Chronic Ischemia Research Articles

Clinical Outcomes of Transradial vs Nontransradial Aortoiliac Endovascular Therapy

BackgroundThe introduction of radial-specific equipment has made transradial (TR) aortoiliac (AI) endovascular therapy (EVT) more convenient. ObjectivesThe authors aimed to investigate the perioperative outcomes of the TR approach in patients undergoing AI EVT for symptomatic peripheral artery disease. MethodsThe COMFORT (Contemporary Strategy for Aortoiliac Intervention) registry was a prospective, multicenter, observational study enrolling patients with symptomatic peripheral artery disease undergoing AI EVT between January 2021 and June 2023. The primary outcome was perioperative complications, whereas the secondary outcomes included core laboratory–evaluated residual stenosis >30%, time to hemostasis, time to ambulation, 30-day patency, and 30-day limb symptoms. These outcomes were compared between TR and non-TR AI EVT after propensity score matching. ResultsThe TR approach was selected for 231 of the 947 patients (24.3%). The TR approach was chosen more in patients with a higher ankle-brachial index, chronic total occlusion, aortic lesion, bare nitinol stent implantation, and plain angioplasty, whereas it was chosen less in patients with dialysis, a history of AI EVT, chronic limb-threatening ischemia, bilateral calcification, and simultaneous infrainguinal EVT (all P < 0.05). After propensity score matching, the incidence of perioperative complications did not differ significantly between the groups (TR group: 6.0% vs non-TR group: 5.1%; P = 0.69). The proportions of residual stenosis, 30-day patency, and 30-day limb symptoms were not significantly different (all P > 0.05); however, the time to hemostasis and the time to ambulation were shorter in the TR group (both P < 0.05). ConclusionsNon-TR AI EVT and TR AI EVT using radial-specific equipment were associated with a similar risk of perioperative complications. The TR approach helps shorten the time required for hemostasis and ambulation.

Current Applications and Future Perspectives of Artificial and Biomimetic Intelligence in Vascular Surgery and Peripheral Artery Disease.

Artificial Intelligence (AI) made its first appearance in 1956, and since then it has progressively introduced itself in healthcare systems and patients' information and care. AI functions can be grouped under the following headings: Machine Learning (ML), Deep Learning (DL), Artificial Neural Network (ANN), Convolutional Neural Network (CNN), Computer Vision (CV). Biomimetic intelligence (BI) applies the principles of systems of nature to create biological algorithms, such as genetic and neural network, to be used in different scenarios. Chronic limb-threatening ischemia (CLTI) represents the last stage of peripheral artery disease (PAD) and has increased over recent years, together with the rise in prevalence of diabetes and population ageing. Nowadays, AI and BI grant the possibility of developing new diagnostic and treatment solutions in the vascular field, given the possibility of accessing clinical, biological, and imaging data. By assessing the vascular anatomy in every patient, as well as the burden of atherosclerosis, and classifying the level and degree of disease, sizing and planning the best endovascular treatment, defining the perioperative complications risk, integrating experiences and resources between different specialties, identifying latent PAD, thus offering evidence-based solutions and guiding surgeons in the choice of the best surgical technique, AI and BI challenge the role of the physician's experience in PAD treatment.

The impact of an anomalous third segment of the vertebral artery on bypass surgery: a case report and literature review.

The horizontal part of the third segment (V3) of the vertebral artery (VA) is a critical anastomotic site for bypass procedures involving either donor or recipient vessels. It is rare for the V3 segment to deviate from its typical course of passing through the atlanto-transverse foramen. V3 anomaly encountered in occipital artery (OA)-V3 bypass surgery has not been previously reported. Here, we present a case involving a patient undergoing bypass surgery due to recurrent post-stent occlusion at the first segment (V1) of the left VA. During the operation, it was noted that the V3 horizontal segment could not be identified within the left VA groove, leading to initial suspicion of left V3 disuse atrophy attributed to prolonged chronic ischaemia. Consequently, there was a need to modify the operative method and to transition from an OA-V3 bypass to an OA-posterior inferior cerebellar artery bypass. Post-operative computed tomography angiography confirmed that indeed, the left V3 did not traverse through the transverse foramen of the atlas and instead entered the dural membrane between the first cervical vertebra (C1) and the second cervical vertebra (C2).

Expression of Osteopontin and Gremlin 1 Proteins in Cardiomyocytes in Ischemic Heart Failure.

