How multidisciplinary clinics may mitigate socioeconomic barriers to care for chronic limb-threatening ischemia.

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 χ2, 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.

Quantification of Skeletal Muscle Perfusion in Peripheral Artery Disease Using 18F-Sodium Fluoride Positron Emission Tomography Imaging.

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 (18F-NaF), to quantify absolute perfusion in PAD. METHODS AND RESULTS: Eight Yorkshire pigs underwent unilateral femoral artery ligation and dynamic 18F-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. 18F-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: 18F-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 18F-NaF PET imaging using a single radioisotope injection. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03622359.

Gluteal and thigh compartment syndrome after open abdominal aortic aneurysm repair.

Although compartment syndrome (CS) can occur in any myofascial compartment, the thigh and buttock are among the least common. CS is characterized by an increase in pressure of a myofascial compartment that results in a reduction of capillary blood flow and myonecrosis. Although >75% of cases of CS occur after long bone fractures, acute CS can also occur from nontraumatic and vascular etiologies. We report a case of gluteal and thigh CS resulting from ischemia-reperfusion injury after abdominal aortic aneurysm repair and left common iliac artery bypass.

Measuring Chief Resident Skill and Entrustment Progression in An Operative Coaching Program: Four Years' Experience.

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.

Revascularization Outcomes Stratified by Glycemic Control in Patients with Diabetes Mellitus and Chronic Limb-Threatening Ischemia.

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.

Detection of multivessel calcific disease progression in a patient with chronic limb-threatening ischemia using fluorine-18 sodium fluoride positron emission tomography imaging.

Vascular calcification contributes to morbidity and poor clinical outcomes for patients with peripheral artery disease; however, the traditional assessment of the calcium burden using computed tomography (CT) imaging or angiography represents already established disease. In the present report, we describe a 69-year-old man with chronic limb-threatening ischemia who had undergone positron emission tomography/CT imaging with fluorine-18 sodium fluoride to evaluate the relationship between baseline levels of positron emission tomography-detectable active vascular microcalcification and CT-detectable calcium progression 1.5 years later. CT imaging at follow-up identified progression of existing lesions and the formation of new calcium in multiple arteries that had demonstrated elevated fluorine-18 sodium fluoride uptake 1.5 years earlier.

The natural history of chronic limb-threatening ischemia after technical failure of endovascular intervention.

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.

Vessel-by-Vessel Computed Tomography Calcium Scoring of the Foot in Peripheral Artery Disease: Association with Patient-Level Factors.

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.

Vessel-by-vessel analysis of lower extremity 18F-NaF PET/CT imaging quantifies diabetes- and chronic kidney disease-induced active microcalcification in patients with peripheral arterial disease.

BACKGROUND: Positron emission tomography (PET)/computed tomography (CT) imaging with fluorine-18 (18F)-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 18F-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 18F-NaF uptake for each lower extremity artery. METHODS: PAD patients (n = 48) and healthy controls (n = 8) underwent lower extremity 18F-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 18F-NaF uptake. 18F-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 18F-NaF uptake in PAD. RESULTS: PAD patients with DM or CKD demonstrated significantly higher active microcalcification (i.e., 18F-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 18F-NaF uptake for 4 out of 5 arteries of interest. CONCLUSIONS: 18F-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. 18F-NaF PET imaging is complementary to and largely independent of established CT-detectable arterial calcification. 18F-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.

Impact of an Ultrasound Demonstration on Vascular Surgery Interest in Preclinical Medical Students.

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.

Extra-Anatomic Bypass and Excision is Superior to Graft Salvage Attempts with Antibiotic Beads to Treat Vascular Graft Infections in the Groin.

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.

In-situ bypass is associated with superior infection-free survival compared with extra-anatomic bypass for the management of secondary aortic graft infections without enteric involvement.

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.

Novel Application of 18F-NaF PET/CT Imaging for Evaluation of Active Bone Remodeling in Diabetic Patients With Charcot Neuropathy: A Proof-of-Concept Report.

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 18F-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 18F-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 18F-NaF in the bones of the feet afflicted with CN, with bone retention of 18F-NaF persisting for up to 5 years following surgical reconstruction of the foot in two cases. On a group level, 18F-NaF bone uptake in the CN foot was significantly higher compared to the healthy, non-CN foot (p = 0.039). 18F-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.

Structurally abnormal collagen fibrils in abdominal aortic aneurysm resist platelet adhesion.

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.

Early Intervention in Ischemic Tissue with Oxygen Nanocarriers Enables Successful Implementation of Restorative Cell Therapies.

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.

Noninvasive Detection of Active Microcalcification in an Occlusive Peripheral Vascular Aneurysm Using 18F-NaF PET/CT Imaging.

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.

Collagen fibril abnormalities in human and mice abdominal aortic aneurysm.

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.

An Updated Physician Workforce Model Predicts a Shortage of Vascular Surgeons for the Next 20 Years.

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.

SPECT/CT Imaging: A Noninvasive Approach for Evaluating Serial Changes in Angiosome Foot Perfusion in Critical Limb Ischemia.

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.