Increased Serum KLF4 in Severe Atheromatosis and Extensive Aneurysmal Disease.

BACKGROUND: Krüppel-like factor 4 (KLF4) is known to preserve vascular homeostasis. In the present study, we sought to correlate serum KLF4 levels with arterial aneurysm size and their clinical presentation. We also explored the association between serum KLF4 levels and the severity of extracranial carotid and peripheral arterial disease. METHODS: Patients undergoing surgery for various forms of atheromatosis (ATH group) or for arterial aneurysm repair (AA group) were eligible for inclusion. KLF4 levels were measured via enzyme-linked immunosorbent assay. RESULTS: Patients in the atheromatic and aneurysmal groups had significantly higher serum KLF4 levels compared with controls. Patients with permanent end-organ damage (ATH3) had higher serum KLF4 (6.96 ± 0.75 pg/mL) compared with patients with asymptomatic internal carotid stenosis >70% or claudication (ATH1) (2.76 ± 0.68 pg/mL; mean difference [MD], -4.20; 95% confidence interval [95% CI], -5.35 to -3.04; P < 0.01) and those with transient ischemic attack or rest pain (ATH2) (4.47 ± 1.08 pg/mL; MD, -2.48; 95% CI, -3.76 to -1.21). Furthermore, patients with an asymptomatic aneurysm of a diameter 250-300% of that of the normal artery (AA1, 5.01 ± 1.08 pg/mL) had considerably lower serum KLF4 compared with those suffering from either a symptomatic aneurysm or an asymptomatic aneurysm of a diameter >350% of that of normal artery (AA3, 6.63 ± 1.92 pg/mL; MD, -2.61; 95% CI, -5.04 to -0.18; P < 0.01). CONCLUSIONS: Serum KLF4 levels are significantly increased in patients with end-organ damage related to atheromatosis as well as those with extensive aneurysmal disease.

Expression of MMP-2, MMP-9, and NGAL in Tissue and Serum of Patients with Vascular Aneurysms and Their Modulation by Statin Treatment: A Pilot Study.

BACKGROUND: Matrix metalloproteinases (MMPs) are involved in vascular wall degradation, and drugs able to modulate MMP activity can be used to prevent or treat aneurysmal disease. In this study, we evaluated the effects of statins on MMP-2, MMP-9, and neutrophil gelatinase-associated lipocalin (NGAL) in both plasma and tissue in patients with aneurysmal disease. METHODS: We performed a prospective, single-blind, multicenter, control group clinical drug trial on 184 patients of both sexes >18 years old with a diagnosis of arterial aneurysmal disease. Enrolled patients were divided into two groups: Group I under statin treatment and Group II not taking statins. In addition, 122 patients without aneurysmal disease and under statin treatment were enrolled as a control group (Group III). The expression of MMPs and NGAL in plasma was evaluated using ELISA, while their expression in endothelial tissues was evaluated using Western blot. RESULTS: The ELISA test revealed greater plasma levels (p < 0.01) of MMPs and NGAL in Groups I and II vs. Group III. Western blot analysis showed higher expression (p < 0.01) of MMPs and NGAL in Group II vs. Group I, and this increase was significantly higher (p < 0.01) in patients treated with low potency statins compared to high potency ones. CONCLUSIONS: MMPs and NGAL seem to play a major role in the development of aneurysms, and their modulation by statins suggests that these drugs could be used to prevent arterial aneurysmal disease.

Comparison of Clinical and Hematologic Factors Associated with Stenosis and Aneurysm Development in Patients with Atherosclerotic Arterial Disease.

BACKGROUND: Atherosclerosis is known to result in individuals with arterial stenosis or occlusion. Alternatively, certain atherosclerotic arteries develop aneurysms. However, there has been no clear explanation regarding the mechanism associated with this alternate clinical presentation. This study aimed to investigate the clinical and hematologic factors that could lead to the development of the different clinical outcomes of stenosis and aneurysm in atherosclerotic arterial disease. METHODS: From March 2016 to January 2018, 219 consecutive atherosclerotic patients, of whom 195 (171 men, 24 women) had stenosis or occlusion and 24 (19 men, 5 women) had aneurysm, were investigated. All patients underwent vascular procedures. Continuous variables studied were age, body mass index, smoking status (pack-years), frequency of alcohol consumption (days), levels of natural anticoagulants (protein C, protein S, and antithrombin III), coagulation-enhancing factors (factor VIII, fibrinogen, and homocysteine), antiphospholipid antibodies (lupus anticoagulant, immunoglobulin [Ig] G/IgM anticardiolipin antibody, and IgG/IgM anti-beta 2 glycoprotein I [anti-ß2GPI]), lipids (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride), and hemoglobin A1c. The investigated nominal variables were sex, diabetes mellitus, and hypertension. RESULTS: A logistic regression analysis of all nominal and continuous variables as independent variables revealed that IgM anticardiolipin antibody was a significant independent factor associated with aneurysm formation in atherosclerotic arterial disease (P = 0.042). CONCLUSIONS: A higher IgM anticardiolipin antibody level may be one of the causative factors behind aneurysm development and may have the clinical potential to be used as a biomarker to predict the development of aneurysms in atherosclerotic arterial disease.

