Enhanced external counterpulsation treatment improves multi-organ hemodynamics for postoperative liver transplantation patient. A case report.

INTRODUCTION: Post liver transplantation (LT) patients endure high morbidity rate of multi-organ ischemic symptoms following reperfusion. We hypothesize that enhanced external counterpulsation (EECP) as a typical non-invasive assisted circulation procedure, which can efficiently inhibit the relative ischemic symptoms via the systemic improvement of hemodynamics. CASE PRESENTATION: A 51-year-old male patient, 76 kg, 172 cm, received orthotopic LT surgery for viral hepatitis B induced acute-on-chronic liver failure hepatic failure. His medical records revealed ischemic symptoms in multi-organ at the time of hospital discharge, including headache, refractory insomnia, abdominal paralysis, and lower limb pain. The EECP treatment was introduced for assisted rehabilitation and to improve the postoperative quality of life. Doppler Ultrasound examination showed significant augmentation of blood flow volume in the carotid arteries, the hepatic artery, the portal vein and the femoral artery during EECP intervention. A standard 35-hour EECP treatment led to significant improvement in quality of life, e.g. sleep quality and walking ability. CONCLUSION: We report a case of multi-organ ischemic symptoms in a post LT patient. EECP treatment can significantly improve the quality of life via the systematic promotion of hemodynamics.

Alginate-Encapsulated Mesenchymal Stromal Cells Improve Hind Limb Ischemia in a Translational Swine Model.

BACKGROUND: Cellular therapies have been investigated to improve blood flow and prevent amputation in peripheral artery disease with limited efficacy in clinical trials. Alginate-encapsulated mesenchymal stromal cells (eMSCs) demonstrated improved retention and survival and promoted vascular generation in murine hind limb ischemia through their secretome, but large animal evaluation is necessary for human applicability. We sought to determine the efficacy of eMSCs for peripheral artery disease-induced limb ischemia through assessment in our durable swine hind limb ischemia model. METHODS AND RESULTS: Autologous bone marrow eMSCs or empty alginate capsules were intramuscularly injected 2 weeks post-hind limb ischemia establishment (N=4/group). Improvements were quantified for 4 weeks through walkway gait analysis, contrast angiography, blood pressures, fluorescent microsphere perfusion, and muscle morphology and histology. Capsules remained intact with mesenchymal stromal cells retained for 4 weeks. Adenosine-induced perfusion deficits and muscle atrophy in ischemic limbs were significantly improved by eMSCs versus empty capsules (mean±SD, 1.07±0.19 versus 0.41±0.16, P=0.002 for perfusion ratios and 2.79±0.12 versus 1.90±0.62 g/kg, P=0.029 for ischemic muscle mass). Force- and temporal-associated walkway parameters normalized (ratio, 0.63±0.35 at week 3 versus 1.02±0.19 preligation; P=0.17), and compensatory footfall patterning was diminished in eMSC-administered swine (12.58±8.46% versus 34.85±15.26%; P=0.043). Delivery of eMSCs was associated with trending benefits in collateralization, local neovascularization, and muscle fibrosis. Hypoxia-cultured porcine mesenchymal stromal cells secreted vascular endothelial growth factor and tissue inhibitor of metalloproteinase 2. CONCLUSIONS: This study demonstrates the promise of the mesenchymal stromal cell secretome at improving peripheral artery disease outcomes and the potential for this novel swine model to serve as a component of the preclinical pipeline for advanced therapies.

Neutrophil extracellular traps induced by IL-1ß promote endothelial dysfunction and aggravate limb ischemia.

