Publications by authors named "Elliot Chaikof"

222 Publications

The NIH Somatic Cell Genome Editing program.

Nature 2021 Apr 7;592(7853):195-204. Epub 2021 Apr 7.

Department of Neurosurgery, Yale University, New Haven, CT, USA.

The move from reading to writing the human genome offers new opportunities to improve human health. The United States National Institutes of Health (NIH) Somatic Cell Genome Editing (SCGE) Consortium aims to accelerate the development of safer and more-effective methods to edit the genomes of disease-relevant somatic cells in patients, even in tissues that are difficult to reach. Here we discuss the consortium's plans to develop and benchmark approaches to induce and measure genome modifications, and to define downstream functional consequences of genome editing within human cells. Central to this effort is a rigorous and innovative approach that requires validation of the technology through third-party testing in small and large animals. New genome editors, delivery technologies and methods for tracking edited cells in vivo, as well as newly developed animal models and human biological systems, will be assembled-along with validated datasets-into an SCGE Toolkit, which will be disseminated widely to the biomedical research community. We visualize this toolkit-and the knowledge generated by its applications-as a means to accelerate the clinical development of new therapies for a wide range of conditions.
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http://dx.doi.org/10.1038/s41586-021-03191-1DOI Listing
April 2021

Standardized User-Independent Confocal Microscopy Image Acquisition and Analysis for Thickness Measurements of Microscale Collagen Scaffolds.

Microsc Microanal 2021 Mar 31:1-6. Epub 2021 Mar 31.

Department of Surgery, Beth Israel Deaconess Medical Center, Center for Life Sciences, 3 Blackfan Circle, Boston, MA02115, USA.

The ability to accurately and precisely measure the thickness of biomaterial constructs is critical for characterizing both specific dimensional features and related mechanical properties. However, in the absence of a standardized approach for thickness measurements, a variety of imaging modalities have been employed, which have been associated with varying limits of accuracy, particularly for ultrathin hydrated structures. Electron microscopy (EM), a commonly used modality, yields thickness values for extensively processed and nonhydrated constructs, potentially resulting in overestimated mechanical properties, including elastic modulus and ultimate tensile strength. Confocal laser scanning microscopy (CLSM) has often been used as a nondestructive imaging alternative. However, published CLSM-derived image analysis protocols use arbitrary signal intensity cutoffs and provide minimal information regarding thickness variability across imaged surfaces. To address the aforementioned limitations, we present a standardized, user-independent CLSM image acquisition and analysis approach developed as a custom ImageJ macro and validated with collagen-based scaffolds. In the process, we also quantify thickness discrepancies in collagen-based scaffolds between CLSM and EM techniques, further illustrating the need for improved strategies. Employing the same image acquisition protocol, we also demonstrate that this approach can be used to estimate the surface roughness of the same scaffolds without the use of specialized instrumentation.
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http://dx.doi.org/10.1017/S1431927621000234DOI Listing
March 2021

Society for Vascular Surgery implementation of clinical practice guidelines for patients with an abdominal aortic aneurysm: Screening for an abdominal aortic aneurysm.

J Vasc Surg 2021 Apr 18;73(4):1126-1127. Epub 2021 Feb 18.

Division of Vascular & Endovascular Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Mass. Electronic address:

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http://dx.doi.org/10.1016/j.jvs.2020.12.051DOI Listing
April 2021

Society for Vascular Surgery implementation of clinical practice guidelines for patients with an abdominal aortic aneurysm: Repair of an abdominal aortic aneurysm.

J Vasc Surg 2021 Feb 4. Epub 2021 Feb 4.

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

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http://dx.doi.org/10.1016/j.jvs.2020.12.103DOI Listing
February 2021

The Surgical Program in Innovation (SPIN): A Design and Prototyping Curriculum for Surgical Trainees.

Acad Med 2021 Feb 2. Epub 2021 Feb 2.

D.J. Wong is a fourth-year resident, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts. D. Miranda-Nieves is a PhD candidate, Health Sciences and Technology, Harvard Medical School and Massachusetts Institute of Technology, Cambridge, Massachusetts. P. Nandivada is a faculty surgeon, Department of Surgery, Boston Children's Hospital, Boston, Massachusetts. M.S. Patel is a surgical fellow, Department of Surgery, University of Toronto, Toronto, Ontario, Canada. D.A. Hashimoto is a fifth-year resident, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts. D.O. Kent is a second-year resident, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts. J. Gómez-Márquez is director, MIT Little Devices Lab, Massachusetts Institute of Technology, Cambridge, Massachusetts. S.J. Lin is a faculty surgeon, Department of Surgery, Beth Israel Deaconess Medical Center, and associate professor of surgery, Harvard Medical School, Boston, Massachusetts. H.J. Feldman is a faculty physician, Department of Medicine, Beth Israel Deaconess Medical Center, and assistant professor of medicine, Harvard Medical School, Boston, Massachusetts, as well as deputy chief medical officer-technology, IBM Watson Health, Cambridge, Massachusetts. E.L. Chaikof is chair and surgeon-in-chief, Department of Surgery, Beth Israel Deaconess Medical Center, and a professor of surgery, Harvard Medical School, Boston, Massachusetts.

