Lumbar Sympathetic Block Leading to Increased Arterial Diameter and Blood Flow: A Mechanism of Therapeutic Benefit.

Lumbar sympathetic blocks (LSBs) have long been used for the treatment of chronic lower extremity pain and for conditions such as complex regional pain syndrome (CRPS). With a better understanding of the autonomic nervous system and its function, these blocks have grown in their utility. Through this growth, however, our understanding of sympathetic-mediated pain is still vaguely understood. Here, we present a case of a patient who underwent a point-of-care ultrasound (POCUS) before and after an LSB, and we were able to show significant dilation of the posterior tibial artery (PTA) following the block. We propose that this arterial dilation plays a mechanistic role in providing pain relief to patients who undergo LSB. This increased blood flow can not only enhance healing properties to surrounding tissues but also allow for nitric oxide to play potential regulatory roles in pain pathways. Here, we also review potential mechanisms of the amelioration of sympathetic-mediated pain as well as the potential utilization of LSBs and neuromodulation in treating visceral pathologies through a better understanding of visceral somatic relationships.

A new notable compression source of left renal vein entrapment: right renal artery.

PURPOSE: To estimate the incidences of left renal vein (LRV) entrapment by right renal artery (RRA), a phenomenon primarily reported as case reports. METHODS: The cross-sectional study consecutively screened renal vessel CT data of 38 (Renal) patients with nephropathy and 305 (Non-renal) patients with peripheral arterial diseases in a teaching hospital in northeast China between November 2018 and March 2023. The LRV compression by adjacent anatomical structures, including but not limited to RRA and multiple compression-related parameters, were investigated through multiplanar analysis of the CT data. RESULTS: The overall LRV entrapment rates by adjacent structures were 41.93% (12/31) and 24.00% (6/25), the rates of RRA-sourced LRV compression 22.58% (7/31) and 20.00% (5/25), and the rates of compression by superior mesenteric artery (SMA) 16.13% (5/31) and 4.00% (1/25) in the Renal and Non-renal groups, respectively, with no significance. The venous segments distal to the RRA-compressed site had a significantly larger transectional lumen area than those of the non-compressed veins in both groups (3.09 ± 1.29 vs. 1.82 ± 0.23, p < 0.001 and 4.30 ± 2.65 vs. 2.12 ± 0.55, p = 0.006; maximum-to-minimum area ratios in Renal and Non-renal groups, respectively). Nearly 80% of RRAs were found arising anteriorly rightwards instead of passing straight to the right. CONCLUSION: RRA-sourced LRV compression was not rare, and its incidence was higher than that of the compression by SMA in both patient cohorts. RRA could be a more common compression source than SMA concerning LRV entrapment. Further investigations involving different populations, including healthy individuals, are needed.

Cuproptosis and copper deficiency in ischemic vascular injury and repair.

Ischemic vascular diseases are on the rise globally, including ischemic heart diseases, ischemic cerebrovascular diseases, and ischemic peripheral arterial diseases, posing a significant threat to life. Copper is an essential element in various biological processes, copper deficiency can reduce blood vessel elasticity and increase platelet aggregation, thereby increasing the risk of ischemic vascular disease; however, excess copper ions can lead to cytotoxicity, trigger cell death, and ultimately result in vascular injury through several signaling pathways. Herein, we review the role of cuproptosis and copper deficiency implicated in ischemic injury and repair including myocardial, cerebral, and limb ischemia. We conclude with a perspective on the therapeutic opportunities and future challenges of copper biology in understanding the pathogenesis of ischemic vascular disease states.

Risk factors for glioblastoma in adults in Japan: an exploratory cohort study based on the Shizuoka Kokuho Database, the Shizuoka study.

PURPOSE: To elucidate the risk factors associated with the onset of glioblastoma (GBM) utilizing a comprehensive administrative claims database from a major governmental district in Japan. METHODS: Using the Shizuoka Kokuho Database (SKDB) for the period from April 2012 to September 2021, we conducted a retrospective analysis of 1,465,353 participants, identifying GBM cases using specific Japanese disease codes in conjunction with associated treatments. Risk factors were assessed using both univariable and multivariable Cox proportional hazards models. RESULTS: Within the cohort, 182 participants (0.012%) received a GBM diagnosis during the study period, resulting in an incidence rate of 2.1 per 100,000 person-years. The multivariable analysis revealed that older age, male sex, and peripheral vascular disease (PVD) significantly influenced the risk of GBM onset. No clear link was found between allergic conditions and GBM risk, in contrast to some previous research. CONCLUSION: Employing a robust health insurance database, this study revealed significant associations between GBM and factors such as age, male sex, and PVD within the Japanese population. It provides key insights into GBM epidemiology and underscores the potential of health insurance databases for large-scale oncological research.

