Polyvascular disease is common in patients undergoing carotid endarterectomy and lower extremity bypass and is associated with worse outcomes.

BACKGROUND: Polyvascular disease is strongly associated with increased risk of cardiovascular morbidity and mortality. However, its prevalence in patients undergoing carotid and lower extremity surgical revascularization and its impact on outcomes are unknown. METHODS: The Vascular Quality Initiative was queried for carotid endarterectomy (CEA) or infrainguinal lower extremity bypass (LEB), 2013-2019. Polyvascular disease was defined as presence of atherosclerotic occlusive disease in more than one arterial bed: carotid, coronary, and infrainguinal. Primary outcomes were (1) composite perioperative myocardial infarction (MI) or death and (2) 5-year survival. Patient characteristics and perioperative outcomes were evaluated using the χ2 test and multivariable logistic regression. Survival was analyzed using Kaplan-Meier method and Cox proportional hazards multivariable models. RESULTS: Polyvascular disease was identified in 47% of CEA (39.0% in 2 arterial beds, 7.6% in 3 arterial beds; n = 93,736) and 47% of LEB (41.0% in 2 arterial beds, 5.7% in 3 arterial beds; n = 25,223). For both CEA and LEB, patients with polyvascular disease had more comorbidities including hypertension, congestive heart disease, chronic obstructive pulmonary disease, smoking, diabetes mellitus, and end-stage renal disease (P < .0001). Perioperative MI/death rates increased with increasing number of vascular beds affected following CEA (0.9% in 1 bed vs 1.5% in 2 beds vs 2.7% in 3 beds; P < .001) and LEB (2.2% in 1 bed vs 5.3% in 2 beds vs 6.6% in 3 beds; P < .001). Polyvascular disease was associated independently with perioperative MI/death after CEA (odds ratio, 1.59; 95% confidence interval [CI], 1.40-1.81;P < .0001) and LEB (odds ratio, 1.78; 95% CI, 1.52-2.08; P < .0001). Five-year survival was decreased in patients with polyvascular disease after CEA (82% in 3 beds vs 88% in 2 beds vs 92% in 1 bed; P < .01) and LEB (72% in 3 beds vs 75% in 2 beds vs 84% in 1 bed; P < .01) in a dose-dependent manner, with the lowest 5-year survival observed in those with three arterial beds involved. Polyvascular disease was independently associated with 5-year mortality after CEA (hazard ratio, 1.33; 95% CI, 1.24-1.40; P = .0001) and LEB (hazard ratio, 1.30; 95% CI, 1.20-1.41; P = .0001). CONCLUSIONS: Polyvascular disease is common in patients undergoing CEA and LEB and is associated with a higher risk of perioperative MI/death and decreased long-term survival. After revascularization, patients with polyvascular disease should be considered for more aggressive cardioprotective medications and closer follow-up.

Long-term outcomes of autologous vein bypass for repair of upper and lower extremity major arterial trauma.

OBJECTIVE: Autologous vein is the preferred bypass conduit for extremity arterial injuries owing to superior patency and low infection risk; however, long-term data on outcomes in civilians are limited. Our goal was to assess short- and long-term outcomes of autologous vein bypass for upper and lower extremity arterial trauma. METHODS: A retrospective review was performed of patients with major extremity arterial injuries (2001-2019) at a level I trauma center. Demographics, injury and intervention details, and outcomes were recorded. Primary outcomes were primary patency at 1 year and 3 years. Secondary outcomes were limb function at 6 months, major amputation, and mortality. Multivariable analysis determined risk factors for functional impairment. RESULTS: There were 107 extremity arterial injuries (31.8% upper and 68.2% lower) treated with autologous vein bypass. Mechanism was penetrating in 77% of cases, of which 79.3% were due to firearms. The most frequently injured vessels were the common and superficial femoral (38%), popliteal (30%), and brachial arteries (29%). For upper extremity trauma, concomitant nerve and orthopedic injuries were found in 15 (44.1%) and 11 (32.4%) cases, respectively. For lower extremities, concomitant nerve injuries were found in 10 (13.7%) cases, and orthopedic injuries in 31 (42.5%). Great saphenous vein was the conduit in 96% of cases. Immediate intraoperative bypass revision occurred in 9.3% of patients, most commonly for graft thrombosis. The in-hospital return to operating room rate was 15.9%, with graft thrombosis (47.1%) and wound infections (23.5%) being the most common reasons. The median follow-up was 3.6 years. Kaplan-Meier analysis showed 92% primary patency at 1 year and 90% at 3 years. At 6 months, 36.1% of patients had functional impairment. Of patients with functional impairment at 6 months, 62.9% had concomitant nerve and 60% concomitant orthopedic injuries. Of those with nerve injury, 91.7% had functional impairment, compared with 17.8% without nerve injury (P < .001). Of patients with orthopedic injuries, 51.2% had functional impairment, vs 25% of those without orthopedic injuries (P = .01). On multivariable analysis, concomitant nerve injury (odds ratio, 127.4; 95% confidence interval, 17-957; P <. 001) and immediate intraoperative revision (odds ratio, 11.03; 95% confidence interval, 1.27-95.55; P = .029) were associated with functional impairment. CONCLUSIONS: Autologous vein bypass for major extremity arterial trauma is durable; however, many patients have long-term limb dysfunction associated with concomitant nerve injury and immediate intraoperative bypass revision. These factors may allow clinicians to identify patients at higher risk for functional impairment, to outline patient expectations and direct rehabilitation efforts toward improving functional outcomes.

