Intravascular Thrombus Formation Research Articles

Endothelial ADAM10 utilization defines a molecular pathway of vascular injury in mice with bacterial sepsis.

The endothelium plays a critical role in the host response to infection and has been a focus of investigation in sepsis. While it is appreciated that intravascular thrombus formation, severe inflammation, and loss of endothelial integrity impair tissue oxygenation during sepsis, the precise molecular mechanisms that lead to endothelial injury remain poorly understood. We demonstrate here that endothelial ADAM10 was essential for the pathogenesis of Staphylococcus aureus sepsis, contributing to α-toxin-mediated (Hla-mediated) microvascular thrombus formation and lethality. As ADAM10 is essential for endothelial development and homeostasis, we examined whether other major human sepsis pathogens also rely on ADAM10-dependent pathways in pathogenesis. Mice harboring an endothelium-specific knockout of ADAM10 were protected against lethal Pseudomonas aeruginosa and Streptococcus pneumoniae sepsis, yet remained fully susceptible to group B streptococci and Candida albicans sepsis. These studies illustrate a previously unknown role for ADAM10 in sepsis-associated endothelial injury and suggest that understanding pathogen-specific divergent host pathways in sepsis may enable more precise targeting of disease.

Genomic Variation Affecting MPV and PLT Count in Association with Development of Ischemic Stroke and Its Subtypes.

Platelets play a significant role in the pathophysiology of ischemic stroke since they are involved in the formation of intravascular thrombus after erosion or rupture of the atherosclerotic plaques. Platelet (PLT) count and mean platelet volume (MPV) are the two significant parameters that affect the functions of platelets. In the current study, MPV and PLT count was evaluated using flow cytometry and a cell counter. SonoClot analysis was carried out to evaluate activated clot timing (ACT), clot rate (CR), and platelet function (PF). Genotyping was carried out using GSA and Sanger sequencing, and expression analysis was performed using RT-PCR. In silico analysis was carried out using the GROMACS tool and UNAFold. The interaction of significant proteins with other proteins was predicted using the STRING database. Ninety-six genes were analyzed, and a significant association of THPO (rs6141) and ARHGEF3 (rs1354034) was observed with the disease and its subtypes. Altered genotypes were associated significantly with increased MPV, decreased PLT count, and CR. Expression analysis revealed a higher expression in patients bearing the variant genotypes of both genes. In silico analysis revealed that mutation in the THPO gene leads to the reduced compactness of protein structure. mRNA encoded by mutated ARHGEF3 gene increases the half-life of mRNA. The two significant proteins interact with many other proteins, especially the ones involved in platelet activation, aggregation, erythropoiesis, megakaryocyte maturation, and cytoskeleton rearrangements, suggesting that they could be important players in the determination of MPV values. In conclusion, the current study demonstrated the role of higher MPV affected by genetic variation in the development of IS and its subtypes. The results of the current study also indicate that higher MPV can be used as a biomarker for the disease and altered genotypes, and higher MPV can be targeted for better therapeutic outcomes.

Validation of the diagnostics algorithm to monitor coagulation parameters in pregnant women

Thrombotic events are among the most dangerous complications of pregnancy. Therefore, selection of appropriate tests and standardization of techniques used for accurate diagnostics of blood coagulation system state is of great importance. In this present study, we monitored several molecular markers of the dangers of intravascular thrombus formation and estimated the platelet function in pregnant women during­ gestation. We performed independent measurements using the same methodology for different cohorts of patients recruited in Kyiv (Ukraine) and in Szeged (Hungary). D-dimer and soluble fibrin were measured using ELISA. Protein C (PC) level was estimated using chromogenic substrate assay. Fibrinogen concentration was measured by spectrophotometry using thrombin-like enzyme. Platelet function was estimated by aggregometry­. Statistical data analysis was performed using the Kruskal-Wallis test. Statistically significant increases of fibrinogen concentration from first to third gestational trimester was shown for both studied cohorts of patients (5-6 mg/ml at third trimester on average). Applied methods allowed us to detect the same tendencies of decreases in PC level as well as the appearance of moderate amounts of D-dimer (up to 300 ng/ml) and SF (up to 10-15 ug/ml). Platelet function was increased on the first trimester of pregnancy and decreased during­ following trimesters slightly. Results indicated the changes in the blood coagulation system of pregnant women during gestation with the same effectiveness independently of the selected cohorts, time and place of measurements. The application of the proposed diagnostics algorithm may allow estimating the risk of thrombotic complications during pregnancy. Keywords: D-dimer, fibrinogen, platelets, pregnancy, soluble fibrin, thrombosis