A relevant role of osteopontin (OPN) and gremlin 1 (Grem1) in regulating cardiac tissue remodeling and formation of heart failure (HF) are documented, with the changes of OPN and Grem1 levels in blood plasma due to acute ischemia, ischemic heart disease-induced advanced HF or dilatative cardiomyopathy being the primary focus in most of these studies. However, knowledge on the early OPN and Grem1 proteins expression changes within cardiomyocytes during remodeling due to chronic ischemia remains insufficient. The aim of this study was to determine the OPN and Grem1 proteins expression changes in human cardiomyocytes at different stages of ischemic HF. A semi-quantitative immunohistochemical analysis was performed in 105 myocardial tissue samples obtained from the left cardiac ventricles. Increased OPN immunostaining intensity was already detected in the stage A HF group, compared to the control group (p < 0.001), and continued to increase in the stage B HF (p < 0.001), achieving the peak of immunostaining in the stages C/D HF group (p < 0.001). Similar data of Grem1 immunostaining intensity changes in cardiomyocytes were documented. Significantly positive correlations were detected between OPN, Grem1 expression in cardiomyocytes and their diameter as well as the length, in addition to positive correlation between OPN and Grem1 expression changes within cardiomyocytes. These novel findings suggest that OPN and Grem1 contribute significantly to reorganization of cellular geometry from the earliest stage of cardiomyocyte remodeling, providing new insights into the ischemic HF pathogenesis.

Clinical Comparison of Drug-Coated Balloon and Drug-Eluting Stent for Femoropopliteal Lesions in Chronic Limb-Threatening Ischemia With Wounds.

Endovascular therapy (EVT) with devices such as drug-coated balloons (DCBs) and drug-eluting stents (DESs) for atherosclerotic disease in the femoropopliteal (FP) artery has been established. However, EVT using drug-based devices for chronic limb-threatening ischemia (CLTI) remains challenging. The optimal device for FP lesions in patients with CLTI remains unknown. This study compared the clinical efficacy of DCB and DES in patients with CLTI and FP lesions.Methods and Results: This retrospective single-center study included 539 consecutive patients (562 lesions) treated with EVT between January 2018 and December 2022; 166 patients with CLTI and Rutherford Class 5 or 6 wounds underwent EVT with DCB or DES. Clinical outcomes were compared between 53 pairs after propensity score matching. There were no significant differences between the DCB and DES groups in the incidence of complete wound healing without death or major amputation (84.8% vs. 80.2%, respectively; P=0.99), primary patency (69.4% vs. 75.6%, respectively; P=0.65), and freedom from target lesion revascularization at 1 year (78.6% vs. 78.0%, respectively; P=0.92). Multivariate analysis showed that complete wound healing at 1 year is negatively associated with hemodialysis and Wound, Ischemia, and foot Infection Stage 4, but positively associated with Global Limb Anatomic Staging System FP Grade 3 or 4. No significant differences in clinical outcomes were found between DCB and DES for patients with CLTI and FP lesions.

The Inhibition of γ-Aminobutyric Acid B1 Receptor Regulates Angiogenesis via the Hippo/YAP Signaling Pathway

Promoting the establishment of collateral circulation is essential for chronic lower extremity ischemia. However, no effective therapeutic drugs have yet been developed. Recent studies discovered that in the peripheral arteries, there are GABAB1 receptors expressed in endothelial cells and smooth muscle cells, these receptors may have some effects in regulating vascular functions, but the precise mechanism is not yet clear. This study explores the effect of GABAB1 receptor inhibition on angiogenesis and its regulatory mechanism. The expression of GABAB1 in HUVECs was knocked down using shRNA transfection, and effects in HUVECs' proliferation, migration, and tube formation ability were detected. Western blot and RT-PCR were used to verify the signal pathway. The murine hind limb ischemia model was used to verify the effect of CGP35348, an antagonist of GABAB1R, on the recovery of blood flow perfusion and angiogenesis in ischemic tissues. Cell proliferation, migration, and tube formation ability were improved after GABAB1 receptor knockdown in HUVECs. The phosphorylation of the HIPPO/YAP pathway decreased, while the effect of promoting angiogenesis increased. After treating the ischemic hindlimbs of mice with GABAB1 receptor antagonists, the blood flow perfusion recovered, and the angiogenesis increased. These findings demonstrate the effect of GABAB1 receptor inhibition on the HIPPO/YAP pathway in regulating angiogenesis, suggesting that inhibiting GABAB1 receptor levels might be a novel approach for chronic lower extremity ischemia diseases.