Aortoiliac Occlusion in a Rare Instance of Leriche Syndrome Type I in a 65-Year-Old Woman With Chronic Leg Discomfort Refractory to Pregabalin.

Aortoiliac occlusive disease (AIOD), also known as Leriche syndrome, is a form of peripheral artery disease (PAD) that involves narrowing, and in severe cases, complete occlusion, of infrarenal abdominal aorta and/or iliac and femoropopliteal arteries. It classically presents as a triad of symptoms, i.e., leg pain, erectile dysfunction, and abnormally weak or absent femoral pulses. If untreated, it can progress to ischemia and gangrene of the affected regions of pelvis and lower extremities. Like any other PAD, AIOD is most commonly caused by atherosclerosis and usually occurs in strong association with severe cardiovascular diseases. Due to the rarity of this disease, its incidence and prevalence are still unknown making it harder to diagnose especially in patients without the classic risk factors and typical presentation. We report a case of AIOD in a 65-year-old woman who presented with atypical symptoms. She was diagnosed with AIOD type I upon further investigation, which was managed successfully.

Hypoglycemia and Cardiovascular Disease: Exploring the Connections.

It has long been known that administering insulin or insulin secretagogues to treat diabetes has the unfavorable side effect of hypoglycemia. Because hypoglycemia can disrupt normal brain function, it can have a profound impact on people's lives. Studies have shown a connection between hypoglycemia and a higher risk of death and cardiovascular disease. Through experimental studies, numerous potential reasons for the start of cardiovascular events have been discovered. In addition, studies on people have demonstrated that hypoglycemia can result in ventricular arrhythmias. According to recent studies, a number of factors may affect the relationship between hypoglycemia, cardiovascular events, and mortality. Confounding factors may explain the apparent correlation, at least in part. People with comorbidities may experience more hypoglycemia, increasing their risk of mortality. Those who have type 1 or type 2 diabetes, however, seem to be more susceptible to the negative effects of hypoglycemia on the cardiovascular system. When choosing appropriate glucose-lowering treatments and setting glycemic objectives with patients, clinicians should be aware of this risk.

Proniosomes Nanoparticle for the Treatment of Peripheral Arterial Disease.

BACKGROUND: The common symptom of systemic atherosclerosis is peripheral arterial disease(PAD), which occurs when the artery lumen in the lower extremities gradually becomes blocked by atherosclerotic plaque. The most frequent symptom of lower extremity PAD, called "vascular claudication," which is pain experienced when walking. Partial or total blockage of the peripheral arteries in the upper and lower limbs is called PAD. The danger of death from concurrent coronary artery and cerebrovascular atherosclerosis outweighs the risk of amputation. OBJECTIVE: However, niosomes have issues with fusion, aggregation, leakage, vesicle sedimentation, and difficulty in sterilizing. A more recent strategy known as pro-vesicular carriers was used to solve these issues. The formulations in Proniosomes are dry and anhydrous, protected with a non-ionic surfactant that serves as a carrier when combined with water. METHODS: Formulation prepared by organic solvent, surfactant, cholesterol, other components and hydration medium. Coacervation Phase separation Technique used for proniosome Nanoparticle. Box Bhenken Design is used for optimization batches. RESULTS: In this context, we shall discuss the development of Proniosome for the treatment of peripheral arterial diseases. From here, we know that proniosome nanoparticles is pro vesicular system good characteristics and effectiveness for treating peripheral arterial diseases. CONCLUSION: Proniosomes may be created using various techniques, which may impact how they develop along with the drug's characteristics. They increase the drug's stability while being delivered while being entrapped. They don't need particular conditions for handling, protection, storage, or industrial manufacturing.

The Prevalence of Cardiovascular Complications and Causes of AngioJet Failure: A Post-Marketing Surveillance Study Based on the MAUDE (Manufacturer and User Facility Device Experience) Database.