Vascular inflammation and endothelial dysfunction contribute to vascular diseases. While neutrophil extracellular traps (NETs) participate in some vascular pathologies, their roles in lower limb ischemia remain poorly defined. This study investigated the functional significance of NETs in vascular inflammation and remodeling associated with limb ischemia. Single-cell RNA sequencing (scRNA-seq) and flow cytometry revealed neutrophil activation and upregulated NETs formation in human limb ischemia, with immunofluorescence confirming IL-1ß-induced release of NETs for vascular inflammation. Endothelial cell activation was examined via scRNA-seq and western blotting, indicating enhanced proliferation, expression of adhesion molecules (VCAM-1, ICAM-1), inflammatory cytokines (IL-1ß, IL-6) and decreased expression of VE-cadherin, that could be mediated by NETs to exacerbate endothelial inflammation. Mechanistically, NETs altered endothelial cell function via increased pSTAT1/STAT1 signaling. Vascular inflammation and subsequent ischemia were alleviated in vivo by NETosis or IL-1ß inhibition in ischemic mice. IL-1ß-NETs induce endothelial activation and inflammation in limb ischemia by stimulating STAT1 signaling. Targeting NETs may thus represent a novel therapeutic strategy for inflammatory vascular diseases associated with limb ischemia. Graphical abstract of NETs regulation of the development of vascular inflammation in lower limb ischemia via pSTAT1/STAT1 signaling pathway.

Novel Angiogenesis Role of GLP-1(32-36) to Rescue Diabetic Ischemic Lower Limbs via GLP-1R-Dependent Glycolysis in Mice.

BACKGROUND: Restoring the capacity of endothelial progenitor cells (EPCs) to promote angiogenesis is the major therapeutic strategy of diabetic peripheral artery disease. The aim of this study was to investigate the effects of GLP-1 (glucagon-like peptide 1; 32-36)-an end product of GLP-1-on angiogenesis of EPCs and T1DM (type 1 diabetes) mice, as well as its interaction with the classical GLP-1R (GLP-1 receptor) pathway and its effect on mitochondrial metabolism. METHODS: In in vivo experiments, we conducted streptozocin-induced type 1 diabetic mice as a murine model of unilateral hind limb ischemia to examine the therapeutic potential of GLP-1(32-36) on angiogenesis. We also generated Glp1r-/- mice to detect whether GLP-1R is required for angiogenic function of GLP-1(32-36). In in vitro experiments, EPCs isolated from the mouse bone marrow and human umbilical cord blood samples were used to detect GLP-1(32-36)-mediated angiogenic capability under high glucose treatment. RESULTS: We demonstrated that GLP-1(32-36) did not affect insulin secretion but could significantly rescue angiogenic function and blood perfusion in ischemic limb of streptozocin-induced T1DM mice, a function similar to its parental GLP-1. We also found that GLP-1(32-36) promotes angiogenesis in EPCs exposed to high glucose. Specifically, GLP-1(32-36) has a causal role in improving fragile mitochondrial function and metabolism via the GLP-1R-mediated pathway. We further demonstrated that GLP-1(32-36) rescued diabetic ischemic lower limbs by activating the GLP-1R-dependent eNOS (endothelial NO synthase)/cGMP/PKG (protein kinase G) pathway. CONCLUSIONS: Our study provides a novel mechanism with which GLP-1(32-36) acts in modulating metabolic reprogramming toward glycolytic flux in partnership with GLP-1R for improved angiogenesis in high glucose-exposed EPCs and T1DM murine models. We propose that GLP-1(32-36) could be used as a monotherapy or add-on therapy with existing treatments for peripheral artery disease. REGISTRATION: URL: www.ebi.ac.uk/metabolights/; Unique identifier: MTBLS9543.

Outcomes of Alprostadil As an Adjuvant Therapy with Indirect Angiosomal Revascularization in Patients with Critical Limb Ischemia after Failure of Direct Revascularization.