Problem: Health professions education does not routinely incorporate training in innovation or creative problem solving. Although some models of innovation education within graduate medical education exist, they often require participants' full-time commitment and removal from clinical training or rely upon participants' existing expertise. There is a need for curricula that teach innovation skills that will enable trainees to identify and solve unmet clinical challenges in everyday practice. To address this gap in surgical graduate education, the authors developed the Surgical Program in Innovation (SPIN).

Approach: SPIN, a 6-month workshop-based curriculum, was established in 2016 in the Beth Israel Deaconess Medical Center Department of Surgery to teach surgical trainees the basics of the innovation process, focusing on surgeon-driven problem identification, product design, prototype fabrication, and initial steps in the commercialization process. Participating surgical residents and graduate students attend monthly workshops taught by medical, engineering, and medical technology (MedTech) industry faculty. Participants collaborate in teams to develop a novel device, fabricate a protype, and pitch their product to a panel of judges.

Outcomes: From academic years 2015-2016 to 2017-2018, 49 trainees, including 41 surgical residents, participated in SPIN. Across this period, 13 teams identified an unmet need, ideated a solution, and designed and pitched a novel device. Ten teams fabricated prototypes. The 22 SPIN participants who responded to both pre- and postcourse surveys reported significant increases in confidence in generating problem statements, computer-aided design, fabrication of a prototype, and initial commercialization steps (product pitching and business planning).

Next Steps: Incorporating innovation education and design thinking into clinical training will prove essential in preparing future physicians to be lifelong problem finders and solvers. The authors plan to expand SPIN to additional clinical specialties, as well as to assess its impact in fostering future innovation and collaboration among program participants.
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http://dx.doi.org/10.1097/ACM.0000000000003958DOI Listing
February 2021

Regenerating Antithrombotic Surfaces through Nucleic Acid Displacement.

ACS Biomater Sci Eng 2020 04 3;6(4):2159-2166. Epub 2020 Mar 3.

John A. Paulson School of Engineering and Applied Sciences, Harvard University, 29 Oxford Street, Cambridge, Massachusetts 02138, United States.

Blood-contacting devices are commonly coated with antithrombotic agents to prevent clot formation and to extend the lifespan of the device. However, in vivo degradation of these bioactive surface agents ultimately limits device efficacy and longevity. Here, a regenerative antithrombotic catheter surface treatment is developed using oligodeoxynucleotide (ODN) toehold exchange. ODN strands modified to carry antithrombotic payloads can inhibit the thrombin enzyme when bound to a surface and exchange with rapid kinetics over multiple cycles, even while carrying large payloads. The surface-bound ODNs inhibit thrombin activity to significantly reduce fibrinogen cleavage and fibrin formation, and this effect is sustained after ODN exchange of the surface-bound strands with a fresh antithrombotic payload. This study presents a unique strategy for achieving a continuous antithrombotic state for blood-contacting devices using an ODN-based regeneration method.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00038DOI Listing
April 2020

Resident and elicited murine macrophages differ in expression of their glycomes and glycan-binding proteins.

Cell Chem Biol 2020 Dec 29. Epub 2020 Dec 29.

Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA. Electronic address:

The pleiotropic functions of macrophages in immune defense, tissue repair, and maintenance of tissue homeostasis are supported by the heterogeneity in macrophage sub-populations that differ both in ontogeny and polarization. Although glycans and glycan-binding proteins (GBPs) are integral to macrophage function and may contribute to macrophage diversity, little is known about the factors governing their expression. Here, we provide a resource for characterizing the N-/O-glycomes of various murine peritoneal macrophage sub-populations, demonstrating that glycosylation primarily reflects developmental origin and, to a lesser degree, cellular polarization. Furthermore, comparative analysis of GBP-coding genes in resident and elicited macrophages indicated that GBP expression is consistent with specialized macrophage functions and correlates with specific types of displayed glycans. An integrated, semi-quantitative approach was used to confirm distinct expression patterns of glycans and their binding proteins across different macrophages. The data suggest that regulation of glycan-protein complexes may be central to macrophage residence and recruitment.
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http://dx.doi.org/10.1016/j.chembiol.2020.12.005DOI Listing
December 2020

Combined Antiplatelet/Anticoagulant Drug for Cardiac Ischemia/Reperfusion Injury.

