Transforming the Future of Surgeon-Scientists.

OBJECTIVE: To create a blueprint for surgical department leaders, academic institutions, and funding agencies to optimally support surgeon-scientists. BACKGROUND: Scientific contributions by surgeons have been transformative across many medical disciplines. Surgeon-scientists provide a distinct approach and mindset toward key scientific questions. However, lack of institutional support, pressure for increased clinical productivity, and growing administrative burden are major challenges for the surgeon-scientist, as is the time-consuming nature of surgical training and practice. METHODS: An American Surgical Association Research Sustainability Task Force was created to outline a blueprint for sustainable science in surgery. Leaders from top NIH-sponsored departments of surgery engaged in video and in-person meetings between January and April 2023. A strength, weakness, opportunities, threats analysis was performed, and workgroups focused on the roles of surgeons, the department and institutions, and funding agencies. RESULTS: Taskforce recommendations: (1) SURGEONS: Growth mindset : identifying research focus, long-term planning, patience/tenacity, team science, collaborations with disparate experts; Skill set : align skills and research, fill critical skill gaps, develop team leadership skills; DEPARTMENT OF SURGERY (DOS): (2) MENTORSHIP: Chair : mentor-mentee matching/regular meetings/accountability, review of junior faculty progress, mentorship training requirement, recognition of mentorship (eg, relative value unit equivalent, awards; Mentor: dedicated time, relevant scientific expertise, extramural funding, experience and/or trained as mentor, trusted advisor; Mentee : enthusiastic/eager, proactive, open to feedback, clear about goals; (3) FINANCIAL SUSTAINABILITY: diversification of research portfolio, identification of matching funding sources, departmental resource awards (eg, T-/P-grants), leveraging of institutional resources, negotiation of formalized/formulaic funds flow investment from academic medical center toward science, philanthropy; (4) STRUCTURAL/STRATEGIC SUPPORT: Structural: grants administrative support, biostats/bioinformatics support, clinical trial and research support, regulatory support, shared departmental laboratory space/equipment; Strategic: hiring diverse surgeon-scientist/scientists faculty across DOS, strategic faculty retention/ recruitment, philanthropy, career development support, progress tracking, grant writing support, DOS-wide research meetings, regular DOS strategic research planning; (5) COMMUNITY AND CULTURE: Community: right mix of faculty, connection surgeon with broad scientific community; Culture: building research infrastructure, financial support for research, projecting importance of research (awards, grand rounds, shoutouts); (6) THE ROLE OF INSTITUTIONS: Foundation: research space co-location, flexible start-up packages, courses/mock study section, awards, diverse institutional mentorship teams; Nurture: institutional infrastructure, funding (eg, endowed chairs), promotion friendly toward surgeon-scientists, surgeon-scientists in institutional leadership positions; Expectations: RVU target relief, salary gap funding, competitive starting salaries, longitudinal salary strategy; (7) THE ROLE OF FUNDING AGENCIES: change surgeon research training paradigm, offer alternate awards to K-awards, increasing salary cap to reflect market reality, time extension for surgeon early-stage investigator status, surgeon representation on study section, focused award strategies for professional societies/foundations. CONCLUSIONS: Authentic recommitment from surgeon leaders with intentional and ambitious actions from institutions, corporations, funders, and society is essential in order to reap the essential benefits of surgeon-scientists toward advancements of science.

An exercise stress test for contrast-enhanced duplex ultrasound assessment of lower limb muscle perfusion in patients with peripheral arterial disease.

OBJECTIVE: The aim of the present study was to develop a standardized contrast-enhanced duplex ultrasound (CE-DUS) protocol to assess lower-extremity muscle perfusion before and after exercise and determine relationships of perfusion with clinical and functional measures. METHODS: CE-DUS (EPIQ 5G, Philips) was used before and immediately after a 10-minute, standardized bout of treadmill walking to compare microvascular perfusion of the gastrocnemius muscle in older (55-82 years) patients with peripheral arterial disease (PAD) (n = 15, mean ankle-brachial index, 0.78 ± 0.04) and controls (n = 13). Microvascular blood volume (MBV) and microvascular flow velocity (MFV) were measured at rest and immediately following treadmill exercise, and the Modified Physical Performance Test (MPPT) was used to assess mobility function. RESULTS: In the resting state (pre-exercise), MBV in patients with PAD was not significantly different than normal controls (5.17 ± 0.71 vs 6.20 ± 0.83 arbitrary units (AU) respectively; P = .36); however, after exercise, MBV was ∼40% lower in patients with PAD compared with normal controls (5.85 ± 1.13 vs 9.53 ± 1.31 AU, respectively; P = .04). Conversely, MFV was ∼60% higher in patients with PAD compared with normal controls after exercise (0.180 ± 0.016 vs 0.113 ± 0.018 AU, respectively; P = .01). There was a significant between-group difference in the exercise-induced changes in both MBV and MFV (P ≤ .05). Both basal and exercise MBV directly correlated with MPPT score in the patients with PAD (r = 0.56-0.62; P < .05). CONCLUSIONS: This standardized protocol for exercise stress testing of the lower extremities quantifies calf muscle perfusion and elicits perfusion deficits in patients with PAD. This technique objectively quantifies microvascular perfusion deficits that are related to reduced mobility function and could be used to assess therapeutic efficacy in patients with PAD.

