BACKGROUND Early hepatic artery thrombosis(E-HAT)is a serious complication after liver transplantation(LT),which often results in graft failure and can lead to patient deaths.Treatments such as re-transplantation and ...BACKGROUND Early hepatic artery thrombosis(E-HAT)is a serious complication after liver transplantation(LT),which often results in graft failure and can lead to patient deaths.Treatments such as re-transplantation and re-anastomosis are conventional therapeutic methods which are restricted by the shortage of donors and the patient’s postoperative intolerance to re-laparotomy.Due to the advances in interventional techniques and thrombolytics,endovascular treatments are increasingly being selected by more and more centers.This study reviews and reports our single-center experience with intra-arterial thrombolysis as the first choice therapy for E-HAT after deceased donor LT.AIM To evaluate the feasibility and reasonability of intra-arterial thrombolysis for EHAT after deceased donor LT.METHODS A total of 147 patients who underwent deceased donor LT were retrospectively reviewed in our hospital between September 2011 and December 2016.Four patients were diagnosed with E-HAT.All of these patients underwent intraarterial thrombolysis with alteplase as the first choice therapy after LT.The method of arterial anastomosis and details of the diagnosis and treatment of EHAT were collated.The long-term prognosis of E-HAT patients was also recorded.The median follow-up period was 26 mo(range:23 to 30 mo).RESULTS The incidence of E-HAT was 2.7%(4/147).E-HAT was considered when Doppler ultrasonography showed no blood flow signals and a definite diagnosis was confirmed by immediate hepatic arterial angiography when complete occlusion of the hepatic artery was observed.The patients were given temporary thrombolytics(mainly alteplase)via a 5-Fr catheter which was placed in the proximal part of the thrombosed hepatic artery followed by continuous alteplase using an infusion pump.Alteplase dose was adjusted according to activated clotting time.The recanalization rate of intra-arterial thrombolysis in our study was 100%(4/4)and no thrombolysis-related mortality was observed.During the follow-up period,patient survival rate was 75%(3/4),and biliary complications were present in 50%of patients(2/4).CONCLUSION Intra-arterial thrombolysis can be considered first-line treatment for E-HAT after deceased donor LT.Early diagnosis of E-HAT is important and follow-up is necessary even if recanalization is successful.展开更多
Objective:To study the different effects of mechanical embolus removal and intra-arterial thrombolysis on neural functional recovery in patients with acute middle cerebral artery occlusion.Methods: Patients with acute...Objective:To study the different effects of mechanical embolus removal and intra-arterial thrombolysis on neural functional recovery in patients with acute middle cerebral artery occlusion.Methods: Patients with acute middle cerebral artery occlusion who were treated in the First Hospital of Yulin between September 2013 and October 2017 were selected and retrospectively studied, and the differences in reperfusion therapies in history data were referred to divide them into study group A and study group B who underwent mechanical embolus removal and intra-arterial thrombolysis respectively. The levels of neurocyte damage markers, apoptosis markers and stress markers in serum as well as the expression of Wnt pathway molecules in peripheral blood were determined before treatment and 24 h after treatment.Results: Compared with those of same group before treatment, serum NSE, S100B, VILIP1, sFas, sFasL, ET-1 and MDA levels as well as peripheral blood GSK3β, LC3-II and Beclin1 expression intensity of both groups were decreasing whereas serum BDNF, NTF, sLivin and SOD levels as well as peripheral bloodβ-catenin and mTOR expression intensity were increasing, and serum NSE, S100B, VILIP1, sFas, sFasL, ET-1 and MDA levels as well as peripheral blood GSK3β, LC3-II and Beclin1 expression intensity of study group A after treatment were lower than those of study group B whereas serum BDNF, NTF, sLivin and SOD levels as well as peripheral bloodβ-catenin and mTOR expression intensity were higher than those of study group B.Conclusion: Mechanical embolus removal for acute middle cerebral artery occlusion can be more effective than intra-arterial thrombolysis to reduce the nerve function damage as well as the corresponding oxidative stress and apoptosis.展开更多
Introduction: Venous thromboembolic disease is the 3rd most common cardiovascular pathology. Acute pulmonary embolism constitutes its most serious presentation and a major cause of mortality, morbidity and hospitaliza...Introduction: Venous thromboembolic disease is the 3rd most common cardiovascular pathology. Acute pulmonary embolism constitutes its most serious presentation and a major cause of mortality, morbidity and hospitalization in Africa and Senegal. The objectives of this work were to study the epidemiological profile of pulmonary embolisms and to evaluate the practice of thrombolysis in patients in a cardiological setting. Methodology: A retrospective, descriptive study was carried out in the Cardiology department of the Aristide le Dantec Hospital (HALD) over the period from August 2011 to December 2019 in patients hospitalized in the cardiology department for pulmonary embolism confirmed by CT angiography and/or with thrombi on cardiac ultrasound and who had also benefited from thrombolysis. Results: Thirty-one patients with pulmonary embolism were thrombolyzed. There was a predominance of the female gender with an average age of 45.97 years. Risk factors were dominated by age (61.29%) followed by obesity (32.26%) and prolonged immobilization (22.5%). The functional signs were dominated by dyspnea (77.42%) followed by chest pain (51.62%) and cough (35.48%). The physical signs were dominated by right heart failure in 22.5% of cases, pulmonary condensation syndrome in 19.35%, and inflammatory large leg in 12.9% of cases. Echocardiography and chest CT angiography were the means of diagnosis. Nine of our patients presented with an intracardiac mass. Thrombotic treatment was administered in all patients. The average length of hospitalization was 12.32 days and in-hospital mortality was 32.26%. Conclusion: Pulmonary embolism does exist in our regions and is responsible for heavy mortality. Rapid and efficient support is essential. Prevention remains the corner-stone in the fight against this pathology.展开更多
BACKGROUND:Bleeding outcomes are crucial primary safety endpoints in studies involving thrombolytic agents.This study aimed to determine the incidence,characteristics and mortality outcomes of bleeding following ST-el...BACKGROUND:Bleeding outcomes are crucial primary safety endpoints in studies involving thrombolytic agents.This study aimed to determine the incidence,characteristics and mortality outcomes of bleeding following ST-elevation myocardial infarction(STEMI)thrombolysis in an Asian population.METHODS:This single-centre retrospective study included all STEMI patients who received thrombolytic therapy from 2016 to 2020 in a Malaysian tertiary hospital.Total population sampling was used in this study.The primary outcome was bleeding events post-thrombolysis,categorised using the Thrombolysis in Myocardial Infarction(TIMI)bleeding criteria.Inferential statistics were used to determine the associations between relevant variables.RESULTS:Data from 941 patients were analysed.A total of 156(16.6%)STEMI patients bled post-thrombolysis.Major,minor,and minimal TIMI occurred in 7(0.7%),17(1.8%),and 132(14.0%)patients,respectively.Age 65 years(P=0.031)and Malaysian Chinese(P=0.008)were associated with a higher incidence of bleeding post-thrombolysis.Conversely,foreigners(P=0.032)and current smoker(P=0.007)were associated with a lower incidence of bleeding.Both TIMI major(P<0.001)and TIMI minor(P<0.001)were associated with a higher incidence of all-cause in-hospital mortality among STEMI patients.TIMI minor bleeding was significantly higher in the streptokinase recipients.The bleeding sites were comparable between streptokinase and tenecteplase recipients,except for a significantly higher incidence of gastrointestinal bleeding in the streptokinase recipients(P=0.027).CONCLUSION:In our Asian population,the incidence of total bleeding events following STEMI thrombolysis is comparable to that previously reported.The development of TIMI major and minor bleeding complications is associated with higher mortality.展开更多
