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Objective: Although multidisciplinary clinics improve outcomes in chronic limb-threatening ischemia (CLTI), their role in addressing socioeconomic disparities is unknown. Our institution treats patients with CLTI at both traditional general vascular clinics and a multidisciplinary Limb Preservation Program (LPP). The LPP is in a minority community, providing expedited care at a single facility by a consistent team. We compared outcomes within the LPP with our institution's traditional clinics and explored patients' perspectives on barriers to care to evaluate if the LPP might address them., Methods: All patients undergoing index revascularization for CLTI from 2014 to 2023 at our institution were stratified by clinic type (LPP or traditional). We collected clinical and socioeconomic variables, including Area Deprivation Index (ADI). Patient characteristics were compared using χ 2 , Student t, or Mood median tests. Outcomes were compared using log-rank and multivariable Cox analysis. We also conducted semi-structured interviews to understand patient-perceived barriers., Results: From 2014 to 2023, 983 limbs from 871 patients were revascularized; 19.5% of limbs were treated within the LPP. Compared with traditional clinic patients, more LPP patients were non-White (43.75% vs 27.43%; P < .0001), diabetic (82.29% vs 61.19%; P < .0001), dialysis-dependent (29.17% vs 13.40%; P < .0001), had ADI in the most deprived decile (29.38% vs 19.54%; P = .0061), resided closer to clinic (median 6.73 vs 28.84 miles; P = .0120), and had worse Wound, Ischemia, and foot Infection (WIfI) stage (P < .001). There were no differences in freedom from death, major adverse limb event (MALE), or patency loss. Within the most deprived subgroup (ADI >90), traditional clinic patients had earlier patency loss (P = .0108) compared with LPP patients. Multivariable analysis of the entire cohort demonstrated that increasing age, heart failure, dialysis, chronic obstructive pulmonary disease, and increasing WIfI stage were independently associated with earlier death, and male sex was associated with earlier MALE. Ten traditional clinic patients were interviewed via convenience sampling. Emerging themes included difficulty understanding their disease, high visit frequency, transportation barriers, distrust of the health care system, and patient-physician racial discordance., Conclusions: LPP patients had worse comorbidities and socioeconomic deprivation yet had similar outcomes to healthier, less deprived non-LPP patients. The multidisciplinary clinic's structure addresses several patient-perceived barriers. Its proximity to disadvantaged patients and ability to conduct multiple appointments at a single visit may address transportation and visit frequency barriers, and the consistent team may facilitate patient education and improve trust. Including these elements in a multidisciplinary clinic and locating it in an area of need may mitigate some negative impacts of socioeconomic deprivation on CLTI outcomes., Competing Interests: Disclosures None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Operative coaching (OC) may facilitate improvement of surgery residents' competencies by optimizing learning and teaching. We investigated how residents' operative skills and prospective entrustment (PE) progress throughout the chief year in our OC program, how OC is perceived by participants, and how OC may facilitate learning and teaching., Design, Setting, and Participants: This is a mixed-methods study conducted within the Ohio State University Wexner Medical Center General Surgery residency. Validated performance evaluations with procedural-specific skill, general skill (GS), step-specific guidance required (SSG) (an autonomy measure), and PE measures completed by chiefs, faculty coaches, and attending surgeons from 7/2018 to 6/2022 were reviewed. We also interviewed OC participants to understand their experience. Descriptive statistical and qualitative content analysis were applied., Results: 441 evaluations from 147 OC cases completed by 22 chiefs, 5 faculty coaches, and 24 attendings were included. Overall, resident GS (p = 0.036), SSG (p = 0.023), and PE (p = 0.002) significantly improved throughout the year. PE significantly correlated (all p < 0.0001) with SSG (r = 0.73), followed by procedural-specific skill (r = 0.59), then GS (r = 0.57). On average, chiefs underestimated their surgical skills while attendings overestimated autonomy they permitted to residents. Chiefs, coaches, and attendings reached consensus on chiefs' PE upon graduation. Five graduated chiefs and 5 attendings were interviewed. Chiefs described OC as effective in improving their self-regulated learning and particularly valued 3 OC elements: neutral authentic feedback, third-party real-time observation, and actionable feedback. Attendings noted OC promoted their engagement in skills assessment and teaching., Conclusions: Our findings suggest chief residents' skills, autonomy, and PE progress steadily along their OC journey. Despite differences in residents', coaches', and attendings' perceptions of skill, measures of autonomy reliably correlate with entrustment. OC promotes resident learning, faculty teaching, and assessment of resident skills, autonomy, and PE in the OR., (Copyright © 2023 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: The prevalence of chronic limb-threatening ischemia (CLTI) has increased alongside rising rates of diabetes mellitus (DM). While diabetic patients with CLTI have worse outcomes compared to patients without diabetes, conflicting data exist on the relationship between the severity of DM and CLTI outcomes. Close inspection of the relationship between DM severity and outcomes in CLTI may benefit surgical decision-making and patient education., Methods: We retrospectively reviewed patients who received endovascular intervention or surgical bypass for CLTI at our multidisciplinary Limb Preservation Program from 2013 to 2019 to collect patient characteristics using Society for Vascular Surgery (SVS) reporting standards, arterial lesion characteristics from recorded angiograms, and outcomes, including survival, amputation, wound healing, and revascularization patency. Controlled DM was defined as SVS Grade 1 (controlled, not requiring insulin) and Grade 2 (controlled, requiring insulin), while uncontrolled DM was defined as SVS Grade 3 (uncontrolled), and DM severity was assessed using preoperative hemoglobin A1c (HgbA1c) values. Product-limit Kaplan-Meier was used to estimate survival functions. Univariable Cox proportional hazards analyses guided variable selection for multivariable analyses., Results: Our Limb Preservation Program treated 177 limbs from 141 patients with DM. Patients with uncontrolled DM were younger (60.44 ± 10.67 vs. 65.93 ± 10.89 years old, P = 0.0009) and had higher HgbA1c values (8.97 ± 1.85% vs. 6.79 ± 1.10%, P < 0.0001). Fewer patients with uncontrolled DM were on dialysis compared to patients with controlled DM (15.6% vs. 30.9%, P = 0.0278). By Kaplan-Meier analysis, DM control did not affect time to mortality, limb salvage, wound healing, or loss of patency. However, multivariable proportional hazards analysis demonstrated increased risk of limb loss in patients with increasing HgbA1C (hazard ratio (HR) = 1.96 [1.42-2.80], P < 0.0001) or dialysis dependence (HR = 15.37 [3.44-68.73], P = 0.0003), increased risk of death in patients with worsening pulmonary status (HR = 1.70 [1.20-2.39], P = 0.0026), and increased risk of delayed wound healing in patients who are male (HR = 0.48 [0.29-0.79], P = 0.0495). No independent association existed between loss of patency with any of the variables we collected., Conclusions: Patients with uncontrolled DM, as defined by SVS reporting standards, do not have worse outcomes following revascularization for CLTI compared to patients with controlled DM. However, increasing HgbA1c is associated with a greater risk for early amputation. Before revascularization, specific attention to the level of glycemic control in patients with DM is important, even if DM is "controlled." In addition to aggressive attempts at improved glycemic control, those with elevated HgbA1c should receive careful education regarding their increased risk of amputation despite revascularization. Future work is necessary to incorporate the severity of DM into risk models of revascularization for the CLTI population., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Perfusion deficits contribute to symptom severity, morbidity, and death in peripheral artery disease (PAD); however, no standard method for quantifying absolute measures of skeletal muscle perfusion exists. This study sought to preclinically test and clinically translate a positron emission tomography (PET) imaging approach using an atherosclerosis-targeted radionuclide, fluorine-18-sodium fluoride ( 18 F-NaF), to quantify absolute perfusion in PAD., Methods and Results: Eight Yorkshire pigs underwent unilateral femoral artery ligation and dynamic 18 F-NaF PET/computed tomography imaging on the day of and 2 weeks after occlusion. Following 2-week imaging, calf muscles were harvested to quantify microvascular density. PET methodology was validated with microspheres in 4 additional pig studies and translated to patients with PAD (n=39) to quantify differences in calf perfusion across clinical symptoms/stages and perfusion responses in a case of revascularization. Associations between PET perfusion, ankle-brachial index, toe-brachial index, and toe pressure were assessed in relation to symptoms. 18 F-NaF PET/computed tomography quantified significant deficits in calf perfusion in pigs following arterial occlusion and perfusion recovery 2 weeks after occlusion that coincided with increased muscle microvascular density. Additional studies confirmed that PET-derived perfusion measures agreed with microsphere-derived perfusion measures. Translation of imaging methods demonstrated significant decreases in calf perfusion with increasing severity of PAD and quantified perfusion responses to revascularization. Perfusion measures were also significantly associated with symptom severity, whereas traditional hemodynamic measures were not., Conclusions: 18 F-NaF PET imaging quantifies perfusion deficits that correspond to clinical stages of PAD and represents a novel perfusion imaging strategy that could be partnered with atherosclerosis-targeted 18 F-NaF PET imaging using a single radioisotope injection., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03622359.

