Limb Ischemia Research Articles

Expression of microRNA-27b in type 2 diabetic patients and relation to microvascular complications

ABSTRACT In this study, we aimed to explore whether circulating microRNA-27b (miR-27b) is affected in diabetic patient with microvascular complications Methods This study was conducted on 90 participants, 30 had type 2 diabetes with chronic limb ischemia, 30 diabetics without chronic limb ischemia and 30 healthy controls. The relative expression of microRNA 27b was assessed in the patient groups and its relation between diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic neuropathy (DN). Results Concerning relation between miR-27b and other microvascular complications, DR & DN, miR-27b plasma expression showed no significant difference between T2DM patients with increased VPT compared to those with normal VPT. Comparably, there was no significant difference in the plasma miR-27b expression between patients with DR and those with normal fundus examination. Additionally, neither DR nor VPT correlated with plasma miR-27bexpression. Conclusion Plasma miR-27b expression showed no change between the patient groups and there was no correlation with microvascular complications and miR-27b expression.

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

ABSTRACT 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

AbstractCell 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 (&gt;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.

Induced blood flow oscillations at 0.1 Hz protects oxygenation of severely ischemic tissue in humans.

Generating 10-s (∼0.1 Hz) fluctuations or "oscillations" in arterial pressure and blood flow blunts reductions in cerebral tissue oxygenation in response to 15%-20% reductions in cerebral blood flow. To examine the effect of 0.1 Hz hemodynamic oscillations on tissue oxygenation during severe ischemia, we developed a partial limb ischemia protocol targeting a 70%-80% reduction in blood flow. We hypothesized that 0.1 Hz hemodynamic oscillations would attenuate reductions in tissue oxygenation during severe ischemia. Thirteen healthy humans (6 M and 7 F; 27.3 ± 4.2 yr) completed two experimental protocols separated by ≥48 h. In both conditions, an upper arm cuff was used to decrease brachial artery (BA) blood velocity by ∼70%-80% from baseline. In the oscillation condition (0.1 Hz), 0.1 Hz hemodynamic oscillations were induced by intermittently inflating and deflating bilateral thigh cuffs every 5 s during forearm ischemia. In the control condition (0 Hz), the thigh cuffs were inactive. BA blood flow, forearm tissue oxygenation (SmO2), and arterial pressure were measured continuously. The initial reduction in BA blood velocity was tightly matched between protocols (0 Hz: -76.9 ± 7.9% vs. 0.1 Hz: -75.5 ± 7.4%, P = 0.49). Although 0.1 Hz oscillations during forearm ischemia had no effect on the reduction in BA velocity (0 Hz: -73.0 ± 9.9% vs. 0.1 Hz: -73.3 ± 8.2%, P = 0.91), the reduction in SmO2 was attenuated (0 Hz: -35.7 ± 8.6% vs. 0.1 Hz: -27.2 ± 8.9%, P = 0.01). These data provide further evidence for the use of 0.1 Hz hemodynamic oscillations as a potential therapeutic intervention for conditions associated with severe tissue ischemia (e.g., hemorrhage and stroke).NEW & NOTEWORTHY We investigated the effects of induced 10-s (0.1 Hz) oscillations in blood flow on forearm tissue oxygenation during severe ischemia. Intermittent inflation of bilateral thigh cuffs was used as a clinically applicable method to drive blood flow oscillations. In support of our hypothesis, 0.1 Hz oscillations in blood flow blunted reductions in forearm tissue oxygenation. These results further support the potential use of oscillatory hemodynamics as a therapeutic intervention for ischemic conditions.

Simultaneous Percutaneous Coronary Intervention (PCI) and Endovascular Aneurysm Repair (EVAR): A Preliminary Report.

