Publications by authors named "Christina Marcaccio"

9 Publications

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Epidemiology of abdominal aortic aneurysms.

Semin Vasc Surg 2021 Mar 6;34(1):29-37. Epub 2021 Feb 6.

Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, 110 Francis Street, Suite 5B, Boston, MA 02215. Electronic address:

Abdominal aortic aneurysm (AAA) disease remains a major source of morbidity in developed countries and can progress to life-threatening rupture if left untreated, with exceedingly high mortality. The goal of AAA management is to identify and electively repair AAAs before rupture. AAA disease burden and outcomes have improved over time with declining tobacco use and advancements in care across patients' disease course. The introduction of endovascular AAA repair, in particular, has allowed for elective AAA repair in patients previously considered too high risk for open surgery and has contributed to lower rates of AAA rupture over time. However, these improved outcomes are not universally experienced, and disparities continue to exist in the detection, treatment, and outcomes of AAA by sex, race, and ethnicity. Mitigating these disparities requires enhanced, focused efforts at preventing disease, promoting health, and delivering appropriate care among an increasingly diverse patient population.
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http://dx.doi.org/10.1053/j.semvascsurg.2021.02.004DOI Listing
March 2021

Racial Differences in Isolated Aortic, Concomitant Aortoiliac, and Isolated Iliac Aneurysms: This is a Retrospective Observational Study.

Ann Surg 2020 Dec 29. Epub 2020 Dec 29.

*The Divisions of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, MA †The Department of Vascular Surgery, University Medical Center, Utrecht, The Netherlands ‡The Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA §The Department of Surgery, Howard University and Hospital, Washington, D.C.

Objective: Our aim was to describe the racial and ethnic differences in presentation, baseline and operative characteristics, and outcomes after aortoiliac aneurysm repair.

Summary Of Background Data: Previous studies have demonstrated racial and ethnic differences in prevalence of abdominal aortic aneurysms and showed more complex iliac anatomy in Asian patients.

Methods: We identified all White, Black, Asian, and Hispanic patients undergoing aortoiliac aneurysm repair in the VQI from 2003 to 2019. We compared baseline comorbidities, operative characteristics, and perioperative outcomes by race and ethnicity.

Results: In our 60,435 patient cohort, Black patients, followed by Asian patients, were most likely to undergo repair for aortoiliac (W:23%, B:38%, A:31%, H:22%, P < 0.001) and isolated iliac aneurysms (W:1.0%, B:3.1%, A:1.5%, H:1.6%, P < 0.001), and White and Hispanic patients were most likely to undergo isolated aortic aneurysm repair (W:76%, B:59%, A:68%, H:76%, P < 0.001). Black patients were more likely to undergo symptomatic repair and underwent rupture repair at a smaller aortic diameter. The iliac aneurysm diameter was largest in Black and Asian patients. Asian patients were most likely to have aortic neck angulation above 60 degree, graft oversizing above 20%, and completion endoleaks. Also, Asian patients were more likely to have a hypogastric artery aneurysm and to undergo hypogastric coiling.

Conclusion: Asian and Black patients were more likely to undergo repair for aortoiliac and isolated iliac aneurysms compared to White and Hispanic patients who were more likely to undergo repair for isolated aortic aneurysms. Moreover, there were significant racial differences in the demographics and anatomic characteristics that could be used to inform operative approach and device development.
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http://dx.doi.org/10.1097/SLA.0000000000004731DOI Listing
December 2020

Epidemiology of Endovascular and Open Repair for Abdominal Aortic Aneurysms in the United States from 2004-2015 and Implications for Screening.

J Vasc Surg 2021 Feb 13. Epub 2021 Feb 13.

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

Introduction: Contemporary national trends in repair of ruptured abdominal aortic aneurysms and intact abdominal aortic aneurysms are relatively unknown. Furthermore, screening is only covered for patient's 65 to 75 years old with a family history or men with a smoking history. It is unclear what proportion of patients who present with a ruptured aneurysm would have been candidates for screening.