BACKGROUND Acute ischemic stroke(AIS)retains a notable stance in global disease burden,with thrombolysis via recombinant tissue plasminogen activator(rtPA)serving as a viable management approach,albeit with variable o...BACKGROUND Acute ischemic stroke(AIS)retains a notable stance in global disease burden,with thrombolysis via recombinant tissue plasminogen activator(rtPA)serving as a viable management approach,albeit with variable outcomes and the potential for complications like hemorrhagic transformation(HT).The platelet-to-neutrophil ratio(P/NR)has been considered for its potential prognostic value in AIS,yet its capacity to predict outcomes following rtPA administration demands further exploration.AIM To elucidate the prognostic utility of P/NR in predicting HT and clinical outcomes following intravenous rtPA administration in AIS patients.METHODS Data from 418 AIS patients treated with intravenous rtPA at Thammasat University Hospital from January 2018 to June 2021 were retrospectively analyzed.The relationship between P/NR and clinical outcomes[early neurological deterioration(E-ND),HT,delayed ND(D-ND),and 3-mo outcomes]was scrutinized.RESULTS Notable variables,such as age,diabetes,and stroke history,exhibited statistical disparities when comparing patients with and without E-ND,HT,D-ND,and 3-mo outcomes.P/NR prognostication revealed an optimal cutoff of 43.4 with a 60.3%sensitivity and a 52.5%specificity for 90-d outcomes.P/NR prognostic accuracy was statistically significant for 90-d outcomes[area under the curve(AUC)=0.562],D-ND(AUC=0.584),and HT(AUC=0.607).CONCLUSION P/NR demonstrated an association with adverse 3-mo clinical outcomes,HT,and D-ND in AIS patients post-rtPA administration,indicating its potential as a predictive tool for complications and prognoses.This infers that a diminished P/NR may serve as a novel prognostic indicator,assisting clinicians in identifying AIS patients at elevated risk for unfavorable outcomes following rtPA therapy.展开更多
Objective This study was to evaluate the efficacy and safety of a short acting reduced dose fibrinolytic regimen to promote early infarct related artery (IRA) patency for acyute myocardial infarction (AMI) patients re...Objective This study was to evaluate the efficacy and safety of a short acting reduced dose fibrinolytic regimen to promote early infarct related artery (IRA) patency for acyute myocardial infarction (AMI) patients referred for percutaneous coronary intervention (PCI).Methods Following aspirin and heparin, 166 patients were randomized to a 50 mg bolus of recombinant tissue type plasminogen activator(rt PA) or to a same volume sodium chloride injection followed by immediate primary PCI. The end points included patency rates on catheterization laboratory (cath lab) arrival, revascularization results when PCI was performed, complication rates, left ventricular function and restored patency rate following PCI. Results Patency on cath lab arrival was 64% with rt PA (34% TIMI 3,30% TIMI 2), while 31% of placebo (13% TIMI 3, 18% TIMI 2). There was no difference in the restored TIMI 3 rates of IRA between the two groups (85% vs 87%). No difference were observed in stroke or major bleeding. Left ventricular function was similar in both groups (52±9% vs 50±8%), but left ventricular ejection fraction fraction (LVEF) was higher with patent IRA (TIMI 3) on cath lab arrival than that of others (56±12% vs 48±10%).Conclusions Strategy thrombolytic regimens were compatible with subsequent PCI lead to more frequenc early recanalization (before cath lab arrival), which facilitates greater left ventricular function preservation with no augmentation of adverse events.展开更多
Background Clearance of coronary arterial thrombosis is necessary in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing urgent percutaneous coronary intervention (PCI). There is currentl...Background Clearance of coronary arterial thrombosis is necessary in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing urgent percutaneous coronary intervention (PCI). There is currently no highly-recommended method of thrombus removal during interventional procedures. We describe a new method for opening culprit vessels to treat STEMI: intracoronary arterial retrograde thrombolysis (ICART) with PCI. Methods & Results Eight patients underwent ICART. The guidewire was advanced to the distal coronary artery through the occlusion lesion. Then, we inserted a microcatheter into the distal end of the occluded coronary artery over the guidewire. Urokinase (5–10 wu) mixed with contrast agents was slowly injected into the occluded section of the coronary artery through the microcatheter. The intracoronary thrombus gradually dissolved in 3–17 min, and the effect of thrombolysis was visible in real time. Stents were then implanted according to the characteristics of the recanalized culprit lesion to achieve full revascularization. One patient experienced premature ventricular contraction during vascular revascularization, and no malignant arrhythmias were seen in any patient. No reflow or slow flow was not observed post PCI. Thrombolysis in myocardial infarction flow grade and myocardial blush grade post-primary PCI was 3 in all eight patients. No patients experienced bleeding or stroke. Conclusions ICART was accurate and effective for treating intracoronary thrombi in patients with STEMI in this preliminary study. ICART was an effective, feasible, and simple approach to the management of STEMI, and no intraprocedural complications occurred in any of the patients. ICART may be a breakthrough in the treatment of acute STEMI.展开更多
To achieve targeted thrombolysis, a targeted delivery system of lumbrokinase(LK) was constructed using RGDfk-conjugated hybrid micelles. Based on the specific affinity of RGDfk to glycoprotein complex of GP Ⅱ b/Ⅲ a ...To achieve targeted thrombolysis, a targeted delivery system of lumbrokinase(LK) was constructed using RGDfk-conjugated hybrid micelles. Based on the specific affinity of RGDfk to glycoprotein complex of GP Ⅱ b/Ⅲ a expressed on the surface of membrane of activated platelet, LK loaded targeted micelles(LKTM) can be delivered to thrombus. The hybrid micelles were composed of polycaprolactone-block-poly(2-(dimethylamino) ethyl methacrylate)(PCL-PDMAEMA), methoxy polyethylene glycol-block-polycaprolactone(mPEG-PCL)and RGDfk conjugated polycaprolactone-block-polyethylene glycol(PCL-PEG-RGDfk). PCLPDMAEMA was synthesized via ring open polymerization(ROP) and atom transfer radical polymerization(ATRP). PCL-PEG-RGDfk was synthesized via ROP and carbodiimide chemistry. The prepared LKTM was characterized by dynamic light scattering(DLS) and transmission electron microscope(TEM). Colloidal stability assay showed the prepared LKTM was stable. Biocompatibility assay was performed to determine the safe concentration range of polymer. The assay of fluorescent distribution in vivo demonstrated that LKTM can be efficiently delivered to thrombi in vivo. Thrombolysis in vivo indicated the thrombolytic potency of LKTM was optimal in all groups. Notably, the laboratory mice treated with LKTM exhibited a significantly shorter tail bleeding time compared to those treated with LK or LK-loaded micelles without RGDfk, which suggested that the targeted delivery of LK using RGDfk-conjugated hybrid micelles effectively reduced the bleeding risk.展开更多
AIM To evaluate the safety and efficacy of agitation thrombolysis(AT) combined with catheter-directed thrombolysis(CDT) for the treatment of non-cirrhotic acute portal vein thrombosis(PVT). METHODS Nine patients with ...AIM To evaluate the safety and efficacy of agitation thrombolysis(AT) combined with catheter-directed thrombolysis(CDT) for the treatment of non-cirrhotic acute portal vein thrombosis(PVT). METHODS Nine patients with non-cirrhotic acute PVT who underwent AT combined with CDT were analyzed retrospectively. Portography was carried out via the transjugular intrahepatic portosystemic(commonly known as TIP) or percutaneous transhepatic(commonly known as PT) route, followed by AT combined with CDT. Complications of the procedure, and the changes in clinical symptoms, hemodynamics of the portal vein and liver function were recorded. Follow-up was scheduled at1, 3 and 6 mo after treatment, and every 6 mo thereafter, or when the patients developed clinical symptoms related to PVT. Color Doppler ultrasound and contrast-enhanced computed tomography/magnetic resonance imaging were performed during the follow-up period to determine the condition of the portal vein.RESULTS AT combined with CDT was successfully performed. The portal vein was reached via the TIP route in 6 patients, and via the PT route in 3 patients. All clinical symptoms were relieved or disappeared, with the exception of 1 patient who died of intestinal necrosis 9 d after treatment. Significant differences in the changes in portal vein hemodynamics were observed, including the maximum lumen occupancy of PVT, portal vein pressure and flow velocity between pre-and posttreatment(P < 0.05). During the follow-up period, recurrence was observed in 1 patient at 19 mo after the procedure, and the portal vein was patent in the remaining patients.CONCLUSION AT combined with CDT is a safe and effective method for the treatment of non-cirrhotic acute PVT.展开更多
