The obesity paradox exists for perioperative complications and mortality following lower extremity arterial bypass surgery.

OBJECTIVE: The obesity paradox refers to a phenomenon by which obese individuals experience lower risk of mortality and even protective associations from chronic disease sequelae when compared with the non-obese and underweight population. Prior literature has demonstrated an obesity paradox after cardiac and other surgical procedures. However, the relationship between body mass index (BMI) and perioperative complications for patients undergoing major open lower extremity arterial revascularization is unclear. METHODS: We queried the Vascular Quality Initiative for individuals receiving unilateral infrainguinal bypass between 2003 and 2020. We used multivariable logistic regression to assess the relationship of BMI categories (underweight [<18.5 kg/m2], non-obese [18.5-24.9 kg/m2], overweight [25-29.9 kg/m2], Class 1 obesity [30-34.9 kg/m2], Class 2 obesity [35-39.9 kg/m2], and Class 3 obesity [>40 kg/m2]) with 30-day mortality, surgical site infection, and adverse cardiovascular events. We adjusted the models for key patient demographics, comorbidities, and technical and perioperative characteristics. RESULTS: From 2003 to 2020, 60,588 arterial bypass procedures met inclusion criteria for analysis. Upon multivariable logistic regression with the non-obese category as the reference group, odds of 30-day mortality were significantly decreased among the overweight (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.53-0.78), Class 1 obese (OR, 0.65; 95% CI, 0.52-0.81), Class 2 obese (OR, 0.66; 95% CI, 0.48-0.90), and Class 3 obese (OR, 0.61; 95% CI, 0.39-0.97) patient categories. Conversely, odds of 30-day mortality were increased in the underweight patient group (OR, 1.58; 95% CI, 1.16-2.13). Furthermore, a BMI-dependent positive association was present, with odds of surgical site infections with patients in Class 3 obesity having the highest odds (OR, 2.10; 95% CI, 1.60-2.76). Finally, among the adverse cardiovascular event outcomes assessed, only myocardial infarction (MI) demonstrated decreased odds among overweight (OR, 0.82; 95% CI, 0.71-0.96), Class 1 obese (OR, 0.78; 95% CI, 0.65-0.93), and Class 2 obese (OR, 0.66; 95% CI, 0.51-0.86) patient populations. Odds of MI among the underweight and Class 3 obesity groups were not significant. CONCLUSIONS: The obesity paradox is evident in patients undergoing lower extremity bypass procedures, particularly with odds of 30-day mortality and MI. Our findings suggest that having higher BMI (overweight and Class 1-3 obesity) is not associated with increased mortality and should not be interpreted as a contraindication for lower extremity arterial bypass surgery. However, these patients should be under vigilant surveillance for surgical site infections. Finally, patients that are underweight have a significantly increased odds of 30-day mortality and may be more suitable candidates for endovascular therapy.

Association of abdominal muscle area and density with glucose regulation: The multi-ethnic study of atherosclerosis (MESA).

AIMS: Previous characterisation of body composition as a type 2 diabetes mellitus (T2DM) risk factor has largely focused on adiposity, but less is known about the independent role of skeletal muscle. We examined associations between abdominal muscle and measures of glucose regulation. MATERIALS AND METHODS: Cross-sectional analysis of 1,891 adults enrolled in the Multi-Ethnic Study of Atherosclerosis. Multivariable regression assessed associations between abdominal muscle area and density (measured by computed tomography) with fasting glucose, homeostasis model assessment of insulin resistance (HOMA-IR), and prevalent T2DM (fasting glucose ≥126 mg/dL or medication use). RESULTS: In minimally adjusted models (age, sex, race/ethnicity, income), a 1-SD increment in abdominal muscle area was associated with higher HOMA-IR (ß = 0.20 ± SE 0.03; 95%CI: 0.15, 0.25; P < 0.01) and odds of T2DM (OR = 1.47; 95%CI: 1.18, 1.84; P < 0.01), while higher density was associated with lower fasting glucose (-4.49 ± 0.90; -6.26, -2.72; P < 0.01), HOMA-IR (-0.16 ± 0.02; -0.20, -0.12; P < 0.01), and odds of T2DM (0.64; 0.52, 0.77; P < 0.01). All associations persisted after adjustment for comorbidities and health behaviours. However, after controlling for height, BMI, and visceral adiposity, increasing muscle area became negatively associated with fasting glucose (-2.23 ± 1.01; -4.22, -0.24; P = 0.03), while density became positively associated with HOMA-IR (0.09 ± 0.02; 0.05, 0.13; P < 0.01). CONCLUSIONS: Increasing muscle density was associated with salutary markers of glucose regulation, but associations inverted with further adjustment for body size and visceral adiposity. Conversely, after full adjustment, increasing muscle area was associated with lower fasting glucose, suggesting some patients may benefit from muscle-building interventions.

