Serum levels of IL-32 in patients with coronary artery disease and its relationship with the serum levels of IL-6 and TNF-α.

The coronary artery disease (CAD) is a chronic inflammatory disease caused by atherosclerosis, in which arteries become clogged due to plaque formation, fat accumulation, and various sorts of immune cells. IL-32 is a proinflammatory cytokine, which enhances inflammation through inducing the secretion of different inflammatory cytokines. The main objective of the current study was to assess the serum levels of IL-32 in subjects with obstructive CAD and its relationship with the serum levels of IL-6 and TNF-α. This study was performed on 42 subjects with obstructive CAD and 42 subjects with non-obstructive CAD. The serum levels of TNF-α, IL-6, and IL-32 were measured using the enzyme-linked immunosorbent assay (ELISA). The serum levels of TNF-α, IL-6, and IL-32 were 3.2, 3.48, and 2.7 times higher in obstructive CAD compared to non-obstructive CAD, respectively. Moreover, the serum levels of TNF-α and IL-32 in obstructive CAD with cardiac arterial stenosis in one major vessel were significantly higher than the levels in obstructive CAD with cardiac arterial stenosis in more than one major vessel. ROC curve analysis revealed that the serum levels of TNF-α, IL-6, and IL-32 were good predictors of obstructive CAD. Moreover, multiple logistic regression analyses suggested that the serum levels of TNF-α, IL-6, IL-32, LDL, and ox-LDL were independently related to the presence of obstructive CAD, while serum levels of HDL were not. TNF-α, IL-32, and IL-6 showed an increase in obstructive CAD, and the serum levels of these cytokines showed a satisfactory ability for predicting obstructive CAD.

Cancer Therapy-Associated Thrombosis.

[Figure: see text].

Low-density lipoprotein (LDL) levels and risk of arterial occlusive events in chronic myeloid leukemia patients treated with nilotinib.

Recommendations for dyslipidemia management aimed at reducing arterial occlusive events (AOEs) have been recently published. So far, no data have been reported on the management of dyslipidemia in chronic myeloid leukemia (CML) patients treated with nilotinib. We investigated 369 CML adult patients, stratified according to the new Systematic Coronary Risk Evaluation (SCORE) scoring system. Plasma levels of cholesterol, HDL, LDL, and triglycerides were measured prior to the start of nilotinib and after 3, 6, and 12 months. The 5-year cumulative incidence of AOEs was 15.9%. Patients with cholesterol levels > 200 mg/dL and LDL > 70 mg/dL 3 months after treatment showed a significantly higher incidence of AOEs (21.9 ± 4.6% vs 6.2 ± 2.5, P = 0.003). Patients belonging to the high and very high SCORE risk group showed a significant increase of AOEs (34.4 ± 6% vs 10 ± 2.1%, P < 0.001). In multivariate analysis, both high cholesterol and LDL levels and a high and very high SCORE risk remained significantly associated with the risk of AOEs (P = 0.008; HR = 3.5; 95% CI = 1.4-8.7 and P < 0.001; HR = 4.4; 95% CI = 2-9.8, respectively). Overall, 78 patients (21.1%) presented dyslipidemia at the time of CML diagnosis and 88 (23.3%) after starting nilotinib, but only 26 of them (29.5%) were treated with statins.Low LDL and cholesterol plasma levels are associated with a significant lower risk of AOEs in CML patients treated with nilotinib in the real life.

Arterial Thrombosis in Coronavirus Disease 2019 Patients: A Rapid Systematic Review.