AIM: To assess role of combined modality of mechanical fragmentation and intralesional thrombolysis in patients with massive pulmonary embolism presenting subacutely. METHODS: Eight of 70 patients presenting in tertia...AIM: To assess role of combined modality of mechanical fragmentation and intralesional thrombolysis in patients with massive pulmonary embolism presenting subacutely. METHODS: Eight of 70 patients presenting in tertiary care centre of North India with massive pulmonary embolism within 4 years had subacute presentation (symptom onset more than 2 wk). These patients were subjected to pulmonary angiography with intention to treat basis via mechanical breakdown and intra lesional thrombolysis. Mechanical breakdown of embolus was accomplished with 5-F multipurpose catheter to reestablish flow, followed by intralesional infusion of urokinase (4400 IU/kg over 10 min followed by 4400 IU/kg per hour over 24 h). RESULTS: Eight patients, mean age 47.77±12.20 years presented with subacute pulmonary embolism (mean duration of symptoms 2.4 wk). At presentation, mean heart rate, shock index, miller score and mean pulmonary pressures were 101.5±15.2/min, 0.995±0.156, 23.87±3.76 and 37.62±6.67 mmHg which reduced to 91.5±12.2/min (P=0.0325), 0.789±0.139 (P=0.0019), 5.87±1.73 (P=0.0000004) and 27.75±8.66 mmHg (P=0.0003) post procedurally. Mean BP improved from 80.00±3.09 mmHg to 90.58±9.13 mmHg (P=0.0100) post procedurally. Minor complications in the form of local hematoma-minor hematoma in 1 (12.5%), and pseudoaneurysm (due to femoral artery puncture) in 1 (12.5 %) patient were seen. At 30 d and 6 mo follow up survival rate was 100% and all the patients were asymptomatic and in New York Heart Association class 1. CONCLUSION: Combined modality of mechanical fragmentation and intralesional thrombolysis appears to be a promising alternative to high risk surgical procedures in patients with subacute massive pulmonary embolism.展开更多
Activity of matrix metalloproteinase-9 increases following cerebral ischemia/reperfusion, and is associated with cerebral microvascular permeability, blood-brain barrier destruction, inflammatory cell infiltration and...Activity of matrix metalloproteinase-9 increases following cerebral ischemia/reperfusion, and is associated with cerebral microvascular permeability, blood-brain barrier destruction, inflammatory cell infiltration and brain edema. Matrix metalloproteinase-9 also likely participates in thrombolysis. A rat model of middle cerebral artery infarction was established by injecting autologous blood clots into the internal carotid artery. At 3 hours following model induction, urokinase was injected into the caudal vein. Decreased neurological severity score, reduced infarct volume, and increased expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were observed in the cerebral cortex 24 hours after urokinase thrombolysis. These results suggest that urokinase can suppress damage in the acute-early stage of cerebral infarction.展开更多
The efficacy and safety of recombinant tissue plasminogen activator (rtPA) need to be improved due to its low bioavailability and requirement of large dose administration. The purpose of this study was to develop a ...The efficacy and safety of recombinant tissue plasminogen activator (rtPA) need to be improved due to its low bioavailability and requirement of large dose administration. The purpose of this study was to develop a fibrin-targeted nanoparticle (NP) drug delivery system for thrombosis combination therapy. We conjugated rtPA to poly(ethylene glycol)- poly(ε-caprolactone) (PEG-PCL) nanoparticles (rtPA-NP) and investigated its physicochemical characteristics such as particle size, zeta potential, enzyme activity of conjugated rtPA and its storage stability at 4℃. The thrombolytic activity of rtPA-NP was evaluated in vitro and in vivo as well as the half-life of rtPA-NP, the properties to fibrin targeting and its influences on systemic hemostasis in vivo. The results showed that rtPA-NP equivalent to 10% of a typical dose of rtPA could dissolve fibrin clots and were demonstrated to have a neuroprotective effect after focal cerebral ischemia as evidenced by decreased infarct volume and improved neurological deficit (P〈0.001). RtPA-NP did not influence the in vivo hemostasis or coagulation system. The half-life of conjugated rtPA was shown to be approximately 18 times longer than that of free rtPA. These experiments suggested that rtPA-conjugated PEG-PCL nanoparticles might be a promising fibrin-targeted delivery system for a combination treatment of thrombosis.展开更多
AIM:To present a series of cases with symptomatic acute extensive portal vein(PV)and superior mesenteric vein(SMV)thrombosis after splenectomy treated by transjugular intrahepatic approach catheter-directed thrombolys...AIM:To present a series of cases with symptomatic acute extensive portal vein(PV)and superior mesenteric vein(SMV)thrombosis after splenectomy treated by transjugular intrahepatic approach catheter-directed thrombolysis. METHODS:A total of 6 patients with acute extensive PV-SMV thrombosis after splenectomy were treated by transjugular approach catheter-directed thrombolysis. The mean age of the patients was 41.2 years.After access to the portal system via the transjugular approach,pigtail catheter fragmentation of clots, local urokinase injection,and manual aspiration thrombectomy were used for the initial treatment of PV-SMV thrombosis,followed by continuous thrombolytic therapy via an indwelling infusion catheter in the SMV,which was performed for three to six days. Adequate anticoagulation was given during treatment, throughout hospitalization,and after discharge. RESULTS:Technical success was achieved in all 6 patients.Clinical improvement was seen in these patients within 12-24 h of the procedure.No complications were observed.The 6 patients were discharged 6-14 d(8±2.5 d)after admission.The mean duration of follow-up after hospital discharge was 40±16.5 mo.Ultrasound and contrast-enhanced computed tomography confirmed patency of the PV and SMV,and no recurrent episodes of PV-SMV thrombosis developed during the follow-up period. CONCLUSION:Catheter-directed thrombolysis via transjugular intrahepatic access is a safe and effective therapy for the management of patients with symptomatic acute extensive PV-SMV thrombosis.展开更多
AIM. To evaluate the time dependence of intra-arterial 5-fluorouracil (5-FU) therapy for advanced hepatocellular carcinoma (aHCC). METHODS: Thirty-seven adult Japanese patients who had aHCC and liver cirrhosis we...AIM. To evaluate the time dependence of intra-arterial 5-fluorouracil (5-FU) therapy for advanced hepatocellular carcinoma (aHCC). METHODS: Thirty-seven adult Japanese patients who had aHCC and liver cirrhosis were treated with combined intra-arterial 5-FU, cisplatin (CDDP), and leucovorin (LV). The Japan Integrated Staging score (JIS score) of each patient was 3 or more. The patients were divided into two groups, alter which the 15 patients in group S were treated with 6-h infusion chemotherapy (LV at 12 mg/h, CDDP at 10 mg/h, and 5-FU at 250 mg/m^2 per 4 h) and the 22 patients in group L were treated with 24-h infusion chemotherapy (LV at 12 mg/h, CDDP at 10 mg/h, and 5-FU at 250 mg/m^2 per 22 h). Continuous infusion chemotherapy was performed v/a the proper hepatic artery every 5 d for 4 wk using an implanted drug reservoir. RESULTS: The percentages of patients with a partial response after 4 wk of chemotherapy were 6.7% in group S and 31.8% in group L. The survival of group L was significantly better than that of group S, with the median survival time being 496 d in group L and 226 d in group S (P 〈 0.05). CONCLUSION: Continuous 24-h intra-arterial infusion is more effective for aHCC and can markedly prolong survival time as compared to 6-h infusion.展开更多
