Predictors of amputation-free survival and wound healing after infrainguinal bypass with alternative conduits.

OBJECTIVE: Inadequate vein quality or prior harvest precludes use of autologous single segment greater saphenous vein (ssGSV) in many patients with chronic limb-threatening ischemia (CLTI). Predictors of patient outcome after infrainguinal bypass with alternative (non-ssGSV) conduits are not well-understood. We explored whether limb presentation, bypass target, and conduit type were associated with amputation-free survival (AFS) after infrainguinal bypass using alternative conduits. METHODS: A single-center retrospective study (2013-2020) was conducted of 139 infrainguinal bypasses performed for CLTI with cryopreserved ssGSV (cryovein) (n = 71), polytetrafluoroethylene (PTFE) (n = 23), or arm/spliced vein grafts (n = 45). Characteristics, Wound, Ischemia, and foot Infection (WIfI) stage, and outcomes were recorded. Multivariable Cox proportional hazards and classification and regression tree analysis modeled predictors of AFS. RESULTS: Within 139 cases, the mean age was 71 years, 59% of patients were male, and 51% of cases were nonelective. More patients undergoing bypass with cryovein were WIfI stage 4 (41%) compared with PTFE (13%) or arm/spliced vein (27%) (P = .04). Across groups, AFS at 2 years was 78% for spliced/arm, 79% for PTFE, and 53% for cryovein (adjusted hazard ratio for cryovein, 2.5; P = .02). Among cases using cryovein, classification and regression tree analysis showed that WIfI stage 3 or 4, age >70 years, and prior failed bypass were predictive of the lowest AFS at 2 years of 36% vs AFS of 58% to 76% among subgroups with less than two of these factors. Although secondary patency at 2 years was worse in the cryovein group (26% vs 68% and 89% in arm/spliced and PTFE groups; P < .01), in patients with tissue loss there was no statistically significant difference in wound healing in the cryovein group (72%) compared with other bypass types (72% vs 87%, respectively; P = .12). CONCLUSIONS: In patients with CLTI lacking suitable ssGSV, bypass with autogenous arm/spliced vein or PTFE has superior AFS compared with cryovein, although data were limited for PTFE conduits for distal targets. Despite poor patency with cryovein, wound healing is achieved in a majority of cases, although it should be used with caution in older patients with high WIfI stage and prior failed bypass, given the low rates of AFS.

Decreasing prevalence of centers meeting the Society for Vascular Surgery abdominal aortic aneurysm guidelines in the United States.

OBJECTIVE: Based on data supporting a volume-outcome relationship in elective aortic aneurysm repair, the Society of Vascular Surgery (SVS) guidelines recommend that endovascular aortic repair (EVAR) be localized to centers that perform ≥10 operations annually and have a perioperative mortality and conversion-to-open rate of ≤2% and that open aortic repair (OAR) be localized to centers that perform ≥10 open aortic operations annually and have a perioperative mortality ≤5%. However, the number and distribution of centers meeting the SVS criteria remains unclear. This study aimed to estimate the temporal trends and geographic distribution of Centers Meeting the SVS Aortic Guidelines (CMAG) in the United States. METHODS: The SVS Vascular Quality Initiative was queried for all OAR, aortic bypasses, and EVAR from 2011 to 2019. Annual OAR and EVAR volume, 30-day elective operative mortality for OAR or EVAR, and EVAR conversion-to-open rate for all centers were calculated. The SVS guidelines for OAR and EVAR, individually and combined, were applied to each institution leading to a CMAG designation. The proportion of CMAGs by region (West, Midwest, South, and Northeast) were compared by year using a χ2 test. Temporal trends were estimated using a multivariable logistic regression for CMAG, adjusting by region. RESULTS: Overall, 67,865 patients (49,264 EVAR; 11,010 OAR; 7591 aortic bypasses) at 336 institutions were examined. The proportion of EVAR CMAGs increased nationally by 1.7% annually from 51.6% (n = 33/64) in 2011 to 67.1% (n = 190/283) in 2019 (ß = .05; 95% confidence interval [CI], 0.01-0.09; P = .02). The proportion of EVAR CMAGs across regions ranged from 27.3% to 66.7% in 2011 to 63.9% to 72.9% in 2019. In contrast, the proportion of OAR CMAGs has decreased nationally by 1.8% annually from 32.8% (n = 21/64) in 2011 to 16.3% (n = 46/283) in 2019 (ß = -.14; 95% CI, -0.19 to -0.10; P < .01). Combined EVAR and OAR CMAGs were even less frequent and decreased by 1.5% annually from 26.6% (n = 17/64) in 2011 to 13.1% (n = 37/283) in 2019 (ß = -.12; 95% CI, -0.17 to -0.07; P < .01). In 2019, there was no significant difference in regional variation of the proportion of combined EVAR and OAR CMAGs (P = .82). CONCLUSIONS: Although an increasing proportion of institutions nationally meet the SVS guidelines for EVAR, a smaller proportion meet them for OAR, with a concerning downward trend. These data question whether we can safely offer OAR at most institutions, have important implications about sufficient OAR exposure for trainees, and support regionalization of OAR.

