Critical Ischemia Research Articles

Lesion Localization and Limb Outcomes in Elderly Patients with and Without Type 2 Diabetes Mellitus Who Undergo Atherectomy-Assisted Endovascular Revascularization due to Symptomatic Peripheral Artery Disease

Background/Objectives: Type 2 diabetes mellitus (T2DM) represents a major risk factor for peripheral artery disease (PAD). We aimed to evaluate the impact of T2DM on lesion localization and complexity, clinical presentation by Rutherford categories, and limb outcomes in elderly patients with symptomatic PAD undergoing endovascular revascularization. Methods: Five hundred consecutive patients with symptomatic infra-inguinal PAD who underwent rotational atherectomy-assisted endovascular revascularization were included. PAD clinical presentation and lesion localization were recorded. The primary endpoints were clinically driven target lesion revascularization (CD-TLR) and major amputation rates during follow-up. Results: Overall, 245/500 (49.0%) patients had T2DM, whereas 179 (35.8%) presented with lifestyle limiting claudication and 321 (64.2%) with critical limb-threatening ischemia (CLTI). Median age was 78.0 (IQR = 70.0–84.0) years, and 201 (40.2%) patients were female. The presence of T2DM was significantly more frequent in patients with CLTI vs. those with claudication (58.6 vs. 31.8%; p < 0.001). Furthermore, the percentage of patients with below-the-knee (BTK) lesions was significantly higher in patients with vs. without T2DM (40.7 vs. 27.5%, p = 0.0002). During median follow-up of 21.9 (IQR = 12.8–28.8) months, CD-TLR rates were similar in patients with vs. without T2DM (HR = 1.2, 95%CI = 0.8–2.0, p = 0.39). However, patients with T2DM had a ~5.5-fold increased risk for major above-the-ankle amputation (HR = 5.5, 95%CI = 1.6–19.0, p = 0.007). After adjustment for age, gender, lesion complexity, and calcification, T2DM remained predictive for major amputation (p = 0.04). Conclusions: T2DM is more frequently associated with CLTI, BTK-PAD, and amputations despite successful endovascular revascularization. More stringent surveillance of patients with PAD and T2DM is warranted to prevent atherosclerosis-related complications.

Polymer Everolimus-Eluting Stent as Bailout Stenting for Below-the-Knee Artery Repair in Patients with Critical Limb-Threatening Ischemia: A Real-World National Registry.

Percutaneous old balloon angioplasty is still the preferred treatment for the treatment of below-the-knee (BTK) arteries in chronic limb-threatening ischemia (CLTI). In the case of a suboptimal angioplasty result, a bailout stenting is required. So far, few data are available to assess the outcomes of bailout stenting after BTK angioplasty. This study aims to investigate the 1-year efficacy and safety after implantation of a polymer everolimus-eluting stent (PEES) as bailout stenting for BTK repair in patients with CLTI in a real-world setting. This was a national multicenter prospective observational study. Patients with CLTI (Rutherford 4 to 6) BTK lesions (including P3) and requiring a bailout PEES due to dissection, thrombosis, or residual stenosis ≥30% after angioplasty were included. The freedom of a major adverse limb event at 12 months of the target limb was the primary endpoint. XIENCE assessed 106 limbs (CLTI, 96.2%; chronic total occlusion, 2.8%) in 106 patients (mean age 77.1 years; males, 71.7%; diabetes mellitus, 66.9%; chronic kidney failure, 36.8%) with CLTI undergoing PEES stenting as a bailout for BTK lesions. Bailout stenting was required after 75.5% and 26.4% of residual stenosis and dissection, respectively. The mean diameter and length of the PEES were 3 mm and 3.4 ± 0.5 cm, respectively. At 1 year, the freedom of a major adverse limb event was 79.6% (95% CI, 71.5%-88.7%), the major amputation rate was 6.2% (95% CI, 1.3%-11%), and the target revascularization rate was 14.9% (95% CI, 6.5%-22.5%). In CLTI patients with BTK lesions, PEES stenting showed safety and efficacy as bailout stenting for BTK arterial lesions. This confirms the need for PEES stenting in a real-world practice. The XIENCE study introduces the PEES as an effective bailout stenting option for patients with CLTI undergoing BTK revascularization, particularly for lesions under 4 cm. The study focuses on real-world cases where POBA alone is insufficient, demonstrating that PEES significantly improves outcomes by enhancing limb salvage and reducing the need for major amputations. For clinicians, this innovation offers a precise, size-adaptable solution, especially in cases where bailout stenting is required for short, focal lesions, improving both clinical and procedural results.

