Current Medical Therapy and Revascularization in Peripheral Artery Disease of the Lower Limbs: Impacts on Subclinical Chronic Inflammation.

Peripheral artery disease (PAD), coronary artery disease (CAD), and cerebrovascular disease (CeVD) are characterized by atherosclerosis and inflammation as their underlying mechanisms. This paper aims to conduct a literature review on pharmacotherapy for PAD, specifically focusing on how different drug classes target pro-inflammatory pathways. The goal is to enhance the choice of therapeutic plans by considering their impact on the chronic subclinical inflammation that is associated with PAD development and progression. We conducted a comprehensive review of currently published original articles, narratives, systematic reviews, and meta-analyses. The aim was to explore the relationship between PAD and inflammation and evaluate the influence of current pharmacological and nonpharmacological interventions on the underlying chronic subclinical inflammation. Our findings indicate that the existing treatments have added anti-inflammatory properties that can potentially delay or prevent PAD progression and improve outcomes, independent of their effects on traditional risk factors. Although inflammation-targeted therapy in PAD shows promising potential, its benefits have not been definitively proven yet. However, it is crucial not to overlook the pleiotropic properties of the currently available treatments, as they may provide valuable insights for therapeutic strategies. Further studies focusing on the anti-inflammatory and immunomodulatory effects of these treatments could enhance our understanding of the mechanisms contributing to the residual risk in PAD and pave the way for the development of novel therapies.

Penumbra aspiration thrombectomy of the superior mesenteric artery for mesenteric ischemia.

Acute mesenteric ischemia from thromboembolic occlusion is a life-threatening emergency associated with a high mortality rate. Prompt diagnosis and intervention are vital to preserve viable bowel and prevent mortality. In the past decade, a shift has occurred toward minimally invasive alternatives such as endovascular therapies. We present a case of acute mesenteric ischemia from superior mesenteric artery thrombosis treated promptly with the Penumbra suction thrombectomy device (Penumbra Inc).

Development of a biomarker panel for assessing cardiovascular risk in diabetic patients with chronic limb-threatening ischemia (CLTI): a prospective study.

BACKGROUND: Lower-extremity endovascular revascularization (LER) is often required for diabetic patients with chronic limb threatening ischemia (CLTI). During the post-revascularization period patients may unpredictably experience major adverse cardiac events (MACE) and major adverse limb events (MALE). Several families of cytokines are involved in the inflammatory process that underlies the progression of atherosclerosis. According to current evidence, we have identified a panel of possible biomarkers related with the risk of developing MACE and MALE after LER. The aim was to study the relationship between a panel of biomarkers - Interleukin-1 (IL-1) and 6 (IL-6), C-Reactive Protein (CRP), Tumor Necrosis Factor-α (TNF-α), High-Mobility Group Box-1 (HMGB-1), Osteoprotegerin (OPG), Sortilin and Omentin-1- at baseline, with cardiovascular outcomes (MACE and MALE) after LER in diabetic patients with CLTI. METHODS: In this prospective non-randomized study, 264 diabetic patients with CLTI undergoing endovascular revascularization were enrolled. Serum levels of each biomarker were collected before revascularization and outcomes' incidence was evaluated after 1, 3, 6 and 12 months. RESULTS: During the follow-up period, 42 cases of MACE and 81 cases of MALE occurred. There was a linear association for each biomarker at baseline and incident MACE and MALE, except Omentin-1 levels that were inversely related to the presence of MACE or MALE. After adjusting for traditional cardiovascular risk factors, the association between each biomarker baseline level and outcomes remained significant in multivariable analysis. Receiver operating characteristics (ROC) models were constructed using traditional clinical and laboratory risk factors and the inclusion of biomarkers significantly improved the prediction of incident events. CONCLUSIONS: Elevated IL-1, IL-6, CRP, TNF-α, HMGB-1, OPG and Sortilin levels and low Omentin-1 levels at baseline correlate with worse vascular outcomes in diabetic patients with CLTI undergoing LER. Assessment of the inflammatory state with this panel of biomarkers may support physicians to identify a subset of patients more susceptible to the procedure failure and to develop cardiovascular adverse events after LER.