BACKGROUND: Emerging evidence suggests that severe form of coronavirus disease 2019 (COVID-19) is mediated, in part, by a hypercoagulable state characterized by micro- and macro-vascular thrombotic angiopathy. Although venous thrombotic events in COVID-19 patients have been well described, data on arterial thrombosis (AT) in these patients is still limited. We, therefore, conducted a rapid systematic review of current scientific literature to identify and consolidate evidence of AT in COVID-19 patients. METHODS: A systematic search of literature was conducted between November 1, 2019, and June 9, 2020, on PubMed and China National Knowledge Infrastructure to identify potentially eligible studies. RESULTS: A total of 27 studies (5 cohort, 5 case series, and 17 case reports) describing arterial thrombotic events in 90 COVID-19 patients were included. The pooled incidence of AT in severe/critically ill intensive care unit-admitted COVID-19 patients across the 5 cohort studies was 4.4% (95% confidence interval 2.8-6.4). Most of the patients were male, elderly, and had comorbidities. AT was symptomatic in >95% of these patients and involved multiple arteries in approximately 18% of patients. The anatomical distribution of arterial thrombotic events was wide, occurring in limb arteries (39%), cerebral arteries (24%), great vessels (aorta, common iliac, common carotid, and brachiocephalic trunk; 19%), coronary arteries (9%), and superior mesenteric artery (8%). The mortality rate in these patients is approximately 20%. CONCLUSIONS: AT occurs in approximately 4% of critically ill COVID-19 patients. It often presents symptomatically and can affect multiple arteries. Further investigation of the underlying mechanism of AT in COVID-19 would be needed to clarify possible therapeutic targets.

Circulatory Rejuvenated EPCs Derived from PAOD Patients Treated by CD34+ Cells and Hyperbaric Oxygen Therapy Salvaged the Nude Mouse Limb against Critical Ischemia.

This study tested whether circulatory endothelial progenitor cells (EPCs) derived from peripheral arterial occlusive disease (PAOD) patients after receiving combined autologous CD34+ cell and hyperbaric oxygen (HBO) therapy (defined as rejuvenated EPCs) would salvage nude mouse limbs against critical limb ischemia (CLI). Adult-male nude mice (n = 40) were equally categorized into group 1 (sham-operated control), group 2 (CLI), group 3 (CLI-EPCs (6 × 105) derived from PAOD patient's circulatory blood prior to CD34+ cell and HBO treatment (EPCPr-T) by intramuscular injection at 3 h after CLI induction) and group 4 (CLI-EPCs (6 × 105) derived from PAOD patient's circulatory blood after CD34+ cell and HBO treatment (EPCAf-T) by the identical injection method). By 2, 7 and 14 days after the CLI procedure, the ischemic to normal blood flow (INBF) ratio was highest in group 1, lowest in group 2 and significantly lower in group 4 than in group 3 (p < 0.0001). The protein levels of endothelial functional integrity (CD31/von Willebrand factor (vWF)/endothelial nitric-oxide synthase (eNOS)) expressed a similar pattern to that of INBF. In contrast, apoptotic/mitochondrial-damaged (mitochondrial-Bax/caspase-3/PARP/cytosolic-cytochrome-C) biomarkers and fibrosis (Smad3/TGF-ß) exhibited an opposite pattern, whereas the protein expressions of anti-fibrosis (Smad1/5 and BMP-2) and mitochondrial integrity (mitochondrial-cytochrome-C) showed an identical pattern of INBF (all p < 0.0001). The protein expressions of angiogenesis biomarkers (VEGF/SDF-1α/HIF-1α) were progressively increased from groups 1 to 3 (all p < 0.0010). The number of small vessels and endothelial cell surface markers (CD31+/vWF+) in the CLI area displayed an identical pattern of INBF (all p < 0.0001). CLI automatic amputation was higher in group 2 than in other groups (all p < 0.001). In conclusion, EPCs from HBO-C34+ cell therapy significantly restored the blood flow and salvaged the CLI in nude mice.

Fufang-Zhenzhu-Tiaozhi capsule ameliorates rabbit's iliac artery restenosis by regulating adiponectin signaling pathway.