Risk factors and associated outcomes of postoperative delirium after open abdominal aortic aneurysm repair.

OBJECTIVE: Open abdominal aortic aneurysm repair (OAR) is a major vascular procedure that incurs a large physiologic demand, increasing the risk for complications such as postoperative delirium (POD). We sought to characterize POD incidence, identify delirium risk factors, and evaluate the effect of delirium on postoperative outcomes. We hypothesized that POD following OAR would be associated with increased postoperative complications and resource utilization. METHODS: This was a retrospective study of all OAR cases from 2012 to 2020 at a single tertiary care center. POD was identified via a validated chart review method based on key words and Confusion Assessment Method assessments. The primary outcome was POD, and secondary outcomes included length of stay, non-home discharge, 90-day mortality, and 1-year survival. Bivariate analysis as appropriate to the data was used to assess the association of delirium with postoperative outcomes. Multivariable binary logistic regression was used to identify risk factors for POD and Cox regression for variables associated with worse 1-year survival. RESULTS: Overall, 198 OAR cases were included, and POD developed in 34% (n = 67). Factors associated with POD included older age (74 vs 69 years; P < .01), frailty (50% vs 28%; P < .01), preoperative dementia (100% vs 32%; P < .01), symptomatic presentation (47% vs 27%; P < .01), preoperative coronary artery disease (44% vs 28%; P = .02), end-stage renal disease (89% vs 32%; P < .01) and Charlson Comorbidity Index score >4 (42% vs 26%; P = .01). POD was associated with 90-day mortality (19% vs 5%; P < .01), non-home discharge (61% vs 30%; P < .01), longer median hospital length of stay (14 vs 8 days; P < .01), longer median intensive care unit length of stay (6 vs 3 days; P < .01), postoperative myocardial infarction (7% vs 2%; P = .045), and postoperative pneumonia (19% vs 8%; P = .01). On multivariable analysis, risk factors for POD included older age, history of end-stage renal disease, lack of epidural, frailty, and symptomatic presentation. A Cox proportional hazards model revealed that POD was associated with worse survival at 1 year (hazard ratio, 3.8; 95% confidence interval, 1.6-9.0; P = .003). CONCLUSIONS: POD is associated with worse postoperative outcomes and increased resource utilization. Future studies should examine the role of improved screening, implementation of delirium prevention bundles, and multidisciplinary care for the most vulnerable patients undergoing OAR.

Structured discharge documentation reduces sex-based disparities in statin prescription in vascular surgery patients.

OBJECTIVE: Perioperative statin use has been shown to improve survival in vascular surgery patients. In 2018, the Northern California Vascular Study Group implemented a quality initiative focused on the use of a SmartText in the discharge summary. We hypothesized that structured discharge documentation would decrease sex-based disparities in evidence-based medical therapy. METHODS: A retrospective analysis was conducted using Vascular Quality Initiative eligible cases at a single institution. Open or endovascular procedures in the abdominal aorta or lower extremity arteries from 2016 to 2021 were included. Bivariate analysis identified factors associated with statin use and sex. Multivariate logistic regression was performed with the end point of statin prescription at discharge and aspirin prescription at discharge. An interaction term assessed the differential impact of the initiative on both sexes. Analysis was then stratified by prior aspirin or statin prescription. An interrupted time series analysis was used to evaluate the trend in statin prescription over time. RESULTS: Overall, 866 patients were included, including 292 (34%) female and 574 (66%) male patients. Before implementation, statins were prescribed in 77% of male and 62% of female patients (P < .01). After implementation, there was no statistically significant difference in statin prescription (91% in male vs 92% in female patients, P = .68). Female patients saw a larger improvement in the adjusted odds of statin prescription compared with male patients (odds ratio: 3.1, 95% confidence interval: 1.1-8.6, P = .04). For patients not prescribed a statin preoperatively, female patients again saw an even larger improvement in the odds of being prescribed a statin at discharge (odds ratio: 6.4, 95% confidence interval: 1.8-22.7, P < .01). Interrupted time series analysis demonstrated a sustained improvement in the frequency of prescription for both sexes over time. The unadjusted frequency of aspirin prescription also improved by 3.5% in male patients vs 5.5% in female patients. For patients not prescribed an aspirin preoperatively, we found that the frequency of aspirin prescription significantly improved for both male (19% increase, P = .006) and female (31% increase, P = .001) patients. There was no significant difference in the perioperative outcomes between male and female patients before and after standardized discharge documentation. CONCLUSIONS: A simple, low-cost regional quality improvement initiative eliminated sex-based disparities in statin prescription at a single institution. These findings highlight the meaningful impact of regional quality improvement projects. Future studies should examine the potential for structured discharge documentation to improve patient outcomes and reduce disparities.

Cognitive Impairment is Common in a Veterans Affairs Population with Peripheral Arterial Disease.

