Predicting the Fracture Toughness of Human Cancellous Bone in Fractured Neck of Femur Patients Using Bone Volume and Micro-Architecture.

The current protocol used to determine if an individual is osteoporotic relies on assessment of the individual's bone mineral density (BMD), which allows clinicians to judge the condition of a patient with respect to their peers. This, in essence, evaluates a person's fracture risk, because BMD is a good surrogate measure for strength and stiffness. In recent studies, the authors were the first to produce fracture toughness (FT) data from osteoporotic (OP) and osteoarthritic (OA) patients, by using a testing technique which basically analyzes the prerequisite stress conditions for the onset of growth of a major crack through cancellous bone tissue. FT depends mainly on bone quantity (BV/TV, bone volume/tissue volume), but also on bone micro-architecture (mArch), the inner trabecular design of the bone. The working research hypothesis of the present study is that mArch offers added prediction power to BV/TV in determining FT parameters. Consequently, our aim was to investigate the use of predictive models for fracture toughness and also to investigate if there are any significant differences between the models produced from samples loaded across (AC, transverse to) the main trabecular orientation and along (AL, in parallel) the trabeculae. In multilinear regression analysis, we found that the strength of the relationships varied for a crack growing in these two orthogonal directions. Adding mArch variables in the Ac direction helped to increase the R2 to 0.798. However, in the AL direction, adding the mArch parameters did not add any predictive power to using BV/TV alone; BV/TV on its own could produce R2 = 0.730. The present results also imply that the anisotropic layout of the trabeculae makes it more difficult for a major crack to grow transversely across them. Cancellous bone models and remodels itself in a certain way to resist fracture in a specific direction, and thus, we should be mindful that architectural quality as well as bone quantity are needed to understand the resistance to fracture.

Sex-specific analysis of intravascular lithotripsy for peripheral artery disease from the Disrupt PAD III observational study.

OBJECTIVE: Endovascular therapy of lower extremity peripheral artery disease (PAD) is associated with higher complication rates and worse outcomes in women vs men. Although intravascular lithotripsy (IVL) has shown similarly favorable outcomes in men and women in calcified coronary arteries, there is no published safety and effectiveness data of peripheral IVL differentiated by sex. This study aims to evaluate sex-specific acute procedural safety and effectiveness following IVL treatment of calcified PAD. METHODS: We performed a secondary analysis of the multicenter Disrupt PAD III Observational Study, which assessed short-term procedural outcomes of patients undergoing treatment of symptomatic calcified lower extremity PAD with the Shockwave peripheral IVL system. Adjudicated acute safety and efficacy outcomes were compared by sex using univariate analysis performed with the χ2 test or Fisher exact test, as appropriate. RESULTS: A total of 1262 patients (29.9% women) were included, with >85% having moderate to severe lesion calcification. Women were older (74 vs 71 years; P < .001), had lower ankle-brachial index (0.7 vs 0.8; P = .003), smaller reference vessel size (5.3 vs 5.6 mm; P = .009), and more severe stenosis at baseline vs men (82.3% vs 79.8%; P = .012). Rates of diabetes, renal insufficiency, chronic limb-threatening ischemia, lesion length, and atherectomy use were similar in both groups. Residual stenosis after IVL alone was significantly reduced in both groups. Final residual stenosis was 21.9% in women and 24.7% in men (P = .001). Serious angiographic complications were infrequent and similar in both groups (1.4% vs 0.6%; P = .21), with no abrupt vessel closure, distal embolization, or thrombotic events during any procedure. CONCLUSIONS: The use of IVL to treat calcified PAD in this observational registry demonstrated favorable acute safety and effectiveness in both women and men.

Alterations in the von Willebrand factor/ADAMTS-13 axis in preeclampsia.