BACKGROUND: This study was carried out to assess the effectiveness of alprostadil (prostaglandin E1) when used as an adjuvant therapy with indirect revascularization in patients with critical limb ischemia (CLI) after the failure of direct revascularization (DR). METHODS: At our centers, 120 patients suffering from infrainguinal peripheral arterial disease with CLI underwent a failed trial of DR procedure, all revascularization procedures were endovascular. Median follow-up was 2 years and 2.5 years for patients with and without diabetes mellitus (DM). In the alprostadil group, the mean age was 63.41 ± 12.52; 36 (60%) for males and 24 (40%) for females. Post-endovascular intervention alprostadil was administrated immediately postoperatively by intravenous infusion of 40 µg alprostadil diluted in 100 ml of normal saline, over 2 hr every 12 hr for 6 days. RESULTS: In the alprostadil group, the mean ± standard deviation (SD) of the baseline ankle-brachial index (ABI) was 0.45 ± 0.175, while the mean ± SD of ABI at the end of our study was 0.65 ± 0.216 with a difference from the baseline of 0.2 ± 0.041 (P value = 0.08, <0.05 meaning that it is significant). Our 1-month primary patency rate was 93.3%, while our 3- and 6-month patency rate was 92.9%. In the control group, the mean ± SD of the baseline ABI was 0.68 ± 0.22, while the mean ± SD of ABI at the end of our study was 0.69 ± 0.23 with a difference from the baseline of 0.01 ± 0.01 (P value >0.05 meaning that it is nonsignificant) 1-month patency rate was 89%, while 3- and 6-month patency rate was 75%. When we compared the patient's leg vessels before and after our intervention, we found that the percentage of the no-runoff-vessels group decreased from 10 (16.7%) to 4 (6.67%). One-runoff-vessel group percentage dropped from 40 (66.7%) to 36 (60%), whereas, in the two-runoff-vessel group, the percentage increased from 10 (16.7%) to 20 (33.3%). We evaluate leg arteries; we do no pedal arch intervention in the alpostradil group. Out of the total of 60 patients, limb salvage occurred in 58 (96.7%) patients, and 2 (3.3%) patients underwent below-the-knee amputation before the study ended. CONCLUSIONS: Our results show the efficacy and safety of alprostadil as an adjuvant therapy with indirect angiosomal revascularization in patients with tissue loss due to CLI.

The Use and Impact of Cilostazol on Patients Undergoing Endovascular Peripheral Interventions.

BACKGROUND: Cilostazol is used for the treatment of intermittent claudication. The impact of cilostazol on the outcomes of peripheral vascular interventions (PVIs) remains controversial. This study assesses the use and impact of cilostazol on patients undergoing PVI for peripheral arterial disease (PAD). METHODS: The Vascular Quality Initiative (VQI) database files for PVI were reviewed. Patients with PAD who underwent PVI for chronic limb threatening-ischemia or claudication were included and divided based on the use of cilostazol preoperatively. After propensity matching for patient demographics and comorbidities, the short-term and long-term outcomes of the 2 groups (preoperative cilostazol use versus no preoperative cilostazol use) were compared. The Kaplan-Meier method was used to determine outcomes. RESULTS: A total of 245,309 patients underwent PVI procedures and 6.6% (N = 16,366) were on cilostazol prior to intervention. Patients that received cilostazol were more likely to be male (62% vs 60%; P < 0.001), White (77% vs. 75%; P < 0.001), and smokers (83% vs. 77%; P < 0.001). They were less likely to have diabetes mellitus (50% vs. 56%; P < 0.001) and congestive heart failure (14% vs. 23%; P < 0.001). Patient on cilostazol were more likely to be treated for claudication (63% vs. 40%, P < 0.001), undergo prior lower extremity revascularization (55% vs. 51%, P < 0.001) and less likely to have undergone prior minor and major amputation (10% vs. 19%; P < 0.001) compared with patients who did not receive cilostazol. After 3:1 propensity matching, there were 50,265 patients included in the analysis with no differences in baseline characteristics. Patients on cilostazol were less likely to develop renal complications and more likely to be discharged home. Patients on cilostazol had significantly lower rates of long-term mortality (11.5% vs. 13.4%, P < 0.001 and major amputation (4.0% vs. 4.7%, P = 0.022). However, there were no significant differences in rates of reintervention, major adverse limb events, or patency after PVI. Amputation-free survival rates were significantly higher for patients on cilostazol, after 4 years of follow up (89% vs. 87%, P = 0.03). CONCLUSIONS: Cilostazol is underutilized in the VQI database and seems to be associated with improved amputation-free survival. Cilostazol therapy should be considered in all patients with PAD who can tolerate it prior to PVI.

Proximal Arterial Inflow Revascularization Improves Pedal Arch Quality and Its Impact on Ischemic Diabetic Foot Ulcer Healing.