Health insurance status and type associated with varying levels of glycemic control in the US: The multi-ethnic study of atherosclerosis (MESA).

AIMS: To investigate associations of health insurance with measures of glucose metabolism, and whether associations vary by diabetes status or insurance type. METHODS: Cross-sectional analysis of baseline data from the Multi-Ethnic Study of Atherosclerosis. Cohort a priori stratified by age <65 (N = 3,665) and ≥65 years (N = 2,924). Multivariable linear and logistic regression assessed associations between insurance and fasting glucose, HOMA-IR, and prevalent diabetes, controlling for relevant confounders, including age, sex, race/ethnicity, income, and education. RESULTS: In participants <65, compared to uninsured, having any insurance was associated with lower fasting glucose in participants with diabetes (Mean Difference = -20.4 mg/dL, P = 0.01), but not in participants without diabetes. Compared to Private insurance, uninsured participants had higher fasting glucose (Mean Difference = 3.8 mg/dL, P = 0.03), while participants with Medicaid had higher HOMA-IR (Mean Difference = 3.5 mg/dL, P < 0.01). In participants ≥65, compared to Private insurance, uninsured participants (Mean Difference = 7.5 mg/dL, P = 0.02), and participants with Medicaid only (Mean Difference = 19.9 mg/dL, P < 0.01) or Medicare + Medicaid (Mean Difference = 5.2 mg/dL, P = 0.03) had higher fasting glucose. CONCLUSIONS: In this large multiethnic cohort, having any insurance was associated with significantly lower fasting glucose for individuals with diabetes. Levels of fasting glucose and insulin resistance varied across different insurance types.

Occupational standing and change in the Ankle-Brachial Index: the Jackson Heart Study.

BACKGROUND: A growing interest in reducing occupational sitting has resulted in public health efforts to encourage intermittent standing in workplaces. However, concerns have been raised that standing for prolonged periods may expose individuals to new health hazards, including lower limb atherosclerosis. These concerns have yet to be corroborated or refuted. The purpose of this study was to investigate the association between occupational standing and adverse changes in the Ankle-Brachial Index (ABI). METHODS: We studied 2121 participants from the Jackson Heart Study, a single-site community-based study of African-Americans residing in Jackson, MS. Occupational standing ('never/seldom', 'sometimes', 'often/always') was self-reported at baseline (2000-2004). ABI was measured at baseline and again at follow-up (2009-2013). RESULTS: Over a median follow-up of 8 years, 247 participants (11.6%) exhibited a significant decline in ABI (eg, ABI decline >0.15). In multivariable-adjusted models, higher occupational standing was not significantly associated with ABI decline (occupational standing sometimes vs never/seldom: OR 1.05; 95% CI 0.67, 1.66; occupational standing often/always vs never/seldom: OR 1.22; 95% CI 0.77, 1.94). Similarly, higher occupational standing was not associated with low ABI at follow-up reflective of peripheral artery disease (ABI <0.90) or high ABI at follow-up reflective of incompressible vessels (ABI >1.40). CONCLUSIONS: In this community-based study of African-Americans, we found no evidence that occupational standing is deleteriously associated with adverse changes in ABI over a median follow-up of 8.0 years. These findings do not provide evidence implicating occupational standing as a risk factor for lower limb atherosclerosis.

Relation of Plasma Renin Activity to Subclinical Peripheral and Coronary Artery Disease (from the Multiethnic Study of Atherosclerosis).