Background: Performing percutaneous coronary intervention (PCI) and endovascular aneurysm repair (EVAR) at the same time represents a groundbreaking development in the multidisciplinary treatment of cardiovascular disease. This combined PCI-EVAR approach bridges a critical gap by offering treatment for patients who have both coronary artery disease and aortic aneurysms. This innovative strategy exemplifies the evolving landscape of cardiovascular care, providing a new solution for complex clinical situations that previously required separate procedures. Methods: Six patients with critical coronary artery lesions and asymptomatic infrarenal aortic aneurysms (AAAs) ≥ 6 cm diameter, as well as one patient with critical coronary artery lesions and endoleak type 1A with aneurysms ≥ 6 cm, underwent simultaneous coronary artery revascularization through percutaneous intervention (PCI) and endovascular aneurysm repair (EVAR). The occurrence of any intraoperative or postoperative complication was considered to be the primary endpoint of the study, including the abortion or failure of either PCI or EVAR, bleeding requiring a conversion to open surgical procedures, the failure of local anesthesia, postoperative myocardial or lower limb ischemia, and a postoperative serum creatinine level of >125 mmol/L or of >180 mmol/L in patients affected by chronic renal failure. The overall length of the procedure, X-ray exposure, the quantity of iodine contrast medium administered, and the length of recovery were considered to be secondary endpoints. Results: Postoperative complications included two episodes of acute renal failure in the two patients already affected by chronic renal failure, which were easily resolved with adequate daily hydration and the elimination of nephrotoxic drugs. In no cases did cardiac ischemia or lower limb ischemia occur. The average procedure duration was 198 min (range: 180-240 min), the average fluoroscopy duration was 41.7 min (range: 35-50 min), the average amount of iodinated contrast medium was 34.8 mL (range: 30-40 mL), and the mean length of hospitalization was 2.7 days (range: 2-5 days). Conclusions: In selected patients, this surgical approach has demonstrated safety, reduced hospitalization times, minimized risks associated with complications from the untreated condition if procedures were performed at different times, and facilitated the effective management of intraoperative complications due to the presence of a multidisciplinary team. However, the limited number of patients necessitates further research.

A comparative study of femoral artery and combined femoral and axillary artery cannulation in veno-arterial extracorporeal membrane oxygenation patients.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a critical support technique for cardiac surgery patients. This study compares the outcomes of femoral artery cannulation vs. combined femoral and axillary artery cannulation in post-cardiotomy VA-ECMO patients. This study aimed to compare the clinical outcomes of critically ill patients post-cardiac surgery under VA-ECMO support using different cannulation strategies. Specifically, the focus was on the impact of femoral artery (FA) cannulation vs. combined femoral artery and axillary artery (FA+AA) cannulation on patient outcomes. Through a retrospective analysis, we compared 51 adult patients who underwent cardiac surgery and received VA-ECMO support based on the cannulation strategy employed-FA cannulation in 27 cases vs. FA+AA cannulation in 24 cases. The FA+AA group showed significant advantages over the FA group in terms of the incidence of chronic renal failure (CRF) (37.50% vs. 14.81%, p = 0.045), preoperative blood filtration requirement (37.50% vs. 11.11%, p = 0.016), decreased platelet count (82.67 ± 44.95 vs. 147.33 ± 108.79, p = 0.014), and elevated creatinine (Cr) levels (151.80 ± 60.73 vs. 110.26 ± 57.99, p = 0.041), although the two groups had similar 30-day mortality rates (FA group 40.74%, FA+AA group 33.33%). These findings underscore that a combined approach may offer more effective hemodynamic support and better clinical outcomes when selecting an ECMO cannulation strategy. Despite the FA+AA group patients presenting with more preoperative risk factors, this group has exhibited lower rates of complications and faster recovery during ECMO treatment. While there has been no significant difference in 30-day mortality rates between the two cannulation strategies, the FA+AA approach may be more effective in reducing complications and improving limb ischemia. These findings highlight the importance of individualized treatment strategies and meticulous monitoring in managing post-cardiac surgery ECMO patients.