Cognitive impairment in asymptomatic carotid artery stenosis is associated with abnormal segments in the Circle of Willis.

OBJECTIVE: Our group has previously demonstrated that patients with asymptomatic carotid artery stenosis (ACAS) demonstrate cognitive impairment. One proposed mechanism for cognitive impairment in patients with ACAS is cerebral hypoperfusion due to flow-restriction. We tested whether the combination of a high-grade carotid stenosis and inadequate cross-collateralization in the Circle of Willis (CoW) resulted in worsened cognitive impairment. METHODS: Twenty-four patients with high-grade (≥70% diameter-reducing) ACAS underwent carotid duplex ultrasound, cognitive assessment, and 3D time-of-flight magnetic resonance angiography. The cognitive battery consisted of nine neuropsychological tests assessing four cognitive domains: learning and recall, attention and working memory, motor and processing speed, and executive function. Raw cognitive scores were converted into standardized T-scores. A structured interpretation of the magnetic resonance angiography images was performed with each segment of the CoW categorized as being either normal or abnormal. Abnormal segments of the CoW were defined as segments characterized as narrowed or occluded due to congenital aplasia or hypoplasia, or acquired atherosclerotic stenosis or occlusion. Linear regression was used to estimate the association between the number of abnormal segments in the CoW, and individual cognitive domain scores. Significance was set to P < .05. RESULTS: The mean age of the patients was 66.1 ± 9.6 years, and 79.2% (n = 19) were male. A significant negative association was found between the number of abnormal segments in the CoW and cognitive scores in the learning and recall (ß = -6.5; P = .01), and attention and working memory (ß = -7.0; P = .02) domains. There was a trend suggesting a negative association in the motor and processing speed (ß = -2.4; P = .35) and executive function (ß = -4.5; P = .06) domains that did not reach significance. CONCLUSIONS: In patients with high-grade ACAS, the concomitant presence of increasing occlusive disease in the CoW correlates with worse cognitive function. This association was significant in the learning and recall and attention and working memory domains. Although motor and processing speed and executive function also declined numerically with increasing abnormal segments in the CoW, the relationship was not significant. Since flow restriction at a carotid stenosis compounded by inadequate collateral compensation across a diseased CoW worsens cerebral perfusion, our findings support the hypothesis that cerebral hypoperfusion underlies the observed cognitive impairment in patients with ACAS.

Recent advances and controversial issues in the optimal management of asymptomatic carotid stenosis.

OBJECTIVE: The optimal management of patients with asymptomatic carotid stenosis (AsxCS) is enduringly controversial. We updated our 2021 Expert Review and Position Statement, focusing on recent advances in the diagnosis and management of patients with AsxCS. METHODS: A systematic review of the literature was performed up to August 1, 2023, using PubMed/PubMed Central, EMBASE and Scopus. The following keywords were used in various combinations: "asymptomatic carotid stenosis," "carotid endarterectomy" (CEA), "carotid artery stenting" (CAS), and "transcarotid artery revascularization" (TCAR). Areas covered included (i) improvements in best medical treatment (BMT) for patients with AsxCS and declining stroke risk, (ii) technological advances in surgical/endovascular skills/techniques and outcomes, (iii) risk factors, clinical/imaging characteristics and risk prediction models for the identification of high-risk AsxCS patient subgroups, and (iv) the association between cognitive dysfunction and AsxCS. RESULTS: BMT is essential for all patients with AsxCS, regardless of whether they will eventually be offered CEA, CAS, or TCAR. Specific patient subgroups at high risk for stroke despite BMT should be considered for a carotid revascularization procedure. These patients include those with severe (≥80%) AsxCS, transcranial Doppler-detected microemboli, plaque echolucency on Duplex ultrasound examination, silent infarcts on brain computed tomography or magnetic resonance angiography scans, decreased cerebrovascular reserve, increased size of juxtaluminal hypoechoic area, AsxCS progression, carotid plaque ulceration, and intraplaque hemorrhage. Treatment of patients with AsxCS should be individualized, taking into consideration individual patient preferences and needs, clinical and imaging characteristics, and cultural, ethnic, and social factors. Solid evidence supporting or refuting an association between AsxCS and cognitive dysfunction is lacking. CONCLUSIONS: The optimal management of patients with AsxCS should include BMT for all individuals and a prophylactic carotid revascularization procedure (CEA, CAS, or TCAR) for some asymptomatic patient subgroups, additionally taking into consideration individual patient needs and preference, clinical and imaging characteristics, social and cultural factors, and the available stroke risk prediction models. Future studies should investigate the association between AsxCS with cognitive function and the role of carotid revascularization procedures in the progression or reversal of cognitive dysfunction.

An international, multispecialty, expert-based Delphi Consensus document on controversial issues in the management of patients with asymptomatic and symptomatic carotid stenosis.