Experimental studies support a link between activation of the renin-angiotensin-aldosterone system and cardiovascular disease (CVD). The relationship with subclinical atherosclerosis is uncertain. Among 1,699 individuals without prevalent CVD from the Multiethnic Study of Atherosclerosis, we measured plasma renin activity (PRA) and aldosterone. Using multivariable logistic regression with restricted cubic splines, we assessed continuous log-transformed PRA and aldosterone associations with the ankle-brachial index (ABI) and coronary artery calcium (CAC) scores (Agatston) with adjustment for cardiovascular disease (CVD) risk factors, kidney function, and inflammatory biomarkers. In fully adjusted models mutually adjusting for PRA and aldosterone, higher PRA was associated with an ABI <1.0 (p overall <0.001, p nonlinear = 0.02) and CAC Agatston score >300 (p overall = 0.02, p nonlinear = 0.22), while aldosterone was not associated with either outcome. For example, compared to the 10th percentile (0.16 ng/ml/hr) of PRA, the 90th percentile (2.68 ng/ml/hr) had 3.6 times (OR 3.62; 95% CI: 2.13 to 6.13) and 1.7 times higher odds (odds ratio 1.67; 95% confidence interval: 1.13 to 2.48) of ABI <1.0 and CAC >300, respectively. These associations persisted after adjustment for levels of C-reactive protein, Interleukin-6, and Tumor Necrosis Factor-alpha. There were no significant differences in these associations by race/ethnicity or antihypertensive medication status. In conclusion, in a multiethnic cohort of community-living adults without prevalent clinical CVD, PRA was associated with greater burden of subclinical peripheral artery and coronary artery disease. These findings provide additional evidence that PRA may have deleterious effects on cardiovascular health through an atherosclerotic pathway.

Associations of abdominal muscle area and density with coronary artery calcium volume and density: The multi-ethnic study of atherosclerosis.

BACKGROUND: Due to the opposing cardiovascular risk profiles of CAC volume and density, we tested the hypothesis that increased abdominal muscle area (AMA) and density (AMD) were significantly associated with lower coronary arterial calcium (CAC) volume and higher CAC density. METHODS: Using data from 787 participants from the Multi-Ethnic Study of Atherosclerosis, Ancillary Body Composition Study, we analyzed abdominal and chest computed tomography (CT) scans. Abdominal scans were scored for muscle area, muscle density (attenuation) and visceral and subcutaneous fat. Chest scans were scored for CAC volume and Agatston values, which were used to derive CAC density scores. RESULTS: The mean (SD) age and BMI of the participants was 67.8 (9.0) years and 27.9 (4.8) kg/m2, respectively. Forty-one percent were female, 46% were Caucasian, 60% had hypertension, 17% had diabetes, and 46% had dyslipidemia. AMA was positively associated with CAC volume (p < .001) and inversely associated with CAC density (p < .001). Conversely, AMD was inversely associated with CAC volume and positively associated with CAC density in minimally adjusted models (p < .001), but not significant in confounder adjusted models. CONCLUSION: AMA and AMD had differing associations with CAC volume and density, with AMA significantly associated with a higher risk CAC profile (high volume, low density) and AMD not significantly associated with CAC volume or density. Future research needs to account for the unique components of both muscle composition and CAC.

Burden of Peripheral Artery Disease on Mortality and Incident Cardiovascular Events.

Using data from the Multi-Ethnic Study of Atherosclerosis (United States, 2000-2015), 6,527 racially/ethnically diverse adults (mean age, 62 (standard deviation, 10) years) free of known cardiovascular (CVD) had ankle brachial index (ABI) assessment of their bilateral dorsalis pedis/posterior tibial arteries (4 vessels total) and were followed for total mortality and incident CVD events/mortality. Individuals were classified into categories of 0-, 1-, 2-, 3- or 4-vessel peripheral artery disease (PAD) (ABI of ≤0.9). There were 1,202 deaths (18%), 656 incident CVD events (10%), and 282 CVD deaths (4.3%). Of the 6,527 individuals, 5,711 (87.5%) had 0-, 460 (7.0%) had 1-, 218 (3.3%) had 2-, 69 (1.1%) had 3-, and 69 (1.1%) had 4-vessel PAD, respectively. In multivariable Cox models, higher number of vessels with PAD was associated with higher risk of mortality (P for trend <0.001), CVD events (P for trend = 0.002), and CVD mortality (P for trend = 0.001). Compared with individuals who had 0-vessel disease, hazard ratios for mortality were 1.29 (95% confidence interval (CI): 1.06, 1.59) for 1-, 1.45 (95% CI: 1.14, 1.86) for 2-, 1.58 (95% CI: 1.13, 2.21) for 3-, and 2.15 (95% CI: 1.58, 2.94) for 4-vessel disease. A similar pattern was seen for CVD events/mortality. These results suggest the importance of accounting for ABI values of all 4 leg arteries in clinical practice and research.

