed that HUVEC-priming induced a 1.5 times increase in cell viability over diabetic controls. This promoting effect was lost with heated HUVEC-CM (P < .001), indicating that the active molecules are of protein origin. After 9 days, ASCs cultured in 30 mmol/L glucose solution showed a 14% reduction in growth from nondiabetic controls (P = .013) and exhibited atrophic morphology. Conversely, diabetic HUVEC-primed stem cells demonstrated a nearly four-fold increase in proliferation (P < .05) and took on a fusiform, endothelial-like phenotype. Polymerase chain reaction demonstrated enhanced expression of CD31 messenger RNA by 4.7-fold after 14 days in the HUVEC-primed group, and endothelial nitric oxide synthase messenger RNA messenger RNA was increased 20.1-fold from controls. Unlike unprimed controls, HUVEC-primed ASCs readily formed capillary-like tube networks on Matrigel. Diabetic mice that were injected with HUVEC-primed ASCs demonstrated greater vessel density than both controls (2.1-fold) and unprimed stem cell treatments (P < .001).

Conclusions: HUVECs secrete protein factors that significantly increase proliferation and endothelial differentiation of ASCs under diabetic conditions. Injection of ischemic hindlimbs in diabetic mice with HUVEC-primed ASCs leads to enhanced angiogenesis.
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http://dx.doi.org/10.1016/j.jvs.2017.05.094DOI Listing
July 2018

Histone Deacetylase Inhibitors Enhance Cytotoxicity Towards Breast Tumors While Preserving the Wound-Healing Function of Adipose-Derived Stem Cells.

Ann Plast Surg 2017 Jun;78(6):728-735

From the *Cooper University Hospital; and †Cooper Medical School of Rowan University, Camden, NJ.

Introduction: Paclitaxel improves the oncologic response of breast cancer resections; however, it may negatively affect the wound-healing potential of human adipose-derived stem cells (hASCs) for fat grafting and reconstructive surgery. Histone deacetylase inhibitors (HDACis) modify the epigenetic regulation of gene expression and stabilize microtubules similarly to paclitaxel, thus, creating a synergistic mechanism of cell cycle arrest. We aim to combine these drugs to enhance cytotoxicity towards breast cancer cells, while preserving the wound-healing function of hASCs for downstream reconstructive applications.

Methods: Triple negative breast cancer cells (MBA-MB-231) and hASCs (institutional review board-approved clinical isolates) were treated with a standard therapeutic dose of paclitaxel (1.0 μM) or with low-dose paclitaxel (0.1 μM) combined with the HDACi suberoylanilide hydroxamic acid or trichostatin A. Cell viability, gene expression, apoptosis, and wound-healing/migration were measured via methylthiazol tetrazolium assay, quantitative real-time polymerase chain reaction, annexin V assay, and fibroblast scratch assay, respectively.

Results: Combined HDACi and low-dose paclitaxel therapy maintained cytotoxicity towards breast cancer cells and preserved adipose-derived stem cell viability. Histone deacetylase inhibitor demonstrated selective anti-inflammatory effects on adipose-derived stem cell gene expression and decreased expression of the proapoptotic gene FAS. Furthermore, HDACi therapy did not increase relative apoptosis within hASCs. A scratch assay demonstrated enhanced wound healing among injured fibroblasts indirectly co-cultured with HDACi-treated hASCs.

Conclusions: Combining HDACi with low-dose paclitaxel improved cytotoxicity towards breast cancer cells and preserved hASC viability. Furthermore, enhanced wound healing was observed by improved migration in a fibroblast scratch assay. These results suggest that the addition of HDACi to taxane chemotherapy regimens may improve oncologic results and wound-healing outcomes after reconstructive surgery.
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http://dx.doi.org/10.1097/SAP.0000000000001066DOI Listing
June 2017

Management of Difficult Access during Endovascular Aneurysm Repair.

Ann Vasc Surg 2017 Oct 4;44:77-82. Epub 2017 May 4.

Division of Vascular and Endovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA.

Background: To describe a large single-institutional experience in managing challenging access situations during endovascular aneurysm repair (EVAR).

Methods: Data from all patients undergoing EVAR at a tertiary academic medical center between 2009 and 2013 were collected retrospectively, including demographics, size of iliac arteries, type of device used, approach to managing difficult access (DA), and outcomes. The median follow-up was 38 months. DA was defined as iliac arteries with a diameter of less than 7 mm bilaterally. Fenestrated and snorkel repairs were excluded.

