Near-infrared spectroscopy with a provocative maneuver to detect the presence of severe peripheral arterial disease.

Current assessment standards for peripheral arterial disease (PAD), such as the ankle brachial index, are limited in their utility and portability. Near-infrared spectroscopy (NIRS) has shown some promise in diagnosing PAD when used in conjunction with a provocative maneuver. The purpose of this study was to assess the viability of NIRS in conjunction with a transient leg elevation provocative maneuver for detecting severe PAD. This retrospective observational cross-sectional study assessed 57 limbs in 34 patients receiving routine vascular screening for PAD at Madigan Army Medical Center. The patient limbs were stratified into normal (n = 17), mild (n = 9), moderate (n = 16), and severe (n = 15) PAD groups based on the clinician assessments. Additionally, the patients were assessed with NIRS measurements taken with the patient in the supine position at rest and using a provocative leg raise maneuver of transient leg elevation of 45° for 60 seconds. The resting tissue oxygen saturation (StO2) and the change in StO2 (ΔStO2) from rest to elevation were recorded and compared between the PAD severity groups via independent measures analysis of variance with the Tukey honest significant difference post hoc test. The supine resting StO2 was not different between the normal (77.5% ± 7.7%), mild (72.5% ± 7.4%), moderate (72.0% ± 10.3%), and severe (74.2% ± 5.4%) PAD groups (P = .23). However, the ΔStO2 with transient leg elevation was significantly greater in the severe PAD group (-17.2% ± 6.0%) compared with the normal (-3.9% ± 4.8%), mild (-6.9% ± 4.7%), and moderate (-9.7% ± 5.2%) PAD groups (P < .002 for all). Similar results were observed in the changes in oxyhemoglobin and deoxyhemoglobin. The leg elevation protocol was also used for two patients before and after lower limb revascularization, which demonstrated that the ΔStO2 corresponded with the clinical assessment of PAD severity. Resting supine NIRS images were unable to detect any differences among normal and limbs with different PAD severity. However, NIRS imaging with 45° leg elevation for 60 seconds showed a significant difference between severe PAD compared healthy patients and those with mild to moderate PAD in a fast, precise, and accurate manner. These preliminary data support the use of NIRS and transient leg elevation as a tool to diagnose severe PAD but do not support the use of NIRS alone as a screening test for PAD. NIRS measurements with leg elevation might be a viable noninvasive, noncontact, and portable method of assessing severe PAD for home monitoring, in rural communities, and/or in standard clinical practice.

Patent Foramen Ovale Secondary to a Paradoxical Embolism Leading to Acute Limb Ischemia: A Case Report and Brief Review of Literature.

Acute limb ischemia, or ALI, is a rapid decrease in limb perfusion due to an occlusion of an artery or a bypass graft. Most cases result from in situ thrombosis or embolism in patients with antecedent peripheral arterial disease. Potential sources of arterial embolism as a cause of this condition include cardiogenic, aortic, peripheral aneurysms with an associated mural thrombus or, less commonly, a paradoxical embolism through a septal defect. We present a rare case of ALI due to an underlying patent foramen ovale that was successfully treated following revascularization. This article emphasizes one of the more unusual mechanisms of ALI. Despite the rarity, physicians should maintain a high index of clinical suspicion for a paradoxical embolism across a patent foramen ovale in unexplained arterial occlusion. Correct mechanism identification ensures adequate referral and prompt treatment that may reduce complications.

Major Lower Limb Amputation for Chronic Limb-Threatening Ischemia Is Associated with Poor Long-Term Survival: 4-Year Follow-Up of a Single-Center Experience.

Objective: Despite advances in medicine, 30% of patients with chronic limb-threatening ischemia (CLTI) require major lower limb amputation (MLLA). The long-term outcome of this cohort is poorly described. Methods: In all, 154 patients undergoing MLLA for CLTI during 2018-2020 were analyzed for short-term and long-term outcomes and prosthesis use. Results: In total, 106 below-knee amputations and 48 above-knee amputations were followed up for a mean duration of 50 months (37-78). The mean age of the cohort was 63 years. The majority were male (60%) with multiple comorbidities, including diabetes (83.8%), hypertension (49.4%), ischemic heart disease (20%), and smoking (32.5%). An equal proportion underwent MLLA as primary (45%) or secondary (55%). 30-day mortality was 6%. The mean length of in-hospital stay was 18 days (3-56). Overall survival rates at 1st, 2nd, and 4th year were 73%, 64%, and 35%, respectively. On a multivariate regression analysis, a higher level of amputation had a significant impact on mortality (p = 0.015). 54% of amputees had a prosthetic limb. However, the primary use of prosthesis was for cosmesis, with only 12% mobile independently. Conclusions: MLLA for CLTI is associated with poor early and long-term survival. Prosthesis use and mobility are extremely poor in the Sri Lankan context.