Methods: Using the National Inpatient Sample from 2004 to 2015, we identified rupture and intact AAA admissions and repairs based on International Classification of Diseases codes. We generated the screening eligible cohort using previously identified proportions of male smokers (87%) and all patients with a family history of aneurysm (10%) and applied these proportions to patients aged 65-75. We accounted for those who may have had a prior AAA diagnosis (17%) either from screening or incidental detection in patients over age 75 presenting with rupture. The primary outcomes were treatment and in-hospital mortality stratified by patients meeting criteria for screening versus those who did not.

Results: We evaluated 65,125 admissions for ruptured AAA and 461,191 repairs for intact AAA. Overall, an estimated 45,037 (68%) of patients admitted and 25,777 (59%) of patients undergoing repair for ruptured AAA did not meet criteria for screening. Of the patients who did not qualify; 27,653 (63%) were older than 75 years old; 10,603 (24%) were younger than 65 years old; and 16,103 (36%) were females. EVAR use increased for ruptured AAA from 10% in 2004 to 55% in 2015 (P<0.001) with an operative mortality of 35%, and for intact AAA from 45% in 2004 to 83% in 2015 (P<0.001) with an operative mortality of 2.0%.

Conclusions: The majority of patients who underwent repair for ruptured AAA did not qualify for screening. EVAR is the primary treatment for both ruptured AAA and intact AAA with a relatively low in-hospital mortality. Therefore, expansion of screening criteria to include selected women and a wider age range should be considered.
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http://dx.doi.org/10.1016/j.jvs.2021.01.044DOI Listing
February 2021

Validation of the Global Limb Anatomic Staging System in first-time lower extremity revascularization.

J Vasc Surg 2020 Oct 20. Epub 2020 Oct 20.

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

Objective: The Global Limb Anatomic Staging System (GLASS) was developed as a new anatomic classification scheme to grade the severity of chronic limb threatening ischemia. We evaluated the ability of this anatomic grading system to determine major adverse limb events after lower extremity revascularization.

Methods: We performed a single-institutional retrospective review of 1060 consecutive patients who had undergone 1180 first-time open or endovascular revascularization procedures for chronic limb threatening ischemia from 2005 to 2014. Using the review of angiographic images, the limbs were classified as GLASS stage 1, 2, or 3. The primary composite outcome was reintervention, major amputation (below- or above-the-knee amputation), and/or restenosis (>3.5× step-up by duplex criteria) events (RAS). The secondary outcomes included all-cause mortality, failure to cross the lesion by endovascular methods, and a comparison between bypass vs endovascular intervention. Kaplan-Meier estimates were used to determine the event rates at 1 and 5 years, and Cox regression analysis was used to adjust for baseline differences among the GLASS stages.

Results: Of all patients undergoing first-time revascularization, imaging studies were available for 1180 procedures (91%) for GLASS grading. Of these procedures, 552 were open bypass (47%) and 628 were endovascular intervention (53%). Compared with GLASS stage 1 disease (n = 267, 23%), stage 2 (n = 367; 31%) and stage 3 (n = 546; 42%) disease were associated with a greater risk of RAS at 1 year (stage 1, 33% vs stage 2, 48% vs stage 3, 53%) and 5 years (stage 1, 45% [reference]; stage 2, 65%; hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.3-2.2; P < .001; stage 3, 69%; HR, 2.3; 95% CI, 1.7-2.9; P < .001). These differences were mainly driven by reintervention and restenosis rather than by major amputation. The 5-year mortality was similar for stage 2 and 3 compared with stage 1 disease (stage 1, 40% [reference]; stage 2, 45%; HR, 1.1; 95% CI, 0.8-1.4; P = .69; stage 3, 49%; HR, 1.2; 95% CI, 1.0-1.6; P = .11). For all attempted endovascular interventions, failure to cross a target lesion increased with advancing GLASS stage (stage 1, 4.5% vs stage 2, 6.3% vs stage 3, 13.3%; P < .01). Compared with open bypass (n = 552; 46.8%), endovascular intervention (n = 628; 53.3%) was associated with a higher rate of 5-year RAS for GLASS stage 1 (49% vs 34%; HR, 1.9; 95% CI, [1.1-3.5; P = .03), stage 2 (69% vs 52%; HR, 1.7; 95% CI, 1.2-2.5; P < .01), and stage 3 (83% vs 61%; HR, 1.5; 95% CI, 1.2-2.0; P < .01) disease.