BACKGROUND: Despite the shared pathogenesis of peripheral arterial disease (PAD) and vascular dementia, there are little data on cognitive impairment in PAD patients. We hypothesized that cognitive impairment will be common and previously unrecognized. METHODS: Cognitive impairment screening was prospectively performed for veterans presenting to a single Veterans Affairs outpatient vascular surgery clinic from 2020-2021 for PAD consultation or disease surveillance. Overall, 125 Veterans were screened. Cognitive impairment was defined as a score of <26 on the Montreal Cognitive Assessment (MoCA) survey. A multivariable logistic regression assessed for independent risk factors for cognitive impairment. RESULTS: Overall, 77 (61%) had cognitive impairment, 92% was previously unrecognized. Cognitive impairment was associated with increased age (74.4 vs. 71.8 years, P = 0.03), Black versus White race (94% vs. 54%, P < 0.01), hypertension (66% vs. 31%, P = 0.01), prior stroke/TIA (79% vs. 58%, P = 0.03), diabetes treated with insulin (79% vs. 58%, P = 0.05), and post-traumatic stress disorder (PTSD) (80% vs. 57%, P = 0.04). On multivariable analysis, risk factors for newly diagnosed cognitive impairment included age ≥70 years, diabetes treated with insulin, PTSD, and Black race. CONCLUSIONS: Many veterans with PAD have evidence of cognitive impairment and is overwhelmingly underdiagnosed. This study suggests cognitive impairment is an unrecognized issue in a VA population with PAD, requiring more study to determine cognitive impairment's impact on surgical outcomes, and how it can be mitigated and incorporated into clinical care.

Racial and ethnic disparities in major adverse limb events persist for chronic limb threatening ischemia despite presenting limb threat severity after peripheral vascular intervention.

OBJECTIVE: Racial and ethnic disparities have been well-documented in the outcomes for chronic limb threatening ischemia (CLTI). One purported explanation has been the disease severity at presentation. We hypothesized that the disparities in major adverse limb events (MALE) after peripheral vascular intervention (PVI) for CLTI would persist despite controlling for disease severity at presentation using the WIfI (Wound, Ischemia, foot Infection) stage. METHODS: The Vascular Quality Initiative PVI dataset (2016-2021) was queried for CLTI. Patients were excluded if they were missing the WIfI stage. The primary end point was the incidence of 1-year MALE, defined as major amputation (through the tibia or fibula or more proximally) or reintervention (endovascular or surgical) of the initial treatment limb. A multivariate hierarchical Fine-Gray analysis was performed, controlling for hospital variation, competing risk of death, and presenting WIfI stage, to assess the independent association of Black/African American race and Latinx/Hispanic ethnicity with MALE. A Cox proportional hazard regression model was used for the 1-year survival analysis. RESULTS: Overall, 47,830 patients (60%) had had WIfI scores reported (73% White, 20% Black, and 7% Latinx). The 1-year unadjusted cumulative incidence of MALE was 13.1% (95% confidence interval [CI], 12.6%-13.5%) for White, 14.3% (95% CI, 13.5%-15.3%) for Black, and 17.0% (95% CI, 15.3%-18.9%) for Latinx patients. On bivariate analysis, the occurrence of MALE was significantly associated with younger age, Black race, Latinx ethnicity, coronary artery disease, cerebrovascular disease, congestive heart failure, hypertension, diabetes, dialysis, intervention level, any prior minor or major amputation, and WIfI stage (P < .001). The cumulative incidence of 1-year MALE increased by increasing WIfI stage: stage 1, 11.7% (95% CI, 10.9%-12.4%); stage 2, 12.4% (95% CI, 11.8%-13.0%); stage 3, 14.8% (95% CI, 13.8%-15.8%); and stage 4, 15.4% (95% CI, 14.3%-16.6%). The cumulative incidence also increased by intervention level: inflow, 10.7% (95% CI, 9.8%-11.7%), femoropopliteal, 12.3% (95% CI, 11.7%-12.9%); and infrapopliteal, 14.1% (95% CI, 13.5%-14.8%). After adjustment for WIfI stage only, Black race (subdistribution hazard ratio [SHR], 1.30; 95% CI, 1.17-1.44; P < .001) and Latinx ethnicity (SHR, 1.58; 95% CI, 1.37-1.81; P < .001) were associated with an increased 1-year hazard of MALE compared with White race. On adjusted multivariable analysis, MALE disparities persisted for Black/African American race (SHR, 1.12; 95% CI, 1.01-1.25; P = .028) and Latinx/Hispanic ethnicity (SHR, 1.34; 95% CI, 1.16-1.54; P < .001) compared with White race. CONCLUSIONS: Black/African American and Latinx/Hispanic patients had a higher associated hazard of MALE after PVI for CLTI compared with White patients despite an adjustment for WIfI stage at presentation. These results suggest that disease severity at presentation does not account for disparities in outcomes. Further work should focus on better understanding the underlying mechanisms for disparities in historically marginalized racial and ethnic groups presenting with CLTI.

Association of Intraoperative and Perioperative Transfusions with Postoperative Cardiovascular Events and Mortality After Infrainguinal Revascularization.