BACKGROUND: Arterial perfusion is a key factor in diabetic foot ulcer (DFU) healing. Although it is associated with pedal arch patency, not all patients are amenable to pedal artery angioplasty. This study aims to determine the impact of angiographic improvement of the pedal arch quality after proximal arterial inflow revascularization (PAIR) and its association with wound healing. METHODS: One hundred and fifty diabetic patients with tissue loss in 163 limbs who had digital subtraction angiography were studied. Cox regression analysis was used to determine independent predictors of wound healing. Wound healing rates in association with pedal arch patency were calculated by Kaplan-Meier analysis. RESULTS: End-stage renal disease, minor amputation, and complete pedal arch patency were significant independent predictors of wound healing following PAIR with hazard ratios for failure: 3.02 (P = 0.008), 0.54 (P = 0.023), and 0.40 (P = 0.039), respectively. The prevalence of complete pedal arches increased by 24.1% with successful intervention (P < 0.001). The overall rates of wound healing at 6, 12, and 24 months were 36%, 64%, and 72%, respectively. The wound healing rate at 1 year in patients with a complete pedal arch was 73% compared to 45% in those with an absent pedal arch (P = 0.017). CONCLUSIONS: PAIR increases complete pedal arch patency, a significant predictor of wound healing in DFU.

Secondary interventions following open vs endovascular revascularization for chronic limb threatening ischemia in the BEST-CLI trial.

OBJECTIVES: Patients undergoing revascularization for chronic limb-threatening ischemia experience a high burden of target limb reinterventions. We analyzed data from the Best Endovascular versus Best Surgical Therapy in Patients with Critical Limb Ischemia (BEST-CLI) randomized trial comparing initial open bypass (OPEN) and endovascular (ENDO) treatment strategies, with a focus on reintervention-related study endpoints. METHODS: In a planned secondary analysis, we examined the rates of major reintervention, any reintervention, and the composite of any reintervention, amputation, or death by intention-to-treat assignment in both trial cohorts (cohort 1 with suitable single-segment great saphenous vein [SSGSV], n = 1434; cohort 2 lacking suitable SSGSV, n = 396). We also compared the cumulative number of major and all index limb reinterventions over time. Comparisons between treatment arms within each cohort were made using univariable and multivariable Cox regression models. RESULTS: In cohort 1, assignment to OPEN was associated with a significantly reduced hazard of a major limb reintervention (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.28-0.49; P < .001), any reintervention (HR, 0.63; 95% CI, 0.53-0.75; P < .001), or any reintervention, amputation, or death (HR, 0.68; 95% CI, 0.60-0.78; P < .001). Findings were similar in cohort 2 for major reintervention (HR, 0.53; 95% CI, 0.33-0.84; P = .007) or any reintervention (HR, 0.71; 95% CI, 0.52-0.98; P = .04). In both cohorts, early (30-day) limb reinterventions were notably higher for patients assigned to ENDO as compared with OPEN (14.7% vs 4.5% of cohort 1 subjects; 16.6% vs 5.6% of cohort 2 subjects). The mean number of major (mean events per subject ratio [MR], 0.45; 95% CI, 0.34-0.58; P < .001) or any target limb reinterventions (MR, 0.67; 95% CI, 0.57-0.80; P < .001) per year was significantly less in the OPEN arm of cohort 1. The mean number of reinterventions per limb salvaged per year was lower in the OPEN arm of cohort 1 (MR, 0.45; 95% CI, 0.35-0.57; P < .001 and MR, 0.66; 95% CI, 0.55-0.79; P < .001 for major and all, respectively). The majority of index limb reinterventions occurred during the first year following randomization, but events continued to accumulate over the duration of follow-up in the trial. CONCLUSIONS: Reintervention is common following revascularization for chronic limb-threatening ischemia. Among patients deemed suitable for either approach, initial treatment with open bypass, particularly in patients with available SSGSV conduit, is associated with a significantly lower number of major and minor target limb reinterventions.

Omniflow® II biosynthetic graft offers acceptable early and mid-term outcomes in redo surgery in patients with critical limb-threatening ischemia with no available autologous vein material.