The role of Klotho and FGF23 in cardiovascular outcomes of diabetic patients with chronic limb threatening ischemia: a prospective study.

Cardiovascular complications after lower extremity revascularization (LER) are common in diabetic patients with peripheral arterial disease (PAD) and chronic limb threatening ischemia (CLTI). The Klotho-fibroblast growth factor 23 (FGF23) axis is associated with endothelial injury and cardiovascular risk. We aimed to analyze the relationship between Klotho and FGF23 serum levels and the incidence of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after LER in diabetic patients with PAD and CLTI. Baseline levels of Klotho and FGF23, and their association with subsequent incidence of MACE and MALE were analyzed in a prospective, non-randomized study in a population of diabetic patients with PAD and CLTI requiring LER. A total of 220 patients were followed for 12 months after LER. Sixty-three MACE and 122 MALE were recorded during follow-up period. Baseline lower Klotho serum levels (295.3 ± 151.3 pg/mL vs. 446.4 ± 171.7 pg/mL, p < 0.01), whereas increased serum levels FGF23 (75.0 ± 11.8 pg/mL vs. 53.2 ± 15.4 pg/mL, p < 0.01) were significantly associated with the development of MACE. Receiver operating characteristic (ROC) analysis confirmed the predictive power of Klotho and FGF23 baseline levels. Furthermore, decreased Klotho levels were associated with the occurrence of MALE after LER (329.1 ± 136.8 pg/mL vs 495.4 ± 183.9 pg/mL, p < 0.01). We found that Klotho and FGF23 baseline levels are a potential biomarker for increased cardiovascular risk after LER in diabetic patients with PAD and CLTI.

External iliac vein aneurysm treated via balloon-assisted aneurysmorrhaphy with a contemporary review of the literature.

Isolated external iliac vein aneurysm is exceedingly rare, not well-described in the literature, and presents several potential surgical approaches. Herein, we describe the case of a 72-year-old woman who presented with incidentally found 4.3 cm × 3.4 cm × 5.6 cm right external iliac vein aneurysm after undergoing magnetic resonance imaging for orthopedic work-up. She was treated via parallel supra- and infra-inguinal incisions and novel combination of primary aneurysmorrhaphy with intraluminal balloon mandrel-assisted closure. The patient was discharged on postoperative day two, and 6-month follow-up ultrasound showed a normal caliber vessel with normal compressibility, suggesting this technique is safe and effective for appropriately selected patients.

Serum high mobility group box-1 levels associated with cardiovascular events after lower extremity revascularization: a prospective study of a diabetic population.

BACKGROUND: Peripheral arterial disease (PAD) is one of the most disabling cardiovascular complications of type 2 diabetes mellitus and is indeed associated with a high risk of cardiovascular and limb adverse events. High mobility group box-1 (HMGB-1) is a nuclear protein involved in the inflammatory response that acts as a pro-inflammatory cytokine when released into the extracellular space. HMBG-1 is associated with PAD in diabetic patients. The aim of this study was to evaluate the association between serum HMGB-1 levels and major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after lower-extremity endovascular revascularization (LER) in a group of diabetic patients with chronic limb-threatening ischemia (CLTI). METHODS: We conducted a prospective observational study of 201 diabetic patients with PAD and CLTI requiring LER. Baseline serum HMGB-1 levels were determined before endovascular procedure. Data on cardiovascular and limb outcomes were collected in a 12-month follow-up. RESULTS: During the follow-up period, 81 cases of MACE and 93 cases of MALE occurred. Patients who subsequently developed MACE and MALE had higher serum HMGB-1 levels. Specifically, 7.5 ng/mL vs 4.9 ng/mL (p < 0.01) for MACE and 7.2 ng/mL vs 4.8 ng/mL (p < 0.01) for MALE. After adjusting for traditional cardiovascular risk factors, the association between serum HMGB-1 levels and cardiovascular outcomes remained significant in multivariable analysis. In our receiver operating characteristic (ROC) curve analysis, serum HMGB-1 levels were a good predictor of MACE incidence (area under the curve [AUC] = 0.78) and MALE incidence (AUC = 0.75). CONCLUSIONS: This study demonstrates that serum HMGB-1 levels are associated with the incidence of MACE and MALE after LER in diabetic populations with PAD and CLTI.

