Long-Term Drug Therapy Following Carotid Endarterectomy Aimed at Reducing Major Adverse Cardiovascular Events.

BACKGROUND: Timely carotid endarterectomy (CEA) reduces the risk of future stroke. This benefit is maximized with lifelong drug therapy aimed at reducing further major adverse cardiovascular events (MACEs), including stroke. Studies suggest that around half discontinue these drugs within 12 months. To assess if this is the case following CEA, we considered the MACE-reducing drugs prescribed several years later and compared this with the drugs they were prescribed at CEA. METHODS: The electronic primary care records of 347 post-CEA patients a mean of 108 (range 43-185) months after surgery were interrogated. The prescriptions of generic MACE-reducing drugs (antithrombotic, lipid-lowering, antihypertension and diabetes) of the 187 alive were compared with their prescriptions at CEA and with the last prescription of the 160 who had died before the late review. The post-CEA incidence of further MACE in survivors was determined. RESULTS: At late review, fewer of the post-CEA patients alive were taking antiplatelet drugs (143, 76% vs. 170, 91% P < 0.01), but more were fully anticoagulated (37v4 P < 0.01) when compared with prescriptions at CEA. Overall, there was no change in antithrombotic drug prescription rates (167, 89% vs. 172, 92%). Lipid-regulating drugs were well prescribed both at late review and at CEA (173, 93% vs. 169, 90%). The number prescribed antihypertension drugs was significantly higher at late review than at CEA (166, 89% vs. 67, 35% P < 0.01). The number treated for diabetes was similar (64, 34% vs. 42, 23%). There was no difference in the numbers of any of the MACE-reducing drugs prescribed between those who had survived to late review and those who had not. At late review, of those alive, there were 22 (12%) new strokes, and 24 (14%) had developed new or worsening ischemic cardiac symptoms. CONCLUSIONS: We found a higher than expected prescription rate of MACE-reducing drugs many years after CEA. This finding may be due, in part, to the nationalized health service in the United Kingdom.

An Analysis of Cost-Effectiveness and Clinical Outcomes of a Comprehensive Aortic Service in a Tertiary Center over One Year.

BACKGROUND: Endovascular aortic repair (EVAR) is an established and attractive alternative to open surgical repair (OSR) of abdominal aortic aneurysms (AAA) due to its superior short-term safety profile. However, opinions are divided regarding its long-term cost-effectiveness. We compared the total yearly cost of running endovascular and OSR services in a single tertiary center to determine whether fenestrated EVAR (FEVAR) represents a clinically efficacious, affordable treatment option. METHODS: A single-center retrospective review was performed on 109 patients undergoing a procedure related to index or previous abdominal aortic repair, with 1 year follow-up. Data was collected from the National Vascular Registry and hospital records. The primary outcome was cost per quality-adjusted life year. Secondary outcomes included 30-day mortality and morbidity, reintervention rates, length of hospital stay, aneurysm, and all-cause mortality at 1 year for elective index procedures. RESULTS: The average cost per patient of all FEVAR was £16,041.53 (±8,857.54), £13,893.51 (±£21,425.25) for standard EVAR, and £15,357.22 (±£15,904.49) for OSR (FEVAR versus EVAR P = 0.55, FEVAR versus OSR P = 0.83, OSR versus EVAR P = 0.76). Of the secondary outcomes, significant findings included increased length of stay and respiratory morbidity for patients undergoing open versus endovascular repair. There was no significant difference in 30-day or 1-year mortality between groups. CONCLUSIONS: FEVAR, EVAR, and OSR all represent cost-effective options for aortic repair with similar outcomes. Our data highlights the potential for FEVAR to present a viable alternative to open repair, particularly in higher-risk groups, when performed in specialist centers.

Patient acceptance and adherence to the COMPASS trial drug recommendations following symptomatic carotid endarterectomy.