Axillary artery access considerations in Impella 5.5insertion: Insights from exclusive axillary approach forsuccessful support.

The Impella 5.5® is commonly inserted via the axillary artery (AX) in patients with cardiogenic shock. The right AX has traditionally been preferred to avoid crossing the aortic arch, and a minimum diameter of 7 mm has been recommended to accommodate the device (21 Fr). There is limited data on choice of laterality of access and AX size required, both in terms of technicality of the procedure as well as outcomes. We performed a single-center retrospective cohort analysis of patients who underwent Impella 5.5® implantation between December 2020 and February 2024 (N = 75). Data including demographics and outcomes were stratified both by diameter (small, <7 mm vs. normal, ≥7 mm) and laterality of access (right vs. left). Adverse events included stroke, limb ischemia, procedural bleeding or infection, and unplanned explant due to complications. Delivery time was defined as time from advancing the first wire to activation of the device. AX approach was attempted in all (N = 74) but one requiring innominate access, with a technical success rate of 95.9% (N = 71/74). The mean age was 58.8 ± 13.3 years, with 81.1% males. The median delivery time was 7.0 (25th, 75th percentiles: 4.0, 11.5) min with a median support duration of 13 (7.7, 24) days. Ten patients (13.5%) had a small AX, with a mean diameter of 6.3 ± 0.5 mm and were more likely to be younger compared to the normal AX group. Fifty-nine patients (79.7%) had insertion via the right AX. Median delivery time was comparable across all groups (small, 5.4 [3.5, 10.9] vs. normal, 7 [4.0, 12.1] min, p = 0.59) and (right, 10.4 [5.3, 15.2] vs. left, 6 [3.7, 10.4] min, p = 0.35). There was no difference between the rates of stroke, ischemia, bleeding, or infection when comparing by size or laterality. Survival to discharge was 59.5%, with 21.1% mortality on support, all in patients with a normal AX diameter, but with no difference between right versus left. In our study, laterality and a small diameter of AX access did not affect outcomes of Impella 5.5®, with a similar safety profile.

The application of cell products for the treatment of critical limb ischemia in patients with diabetes mellitus: a review of the literature

The number of patients with diabetes mellitus (DM) has been progressively increasing worldwide over the past decades, and many international organizations consider DM as a public health emergency of the 21st century.Critical limb ischemia (CLI) is the most severe stage of peripheral arterial disease (PAD) in DM and is characterized by a high risk of limb loss without revascularization. Traditional treatment tactics include open and endovascular revascularization surgical techniques. However, in patients not eligible for revascularization and in cases where performed surgical treatment performed has been ineffective, there are almost no therapeutic alternatives, often leading to amputations and death. As of today, one of the newest non-surgical treatment options is cell therapy. Among different cells, mesenchymal stromal cells (MSCs) are potentially one of the most prospective for use in this patient population.This article provides an overview of clinical trials using cell therapy in patients with CLI.To analyze publications, electronic databases PubMed, SCOPUS, ClinicalTrials, and ScienceDirect were searched to identify published data from clinical trials, research studies, and review articles on cell therapy for critical lower extremity ischemia. After the search, 489 results were received.As a result of systematic selection, 22 clinical trials were analyzed.According to the analyzed literature data, the use of cell products in this category of patients is effective and safe. Cell therapy can stimulate the formation of new vessels and enhances collateral circulation; it is also reported improved distal perfusion, increased pain-free walking distance, decreased amputation rates, and increased survival rates.Nevertheless, further study of the potential use of this category of drugs is needed.