OBJECTIVE: Despite the publication of various national/international guidelines, several questions concerning the management of patients with asymptomatic (AsxCS) and symptomatic (SxCS) carotid stenosis remain unanswered. The aim of this international, multi-specialty, expert-based Delphi Consensus document was to address these issues to help clinicians make decisions when guidelines are unclear. METHODS: Fourteen controversial topics were identified. A three-round Delphi Consensus process was performed including 61 experts. The aim of Round 1 was to investigate the differing views and opinions regarding these unresolved topics. In Round 2, clarifications were asked from each participant. In Round 3, the questionnaire was resent to all participants for their final vote. Consensus was reached when ≥75% of experts agreed on a specific response. RESULTS: Most experts agreed that: (1) the current periprocedural/in-hospital stroke/death thresholds for performing a carotid intervention should be lowered from 6% to 4% in patients with SxCS and from 3% to 2% in patients with AsxCS; (2) the time threshold for a patient being considered "recently symptomatic" should be reduced from the current definition of "6 months" to 3 months or less; (3) 80% to 99% AsxCS carries a higher risk of stroke compared with 60% to 79% AsxCS; (4) factors beyond the grade of stenosis and symptoms should be added to the indications for revascularization in AsxCS patients (eg, plaque features of vulnerability and silent infarctions on brain computed tomography scans); and (5) shunting should be used selectively, rather than always or never. Consensus could not be reached on the remaining topics due to conflicting, inadequate, or controversial evidence. CONCLUSIONS: The present international, multi-specialty expert-based Delphi Consensus document attempted to provide responses to several unanswered/unresolved issues. However, consensus could not be achieved on some topics, highlighting areas requiring future research.

When Will We Have What We Need to Advise Patients How to Manage Their Carotid Stenosis?: Lessons From SPACE-2.

The recently published SPACE-2 trial (Stent-Supported Percutaneous Angioplasty of the Carotid Artery Versus Endarterectomy-2) compared 3 treatments to prevent stroke in patients with asymptomatic carotid stenosis ≥70%: (1) carotid endarterectomy plus best medical treatment (BMT), (2) transfemoral carotid artery stenting plus BMT, or (3) BMT alone. Because of low enrollment, the findings of similar safety and efficacy for carotid endarterectomy, carotid artery stenting, or BMT alone were inconclusive. Publication of the CREST (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial)-2 results should provide level A evidence that has been lacking for 2 to 3 decades, to guide treatment of asymptomatic patients with severe carotid stenosis. For symptomatic patients with ≥70% stenosis, no trials are underway to update the degree of benefit reported for carotid endarterectomy by NASCET (North American Carotid Endarterectomy Trial) and ECST (European Carotid Surgery Trial), published in 1991. Subsequently, the use of cigarettes has plummeted, and major improvements in medical treatments and in carotid revascularization have emerged. These advances have coincided with abrupt decline in the clinical end points necessary for treatment comparisons in procedural trials. One of the advances in the invasive management of carotid disease has been transcarotid artery revascularization, already with limited approval by the US Food and Drug Administration. Establishing safety and efficacy of transcarotid artery revascularization compared with carotid endarterectomy, carotid artery stenting, or BMT alone may be challenging because of enrollment, regulatory, and funding barriers to design and complete an adequately powered randomized trial.

Mid-term Surgery Outcomes in Patients With COVID-19: Results From a Nationwide Analysis.

OBJECTIVE: Determine mid-term postoperative outcomes among coronavirus disease 2019 (COVID-19)-positive (+) patients compared with those who never tested positive before surgery. BACKGROUND: COVID-19 is thought to be associated with prohibitively high rates of postoperative complications. However, prior studies have only evaluated 30-day outcomes, and most did not adjust for demographic, clinical, or procedural characteristics. METHODS: We analyzed data from surgeries performed at all Veterans Affairs hospitals between March 2020 and 2021. Kaplan-Meier curves compared trends in mortality and Cox proportional hazards models estimated rates of mortality and pulmonary, thrombotic, and septic postoperative complications between patients with a positive preoperative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test [COVID (+)] and propensity score-matched COVID-negative (-) patients. RESULTS: Of 153,741 surgical patients, 4778 COVID (+) were matched to 14,101 COVID (-). COVID (+) status was associated with higher postoperative mortality ( P <0.0001) with a 6-month survival of 94.2% (95% confidence interval: 93.2-95.2) versus 96.0% (95% confidence interval: 95.7.0-96.4) in COVID (-). The highest mortality was in the first 30 postoperative days. Hazards for mortality and postoperative complications in COVID (+) decreased with increasing time between testing COVID (+) and date of surgery. COVID (+) patients undergoing elective surgery had similar rates of mortality, thrombotic and septic complications, but higher rates of pulmonary complications than COVID (-) patients. CONCLUSIONS: This is the first report of mid-term outcomes among COVID-19 patients undergoing surgery. COVID-19 is associated with decreased overall and complication-free survival primarily in the early postoperative period, delaying surgery by 5 weeks or more reduces risk of complications. Case urgency has a multiplicative effect on short-term and long-term risk of postoperative mortality and complications.