AIM: To investigate the poor prognosis of HCC with PVTT, we evaluated the efficacy by a new combination chemotherapy for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). METHODS: F...AIM: To investigate the poor prognosis of HCC with PVTT, we evaluated the efficacy by a new combination chemotherapy for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). METHODS: From 2002 to 2007, a total of 10 consecutive patients with Stage IVA HCC accompanied by PVTT were studied prospectively to examine the efficacy of treatment by intra-arterial infusion of a chemotherapeutic agents consisting of etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil. RESULTS: The mean course of chemotherapy was 14.4 (range, 9-21) too. One patient showed complete response (CR) with disappearance of HCC and PVI-F after treatment, and the two patients showed partial response (PR), response rate (CR + PR/All cases 30%). The median survival time after the therapy was 457.2 d. The one-year survival rate was 70%. Adverse reactions were tolerable.CONCLUSION: Although the prognosis of most patients with Stage IVA HCC by PVTT is poor, our combination chemotherapy may induces long-term survival and is an effective treatment and produced anti-tumor activity with tolerable adverse effects in patients for advanced Stage IVA HCC accompanied by PVTT.展开更多
BACKGROUND: Massive pulmonary embolism(MPE) and acute myocardial infarction are the two most common causes of cardiac arrest(CA). At present, lethal hemorrhage makes thrombolytic therapy underused during cardiopulmona...BACKGROUND: Massive pulmonary embolism(MPE) and acute myocardial infarction are the two most common causes of cardiac arrest(CA). At present, lethal hemorrhage makes thrombolytic therapy underused during cardiopulmonary resuscitation, despite the potential benefits for these underlying conditions. Hypercoagulability of the blood in autoimmune disorders(such as autoimmune hemolytic anemia) carries a risk of MPE. It is critical to find out the etiology of CA for timely thrombolytic intervention.METHODS: A 23-year-old woman with a 10-year medical history of autoimmune hemolytic anemia suffered from CA in our emergency intensive care unit. ECG and echocardiogram indicated the possibility of MPE, so f ibrinolytic therapy(alteplase) was successful during prolonged resuscitation.RESULTS: Neurological recovery of the patient was generally good, and no fatal bleeding developed. MPE was documented by CT pulmonary angiography.CONCLUSIONS: A medical history of autoimmune disease poses a risk of PE, and the causes of CA(such as this) should be investigated etiologically. A therapy with alteplase may be used early during cardiopulmonary resuscitation once there is presumptive evidence of PE. Clinical trials are needed in this setting to study patients with hypercoagulable states.展开更多
AIM To assess the usefulness of intra-arterial contrastenhanced ultrasonography(IAUS) during transarterial chemoembolization(TACE) with drug-eluting beads(DEB) for hepatocellular carcinoma(HCC).METHODS Thirty two pati...AIM To assess the usefulness of intra-arterial contrastenhanced ultrasonography(IAUS) during transarterial chemoembolization(TACE) with drug-eluting beads(DEB) for hepatocellular carcinoma(HCC).METHODS Thirty two patients with 39 HCC underwent DEB-TACE guided with IAUS, and examined by contrast-enhanced ultrasonography(CEUS) or dynamic CT after DEB-TACE were enrolled in this study. CEUS findings before DEBTACE and IAUS findings were compared. Treatments judged to be complete and incomplete for lesions were appropriate and insufficient, respectively. Findings on CEUS and/or dynamic CT performed 1, 3 and 6 mo after DEB-TACE were evaluated using m RECIST(CR/PR/SD/PD).RESULTS The treatments were complete and incomplete in 26 and 13 lesions, respectively. On imaging evaluation using CEUS and/or dynamic CT one month after treatment, 25 and 1 lesions were judged to be CR and PR, respectively, and at 6 mo after treatment, the results were CR, PR, SD and PD for 24, 1, 0 and 1 of these lesions, respectively, in the 26 completely treated lesions. Of the 13 lesions in which treatment was incomplete, the results on imaging at one month after treatment were CR, PR, SD and PD for 0, 6, 4 and 3 lesions, respectively. The overall CR rate at 6 mo after treatment was 61.5%(24/39).CONCLUSION A combination of DEB-TACE with IAUS can improve the therapeutic effects in patients with HCC.展开更多
AIM: To determine the optimal initial treatment modality for acute superior mesenteric vein thrombosis (ASMVT) in patients with circumscribed peritonitis.
·AIM: To obtain baseline knowledge about the current use of intra-arterial chemotherapy(SSOAIC) in centers worldwide.·METHODS: A survey including questions about the use of SSOAIC was emailed to retinoblasto...·AIM: To obtain baseline knowledge about the current use of intra-arterial chemotherapy(SSOAIC) in centers worldwide.·METHODS: A survey including questions about the use of SSOAIC was emailed to retinoblastoma experts.·RESULTS:Seventy-nine(response rate 69.9%) doctors from 63 centers in 35 countries responded. Thirty-one centers from 19 countries use SSOAIC. Twelve performed more than 50 procedures. Melphalan is the most commonly used drug but 15 centers use more than one drug. First line therapy for advanced unilateral disease is the most common use of SSOAIC(74.2%). Centers with larger experience(】50 applications) were less likely using melphalan alone(P =0.06) and significantly more likely using SSOAIC in more situations such as second line in preference to radiotherapy P =0.05. Nineteen(61.2%)stated that SSOAIC improved their results and 21(77.8%)reported less toxicity compared to other treatments.Three centers reported that SSOAIC did not improve their results. There were regional variations in the use of SSOAIC which is used more frequently as secondary treatment in Europe compared to the USA and Japan.Ten centers identified cost is the major limiting factor for SSOAIC.· CONCLUSION: SSOAIC is used in an increasing number of centers worldwide with regional variations.Centers with more experience in SSOAIC use it in more situations including other drugs than melphalan. The majority of the centers using this technique reportedimproved results and few complications.展开更多
The present study investigated the association between pre-treatment with a cholesterol-lowering drug(statin) or new setting hereon and the effect on the mortality rate in patients with acute ischemic stroke who recei...The present study investigated the association between pre-treatment with a cholesterol-lowering drug(statin) or new setting hereon and the effect on the mortality rate in patients with acute ischemic stroke who received intravenous systemic thrombolysis. During a 5-year period(starting in October 2008), 542 consecutive stroke patients who received intravenous systemic thrombolysis with recombinant tissue plasminogen activator(rt-PA) at the Department of Neurology, University Hospital Schleswig-Holstein, Campus Lübeck, Germany, were included. Patients were characterized according to statins. The primary endpoint was mortality;it was assessed twice: in hospital and 3 months after discharge. The secondary outcome was the rate of symptomatic intracerebral hemorrhage. Of the 542 stroke patients examined(mean age 72 ± 13 years;51% women, mean National Institutes of Health Stroke Scale(NIHSS) score 11), 138 patients(25.5%) had been pretreated with statin, while in 190 patients(35.1%) statin therapy was initiated during their stay in hospital, whereas 193(35.6%) never received statins. Patients pre-treated with statin were older and more frequently had previous illnesses(arterial hypertension, diabetes mellitus and previous cerebral infarctions), but were comparably similarly affected by the stroke(NIHSS 11 vs. 11;P = 0.76) compared to patients who were not on statin treatment at the time of cerebral infarction. Patients pretreated with statin did not differ in 3-month mortality from those newly treated to a statin(7.6% vs. 8%;P = 0.9). Interestingly, the group of patients pretreated with statin showed a lower rate of in hospital mortality(6.6% vs. 17.0;P = 0.005) and 3-month mortality(10.7% vs. 23.7%;P = 0.005) than the group of patients who had no statin treatment at all. The same effect was seen for patients newly adjusted to a statin during the hospital stay compared to patients who did not receive statins(3-month mortality: 7.1% vs. 23.7%;P < 0.001). With a good functional outcome(mRS ≤ 2), 60% of patients were discharged, the majority(69.6%;P < 0.001) of whom received a statin at discharge. The rate of symptomatic intracerebral hemorrhages in the course of cranial computed tomography was independent of whether the patients were pretreated with a statin or not(8.8% vs. 8.7%, P = 0.96). Pre-treatment with statin as well as new adjustment could reveal positive effect on prognosis of intravenous thrombolyzed stroke patients. Further investigations are required. The study was approved by the Ethic Committee of the University of Lübeck(approval No. 4-147).展开更多
基金The Science and Technology Department of Jilin Province,No.20180622004JC and No.20190101002JHthe Finance Department of Jilin Province,No.2017F004 and No.2018SCZWSZX-044.