BACKGROUND: Patients undergoing open or endovascular infrainguinal revascularization are at an elevated risk for postoperative cardiovascular complications due to high rates of comorbidities and the physiologic stress of surgery. Transfusions are known to be associated with adverse events but knowledge of specific risks associated with transfusion timing, product type, and long-term outcomes while accounting for preoperative cardiovascular risk factors is not well understood in this population. This study aimed to characterize the association of intraoperative and perioperative transfusion, anemia, and cardiovascular risk factors with cardiovascular events and mortality in patients undergoing infrainguinal revascularization. METHODS: A single-center retrospective study was performed on 564 infrainguinal revascularization procedures, including both open (n = 250) and endovascular (n = 314) approaches (2016-2020). Comprehensive clinical data were collected including patient demographics, cardiovascular risk factors, preoperative hemoglobin, and detailed transfusion data. Multivariable logistic regression tested the association of transfusions with composite 30-day outcomes of cardiac complications (postoperative myocardial infarction [postop-MI], congestive heart failure, or dysrhythmia) and with major adverse cardiovascular events (MACE-postop-MI or death). Kaplan-Meier analysis and Cox proportional hazard modeling examined the association of transfusions, anemia, and cardiovascular risk factors with mortality up to 1 year. RESULTS: Intraoperative transfusion was performed in 15% of cases and 13% underwent transfusion in the early postoperative period. Intraoperative transfusion was associated with higher Revised Cardiac Risk Index (RCRI), lower preoperative hemoglobin, increased blood loss, and open procedures (all P < 0.05). Within each RCRI score, intraoperative transfusion was associated with 2-4-fold increased MACE at 30 days. Intraoperative packed red blood cells transfusion and early postoperative packed red blood cells transfusion was associated with more than 2-fold adjusted odds of any cardiovascular complication and intraoperative transfusion was also associated with MACE (all P < 0.05). Intraoperative transfusion was associated with mortality at 1 year on unadjusted analysis, but after adjustment for RCRI, age, and preoperative hemoglobin, only RCRI scores of 2 and 3+ and preoperatively hemoglobin remained significant risk factors for mortality. CONCLUSIONS: Intraoperative and early perioperative transfusions are strongly associated with worse cardiovascular outcomes after infrainguinal revascularization. These findings may have a prognostic value for further risk stratifying patients perioperatively at a high risk for complications. However, prospective studies are needed to elucidate whether optimizing transfusion strategies mitigates these risks.

Clinical Predictors and Outcomes Associated with Postoperative Delirium Following Infrainguinal Bypass Surgery.

BACKGROUND: Post-operative delirium (POD) is common yet often underdiagnosed following vascular surgery. Elderly patients with advanced peripheral artery disease may be at particular risk for POD yet understanding of the clinical predictors and impact of POD is incomplete. We sought to identify POD predictors and associated resource utilization after infrainguinal lower extremity bypass. METHODS: This single center retrospective analysis included all infrainguinal bypass cases performed for peripheral arterial disease from 2012-2020. The primary outcome was inpatient POD. Delirium sequelae were also evaluated. Key secondary outcomes were length of stay, nonhome discharge, readmission, 30-day amputation, post-operative myocardial infarction, mortality, and 2-year survival. Regression analysis was used to evaluate risk factors for delirium in addition to association with 2-year survival and amputation free survival. RESULTS: Among 420 subjects undergoing infrainguinal lower extremity bypass, 105 (25%) developed POD. Individuals with POD were older and more likely to have non-elective surgery (P < 0.05). On multivariable analysis, independent predictors of POD were age 60-89 years old, chronic limb threatening ischemia, female sex, and nonelective procedure. Consultations for POD took place for 25 cases (24%); 13 (52%) were with pharmacists, and only 4 (16%) resulted in recommendations. The average length of stay for those with POD was higher (17 days vs. 9 days; P < 0.001). POD was associated with increased non-home discharge (61.8% vs. 22.1%; P < 0.001), 30-day major amputation (6.7% vs. 1.6%; P < 0.01), 30-day postoperative myocardial infarction (11.4% vs. 4.1%; P < 0.01), and 90-day mortality (7.6% vs. 2.9%; P = 0.03). Survival at 2 years was lower in those with delirium (89% vs. 75%; P < 0.001). In a Cox proportional hazards model, delirium was independently associated with decreased survival (HR = 2.0; 95% CI = 1.15-3.38; P = 0.014) and decreased major-amputation free survival (HR = 1.9; 95% CI = 1.18-2.96; P = 0.007). CONCLUSIONS: POD is common following infrainguinal lower extremity bypass and is associated with other adverse post-operative outcomes and increased resource utilization, including increased hospital length of stay, nonhome discharge, and worse 2-year survival. Future studies should evaluate the role of routine multidisciplinary care for high-risk patients to improve perioperative outcomes for vulnerable older adults undergoing infrainguinal lower extremity bypass.

Cadaver Simulation is Associated with Increased Comfort in Performing Open Vascular Surgery Among Integrated Vascular Surgery (0+5) Residents and Recent Graduates.