Objective: Peripheral artery disease (PAD) is associated with increased risk of nonhealing ulcers, amputation, and mortality due to occlusive atherosclerotic plaques. Computed tomography (CT) imaging detects vascular calcification in PAD; however, quantitative vessel-by-vessel analysis of calcium burden in the feet of PAD patients has not been assessed. This study sought to perform quantitative analysis of vessel-specific calcium burden and examine the patient-level determinants of foot calcium burden in PAD patients. Approach: PAD patients ( n  = 41) were prospectively enrolled and underwent CT imaging of the lower extremities. Manual segmentation of the medial plantar, lateral plantar, and dorsalis pedis arteries was performed. CT image Hounsfield units (HUs) were obtained for each artery to quantify vessel-by-vessel calcium mass using a cutoff value of ≥130 HU. Univariate analyses were performed to evaluate patient-level determinants of calcium burden for each foot artery. STROBE guidelines were used for reporting of data. Results: Univariate analyses revealed that body mass index, diabetes mellitus (DM), and chronic kidney disease (CKD) were significant determinants of foot calcium burden in PAD patients. Image analysis demonstrated that PAD patients with DM had significantly higher calcium mass for the medial plantar ( p  = 0.005), lateral plantar ( p  = 0.039), and dorsalis pedis ( p  = 0.001) arteries compared with PAD patients without DM. Innovation: This is the first study to use CT imaging to quantify vessel-specific calcium burden in the feet of patients with PAD and evaluate the patient-level determinants of foot calcium burden in the setting of PAD. Conclusion: CT imaging quantifies vessel-specific calcification in the feet of PAD patients, which is exacerbated with concomitant DM, CKD, and/or obesity.

Objectives: The treatment for chronic limb-threatening ischemia (CLTI) has changed dramatically in the last few decades with a shift toward an endovascular-first approach and aggressive revascularization to achieve limb salvage. As the size of the CLTI population and intervention rates increase, patients will continue to experience technical failure (TF). Here, we describe the natural history of patients after TF of endovascular intervention for CLTI., Methods: We conducted a retrospective cohort study of patients with CLTI who attempted endovascular intervention or bypass at our multidisciplinary limb salvage center from 2013 to 2019. Patient characteristics were collected according to the Society for Vascular Surgery's reporting standards. Primary outcomes included survival, limb salvage, wound healing, and revascularization patency. Product-limit Kaplan-Meier estimated survival functions for these outcomes, and between-group comparisons were made using Mantel-Cox log-rank nonparametric tests., Results: We identified 242 limbs from 220 unique patients who underwent primary bypass (n = 30) or attempted endovascular intervention (n = 212) at our limb salvage center. Endovascular intervention was a TF in 31 (14.6%) limbs. After TF, 13 limbs underwent secondary bypass and 18 limbs were managed medically. Patients who experienced TF tended to be older (P < .001), male (P = .003), current tobacco users (P = .014), have longer lesions (P = .001), and have chronic total occlusions of target arteries (P < .001) as compared with those who experienced technical success. Furthermore, the TF group had worse limb salvage (P = .047) and slower wound healing (P = .028), but their survival was not different. Survival, limb salvage, and wound healing were not different in patients who received secondary bypass or medical management after TF. The secondary bypass group was older (P = .012) and had a lower prevalence of tibial disease (P = .049) than the primary bypass group and trended toward decreased survival, limb salvage, and wound healing (P = .059, P = .083, and P = .051, respectively)., Conclusions: Increased age, male sex, current tobacco use, longer arterial lesions, and occluded target arteries are associated with TF of endovascular intervention. Limb salvage and wound healing are relatively poor after TF of endovascular intervention, but survival appears comparable with patients who experience technical success. Secondary bypass may not always rescue patients after TF, though our sample size limits statistical power. Interestingly, patients who received a secondary bypass after TF trended toward decreased survival, limb salvage, and wound healing compared with primary bypass., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Positron emission tomography (PET)/computed tomography (CT) imaging with fluorine-18 ( 18 F)-sodium fluoride (NaF) provides assessment of active vascular microcalcification, but its utility for evaluating diabetes mellitus (DM)- and chronic kidney disease (CKD)-induced atherosclerosis in peripheral arterial disease (PAD) has not been comprehensively evaluated. This study sought to use 18 F-NaF PET/CT to quantify and compare active microcalcification on an artery-by-artery basis in healthy subjects, PAD patients with or without DM, and PAD patients with or without CKD. Additionally, we evaluated the contributions of DM, CKD, statin use and established CT-detectable calcium to 18 F-NaF uptake for each lower extremity artery., Methods: PAD patients (n = 48) and healthy controls (n = 8) underwent lower extremity 18 F-NaF PET/CT imaging. Fused PET/CT images guided segmentation of arteries of interest (i.e., femoral-popliteal, anterior tibial, tibioperoneal trunk, posterior tibial, and peroneal) and quantification of 18 F-NaF uptake. 18 F-NaF uptake was assessed for each artery and compared between subject groups. Additionally, established calcium burden was quantified for each artery using CT calcium mass score. Univariate and multivariate analyses were performed to evaluate DM, CKD, statin use, and CT calcium mass as predictors of 18 F-NaF uptake in PAD., Results: PAD patients with DM or CKD demonstrated significantly higher active microcalcification (i.e., 18 F-NaF uptake) for all arteries when compared to PAD patients without DM or CKD. Univariate and multivariate analyses revealed that concomitant DM or CKD was associated with increased microcalcification for all arteries of interest and this increased disease risk remained significant after adjusting for patient age, sex, and body mass index. Statin use was only associated with decreased microcalcification for the femoral-popliteal artery in multivariate analyses. Established CT-detectable calcium was not significantly associated with 18 F-NaF uptake for 4 out of 5 arteries of interest., Conclusions: 18 F-NaF PET/CT imaging quantifies vessel-specific active microcalcification in PAD that is increased in multiple lower extremity arteries by DM and CKD and decreased in the femoral-popliteal artery by statin use. 18 F-NaF PET imaging is complementary to and largely independent of established CT-detectable arterial calcification. 18 F-NaF PET/CT imaging may provide an approach for non-invasively quantifying vessel-specific responses to emerging anti-atherogenic therapies or CKD treatment in patients with PAD., (© 2023. The Author(s).)

Background: This study aimed to determine if conventional extra-anatomic bypass and graft removal versus aggressive attempts at graft preservation have better survival and limb salvage in patients with localized groin wound infections of vascular grafts., Methods: We conducted a retrospective review of 53 consecutive patients with vascular graft infections presenting in the groin. Treatment groups consisted of group 1 (extra-anatomic bypass and graft excision, n = 22) and group 2 (initial graft preservation attempts with utilization of antibiotic beads, n = 31). In group 2, patients underwent serial debridement and placement of antibiotic beads until culture-negative wounds were achieved. Significantly more patients underwent muscle flap coverage in group 2 (27/31) compared with group 1 (7/22; P < 0.001). Data collected included demographics, comorbidities, intraoperative details, and outcomes, including patency, limb salvage, mortality, and number of procedures. Continuous variables were examined with Student's t-test, and dichotomous variables were examined with chi-squared test. Linear and logistic regressions were used to analyze factors associated with outcomes, in addition to Kaplan-Meier analysis with log rank for actuarial analysis., Results: Both groups were similar with respect to demographics. The overall Kaplan-Meier 1- and 3-year survival rates were 66.2% and 34.1%, with no statistically significant difference between groups. The Kaplan-Meier 1- and 3-year limb salvage rates were 68.8% and 36.6% for group 1 vs. 58.5% and 38.7% for group 2 (P = not significant [NS]). The 1- and 3-year primary patency rates were 71% and 71% in traditional group 1 vs. 72% and 56% in group 2 (P = NS). One-year and 3-year secondary patency rates in traditional group 1 were 83% and 71% vs. 85% and 61% in group 2 (P = NS). Patients in group 1 underwent fewer total procedures when compared with group 2 (2.3 ± 0.2 vs. 5.1 ± 0.7, P = 0.03). The late reinfection rate was significantly less in group 1 (4.5%) compared with group 2 (26%; P = 0.04). Freedom from reinfection at 1 and 3 years were 94% and 94% in traditional group 1 vs. 74% and 62% in group 2 (P = 0.03). Multivariable analysis showed a higher incidence of amputation in patients who suffered reinfection (n = 13, P = 0.049). There was a higher mortality in patients with septic shock (n = 10, P = 0.007) and reinfection (n = 13, P = 0.036). Reinfection was associated with the highest mortality (P = 0.03)., Conclusions: Conventional graft excision with extra-anatomic bypass resulted in similar mortality when compared with aggressive attempts at graft preservation and trended toward improved limb salvage and patency. However, attempts at graft preservation with antibiotic beads resulted in a significantly higher reinfection rate and greater number of procedures, and therefore, this approach should be used very selectively., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: One strategy to address the impending shortage of vascular surgeons is to augment interest in the trainee pipeline. Endovascular procedures are unique to vascular surgery (VS) and endovascular simulations have proven effective at generating VS interest in the past. Like endovascular techniques, the use of ultrasound (US) testing in VS is unique among medical specialties. We hypothesized that an interactive US demonstration would increase VS interest in preclinical medical students., Methods: We created a 5-point Likert scale survey assessing interest in VS, understanding of VS, likelihood to further investigate VS, choosing VS as a rotational elective, and pursuing VS shadowing and research opportunities. This survey was administered 1 day before and 1 day after the demonstration. Results were compared via paired t-test. A VS attending assisted by a senior registered vascular technologist covered physics, B-mode, continuous, pulsed wave, and color Doppler in an interactive, hands-on experience. Our dedicated US simulation laboratory enabled simultaneous interactive virtual broadcast and in-person learning. All first-year and second-year students at our medical school were invited via e-mail., Results: Five hundred twelve students were invited, 39 attended, and 19 students who completed surveys were included. Sixty eight percent were female. Attendance at the US demonstration resulted in a significant increase in students' interest in vascular surgery (P = 0.012), understanding of vascular surgery (P < 0.001), likelihood to further investigate vascular surgery (P < 0.001), likelihood to choose a vascular surgery rotation (P < 0.001), and likelihood to pursue vascular surgery shadowing and research opportunities (P < 0.001). Although only 2 of 6 in-person attendees returned surveys, their increase in average response to all questions was higher than virtual attendees (+1.80 vs. +0.91, P = 0.043)., Conclusions: Attending an interactive US demonstration significantly increased preclinical medical students' interest in understanding of VS. In-person and virtual attendance both had a positive impact. Such a demonstration may be an effective tool to recruit students. It is imperative that we continue innovating to address the future shortage of vascular surgeons., (Published by Elsevier Inc.)