Limb Salvage With Continuous Intra-Arterial Infusion for Below-the-Ankle Arterial Occlusions in Acute Limb Ischemia.

A 79-year-old man presented with acute-onset coldness and severe pain in his left foot 4 hours prior. His foot (distal to the left Lisfranc joint) was pale and cold with slight motor and sensory deficits. Angiography demonstrated occlusion of the lateral plantar artery and plantar metatarsal arteries (PMAs). Angioplasty using balloons for each PMA and lateral plantar artery was conducted, but failed to achieve satisfactory blood flow. The foot condition subsequently worsened. A 22-gauge cannula was then inserted into the dorsalis pedis artery, and continuous local intra-arterial infusion of heparin, alprostadil, and nicorandil was administered. A marked reduction in the cyanotic areas of the foot was observed, with improved motor and sensory deficits post-continuous local intra-arterial infusion therapy. Follow-up angiography via the cannula on day 3 of hospitalization demonstrated significant flow improvement in the first to third PMAs. Foot salvage was achieved without tissue necrosis or amputation.

Dynamic Perioperative Platelet Activity and Cardiovascular Events in Peripheral Artery Disease.

OBJECTIVE: Patients with peripheral artery disease (PAD) undergo lower extremity revascularization (LER) for symptomatic relief or limb salvage. Despite LER, patients remain at increased risk of platelet-mediated complications, such as major adverse cardiac and limb events (MACLE). Platelet activity is associated with cardiovascular events; yet little is known about the dynamic nature of platelet activity over time. We therefore investigated the change in platelet activity over time and its association with long-term cardiovascular risk. METHODS: Patients with PAD undergoing LER were enrolled into the multicenter, prospective Platelet Activity and Cardiovascular Events (PACE) study. Platelet aggregation was assessed by light transmission aggregometry (LTA) to submaximal epinephrine (0.4µ M) immediately prior to LER, and on post-operative day 1 or 2 (POD1) and 30 (POD30). A hyperreactive platelet phenotype was defined as >60% aggregation. Patients were followed longitudinally for MACLE, defined as the composite of death, myocardial infarction, stroke, major lower extremity amputation, or acute limb ischemia leading to reintervention. RESULTS: Among 287 patients undergoing LER, mean age was 70 ± 11 years, 33% were female, 61% were white, and 89% were on baseline antiplatelet therapy. Platelet aggregation to submaximal epinephrine induced a bimodal response; 15.5%, 16.8%, and 16.4% of patients demonstrated a hyperreactive platelet phenotype at baseline, POD1, and POD30, respectively. Platelet aggregation increased by 18.5% (P=0.001) from baseline to POD1, which subsequently returned to baseline at POD30. After a median follow-up of 19 months, MACLE occurred in 165 (57%) patients. After adjustment for demographics, clinical risk factors, procedure type, and antiplatelet therapy, platelet hyperreactivity at POD1 was associated with a significant hazard of long-term MACLE (aHR 4.61, 95% CI 2.08-10.20, P<0.001). CONCLUSION: Among patients with severe PAD, platelet activity increases following LER. Platelet hyperreactivity to submaximal epinephrine on POD1 is associated with long-term MACLE. Platelet activity following LER may represent a modifiable biomarker associated with excess cardiovascular risk.

Mesenchymal stromal cell therapy (REGENACIP®), a promising treatment option in chronic limb threatening ischemia - a narrative review.

