Limb Ischemia Research Articles

Outcomes of contemporary stents with deep femoral artery coverage.

We aimed to investigate deep femoral artery (DFA) status during endovascular treatment (EVT) and the patency of the femoropopliteal (FP) artery and DFA using current stent devices for ostial FP lesions. A multicenter, retrospective study analyzed data from 457 patients who underwent EVT with stent deployment for de novo ostial FP lesions between April 2018 and December 2021 at eight centers in Japan. Propensity score-matched analysis was performed to compare the clinical impacts of DFA coverage for ostial FP lesions with stent deployment. The prognostic value was analyzed based on DFA status during EVT, primary patency of the FP artery, clinically driven-target lesion revascularization (CD-TLR) of the FP artery, and incidence of DFA occlusion/major amputation/acute limb ischemia (ALI) at 3 years. A total of 132 matched pairs of patients was analyzed using propensity score matching. The percentage of DFA occlusion and stenosis was significantly higher in the DFA coverage group. However, there were no significant differences in terms of primary patency of the FP artery, CD-TLR, DFA occlusion, major amputation, or ALI after 3 years. Stent deployment in DFA coverage significantly led to the DFA stenotic events of EVT during the procedure, but patency of the FP artery and DFA, major amputation, and ALI up to 3 years did not differ according to stent deployment for ostial FP lesions.

Endovascular treatment versus bypass in long SFA atherosclerotic lesions: a non-randomized comparative study

Background: The TransAtlantic Inter-Society Consensus (TASC II) classification categorizes superficial femoral artery (SFA) lesions. This study compares endovascular therapy and bypass surgery for treating challenging TASC II C and D SFA lesions, which are typically complex and involve severe disease. Purpose: the aim is to compare the outcome of endovascular interventions versus surgical bypass in treatment of superficial femoral artery atherosclerotic TASC II C&D lesions in patients with critical limb ischemia in terms of patency and limb salvage within one year follow up. Patients and methods: our study included 41 patients in bypass group (groub A) and 74 patients in endovascular group (groub B) with atherosclerotic TASC II C&D SFA lesion. Patients with non-salvageable limbs, acute ischemia, trauma, aneurysms, connective tissue disorders and arteritis were excluded. All patients had Rutherford 4 to 6. Saphenous vein and synthetic grafts were used in bypass group. POBA, DCB and stents were used in endovascular group. The patients were followed up for 1 year.Results: mean Patients’ age was 63.15 years in endo group and 58.76 years in bypass group, male 78.4% in endo group and 85.4% in bypass group. Patients’ presentation was incapacitating claudications, rest pain, minor tissue loss, and major tissue loss. Technical success achieved in 100% in bypass cases and 95.9%in endo group. 1ry patency rate was 71.4% in the bypass group versus 57.6% in the endo group, still not significant statistically (p-value 0.171). The assisted 1ry patency was 77.1% in bypass group and 83.3% in the endo group,.(p.value 0.449) 2ry patency rates was 82.9% and 89.4% in bypass and endo groups respectively. Our 1-year limb salvage rates were 85% in the bypass group versus 91.7%, the rate was better in the endo group but with statistically insignificant p.value between them (p: 0.343). The rate of reintervention was higher in endo group (31.8%) than bypass group (11.4%) which was statistically significant, (p.value 0.024). Overall mortality during follow up was only 1 patient in the bypass group (2.4%). the bypass group had higher complication rate (41.5%) than the endovascular group (12.2%) with statistically significant (p.value <0.001). Conclusion: Bypass surgery and endovascular management have comparable short terms outcomes in terms of patency and limb salvage in treating long SFA atherosclerotic lesion TASC II C&D. Rate of reintervention is higher with endovascular strategy. However, with lower morbidity and mortality compared with surgery.