Dietary Risk Factors and Eating Behaviors in Peripheral Arterial Disease (PAD).

Dietary risk factors play a fundamental role in the prevention and progression of atherosclerosis and PAD (Peripheral Arterial Disease). The impact of nutrition, however, defined as the process of taking in food and using it for growth, metabolism and repair, remains undefined with regard to PAD. This article describes the interplay between nutrition and the development/progression of PAD. We reviewed 688 articles, including key articles, narrative and systematic reviews, meta-analyses and clinical studies. We analyzed the interaction between nutrition and PAD predictors, and subsequently created four descriptive tables to summarize the relationship between PAD, dietary risk factors and outcomes. We comprehensively reviewed the role of well-studied diets (Mediterranean, vegetarian/vegan, low-carbohydrate ketogenic and intermittent fasting diet) and prevalent eating behaviors (emotional and binge eating, night eating and sleeping disorders, anorexia, bulimia, skipping meals, home cooking and fast/ultra-processed food consumption) on the traditional risk factors of PAD. Moreover, we analyzed the interplay between PAD and nutritional status, nutrients, dietary patterns and eating habits. Dietary patterns and eating disorders affect the development and progression of PAD, as well as its disabling complications including major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Nutrition and dietary risk factor modification are important targets to reduce the risk of PAD as well as the subsequent development of MACE and MALE.

Acute occlusion of aortic endovascular aneurysm repair stent graft with bilateral limb ischemia.

Endovascular aneurysm repair has dramatically changed the management of abdominal aortic aneurysms as an alternative to open repair. However, complications can occur, including stent graft migration, kinking, and occlusion, leading to compromise of the excluded aneurysm walls and acute limb ischemia. In the present report, we have described a case of migration and kinking of an abdominal aortic stent graft in the main body that led to occlusion of the abdominal aorta and bilateral acute limb ischemia. The patient required emergent explantation of the stent graft and open repair of the abdominal aneurysm with a rifampin-soaked Dacron graft, which achieved a favorable outcome.

Complications of Peripheral Cannulation Site in Obese Patients on Adult Extracorporeal Membrane Oxygenation.

Placement of extracorporeal membrane oxygenation (ECMO) in obese patients has been challenging; however, cannulation risk in obese patients has not been clearly investigated. We therefore explored ECMO cannulation complications in this obese population. Data were reviewed from adult ECMO database from 2010 to 2019. Patients were stratified by body mass index (BMI) (normal weight [NW] [BMI 18.5-24.9], overweight [BMI 25-29.9], class I [BMI 30-34.9], class II [BMI 35-39.9], class III [BMI >40]). Patients with central cannulation were excluded from this study. Combined ECMO cannulation complications and survival data were retrospectively analyzed. There were 233 patients, 156 venoarterial (VA) ECMO patients (45 [28%] NW, 51 [33%] overweight, 37 [24%] class I, 12 [8%] class II, and 11 [7.0%] class III) and 77 venovenous (VV) ECMO patients (14 [18%] NW, 13 [17%] overweight, 17 [22%] class I, 11 [14%] class II, and 22 [29%] class III). There were significantly more cannulation site bleeds in VA class III (55%) patients compared with VA NW patients (22%), p = 0.006. There was no significant difference in cannulation site bleeding between BMI groups for VV ECMO. There was no difference in 30 day mortality, ECMO survival for all BMI groups in both VA and VV ECMO. There is significant increased risk of bleeding with peripheral VA cannulation of obese patients with BMI > 35. Cannulating surgeon should be aware of this bleeding risk in morbidly obese patient who undergo VA ECMO.