An Assessment of the Society for Vascular Surgery Appropriate Use Criteria for the Management of Intermittent Claudication: Key Findings and Considerations for Implementation.

BACKGROUND: Several concerns have been raised over the past several years about the potential for overuse of vascular interventions for peripheral artery disease. These interventions can have serious complications, including limb loss. Given that the natural history of intermittent claudication rarely includes limb loss, it is critically important that interventions to treat it have appropriate indications. METHODS: To address this matter, the Society for Vascular Surgery published an appropriate use criteria (AUC) document for the management of intermittent claudication in 2022. Using the rigorously studied University of California Los Angeles RAND Appropriateness Method, the rating panel assessed the appropriateness of 2,280 scenarios for [1] the initial management and [2] the management after a failed trial of exercise therapy. RESULTS: The findings of the rating panel included that medical management and exercise therapy are appropriate initial management in all scenarios. There were several scenarios in which revascularization was also considered appropriate, mainly influenced by severity of physical limitations and favorable lesion characteristics. When considering management after a failed trial of exercise, guiding principles cited by the rating panel included durability of intervention, smoking cessation, and evidence of prior good-faith effort at exercise therapy. There were many scenarios which were indeterminate. With respect to the infrapopliteal segment, the rating panelists unanimously agreed to forgo individual scenario ratings, since they deemed the risks outweigh the benefits in all cases. CONCLUSIONS: The Society for Vascular Surgery (SVS) AUC for intermittent claudication represents an important effort to identify and reduce overuse. There are several considerations for how they should be used. The simplest application is by practicing clinicians, at the bedside, as they engage in shared decision-making with patients. The matter of their use by payors is more complex. Ideally, decisions on how to best use AUC require additional study of their performance before they are used by payors for anything. Finally, these AUC have identified a myriad of areas where evidence is lacking. The AUC provide important targets for future research to improve the care of patients with intermittent claudication.

Predictors of Ambulatory Status at 1 Year Following Major Lower Extremity Amputation.

Nearly 60,000 major lower extremity amputations (AKA/BKA) are performed annually in the United States. We created a simple risk score for predicting ambulation at 1 year following AKA/BKA. We queried the Vascular Quality Initiative amputation database for patients who underwent above-knee (AKA) or below-knee (BKA) amputation (2013-2018). The primary endpoint was ambulation at 1 year either independently or with assistance. The cohort was divided into 80% derivation and 20% validation. Using the derivation set, a multivariable model identified preoperatively available independent predictors of 1 year ambulation and an integer-based risk-score was created. Scores were calculated to assign patients to risk groups-low, medium, or high chance of being ambulatory at 1 year. Internal validation was performed by applying the risk score to the validation set. Of 8725 AKA/BKA, 2055 met inclusion criteria-excluded: 2644 nonambulatory prior to amputation, 3753 missing 1-year follow-up ambulatory status. The majority-n = 1366, 66% were BKAs. The indications were CLTI; 47%, ischemic tissue loss; 9%, ischemic rest pain; 35%, infection/neuropathic; 9%, acute limb ischemia. Ambulation at 1 year was higher for BKA than AKA: 67%, versus 50%, p < .0001. In the final prediction model, contralateral BKA/AKA was the strongest predictor of nonambulation. The score provided reasonable discrimination (C-statistic = 0.65) and was well calibrated (Hosmer-Lemeshow p = .24). Sixty-two percent of patients who were ambulatory preoperatively remained ambulatory at 1 year. An integer-based risk score can stratify patients according to chance of ambulation at 1 year after major amputation and may be useful for preoperative patient counseling and selection.