The Thresholds of Caprini Score Associated With Increased Risk of Venous Thromboembolism Across Different Specialties: A Systematic Review.

OBJECTIVE: Estimation of the specific thresholds of the Caprini risk score (CRS) that are associated with the increased incidence of venous thromboembolism (VTE) across different specialties, including identifying the highest level of risk. BACKGROUND: Accurate risk assessment remains an important but often challenging aspect of VTE prophylaxis. One well-established risk assessment model is CRS, which has been validated in thousands of patients from many different medical and surgical specialties. METHODS: A search of MEDLINE and the Cochrane Library was performed in March 2022. Manuscripts that reported on (1) patients admitted to medical or surgical departments and (2) had their VTE risk assessed by CRS and (3) reported on the correlation between the score and VTE incidence, were included in the analysis. RESULTS: A total of 4562 references were identified, and the full text of 202 papers was assessed for eligibility. The correlation between CRS and VTE incidence was reported in 68 studies that enrolled 4,207,895 patients. In all specialties, a significant increase in VTE incidence was observed in patients with a CRS of ≥5. In most specialties thresholds of ≥7, ≥9, and ≥11 to 12 were associated with dramatically increased incidences of VTE. In COVID-19, cancer, trauma, vascular, general, head and neck, and thoracic surgery patients with ≥9 and ≥11 to 12 scores the VTE incidence was extremely high (ranging from 13% to 47%). CONCLUSION: The Caprini score is being used increasingly to predict VTE in many medical and surgical specialties. In most cases, the VTE risk for individual patients increases dramatically at a threshold CRS of 7 to 11.

Growing Deficit in New Cancer Diagnoses 2 Years Into the COVID-19 Pandemic: A National Multicenter Study.

BACKGROUND: Large decreases in cancer diagnoses were seen early in the COVID-19 pandemic. However, the evolution of these deficits since the end of 2020 and the advent of widespread vaccination is unknown. METHODS: This study examined data from the Veterans Health Administration (VA) from 1 January 2018 through 28 February 2022 and identified patients with screening or diagnostic procedures or new cancer diagnoses for the four most common cancers in the VA health system: prostate, lung, colorectal, and bladder cancers. Monthly procedures and new diagnoses were calculated, and the pre-COVID era (January 2018 to February 2020) was compared with the COVID era (March 2020 to February 2022). RESULTS: The study identified 2.5 million patients who underwent a diagnostic or screening procedure related to the four cancers. A new cancer was diagnosed for 317,833 patients. During the first 2 years of the pandemic, VA medical centers performed 13,022 fewer prostate biopsies, 32,348 fewer cystoscopies, and 200,710 fewer colonoscopies than in 2018-2019. These persistent deficits added a cumulative deficit of nearly 19,000 undiagnosed prostate cancers and 3300 to 3700 undiagnosed cancers each for lung, colon, and bladder. Decreased diagnostic and screening procedures correlated with decreased new diagnoses of cancer, particularly cancer of the prostate (R = 0.44) and bladder (R = 0.27). CONCLUSION: Disruptions in new diagnoses of four common cancers (prostate, lung, bladder, and colorectal) seen early in the COVID-19 pandemic have persisted for 2 years. Although reductions improved from the early pandemic, new reductions during the Delta and Omicron waves demonstrate the continued impact of the COVID-19 pandemic on cancer care.

Health Screening Program to Enhance Enrollment of Women and Minorities in CREST-2.

BACKGROUND AND PURPOSE: The CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial) consists of 2 parallel randomized stroke prevention trials in patients with asymptomatic high-grade stenosis of the cervical carotid artery. The purpose of this report is to detail the outcomes of a health screening effort to increase trial enrollment of women and minorities. METHODS: Life Line screening (LLS) conducts nationwide screening for vascular disease. Screenings within a 50-mile radius of each CREST-2 center were identified for participation in a joint CREST-LLS program over the course of one year (November 2018 to October 2019) whereby patients with an abnormal carotid ultrasound were referred to the local CREST-2 center for further workup, management, and potential consideration for trial enrollment. RESULTS: LLS completed the screening of 588 198 individuals in 29 732 zip codes across the United States. Of those, 230 021 individuals were screened at events occurring near a CREST-2 clinical center and 646 (0.3%) were found to have abnormal carotid ultrasound findings. Each of the 646 individuals was contacted by CREST-LLS program staff for permission to be referred to their local CREST-2 center; 200 (31%) consented to be contacted by CREST-2. Of those, 39 (19.5%) agreed to be, and were, evaluated at their local CREST-2 center. High-grade stenosis was confirmed in 27 patients. A total of 3 patients were eligible for the trial and were enrolled, one woman but no racial/ethnic minorities. CONCLUSIONS: The LLS program appears to identify community-living individuals with high-grade carotid stenosis through ultrasonography. However, the prevalence of abnormal carotid findings was low. In addition, screening and offering participation into the CREST-2 trial had no substantial impact on the proportion of women and minorities enrolled in the trial. Additional innovative strategies are needed to promote enrollment of diverse patients with carotid stenosis into stroke prevention trials.