Evolving concepts in the pathophysiology of atherosclerosis: from endothelial dysfunction to thrombus formation through multiple shades of inflammation

Atherosclerosis is the anatomo-pathological substrate of most cardio, cerebro and vascular diseases such as acute and chronic coronary syndromes, stroke and peripheral artery diseases. The pathophysiology of atherosclerotic plaque and its complications are under continuous investigation. In the last 2 decades our understanding on the formation, progression and complication of the atherosclerotic lesion has greatly improved and the role of immunity and inflammation is now well documented and accepted. The conventional risk factors modulate endothelial function determining the switch to a proatherosclerotic phenotype. From this point, lipid accumulation with an imbalance from cholesterol influx and efflux, foam cells formation, T-cell activation, cytokines release and matrix-degrading enzymes production occur. Lesions with high inflammatory rate become vulnerable and prone to rupture. Once complicated, the intraplaque thrombogenic material, such as the tissue factor, is exposed to the flowing blood, thus inducing coagulation cascade activation, platelets aggregation and finally intravascular thrombus formation that leads to clinical manifestations of this disease. Nonconventional risk factors, such as gut microbiome, are emerging novel markers of atherosclerosis. Several data indicate that gut microbiota may play a causative role in formation, progression and complication of atherosclerotic lesions. The gut dysbiosis-related inflammation and gut microbiota-derived metabolites have been proposed as the main working hypothesis in contributing to disease formation and progression. The current evidence suggest that the conventional and nonconventional risk factors may modulate the degree of inflammation of the atherosclerotic lesion, thus influencing its final fate. Based on this hypothesis, targeting inflammation seems to be a promising approach to further improve our management of atherosclerotic-related diseases.

Relationship Between Attenuated Plaque Identified by Intravascular Ultrasound and Thrombus Formation After Excimer Laser Coronary Angioplasty

BackgroundExcimer laser coronary angioplasty (ELCA) has been reported to be a safe and effective atherectomy device in percutaneous coronary intervention (PCI). However, thrombotic complications after ELCA have been occasionally observed. In this study, we evaluated the impact of attenuated plaque on thrombus formation and transient no-reflow after ELCA. MethodsThis study enrolled 58 lesions in 56 patients who underwent PCI with ELCA. It was a retrospective observational study at a single center. All lesions were imaged by intravascular ultrasound (IVUS) before and immediately after ELCA. On the plaque with ultrasound attenuation, attenuation angle per millimeter and attenuation length were measured. ELCA-induced thrombus was detected by IVUS, and transient no-reflow after ELCA was recorded. ResultsThrombus was detected in 14 lesions (30 %), and transient no-reflow occurred in 3 lesions (5 %). Lesions with thrombus had a higher mean attenuation angle (median [interquartile range] 142° [112°-152°] vs. 64° [0°-115°]; p = 0.001), maximum attenuation angle (209° [174°-262°] vs. 86° [0°-173°]; p < 0.001), and longer attenuation length (12 mm [8 mm–17 mm] vs. 2 mm [0 mm–5 mm]; p < 0.001). Lesions with thrombus leading to transient no-reflow had a longer lipid length and a significantly higher troponin I level after PCI. ConclusionsIVUS-identified attenuated plaque was strongly correlated with ELCA-induced thrombus. Furthermore, attenuation length may predict transient no-reflow.

Purification, biochemical characterization and fibrinolytic potential of proteases produced by bacteria of the genus Bacillus: a systematic literature review.

Thrombosis is a hematological disorder characterized by the formation of intravascular thrombi, which contributes to the development of cardiovascular diseases. Fibrinolytic enzymes are proteases that promote the hydrolysis of fibrin, promoting the dissolution of thrombi, contributing to the maintenance of adequate blood flow. The characterization of new effective, safe and low-cost fibrinolytic agents is an important strategy for the prevention and treatment of thrombosis. However, the development of new fibrinolytics requires the use of complex methodologies for purification, physicochemical characterization and evaluation of the action potential and toxicity of these enzymes. In this context, microbial enzymes produced by bacteria of the Bacillus genus are promising and widely researched sources to produce new fibrinolytics, with high thrombolytic potential and reduced toxicity. Thus, this review aims to provide a current and comprehensive understanding of the different Bacillus species used for the production of fibrinolytic proteases, highlighting the purification techniques, biochemical characteristics, enzymatic activity and toxicological evaluations used.