文摘BACKGROUND Early hepatic artery thrombosis(E-HAT)is a serious complication after liver transplantation(LT),which often results in graft failure and can lead to patient deaths.Treatments such as re-transplantation and re-anastomosis are conventional therapeutic methods which are restricted by the shortage of donors and the patient’s postoperative intolerance to re-laparotomy.Due to the advances in interventional techniques and thrombolytics,endovascular treatments are increasingly being selected by more and more centers.This study reviews and reports our single-center experience with intra-arterial thrombolysis as the first choice therapy for E-HAT after deceased donor LT.AIM To evaluate the feasibility and reasonability of intra-arterial thrombolysis for EHAT after deceased donor LT.METHODS A total of 147 patients who underwent deceased donor LT were retrospectively reviewed in our hospital between September 2011 and December 2016.Four patients were diagnosed with E-HAT.All of these patients underwent intraarterial thrombolysis with alteplase as the first choice therapy after LT.The method of arterial anastomosis and details of the diagnosis and treatment of EHAT were collated.The long-term prognosis of E-HAT patients was also recorded.The median follow-up period was 26 mo(range:23 to 30 mo).RESULTS The incidence of E-HAT was 2.7%(4/147).E-HAT was considered when Doppler ultrasonography showed no blood flow signals and a definite diagnosis was confirmed by immediate hepatic arterial angiography when complete occlusion of the hepatic artery was observed.The patients were given temporary thrombolytics(mainly alteplase)via a 5-Fr catheter which was placed in the proximal part of the thrombosed hepatic artery followed by continuous alteplase using an infusion pump.Alteplase dose was adjusted according to activated clotting time.The recanalization rate of intra-arterial thrombolysis in our study was 100%(4/4)and no thrombolysis-related mortality was observed.During the follow-up period,patient survival rate was 75%(3/4),and biliary complications were present in 50%of patients(2/4).CONCLUSION Intra-arterial thrombolysis can be considered first-line treatment for E-HAT after deceased donor LT.Early diagnosis of E-HAT is important and follow-up is necessary even if recanalization is successful.
文摘Objective:To study the different effects of mechanical embolus removal and intra-arterial thrombolysis on neural functional recovery in patients with acute middle cerebral artery occlusion.Methods: Patients with acute middle cerebral artery occlusion who were treated in the First Hospital of Yulin between September 2013 and October 2017 were selected and retrospectively studied, and the differences in reperfusion therapies in history data were referred to divide them into study group A and study group B who underwent mechanical embolus removal and intra-arterial thrombolysis respectively. The levels of neurocyte damage markers, apoptosis markers and stress markers in serum as well as the expression of Wnt pathway molecules in peripheral blood were determined before treatment and 24 h after treatment.Results: Compared with those of same group before treatment, serum NSE, S100B, VILIP1, sFas, sFasL, ET-1 and MDA levels as well as peripheral blood GSK3β, LC3-II and Beclin1 expression intensity of both groups were decreasing whereas serum BDNF, NTF, sLivin and SOD levels as well as peripheral bloodβ-catenin and mTOR expression intensity were increasing, and serum NSE, S100B, VILIP1, sFas, sFasL, ET-1 and MDA levels as well as peripheral blood GSK3β, LC3-II and Beclin1 expression intensity of study group A after treatment were lower than those of study group B whereas serum BDNF, NTF, sLivin and SOD levels as well as peripheral bloodβ-catenin and mTOR expression intensity were higher than those of study group B.Conclusion: Mechanical embolus removal for acute middle cerebral artery occlusion can be more effective than intra-arterial thrombolysis to reduce the nerve function damage as well as the corresponding oxidative stress and apoptosis.
文摘Introduction: Venous thromboembolic disease is the 3rd most common cardiovascular pathology. Acute pulmonary embolism constitutes its most serious presentation and a major cause of mortality, morbidity and hospitalization in Africa and Senegal. The objectives of this work were to study the epidemiological profile of pulmonary embolisms and to evaluate the practice of thrombolysis in patients in a cardiological setting. Methodology: A retrospective, descriptive study was carried out in the Cardiology department of the Aristide le Dantec Hospital (HALD) over the period from August 2011 to December 2019 in patients hospitalized in the cardiology department for pulmonary embolism confirmed by CT angiography and/or with thrombi on cardiac ultrasound and who had also benefited from thrombolysis. Results: Thirty-one patients with pulmonary embolism were thrombolyzed. There was a predominance of the female gender with an average age of 45.97 years. Risk factors were dominated by age (61.29%) followed by obesity (32.26%) and prolonged immobilization (22.5%). The functional signs were dominated by dyspnea (77.42%) followed by chest pain (51.62%) and cough (35.48%). The physical signs were dominated by right heart failure in 22.5% of cases, pulmonary condensation syndrome in 19.35%, and inflammatory large leg in 12.9% of cases. Echocardiography and chest CT angiography were the means of diagnosis. Nine of our patients presented with an intracardiac mass. Thrombotic treatment was administered in all patients. The average length of hospitalization was 12.32 days and in-hospital mortality was 32.26%. Conclusion: Pulmonary embolism does exist in our regions and is responsible for heavy mortality. Rapid and efficient support is essential. Prevention remains the corner-stone in the fight against this pathology.
文摘BACKGROUND:Bleeding outcomes are crucial primary safety endpoints in studies involving thrombolytic agents.This study aimed to determine the incidence,characteristics and mortality outcomes of bleeding following ST-elevation myocardial infarction(STEMI)thrombolysis in an Asian population.METHODS:This single-centre retrospective study included all STEMI patients who received thrombolytic therapy from 2016 to 2020 in a Malaysian tertiary hospital.Total population sampling was used in this study.The primary outcome was bleeding events post-thrombolysis,categorised using the Thrombolysis in Myocardial Infarction(TIMI)bleeding criteria.Inferential statistics were used to determine the associations between relevant variables.RESULTS:Data from 941 patients were analysed.A total of 156(16.6%)STEMI patients bled post-thrombolysis.Major,minor,and minimal TIMI occurred in 7(0.7%),17(1.8%),and 132(14.0%)patients,respectively.Age 65 years(P=0.031)and Malaysian Chinese(P=0.008)were associated with a higher incidence of bleeding post-thrombolysis.Conversely,foreigners(P=0.032)and current smoker(P=0.007)were associated with a lower incidence of bleeding.Both TIMI major(P<0.001)and TIMI minor(P<0.001)were associated with a higher incidence of all-cause in-hospital mortality among STEMI patients.TIMI minor bleeding was significantly higher in the streptokinase recipients.The bleeding sites were comparable between streptokinase and tenecteplase recipients,except for a significantly higher incidence of gastrointestinal bleeding in the streptokinase recipients(P=0.027).CONCLUSION:In our Asian population,the incidence of total bleeding events following STEMI thrombolysis is comparable to that previously reported.The development of TIMI major and minor bleeding complications is associated with higher mortality.