Impact of the COVID-19 pandemic on diagnosis of new cancers: A national multicenter study of the Veterans Affairs Healthcare System.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused disruptions in treatment for cancer. Less is known about its impact on new cancer diagnoses, where delays could cause worsening long-term outcomes. This study quantifies decreases in encounters related to prostate, lung, bladder and colorectal cancers, procedures that facilitate their diagnosis, and new diagnoses of those cancers in the COVID era compared to pre-COVID era. METHODS: All encounters at Veterans' Affairs facilities nationwide from 2016 through 2020 were reviewed. The authors quantified trends in new diagnoses of cancer and in procedures facilitating their diagnosis, from January 1, 2018 onward. Using 2018 to 2019 as baseline, reductions in procedures and new cancer diagnoses in 2020 were estimated. Calculated absolute and percentage differences in annual volume and observed-to-expected volume ratios were calculated. Heat maps and funnel plots of volume changes were generated. RESULTS: From 2018 through 2020, there were 4.1 million cancer-related encounters, 3.9 million relevant procedures, and 251,647 new cancers diagnosed. Compared to the annual averages in 2018 through 2019, colonoscopies in 2020 decreased by 45% whereas prostate biopsies, chest computed tomography scans, and cystoscopies decreased by 29%, 10%, and 21%, respectively. New cancer diagnoses decreased by 13% to 23%. These drops varied by state and continued to accumulate despite reductions in pandemic-related restrictions. CONCLUSION: The authors identified substantial reductions in procedures used to diagnose cancer and subsequent reductions in new diagnoses of cancer across the United States because of the COVID-19 pandemic. A nomogram is provided to identify and resolve these unmet health care needs and avoid worse long-term cancer outcomes. LAY SUMMARY: The disruptions due to the COVID-19 pandemic have led to substantial reductions in new cancers being diagnosed. This study quantifies those reductions in a national health care system and offers a method for understanding the backlog of cases and the resources needed to resolve them.

COVID-19 Vaccination Associated With Reduced Postoperative SARS-CoV-2 Infection and Morbidity.

OBJECTIVE: The purpose of this study was to determine the effect of COVID-19 vaccination on postoperative mortality, pulmonary and thrombotic complications, readmissions and hospital lengths of stay among patients undergoing surgery in the United States. BACKGROUND: While vaccination prevents COVID-19, little is known about its impact on postoperative complications. METHODS: This is a nationwide observational cohort study of all 1,255 Veterans Affairs facilities nationwide. We compared patients undergoing surgery at least 2 weeks after their second dose of the Pfizer BioNTech or Moderna vaccines, to contemporary propensity score matched controls. Primary endpoints were 30-day mortality and postoperative COVID-19 infection. Secondary endpoints were pulmonary or thrombotic complications, readmissions, and hospital lengths of stay. RESULTS: 30,681 patients met inclusion criteria. After matching, there were 3,104 in the vaccination group (1,903 received the Pfizer BioNTech, and 1,201 received the Moderna vaccine) and 7,438 controls. Full COVID-19 vaccination was associated with lower rates of postoperative 30-day COVID-19 infection (Incidence Rate Ratio and 95% confidence intervals, 0.09 [0.01,0.44]), pulmonary complications (0.54 [0.39, 0.72]), thrombotic complications (0.68 [0.46, 0.99]) and decreased hospital lengths of stay (0.78 [0.69, 0.89]). Complications were also low in vaccinated patients who tested COVID-19 positive before surgery but events were too few to detect a significant difference compared to controls. CONCLUSION: COVID-19 vaccination is associated with lower rates of postoperative morbidity. The benefit is most pronounced among individuals who have never had a COVID-19 infection before surgery.

Learning curve and proficiency metrics for transcarotid artery revascularization.

BACKGROUND: When introduced to a new procedure, physicians improve their performance and reduce their procedural adverse event rates rapidly during the initial cases and then improvement slows, signaling that proficiency has been achieved. Determining when they have acquired proficiency has important implications for procedural innovation, education, credentialing, and patient safety. We analyzed the worldwide experience with transcarotid artery revascularization (TCAR), a hybrid approach to carotid revascularization, to identify the (1) procedural performance measures associated with clinical and technical adverse events; (2) target levels of performance measures that minimize adverse event rates; and (3) number of TCAR cases needed to achieve the target levels for the performance measures. METHODS: The patient, lesion, and physician characteristics were collected for each TCAR procedure performed by each physician worldwide in an international quality assurance database. Four procedural performance measures were recorded for each procedure: flow-reversal time, fluoroscopy time, contrast volume, and total skin-to-skin time. Composite clinical adverse events (ie, transient ischemic attack, stroke, myocardial infarction, death) and composite technical adverse events (ie, aborted procedure, conversion to surgery, bleeding, dissection, cranial nerve injury, device failure), occurring within 24 hours were also recorded. Correlations between each performance measure and the clinical and technical adverse event rates were computed. The inflection points in the performance measures were identified at which no further improvements occurred in the adverse event rates. Finally, the minimum number of TCAR cases required to achieve the target performance measure levels was computed. RESULTS: A total of 18,240 procedures performed by 1273 physicians were analyzed. Of the 18,240 patients, 34.9% were women and 62.5% were asymptomatic. The flow-reversal time correlated with clinical adverse events adjusted for age, sex, and symptomatic status (R2 = 0.91; P < .0001) and adjusted technical adverse events (R2 = 0.86; P < .0001). The skin-to-skin time correlated with adjusted technical adverse events (R2 = 0.92; P < .0001). A reduction in flow-reversal times to <13.1 minutes and the skin-to-skin time to <81 minutes did not translate into further improvements in the adverse event rates. A minimum of 26 TCAR cases was required to achieve the target flow-reversal time, and a minimum of 15 cases was required to achieve the target skin-to-skin time. CONCLUSIONS: The flow-reversal time and skin-to-skin time are appropriate performance measures for establishing the level of expertise of physicians as they acquire skills to perform TCAR. A target time of ≤13.1 minutes for flow-reversal and 81 minutes for skin-to-skin time minimized the adverse event rates. Familiarity with the steps involved in performing TCAR was achieved after ≥15 cases, and minimizing clinical adverse events occurred after ≥26 cases.

