Efficacy and safety comparison between pro-urokinase and reteplase in the treatment of patients with acute ST elevation myocardial infarction / 中华心血管病杂志

Objective: To compare the efficacy and safety of pro-urokinase and reteplase in the treatment of patients with acute ST elevation myocardial infarction (STEMI). Methods: STEMI patients, who received intravenous thrombolytic therapy in Henan STEMI registry between September 2016 and August 2018, were eligible for this study. A total of 5479 patients from 66 hospitals were screened and patients were divided into pro-urokinase group (n=638) and reteplase group (n=702) according to thrombolytic drugs. Data including patient demographics, risk factors, medical histories, patient information at admission, in-hospital treatment, time delays, and clinical events were collected. The clinical recanalization rate, in-hospital mortality, in-hospital death or treatment withdrawal, in-hospital main adverse cardiovascular and cerebrovascular events (MACCE, death or treatment withdrawal, congestive heart failure, reinfarction and ischemic stroke) and post-thrombolysis bleeding were compared between the two groups. Bleeding events were evaluated with Bleeding Academic Research Consortium (BARC) criteria. Results: The median age [61.8 (53.2, 69.0) vs. 62.6 (52.1, 69.8), P=0.833] or the proportion of women [23.0% (147/638) vs. 25.1% (176/702), P=0.385] were similar between the pro-urokinase and reteplase groups. Clinical recanalization rates were similar between the pro-urokinase and reteplase groups [82.1% (524/638) vs. 84.9% (596/702), P=0.172], and there was no difference in the median time from onset to thrombolysis [194.5 (135.0,290.0) min vs. 190 (126.0,292.0) min, P=0.431] and the median recanalization time [95 (67.5,120.0) min vs. 95 (71.0,119.0) min, P=0.561] between the two groups. There was no significant difference in in-hospital mortality [5.5% (35/638) vs. 5.1% (36/702), P =0.770], in-hospital all-cause mortality, treatment withdrawal [8.9% (57/638) vs.7.7% (54/702), P=0.410], and in-hospital MACCE [13.0% (83/638) vs. 10.4% (73/702), P=0.137] between pro-urokinase and reteplase groups. However, the incidence of post-thrombolysis bleeding was significantly higher in reteplase group than in pro-urokinase group [7.8% (55/702) vs. 3.8% (24/638), P=0.002]. Further analysis found that the incidence of oral bleeding and the BARC grades 1-2 bleeding were significantly higher in reteplase group than in pro-urokinase group, whereas the incidence of cerebral hemorrhage was similar between the two groups [0.6% (4/638) vs. 0.4% (3/702), P=0.715]. The comparison of efficacy and safety outcomes between the two groups after adjusting for baseline characteristics using general linear mixed models was consistent with those before the adjustment. There was no significant difference in in-hospital mortality, in-hospital death or treatment withdrawal, in-hospital MACCE after adjusting for baseline characteristics and post-thrombolysis bleeding between the two groups. Conclusions: Pro-urokinase and reteplase have similar clinical efficacy in the treatment of STEMI. In terms of safety, the incidence of cerebral hemorrhage is similar, while the incidence of BARC grades 1-2 bleeding and oral bleeding is higher in reteplase group than in pro-urokinase group, which has no impact on in-hospital outcomes.

Estudo imuno-histoquímico e in vitro de proteínas do sistema ativador de plasminogênio em carcinomas de células escamosas de língua oral / Immunohistochemical and in vitro study of plasminogen activator system proteins in oral tongue squamous cell carcinomas