Circ Res 2020 Oct 17;127(9):1211-1213. Epub 2020 Aug 17.

Molecular Imaging and Theranostics Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia (L.A.B., A.M., A.K.S., E.Y., X.W.).

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http://dx.doi.org/10.1161/CIRCRESAHA.120.317450DOI Listing
October 2020

Inferring causality.

J Vasc Surg 2020 08;72(2):387-388

Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass. Electronic address:

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http://dx.doi.org/10.1016/j.jvs.2020.01.036DOI Listing
August 2020

Continuous Formation of Ultrathin, Strong Collagen Sheets with Tunable Anisotropy and Compaction.

ACS Biomater Sci Eng 2020 07 26;6(7):4236-4246. Epub 2020 May 26.

Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Ontario M5S3G8, Canada.

The multiscale organization of protein-based fibrillar materials is a hallmark of many organs, but the recapitulation of hierarchal structures down to fibrillar scales, which is a requirement for withstanding physiological loading forces, has been challenging. We present a microfluidic strategy for the continuous, large-scale formation of strong, handleable, free-standing, multicentimeter-wide collagen sheets of unprecedented thinness through the application of hydrodynamic focusing with the simultaneous imposition of strain. Sheets as thin as 1.9 μm displayed tensile strengths of 0.5-2.7 MPa, Young's moduli of 3-36 MPa, and modulated the diffusion of molecules as a function of collagen nanoscale structure. Smooth muscle cells cultured on engineered sheets oriented in the direction of aligned collagen fibrils and generated coordinated vasomotor responses. The described biofabrication approach enables rapid formation of ultrathin collagen sheets that withstand physiologically relevant loads for applications in tissue engineering and regenerative medicine, as well as in organ-on-chip and biohybrid devices.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362332PMC
July 2020

The ESSEA Trial: A Clear Image of a Fuzzy Problem.

Circ Cardiovasc Imaging 2020 06 8;13(6):e010990. Epub 2020 Jun 8.

Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.

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http://dx.doi.org/10.1161/CIRCIMAGING.120.010990DOI Listing
June 2020

Safety in numbers as administrative data supports the use of endovascular aneurysm repair in ruptured abdominal aortic aneurysms.

J Vasc Surg 2020 06;71(6):1879-1880

Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass.

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http://dx.doi.org/10.1016/j.jvs.2019.07.071DOI Listing
June 2020

Modulation of lymphocyte-mediated tissue repair by rational design of heterocyclic aryl hydrocarbon receptor agonists.

Sci Adv 2020 01 15;6(3):eaay8230. Epub 2020 Jan 15.

Department of Surgery, Center for Drug Discovery and Translational Research, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.

Aryl hydrocarbon receptor (AHR) is an essential regulator of gut immunity and a promising therapeutic target for inflammatory bowel disease (IBD). Current AHR agonists are inadequate for clinical translation due to low activity, inadequate pharmacokinetics, or toxicity. We synthesized a structurally diverse library and used integrated computational and experimental studies to discover mechanisms governing ligand-receptor interaction and to design potent drug leads PY109 and PY108, which display physiochemical drug-likeness properties, desirable pharmacokinetic profiles, and low toxicity. In a murine model of dextran sulfate sodium-induced colitis, orally administered compounds increase interleukin-22 (IL-22) production and accelerate mucosal healing by modulating mucosal adaptive and innate lymphoid cells. AHR and IL-22 pathway induction was confirmed using RNA sequencing and characterization of the lymphocyte protein-protein interaction network. Significant induction of IL-22 was also observed using human T cells from patients with IBD. Our findings support rationally designed AHR agonists for IBD therapy.
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http://dx.doi.org/10.1126/sciadv.aay8230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962035PMC
January 2020

Vascular Quality Initiative assessment of compliance with Society for Vascular Surgery clinical practice guidelines on the care of patients with abdominal aortic aneurysm.

J Vasc Surg 2020 09 20;72(3):874-885. Epub 2020 Jan 20.

Division of Vascular Surgery, Peter Munk Cardiac Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.

Objective: Professional societies publish clinical practice guidelines to provide evidence-based recommendations to improve care and to reduce practice variation. However, the degree of compliance with the guidelines and its impact on outcomes have not been well defined. This study used the Vascular Quality Initiative (VQI) abdominal aortic aneurysm (AAA) registries to determine current compliance with and impact of recent Society for Vascular Surgery (SVS) AAA guidelines.

Methods: Recommendations from the SVS AAA guidelines were reviewed and assessed as to whether they could be evaluated with current VQI data sets. The degree of compliance with these individual recommendations was calculated by center and correlated with clinical outcomes. Data were analyzed by univariate analysis and mixed effects multivariable logistic regression. Statistical significance was measured at P < .05.