Results: Of 400 EVARs performed during the study period, 191 (48%) were done in patients with DA. Of the DA patients, 35 (18.3%) underwent 42 adjuncts before the introduction of the main body device: including 15 dilators, 11 balloon angioplasties, 9 aortouniiliac devices, 3 SoloPath sheaths, 1 retroperitoneal cutdown, and 3 iliac stents. In another 29 patients, iliac stents were used to correct stenoses or kinks in the limbs after EVAR devices were deployed. The average diameter of the iliac artery used to deliver main body component was 4.6 mm in the group of patients requiring adjuncts and 5.4 mm in the remainder of the patients with small iliac arteries (P = 0.008). The median size of the main body device was 28 mm. Two cases were aborted due to inability to deliver the device. Other complications included 7 (3.6%) iliac ruptures, 3 (1.6%) instances of limb ischemia, and 5 (2.6%) patients needed early reoperation (within 30 days). Two patients (1%) had type I endoleaks at the conclusion of EVAR. During follow-up, 12 (6.3%) patients required EVAR revisions. Seven patients (3.6%) had limb thrombosis which occurred only in patients who did not have adjective procedures during the initial EVAR. Limb thrombosis and rate of revisions in patients with DA were not significantly different from the rates observed in non-DA patients. Perioperative mortality after elective repairs was 1.6% in DA patients and 0% in non-DA patients (P = 0.12).

Conclusions: EVAR can be successfully performed in patients with bilateral small iliac arteries. Adjunctive procedures might increase the technical success rate of EVAR in these patients and should definitely be considered in patients with iliac arteries less than 5 mm in diameter. Next generation and "low-profile" devices might minimize the need for adjunctive procedures and facilitate EVAR in these patients.
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http://dx.doi.org/10.1016/j.avsg.2017.03.190DOI Listing
October 2017

One-year pivotal trial outcomes of the Nellix system for endovascular aneurysm sealing.

J Vasc Surg 2017 Feb 13;65(2):330-336.e4. Epub 2016 Dec 13.

Department of Vascular Surgery, Heidelberg University Hospital, Heidelberg, Germany.

Objective: The Nellix EndoVascular Aneurysm Sealing (EVAS) System (Endologix, Inc, Irvine, Calif) is a novel approach to abdominal aortic aneurysm (AAA) treatment whereby polymer is used to fill the AAA sac. We report 1-year results of the investigational device exemption pivotal trial.

Methods: Eligible patients were treated at 30 sites in the United States and Europe. Inclusion criteria required an asymptomatic infrarenal AAA, with a neck length ≥10 mm and ≤60° angle, iliac artery blood lumen diameter 9 to 35 mm, access artery diameter ≥6 mm, and serum creatinine ≤2 mg/dL. Follow-up included computed tomography angiography scans at 30 days, 6 months, and 1 year that were evaluated by a core laboratory. The primary safety end point was 30-day major adverse events (MAEs), which were compared with a performance goal of <56% (the Society for Vascular Surgery open repair control group rate). The primary effectiveness end point was treatment success at 1 year, which was compared with a performance goal of >80%. Treatment success required procedural technical success and absence of AAA rupture during follow-up, conversion to open surgical repair, endoleak (type I or III) at 1 year, migration >10 mm causing complications or requiring secondary intervention, aneurysm enlargement, or secondary procedures through 1 year for resolution of endoleak, device obstruction or occlusion, or device defect.

Results: Of 150 treated patients, 149 (99.3%) completed 1-year follow-up. The MAEs rate at 30 days was 2.7% (95% confidence interval, 0.7%-6.7%), satisfying the primary safety end point (<56%). The 1-year treatment success was 94% (95% confidence interval, 88.6%-97.4%), achieving the primary effectiveness end point (>80%). At 1 year, key secondary outcomes included 6.7% MAEs, 4.7% serious device-related events, 1.3% AAA-related mortality, 3.7% secondary interventions, and 0.7% surgical conversions. MAEs through 1 year included death (n = 6), stroke (n = 3), bowel ischemia (n = 2), renal failure (n = 2), respiratory failure (n = 2), and myocardial infarction (n =1). One iatrogenic AAA rupture occurred and one AAA rupture was reported during follow-up. AAA sac enlargement (>5 mm) was 1.5% at 1 year. Endoleaks were present in four patients (3.1%) at 1 year (1 type Ib and 3 type II). Migration >10 mm occurred in three patients (2.3%), but none required secondary intervention.