BACKGROUND AND PURPOSE: Fufang-Zhenzhu-Tiaozhi Capsule (FTZ), a traditional Chinese medicine, has been shown obvious effects on the treatment of dyslipidemia and atherosclerosis. The aim of this study was to evaluate whether FTZ can ameliorate rabbit iliac artery restenosis after angioplasty by regulating adiponectin signaling pathway. EXPERIMENTAL APPROACH: The rabbit iliac artery restenosis model was established through percutaneous iliac artery transluminal balloon angioplasty and a high-fat diet. Twenty eight male New Zealand rabbits (8-week-old) were divided into sham operation group (Group Ⅰ), model group (Group Ⅱ), atorvastatin group (Group Ⅲ) and FTZ group (Group Ⅳ), with 7 rabbits in each group. Vascular stenosis was analyzed with Digital Subtraction Angiography. Level of adiponectin (APN), and inflammatory factor including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) as well as monocyte chemoattractant protein-1 (MCP-1) was measured by Enzyme Linked Immunosorbent Assay; and injured iliac artery was collected for Hematoxylin-eosin staining and Western Blotting detection of expression of peroxisome proliferator-activated receptor-alpha (PPAR-α), adenosine 5'-monophosphate -activated protein kinase (AMPK) and phosphorylated adenosine 5'-monophosphate -activated protein kinase (p-AMPK). Besides, we evaluated FTZ's safety for the first time. KEY RESULTS: Percutaneous iliac artery transluminal balloon angioplasty and high-fat diet result in inflammatory response and restenosis. Compared with Group Ⅱ, iliac artery restenosis was significantly ameliorated in Group Ⅳ (P < 0.05). Treated with FTZ, serum lipids were significantly decreased (P < 0.01), while the level of APN was elevated significantly (P < 0.01). Western blotting detection of the injured iliac artery showed that the expressions of PPAR-α, AMPK and p-AMPK were significantly increased in Group Ⅳ (P < 0.01) than that in Group Ⅱ. Besides, before and after taking drugs, liver and kidney function indicators, creatine kinase, as well as measurement of echocardiography were of no statistical difference in four groups(P > 0.05). CONCLUSIONS AND IMPLICATIONS: FTZ could effectively reduce serum lipids and ameliorate rabbit's iliac artery restenosis after angioplasty, and its mechanism may be related to activation of APN signaling pathway.

Relation between serum cotinine levels and trophic lesions in patients with critical limb ischemia: a pilot study.

Aim: To evaluate if smoking, quantified by the serum cotinine levels, is related to the evolution of patients with critical limb ischemia (CLI).Method: A pilot study was conducted on CLI patients who addressed at the Second Surgery Clinic of the Emergency County Hospital, Cluj-Napoca, Romania between November 2015 and December 2016. The sample of patients was split into two groups using the threshold of 15 ng/mL for the serum level of cotinine (low cotinine level - LCL vs. high cotinine level - HCL). Furthermore, the ROC analysis was conducted to identify the threshold of cotinine level able to discriminate between CLI patients with and without trophic lesions.Results: The mean age of patients was 60.7 ± 10.5 years with a significantly higher percentage of male patients (84%). A significant association was identified between urban origin and serum cotinine level, which is related to the increased number of cigarettes smoked per day among urban participants. Excepting necrectomy and toe disarticulation, no differences were found between LCL and HCL group regarding symptoms, signs or comorbidities. In smokers with CLI (38/43), a serum cotinine cut-off of 9.765 ng/mL was observed on eight out of 10 CLI patients with necrectomy and five out of 28 patients without necrectomy.Conclusion: Our study showed higher serum cotinine levels associated with a higher number of smoked cigarettes and necrectomy in patients with CLI. The serum cotinine could be a fair screening test for necrectomy in smokers CLI patients.

Impact of hepatitis virus infection on arterial calcification among incident hemodialysis patients.