TREATMENT OF TROPHIC COMPLICATIONS IN DECOMPENSATED FORMS OF IMPAIRED ARTERIAL BLOOD CIRCULATION OF THE LOWER EXTREMITIES

Summary. The aim of the study was to study the clinical effectiveness of using the developed method of cryopreservation on wound surfaces using a cryopreservation device. Materials and methods. 87 patients with ulcerative-necrotic defects of the lower legs and feet were selected for the study. The condition for inclusion in the study was Phase I of the wound process. Patients were divided into the main and comparison groups. The main group included 41 patients who had their wounds cleaned according to the proposed method, and the comparison group consisted of 46 patients who underwent surgical treatment. Results. The use of cryodestruction of the surface of trophic ulcers of arterial etiology led to rapid cleaning of necrotic masses, fibrin, a decrease in exudation and pain intensity, and the disappearance of unpleasant odors. The effectiveness of the methods lies in the fact that not only necrotic components of the wound surface, fibrin films, as well as the surface layers of ulcer surface cells are destroyed, that is, phenotypically altered cells of the wound edge and base are removed, leading to a violation of regeneration processes. Conclusions. Debridment methods based on the use of controlled cryodestruction of pathological tissues on the surface of trophic ulcers accelerate the transition of the wound process to phase II by 25% in patients with trophic ulcers with critical ischemia of the lower extremities.

Quantitative Comparison of Color-Coded Parametric Imaging Technologies Based on Digital Subtraction and Digital Variance Angiography: A Retrospective Observational Study.

The evaluation of hemodynamic conditions in critical limb-threatening ischemia (CLTI) patients is inevitable in endovascular interventions. In this study, the performance of color-coded digital subtraction angiography (ccDSA) and the recently developed color-coded digital variance angiography (ccDVA) was compared in the assessment of key time parameters in lower extremity interventions. The observational study included 19 CLTI patients who underwent peripheral vascular intervention at our institution in 2020. Pre- and post-dilatational images were retrospectively processed and analyzed by a commercially available ccDSA software (Kinepict Medical Imaging Tool 6.0.3; Kinepict Health Ltd., Budapest, Hungary) and by the recently developed ccDVA technology. Two protocols were applied using both a 4 and 7.5 frames per second acquisition rate. Time-to-peak (TTP) parameters were determined in four pre- and poststenotic regions of interest (ROI), and ccDVA values were compared to ccDSA read-outs. The ccDVA technology provided practically the same TTP values as ccDSA (r = 0.99, R2 = 0.98, p < 0.0001). The correlation was extremely high independently of the applied protocol or the position of ROI; the r value was 0.99 (R2 = 0.98, p < 0.0001) in all groups. A similar correlation was observed in the change in passage time (r = 0.98, R2 = 0.96, p < 0.0001). The color-coded DVA technology can reproduce the same hemodynamic data as a commercially available DSA-based software; therefore, it has the potential to be an alternative decision-supporting tool in catheter labs.

Intravascular Lithotripsy for Peripheral Artery Calcification: 30-Day Outcomes From the Disrupt PAD III Observational Study.