Conclusions: Outcomes with this novel endovascular therapy for AAA, the Nellix EVAS System, are encouraging. The primary safety and effectiveness end points have been met. Low morbidity, low mortality, and high procedural and treatment success were achieved despite the inevitability of a learning curve and unique risks associated with a new device and technique. Long-term follow-up is in progress.
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http://dx.doi.org/10.1016/j.jvs.2016.09.024DOI Listing
February 2017

Evaluation of function and recovery of adipose-derived stem cells after exposure to paclitaxel.

Cytotherapy 2017 02 22;19(2):211-221. Epub 2016 Nov 22.

Department of Surgery, Cooper University Hospital, Camden, New Jersey, USA.

Background Aims: Adipose-derived stem cells (ASCs) are considered to play a positive role in wound healing as evidenced by their increasing use in breast reconstructive procedures. After chemotherapy for breast cancer, poor soft tissue wound healing is a major problem. In the present study, the functional capabilities and recovery of ASCs after exposure to chemotherapeutic agent paclitaxel (PTX) using in vitro and ex vivo models were demonstrated.

Methods: Human ASCs were isolated from periumbilical fat tissue and treated with PTX at various concentrations. Adult Sprague-Dawley rats were given intravenous injections with PTX. Two and four weeks after the initial PTX treatment, ASCs were isolated from rat adipose tissue. Proliferation, cell viability, apoptosis and cell migration rates were measured by growth curves, MTT assays, flow cytometry and scratch assays. ASCs were cultured in derivative-specific differentiation media with or without PTX for 3 weeks. Adipogenic, osteogenic and endothelial differentiation levels were measured by quantitative reverse transcriptase polymerase chain reaction and histological staining.

Results: PTX induced apoptosis, decreased the proliferation and cell migration rates of ASCs and inhibited ASCs multipotent differentiation in both in vitro human ASC populations and ex vivo rat ASC populations with PTX treatment. Furthermore, after cessation of PTX, ASCs exhibited recovery potential of differentiation capacity in both in vitro and animal studies.

Conclusions: Our results provide insight into poor soft tissue wound healing and promote further understanding of the potential capability of ASCs to serve as a cell source for fat grafting and reconstruction in cancer patients undergoing chemotherapy treatment.
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http://dx.doi.org/10.1016/j.jcyt.2016.10.010DOI Listing
February 2017

Relative value unit-based compensation incentivization in an academic vascular practice improves productivity with no early adverse impact on quality.

J Vasc Surg 2017 02 19;65(2):579-582. Epub 2016 Nov 19.

Division of Vascular Surgery, Department of Surgery, Cooper University Hospital, Camden, NJ. Electronic address:

Objective: Given the increased pressure from governmental programs to restructure reimbursements to reflect quality metrics achieved by physicians, review of current reimbursement schemes is necessary to ensure sustainability of the physician's performance while maintaining and ultimately improving patient outcomes. This study reviewed the impact of reimbursement incentives on evidence-based care outcomes within a vascular surgical program at an academic tertiary care center.

Methods: Data for patients with a confirmed 30-day follow-up for the vascular surgery subset of our institution's National Surgical Quality Improvement Program submission for the years 2013 and 2014 were reviewed. The outcomes reviewed included 30-day mortality, readmission, unplanned returns to the operating room, and all major morbidities. A comparison of both total charges and work relative value units (RVUs) generated was performed before and after changes were made from a salary-based to a productivity-based compensation model. P value analysis was used to determine if there were any statistically significant differences in patient outcomes between the two study years.

Results: No statistically significant difference in outcomes of the core measures studied was identified between the two periods. There was a trend toward a lower incidence of respiratory complications, largely driven by a lower incidence in pneumonia between 2013 and 2014. The vascular division had a net increase of 8.2% in total charges and 5.7% in work RVUs after the RVU-based incentivization program was instituted.

Conclusions: Revenue-improving measures can improve sustainability of a vascular program without negatively affecting patient care as evidenced by the lack of difference in evidence-based core outcome measures in our study period. Further studies are needed to elucidate the long-term effects of incentivization programs on both patient care and program viability.
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http://dx.doi.org/10.1016/j.jvs.2016.08.104DOI Listing
February 2017

Invited commentary.

J Vasc Surg 2016 08;64(2):312

Camden, NJ.

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http://dx.doi.org/10.1016/j.jvs.2016.06.049DOI Listing
August 2016

Open abdominal aortic aneurysm repair is still necessary in an era of advanced endovascular repair.