BACKGROUND: In this study, the early and mid-term outcomes of Omniflow® II (LeMaitre Vascular, Inc., Burlington, MA, USA) biosynthetic graft in redo surgery in patients with critical limb-threatening ischemia (CLTI) with no available autologous vein material were investigated with the aim to compare the outcomes obtained in "de novo" surgery versus redo surgery. METHODS: From January 2018 until December 2022, data of CLTI patients from 18 centers in Italy with no autologous vein material underwent infrainguinal bypass with Omniflow® II biosynthetic graft were collected. Thirty-day outcome measures including intraoperative technical success, major morbidity, mortality, and graft patency were assessed and compared. At two-year follow-up, estimated outcomes of survival, primary patency, primary assisted patency, secondary patency, freedom from reintervention, and amputation-free survival were analyzed using Kaplan-Meier curves and compared between groups using the log-rank test. RESULTS: In the study period 119 CLTI patients had an infrainguinal bypass with Omniflow® II biosynthetic graft. Seventy-seven patients (64.7%) underwent bypass as "de novo" treatment (group de novo), whilst in the remaining 42 patients (35.3%) the procedure was performed as redo surgery due to occlusion and/or infection of a previous bypass graft (group redo). Two groups were homogeneous in terms of demographic, clinical, and morphological data. In group redo explantation of an infected prosthetic graft was needed in 4 cases (9.5%). Intraoperative technical success was achieved in all cases in both groups. At 30 days, the overall patency rate did not differ between the two groups (69/77, 89.6%, group de novo vs. 35/42, 83.3%, group redo; P=0.24), whilst in group redo limb loss was higher with a statistically significant different 30-day major amputation rate between the two groups (11.9% group redo vs. 1.3% group de novo; P<0.001). Overall median duration of follow-up was eight months (IQR 6-13). At two-year follow-up there were no differences between the two groups in terms of survival (67.7% group de novo vs. 55.8% group redo, P=0.53), primary patency (34.4% group de novo vs. 26.8% group redo, P=0.25), primary assisted patency (43.6% group de novo vs. 28.8% group redo, P=0.12), freedom from reintervention (64.1% group de novo vs. 68.8% group redo, P=0.98), and amputation-free survival (67.8% group de novo vs. 60% group redo, P=0.12). Secondary patency was significantly higher in group de novo (53.7% vs. 32.3%, P=0.05). During the follow-up, the overall rates of graft infection and aneurysmal degeneration were 3.4%, and 0.8%, respectively. CONCLUSIONS: Nevertheless, poorer early outcomes in terms of limb salvage, Omniflow® II biosynthetic graft offers acceptable ywo-year outcomes in redo surgery in CLTI patients with no available autologous vein material. Further studies with larger population sizes are needed to validate these outcomes.

Optical coherence tomography angiography macular biomarkers of peripheral retinal ischemia in diabetic macular edema: secondary endpoints from the clinical study "FOVEA".

PURPOSE: To investigate the relationship between the macular values of fractal dimension (FD) and lacunarity (LAC) on optical coherence tomography angiography (OCTA) images and the presence of peripheral retina non-perfusion areas (NPAs) on fluorescein angiography (FA) in patients with treatment-naïve diabetic macular edema (DME). METHODS: Fifty patients with treatment-naïve DME underwent a full ophthalmic examination, including best-corrected visual acuity measurement, FA, spectral-domain optical coherence tomography, and OCTA. Specifically, FA was performed to detect the presence of retinal NPAs, whereas fractal OCTA analysis was used to determine macular FD and LAC values at the level of the superficial and deep capillary plexus (SCP and DCP). FA montage frames of the posterior pole and peripheral retina, as well as macular OCTA slabs of the SCP and DCP, were obtained. RESULTS: Thirty (60%) eyes with FA evidence of peripheral retinal NPAs in at least one quadrant showed significantly lower FD and higher LAC in both SCP and DCP, when compared with eyes presenting a well-perfused peripheral retina. Furthermore, macular FD and LAC values were found to be significantly associated with the extent of retinal NPAs. CONCLUSIONS: Macular FD and LAC of both SCP and DCP seem to be strongly associated with the extent of peripheral retinal NPAs, thus suggesting that may be useful predictive biomarkers of peripheral ischemia in treatment-naïve DME eyes.

Percutaneous Aortoiliac Thromboendarterectomy for Acute Limb Ischemia.