Intravascular lithotripsy (IVL) has shown promising safety and effectiveness in calcified peripheral artery disease (PAD) in large trials and small real-world experiences. Real-world evidence from a larger cohort is lacking, so we aimed to evaluate the real-world acute performance of IVL in the treatment of calcified PAD. The Disrupt PAD III Observational Study (OS) is a prospective, multicenter, single-arm study. Patients with claudication or critical limb-threatening ischemia (CLTI) and at least moderate calcification were eligible. Independent predictors of procedural outcomes were assessed by multivariable analysis. Between November 2017 and June 2021 across 30 global sites, 1373 patients with 1677 lesions (1531, 91.3% core lab evaluable) were enrolled. Diameter stenosis and lesion length was 80.6±17.6% and 93.5±74.3 mm, respectively. Target vessels included femoropopliteal (61%), iliac (15.8%), common femoral (10.7%), and infrapopliteal arteries (12.8%). Lesion characteristics included 31.1% chronic total occlusions (CTOs) and 19.3% long lesions (≥15 cm). At final assessment, residual stenosis was 23.8±11.3%, with 0.9% serious angiographic complications, no abrupt closures, distal embolization, no flow, or thrombotic events. Independent predictors of ≤30% residual stenosis were lesion length ≥15 cm (odds ratio [OR]=0.384), female sex (OR=1.850), age ≤75 years (OR=1.625), IVL balloon to artery ratio ≥1.0 (OR=1.538), and CTO lesions (OR=0.638). Lesion length ≥15 cm (OR=16.076) was an independent predictor of procedural complications. The Disrupt PAD III OS represents the largest assessment of IVL periprocedural outcomes in calcified PAD. It confirmed excellent procedural safety and effectiveness in complex lesions across multiple peripheral vascular beds. This final analysis of the PAD III OS represents the largest report of peripheral IVL utilization in daily clinical practice. The outcomes of this study indicate that previously reported procedural results in clinical trial settings can be translated to a broader patient population. Treatment with peripheral IVL in severely calcified stenotic lower limb lesions demonstrated consistent acute safety and stenosis reduction, even in complex patients across multiple vessel beds. In addition, the importance of proper IVL balloon sizing to achieve excellent acute stenosis reduction was confirmed by multivariate analysis.

Predictive ability of the pedal medial arterial calcification (pMAC) score for major adverse limb events among patients with Chronic Limb-Threatening Ischemia

ObjectivePedal medial arterial calcification (pMAC) is a potential predictor of major adverse limb events (MALE) among patients with critical limb-threatening ischemia (CLTI). This study aims to validate the prognostic value of the pMAC score in predicting major lower limb amputation (MLLA) and need for re-do revascularisation. MethodsA single centre study involving 196 patients diagnosed with CLTI, reviewed between 2012 and 2022. Patients’ pMAC scores were obtained through X-ray assessments. Correlations between pMAC scores and the incidence of MALE and re-do revascularisation, were analysed. A power analysis using G* Power 3 software determined a needed sample size of 157 participants. Statistical analysis employed SPSS 26, utilising descriptive statistics, Chi Square, Mann-Whitney, Kaplan-Meier with log-rank test, and Cox regression for predictor identification. ResultsThe cohort was predominantly male (79.1%) and diabetic (59.2%). Re-do revascularisation need was 15.3%, increasing with pMAC scores: 3.3% (low), 24.5% (medium), and 50% (high) (p<0.001). MLLA frequency also rose with pMAC scores: 6.7%, 27.5%, and 50% respectively (p<0.001). Higher pMAC scores correlated with a higher incidence of MALE (p=0.029). Multivariate analysis showed medium pMAC (HR 4.159, p=0.002), high pMAC (HR 7.366, p=0.015), and GLASS stage 3 (HR 3.529, p=0.011) as independent MLLA predictors. Re-do revascularisation predictors included female sex (HR 2.106, p=0.063), Black race (HR 64.498, p=0.001), medium pMAC (HR 6.812, p=0.002), high pMAC (HR 11.455, p=0.008), and GLASS stage 3 (HR 2.899, p=0.037). ConclusionThe pMAC score effectively predicts MALE in CLTI patients and enhances risk stratification. Using both, pMAC scores and GLASS stages enhances predictive accuracy, identifying patients at higher risk for MLLA, Informing clinical decision-making and therapeutic strategies.

Salvataje de amputación mediante la aplicación de células madre autólogas de médula ósea en isquemia crítica de miembro inferior: reporte de caso

Critical ischemia of the lower limbs can seriously impair the quality of life of patients due to the intense pain associated with it and the amputation that can result in those who are not candidates for revascularization. Therefore, it is worthwhile to search for therapies that provide a recovery option for this group of patients. We describe the case of a 71-year-old male patient with critical ischemia in the right lower limb, associated with severe ulceration and infection, with an indication for amputation, who was saved from this procedure by the intramuscular administration of autologous bone marrow stem cells. The intramuscular administration of autologous bone marrow stem cells could promote angiogenesis and the survival of amputation.