J Vasc Surg 2016 Aug 13;64(2):333-337. Epub 2016 May 13.

Department of Surgery, Cooper University Hospital and Cooper Medical School of Rowan University, Camden, NJ. Electronic address:

Objective: Recent advances in endovascular aneurysm repair have overcome substantial anatomic barriers associated with short and challenging necks. With greater range to treat more difficult anatomy from an endovascular approach, one would assume the need of open surgical repair (OSR) would be diminished. The purpose of our study was to determine the need for OSR for abdominal aortic aneurysms, in a tertiary academic setting, with a moderate volume (10-15 cases/year) of fenestrated endografting being performed.

Methods: An Institutional Review Board approved retrospective review was performed of all patients who underwent elective aortic aneurysm repair between January 2010 and July 2014. Computed tomography scans for patients who underwent OSR were reviewed and anatomic characteristics obtained. Instructions for use of (IFU) a commercially available fenestrated device (Cook Medical, Bloomington, Ind) were used to determine if open repair patients had anatomy amenable to advanced endovascular repair.

Results: During the study interval, 415 patients underwent abdominal aortic aneurysm repair. Of those patients who underwent elective aneurysm repair, 105 patients had OSR. The study subsequently excluded 11 patients because they underwent secondary interventions after a failed endovascular repair and thus were not further evaluated. Also excluded were 18 patients who had OSR for an emergency intervention. The remaining 76 patients (35 female, 41 male; average age, 72 ± 8 years) had OSR and were outside the IFU of the fenestrated endovascular aneurysm repair (FEVAR) device. The average diameter of the abdominal aorta was 5.9 cm. Indications for OSR were an aneurysm neck <4 mm (71%), inclusion of at least 1 visceral vessel (69.7%), unilateral iliac artery aneurysms (15.5%), bilateral iliac artery aneurysms (14.3%), iliac artery tortuosity >40° of angulation (37.6%), extensive aortic thrombus (23.2%), and aortic neck angulation >45° (11.8%). Rejected patients had an average of 1.7 ± 0.8 anatomic constraints (range 1-4) that prevented use of the FEVAR device.

Conclusions: With evidence to support the strict adherence to IFU protocols of the FEVAR device in patients, our institution's practice has been to continue to perform open abdominal aortic aneurysm repair for patients with anatomy outside device protocols. Although it was thought that the decreased requirement of aortic neck required to deploy an endograft would lead to an increased patient population amenable to endovascular repair, there is still a clinically significant need for open aortic surgery.
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http://dx.doi.org/10.1016/j.jvs.2016.02.027DOI Listing
August 2016

Fibroblast growth factor and vascular endothelial growth factor play a critical role in endotheliogenesis from human adipose-derived stem cells.

J Vasc Surg 2017 05 8;65(5):1483-1492. Epub 2016 Aug 8.

Department of Surgery, Cooper University Hospital and Cooper Medical School of Rowan University, Camden, NJ. Electronic address:

Objective: Adipose-derived stem cells (ASCs) are a potential adult mesenchymal stem cell source for restoring endothelial function in patients with critical limb ischemia. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor (VEGF) play a major role in angiogenesis and wound healing. This study evaluated the effects of FGF and VEGF on the proliferation, migration, and potential endothelial differentiation of human ASCs with regards to their use as endothelial cell substitutes.

Methods: ASCs were isolated from clinical lipoaspirates and cultured in M199 medium with fetal bovine serum (10%), FGF2 (10 ng/mL), VEGF (50 ng/mL), or combinations of FGF2 and VEGF. Cell proliferation rates, viability, and migration were measured by growth curves, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), and scratch assays. For cell attachment determinations, ASCs were seeded onto a scaffold of small intestinal submucosa for 5 days. Endothelial differentiation capabilities of ASCs were confirmed by expression of endothelial cell-specific markers using quantitative polymerase chain reaction, immunofluorescence staining, and cord formation on Matrigel (BD Biosciences, San Jose, Calif). PD173074, a selective inhibitor of FGF receptor, was used to confirm the importance of FGF signaling.

Results: ASCs treated with FGF or combinations of FGF and VEGF showed increased proliferation rates and consistent differentiation toward an endothelial cell lineage increase in platelet endothelial cell adhesion molecule (CD31), von Willebrand factor, endothelial nitric oxide synthase, and vascular endothelial cadherin message, and in protein and cord formation on Matrigel. FGF and VEGF stimulated ASC migration and increased the attachment and retention after seeding onto a matrix graft of small intestinal submucosa. Blockade of FGF signaling with PD173074 abrogated ASC endothelial cell differentiation potential.