Is there an association between arteriovenous fistulas and axillary artery aneurysms? A report of two cases

IntroductionAxillary artery aneurysms are rare vascular conditions that can present with various clinical manifestations, including neurological deficits and vascular compromise. While the underlying pathophysiology remains complex and multifactorial, potential associations with trauma, arteriovenous fistula formation, and atherosclerosis have been reported.Presentation Of Case.Two male patients, aged 33 and 38, with a history of kidney transplantation and previous arteriovenous fistula (AVF) presented with symptoms of upper limb ischemia and neurological compromise. Imaging revealed large axillary artery aneurysms. Open surgical repair was performed for both cases. Two weeks after discharge, one patient showed good pronation and supination with mildly limited extension. The other patient's wrist drop gradually improved with physiotherapy. DiscussionMultifactorial pathophysiology encompassed altered blood flow dynamics, inflammation, and the underlying vascular pathology. Chief complaints and prior vascular interventions contributed. Open surgical repair was preferred to endovascular approaches, achieving favorable outcomes. ConclusionAxillary artery aneurysms in patients with a history of AVF are rare but potentially serious complications. The cases highlight the complexity of axillary artery aneurysms and the need for careful evaluation and surgical intervention This strategy is crucial to prevent potential complications and optimize patient outcomes. Further research is needed to elucidate the precise pathophysiology and the potential association between AVF and the subsequent development of axillary artery aneurysms. Increasing awareness among surgeons could enable earlier detection of aneurysms, thereby reducing the risk of complications.

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.

Injectable Alginate-Based Hydrogels Encapsulating Engineered Endothelial Extracellular Vesicles for the Treatment of Critical Limb Ischemia.

Critical limb ischemia (CLI) is a peripheral arterial disease resulting from chronic inflammation of vascular systems. Recent studies have shown that inhibiting macrophage inflammation has the potential to treat CLI, and extracellular vesicles (EVs) from endothelial cells can inhibit macrophage activation. However, the limited cell-targeting capabilities and rapid clearance of EVs from the injection site limit the in vivo application of the EVs. Here, we modified endothelial EVs with platelet membranes (pM/EVs) to boost the inhibition effects on macrophage inflammation and developed an injectable alginate-based collagen composite (ACC) hydrogel for localized delivery of pM/EVs (pM/EVs@ACC) for CLI treatment. We found that pM/EVs can effectively inhibit macrophage inflammation in vitro. Furthermore, pM/EVs@ACC treatment significantly promotes the recovery of limb functions, restoring the feet' blood supply and relieving inflammation. Our findings provide compelling evidence that the pM/EVs@ACC injectable system mediating delivery of pM/EVs is a promising strategy for CLI treatment.

Extracorporeal life support for severe leptospirosis: Case series and narrative review

Introduction: Leptospirosis can be associated with multi-system organ failure (MSOF) and significant morbidity and mortality. Extracorporeal life support (ECLS) has been used as salvage therapy for severe leptospirosis complicated by acute respiratory distress syndrome (ARDS). Current knowledge in this field is limited, with no standardized treatment approaches. We aim to describe the literature to date on the use of ECLS in patients with leptospirosis, highlighting associations, outcomes, and complications. Methods: We report on the successful use of ECLS in two cases of severe leptospirosis and conduct a narrative review of the literature. Using a search strategy developed in consultation with a medical librarian and validated across pre-selected articles, several databases were searched. We included case reports, case series, cohort studies, and prospective studies of adult patients with confirmed leptospirosis undergoing ECLS. Editorials, surveys, or opinion articles without primary patient data were excluded. Overall mortality was our primary outcome. Results: Two cases of previously healthy males presenting with ARDS due to leptospiral infection are described. Literature review identified 25 articles containing 43 reported cases of patients treated with ECLS for severe leptospirosis. Patients were mostly young and male. Overall mortality was 16%. The most common complication recognized was acute renal failure requiring renal replacement therapy. Additional complications included diffuse intravascular coagulation, necrotizing pancreatitis, and limb ischemia. Conclusion: Leptospirosis should be considered in patients with epidemiologic exposure(s) presenting with critical illness, including ARDS and MSOF. ECLS is a viable rescue strategy in severe leptospirosis, even with established MSOF.