BACKGROUND: With the evolution in vascular surgery toward increased endovascular therapy and decreased open surgical training, comfort with open procedures by current trainees is declining. A proposed method to improve this discomfort is simulator training. We hypothesized that open, cadaver, and endovascular surgery simulation would be associated with increased self-perceived comfort in performing corresponding procedures. METHODS: Integrated (0 + 5) vascular surgery residents and recent graduates in the United States were asked to complete a survey quantifying comfort via a Likert scale with procedures and experience with simulation training. Simulation groups were then matched using coarsened exact matching. Ordinal logistic regression assessed the association between simulation experience and comfort in performing procedures. RESULTS: Surveys were completed by 68 trainees and 20 attending surgeons in their first 5 years of practice. On unmatched analyses, there were no significant differences in comfort in performing any open or endovascular aorto-mesenteric or peripheral vascular procedures between respondents who reported experience with open or endovascular simulation, respectively. However, respondents who reported cadaver simulation experience (58%, 51/88) had a significantly higher reported comfort score performing open juxtarenal aortic repair (2.4 vs. 1.7), superior mesenteric artery thrombectomy or bypass (2.5 vs. 1.9), inferior vena cava or iliac vein repair (2.2 vs. 1.7), axillary-femoral artery bypass (3.4 vs. 2.5), femoral-popliteal artery bypass (3.7 vs. 2.8), and inframalleolar artery bypass (2.8 vs. 2.1; all P < 0.05). After matching on training level, number of abdominal cases completed, and number of open vascular cases completed, ordinal logistic regression demonstrated that previous cadaver simulation was significantly associated with increased comfort in performing open aortic repairs, venous repair, visceral revascularization, and peripheral bypasses. CONCLUSIONS: In this nationally representative sample, cadaver, but not open or endovascular, simulation was associated with increased comfort in performing open vascular surgery. Providing cadaver simulation to trainees may help to improve comfort levels in performing open surgery. Integrated vascular surgery training programs should consider implementing these experiences into their curriculum.

Statistical Fragility of Single-Row Versus Double-Row Anchoring for Rotator Cuff Repair: A Systematic Review of Comparative Studies.

Background: Comparative studies and randomized controlled trials (RCTs) often use the P (probability) value to convey the statistical significance of their findings. P values are an imperfect measure, however, and are vulnerable to a small number of outcome reversals to alter statistical significance. The inclusion of a fragility index (FI) and fragility quotient (FQ) may aid in the interpretation of a study's statistical strength. Purpose/Hypothesis: The purpose of this study was to examine the statistical stability of studies comparing single-row to double-row rotator cuff repair. It was hypothesized that the findings of these studies would be vulnerable to a small number of outcome event reversals, often fewer than the number of patients lost to follow-up. Study Design: Systematic review; Level of evidence, 3. Methods: We analyzed comparative studies and RCTs on primary single-row versus double-row rotator cuff repair that were published between 2000 and 2021 in 10 leading orthopaedic journals. Statistical significance was defined as a P < .05. The FI for each outcome was determined by the number of event reversals necessary to alter significance. The FQ was calculated by dividing the FI by the respective sample size. Results: Of 4896 studies screened, 22 comparative studies, 10 of which were RCTs, were ultimately included for analysis. A total of 74 outcomes were examined. Overall, the median FI was 2 (interquartile range [IQR], 1-3), and the median FQ was 0.035 (IQR, 0.020-0.057). The mean FI was 2.55 ± 1.29, and the mean FQ was 0.043 ± 0.027. In 64% of outcomes, the FI was less than the number of patients lost to follow-up.) Additionally, 81% of significant outcomes needed just a single outcome reversal to lose their significance. Conclusion: Over half of the studies currently used to guide clinical practice have a number of patients lost to follow-up greater than their FI. The results of these studies should be interpreted within the context of these limitations. Future analyses may benefit from the inclusion of the FI and the FQ in their statistical analyses.

Translational findings for odronextamab: From preclinical research to a first-in-human study in patients with CD20+ B-cell malignancies.

Odronextamab is a fully-human IgG4-based CD20xCD3 bispecific antibody that binds to CD3 on T cells and CD20 on B cells, triggering T-cell-mediated cytotoxicity independent of T-cell-receptor recognition. Adequate safety, tolerability, and encouraging durable complete responses have been observed in an ongoing first-in-human (FIH) study of odronextamab in patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL; NCT02290951). We retrospectively evaluated the pharmacokinetic, pharmacodynamic, and antitumor characteristics of odronextamab in a series of in vitro/in vivo preclinical experiments, to assess their translational value to inform dose escalation for the FIH study. Half-maximal effective concentration values from in vitro cytokine release assays (range: 0.05-0.08 mg/L) provided a reasonable estimate of odronextamab concentrations in patients associated with cytokine release at a 0.5 mg dose (maximum serum concentration: 0.081 mg/L) on week 1/day 1, which could therefore be used to determine the week 1 clinical dose. Odronextamab concentrations resulting in 100% inhibition of tumor growth in a Raji xenograft tumor mouse model (1-10 mg/L) were useful to predict efficacious concentrations in patients and inform dose-escalation strategy. Although predicted human pharmacokinetic parameters derived from monkey data overestimated projected odronextamab exposure, they provided a conservative estimate for FIH starting doses. With step-up dosing, the highest-tested weekly odronextamab dose in patients (320 mg) exceeded the 1 mg/kg single dose in monkeys without step-up dosing. In conclusion, combination of odronextamab in vitro cytokine data, efficacious concentration data from mouse tumor models, and pharmacokinetic evaluations in monkeys has translational value to inform odronextamab FIH study design in patients with R/R B-NHL.