Conclusions: For patients undergoing first-time lower extremity revascularization, the GLASS can be used to predict for reintervention and restenosis. Bypass resulted in better long-term outcomes compared with endovascular intervention for all GLASS stages.
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http://dx.doi.org/10.1016/j.jvs.2020.08.151DOI Listing
October 2020

Attitudes and Habits of Highly Humanistic Surgeons: A Single-Institution, Mixed-Methods Study.

Acad Med 2019 07;94(7):1027-1032

R.A. Swendiman is a general surgery resident, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. C.L. Marcaccio is a vascular surgery resident, Beth Israel Deaconess Medical Center, Boston, Massachusetts. J. Han is a cardiothoracic surgery resident, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. D.I. Hoffman is a medical student, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. T.M. Weiner is a pediatric surgeon, New Hanover Regional Medical Center, Wilmington, North Carolina, and adjunct professor of surgery, University of North Carolina School of Medicine, Chapel Hill, North Carolina. M.L. Nance is Josephine J. and John M. Templeton Jr. Endowed Chair in Pediatric Trauma, Children's Hospital of Philadelphia, and professor of pediatric surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. C.M. Chou is associate professor of clinical medicine, Department of Medicine, Division of General Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.

Purpose: Humanism in medicine is associated with increased patient satisfaction, trust of patients in their doctors, and better outcomes. The authors sought to identify attitudes, habits, and other factors that sustain humanism in academic surgical faculty, and compare these with attributes determined from a previous study of internal medicine faculty.

Method: A mixed-methods study design at University of Pennsylvania Health System was employed from 2016 to 2018 using a survey instrument and semistructured interviews. Surgical residents nominated faculty who exemplified humanism. In-depth interviews were then conducted with surgeons receiving the most nominations. The interviews were transcribed, and common themes were identified using the grounded theory method. These were compared with findings from a previous internal medicine study.

Results: Ten faculty described three strongly shared attitudes: humility, responsibility, and a desire to live up to a high standard of professional behavior. Five habits were found important to sustaining these attitudes and their practice: self-reflection, finding deep connections with patients, maintaining personal and professional relationships, "having fun" at work, and paying it forward to surgical trainees. Surgeons also cited the importance of past role models in developing humanistic attitudes and sustaining practice. Responses were compared with previously documented attitudes and habits of humanistic internal medicine faculty at the institution.

Conclusions: This study identified recurring attitudes and habits that characterize humanistic behaviors in a cohort of academic surgeons. Learning from these exemplary humanistic surgeons may inform the development of future educational programs for residents and faculty in sustaining humanism.
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http://dx.doi.org/10.1097/ACM.0000000000002690DOI Listing
July 2019

Delayed endovascular aortic repair is associated with reduced in-hospital mortality in patients with blunt thoracic aortic injury.

J Vasc Surg 2018 07 13;68(1):64-73. Epub 2018 Feb 13.

Division of Traumatology, Surgical Critical Care and Emergency Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pa; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa. Electronic address:

Objective: The traditional approach to stable blunt thoracic aortic injury (BTAI) endorsed by the Society for Vascular Surgery is early (<24 hours) thoracic endovascular aortic repair (TEVAR). Recently, some studies have shown improved mortality in stable BTAI patients repaired in a delayed manner (≥24 hours). However, the indications for use of delayed TEVAR for BTAI are not well characterized, and its overall impact on the patient's survival remains poorly understood. We sought to determine whether delayed TEVAR is associated with a decrease in mortality compared with early TEVAR in this population.