Objective: The optimal revascularization modality following complete resection of aortic graft infection (AGI) without enteric involvement remains unclear. The purpose of this investigation is to determine the revascularization approach associated with the lowest morbidity and mortality using real-world data in patients undergoing complete excision of AGI., Methods: A retrospective, multi-institutional study of AGI from 2002 to 2014 was performed using a standardized database. Baseline demographics, comorbidities, and perioperative variables were recorded. The primary outcome was infection-free survival. Descriptive statistics, Kaplan-Meier survival analysis, and univariate and multivariable analyses were performed., Results: A total of 241 patients at 34 institutions from seven countries presented with AGI during the study period (median age, 68 years; 75% male). The initial aortic procedures that resulted in AGI were 172 surgical grafts (71%), 66 endografts (27%), and three unknown (2%). Of the patients, 172 (71%) underwent complete excision of infected aortic graft material followed by in situ (in-line) bypass (ISB), including antibiotic-treated prosthetic graft (35%), autogenous femoral vein (neo-aortoiliac surgery) (24%), and cryopreserved allograft (41%). Sixty-nine patients (29%) underwent extra-anatomic bypass (EAB). Overall median Kaplan-Meier estimated survival was 5.8 years. Perioperative mortality was 16%. When stratified by ISB vs EAB, there was a significant difference in Kaplan-Meier estimated infection-free survival (2910 days; interquartile range, 391-3771 days vs 180 days; interquartile range, 27-3750 days; P < .001). There were otherwise no significant differences in presentation, comorbidities, or perioperative variables. Multivariable Cox regression showed lower infection-free survival among patients with EAB (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.6-3.6; P < .001), polymicrobial infection (HR, 2.2; 95% CI, 1.4-3.5; P = .001), methicillin-resistant Staphylococcus aureus infection (HR, 1.7; 95% CI, 1.1-2.7; P = .02), as well as the protective effect of omental/muscle flap coverage (HR, 0.59; 95% CI, 0.37-0.92; P = .02)., Conclusions: After complete resection of AGI, perioperative mortality is 16% and median overall survival is 5.8 years. EAB is associated with nearly a two and one-half-fold higher reinfection/mortality compared with ISB. Omental and/or muscle flap coverage of the repair appear protective., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Charcot neuropathic osteoarthropathy (CN) is a serious and potentially limb-threatening complication for patients with diabetes mellitus and peripheral arterial disease. In recent decades, nuclear medicine-based approaches have been used for non-invasive detection of CN; however, to date, a positron emission tomography (PET) radionuclide specifically focused on targeted imaging of active bone remodeling has not been explored or validated for patients with CN. The radionuclide 18 F-sodium fluoride (NaF) has historically been used as a bone imaging probe due to its high sensitivity for targeting hydroxyapatite and bone turnover, but has not been applied in the context of CN. Therefore, the present study focused on novel application of 18 F-NaF PET/computed tomography (CT) imaging to three clinical cases of CN to evaluate active bone remodeling at various time courses of CN. PET/CT imaging in all 3 cases demonstrated focal uptake of 18 F-NaF in the bones of the feet afflicted with CN, with bone retention of 18 F-NaF persisting for up to 5 years following surgical reconstruction of the foot in two cases. On a group level, 18 F-NaF bone uptake in the CN foot was significantly higher compared to the healthy, non-CN foot ( p = 0.039). 18 F-NaF PET/CT imaging may provide a non-invasive tool for monitoring active bone remodeling in the setting of CN, thereby offering novel opportunities for tracking disease progression and improving treatment and surgical intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tram, Chou, Patel, Ettefagh, Go, Atway and Stacy.)

Background: Platelet adhesion to the subendothelial collagen fibrils is one of the first steps in hemostasis. Understanding how structural perturbations in the collagen fibril affect platelet adhesion can provide novel insights into disruption of hemostasis in various diseases. We have recently identified the presence of abnormal collagen fibrils with compromised D-periodic banding in the extracellular matrix remodeling present in abdominal aortic aneurysms (AAA)., Objective: In this study, we employed multimodal microscopy approaches to characterize how collagen fibril structure impacts platelet adhesion in clinical AAA tissues., Methods: Ultrastructural atomic force microscopy (AFM) analysis was performed on tissue sections after staining with fluorescently labeled collagen hybridizing peptide (CHP) to recognize degraded collagen. Second harmonic generation (SHG) microscopy was used on CHP-stained sections to identify regions of intact versus degraded collagen. Finally, platelet adhesion was identified via SHG and indirect immunofluorescence on the same tissue sections., Results: Our results indicate that ultrastructural features characterizing collagen fibril abnormalities coincide with CHP staining. SHG signal was absent from CHP-positive regions. Additionally, platelet binding was primarily localized to regions with SHG signal. Abnormal collagen fibrils present in AAA (in SHG negative regions) were thus found to inhibit platelet adhesion compared to normal fibrils., Conclusions: Our investigations reveal how the collagen fibril structure in the vessel wall can serve as another regulator of platelet-collagen adhesion. These results can be broadly applied to understand the role of collagen fibril structure in regulating thrombosis or bleeding disorders., (© 2021 International Society on Thrombosis and Haemostasis.)

Introduction: Aortic graft infection remains a considerable clinical challenge, and it is unclear which variables are associated with adverse outcomes among patients undergoing partial resection., Methods: A retrospective, multi-institutional study of patients who underwent partial resection of infected aortic grafts from 2002 to 2014 was performed using a standard database. Baseline demographics, comorbidities, operative, and postoperative variables were recorded. The primary outcome was mortality. Descriptive statistics, Kaplan-Meier (KM) survival analysis, and Cox regression analysis were performed., Results: One hundred fourteen patients at 22 medical centers in 6 countries underwent partial resection of an infected aortic graft. Seventy percent were men with median age 70 years. Ninety-seven percent had a history of open aortic bypass graft: 88 (77%) patients had infected aortobifemoral bypass, 18 (16%) had infected aortobiiliac bypass, and 1 (0.8%) had an infected thoracic graft. Infection was diagnosed at a median 4.3 years post-implant. All patients underwent partial resection followed by either extra-anatomic (47%) or in situ (53%) vascular reconstruction. Median follow-up period was 17 months (IQR 1, 50 months). Thirty-day mortality was 17.5%. The KM-estimated median survival from time of partial resection was 3.6 years. There was no significant survival difference between those undergoing in situ reconstruction or extra-anatomic bypass (P = 0.6). During follow up, 72% of repairs remained patent and 11% of patients underwent major amputation. On univariate Cox regression analysis, Candida infection was associated with increased risk of mortality (HR 2.4; P = 0.01) as well as aortoenteric fistula (HR 1.9, P = 0.03). Resection of a single graft limb only to resection of abdominal (graft main body) infection was associated with decreased risk of mortality (HR 0.57, P = 0.04), as well as those with American Society of Anesthesiologists classification less than 3 (HR 0.35, P = 0.04). Multivariate analysis did not reveal any factors significantly associated with mortality. Persistent early infection was noted in 26% of patients within 30 days postoperatively, and 39% of patients were found to have any post-repair infection during the follow-up period. Two patients (1.8%) were found to have a late reinfection without early persistent postoperative infection. Patients with any post-repair infection were older (67 vs. 60 years, P = 0.01) and less likely to have patent repairs during follow up (59% vs. 32%, P = 0.01). Patients with aortoenteric fistula had a higher rate of any post-repair infection (63% vs. 29%, P < 0.01) CONCLUSION: This large multi-center study suggests that patients who have undergone partial resection of infected aortic grafts may be at high risk of death or post-repair infection, especially older patients with abdominal infection not isolated to a single graft limb, or with Candida infection or aortoenteric fistula. Late reinfection correlated strongly with early persistent postoperative infection, raising concern for occult retained infected graft material., (Copyright © 2021. Published by Elsevier Inc.)