The Association Between Completion of Supervised Exercise Therapy and Long-Term Outcomes in Patients with Intermittent Claudication, Concomitant Sarcopenia, and Cardiometabolic Multimorbidity

The combination of intermittent claudication (IC), cardiometabolic multimorbidity (CMM) and sarcopenia is associated with worse outcomes than IC alone. This study aimed to identify whether the completion of Supervised exercise therapy(SET) attenuates these adverse outcomes in patients with combined IC, sarcopenia and CMM. This registry review included consecutive IC patients with concomitant CMM and sarcopenia, who were referred for SET from 2014 to 2017. CMM was defined as two or more comorbidities (diabetes, heart disease, stroke, or chronic kidney disease). Sarcopenia was assessed using the L3-skeletal muscle index (L3SMI) from CT scans in the preceding 18 months. Outcomes of interest were progression to chronic limb-threatening ischemia (CLTI), major adverse cardiovascular events (MACE), and major adverse limb events (MALE). Survival and Cox regression analyses were performed. Eighty-two patients with a combination of IC, CMM and sarcopenia were included. Of these, 56 declined or prematurely discontinued SET and 26 completed SET. Baseline characteristics and L3SMI did not significantly differ between groups. Completion of SET was associated with slower progression to CLTI (HR: 0.23; 95% CI: 0.07-0.69; p = 0.02) and a reduced risk of MALE (HR: 0.21; 95%CI: 0.057-0.775;p=0.02). However, there was no reduction in the risk of MACE (HR: 0.88; 95%CI: 0.423-1.629; p=0.73). Models demonstrated good predictive accuracy (Harrell's C-index>0.6). Completion of SET was associated with significant improvements in adverse limb outcomes in patients with IC, concomitant sarcopenia and CMM.

Microglia Involvement into Acute and Chronic Brain Damage in Diabetic Rats: Impact of GLP-1RA and SGLT-2i.

Acute and chronic brain damage in type 2 diabetes mellitus (DM) determines the need to investigate the neuroprotective potential of glucose-lowering drugs. The purpose was to directly compare the neuroprotective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) with different duration of action and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in type 2 diabetic rats with and without stroke. DM was modelled using high-fat diet and nicotinamide+streptozotocin protocol. The following groups (n = 15 each) were formed: DM without treatment, treatment with liraglutide, dulaglutide, canagliflozin as well as control group without DM and treatment. After 8 weeks, 10 rats from each group underwent middle cerebral artery occlusion. In the reperfusion period neurological deficit, neuroglial damage markers and brain necrosis were evaluated. Brain slices from the remaining 5 animals in each group were histologically examined for microglial activation and neuronal damage. Brain damage was similar in "DM" and "Control" (17.53 [14.23; 26.58] and 15.87 [13.40; 22.68] % of total brain volume, respectively). All study drugs diminished damage volume comparing with "DM" and "Control" whereas the necrosis volume in "DM+Liraglutide" was smaller than in "DM+Canagliflozin" and did not significantly differ from "DM+Dulaglutide" (2.9 [1.83; 4.71], 6.17 [3.88; 8.88] and 4.57 [3.27; 7.90] %). The neurological deficit was more prominent in "DM" than in "Control", while all the drugs demonstrated similar positive effect. Neurofilament light chains (NLC) did not differ between "DM" and "Control". Dulaglutide and canagliflozin caused a marked decrease in NLC. Protein S100BB level was similar in "DM" and "Control". Liraglutide caused the largest S100BB decrease, while canagliflozin did not influence it. In chronic brain ischaemia, all drugs increased the number of normal neurons, but GLP-1RAs had a more pronounced effect. DM was accompanied by increased number of activated microglial cells in Cornu Ammonis (CA)1 hippocampal region. Both GLP-1RAs reduced the number of Iba-1-positive cells, with dulaglutide being more effective than liraglutide, whereas canagliflozin did not affect this parameter. GLP-1RAs and SGLT-2i have neuroprotective properties against acute and chronic brain damage in diabetic rats, although the infarct-limiting effect of GLP-1RAs may be more pronounced. GLP-1RAs and SGLT-2i exert their protective effects by directly influencing neuronal survival, whereas GLP-1RAs also affect microglia.