Results: Of the 111 SVS recommendations, 10 could be evaluated using VQI registries. The mean center-specific compliance rate ranged from 40% (smoking cessation 2 weeks before open AAA [OAAA] repair) to 99% (preservation of flow to one internal iliac artery during endovascular aneurysm repair [EVAR]). Some recommendations were associated with improved outcomes (eg, cell salvage for OAAA repair and antibiotic prophylaxis), whereas others were not (eg, EVAR at a center with >10 cases per year or door-to-intervention time <90 minutes for ruptured AAA). With multivariable analysis, compliance with preservation of flow to the internal iliac artery decreased major adverse cardiac events in EVAR and marginally decreased in-hospital and 1-year mortality in OAAA repair. Antibiotic administration decreased surgical site infection, major adverse cardiac events, and in-hospital mortality and marginally decreased respiratory complications and 1-year mortality in EVAR. Cell salvage for OAAA repair decreased 1-year mortality. Tobacco cessation before EVAR or OAAA repair decreased respiratory complications and 1-year mortality.

Conclusions: The VQI registry is a valuable tool that can be used to measure compliance with SVS AAA guidelines. Compliance with recommendations was associated with improved outcomes and should be encouraged for providers. Participation in the VQI registry provides an objective assessment of performance and compliance with guidelines. VQI provider and center reports may be used as a focus for quality improvement efforts.
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http://dx.doi.org/10.1016/j.jvs.2019.10.097DOI Listing
September 2020

Identification of Tn antigen O-GalNAc-expressing glycoproteins in human carcinomas using novel anti-Tn recombinant antibodies.

Glycobiology 2020 04;30(5):282-300

Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, CLS 11090, 3 Blackfan Circle, Boston, MA 02115, USA.

The Tn antigen is a neoantigen abnormally expressed in many human carcinomas and expression correlates with metastasis and poor survival. To explore its biomarker potential, new antibodies are needed that specifically recognize this antigen in tumors. Here we generated two recombinant antibodies to the Tn antigen, Remab6 as a chimeric human IgG1 antibody and ReBaGs6 as a murine IgM antibody and characterized their specificities using multiple biochemical and biological approaches. Both Remab6 and ReBaGs6 recognize clustered Tn structures, but most importantly do not recognize glycoforms of human IgA1 that contain potential cross-reactive Tn antigen structures. In flow cytometry and immunofluorescence analyses, Remab6 recognizes human cancer cell lines expressing the Tn antigen, but not their Tn-negative counterparts. In immunohistochemistry (IHC), Remab6 stains many human cancers in tissue array format but rarely stains normal tissues and then mostly intracellularly. We used these antibodies to identify several unique Tn-containing glycoproteins in Tn-positive Colo205 cells, indicating their utility for glycoproteomics in future biomarker studies. Thus, recombinant Remab6 and ReBaGs6 are useful for biochemical characterization of cancer cells and IHC of tumors and represent promising tools for Tn biomarker discovery independently of recognition of IgA1.
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http://dx.doi.org/10.1093/glycob/cwz095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175968PMC
April 2020

The Learning Environment in Surgery Clerkship: What are Faculty Perceptions?

J Surg Educ 2020 Jan - Feb;77(1):61-68. Epub 2019 Jul 30.

Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts. Electronic address:

Objective: Multiple efforts have sought to improve teaching effectiveness and the learning environment (LE), but prior research has not focused on attending physicians' perceptions of mistreatment or contribution to the LE. The purpose of this study was to assess the perception and role of surgical faculty in the medical student LE.

Design: A semistructured interview guide was developed using a comprehensive approach including extensive literature search and focus groups. Data were audio-recorded and transcribed verbatim. Content analysis was used to identify emergent themes.

Setting: Beth Israel Deaconess Medical Center, an academic tertiary care facility located in Boston, Massachusetts.

Participants: Fifteen faculty in the Department of Surgery underwent detailed interviews. Participants were selected using purposive-stratified criterion-based sampling.

Results: Multiple themes emerged: (1) The competing demands on medical student's time are a negative factor in the LE; (2) Faculty expectations conflict with the existing curriculum; (3) Faculty are concerned with the possibility of being reported for providing negative feedback; (4) Faculty remain unfamiliar with policies regarding the LE/mistreatment; (5) A motivated medical student makes the educational interaction more productive independent of specialty of choice.

Conclusions: Faculty identified that the most important factors contributing to a negative LE were a mismatch between expectations of medical students and faculty, and the conflict between the current curriculum and the faculty member's perceived ideal educational framework. Importantly, faculties were largely unfamiliar with LE/mistreatment policies and standards. These findings suggest a need for targeted curricula for faculty to raise awareness of components of a positive LE and tools to teach effectively within the contemporary medical school curriculum.
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http://dx.doi.org/10.1016/j.jsurg.2019.07.003DOI Listing
July 2019

The blood compatibility challenge. Part 4: Surface modification for hemocompatible materials: Passive and active approaches to guide blood-material interactions.