Late type III endoleaks are common in early generation Endologix AFX stent grafts.

OBJECTIVE: Early generation Endologix AFX endovascular abdominal aortic aneurysm (AAA) stent graft devices are at risk of developing type IIIa (intercomponent/overlap-related) as well as type IIIb (fabric tear) endoleaks over time. Current follow-up studies are limited to short (<24 months) and midterm (24-48 months) reports. The purpose of this study was to identify the incidence of type III endoleaks associated with these endografts over a long-term follow-up (>4 years) period and discuss current management strategies. METHODS: A retrospective, single-institution cohort analysis of all Endologix AFX endografts implanted from October 2011 to October 2016 was performed. Patient characteristics, imaging, and follow-up were obtained via chart review. Type III endoleaks were characterized based on computed tomography angiogram/operative findings and confirmed by two surgeons. Statistical analysis was performed with SAS v9.4. RESULTS: Sixty-three patients underwent AFX stent graft implantation for aneurysmal disease. Forty-seven patients comprised the final cohort for analysis after exclusions were made for primary iliac aneurysms as well as off-label use of the device (eg, hypogastric snorkel) or primary occlusive indications. The average age was 73.3 years, with the longest follow-up being 8.7 years (median, 5.2 years). Most AAAs (89.2%) were fusiform, with initial median diameter 5.5 cm. Initial 30-day mortality was 0%. Of the initial cohort, 10 (21.3%) type III endoleaks were treated, of which six (60%) were type IIIa and four (40%) were type IIIb. By time-to-event analysis at latest follow-up, freedom from type III intervention was 48% at 8 years. The median time to type III endoleak discovery was 4.7 years (range, 1.1-7.2 years), an interval that was similar for type IIIa and type IIIb leak types (P = .73). Patients with type III endoleaks had average sac growth of 1.3 cm over the follow-up interval compared with a net decrease for patients without type III endoleaks (P < .0001). Of the 10 patients treated for type III leaks, seven (70%) underwent complete endovascular re-lining, one (10%) had partial re-lining, and two (20.0%) underwent open endograft explant with aortic graft reconstruction. Reintervention 30-day mortality was 0% for all approaches. CONCLUSIONS: Early generation Endologix AFX stent grafts have a high rate of type III endoleaks, with freedom from type III leak <50% at 8-year follow-up. Most of these are not detected until several years (>4.5 years) after initial implantation, beyond the range of the follow-up interval of most published reports. Long-term imaging surveillance is critical, and a low threshold for complete relining should be considered with any sign of sac enlargement, even if endoleak is not clearly demonstrated in patients with early generation Endologix AFX grafts.

Vascular surgery-related violations of the Emergency Medical Treatment and Labor Act.

OBJECTIVE: The Emergency Medical Treatment and Labor Act (EMTALA) is a federal law established in 1986 to ensure that patients who present to an emergency department receive medical care regardless of means. Violations are reported to the Centers for Medicare and Medicaid Services and can result in significant financial penalties. Our objective was to assess all available EMTALA violations for vascular-related issues. METHODS: EMTALA violations in the Centers for Medicare and Medicaid Services publicly available hospital violations database from 2011 to 2018 were evaluated for vascular-related issues. Details recorded were case type, hospital type, hospital region, reasons for violation, disposition, and mortality. RESULTS: There were 7001 patients identified with any EMTALA violation and 98 (1.4%) were deemed vascular related. The majority (82.7%) of EMTALA violations occurred at urban/suburban hospitals. Based on the Association of American Medical Colleges United States region, vascular-related EMTALA violations occurred in the Northeast (7.1%), Southern (56.1%), Central (18.4%), and Western (18.4%) United States. Case types included cerebrovascular (28.6%), aortic related (22.4%; which consisted of ruptured aortic aneurysms [8.2%], aortic dissection [11.2%], and other aortic [3.1%]), vascular trauma (15.3%), venous-thromboembolic (15.3%), peripheral arterial disease (9.2%), dialysis access (5.1%), bowel ischemia (3.1%), and other (1%) cases. Patients were transferred to another facility in 41.8% of cases. The most common reasons for violation were specialty refusal or unavailability (30.6%), inappropriate documentation (29.6%), misdiagnosis (18.4%), poor communication (17.3%), inappropriate triage (13.3%), failure to obtain diagnostic laboratory tests or imaging (12.2%), and ancillary or nursing staff issues (7.1%). The overall mortality was 19.4% and 31.6% died during the index emergency department visit. Vascular conditions associated with death were venous thromboembolism (31.6%), ruptured aortic aneurysm (21.1%), aortic dissection (21.1%), other aortic causes (10.5%), vascular trauma (10.5%), and bowel ischemia (5.3%). CONCLUSIONS: Although the frequency of vascular-related EMTALA violations was low, improvements in communication, awareness of vascular disease among staff, specialty staffing, and the development of referral networks and processes are needed to ensure that patients receive adequate care and that institutions are not placed at undue risk.