Hand Acceleration Time is a Valuable Ultrasonographic Tool in Hand Perfusion as Adjuvant Evaluation for Diagnosing Chronic Upper Limb Ischemia

Diagnosis of chronic upper limb ischemia is mainly clinical. Although hand perfusion can be evaluated by different noninvasive methods (e.g., digital-brachial index, digital pressures, oxygen saturation measurements, and plethysmography), these have not been standardized for the diagnosis of chronic upper limb ischemia. Initial reports suggested that the hand acceleration time (HAT) measured by duplex ultrasound could be a useful diagnostic tool. However, the HAT has neither been properly characterized nor validated. This study aimed to provide evidence that HAT is a sensitive diagnostic tool for chronic upper limb ischemia. We conducted a prospective, single-center, cross-sectional study with adult patients diagnosed with chronic upper limb ischemia and healthy adult volunteers without cardiovascular risk factors. Hand vascular duplex ultrasound and HAT measurement were performed in 4 artery locations: princeps pollicis artery, radialis indicis artery, first common digital palmar artery, and third common digital palmar artery. It was also measured in the ulnar and radial arteries. Descriptive and exploratory analyses were performed between patients and healthy volunteers. Thirty participants were included, being 15 patients (median [standard deviation] age: 51 [18] years; 47% women) and 15 healthy volunteers (median [standard deviation] age: 35 [10] years; 60% women). In total, 15 ischemic and 30 nonischemic hands were analyzed. Humeral artery stenosis/occlusion (n=6, 40.0%) and distal artery stenosis (n=5, 33.3%) were the main causes of ischemia. Median (interquartile range) HAT measurements were significantly different between patients and healthy volunteers in the 4 hand arterial locations, the radial artery, and ulnar artery: princeps pollicis artery: 164 (124-252) vs. 60 (40-88), P<0.001; radialis indicis artery: 176 (140-348) vs. 60 (36-80), P<0.001; first common digital palmar artery: 180 (92-320) vs. 64 (36-88), P<0.001; third common digital palmar artery: 180 (104-240) vs. 56 (44-92), P<0.001; radial artery: 156 (120-248) vs. 68 (55-76), P<0.001; and ulnar artery: 152 (76-220) vs. 61 (48-76), P<0.001. Vascular duplex ultrasound with HAT measurement seems to be an easy-access, sensitive diagnostic tool for chronic upper limb ischemia. HAT provides valuable information on hand perfusion and may be complementary to current noninvasive methods.

Patient experience of the process to diagnosis of chronic limb-threatening ischaemia: A qualitative study.

Delays exist at each stage of the chronic limb-threatening ischaemia (CLTI) care pathway, but there is little known about patient factors influencing delay to diagnosis of CLTI. This study explores the experiences and perceptions of patients recently diagnosed with CLTI. A qualitative interview study was conducted. Sixteen participants underwent semi-structured interviews. Reflexive thematic analysis was performed on the data, aiming to understand factors which can influence delay in the CLTI care pathway. Five interrelated themes were developed: CLTI is a devastating condition; Reluctance to ask for help; When we are empowered we get better care; Luck plays a role in the process to diagnosis; and Vascular units can do better, comprising sub-themes of information transfer-consider communication and arterial versus non-arterial centres-proximity isn't everything. The five themes generated from the interview data describe factors relevant to delay given meaning by participants who have lived experience of CLTI. Theme content should be noted by clinicians, commissioners and providers looking to improve care pathways for patients with CLTI. The importance of awareness for the public, patients and clinicians linked ideas in some themes and interventions to raise awareness should be considered.

Long-Term Outcome of Lower Extremity Bypass Surgery in Patients with Chronic Kidney Disease and Critical Limb Ischemia in Germany