Surgical management of giant pulmonary artery aneurysms in patients with severe pulmonary arterial hypertension.

Giant aneurysm of the pulmonary artery (PAA) is an extremely rare condition that may develop in patients with pulmonary arterial hypertension (PAH) which may be complicated by rupture, dissection or intravascular thrombus formation. The aim of this study was to examine available literature with regard to surgical strategies in patients undergoing transplantation for PAH with PAA. These patients were traditionally considered for heart-lung transplantation but more recently, there have been reports of successful lung transplantation with reconstruction of the pulmonary artery. Unless there is a mandatory indication for heart-lung transplantation, patients with PAH and PAA can undergo lung transplantation and reconstruction of the pulmonary artery without compromising the outcome.

Vascular mechanisms and manifestations of COVID-19

Vascular mechanisms and manifestations of COVID-19

Proteolytic enzyme and adiponectin receptors as potential targets for COVID-19 therapy

The coronavirus disease 2019 (COVID-19) pandemic requires not only the creation of vaccines to prevent the spread of the disease, but also the development of novel drugs aimed at reducing viral load, suppressing an excessive immune response and preventing the severe complications such as lung fibrosis and acute respiratory distress syndrome. One of the promising targets for studying the development of pneumonia, systemic inflammation and disseminated intravascular coagulation in COVID-19 is the plasminogen activator system. In patients with a severe disease course, impaired activity or expression of plasminogen activators significantly increases the blood level of D-dimer and fibrinogen, as well as correlates with intravascular coagulation and thrombus formation. The second promising target for studying the pathogenesis of COVID-19 is the adiponectin/T-cadherin system: adiponectin is able to reduce the content of pro-inflammatory cytokines, the increase of which is characteristic of COVID-19, and stimulate the production of an anti-inflammatory cytokine interleukin-10. The review describes the role of plasminogen and T-cadherin activators in their possible participation in the development of pulmonary fibrosis in COVID-19 and hemostasis regulation, as well as cardio- and vasculoprotective function of adiponectin and its receptor, T-cadherin.

Infarto agudo al miocardio asociado al uso de cocaína

El abuso de cocaína se asocia con un mayor riesgo de eventos cardiovasculares, como infarto de miocardio y accidente cerebrovascular isquémico. Los mecanismos fisiopatológicos no se entienden completamente, aunque la formación de trombos intravasculares y la aterosclerosis acelerada son hallazgos destacados. Reportamos a un hombre de 38 años adicto a la cocaína, que presentó eventos isquémicos caracterizados por infarto agudo de miocardio complicado por insuficiencia cardíaca. Se discute la fisiopatología del daño vascular inducido por la cocaína y el manejo de las complicaciones.

Non-Cardiogenic Thromboembolism in a Persian Cat with Hypertrophic Cardiomyopathy