INTRODUCTION: The COMPASS trial demonstrated that in patients with atherosclerotic diseases, low-dose rivaroxaban and aspirin provides greater protection against subsequent major adverse cardiovascular events (MACE) than mono-antiplatelet therapy (MAPT) alone. Drug acceptance and adherence maximises this benefit. We have assessed drug acceptance and adherence to the COMPASS drug regime in patients following carotid endarterectomy (CEA) for symptomatic carotid artery stenosis. METHODS: Following CEA, the views of 63 patients on the COMPASS drug regime were assessed using the Beliefs about Medicine Questionnaire (BMQ) and drug adherence was determined using the Sidorkiewicz scoring system. These views were compared with those of 54 patients on MAPT. Side effects (bleeding and drug reactions) and new MACE were recorded. RESULTS: Post-CEA patients on the COMPASS drug regimen had strong positive views on the necessity to take these drugs (Necessity Scale 19.6 +/- 3.6). Although there were some concerns about the COMPASS drug regimen, these were not strongly held (Concern Scale 11.8 +/-4.9) and the Necessity-Concerns Differential was positive (7.8 +/- 6.2). The Drug Adherence Score was "High" to "Good" (level of drug adherence 1.7+/-1.0). The BMQ scales and Drug Adherence Score of post-CEA patients on the COMPASS drug regimen were similar to those on MAPT. The incidence of post-CEA MACE and side effects were similar for those on the COMPASS drug regimen and MAPT. CONCLUSIONS: Post-CEA patients on the COMPASS drug regimen had positive views on taking the drugs and drug adherence was high. We did not identify any patient-related barriers to the use of the COMPASS drug regimen to further reduce cardiovascular events.

Infective Native Extracranial Carotid Artery Aneurysms: A Systematic Review.

BACKGROUND: Infective native extracranial carotid artery aneurysms are rare, and their management is variable due to a lack of evidence assessing outcomes. METHODS: We performed a systematic literature review following PRISMA guidelines to identify all reported cases of infective native extracranial carotid artery aneurysms between January 1970 and March 2021. RESULTS: This study identified 193 infective native aneurysms of the extracranial carotid artery from 154 sources. Patients were predominantly male (71.4%), and age ranged from 6 months to 89 years old. The most common presenting features were a neck mass and fever, but also included hemorrhage, respiratory distress, and neurological symptoms. Most aneurysms were located in the internal carotid artery (47.4%). Staphylococcus (23.3%) was the most commonly identified causative pathogen, followed by Mycobacterium tuberculosis (20.9%). Most appeared to become infected by direct local spread. Treatment strategies involved open surgical methods in 101 cases and an endovascular approach in 41 cases. In 4 cases, a hybrid method involving concurrent endovascular and open surgical management was undertaken. In 5 cases, there was antibiotic treatment alone. In the open surgery-treated group, the complication rate was 20.8% compared to 13.2% in the endovascular group. Mortality rate was 5.6%. CONCLUSIONS: Our review identified 193 cases of infective native extracranial carotid artery aneurysms. Direct local spread of a staphylococcus infection was the commonest cause. Endovascular management was associated with fewer early complications than open surgical management.

Does Modified Rankin Score (mRS) Matter? The Impact of Stroke Severity on Carotid Artery Endarterectomy (CEA) Outcomes.

BACKGROUND: Carotid artery endarterectomy (CEA) is recommended to reduce stroke risk in patients following nondisabling ischemic stroke (modified Rankin Score mRS<3). We reviewed CEA outcomes in patients after more devastating strokes (mRS≥3). METHODS: An observational cohort study was performed, and data were collected from 1013 CEA cases over 15 years. Patient demographics, comorbidities and postoperative outcomes were compared between preoperative mRS<3 (Group 1) and mRS≥3 (Group 2). Statistical significance was determined by P < 0.05. RESULTS: Ninety-one (9%) patients were mRS ≥3. There was no significant difference between age, gender, and operated side. Group 2 had significantly higher rates of diabetes and frailty. There was no significant difference in anesthetic type. Group 2 spent longer in High Dependency. Return to theater and postoperative complications were similar. Incidence of perioperative stroke, mortality, and readmission rates were not significant at 30 days postoperation between the 2 groups. CONCLUSIONS: Patients with a higher mRS have more preoperative comorbidities but short-term perioperative complication rate is not significantly different. Patient selection should be undertaken with care.