Transcarotid revascularization outcomes do not differ by patient age or sex.

BACKGROUND: Transcarotid artery revascularization (TCAR) is a hybrid approach to carotid revascularization. Limited information is available on the differences in periprocedural complications and performance measures of TCAR for men compared with women and for older vs younger adults. METHODS: The patient, lesion, and physician characteristics were collected for all TCAR procedures performed by each physician worldwide in an international quality assurance database between March 3, 2009 and May 7, 2020. Clinical composite (ie, death, stroke, transient ischemic attack, myocardial infarction) and technical composite (ie, aborted procedure, conversion to surgery, bleeding, dissection, cranial nerve injury, device failure) adverse events within 24 hours of the procedure were recorded. Four performance measures were recorded: flow-reversal time, fluoroscopy time, contrast volume, and skin-to-skin time. Poisson regressions were used to assess the effects of age and sex on the incidence of clinical and technical composite adverse events. Linear regressions were used to compare the four performance measures. RESULTS: A total of 18,240 TCARs were performed by 1273 physicians; 34.9% of the patients were women and 37.5% were symptomatic. The overall incidence of clinical and technical composite adverse events was low. The adjusted clinical (1.62% [95% confidence interval (CI), 1.17%-2.23%] vs 1.35% [95% CI, 1.01%-1.79%]; P = .22) and technical (7.84% [95% CI, 6.85%-8.97%] vs 7.80% [95% CI, 6.94%-8.77%]; P = .93) composite adverse event rates did not vary for women vs men. The adjusted clinical (P = .65) and technical (P = .55) composite adverse event rates also did not vary by age. The adjusted skin-to-skin time was shorter for the women (76.6 minutes; 95% CI, 74.6-78.6) than for the men (77.7 minutes; 95% CI, 75.7-79.6; P = .002). Significant differences were found by age group for fluoroscopy time, flow-reversal time, and skin-to-skin time, although the magnitude of these differences was small (<1 minute for each). CONCLUSIONS: The clinical and technical outcomes of TCAR are not affected by age or sex. We found clinically minor differences in the procedural performance measures when stratified by age and sex. In addition to being safe for younger individuals, TCAR could also be the preferred method for performing carotid stenting in women and older patients, in particular, older women.

Evaluating the optimal training paradigm for transcarotid artery revascularization based on worldwide experience.

BACKGROUND: Transcarotid artery revascularization (TCAR) is a new hybrid approach to carotid artery revascularization. Proctored training on live cases is an effort-, time-, and resource-intensive approach to learning new procedures. We analyzed the worldwide experience with TCAR to develop objective performance metrics for the procedure and compared the effectiveness of training physicians using cadavers or synthetic models to that of traditional in-person training on live cases. METHODS: Physicians underwent one of three mandatory training programs: (1) in-person proctoring on live TCAR procedures, (2) supervised training on human cadavers, and (3) supervised training on synthetic models. The training details and information from all subsequent independently performed TCAR procedures were recorded. The composite clinical adverse events (ie, transient ischemic attack, stroke, myocardial infarction, death) and composite technical adverse events (ie, aborted procedure, conversion to surgery, bleeding, dissection, cranial nerve injury, or device failure, occurring within 24 hours were recorded). Four procedural proficiency measures were recorded: procedure time, flow-reversal time, fluoroscopy time, and contrast volume. We compared the adverse event rates between the procedures performed by physicians after undergoing the three training modes and tested whether the proficiency measures achieved during TCAR after training on cadavers and synthetic models were noninferior to proctored training. RESULTS: From March 3, 2009 to May 7, 2020, 1160 physicians had undergone proctored (19.1%), cadaver-based (27.4%), and synthetic model-based (53.5%) TCAR training and had subsequently performed 17,283 TCAR procedures. The proctored physicians had treated younger patients and more patients with asymptomatic carotid stenosis and had had more prior experience with transfemoral carotid stenting. The overall 24-hour composite clinical and technical adverse event rates, adjusted for age, sex, and symptomatic status, were 1.0% (95% confidence interval, 0.8%-1.3%) and 6.0% (95% confidence interval, 5.4%-6.6%), respectively, and did not differ significantly by training mode. The proficiency measures of cadaver-trained and synthetic model-trained physicians were not inferior to those for the proctored physicians. CONCLUSIONS: We have presented key objective proficiency metrics for performing TCAR and an analytic framework to assess adequate training for the procedure. Training on cadavers or synthetic models achieved clinical outcomes, technical outcomes, and proficiency measures for subsequently performed TCAR procedures similar to those achieved with training using traditional proctoring on live cases.