Acta Biomater 2019 08 19;94:33-43. Epub 2019 Jun 19.

Institute Biofunctional Polymer Materials, Max Bergmann Center of Biomaterials, Leibniz-Institut für Polymerforschung Dresden e.V., Dresden, Germany.

Biomedical devices in the blood flow disturb the fine-tuned balance of pro- and anti-coagulant factors in blood and vessel wall. Numerous technologies have been suggested to reduce coagulant and inflammatory responses of the body towards the device material, ranging from camouflage effects to permanent activity and further to a responsive interaction with the host systems. However, not all types of modification are suitable for all types of medical products. This review has a focus on application-oriented considerations of hemocompatible surface fittings. Thus, passive versus bioactive modifications are discussed along with the control of protein adsorption, stability of the immobilization, and the type of bioactive substance, biological or synthetic. Further considerations are related to the target system, whether enzymes or cells should be addressed in arterial or venous system, or whether the blood vessel wall is addressed. Recent developments like feedback controlled or self-renewing systems for drug release or addressing cellular regulation pathways of blood platelets and endothelial cells are paradigms for a generation of blood contacting devices, which are hemocompatible by cooperation with the host system. STATEMENT OF SIGNIFICANCE: This paper is part 4 of a series of 4 reviews discussing the problem of biomaterial associated thrombogenicity. The objective was to highlight features of broad agreement and provide commentary on those aspects of the problem that were subject to dispute. We hope that future investigators will update these reviews as new scholarship resolves the uncertainties of today.
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http://dx.doi.org/10.1016/j.actbio.2019.06.019DOI Listing
August 2019

Design and Implementation of an Infrastructure Program to Support Clinical Research in Surgery.

J Surg Res 2019 09 28;241:264-270. Epub 2019 Apr 28.

Department of Surgery, Beth Israel Deaconess Medical Center, Boston Massachusetts; Department of Surgery, Harvard Medical School, Boston Massachusetts. Electronic address:

Barriers to active participation in clinical research among academic surgeons include insufficient research training and mentorship, increased clinical demands, lack of protected research time, limited access to resources, complex regulatory requirements, and a highly competitive research funding environment. We describe the development and implementation of a novel clinical research infrastructure program designed to attenuate these barriers and increase clinical research engagement and productivity in a large academic surgery department. Interim outcomes show a high utilization of program services across all divisions within the department, a substantial increase in new clinical research protocols, more applications submitted to funding agencies, and a high level of user satisfaction. We discuss how a departmental infrastructure program can simultaneously address barriers faced by surgeon clinical researchers and foster continuation of the longstanding tradition of innovation and discovery in academic surgery.
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http://dx.doi.org/10.1016/j.jss.2019.03.044DOI Listing
September 2019

Reply.

Authors:
Elliot L Chaikof

J Vasc Surg 2019 03;69(3):975-976

Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass.

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http://dx.doi.org/10.1016/j.jvs.2018.11.010DOI Listing
March 2019

Vascular fellow and resident experience performing infrapopliteal revascularization with endovascular procedures and vein bypass during training.

J Vasc Surg 2018 11;68(5):1533-1537

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

Objective: Endovascular aneurysm repair has led to a significant reduction in vascular trainee experience in the surgical treatment of aortic aneurysms. We sought to evaluate whether the vascular training paradigm or the "endovascular first" approach to lower extremity vascular disease has had a similar effect on trainee experience with infrapopliteal endovascular therapy and vein bypass.

Methods: Deidentified data were provided by the Vascular Surgery Board on the number of procedures performed by each 2014 fellowship and residency (0 + 5) graduate during training. Data were analyzed using parametric and nonparametric methods, where appropriate.

Results: Of 125 trainees (109 fellows, 16 residents), 33 (27%) performed 10 or fewer infrapopliteal vein bypasses and 37 (29%) performed 10 or fewer infrapopliteal endovascular procedures during their training. Eleven trainees (9%) performed 10 or fewer of both procedures. There was a positive correlation between number of infrapopliteal vein bypass and endovascular procedures performed (r = 0.19; P = .03). There was no difference between fellows and residents in the mean number of bypass operations performed during training (17.3 vs 19.1; P = .50; range, 0-53). However, residents performed more infrapopliteal endovascular procedures than fellows did (median, 29 vs 16; P = .03; range, 0-128).

Conclusions: More than one in four graduates of both training paradigms finish with a low number of infrapopliteal bypasses and endovascular interventions. The number of these procedures needed for proficiency is not known. Vascular surgery training programs should critically evaluate the number of infrapopliteal procedures required to achieve proficiency.
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http://dx.doi.org/10.1016/j.jvs.2018.01.054DOI Listing
November 2018

Identifying Complications and Optimizing Consultations following Transradial Arterial Access for Cardiac Procedures.