Risk factors for venous thromboembolism after vascular surgery and implications for chemoprophylaxis strategies.

OBJECTIVE: Venous thromboembolism (VTE) is an important cause of postoperative morbidity and mortality. However, the reported incidence after major vascular surgery has ranged from as low as 1% to >10%. Furthermore, little is known about optimal chemoprophylaxis regimens or rates of postdischarge VTE in this population. In the present study, we aimed to better characterize the rates of in-hospital and postdischarge VTE after major vascular surgery, the role of chemoprophylaxis timing, and the association of VTE with mortality. METHODS: A single-center retrospective study of 1449 major vascular operations (2013-2020) was performed and included 189 endovascular abdominal aortic aneurysm repairs (13%), 169 thoracic endovascular aortic aneurysm repairs (12%), 318 open aortic operations (22%), 640 lower extremity bypasses (44%), and 133 femoral endarterectomies (9%). The baseline characteristics, anticoagulant and antiplatelet medications, and outcomes were abstracted from an electronic database with medical record auditing. Postoperative VTE (pulmonary embolism and deep vein thrombosis) within 90 days of surgery was classified by the location, symptoms, and treatment. A cut point analysis using Youden's index identified the most VTE discriminating timing of chemoprophylaxis (including therapeutic vs prophylactic anticoagulant and antiplatelet medications) and Caprini score. Multivariable logistic regression was used to test the association of VTE with chemoprophylaxis timing, Caprini score, and additional risk factors. Cox proportional hazard modeling was used to measure the association between VTE and mortality. RESULTS: The overall VTE incidence was 3.4% (65% deep vein thrombosis; 25% pulmonary embolism; 10% both), and 37% had occurred after discharge. The rate of symptomatic VTE was 2.4%, which was lowest for endovascular abdominal aortic aneurysm repair (0.0%) and highest for open aortic surgery (4.1%; P = .02). Those who had developed VTE had had a longer length of stay, higher rates of end-stage renal disease and prior VTE, and higher Caprini scores (8 vs 5 points; P < .01 for all). Those who had developed VTE were also more likely to have received ≥2 U of blood postoperatively, required an unplanned return to the operating room, had delayed chemoprophylaxis, anticoagulation, and/or antiplatelet initiation of >4 days postoperatively, and had increased 90-day mortality (P < .01 for all). A Caprini score of ≥7 (29% of patients) was associated with postdischarge VTE (2.6% vs 0.7%; P = .01), and chemoprophylaxis, anticoagulation, and antiplatelet timing of >4 days was associated with an increased adjusted odds of VTE (odds ratio, 2.4; 95% confidence interval, 1.1-4.9). Although no fatal VTEs were identified, VTE was an independent predictor of 90-day mortality (adjusted hazard ratio, 2.7; 95% confidence interval, 1.3-5.9). CONCLUSIONS: These data have shown that patients undergoing major vascular surgery are particularly prone to the development of VTE, with frequent hypercoagulable comorbidities. The earlier initiation of chemoprophylaxis was associated with a reduced risk of VTE development. Furthermore, the postdischarge VTE rates might reach thresholds warranting postdischarge chemoprophylaxis, especially for patients with a Caprini score of ≥7.

A Primer on Meta-Analytic Structural Equation Modeling: the Case of Depression.

In this paper, we show how the methods of systematic reviewing and meta-analysis can be used in conjunction with structural equation modeling to summarize the results of studies in a way that will facilitate the theory development and testing needed to advance prevention science. We begin with a high-level overview of the considerations that researchers need to address when using meta-analytic structural equation modeling (MASEM) and then discuss a research project that brings together theoretically important cognitive constructs related to depression to (a) show how these constructs are related, (b) test the direct and indirect effects of dysfunctional attitudes on depression, and (c) test the effects of study-level moderating variables. Our results suggest that the indirect effect of dysfunctional attitudes (via negative automatic thinking) on depression is two and a half times larger than the direct effect of dysfunctional attitudes on depression. Of the three study-level moderators tested, only sample recruitment method (clinical vs general vs mixed) yielded different patterns of results. The primary difference observed was that the dysfunctional attitudes → automatic thoughts path was less strong for clinical samples than it was for general and mixed samples. These results illustrate how MASEM can be used to compare theoretically derived models and predictions resulting in a richer understanding of both the empirical results and the theories underlying them.

Closure device use for common femoral artery antegrade access is higher risk than retrograde access.