文摘BACKGROUND Acute ischemic stroke(AIS)retains a notable stance in global disease burden,with thrombolysis via recombinant tissue plasminogen activator(rtPA)serving as a viable management approach,albeit with variable outcomes and the potential for complications like hemorrhagic transformation(HT).The platelet-to-neutrophil ratio(P/NR)has been considered for its potential prognostic value in AIS,yet its capacity to predict outcomes following rtPA administration demands further exploration.AIM To elucidate the prognostic utility of P/NR in predicting HT and clinical outcomes following intravenous rtPA administration in AIS patients.METHODS Data from 418 AIS patients treated with intravenous rtPA at Thammasat University Hospital from January 2018 to June 2021 were retrospectively analyzed.The relationship between P/NR and clinical outcomes[early neurological deterioration(E-ND),HT,delayed ND(D-ND),and 3-mo outcomes]was scrutinized.RESULTS Notable variables,such as age,diabetes,and stroke history,exhibited statistical disparities when comparing patients with and without E-ND,HT,D-ND,and 3-mo outcomes.P/NR prognostication revealed an optimal cutoff of 43.4 with a 60.3%sensitivity and a 52.5%specificity for 90-d outcomes.P/NR prognostic accuracy was statistically significant for 90-d outcomes[area under the curve(AUC)=0.562],D-ND(AUC=0.584),and HT(AUC=0.607).CONCLUSION P/NR demonstrated an association with adverse 3-mo clinical outcomes,HT,and D-ND in AIS patients post-rtPA administration,indicating its potential as a predictive tool for complications and prognoses.This infers that a diminished P/NR may serve as a novel prognostic indicator,assisting clinicians in identifying AIS patients at elevated risk for unfavorable outcomes following rtPA therapy.
文摘Objective This study was to evaluate the efficacy and safety of a short acting reduced dose fibrinolytic regimen to promote early infarct related artery (IRA) patency for acyute myocardial infarction (AMI) patients referred for percutaneous coronary intervention (PCI).Methods Following aspirin and heparin, 166 patients were randomized to a 50 mg bolus of recombinant tissue type plasminogen activator(rt PA) or to a same volume sodium chloride injection followed by immediate primary PCI. The end points included patency rates on catheterization laboratory (cath lab) arrival, revascularization results when PCI was performed, complication rates, left ventricular function and restored patency rate following PCI. Results Patency on cath lab arrival was 64% with rt PA (34% TIMI 3,30% TIMI 2), while 31% of placebo (13% TIMI 3, 18% TIMI 2). There was no difference in the restored TIMI 3 rates of IRA between the two groups (85% vs 87%). No difference were observed in stroke or major bleeding. Left ventricular function was similar in both groups (52±9% vs 50±8%), but left ventricular ejection fraction fraction (LVEF) was higher with patent IRA (TIMI 3) on cath lab arrival than that of others (56±12% vs 48±10%).Conclusions Strategy thrombolytic regimens were compatible with subsequent PCI lead to more frequenc early recanalization (before cath lab arrival), which facilitates greater left ventricular function preservation with no augmentation of adverse events.
基金supported by the Hainan Province’s Key Research and Development Project(ZDYF 2017096&ZDYF2018118)National Natural Science Foundation of China(NSFC:81500202)+2 种基金Beijing Lisheng Cardiovascular Health Foundation Pilot Fund Project(LHJJ201610620)Provincial Key Science and Technology Projects supporting projects in Sanya(2018PT48)Sanya Medical and Health Science and Technology Innovation Project(2017YW10)
文摘Background Clearance of coronary arterial thrombosis is necessary in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing urgent percutaneous coronary intervention (PCI). There is currently no highly-recommended method of thrombus removal during interventional procedures. We describe a new method for opening culprit vessels to treat STEMI: intracoronary arterial retrograde thrombolysis (ICART) with PCI. Methods & Results Eight patients underwent ICART. The guidewire was advanced to the distal coronary artery through the occlusion lesion. Then, we inserted a microcatheter into the distal end of the occluded coronary artery over the guidewire. Urokinase (5–10 wu) mixed with contrast agents was slowly injected into the occluded section of the coronary artery through the microcatheter. The intracoronary thrombus gradually dissolved in 3–17 min, and the effect of thrombolysis was visible in real time. Stents were then implanted according to the characteristics of the recanalized culprit lesion to achieve full revascularization. One patient experienced premature ventricular contraction during vascular revascularization, and no malignant arrhythmias were seen in any patient. No reflow or slow flow was not observed post PCI. Thrombolysis in myocardial infarction flow grade and myocardial blush grade post-primary PCI was 3 in all eight patients. No patients experienced bleeding or stroke. Conclusions ICART was accurate and effective for treating intracoronary thrombi in patients with STEMI in this preliminary study. ICART was an effective, feasible, and simple approach to the management of STEMI, and no intraprocedural complications occurred in any of the patients. ICART may be a breakthrough in the treatment of acute STEMI.
基金financially supported by National Natural Science Foundation of China(No.81673363)
文摘To achieve targeted thrombolysis, a targeted delivery system of lumbrokinase(LK) was constructed using RGDfk-conjugated hybrid micelles. Based on the specific affinity of RGDfk to glycoprotein complex of GP Ⅱ b/Ⅲ a expressed on the surface of membrane of activated platelet, LK loaded targeted micelles(LKTM) can be delivered to thrombus. The hybrid micelles were composed of polycaprolactone-block-poly(2-(dimethylamino) ethyl methacrylate)(PCL-PDMAEMA), methoxy polyethylene glycol-block-polycaprolactone(mPEG-PCL)and RGDfk conjugated polycaprolactone-block-polyethylene glycol(PCL-PEG-RGDfk). PCLPDMAEMA was synthesized via ring open polymerization(ROP) and atom transfer radical polymerization(ATRP). PCL-PEG-RGDfk was synthesized via ROP and carbodiimide chemistry. The prepared LKTM was characterized by dynamic light scattering(DLS) and transmission electron microscope(TEM). Colloidal stability assay showed the prepared LKTM was stable. Biocompatibility assay was performed to determine the safe concentration range of polymer. The assay of fluorescent distribution in vivo demonstrated that LKTM can be efficiently delivered to thrombi in vivo. Thrombolysis in vivo indicated the thrombolytic potency of LKTM was optimal in all groups. Notably, the laboratory mice treated with LKTM exhibited a significantly shorter tail bleeding time compared to those treated with LK or LK-loaded micelles without RGDfk, which suggested that the targeted delivery of LK using RGDfk-conjugated hybrid micelles effectively reduced the bleeding risk.
文摘AIM To evaluate the safety and efficacy of agitation thrombolysis(AT) combined with catheter-directed thrombolysis(CDT) for the treatment of non-cirrhotic acute portal vein thrombosis(PVT). METHODS Nine patients with non-cirrhotic acute PVT who underwent AT combined with CDT were analyzed retrospectively. Portography was carried out via the transjugular intrahepatic portosystemic(commonly known as TIP) or percutaneous transhepatic(commonly known as PT) route, followed by AT combined with CDT. Complications of the procedure, and the changes in clinical symptoms, hemodynamics of the portal vein and liver function were recorded. Follow-up was scheduled at1, 3 and 6 mo after treatment, and every 6 mo thereafter, or when the patients developed clinical symptoms related to PVT. Color Doppler ultrasound and contrast-enhanced computed tomography/magnetic resonance imaging were performed during the follow-up period to determine the condition of the portal vein.RESULTS AT combined with CDT was successfully performed. The portal vein was reached via the TIP route in 6 patients, and via the PT route in 3 patients. All clinical symptoms were relieved or disappeared, with the exception of 1 patient who died of intestinal necrosis 9 d after treatment. Significant differences in the changes in portal vein hemodynamics were observed, including the maximum lumen occupancy of PVT, portal vein pressure and flow velocity between pre-and posttreatment(P < 0.05). During the follow-up period, recurrence was observed in 1 patient at 19 mo after the procedure, and the portal vein was patent in the remaining patients.CONCLUSION AT combined with CDT is a safe and effective method for the treatment of non-cirrhotic acute PVT.