A Retrospective Cohort Study of Cerebrovascular Fibromuscular Dysplasia.

BACKGROUND: Fibromuscular dysplasia (FMD) is a rare vasculopathy for which limited data are available particularly from Europe. Our aim was to study the clinical characteristics of a regional cohort of carotid fibromuscular dysplasia patients to assess their clinical outcomes and the rate of vascular complications. METHODS: A retrospective cohort study of all cases of carotid/cerebrovascular FMD presenting to our regional vascular service (catchment population approximately 2 million), between 1998 and 2020. Imaging reports and patient case notes were screened using the keywords "FMD", "Fibromuscular Dysplasia", and "carotid". From case-note and imaging review, all relevant clinical data were extracted and the anatomical extent of vascular disease recorded. RESULTS: Eighty six patients with a diagnosis of cerebrovascular fibromuscular dysplasia were identified on imaging (31 computed tomography angiography, 46 magnetic resonance angiography, and 9 digital subtraction angiography) by a neurovascular radiologist. The mean age was 64 years, 78 (90%) patients were female, and 45/59 (75%) were Caucasian. Presenting clinical syndromes were Stroke/transient ischemic attack in 54 (63%) patients, symptomatic intracranial aneurysm in 6 (10%), and other neurological symptoms (headache/migraine, tinnitus) in 14 (16%), with 11 (13%) presenting incidentally. Six patients (7%) had a positive family history of FMD (2 patients) or other cerebrovascular event (4 patients: carotid dissection, intracerebral bleed, or stroke). Eight patients (9%) had a known or suspected hereditary connective tissue disorder (2 Ehlers-Danlos syndrome). Involved vessels were as follows: Carotid (mainly extracranial) in 79 (92%), vertebral 19 (22%), and a combination of these in 15 (17%) patients. Fifty eight (67%) patients had bilateral disease. Cerebrovascular complications were observed in 35 (41%) patients as follows: carotid dissection 11 (23%), carotid stenosis or occlusion 8 (9%), carotid aneurysm 8 (9%), cerebral aneurysm 9 (11%), vertebral aneurysm/dissection 2 (2%), and carotid-cavernous fistula 2 (2%). Of the 22 patients who had extracranial imaging, 14 (60%) had FMD affecting other beds-renal artery in 8 (36%) patients, other visceral arteries in 4 (18%), and aorta in 2 (9%). In addition, 4 (18%) patients had aneurysm or dissection affecting renal, splenic, and lower limb arteries. Overall, 67 (80%) patients had FMD affecting more than 1 vessel and 50 (58%) had multisite FMD (>/ = 2 vascular beds involved). Fifty nine (68%) patients were managed conservatively on close surveillance. Nineteen (21%) patients required carotid/cerebrovascular intervention and 9 (10%) required vascular intervention at other sites. Recurrent cerebrovascular events (stroke/transient ischemic attack, symptomatic Berry aneurysm) were seen in 20 (23%) patients. Overall mortality was 7% over a median follow-up period of 47 months. CONCLUSIONS: Carotid FMD patients have a high rate of multisite involvement, extracerebral vascular complications, and evidence of hereditary vasculopathy, requiring careful screening and surveillance.

Can Styloid Process and Internal Carotid Artery Anatomy be Used to Predict Carotid Artery Dissection?