Arterial protocol including prophylactic distal perfusion catheter decreases limb ischemia complications in patients undergoing extracorporeal membrane oxygenation.

OBJECTIVE: Venoarterial extracorporeal membrane oxygenation (ECMO) is a salvage therapy in patients with severe cardiopulmonary failure. Owing to the large size of the cannulas inserted via the femoral vessels (≤24-F) required for adequate oxygenation, this procedure could result in significant limb ischemic complications (10%-70%). This study evaluates the results of a distal limb perfusion arterial protocol designed to reduce associated complications. METHODS: We conducted a retrospective institutional review board-approved review of consecutive patients requiring ECMO via femoral cannulation (July 2010-January 2015). To prevent arterial ischemia, a distal perfusion catheter (DPC) was placed antegrade into the superficial femoral artery and connected to the ECMO circuit. Limb perfusion was monitored via near-infrared spectroscopy (NIRS) placed on both calves. Decannulation involved open repair, patch angioplasty, and femoral thrombectomy as needed. RESULTS: A total of 91 patients were placed on ECMO via femoral arterial cannula (16-F to 24-F) for a mean duration of 9 days (range, 1-40 days). A percutaneous DPC was inserted prophylactically at the time of cannulation in 55 of 91 patients, without subsequent ischemia. Of the remaining 36 patients without initial DPC placement, 12 (33% without DPC) developed ipsilateral limb ischemia related to arterial insufficiency, as detected by NIRS and clinical findings. In these patients, the placement of a DPC (n = 7) with or without a fasciotomy, or with a fasciotomy alone (n = 4), resulted in limb salvage; only one patient required subsequent amputation. After decannulation (n = 7), no patients had further evidence of limb ischemia. Risk factors for the development of limb ischemia identified by categorical analysis included lack of DPC at time of cannulation and ECMO cannula size of less than 20-Fr. There was a trend toward younger patient age. Overall ECMO survival rate was 42%, whereas survival in patients with limb ischemia was only 25%. CONCLUSIONS: Limb ischemia complications from ECMO may be decreased by prophylactic placement of an antegrade DPC. Without DPC, continuous monitoring using NIRS may identify limb ischemia, which can be treated subsequently with DPC and or fasciotomy.

Atypical Mycotic Aortic Aneurysms.

Mycotic aortic aneurysms are rare occurrences and such aneurysms associated with Streptococcus pneumoniae are seldom seen in the current antibiotic era. We present the unusual case of a 68-year-old healthy female with a Streptococcal mycotic abdominal aortic aneurysm of unknown etiology treated with antibiotics and open surgical intervention. Postoperative imaging revealed multiple new thoracic mycotic aortic aneurysms for which she was treated with thoracic endovascular aortic repair. Sequential abdominal and thoracic Streptococcal mycotic aortic aneurysms treated with a combination of open and endovascular surgery demonstrate a unique and rare case.

Endovascular Repair of Ruptured Infected Arteries as a Temporizing Measure Versus Destination Therapy.

OBJECTIVE: Mycotic rupture of the arteries is a rare but deadly disorder. Current management typically involves open surgical repair. However, endovascular repair is a potential treatment that can be used to delay open repair, especially in acutely unstable patients. A case report and review of the literature was conducted to determine whether endovascular therapy could be a destination therapy for patients with arterial rupture secondary to infection. METHODS: We present the case of a 72-year-old man with a left common iliac artery aneurysm rupture secondary to Salmonella infection treated with endovascular therapy upon initial presentation. A literature review of PubMed yielded 29 patients with ruptured aortic and iliac infected aneurysms that were initially treated with endovascular repair. RESULTS: Majority of the patients (76.7%, 23 of 30) were successfully treated with the endovascular treatment and did not require open revision. These patients were often placed on long-term antibiotics. CONCLUSION: The literature review supports endovascular repair with a stent graft as a temporizing measure for infected ruptured arteries in an emergent setting and, in select cases, as a destination therapy.