Ann Vasc Surg 2019 Apr 18;56:87-96. Epub 2018 Oct 18.

Division of Plastic and Reconstructive Surgery, University of Colorado School of Medicine, Aurora, CO. Electronic address:

Background: The radial approach to cardiac procedures has become increasingly common. Although previous studies have suggested a favorable risk profile, serious complications can occur. The purpose of this study is to examine the incidence, subsequent treatment, and outcome of all suspected significant neurovascular complications following transradial cardiac procedures at a large US hospital.

Methods: We reviewed all patients who underwent a left heart catheterization, coronary angiogram, or percutaneous coronary intervention via the transradial approach at a single large academic medical center in the United States between 2010 and 2016. Consultations to the vascular and hand surgery services were examined to assess demographic variables, risk factors, presenting symptoms, subsequent treatment, and outcome of all serious complications.

Results: A total of 9,681 radial access cardiac procedures were performed during the study period. Twenty-four cases (0.25%) were suspected to have major complications and subsequently received consults. A total of 18 complications were diagnosed, including 8 vascular injuries or perforations, 4 hematomas, 4 radial artery occlusions, 1 case of compartment syndrome, and 1 severe radial artery spasm. Of the complications noted, 3 (16.7%) required operative interventions, but all recovered neurovascular function.

Conclusions: Radial artery access for cardiac procedures has become increasingly common and has been associated with a low rate of major peripheral neurovascular complications. The majority (83.3%) of complications were successfully treated with a nonoperative management algorithm.
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http://dx.doi.org/10.1016/j.avsg.2018.07.064DOI Listing
April 2019

Platelet-targeted dual pathway antithrombotic inhibits thrombosis with preserved hemostasis.

JCI Insight 2018 08 9;3(15). Epub 2018 Aug 9.

Department of Surgery, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, Massachusetts, USA.

Despite advances in antithrombotic therapy, the risk of recurrent coronary/cerebrovascular ischemia or venous thromboembolism remains high. Dual pathway antithrombotic blockade, using both antiplatelet and anticoagulant therapy, offers the promise of improved thrombotic protection; however, widespread adoption remains tempered by substantial risk of major bleeding. Here, we report a dual pathway therapeutic capable of site-specific targeting to activated platelets and therapeutic enrichment at the site of thrombus growth to allow reduced dosing without compromised antithrombotic efficacy. We engineered a recombinant fusion protein, SCE5-TAP, which consists of a single-chain antibody (SCE5) that targets and blocks the activated GPIIb/IIIa complex, and tick anticoagulant peptide (TAP), a potent direct inhibitor of activated factor X (FXa). SCE5-TAP demonstrated selective platelet targeting and inhibition of thrombosis in murine models of both carotid artery and inferior vena cava thrombosis, without a significant impact on hemostasis. Selective targeting to activated platelets provides an attractive strategy to achieve high antithrombotic efficacy with reduced risk of bleeding complications.
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http://dx.doi.org/10.1172/jci.insight.99329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129120PMC
August 2018

Convergent Synthesis of Sialyl Lewis- O-Core-1 Threonine.

J Org Chem 2018 05 23;83(9):4963-4972. Epub 2018 Apr 23.

Department of Surgery, Center for Drug Discovery and Translational Research , Beth Israel Deaconess Medical Center, Harvard Medical School , 110 Francis Street, Suite 9F , Boston , Massachusetts 02215 , United States.

Selectins are a class of cell adhesion molecules that play a critical role during the initial steps of inflammation. The N-terminal domain of P-selectin glycoprotein ligand-1 (PSGL-1) binds to all selectins, but with the highest affinity to P-selectin. Recent evidence suggests that the blockade of P-selectin/PSGL-1 interactions provides a viable therapeutic option for the treatment of many inflammatory diseases. Herein, we report the total synthesis of threonine bearing sialyl Lewis (sLe) linked to a Core-1- O-hexasaccharide 1, as a key glycan of the N-terminal domain of PSGL-1. A convergent synthesis using α-selective sialylation and a regioselective [4+2] glycosylation are the key features of this synthesis.
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http://dx.doi.org/10.1021/acs.joc.7b03117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648531PMC
May 2018

Multisource Evaluation of Surgeon Behavior Is Associated With Malpractice Claims.

Ann Surg 2019 07;270(1):84-90

Ariadne Labs, Boston, MA.

Objective: We merged direct, multisource, and systematic assessments of surgeon behavior with malpractice claims, to analyze the relationship between surgeon 360-degree reviews and malpractice history.