BACKGROUND: Carotid artery dissection is a common cause of stroke in the young. It has been related to the association of the carotid artery with fixed neighboring anatomical structures. This study assesses the association between styloid process length, internal carotid artery position and cervical carotid artery dissection (CCAD). This information would provide potential predicative radiological measurements, which could prevent delays in CCAD diagnosis. METHODS: Retrospective data was collected from 2 central London hospitals over 5 years. CCAD cases were identified from individuals who underwent computer topography angiography of the neck for suspected CCAD. The following data was collected: evidence of CCAD; bilateral styloid process length and presence of styloid-hyoid ligament calcification; bilateral styloid process-internal carotid distance; calcification of carotid arteries and whether their position was aberrant. Cases were dissection-side, age and gender matched with two non-dissection controls. RESULTS: Three hundred and fifty-five individuals were identified. Fifty individuals had CCAD, of which 4 had bilateral dissection. In individuals with CCAD, average styloid process length was 27.5 mm and styloid process-internal carotid distance was 5.14 mm. There was no significant association between styloid process length or styloid process-internal carotid distance, and CCAD when compared with matched controls. Internal carotid artery aberrancy was significant for nondissection. CONCLUSIONS: In this study, there was no association between styloid process length and styloid process-internal carotid distance with CCAD. These measurements can not be used to predict the possibility of a CCAD following trauma.

Transmission of infection among health care personnel performing surgical tracheostomies on COVID-19 patients.

BACKGROUND: Staff and patient safety are of paramount importance while performing a surgical tracheostomy (ST) during the corona virus disease (COVID-19) pandemic. The aim was to assess the incidence of COVID-19 infection among the healthcare personnel (HCP) performing ST on COVID-19 patients. METHODS: One hundred and twenty-two HCP participating in 71 ST procedures performed at our institution between 26th March 2020 and 27th May 2020 were identified. A COVID-19 health questionnaire was distributed among staff with their consent. Data related to the presence of COVID-19 symptoms (new onset continuous cough, fever, loss of taste and/or loss of smell) among HCP involved in ST as well as patient related data were collected. RESULTS: Of the HCP who responded, eleven (15%,11/72) reported key COVID-19 symptoms and went into self-isolation. Ten members from this group underwent a COVID-19 swab test and three tested positive. Only one HCP attended hospital for symptomatic treatment, none required hospitalisation. Sixty percent (43/72) of the responders had a COVID-19 antibody test with a positive rate of 18.6% (8/43). Among the patients undergoing a ST, 67% (37/55) required a direct intensive care unit (ICU) admission; the mean age was 58 years (29-78) with a male preponderance (65.5%). The median time from intubation to ST was 15 days (range 5-33,IQR = 9). The overall mortality was 11% (6/55). CONCLUSIONS: ST can be carried out safely with strict adherence to both, personnel protective equipment and ST protocols which are vital to mitigate the potential transmission of COVID-19 to the HCP.

Aberrant right subclavian artery - a rare congenital anatomical variation causing dysphagia lusoria.

An aberrant right subclavian artery (ARSA) is a rare anatomical variation of the aortic arch. Although an incidental finding and asymptomatic in the majority of individuals, an ARSA can cause troubling symptoms during both childhood and in later life. In adulthood, the most common symptom is dysphagia, where the condition is named dysphagia lusoria. In other rare cases it can cause shortness of breath, chronic cough and hoarseness of voice amongst others. We present a case of a 65-year-old female patient who was diagnosed with dysphagia lusoria following a barium swallow examination to investigate a 10-year history of dysphagia. She was further investigated with other imaging modalities to establish her diagnosis. The dysphagia was not progressive, nor did it result in malnutrition, and hence the patient was managed conservatively. There is currently no established guideline to classify the severity of symptoms or radiological findings of this anatomical anomaly. Our case reiterates the importance of such protocols, in order to be able to avoid the risks of an unnecessary surgical procedure, whilst being sure to prevent the undertreatment of affected individuals.

Hyperglycaemia and Ischaemia Impair Wound Healing via Toll-like Receptor 4 Pathway Activation in vitro and in an Experimental Murine Model.