Lack of association between cognitive impairment and systemic inflammation in asymptomatic carotid stenosis.

BACKGROUND: Asymptomatic carotid atherosclerotic stenosis (ACAS) is associated with cognitive impairment. Systemic inflammation occurs in patients with systemic atherosclerosis and is also associated with cognitive impairment. The goal of this study was to determine if cognitive impairment in patients with ACAS is the result of systemic inflammation. METHODS: A cross-sectional analysis of 104 patients (63 patients with ACAS, 41 controls) with cognitive function and inflammatory biomarker assessments was performed. Venous blood was assayed for proinflammatory biomarkers (IL-1ß, IL-6, IL-6R, IL-8, IL-17, tumor necrosis factor-α, matrix metalloproteinase [MMP]-1, MMP-2, MMP-7, MMP-9, vascular cell adhesion molecule, and high-sensitivity C-reactive protein). The patients also underwent comprehensive cognitive testing to compute five domain-specific cognitive scores per patient. We first assessed the associations between carotid stenosis and cognitive function, and between carotid stenosis and systemic inflammation in separate regression models. We then determined whether cognitive impairments persisted in patients with carotid stenosis after accounting for inflammation by adjusting for inflammatory biomarker levels in a combined model. RESULTS: Patients with ACAS and control patients differed in age, race, coronary artery disease prevalence, and education. Stenosis patients had worse cognitive scores in two domains: learning and memory (P = .05) and motor and processing speed (P = .002). Despite adjusting for inflammatory biomarker levels, patients with ACAS still demonstrated deficits in the domains of learning and memory and motor and processing speed. CONCLUSIONS: Although systemic atherosclerosis-induced inflammation is a well-recognized cause for cognitive impairment, our data suggest that it is not the primary underlying mechanism behind cognitive impairments seen in ACAS. Cognitive impairments in learning and memory and motor and processing speed seen in patients with ACAS persist after adjusting for systemic inflammation. Thus, alternative mechanisms should be explored to account for the observed functional impairments.

Computed tomography angiographic biomarkers help identify vulnerable carotid artery plaque.

OBJECTIVE: The current risk assessment for patients with carotid atherosclerosis relies primarily on measuring the degree of stenosis. More reliable risk stratification could improve patient selection for targeted treatment. We have developed and validated a model to predict for major adverse neurologic events (MANE; stroke, transient ischemic attack, amaurosis fugax) that incorporates a combination of plaque morphology, patient demographics, and patient clinical information. METHODS: We enrolled 221 patients with asymptomatic carotid stenosis of any severity who had undergone computed tomography angiography at baseline and ≥6 months later. The images were analyzed for carotid plaque morphology (plaque geometry and tissue composition). The data were partitioned into training and validation cohorts. Of the 221 patients, 190 had complete records available and were included in the present analysis. The training cohort was used to develop the best model for predicting MANE, incorporating the patient and plaque features. First, single-variable correlation and unsupervised clustering were performed. Next, several multivariable models were implemented for the response variable of MANE. The best model was selected by optimizing the area under the receiver operating characteristic curve (AUC) and Cohen's kappa statistic. The model was validated using the sequestered data to demonstrate generalizability. RESULTS: A total of 62 patients had experienced a MANE during follow-up. Unsupervised clustering of the patient and plaque features identified single-variable predictors of MANE. Multivariable predictive modeling showed that a combination of the plaque features at baseline (matrix, intraplaque hemorrhage [IPH], wall thickness, plaque burden) with the clinical features (age, body mass index, lipid levels) best predicted for MANE (AUC, 0.79), In contrast, the percent diameter stenosis performed the worst (AUC, 0.55). The strongest single variable for discriminating between patients with and without MANE was IPH, and the most predictive model was produced when IPH was considered with wall remodeling. The selected model also performed well for the validation dataset (AUC, 0.64) and maintained superiority compared with percent diameter stenosis (AUC, 0.49). CONCLUSIONS: A composite of plaque geometry, plaque tissue composition, patient demographics, and clinical information predicted for MANE better than did the traditionally used degree of stenosis alone for those with carotid atherosclerosis. Implementing this predictive model in the clinical setting could help identify patients at high risk of MANE.

Safety of the transradial approach to carotid stenting.