OBJECTIVE: Although the use of closure devices (CD) for femoral artery antegrade access (AA) is not in the instructions for use (IFU) for many devices, AA has been reported to be associated with a lower incidence of access site complications compared to manual compression alone. We hypothesized that CD use for AA would not be associated with a clinically significant increased odds of access site complications compared to CD use for retrograde access (RA). METHODS: This was a retrospective review of the Vascular Quality Initiative from 2010 to 2019 for infrainguinal peripheral vascular interventions with common femoral artery access closed with a CD. Patients who had a cutdown or multiple access sites were excluded. Cases were then stratified into whether access was antegrade or retrograde. Hierarchical multivariable logistic regressions controlling for hospital level variation were used to examine the independent association between AA and access site complications. The primary outcomes were access site hematoma, stenosis, or occlusion as defined in the VQI. The secondary outcome was the development of an access site hematoma requiring an intervention, which was defined as transfusion, thrombin injection, or surgery. Sensitivity analyses after coarsened exact matching were performed to reduce residual bias. RESULTS: Overall, 72,463 cases were identified and 6,070 (8.4%) had AA. Patients with AA were less likely to be smokers (27.2% vs 33.0%) or obese (31.5% vs 35.6%; all P<0.05). Patients with AA were more likely to be on dialysis (12.8% vs 10.1%) and have ultrasound-guided access (76.4% vs 66.2%; P<0.05 for all). Compared to RA, patients with AA were more likely to develop any access site hematoma (2.5% vs 1.8%; P<0.01) and a hematoma requiring intervention (0.7% vs 0.5%; P=0.03), but had no difference in access site stenosis or occlusion (0.3% vs 0.2%; P=0.21). On multivariable analyses, AA had increased odds of developing any access site hematoma (OR=1.46; 95% CI=1.22-1.76) and a hematoma requiring intervention (OR=1.48; 95% CI=1.10-1.98). Sensitivity analyses after coarsened exact matching confirmed these findings. CONCLUSION: In this nationally representative sample, the use of CDs for femoral access was associated with an overall low rate of access site complications. However, there was an increased odds of access site hematomas with AA. Patient selection for AA remains important and ultrasound guided access should be the standard of care for this approach.

Living in a Food Desert is Associated with 30-day Readmission after Revascularization for Chronic Limb-Threatening Ischemia.

BACKGROUND: Living in a food desert has been associated with increased cardiovascular risk; however, its impact on vascular surgery outcomes is unknown. This study hypothesized that living in a food desert would be associated with increased postoperative complications in patients undergoing revascularization for chronic limb-threatening ischemia (CLTI). METHODS: This was a single-center retrospective analysis of open and endovascular infrainguinal revascularization for CLTI between April 2013 and December 2015. A food desert was defined using the US Department of Agriculture's Food Access Research Atlas. Bivariate analyses were performed appropriate to the data. Binary logistic regression was performed assessing the association of food desert status with 30-day postoperative complications. RESULTS: In total, 152 cases were included, of which 17% (n = 26) resided in food deserts. Patients in the food desert cohort were less likely to be low income (27% vs. 54%, P = 0.01). Living in a food desert was associated with increased 30-day readmission [(39% vs. 20%, P = 0.04), unadjusted OR: 2.5 (CI: 1.0-6.2)]. FD cases also had a higher proportion of wound complications [12 (46%) vs. 28 (22%), P = 0.01)]. The overall wound complication rate was 27% with the majority being due to infections (63%). On multivariable analysis, food desert status remained associated with increased odds of 30-day readmission (OR: 2.7, CI: 1.2-8.4, P = 0.047). Reasons for readmission in the food desert group were all due to wound complications (100% vs. 72%, P = 0.08). CONCLUSIONS: Living in a food desert was associated with nearly three times the odds of 30-day readmission after lower extremity revascularization for CLTI. This increase in readmission may be explained through increased wound complications. These findings support considering access to healthy food as a potential modifiable risk factor for adverse outcomes, particularly in CLTI revascularization.

The Effect of Diabetes Mellitus on Revision Discectomy after Single-level Lumbar Discectomy.

Diabetes currently affects over 25 million Americans, with the elderly carrying much of the disease burden. It's well known that diabetes increases the risk of surgical complications, but few studies have analyzed its effects on reoperation rates after single-level lumbar discectomy. Data was obtained using the commercially available Explorys software, which houses de-identified data for several healthcare systems. A database search was conducted to find all patients who'd undergone a lumbar discectomy. Scoliosis, spondylolisthesis, smoking history and obesity were excluded as possible confounding variables, after which 31,210 patients remained. Of them, 950 were found to have undergone a revision discectomy within 2 years. Those with diabetes were found to have a relative risk of 1.29 for revision discectomy compared to those who did not, 95% confidence interval (95% CI) 1.10-1.52, p < 0.002. These findings contribute to the importance of modifiable risk factor assessment preoperatively and their effects on surgical complications. (Journal of Surgical Orthopaedic Advances 29(3):159-161, 2020).

Effect of Nicotine Dependence and Smoking on Revision Diskectomy After Single-Level Lumbar Diskectomy.