Total Sitting Time and Sitting Pattern in Postmenopausal Women Differ by Hispanic Ethnicity and are Associated With Cardiometabolic Risk Biomarkers.

Background Sedentary behavior is pervasive, especially in older adults, and is associated with cardiometabolic disease and mortality. Relationships between cardiometabolic biomarkers and sitting time are unexplored in older women, as are possible ethnic differences. Methods and Results Ethnic differences in sitting behavior and associations with cardiometabolic risk were explored in overweight/obese postmenopausal women (n=518; mean±SD age 63±6 years; mean body mass index 31.4±4.8 kg/m2). Accelerometer data were processed using validated machine-learned algorithms to measure total daily sitting time and mean sitting bout duration (an indicator of sitting behavior pattern). Multivariable linear regression was used to compare sitting among Hispanic women (n=102) and non-Hispanic women (n=416) and tested associations with cardiometabolic risk biomarkers. Hispanic women sat, on average, 50.3 minutes less/day than non-Hispanic women (P<0.001) and had shorter (3.6 minutes less, P=0.02) mean sitting bout duration. Among all women, longer total sitting time was deleteriously associated with fasting insulin and triglyceride concentrations, insulin resistance, body mass index and waist circumference; longer mean sitting bout duration was deleteriously associated with fasting glucose and insulin concentrations, insulin resistance, body mass index and waist circumference. Exploratory interaction analysis showed that the association between mean sitting bout duration and fasting glucose concentration was significantly stronger among Hispanic women than non-Hispanic women (P-interaction=0.03). Conclusions Ethnic differences in 2 objectively measured parameters of sitting behavior, as well as detrimental associations between parameters and cardiometabolic biomarkers were observed in overweight/obese older women. The detrimental association between mean sitting bout duration and fasting glucose may be greater in Hispanic women than in non-Hispanic women. Corroboration in larger studies is warranted.

Sedentary time and peripheral artery disease: The Hispanic Community Health Study/Study of Latinos.

BACKGROUND: Experimental evidence suggests that sedentary time (ST) may contribute to cardiovascular disease by eliciting detrimental hemodynamic changes in the lower limbs. However, little is known about objectively measured ST and lower extremity peripheral artery disease (PAD). METHODS: We included 7,609 Hispanic/Latinos (ages 45-74) from the Hispanic Community Health Study/Study of Latinos. PAD was measured using the ankle brachial index (≤0.9). ST was measured using accelerometry. We used multivariable logistic regression to assess associations of quartiles of ST and PAD, and then used the same logistic models with restricted cubic splines to investigate continuous nonlinear associations of ST and PAD. Models were sequentially adjusted for traditional PAD risk factors, leg pain, and moderate- to vigorous-intensity physical activity (MVPA). RESULTS: Median ST was 12.2 h/d, and 5.4% of individuals had PAD. In fully adjusted restricted cubic splines models accounting for traditional PAD risk factors, leg pain, and MVPA, ST had a significant overall (P = .048) and nonlinear (P = .024) association with PAD. A threshold effect was seen such that time spent above median ST was associated with higher odds of PAD. That is, compared to median ST, 1, 2, and 3 hours above median ST were associated with a PAD odds ratio of 1.16 (95% CI = 1.02-1.31), 1.44 (1.06-1.94), and 1.80 (1.11-2.90), respectively. CONCLUSIONS: Among Hispanic/Latino adults, ST was associated with higher odds of PAD, independent of leg pain, MVPA, and traditional PAD risk factors. Notably, we observed a threshold effect such that these associations were only observed at the highest levels of ST.