The aim of this study is to present short- and long-term outcomes after lower extremity bypass (LEB) surgery in patients with chronic limb-threatening ischemia (CLTI) and chronic kidney disease (CKD), differentiated by peripheral artery disease (PAD) Fontaine stage III and IV. Methods: Retrospective analysis of anonymized data from a nationwide German health insurance company (AOK). Data from 22,633 patients (14,523 men) who underwent LEB from 2010 to 2015, were analyzed, presenting 18,271 with CKD stage 1/2, 2,483 patients with CKD stage 3 and 1,879 with CKD stage 4/5. Results: Perioperative mortality (60-day mortality) was 7.2% for CKD stage 1/2, 12.4% for CKD stage 3, and 18.0% for CKD stage 4/5. Patients with PAD stage IV had a significantly higher perioperative mortality (43.2%) than patients with PAD stage III (22.7%). The perioperative major amputation rate depended significantly on PAD stage IV (Odds Ratio (OR): 2.57 CI: 2.16 – 3.05, p < .001), the LEB level below the knee and crural/pedal (OR: 2.49 CI: 2.14 – 2.90, p < .001), CKD stage 4/5 (OR: 1.28, CI: 1.06 – 1.54, p = .009), and the presence of diabetes mellitus type 2 (OR: 1.19, CI: 1.05 – 1.36, p = .007). Kaplan-Meier estimated long-term survival of up to 9 years after surgery was 31.7% for patients with CKD stage 1 and 2, 14.3% for CKD stage 3, and only 10.1% for CKD stage 4 and 5 (p < .001). PAD Fontaine stage IV vs. III (Hazard Ratio (HR): 1.64, CI: 1.56 – 1.71, p < .001), but not bypass level had an independent adverse influence on long-term survival. Conclusion: CKD and PAD stage were equally significant independent predictors of patient survival and MACE with higher PAD and CKD stages associated with less favorable long-term outcomes.

Risk Factors for Unplanned Higher-Level Re-Amputation and Mortality after Lower Extremity Amputation in Chronic Limb-Threatening Ischemia.

Background: The factors associated with unplanned higher-level re-amputation (UHRA) and one-year mortality among patients with chronic limb-threatening ischemia (CLTI) after lower extremity amputation are poorly understood. Methods: This was a single-center retrospective study of patients who underwent amputations for CLTI between 2014 and 2017. Unadjusted bivariate analyses and adjusted odds ratios (AOR) from logistic regression models were used to assess associations between pre-amputation risk factors and outcomes (UHRA and one-year mortality). Results: We obtained data on 203 amputations from 182 patients (median age 65 years [interquartile range (IQR) 57, 75]; 70.7% males), including 118 (58.1%) toe, 20 (9.9%) transmetatarsal (TMA), 37 (18.2%) below-knee (BKA), and 28 (13.8%) amputations at or above the knee. Median follow-up was 285 days (IQR 62, 1348). Thirty-six limbs (17.7%) had a UHRA, and the majority of these (72.2%) were following index forefoot amputations. Risk factors for UHRA included non-ambulatory status (AOR 6.74, 95% confidence interval (CI) 1.74-26.18; p < 0.10) and toe pressure < 30 mm Hg (AOR 4.89, 95% CI 1.52-15.78; p < 0.01). One-year mortality was 17.2% (n = 32), and risk factors included coronary artery disease (AOR 3.93, 95% CI 1.56-9.87; p < 0.05), congestive heart failure (AOR 4.90, 95% CI 1.96-12.29; p = 0.001), end-stage renal disease (AOR 7.54, 95% CI 3.10-18.34; p < 0.001), and non-independent ambulation (AOR 4.31, 95% CI 1.20-15.49; p = 0.03). Male sex was associated with a reduced odds of death at 1 year (AOR 0.37, 95% CI 0.15-0.89; p < 0.05). UHRA was not associated with one-year mortality. Conclusions: Rates of UHRA after toe amputations and TMA are high despite revascularization and one-year mortality is high among patients with CLTI requiring amputation.

The Effect of Revascularization on Lower Limb Circulation Parameters in Symptomatic Peripheral Arterial Disease.