BACKGROUND: The impact of hepatitis virus infection on arterial calcification (AC) was not studied. OBJECTIVE: To study the prevalence, severity and distribution of AC in incident hemodialysis patients with hepatitis B and C viral infection. CASES AND METHODS: 172 stage 5 CKD adults (98 male and 74 female) were included; 58 of them were seronegative for both hepatitis B and C (SN group), 48 were positive for hepatitis B virus infection (HBV group) and 66 were hepatitis C virus positive (HCV group). Beside histopathology of the obtained arterial samples, all these cases were examined for body mass index (BMI), serum calcium (Ca), phosphorus (P), alkaline phosphatase (AP), serum albumin, uric acid (UA), alanine transaminase (ALT), parathormone (PTH), fibroblast growth factor 23(FGF23), interleukin 6 (IL6), and 25 hydroxy vitamin D (25 (OH) vit D), hemoglobin concentration, and serum ferritin. RESULTS: 86 (50%) of the cases had AC; 11 of them were in SN group (19%), 9 in HBV group (18.8%) and all the 66 HCV group (100%). In SN group, 4 had intimal calcification, 5 had medial calcification, and 2 had both intimal and medial calcification. In HBV group, 9 had intimal calcification, while no cases were encountered with either medial or both site calcifications. In HCV group, 16 had intimal calcification, 31 had medial calcification, and 19 had both intimal and medial calcification. Calcification was in the form of spots in one case in SN group, and 6 cases in HBV group, a single plaque of calcification in 5 cases of SN group, 3 cases of HBV group, and 16 cases of HCV group, multiple plaques were detected in 4 cases in SN group, and 31 cases in HCV group, and diffuse calcification in one case in SN group, and 19 cases in HCV group. In HBV group, calcification was only detected in patients with high viremia, while all patients with low or moderate viremia were devoid of calcification. In HCV group, all patients with low viremia had intimal solitary plaque of calcification, all patients with moderate viremia had multiple plaques of medial calcification, while all patients with high viremia had diffuse intimal and medial calcification. Both groups of viral hepatitis were significantly different in comparison to SN group in either distribution or calcification score (P<0.001 in all). HBV group had significantly lower serum P, CaxP and PTH in comparison to SN group (4.6±0.66 vs. 5.45±0.77mg/dL, 36.4±7.2 vs. 44.1±8.69, and 348±65.4 vs. 405.9±83.2pg/mL, P<0.001, <0.001, and 0.035 respectively). On the other hand, HCV group did not show any significant difference in any of the studied parameters compared to SN group. CONCLUSION: HCV positive patients are more prone to develop AC that is more extensive. HBV positive patients were less likely to have arterial medial calcification, probably related to lower serum phosphorus, CaxP product and PTH. HCV infection should be added as risk factor for AC among CKD patients. Further studies are needed to confirm these findings.

Arterial and venous thrombosis by high platelet count and high hematocrit: 108 521 individuals from the Copenhagen General Population Study.

BACKGROUND: It is unclear whether high platelet count or high hematocrit predict risk of thrombosis in individuals from the general population. OBJECTIVES: We tested the hypothesis that individuals from the general population with high platelet count or high hematocrit have high risk of arterial and venous thrombosis. METHODS: We prospectively followed 108 521 individuals from The Copenhagen General Population Study for a median of 8 years. Platelet count and blood hematocrit were measured at study entry. RESULTS AND CONCLUSION: Multivariable adjusted hazard ratios for individuals with platelet counts in the top 5 percentiles (>398 × 109 /L) vs in the 25th-75th percentiles (231-316 × 109 /L) were 1.77 (95% confidence interval [CI], 1.38-2.24) for arterial thrombosis in the brain (38 and 26 events/10 000 person-years) and 0.82 (95%, 0.61-1.11) for arterial thrombosis in the heart (23 and 28 events/10 000 person-years). For individuals with hematocrit values in the top 5 percentiles (women/men: >45/>48%) vs the 25th-75th percentiles (women/men: 38.1-42/41.1-45%), hazard ratios were 1.27 (95% CI, 0.91-1.75) for arterial thrombosis in the brain (40 and 26 events/10 000 person-years) and 1.46 (95% CI, 1.06-2.00) for arterial thrombosis in the heart (43 and 25 events/10 000 person-years). Neither high platelet count nor high hematocrit was associated with risk of venous thromboembolism. When excluding individuals with myeloproliferative neoplasia from the main analyses, results on risk of thrombosis were similar. In this prospective study, high platelet counts were associated with 1.8-fold risk of arterial thrombosis in the brain, whereas high hematocrit was associated with 1.5-fold risk of arterial thrombosis in the heart.

Association of complete blood count parameters, d-dimer, and soluble P-selectin with risk of arterial thromboembolism in patients with cancer.