Skeletal muscle area and density are associated with lipid and lipoprotein cholesterol levels: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Loss of muscle mass with age may be a key player in metabolic dysregulation. We examined the associations between abdominal muscle area and density with lipids and lipoproteins. METHODS: One thousand eight hundred and sixty eight adults completed health history and physical activity questionnaires, provided venous blood samples for lipids and inflammatory biomarkers, and underwent computed tomography to quantify body composition. Associations between muscle area and density with multiple lipid measures were assessed with multivariable linear and logistic regression. RESULTS: The mean age and body mass index of participants was 65 years and 28 kg/m2, respectively, and 50% were female. After adjustment for demographics, cardiovascular disease risk factors, lipid-lowering medications, physical activity, sedentary behavior, inflammatory biomarkers, and central obesity, a 1-standard deviation increase in total abdominal, stability, and locomotor muscle areas was associated with a 13%, 11%, and 8% lower high-density lipoprotein cholesterol level, respectively (P < .05). With similar adjustment, a 1-standard deviation increase in total abdominal and stability muscle area was associated with a 13% and 12% lower total cholesterol level, respectively (P < .01). Compared to the lowest quartiles of total, stability, and locomotor muscle area, those in the higher quartiles of muscle area had over a 40% reduction in the odds of triglyceride levels greater than 150 mg/dL (P < .05). Total abdominal muscle density was positively associated with total cholesterol (P < .05) but was not associated with the other lipid outcomes. CONCLUSION: Maintaining adequate skeletal muscle mass with age may decrease specific lipid levels related to hyperlipidemia and development of cardiometabolic disease.

Life's Simple 7 and Peripheral Artery Disease: The Multi-Ethnic Study of Atherosclerosis.

INTRODUCTION: In 2010, the American Heart Association initiated Life's Simple 7 with the goal of significantly improving cardiovascular health by the year 2020. The association of Life's Simple 7 with risk of peripheral artery disease has not been thoroughly explored. METHODS: Racially diverse individuals from the Multi-Ethnic Study of Atherosclerosis (2000-2012) were followed for incident peripheral artery disease (ankle brachial index ≤0.90) and decline in ankle brachial index (≥0.15) over approximately 10 years of follow-up. Cox and logistic regression were used to assess associations of individual Life's Simple 7 components (score 0-2) and overall Life's Simple 7 score (score 0-14) with incident peripheral artery disease and ankle brachial index decline, respectively, adjusted for age, sex, race/ethnicity, education, and income. Analyses were performed in 2016-2018. RESULTS: Of 5,529 participants, 251 (4.5%) developed incident peripheral artery disease; 419 (9.8%) of 4,267 participants experienced a decline in ankle brachial index. Each point higher for the overall Life's Simple 7 score was associated with a 17% lower rate of incident peripheral artery disease (hazard ratio=0.83, 95% CI=0.78, 0.88, p<0.001). Additionally, each point higher in overall Life's Simple 7 was associated with a 0.94-fold lower odds of decline in ankle brachial index (OR=0.94, 95% CI=0.87, 0.97, p=0.003). Four components (smoking, physical activity, glucose, and blood pressure) were associated with incident peripheral artery disease and two (smoking and glucose) with decline in ankle brachial index. CONCLUSIONS: Better cardiovascular health as measured by Life's Simple 7 is associated with lower incidence of peripheral artery disease and less decline in ankle brachial index. Use of the Life's Simple 7 to target modifiable health behaviors may aid in decreasing the population burden of peripheral artery disease-related morbidity and mortality.

Outcomes of "one-day" vs "two-day" injection protocols using Tc-99m tilmanocept for sentinel lymph node biopsy in breast cancer.