Background: The prevalence of peripheral arterial disease and the number of revascularization procedures performed in symptomatic patients are steadily increasing. However, uncertainties remain regarding hemodynamic monitoring after revascularization and the prediction of clinical outcomes. This study aimed to investigate hemodynamic parameters with a focus on the microvasculature. Methods: This prospective, single-center study included 29 patients (15 with intermittent claudication [IC] and 14 with chronic limb-threatening ischemia [CLTI]). Before and after the revascularization procedure, in addition to the ankle-brachial index (ABI), microperfusion parameters, including microvascular blood flow, capillary oxygen saturation (SO2), and relative hemoglobin content (rHb), were assessed with lightguide spectrophotometry combined with laser Doppler flowmetry using an oxygen-to-see (O2C) device in the horizontal and elevated leg positions. Results: At baseline, SO2 in the elevated leg position was significantly lower in patients with CLTI than in those with IC (p = 0.0189), whereas the other microcirculatory parameters and ABI values were not significantly different. Patients with diabetes mellitus had a higher flow rate than those without in the horizontal leg position (p = 0.0162) but not in the elevated leg position. After successful revascularization, the flow increased immediately and significantly in both positions, whereas SO2, rHb, and the ABI did not. Conclusions: Elevated leg SO2 was significantly lower in CLTI than in clinically compensated peripheral arterial disease, whereas microvascular flow was a suitable surrogate parameter indicating successful revascularization. In studies using surgical or interventional revascularization procedures, noninvasive hemodynamic monitoring of the microcirculation at the foot level might be beneficial.

Mesenchymal Stem Cell-Loaded Hydrogel Improves Surgical Treatment for Chronic Cerebral Ischemia.

Chronic cerebral ischemia (CCI) results in a prolonged insufficient blood supply to the brain tissue, leading to impaired neuronal function and subsequent impairment of cognitive and motor abilities. Our previous research showed that in mice with bilateral carotid artery stenosis, the collateral neovascularization post Encephalo-myo-synangiosis (EMS) treatment could be facilitated by bone marrow mesenchymal stem cells (MSCs) transplantation. Considering the advantages of biomaterials, we synthesized and modified a gelatin hydrogel for MSCs encapsulation. We then applied this hydrogel on the brain surface during EMS operation in rats with CCI, and evaluated its impact on cognitive performance and collateral circulation. Consequently, MSCs encapsulated in hydrogel significantly augment the therapeutic effects of EMS, potentially by promoting neovascularization, facilitating neuronal differentiation, and suppressing neuroinflammation. Furthermore, taking advantage of multi-RNA-sequencing and in silico analysis, we revealed that MSCs loaded in hydrogel regulate PDCD4 and CASP2 through the overexpression of miR-183-5p and miR-96-5p, thereby downregulating the expression of apoptosis-related proteins and inhibiting early apoptosis. In conclusion, a gelatin hydrogel to enhance the functionality of MSCs has been developed, and its combination with EMS treatment can improve the therapeutic effect in rats with CCI, suggesting its potential clinical benefit.

Codon-Optimized and de novo-Synthesized E-Selectin/AAV2 Dose-Response Study for Vascular Regeneration Gene Therapy.

This study focuses on dose-response investigation using a codon-optimized and de novo-synthesized E-Selectin/AAV2 (E-Sel/AAV2) vector in preparation for Investigational New Drug enabling of subsequent clinical studies. Gene therapy is a potential solution for patients suffering from chronic limb-threatening ischemia. Understanding the dose for effective gene delivery is crucial for future Investigational New Drug-enabling studies. Expression of the codon-optimized E-Selectin gene was assessed by flow cytometry following in vitro cell transfection assay and RT-qPCR for murine limbs injected in vivo with AAV-m-E-Selectin (E-Sel/AAV2). Dose-response studies involved 3 cohorts of FVB/NJ mice (n=6/group) with escalating log doses of E-Selectin/AAV2 injected intramuscularly in divided aliquots, ranging from 2 × 10 9 VG to 2 × 10 11 VG, into ischemic limbs created by left femoral artery/vein ligation/excision and administration of nitric oxide synthase inhibitor, L-NAME. Limb perfusion, extent of gangrene free limb, functional limb recovery, and therapeutic angiogenesis were assessed. Codon-optimized E-Sel/AAV2 gene therapy exhibits a superior expression level than WT E-Sel/AAV2 gene therapy both in vitro and in vivo. Mice treated with a high dose (2 × 10 11 VG) of E-Sel/AAV2 showed significantly improved perfusion indices, lower Faber scores, increased running stamina, and neovascularization compared with lower doses tested with control groups, indicating a distinct dose-dependent response. No toxicity was detected in any of the animal groups studied. E-Sel/AAV2 Vascular Regeneration Gene Therapy holds promise for enhancing the recovery of ischemic hindlimb perfusion and function, with the effective dose identified in this study as 2 × 10 11 VG aliquots injected intramuscularly.