Outcomes of Proximal Hybrid Arterial Reconstruction in Combination with Simultaneous Amputation in Dry Atherosclerotic Gangrene of Toes

INTRODUCTION: When treating atherosclerotic gangrene of the lower limb (LL), the surgeon faces the questions about the reasonability of vascular reconstruction and the optimal timing of amputation after surgery on the LL arteries. The answer to these questions is given by assessing the state of the microvasculature of the operated limb. With sufficient development of the microvasculature and good collateral circulation, it is possible to perform a simultaneous amputation after proximal reconstruction. In this situation, a clear demarcation of the zone of necrosis and reversible ischemia is required, which can be realized by the method of ultraviolet luminescence spectroscopy. AIM: To analyze the results of hybrid reconstructions on the LL arteries with multilevel diffuse atherosclerotic lesions and dry gangrene of toes (DGT). MATERIALS AND METHODS: A prospective, controlled, non-randomized study included 29 patients suffering from critical ischemia of the lower limbs and having DGT, who were operated on in the amount of hybrid arterial reconstruction. The patients were divided into two groups: patients of group 1 (n = 14) underwent restoration of the main blood flow at the level of the iliofemoral arterial segment using a hybrid method, with simultaneous minor amputation of LL at various levels; patients of group 2 (control group, n = 15) underwent a simultaneous proximal and distal hybrid operation, providing main blood flow through at least one of the lower leg arteries, followed by a minor amputation of the lower leg at various levels over the next 4–5 days. RESULTS: There were no statistically significant differences in the groups in the degree of decrease in luminescence intensity after vascular surgery. A histological examination of intraoperative preparations of DGT revealed necrosis of the cellular microenvironment at luminescence amplitude (1.0 ± 0.05) × 105 photons at 410 nm frequency. At luminescence amplitude not exceeding this level, signs of necrobiosis were noted. Luminescence level of ≥ 1.0 × 105 photons was used as the amputation boundary. In the case of an uncomplicated vascular stage of the operation, a comparable decrease in the conventional amputation boundary was noted in the study groups. In the early postoperative period, in patients of group 1, the level of inflammation markers, average number of bed-days, and the number of thrombotic complications were lower than in the control group (p 0.05). A strong correlation was recorded between the morphological signs of the acute phase of inflammation and the intensity of chemiluminescence (r = 0.7, p 0.005). CONCLUSION: In patients with DGT, at a luminescence amplitude on the lower leg and foot not exceeding 1.0 × 105 photons at 410 nm frequency and 0.7 × 105 photons at 450 nm frequency, an effective treatment method is restoration of the main blood flow in the iliofemoral segment using a hybrid method with simultaneous minor amputation at various levels of the foot. This luminescence level is the conventional boundary between necrotic changes and reversible ischemia (necrobiosis) of the soft tissues of the LL.

Clinical outcomes following invasive treatment of femoropopliteal artery disease: a retrospective single-center cohort study

To identify predictors of clinical success in invasive treatment for femoropopliteal disease aiding clinical decision-making. A retrospective analysis was performed on 676 consecutive patients who underwent a first episode of invasive treatment for femoropopliteal disease, either endovasular therapy (EVT) or femoropopliteal bypass (FPB), between 2004 and 2015. Primary endpoints were primary and secondary clinical patency and amputation rate. Kaplan-Meier curves were used to evaluate clinical patency. A Cox proportional hazard model explored predictors of primary endpoints. Most patients (58%) underwent EVT as primary intervention, while 42% underwent FPB. Median follow-up was 43 months. The only independent predictor for loss of primary clinical patency was critical limb-threatening ischemia (CLTI) (P=0.008, HR 1.25; 95% CI 1.07 to 1.47). Secondary clinical patency was positively associated with FPB surgery (P=0.037, HR 0.66; 95% CI 0.44 to 0.97), a higher pre-interventional ankle-brachial index (ABI) (P=0.029, HR 0.43; 95% CI 0.20 to 0.92), more distal runoff vessels (P=0.036, HR 0.77; 95% CI 0.60 to 0.98) and the absence of ischemic heart disease (P=0.006, HR 1.69; 95% CI 1.16 to 2.47). In CLTI patients, chronic renal failure predicted loss of primary and secondary clinical patency and increased amputation risk. In this cohort, CLTI was independently associated with decreased primary clinical patency in invasive treatment for femoropopliteal disease. Secondary clinical patency was positively associated with FPB, higher ABI, more runoff vessels and the absence of ischemic heart disease.