RESISTANCE INDEX AS A PROGNOSTIC FACTOR FOR PATENCY IN DISTAL LOWER LIMB ARTERIAL REVASCULARIZATION

Critical limb ischemia (CLI) of the lower limbs (LLs) is a severe condition caused by peripheral arterial obstructive disease (PAOD). Surgical planning for CLI requires the study of limb circulation, and the vascular resistance index (RI) measured by Doppler ultrasound (US) has been used to aid in surgical decision-making. The objective is to correlate the RI of recipient arteries with the patency of LL revascularization surgeries in patients with CLI. Prospective cohort study conducted from July 2021 to March 2023. The RI of the recipient arteries was evaluated preoperatively by US in 58 patients with CLI who underwent infrainguinal open or endovascular revascularizations, hospitalized in the Vascular Surgery Department of the Hospital das Clínicas of Empresa Brasileira de Serviços Hospitalares/Universidade Federal de Pernambuco. After 30days of surgery, all patients were evaluated for the presence of pulses in the revascularized limb and the ankle brachial index (ABI) was measured in all cases. Statistical analysis was conducted with a 95% confidence level, and the Student's t-test was used to compare 2 independent samples. Clinical evaluation and ABI assessment of revascularization patency after 30days revealed that infragenicular revascularizations that occluded had an average RI of 0.72 (SD±0.16), while patent revascularizations had a mean RI of 0.69 (SD±0.17) without statistical significance (P=0.658). Despite the lack of statistical significance, the study observed that a lower preoperative RI of the distal recipient artery was associated with greater patency of the revascularization surgery after 30days.

PCL-Fibrin-Alginate Hydrogel Based Cell Co-Culture System for Improving Angiogenesis and Immune Modulation in Limb Ischemia

PCL-Fibrin-Alginate Hydrogel Based Cell Co-Culture System for Improving Angiogenesis and Immune Modulation in Limb Ischemia

Comparison of Clinical Outcomes in Patients with Acute Lower Limb Ischaemia Undergoing Endovascular Therapy and Open Surgical Revascularisation: A Large Scale Analysis in Japan

Comparison of Clinical Outcomes in Patients with Acute Lower Limb Ischaemia Undergoing Endovascular Therapy and Open Surgical Revascularisation: A Large Scale Analysis in Japan

174 Heart going out on a limb: unmasking infective endocarditis as a covert cause of acute limb ischemia

174 Heart going out on a limb: unmasking infective endocarditis as a covert cause of acute limb ischemia

Unrecognized Rupture of Angioplasty Balloon: A Hidden Underlying Reason for the Delayed Occlusion of the Graft

Rupture of angioplasty balloons is a recognized complication of percutaneous transluminal angioplasty (PTA), occurring in approximately 5-10% of cases. If a rupture occurs, balloon fragments may embolize or cause thrombotic artery occlusion. Immediate recognition of a damaged balloon allows for prompt surgical or endovascular removal, depending on the patient’s condition and the location of the balloon inside the vessel. However, unrecognized balloon rupture with delayed symptoms is rare. We present a case of acute lower limb ischemia in a patient with a prior aortobifemoral reconstruction. Several years after an aortobifemoral bypass due to a failing right limb graft, endovascular graft treatment was performed. Eight years later, the patient required surgical treatment for acute ischemia, during which a piece of cup-shaped remnants from a ruptured balloon was found, with a confirmed circumferential balloon tear. Successful surgical extraction restored adequate inflow. The literature reports successful percutaneous retrieval of balloon fragments using techniques such as endoscopic biopsy forceps, grasping forceps, and subintimal angioplasty, but in our case, neither the rupture nor the balloon remnants were identified during the PTA procedure or on angiography eight years later. The retained fragment ultimately caused acute ischemia and limb graft occlusion, necessitating surgical intervention

Comparing the accuracy and safety of automated CO2 angiography to iodine angiography in peripheral arterial disease with chronic limb ischemia: a prospective cohort study