文摘AIM: To assess role of combined modality of mechanical fragmentation and intralesional thrombolysis in patients with massive pulmonary embolism presenting subacutely. METHODS: Eight of 70 patients presenting in tertiary care centre of North India with massive pulmonary embolism within 4 years had subacute presentation (symptom onset more than 2 wk). These patients were subjected to pulmonary angiography with intention to treat basis via mechanical breakdown and intra lesional thrombolysis. Mechanical breakdown of embolus was accomplished with 5-F multipurpose catheter to reestablish flow, followed by intralesional infusion of urokinase (4400 IU/kg over 10 min followed by 4400 IU/kg per hour over 24 h). RESULTS: Eight patients, mean age 47.77±12.20 years presented with subacute pulmonary embolism (mean duration of symptoms 2.4 wk). At presentation, mean heart rate, shock index, miller score and mean pulmonary pressures were 101.5±15.2/min, 0.995±0.156, 23.87±3.76 and 37.62±6.67 mmHg which reduced to 91.5±12.2/min (P=0.0325), 0.789±0.139 (P=0.0019), 5.87±1.73 (P=0.0000004) and 27.75±8.66 mmHg (P=0.0003) post procedurally. Mean BP improved from 80.00±3.09 mmHg to 90.58±9.13 mmHg (P=0.0100) post procedurally. Minor complications in the form of local hematoma-minor hematoma in 1 (12.5%), and pseudoaneurysm (due to femoral artery puncture) in 1 (12.5 %) patient were seen. At 30 d and 6 mo follow up survival rate was 100% and all the patients were asymptomatic and in New York Heart Association class 1. CONCLUSION: Combined modality of mechanical fragmentation and intralesional thrombolysis appears to be a promising alternative to high risk surgical procedures in patients with subacute massive pulmonary embolism.
基金funded by the Natural Science Foundation of Shandong Province (Therapeutic effects and mechanisms of low-frequency ultrasound combined with urokinase thrombolysis in treatment of cerebral infarction in rats),No. 2009ZRB14007
文摘Activity of matrix metalloproteinase-9 increases following cerebral ischemia/reperfusion, and is associated with cerebral microvascular permeability, blood-brain barrier destruction, inflammatory cell infiltration and brain edema. Matrix metalloproteinase-9 also likely participates in thrombolysis. A rat model of middle cerebral artery infarction was established by injecting autologous blood clots into the internal carotid artery. At 3 hours following model induction, urokinase was injected into the caudal vein. Decreased neurological severity score, reduced infarct volume, and increased expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were observed in the cerebral cortex 24 hours after urokinase thrombolysis. These results suggest that urokinase can suppress damage in the acute-early stage of cerebral infarction.
基金This work was supported by the National Basic Scientific Research Program of China (973 Program, No. 2007CB935803), the National Natural Science Foundation of China (No. 30825018) and the Key Clinical Program of the Ministry of Health of China (No. 2010439).
文摘The efficacy and safety of recombinant tissue plasminogen activator (rtPA) need to be improved due to its low bioavailability and requirement of large dose administration. The purpose of this study was to develop a fibrin-targeted nanoparticle (NP) drug delivery system for thrombosis combination therapy. We conjugated rtPA to poly(ethylene glycol)- poly(ε-caprolactone) (PEG-PCL) nanoparticles (rtPA-NP) and investigated its physicochemical characteristics such as particle size, zeta potential, enzyme activity of conjugated rtPA and its storage stability at 4℃. The thrombolytic activity of rtPA-NP was evaluated in vitro and in vivo as well as the half-life of rtPA-NP, the properties to fibrin targeting and its influences on systemic hemostasis in vivo. The results showed that rtPA-NP equivalent to 10% of a typical dose of rtPA could dissolve fibrin clots and were demonstrated to have a neuroprotective effect after focal cerebral ischemia as evidenced by decreased infarct volume and improved neurological deficit (P〈0.001). RtPA-NP did not influence the in vivo hemostasis or coagulation system. The half-life of conjugated rtPA was shown to be approximately 18 times longer than that of free rtPA. These experiments suggested that rtPA-conjugated PEG-PCL nanoparticles might be a promising fibrin-targeted delivery system for a combination treatment of thrombosis.
基金Supported by Grant from the National Scientific FoundationCommittee of China,30670606 from Chinese PLA Scientific Foundation of the Eleventh-Five programme,06MA263
文摘AIM:To present a series of cases with symptomatic acute extensive portal vein(PV)and superior mesenteric vein(SMV)thrombosis after splenectomy treated by transjugular intrahepatic approach catheter-directed thrombolysis. METHODS:A total of 6 patients with acute extensive PV-SMV thrombosis after splenectomy were treated by transjugular approach catheter-directed thrombolysis. The mean age of the patients was 41.2 years.After access to the portal system via the transjugular approach,pigtail catheter fragmentation of clots, local urokinase injection,and manual aspiration thrombectomy were used for the initial treatment of PV-SMV thrombosis,followed by continuous thrombolytic therapy via an indwelling infusion catheter in the SMV,which was performed for three to six days. Adequate anticoagulation was given during treatment, throughout hospitalization,and after discharge. RESULTS:Technical success was achieved in all 6 patients.Clinical improvement was seen in these patients within 12-24 h of the procedure.No complications were observed.The 6 patients were discharged 6-14 d(8±2.5 d)after admission.The mean duration of follow-up after hospital discharge was 40±16.5 mo.Ultrasound and contrast-enhanced computed tomography confirmed patency of the PV and SMV,and no recurrent episodes of PV-SMV thrombosis developed during the follow-up period. CONCLUSION:Catheter-directed thrombolysis via transjugular intrahepatic access is a safe and effective therapy for the management of patients with symptomatic acute extensive PV-SMV thrombosis.
文摘AIM. To evaluate the time dependence of intra-arterial 5-fluorouracil (5-FU) therapy for advanced hepatocellular carcinoma (aHCC). METHODS: Thirty-seven adult Japanese patients who had aHCC and liver cirrhosis were treated with combined intra-arterial 5-FU, cisplatin (CDDP), and leucovorin (LV). The Japan Integrated Staging score (JIS score) of each patient was 3 or more. The patients were divided into two groups, alter which the 15 patients in group S were treated with 6-h infusion chemotherapy (LV at 12 mg/h, CDDP at 10 mg/h, and 5-FU at 250 mg/m^2 per 4 h) and the 22 patients in group L were treated with 24-h infusion chemotherapy (LV at 12 mg/h, CDDP at 10 mg/h, and 5-FU at 250 mg/m^2 per 22 h). Continuous infusion chemotherapy was performed v/a the proper hepatic artery every 5 d for 4 wk using an implanted drug reservoir. RESULTS: The percentages of patients with a partial response after 4 wk of chemotherapy were 6.7% in group S and 31.8% in group L. The survival of group L was significantly better than that of group S, with the median survival time being 496 d in group L and 226 d in group S (P 〈 0.05). CONCLUSION: Continuous 24-h intra-arterial infusion is more effective for aHCC and can markedly prolong survival time as compared to 6-h infusion.