Objective: The optimal revascularization modality in secondary aortoenteric fistula (SAEF) remains unclear in the literature. The purpose of this investigation was to determine the revascularization approach associated with the lowest morbidity and mortality using real-world data in patients with SAEF., Methods: A retrospective, multi-institutional study of SAEF from 2002 to 2014 was performed using a standardized database. Baseline demographics, comorbidities, and operative and postoperative variables were recorded. The primary outcome was long-term mortality. Descriptive statistics, Kaplan-Meier survival analysis, and univariate and multivariate analyses were performed., Results: During the study period, 182 patients at 34 institutions from 11 countries presented with SAEF (median age, 72 years; 79% male). The initial aortic procedures that resulted in SAEF were 138 surgical grafts (76%) and 42 endografts (23%), with 2 unknown; 102 of the SAEFs (56%) underwent complete excision of infected aortic graft material, followed by in situ (in-line) bypass (ISB), including antibiotic-soaked prosthetic graft (53), autogenous femoral vein (neoaortoiliac surgery; 17), cryopreserved allograft (28), and untreated prosthetic grafts (4). There were 80 patients (44%) who underwent extra-anatomic bypass (EAB) with infected graft excision. Overall median Kaplan-Meier estimated survival was 319 days (interquartile range, 20-2410 days). Stratified by EAB vs ISB, there was no significant difference in Kaplan-Meier estimated survival (P = .82). In comparing EAB vs ISB, EAB patients were older (74 vs 70 years; P = .01), had less operative hemorrhage (1200 mL vs 2000 mL; P = .04), were more likely to initiate dialysis within 30 days postoperatively (15% vs 5%; P = .02), and were less likely to experience aorta-related hemorrhage within 30 days postoperatively (3% aortic stump dehiscence vs 11% anastomotic rupture; P = .03). There were otherwise no significant differences in presentation, comorbidities, and intraoperative or postoperative variables. Multivariable Cox regression showed that the duration of antibiotic use (hazard ratio, 0.92; 95% confidence interval, 0.86-0.98; P = .01) and rifampin use at time of discharge (hazard ratio, 0.20; 95% confidence interval, 0.05-0.86; P = .03) independently decreased mortality., Conclusions: These data suggest that ISB does not offer a survival advantage compared with EAB and does not decrease the risk of postoperative aorta-related hemorrhage. After repair, <50% of SAEF patients survive 10 months. Each week of antibiotic use decreases mortality by 8%. Further study with risk modeling is imperative for this population., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

A 65-year-old man with an occluded popliteal artery aneurysm and calf claudication underwent PET/CT imaging with F-NaF to assess the status of active microcalcification in the aneurysm site and additional lower extremity arteries. CT imaging revealed macrocalcification of the aneurysm that colocalized with elevated retention of F-NaF on PET images. PET/CT detected additional distal arterial sites with focal uptake of F-NaF that did not coincide with CT-detectable macrocalcification. This report highlights a case of active microcalcification in an occlusive peripheral aneurysm using PET/CT. PET/CT may provide molecular insight into the remodeling of lower extremity aneurysms and atherosclerotic lesions.

Vascular diseases like abdominal aortic aneurysms (AAA) are characterized by a drastic remodeling of the vessel wall, accompanied with changes in the elastin and collagen content. At the macromolecular level, the elastin fibers in AAA have been reported to undergo significant structural alterations. While the undulations (waviness) of the collagen fibers is also reduced in AAA, very little is understood about changes in the collagen fibril at the sub-fiber level in AAA as well as in other vascular pathologies. In this study we investigated structural changes in collagen fibrils in human AAA tissue extracted at the time of vascular surgery and in aorta extracted from angiotensin II (AngII) infused ApoE -/- mouse model of AAA. Collagen fibril structure was examined using transmission electron microscopy and atomic force microscopy. Images were analyzed to ascertain length and depth of D-periodicity, fibril diameter and fibril curvature. Abnormal collagen fibrils with compromised D-periodic banding were observed in the excised human tissue and in remodeled regions of AAA in AngII infused mice. These abnormal fibrils were characterized by statistically significant reduction in depths of D-periods and an increased curvature of collagen fibrils. These features were more pronounced in human AAA as compared to murine samples. Thoracic aorta from Ang II-infused mice, abdominal aorta from saline-infused mice, and abdominal aorta from non-AAA human controls did not contain abnormal collagen fibrils. The structural alterations in abnormal collagen fibrils appear similar to those reported for collagen fibrils subjected to mechanical overload or chronic inflammation in other tissues. Detection of abnormal collagen could be utilized to better understand the functional properties of the underlying extracellular matrix in vascular as well as other pathologies. STATEMENT OF SIGNIFICANCE: Several vascular diseases including abdominal aortic aneurysm (AAA) are characterized by extensive remodeling in the vessel wall. Although structural alterations in elastin fibers are well characterized in vascular diseases, very little is known about the collagen fibril structure in these diseases. We report here a comprehensive ultrastructural evaluation of the collagen fibrils in AAA, using high-resolution microscopy techniques like transmission electron microscopy (TEM) and atomic force microscopy (AFM). We elucidate how abnormal collagen fibrils with compromised D-periodicity and increased fibril curvature are present in the vascular tissue in both clinical AAA as well as in murine models. We discuss how these abnormal collagen fibrils are likely a consequence of mechanical overload accompanying AAA and could impact the functional properties of the underlying tissue., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Concern regarding the adequacy of the vascular surgery workforce persists. We aimed to predict future vascular surgery workforce size and capacity using contemporary data on the US population and number, productivity, and practice patterns of vascular surgeons., Methods: The workforce size needed to maintain current levels of access was estimated to be 1.4 vascular surgeons/100,000 population. Updated population estimates were obtained from the US Census Bureau. We calculated future vascular surgery workforce needs based on the estimated population for every 10 years from 2020 to 2050. American Medical Association Physician Masterfile data from 1997 to 2017 were used to establish the existing vascular surgery workforce size and predict future workforce size, accounting for annual rates of new certificates (increased to an average of 133/year since 2013), retirement (17%/year), and the effects of burnout, reduced work hours, transitions to nonclinical jobs, or early retirement. Based on Medical Group Management Association data that estimate median vascular surgeon productivity to be 8,481 work relative value units (wRVUs)/year, excess/deficits in wRVU capacity were calculated based on the number of anticipated practicing vascular surgeons., Results: Our model predicts declining shortages of vascular surgeons through 2040, with workforce size meeting demand by 2050. In 2030, each surgeon would need to increase yearly wRVU production by 22%, and in 2040 by 8%, to accommodate the workload volume., Conclusions: Our model predicts a shortage of vascular surgeons in the coming decades, with workforce size meeting demand by 2050. Congruence between workforce and demand for services in 2050 may be related to increases in the number of trainees from integrated residencies combined with decreases in population estimates. Until then, vascular surgeons will be required to work harder to accommodate the workload. Burnout, changing practice patterns, geographic maldistribution, and expansion of health care coverage and utilization may adversely affect the ability of the future workforce to accommodate population needs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Tissue ischemia contributes to necrosis and infection. While angiogenic cell therapies have emerged as a promising strategy against ischemia, current approaches to cell therapies face multiple hurdles. Recent advances in nuclear reprogramming could potentially overcome some of these limitations. However, under severely ischemic conditions necrosis could outpace reprogramming-based repair. As such, adjunctive measures are required to maintain a minimum level of tissue viability/activity for optimal response to restorative interventions., Methods: Here we explored the combined use of polymerized hemoglobin (PolyHb)-based oxygen nanocarriers with Tissue Nano-Transfection (TNT)-driven restoration to develop tissue preservation/repair strategies that could potentially be used as a first line of care. Random-pattern cutaneous flaps were created in a mouse model of ischemic injury. PolyHbs with high and low oxygen affinity were synthesized and injected into the tissue flap at various timepoints of ischemic injury. The degree of tissue preservation was evaluated in terms of perfusion, oxygenation, and resulting necrosis. TNT was then used to deploy reprogramming-based vasculogenic cell therapies to the flaps via nanochannels. Reprogramming/repair outcomes were evaluated in terms of vascularity and necrosis., Results: Flaps treated with PolyHbs exhibited a gradual decrease in necrosis as a function of time-to-intervention, with low oxygen affinity PolyHb showing the best outcomes. TNT-based intervention of the flap in combination with PolyHb successfully curtailed advanced necrosis compared to flaps treated with only PolyHb or TNT alone., Conclusions: These results indicate that PolyHb and TNT technologies could potentially be synergistically deployed and used as early intervention measures to combat severe tissue ischemia., (© Biomedical Engineering Society 2020.)