Introduction: Diagnostic angiography of peripheral arteries using carbon dioxide (CO2) is feasible in nearly all areas below the diaphragm. Using carbon dioxide as a contrast material in angiography provides the highest quality diagnostic results in the vascular segments above the knee. However, its diagnostic reliability decreases as it moves toward the distal side of the vessels below the knee. This study investigated the diagnostic accuracy and consistency between CO2 and iodine contrast angiography in patients with peripheral vascular disease (PVD) with chronic limb ischemia (CLI). Methods: The study prospectively enrolled 35 patients with PVD and CLI and performed both CO2 and iodine contrast angiography, comparing the results for each patient. Image quality, stenosis severity, and anatomical location were analyzed. Results: In this study, a total of 35 patients (19 male) with an average age of 56.91 ± 10.73 were examined. Among them, 13 patients (37.1%) had involvement in the femoral region, 8 patients (22.9%) in the popliteal region, 8 patients (22.9%) in the tibial region, and 6 patients (17.1%) in the foot region. CO2 angiography produced excellent image quality in 40% of cases, with good quality in another 25.7%. The quality decreased in the popliteal and foot regions. While stenosis assessment was comparable between the two methods in the femoral, popliteal, and tibial regions, there was a significant difference in the foot region. The sensitivity, specificity, positive predictive value, and negative predictive value of CO2 angiography were all 100% in the femoral and popliteal areas. However, these values were lower in the tibial and foot areas. Discussion: The study concluded that the use of CO2 angiography, particularly for vascular lesions above the popliteal cavity, is a valuable and safe method for peripheral vascular examination of the lower limbs. It can serve as an alternative to iodine contrast angiography, especially in patients with kidney failure.

A Study on Description of Collateral Pathway Patterns in Patients with Aortoiliac Occlusive Disease and Its Prospective Implication in Clinical Practice

Objectives: Collateral pathways in aortoiliac occlusive disease are essential for arterial blood flow to the lower abdomen and limbs. These different pathways further indicates the severity of disease and need of an appropriate treatment. The present study attempts in describing the various collateral pathways and its implication in the clinical practice. Materials: This is a retrospective study from January 2023 to June 2024 and reviewed all the records. Twelve patients (10 males, 2 females) with a mean age of 60 years were included in this study. All the patients were evaluated with three dimensional volume rendered rotational CT angiography and non invasive segmental blood pressure, pulse volume recording with ankle brachial index. Results: Nine patients had diabetes mellitus, 8 hypertension, and 6 dyslipidemia. Ten were active smokers. Five patients presented with intermittent claudication and 7 presented with critical limb ischemia. Two dominant collateral pathways were observed. Systemic collateral pathways were dominant in 7 patients, whereas visceral collaterals pathways were prominent in 5 patients. It is noted that complete occlusion of infrarenal aorta tends to have visceral collaterals pathways, whereas distal aortic occlusions had systemic collaterals pathways. Patients with visceral pathways had lower ABI and required early revascularisation. Knowledge of these pathways, demands careful surgical dissection; however we did not find any difference in the post operative outcome after successful revascularisation. Conclusions: Collateral pathways are defined mainly by the location of the lesion and helps in deciding the appropriate treatment. Patients with visceral collaterals pathways are more symptomatic and needs early revascularisation. Failure to recognize these pathways particularly during non vascular surgeries could lead to limb threatening situations.

Heart Rate Recovery after a 6-minute Walk test in Patients with Lower Extremity Artery Disease in Burkina Faso, sub-Saharan Africa

Background: Heart rate recovery (HRR) is a measure of fitness and an indication of cardiac health. The decrease in heart rate occurring immediately after exercise is caused by increased vagal activity and sympathetic withdrawal occurring after exercise.Objective: Our aim was to study the relationship between of the clinical severity of the lower limb artery disease (Fontaine classification) assessed during a 6-minute walking test and the decrease in heart rate (HR) from maximal exercise HR at 1-minute post-exercise (HRR1).Material and method: We studied patients were enrolled from January to December 2021 and screened in the vascular function exploration unit of the Souro SANOU University Hospitalof Bobo-Dioulasso, Burkina Faso, sub-Saharan Africa.Results: A total of 98 patients were included with a mean age of 53.6 ± 11.2 years, predominantly female (60.2%). The mean values were:0.834 ± 0.16 for ABI, 77± 11 bpm for resting HR, 108 ± 14bpm for end-exercise HR, 15bpm ± 8bpm for HRR1, 296± 95 m for maximum walking distance. Among the groups of the Fontaine classification, group IV walked the least (224±115m) and had the smallest HRR1 (11±8 bpm). Conclusion: Our study showed a significant relationship between HRR1 after a 6-minute walk test and the severity of lower limb ischemia. This could potentially lead to better peripheral arterial disease management strategies based on post-exercise cardiac recovery.