Systemic response of coated-platelet and peripheral blood inflammatory cell indices after aneurysmal subarachnoid hemorrhage and long-term clinical outcome.

PURPOSE: Post-hemorrhage period after aneurysmal subarachnoid hemorrhage (aSAH) has several systemic manifestations including prothrombotic and pro-inflammatory states. Inter-relationship between these states using established/routine laboratory biomarkers and its long-term effect on clinical outcome is not well-defined. MATERIALS AND METHODS: Retrospective analysis of prospective cohort of 44 aSAH patients. Trend of procoagulant biomarkers [coated-platelets, mean platelet volume to platelet count (MPV:PLT)] and peripheral inflammatory biomarkers [platelet-lymphocyte ratio (PLR), neutrophil-platelet ratio (NLR)] were analyzed using regression analysis. Occurrence of delayed cerebral ischemia (DCI), modified Rankin score (mRS) of 3-6 and Montreal cognitive assessment (MoCA) of <26 at 1-year defined adverse clinical outcome. RESULTS: Patients with worse mRS and MoCA score had higher rise in coated-platelet compared to those with better scores [20.4 (IQR: 15.6, 32.9) vs. 10.95 (IQR: 6.1, 18.9), p = 0.003] and [16.9 (IQR: 13.4, 28.1) vs. 10.95 (IQR: 6.35, 18.65), p = 0.02] respectively. NLR and PLR trends showed significant initial decline followed by a gradual rise in NLR among those without DCI as compared to persistent low levels in those developing DCI (0.13 units/day vs. -0.07 units/day, p = 0.06). CONCLUSIONS: Coated-platelet rise after aSAH is associated with adverse long-term clinical outcome. NLR and PLR trends show an early immune-depressed state after aSAH.

Anaemia in patients who underwent vascular surgery: a significant predictor of amputation and death. / Anemia en pacientes sometidos a cirugía vascular, factor predictor de amputación y muerte.

BACKGROUND AND OBJECTIVE: In patients with peripheral artery disease requiring surgery, anaemia has been found to independently predict short and medium term higher morbidity and mortality. PATIENTS AND METHODS: We retrospectively studied all patients undergoing surgery, consecutively during 2months in 12 vascular surgery units. We analysed cardiovascular risk factors and preoperative haemoglobin. Statistical analysis was done with Kaplan-Meier for survival and logistic regression modelling to identify predictors of mortality. RESULTS: 518 patients were consecutively operated on in our vascular units, the mortality rate was 21% the first year and 34% for cardiovascular events. Preoperative anaemia was present in 63% of the ischemic patients and in 23% of the patients requiring aneurysm repair, one year after surgery it increased to 68% and 50% respectively. When preoperative anaemia was superior to 10mg/dl, one year survival increased (96% vs. 90%), fewer cardiovascular events occurred and there were fewer amputations (24% vs. 68%). CONCLUSIONS: On multivariable analysis: age, renal failure, chronic lung disease, coronary artery disease, postoperative complications and previous cardiovascular events were associated with an increased risk mortality rate. Preoperative haemoglobin influenced proportionally such that for every 1mg /dl increase, the probability of mortality decreases by 0.81. Preoperative anaemia, especially when haemoglobin is inferior to 10mg/dl, is associated with an increased risk of death and amputation.

Associations between serum relaxin 2, aneurysm formation/size and severity of atherosclerosis: a preliminary prospective analysis.