Objective: To investigate the feasibility of serial radiotracer-based imaging as a noninvasive approach for quantifying volumetric changes in microvascular perfusion within angiosomes of the foot following lower extremity revascularization in the setting of critical limb ischemia (CLI). Approach: A CLI patient with a nonhealing foot ulcer underwent single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging of the feet before and after balloon angioplasty of the superficial femoral artery (SFA) and popliteal artery. SPECT/CT imaging was used to evaluate serial changes in angiosome perfusion, which was compared to quantitative changes in peripheral vascular anatomy and hemodynamics, as assessed by standard clinical tools that included digital subtraction angiography (DSA), ankle-brachial index (ABI), and toe-brachial index (TBI). Results: Following revascularization, upstream quantitative improvements in stenosis of the SFA (pre: 35.4% to post: 11.9%) and popliteal artery (pre: 59.1% to post: 21.7%) shown by DSA were associated with downstream angiosome-dependent improvements in SPECT microvascular foot perfusion that ranged from 2% to 16%. ABI measurement was not possible due to extensive arterial calcification, while TBI values decreased from 0.26 to 0.16 following revascularization. Innovation: This is the first study to demonstrate the feasibility of assessing noninvasive volumetric changes in angiosome foot perfusion in response to lower extremity revascularization in a patient with CLI by utilizing radiotracer-based imaging. Conclusion: SPECT/CT imaging allows for quantification of serial perfusion changes within angiosomes containing nonhealing ulcers and provides physiological assessment that is complementary to conventional anatomical (DSA) and hemodynamic (ABI/TBI) measures in the evaluation of lower extremity revascularization., Competing Interests: No competing financial interests exist. The content of this article was expressly written by the author(s) listed. No ghostwriters were used to write this article., (© Ting-Heng Chuo et al., 2019; Published by Mary Ann Liebert, Inc.)

Background: Although a Registered Physician in Vascular Interpretation certification is required for vascular surgery board certification, no standardized noninvasive vascular laboratory (NIVL) curriculum for vascular surgery trainees exists. The purpose of this study is to investigate the NIVL experience of trainees and understand what helps them feel well prepared., Methods: Current trainees in all 0 + 5 and 5 + 2 vascular surgery training programs (114) were surveyed. The most complete survey from each program was included in the analysis. Programs were divided into those in which trainees felt well prepared (WP) and those in which trainees felt unprepared (UP) for the Physician Vascular Interpretation (PVI) examination. Responses for the 2 groups were compared., Results: Responses from 61 of the 114 programs (53.5%) were analyzed. Most programs devote <0.5 days per week to the NIVL (52.5%), assign lectures and textbook reading (55.7% and 47.5%), and provide hands-on experience with vascular technologists (60.7%) and attending surgeons (52.5%). Respondents from 15 programs (24.6%) took a PVI examination review course. The first-time PVI examination pass rate was 92.9% (13 of 14 trainees). The WP group reported higher rates of a structured curriculum for the NIVL (100% vs. 33.3%, P = 0.0001), one-on-one time with vascular technologists (78.6% vs. 44.4%, P = 0.05), mandatory lectures (78.6% vs. 33.3%, P = 0.004), and assigned articles (64.3% vs. 11.1%, P = 0.002)., Conclusions: There is wide variation in NIVL experience among vascular surgery training programs. Many trainees feel unprepared for the PVI examination, especially those without a structured curriculum. These results suggest that a structured NIVL curriculum that includes dedicated time with vascular technologists, lectures, and articles should be established., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To investigate treatment-related outcomes, namely radiological clot resolution, post-thrombotic syndrome (PTS), and health related quality-of-life (HRQoL) scores, in children with Paget-Schroetter syndrome (PSS) undergoing multidisciplinary management, including anticoagulation and decompressive rib-resection surgery, with or without thrombolytic therapy., Study Design: We identified all patients treated for PSS at our institution between the years 2010 and 2017. Baseline clinical and radiologic data were abstracted from medical records. Two validated survey instruments to quantify PTS and HRQoL were mailed to eligible patients. Standard statistical methods were used to summarize these measures., Results: In total, 22 eligible patients were identified; 10 were treated with thrombolysis followed by anticoagulation and rib resection, and 12 were treated with anticoagulation and rib resection alone. Nineteen patients responded to the survey instruments. Median age at deep vein thrombosis diagnosis and survey completion were 16.3 and 20.4 years, respectively. Nineteen of 22 patients had thrombus resolution on radiologic follow-up. Fourteen of 19 survey respondents reported signs/symptoms of PTS of which the majority (12/14) reported mild PTS. Aggregate total, physical, and psychosocial HRQoL scores reported were 90.6, 96.7, and 93.3, respectively. Thrombolytic therapy was not associated with a significant improvement in radiologic, clinical or HRQoL outcomes., Conclusions: Most patients with PSS had complete thrombus resolution on imaging. Only 11% of survey respondents reported moderate PTS. The entire cohort reported excellent HRQoL scores. The role for thrombolytic therapy in the management of childhood PSS remains incompletely elucidated., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Maesil ( Prunus mume, green plum)-based products have been widely used in Asian cooking, which may contain amygdalin enzymatically converted to hydrogen cyanide after oral ingestion. In this study, the toxicity of Maesil syrups matured with and without Maesils was evaluated by focusing on relationship between amygdalin toxicity and its metabolic change. The cytotoxicity of amygdalin was highly related to its metabolites converted by β-glucosidase, and the metabolic change was retarded in Maesil syrup. Toxicokinetics revealed extremely low oral absorption and short half-life of amygdalin standard and Maesil syrups, and delayed metabolic change of amygdalin in Maesil syrup was found. It seems that complex Maesil syrup components play roles against amygdalin degradation. Maesil syrup matured with Maesils had higher total polyphenols, lower amygdalin, and shorter half-life in bloodstream than Maesil syrup without Maesils, suggesting more safety benefit. No significant oral toxicity of Maesil syrups was found after 14-day repeated administration, implying their safety.

Zinc oxide (ZnO) nanoparticles (NPs) are widely used as a Zn supplement, because Zn plays a role in many cellular and immune functions but public concern about their potentially undesirable effects on the human body is growing. When NPs are added in food matrices, interactions between NPs and food components occur, which can affect biological systems. In this study, interactions between ZnO NPs and saccharides were investigated by measuring changes in hydrodynamic radius, zeta potential and solubility and by quantifying amounts of adsorbed saccharides on NPs; acacia honey, sugar mixtures (containing equivalent amounts of fructose, glucose, sucrose and maltose) and monosaccharide solutions were used as model compounds. Biological responses of NPs dispersed in different saccharides were also evaluated in human intestinal cells and rats in terms of cytotoxicity, cellular uptake, intestinal transport and oral absorption. The results demonstrate that the hydrodynamic radii and zeta potentials of NPs were highly affected by saccharides. In addition, trace nutrients influenced NP/saccharide interactions and interactive effects between saccharides on the interactions were found. NPs in all saccharides increased inhibition of cell proliferation and enhanced cellular uptake. Oral absorption of NPs was highly enhanced by 5% glucose, which is in-line with intestinal transport result. These findings show that ZnO NPs interact with saccharides and these interactions affects biological responses., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript and in the decision to publish the results.

Controversies in the treatment of venous thoracic outlet syndrome (VTOS) have been discussed for decades, but still persist. Calls for more objective reporting standards have pushed practice towards comprehensive venous evaluations and interventions after first rib resection (FRR) for all patients. In our practice, we have relied on patient-centered, patient-reported outcomes to guide adjunctive treatment and measure success. Thus, we sought to investigate the use of thrombolysis versus anticoagulation alone, timing of FRR following thrombolysis, post-FRR venous intervention, and FRR for McCleery syndrome (MCS) and their impact on patient symptoms and return to function. All patients undergoing FRR for VTOS at our institution from 4 April 2000 through 31 December 2013 were reviewed. Demographics, symptoms, diagnostic and treatment details, and outcomes were collected. Per "Reporting Standards of the Society for Vascular Surgery for Thoracic Outlet Syndrome", symptoms were described as swelling/discoloration/heaviness, collaterals, concomitant neurogenic symptoms, and functional impairment. Patient-reported response to treatment was defined as complete (no residual symptoms and return to function), partial (any residual symptoms present but no functional impairment), temporary (initial improvement but subsequent recurrence of any symptoms or functional impairment), or none (persistent symptoms or functional impairment). Sixty FRR were performed on 59 patients. 54.2% were female with a mean age of 34.3 years. Swelling/discoloration/heaviness was present in all but one patient, deep vein thrombosis in 80%, and visible collaterals in 41.7%. Four patients had pulmonary embolus while 65% had concomitant neurogenic symptoms. In addition, 74.6% of patients were anticoagulated and 44.1% also underwent thrombolysis prior to FRR. Complete or partial response occurred in 93.4%. Of the four patients with temporary or no response, further diagnostics revealed residual venous disease in two and occult alternative diagnoses in two. Use of thrombolysis was not related to FRR outcomes ( p = 0.600). Performance of FRR less than or greater than six weeks after the initiation of anticoagulation or treatment with thrombolysis was not related to FRR outcomes ( p = 1). Whether patients had DVT or MCS was not related to FRR outcomes ( p = 1). No patient had recurrent DVT. From a patient-centered, patient-reported standpoint, VTOS is equally effectively treated with FRR regardless of preoperative thrombolysis or timing of surgery after thrombolysis. A conservative approach to venous interrogation and intervention after FRR is safe and effective for symptom control and return to function. Additionally, patients with MCS are effectively treated with FRR., Competing Interests: The authors declare no conflict of interest.