O carcinoma de células escamosas (CCE) é a neoplasia maligna mais frequente da cavidade oral e apresenta prognóstico desfavorável. Assim sendo, pesquisas têm buscado esclarecer o papel de biomarcadores no comportamento biológico do CCE oral. Nesta perspectiva, destacam-se o ativador de plasminogênio tipo uroquinase (uPA) e seu receptor (uPAR), além do inibidor do ativador de plasminogênio-1 (PAI-1). O presente trabalho analisou, por meio de imuno-histoquímica, a expressão das proteínas uPA, uPAR e PAI-1 no CCE de língua oral (CCELO) e sua relação com parâmetros clinicopatológicos. Este experimento também avaliou os efeitos in vitro da proteína recombinante humana PAI-1 (rhPAI-1) na linhagem celular SCC25, derivada de CCELO. A imunoexpressão de uPA, uPAR e PAI-1 foi analisada em 60 casos de CCELO, de forma semiquantitativa, nas células neoplásicas do front de invasão tumoral. Visando a associação dos achados imuno-histoquímicos com variáveis clinicopatológicas e taxas de sobrevida, os casos foram classificados nas categorias baixa expressão (≤50% das células positivas) e alta expressão (>50% das células positivas). No experimento in vitro, foram analisados os seguintes grupos: G0 (controle; células cultivadas na ausência de rhPAI-1), G10 (células tratadas com rhPAI-1 a 10 nM) e G20 (células tratadas com rhPAI-1 a 20 nM). Diferenças entre estes grupos foram investigadas através dos ensaios: viabilidade celular (Alamar Blue), ciclo celular (marcação com iodeto de propídio, PI), apoptose/necrose (marcação com Anexina V e PI), atividade migratória (Wound healing) e invasão celular (Transwell). A análise imuno-histoquímica revelou alta expressão do uPA na maioria dos CCELOs, mas sem relações significativas com parâmetros clinicopatológicos. As expressões do uPAR e do PAI-1, em nível membranar, foram associadas a recidivas locais (p=0,019) e ao elevado tumor budding (p=0,046), respectivamente. A expressão membranar do PAI-1 também apresentou associação significativa com o alto escore de risco histopatológico (p=0,043). A análise estatística evidenciou ausência de associações significativas entre as variáveis imunohistoquímicas (uPA, uPAR e PAI-1) e indicadores de prognóstico do CCELO (sobrevida específica e sobrevida livre da doença). No estudo in vitro, decorridas 24 horas da administração da rhPAI-1, os grupos G10 e G20 exibiram maior viabilidade celular em comparação ao grupo controle (p=0,020), assim como aumento da progressão para a fase S do ciclo celular (p=0,024). No que concerne aos percentuais de células apoptóticas e necróticas, não foram encontradas diferenças significativas entre os grupos. Nos grupos celulares cultivados na presença da rhPAI1, também foi constatado aumento da atividade migratória (p=0,039) e do potencial de invasão (p=0,039), respectivamente, nos intervalos de 24 horas e 72 horas. Os achados deste estudo sugerem o envolvimento das proteínas uPA, uPAR e PAI-1 na patogênese do CCELO. Entretanto, a expressão destes biomarcadores pode não estar relacionada com a sobrevida dos pacientes. Os resultados in vitro demonstram que o PAI-1 exerce efeitos estimulatórios na proliferação, migração e invasão celular, podendo assim contribuir para a agressividade biológica do CCELO (AU).

Squamous cell carcinoma (SCC) is the most frequent malignant neoplasm of the oral cavity and has an unfavorable prognosis. Thus, studies have sought to clarify the role of biomarkers in the biological behavior of oral SCC. Within this context, urokinase-type plasminogen activator (uPA) and its receptor (uPAR), as well as plasminogen activator inhibitor 1 (PAI-1), are particularly interesting. The present study analyzed, by means of immunohistochemistry, the expressions of uPA, uPAR and PAI-1 in oral tongue SCC (OTSCC) and their relationship with clinicopathological parameters. This experiment also evaluated the in vitro effects of recombinant human PAI-1 (rhPAI-1) on the OTSCC-derived cell line SCC-25. The immunoexpression of uPA, uPAR and PAI-1 was analyzed semiquantitatively in neoplastic cells of the invasion front of 60 OTSCC cases. Aiming to determine the association between immunohistochemical findings, clinicopathological variables and survival rates, the cases were classified as low expression (≤50% of positive cells) and high expression (>50% of positive cells). The following groups were analyzed in the in vitro experiment: G0 (control; cells cultured in the absence of rhPAI-1), G10 (cells treated with 10 nM rhPAI-1), and G20 (cells treated with 20 nM rhPAI-1). Differences between these groups were investigated using the following assays: cell viability (Alamar Blue), cell cycle (staining with propidium iodide, PI), apoptosis/necrosis (staining with Annexin V and PI), migratory activity (Wound healing), and cell invasion (Transwell). Immunohistochemical analysis revealed high expression of uPA in most OTSCC cases, but there were no significant associations with clinicopathological parameters. The high membrane expression of uPAR and PAI-1 was associated with local recurrence (p=0.019) and high tumor budding (p=0.046), respectively. Membrane expression of PAI-1 also presented a significant association with high-risk cases (p=0,043). Statistical analysis demonstrated no significant associations between the immunohistochemical variables (uPA, uPAR and PAI-1) and prognostic indicators of OTSCC (disease-specific and disease-free survival). In the in vitro experiment, 24 hours after administration of rhPAI-1, G10 and G20 exhibited greater cell viability compared to the control group (p=0.02), as well as increased progression to the S phase of the cell cycle (p=0.024). There were no significant differences in the percentages of apoptotic or necrotic cells between groups. In the groups cultured in the presence of rhPAI-1, migratory activity (p=0.039) and invasion potential (p=0.039) were found to be increased after 24 and 72 hours, respectively. The findings of this study suggest the involvement of uPA, uPAR and PAI-1 in the pathogenesis of OTSCC. Nevertheless, the expression of these biomarkers may not be related to survival of patients. The in vitro results suggest that PAI-1 exerts stimulatory effects on cell proliferation, migration and invasion and may therefore contribute to the biological aggressiveness of OTSCC (AU).