Acrocyanosis as a rare presentation of drug-induced cutaneous vasculitis: a case report

BackgroundAcrocyanosis is characterised by persistent bluish discolouration of the extremities, resulting from reduced peripheral blood flow leading to increased oxygen extraction. The aetiology can be divided into primary and secondary causes. While primary acrocyanosis is generally painless and has a benign course, secondary causes may lead to complications. This case reported acrocyanosis secondary to cutaneous vasculitis which progressed to digital gangrene, which is a rare complication of cutaneous vasculitis.Case presentationA 68-year-old man presented with a four-day history of bluish discolouration involving bilateral toes associated with pain and started to become gangrenous. Investigations for critical limb ischemia did not show evidence of critical arterial stenosis. Further history revealed history of recent administration of intramuscular injections with diclofenac, a non-steroidal anti-inflammatory agent for renal colic pain a few days prior to the onset of the. Thorough skin search showed multiple purpuric rash of his thighs, buttocks and abdomen. Skin biopsy confirmed the diagnosis of cutaneous (lymphocytic) vasculitis, which was likely to be drug-induced. The acrocyanosis initially responded to methylprednisolone, however unfortunately it progressed further to digital gangrene which required bilateral transmetatarsal amputations.ConclusionKnowledge on clinical features, aetiology and investigations of secondary acrocyanosis is crucial for early recognition and treatment of the underlying cause to prevent irreversible complications.

Anticoagulation in embolic acute limb ischaemia-an observational study.

The management of embolic acute limb ischaemia commonly involves determining aetiology and performing emergency invasive procedures. This detailed study aimed to determine the impact of manipulation of anticoagulation in the aetiology of emboli in acute limb ischaemia and determine the efficacy of primary anticoagulation therapy vs. invasive interventions. Material and methods: Data collection was conducted at a single institution on a cohort of patients presenting consecutively with embolic acute limb ischaemia over one year. Two groups were compared, one receiving anticoagulation as primary therapy with those undergoing invasive treatment as the internal comparison group. Results: A likely haematological causation was identified in 22 of 38 presentations, related to interruption of anticoagulation in cardiac conditions, the majority atrial fibrillation (n=12), or hypercoagulable states (n=10). Limb salvage was pursued in 36 patients employing anticoagulation (n=19) or surgical embolectomy (n=17) as the primary therapy in upper and lower limbs (n=17 vs n=19 respectively). Despite delays often well beyond six hours and a range of ischaemic severity in both groups, 35 of 36 patients achieved full or substantive restoration of function with improved perfusion. Regarding anatomical distribution of arterial disease and therapy, three patients with multi-level disease proceeded to embolectomy following anticoagulation. Embolectomy was undertaken most often for proximal emboli and more profound paralysis. Conclusions: Anticoagulation and coagulopathy are commonly implicated in the aetiology of arterial emboli, with omission of effective anticoagulation in atrial fibrillation being associated in almost 1/3 of presentations. Whilst more profound limb paralysis and proximal or multi-level disease tended to be managed surgically, primary anticoagulation therapy alone or with a secondary embolectomy was effective across the spectrum of ischaemia severity and despite significant delays beyond guideline recommendations.

REBOA in trauma: a life-saving intervention or a spectacular failure?

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a controversial haemorrhage control intervention often touted as the bridge to definitive haemorrhage control. This review summarizes the evolution of REBOA from its inception to the latest applications with an emphasis on clinical outcomes. This is a narrative review based on a selective review of the literature. REBOA remains a rarely utilized intervention in trauma patients. Complications have remained consistent over time despite purported improvements in catheter technology. Ischemia-reperfusion injuries, end-organ dysfunction, limb ischemia, and amputations have all been reported. Evidence-based guidelines are lacking, and appropriate indications and the ideal patient population for this intervention are yet to be defined. Despite the hype, purported technological advancements, and the mirage of high-quality studies over the last decade, REBOA has failed to keep up to its expectations. The quest to find the solution for uncontrolled NCTH remains unsolved.