Aortoiliac occlusive disease (AIOD) can occur from either chronic, progressive atherosclerotic disease, acute on chronic thrombosis or acute arterial embolism, and can all result in limb ischemia. Bypass surgery had long been the gold standard for treatment for AIOD, however, with advances in endovascular techniques, minimally invasive treatment of aortoiliac lesions has become the first line choice of management in many cases. Herein, we describe a case of utilizing the Inari ClotTriever to perform aortoiliac mechanical thrombectomy and the ARTIX thrombectomy system to perform an embolectomy the superficial femoral artery, highlighting new therapies to treat AIOD.

Association between macrophage-like cell density and ischemia metrics in diabetic eyes.

We previously showed that macrophage-like cells (MLCs) are increased in eyes with advanced diabetic retinopathy (DR). Here, we hypothesized that MLC density was correlated with ischemia using optical coherence tomography angiography (OCTA) and ultra-widefield fluorescein angiography (UWF-FA). Treatment-naïve diabetic eyes were prospectively imaged with repeated OCTA (average 5.3 scans per eye) and UWF-FA imaging. OCTA images were registered and averaged to generate a superficial capillary plexus (SCP), deep capillary plexus (DCP), and MLC slab. We calculated geometric perfusion deficit (GPD), vessel length density, and vessel density for the SCP and DCP. MLC density was quantified by two masked graders and averaged. Ischemia on UWF-FA was measured to generate a non-perfusion area (NPA) and index (NPI). Since MLC density was non-parametrically distributed, MLC density was correlated with ischemia metrics using Spearman correlations. Forty-five treatment-naïve eyes of 45 patients (59 ± 12 years of age; 56% female) were imaged. We included 6 eyes with no DR, 7 eyes with mild non-proliferative DR (NPDR), 22 moderate NPDR, 4 severe NPDR, and 6 PDR eyes. MLC density between graders was highly correlated (r = 0.9592, p < 0.0001). MLC density was correlated with DCP GPD (r = 0.296, p = 0.049), but no other OCTA ischemia metrics. MLC density was also correlated with UWF-FA NPA (r = 0.330, p = 0.035) and NPI (r = 0.332, p = 0.034). MLC density was correlated with total ischemia on UWF-FA and local DCP GPD. Since both UWF-FA and DCP non-perfusion are associated with higher risk for DR progression, MLC density could be another potential biomarker for DR progression.

Cerebral microcirculation mapped by echo particle tracking velocimetry quantifies the intracranial pressure and detects ischemia.

Affecting 1.1‰ of infants, hydrocephalus involves abnormal accumulation of cerebrospinal fluid, resulting in elevated intracranial pressure (ICP). It is the leading cause for brain surgery in newborns, often causing long-term neurologic disabilities or even death. Since conventional invasive ICP monitoring is risky, early neurosurgical interventions could benefit from noninvasive techniques. Here we use clinical contrast-enhanced ultrasound (CEUS) imaging and intravascular microbubble tracking algorithms to map the cerebral blood flow in hydrocephalic pediatric porcine models. Regional microvascular perfusions are quantified by the cerebral microcirculation (CMC) parameter, which accounts for the concentration of micro-vessels and flow velocity in them. Combining CMC with hemodynamic parameters yields functional relationships between cortical micro-perfusion and ICP, with correlation coefficients exceeding 0.85. For cerebral ischemia cases, the nondimensionalized cortical micro-perfusion decreases by an order of magnitude when ICP exceeds 50% of the MAP. These findings suggest that CEUS-based CMC measurement is a plausible noninvasive method for assessing the ICP and detecting ischemia.

Protection of ischemic white matter and oligodendrocytes in mice by 3K3A-activated protein C.

Subcortical white matter (WM) stroke accounts for 25% of all strokes and is the second leading cause of dementia. Despite such clinical importance, we still do not have an effective treatment for ischemic WM stroke, and the mechanisms of WM postischemic neuroprotection remain elusive. 3K3A-activated protein C (APC) is a signaling-selective analogue of endogenous blood protease APC that is currently in development as a neuroprotectant for ischemic stroke patients. Here, we show that 3K3A-APC protects WM tracts and oligodendrocytes from ischemic injury in the corpus callosum in middle-aged mice by activating protease-activated receptor 1 (PAR1) and PAR3. We show that PAR1 and PAR3 were also required for 3K3A-APC's suppression of post-WM stroke microglia and astrocyte responses and overall improvement in neuropathologic and functional outcomes. Our data provide new insights into the neuroprotective APC pathway in the WM and illustrate 3K3A-APC's potential for treating WM stroke in humans, possibly including multiple WM strokes that result in vascular dementia.