Outcomes following ipsilateral great saphenous vein bypass for lower extremity arterial injuries.

OBJECTIVE: Use of autologous great saphenous vein (GSV) grafts for repair of extremity arterial injuries is well established. Contralateral great saphenous vein (cGSV) is traditionally used in the setting of lower extremity vascular injury given the risk of occult ipsilateral superficial and deep venous injury. We evaluated outcomes of ipsilateral GSV (iGSV) bypass in patients with lower extremity vascular trauma. METHODS: Patient records at an ACS verified Level I urban trauma center between 2001 and 2019 were retrospectively reviewed. Patients who sustained lower extremity arterial injuries managed with autologous GSV bypass were included. Propensity-matched analysis compared the iGSV and cGSV groups. Primary graft patency was assessed via Kaplan-Meier analysis at 1-year and 3-years following the index operation. RESULTS: A total of 76 patients underwent autologous GSV bypass for lower extremity vascular injuries. 61 cases (80%) were secondary to penetrating trauma, and 15 patients (20%) underwent repair with iGSV bypass. Arteries injured in the iGSV group included popliteal (33.3%), common femoral (6.7%), superficial femoral (33.3%), and tibial (26.7%), while those in the cGSV group included common femoral (3.3%), superficial femoral (54.1%), and popliteal (42.6%). Reasons for using iGSV included trauma to the contralateral leg (26.7%), relative accessibility (33.3%), and other/unknown (40%). On unadjusted analysis, iGSV patients had a higher rate of 1-year amputation than cGSV patients (20% vs. 4.9%), but this was not statistically significant (P = 0.09). Propensity matched analysis also found no significant difference in 1-year major amputation (8.3% vs. 4.8%, P = 0.99). Regarding ambulatory status, iGSV patients had similar rates of independent ambulation (33.3% vs. 38.1%), need for assistive devices (58.3% vs. 57.1%), and use of a wheelchair (8.3% vs. 4.8%) compared cGSV patients at subsequent follow-up (P = 0.90). Kaplan-Meier analysis of bypass grafts revealed comparable primary patency rates for iGSV versus cGSV bypasses at 1-year (84% vs. 91%) and 3-years post-intervention (83% vs. 90%, P = 0.364). CONCLUSION: Ipsilateral GSV may be used as a durable conduit for bypass in cases of lower extremity arterial trauma where use of contralateral GSV is not feasible, with comparable long-term primary graft patency rates and ambulatory status.

Pediatric laryngeal tumors and demographics, management, and survival in laryngeal squamous cell carcinoma.

OBJECTIVES: To evaluate the prevalence and features of pediatric laryngeal malignancies and to review the demographics, management, and survival of pediatric patients with laryngeal squamous cell carcinoma as compared to adult patients. METHODS: Patients aged 0 (younger than 1) to 18 with laryngeal malignancy identified in the Surveillance, Epidemiology, and End Results (SEER) database were included from 1973 to 2016 published April 2019. Diagnosis of malignant laryngeal tumor was made using the 3rd edition of the International Classification of Diseases for Oncology (ICDO-3) code: C32.0 Glottis, C32.1 Supraglottis, C32.2Subglottis, andC32.9 Larynx primary site. RESULTS: 23 cases of pediatric laryngeal malignancies were identified. 16 cases were squamous cell carcinomas and 7 were other histologic types. Pediatric laryngeal SCC tended to be diagnosed in adolescence (mean age 14.8 years, range younger than 1 to 18, 82.6% of cases were age 12 and above). Management of laryngeal SCC included no recorded treatment (18.8%), primary radiation (18.8%), primary surgery (12.5%), radiation and surgery (25%), radiation and chemotherapy combined (18.8%), and surgery with radiation and chemotherapy (12.5%). Surgeries were local excision, excision and lymphnode dissection, as well as total laryngectomy, and not otherwise specified. The 2-year and 5-year overall and disease-specific survivals were 78.6%. CONCLUSIONS: Pediatric laryngeal cancer is rare. Squamous cell carcinoma is the most commonly diagnosed malignant laryngeal histology affecting pediatric patients. Despite different risk factors, survival rates remain similar for pediatric patients with laryngeal squamous cell carcinoma as compared to adults. Physicians should include laryngeal cancer in the differential for pediatric patients with hoarseness, dysphagia, and progressive airway obstruction to avoid a late diagnosis.