BACKGROUND: Patients with cancer are at risk of developing arterial thromboembolism (ATE). With the prevalence of cancer and cardiovascular diseases on the rise, the identification of risk factors for ATE in patients with cancer is of emerging importance. OBJECTIVES: As data on the association of potential biomarkers with risk of ATE in patients with cancer are scarce, we conducted a cohort study with the aim to identify blood-based biomarkers for ATE risk prediction in patients with cancer. PATIENTS/METHODS: Overall, 1883 patients with newly diagnosed cancer or progressive disease after complete or partial remission were included and followed for 2 years. Venous blood was drawn at study inclusion for measurement of complete blood count parameters, total cholesterol, d-dimer, and soluble P-selectin (sP-selectin) levels. RESULTS: The 2-year cumulative incidence of ATE was 2.5%. In univariable analysis, red cell distribution width (subdistribution hazard ratio (SHR) per doubling: 4.4, 95% CI: 1.4-14.1), leukocyte count (1.2, 1.1-1.5), neutrophil count (1.6, 1.1-2.3), and sP-selectin levels (1.9, 1.3-2.7) were associated with risk of ATE in patients with cancer; d-dimer was not associated with the risk of ATE (1.1, 0.9-1.4). After adjustment for age, sex, and smoking status the association prevailed for the neutrophil count (adjusted [adj.] SHR per doubling: 1.6, 1.1-2.4), and sP-selectin levels (1.8, 1.2-2.8). CONCLUSIONS: An elevated absolute neutrophil count and higher sP-selectin levels were associated with an increased risk of ATE in patients with cancer. Their role for predicting cancer-related ATE needs to be validated in further studies.

Effect of Different Doses of Acetylsalicylic Acid on the Antithrombotic Activity of Clopidogrel in a Mouse Arterial Thrombosis Model.

Objective- Dual-antiplatelet therapy with acetylsalicylic acid and a P2Y12 antagonist, such as clopidogrel, is the standard of care for acute coronary syndromes. However, the drugs have divergent effects on the formation of cAMP, an inhibitory second messenger. Thus, by inhibiting the synthesis of prostacyclin, acetylsalicylic acid reduces cAMP formation, whereas clopidogrel potentiates it. Therefore, with higher doses of acetylsalicylic acid, the potentiation of cAMP production by clopidogrel may be attenuated, which could limit the antithrombotic potential of the drug combination. The purpose of this study was to examine this possibility in vivo. Approach and Results- Mice were given oral acetylsalicylic acid at varying doses, oral clopidogrel (5 mg/kg body weight), or both. At doses of 0.15 and 0.6 mg/kg, acetylsalicylic acid inhibited arachidonic acid-induced platelet aggregation, but only 0.6 mg/kg acetylsalicylic acid, or higher, decreased the plasma levels of 6-keto-prostaglandin-F1α, the stable metabolite of prostacyclin. When given with clopidogrel, laser injury-induced arterial thrombi were significantly larger with the 0.6 mg/kg dose of acetylsalicylic acid than with the 0.15 mg/kg dose. Thrombi in mice treated with clopidogrel and the 0.15 mg/kg dose of acetylsalicylic acid were smaller than in mice treated with clopidogrel alone, suggesting that acetylsalicylic acid can add to the antithrombotic effect of clopidogrel but that higher doses of acetylsalicylic acid blunt the antithrombotic effect of clopidogrel. Conclusions- These findings support the use of lower, prostacyclin-preserving, doses of acetylsalicylic acid in conjunction with clopidogrel.

Passive Smoking Exacerbates Nicotinamide-Adenine Dinucleotide Phosphate Oxidase Isoform 2-Induced Oxidative Stress and Arterial Dysfunction in Children with Persistent Allergic Rhinitis.

OBJECTIVE: To characterize nicotinamide-adenine dinucleotide phosphate oxidase isoform 2 (NOX2), oxidative stress, and endothelial function in children with and without allergic rhinitis and to ascertain the effect of passive smoke exposure on these factors, because there is an established association between allergic rhinitis and increased cardiovascular risk in adults. METHODS: We recruited 130 children-65 with persistent allergic rhinitis and 65 healthy controls. A cross-sectional study was performed to compare endothelial function by flow-mediated dilation, blood levels of isoprostanes, serum activity of soluble NOX2-dp (sNOX2-dp), and nitric oxide bioavailability, in these 2 groups of children. Serum cotinine levels were assessed to measure exposure to passive smoking. RESULTS: Compared with healthy controls, children with persistent allergic rhinitis had significantly higher sNOX2-dp and isoprostanes levels, lower flow-mediated dilation, and reduced nitric oxide bioavailability. Multivariable linear regression analysis showed that flow-mediated dilation, isoprostanes, and cotinine were independently associated with sNOX2-dp levels. Of note, sNOX2-dp serum levels were significantly higher in children with allergic rhinitis exposed to smoke, as compared with unexposed children with allergic rhinitis. CONCLUSION: NOX2 is activated in children with persistent allergic rhinitis and passive smoke exposure exacerbates this effect. We further demonstrate an association between higher sNOX2-dp and oxidative stress and endothelial dysfunction.