Zinc oxide (ZnO) nanoparticles (NPs) have been widely used for food fortification, because zinc is essential for many enzyme and hormone activities and cellular functions, but public concern about their potential toxicity is increasing. Interactions between ZnO and biomatrices might affect the oral absorption, distribution, and toxicity of ZnO, which may be influenced by particle size. In this study, ZnO interactions with biomatrices were investigated by examining the physicochemical properties, solubility, protein fluorescence quenching, particle-protein corona, and intestinal transport with respect to the particle size (bulk vs. nano) in simulated gastrointestinal (GI) and plasma fluids and in rat-extracted fluids. The results demonstrate that the hydrodynamic radii and zeta potentials of bulk ZnO and nano ZnO in biofluids changed in different ways, and that nano ZnO induced higher protein fluorescence quenching than bulk ZnO. However, ZnO solubility and its intestinal transport mechanism were unaffected by particle size. Proteomic analysis revealed that albumin, fibrinogen, and fibronectin play roles in particle-plasma protein corona, regardless of particle size. Furthermore, nano ZnO was found to interact more strongly with plasma proteins. These observations show that bulk ZnO and nano ZnO interact with biomatrices in different ways and highlight the need for further study of their long-term toxicity., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Background: Isolated great saphenous vein thrombus (GSVT) is generally regarded as benign, and treatment is heterogeneous. Complications include thrombus propagation, new saphenous vein thrombosis, deep vein thrombosis (DVT), pulmonary embolism (PE), and symptom persistence. Our objective was to review our institution's experience with isolated GSVT to understand its natural history, the frequency of complications, real-world treatment, and the impact of proximity to the saphenofemoral junction (SFJ), on the rate of complications., Methods: Records of patients who had lower extremity venous duplex (LEVD) demonstrating GSVT without concomitant DVT between July 2008 and June 2014 were reviewed. Demographic, medical, management, outcomes, and follow-up LEVD data were collected., Results: Of 605 patients with acute GSVT, 67 limbs in 61 patients with isolated GSVT were the study group; 14.8% of patients had a hypercoagulable state, 31.1% had prior GSVT or DVT, and 23.0% of patients had malignancy; 28.4% of GSVT were observed, 13.4% were treated with aspirin/NSAIDs, and 58.2% were anticoagulated; 38.8% of limbs remained symptomatic following treatment at a mean follow-up period of 761 days; 37 limbs had GSVT <5 cm of the SFJ (group 1), and 30 had GSVT >5 cm from the SFJ (group 2). Seven patients developed PE, all in group 1 (P = 0.02). Twenty-nine limbs (43.3%) had follow-up LEVD at a mean of 23 days. In this subset, 13 patients at the initial scan (44.8%) had thrombus <5 cm of the SFJ (group 1) and 16 (55.2%) had thrombus >5 cm from the SFJ (group 2). Five limbs (17.2%) had GSVT propagation/new superficial vein thrombosis (SVT), and 6 (20.7%) developed new DVT. There was no GSVT propagation/new SVT in group 1, whereas 5 limbs (31.2%) had GSVT propagation/new SVT in group 2 (P = 0.048). DVT occurred in 2 limbs (15.3%) in group 1 and 4 limbs (25%) in group 2., Conclusions: Isolated GSVT tends to affect patients with hypercoagulable states, prior venous thromboembolism, malignancy, or recent surgery. Management is heterogeneous, and type of treatment does not seem to affect outcomes. Patients with GSVT have significant risk of persistent symptoms, recurrence, DVT, and PE. GSVT within 5 cm of the SFJ seemed to be associated with an increased rate of PE. GSVT more than 5 cm from the SFJ seemed to be associated with propagation/new SVT. Proximity to the SFJ did not impact occurrence of DVT., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Ultrasound-guided thrombin injection (UGTI) is a well-established practice for the treatment of femoral artery pseudoaneurysm. This procedure is highly successful but dependent on appropriate pseudoaneurysm anatomy and adequate ultrasound visualization. Morbid obesity can present a significant technical challenge due to increased groin adiposity, resulting in poor visualization of critical structures needed to safely perform the procedure. We aim to evaluate the safety and efficacy of UGTI to treat femoral artery pseudoaneurysm in the morbidly obese., Methods: This is a retrospective cohort study in which all patients who underwent UGTI at The Ohio State University Ross Heart Hospital from 2009 to 2014 were analyzed for patient characteristics and stratified by body mass index (BMI). Patients with BMI ≥ 35 were considered morbidly obese and were compared to patients with a BMI < 35. Outcome was failed treatment resulting in residual pseudoaneurysm., Results: Our cohort consisted of 54 patients who underwent thrombin injection. There were 41 nonmorbidly obese and 13 morbidly obese patients. Mean age was 64.5 years. The cohort was 44.4% male. There were 6 failures, of which 1 underwent successful repeat injection and 5 underwent open surgical repair. There was no statistically significant difference in failure between nonmorbidly obese and morbidly obese patients (9.8% vs 15.4%, P = .45). There were no embolic/thrombotic complications., Conclusion: Ultrasound-guided thrombin injection is a safe and effective therapy in the morbidly obese for the treatment of femoral artery pseudoaneurysm. In the hands of experienced sonographers and surgeons with adequate visualization of the pseudoaneurysm sac, UGTI should remain a standard therapy in the morbidly obese.

Objective: Whereas duplex ultrasound parameters for predicting internal carotid artery (ICA) stenosis are well defined, the use of common carotid artery (CCA) Doppler characteristics to predict ICA stenosis when the ICA cannot be insonated directly or accurately because of anatomy, calcification, or tortuosity has not been studied. The objective of this study was to identify CCA Doppler parameters that may predict ICA stenosis., Methods: We reviewed all patients at our institution who underwent carotid duplex ultrasound (CDU) from 2008 to 2015 and also had a comparison computed tomography, magnetic resonance, or catheter angiogram. We excluded patients whose CDU examination did not correlate with the comparison study, those whose arteries were not visualized on the comparison study, and those with complete occlusion of the CCA. We collected CCA peak systolic velocity (PSV), end-diastolic velocity (EDV), and acceleration time (AT) in addition to CDU and comparison imaging interpretation of degree of stenosis. A multivariate model was used to identify predictors of ICA stenosis., Results: There were 99 CDU examinations with corresponding comparison imaging included. For every increase of 10 cm/s in EDV in the CCA, the odds of a >50% ICA stenosis being present vs a ≤50% ICA stenosis decreased by 37% (odds ratio [OR], 0.63; 95% confidence interval [CI], 0.41-0.97; P = .03). For every increase of 10 cm/s in EDV in the CCA, the odds of a 70% to 99% ICA stenosis being present vs a ≤50% ICA stenosis decreased by 48% (OR, 0.52; 95% CI, 0.28-0.94; P = .03). A CCA EDV of 19 cm/s or below was associated with a 64% probability of a 70% to 99% ICA stenosis. For every 50-millisecond increase in AT in the CCA, the odds of a >50% stenosis being present vs a ≤50% ICA stenosis increased by 56% (OR, 1.56; 95% CI, 1.03-2.35; P = .04). A CCA AT of 80 milliseconds or above was associated with a 69% probability of a >50% ICA stenosis. There was no correlation between CCA PSV and ICA stenosis., Conclusions: CCA EDV and AT are independent predictors of ICA stenosis and may be used in the setting of patients whose ICA cannot be directly insonated or when standard duplex ultrasound parameters of ICA PSV, EDV, or ICA/CCA ratio conflict., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Nanoparticles (NPs) have been widely utilized in the food industry as additives with their beneficial characteristics, such as improving sensory property and processing suitability, enhancing functional and nutritional values, and extending shelf-life of foods. Silica is used as an anti-caking agent to improve flow property of powered ingredients and as a carrier for flavors or active compounds in food. Along with the rapid development of nanotechnology, the sizes of silica fall into nanoscale, thereby raising concerns about the potential toxicity of nano-sized silica materials. There have been a number of studies carried out to investigate possible adverse effects of NPs on the gastrointestinal tract. The interactions between NPs and surrounding food matrices should be also taken into account since the interactions can affect their bioavailability, efficacy, and toxicity. In the present study, we investigated the interactions between food additive silica NPs and food matrices, such as saccharides, proteins, lipids, and minerals. Quantitative analysis was performed to determine food component-NP corona using HPLC, fluorescence quenching, GC-MS, and ICP-AES. The results demonstrate that zeta potential and hydrodynamic radius of silica NPs changed in the presence of all food matrices, but their solubility was not affected. However, quantitative analysis on the interactions revealed that a small portion of food matrices interacted with silica NPs and the interactions were highly dependent on the type of food component. Moreover, minor nutrients could also affect the interactions, as evidenced by higher NP interaction with honey rather than with a simple sugar mixture containing an equivalent amount of fructose, glucose, sucrose, and maltose. These findings provide fundamental information to extend our understanding about the interactions between silica NPs and food components and to predict the interaction effect on the safety aspects of food-grade NPs.