Comparison of nerve conduction velocity distribution methods by cold exposure and ischemia.

PURPOSE: Non-invasive estimation of the conduction velocity distribution (CVD) of a peripheral nerve has the potential to both improve clinical diagnoses of pathology and to observe the progress of the disease or the efficacy of treatments. Comparisons were made of the performance of three non-invasive CVD estimation methods proposed by independent research groups on peripheral nerve bundles under different conditions. METHODS: The first method (Cummins) uses a nerve compound action potential (CAP) with temporal dispersion and a mathematical single fiber action potential (SFAP). The second method (Barker) uses two CAPs and a non-mathematical SFAP waveform. The third method (Hirose) uses two CAPs recorded from distal and proximal sites. The Cummins and Barker methods have iterative solutions in the time domain while the Hirose method is a deconvolution estimator in the frequency domain. In order to compare these methods, we used cold exposure to affect primarily motor fibers and ischemia to affect primarily sensory fibers on rat caudal nerve bundles. RESULTS: The Cummins method is sensitive to changes in motor and sensory fiber percentages in CVD if it is used with the volume conductor model. The Barker and Hirose methods are sensitive to motor fiber percentages in CVD but they cannot detect changes in sensory fiber percentages accurately. CONCLUSIONS: Estimation of the CVD using a priori SFAP created with a volume conductor model can non-invasively supply accurate and precise information about fiber groups in a peripheral nerve bundle.

Viabahn-Assisted Extra-Arterial Bypass Combined With Surgical Arterial Endarterectomy as a Salvage Technique to Treat Critical Limb Ischemia.

BACKGROUND: Revascularization of patients with critical limb ischemia (CLI) is always challenging because of long occlusive arterial lesions with severe calcification and poor general condition. Here we describe a novel hybrid technique to treat a CLI patient. METHODS: The patient was a 60-year-old male with left foot ulcer. Preoperative scan showed long calcific and occlusive lesions running from the left proximal common femoral artery to P1 of the popliteal artery (PA). Surgical endarterectomy was performed on the proximal femoral artery. Then, retrograde PA access was achieved to protect the vital collateral artery at the proximal PA. When the retrograde V18 guidewire failed to advance because of severe occlusion in the middle one-third of the SFA, we punctured the artery with the V18 guidewire, and manually introduced it into the lumen of the proximal SFA. Three Viabahn stent grafts were successively implanted, parts of which were situated outside the SFA. RESULTS: Computed tomography 1 week after surgery showed patent blood flow to the left toes. Good recovery was observed during a 1-year follow up, the toe wound healed after amputation, and no rest pain recurred. Ultrasound showed 60% stenosis in the PA stent, while the other stents were patent. The anklebrachial index of the left limb was 0.48. CONCLUSIONS: This case illustrates successful use of Viabahn-assisted extra-arterial bypass combined with surgical arterial endarterectomy to salvage the limb after CLI. This novel technique might be an alternative in carefully selected patients.

Early ABI Testing May Decrease Risk of Amputation for Patients With Lower Extremity Ulcers.

BACKGROUND: Patients with lower extremity wounds from diabetes mellitus or peripheral artery disease (PAD) have a risk of amputation as high as 25%. In patients with arterial disease, revascularization decreases the risk of amputation. We aimed to determine if the early assessment of arterial perfusion correlates with the risk of amputation. METHODS: We retrospectively reviewed patients referred to the vascular clinic over 18 months with Rutherford Grade 5 and 6 chronic limb-threatening ischemia to determine if patients had a pulse exam done at the time the wound was identified and when ankle brachial index (ABI) testing to evaluate perfusion was performed. Kaplan Meier analysis was used to determine if the timing of ABI testing affected the time to revascularization, wound healing, and risk of amputation. RESULTS: Ninety-three patients with lower extremity wounds were identified. Of these, 59 patients (63%) did not have a pulse exam performed by their primary care provider when the wound was identified. Patients were classified by when they underwent ankle brachial index testing to assess arterial perfusion. Twenty-four had early ABI (<30 days) testing, with the remaining 69 patients having late ABI testing. Patients in the early ABI group were more likely to have a pulse exam done by their PCP than those in the late group, 12 (50%) vs. 22 (32%), P = 0.03. Early ABI patients had a quicker time to vascular referral (13 days vs. 91 days, P < 0.001). Early ABI patients also had quicker times to wound healing than those in the late group (117 days vs. 287 days, P < 0.001). Finally, patients that underwent early ABI were less likely to require amputation (Fig. 1), although this did not reach statistical significance (P = 0.07). CONCLUSIONS: Early ABI testing expedites specialty referral and time to revascularization. It can decrease the time to wound healing. Larger cohort studies are needed to determine the overall effect of early ABI testing to decrease amputation rates.