OBJECTIVE: Diabetes mellitus has reached epidemic proportions. Foot ulceration is a multifactorial complication of diabetes associated with marked morbidity and mortality. Innate immune Toll-like receptor 4 (TLR4) mediated inflammation has been implicated in the systemic pathogenesis of diabetes and may contribute to impairment of wound healing. This study investigates the effect of high glucose and hypoxic conditions on TLR4 activation and signalling in vitro and in vivo. METHODS: Fibroblasts cultured at physiological glucose concentration (5.5 mM) were exposed to glucose concentrations from 0 mM to 25 mM, with duplicates placed in a hypoxic chamber. TLR4 inhibition was assessed in the 25 mM glucose groups. Diabetes was induced in wild type (WT) and TLR4 knockout (KO) C57BL/6 mice by intraperitoneal injection of low dose streptozocin (STZ). Hindlimb ischaemia was induced by femoral artery ligation four weeks post streptozocin, and a full thickness 4 mm skin wound inflicted below the knee. Wound healing was assessed via digital planimetry on days 3, 7, and 14 post surgery. RESULTS: Hypoxic and high glucose (25 mM) conditions led to an increase in TLR4 protein expression, apoptosis, and interleukin (IL)-6 release. Inhibition with a TLR4 neutralising antibody and specific TLR4 antagonist ameliorated the effects of high glucose and ischaemia (p < .05). In vivo, wound healing was significantly impaired in the diabetic ischaemic group at day 14 (p < .05). Diabetic ischaemic wounds in TLR4 KO mice exhibited significantly improved healing rates compared with those in WT mice at all time points. CONCLUSION: Hypoxia stimulates upregulation of TLR4 protein expression and this effect is exaggerated by hyperglycaemia. In TLR4 KO mice, there is a significant improvement in the healing of diabetic ischaemic wounds compared with WT. It is suggested that a synergistic effect between hypoxia and hyperglycaemia impairing wound healing exists, through TLR4 mediated inflammation.

Toll-like receptors 2 and 6 mediate apoptosis and inflammation in ischemic skeletal myotubes.

Critical limb ischemia (CLI) is associated with skeletal muscle damage. However, the pathophysiology of the muscle damage is poorly understood. Toll-like receptors (TLR) have been attributed to play a role in ischemia-induced tissue damage but their role in skeletal muscle damage in CLI is unknown. TLR2 and TLR6 expression was found to be upregulated in skeletal muscle of patients with CLI. In vitro, ischemia led to upregulation of TLR2 and TLR6 by myotubes, and activation of the downstream TLR signaling pathway. Ischemia-induced activation of the TLR signaling pathway led to secretion of the pro-inflammatory cytokine interleukin-6 and muscle apoptosis, which were abrogated by neutralising TLR2 and TLR6 antibodies. Our study demonstrates that TLR2 and TLR6 are upregulated in ischemic muscle and play a role in ischemia-induced muscle damage. Thus, manipulating the TLR pathway locally may be of potential therapeutic benefit.

Role of toll-like receptor 4 in skeletal muscle damage in chronic limb-threatening ischemia.

Objective: Toll-like receptors (TLRs) are key pattern recognition receptors in the innate immune system. In particular, the TLR4-mediated immune response has been implicated in ischemia-induced tissue injury. Mounting evidence supports a detrimental role of the innate immune system in the pathophysiology of skeletal muscle damage in patients with chronic limb-threatening ischemia (CLTI), in whom patient-oriented functional outcomes are poor. The overall aim of this study was to investigate the potential role of TLR4 in skeletal muscle dysfunction and damage in CLTI. Methods: The role of TLR4 in ischemic muscle was investigated by (1) studying TLR4 expression and distribution in human gastrocnemius muscle biopsies, (2) evaluating the functional consequences of TLR4 inhibition in myotubes derived from human muscle biopsies, and (3) assessing the therapeutic potential of modulating TLR4 signaling in ischemic muscle in a mouse hindlimb ischemia model. Results: TLR4 was found to be expressed in human muscle biopsies, with significant upregulation in samples from patients with CLTI. In vitro studies using cultured human myotubes demonstrated upregulation of TLR4 in ischemia, with activation of the downstream signaling pathway. Inhibition of TLR4 before ischemia was associated with reduced ischemia-induced apoptosis. Upregulation of TLR4 also occurred in ischemia in vivo and TLR4 inhibition was associated with decreased inflammatory cell infiltration and diminished apoptosis in the ischemic limb. Conclusions: TLR4 is upregulated and activated in ischemic skeletal muscle in patients with CLTI. Modulating TLR4 signaling in vitro and in vivo was associated with attenuation of ischemia-induced skeletal muscle damage. This strategy could be explored further for potential clinical application.