Background and objective Aspiration thrombectomy devices, such as the AngioJet Solent Omni (Boston Scientific Corporation, Marlborough, MA) have been approved by the US FDA for the treatment of thrombi in peripheral arterial disease, venous disease, and AV fistulas. However, there is a dearth of real-world data on the most common modes of failure and complications associated with the AngioJet Solent Omni. In this study, we aimed to address this scarcity of data. Methods The MAUDE (Manufacturer and User Facility Device Experience) database was queried for reports of device failure and adverse events spanning the period from October 2012 to December 2021. Results A total of 499 events were reported during the study period. After the exclusion of duplicate reports, the final analysis included 450 reports. The most common mode of failure was catheter breakage/kinking during suction thrombectomy with 137 reports (30%). The most common vessel associated with events was the superficial femoral artery or vein, which was documented in 82 reports (18.2%). The most common adverse clinical outcome was the embedding of a piece of the device in the patient, which occurred in seven reports (1.6%). There were seven (1.6%) events of death reported during the period studied. Conclusions Based on our findings, theAngioJet Solent Omni device provides promising results; however, it is important to evaluate device safety. It is associated with complications including device embedment, catheter breakage/kinking, and death, and these adverse events are linked to patient characteristics and risk factors.

Unveiling the Genetic Footprint: Exploring Somatic Mutations in Peripheral Arterial Disease Progression.

Peripheral arterial diseases (PADs) are complex cardiovascular conditions influenced by environmental factors and somatic mutations in multiple genes involved in hematopoiesis and inflammation. While traditional risk factors, such as smoking, hypercholesterolemia, and hypertension, have been extensively studied, the role of somatic mutations in PAD progression remains underexplored. The present article intends to provide a comprehensive commentary of the molecular mechanisms, genetic landscape, prognostic significance, and clinical implications of somatic mutations in PADs. The expansion of clonal hematopoiesis of indeterminate potential (CHIP) clones in the circulating blood, named clonal hematopoiesis (CH), leads to the infiltration of these clones into atherosclerotic plaques and the production of inflammatory cytokines, increasing the risk of cardiovascular diseases, including PADs. Furthermore, recent experimental evidence has demonstrated the involvement of somatically mutated TP53 genes with a high variant allele frequency (VAF) in PAD development and prognosis. This review delves into the relationship between CH and PADs, elucidating the prevalence, impact, and underlying mechanisms of this association. This understanding paves the way for novel therapeutic approaches targeting CHIP to promote tissue regeneration and improve outcomes in PAD patients. It emphasizes the need for further research to fully unravel the genetic footprint of the disease and highlights potential clinical implications. The findings presented in this article lay the foundation for personalized medicine approaches and open avenues for the development of targeted therapies based on somatic mutation profiling.

Potential metabolic biomarkers of critical limb ischemia in people with type 2 diabetes mellitus.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a significant risk factor for the development of critical limb ischemia (CLI), the most advanced stage of peripheral arterial disease. The concurrent existence of T2DM and CLI often leads to adverse outcomes, namely limb amputation. OBJECTIVE: To identify biomarkers for improving the screening of CLI in high-risk people with T2DM. METHODS: We investigated metabolome profiles in serum samples of 113 T2DM people with CLI (n = 23, G2) and without CLI (n = 45, G0: no lower limb stenosis (LLS) and n = 45, G1: LLS < 50%), using hydrogen nuclear magnetic resonance (1H NMR) approach. Principle component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used to analyze 1H NMR data. RESULTS: Twenty potential metabolites that could discriminate people with T2DM and CLI (G2) from non-CLI patients without LLS (G0) were determined in serum samples. The correct percent of classification for the PLS-DA model for the test set samples was 85% (n = 20) and 100% (n = 5) for G0 and G2 groups, respectively. Non-CLI patients with LLS < 50% (G1) were projected on the PCA abstract space built using 20 discriminatory metabolites. Eleven people with T2DM and LLS < 50% were prospectively followed, and their ankle-brachial index (ABI) was measured after 4 years. A promising agreement existed between the PCA model's predictions and those obtained by ABI values. CONCLUSION: The findings suggest that confirmation of blood potential metabolic biomarkers as a complement to ABI for screening of CLI in a large group of high-risk people with T2DM is needed.

Predictive Factors for Lower Limb Amputation in Type 2 Diabetics.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a major public health problem. Foot-related complications are common in diabetic patients. The aim of this study is to identify predictive factors for lower limb amputation (LLA) in order to better identify this at-risk population. METHODS: This was a cross-sectional study involving 134 patients who were hospitalised for the management of T2DM complicated by diabetic foot, in the department of endocrinology and diabetology. We included patients with T2DM whose diabetes was diagnosed 10 years ago or more, and who had a diabetic foot problem. Statistical differences between predictors of amputations were tested using: t-tests for numerical variables and chi-square tests for categorical variables. Significant variables were analysed by logistic regression to determine significant predictors. RESULTS: The mean duration of diabetes was 17±7 years. We found that 70% of patients with LLA were older than 50 years (p<10-3). The prevalence of LLA was higher (p=0.015) in patients with diabetes for more than 20 years. We noted that 58% of patients who underwent LLA were hypertensive (p<10-3). The majority of patients with LLA (58%) had abnormal micro-albuminuria (p<10-3). We found that 70% (n=12) of patients with LLA had low-density protein cholesterol levels above the target value (p<10-3). Diabetic foot grade ≥4 (4 or 5) according to Wagner's classification, was present in 24% of amputee patients. Based on a 95% confidence interval level, the independent significant predictive factors for LLA in our patients were: T2DM for more than 20 years, hypertension and diabetic foot grade ≥4. CONCLUSIONS: After multivariate analysis, the significant independent predictive factors associated with LLA were: T2DM for more than 20 years, hypertension, and diabetic foot grade ≥4. Early management of diabetic foot problems is therefore recommended to avoid amputations.