Keyhole Approach Endoscopic Surgery versus Stereotactic Aspiration plus Urokinase in Treating Basal Ganglia Hypertensive Intracerebral Hemorrhage / 中国医学科学院学报

To compare the short-and long-term effect of two minimal invasive surgical therapies including keyhole approach endoscopic surgery(KAES)and stereotactic aspiration plus urokinase(SAU)in treating basal ganglia hypertensive intracerebral hemorrhage(hICH). The clinical data of 117 hICH patients(63 received KAES and 54 received SAU)were retrospectively analyzed.The operation time,blood loss during surgery,and drainage time were compared between two groups.The residual hematoma volume,hematoma clearance rate(HCR),Glasgow coma scale(GCS)score,and National Institute of Health Stroke Scale(NIHSS)score were recorded at baseline and in the ultra-early stage,early stage,and sub-early stage after surgery.The 30-day mortality and serious adverse events were assessed and the 6-month modified Rankin scale(mRS)score was rated. Baseline data showed no significant difference between these two groups.Compared with the SAU group,the KAES group had significantly longer operation time,more intraoperative blood loss,and shorter drainage time(all 0.05).In the ultra-early and early stage,the GCS and NIHSS scores showed no significant differences between two groups(all >0.05),whereas in the sub-early stage,the NIHSS score was better in the SAU group(=0.034).The 30-day mortality and incidences of serious adverse events showed no significant difference(all >0.05).The good recovery(mRS≤3)at 6-months follow-up showed no significant difference between the two groups(=0.413). Both KAES and SAU are safe and effective in treating basal ganglia hICH.In the ultra-early stage after surgery,KAES achieves better residual hematoma volume and HCR,and patients undergoing SAU quickly catch up.The short-and long-term effectiveness of SAU is comparable or even superior to KAES.

Delayed Operation of Acute Subdural Hematoma in Subacute Stage by Trephine Drainage using Urokinase / 대한신경손상학회지

OBJECTIVE: The principle operation of acute subdural hematoma (ASDH) is a craniotomy with hematoma removal, but a trephination with hematoma evacuation may be another method in selected cases. Trephine drainage was performed for ASDH patients in subacute stage using urokinase (UK) instillation, and its results were evaluated. METHODS: Between January 2016 and December 2018, the trephine evacuation using UK was performed in 9 patients. The interval between injury and operation was from 1 to 2 weeks. We underwent a burr hole trephination with drainage initially, and waited until the flow of liquefied hematoma stopped, then instilled UK for the purpose of clot liquefaction. RESULTS: The mean age of patients was 71.6 years (range, 38–90 years). The cause of ASDH was trauma in 8 cases, and supposed a complication of anticoagulant medication in 1 case. Four out of 8 patients took antiplatelet medications and one of them was a chronic alcoholism. The range of the Glasgow Coma Scale score before surgery was from 13 to 15. Most of patients, main symptom was headache at admission. The Glasgow Outcome Scale score was 5 in 8 cases and 3 in 1 case. CONCLUSION: It is thought to be a useful operation method in selected patients with ASDH that the subdural drainage in subacute stage with UK instillation. This method might be another useful option for the patients with good mental state regardless of age and the patients with a risk of bleeding due to antithrombotic medications.