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

BackgroundSingle-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. MethodsCLTI 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. ResultsThere 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. ConclusionSpliced-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.

Efficacy of a novel method: VaSodilator injection via the Over-the-wire lumen during drug-coated balloon dilatation to Prevent the slow-flow phenomenon in treatment of femoropopliteal lesions.

In drug-coated balloon (DCB) angioplasty for femoropopliteal lesions, there are adverse effects of drug embolization on downstream non-target organs following the slow-flow phenomenon. We devised a novel method, known as VaSodilator injection via the Over-the-wire lumen during DCB dilatation to Prevent the slow-flow phenomenon in treatment of femoropopliteal lesions (V.S.O.P.), and evaluated its efficacy and safety. This single-center, retrospective, observational study analyzed 196 femoropopliteal lesions treated with IN.PACT Admiral between April 2018 and July 2023. The IN.PACT Admiral is a DCB consisting of a 0.035-inch over-the-wire (OTW) lumen balloon coated with high-dose paclitaxel. Regarding the V.S.O.P. method, we injected vasodilators through the OTW lumen during DCB dilation of the lesions. The cohort was classified into two groups according to the use of the V.S.O.P. method (V.S.O.P. group: n = 53; non-V.S.O.P. group: n = 143). The V.S.O.P. group had lower rates of hemodialysis (21% vs. 43%, p = 0.01) and higher rates of critical limb-threatening ischemia (56% vs. 23%, p < 0.01) and severe calcification lesions (Peripheral Arterial Calcium Scoring Systems score 3/4) (53% vs. 34%, p = 0.01) than the non-V.S.O.P. group. The occurrence of the slow-flow phenomenon was significantly lower in the V.S.O.P. group than in the non-V.S.O.P. group. The V.S.O.P. method could be an effective method for preventing the slow-flow phenomenon after DCB angioplasty for femoropopliteal lesions.

Clinical outcomes in patients with critical limb-threatening ischemia and infected ulcers following endovascular therapy are pathogen dependent: A single-center experience from 2012 to 2021

Clinical outcomes in patients with critical limb-threatening ischemia and infected ulcers following endovascular therapy are pathogen dependent: A single-center experience from 2012 to 2021

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.

ThP8.1 - Long-Term Impact of COVID-19 related disruption of NHS Elective services on Emergency Major Lower Limb Amputations

Abstract Background The COVID-19 pandemic has affected the healthcare systems worldwide since the dawn of 2020. In March 2020, the United Kingdom government announced the first national lockdown which severely disturbed all NHS healthcare elective services. Our aim is to assess the long-term impact of COVID-19 related disruption of NHS elective services on emergency major lower limb amputations. Method Patients' data for emergency major lower limb amputations (MLLA) for critical limbthreatening ischemia and diabetic foot infections performed at Aberdeen Royal Infirmary was collected through Trakcare® and divided into the control pre-pandemic group (April 2018 to March 2020) and the pandemic group (April 2020 to March 2022). The statistical analysis was conducted using the IBM SPSS software [v28.0.1.1 (14)]. Results A total of 358 patients underwent MLLA and 206 (57.5%) of these had diabetes mellitus. There was a 17% increase in the number of urgent referrals and every one in five of these finally underwent an amputation. There was an increase in the absolute number of Above- and Below-Knee amputations. There was a statistically significant increase by 33% in emergency MLLAs during the pandemic period (p-value &amp;lt;0.05). A total of 165 postoperative deaths up to December 2022 were recorded with 30-day mortality rate of 7.26% (n=26). Conclusion NHS vascular management groups should update themselves with evolving technologies to optimise the care provided during future unprecedented times. Furthermore, more effective measures should also be implemented to avoid delayed presentations, which can potentially lead to higher rates of major limb amputations.

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.