Background: Hypertrophic cardiomyopathy is the most common acquired cardiovascular disease in the feline species. A frequent complication of this cardiomyopathy is the development of cardiac congestive failure, left atrial enlargement and subsequent development of arterial thromboembolism. In a significant percentage of affected animals there is progression to congestive heart failure, resulting in cyanosis and dyspnea, often the first clinical signs reported by owners. This is a report of a 10-year-old Persian cat with hypertrophic cardiomyopathy and venous and arterial thromboembolism of non-cardiogenic origin.Case: The patient was referred for cardiac evaluation, arterial thromboembolism was the suspected cause of tetraparesis. On clinical examination, a metacarpal pulse was present in all limbs; there was no cyanosis or peripheral hypothermia thus, ruling out a thromboembolic event in the limbs. Changes consistent with feline asthma and pulmonary edema were seen on radiographs, therefore hypertrophic cardiomyopathy was suspected. Treatment with enalapril (0.25 mg/kg every 12 h) for the heart condition and prednisolone (1 mg/kg every 24 h) for asthma was started. Nine days later, the patient developed mixed dyspnea (inspiratory and expiratory) and was hospitalized with signs consistent with arterial thromboembolism: paralysis and cold extremities in the right and left pelvic limbs. The patient was euthanized due to the poor prognosis. Post mortem and histopathological findings revealed left ventricular concentric hypertrophy, with no valvular changes; disseminated intravascular coagulation, with thrombi in the arterial (iliac arteries, pancreatic and renal vessels) and venous (pulmonary and renal veins) beds; as well as multiple neoplastic lung masses, identified as scirrhous pulmonary adenocarcinoma, responsible for increased interstitial radiopacity. Metastasis was also identified at the tracheal bifurcation, causing radiographic changes similar to the alveolar pattern of pulmonary edema.Discussion: The origin of the concentric left ventricular hypertrophy was not established. Both primary hypertrophy, due to breed-related genetic predisposition or secondary hypertrophy, due to systemic hypertension from chronic kidney disease are possibilities. However, despite the left ventricular concentric hypertrophy and the presence of thrombus under the mitral valve, it was not thought that the patient had cardiogenic thromboembolism, since this would not explain the venous thrombi. The arterial and venous thromboembolism in this case were the result of paraneoplastic syndrome due to pulmonary adenocarcinoma, which was a triggering factor for disseminated intravascular coagulation and multiple thrombus formation, both in arterial and venous beds. Tumor cells may promote direct and indirect modifications in the coagulation cascade and, thus hypercoagulability. The hypercoagulatory state promoted by the tumor associated with the Virchow triad seen in feline species, explains the occurrence of thrombosis in this case report. Sensitive imaging tests, such as computed tomography or magnetic resonance imaging, may be required in middle-aged cats with hypertrophic cardiomyopathy and clinical presentations of thromboembolism or respiratory signs, in order to exclude pulmonary neoplasm as a differential diagnosis for thrombus formation and dyspnea. Furthermore, it is speculated that the antitumor effect of heparin used in the treatment for arterial thromboembolism may delay the diagnosis of lung neoplasia in cats.

Platelets as key players in inflammation and infection.

This review highlights recent insights into the role of platelets in acute inflammation and infection. Platelets exhibit intravascular crawling behavior and can collect and bundle bacteria. In addition, platelets are key in promoting intravascular thrombus formation in infection, a process termed 'immunothrombosis', which contributes to pathogen containment, but also potentially damages the host. Platelets are at the nexus of leukocyte recruitment and activation, yet they are at the same time crucial in preventing inflammation-associated hemorrhage and tissue damage. This multitasking requires specific receptors and pathways, depending on stimulus, organ and effector function. New findings highlight the complex interplay of innate immunity, coagulation and platelets in inflammation and infection, and unravel novel molecular pathways and effector functions. These offer new potential therapeutic approaches, but require further extensive research to distinguish treatable proinflammatory from host-protective pathways.

Recombinant activated factor VII in neonatal cardiac surgery

The aim of this study is to determine whether recombinant activated factor VII (rVIIa) was associated with thrombus formation in neonates undergoing cardiac surgery. This is a retrospective study of neonates undergoing surgical repair of congenital cardiac lesions during a 9-year period. In our study, 416 cardiac operations requiring cardiopulmonary bypass (CPB) were performed on 414 neonates. The overall intravascular thrombus (thrombus) frequency for all operations was 45 of 416 (11%). A thrombus developed in 17 of 287 (6%) operations when rVIIa was not given. rVIIa was administered in 129 of 416 (31%) operations. Thrombus formation occurred in 28 of 129 (22%) operations when rVIIa was administered. There was an association between rVIIa use and thrombus formation [odds ratio (OR) 4.4, 95% confidence interval (CI) 2.3-8.4; P < 0.0001]. Patients with thrombus formation had an increased length of stay compared to those without thrombus. Neonates who underwent the Norwood procedures and received rVIIa and developed thrombus were more likely to be supported with extracorporeal membrane oxygenation (ECMO) and had a higher mortality compared to Norwood patients without thrombus. Logistic analysis adjusted for the paediatric index of mortality 2 score, the risk adjustment for congenital heart surgery and the use of ECMO demonstrated a strong association between rVIIa administration and thrombus formation (OR 3.5, 95% CI 1.7-6.9; P = 0.0004). However, there was no effect of the risk adjustment for congenital heart surgery-1 category or the paediatric index of mortality 2 score on thrombus formation. In neonates who underwent CPB surgery, administration of rVIIa was associated with an increased occurrence of intravascular thrombus formation compared to neonates not given rVIIa. In the Norwood population, thrombus formation was associated with a higher mortality.