Features of dissomnia and cognitive impairments in chronic cerebral ischemia due to diabetes mellitus type 2

Introduction. Currently, diabetes mellitus occupies a leading position in terms of prevalence, disability, mortality and it is a medical and social problem. Microvascular and macrovascular diabetic complications negatively affect the quality and duration of sleep with detrimental effects on metabolism and weight regulation. The cognitive sphere is more impaired in type 2 diabetes mellitus in the form of a decrease in the speed of reaction to external stimuli and the ability to concentrate for a long time, so thinking becomes slower, and clinically significant cognitive impairments leads to work and social maladaptation and a decrease in adequate glycemic control. Aim of the study: to study the nature of diagnosed cognitive impairments and variants of dissomnias in chronic cerebral ischemia and to evaluate the features of identified dissomnias in the development of early dementia in type 2 diabetes mellitus. Object and methods. During the period from 2017 to 2023, 207 patients with chronic cerebral ischemia and neurological deficits of varying severity were examined. All patients underwent a comprehensive clinical and neurological examination using specialized scales to study the cognitive sphere and sleep level, laboratory and instrumental methods of examination. The study applied non-inclusion, inclusion and exclusion criteria and selected 147 patients with chronic cerebral ischemia and type 2 diabetes mellitus. The data has been processed statistically. Results. Cognitive impairments (95,1 ± 2,4%) and dyssomnia (88,9 ± 3,5%) develop in patients with type 2 diabetes mellitus with chronic cerebral ischemia, and their combination is significant (p &lt; 0,05) prevailed (82,7 ± 4,2%) with dysmetabolic signs. At the same time, moderate (43,2 ± 5,5%) and severe (34,6 ± 5,3%) cognitive disorders with moderate dyssomnia (63,0 ± 5,4%) and increased sleepiness (64,2 ± 5,3%) with episodes of obstructive sleep apnea (16,0 ± 4,1%) and narcolepsy (6,2 ± 2,7%) compared with patients without type 2 diabetes mellitus (p &lt; 0,05). Conclusions. The presence of type 2 diabetes mellitus increased the risk of developing dyssomnia and cognitive disorders, and the identification of dyssomnia led to an increased chance of a deterioration in the intellectual-mnestic level to the degree of moderate and severe impairments. Neuropsychological testing in combination with dyssomnia questionnaires and quantitative assessment of the severity of cognitive dysfunction is absolutely necessary.

Endovascular Management of Intestinal Ischemia

Abstract Background Mesenteric ischemia requiring revascularization is associated with high mortality in both chronic and acute forms. Disparate etiologies and nonspecific symptoms make the diagnosis challenging and often result in delayed diagnosis and intervention. More often surgery is required and is frequently lifesaving. Percutaneous transcatheter techniques are increasingly employed in both diagnosis and treatment. Aim and Objectives To highlight the recent trends in management of patients with mesenteric vascular occlusion. Subjects and Methods This was is a prospective study, conducted at Ain Shams University Hospitals and Nasser institute Hospital in Cairo on 30 patients complaining of acute or chronic intestinal ischemia in the form of abdominal pain and post prandial meal. Result Among the studied cases there were 4 (13.3%) with complete effect of thrombolysis, 1 (3.3%) with partial effect, 2 (6.7%) with no lysis, 8 (25.7%) with dilatation, 13 (43.3%) dilatation and stent and 13 (43.3%) with failed dilatation. Conclusion Endovascular intervention can be an alternative to open surgery for intestinal revascularization for the management of early cases of acute SMA occlusion. CTA rapid diagnosis, urgent endovascular management and intensive care and follow up are the cornerstone for good prognosis.

Impact of Cilostazol Administration on Prevention of Aspiration Pneumonia in Patients With Chronic Limb-Threatening Ischemia.

Cilostazol has reported effectiveness for preventing aspiration pneumonia in patients with ischemic stroke, but whether it is similarly beneficial for patients with chronic limb-threatening ischemia (CLTI) is unclear. This retrospective single-center study enrolled 1,368 CLTI patients treated with endovascular therapy (EVT). In the multivariate analysis, predictors for aspiration pneumonia were age (hazard ratio [HR] 1.06 [95% confidence interval (CI) 1.03-1.10]), non-ambulatory status (HR 2.54 [95% CI 1.38-4.65]), the Geriatric Nutritional Risk Index (HR 0.97 [95% CI 0.95-0.99]), and cilostazol (HR 0.37 [95% CI 0.16-0.87]). Cilostazol administration reduced the risk of aspiration pneumonia in patients with CLTI undergoing EVT.