Background: Previous work suggests that malpractice claims are associated with a poor physician-patient relationship, which is likely related to behaviors captured by 360-degree review. We hypothesize that 360-degree review results are associated with malpractice claims.

Methods: Surgeons from 4 academic medical centers covered by a common malpractice carrier underwent 360-degree review in 2012 to 2013 (n = 385). Matched, de-identified reviews and malpractice claims data were available for 264 surgeons from 2000 to 2015. We analyzed 23 questions, highlighting positive and negative behaviors within the domains of education, excellence, humility, openness, respect, service, and teamwork. Regression analysis with robust standard error was used to assess the potential association between 360-degree review results and malpractice claims.

Results: The range of claims among the 264 surgeons was 0 to 8, with 48.1% of surgeons having at least 1 claim. Multiple positive and negative behaviors were significantly associated with the risk of having malpractice claims (P < 0.05). Surgeons in the bottom decile for several items had an increased likelihood of having at least 1 claim.

Conclusion: Surgeon behavior, as assessed by 360-degree review, is associated with malpractice claims. These findings highlight the importance of teamwork and communication in exposure to malpractice. Although the nature of malpractice claims is complex and multifactorial, the identification and modification of negative physician behaviors may mitigate malpractice risk and ultimately result in the improved quality of patient care.
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http://dx.doi.org/10.1097/SLA.0000000000002742DOI Listing
July 2019

A Program for Promoting Clinical Scholarship in General Surgery.

J Surg Educ 2018 Jul - Aug;75(4):854-860. Epub 2018 Feb 3.

Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, Massachusetts. Electronic address:

Objective: The Accreditation Council for Graduate Medical Education mandates resident physician training in the principles and applications of research. To provide a robust early foundation for effective engagement in scholarship, we designed a novel clinical scholarship program (CSP) for PGY1 general surgery residents.

Setting, Design And Outcomes: In a general surgery residency training program, we assessed resident academic productivity (i.e., presentations, publications, and sustained engagement in clinical research) and self-efficacy to conduct clinical research, as well as the overall satisfaction of both residents and faculty mentors. The clinical research appraisal inventory was administered both before and after completion of the CSP rotation.

Results: Totally, 44 categorical general surgery trainees and 23 faculty research mentors participated in the CSP from 2011 to 2016; 26 residents (59%) presented at regional or national meetings. Of the 35 residents who were 24 or more months beyond their PGY1 training period, 16 (46%) have published their CSP project, 5 (14%) report continued commitment towards publication, and 22 (63%) have ≥1 clinical research publications beyond their CSP participation during residency, excluding publications arising from subsequent formal research fellowships. Clinical research appraisal inventory responses indicate significant improvement (p < 0.005) in clinical research self-efficacy.

Conclusions: A structured CSP increases the confidence of trainees to perform clinical research and leads to significant contributions directed at addressing clinically meaningful problems in surgery. Faculty-guided resident research at a very early stage of clinical training supplements other mentorship experiences and encourages the development of surgeons who will engage in life-long clinical problem solving.
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http://dx.doi.org/10.1016/j.jsurg.2018.01.001DOI Listing
August 2019

Isotopic labeling with cellular O-glycome reporter/amplification (ICORA) for comparative O-glycomics of cultured cells.

Glycobiology 2018 04;28(4):214-222

Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Mucin-type O-glycans decorate >80% of secretory and cell surface proteins and contribute to health and disease. However, dynamic alterations in the O-glycome are poorly understood because current O-glycomic methodologies are not sufficiently sensitive nor quantitative. Here we describe a novel isotope labeling approach termed Isotope-Cellular O-glycome Reporter Amplification (ICORA) to amplify and analyze the O-glycome from cells. In this approach, cells are incubated with Ac3GalNAc-Bn (Ac3GalNAc-[1H7]Bn) or a heavy labeled Ac3GalNAc-BnD7 (Ac3GalNAc-[2D7]Bn) O-glycan precursor (7 Da mass difference), which enters cells and upon de-esterification is modified by Golgi enzymes to generate Bn-O-glycans secreted into the culture media. After recovery, heavy and light Bn-O-glycans from two separate conditions are mixed, analyzed by MS, and statistically interrogated for changes in O-glycan abundance using a semi-automated approach. ICORA enables ~100-1000-fold enhanced sensitivity and increased throughput compared to traditional O-glycomics. We validated ICORA with model cell lines and used it to define alterations in the O-glycome in colorectal cancer. ICORA is a useful tool to explore the dynamic regulation of the O-glycome in health and disease.
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http://dx.doi.org/10.1093/glycob/cwy005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067123PMC
April 2018

The Society for Vascular Surgery practice guidelines on the care of patients with an abdominal aortic aneurysm.

J Vasc Surg 2018 01;67(1):2-77.e2

Department of Surgery, University of Washington, Seattle, Wash.