Sex differences in outcomes and associated factors among stroke patients with small artery occlusion in China.

BACKGROUND: Sex differences in outcomes after small artery occlusion (SAO) stroke have not been well described, particularly in a Chinese population. We aimed to assess sex differences in outcomes and related risk factors among patients with SAO. METHODS: All consecutive patients with SAO were recruited between May 2005 and September 2014. Clinical features and risk factors were recorded. The mortality, recurrence, and dependency rates at 3 months after stroke were assessed. RESULTS: A total of 2524 patients with SAO were included in this study. There was a higher frequency of mild stroke, current smoking, and alcohol consumption in men than in women. Women were more likely than men to be older, to have diabetes and obesity, and to have higher total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels. There were worse outcomes in men than in women at 3 months after stroke (P < 0.05). There were more independent risk factors of poor outcome in men than in women. Older age was a common predictive factor of outcome both in men and in women. In men, low triglyceride levels and high fasting plasma glucose levels were independent risk factors for mortality; in addition, a high low-density lipoprotein cholesterol level was associated with recurrence. Moreover, in men, moderate and severe stroke, and high total cholesterol and fasting plasma glucose levels were risk factors for dependency. A negative association was found between low-density lipoprotein cholesterol level and risk of mortality and between total cholesterol level and risk of recurrence in women. CONCLUSIONS: These findings suggest that it is crucial to control conventional risk factors and fasting plasma glucose and lipid levels among patients with SAO, especially male patients, to reduce the burden of stroke in China.

Coagulopathy as a complication of kidney biopsies in paediatric systemic lupus erythematosus patients with antiphospholipid syndrome.

Children with systemic lupus erythematosus (SLE) generally undergo a pretreatment kidney biopsy. However, some of these patients, especially those with antiphospholipid syndrome (APS), may experience serious coagulopathic complications. We report herein two cases of paediatric SLE with APS in which, despite normal blood test results, the disparate coagulopathic complications of haemorrhage and embolism developed following a kidney biopsy. Case 1 was, an 8-year-old male in whom, primary APS was initially diagnosed. Fourteen months later SLE was diagnosed. Based on a percutaneous kidney biopsy, International Society of Nephrology and the Renal Pathology Society (ISN/RPS) class III-A lupus nephritis was histologically diagnosed. On post-biopsy Day 9, a giant haematoma in the fascia of the left kidney developed and was accompanied by changes in the vital signs. Case 2, a 13-year-old male, initially received the diagnosis of SLE with APS and underwent two courses of pulse methylprednisolone therapy. His coagulation abnormalities improved, and a percutaneous needle kidney biopsy was performed, leading to the histological diagnosis of ISN/RPS class III-A lupus nephritis. Furthermore, thrombotic microangiopathy was also detected in the renal histopathology. On post biopsy Day 6, the patient experienced right leg pain. A contrast CT and lower extremity ultrasonography detected a massive deep vein thrombosis and partial left pulmonary artery thrombosis. A kidney biopsy in children with SLE and APS can cause lethal coagulopathic complications, and the risks to such patients should be weighed carefully before the procedure is performed.

Elevated levels of soluble CD40 ligand are associated with antiphospholipid antibodies in patients with systemic lupus erythematosus.

OBJECTIVES: The CD40L/CD40 pathway is involved in the pathophysiology of atherothrombotic disease, and elevated levels of soluble CD40L (sCD40L) were reported in SLE patients. However, the clinical implication of sCD40L in SLE remains elusive. METHODS: We measured levels of plasma sCD40L in 241 SLE patients and 37 healthy controls and investigated its association with clinical manifestation and laboratory parameters. RESULTS: Levels of plasma sCD40L in SLE patients were significantly elevated compared with healthy controls (p=0.013) and positively correlated with levels of soluble P-selectin (γ=0.336, p<0.001). SLE patients who experienced arterial thrombosis had a higher level of sCD40L than those who did not (p=0.029). Plasma sCD40L levels were positively correlated with the titers of anti-cardiolipin and anti-ß2 glycoprotein I antibodies (γ=0.338, p<0.001 and γ=0.364, p<0.001, respectively). Its levels were also significantly higher in patients with clinical antiphospholipid syndrome (APS) than in non-APS patients, irrespective of antiphospholipid antibody (aPL) positivity. Of those with arterial thrombosis, sCD40L levels were significantly elevated in patients with positive aPL, compared to those with negative aPL (p=0.011). Multiple regression analysis revealed that the presence of hypertension and positive aPL were independently associated with the occurrence of arterial thrombosis in SLE patients. A parallel analysis showed that sCD40L was also an independent variable for arterial thrombosis; however, this association disappeared when aPL, a strong variable, was included in the model because of collinearity between aPL and sCD40L. CONCLUSIONS: Plasma sCD40L levels were elevated in SLE patients who had positive aPL and experienced arterial thrombosis, suggesting that enhanced release of sCD40L through platelet activation presumably by aPL could contribute to the development of atherothrombotic disease.