BACKGROUND: Preeclampsia is a gestational hypertensive disorder characterized by maternal endothelial activation and increased ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) inhibitor to placental growth factor (PlGF). The von Willebrand factor (VWF)/ADAMTS-13 axis is of interest because of the underlying endothelial activation and clinical overlap with pregnancy-associated thrombotic thrombocytopenic purpura. OBJECTIVES: To assess VWF, ADAMTS-13, and VWF/ADAMTS-13 ratio in preeclampsia and look for associations with sFlt-1/PlGF ratio and clinical features. METHODS: Thirty-four preeclampsia cases and 48 normal pregnancies were assessed in a case-control study. Twelve normal pregnancies in women with a history of preeclampsia formed an additional comparator group. VWF antigen (VWF:Ag) and VWF activity (VWF:Ac [VWF:glycoprotein IbM]) were measured via automated immunoturbidimetric assay, ADAMTS-13 activity was measured via fluorescence resonance energy transfer-VWF73 assay, and sFlt-1 and PlGF were measured via enzyme-linked immunosorbent assay. RESULTS: VWF:Ag was higher in preeclampsia than in normal pregnancy (median, 3.07 vs 1.87 IU/mL; P < .0001). ADAMTS-13 activity was slightly lower (median, 89.6 vs 94.4 IU/dL; P = .02), with no severe deficiencies. Significant elevations in VWF:Ac were not observed in preeclampsia, resulting in reduced VWF:Ac/VWF:Ag ratios (median, 0.77 vs 0.97; P < .0001). VWF:Ag/ADAMTS-13 ratios were significantly higher in preeclampsia (median, 3.42 vs 2.06; P < .0001), with an adjusted odds ratio of 19.2 for a ratio of >2.7 (>75th centile of normal pregnancy). Those with a history of preeclampsia had similar ratios to normal pregnant controls. VWF:Ag/ADAMTS-13 and sFlt-1/PlGF were not correlated. However, percentage reduction in platelets correlated positively with VWF:Ac (P = .01), VWF:Ac/VWF:Ag ratio (P = .004), and sFlt-1/PlGF ratio (P = .01). CONCLUSION: The VWF/ADAMTS-13 axis is significantly altered in preeclampsia. Further investigation of potential clinical utility is warranted.

Radial access for peripheral vascular intervention: the S.M.A.R.T. RADIANZ Vascular Stent System.

INTRODUCTION: Radial access is the standard of care for nearly all cardiac catheterization procedures. It improves patient satisfaction, reduces the length of stay, and is associated with fewer complications. However, few devices and tools are available for the treatment of peripheral arterial disease via a transradial approach (TRA). The S.M.A.R.T. RADIANZ Vascular Stent System is among the RADIANZ suite of products, which is aimed at expanding the portfolio of devices to treat peripheral arterial disease. AREAS COVERED: In this Expert review, the following areas will be covered: (1) Current Landscape of peripheral vascular intervention (PVI) using TRA (2) Detailed description of the S.M.A.R.T. RADIANZ Vascular Stent System. (3) Ongoing clinical trials to evaluate safety of this approach. (4) Future directions and current regulatory status. EXPERT OPINION: TRA for PVI is a promising approach. It holds the possibility of substantially improving the care of patients with peripheral arterial disease (PAD). Numerous challenges must be overcome to realize the full potential of a radial-to-peripheral (RTP) approach. The length of devices and the small sheath size are the main constraints of this approach. The results of the ongoing RADIANCY trial will demonstrate the safety, in selected patients, of the RADIANZ suite of products.

Clinical Outcomes of Additional Below-The-Ankle Intervention Compared to Below-The-Knee Intervention Alone: A Post-Hoc Analysis of a Prospective Multicenter Study.

PURPOSE: To investigate the clinical implication of additional below-the-ankle (BTA) intervention in patients with chronic limb-threatening ischemia (CLTI) undergoing below-the-knee (BTK) intervention. MATERIALS AND METHODS: A sub-analysis was performed using data from the LIBERTY trial (ClinicalTrials.gov identifier NCT01855412), a prospective, observational, core-laboratory adjudicated, multicenter study of endovascular intervention in 1204 patients. Patients with CLTI (Rutherford Classification 4-6) who underwent BTK intervention were included in this sub-analysis. Participants were then stratified into 2 treatment groups according to whether at least one lesion intervened on was BTA (n=66) or not (n=273). The decision on whether and where to intervene was made during the procedure. The main outcome measures included major amputation, target vessel revascularization (TVR), major adverse events (MAE), survival, amputation-free survival, major adverse limb events or peri-operative death (MALE-POD), and all-cause death. Other outcome measures included procedural success, procedural complications, and wound healing rate. RESULTS: There were no differences in procedural success or severe angiographic complications between the 2 groups. At 1-year post-procedure, patients in the BTK group had a higher rate of freedom from major amputation (95.0% vs. 86.9%, respectively; HR: 2.87, 95% CI: 1.17-7.03), a higher rate of freedom from TVR (80.1% vs. 66.9%, respectively; HR: 1.94, 95% CI: 1.14-3.32), a higher rate of freedom from MALE-POD (94.6% vs. 86.9%, respectively; HR: 2.65, 95% CI: 1.10-6.41), and a higher rate of freedom from MAE at both 1 (76.0% vs. 60.1%, respectively; HR: 2.00, 95% CI: 1.24-3.22) and 3 years post procedure (67.5% vs. 55.8%, respectively; HR: 1.69, 95% CI: 1.08-2.65). There was a significantly lower rate of survival in the BTK group at 3 years (74.3% vs. 91.1%, respectively; HR: 0.35, 95% CI: 0.14-0.87). After risk adjustment, there was a higher rate of all-cause death in the BTK group at 3 years (19.4% vs. 9.1%, respectively; p=0.023) post-intervention. CONCLUSION: Patients with disease requiring intervention to BTA lesions have a potential increased amputation rate in the short term, but BTA intervention carries a potential survival benefit in the long term when compared to BTK intervention alone.