Removal of a herniated disk that is causing neural compression is among the most common indications for spinal surgery. Previous population database studies of risk factors for reoperation after this procedure analyzed small to medium numbers of patients. To date, no study has concurrently assessed the effect of modifiable risk factors, such as smoking and nicotine dependence, with a large number of patients. Data were obtained with commercially available software that houses de-identified data for several major US health care systems. A database search was conducted to find all patients who had undergone lumbar diskectomy. Obesity, scoliosis, spondylolisthesis, and depression were excluded as possible confounding variables. The remaining patients were divided into smoking and nonsmoking groups. Those who had undergone revision lumbar diskectomy within 2 years were counted. Pearson's chi-square statistical test was used to determine significance at P<.05. Of the 50 million patient records in the software platform, 53,360 patients were identified who had undergone single-level lumbar diskectomy. Of these, 26,980 fulfilled the inclusion criteria. A total of 890 of those patients had undergone revision lumbar diskectomy within 2 years of their original procedure. Those who smoked were found to have a relative risk of 2.47 compared with nonsmokers (95% confidence interval, 2.17-2.82; P<.0001). Nicotine dependence and smoking had a significant effect on the rate of reoperation. These findings support the importance of preoperative assessment of modifiable risk factors and their effects on surgical complications. [Orthopedics. 2020;43(5):e438-e441.].

The Effect of Obesity on Revision Discectomy After Singlelevel Lumbar Discectomy.

The prevalence of obesity has been rising, creating a major public health concern. While several studies have shown obesity to increase the risk of surgical complications, few have analyzed its effects on reoperation, specifically after singlelevel lumbar discectomy. Data was obtained using the commercially available Explorys software that houses deidentified data for several major healthcare systems. A database search was used to find all patients who had undergone a lumbar discectomy. Scoliosis, spondylolisthesis, smoking history and depression were excluded as possible confounding variables, after which 25,960 patients remained. Of them, 690 were found to have undergone a revision discectomy within 2 years. Those who were obese were found to have a relative risk of 1.64 for revision discectomy compared to those who were nonobese, 95% confidence interval (95%CI) 1.322.03, p 0.0001. These findings contribute to the importance of modifiable risk factor assessment preoperatively and their effects on surgical complications. (Journal of Surgical Orthopaedic Advances 29(1):1012, 2020).

The Incremental Cost of Inpatient Venous Thromboembolism After Hip Fracture Surgery.

OBJECTIVES: To (1) identify trends in the rates of deep venous thrombosis (DVT) and pulmonary embolism (PE) and (2) calculate the additional incremental inpatient cost and length of stay associated with venous thromboembolism (VTE) after hip fracture surgery. DESIGN: Retrospective database analysis. SETTING: Hospital discharge data. PATIENTS/PARTICIPANTS: A total of 838,054 patients undergoing operative treatment of hip fractures in the National Inpatient Sample from 2003 to 2014. INTERVENTION: Internal fixation or partial/total hip replacement. MAIN OUTCOME MEASURES: The length of stay and cost of hospitalization were compared between patients with VTE and those without using a Student t-test. A logistic regression model was performed to evaluate the trends in VTE rates, and a multivariable linear regression model was performed to evaluate inpatient hospital costs. RESULTS: The overall rates of DVT and PE were 0.3% and 0.53%, respectively. VTE was associated with an increased length of stay (9 days vs. 5 days) and increased inpatient cost ($103,860.83 vs. $51,576.00). The rate of DVT over the study period decreased, whereas the rate of PE increased. CONCLUSIONS: Each episode of VTE after hip fracture is a significant source of additional inpatient cost. Patients who sustain a VTE have approximately twice the length of stay and total inpatient cost compared with those who do not. The rates of DVT after hip fracture surgery are decreasing, whereas the rates of PE are increasing. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Comparison of Clinical Outcomes After Intramedullary Fixation of Tibia Fractures Caused by Blunt Trauma and Civilian Gunshot Wounds: A Retrospective Review.

OBJECTIVE: To assess the outcomes of patients who sustained blunt trauma tibia fractures compared with tibia fractures from civilian gunshot injuries when treated with intramedullary fixation. DESIGN: Retrospective chart review. SETTING: Level I trauma center. PATIENTS/PARTICIPANTS: Two hundred and seven patients underwent intramedullary nailing for 211 tibia fractures. METHODS: A retrospective review of tibia fracture(s) treated with intramedullary fixation with comparison of closed, open, and gunshot wound (GSW) fracture outcomes. MAIN OUTCOME MEASUREMENTS: Outcomes included infection and nonunion. RESULTS: The infection rate in closed and GSW tibia fractures was significantly lower compared with the infection rate of open fractures (1% vs. 9% vs. 20%; P = 0.00005). Significantly lower rates of nonunion in closed fractures compared with open fractures and GSW fractures were appreciated (8% vs. 20% vs. 30%; P = 0.003). There was no difference in infection or nonunion between GSW fractures with small wounds, no exposed bone, and minimal comminution and closed injuries (P = 0.24, P = 0.60). Conversely, there was a significantly higher nonunion rate in GSW fractures with large wounds, exposed tibia, and comminution compared with blunt injuries (P = 0.0014). CONCLUSIONS: This study suggests that tibia fractures from civilian GSWs are heterogeneous injuries, and outcomes are dependent on the extent of soft-tissue injury, bone exposure, and bone loss. There are comparable infection rates in all fractures due to civilian GSWs and closed fractures, which are lower than high-grade open fractures. Tibia GSW fractures with exposed bone and comminution have higher complication rates and should be treated accordingly. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.