Expression and its significance of long non-coding transcription factor 7 in gastric cancer

Objective To explore the expression and clinical pathological significance of long non-coding transcription factor 7 (lncTCF7) in gastric cancer tissues and to investigate the role of lncTCF7 in the invasion and metastasis of gastric cancer by in vitro experimental study. Methods From January to June 2011, one hundred patients with gastric cancer who underwent radical gastrectomy were selected from Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. The expression of lncTCF7 at mRNA level was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The patients were divided into high expression group (50 cases) and low expression group (50 cases) according to the lncTCF7 mRNA expression level. The stable interferenced lncTCF7 cell line (stable interference group) and blank control lncTCF7 cell line (blank control group) were established. Then the relationship between lncTCF7 expression level and clinical pathological characteristics and prognosis was analyzed. The interferenced lncTCF7 cell line was constructed and utilized, and the role of lncTCF7 in the invasion and metastasis of gastric cancer was detected by wound healing, Transwell and Western blotting method. The Chi square test and t test were performed for statistical analysis. The Kaplan-Meier curve was used for survival analysis. Univariate and multivariate analyses were used for screening the independent factors affecting prognosis. Results The results of qRT-PCR showed that the expression levels of lncTCF7 mRNA in high expression group and low expression group were 0.019±0.003 and 0.002±0.001, respectively. The survival rate of high expression group was lower than that of low expression group (46%, 23/50 vs. 72%, 36/50), and the difference was statistically significant (P=0.002 5). The expression level of lncTCF7 was correlated with intravascular tumor thrombus formation, nerve invasion, depth of invasion and lymph node metastasis (χ2=7.862, 7.162, 11.903 and 8.280, all P<0.05). The results of univariate and multivariate analyses showed that the expression level of lncTCF7 was significantly correlated with the depth of invasion (hazard ratio (HR)=4.205, P=0.002; HR=3.125, P=0.018). The results of wound healing assay indicated that lncTCF7 interference could significantly inhibit wound healing ((92.90±1.51)% vs. (12.33±0.67)%, t=48.72, P<0.01). The results of Transwell assay demonstrated that after 24 hours of culture the number of cells passed through the membrane of the chamber of blank control group was higher than that of stable interference group (83.6±12.5 vs. 26.6±4.3), and the difference was statistically significant (t=9.65, P<0.01). The results of Western blotting showed that the expression of E-cadherin, a marker of epithelial origin, of stable interference group was significantly increased compared with that of blank control group (0.32±0.01 vs. 0.76±0.01), however the expression levels of vimentin and N-cadherin, markers of mesenchymal origin, were significantly decreased (0.56±0.01 vs. 0.39±0.01 and 0.67±0.01 vs. 0.33±0.01), and the differences were all statistically significant (t=26.68, 10.09 and 24.14, all P<0.05). Conclusions The prognosis of gastric cancer patients with high expression of lncTCF7 is poor. lncTCF7 may promote the invasion and metastasis of gastric cancer by influencing epithelial-mesenchymal transition in gastric cancer cells. Key words: Stomach neoplasms; Long non-coding RNA; Invasion and metastasis; Epithelial-mesenchymal transition

CpaA Is a Glycan-Specific Adamalysin-like Protease Secreted by Acinetobacter baumannii That Inactivates Coagulation Factor XII.