Twenty-Four Month Results of Tack-Optimized Balloon Angioplasty Using the Tack Endovascular System in Below-the-Knee Arteries.

PURPOSE: To report 24 month safety and efficacy of the Tack Endovascular System for treatment of post-percutaneous transluminal angioplasty (PTA) infrapopliteal dissections in patients with critical limb-threatening ischemia (CLTI). MATERIALS AND METHODS: The Tack-Optimized Balloon Angioplasty (TOBA) II below-the-knee (BTK) study was a prospective, multicenter, single-arm evaluation of the Tack Endovascular system for post-PTA infrapopliteal dissection repair. Patients with Rutherford Clinical Category (RC) 3 to 5 and a post-PTA dissection(s) of the BTK arteries were enrolled. The 30 day primary safety endpoint was a composite of major adverse limb events (MALE) and all-cause perioperative death (POD). The primary effectiveness endpoint was a composite of MALE at 6 months and 30 day POD. Outcomes were assessed as observational endpoints at 24 months. RESULTS: Tack-Optimized Balloon Angioplasty II BTK enrolled 233 patients; all patients had a post-PTA dissection(s) and received ≥1 Tack implant (range, 1-16). Mean age was 74.4±10.0 years and 67.4% were men. Most patients had CLTI (RC 3: 16.3%; RC 4/5: 83.7%). Mean target lesion length was 80±49 mm. Moderate to severe calcium was present in 89 (35.8%) lesions and total occlusions were present in 118 (47.6%) lesions. Kaplan-Meier freedom from MALE at 24 months + POD at 30 days was 92.2% and 24 month freedom from clinically-driven target lesions revascularization was 73.6%. Kaplan-Meier target limb salvage was 95.7% and amputation-free survival was 75.4%. Improvements in functional status and quality of life were observed through 24 months. CONCLUSION: The TOBA II BTK study demonstrated sustained safety and efficacy through 24 months in patients treated for post-PTA dissection(s) of BTK lesions. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02942966.

Heterogeneous run-and-tumble motion accounts for transient non-Gaussian super-diffusion in haematopoietic multi-potent progenitor cells.

Multi-potent progenitor (MPP) cells act as a key intermediary step between haematopoietic stem cells and the entirety of the mature blood cell system. Their eventual fate determination is thought to be achieved through migration in and out of spatially distinct niches. Here we first analyze statistically MPP cell trajectory data obtained from a series of long time-course 3D in vivo imaging experiments on irradiated mouse calvaria, and report that MPPs display transient super-diffusion with apparent non-Gaussian displacement distributions. Second, we explain these experimental findings using a run-and-tumble model of cell motion which incorporates the observed dynamical heterogeneity of the MPPs. Third, we use our model to extrapolate the dynamics to time-periods currently inaccessible experimentally, which enables us to quantitatively estimate the time and length scales at which super-diffusion transitions to Fickian diffusion. Our work sheds light on the potential importance of motility in early haematopoietic progenitor function.

Changes to Drug-Coated Balloon Reimbursement Affect Peripheral Arterial Disease Patient Care: A Single-Center Experience.