Chronic Limb Threatening Ischemia (CLTI) is a challenging clinical problem associated with high morbidity and mortality. Endovascular interventions have been the cornerstone of treatment whenever possible. It is estimated that CLTI represents < 10% of all Peripheral Artery Disease patients, yet 50% of the patients end up either with a major amputation of the lower limbs or die of cardiovascular causes within one year period, especially in those with unsuccessful revascularization or "no-option" CLTI. Cell-based therapeutics, especially bone marrow-derived mesenchymal stromal cells have emerged as a potential, promising, and novel alternate therapeutic modality in the management of CLTI, bolstered with positive results in numerous research, including randomized and nonrandomized trials. REGENACIP® is one such BM-MSC therapy approved by Central Drugs Standard Control Organization in India for the management of "no-option" Atherosclerotic Peripheral Arterial disease / Buerger's disease patients with established critical limb ischemia in Rutherford Grade III-5 or III-6, not eligible for or have failed traditional revascularization treatment, with rest pain and / or ulcers in the affected limb. The current review aims to deliberate upon the various aspects of CLTI and clinical benefits of REGENACIP® therein.

Endovascular clot removal in small and tortuous arteries: a case series.

Acute limb ischemia (ALI) due to arterial thromboembolic occlusion is a critical emergency in vascular medicine, requiring attention for rapid diagnosis and intervention, to prevent limb loss and major amputation, which is associated with patient disability in the long term. Traditionally, surgical embolectomy has been used for the treatment of ALI. Endovascular treatment of ALI traditionally involved catheter-directed thrombolysis. This option, however, poses some limitations, including an increased risk for access site and systemic bleeding complications, especially in patients with high bleeding risk. Therefore, in the last decades, several devices have been developed and tested for the mechanical endovascular treatment of ALI. Such devices involve either rotational thrombectomy or continuous thrombus aspiration. While rotational thrombectomy is limited in rather large arteries due to the risk of dissection and perforation in arteries <3 mm, continuous thrombus aspiration can be applied in smaller vessels and tortuous anatomies. In our case series we present a minimal-invasive endovascular approach for the treatment of two patients with ALI due to thrombotic occlusion of tortious and small diameter arteries. Minimal-invasive mechanical thrombectomy using the Penumbra Aspiration System emerged as a successful alternative to surgical embolectomy, enabling prompt treatment and with a short hospital stay for both patients. Our article therefore highlights the use of continuous thrombus aspiration in small diameter vessels and tortuous anatomies, which may represent a contraindication for the use of rotational thrombectomy. In addition, this technique may be applied even in patients with higher bleeding risk since additional lysis is not necessary in patients, where complete thrombus removal can be achieved by this device.

Outcomes of Patients with Critical Limb Ischemia and Chronic Kidney Disease: A National Perspective.

INTRODUCTION: Studies exploring the relationship between peripheral arterial disease (PAD), critical limb ischemia (CLI), and chronic kidney disease (CKD) and its effect on in-hospital outcomes are limited. We aimed to analyze the outcomes of patients with CKD and PAD who are admitted for CLI. METHODS: We utilized the National Inpatient Sample (NIS) to capture hospitalizations for CLI from 2012 to 2020 and then identified cases with concomitant CKD. The primary outcome was mortality, and secondary outcomes were cerebrovascular accident, major bleeding, vasopressor requirement, percutaneous coronary intervention, cardiac arrest, acute respiratory failure, transfusion, length of stay, and total hospital charges. Multivariable logistic regression was performed to adjust for covariates. RESULTS: A total of 441,245 patients with CLI were identified, of which 122,370 (27.7%) reported concomitant CKD. Patients with CKD had higher in-patient mortality (odds ratio [OR] 1.68, 95% confidence interval [CI], 1.17-1.68, p < 0.001), vascular complications (OR 1.31, 95% CI, 1.17-1.48, p < 0.001), acute kidney injury requiring hemodialysis (OR 3.17, 95% CI, 2.64-3.80, p < 0.001), and major bleeding (OR 1.12, 95% CI, 1.05-1.19, p < 0.001). Patients with CKD underwent minimally invasive endovascular therapy (31.08% vs. 36.73%, p < 0.0001) and invasive procedures (14.73% vs. 23.55%, p < 0.0001) less often. PAD-CLI with CKD was associated with major (20.54% vs. 16.17%, OR 1.04; p < 0.0001) and minor (26.87% vs. 19.53%, OR 1.2, p < 0.0001) amputations more often. CONCLUSION: Patients admitted for PAD-CLI with concomitant CKD have significantly higher in-hospital mortality as compared to patients without CKD. Moreover, patients with CKD and PAD-CLI are less likely to receive revascularization and more likely to undergo amputation.