Median Arcuate Ligament Syndrome-Review of This Rare Disease.

IMPORTANCE: Median arcuate ligament (MAL) syndrome is a rare disease resulting from compression of the celiac axis by fibrous attachments of the diaphragmatic crura, the median arcuate ligament. Diagnostic workup and therapeutic intervention can be challenging. OBJECTIVE: To review the literature to define an algorithm for accurate diagnosis and successful treatment for patients with MAL syndrome. EVIDENCE REVIEW: A search of PubMed (1995-September 28, 2015) was conducted, using the key terms median arcuate ligament syndrome and celiac artery compression syndrome. FINDINGS: Typically a diagnosis of exclusion, MAL syndrome involves a vague constellation of symptoms including epigastric pain, postprandial pain, nausea, vomiting, and weight loss. Extrinsic compression of the vasculature and surrounding neural ganglion has been implicated as the cause of these symptoms. Multiple imaging techniques can be used to demonstrate celiac artery compression by the MAL including mesenteric duplex ultrasonography, computed tomography angiography, magnetic resonance angiography, gastric tonometry, and mesenteric arteriography. Surgical intervention involves open, laparoscopic, or robotic ligament release; celiac ganglionectomy; and celiac artery revascularization. There remains a limited role for angioplasty because this intervention does not address the underlying extrinsic compression resulting in symptoms, although angioplasty with stenting may be used in recalcitrant cases. CONCLUSIONS AND RELEVANCE: Median arcuate ligament syndrome is rare, and as a diagnosis of exclusion, diagnosis and treatment paradigms can be unclear. Based on previously published studies, symptom relief can be achieved with a variety of interventions including celiac ganglionectomy as well as open, laparoscopic, or robotic intervention.

Posterior tibial vein aneurysm presenting as tarsal tunnel syndrome.

Tarsal tunnel syndrome is a compressive neuropathy of the posterior tibial nerve within the tarsal tunnel. Its etiology varies, including space occupying lesions, trauma, inflammation, anatomic deformity, iatrogenic injury, and idiopathic and systemic causes. Herein, we describe a 46-year-old man who presented with left foot pain. Work up revealed a venous aneurysm impinging on the posterior tibial nerve. Following resection of the aneurysm and lysis of the nerve, his symptoms were alleviated. Review of the literature reveals an association between venous disease and tarsal tunnel syndrome; however, this report represents the first case of venous aneurysm causing symptomatic compression of the nerve.

Elevated Autophagy and Mitochondrial Dysfunction in the Smith-Lemli-Opitz Syndrome.

Smith-Lemli-Opitz syndrome (SLOS) is a congenital, autosomal recessive metabolic and developmental disorder caused by mutations in the enzyme which catalyzes the reduction of 7-dehydrocholesterol (7DHC) to cholesterol. Herein we show that dermal fibroblasts obtained from SLOS children display increased basal levels of LC3B-II, the hallmark protein signifying increased autophagy. The elevated LC3B-II is accompanied by increased beclin-1 and cellular autophagosome content. We also show that the LC3B-II concentration in SLOS cells is directly proportional to the cellular concentration of 7DHC, suggesting that the increased autophagy is caused by 7DHC accumulation secondary to defective DHCR7. Further, the increased basal LC3B-II levels were decreased significantly by pretreating the cells with antioxidants implicating a role for oxidative stress in elevating autophagy in SLOS cells. Considering the possible source of oxidative stress, we examined mitochondrial function in the SLOS cells using JC-1 assay and found significant mitochondrial dysfunction compared to mitochondria in control cells. In addition, the levels of PINK1 which targets dysfunctional mitochondria for removal by the autophagic pathway are elevated in SLOS cells, consistent with mitochondrial dysfunction as a stimulant of mitophagy in SLOS. This suggests the increase in autophagic activity may be protective, i.e., to remove dysfunctional mitochondria. Taken together, these studies are consistent with a role for mitochondrial dysfunction leading to increased autophagy in SLOS pathophysiology.