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Peripheral artery disease is a considered as one of the major macrovascular complications in diabetes mellitus type 2. It is chronic arteriosclerotic illness that mainly affects the lower limbs and is presented as narrowed or blocked blood vessels. The prevalence increases with the age, it affects 15-20% of persons older than 70 years age, 10-15% of the general population. Smoking and high cholesterol levels increase the risk for PAD progression in large blood vessels such as legs, while diabetes increases the risk for PAD in small blood vessels such as the feet. Critical ischemia, its most severe form can lead to limb amputation and the patient’s death, and even its asymptomatic forms are associated with a high risk of cardiovascular morbidity and mortality. Approximately more than half of all patients are asymptomatic and preventive therapy reduces the risk of complications and death, so it’s important to recognize the subclinical forms in time and to control risk factors of disease. The risk factors that can be modified are tobacco use, hypertension, hyperlipidemia, diabetes mellitus, obesity and some of them cannot be modified such as age, sex or family medical history. Diabetes mellitus type 2 is considered as the most important risk factor for development of peripheral artery disease. The experts suggest that is necessary to establish an HBA1C therapeutic target below 8% in patient with DM and PAD.

ENDOVASCULAR ANGIOPLASTY FOR REPEATED REVASCULARIZATION OF THE ARTERIAL BED IN PATIENTS WITH RECURRENT CHRONIC ARTERIAL INSUFFICIENCY

Aim. To improve the results of repeated reconstruction of the great vessels in case of relapse of chronic arterial insufficiency by differentiated use of popliteal tibial autovenous bypass grafting and endovascular angioplasty for revascularization of the arteries of the leg. Materials and methods. The long-term results of surgical treatment of 522 patients were examined, including 353 patients with bilateral atherosclerotic occlusion of the aortic-femoral zone and 159 patients with unilateral occlusion of the ileo-femoral segment. At the primary surgical intervention, 98 patients were diagnosed with chronic arterial insufficiency (CAI) of stage II B, in 228 – CAI of stage III, in 196 – chronic critical ischemia of the lower extremities, stage III – IV. In the long-term postoperative period, 146 (27.97 %) late complications were diagnosed, of which 78 (56.1 %) had a relapse of chronic arterial insufficiency. In 36 patients, CAI stage II B was established, and in 42 – CAI stage III. Patients were re-operated in the period of 5.4 ± 1.9 years after primary revascularization. All men were 64.4 ± 3.1 years old. Results. The multilevel atherosclerotic lesions of the reconstructed arterial bed, cicatricial changes after the initial surgical intervention, progressive atherosclerotic lesions of the outflow tract required multi-story shunting operations. The success of shunting surgery depends on sufficient revascularization of the outflow paths – the arterial bed of the ankle segment. Revascularization of the distal arterial bed was achieved using popliteal-tibial autovenous bypass grafting (19 cases) and endovascular angioplasty (30 observations). To reduce peripheral vascular resistance and increase the volume of the peripheral vascular bed in 19 (63.3%) cases, endovascular balloon angioplasty of two tibial arteries was performed simultaneously. The postoperative period in 10 (12.8%) patients was complicated by the development of thrombosis of the reconstruction segment. In 7 cases, thrombosis of the reconstruction segment was eliminated. The using of popliteal-tibial autogenous bypass grafting and endovascular angioplasty during revascularization of the ankle segment provided satisfactory results in repeated reconstructive operations in 87.2 % of cases. Conclusions. For the revascularization of the lower leg arteries, the use of popliteal autovenous shunting and endovascular angioplasty provides 87.2% satisfactory results in repeated reconstructive operations for chronic arterial insufficiency relapse.

Role of blood-brain barrier dysfunction in the development of poststroke epilepsy.