Iron or zinc deficiency is one of the most important nutritional disorders which causes health problem. However, food fortification with minerals often induces unacceptable organoleptic changes during preparation process and storage, has low bioavailability and solubility, and is expensive. Nanotechnology surface modification to obtain novel characteristics can be a useful tool to overcome these problems. In this study, the efficacy and potential toxicity of dispersible Fe or Zn supplement coated in dextrin and glycerides (SunActive Fe TM and SunActive Zn TM ) were evaluated in terms of cytotoxicity, intestinal transport, and bioavailability, as compared with each counterpart without coating, ferric pyrophosphate (FePP) and zinc oxide (ZnO) nanoparticles (NPs), respectively. The results demonstrate that the cytotoxicity of FePP was not significantly affected by surface modification (SunActive Fe TM ), while SunActive Zn TM was more cytotoxic than ZnO-NPs. Cellular uptake and intestinal transport efficiency of SunActive Fe TM were significantly higher than those of its counterpart material, which was in good agreement with enhanced oral absorption efficacy after a single-dose oral administration to rats. These results seem to be related to dissolution, particle dispersibility, and coating stability of materials depending on suspending media. Both SunActive TM products and their counterpart materials were determined to be primarily transported by microfold (M) cells through the intestinal epithelium. It was, therefore, concluded that surface modification of food fortification will be a useful strategy to enhance oral absorption efficiency at safe levels.

Abdominal aortic aneurysm (AAA) is a localized enlargement of the abdominal aorta, such that the diameter exceeds 3 cm. The natural history of AAA is progressive growth leading to rupture, an event that carries up to 90% risk of mortality. Hence there is a need to predict the growth of the diameter of the aorta based on the diameter of a patient's aneurysm at initial screening and aided by non-invasive biomarkers. IL-6 is overexpressed in AAA and was suggested as a prognostic marker for the risk in AAA. The present paper develops a mathematical model which relates the growth of the abdominal aorta to the serum concentration of IL-6. Given the initial diameter of the aorta and the serum concentration of IL-6, the model predicts the growth of the diameter at subsequent times. Such a prediction can provide guidance to how closely the patient's abdominal aorta should be monitored. The mathematical model is represented by a system of partial differential equations taking place in the aortic wall, where the media is assumed to have the constituency of an hyperelastic material.

Background: We present 6 patients who had operative repair of symptomatic popliteal cystic adventitial disease (pCAD). Developmental theories for pCAD and surgical alternatives are presented., Methods: All patients who had repair of pCAD over the past 3 years are included., Results: Three patients had cyst excision alone, whereas the remaining 3 had cyst and artery excision with interposition vein grafting. Cyst recurrence occurred in 2 patients who had cyst excision alone. Four of the patients had a patent communication between the cyst and the joint capsule., Conclusions: Our small series suggests that the articular (synovial) theory of development may be the most likely and that cyst and artery excision with interposition vein grafting may be preferred over cyst excision alone., (Copyright © 2016 Elsevier Inc. All rights reserved.)

(1) Background: Application of nanotechnology or nanomaterials in agricultural food crops has attracted increasing attention with regard to improving crop production, quality, and nutrient utilization. Gold nanoparticles (Au-NPs) have been reported to enhance seed yield, germination rate, and anti-oxidant potential in food crops, raising concerns about their toxicity potential. In this study, we evaluated the oral toxicity of red ginseng exposed to colloidal Au-NPs during cultivation (G-red ginseng) in rats and their intestinal transport mechanism. (2) Methods: 14-day repeated oral administration of G-red ginseng extract to rats was performed, and body weight, hematological, serum biochemical, and histopathological values were analyzed. An in vitro model of human intestinal follicle-associated epithelium (FAE) and an intestinal epithelial monolayer system were used for intestinal transport mechanistic study. (3) Results: No remarkable oral toxicity of G-red ginseng extract in rats was found, and Au-NPs did not accumulate in any organ, although Au-NP transfer to G-red ginseng and some increased saponin levels were confirmed. Au-NPs were transcytozed by microfold (M) cells, but not by a paracellular pathway in the intestinal epithelium. (4) Conclusion: These findings suggest great potential of Au-NPs for agricultural food crops at safe levels. Further study is required to elucidate the functional effects of Au-NPs on ginseng and long-term toxicity.

Objective: Abdominal aortic aneurysm (AAA) wall stiffness has been suggested to be an important factor in the overall rupture risk assessment compared with anatomic measure. We hypothesize that AAA diameter will have no correlation to AAA wall stiffness. The aim of this study is to (1) determine magnetic resonance elastography (MRE)-derived aortic wall stiffness in AAA patients and its correlation to AAA diameter; (2) determine the correlation between AAA stiffness and amount of thrombus and calcium; and (3) compare the AAA stiffness measurements against age-matched healthy individuals., Methods: In vivo abdominal aortic MRE was performed on 36 individuals (24 patients with AAA measuring 3-10 cm and 12 healthy volunteers), aged 36 to 78 years, after obtaining written informed consent under the approval of the Institutional Review Board. MRE images were processed to obtain spatial stiffness maps of the aorta. AAA diameter, amount of thrombus, and calcium score were reported by experienced interventional radiologists. Spearman correlation, Wilcoxon signed rank test, and Mann-Whitney test were performed to determine the correlation between AAA stiffness and diameter and to determine the significant difference in stiffness measurements between AAA patients and healthy individuals., Results: No significant correlation (P > .1) was found between AAA stiffness and diameter or amount of thrombus or calcium score. AAA stiffness (mean 13.97 ± 4.2 kPa) is significantly (P ≤ .02) higher than remote normal aorta in AAA (mean 8.87 ± 2.2 kPa) patients and in normal individuals (mean 7.1 ± 1.9 kPa)., Conclusions: Our results suggest that AAA wall stiffness may provide additional information independent of AAA diameter, which may contribute to our understanding of AAA pathophysiology, biomechanics, and risk for rupture., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: To curb increasing volumes of diagnostic imaging and costs, reimbursement for carotid duplex ultrasound (CDU) is dependent on "appropriate" indications as documented by International Classification of Diseases (ICD) codes entered by ordering physicians. Historically, asymptomatic indications for CDU yield lower rates of abnormal results than symptomatic indications, and consensus documents agree that most asymptomatic indications for CDU are inappropriate. In our vascular laboratory, we perceived an increased rate of incorrect or inappropriate ICD codes. We therefore sought to determine if ICD codes were useful in predicting the frequency of abnormal CDU. We hypothesized that asymptomatic or nonspecific ICD codes would yield a lower rate of abnormal CDU than symptomatic codes, validating efforts to limit reimbursement in asymptomatic, low-yield groups., Material and Methods: We reviewed all outpatient CDU done in 2011 at our institution. ICD codes were recorded, and each medical record was then reviewed by a vascular surgeon to determine if the assigned ICD code appropriately reflected the clinical scenario. CDU findings categorized as abnormal (>50% stenosis) or normal (<50% stenosis) were recorded. Each individual ICD code and group 1 (asymptomatic), group 2 (nonhemispheric symptoms), group 3 (hemispheric symptoms), group 4 (preoperative cardiovascular examination), and group 5 (nonspecific) ICD codes were analyzed for correlation with CDU results., Results: Nine hundred ninety-four patients had 74 primary ICD codes listed as indications for CDU. Of assigned ICD codes, 17.4% were deemed inaccurate. Overall, 14.8% of CDU were abnormal. Of the 13 highest frequency ICD codes, only 433.10, an asymptomatic code, was associated with abnormal CDU. Four symptomatic codes were associated with normal CDU; none of the other high frequency codes were associated with CDU result. Patients in group 1 (asymptomatic) were significantly more likely to have an abnormal CDU compared to each of the other groups (P < 0.001, P < 0.001, P = 0.020, P = 0.002) and to all other groups combined (P < 0.001)., Conclusions: Asymptomatic indications by ICD codes yielded higher rates of abnormal CDU than symptomatic indications. This finding is inconsistent with clinical experience and historical data, and we suggest that inaccurate coding may play a role. Limiting reimbursement for CDU in low-yield groups is reasonable. However, reimbursement policies based on ICD coding, for example, limiting payment for asymptomatic ICD codes, may impede use of CDU in high-yield patient groups., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Axillary-femoral bypass is sometimes performed for complex aortoiliac occlusive disease in patients unfit for aortic surgery or in those with aortic infection. Typically, older patients with medical comorbidities that commonly accompany atherosclerotic or aneurysmal disease are involved and can tolerate the theoretic risk of limited flow volume associated with long, small diameter, axillary-femoral grafts. However, a subset of younger, healthier, more vigorous patients outside the typical atherosclerotic or aneurysmal demographic occasionally come to axillary-femoral bypass and may experience symptoms of distal hypoperfusion if flow volumes cannot meet demand. We present a series of patients with primary aortic infection treated with aortic ligation and axillary-femoral bypass, who then progressed to symptoms of visceral, spinal, or extremity ischemia from inadequate distal perfusion., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Clamping and shunting during carotid endarterectomy (CEA) surgery causes changes in cerebral blood flow. The purpose of this study was to assess and compare, side by side, the cerebral oxygenation (rSO2) and processed electroencephalogram (EEG) response bilaterally to carotid artery clamping and shunting in patients undergoing CEA under general anesthesia. With institutional approval and written informed consent, patients undergoing CEA under general anesthesia and routine carotid artery shunting were recorded bilaterally, simultaneously and continuously with an rSO2 and processed EEG monitor. The response of the monitors during carotid artery clamping and shunting were assessed and compared between monitors and bilaterally within each monitor. Sixty-nine patients were included in the study. At clamping the surgical-side and contralateral-side rSO2 dropped significantly below the baseline incision value (-17.6 and -9.4% respectively). After shunting, the contralateral-side rSO2 returned to baseline while the surgical-side rSO2 remained significantly below baseline (-9.0%) until the shunt was removed following surgery. At clamping the surgical-side and contralateral-side processed EEG also dropped below baseline (-19.9 and -20.6% respectively). However, following shunt activation, the processed EEG returned bilaterally to baseline. During the course of this research, we found the rSO2 monitor to be clinically more robust (4.4% failure rate) than the processed EEG monitor (20.0% failure rate). There was no correlation between the rSO2 or processed EEG changes that occurred immediately after clamping and the degree of surgical side stenosis measured pre-operatively. Both rSO2 and processed EEG respond to clamping and shunting during CEA. Cerebral oximetry discriminates between the surgical and contralateral side during surgery. The rSO2 monitor is more reliable in the real-world clinical setting. Future studies should focus on developing algorithms based on these monitors that can predict clamping-induced cerebral ischemia during CEA in order to decide whether carotid artery shunting is worth the associated risks. From the practical point of view, the rSO2 monitor may be the better monitor for this purpose.