Clinical and Cardiovascular Profile in Patients With Peripheral Artery Disease.

Background  Peripheral artery disease (PAD) is a vascular disorder leading to serious complications if not managed promptly. This study is conducted to analyze clinical and cardiovascular risk factors in PAD patients presenting at a tertiary care hospital and management strategies. Methodology This observational study was conducted at the Department of Cardiology, Mohamed Bin Khalifa Specialist Cardiac Centre. One hundred and twenty patients aged more than 35 years with PAD were included in the study. Data regarding age, gender, physical exam, cardiovascular risk profile, carotid disease, coronary artery disease, and treatment strategy were recorded on a pre-designed questionnaire by the researcher himself. The data were analyzed using IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp. Results The mean age of patients with PAD was 65.46±10.56 years. About 79.2% were hypertensive, 81.7% had hyperlipidemia, 83.3% had diabetes, 29.2% had renal insufficiency, and 38.3% were active smokers, respectively. In age ≥65 years, infra-popliteal PAD was significantly lower as compared to above-knee PAD (23.4% vs. 76.6%, p=0.002). In diabetic patients, the proportion of above-knee PAD was higher than below-knee PAD (60% vs. 40%, p=0.033). Conclusion Older age, diabetes, and carotid disease were significant predictors for peripheral artery disease, and these are significantly associated with above-the-knee peripheral artery disease.

Blood flow restricted walking in patients suffering from intermittent claudication: a case series feasibility and safety study.

To examine the feasibility and safety of blood flow restricted walking (BFR-W) in patients with intermittent claudication (IC). Moreover, to evaluate changes in objective performance-based and self-reported functioning following 12 weeks of BFR-W. Materials and methods: Sixteen patients with IC were recruited from two departments of vascular surgery. The BFR-W programme implied the application of a pneumatic cuff around the proximal part of the affected limb at 60% limb occlusion pressure in five intervals of 2 min, four times per week for 12 weeks. Feasibility was evaluated by adherence and completion rates of the BFR-W programme. Safety was evaluated by adverse events, ankle-brachial index (ABI) at baseline and follow-up, and pain on a numerical rating scale (NRS pain) before and 2 min after training sessions. Furthermore, changes in performance between baseline and follow-up were evaluated with the 30 seconds sit-to-stand test (30STS), the 6-minute walk test (6MWT) and the IC questionnaire (ICQ). Results: Fifteen out of 16 patients completed the 12-week BFR-W programme and adherence was 92.8% (95% CI: 83.4; 100%). One adverse event unrelated to the intervention was reported causing one patient to terminate the programme 2 weeks prematurely. Mean NRS pain 2 min following BFR-W was 1.8 (95% CI [1.7-2]). ABI, 30STS, 6MWT and ICQ score were improved at follow-up. Conclusions: BFR-W is feasible and appears to be safe in terms of completion rate, adherence to the training protocol, and adverse events in patients with IC. Further investigation of the effectiveness and safety of BFR-W compared to regular walking exercise is needed.

Ruptured Penetrating Atherosclerotic Ulcer Repaired With an Amplatzer Atrial Septal Occluder.

Ascending aortic pseudoaneurysms are an infrequent but life-threatening complication of cardiac and aortic surgery. Although rare, these pseudoaneurysms can form as a complication of penetrating atherosclerotic ulcers. We report a case of a ruptured penetrating atherosclerotic ulcer repaired percutaneously with an Amplatzer Atrial Septal Occluder (Abbott, Plymouth, MN, USA).

The Prevalence and Risk Factors for Peripheral Arterial Disease in Adults Living With Human Immunodeficiency Virus.