INTRODUCTION: Balloon angioplasty (BA) and stenting have long been the mainstays of endovascular therapy in peripheral arterial disease (PAD). However, the rise of drug-coated balloons (DCBs) has revolutionized care in recent years, with multiple clinical trials showing superiority over BA in maintaining primary patency and freedom from target lesion revascularization (TLR). With the recent drop of the add-on payment for DCBs, a barrier for their use and consequently reduced therapy adoption in PAD might arise. We assessed if this affected physicians' behavior and hospital administration towards stocking and using DCBs. METHODS: This single-center, retrospective study evaluated DCB utilization in 2017 versus 2018. Data were collected in two groups: 1) July 1, 2017, to December 31, 2017 - with pass-through code (PTC) - prior medical billing reimbursement - and 2) January 1, 2018, to June 30, 2018 - without PTC - markedly reduced reimbursement. Patients treated for superficial femoral artery (SFA) or popliteal artery (POP) disease were included. The study aimed to determine changes in DCB utilization between the years with and without PTC, and we investigated the treatments that have replaced DCBs. Additionally, we aimed to collect data on readmissions and procedure costs compared to national data. RESULTS: From July through December 2017, 350 DCBs were used in 209 patients (1.675 DCBs per patient), while from January through June 2018, 256 DCBs were used in 180 patients (1.422 DCBs per patient) - a 15.07% reduction in DCBs per patient. The detailed numbers of DCB-treated patients were presented as fractions of total interventions in the groups with and without PTC. CONCLUSION: The findings of this study show a statistically significant reduction in DCB usage following PTC withdrawal. There are several ethical implications to these findings, primarily highlighting patient beneficence and justice. Moving forward, it will be important to determine if this shift in treatment is owed to other treatment strategies such as BA, BA and atherectomy, BA and bare-metal stents (BMS), or BA and drug-eluting-stents (DES). The next steps should also include determining procedure costs and comparing readmission rates.

Comparison of Angiographic and Intravascular Ultrasound Vessel Measurements in Infra-Popliteal Endovascular Interventions: The Below-the-Knee Calibration Study.

BACKGROUND: Endovascular revascularization (ER) via percutaneous transluminal angioplasty (PTA) and stenting are viable options for revascularization in below-the-knee (BTK) peripheral arterial disease. Two-dimensional angiography has been the standard of practice for estimating vessel size and selecting treatment devices during ER. However, in other vascular territories, intravascular ultrasound (IVUS) offers better visualization of the lumen dimensions. PURPOSE: To compare angiographic and intravascular ultrasound reference vessel (lumen) measurements in below-the-knee peripheral artery interventions. METHODS: Twenty consecutive patients were enrolled in the BTK Calibration study from 2 sites in the United States and Australia. Patients with at least one diseased segment in a native infra-popliteal artery (below-the-knee) and a clinical indication for endovascular therapy (EVT) were included with no limitations with regard to vessel diameter or lesion length. Digital subtraction angiography and IVUS imaging were collected pre- and post-PTA and images were sent to an independent core lab for standardized quantitative analysis of the normal-looking reference vessel dimensions when available. The results were presented as least square means with 95% confidence intervals and a p-value of <0.05 was considered significant. RESULTS: The overall (N = 19) mean reference vessel diameter for QVA was 2.98 ± 1.24 mm vs. 3.47 ± 0.72 mm for IVUS (mean difference was -0.50 mm, (95% CI: -0.80, -0.20; p = 0.14). As expected, in the proximal segments (N = 12), the mean reference vessel diameters were larger: for QVA, it was 3.17 ± 1.34 mm vs. 3.55 ± 0.76 mm in IVUS, (mean difference was -0.38 mm, (95% CI: -0.79, 0.03; p = 0.40); while in the distal segments (N = 7), mean reference vessel diameters were smaller: for QVA, it was 2.64 ± 1.06 mm vs. 3.33 ± 0.67 mm in IVUS, (mean difference was -0.69 mm, (95% CI: -1.04, 0.34; p = 0.17). We observed a greater degree of acute gain in cases where the treatment balloon size correlated with the IVUS measured reference size. CONCLUSION: Angiography underestimates infrapopliteal reference vessel lumen size even when quantitatively assessed. Adjunctive IVUS imaging use in guiding BTK procedures could help ensure adequate sizing and possibly impact immediate post-procedure indices.

Intravascular Lithotripsy for Treatment of Calcified Infrapopliteal Lesions: Results from the Disrupt PAD III Observational Study.