Serum relaxin 2 (RL2) is a pleiotropic hormone that acts on various organs and systems, particularly the cardiovascular system. Although RL2 seems to upregulate the synthesis of nitric monoxide (NO) and matrix metalloproteinase (MMP)-2 and -9, current literature on its role in atherosclerosis and aneurysm formation is scarce. The aim of this study was to investigate the levels of serum RL2 in patients with an arterial aneurysm as well as in atherosclerotic patients, and correlate them with the severity of their related vascular disease. A total of 53 subjects were enrolled in this study: 37 patients were scheduled to undergo surgery: 21 patients for different forms of atherosclerotic disease (ATH), 16 patients for an arterial aneurysm (AA), 6 patients for undergoing temporal artery biopsy (TAB), and 10 healthy blood donors (HBD) served as the control groups. RL2 was measured using enzymelinked immunosorbent assay. RL2 was significantly higher in AA patients compared to ATH (P<0.01), TAB (P<0.001) and HBD (P<0.01). No significant difference was found between the ATH and TAB groups (P>0.05). In addition, ATH and AA patients were further subdivided based on the severity of their disease. Serum RL2 was progressively increased in patients with arterial aneurysms, showing a positive relationship with the size of the aneurysmatic dilatation. By contrast, the RL2 level was inversely related to the severity of the atherosclerotic disease. Studies with a larger cohort incorporating a consistent study population are warranted to verify our results and shed light on the mechanistic background of these processes.

Population Pharmacokinetics of Combined Intravenous and Local Intrathecal Administration of Meropenem in Aneurysm Patients with Suspected Intracranial Infections After Craniotomy.

BACKGROUND AND OBJECTIVE: For patients with intracranial infection, local intrathecal administration of meropenem may be a useful method to obtain a sufficient drug concentration in the cerebral spinal fluid (CSF). However, a large inter-individual variability may pose treatment efficacy at risk. This study aimed to identify factors affecting drug concentration in the CSF using population pharmacokinetics method. METHODS: After craniotomy, aneurysm patients with an indwelling lumbar cistern drainage tube who received a combined intravenous and intrathecal administration of meropenem for the treatment of suspected intracranial infection were enrolled. Venous blood and CSF specimens were collected for determining meropenem concentrations. Nonlinear mixed-effects modeling method was used to fit blood and CSF concentrations simultaneously and to develop the population pharmacokinetic model. The proposed model was applied to simulate dosage regimens. RESULTS: A three-compartmental model was established to describe meropenem in vivo behavior. Lumbar CSF drainage resulted in a drug loss, and drug clearance in CSF (CLCSF) was employed to describe this. The covariate analysis found that the drainage volume (mL/day) was strongly associated with CLCSF, and the effect of creatinine clearance was significant on the clearance of meropenem in blood (CL). Visual predictive check suggested that the proposed pharmacokinetic model agreed well with the observations. Simulation showed that both intravenous and intrathecal doses should be increased with the increases of minimum inhibitory concentration and daily CSF drainage volume. CONCLUSION: This model incorporates covariates of the creatinine clearance and the drainage volume, and a simple to use dosage regimen table was created to guide clinicians with meropenem dosing.

Myocardial infarction masquerading as myocarditis in a patient with factor V Leiden: unmasked with MR.

We present a case of a 21-year-old man presenting with sharp left-sided chest pain. A CT pulmonary angiogram was negative, ECG was unremarkable and a mild troponin rise was observed. Myocarditis was suspected as the most likely diagnosis, particularly in view of the patient's previous diagnosis of myocarditis 3 years prior. A cardiac MRI was indicative of an acute mid-anterior myocardial infarction (MI) and an old inferior MI with an associated aneurysm. A subsequent angiogram revealed a subtotal occlusion in the second diagonal artery, likely precipitated by homozygous factor V Leiden.This case illustrates the value of MRI in differentiating acute MI from myocarditis when clinical suspicion is low, as in this young patient with atypical chest pain. Further, it demonstrates the value of MRI in detecting previous MIs and reinforces the importance of searching for precipitants of MI in young patients.

Rotura de un aneurisma gigante de arteria hepática / Ruptured giant hepatic artery aneurysm

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Tratamiento endovascular de la enfermedad aneurismática renal / Endovascular treatment of renal aneurysm disease

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Plasma D-dimer as a predictor of the progression of abdominal aortic aneurysm.

