Midterm outcomes in patients with upper extremity deep vein thrombosis.

BACKGROUND: Outcomes and the necessity for anticoagulation in patients with upper extremity deep vein thrombosis (UE DVT) are unclear. The purpose of this study was to determine the incidence of UE DVT, the outcomes of patients stratified by anticoagulation treatment, and which factors were significantly associated with mortality. METHODS: This study was a single-center, retrospective review of all patients undergoing UE venous duplex imaging in 2016. Information on patients' demographics, relevant comorbidities, use of anticoagulation at the time of diagnosis, characteristics of the UE DVT, treatment regimen(s), and outcomes was collected. Data were analyzed using descriptive and univariate statistics; multivariate logistic regression and Cox proportional hazard models were used to identify which of the aforementioned covariates are significantly associated with mortality rates at 30 days and 6 months, respectively, at a 95% confidence level. RESULTS: Of the 911 patients undergoing UE venous duplex imaging, 182 (20.0%) were positive for UE DVT. Within the first 30 days, 30 patients (16.5%) died, 13 (7.1%) had pulmonary emboli, 42 (23.1%) had either pulmonary emboli or died, and 3 (1.6%) had ischemic strokes. Within the first 6 months, 50 patients (27.5%) died. The mortality rate at 30 days was found to be significantly increased in patients who were older (odds ratio [OR], 1.06; P < .01), had high-risk contraindications to anticoagulation (OR, 5.14; P < .01), were on dialysis (OR, 3.03; P = .04), had centrally located UE DVTs (OR, 2.72; P < .05), and had a stroke (OR, 20.34; P = .03). Mortality was significantly decreased in patients who were treated with anticoagulation (OR, 0.16; P < .05). At 6 months, however, age (hazard ratio [HR], 1.05; P < .001), male sex (HR, 2.16; P = .02), dialysis (HR, 2.90; P = .01), high-risk contraindications to anticoagulation (HR, 2.67; P = .02), UE DVTs in both central and peripheral veins (HR, 4.55; P = .03), and ischemic stroke in the first 30 days (HR, 71.63; P < .001) were associated with significant increases in mortality. CONCLUSIONS: These data suggest that mortality rates among patients with UE DVT are relatively high and that treatment with anticoagulation is associated with a decrease in mortality at 30 days. Mortality was also associated with multiple comorbid conditions and demographics and not necessarily venous thromboembolism.

A systematic review of the efficacy of aspirin monotherapy versus other antiplatelet therapy regimens in peripheral arterial disease.

BACKGROUND: Dual antiplatelet therapy (DAPT) usually refers to the administration of aspirin plus a platelet P2Y12 receptor blocker. This combination is commonly prescribed after revascularization procedures in patients with peripheral arterial disease (PAD) to prevent failure of the intervention. However, there is not a consensus among peripheral vascular specialists regarding whether the optimal treatment regimen for their patients is mono antiplatelet therapy (MAPT) or DAPT. Furthermore, there is no consensus regarding the optimal duration of DAPT. This study was undertaken to systematically and critically review the evidence for the use of DAPT after revascularization in PAD, hypothesizing that longer durations of DAPT will result in decreased rates of major adverse cardiac events, major adverse limb events, and mortality, without a significant increase in severe bleeding episodes compared with MAPT or shorter durations of DAPT. METHODS: A systematic search strategy encompassing DAPT and PAD was deployed in two databases. Studies including arterial bypasses using venous or prosthetic conduits, endovascular procedures, diagnostic angiography of lower extremity arteries, and patients with high risk factors were included. RESULTS: We included 14 studies, 10 of which were randomized controlled trials (RCTs). The overall risk of bias for the RCTs ranged from low to moderate, whereas nonrandomized studies had moderate to high risk of bias. The results of this review suggest that use of DAPT in patients with PAD reduces rates of major adverse cardiac events (risk ratio [RR], 0.79; 95% confidence interval [CI], 0.68-0.91; P = .002), major adverse cardiac and cerebrovascular events, and mortality (RR, 0.57; 95% CI, 0.45-0.72; P < .00,001) compared with those of patients treated with MAPT. Lower extremity-specific end points, such as major adverse limb events and target lesion revascularization (RR, 0.70; 95% CI, 0.49-1.01; P = .06) were also decreased in the DAPT cohort. Rates of moderate bleeding, however, were increased in those treated with DAPT, whereas rates of major bleeding (RR, 0.98; 95% CI, 0.68-1.41; P = .92) remained similar in both treatment groups. The effects of DAPT duration on outcomes of revascularization in patients with PAD have yet to be studied in an RCT. CONCLUSIONS: DAPT appears to be beneficial for preventing complications after revascularization in PAD, including thrombotic failure of the intervention. However, the durations of DAPT use in these studies are heterogeneous, suggesting that additional data are needed to determine the optimal use of DAPT in PAD patients.