PURPOSE: To evaluate the safety and effectiveness of the Shockwave S4 intravascular lithotripsy (IVL) catheter in an "all-comers" cohort of patients with calcified infrapopliteal lesions. MATERIALS AND METHODS: The Disrupt PAD III Observational Study (NCT02923193) is a prospective, nonrandomized, multicenter single-arm study designed to assess the "real-world" acute safety and effectiveness of the Shockwave Peripheral IVL System for the treatment of de novo calcified, stenotic peripheral arteries. Patients were eligible for enrollment if they had claudication or critical limb ischemia (CLI) and at least moderate calcification as assessed by angiography. This subanalysis includes consecutive patients enrolled with angiographic core lab-assessed treatment of infrapopliteal arteries using the Shockwave S4 IVL catheter. RESULTS: From July 2018 to August 2020, 101 patients with 114 calcified infrapopliteal arteries treated with the S4 IVL catheter were enrolled at 15 sites in 3 countries. CLI was present in 69.3% of patients. The anterior tibial and tiboperoneal trunk were the most commonly treated vessels with an overall mean reference vessel diameter (RVD) of 3.1±0.8 mm, minimum lumen diameter (MLD) of 0.5±0.6 mm, and a corresponding diameter stenosis of 83.4%±15.8% by core lab assessment. Mean lesion length was 64.7±54.7 mm with moderate to severe calcification in 69.3% of lesions by the Peripheral Academic Research Consortium (PARC) criteria. Adjunctive calcium-modifying technology, defined as scoring or cutting balloon and/or atherectomy, was used in 22.7% of procedures. The average acute gain at the end of the procedure was 2.0±0.7 mm with a residual stenosis <50% achieved in 99.0% of lesions and a mean residual stenosis of 23.3±12.5%. There were no flow-limiting dissection, embolization, slow flow/no-reflow, or abrupt closure events at the end of the procedure. CONCLUSION: This subanalysis of the PAD III Observational Study represents the largest report to-date of IVL treatment of heavily calcified below-the-knee (BTK) lesions in a "real-world" patient cohort. The use of S4 IVL demonstrated consistent acute safety and effectiveness outcomes consistent with prior IVL peripheral studies. These consistent outcomes were achieved with the initial use of the S4 IVL catheter for treatment of complex BTK lesions.

Procedural Effectiveness With a Focused Force Scoring Angioplasty Catheter: Procedural and Clinical Outcomes From the Scoreflex NC Trial.

BACKGROUND: The Scoreflex NC scoring angioplasty catheter is designed with a short rapid-exchange tip distal to a non-compliant, high-pressure balloon and an integral wire outside of the balloon, such that the guidewire and the integral wire act as scoring elements during balloon inflation. The external scoring elements enable a focal stress pattern facilitating expansion of resistant lesions at lower pressures using a focused force angioplasty effect. METHODS: Patients undergoing elective percutaneous coronary intervention (PCI) were enrolled in a prospective, single-arm study conducted at 12 centers in the United States. The primary endpoint was device procedural success, defined as the composite of successful device delivery to the target lesion with balloon inflation and deflation; absence of vessel perforation, flow-limiting dissection or reduction in TIMI flow from baseline; and achievement of final TIMI 3 flow. RESULTS: Among 200 patients (234 lesions), lesion complexities included: bifurcation disease (37.6%), moderate/severe calcification (36.6%), and total occlusions (5.0%). Successful delivery to the target lesion, inflation and removal of the balloon catheter was achieved in 95.5% of patients (191/200). Procedural success was achieved in 93.5% (187/200) of patients, and final TIMI 3 flow was observed in 99.0% of cases (198/200). No unanticipated device-related events occurred. In-hospital major adverse events were reported in 4.5% of patients (9/200), related to periprocedural myocardial infarction (8/200, 4.0%) and target lesion revascularization (1/200, 0.5%). CONCLUSIONS: Among patients undergoing elective PCI and with varied lesion complexity, these results support the safety and effectiveness of a dilation strategy using the Scoreflex NC scoring catheter.

Outcomes of Orbital Atherectomy in Patients with Critical Limb Threatening Ischemia and Diabetes.

