Vlazny, Danielle T.

Background: Popliteal fossa cysts (PFCs aka Baker's cysts) are synovial cysts of the knee joint that can be symptomatic or asymptomatic and incidentally identified on ultrasound. Whether PFCs are associated with deep vein thrombosis (DVT) is unknown. Possible mechanisms for an association include direct compression of the popliteal vein, indirect compression on the popliteal vein with leg flexion, adjacent inflammation of the cyst, or relative immobility due to underlying joint disease itself. Methods: Lower extremity venous Duplex ultrasound radiology reports from the inception of electronic archiving through 11/14/2019 were evaluated across the Mayo Clinic Enterprise (Rochester MN, Jacksonville, FL, Scottsdale AZ, and Mayo Clinic Health System) in patients >18 years of age. Natural language processing (NLP) algorithms were created and validated to identify acute DVT (proximal or distal) and PFCs. A random sample of 1,752 ultrasound reports underwent manual review to calculate the sensitivity and specificity of the NLP algorithm. Cases (ultrasounds with acute DVT) were compared to controls (ultrasound without acute DVT) to examine the frequency of PFCs. IRB approval was obtained and patients lacking Minnesota research authorization were excluded. Results: A total of 332,016 lower extremity venous ultrasounds were performed in 223,035 patients; 156,846 unilateral and 175,170 bilateral lower extremities exams. The mean age at ultrasound was 63.3 (SD 16.5) and 54.7% were female. Ultrasound reports were available for analysis starting in 1992 with a significant increase in the number of ultrasounds performed over the study period across the enterprise (Figure 1). Overall, acute DVT was identified in 24,179 (7.3%) of ultrasounds, and PFCs were identified in 32,427 (9.8%) of ultrasounds. The sensitivity and specificity of the NLP algorithm in the full dataset to identify acute DVT was 86.0% and 97.2%, respectfully. The sensitivity and specificity of the NLP algorithm to identify PFCs was 97.8% and 99.5%, respectively. PFCs were present in 9.3% of ultrasounds with acute DVT and 9.8% of ultrasounds without acute DVT (p=0.007), OR 0.94 (95% CI 0.90-0.98). In a multivariate logistic regression model, after adjusting for age and sex, results remained significant (aOR 0.95, 95% CI 0.91-0.995). Comparing ultrasounds before and after 2010, there was a higher percentage of PFCs and acute DVT reported after 2010 (p<0.001 for both). Sensitivity analyses comparing results before or after 2010, by sex, and only in the first ultrasound performed per person, demonstrated similar results. Conclusions: PFCs are negatively associated with the presence of acute DVT on lower extremity venous Duplex ultrasound. This data does not support PFCs as a contributing or causative factor in the development of lower extremity DVT. Figure 1 Disclosures No relevant conflicts of interest to declare.

Abstract Background The objective of this study was to characterize clinical features and outcomes among patients with calf deep vein thrombosis (DVT) limited to the muscular veins compared with axial veins. Methods Consecutive patients with ultrasound confirmed acute DVT involving the calf veins (January 1, 2016–August 1, 2018) were identified from the Gonda Vascular Center ultrasound database. Patients were divided into axial or muscular groups based on thrombus location. Demographics, management, and outcomes were compared. Results Over the study period, there were 647 patients with calf DVT equally distributed between axial (n = 321) and muscular (n = 326) locations. Within these groups, peroneal and soleal veins were most commonly involved. Nearly all cases were provoked (97%). Synchronous pulmonary embolism (PE) were more common for axial (30.8%) compared to muscular groups (20.2%; p = 0.001); nearly one-third had no pulmonary symptoms. Anticoagulation for a median of 3 months was initiated for 85.5% of both groups. Venous thromboembolism (VTE) recurrence was more common in the axial group (15.9% vs. 7.1%, p = 0.0015) including more frequent DVT propagation (9.4% vs. 3.1%; p = 0.0017) and PE (3.4% vs. 0.6%; p = 0.0168). Major bleeding, clinically relevant nonmajor bleeding, and mortality rates did not differ between groups. Withholding anticoagulation led to more frequent thrombus propagation in the axial group (3.4% vs. 0.9%; p = 0.029). Conclusion Several important features distinguish muscular from axial DVT. Axial DVT are more likely to have an associated PE and are more likely to experience recurrent VTE, particularly if anticoagulation is withheld.