No prior studies have compared Tc-99m tilmanocept (TcTM) one-day and two-day injection protocols for sentinel lymph node (SLN) biopsy in breast cancer (BC). We retrospectively identified patients with clinically node-negative BC undergoing SLN biopsy at our institution. Patients received a single, intradermal peritumoral injection of TcTM on day of surgery or day prior to surgery in addition to an intraoperative injection of isosulfan blue dye. Univariable and multivariable Poisson regression count models were constructed to assess the effects of injection timing, radiologist, patient and surgeon characteristics on the number of removed SLNs. A total of 617 patients underwent SLN biopsy with TcTM and blue dye. Sixty-seven (10.9%) patients were injected with the two-day protocol. Patients in the one-day protocol had a mean of 3.0 (standard deviation (SD) 1.9) SLNs removed compared with 2.7 (SD 1.4) SLNs in the two-day protocol, P-value = .13. On multivariable analysis, patient age and operating surgeon significantly affected the number of removed SLNs; however, the injection timing and the nuclear radiologist did not influence the number of removed SLNs. The performance of Tc-99m tilmanocept did not differ significantly between one-day and two-day injection protocols. These results are similar to other radiotracers used for SLN biopsy in BC.

Process of Care in Breast Reconstruction and the Impact of a Dual-Trained Surgeon.

BACKGROUND: For postmastectomy reconstruction, the most common model in the United States is a two-team approach, consisting of breast and plastic surgeon. In other countries, a single-surgeon approach trained in both plastic and oncologic surgery is well described. We hypothesized that a dual-trained breast and plastic surgeon would decrease the postoperative care burden for the patient without compromising outcomes and serve as a model for team-centered breast reconstruction care. METHODS: A retrospective review was performed of patients undergoing mastectomy with immediate expander reconstruction from January 2013 to October 2014. Patient data up to 1 year postoperatively was recorded. Patients were stratified by treatment to "single-surgeon" or "two-surgeon" team. Demographic and operative data were recorded. Google Maps was used to calculate travel distance. A standard of mean cost of travel per mile and mean hourly wage for San Diego County was used. The primary outcome was the total number of postoperative clinic visits. In addition, factors predictive of postoperative clinic visits were evaluated. RESULTS: During the study period, 147 patients were included in analysis (69, single-surgeon; 78, two-surgeon). The mean cost of travel per mile was US $59.2 cents and mean hourly wage for San Diego County was US $25.49. For the 1-year follow-up period, patients with the single surgeon had a mean (SD) of 9.3 (3.72) postoperative visits compared with 15.6 (3.96) for patients in the two-surgeon team (P < 0.0001).There were no statistical differences between groups in the rate of complications. In the final model, treatment team, bilateral mastectomies, and complications (operative and nonoperative) were significant predictors of the total number of postoperative visits. Patients in the two-surgeon team spent an additional 11.13 hours and 216 miles commuting and in clinic. In total, the additional 6.3 clinic visits for patients in the two-surgeon team resulted in an average of US $695.33 additional dollars spent on travel and lost wages. CONCLUSIONS: Single-surgeon patients required fewer postoperative visits. Fewer postoperative clinic visits may have significant socioeconomic and psychological benefits to patients. Given these results, we believe that streamlining care into an integrated multidisciplinary model would be beneficial.

Influence of Distance to Hospital and Insurance Status on the Rates of Contralateral Prophylactic Mastectomy, a National Cancer Data Base study.

INTRODUCTION: We evaluated the impact of travel distance and insurance status on contralateral prophylactic mastectomy (CPM) rates in breast cancer. METHODS: We queried the National Cancer Data Base (NCDB) for women >18 years of age with a nonmetastatic primary breast cancer of ductal, lobular, or mixed histology. Patient- and facility-specific CPM rates were calculated based on insurance, race, and distance to treatment center. Standard univariable and multivariable regression analysis was performed. RESULTS: Overall, the CPM rate was 6.5% for the 864,105 patients identified. Most patients traveled <20 miles to a treatment center (79.5%) and had private insurance or Medicare (58.3 and 33.4%, respectively). In general, younger, White, non-Hispanic, and privately insured patients residing further from a treatment center was associated with increased rates of CPM. However, distance to the treatment center and insurance type had a greater absolute impact on rates of CPM for Black and Hispanic patients. Absolute CPM rate increases for patients >100 miles from a treatment center compared with those <20 miles from a treatment center were observed to be greater for Black and Hispanic patients (3.5 and 3.9%, respectively) compared with White and non-Hispanic patients (2.5 and 2.6%). Additionally, further patient travel distance was associated with higher treatment center-specific CPM rates. CONCLUSION: Increased travel distance is independently associated with increased rates of CPM for all patients and increased facility-specific rates of CPM. Black and Hispanic patients were found to be more vulnerable to the impact of travel distance and insurance status on rates of CPM.