Spinal Cord Stimulation for Intractable Chronic Limb Ischemia: A Narrative Review.

Critical limb ischemia (CLI) is the most severe form of peripheral arterial disease, significantly impacting quality of life, morbidity and mortality. Common complications include severe limb pain, walking difficulties, ulcerations and limb amputations. For cases of CLI where surgical or endovascular reconstruction is not possible or fails, spinal cord stimulation (SCS) may be a treatment option. Currently, SCS is primarily prescribed as a symptomatic treatment for painful symptoms. It is used to treat intractable pain arising from various disorders, such as neuropathic pain secondary to persistent spinal pain syndrome (PSPS) and painful diabetic neuropathy. Data regarding the effect of SCS in treating CLI are varied, with the mechanism of action of vasodilatation in the peripheral microcirculatory system not yet fully understood. This review focuses on the surgical technique, new modalities of SCS, the mechanisms of action of SCS in vascular diseases and the parameters for selecting CLI patients, along with the clinical outcomes and complications. SCS is a safe and effective surgical option in selected patients with CLI, where surgical or endovascular revascularization is not feasible.

Spliced-vein Conduit Offers Better Patency and Limb Salvage Than Prosthetic Graft for Femoral-Tibial Bypasses in Critical Limb Threatening Ischemia.

BACKGROUND: Single-segment great saphenous vein (ssGSV) is the gold standard conduit for femoral-tibial bypasses in patients with critical limb-threatening ischemia (CLTI). In the absence of a good single-segment saphenous vein, alternative options are prosthetic grafts or spliced-vein conduits. Although spliced-vein conduits may provide better long-term patency/limb salvage, prosthetic grafts are more often the chosen conduit due to shorter operative and presumably better immediate postoperative outcomes; nevertheless, there is little data supporting this practice. In this study, we compared 30-day outcomes between spliced-vein and prosthetic conduits in CLTI bypass using a national registry. METHODS: CLTI patients who underwent lower extremity bypass using spliced vein (SpV) or prosthetic conduits only were selected from National Surgical Quality Improvement Program (NSQIP) targeted database. A 1:5 propensity-score matching was conducted between SpV and prosthetic groups to address preoperative differences. Thirty-day outcomes, including primary patency, reintervention, major amputation, mortality, major morbidity, transfusion, and wound complications, were compared between the two groups. RESULTS: There were 886 patients who underwent femoral-tibial bypass without ssGSV (104 SpV and 782 prosthetic grafts). All SpV patients were propensity-score matched to 445 prosthetic patients. SpV exhibited significantly better 30-day primary patency than prosthetic (87.5% vs 74.38%, P = 0.004). SpV was associated with significantly longer operative time (346 min vs 222 min, P < .001) and higher transfusion (43.3% vs 27.87%, P =0.003), but those did not translate into higher 30-day mortality or major systemic complications. There was no difference in wound complications or 30-day limb loss. CONCLUSION: Spliced-vein conduit affords significantly better 30-day primary patency than prosthetic grafts without increased mortality and morbidities. Therefore, despite greater procedural complexity and longer operative time, spliced-vein conduit should be considered when available. Future prospective studies are needed to investigate the long-term outcomes of these two conduits.

Quality of Life Predictors in Patients with Acute Lower Limb Ischemia Quality of Life in Acute Limb Ischemia.

OBJECTIVE: While existing literature has established factors associated with improved health-related quality of life (HRQOL) in patients with chronic limb-threatening ischemia, similar work has not been done in individuals with acute lower limb ischemia (ALLI). This study aims to identify the factors associated with HRQOL in patients presenting with ALLI. METHODS: Using a prospectively collected registry, all patients who received treatment for ALLI between May 2016 and July 2023 at a quaternary medical center were identified and invited to complete two HRQOL questionnaires: the VascuQoL-6 and the EQ-5D-5L. Simple linear regression followed by multivariate analysis using multiple linear regression were used to determine the patient variables independently associated with HRQOL. RESULTS: Of the 216 eligible patients treated for ALLI during the study period, 47 (20%) of patients with a mean age of 58 ± 10 years completed the HRQOL questionnaires. Questionnaires were completed at a median time of 16.5 months after the episode of ALLI. On multiple linear regression, higher age was associated with higher VascuQoL-6 (p=0.037) and EQ-5D-5L (p=0.041) scores, while hypertension and non-ambulatory status were significant predictors of lower VascuQoL-6 (p=0.006, p=0.013) and EQ-5D-5L (p=0.009, p=0.026) scores. Any ambulation had a significantly higher HRQOL compared to non-ambulatory status, but no significant HRQOL difference was observed between patients with any type of ambulation (unhindered ambulation, ambulation with pain, and ambulation using a prosthesis). CONCLUSION: This study demonstrates that the ability to ambulate after ALLI, and not amputation per se, is an important predictor of HRQOL. As such, early rehabilitation strategies should be a focus of post-ALLI care. Further exploration of factors that shape HRQOL after ALLI is needed.