Abstract Objectives To investigate the association of extremes in bodyweight (EBW) and outcomes in patients with acute venous thromboembolism (VTE). Recurrent VTE, major bleeding, and clinically relevant non‐major bleeding were compared between patients with bodyweight <60 kg, 60‐120 kg, and >120 kg. Methods Consecutive patients enrolled in the Mayo Clinic VTE Registry (03/28/2013‐8/31/2019) with acute VTE were followed prospectively. Patient status was assessed in person, by mailing a written questionnaire, or by a scripted phone interview. Results Among 2577 patients with weight ranging from 27.0 kg to 263.2 kg, 2123 (82%) had a bodyweight between 60 and 120 kg, 223 (8.7%) had bodyweight < 60 kg, and 230 (8.9%) had bodyweight >120 kg. Patients with bodyweight <60 kg treated with DOACs had higher 3‐ and 6‐month incidence of major bleeding compared to the bodyweight 60‐120kg group (4.4% vs 1.1%, P = .03, and 4.4% vs 1.4%, P = .05, respectively). Patients with bodyweight >120 kg and cancer on rivaroxaban had higher VTE recurrence compared to bodyweight 60‐120kg group ( P = .01). Conclusions Treatment of acute VTE is associated with a higher incidence of bleeding in patients with bodyweight <60 kg. A higher VTE recurrence rate occurred only in cancer patients with bodyweight >120 kg on rivaroxaban.

AbstractRandomized controlled trials leading to the approval of apixaban and rivaroxaban for venous thromboembolism (VTE) did not include patients with upper extremity deep vein thrombosis (UE‐DVT). We sought to evaluate the safety and effectiveness of rivaroxaban and apixaban for the treatment of acute UE‐DVT. Consecutive patients with VTE enrolled into the Mayo Clinic VTE Registry, between March 1, 2013 and December 31, 2019, were followed prospectively. Clinical, demographic and imaging data were collected at the time of study recruitment. Patients with a diagnosis of acute UE‐DVT who received rivaroxaban, apixaban, LMWH or warfarin were included. Recurrent VTE, major bleeding, clinical‐relevant non‐major bleeding (CRNMB), and death were assessed at 3‐month intervals. During the study period, 210 patients with acute UE‐DVT were included; 63 were treated with apixaban, 39 with rivaroxaban, and 108 with LWMH and/or warfarin. Overall 51% had catheter‐associated UE‐DVT, 60% had a diagnosis of malignancy, and 14% had concurrent pulmonary embolism. Malignancy was more common in patients treated with LMWH/warfarin (67% vs 52%, P = .03). At 3 months of follow up, one (0.9%) recurrent VTE occurred in a patient treated with LMWH/warfarin and one (1.0%) patient treated with apixaban or rivaroxaban (P = .97). Major bleeding occurred in three patients treated with LMWH/warfarin, and in none of those treated with apixaban or rivaroxaban (P = .09). Clinical‐relevant non‐major bleeding occurred in one patient (0.9%) treated with LWMH/warfarin and two patients (2.0%) treated with apixaban or rivaroxaban (P = .53). Treatment of UE‐DVT with apixaban or rivaroxaban appears to be as safe and effective as LMWH/warfarin.

Background: Randomized controlled trials leading to the approval of apixaban and rivaroxaban for venous thromboembolism (VTE) did not include patients with UE-DVT. Limited observational data has been published on outcomes in this setting and no direct comparison to traditional anticoagulation has been performed. Objective: Evaluate the safety and effectiveness of rivaroxaban and apixaban for the treatment of acute UE-DVT compared to low-molecular weight (LWMH) and warfarin. Methods: Consecutive patients with VTE were enrolled into the Mayo Clinic VTE Registry, between March 1, 2013 and July 22, 2019, were followed prospectively. Clinical, demographic and imaging data were collected at the time of study recruitment. Patients with a diagnosis of acute UE-DVT who received either rivaroxaban, apixaban, LMWH or warfarin within the first 14 days after diagnosis and who completed at least 3 months of anticoagulant therapy or had an outcome event in that period were included into the analysis. Recurrent VTE, major bleeding, clinical relevant non-major bleeding (CRNMB), and death were assessed at 3 months, in person whenever feasible, or by mailing a written questionnaire or a scripted phone interview. The study was approved by Mayo Clinic Institutional Review Board. Results: One hundred and thirty-four patients with acute UE-DVT were included. Forty-one were treated with apixaban, 32 with rivaroxaban, and 61 with LWMH and/or warfarin. The mean age was 58.3 years, mean BMI was 28.2, and 59% were male (Table 1). Patients treated with LMWH / warfarin were older (61.3 vs 55.8, p=0.04) and had a lower BMI (27.1 vs 29.0, p=0.0496). Twenty-six (19%) patients had catheter-associated UE-DVT, 93 (69.4%) had a diagnosis of malignancy, and 16 (11.9%) had concurrent pulmonary embolism, which were similar between groups. More patients on apixaban /rivaroxaban were receiving chemotherapy (53.4% vs 47.5%, p=0.04) and had recent surgery (13.7% vs 3.3%, p=0.04) compared to LMWH / warfarin. At 3 months of follow up, 1 recurrent VTE occurred in patients treated with LMWH /warfarin and none of those treated with apixaban /rivaroxaban (p=0.27). Major bleeding occurred in 2 patients treated with LMWH /warfarin and in none of those treated with apixaban /rivaroxaban (p=0.12). CRNMB occurred in 1 patient treated with LWMH /warfarin and 5 patients treated with apixaban / rivaroxaban (p=0.15). Two of the CRNMBs occurred with rivaroxaban and 3 occurred with apixaban. Death occurred in 5 patients treated with LMWH /warfarin and in none of the apixaban /rivaroxaban treated patients (p=0.01). Conclusion: This single institution prospective study adds to the limited experience with apixaban and rivaroxaban for acute UE-DVT. Treatment of UE-DVT with rivaroxaban and apixaban appears to be as safe and effective as LMWH/warfarin after 3 months of anticoagulation. Disclosures McBane: BMS: Research Funding.