Antibiotic-resistant Acinetobacter baumannii is increasingly recognized as a cause of difficult-to-treat nosocomial infections, including pneumonia, wound infections, and bacteremia. Previous studies have demonstrated that the metalloprotease CpaA contributes to virulence and prolongs clotting time when added to human plasma as measured by the activated partial thromboplastin time (aPTT) assay. Here, we show that CpaA interferes with the intrinsic coagulation pathway, also called the contact activation system, in human as well as murine plasma, but has no discernible effect on the extrinsic pathway. By utilizing a modified aPTT assay, we demonstrate that coagulation factor XII (fXII) is a target of CpaA. In addition, we map the cleavage by CpaA to two positions, 279-280 and 308-309, within the highly glycosylated proline-rich region of human fXII, and show that cleavage at the 308-309 site is responsible for inactivation of fXII. At both sites, cleavage occurs between proline and an O-linked glycosylated threonine, and deglycosylation of fXII prevents cleavage by CpaA. Consistent with this, mutant fXII (fXII-Thr309Lys) from patients with hereditary angioedema type III (HAEIII) is protected from CpaA inactivation. This raises the possibility that individuals with HAEIII who harbor this mutation may be partially protected from A. baumannii infection if CpaA contributes to human disease. By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII. We propose adding CpaA to a small, but growing list of bacterial proteases that are specific for highly glycosylated components of the host defense system.

Complications of Acute Myocardial Infarction or Takotsubo Cardiomyopathy: from Intravascular Thrombus Formation to Disseminated Intravascular Coagulation

Two cases of suggested takotsubo syndrome and severe complications have been described. It has been discussed whether these two cases are complications of acute myocardial infarction or suggested takotsubo syndrome.

Anxiety-Related Bleeding and Thrombosis.

Anxiety, a normal response to stressful situations, is characterized by increased levels of factor VIII, fibrinogen, and von Willebrand factor, and by enhanced platelet aggregability. One would expect acute anxiety to be a prothrombotic state, but since acute mental stress induces tissue plasminogen activator (tPA) release from endothelial and chromaffin cells, fibrinolysis counteracts procoagulant stimuli. It could be said that procoagulant changes accompanying the fight-or-flight response reduce the risk of bleeding in case of potential injuries, while activation of fibrinolysis counteracts activation of hemostasis to prevent intravascular thrombus formation before injuries occur. Acutely anxious patients are prone to bleeding or thrombosis when the balance between hypercoagulation and hyperfibrinolysis is disturbed. Acute anxiety not only increases the risk of bleeding in hemophilia or von Willebrand disease, but many reports have shown that anxiolytic interventions such as hypnosis are effective in controlling bleeding in hemostatic disorders. The pathogenesis of cardiovascular and thrombotic diseases in highly anxious patients is multifactorial. An important element is α-adrenergic vasoconstriction, which increases viscosity due to leakage of intravascular fluid into the interstitium, and also causes hypertension, favoring plaque rupture. Paradoxical as it may seem, over secretion of tPA may increase cardiovascular risk. This is because tPA degrades the extracellular matrix, causing vascular stiffness that increases cardiac workload, and thus oxygen requirements. Anxious patients with conditions associated with increased plasminogen activator inhibitor-1 levels, such as depression or postprandial hyperinsulinemia, are at high risk of thrombosis. Postprandial hyperinsulinemia may result from consumption of high-carbohydrate foods, considered anxiolytic, combined with a sedentary life, which is common among anxious individuals. Preliminary evidence suggests that high anxiety combined with either depression or a lifestyle that results in hyperinsulinemia has an important role in the pathogenesis of thrombotic events currently classified as unprovoked.

Treatment of acute myocardial infarction in 2017

Acute myocardial infarction is a clinical cardiac emergency associated with potential and substantial morbidity and mortality. This disorder is triggered by an acute coronary syndrome caused by episodes of plaque ulceration, fissuration, or rupture with subsequent production of thrombogenic material and intravascular thrombus formation. The presence or absence of ST-segment elevation on the ECG defines the two main clinical spectrum of ST-segment elevation or non-ST-segment elevation myocardial infarction. In the last three decades, pharmacological and interventional management as well as in-hospital care have dramatically improved. Recent advances in antithrombotic strategies, percutaneous access (radial versus femoral), timing of revascularization, new generation coronary stents, lipid profile management, and cardiac rehabilitation programs at discharge have lead the European Task Force on ST-Elevation Myocardial Infarction to revise the 2012 guidelines and to release, in the current year, an updated version.