The impact of travel distance in patient outcomes following revascularization for chronic limb-threatening ischemia

BackgroundPatient travel distance to the hospital is a key metric of individual and social disadvantage and its impact on the management and outcomes following intervention for chronic limb-threatening ischemia (CLTI) is likely underestimated. We sought to evaluate the effect of travel distance on outcomes in patients undergoing first-time lower extremity revascularization at our institution. MethodsWe retrospectively reviewed all consecutive patients undergoing first-time lower extremity revascularization, both endovascular and open, for CLTI from 2005 to 2014. Patients were stratified into 2 groups based on travel distance from home to hospital greater than or less than 30 miles. Outcomes included reintervention, major amputation, restenosis, primary patency, wound healing, length of stay, length of follow-up and mortality. Kaplan-Meier estimates were used to determine event rates. Logistic and cox regression was used to evaluate for an independent association between travel distance and these outcomes. ResultsOf the 1293 patients were identified, 38% traveled >30 miles. Patients with longer travel distances were younger (70 years vs 73 years; P = .001), more likely to undergo open revascularization (65% vs 41%; P < .001), and had similar Wound, Ischemia, foot Infection stages (P = .404). Longer distance travelled was associated with an increase in total hospital length of stay (9.6 days vs 8.6 days; P = .031) and shorter total duration of postoperative follow-up (2.1 years vs 3.0 years; P = .001). At 5 years, there was no definitive difference in the rate of restenosis (hzard ratio [HR], 1.3; 95% confidence interval [CI], 0.91-1.9; P = .155) or reintervention (HR, 1.4; 95% CI, 0.96-2.1; P = .065), but longer travel distance was associated with an increased rate of major amputation (HR, 2.1; 95% CI, 1.2-3.7; P = .011), and death (HR, 1.6; 95% CI, 1.2-2.2; P = .002). Longer travel distance was also associated with higher rate of nonhealing wounds (HR, 2.3; 95% CI, 1.5-3.5; P = .001). ConclusionsLonger patient travel distance was found to be associated with a lower likelihood of limb salvage and survival in patients undergoing first-time lower extremity revascularization for CLTI. Understanding and addressing the barriers to discharge, need for multidisciplinary follow-up, and appropriate postoperative wound care management will be key in improving outcomes at tertiary care regional specialty centers.

Staged versus nonstaged elective hybrid iliofemoral revascularization – analysis of ten years of prospective data

Reports of large series of hybrid iliofemoral revascularization for chronic lower limb ischemia are scarce. The aims of this study were to evaluate outcomes for staged and non-staged procedures, and to evaluate risk factors for outcomes at 90 days. Patients were consecutively included between 2013 and 2023. Surgical site infection (SSI) was defined by the ASEPSIS criteria and major adverse limb events (MALE) as onset of acute or continuing or worsening chronic limb ischemia or major amputation. Factors associated with outcomes were tested in a multivariable logistic regression analysis and expressed in Odds ratios (OR) with 95% confidence intervals (CI). Patients undergoing non-staged procedures (n=124) had higher TASC (Trans-Atlantic Inter-Society Consensus) class representing anatomical occlusive complexity, more often through-and through femoral guidewire access, more endoprosthesis, more covered stents, longer procedure time with open groin wounds, and less contralateral femoral access, than those undergoing staged procedures (n=31). The median time interval between the staged procedures was one day, and iliac stenting was done first in 77%. The median in-hospital stay was non-significantly longer in staged procedure (8 versus 6 days, p=0.053). The overall SSI and MALE rates were 25.8% and 20.0%, respectively, without differences between groups. Diabetes mellitus (OR 3.7, 95% CI 1.2 - 7.2]) and presence of a foot ulcer (OR 3.7, 95% CI [1.5 - 9.4]) were independently associated with MALE at 90 days. Postoperative hyperglycemia was non-significantly associated with SSI (OR 2.1 [95% CI 1.0 - 4.5], p=0.066) in multivariable analysis. The risks of SSI and MALE after elective hybrid iliofemoral revascularization were high. There appears to be no benefit in performing staged as opposed to non-staged procedures. The extent of iliofemoral occlusive disease according to the TASC classification had little influence on outcomes whereas diabetes mellitus and presence of a foot ulcer had greater impact on MALE.