Bilateral Acute Limb Ischemia due to Severe Rheumatic Mitral Stenosis and Atrial Fibrillation with Neglected International Normalized Ratio Control

Bilateral Acute Limb Ischemia due to Severe Rheumatic Mitral Stenosis and Atrial Fibrillation with Neglected International Normalized Ratio Control

Neutrophil extracellular traps and citrullinated fibrinogen contribute to injury in a porcine model of limb ischemia and reperfusion.

Ischemia/reperfusion injury (IRI) is a complex pathological process, triggered by the restoration of blood flow following an interrupted blood supply. While restoring the blood flow is the only option to salvage the ischemic tissue, reperfusion after a prolonged period of ischemia initiates IRI, triggering a cascade of inflammatory responses ultimately leading to neutrophil recruitment to the inflamed tissue, where they release neutrophil extracellular traps (NETs). NETs are web-like structures of decondensed chromatin and neutrophilic proteins, including peptidyl-arginine deiminase 2 and 4 (PAD2, PAD4), that, once outside, can citrullinate plasma proteins, irreversibly changing their conformation and potentially their function. While the involvement of NETs in IRI is known mainly from rodent models, we aimed to determine the effect of NET formation and especially PADs-mediated extracellular protein citrullination in a porcine model of limb IRI. We conducted our study on amputated pig forelimbs exposed to 1h or 9h of ischemia and then reperfused in vivo for 12h. Limb weight, edema formation, compartmental pressure were measured, and skeletal muscle was analyzed by immunofluorescence (TUNEL assay and dystrophin staining) to evaluate tissue damage. Fibrin tissue deposition, complement deposition and NETs were investigated by immunofluorescence. Citrullinated plasma proteins were immunoprecipitated and citrullinated fibrinogen was identified in the plasma by Western blot and in the tissue by immunofluorescence and Western blot. Our data consolidate the involvement of NETs in a porcine model of limb IRI, correlating their contribution to damage extension with the duration of the ischemic time. We found a massive infiltration of NETs in the group subjected to 9h ischemia compared to the 1h and citrullinated fibrinogen levels, in plasma and tissue, were higher in 9h ischemia group. We propose fibrinogen citrullination as one of the mechanisms contributing to the worsening of IRI. NETs and protein citrullination represent a potential therapeutic target, but approaches are still a matter of debate. Here we introduce the idea of therapeutic approaches against citrullination to specifically inhibit PADs extracellularly, avoiding the downstream effects of hypercitrullination and keeping PADs' and NETs' intracellular regulatory functions.

Incidence of Acute Mesenteric and Limb Ischemia in Post COVID19 Patients: A Retrospective Comparative Study

Incidence of Acute Mesenteric and Limb Ischemia in Post COVID19 Patients: A Retrospective Comparative Study

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.

Progressive Acute Lower Extremity Ischemia Resulting From Cardiac Myxoma Embolization: A Case Report.

Cardiac myxomas are the most common primary benign tumors of the heart. The occlusion of peripheral arteries and complete obstruction of the abdominal aorta by a tumor embolus presents with distinct clinical manifestations. Herein, we present the case of a 38-year-old male with acute paresthesia, muscle weakness, erythematous, and violaceous changes in skin color localized to the dorsum of the left forefoot initially treated as cutaneous vasculitis. Further studies revealed the total occlusion of the terminal abdominal aorta by a saddle embolus from a cardiac myxoma. A multidisciplinary team consisting of cardiothoracic and vascular surgeons were involved in treating the patient, which resulted in full resolution of the case. This paper details the progression of acute bilateral limb ischemia to chronic limb threatening ischemia resulting from the total occlusion of the terminal abdominal aorta by a saddle embolus.