Burr Hole Drainage with Urokinase Irrigation for the Treatment of Acute Subdural Hematoma: A Case Report / 대한신경손상학회지

We describe the case of a patient with an acute subdural hematoma (SDH) that was removed using urokinase irrigation after burr hole trephination in a limited situation where craniotomy was not possible. A 90-year-old woman was admitted to our hospital with a stuporous mental status. Computed tomography (CT) scans revealed a chronic SDH, and a burr hole procedure was performed. The patient's postoperative progression was good until the third day after surgery when we found that the acute SDH had increased on CT scans. The patient's guardian refused further surgery, and thus we drained the blood from the hematoma by injecting urokinase through a drainage catheter. We used urokinase for two days, and removed the catheter after confirming via CT scans that the hematoma was almost alleviated. The patient recovered gradually; she was discharged with few neurological deficits.

Expression of urokinase-type plasminogen activator and its receptor in squamous cell carcinoma of the oral tongue

Abstract Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) act in the proteolysis of basement membrane and extracellular matrix structures, facilitating tumor invasion. The purpose of this study was to evaluate the relationship between these proteins and clinicopathological parameters in squamous cell carcinoma of the oral tongue (SCCOT). Sixty cases of SCCOT were submitted to immunohistochemistry and analyzed semiquantitatively at the invasion front and in the tumor core. The results were associated with lymph node metastasis, clinical stage, locoregional recurrence, clinical outcome and histological grade of malignancy. A higher expression of uPA was observed in cases of tumors of high-grade versus low-grade malignancy (p = 0.010). Moreover, the cases with the worst pattern of invasion presented an overexpression of uPA (p = 0.011). The presence of locoregional recurrence was associated with uPAR (p = 0.039), and the expression of both biomarkers was much higher at the invasion front than in the tumor core (p < 0.001). The results suggest uPA and uPAR are involved in the progression and aggressiveness of SCCOT, mainly at the tumor-host interface.

Treatment by Transradial Urokinase Infusion and Percutaneus Transhepatic Thrombectomy in Superior Mesenteric Veno us Thrombosis with Intestinal Infarction / 대한내과학회지

Mesenteric venous thrombosis has a low prevalence and nonspecific clinical symptoms, and it may cause bowel infarction and death. Early diagnosis and prompt surgical intervention with anticoagulants are important to patients. We examined a 27-year-old woman complaining of diffuse abdominal pain and hematochezia, and diagnosed extensive mesenteric venous thrombosis with intestinal infarction and pulmonary thromboembolism. In light of the patient's symptoms, an operation seemed necessary. However, because of the high risk of mortality, we decided to look for another option. The patient was successfully treated with intensive medical care and a radiological procedure in spite of intestinal infarction.

A Successfully Treated Case of Recurrent Focal Segmental Glomerulosclerosis (FSGS) with Plasmapheresis and High dose Methylprednisolone Pulse Therapy

Focal segmental glomerulosclerosis (FSGS) in children, which is a kind of nephrotic syndrome showing steroid resistance, usually progresses to a substantial number of end stage renal disease (ESRD). Although the pathogenesis of primary FSGS is unclear, several recent studies have reported that FSGS is associated with circulating immune factors such as soluble urokinase-type plasminogen activator receptor (suPAR) or anti-CD40 autoantibody. We report a successfully treated case of a 19-year-old female patient who experienced a recurrence of primary FSGS. After the diagnosis of FSGS, the patient progressed to ESRD and received a kidney transplantation (KT). Three days later, recurrence was suspected through proteinuria and hypoalbuminemia. She has been performed plasmapheresis and high dose methylprednisolone pulse therapy and shown remission status without increasing proteinuria for four years after KT. In conclusion, strong immunosuppressive therapy may be helpful for a good prognosis of recurrent FSGS, suppressing several immunologic circulating factors related disease pathogenesis.

A Less Invasive Strategy for Ruptured Cerebral Aneurysms with Intracerebral Hematomas: Endovascular Coil Embolization Followed by Stereotactic Aspiration of Hematomas Using Urokinase