Essentials D-dimer could provide important information about abdominal aortic aneurysm (AAA) progression. The greatest diameter of the infrarenal aorta and the value of plasma D-dimer were determined. AAA progression is correlated with increasing plasma D-dimer levels. The increasing value of plasma D-dimer could be a predictor of aneurysm progression. SUMMARY: Background The natural course of abdominal aortic aneurysm (AAA) is mostly asymptomatic and unpredictable. D-dimer could provide potentially important information about subsequent AAA progression. Objectives The aims of this study were to establish the relationship between the progression of an abdominal aortic aneurysm (AAA) and plasma D-dimer concentration over a 12-month period and determine the value of plasma D-dimer in patients with sub-aneurysmal aortic dilatation. Patients/Methods This was a prospective observational study that involved 33 patients with an AAA, 30 patients with sub-aneurysmal aortic dilatation and 30 control subjects. The greatest diameter of the infrarenal aorta, which was assessed by ultrasound, and the value of plasma D-dimer were determined for all subjects at baseline assessment, as well as after 12 months for those with an AAA. Results A positive correlation was found between the diameter of an AAA and plasma D-dimer concentration at the baseline and the control measurement stages. There was a strong positive correlation between AAA progression and increasing plasma D-dimer concentration over a 12-month period. Among patients with sub-aneurysmal aortic dilatation (n = 30), the value of plasma D-dimer was higher compared with matched controls (n = 30). Conclusions There is a strongly positive correlation between AAA progression and increasing plasma D-dimer concentration. The value of plasma D-dimer is higher in patients with sub-aneurysmal aortic dilatation than in control subjects.

Hyperglycemia Suppresses Calcium Phosphate-Induced Aneurysm Formation Through Inhibition of Macrophage Activation.

BACKGROUND: The aim of this study was to elucidate aspects of diabetes mellitus-induced suppression of aneurysm. We hypothesized that high glucose suppresses aneurysm by inhibiting macrophage activation via activation of Nr1h2 (also known as liver X receptor ß), recently characterized as a glucose-sensing nuclear receptor. METHODS AND RESULTS: Calcium phosphate (CaPO4)-induced aneurysm formation was significantly suppressed in the arterial wall in type 1 and 2 diabetic mice. A murine macrophage cell line, RAW264.7, was treated with tumor necrosis factor α (TNF-α) plus CaPO4 and showed a significant increase in matrix metalloproteinase 9 (Mmp9) mRNA and secreted protein expression compared with TNF-α alone. Elevated Mmp9 expression was significantly suppressed by hyperglycemic conditions (15.5 mmol/L glucose) compared with normoglycemic conditions (5.5 mmol/L glucose) or normoglycemic conditions with high osmotic pressure (5.5 mmol/L glucose +10.0 mmol/L mannitol). Nr1h2 mRNA and protein expression were suppressed by treatment with TNF-α plus CaPO4 but were restored by hyperglycemic conditions. Activation of Nr1h2 by the antagonist GW3965 during stimulation with TNF-α plus CaPO4 mimicked hyperglycemic conditions and inhibited Mmp9 upregulation, whereas the deactivation of Nr1h2 by small interfering RNA (siRNA) under hyperglycemic conditions canceled the suppressive effect and restored Mmp9 expression induced by TNF-α plus CaPO4. Moreover, Nr1h2 activation with GW3965 significantly suppressed CaPO4-induced aneurysm in mice compared with vehicle-injected control mice. CONCLUSIONS: Our results show that hyperglycemia suppresses macrophage activation and aneurysmal degeneration through the activation of Nr1h2. Although further validation of the underlying pathway is necessary, targeting Nr1h2 is a potential therapeutic approach to treating aneurysm.

Numerical simulation of unsteady micropolar hemodynamics in a tapered catheterized artery with a combination of stenosis and aneurysm.

The unsteady flow characteristics of blood are analyzed through a catheterized stenotic artery with post-stenotic dilatation. A rigid tube with a pair of abnormal wall segments in close proximity to each other is employed to geometrically simulate the diseased artery. A micropolar fluid model is used to capture the rheological characteristics of the streaming blood in the annulus. The mild stenosis approximation is employed to derive the governing flow equation which is then solved using a robust finite difference method. Particular attention is paid to the effects of geometrical parameters of the arterial wall and rheological parameters of the blood on axial velocity, flow rate, resistance impedance and wall shear stress. The global behavior of blood is also analyzed through instantaneous pattern of streamlines.

Aneurisma gastroduodenal presentado como masa pancreática / Gastroduodenal artery aneurysm presenting as a pancreatic mass

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Surgical treatment of giant aneurysm of hepatic artery: report of three cases.

BACKGROUND/AIMS: To explore the surgical way of treating giant hepatic artery aneurysm(HAA). METHODOLOGY: Three hepatic artery aneurysm patients who were performed aneurysm resection without revascularization of the hepatic artery were reviewed. After surgery, the values of liver function and enhanced CT scan of the patients were followed. RESULTS: All the three patients were recovered well postoperatively and only several values of biochemistry marks of liver function as ALT, AST, TBIL and DB in one case with liver cirrhosis were elevated and decreased to normal ranges in a few days postoperatively. The values of biochemistry marks of liver function in other two cases were within normal limits. The enhanced CT scan also showed arteries in the liver after hepatic artery aneurysm resection. CONCLUSIONS: Giant HAA may be safely removed without revascularization of the hepatic artery.