A Stepwise Haemostasis Intraoperative Protocol Driven Reduction of Haematoma Rate Following Symptomatic Carotidendarterectomy.

INTRODUCTION: Carotid endarterectomy (CEA) for symptomatic stenosis reduces further stroke risk. Post-CEA haematoma increases the risk of complications including stroke. There are few studies considering protocols aimed at reducing post-CEA haematoma rates. Presented are the outcomes of a protocol developed to reduce this surgical complication. METHOD: The protocol was implemented in 112 consecutive CEA. It involves stepwise additional measures to ensure haemostasis before wound closure. Attention to bleeding points is followed by light compression for 10 min. Protamine is then given if haemostasis has not been achieved. If after 20 min the problem persists Tranexamic acid is given. Following a further 20 min if haemostasis is not yet achieved a platelet transfusion is undertaken. Haematoma rates, return to theatre for post-operative haematoma and other complications were compared with 100 consecutive pre-protocol introduction CEA cases. RESULTS: Of 112 CEA patients, 19 received protamine, 8 protamine and tranexamic acid. One case required platelet transfusion. Neck haematoma rate fell from 10 to 3 cases (P = .02, OR: 0.25 [95% CI .07-.94]), of which returned to theatre for haematoma evacuation fell from 6 to 1 case (P = .03, OR: 0.14 [95% CI .02-1.19]). 30 day stroke and death rate reduced from 5% to 1.8% (P = .11, OR: 0.35 [95% CI .07-1.82]). CONCLUSION: The stepwise haemostasis intraoperative protocol can reduce post-CEA haematoma rates.

Development of an in vitro model of myotube ischemia.

Critical limb ischemia causes severe damage to the skeletal muscle. This study develops a reproducible model of myotube ischemia by simulating, in vitro, the critical parameters that occur in skeletal muscle ischemia. Monolayers of C2C12 myoblasts were differentiated into mature myotubes and exposed to nutrition depletion, hypoxia and hypercapnia for variable time periods. A range of culture media and gas mixture combinations were used to obtain an optimum ischemic environment. Nuclear staining, cleaved caspase-3 and lactate dehydrogenase (LDH) release assay were used to assess apoptosis and myotube survival. HIF-1α concentration of cell lysates, pH of conditioned media as well as partial pressures of oxygen (PO2) and carbon dioxide (PCO2) in the media were used to confirm ischemic simulation. Culturing myotubes in depleted media, in a gas mixture containing 20% CO+80% N2 for 6-12 h increased the PCO2 and decreased the pH and PO2 of culture media. This attempts to mimic the in vivo ischemic state of skeletal muscle. These conditions were used to study the potential tissue-protective effects of erythropoietin (EPO) in C2C12 myotubes exposed to ischemia. EPO (60 ng/ml) suppressed LDH release, decreased cleaved caspase-3 and reduced the number of apoptotic nuclei, suggesting significantly decreased ischemia-induced apoptosis in myotubes (P<0.01) and a potential role in tissue protection. Additional therapeutic agents designed for tissue protection can also be evaluated using this model.

SARS-CoV-2 and Pre-existing Vascular Diseases: Guilt by Association?