Veno-Arterial Extracorporeal Membrane Oxygenation (V-A ECMO) In Adults with Septic Shock: Hope or Hype?

Septic shock is associated with significant morbidity and mortality, but a subset of patients with sepsis will experience transient myocardial depression, termed sepsis-associated cardiomyopathy, which markedly increases observed mortality. Although veno-arterial extracorporeal membrane oxygenation (V-A ECMO) can provide temporary mechanical circulatory support in medically refractory sepsis, survival in patients with V-A ECMO for sepsis has historically been poor. Concerns regarding numerous potential harms associated with V-A ECMO, including further seeding of infection, exacerbation of inflammation and vasoplegia, bleeding, thrombosis, and distal limb ischemia have further tempered enthusiasm in the setting of sepsis. However, there may be a subset of patients with profound sepsis refractory to medical therapy who could potentially derive some benefit from V-A ECMO. This review provides an overview of the pathophysiology, diagnosis, and treatment of sepsis-associated cardiomyopathy, then focuses on the utility of V-A ECMO in this patient population. A summary of the scant published outcomes of V-A ECMO in sepsis-associated cardiomyopathy is provided, followed by a discussion of important management considerations to optimize outcomes in these extremely sick patients, and finally the pros and cons of V-A ECMO in the setting of sepsis are presented. Using available published data and current state-of-the-art practice, we conclude that V-A ECMO may be a reasonable consideration in highly selected patients with low ejection fraction sepsis-associated cardiomyopathy and refractory hypoperfusion in appropriately equipped healthcare systems, but more supportive data are required before V-A ECMO can be generally recommended in patients with septic shock.

Assessment of safety and effectiveness after percutaneous closure for decannulation of Veno-Arterial Extracorporeal Membrane Oxygenation: A systematic review and meta-analysis.

Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO) has emerged as a crucial component of critical care medicine, mainly as a lifesaving intervention for patients experiencing refractory cardiac arrest and respiratory failure. In the past, VA-ECMO decannulation was surgical and often associated with a high rate of periprocedural complications, such as surgical site infection, bleeding, and patient mobilization costs. To reduce the rate of these adverse events, many percutaneous techniques utilizing suture-mediated closing devices have been adopted. One of those devices is the Perclose Proglide® (PP). This study's goal was to perform a systematic review to evaluate PP devices' success and complication rates for VA-ECMO decannulation. To analyze the outcomes of PP in VA-ECMO decannulation, a systematic review of the most recent literature was conducted. The Medline, Web of Science, and Cochrane databases were systematically searched up to September 2023. The National Health, Blood, and Lung Institute Study quality assessment tools were used. The final analysis included 10 observational studies comprising 418 patients. The efficacy of PP in VA-ECMO decannulation was 93.0% (95% CI 90.1%-96.0%). In 381 patients, the incidence of acute limb ischemia after VA-ECMO decannulation was 2.5% (95% CI 0.9%-4.%), the infection of the puncture site after decannulation was 1% (95% CI 0%-2%) in 385 patients. The incidence of patients with pseudoaneurysm after decannulation was 1.1% (95% CI 0.1%-2.1%). This systematic review and meta-analysis demonstrate the safety and efficacy of the PP for achieving hemostasis after VA-ECMO decannulation, with a high success rate and low rate of major complications.

Extracorporeal shockwave therapy rescued mouse critical limb ischemia via upregulating GPR120 against inflammation and promoting angiogenesis for restoring the blood flow in ischemic zone-experimental study.

