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.

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.

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.

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.

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.