Severe Acute Respiratory Syndrome coronavirus-2 has rapidly spread and emerged as a pandemic. Although evidence on its pathophysiology is growing, there are still issues that should be taken into consideration, including its effects on pre-existing peripheral vascular disease. The aim of this review is to describe the thrombotic and endothelial dysfunctions caused by SARS-CoV-2, assess if cardiovascular comorbidities render an individual susceptible to the infection and determine the course of pre-existing vascular diseases in infected individuals. A search through MEDLINE, PubMed and EMBASE was conducted and more than 260 articles were identified and 97 of them were reviewed; the rest were excluded because they were not related to the aim of this study. Hypertension, cardiovascular disease, diabetes mellitus and cerebrovascular diseases comprised 24.30% ± 16.23%, 13.29% ± 12.88%, 14.82% ± 7.57% and 10.82% ± 11.64% of the cohorts reviewed, respectively. Arterial and venous thrombotic complications rocketed up to 31% in severely infected individuals in some studies. We suggest that hypertension, cardiovascular diseases, diabetes and cerebrovascular diseases may render an individual susceptible to severe COVID-19 infection. Pre-existing vascular diseases are expected to deteriorate with SARS-CoV-2 infection as a consequence of its increased thrombotic burden and the development of endothelial dysfunction. COVID-19 has emerged only a few months ago and it is premature to predict the long-term effects to the vascular system. Its disturbances of the coagulation mechanisms and effects on vascular endothelium will likely provoke a surge of vascular complications in the coming months.

Dual-modality emergency management of a rare cause of an aorto-oesophageal fistula: a case report.

Aorto-oesophageal fistula (AOF) is a life-threatening condition that usually presents with upper gastro-intestinal haemorrhage. This case report details the emergency presentation and management of a 51-year-old male who presented with hematemesis secondary to an impacted denture (ingested two years previously) in the oesophagus that had led to an AOF. This necessitated urgent thoracic endovascular aortic repair followed by thoracotomy, oesophagotomy, T-tube insertion and oesophagostomy. This is the first documentation in the literature of the dual-modality management for this rare cause of AOF and demonstrates the multidisciplinary approach to successful management of this complex yet rare presentation.

Angiogenic effects of stromal cell-derived factor-1 (SDF-1/CXCL12) variants in vitro and the in vivo expressions of CXCL12 variants and CXCR4 in human critical leg ischemia.

PURPOSE: Critical leg ischemia (CLI) is associated with a high morbidity and mortality. Therapeutic angiogenesis is still being investigated as a possible alternative treatment option for CLI. CXCL12, a chemokine, is known to have two spliced variants, CXCL12alpha and CXCL12beta, but the significance remains unknown. The study investigated the angiogenic effects of CXCL12, protein expressions of CXCL12, and the receptor CXCR4 in human CLI. METHODS: In vitro, human microvascular endothelial cells (HMEC-1) were used. Cell proliferation was assessed using methylene blue assay and cell count method. Apoptosis was determined by counting the pyknotic nuclei after 4'-6-diamidino-2-phenylindole staining and confirmed by caspase-3 assay. We employed matrigel as capillary tube formation assay. The activity of signaling pathways was measured using Western blotting. In vivo, gastrocnemius biopsies were obtained from the lower limbs of patients with CLI and controls (n = 12 each). Immunohistochemistry, double immunofluorescence labeling, and Western blotting were then performed. RESULTS: CXCL12 attenuated HMEC-1 apoptosis (P < .01), stimulated cell proliferation (P < .05) and capillary tube formation (P < .01). Compared with CXCL12alpha, CXCL12beta has a greater effect on apoptosis and cell proliferation (P < .01). Treatment with both variants resulted in time-dependent activation of PI3K/Akt and p44/42 but not p38 MAP kinase. In CLI, CXCL12alpha was expressed by skeletal muscle fibers with minimal expression of CXCL12beta. CXCR4 was extensively expressed and colocalized to microvessels. A significant 2.6-fold increase in CXCL12alpha and CXCR4 expressions (P < .01) were noted in CLI but not for CXCL12beta (P > .05). CONCLUSIONS: The study showed that CXCL12beta had more potent angiogenic properties but was not elevated in human CLI biopsies. This provided an interesting finding on the role of CXCL12 variants in pathophysiologic angiogenic response in CLI.