OBJECTIVE: Aneurysm clipping and simultaneous hematoma evacuation through open craniotomy is traditionally recommended for ruptured cerebral aneurysms accompanied by intracerebral or intrasylvian hemorrhages. We report our experience of adapting a less invasive treatment strategy in poor-grade patients with intracerebral or intrasylvian hemorrhages associated with ruptured cerebral aneurysms, where the associated ruptured cerebral aneurysms were managed by endovascular coil embolization, followed by stereotactic aspiration of hematomas (SRH) using urokinase. MATERIALS AND METHODS: We retrospectively analyzed 112 patients with ruptured cerebral aneurysms. There were accompanying intracerebral or intrasylvian hemorrhages in 36 patients (32.1%). The most common site for these ruptured aneurysms was the middle cerebral artery (MCA) (n = 15; 41.6%). Endovascular coil embolization followed by SRH using urokinase was performed in 9 patients (25%). RESULTS: In these 9 patients, the most common site of aneurysms was the MCA (n = 3; 33.4%); the hematoma volume ranged from 19.24 to 61.68 mL. Four patients who were World Federation of Neurological Surgeons (WFNS) grade-IV on admission, achieved favorable outcomes (Glasgow Outcome Score [GOS] 4 or 5) at 6-months postoperatively. In the five patients who were WFNS grade-V on admission, one achieved a favorable outcome, whereas 4 achieved GOS scores of 2 or 3, 6-months postoperatively. There was no mortality. CONCLUSION: If immediate hematoma evacuation is not mandated by clinical or radiological signs of brain herniation, a less invasive strategy, such as endovascular coil embolization followed by SRH using urokinase, may be a good alternative in poor-grade patients with intracerebral or intrasylvian hemorrhages associated with ruptured cerebral aneurysms.

Anti-proliferative Effect of Engineered Neural Stem Cells Expressing Cytosine Deaminase and Interferon-β against Lymph Node–Derived Metastatic Colorectal Adenocarcinoma in Cellular and Xenograft Mouse Models / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Genetically engineered stem cells may be advantageous for gene therapy against various human cancers due to their inherent tumor-tropic properties. In this study, genetically engineered human neural stem cells (HB1.F3) expressing Escherichia coli cytosine deaminase (CD) (HB1.F3.CD) and human interferon-β (IFN-β) (HB1.F3.CD.IFN-β) were employed against lymph node–derived metastatic colorectal adenocarcinoma. MATERIALS AND METHODS: CD can convert a prodrug, 5-fluorocytosine (5-FC), to active 5-fluorouracil, which inhibits tumor growth through the inhibition of DNA synthesis,while IFN-β also strongly inhibits tumor growth by inducing the apoptotic process. In reverse transcription polymerase chain reaction analysis, we confirmed that HB1.F3.CD cells expressed the CD gene and HB1.F3.CD.IFN-β cells expressed both CD and IFN-β genes. RESULTS: In results of a modified trans-well migration assay, HB1.F3.CD and HB1.F3.CD.IFN-β cells selectively migrated toward SW-620, human lymph node–derived metastatic colorectal adenocarcinoma cells. The viability of SW-620 cells was significantly reduced when co-cultured with HB1.F3.CD or HB1.F3.CD.IFN-β cells in the presence of 5-FC. In addition, it was found that the tumor-tropic properties of these engineered human neural stem cells (hNSCs) were attributed to chemoattractant molecules including stromal cell-derived factor 1, c-Kit, urokinase receptor, urokinase-type plasminogen activator, and C-C chemokine receptor type 2 secreted by SW-620 cells. In a xenograft mouse model, treatment with hNSC resulted in significantly inhibited growth of the tumor mass without virulent effects on the animals. CONCLUSION: The current results indicate that engineered hNSCs and a prodrug treatment inhibited the growth of SW-620 cells. Therefore, hNSC therapy may be a clinically effective tool for the treatment of lymph node metastatic colorectal cancer.

Endovascular treatment of acute limb ischemia due to thrombotic occlusion of the suprainguinal artery / 고신대학교의과대학학술지

Acute limb ischemia (ALI) is a serious condition requiring prompt intervention due to a sudden decrease in limb perfusion threatening limb viability. Treatment of ALI depends on the clinical status of the affected limb and patient comorbidities. Surgical therapy has been the historical standard of care for restoring limb perfusion; however, percutaneous endovascular intervention has been shown to be a promising treatment option in selected patients of ALI at high surgical risk. We report on a case of a 75-year-old man with ALI caused by thrombotic occlusion of the suprainguinal artery, successfully treated with endovascular therapy including stent insertion and thrombus aspiration and catheter-directed urokinase infusion in view of the clinical findings and imaging studies.