Purpose: Patients with diabetes and critical limb threatening ischemia (CLTI) are at significantly higher risk of limb loss and death. Here we evaluate the outcomes of orbital atherectomy (OA) for treatment of CLTI in patients with and without diabetes. Methods: Retrospective analysis of the LIBERTY 360 study was performed to evaluate baseline demographics, and peri-procedural outcomes between patients with CLTI, and with and without diabetes. Hazard ratios (HRs) were determined with Cox regression to examine the impact of OA in patients with diabetes and CLTI over a 3-year follow-up. Results: A total of 289 patients (201 with diabetes, 88 without diabetes) with Rutherford classification 4-6 were included. Patients with diabetes had higher proportion of renal disease (48.3% vs 28.4%, p=0.002), prior minor/major limb amputation (26% vs 8%, p<0.005), and presence of wounds (63.2% vs 48.9%, p=0.027). Operative times, radiation dosage, and contrast volume were similar between groups. The rate of distal embolization was higher in patients with diabetes (7.8% vs 1.9%, p=0.01; OR 4.33 [0.99, 18.88], p=0.05). However, at 3-years post-procedure, patients with diabetes had no differences in freedom from target vessel/lesion revascularization (HR 1.09, p=0.73), major adverse events (MAE; HR 1.25, p=0.36), major target limb amputation (HR 1.74, p=0.39), and death (HR 1.11, p=0.72). Conclusion: The LIBERTY 360 observed high limb preservation and low MAEs in patients with diabetes and CLTI. Higher distal embolization was observed with OA in patients with diabetes, but OR did not indicate a significant difference in risk between groups.

Anterior, posterior, or all-vessel infrapopliteal revascularization in patients with moderate-severe claudication: Insights from the LIBERTY 360 study.

BACKGROUND: Little data guides revascularization of infrapopliteal peripheral arterial disease (PAD) in patients with claudication. We assessed outcomes after infrapopliteal-only intervention for claudication in the LIBERTY 360 observational study. METHODS: In this post hoc analysis, LIBERTY 360 patients (N = 128) with claudication and isolated infrapopliteal disease undergoing endovascular revascularization were divided by territory into anterior-vessel, posterior-vessel, or all-vessel groups. Patients were followed for periprocedural, in-hospital, and long-term outcomes. Logistic regression for odds ratios, Cox proportional hazard models, ANOVA, and Kaplan-Meier estimates were utilized to compare outcomes. RESULTS: Patients underwent anterior (N = 37), posterior (N = 76), or all-vessel (N = 15) infrapopliteal revascularization. Initial procedural success was 86%, 86%, and 69% for anterior, posterior, and all-vessel groups, respectively. Each group had improvements in Rutherford classification (RC) from baseline to 2 years (mean RC change: -1.3, -1.5, and -1.5, respectively). Compared with all-vessel intervention, both anterior and posterior groups had lower rate of major adverse events (MAE) and target vessel revascularization (TVR) at 3 years (MAE: 12% and 15% in anterior and posterior groups, respectively compared with 51% in the all-vessel group; hazard ratios and 95% CIs 0.22 [0.06-0.74], p = .015; 0.24 [0.09-0.64], p = .004). Other outcomes were similar among the three groups. The anterior group showed more improvement in pain subdomain and total VascuQoL scores compared with posterior and all-vessel groups at 2 years (p = .016, p = .020 and p = .068, p = .009, respectively). CONCLUSIONS: Both anterior or posterior revascularization have favorable outcomes and may be beneficial for improvement of symptoms in claudicants with isolated infrapopliteal PAD.

Two-year PAD-related health care costs in patients undergoing lower extremity endovascular revascularization: results from the LIBERTY 360° trial.

BACKGROUND: Multiple studies have demonstrated the high economic burden related to the management of lower extremity peripheral artery disease (PAD). This is the first study to examine long-term PAD-related costs among unselected patients undergoing endovascular intervention, and to investigate how clinical and anatomic factors impact cost outcomes over time. METHODS AND RESULTS: We performed a prospective health economic study alongside the LIBERTY 360° trial (ClinicalTrials.gov; identifier NCT01855412) - a prospective, multi-center study evaluating the long-term outcomes of endovascular revascularization to treat claudication or critical limb ischemia. Costs (2018) were calculated using a combination of standard "bottom-up" cost accounting methods (for index procedures), itemized hospital charges and department level cost-to-charge ratios (for non-procedural hospital resources), national Medicare Severity-Diagnosis Related Group-specific average reimbursements (for follow-up hospitalizations) and Medicare payments (for outpatient/chronic care). Methods for the analysis of censored cost data were used to adjust cost estimates for patients with incomplete follow-up. Independent predictors of cumulative 2-year costs were explored using generalized linear models. A total of 1,189 patients were included (500 Rutherford 2-3, 589 Rutherford 4-5, 100 Rutherford 6). Mean total costs associated with the index procedure hospitalization increased with Rutherford classification ($10,304, $11,418, and $19,403 for Rutherford 2-3, 4-5, and 6, respectively; p < 0.01 in all pairwise comparisons). Mean total 2-year follow-up costs were $11,416, $24,846, and $25,720 for Rutherford 2-3, 4-5, and 6, respectively (p < 0.001 comparing Rutherford 2-3 to the other 2 groups; p = 0.09 comparing Rutherford 4-5 and Rutherford 6). Key predictors of higher cumulative 2-year costs included female sex, pedal lesion location, severe lesion calcification, the presence of one or more chronic total occlusions, the number of wounds present on the target limb at baseline, and Rutherford classification. CONCLUSIONS: Among patients with symptomatic lower extremity PAD undergoing endovascular revascularization, initial treatment costs and total 2-year costs vary significantly according to clinical and lesion-level characteristics, as well as symptom burden.