This study tested the hypothesis that extracorporeal shockwave therapy (ECSWT) effectively rescues critical limb ischemia (CLI) in mice through the upregulation of GPR120, which protects against inflammation and angiogenesis to restore blood flow in the ischemic area. Compared with the control, ECSWT-induced GPR120-mediated anti-inflammatory effects significantly suppressed the expression of inflammatory signaling biomarkers (TAK1/MAPK family/NF-κB/IL-1β/IL-6/TNF-α/MCP-1) in HUVECs, and these effects were abolished by silencing GPR120 or by the GPR120 antagonist AH7614 (all P < 0.001). C57BL/6 mice (n =40) were equally categorized into Groups 1 (sham-operated control), 2 (CLI), 3 (CLI+ECSWT), and 4 (CLI+ECSWT+AH7614). By Days 7, 14, and 28 just prior to harvesting the quadriceps muscle, the laser Doppler results showed that the ratio of ischemia to normal blood flow (INBF) in the CLI area was highest in Group 1, lowest in Group 2, and significantly greater in Group 3 than in Group 4 (all P < 0.0001). Endothelial cell markers (CD31/vWF) and GPR120+cells exhibited identical patterns of INBF among the groups, whereas angiogenesis biomarkers (CXCR4/SDF-1/VEGF/VEGFR2) were significantly and progressively upregulated from Groups 1 to 4 (all P < 0.0001). The protein levels of inflammation (MMP-9, IL-6, and TNF-α) and oxidative stress (NOX-1 and NOX-2) and the cellular levels of inflammation (CD68+)/DNA damage (γ-H2AX+) displayed opposite patterns, whereas the small vessel density in the CLI area displayed an identical pattern of INBF among the groups (all P < 0.0001). ECSWT rescued CLI by increasing GPR120-mediated suppression of inflammation and enhancing angiogenesis via activation of VEGFR2.

Urgical Challenges In Managing Haemodialysis Arteriovenous Fistula Complications In Tertiary Care Centre: Our Approach.

Arteriovenous (AV) fistula creation is the most common surgical procedure for providing vascular access for haemodialysis in patients with chronic kidney disease (CKD). The functioning of fistula dictates the quality of dialysis and the longevity of patients. The most common circumstances that require surgical takedown of AV fistula are thrombosis and rupture. While some patients undergo elective AV fistula takedown post renal transplantation or for cosmesis, majority of patients presenting with life-threatening rupture require emergency surgery for AV fistula takedown with or without maintaining arterial continuity. This study aims to compile our experience with surgical management of various AF fistula complications. This is a retrospective study of 29 patients who underwent Arteriovenous Fistula takedown in our institute over a period of 3years from May 2021 to May 2024. The most common cause of fistula takedown in our setup was rupture (n=25, 86.21%). AV fistula takedown was done in all cases (n=29, 100%). Arterial ligation was done in all infected cases (n=22, 75.86%) whereas in non-infected cases arterial continuity was maintained by repair or interposition venous graft. There was no aneurysm or psedoaneurysm formation or limb ischaemia in a follow up period ranging from 1month to 3 years. Erroneous ways of cannulation and lack of awareness of fistula care were the prime cause of AV fistula complications. Early detection and presentation to healthcare setup could offer a better prognosis for limb salvage in the long term and decrease the incidence of morbidity and mortality.

Mucinous tubular and spindle cell carcinoma of the kidney: Clinical, imaging and pathological features

Background: Mucinous Tubular and Spindle Cell Carcinoma (MTSCC) is a rare variant of Renal Cell Carcinoma (RCC). MTSCC has been regarded as an indolent subtype of RCC conveying a good prognosis. However, recently some cases of MTSCC have been described presenting or evolving with metastasis, showing an aggressive behaviour. We aim to describe MTSCC clinical characteristics, treatment, prognosis and survival. Methods: We retrospectively reviewed all cases of MTSCC diagnosed at our institution from 1 January 2008 to 31 December 2022. Electronic health records were reviewed, and data were retrieved and analysed. This study was approved by our institution’s ethics committee. Data confidentiality was assured. Results: We identified eight cases of MTSCC among the 15 years of the study timeframe diagnosed in our hospital. The median age at diagnosis was 59 years (range = 32–80 years), and half of the patients were women (n = 4; 50%). In six (75%) of the patients, presentation was incidental, while the remaining two presented with flank pain. One patient had metastasis at presentation, while the remaining cases were localised at the time of diagnosis. Six patients were submitted to radical nephrectomy: four by open approach and two by transperitoneal laparoscopic approach. Two patients were submitted to a partial nephrectomy by an open approach. Mean (SD) postoperative haemoglobin drop was 2.18 (1.12) g/dL. Median follow-up was 36.5 months (range = 2–157). During the study timeframe, no other patients were diagnosed with local recurrence or distant metastasis. Two patients died during follow-up: the one that was metastatic at diagnosis died due to disease progression 2 months after surgery and another died due to a competitive disease (acute lower limb ischaemia). Conclusion: MTSCC is a rare variant of RCC that, despite being initially regarded as an indolent disease with good prognosis, might harbour an aggressive behaviour and grim prognosis. Level of evidence: 2b

Outcomes of Suction Debulking and Surgery in Patients With Isolated Tricuspid Valve Endocarditis.