Acute Ischemic Stroke Involving Both Anterior and Posterior Circulation Treated by Endovascular Revascularization for Acute Basilar Artery Occlusion via Persistent Primitive Trigeminal Artery

We report a case of acute ischemic stroke involving both the anterior and posterior circulation associated with a persistent primitive trigeminal artery (PPTA), treated by endovascular revascularization for acute basilar artery (BA) occlusion via the PPTA. An otherwise healthy 67-year-old man experienced sudden loss of consciousness and quadriplegia. Magnetic resonance imaging showed an extensive acute infarction in the right cerebral hemisphere, and magnetic resonance angiography showed occlusion of the right middle cerebral artery (MCA) and BA. Because the volume of infarction in the territory of the right MCA was extensive, we judged the use of intravenous tissue plasminogen activator to be contraindicated. Cerebral angiography revealed hypoplasia of both vertebral arteries and the presence of a PPTA from the right internal carotid artery. A microcatheter was introduced into the BA via the PPTA and revascularization was successfully performed using a Merci Retriever with adjuvant low-dose intraarterial urokinase. After treatment, his consciousness level and right motor weakness improved. Although persistent carotid-vertebrobasilar anastomoses such as a PPTA are relatively rare vascular anomalies, if the persistent primitive artery is present, it can be an access route for mechanical thrombectomy for acute ischemic stroke.

The Effectiveness of Subdural Drains Using Urokinase after Burr Hole Evacuation of Subacute Subdural Hematoma in Elderly Patients: A Prelimilary Report / 대한신경손상학회지

OBJECTIVE: A subdural drain using urokinase after a burr hole hematoma evacuation was performed for subacute subdural hematoma (SASDH), and its effectiveness and safety in elderly patients were evaluated. METHODS: Between January 2013 and May 2015, subdural drains using urokinase after burr hole hematoma evacuation were performed in 19 elderly patients. The inclusion criteria were as follows: 1) a subdural hematoma occurring between 4 and 20 days after injury; 2) worsening neurological symptoms, from mild to moderate or severe, due to injury during the subacute stage; 3) a mix of solid clots (high-density lighter shadow) and fluid hematoma (low-density darker shadow) on the computed tomography (CT) scan; 4) a score of ≥9 on the Glasgow Coma Scale (GCS) assessed immediately before surgery; and 5) an age of ≥65 years. When the majority of the hematoma was evacuated on the CT, we removed the catheter. RESULTS: Under local anesthesia, a catheter was inserted into the hematoma through a burr hole. The mean age of the patients was 73.7 years (range, 65-87 years). The mean preoperative GCS score was 11.2 (range, 10-13), and the mean Glasgow Outcome Scale score for all patients was 5 at discharge. No recurrences of hematomas or surgical complications were observed. CONCLUSION: A subdural drain using urokinase after burr hole hematoma evacuation under local anesthesia is thought to be an effective and safe method of blood clot removal with low morbidity. This surgical method is less invasive for treating elderly patients with SASDH.

Lower limb ischemia after bee sting / 영남의대학술지

Bee sting causes mild symptoms such as urticaria and localized pain, and severe symptoms including anaphylaxis, cardiovascular collapse, and death. We reported on a patient with arterial thrombotic occlusion and severe ischemia in the lower limb after multiple bee stings. The patient was stung 5 times and complained of pallor, pain, and coldness in the left toe, and did not have dorsalis pedis pulsation. Computed tomography angiography showed multiple thrombotic occlusion of the anterior and posterial tibial artery below the knee. Local thrombolytic therapy using urokinase was administered and the occluded arteries were successfully recanalized.

High Expression of Urokinase-Type Plasminogen Activator Is Associated with Lymph Node Metastasis of Invasive Ductal Carcinoma of the Breast / 한국유방암학회지

PURPOSE: In the present study, we evaluated the levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1) by performing immunohistochemical staining to determine whether they were reliable prognostic markers in patients with breast cancer. METHODS: Demographic and clinicopathological parameters of 214 patients with invasive ductal carcinoma (IDC) and 80 patients with ductal carcinoma in situ (DCIS) who were diagnosed and treated from 2006 to 2010 were analyzed. Tissue microarray was constructed and immunohistochemical staining was performed for each specimen. RESULTS: Univariate analyses showed that age at diagnosis, history of hormone replacement therapy, radiation therapy, skin and chest wall invasion, Paget disease, lymphovascular invasion, estrogen receptor positivity, and triple-negative subtype were significantly associated with patient prognosis (p<0.005). Patients with DCIS showed higher PAI-1 expression than patients with IDC (82.5% and 36.2%, respectively; p=0.012). Lymph node metastasis was more frequent in patients with high uPA levels than in patients with low uPA levels (p=0.001). CONCLUSION: Our results suggested that PAI-1 was involved in tumor progression in the early stages of breast cancer, such as DCIS. In addition, our results suggested that high uPA levels were associated with the lymph node metastasis of IDC.