Demographic and Comorbidity Pattern of Patients with Critical Limb Ischemia.

AIM: The present study aimed at identifying the pattern of patients with critical limb ischemia (CLI) compared with those with peripheral arterial occlusive disease (PAOD). MATERIALS AND METHODS: A four-year retrospective study was conducted with patients hospitalized in the Second Surgical Clinic at the Emergency County Hospital Cluj-Napoca. The medical charts of patients with PAOD (n=466) and CLI (n=223) were reviewed and data were collected. RESULTS: The study included 689 patients; mean age 67 years for PAOD patients and 65 years for CLI patients. A significantly higher percentage of patients were male in both groups (79.25%, P < 0.0001). Most of the patients in both groups had received at least a secondary education (P < 0.0001). Most of the subjects in both groups were smokers (>71.30%) with no difference between groups (P = 0.566). No significant differences were found between the groups in comorbidities (diabetes, arterial blood hypertension, cardiac ischemia, rhythm disorders, P > 0.05). There were more CLI patients that were overweight than overweight patients with PAOD (P = 0.0004). High serum cholesterol (>200 mg/dL) and triglycerides (>150 mg/dL) levels were found in the CLI group (P < 0.05). Age was identified as a risk factors for amputation (OR = 1.03, 95%Cl [1.01-1.05], P = 0.0012). CONCLUSIONS: The profile of a patient with critical limb ischemia and peripheral arterial occlusive disease is a 65-67-year-old male smoker with at least a secondary education. The CLI patient is overweight with pathological serum levels of cholesterol and triglycerides.

Shear-sensitive nanocapsule drug release for site-specific inhibition of occlusive thrombus formation.

Essentials Vessel stenosis due to large thrombus formation increases local shear 1-2 orders of magnitude. High shear at stenotic sites was exploited to trigger eptifibatide release from nanocapsules. Local delivery of eptifibatide prevented vessel occlusion without increased tail bleeding times. Local nanocapsule delivery of eptifibatide may be safer than systemic antiplatelet therapies. SUMMARY: Background Myocardial infarction and stroke remain the leading causes of mortality and morbidity. The major limitation of current antiplatelet therapy is that the effective concentrations are limited because of bleeding complications. Targeted delivery of antiplatelet drug to sites of thrombosis would overcome these limitations. Objectives Here, we have exploited a key biomechanical feature specific to thrombosis, i.e. significantly increased blood shear stress resulting from a reduction in the lumen of the vessel, to achieve site-directed delivery of the clinically used antiplatelet agent eptifibatide by using shear-sensitive phosphatidylcholine (PC)-based nanocapsules. Methods PC-based nanocapsules (2.8 × 1012 ) with high-dose encapsulated eptifibatide were introduced into microfluidic blood perfusion assays and into in vivo models of thrombosis and tail bleeding. Results Shear-triggered nanocapsule delivery of eptifibatide inhibited in vitro thrombus formation selectively under stenotic and high shear flow conditions above a shear rate of 1000 s-1 while leaving thrombus formation under physiologic shear rates unaffected. Thrombosis was effectively prevented in in vivo models of vessel wall damage. Importantly, mice infused with shear-sensitive antiplatelet nanocapsules did not show prolonged bleeding times. Conclusions Targeted delivery of eptifibatide by shear-sensitive nanocapsules offers site-specific antiplatelet potential, and may form a basis for developing more potent and safer antiplatelet drugs.