Compression of the neurovascular contents of the popliteal fossa is a rare condition that leads to exercise-induced pain and paresthesias in young athletes. Most frequently, it is caused by musculotendinous abnormalities resulting in popliteal entrapment syndrome. Bony abnormalities rarely are implicated but can produce symptoms that mimic popliteal entrapment syndrome. We present a patient with a tibial metaphysis osteochondroma inducing popliteal artery compression that was relieved after resection., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Gold nanoparticles (Au-NPs) have promising potential for diverse biological application, but it has not been completely determined whether Au-NP has potential toxicity in vitro and in vivo . In the present study, toxicity of Au-NP was evaluated in human intestinal cells as well as in rats after 14-day repeated oral administration. Biokinetic study was also performed to assess oral absorption and tissue distribution. The results demonstrated that Au-NP did not cause cytotoxic effects on cells after 24 h exposure in terms of inhibition of cell proliferation, membrane damage, and oxidative stress. However, when a small number of cells were exposed to Au-NP for seven days, colony forming ability remarkably decreased by Au-NP treatment, suggesting its potential toxicity after long-term exposure at high concentration. Biokinetic study revealed that Au-NP slowly entered the blood stream and slightly accumulated only in kidney after oral administration to rats. Whereas, orally administered Au ions were rapidly absorbed, and then distributed in kidney, liver, lung, and spleen at high levels, suggesting that the biological fate of Au-NP is primarily in nanoparticulate form, not in ionic Au. Fourteen-day repeated oral toxicity evaluation showed that Au-NP did not cause severe toxicity in rats based on histopathological, hematological, and serum biochemical analysis.

Objective: The utility of duplex venous scanning (DVS) for suspected deep venous thrombosis in the emergency department (ED) remains controversial. We aimed to measure potential cost savings and economic impact in our institution and nationally for unnecessary DVS in Medicare patients seen in the ED., Methods: We have previously calculated that 15.3% of DVS studies can safely be avoided in patients with suspected deep venous thrombosis in our ED with adherence to our protocol. The Medicare database was queried for the number of DVS studies performed in the ED and charges/payments made in 2011. Cost savings at our institution and nationally by Medicare were computed with the 15.3% number., Results: In the study period, 2087 DVS studies were performed in our ED across all payers; 572 Medicare patients had 249 (43%) bilateral and 323 (57%) unilateral studies. Annual savings at our institution, with use of our protocol, were estimated at $113,778. Eliminating unnecessary after-hours DVS for 306,307 Medicare beneficiaries would result in $5,285,090 savings annually., Conclusions: Increasing pressure for cost containment under a value-based payment model necessitates critical evaluation of resource utilization. Applying this schema for all noninvasive vascular tests is an opportunity for responsible management of finite resources, reducing wasteful care, and significant cost containment., (Published by Elsevier Inc.)

Invasive hemodynamic monitoring with a pulmonary catheter has been relatively routine in cardiovascular and complex surgical operations as well as in the management of critical illnesses. However, due to multiple potential complications and its invasive nature, its use has decreased over the years and less invasive methods such as transesophageal echocardiography and hemodynamic sensors have gained widespread favor. Unlike these less invasive forms of hemodynamic monitoring, pulmonary artery catheters require an advanced understanding of cardiopulmonary physiology, anatomy, and the potential for complications in order to properly place, manage, and interpret the device. We describe a case wherein significant resistance was encountered during multiple unsuccessful attempts at removing a patient's catheter secondary to kinking and twisting of the catheter tip. These attempts to remove the catheter serve to demonstrate potential rescue options for such a situation. Ultimately, successful removal of the catheter was accomplished by simultaneous catheter retraction and sheath advancement while gently pulling both objects from the cannulation site. In addition to being skilled in catheter placement, it is imperative that providers comprehend the risks and complications of this invasive monitoring tool.

Surgical management of acute aortic infection is challenging, including excision of the infected segment and reconstruction either through extra-anatomical bypass or in situ graft replacement with higher risk of re-infection. Here in, we present a case of delayed paralysis developed after an extra-anatomic (axillary-bifemoral) bypass of infected thoracic aorta in a 51 year old Caucasian male. Reversal of paralysis was successfully achieved via larger extra-anatomical ascending aorta to infra-renal aorta bypass and cerebrospinal fluid (CSF) drainage.

Objective: Pelvic congestion syndrome (PCS) is difficult to diagnose, poorly understood, and often confused with other causes of chronic pelvic pain. Thus, gonadal vein reflux, its relation to lower extremity venous insufficiency (LEVI), and treatment remains controversial to physicians and payors. We present our experience with endovascular PCS treatment and hypothesize that properly selected patients can realize significant improvement., Methods: A retrospective study of patients treated for PCS at our institution from 2008 to 2012 was performed. Diagnosis was made clinically by the presence of pelvic pain, dyspareunia, and/or perineal varicosities. Clinical parameters, procedural details, and follow-up were reviewed. A questionnaire including a visual analog scale was sent to patients., Results: Diagnosis was made in 15 women (mean age, 36 years; mean parity, two). All had pelvic pain, 6 had dyspareunia, 14 had perineal varicosities, and 10 had concomitant LEVI. Fourteen had gonadal vein reflux (mean diameter, 7.4 mm) and pelvic varicosities at angiography and had coiling (n = 12) and/or Amplatzer plug (St. Jude Medical, Inc, St. Paul, Minn) (n = 4). One patient had stenting of a stenotic left common iliac vein. All patients with concomitant LEVI had successful appropriate treatment. Eight patients completed the questionnaire at a mean follow-up of 4 years. The mean pelvic pain score went from 9.375 to 1.875 post-procedure (P < .0001; Student t-test). Mean dyspareunia score went from 8.875 to 1.5 (P < .0001). Mean perineal varicosity pain score went from 9.285 to 1.285 (P < .0001). Two patients had recurrence with a mean pelvic pain score of 4.5 at a mean 21 months. On a five-point Likert scale, all patients were satisfied (one) or extremely satisfied (seven) with treatment., Conclusions: Endovascular PCS treatment offers excellent pelvic pain relief and patient satisfaction. Women with pelvic pain, dyspareunia, or perineal varicosities with gonadal vein reflux and pelvic varicosities or iliac vein stenosis should not be denied treatment. A significant number may have concomitant LEVI and should be screened accordingly., (Copyright © 2014 Society for Vascular Surgery. All rights reserved.)