Delayed Presentation of Endovenous Heat-Induced Thrombosis Treated by Thrombolysis and Subsequent Open Thrombectomy

Although endovenous heat-induced thrombosis (EHIT) is frequently reported after endovenous laser ablation (EVLA), the incidence and timing of occurrence of EHIT are not fully understood. We present a case of EHIT successfully treated with a combination of surgical and endovascular treatments. A 57-year-old woman, two months post bilateral EVLA, presented with a swollen leg. Deep vein thrombosis was diagnosed by Doppler ultrasonography and computerized tomographic venography. We treated the patient with catheter-directed thrombolysis with urokinase after insertion of an inferior vena cava filter. After thrombolytic treatment, we performed surgical venous thrombectomy, due to the presence of a large thrombus in the femoral vein. During the operation, we found organized old thrombus at the great saphenous vein which connected to the deep femoral vein. From these findings, we confirmed the presence of EHIT despite a long time having passed after EVLA. The patient was placed on anticoagulation therapy with oral rivaroxaban for three months.

A Viewpoint on Treatment of Traumatic Bilateral Basal Ganglia Hemorrhage in a Child: Case Report / 대한신경손상학회지

Traumatic basal ganglia hemorrhage (TBGH) is a rare presentation of head injuries. Bilateral lesions are extremely rare. The pathophysiologic mechanism of bilateral TBGH seems to be the same as diffuse axonal injury. However, limited information about childhood bilateral TBGH is available in the literature. We report the case of a child with bilateral TBGH treated with stereotactic aspiration of hemorrhage and periodic urokinase irrigation.

Fibrinólisis como tratamiento en la trombosis de la vena subclavia: nuestra experiencia en causas primarias y secundarias / Fibrinolysis as Treatment in Subclavian Vein Thrombosis: Our Experience in Primary and Secondary Causes

La trombosis de la vena subclavia reviste especial gravedad por las secuelas funcionales y las posibles complicaciones sistémicas que puede desencadenar cuando no se diagnostica a tiempo. Aunque en muchos casos la presentación clínica puede ser diagnóstica, siempre se requieren pruebas de imagen, ya sean no invasivas, como la ecografía con Doppler color, o invasivas, como la flebografía, que es considerada el patrón de oro, ya que demuestra el trombo y confirma la permeabilidad de la circulación colateral. El objetivo de este estudio es demostrar los resultados de la fibrinólisis por catéter y comprobar que su tratamiento agresivo está justificado para evitar secuelas incapacitantes, especialmente en gente joven. Entre el 1 enero de 2006 y el 31 de diciembre de 2012 se atendieron cinco pacientes diagnosticados con trombosis en la vena subclavia, y fueron tratados con fibrinólisis endovenosa con uroquinasa a 100.000 UI/hora. El criterio para escoger los pacientes a trombolizar, fue el tiempo de evolución menor de 6 días y las características agudas del trombo (trombo hipoecogénico-homogéneo, que ocasiona aumento del calibre venoso), así como las características del paciente, edad y repercusión clínica. En nuestra limitada experiencia hemos tenido un éxito del 80 %, con resolución de la sintomatología en el 100 % en trombólisis con uroquinasa, por lo cual la recomendamos como el manejo inicial de las trombosis subclavias, siempre y cuando cumplan las indicaciones y haya ausencia de contraindicaciones absolutas o relativas para trombólisis.

Subclavian vein thrombosis can be particularly serious due to the functional consequences and possible systemic complications that can be triggered when not diagnosed early. Although in many cases the clinical presentation may be diagnostic, imaging is always required, either non-invasive (Doppler ultrasound) and / or invasive, as is the case with venography which is considered the gold standard because it shows the thrombus and confirms the permeability of the collateral circulation. The purpose of the study is to demonstrate the results of catheter directed fibrinolysis and suggests that aggressive treatment of this condition is justified to prevent the possible disabling sequelae, particularly in young people. During the period between January 1, 2006 to December 31, 2012, 5 patients were treated for thrombosis in the subclavian vein with catheter directed thrombolysis with urokinase at 100,000 UI/hour. The selection criteria for thrombolysis, was the time of evolution (less than 6 days) and acute characteristics of thrombus in ultrasound (hypo echogenic-homogenous thrombus, which causes an increase in venous caliber), as well as the characteristics of the patient, the age, and clinical repercussions. In our limited experience we had a success rate of 80% due to the dissolution of the thrombus, with a 100% resolution of symptoms in thrombolysis with urokinase; so we recommend it as the initial management of the subclavian thrombosis as long as the patients are symptomatic and have not contraindications to thrombolysis.