文摘AIM: To investigate the poor prognosis of HCC with PVTT, we evaluated the efficacy by a new combination chemotherapy for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). METHODS: From 2002 to 2007, a total of 10 consecutive patients with Stage IVA HCC accompanied by PVTT were studied prospectively to examine the efficacy of treatment by intra-arterial infusion of a chemotherapeutic agents consisting of etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil. RESULTS: The mean course of chemotherapy was 14.4 (range, 9-21) too. One patient showed complete response (CR) with disappearance of HCC and PVI-F after treatment, and the two patients showed partial response (PR), response rate (CR + PR/All cases 30%). The median survival time after the therapy was 457.2 d. The one-year survival rate was 70%. Adverse reactions were tolerable.CONCLUSION: Although the prognosis of most patients with Stage IVA HCC by PVTT is poor, our combination chemotherapy may induces long-term survival and is an effective treatment and produced anti-tumor activity with tolerable adverse effects in patients for advanced Stage IVA HCC accompanied by PVTT.
文摘BACKGROUND: Massive pulmonary embolism(MPE) and acute myocardial infarction are the two most common causes of cardiac arrest(CA). At present, lethal hemorrhage makes thrombolytic therapy underused during cardiopulmonary resuscitation, despite the potential benefits for these underlying conditions. Hypercoagulability of the blood in autoimmune disorders(such as autoimmune hemolytic anemia) carries a risk of MPE. It is critical to find out the etiology of CA for timely thrombolytic intervention.METHODS: A 23-year-old woman with a 10-year medical history of autoimmune hemolytic anemia suffered from CA in our emergency intensive care unit. ECG and echocardiogram indicated the possibility of MPE, so f ibrinolytic therapy(alteplase) was successful during prolonged resuscitation.RESULTS: Neurological recovery of the patient was generally good, and no fatal bleeding developed. MPE was documented by CT pulmonary angiography.CONCLUSIONS: A medical history of autoimmune disease poses a risk of PE, and the causes of CA(such as this) should be investigated etiologically. A therapy with alteplase may be used early during cardiopulmonary resuscitation once there is presumptive evidence of PE. Clinical trials are needed in this setting to study patients with hypercoagulable states.
文摘AIM To assess the usefulness of intra-arterial contrastenhanced ultrasonography(IAUS) during transarterial chemoembolization(TACE) with drug-eluting beads(DEB) for hepatocellular carcinoma(HCC).METHODS Thirty two patients with 39 HCC underwent DEB-TACE guided with IAUS, and examined by contrast-enhanced ultrasonography(CEUS) or dynamic CT after DEB-TACE were enrolled in this study. CEUS findings before DEBTACE and IAUS findings were compared. Treatments judged to be complete and incomplete for lesions were appropriate and insufficient, respectively. Findings on CEUS and/or dynamic CT performed 1, 3 and 6 mo after DEB-TACE were evaluated using m RECIST(CR/PR/SD/PD).RESULTS The treatments were complete and incomplete in 26 and 13 lesions, respectively. On imaging evaluation using CEUS and/or dynamic CT one month after treatment, 25 and 1 lesions were judged to be CR and PR, respectively, and at 6 mo after treatment, the results were CR, PR, SD and PD for 24, 1, 0 and 1 of these lesions, respectively, in the 26 completely treated lesions. Of the 13 lesions in which treatment was incomplete, the results on imaging at one month after treatment were CR, PR, SD and PD for 0, 6, 4 and 3 lesions, respectively. The overall CR rate at 6 mo after treatment was 61.5%(24/39).CONCLUSION A combination of DEB-TACE with IAUS can improve the therapeutic effects in patients with HCC.
基金Supported by Grants from the National Science Foundation of China,No.81300278the Natural Science Foundation of Jiangsu Province,No.BK20130697the Jiangsu Provincial Special Program of Medical Science,No.BL2012006
文摘AIM: To determine the optimal initial treatment modality for acute superior mesenteric vein thrombosis (ASMVT) in patients with circumscribed peritonitis.
基金Supported in part by the Fund for Ophthalmic Knowledge (New York, USA)the Natali Dafne Flexer (Buenos Aires, Argentina)
文摘·AIM: To obtain baseline knowledge about the current use of intra-arterial chemotherapy(SSOAIC) in centers worldwide.·METHODS: A survey including questions about the use of SSOAIC was emailed to retinoblastoma experts.·RESULTS:Seventy-nine(response rate 69.9%) doctors from 63 centers in 35 countries responded. Thirty-one centers from 19 countries use SSOAIC. Twelve performed more than 50 procedures. Melphalan is the most commonly used drug but 15 centers use more than one drug. First line therapy for advanced unilateral disease is the most common use of SSOAIC(74.2%). Centers with larger experience(】50 applications) were less likely using melphalan alone(P =0.06) and significantly more likely using SSOAIC in more situations such as second line in preference to radiotherapy P =0.05. Nineteen(61.2%)stated that SSOAIC improved their results and 21(77.8%)reported less toxicity compared to other treatments.Three centers reported that SSOAIC did not improve their results. There were regional variations in the use of SSOAIC which is used more frequently as secondary treatment in Europe compared to the USA and Japan.Ten centers identified cost is the major limiting factor for SSOAIC.· CONCLUSION: SSOAIC is used in an increasing number of centers worldwide with regional variations.Centers with more experience in SSOAIC use it in more situations including other drugs than melphalan. The majority of the centers using this technique reportedimproved results and few complications.
文摘The present study investigated the association between pre-treatment with a cholesterol-lowering drug(statin) or new setting hereon and the effect on the mortality rate in patients with acute ischemic stroke who received intravenous systemic thrombolysis. During a 5-year period(starting in October 2008), 542 consecutive stroke patients who received intravenous systemic thrombolysis with recombinant tissue plasminogen activator(rt-PA) at the Department of Neurology, University Hospital Schleswig-Holstein, Campus Lübeck, Germany, were included. Patients were characterized according to statins. The primary endpoint was mortality;it was assessed twice: in hospital and 3 months after discharge. The secondary outcome was the rate of symptomatic intracerebral hemorrhage. Of the 542 stroke patients examined(mean age 72 ± 13 years;51% women, mean National Institutes of Health Stroke Scale(NIHSS) score 11), 138 patients(25.5%) had been pretreated with statin, while in 190 patients(35.1%) statin therapy was initiated during their stay in hospital, whereas 193(35.6%) never received statins. Patients pre-treated with statin were older and more frequently had previous illnesses(arterial hypertension, diabetes mellitus and previous cerebral infarctions), but were comparably similarly affected by the stroke(NIHSS 11 vs. 11;P = 0.76) compared to patients who were not on statin treatment at the time of cerebral infarction. Patients pretreated with statin did not differ in 3-month mortality from those newly treated to a statin(7.6% vs. 8%;P = 0.9). Interestingly, the group of patients pretreated with statin showed a lower rate of in hospital mortality(6.6% vs. 17.0;P = 0.005) and 3-month mortality(10.7% vs. 23.7%;P = 0.005) than the group of patients who had no statin treatment at all. The same effect was seen for patients newly adjusted to a statin during the hospital stay compared to patients who did not receive statins(3-month mortality: 7.1% vs. 23.7%;P < 0.001). With a good functional outcome(mRS ≤ 2), 60% of patients were discharged, the majority(69.6%;P < 0.001) of whom received a statin at discharge. The rate of symptomatic intracerebral hemorrhages in the course of cranial computed tomography was independent of whether the patients were pretreated with a statin or not(8.8% vs. 8.7%, P = 0.96). Pre-treatment with statin as well as new adjustment could reveal positive effect on prognosis of intravenous thrombolyzed stroke patients. Further investigations are required. The study was approved by the Ethic Committee of the University of Lübeck(approval No. 4-147).