Acute lower limb ischemia caused by repeat deployment of vascular closure device.

Vascular closure devices are used to facilitate faster hemostasis and earlier ambulation, improve patient comfort, and reduce length of hospital stay after percutaneous endovascular procedures. However, their use may rarely be associated with limb ischemia due to endothelial damage and arterial thrombosis. This report illustrates the case of a patient who experienced acute lower limb ischemia due to superficial femoral artery occlusion caused by repeat closure with Angio-Seal vascular closure device within 30 days in a small-caliber superficial femoral artery. The patient was surgically treated by vascular repair with a synthetic graft, and remains symptom-free in 3-year follow-up. Repeat deployment of vascular closure devices in the same access site within a period of 30 days may cause acute limb ischemia due to arterial thrombosis, especially in patients with small-caliber arteries, even in the absence of evident risk factors.

miRNA in the Diagnosis and Treatment of Critical Limb Ischemia.

Chronic threatening limb ischemia of the inferior limbs (CLTI) is the final stage of peripheral arterial disease (PAD) and is one of the most feared atherosclerotic manifestations because if left untreated, in time, it can lead to amputation. Although there are currently numerous treatment techniques, both open and endovascular, it is a pathology that has no underlying treatment. Therefore, current studies are very much focused on new therapeutic possibilities that can be applied in the early stages of the atherosclerotic process. In numerous studies in the literature, miRNAs have been identified as important markers of atherosclerosis. The present study aims to identify the expression of three miRNAs-miR-199a, miR-20a, and miR-30c-in patients with chronic limb-threatening ischemia in the pre- and post-revascularization periods. The aim of the study is to identify whether these three markers play a role in critical ischemia and whether they have the potential for future use in new treatments of this pathology.

Comparison of Different Animal Models in Hindlimb Functional Recovery after Acute Limb Ischemia-Reperfusion Injury.

Acute limb ischemia (ALI) is a sudden lack of blood flow to a limb, primarily caused by arterial embolism and thrombosis. Various experimental animal models, including non-invasive and invasive methods, have been developed and successfully used to induce limb ischemia-reperfusion injuries (L-IRI). However, there is no consensus on the methodologies used in animal models for L-IRI, particularly regarding the assessment of functional recovery. The present study aims to compare different approaches that induce L-IRI and determine the optimal animal model to study functional limb recovery. In this study, we applied a pneumatic cuff as a non-invasive method and ligated the aorta, iliac, or femoral artery as invasive methods to induce L-IRI. We have measured grip strength, motor function, creatine kinase level, inflammatory markers such as nuclear factor NF-κB, interleukin-6 (IL-6), hypoxia markers such as hypoxia-induced factor-1α (HIF-1α), and evaluated the muscle injury with hematoxylin and eosin (H&E) staining in Sprague Dawley rats after inducing L-IRI. The pneumatic pressure cuff method significantly decreased the muscle strength of the rats, causing the loss of ability to hold the grid and inducing significant limb function impairment, while artery ligations did not. We conclude from this study that the tourniquet cuff method could be ideal for studying functional recovery after L-IRI in the rat model.

A Circular Network of Coregulated L-Threonine and L-Tryptophan Metabolism Dictates Acute Lower Limb Ischemic Injury.