Six-month pivotal results of tack optimized balloon angioplasty using the Tack Endovascular System in below-the-knee arteries.

OBJECTIVE: No vascular implant is commercially available in the United States to treat post-angioplasty dissections in below-the-knee (BTK) arteries. The Tack Endovascular System (Intact Vascular, Wayne, Pa) is purpose-built to repair postpercutaneous transluminal angioplasty (PTA) BTK dissections. A trial was conducted to investigate the safety and efficacy of the first-of-a-kind implantable BTK device to treat post-PTA dissections in the setting of critical limb ischemia. METHODS: The present prospective, single-arm, multicenter study evaluated the Tack Endovascular System for treating post-PTA dissections in the mid/distal popliteal, tibial, and peroneal arteries. The primary safety endpoint was major adverse limb events (MALE) plus perioperative death (POD), assessed at 30 days after the index procedure. The primary efficacy endpoint was a composite of MALE at 6 months and POD. The unpowered secondary endpoint was primary patency at 6 months. With no available on-label comparator, the primary endpoints of the present trial were determined using objective performance goals from a systematic literature search. The secondary endpoints included Tacked segment patency and target limb salvage at 6 months. The 6-month results are reported. RESULTS: Of the 233 patients enrolled, 117 (50.2%) had Rutherford class 5 and 78 (33.5%) had Rutherford class 4. A total of 341 post-PTA dissections were treated. Each patient received at least one Tack implant, and 100% of the dissections resolved according to the angiographic core laboratory findings. The primary safety and efficacy endpoints were both met. The rate of MALE plus POD at 30 days was 1.3% (3 of 228) and freedom from MALE at 6 months plus POD at 30 days was 95.6% (196 of 205). The 6-month Tacked segment patency was 82.1% (247 of 301) and target limb salvage was 98.5% (202 of 205). The Kaplan-Meier freedom from clinically driven target lesion revascularization and amputation-free survival at 6 months was 92.0% and 95.7%, respectively. Rutherford improvement was reported in 79.4% (158 of 199). Most (90 of 122; 73.8%) preexisting wounds had healed or were improving. CONCLUSIONS: The Tack Endovascular System is safe and effective for treating post-PTA BTK dissections through 6 months, with favorable rates of MALE plus POD, patency, clinically driven target lesion revascularization, limb salvage, and wound healing.

Characteristics and Outcomes of Patients With Diabetes Mellitus Undergoing Peripheral Vascular Intervention for Infrainguinal Symptomatic Peripheral Artery Disease.

PURPOSE: Patients with diabetes mellitus (DM) are known to be at higher risk for peripheral artery disease (PAD), amputations, and major adverse cardiovascular events, though it is unclear whether they are at any higher risk for repeat intervention. LIBERTY 360 offered an opportunity to study a real-world cohort of patients who underwent distal superficial femoral artery endovascular revascularizations. We aimed to describe patients with DM, their outcomes following peripheral vascular intervention, and the effect of DM on outcomes in the LIBERTY 360 cohort. METHODS: LIBERTY 360 is a prospective, multi-center, non-randomized, mono-industry funded observational study of patients undergoing endovascular revascularization. Outcomes included 30-day and 1-year all-cause mortality, major amputation, target vessel/lesion revascularization, and a composite of those events. A multivariable regression model including DM was constructed to examine the effect of DM on outcomes. Multivariable survival estimates were made using Cox proportional hazards models. RESULTS: A total of 1,204 patients were enrolled, of whom 727 had DM (60.4%). Patients with DM had significantly more comorbidities and a third required insulin for DM management. Patients with DM had more severe disease based on Rutherford classification at baseline. After adjusting for comorbidities and disease severity, DM patients had more frequent major amputations at 1 year (5.2% versus 1.2%; HR 2.71, 95%CI 1.05-6.98, p = 0.040). The 1-year rates of all-cause mortality and target vessel/lesion revascularization were not significantly higher for patients with DM. CONCLUSIONS: Diabetes mellitus was associated with increased major amputations at 1 year following endovascular revascularization after accounting for demographics, comorbidities, and PAD-related characteristics. Further research is needed to determine which aspects of PAD and DM are most strongly associated with poor outcomes following lower extremity revascularization.