Stroke is a major contributor to mortality and morbidity worldwide and the most common cause of epilepsy in the elderly in high income nations. In recent years, it has become increasingly evident that both ischemic and hemorrhagic strokes induce dysfunction of the blood-brain barrier (BBB), and that this impairment can contribute to epileptogenesis. Nevertheless, studies directly comparing BBB dysfunction and poststroke epilepsy (PSE) are largely absent. Therefore, this review summarizes the role of BBB dysfunction in the development of PSE in animal models and clinical studies. There are multiple mechanisms whereby stroke induces BBB dysfunction, including increased transcytosis, tight junction dysfunction, spreading depolarizations, astrocyte and pericyte loss, reactive astrocytosis, angiogenesis, matrix metalloproteinase activation, neuroinflammation, adenosine triphosphate depletion, oxidative stress, and finally cell death. The degree to which these effects occur is dependent on the severity of the ischemia, whereby cell death is a more prominent mechanism of BBB disruption in regions of critical ischemia. BBB dysfunction can contribute to epileptogenesis by increasing the risk of hemorrhagic transformation, increasing stroke size and the amount of cerebral vasogenic edema, extravasation of excitatory compounds, and increasing neuroinflammation. Furthermore, albumin extravasation after BBB dysfunction contributes to epileptogenesis primarily via increased transforming growth factor β signaling. Finally, seizures themselves induce BBB dysfunction, thereby contributing to epileptogenesis in a cyclical manner. In repairing this BBB dysfunction, pericyte migration via platelet-derived growth factor β signaling is indispensable and required for reconstruction of the BBB, whereby astrocytes also play a role. Although animal stroke models have their limitations, they provide valuable insights into the development of potential therapeutics designed to restore the BBB after stroke, with the ultimate goal of improving outcomes and minimizing the occurrence of PSE. In pursuit of this goal, rapamycin, statins, losartan, semaglutide, and metformin show promise, whereby modulation of pericyte migration could also be beneficial.

Predictive model for novel subtypes of patients undergoing lower extremity amputation for peripheral artery disease: An unsupervised machine learning study

BackgroundPeripheral artery disease (PAD) represents the frequently seen circulatory condition related to a risk of critical limb ischemia and amputation. Critical lower extremity ischemia may require amputation, and the outcomes vary. In this study, we developed an artificial intelligence (AI)-driven predictive model for PAD subtypes to assess risk among patients more precisely and accurately to predict disease progression. MethodsThe present retrospective study examined clinical data in PAD patents undergoing lower extremity amputation. The data were analyzed using an unsupervised machine learning algorithm (UMLA) for subgroup identification and risk stratification. The clustering result accuracy was validated by analyzing the follow-up data of clusters. Finally, we built the prediction model with binary logistic regression. ResultsIn total, we enrolled 507 cases into this work. Two distinct subgroups, consisting of Clusters 1 and 2, were identified by UMLA; those from Cluster 1 showed markedly poorer conditions and prognostic outcomes compared with those from Cluster 2. With regard to the new PAD subtype, we established a nomogram with eight predictive factors, including gender, age, smoking history, diabetes and coronary heart disease history, albumin levels, endovascular intervention, and amputation level. The nomogram could accurately categorize patients into two identified clusters, and the area under receiver operating characteristic curve was 0.861 (95 % confidence interval: 0.830–0.893). ConclusionIn this study, UMLA was used to identify new phenotypic subgroups among PAD cases who showed different risks of amputation. Our constructed AI-driven predictive model for PAD subtypes showed that it can be used for risk stratification and clinical management with high accuracy and reliability.

Auto/Paracrine C-Type Natriuretic Peptide/Cyclic GMP Signaling Prevents Endothelial Dysfunction.

Endothelial dysfunction is cause and consequence of cardiovascular diseases. The endothelial hormone C-type natriuretic peptide (CNP) regulates vascular tone and the vascular barrier. Its cGMP-synthesizing guanylyl cyclase-B (GC-B) receptor is expressed in endothelial cells themselves. To characterize the role of endothelial CNP/cGMP signaling, we studied mice with endothelial-selective GC-B deletion. Endothelial EC GC-B KO mice had thicker, stiffer aortae and isolated systolic hypertension. This was associated with increased proinflammatory E-selectin and VCAM-1 expression and impaired nitric oxide bioavailability. Atherosclerosis susceptibility was evaluated in such KO and control littermates on Ldlr (low-density lipoprotein receptor)-deficient background fed a Western diet for 10 weeks. Notably, the plaque areas and heights within the aortic roots were markedly increased in the double EC GC-B/Ldlr KO mice. This was accompanied by enhanced macrophage infiltration and greater necrotic cores, indicating unstable plaques. Finally, we found that EC GC-B KO mice had diminished vascular regeneration after critical hind-limb ischemia. Remarkably, all these genotype-dependent changes were only observed in female and not in male mice. Auto/paracrine endothelial CNP/GC-B/cGMP signaling protects from arterial stiffness, systolic hypertension, and atherosclerosis and improves reparative angiogenesis. Interestingly, our data indicate a sex disparity in the connection of diminished CNP/GC-B activity to endothelial dysfunction.