Noninvasive characterization of the effect of varying PLGA molecular weight blends on in situ forming implant behavior using ultrasound imaging.

In situ forming implants (ISFIs) have shown promise in drug delivery applications due to their simple manufacturing and minimally invasive administration. Precise, reproducible control of drug release from ISFIs is essential to their successful clinical application. This study investigated the effect of varying the molar ratio of different molecular weight (Mw) poly(D,L-lactic-co-glycolic acid) (PLGA) polymers within a single implant on the release of a small Mw mock drug (sodium fluorescein) both in vitro and in vivo. Implants were formulated by dissolving three different PLGA Mw (15, 29, and 53 kDa), as well as three 1:1 molar ratio combinations of each PLGA Mw in 1-methyl-2-pyrrolidinone (NMP) with the mock drug fluorescein. Since implant morphology and microstructure during ISFI formation and degradation is a crucial determinant of implant performance, and the rate of phase inversion has been shown to have an effect on the implant microstructure, diagnostic ultrasound was used to noninvasively quantify the extent of phase inversion and swelling behavior in both environments. Implant erosion, degradation, as well as the in vitro and in vivo release profiles were also measured using standard techniques. A non-linear mathematical model was used to correlate the drug release behavior with polymer phase inversion, with all formulations yielding an R(2) value greater than 0.95. Ultrasound was also used to create a 3D image reconstruction of an implant over a 12 day span. In this study, swelling and phase inversion were shown to be inversely related to the polymer Mw with 53 kDa polymer implants increasing at an average rate of 9.4%/day compared with 18.6%/day in the case of the 15 kDa PLGA. Additionally the onset of erosion, complete phase inversion, and degradation facilitated release required 9 d for 53 kDa implants, while these same processes began 3 d after injection into PBS with the 15 kDa implants. It was also observed that PLGA blends generally had intermediate properties when compared to pure polymer formulations. However, release profiles from the blend formulations were governed by a more complex set of processes and were not simply averages of release profiles from the pure polymers preparations. This study demonstrated that implant properties such as phase inversion, swelling and drug release could be tailored to by altering the molar ratio of the polymers used in the depot formulation.

Effect of cargo properties on in situ forming implant behavior determined by noninvasive ultrasound imaging.

Diagnostic ultrasound has been shown to be an effective method for the noninvasive characterization of in situ forming implant behavior both in vivo and in vitro through the evaluation of the echogenic signal that forms as a consequence of the polymer phase transition from liquid to solid. The kinetics of this phase transition have a direct effect on drug release and can be altered through factors that change the mass transfer events of the solvent and aqueous environment, including properties of the entrapped active agent. This study examined the effect of payload properties on implant phase inversion, swelling, drug release, and polymer degradation. Poly(DL-lactide-co-gylcolide) implants were loaded with either: sodium fluorescein, bovine serum albumin (BSA), doxorubicin (Dox), or 1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI). Fluorescein and Dox were released at near equivalent rates throughout the diffusion phase of release but due to differing drug-matrix interactions, Dox-loaded implants released a lower mass of drug during the degradation phase of release. DiI was not readily released, and due to increased depot hydrophobicity, resulted in significantly lower swelling than the other formulations. The initial echogenicity was higher in Dox-loaded implants than those loaded with fluorescein, but after the initial precipitation, phase inversion and drug release occurred at near equivalent rates for both Dox and fluorescein-loaded implants. Nonlinear mathematical fitting was used to correlate drug release and phase inversion, providing a noninvasive method for evaluating implant release (R(2)>0.97 for Dox, BSA, and fluorescein; DiI had a correlation coefficient of 0.56).