Conclusions: These results indicate that FGF and VEGF are ASC promoters for proliferation, migration, attachment, and endothelial differentiation. FGF and VEGF have a costimulatory effect on ASC endotheliogenesis. These results further suggest that ASCs with enhanced FGF signaling may potentially be used for tissue engineering and cell-based therapies in patients with critical limb ischemia.
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http://dx.doi.org/10.1016/j.jvs.2016.04.034DOI Listing
May 2017

Imaging After Nellix Endovascular Aneurysm Sealing: A Consensus Document.

J Endovasc Ther 2016 Feb 12;23(1):7-20. Epub 2015 Nov 12.

St George's Vascular Institute, St George's NHS Trust Hospital, London, UK.

Endovascular aneurysm sealing (EVAS) using the Nellix system is a new and different method of abdominal aortic aneurysm repair. Normal postoperative imaging has unique appearances that change with time; complications also have different and specific appearances. This consensus document on the imaging findings after Nellix EVAS is based on the collective experience of the sites involved in the Nellix EVAS Global Forward Registry and the US Investigational Device Exemption Trial. The normal findings on computed tomography (CT), duplex ultrasound, magnetic resonance imaging, and plain radiography are described. With time, endobag appearances change on CT due to contrast migration to the margins of the hydrogel polymer within the endobag. Air within the endobag also has unique appearances that change over time. Among the complications after Nellix EVAS, type I endoleak usually presents as a curvilinear area of flow between the endobag and aortic wall, while type II endoleak is typically small and usually occurs where an aortic branch artery lies adjacent to an irregular aortic blood lumen that is not completely filled by the endobag. Procedural aortic injury is an uncommon but important complication that occurs as a result of overfilling of the endobags during Nellix EVAS. The optimum imaging surveillance algorithm after Nellix EVAS has yet to be defined but is largely CT-based, especially in the first year postprocedure. However, duplex ultrasound also appears to be a sensitive modality in identifying normal appearances and complications.
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http://dx.doi.org/10.1177/1526602815616251DOI Listing
February 2016

Results of the Nellix system investigational device exemption pivotal trial for endovascular aneurysm sealing.

J Vasc Surg 2016 Jan 21;63(1):23-31.e1. Epub 2015 Oct 21.

Department of Vascular Surgery, University of Heidelberg, Heidelberg, Germany.

Objective: The Nellix EndoVascular Aneurysm Sealing system (Endologix, Inc, Irvine, Calif) is a novel approach to abdominal aortic aneurysm (AAA) endovascular repair whereby biocompatible polymer is employed to exclude and to seal the AAA sac. We report 30-day results of the U.S. pivotal trial.

Methods: Consecutive, eligible, consenting patients were enrolled at 29 sites in the United States and Europe. Inclusion criteria required an asymptomatic infrarenal AAA, with aortic neck length ≥10 mm and angle to the sac ≤60 degrees, aortic neck diameter of 18 to 32 mm, aneurysm blood lumen diameter ≤6 cm, common iliac artery lumen diameter of 9 to 35 mm, access artery diameter ≥6 mm, and serum creatinine level ≤2 mg/dL. Follow-up at 30 days included clinical assessment and computed tomography angiography evaluation of endoleaks and device integrity as assessed by a core laboratory. The primary safety end point is the incidence of independently adjudicated 30-day major adverse events (MAEs), with success defined as superiority with reference to the Society for Vascular Surgery open repair control group (56%).

Results: Between January and November 2014, 150 trial patients having a mean AAA diameter of 5.8 cm were enrolled and treated with the Nellix system with 100% procedural success. One early death (0.7%) occurred secondary to multisystem organ failure. All 149 surviving patients completed 30-day follow-up. There were no aneurysm ruptures, conversions, limb thromboses, stent fractures, or stent kinking. Five early MAEs occurred in four patients (2.7%) and included one death, bowel ischemia (1), renal failure (2), and respiratory failure (1). One (0.7%) secondary intervention to treat inadvertent coverage of a renal artery was performed. The core laboratory identified nine (6%) endoleaks (one type I, eight type II) on 30-day computed tomography angiography. Freedom from MAE was 97.3% (95% confidence interval, 93.3%-99.0%).