Middle aortic coarctation.

BACKGROUND: Middle aortic coarctation (MAC), a variant of middle aortic syndrome, is a rare entity with only ∼200 cases described in the literature. It classically presents with early onset and refractory hypertension, abdominal angina, and lower extremity claudication. Although endovascular repair has been described for focal stenoses, open bypass remains the standard to restore abdominal inflow and correct renovascular hypertension. METHODS: We describe an unusually late presentation of MAC in a 52-year-old man from El Salvador with refractory hypertension since age 8 requiring 5 antihypertensive medications. He presented with acute chest pain and severe hypertension. He denied mesenteric and peripheral vascular symptoms. Distal pulses were not palpable. Creatinine was 1.9 mg/dL (peak 4.0 mg/dL). Computed tomography angiography demonstrated coarctation of the descending thoracic aorta with extensive collateralization. RESULTS: After control of blood pressure, the patient's singular anatomy dictated a descending thoracic aorta-infrarenal aortic bypass using a 16-mm woven Hemashield tube graft via a left fifth-interspace anterolateral thoracotomy and left retroperitoneal incision. The graft was tunneled through the posterior left hemidiaphragm. Patient had excellent recovery, with decrease in antihypertensive medications (5 to 2), restoration of all distal pulses, and no neurologic complications. Postoperative creatinine was 0.9 mg/dL. CONCLUSIONS: MACs are rare entities with presentation usually in youth or adolescence, comprising only 0.5-2% of all aortic coarctation cases. Etiologies include congenital, acquired, inflammatory, and infectious causes. If untreated, most patients do not survive past the fourth decade because of the sequelae of renovascular hypertension including myocardial infarction, heart failure, intracranial hemorrhage, and aortic rupture. Depending on technical considerations, open surgical bypass remains the standard repair for MAC.

Contained rupture of a pseudoaneurysm of the descending thoracic aorta related to remnant outflow graft of left ventricular assist device after heart transplantation.

The Jarvik 2000 left ventricular assist device is inserted via a left thoracotomy with the outflow graft anastomosed to the descending thoracic aorta. Removal of the device during heart transplantation involves division of the outflow graft, resulting in a retained remnant. We describe the first reported case of a mycotic pseudoaneurysm of the descending thoracic aorta related to the remnant of a left ventricular assist device outflow graft in an immunosuppressed heart recipient complicated with systemic Pseudomonas infection. The pseudoaneurysm was temporarily treated with endovascular stent grafting followed by delayed thoracotomy, pseudoaneurysm excision, and placement of an aortic interposition graft using an aortic allograft.

Management of infected caval filter with simultaneous aortic pseudoaneurysm and retroperitoneal perforation: a case report and literature review.

Inferior vena cava (IVC) filters have been reported to have complication rates up to 35%. Penetration of surrounding retroperitoneal structures is an uncommon, but potentially serious, complication, with several reports in the literature. We present a unique case of a 34-year-old intravenous drug user with infected IVC filter struts penetrating multiple structures simultaneously. Definitive operative management was necessary for removal of filter struts from the aorta, the second part of the duodenum and the iliopsoas muscle. Drainage and debridement of an associated iliopsoas abscess was performed, followed by aortic and caval reconstruction.

The role of hypoxia in stem cell differentiation and therapeutics.

Stem cells differentiate into a variety of cell lines, making them attractive for tissue engineering and regenerative medicine. Specific microenvironmental cues regulate self-renewal and differentiation capabilities. Oxygen is an important component of the cellular microenvironment, serving as both metabolic substrate and signaling molecule. Oxygen has been shown to have a variety of effects on embryonic and adult stem cells. This review examines the role of hypoxia in regulating stem cell biology, specifically focusing on growth, maintenance of pluripotency, differentiation, and production of growth factors. Particular attention is paid to hypoxia and stem cells in relation to therapeutic angiogenesis. We conclude that further study is needed to optimize the use of hypoxia as a stimulus for various stem cell functions, including its potential role in therapeutic angiogenesis.