BACKGROUND: The multicenter prospective CREST-2 Registry (C2R) provides recent experience in performing carotid artery stenting (CAS) for interventionists to ensure safe performance of CAS. OBJECTIVE: To determine the periprocedural safety of CAS performed using a transradial approach relative to CAS performed using a transfemoral approach. METHODS: Patients with ≥70% asymptomatic and ≥50% symptomatic carotid stenosis, ≤80 years of age and at standard or high risk for carotid endarterectomy (CEA) are eligible for the C2R. The primary endpoint was a composite of severe access-related complications. Comparisons were made using propensity-score matched logistic regression. RESULTS: The mean age of the cohort was 67.6 ± 8.2 years and 1906 (35.1%) were female. Indications for CAS included 4063 (74.9%) for primary atherosclerosis. A total of 2868 (52.8%) cases underwent CAS for asymptomatic disease. Transradial access was used in 213 (3.9%) patients. The transradial cohort had lower use of general anesthesia (1.5% vs. 6.3%, p = 0.007) and higher use of distal embolic protection (96.7% vs. 89.4%, p = 0.0004). There were no significant differences between radial and femoral access groups in terms of a composite of major access-related complications (0% vs. 1.1%) or a composite of periprocedural stroke or death (3.3% vs. 2.4%; OR = 1.4 [confidence intervals 0.6, 3.1]; p = 0.42). CONCLUSION: We found no significant differences in rates of major access-related complications or periprocedural stroke or death with CAS performed using transradial compared to transfemoral access. Our results support incorporation of the transradial approach to clinical trials comparing CAS to other revascularization techniques.

Race Differences in High-Grade Carotid Artery Stenosis.

Background and Purpose: Despite a higher incidence of stroke and a more adverse cardiovascular risk factor profile in Blacks and Hispanics compared with Whites, carotid artery revascularization is performed less frequently among these subpopulations. We assessed racial differences in high-grade (≥70% diameter-reducing) carotid stenosis. Methods: Consecutive clients in a Nationwide Life Line for-Profit Service to screen for vascular disease, 2005 to 2019 were evaluated in a cross-sectional study. The prevalence of high-grade stenosis, defined by a carotid ultrasound peak systolic velocity of ≥230 cm/s, was assessed. Participants self-identified as White, Black, Hispanic, Asian, Native American, or other. Race/ethnic differences were assessed using Poisson regression. The number of individuals in the United States with high-grade stenosis was estimated by applying prevalence estimates to 2015 US Census population estimates. Results: The prevalence of high-grade carotid stenosis was estimated in 6 130 481 individuals. The prevalence of high-grade stenosis was higher with increasing age in all race-sex strata. Generally, Blacks and Hispanics had a lower prevalence of high-grade stenosis compared with Whites, while Native Americans had a higher prevalence. For example, for men aged 55 to 65, the relative risk of stenosis compared with Whites was 0.40 (95% CI, 0.29­0.55) and 0.61 (95% CI, 0.46­0.81) for Blacks and Hispanics, respectively; and 1.53 (95% CI, 1.12­2.10) for Native Americans. When these prevalence estimates were applied to the Census estimates of the US population, an estimated 327 721 individuals have high-grade stenosis, of whom 7% are Black, 7% Hispanic, and 43% women. Conclusions: Despite their having a more adverse cardiovascular risk profile, there was a lower prevalence of high-grade carotid artery stenosis for both the Black and Hispanic relative to the White clients. This lower prevalence of high-grade stenosis is a potential contributor to the lower use of carotid revascularization procedures in these minority populations.

Baseline Cognitive Impairment in Patients With Asymptomatic Carotid Stenosis in the CREST-2 Trial.

BACKGROUND AND PURPOSE: Studies of carotid artery disease have suggested that high-grade stenosis can affect cognition, even without stroke. The presence and degree of cognitive impairment in such patients have not been reported and compared with a demographically matched population-based cohort. METHODS: We studied cognition in 1000 consecutive CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial) patients, a treatment trial for asymptomatic carotid disease. Cognitive assessment was after randomization but before assigned treatment. The cognitive battery was developed in the general population REGARDS Study (Reasons for Geographic and Racial Differences in Stroke), involving Word List Learning Sum, Word List Recall, and Word List fluency for animal names and the letter F. The carotid stenosis patients were >45 years old with ≥70% asymptomatic carotid stenosis and no history of prevalent stroke. The distribution of cognitive performance for the patients was standardized, accounting for age, race, and education using performance from REGARDS, and after further adjustment for hypertension, diabetes, dyslipidemia, and smoking. Using the Wald Test, we tabulated the proportion of Z scores less than the anticipated deviate for the population-based cohort for representative percentiles. RESULTS: There were 786 baseline assessments. Mean age was 70 years, 58% men, and 52% right-sided stenosis. The overall Z score for patients was significantly below expected for higher percentiles (P<0.0001 for 50th, 75th, and 95th percentiles) and marginally below expected for the 25th percentile (P=0.015). Lower performance was attributed largely to Word List Recall (P<0.0001 for all percentiles) and for Word List Learning (50th, 75th, and 95th percentiles below expected, P≤0.01). The scores for left versus right carotid disease were similar. CONCLUSIONS: Baseline cognition of patients with severe carotid stenosis showed below normal cognition compared to the population-based cohort, controlling for demographic and cardiovascular risk factors. This cohort represents the largest group to date to demonstrate that poorer cognition, especially memory, in this disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02089217.