Background: Incidental pulmonary embolism (PE) is not infrequently found on CT scans with highest incidence reported in patients with cancer. It is unclear whether patients with symptomatic pulmonary embolism (iPE) have different clinical profile or outcomes compared to patients with symptomatic PE (sPE) and whether this is affected by the presence or type of malignancy. Objective: Compare baseline characteristics of patients diagnosed with iPE to patients with sPE with attention to cancer-specific risk factors as well as evaluate clinical outcomes. Methods: Consecutive patients enrolled in the Mayo Thrombophilia Clinic VTE Registry between March 1, 2013 and December 31st, 2018 with PE were followed prospectively. Outcomes of recurrent venous thromboembolism (VTE), major bleeding, clinically relevant non-major bleeding (CRNMB) and mortality data were collected every 3 months. Clinical outcomes were analyzed with specific focus on patients with cancer. Information was collected and managed using REDCap (Research Electronic Data Capture) and data analysis was performed using SAS software (SAS Institute Inc., Cary, North Carolina). Results: Out of a total of 1033 patients with PE in VTE registry, there were 655 patients with PE (284 with incidental and 363 symptomatic) who completed at least 3 months of anticoagulation and were started on treatment within 14 days of diagnosis. Apixaban was used in 220 (34 %), Rivaroxaban 175 (27 %), Enoxaparin 179 (27%), and Warfarin in 81 (12 %) patients. Overall cancer was present in 61% of patients and was more common in patients with iPE compared to sPE (80.2% vs 45.2%, p<0.001). Patients with iPE were less likely to have previous VTE (8.2% vs 25.5%, p< 0.0001) and tended to have lower BMI (mean 28.8 vs 31.4, p<0.0001) Characteristics of the subgroup of only cancer patients with PE are summarized in the Table. Of note, pancreatic and GI cancers were more common in patients with iPE. There were no differences in recurrent VTE, major bleeding and CRNMB in patients with iPE compared to sPE. This also held true for patients with underlying malignancies. Mortality rates were significantly higher in all patients with iPE even when adjusting for presence of malignancy (p=0.03). When adjusting for presence of metastatic malignancy though the difference was no longer present (p=0.33). Conclusion: Patients with iPE were more likely to have an underlying malignancy, potentially due to higher likelihood of undergoing staging imaging studies. Additionally, patients with iPE more often had metastatic disease which was associated with higher mortality. Recurrent VTE and bleeding outcomes were similar in patients with iPE and sPE, this was independent of the presence of underlying malignancy. Disclosures McBane: BMS: Research Funding.

Abstract To provide direct comparison between apixaban and rivaroxaban in patients with acute cancer‐associated venous thromboembolism (Ca‐VTE), consecutive patients treated with apixaban, rivaroxaban, or enoxaparin at Mayo Thrombophilia Clinic (March 1, 2013 to January 31, 2018)) were followed prospectively. The primary effectiveness outcome was venous thromboembolism (VTE) recurrence, and the secondary was mortality. The primary safety outcome was major bleeding, the secondary clinically relevant safety outcome was non‐major bleeding (CRNMB), and the third a composite of major and CRNMB. There were 750 patients treated for acute Ca‐VTE with apixaban (n = 224), rivaroxaban (n = 163), and enoxaparin (n = 363) within 14 days of diagnosis and for at least 3 months, or until study event. Recurrent VTE was diagnosed in 11 receiving apixaban, 7 receiving rivaroxaban (apixaban vs rivaroxaban hazard ratio (HR) 1.31, 95% confidence interval (95% CI) 0.51‐3.36) and 17 in the enoxaparin receiving group (apixaban vs enoxaparin HR 1.14, 95% CI: 0.54, 2.42 and rivaroxaban vs enoxaparin HR 0.85, 95% Cl: 0.36, 2.06). There were 82 deaths in apixaban, 74 rivaroxaban (apixaban vs rivaroxaban HR 1.67, 95% Cl: 1.20, 2.33) and 171 in enoxaparin group (rivaroxaban vs enoxaparin HR 0.73, 95% Cl: 0.56, 0.96). Major bleeding occurred in 11 apixaban, 12 rivaroxaban (apixaban vs rivaroxaban HR 0.73, 95% Cl: 0.32, 1.66) and 21 enoxaparin group (apixaban vs enoxaparin HR 0.89, 95% Cl: 0.43, 1.84 and rivaroxaban vs enoxaparin HR 1.23, 95% Cl: 0.61, 2.50). The CRNMB rate was higher in rivaroxaban compared to apixaban ( P = .03) and LMWH ( P = .01) groups. Recurrence of VTE and major bleeding were similar in apixaban, rivaroxaban, and enoxaparin groups. Rivaroxaban was associated with higher CRNMB but lower mortality compared to apixaban and enoxaparin.