Clinicopathologic characteristics and prognosis of gastric hepatoid adenocarcinoma

To investigate the clinicopathological characteristics, diagnosis, treatment and prognosis of gastric hepatoid adenocarcinoma(HAS). Retrospective analysis of clinicopathological data of 24 cases with gastric HAS diagnosed by surgery and pathology in Chinese PLA General Hospital from January 2013 to May 2016 were carried out. All the patients underwent preoperative serum alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), endoscopy and imaging examination (CT or B-mode ultrasonography), and those with elevated AFP were excluded from liver cancer, cirrhosis, endodermal sinus tumor and other diseases. The follow-up ended in June 2016 or the death of the patient. The survival was from the operation to the death of the patient or the end of follow-up. There were a total of 24 cases with gastic HAS, accounting for 1.03%(24/2 326) of the total number of patients with gastric cancer diagnosed at the same time in our center. There were 19 males and 5 females, the ratio of male to female was 3.8:1.0, the mean age of the patients was 55.9 (31 to 72) years, and 2 of them had liver metastasis. The first symptom in 50% (12/24) patients was epigastric pain, in 25%(6/24) was abdominal distension with vomiting, and the rest included dysphagia (12.5%, 3/24), hematemesis (8.3%, 2/24) and melena (4.2%, 1/24). Preoperative serum levels of AFP and CEA were elevated in 10 (41.7%) and 5 patients (20.8%) respectively. All the patients underwent surgical treatment, including 23 cases with D2 radical resection of gastric cancer and R0 resection, and the other of palliative gastrojejunostomy. Lesions of HAS located in gastric antrum in 11 cases (45.8%), in cardia in 7 cases (29.2%), and in gastric body in 6 cases (25%). Tumor maximum diameter of 10 cases was larger than 5 cm, and the average diameter was 5.7(1.0 to 12.0) cm. Postoperative pathological TNM staging: stage I(b was in 1 cases, stage II( in 7 cases, stage III( in 14 cases, stage IIII( in 2 cases; lymph node metastasis in stage N1-3 in 20 cases (83.3%). Poorly-differentiated tumors were found in 21 cases (87.5%), and no well-differentiated tumors were found. There were 11 cases (45.8%) with formation of intravascular tumor thrombi. In immunohistochemistry, AFP positive expression was found in 11 cases(45.8%). Seventeen HAS cases (70.8%, 17/24) received postoperative SOX(oxaliplatin + S-1) or XELOX (oxaliplatin + capecitabine) as adjuvant chemotherapy, 5 cases postoperative immune therapy, and 2 cases postoperative traditional Chinese medicine. All the patients were followed up for 0.7 to 42.0 months (median 8 months). A total of 9 patients died, of whom, 1 case underwent gastrojejunostomy because of liver and peritoneal metastasis before operation, and died 20 days after surgery; 4 cases died of multiple liver metastases after 1.5 to 12.0 months with survival of 3 to 18 months; 3 cases presented local recurrence after 2 to 17 months with survival of 6 to 22 months; 1 cases had peritoneal metastasis after 12 month with survival of 26 months. HAS is a rare type of gastric cancer with poor prognosis. The diagnosis is mainly based on histopathology, and radical resection is the mainstay treatment.

Abordarea terapeutică a pacientului cu insuficienţă venoasă cronică

Chronic venous insufficiency (CVI), frequent cause of lower limb edema, represents a severe consequence of the dysfunction of the venous valve, which results from the venous hypertension together with the degenerative processes at this level. CVI defines only the severe stages of the chronic venous disease (CVD), accompanied by morphological and functional damage, with significant alteration in quality of life. The treatment of CVI involves, depending on the severity of the case, a combination of general nonpharmacologic, pharmacologic, and surgical measures. Non-pharmacologic measures involve the use of a continuous and controlled external pressure represented by compression stockings which can significantly improve the venous return and lead to a major symptoms improvement. Pharmacologic treatment aims on one hand to alleviate hemodinamics by lowering blood viscosity, decreasing venous pressure and preventing intravascular thrombus formation and, on the other hand, restoring thevascular glycocalyx/endothelium, reducing parietal inflammation and increasing the venous wall tone. Within this pathology, sulodexide represents an innovative biological product with polypharmacological actions targeting more sites involved in the pathogenesis of CVD/CVI that alleviate hemodynamics and restore vascular structure which lead to a significant symptoms improvement and a slow disease progression. Surgery remains the procedure of choice in patients initially treated conservatively in whom symptoms persist or worsen, but also in case of those who already come to doctor in a severe stage of the disease.