Conclusions: In selected patients, perioperative outcomes with the Nellix system for endovascular aneurysm sealing are encouraging, with very low 30-day morbidity and mortality and high procedural success. The primary safety end point has been achieved. Longer term follow-up is in progress.
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http://dx.doi.org/10.1016/j.jvs.2015.07.096DOI Listing
January 2016

Secondary interventions after endovascular repair of aortic dissections.

Ann Vasc Surg 2015 Aug 22;29(6):1160-6. Epub 2015 May 22.

Division of Vascular and Endovascular Surgery, Cooper University Hospital, Camden, NJ. Electronic address:

Background: Review the literature on secondary interventions performed for patients who underwent endovascular repair of their type B aortic dissection. Endovascular repair for type B aortic dissection (TBAD) has been proven to be both technically feasible and beneficial in some patients. However, the information regarding secondary interventions is not cohesive. To date, there are little data to help guide physicians on the indications and benefits of secondary interventions in the setting of previous endovascular repair for TBAD.

Methods: PubMed database was queried for publications using the following combination of keywords; "aortic dissection," "type B," "secondary intervention," "false lumen thrombosis," "stent graft," "aortic remodeling," and endovascular repair. Sixteen articles were selected and reviewed for secondary interventions, indications for procedure, and effects on false lumen thrombosis. Data were collected, and a composite database of patients was created.

Results: Literature review demonstrated 161 of 862 patients required secondary interventions for entry tears, retrograde type A dissection, false lumen degeneration with aortic expansion, graft malfunction, and various access complications. The complete false lumen thrombosis rate was 33%, and overall mortality was 18.2%.

Conclusions: Secondary interventions provide a useful adjunct to failing endovascular repair of aortic dissections. A variety of treatment options are available for aneurysmal degeneration after thoracic endovascular aneurysm repair. This review also shows that these secondary interventions, in combination with proper surveillance and optimal medical management, are feasible but carry a high all-cause mortality.
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http://dx.doi.org/10.1016/j.avsg.2015.02.017DOI Listing
August 2015

Paclitaxel impairs adipose stem cell proliferation and differentiation.

J Surg Res 2015 Jun 18;196(2):404-15. Epub 2015 Mar 18.

Department of Plastic Surgery, Cooper University Hospital, Camden, New Jersey.

Background: Cancer patients with chemotherapy-induced immunosuppression have poor surgical site wound healing. Prior literature supports the use of human adipose-derived stem cell (hASC) lipoinjection to improve wound healing. It has been established that multipotent hASCs facilitate neovascularization, accelerate epithelialization, and quicken wound closure in animal models. Although hASC wound therapy may benefit surgical cancer patients, the chemotherapeutic effects on hASCs are unknown. We hypothesized that paclitaxel, a chemotherapeutic agent, impairs hASC growth, multipotency, and induces apoptosis.

Methods: hASCs were isolated and harvested from consented, chemotherapy and radiation naive patients. Growth curves, MTT (3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide), and EdU (5-ethynyl-2-deoxyguridine) assays measured cytotoxicity and proliferation. Oil Red O stain, Alizarin Red stain, matrigel tube formation assay, and quantitative polymerase chain reaction analyzed hASC differentiation. Annexin V assay measured apoptosis. Immunostaining and Western blot determined tumor necrosis factor α (TNF-α) expression.

Results: hASCs were selectively more sensitive to paclitaxel (0.01-30 μM) than fibroblasts (P < 0.05). After 12 d, paclitaxel caused hASC growth arrest, whereas control hASCs proliferated (P = 0.006). Paclitaxel caused an 80.6% reduction in new DNA synthesis (P < 0.001). Paclitaxel severely inhibited endothelial differentiation and capillary-like tube formation. Differentiation markers, lipoprotein lipase (adipogenic), alkaline phosphatase (osteogenic), CD31, and van Willebrand factor (endothelial), were significantly decreased (all P < 0.05) confirming paclitaxel impaired differentiation. Paclitaxel was also found to induce apoptosis and TNF-α was upregulated in paclitaxel-treated hASCs (P < 0.001).

Conclusions: Paclitaxel is more cytotoxic to hASCs than fibroblasts. Paclitaxel inhibits hASC proliferation, differentiation, and induces apoptosis, possibly through the TNF-α pathway. Paclitaxel's severe inhibition of endothelial differentiation indicates neovascularization disruption, possibly causing poor wound healing in cancer patients receiving chemotherapy.
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http://dx.doi.org/10.1016/j.jss.2015.03.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4442730PMC
June 2015

Peripheral occlusive disease may provide the highest hospital margins despite rising costs.