Lower limb ischemia is characterized by reduced arterial perfusion in the lower limbs, leading to tissue ischemia and cell death. It is primarily caused by thrombosis and the rupture of arterial plaques, resulting in damage to ischemic muscle tissues. Metabolic processes are crucial in its development. Herein we combined single-cell data with metabolomics data to explore the pathways and mechanisms influencing lower limb ischemia. We analyzed single-cell and metabolomics data. In single-cell analysis, we identified different cell subpopulations and key regulatory genes, and biological enrichment analysis was performed to understand their functions and relationships. For metabolomics, mass spectrometry and chromatography techniques were employed to analyze metabolites in clinical samples. We performed differential analysis, correlation analysis, and Mendelian randomization to determine the relationships between key metabolites and genes. Nebl, Dapl1, Igfbp4, Lef1, Klrd1, Ciita, Il17f, Cd8b1, Il17a, Cd180, Il17re, Trim7, and Slc6a19 were identified to play a crucial role in lower limb ischemia. Important metabolites included L-threonine and L-tryptophan. The metabolism of L-threonine and L-tryptophan is linked to lower limb ischemia and thrombosis. B0AT1, encoded by SLC6A19, is closely related to these metabolites and appears to play a key role in lower limb ischemia development. Our analysis revealed the roles of key genes and metabolites in lower limb ischemia. These findings enhance our understanding of the pathogenesis of lower limb ischemia and provide new insights into its prevention and treatment.

Renal cell carcinoma as a cause of aortic tumor thrombus embolization and acute limb ischemia.

This article presents a unique case of acute limb ischemia resulting from arterial tumor embolism secondary to renal cell carcinoma involving an aortobi-iliac bypass graft. To the best of our knowledge, this instance is the first documented in the literature of such a complication. The patient, a man in his 70s with a complex medical history, underwent bilateral femoral embolectomy and subsequent endovascular intervention for the resolution of the tumor thrombus. The rarity of this phenomenon poses challenges in formulating a standardized management strategy.

Incidence and predictors of acute coronary syndrome after transcatheter mitral valve repair.

BACKGROUND: Acute coronary syndrome (ACS) post-transcatheter mitral valve repair (TMVR) carries high mortality. We aim to study the incidence and predictors of ACS in patients who underwent TMVR. RESEARCH DESIGN AND METHODS: We queried the U.S. National Readmission Database to identify all cases of TMVR from 2016 to 2019. We further evaluated the incidence of ACS and used multivariable logistic regression to determine independent predictors of ACS in this population. RESULTS: Among 3,742 patients who underwent TMVR, 264 (7.05%) developed ACS. Among ACS patients, 204 (77%) had non-ST-segment elevation ACS and 66 (25%) had ST-segment elevation ACS. Independent predictors of ACS were acute limb ischemia, cardiogenic shock, history of coronary artery disease (CAD), smoking, cardiac arrest, respiratory failure requiring mechanical ventilation, and acute kidney injury. In-hospital mortality among ACS was three times higher in ACS patients than without ACS (16.76% vs. 5.45%, p-value < 0.01). CONCLUSIONS: ACS is not an uncommon complication after TMVR. The occurrence of ACS after TMVR is associated with high in-hospital mortality, longer length of stay, and higher hospital charges. The strongest predictors of ACS in these patients are the development of acute limb ischemia, cardiogenic shock, and a history of CAD.

Probing the effects of polysaccharide hydrogel composition on the viability and pro-angiogenic function of human adipose-derived stromal cells.