Adult patients with human immunodeficiency virus (HIV) appear to be at high risk of cardiovascular disease (CVD). Peripheral arterial disease (PAD) is particularly concerning as it is associated with myocardial infarction and stroke. Nevertheless, the incidence of PAD is still unknown. The authors prospectively recruited HIV-infected patients from the outpatient clinic of the Department of Internal Medicine in our center. We assessed ankle-brachial index (ABI) using the VaSera system™ (Fukuda Denshi Co., Ltd). Patients were grouped into 3 ABI levels: an ABI ≤0.90 was considered abnormal and evidence of PAD, an ABI 1.0 to 1.40 was considered normal, and 0.91 to 0.99 was considered borderline. Cardiovascular risk factors were compared across all 3 levels of ABI and were analyzed using multivariate ordinal logistic regression. Eight hundred ninety-two patients were recruited. The mean age was 42.9 ± 10.0 years and 458 (51.4%) were males. There were 704, 149, and 39 patients in the normal, borderline, and abnormal ABI groups, respectively. The latter group of 39 patients was considered to have PAD, yielding a prevalence of 4.37% (95% confidence interval [CI] 3.21-5.93). Sex ratio, age, education levels, smoking rate, body mass index (BMI), blood pressure, prevalence of comorbidities with hypertension and coronary heart disease, median triglyceride level, reduced kidney function and HIV-1 RNA undetectable ratio, duration of HIV diagnosis, and duration on antiretroviral treatment were significantly different among 3 ABI subgroups. Independent risk factors associated with PAD were being female (odds ratio [OR]: 2.86; 95% CI: 1.94-4.22), being <30 years of age (OR: 4.66; 95% CI: 2.78-7.81), being overweight (BMI 25-25.9; OR: 0.39; 95% CI: 0.20-0.76), being obese (BMI: 30; OR: 3.53; 95% CI: 1.51-8.22), having a diastolic blood pressure ≥80 mmHg (OR: 0.50; 95% CI: 0.35-0.71), and having detectable HIV-1 RNA ≥20 copies/mL (OR: 1.85; 95% CI: 1.13-3.03). In conclusion, the prevalence of PAD in HIV-infected Thais was 4.37% in infected patients on therapy attending outpatient clinics. For this population, PAD appears to be relatively poorly correlated with traditional risk factors of CVD.

Fasudil, a ROCK inhibitor, preserves limb integrity in a mouse model of unilateral critical limb ischemia: Possible interplay of inflammatory and angiogenic signaling pathways.

Peripheral arterial diseases (PAD) had a great attention owing to devastating consequences of disability and cardiovascular morbidity and mortality. Yet, current therapeutic options are limited to surgical revascularization with no effective pharmacotherapy available. Excessive activity of Rho-associated coiled-coil protein kinase (ROCK) is implicated with several vascular diseases, rendering ROCK inhibition as a potential therapeutic strategy for patients suffering vascular disorders. AIM: The current study was dedicated to investigating the vascular protective potential of Fasudil, a ROCK inhibitor, on an experimentally induced unilateral critical limb ischemia (CLI) model in mice and demonstrated the possible underlying mechanisms. METHODS: Unilateral CLI was induced by ligation and excision of femoral artery followed by daily i.p. injection of Fasudil (10 mg/kg or 25 mg/kg) up to two weeks post-surgery. KEY FINDINGS: Mice underwent CLI showed decreased antioxidant capacity and increased inflammatory signal, evident by elevation of ERK1/2 in both serum and GC muscles that coincided with increases in VEGFA, HIF-1α and CD34+ cells of GC muscles. CLI resulted in structural damage of GC muscle fibers, with marked apoptosis, declined proliferation and deteriorated peripheral limb function. Treatment with Fasudil restored antioxidant capacity and attenuated VEGFA, HIF-1α, CD34+ cells and inflammatory markers in ischemic limbs. Furthermore, Fasudil preserved histological integrity of ischemic GC muscles, with amelioration of apoptosis, preserved proliferation rate and improvement in peripheral limb function. SIGNIFICANCE: Fasudil could protect against experimentally induced unilateral CLI, in a dose-dependent manner, which could pave the way for future clinical application of Fasudil in patients suffering PAD.

A Case of Hypoglycemia With Concomitant Use of a Sulfonylurea and Clopidogrel.

Hypoglycemia secondary to sulfonylureas and clopidogrel have been independently described in the literature. However, there has been minimal investigation into the risk of clopidogrel-induced hypoglycemia in the setting of long-term or concomitant sulfonylurea use in patients with Type 2 diabetes mellitus. We present a case of a patient with diabetes well managed on glimepiride (second-generation sulfonylurea) for more than 10 years who presented with an episode of hypoglycemia shortly after initiation of clopidogrel for peripheral vascular disease.