Methods: We conducted a retrospective cohort study of adult patients with BTAI (International Classification of Diseases, Ninth Revision diagnosis code 901.0) who underwent TEVAR (International Classification of Diseases, Ninth Revision procedure code 39.73) from 2009 to 2013 using the National Sample Program data set. Missing physiologic data were imputed using chained multiple imputation. Patients were parsed into groups based on the timing of TEVAR (early, <24 hours, vs delayed, ≥24 hours). The χ, Mann-Whitney, and Fisher exact tests were used to compare baseline characteristics and outcomes of interest between groups. Multivariable logistic regression for mortality was performed that included all variables significant at P ≤ .2 in univariate analyses.

Results: A total of 2045 adult patients with BTAI were identified, of whom 534 (26%) underwent TEVAR. Patients with missing data on TEVAR timing were excluded (n = 27), leaving a total of 507 patients for analysis (75% male; 69% white; median age, 40 years [interquartile range, 27-56 years]; median Injury Severity Score [ISS], 34 [interquartile range, 26-41]). Of these, 378 patients underwent early TEVAR and 129 underwent delayed TEVAR. The two groups were similar with regard to age, sex, race, ISS, and presenting physiology. Mortality was 11.9% in the early TEVAR group vs 5.4% in the delayed group, with the early group displaying a higher odds of death (odds ratio, 2.36; 95% confidence interval, 1.03-5.36; P = .042). After adjustment for age, ISS, and admission physiology, the association between early TEVAR and mortality was preserved (adjusted odds ratio, 2.39; 95% confidence interval, 1.01-5.67; P = .047).

Conclusions: Consistent with current Society for Vascular Surgery recommendations, more BTAI patients underwent early TEVAR than delayed TEVAR during the study period. However, delayed TEVAR was associated with significantly reduced mortality in this population. Together, these findings support a need for critical appraisal and clarification of existing practice guidelines in management of BTAI. Future studies should seek to understand this survival disparity and to determine optimal selection of patients for early vs delayed TEVAR.
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http://dx.doi.org/10.1016/j.jvs.2017.10.084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019106PMC
July 2018

Olfactory sensory axons target specific protoglomeruli in the olfactory bulb of zebrafish.

Neural Dev 2017 Oct 11;12(1):18. Epub 2017 Oct 11.

Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.

Background: The axons of Olfactory Sensory Neurons (OSNs) project to reproducible target locations within the Olfactory Bulb (OB), converting odorant experience into a spatial map of neural activity. We characterized the initial targeting of OSN axons in the zebrafish, a model system suitable for studying axonal targeting early in development. In this system the initial targets of OSN axons are a small number of distinct, individually identifiable neuropilar regions called protoglomeruli. Previously, Olfactory Marker Protein-expressing and TRPC2-expressing classes of OSNs were shown to project to specific, non-overlapping sets of protoglomeruli, indicating that particular subsets of OSNs project to specific protoglomerular targets. We set out to map the relationship between the classical Odorant Receptor (OR) an OSN chooses to express and the protoglomerulus its axon targets.

Methods: A panel of BACs were recombineered so that the axons of OSNs choosing to express modified ORs were fluorescently labeled. Axon projections were followed into the olfactory bulb to determine the protoglomeruli in which they terminated.

Results: RNA-seq demonstrates that OSNs express a surprisingly wide variety of ORs and Trace Amine Associated Receptors (TAARs) very early when sensory axons are arriving in the bulb. Only a single OR is expressed in any given OSN even at these early developmental times. We used a BAC expression technique to map the trajectories of OSNs expressing specific odorant receptors. ORs can be divided into three clades based upon their sequence similarities. OSNs expressing ORs from two of these clades project to the CZ protoglomerulus, while OSNs expressing ORs from the third clade project to the DZ protoglomerulus. In contrast, OSNs expressing a particular TAAR project to multiple protoglomeruli. Neither OR choice nor axonal targeting are related to the position an OSN occupies within the olfactory pit.