Hybrid Deep Venous ARterialisation (DVAR) for No-Option Chronic Limb Threatening Ischemia.

BACKGROUND: Hybrid Deep Venous ARterialisation (DVAR) is offered as a last-ditch attempt for limb salvage in patients with chronic limb threatening ischemia (CLTI). It provides non-selective arterialisation independent of the angiosome, which harnesses the complex venous capillary network bed developed in the leg and foot. METHODS: We present two elderly men who underwent DVAR to salvage limb with CLTI. DVAR was performed by creating an arteriovenous connection by anastomosis of the great saphenous vein (GSV) at the level of the distal popliteal and proximal tibio-peroneal trunk. Fasciotomy was performed over the length of the GSV. Subsequently, proximal in-situ catheter valvotomies of the GSV valves were undergone with the adjuvant on-table balloon maturation. The distal tarsal veins underwent balloon valvotomy under direct vision with subsequent proximal and distal tarsal veins valvuloplasties. Completion angiogram demonstrated restoration of the flow in the foot and both the patients were relieved of rest pain. CONCLUSION: We successfully performed DVAR in 2 elderly patients. Our experience shows that DVAR is a simple and safe option that is easily reproducible without the need for complex endovascular hardware, only if a suitable GSV to the foot is available with no history of deep vein thrombosis.

Evaluation of Long-Term Outcomes of Femoropopliteal Bypass Surgery in Patients With Chronic Limb-Threatening Ischemia in an Endovascular Era.

BACKGROUND: To investigate the long-term outcomes of femoropopliteal bypass surgery in patients with chronic limb-threatening ischemia (CLTI) and TransAtlantic Inter-Society Consensus II (TASC II), type D (TASC D) femoropopliteal disease. METHODS: A retrospective analysis was performed for all consecutive patients undergoing above-knee (AK) femoropopliteal bypass surgery at an academic vascular centre between January 2007 and March 2019. Patients with claudication (IC) and patients with CLTI were included. Patency rates and freedom from major adverse limb events (MALE) after 5 years were analysed. RESULTS: In total, 432 femoropopliteal grafts were performed. Indications for surgery were claudication and CLTI in 232 (53.7%) and 200 (46.3%) patients, respectively. Graft material was autologous vein in 186 patients (43.1%), polytetrafluoroethylene (PTFE) in 128 patients (29.6%), and heparin-bonded expanded polytetrafluoroethylene (HePTFE) in 118 patients (27.3%). At the 5-year follow-up, the primary patency rate was 58.1% and 58.3% in patients with CLTI and claudication, respectively. Secondary patency rates were 74.1% and 68.6%, respectively. Freedom from MALE was 64.5% and 61.9%, respectively. Analyses of graft material in the CLTI group showed that, at 5 years, autologous vein grafts had better long-term patency rates than PTFE and HePTFE grafts. At 5 years, the primary and secondary patency rate for autologous vein grafts were 63.2% (P= 0.324) and 83.2% (P = 0.020), respectively. Freedom from MALE was 72.0% with the use of autologous vein grafts, 47.9% using PTFE and, 52.9% using HePTFE, respectively (P= 0.021). CONCLUSIONS: Our study shows that femoropopliteal bypass surgery in patients with TASC D lesions is safe and effective in the long term. Autologous vein grafts remain the first choice for patients with CLTI, also for bypasses in AK position. However, prosthetic grafts in AK the position are an acceptable alternative for revascularisation when the saphenous vein is not available.