Tc-99m tilmanocept versus Tc-99m sulfur colloid in breast cancer sentinel lymph node identification: Results from a randomized, blinded clinical trial.

INTRODUCTION: No prior trials have compared sentinel lymph node (SLN) identification outcomes between Tc-99m tilmanocept (TcTM) and Tc-99m sulfur colloid (TcSC) in breast cancer (BC). METHODS: We report on the secondary outcomes from a randomized, double-blinded, single surgeon clinical trial comparing post-injection site pain between TcTM and TcSC. Patients were randomized to receive a preoperative single, peritumoral intradermal injection of TcTM or TcSC. The number of total, "hot", and blue nodes detected and removed were compared between groups. RESULTS: Fifty-two (27-TcSC and 25-TcTM) patients were enrolled and underwent definitive surgical treatment. At least one "hot" SLN was detected in all patients. Three (5.8%) patients had a disease positive-SLN. The total number of SLNs removed was 61 (mean 2.26 (standard deviation (SD) 0.90)) in the TcSC group and 54 (mean 2.16 (SD 0.90)) in the TcTM group, P = 0.69. The total number of "hot" nodes in the TcSC group was 1.96 (SD 0.76) compared to 2.04 (SD 0.73) in the TcTM group, P = 0.71. CONCLUSIONS: The number of identified SLNs did not differ significantly between TcTM and TcSC. Given that no significant technical advantages exist between the two agents, surgeons should choose a radiopharmaceutical based on cost and side effect profile.

Intraoperative Tumor Detection Using a Ratiometric Activatable Fluorescent Peptide: A First-in-Human Phase 1 Study.

BACKGROUND: Positive surgical margins remain a significant challenge in breast cancer surgery. This report describes the use of a novel, first-in-human ratiometric activatable cell-penetrating peptide in breast cancer surgery. METHODS: A two-part, multi-institutional phase 1 trial of AVB-620 with a 3+3 dose escalation and dose-expansion cohorts was conducted. The patients received an infusion of AVB-620 2-20 h before planned lumpectomy/mastectomy and sentinel node biopsy/axillary dissection. Imaging analysis was performed on images obtained from the surgical field as well as post-excision surgical specimens. Pathology reports were obtained to correlate imaging results with histopathologic data. Information on physical adverse events and laboratory abnormalities were recorded. RESULTS: A total of 27 patients received infusion of AVB-620 and underwent surgical excision of breast cancer. The findings showed no adverse events or laboratory values attributable to infusion of AVB-620. The 8-mg dose was selected from the dose-escalation cohort for use with the expansion cohort based on imaging data. Region-of-interest (ROI) imaging analysis from the 8-mg cohort demonstrated measurable changes between pathology confirmed tumor-positive and tumor-negative tissue. CONCLUSION: Intraoperative imaging of surgical specimens after infusion with AVB-620 allowed for real-time tumor detection. Infusion of AVB-620 is safe and may improve intraoperative detection of malignant tissue during breast cancer operations.

Use of 99mTc-Tilmanocept as a Single Agent for Sentinel Lymph Node Identification in Breast Cancer: A Retrospective Pilot Study.

99mTc-tilmanocept received recent Food and Drug Administration approval for lymphatic mapping in 2013. However, to our knowledge, no prior studies have evaluated the use of 99mTc-tilmanocept as a single agent in sentinel lymph node (SLN) biopsy in breast cancer. Methods: We executed this retrospective pilot study to assess the ability of 99mTc-tilmanocept to identify sentinel nodes as a single agent in clinically node-negative breast cancer patients. Patients received a single intradermal injection overlying the tumor of either 18.5 MBq (0.5 mCi) of 99mTc-tilmanocept on the day of surgery or 74.0 MBq (2.0 mCi) on the day before surgery by a radiologist. Immediate 3-view lymphoscintigraphy was performed. Intraoperatively, SLNs were identified with a portable γ-probe. A node was classified as hot if the count (per second) of the node was more than 3 times the background count. Descriptive statistics are reported. Results: Nineteen patients underwent SLN biopsy with single-agent 99mTc-tilmanocept. Immediate lymphoscintigraphy identified at least 1 sentinel node in 13 of 17 patients (76.5%). Intraoperatively, at least 1 (mean, 1.7 ± 0.8; range, 1-3) hot node was identified in all patients. Three patients (15.8%) had 1 disease-positive SLN. Conclusion: In this small, retrospective pilot study, 99mTc-tilmanocept performed well as a single agent for intraoperative sentinel node identification in breast cancer. A larger, randomized clinical trial is warranted to compare 99mTc-tilmanocept as a single agent with other radiopharmaceuticals for sentinel node identification in breast cancer.