Percutaneous vegetation debulking has been reported to treat tricuspid valve infective endocarditis (TVIE), but data on feasibility compared with conventional surgical strategies are limited. We aimed to compare short-term outcomes of suction debulking with partial venovenous bypass to conventional open surgery in this population. This was a single-center, retrospective study that included all patients with isolated TVIE who underwent suction debulking with partial venovenous bypass or tricuspid valve surgery between January 2010 and December 2022. Patient characteristics, procedural data, and clinical outcomes were compared. Of the 45 patients included, 16 (35.6%) underwent suction debulking and the remainder (64.4%) underwent surgery. Baseline characteristics were comparable, including high rates of preprocedure hemodialysis (11.1%), prior infectious endocarditis (44.4%), intravenous drug use (60.0%), presence of tricuspid bioprostheses (24.4%), and septic shock (40.0%). Suction debulking had a shorter procedure time than surgery (206 [176 to 224] min vs 400 [325 to 487] min, P < 0.001) and was associated with numerically lower rates of various complications including acute kidney injury requiring hemodialysis, limb ischemia, and dysrhythmia requiring pacemaker. Over a mean follow-up period of 473 ± 604 days, recurrent endocarditis (37.5% vs 17.2%, P = 0.25) and the need for reintervention (50.0% vs 17.2%, P = 0.048) were higher with suction debulking. However, all-cause mortality was similar between the groups (12.5% vs 10.3%, P > 0.99). Suction debulking can safely be performed in patients with isolated TVIE with shorter procedural times and similar midterm all-cause mortality compared with surgery. Suction debulking may be appropriate initial therapy for this complex population.

A bioactive Hydrogel Patch Accelerates Revascularization in Ischemic Lesions for Tissue Repair

Abstract Background Magnesium ions play crucial roles in maintaining cellular functions. Research has shown that Mg2+ can promote angiogenesis, indicating its potential for treating cardiovascular ischemic diseases. However, conventional intravenous or oral administration of Mg2+ presents several challenges, including the risk of systemic side effects, diminished bioavailability, and a lack of targeted delivery mechanisms. In this study, we designed a Mg2+-releasing adhesive tissue patch (MgAP) that enables the dural release of Mg2+ ions. Methods A novel Mg2+-releasing adhesive patch (MgAP) was developed on the basis of ionic crosslinking. Fourier transform infrared spectroscopy confirmed the chemical structure, whereas rheological analysis demonstrated stable mechanical properties and adaptability to dynamic loads. Sustained Mg2+ release was quantified over 7 days by inductively coupled plasma–mass spectrometry. In a rat acute myocardial infarction model, we performed echocardiography and strain analysis to assess cardiac function and histological staining to evaluate adverse remodeling. We also verified the proangiogenic effect through in vitro tube formation and in vivo immunofluorescence assays. Furthermore, transcriptomics and Western blotting were performed to explore the underlying mechanism. Additional assessments were also carried out in a rat model of lower limb ischemia. Results Compared with intravenous administration of magnesium chloride, MgAP application effectively improved cardiac function and reduced adverse remodeling in the myocardial infarction rat model. The left ventricular ejection fraction increased by 20.3 ± 6.6%, and the cardiac radial strain improved by 27.4 ± 4.1%. The cardiac fibrosis area and cell apoptosis rate decreased by 10.9 ± 1.2% and 32.1 ± 5.5%, respectively. RNA sequencing analysis also highlighted the upregulation of genes related to cardiac electrophysiological properties, structural and functional intercellular connections, and revascularization. The increased gap junction protein expression and restored local blood supply could contribute to the cardiac repair process posttreatment. The proangiogenic effect of MgAP was also observed in the rat limb ischemia model. Conclusions The above results revealed the convincing vascular regeneration effect of an ion therapy-based hydrogel, which enabled the local delivery of Mg2+ to the targeted ischemic tissue, aiding in cardiac and lower limb repair. This study presents a novel strategy and highlights its potential for use across various ischemic conditions.