Conclusions: Our results demonstrate that it is not the choice of a particular OR, but of one from a category of ORs, that is related to initial OSN target location within the olfactory bulb. These choices are not related to OSN position within the olfactory epithelium.
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http://dx.doi.org/10.1186/s13064-017-0095-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637265PMC
October 2017

Attractant and repellent cues cooperate in guiding a subset of olfactory sensory axons to a well-defined protoglomerular target.

Development 2016 Jan;143(1):123-32

Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA

Olfactory sensory axons target well-defined intermediate targets in the zebrafish olfactory bulb called protoglomeruli well before they form odorant receptor-specific glomeruli. A subset of olfactory sensory neurons are labeled by expression of the or111-7:IRES:GAL4 transgene whose axons terminate in the central zone (CZ) protoglomerulus. Previous work has shown that some of these axons misproject to the more dorsal and anterior dorsal zone (DZ) protoglomerulus in the absence of Netrin 1/Dcc signaling. In search of additional cues that guide these axons to the CZ, we found that Semaphorin 3D (Sema3D) is expressed in the anterior bulb and acts as a repellent that pushes them towards the CZ. Further analysis indicates that Sema3D signaling is mediated through Nrp1a, while Nrp2b also promotes CZ targeting but in a Sema3D-independent manner. nrp1a, nrp2b and dcc transcripts are detected in or111-7 transgene-expressing neurons early in development and both Nrp1a and Dcc act cell-autonomously in sensory neurons to promote accurate targeting to the CZ. dcc and nrp1a double mutants have significantly more DZ misprojections than either single mutant, suggesting that the two signaling systems act independently and in parallel to direct a specific subset of sensory axons to their initial protoglomerular target.
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http://dx.doi.org/10.1242/dev.127985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4725209PMC
January 2016

Netrin/DCC signaling guides olfactory sensory axons to their correct location in the olfactory bulb.

J Neurosci 2012 Mar;32(13):4440-56

Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Olfactory sensory neurons expressing particular olfactory receptors project to specific reproducible locations within the bulb. The axonal guidance cues that organize this precise projection pattern are only beginning to be identified. To aid in their identification and characterization, we generated a transgenic zebrafish line, OR111-7:IRES:Gal4, in which a small subset of olfactory sensory neurons is labeled. Most sensory neurons expressing the OR111-7 transgene project to a specific location within the bulb, the central zone protoglomerulus, while a smaller number project to the lateral glomerulus 1 protoglomerulus. Inhibiting Netrin/DCC (deleted in colorectal cancer) signaling perturbs the ability of OR111-7-expressing axons to enter the olfactory bulb and alters their patterns of termination within the bulb. The Netrin receptor DCC is expressed in olfactory sensory neurons around the time that they elaborate their axons, netrin1a is expressed near the medial-most margin of the olfactory bulb, and netrin1b is expressed within the ventral region of the bulb. Loss of Netrin/DCC signaling components causes some OR111-7-expressing sensory axons to wander posteriorly after exiting the olfactory pit, away from netrin-expressing areas in the bulb. OR111-7-expressing axons that enter the bulb target the central zone less precisely than normal, spreading away from netrin-expressing regions. These pathfinding errors can be corrected by the reexpression of DCC within OR111-7 transgene-expressing neurons in DCC morphant embryos. These findings implicate Netrins as the only known attractants for olfactory sensory neurons, first drawing OR111-7-expressing axons into the bulb and then into the ventromedially positioned central zone protoglomerulus.
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http://dx.doi.org/10.1523/JNEUROSCI.4442-11.2012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356094PMC
March 2012