Prognostic significance of marital status in breast cancer survival: A population-based study.

Research shows that married cancer patients have lower mortality than unmarried patients but few data exist for breast cancer. We assessed total mortality associated with marital status, with attention to differences by race/ethnicity, tumor subtype, and neighborhood socioeconomic status (nSES). We included, from the population-based California Cancer Registry, women ages 18 and older with invasive breast cancer diagnosed between 2005 and 2012 with follow-up through December 2013. We estimated mortality rate ratios (MRR) and 95% confidence intervals (CI) for total mortality by nSES, race/ethnicity, and tumor subtype. Among 145,564 breast cancer cases, 42.7% were unmarried at the time of diagnosis. In multivariable-adjusted models, the MRR (95% CI) for unmarried compared to married women was 1.28 (1.24-1.32) for total mortality. Significant interactions were observed by race/ethnicity (P<0.001), tumor subtype (P<0.001), and nSES (P = 0.009). Higher MRRs were observed for non-Hispanic whites and Asians/Pacific Islanders than for blacks or Hispanics, and for HR+/HER2+ tumors than other subtypes. Assessment of interactive effect between marital status and nSES showed that unmarried women living in low SES neighborhoods had a higher risk of dying compared with married women in high SES neighborhoods (MRR = 1.60; 95% CI: 1.53-1.67). Unmarried breast cancer patients have higher total mortality than married patients; the association varies by race/ethnicity, tumor subtype, and nSES. Unmarried status should be further evaluated as a breast cancer prognostic factor. Identification of underlying causes of the marital status associations is needed to design interventions that could improve survival for unmarried breast cancer patients.

Post-mastectomy cancer recurrence with and without a continuous paravertebral block in the immediate postoperative period: a prospective multi-year follow-up pilot study of a randomized, triple-masked, placebo-controlled investigation.

PURPOSE: Retrospective studies have associated perioperative regional anesthesia/analgesia during mastectomy for breast cancer with a decreased incidence of cancer recurrence. However, to date, no prospective data from a randomized controlled trial have been reported. In a previous study we found that extending a single-injection paravertebral block with a multiple-day perineural local anesthetic infusion improves analgesia. This follow-up study investigates the rates of cancer recurrence for the single-injection and multiple-day infusion treatments. METHODS: Patients undergoing unilateral (n = 24) or bilateral mastectomy (n = 36) were included in the study. All patients had been diagnosed with breast cancer or tumor in situ, except for six patients who were receiving prophylactic bilateral mastectomy and were excluded from analyses. Patients received unilateral or bilateral single-injection thoracic paravertebral block(s) corresponding to their surgical site(s) with ropivacaine and perineural catheter(s). Subsequently, patients were randomized to receive either ropivacaine 0.4% (n = 30) or normal saline (n = 30) via their catheter(s) until catheter removal on postoperative day 3. Cancer recurrence from the date of surgery until at least 2 years post surgery was investigated via chart review. RESULTS: Five of the 54 (9.2%) patients experienced a cancer recurrence following mastectomy-3 of 26 (11.5%) of the patients with perineural ropivacaine and 2 of 28 (7.1%) of the patients with perineural saline. CONCLUSIONS: This pilot study found no evidence that extending a single-injection paravertebral block with a multi-day perineural local anesthetic infusion decreases the risk of post-mastectomy cancer recurrence. However, due to the small sample size of this investigation, further research is needed to draw definitive conclusions.