Emerging Strategies for Revascularization: Use of Cell-Derived Extracellular Vesicles and Artificial Nanovesicles in Critical Limb Ischemia.

Critical limb ischemia (CLI) poses a substantial and intricate challenge in vascular medicine, necessitating the development of innovative therapeutic strategies to address its multifaceted pathophysiology. Conventional revascularization approaches often fail to adequately address the complexity of CLI, necessitating the identification of alternative methodologies. This review explores uncharted territory beyond traditional therapies, focusing on the potential of two distinct yet interrelated entities: cell-derived extracellular vesicles (EVs) and artificial nanovesicles. Cell-derived EVs are small membranous structures naturally released by cells, and artificial nanovesicles are artificially engineered nanosized vesicles. Both these vesicles represent promising avenues for therapeutic intervention. They act as carriers of bioactive cargo, including proteins, nucleic acids, and lipids, that can modulate intricate cellular responses associated with ischemic tissue repair and angiogenesis. This review also assesses the evolving landscape of CLI revascularization through the unique perspective of cell-derived EVs and artificial nanovesicles. The review spans the spectrum from early preclinical investigations to the latest translational advancements, providing a comprehensive overview of the current state of research in this emerging field. These groundbreaking vesicle therapies hold immense potential for revolutionizing CLI treatment paradigms.

ICAM1 blockade improves ischemic muscle reperfusion in diabetic mice

BackgroundChronic Limb-Threatening Ischemia (CLTI) represents the most advanced stage of Peripheral Artery Disease (PAD) and is associated with dire prognosis, characterized by a substantial risk of limb amputation and diminished life expectancy. Despite significant advancements in therapeutic interventions, the underlying mechanisms precipitating the progression of PAD to CLTI remain elusive.MethodsConsidering diabetes is one of the main risk factors contributing to PAD exacerbation into CLTI, we compared hind limb ischemia recovery in HFD STZ vs. non-HFD STZ mice to identify new mechanisms responsible for the exacerbation of PAD.ResultsWe used three different mouse models of diabetes and found that blood flow recovery in HFD STZ mice is altered only from day 14 post-surgery. Consistent with this kinetics, we found that angiogenesis and myogenesis which typically occur between day five and day 14 post-surgery are not impaired in mice in which diabetes was induced by a high fat diet and streptozotocin injections (HFD STZ mice). On the contrary, we found that capillary functionality e.i. acquisition of functional intercellular junctions and immune quiescence is impaired in HFD + STZ mice. Notably, 28 days after hind limb ischemia surgery, HFD + STZ mice display significantly increased capillary permeability to IgG and significantly increased levels of ICAM1. This was associated with an increased macrophage infiltration and an impaired myocyte differentiation. Importantly, we used ICAM1-blocking antibodies to demonstrate that increased ICAM1 expression in HFD + STZ mice decreases white blood cell circulation velocity within the microcirculation, which impairs its perfusion. Notably anti-ICAM1 therapy did diminish macrophage infiltration and oxidative stress but not myopathy suggesting that myopathy characterized by small myocytes expressing higher level of MYH2 could be responsible for microangiopathy.ConclusionICAM1 expression by the microvasculature impairs ischemic muscle reperfusion in HFD + STZ mice. Importantly, the increase in blood flow between day 14 and day 90 post-HLI surgery is not associated with an increased capillary density but with an improved functionality of capillaries.

Cultivatable Bacteriota of Chronic Wound of Patients with Diabetic Foot Syndrome with Critical Limb Ischemia Based on Wound Biopsy in Peri-Revascularization Period

Cultivatable Bacteriota of Chronic Wound of Patients with Diabetic Foot Syndrome with Critical Limb Ischemia Based on Wound Biopsy in Peri-Revascularization Period