J Vasc Surg 2014 Aug;60(2):528-31

Department of Surgery, Albert Einstein Medical Center, Philadelphia, Pa.

Objective: The objective of this study was to review vascular surgical financial trends in a tertiary care setting and to evaluate the impact of a vascular program within a health care system in the face of lower reimbursements and rising costs.

Methods: With use of Current Procedural Terminology codes and diagnosis-related groups, vascular categories of aortic disease, cerebrovascular disease, and peripheral occlusive disease (POCD) were identified at an academic tertiary health care center. Hospital margins were calculated for each of the defined categories by Health Quest cost accounting data cross-walked with Current Procedural Terminology codes, date of service, and admitting physician for each year from 2010 to 2012.

Results: All categories realized volume growth and a positive margin for the hospital. In comparison of 2010 and 2012, aortic cases showed an overall volume growth of 19%, revenue increase of 31%, and cost increase of 54%, resulting in an overall margin decrease of 7%. Cerebrovascular cases showed a 30% increase in volume growth, revenue increase of 13%, and cost increase of 5%, resulting in a margin increase of 18%. POCD cases showed overall volume growth of 35%, revenue increase of 37%, cost increase of 54%, and a margin increase of 15%. The margin for POCD exceeded the margin for aortic and cerebrovascular cases combined by 77%.

Conclusions: In evaluating a vascular program's fiscal viability, volume-driven POCD was the only category producing growing hospital margins in the face of significant cost increases.
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http://dx.doi.org/10.1016/j.jvs.2014.04.065DOI Listing
August 2014

No increased risk of spinal cord ischemia in delayed AAA repair following thoracic aortic surgery.

Vasc Endovascular Surg 2013 Feb 20;47(2):85-91. Epub 2013 Jan 20.

Division of Vascular Surgery and Endovascular Therapy, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.

Objective: To examine the results of open or endovascular abdominal aortic aneurysm (AAA) repair following prior open or endovascular thoracic aortic surgery.

Methods: A retrospective review of all patients who underwent AAA repair in a delayed fashion following prior thoracic aortic surgery at a single university hospital between 1999 and 2011 was performed.

Results: Thirteen patients underwent AAA repair following prior thoracic aortic repair. Mean age was 68.9 ± 6.9 years and 77% (n = 10) were male. Three patients experienced transient delayed-onset spinal cord ischemia (SCI) following initial thoracic surgery. Mean time interval between initial thoracic aortic surgery and subsequent AAA repair was 2.0 ± 1.8 years. Overall rate of SCI and 30-day mortality after delayed AAA repair was 0%.

Conclusions: This series does not demonstrate any evidence of increased risk of perioperative mortality or SCI in patients undergoing delayed AAA repair after prior thoracic aortic surgery.
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http://dx.doi.org/10.1177/1538574412474500DOI Listing
February 2013

Modified eversion carotid endarterectomy.

Ann Vasc Surg 2013 Feb 28;27(2):178-85. Epub 2012 Jun 28.

Division of Vascular and Endovascular Surgery, Cooper Medical School, Rowan University, Cooper University Hospital, Camden, NJ 08103, USA.

Background: Eversion carotid endarterectomy is a well-described technique for carotid endarterectomy (CEA). The advantage of this technique is a completely autogenous repair. We describe a modification of eversion endarterectomy (MEE) that expeditiously extracts the plaque through a linear incision over the common carotid artery and the proximal bulbous internal carotid artery (ICA) only, allowing primary closure. Selective shunting can also be performed without difficulty.

Methods: A retrospective review of CEAs using MEE at two institutions by three vascular surgeons during a 5-year period was performed. Data were collected from the medical records, with institutional review board approval. Information regarding neurologic symptoms, degree of ICA stenosis, CEA technique, ICA clamp time, shunting, electroencephalographic monitoring, and postoperative complications was tabulated. Rate of significant restenosis (stenosis >50% by duplex criteria) was also calculated during the follow-up period.