Three-Year Outcomes From the LIBERTY 360 Study of Endovascular Interventions for Peripheral Artery Disease Stratified by Rutherford Category.

PURPOSE: To report the 3-year results of the LIBERTY 360 study, which investigated outcomes of endovascular treatment of symptomatic peripheral artery disease (PAD). MATERIALS AND METHODS: The LIBERTY trial (ClinicalTrials.gov identifier NCT01855412) was a prospective, observational, core laboratory-assessed, multicenter study of endovascular interventions enrolling >1200 participants treated at 51 sites. Data from 1189 patients were stratified according to Rutherford category (RC) and analyzed [RC 2-3 (n=500), RC 4-5 (n=589), and RC 6 (n=100)]. The primary outcomes were major amputation of the target limb and all-cause death; secondary outcomes were target vessel revascularization (TVR) or target lesion revascularization (TLR); major adverse events (MAEs; death within 30 days, TVR or TLR, and major amputation); death or major amputation combined; and change in self-reported quality of life (QoL) measures (VascuQol-25). The Kaplan-Meier (KM) method was employed to estimate the outcomes; estimates are presented with the 95% confidence intervals (CI). Predictors of 3-year MAE, death, TVR, and major amputation were analyzed using Cox proportional hazard regression modeling. RESULTS: The 36-month KM survival rates were 86.0% in RC 2-3, 79.8% in RC 4-5, and 62.0% in RC 6 groups. The KM estimates of freedom from major amputation at 36 months were 98.5% in RC 2-3, 94.0% in RC 4-5, and 79.9% in RC 6. The 36-month KM estimates for freedom from TVR/TLR were 71.1% in RC 2-3, 64.2% in RC 4-5 and 61.9% in RC 6 groups. Patients with claudication at baseline were at lower risk for MAEs compared with RC 4-5 and RC 6 patients during the 36-month follow-up. Vascular QoL improved from baseline and persisted up to 36 months in all patients. CONCLUSION: Endovascular therapy is a viable treatment option for patients with symptomatic PAD, with sustained improved quality of life in both claudicants and patients with chronic limb-threatening ischemia. These results provide important point estimates for midterm outcomes after modern endovascular interventions for PAD.

Microbiological evaluation of resection margins of the infected diabetic foot ulcer.

AIM: To evaluate the impact of surgical debridement on the microbiology of resection margins of an infected diabetic foot ulcer and to compare the use of marginal sampling as a guide for antimicrobial therapy. METHODS: Forty consecutive participants were studied. Tissue samples from infected diabetic foot ulcers were obtained at first contact by podiatrists. After surgical debridement to macroscopically healthy tissue, multiple samples were obtained from the margins of the residuum and also from excised non-viable tissue. Debridement was done by a single surgeon. Bacterial species were classified according to pathogenic potential a priori into Red Group-Definite pathogen causing infection, Yellow Group-Likely to be causing infection if present in more than one specimen and Green Group -Commensals, not causing infection. RESULTS: There was a relative reduction of 49% (p = 0.002) in bacteria in the most pathogenic (red) group, and 59% (p = 0.002) in the yellow group in podiatry samples compared with resection specimen. Positive cultures from margins of the residuum were observed in 75% of cases. There was a relative reduction of 67% (p = 0.0001) in bacteria in the red and 48% (p = 0.06) in the yellow group in marginal samples from the residuum compared with podiatry samples. CONCLUSIONS: After surgical debridement to healthy tissue, positive cultures from marginal tissue samples provided vital information on the presence of pathogenic bacteria. This allowed antibiotics to be individualised post-surgical debridement.