Spillover of lipoprotein lipase-generated fatty acids from chylomicrons into the plasma free fatty acid (FFA) pool is an important source of FFA and reflects inefficiency in dietary fat storage. We measured spillover in 13 people with type 2 diabetes using infusions of a [3H]triolein-labeled lipid emulsion and [U-13C]oleate during continuous feeding, before and after weight loss. Body fat was measured with dual energy X-ray absorptiometry and computed tomography. Participants lost ∼14% of body weight. There was an ∼38% decrease in meal-suppressed FFA concentration (P &lt; 0.0001) and an ∼23% decrease in oleate flux (P = 0.007). Fractional spillover did not change (P = NS). At baseline, there was a strong negative correlation between spillover and leg fat (r = −0.79, P = 0.001) and a positive correlation with the trunk-to-leg fat ratio (R = 0.56, P = 0.047). These correlations disappeared after weight loss. Baseline leg fat (R = −0.61, P = 0.027) but not trunk fat (R = −0.27, P = 0.38) negatively predicted decreases in spillover with weight loss. These results indicate that spillover, a measure of inefficiency in dietary fat storage, is inversely associated with lower body fat in type 2 diabetes.

Plasma free fatty acid (FFA) kinetics in humans are often measured with only one tracer. In study 1, healthy volunteers received infusions of [U-13C]linoleate, [U-13C]oleate, and [U-13C]palmitate during continuous feeding with liquid meals low (n = 12) and high (n = 5) in palmitate and containing three labeled fatty acids to measure FFA appearance and fractional spillover of lipoprotein lipase–generated fatty acids. Study 2 used an intravenous lipid emulsion to increase FFA concentrations during infusion of linoleate and palmitate tracers. In study 1, there were no differences in spillover of the three fatty acids for the low-palmitate meal, but linoleate spillover was greater than oleate or palmitate for the high-palmitate meal. In studies 1 and 2, clearance was significantly greater for linoleate than for the other FFAs. There was a negative correlation between clearance and concentration for each fatty acid in the two studies. In study 1, concentration and spillover correlated positively for oleate and palmitate but negatively for linoleate. In conclusion, linoleate spillover is greater than that of other fatty acids under some circumstances. Linoleate clearance is greater than that of palmitate or oleate, indicating a need for caution when using a single FFA to infer the behavior of all fatty acids.

Spillover of fatty acids released by lipoprotein lipase hydrolysis of meal triglycerides may be a major contributor to the free fatty acid (FFA) pool. We studied lean (n = 6) and overweight and obese (n = 5) subjects during continuous feeding on two occasions: during intravenous infusion of niacin (2.8 mg/min) and saline. After establishment of steady-state chylomicronemia and suppression of adipose tissue lipolysis with a liquid meal, spillover was measured with infusions of [U-13C]oleate and [3H]triolein. Total FFA concentrations were lower during niacin infusion in both lean (50 ± 4 vs. 102 ± 7 μmol/L; P &lt; 0.002) and obese (75 ± 6 vs. 143 ± 13 μmol/L; P &lt; 0.01) subjects. Oleate appearance was lower during niacin infusion than during saline infusion in both lean (21 ± 2 vs. 32 ± 5 μmol/min; P = 0.07) and obese subjects (25 ± 3 vs. 46 ± 8 μmol/min; P &lt; 0.02). Spillover was lower during niacin infusion than during saline infusion in lean (21 ± 4 vs. 29 ± 3%) and obese (21 ± 2 vs. 29 ± 5%) subjects (P &lt; 0.03 for both). In summary, during meal absorption, niacin produces additional suppression of lipolysis and a reduction in fractional spillover compared with saline in both normal and obese subjects. Infusion of intravenous niacin provides a model for acutely improving dietary fat storage, perhaps by suppressing lipolysis in visceral adipose tissue.