Cell therapies harnessing the pro-vascular regenerative capacities of mesenchymal stromal cell (MSC) populations, including human adipose-derived stromal cells (hASCs), have generated considerable interest as an emerging treatment strategy for peripheral arterial disease (PAD) and its progression to critical limb ischemia (CLI). There is evidence to support that polysaccharide hydrogels can enhance therapeutic efficacy when applied as minimally-invasive delivery systems to support MSC survival and retention within ischemic tissues. However, there has been limited research to date on the effects of hydrogel composition on the phenotype and function of encapsulated cell populations. Recognizing this knowledge gap, this study compared the pro-angiogenic function of hASCs encapsulated in distinct but similarly-modified natural polysaccharide hydrogels composed of methacrylated glycol chitosan (MGC) and methacrylated hyaluronic acid (MHA). Initial in vitro studies confirmed high viability (>85%) of the hASCs following encapsulation and culture in the MGC and MHA hydrogels over 14 days, with a decrease in the cell density observed over time. Moreover, higher levels of a variety of secreted pro-angiogenic and immunomodulatory factors were detected in conditioned media samples collected from the hASCs encapsulated in the MGC-based hydrogels compared to the MHA hydrogels. Subsequent testing focused on comparing hASC delivery within the MGC and MHA hydrogels to saline controls in a femoral artery ligation-induced CLI (FAL-CLI) model in athymic nu/nu mice over 28 days. For the in vivo studies, the hASCs were engineered to express tdTomato and firefly luciferase to quantitatively compare the efficacy of the two platforms in supporting the localized retention of viable hASCs through longitudinal cell tracking with bioluminescence imaging (BLI). Interestingly, hASC retention was significantly enhanced when the cells were delivered in the MHA hydrogels as compared to the MGC hydrogels or saline. However, laser Doppler perfusion imaging (LDPI) indicated that the restoration of hindlimb perfusion was similar between the treatment groups and controls. These findings were corroborated by endpoint immunofluorescence (IF) staining showing similar levels of CD31+ cells in the ligated limbs at 28 days in all groups. Overall, this study demonstrates that enhanced MSC retention may be insufficient to augment vascular regeneration, emphasizing the complexity of designing biomaterials platforms for MSC delivery for therapeutic angiogenesis. In addition, the data points to a potential challenge in approaches that seek to harness the paracrine functionality of MSCs, as strategies that increase the secretion of immunomodulatory factors that can aid in regeneration may also lead to more rapid MSC clearance in vivo.

Successful revascularization of the occluded anterior tibial artery using ultrasound-guided puncture of the occluded dorsal pedal artery: A case report with literature review.

A bidirectional approach is necessary for treating critical limb ischemia with complex, multiple lesions. We report an ultrasound-guided bidirectional puncture through an occluded vessel to treat an obstruction extending from the anterior tibial artery to the dorsal foot artery in a patient with toe gangrene and rest pain. This technique effectively restored arterial patency and is a promising approach for managing challenging critical limb ischemia occlusions.

Maximal Systolic Acceleration and Near-Infrared Fluorescence Imaging With Indocyanine Green as Predictors for Successful Lower Extremity Revascularization.

BACKGROUND: Patients with lower extremity arterial disease (LEAD) frequently require revascularization procedures. Currently used diagnostic methods are insufficient in predicting successful outcomes and focus on macrovascular rather than microvascular state. Several promising modalities to increase diagnostic accuracy are emerging, including maximal systolic acceleration (ACCmax), measured by duplex ultrasound (DUS). For the assessment of tissue perfusion, near-infrared fluorescence (NIR) imaging using indocyanine green (ICG) demonstrates promising results. This study aims to identify the usefulness of combining these two methods for macrovascular and microvascular perfusion assessment to predict successful clinical outcomes. METHODS: A retrospective study was performed collecting preinterventional and postinterventional DUS and ICG NIR fluorescence imaging measurements from LEAD patients undergoing revascularization. The correlation between the preinterventional and postinterventional perfusion parameters, described as the delta (Δ) ACCmax and ΔICG NIR fluorescence parameters, were analyzed. Improvements in perfusion parameters were compared to clinical outcomes, defined as improvement in pain-free walking distance, freedom from rest pain, or tendency toward wound and ulcer healing. RESULTS: A total of 38 patients (42 limbs) were included. ACCmax and ICG NIR fluorescence perfusion parameters improved significantly after revascularization (p<0.001). Patients with a poor clinical outcome had a significantly lower improvement of both parameters after revascularization (p<0.001-0.016). Lack of correlation was found between the delta of ACCmax and ICG NIR fluorescence imaging. Multiple non-congruent improvements of macrovascular parameters (ACCmax) and perfusion (ICG NIR fluorescence) were seen within patients. However, for all patients with a successful clinical outcome, at least one parameter improved. CONCLUSION: Combining ACCmax and ICG NIR fluorescence imaging revealed improvement in at least one parameter within all patients with a successful clinical outcome. This study highlights the potential of assessing both the macrovascular state and tissue perfusion following lower extremity revascularization, as both appear to reflect different aspects of vascularization. CLINICAL IMPACT: Numerous techniques have been developed to assess tissue perfusion to predict clinical outcomes following revascularization in patients with peripheral artery disease. However, none are widely implemented in clinical practice. This study emphasized the importance of employing multiple modalities from different perspectives for more accurate prediction. By focusing on both the macrovascular state and tissue perfusion, clinicians can better guide themselves in their treatment strategies.