Safety and Efficacy of Low Dosage of Urokinase for Catheter-directed Thrombolysis of Deep Venous Thrombosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Catheter-directed thrombolysis (CDT) has been a mainstay in treating deep venous thrombosis (DVT). However, the optimal dosage of a thrombolytic agent is still controversial. The goal of this study was to evaluate the safety and efficacy of low dosage urokinase with CDT for DVT.</p><p><b>METHODS</b>A retrospective analysis was performed using data from a total of 427 patients with DVT treated with CDT in our single center between July 2009 and December 2012. Early efficacy of thrombolysis was assessed with a thrombus score based on daily venography. The therapeutic safety was evaluated by adverse events. A venography or duplex ultrasound was performed to assess the outcome at 6 months, 1 year and 2 years postoperatively.</p><p><b>RESULTS</b>The mean total dose of 3.34 (standard deviation [SD] 1.38) million units of urokinase was administered during a mean of 5.18 (SD 2.28) days. Prior to discharge, Grade III (complete lysis) was achieved in 154 (36%) patients; Grade II (50-99% lysis) in 222 (52%); and Grade I (50% lysis) in 51 (12%). The major complications included one intracranial hemorrhage, one hematochezia, five gross hematuria, and one pulmonary embolism. Moreover, no death occurred in the study.</p><p><b>CONCLUSIONS</b>Treatment of low-dose catheter-directed thrombosis is an efficacious and safe therapeutic approach in patients with DVT offering good long-term outcomes and minimal complications.</p>

Effects of urokinase type plasminogen activator and plasminogen activator inhibitor-1 expressions on the formation of aneurysm of perimembranous ventricular septal defect / 中华儿科杂志

<p><b>OBJECTIVE</b>The exact mechanisms of defect closure in patients with perimembranous ventricular septal defect (PMVSD) remain unknown. We hypothesized that the expression of urokinase type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) may mediate extracellular matrix (ECM) remodeling in aneurysms.</p><p><b>METHOD</b>Seven normal heart tricuspid septal leaflet and 33 aneurysms were collected in Shanghai Renji Hospital and Shanghai Children's Medical Center from January 2008 to June 2010. Immunohistochemical expression of uPA and PAI-1 in 4 normal heart valvular tissues and 15 aneurysms was detected with immunohistochemical methods. The expression of uPA and PAI-1 mRNA in 3 normal heart valvular tissues and 7 aneurysms was studied by real time fluorescent PCR; the protein expression of uPA and PAI-1 in 4 normal heart valvular tissues and 11 aneurysms was tested with Western blotting.</p><p><b>RESULT</b>The surface of the aneurysms were completely covered by endothelial cells. Two types of granulation tissue, myxoid and fibrous, were associated with the aneurismal formation. uPA were recognized predominantly in valvar interstitial cells (VICs) which located mainly in regions adjacent to the endothelium and smooth muscle cells of blood vessels. PAI-1 was found in both VICs which located mainly in granulation tissue and endothelial cells. Nine aneurysms expressed a higher uPA activity than 4 normal valvular tissues ((74.6±11.8)% vs. (49.5±7.4)%; t = 3.87, P = 0.003) and six aneurysms expressed a low uPA activity ((10.3±3.1)% vs. (49.5±7.4)%; t=11.78, P=0.000) and a high PAI-1 activity ((55.2±1.7)% vs. (50.8±3.8)%; t=2.55, P=0.034) using immunohistochemical methods. uPA / PAI-1 ratio of protein expression tested by Western blot was 0.88±0.22 in four normal heart vavular tissues; five aneurysms expressed high uPA activity and low PAI-1 activity and uPA/PAI-1 ratio was 4.26±2.04; while the other 6 cases expressed low uPA activity and high PAI-1 activity and uPA/PAI-1 ratio was 0.30±0.07; the difference among the three groups was statistically significant (P<0.05). The rate of uPA/PAI-1 in relative copy of mRNA expression among normal heart valvular tissue, high uPA expressed aneurysms and low uPA expressed aneurysms are also significantly different (2.14±0.17 vs. 0.45±0.04; 2.14±0.17 vs. 4.38±1.41, P<0.05) respectively.</p><p><b>CONCLUSION</b>The expression of uPA and PAI-1 in VICs suggests that interactions among these molecules contribute to the aneurysm formation and development. This provides a potential mechanism for defect closure in patients with PMVSD.</p>