Cord blood maternal microchimerism following unrelated cord blood transplantation.

Cord blood transplantation (CBT) is associated with low risk of leukemia relapse. Mechanisms underlying antileukemia benefit of CBT are not well understood, however a previous study strongly but indirectly implicated cells from the mother of the cord blood (CB) donor. A fetus acquires a small number of maternal cells referred to as maternal microchimerism (MMc) and MMc is sometimes detectable in CB. From a series of 95 patients who underwent double or single CBT at our center, we obtained or generated HLA-genotyping of CB mothers in 68. We employed a technique of highly sensitive HLA-specific quantitative-PCR assays targeting polymorphisms unique to the CB mother to assay CB-MMc in patients post-CBT. After additional exclusion criteria, CB-MMc was evaluated at multiple timepoints in 36 patients (529 specimens). CB-MMc was present in seven (19.4%) patients in bone marrow, peripheral blood, innate and adaptive immune cell subsets, and was detected up to 1-year post-CBT. Statistical trends to lower relapse, mortality, and treatment failure were observed for patients with vs. without CB-MMc post-CBT. Our study provides proof-of-concept that maternal cells of the CB graft can be tracked in recipients post-CBT, and underscore the importance of further investigating CB-MMc in sustained remission from leukemia following CBT.

Complement C5a Fosters Squamous Carcinogenesis and Limits T Cell Response to Chemotherapy.

Complement is a critical component of humoral immunity implicated in cancer development; however, its biological contributions to tumorigenesis remain poorly understood. Using the K14-HPV16 transgenic mouse model of squamous carcinogenesis, we report that urokinase (uPA)+ macrophages regulate C3-independent release of C5a during premalignant progression, which in turn regulates protumorigenic properties of C5aR1+ mast cells and macrophages, including suppression of CD8+ T cell cytotoxicity. Therapeutic inhibition of C5aR1 via the peptide antagonist PMX-53 improved efficacy of paclitaxel chemotherapy associated with increased presence and cytotoxic properties of CXCR3+ effector memory CD8+ T cells in carcinomas, dependent on both macrophage transcriptional programming and IFNγ. Together, these data identify C5aR1-dependent signaling as an important immunomodulatory program in neoplastic tissue tractable for combinatorial cancer immunotherapy.

Maternal microchimerism is prevalent in cord blood in memory T cells and other cell subsets, and persists post-transplant.

Among reported advantages of umbilical cord blood (CB) in transplantation is lower leukemia relapse probability. Underlying cellular mechanisms of graft-vs.-leukemia (GVL) are thought to include a prominent role for T cells. Cells of the CB's mother, maternal microchimerism (MMc), were recently strongly, but indirectly, implicated in this GVL benefit. We assayed MMc directly and hypothesized benefit accrues from CB maternal T cells. MMc was quantified in 51 CBs and, within memory T, naïve T, B, NK cells, and monocytes in 27 CBs. Polymorphism-specific quantitative-PCR assays targeted maternal genotypes non-shared with CBs. Overall MMc was common and often at substantial levels. It was present in 52.9% of CB and in 33.3-55.6% of tested subsets. Remarkably, MMc quantities were greater in memory T cells than other subsets (p < 0.001). Expressed as genome equivalents (gEq) per 105 total gEq tested (gEq/105), memory T cell MMc averaged 850.2 gEq/105, while other subset mean quantities were 13.8-30.1 gEq/105. After adjustment for proportionality in CB, MMc remained 6-17 times greater in memory T, and 3-9 times greater in naïve T, vs. non-T-cell subsets. Further, CB-origin MMc was detected in vivo in a patient up to 6 mo post-transplantation, including among T cells. Overall, results revealed levels and phenotypes of CB MMc with potential relevance to CB transplantation and, more broadly, to offspring health.