Background: Decision-making related to the care of patients with an abdominal aortic aneurysm (AAA) is complex. Aneurysms present with varying risks of rupture, and patient-specific factors influence anticipated life expectancy, operative risk, and need to intervene. Careful attention to the choice of operative strategy along with optimal treatment of medical comorbidities is critical to achieving excellent outcomes. Moreover, appropriate postoperative surveillance is necessary to minimize subsequent aneurysm-related death or morbidity.

Methods: The committee made specific practice recommendations using the Grading of Recommendations Assessment, Development, and Evaluation system. Three systematic reviews were conducted to support this guideline. Two focused on evaluating the best modalities and optimal frequency for surveillance after endovascular aneurysm repair (EVAR). A third focused on identifying the best available evidence on the diagnosis and management of AAA. Specific areas of focus included (1) general approach to the patient, (2) treatment of the patient with an AAA, (3) anesthetic considerations and perioperative management, (4) postoperative and long-term management, and (5) cost and economic considerations.

Results: Along with providing guidance regarding the management of patients throughout the continuum of care, we have revised a number of prior recommendations and addressed a number of new areas of significance. New guidelines are provided for the surveillance of patients with an AAA, including recommended surveillance imaging at 12-month intervals for patients with an AAA of 4.0 to 4.9 cm in diameter. We recommend endovascular repair as the preferred method of treatment for ruptured aneurysms. Incorporating knowledge gained through the Vascular Quality Initiative and other regional quality collaboratives, we suggest that the Vascular Quality Initiative mortality risk score be used for mutual decision-making with patients considering aneurysm repair. We also suggest that elective EVAR be limited to hospitals with a documented mortality and conversion rate to open surgical repair of 2% or less and that perform at least 10 EVAR cases each year. We also suggest that elective open aneurysm repair be limited to hospitals with a documented mortality of 5% or less and that perform at least 10 open aortic operations of any type each year. To encourage the development of effective systems of care that would lead to improved outcomes for those patients undergoing emergent repair, we suggest a door-to-intervention time of <90 minutes, based on a framework of 30-30-30 minutes, for the management of the patient with a ruptured aneurysm. We recommend treatment of type I and III endoleaks as well as of type II endoleaks with aneurysm expansion but recommend continued surveillance of type II endoleaks not associated with aneurysm expansion. Whereas antibiotic prophylaxis is recommended for patients with an aortic prosthesis before any dental procedure involving the manipulation of the gingival or periapical region of teeth or perforation of the oral mucosa, antibiotic prophylaxis is not recommended before respiratory tract procedures, gastrointestinal or genitourinary procedures, and dermatologic or musculoskeletal procedures unless the potential for infection exists or the patient is immunocompromised. Increased utilization of color duplex ultrasound is suggested for postoperative surveillance after EVAR in the absence of endoleak or aneurysm expansion.

Conclusions: Important new recommendations are provided for the care of patients with an AAA, including suggestions to improve mutual decision-making between the treating physician and the patients and their families as well as a number of new strategies to enhance perioperative outcomes for patients undergoing elective and emergent repair. Areas of uncertainty are highlighted that would benefit from further investigation in addition to existing limitations in diagnostic tests, pharmacologic agents, intraoperative tools, and devices.
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http://dx.doi.org/10.1016/j.jvs.2017.10.044DOI Listing
January 2018

Evaluation of a bioengineered construct for tissue engineering applications.

J Biomed Mater Res B Appl Biomater 2018 08 11;106(6):2345-2354. Epub 2017 Nov 11.

Department of Surgery, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215.

Effective biomaterial options for tissue repair and regeneration are limited. Current biologic meshes are derived from different tissue sources and are generally sold as decellularized tissues. This work evaluated two collagen based bioengineered constructs and a commercial product in a model of abdominal full thickness defect repair. To prepare the bioengineered construct, collagen type 1 from porcine skin was isolated using an acid solubilization method. After purification, the collagen was formed into collagen sheets that were physically bonded to form a mechanically robust construct that was subsequently laser micropatterned with pores as a means to promote tissue integration (collagen only construct). A second engineered construct consisted of the aforementioned collagen construct embedded in an RGD-functionalized alginate gel that serves as a bioactive interface (collagen-alginate construct). The commercial product is a biologic mesh derived from bovine pericardium (Veritas ). We observed enhanced vascularization in the midportion of the engineered collagen-alginate construct 2 weeks after implantation. Overall, the performance of the bioengineered constructs was similar to that of the commercial product with comparable integration strength at 8 weeks. Bioengineered constructs derived from monomeric collagen demonstrate promise for a variety of load bearing applications in tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2345-2354, 2018.
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http://dx.doi.org/10.1002/jbm.b.34042DOI Listing
August 2018