Results: Between 2005 and 2009, a total of 221 patients underwent MEE for carotid artery stenosis (CAS): 69 patients (31%) underwent MEE for symptomatic and 152 (68.8%) underwent MEE for asymptomatic CAS. Neuromonitoring in the form of electroencephalography was used in 85 (39%) patients, and an intraluminal shunt was used in 29 patients (13%) who had either severe contralateral disease or a previous ipsilateral cerebral infarction. Postoperative complications included transient ischemic attack (four, 2%), cerebral infarction (three, 1%), myocardial infarction (three, 1%), and hematoma (six, 3%). Four patients (2%) required a return to the operating room (OR). within 24 hours for hematoma (one, 1%) or postoperative neurologic deficit (three, %). The 30-day mortality was 1%. One patient (1%) required patch angioplasty because of the extent of disease and inability to obtain a good end point. Average cross-clamp time for MEE was 12.8 minutes. Two patients (1%) were reported to have hemodynamically significant restenosis within 2 years, with one patient requiring intervention.

Conclusions: MEE is a safe and effective way of treating CAS, with acceptable morbidity, mortality, and low rate of recurrent stenosis despite the absence of a patch. Given the brief clamp time required, routine shunting and/or neuromonitoring for this technique may have questionable clinical value and expense.
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http://dx.doi.org/10.1016/j.avsg.2012.01.008DOI Listing
February 2013

Predictors of decreased short- and long-term survival following open abdominal aortic aneurysm repair.

J Vasc Surg 2011 Nov 15;54(5):1237-43. Epub 2011 Aug 15.

Department of Surgery, Hospital of the University of Pennsylvania, 4 Maloney Building, Philadelphia, PA 19104, USA.

Objectives: The purpose of this study was to identify predictors of decreased survival after open abdominal aortic aneurysm (AAA) repair at a single university hospital.

Methods: Patients undergoing open AAA repair from June 2003 to June 2009 were identified. Primary outcomes were 30-day and 5-year survival. Preoperative, intraoperative, and postoperative variables were assessed for their influence on outcomes using univariate and multivariate analysis, as appropriate. One- and 5-year survival were determined by Kaplan-Meier analysis.

Results: Four hundred eight patients (289 men; 70.8%) with a mean age of 72.4 ± 8.3 years underwent open AAA repair. Sixty-seven patients (16.4%) underwent nonelective repair. The clamp site was infrarenal in 137 patients (33.6%), suprarenal in 97 patients (23.8%), and supraceliac in 174 patients (42.6%). Thirty-day survival was 95.6%. One- and 5-year survival were 90.0% ± 1.5% and 65.1% ± 3.0%, respectively. Seventy-nine patients (19.4%) had decreased renal function postoperatively compared to preoperatively, 71 patients (17.4%) sustained cardiac complications, and 45 patients (11.0%) sustained pulmonary complications. Patients with chronic obstructive pulmonary disease (91.9% vs 97.2%; P = .004) and chronic renal insufficiency (92.0% vs 98.3%; P = .009) had decreased 30-day survival. Patients with chronic obstructive pulmonary disease (55.8% ± 5.8% vs 67.3% ± 3.6%; P = .013), chronic renal insufficiency (51.2% ± 5.2% vs 72.8% ± 3.7%; P = .043), and cerebrovascular disease (46.8% ± 7.4% vs 67.4% ± 3.4%; P = .003) had decreased 5-year survival. Patients who had decreased postoperative renal function (41.0% ± 7.4% vs 72.2% ± 3.4%; P = .004), and patients who sustained pulmonary complications (45.6% ± 8.8% vs 66.3% ± 3.3%; P = .042) had worse 5-year survival.

Conclusions: Open AAA repair can be done with low morbidity and mortality in the era of endovascular aneurysm repair. Careful consideration should be given to preoperative optimization and perioperative care in patients with chronic obstructive pulmonary disease, chronic renal insufficiency, and cerebrovascular disease. Postoperative decrease in renal function and pulmonary complication portend decreased 5-year survival; strategies to ameliorate these factors should be sought.
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http://dx.doi.org/10.1016/j.jvs.2011.05.028DOI Listing
November 2011

Delayed complications of inferior vena cava filters: case report and literature review.

Vasc Endovascular Surg 2011 Apr 28;45(3):290-4. Epub 2011 Jan 28.

Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.

Inferior vena cava (IVC) filters are frequently placed to prevent pulmonary embolism in patients in whom anticoagulation is contraindicated or ineffective. Delayed erosion of the filter into adjacent vital structures is a rare complication. We report 3 complications of IVC filters managed with both surgical and endovascular therapies. A review of the available literature addresses incidence of delayed IVC filter complications, the approach to these problems, and the role of retrievable IVC filters.
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http://dx.doi.org/10.1177/1538574410395038DOI Listing
April 2011