The role of fibrinogen and fibrinolysis in peripheral arterial disease.

Peripheral arterial disease (PAD) is associated with high rates of cerebrovascular and cardiovascular events; PAD is a marker of systemic atherosclerosis. As a result, standard therapy for all PAD patients should be directed at both peripheral and systemic atherosclerosis. Modification of established risk factors in the form of smoking cessation, correcting hypertension, optimizing diabetic control and normalizing lipids is essential. Furthermore, novel risk factors have emerged including fibrinogen and other hemostatic factors. Fibrinogen is a coagulation factor and a marker of the acute phase response (inflammation), a platelet activator, a major determinant of plasma viscosity and a component of the atherosclerotic plaque. Fibrinogen appears not only to predict the severity of PAD, but also serves as a marker for future development of PAD. Whether reducing the levels of fibrinogen and other coagulation factors will decrease the incidence and progression of PAD remains to be resolved. This review summarizes the role of fibrinogen in the pathogenesis of PAD and its association with other hemostatic factors. The role of fibrinolysis in patients with PAD is also considered.

Does diabetes mellitus play a role in restenosis and patency rates following lower extremity peripheral arterial revascularization? A critical overview.

Patients with diabetes mellitus (DM) are at increased risk of developing lower extremity peripheral arterial disease (PAD). The effect of DM on restenosis and patency rates in patients with PAD undergoing surgical revascularization or percutaneous interventions has not been fully clarified. We therefore critically reviewed the role of DM in restenosis, as well as primary and secondary patency rates in these patients. We searched Medline for studies investigating the effect of DM on restenosis (primary and secondary patency) rates in patients undergoing surgical/percutaneous interventions for the treatment of lower extremity PAD. Search terms used were "diabetes and peripheral arterial disease," "angioplasty," "restenosis," "revascularization," "patency rates," and "in-stent restenosis." Diabetic patients with PAD have similar restenosis, primary patency, and secondary patency rates compared with nondiabetic patients. However, mortality and amputation rates are increased in patients with DM. This increased risk of mortality and amputation may distort the estimation of restenosis and patency rates. Strict glucose control should be implemented in diabetic patients. Additionally, the use of antiplatelet agents and statins may have a beneficial effect on restenosis and patency rates. The role of radiation therapy in preventing restenosis remains to be determined. Patients with PAD and DM should receive optimal medical therapy to improve cardiovascular outcome and decrease functional decline. The direct involvement of vascular surgeons in the management of PAD patients is essential to reduce the incidence of cardiovascular events and mortality rates.

Endovascular aortic aneurysm repair (EVAR) has significantly lower perioperative mortality in comparison to open repair: a systematic review.

OBJECTIVE: The objective of this meta-analysis was to evaluate the effectiveness of endovascular abdominal aortic aneurysm repair (EVAR) in reducing inhospital mortality against open graft replacement for aortic aneurysm. METHODS: Generic terms including EVAR, endovascular aneurysm repair and aortic endografting were used to search a variety of electronic databases. Based on selection criteria, decisions regarding inclusion and exclusion of primary studies were made. RESULTS: A total of three randomized controlled trials on 1,468 patients were included. In the EVAR group, 12 of 759 (1.5%) patients died, compared to 33 of 709 (4.6%) patients who died in the open surgery group. In both the fixed and random effect models, EVAR was associated with statistically significantly lower perioperative mortality when compared to open surgical repair of aortic aneurysm. The risk ratio of 0.33 indicates that mortality is 3.3 times more likely in the open surgery group compared to the EVAR group. CONCLUSION: EVAR carries a threefold lower risk of perioperative death in comparison to open repair of abdominal aortic aneurysm. This early advantage must be offset against the increased need for later re-intervention and probable equivalence of long-term outcome. In older and high operative risk patients, EVAR should be the treatment of choice.