Microaneurysm formation rate as a predictive marker for progression to clinically significant macular edema in nonproliferative diabetic retinopathy.

PURPOSE: To evaluate the predictive value of microaneurysm (MA) formation rate concerning the development of clinically significant macular edema (CSME) in patients with mild-to-moderate nonproliferative diabetic retinopathy as evaluated by an automated analysis of central field fundus 30° photographs. METHODS: Two hundred and eighty-seven eyes were included in the study. Photographs obtained at Day 0, at 6, and 12 months were analyzed using the RetmarkerDR software (Critical Health SA) in a masked manner, and the MA formation rate was documented. A threshold of a calculated MA formation rate of 2 or more was chosen to consider a patient "positive." The ability to predict CSME development was then calculated for a period of up to 5 years. HbA1c values, blood pressure, or duration of diabetes were also evaluated. RESULTS: The study population consisted of 89 male and 59 female patients with a mean age of 57.6 years, a mean HbA1c of 7.8, and a mean duration of diabetes of 12.3 years. Forty-seven of 287 eyes (16.4%) developed CSME during follow-up. An increased MA formation rate of >2 MA was clearly associated with development of CSME. Using the automated analysis and a threshold of 2 or more new MA, the authors were able to identify 70.2% of the eyes that developed CSME during follow-up ("true positive") and using a threshold of up to 2 new MA, 71.7% of the patients that did not develop CSME ("true negative"). No significant differences concerning baseline and 1-year HbA1c levels within patient eyes that developed CSME compared with patient eyes below or over the calculated threshold of 2 MA (P = 0.554 and P = 0.890, respectively) were seen. The positive and negative predictive value was calculated to be 33% versus 92.5%, sensitivity was 70%, and specificity was 72%. CONCLUSION: Using the RetmarkerDR software, the authors were able to identify patients with higher risk to develop CSME during follow-up using a threshold of 2 or more MA formation rate. Together with the high negative predictive value, the automated analysis may help to determine the individual risk of a patient to develop sight-threatening complications related to diabetic retinopathy and schedule individual screening intervals.

Decreased levels and function of circulating endothelial progenitor cells in unruptured intracranial saccular aneurysm patients.

Circulating endothelial progenitor cells (EPCs) play a critical role in maintaining endothelial integrity and keeping vascular homeostasis. Previously, we reported that EPCs were involved in repair and remodeling of aneurismal wall. In the present study, we verified this hypothesis by investigating the proliferative ability and count of EPCs in peripheral blood of patients with unruptured intracranial aneurysms (UIAs). Twenty-four patients with UIAs (UIA group) and 24 negative controls (control group) were included in this study. Peripheral blood monocytes (PBMCs) were harvested and selectively cultured. The colony-forming ability of cultured cells was analyzed and the biological functions were examined by testing the adsorption of ulex europaeus agglutinin-1 labeled by fluorescein isothiocyanate and acetylated low-density lipoprotein internalization. The migratory and adhesive ability of cultured EPCs were assessed. In vitro cultured PBMCs were identified as EPCs by examining surface markers CD34, CD133 and vascular endothelial growth factor receptor 2 using flow cytometry. EPCs from UIA group possessed significantly decreased proliferative, migratory and adhesive capacities compared with EPCs from control group. Furthermore, EPCs count in UIA group was significantly decreased. Collectively, these results indicated that the circulating EPCs of UIA patients may be involved in intracranial aneurysm repair and remodeling.

Repair of a large main pulmonary artery aneurysm in a 71-year-old Jehovah's Witness patient.

Pulmonary artery aneurysm is a rarely reported and poorly studied entity; most mentions in the literature are in case series and case reports. Cardiac surgery in Jehovah's Witness patients is occurring more frequently because of improved techniques of blood conservation. We report the repair of a large pulmonary artery aneurysm in a 71-year-old woman who was a Jehovah's Witness. Using total cardiopulmonary bypass, we replaced the main pulmonary artery and both branches with Gelweave tube-grafts, because the fragility of a homograft presented possible bleeding problems. The patient recovered rapidly, and her symptoms were greatly improved. We think that a patient's status as a Jehovah's Witness need not preclude potentially life-saving cardiac operations.