BACKGROUND Cardiac arrest caused by acute pulmonary embolism(PE)is the most serious clinical circumstance,necessitating rapid identification,immediate cardiopulmonary resuscitation(CPR),and systemic thrombolytic thera...BACKGROUND Cardiac arrest caused by acute pulmonary embolism(PE)is the most serious clinical circumstance,necessitating rapid identification,immediate cardiopulmonary resuscitation(CPR),and systemic thrombolytic therapy.Extracorporeal CPR(ECPR)is typically employed as a rescue therapy for selected patients when conventional CPR is failing in settings where it can be implemented.CASE SUMMARY We present a case of a 69-year-old male who experienced a prolonged cardiac arrest in an ambulance with pulseless electrical activity.Upon arrival at the emergency department with ongoing manual chest compressions,bedside pointof-care ultrasound revealed an enlarged right ventricle without contractility.Acute PE was suspected as the cause of cardiac arrest,and intravenous thrombolytic therapy with 50 mg tissue plasminogen activator was administered during mechanical chest compressions.Despite 31 minutes of CPR,return of spontaneous circulation was not achieved until 8 minutes after initiation of Veno-arterial extracorporeal membrane oxygenation(ECMO)support.Under ECMO support,the hemodynamic status and myocardial contractility significantly improved.However,the patient ultimately did not survive due to intracerebral hemorrhagic complications,leading to death a few days later in the hospital.CONCLUSION This case illustrates the potential of combining systemic thrombolysis with ECPR for refractory cardiac arrest caused by acute PE,but it also highlights the increased risk of significant bleeding complications,including fatal intracranial hemorrhage.展开更多
Background Administrative data are frequently used in stroke research.Ensuring accurate identification of patients who had an ischaemic stroke,and those receiving thrombolysis and endovascular thrombectomy(EVT)is crit...Background Administrative data are frequently used in stroke research.Ensuring accurate identification of patients who had an ischaemic stroke,and those receiving thrombolysis and endovascular thrombectomy(EVT)is critical to ensure representativeness and generalisability.We examined differences in patient samples based on mode of identification,and propose a strategy for future patient and procedure identification in large administrative databases.Methods We used non-public administrative data from the state of California to identify all patients who had an ischaemic stroke discharged from an emergency department(ED)or inpatient hospitalisation from 2010 to 2017 based on International Classification of Disease(ICD-9)(2010-2015),ICD-10(2015-2017)and Medicare Severity-Diagnosis-related Group(MS-DRG)discharge codes.We identified patients with interhospital transfers,patients receiving thrombolytics and patients treated with EVT based on ICD,Current Procedural Terminology(CPT)and MS-DRG codes.We determined what proportion of these transfers and procedures would have been identified with ICD versus MS-DRG discharge codes.Results Of 365099 ischaemic stroke encounters,most(87.70%)had both a stroke-related ICD-9 or ICD-10 code and stroke-related MS-DRG code;12.28% had only an ICD-9 or ICD-10 code and 0.02% had only an MS-DRG code.Nearly all transfers(99.99%)were identified using ICD codes.We identified 32433 thrombolytic-treated patients(8.9% of total)using ICD,CPT and MS-DRG codes;the combination of ICD and CPT codes identified nearly all(98%).We identified 7691 patients treated with EVT(2.1%of total)using ICD and MS-DRG codes;both MS-DRG and ICD-9/ICD-10 codes were necessary because ICD codes alone missed 13.2%of EVTs.CPT codes only pertain to outpatient/ED patients and are not useful for EVT identification.Conclusions ICD-9/ICD-10 diagnosis codes capture nearly all ischaemic stroke encounters and transfers,while the combination of ICD-9/ICD-10 and CPT codes are adequate for identifying thrombolytic treatment in administrative datasets.However,MS-DRG codes are necessary in addition to ICD codes for identifying EVT,likely due to favourable reimbursement for EVT-related MS-DRG codes incentivising accurate coding.展开更多
Based on the mobile Internet, Internet of Things, big data, cloud computing,“intelligentization” and other technologies, a safe and reliable management platform for integrating information about acute ischemic strok...Based on the mobile Internet, Internet of Things, big data, cloud computing,“intelligentization” and other technologies, a safe and reliable management platform for integrating information about acute ischemic stroke (AIS) thrombolysis with unified standards should be established. The management platform should include intelligent screening of high-risk groups and servers for monitoring them, server analysis of patient medical records, a server for supervision and integrated management of patient education, an integrated system of healthcare records, and a clinical decision-support system for AIS emergencies. Such a system would constitute a standardized data capture and integrated intelligent analysis system for the key information necessary in thrombolytics. In this way a human-oriented prevention and intervention mechanism for continuous care and prevention of stroke would be formed to achieve the collection and intelligent analysis of key information in drug thrombolysis. It would provide data support for AIS thrombolytics management strategies that would improve the coverage of drug thrombolysis in primary hospitals, and also optimize AIS emergency processes to increase the success rate of thrombolysis.展开更多
Objective:Early thrombolytic therapy for ischemic stroke within the therapeutic window is associated with improved clinical outcomes.This study investigated whether optimizing intravenous thrombolytic(IVT)therapy stra...Objective:Early thrombolytic therapy for ischemic stroke within the therapeutic window is associated with improved clinical outcomes.This study investigated whether optimizing intravenous thrombolytic(IVT)therapy strategies for stroke could reduce treatment delays.Methods:To reduce delays in IVT therapy for ischemic stroke,a series of quality improvement measures were implemented at a tertiary hospital in Hangzhou,Zhejiang Province,from June 2021 to August 2023,which included developing a timeline process management system,forming a nurse-led stroke process management team,providing homogeneous training,standardizing the IVT therapy process for ischemic stroke,and introducing an incentive policy.During the pre-(from June 2021 to February 2022,group A)and post-(from March to November 2022,group B1;from December 2022 to August 2023,group B2[implementation of an additional incentive policy])of the implementation the strategy,the door-tocomputed tomographic angiography(CTA)time(DCT),CTA time,neurology consultation to consent for IVT,CTA-to-needle time(CNT),and door-to-needle time(DNT),the percentage of people who underwent CTA within 20 min,15 min,and 10 min and DNT within 60 min,45 min,and 30 min were collected and compared.Results:Following the implementation of the standardized IVT process management strategy for stroke,the DNT for group B1 and group B2 were 30(24,44)min and 31(24,41)min,respectively,both significantly lower than the 46(38,58)min in group A(P<0.001);the median DCT were both 13 min in group B1 and B2 lower than 17min in group A(P<0.001);the median CTA were 12 min in Group B1 and 9 min in Group B2 lower than 14 min in group A(P<0.001);similar results were observed during the neurology consultation to obtain consent for IVT and CNT.Compared with group A,the proportion of DCT20 min,15 min,and 10 min was higher in groups B1 and B2(P<0.05),and the same result was observed at DNT60 min,45 min,and 30 min(P<0.05).However,the additional incentive policy did not significantly differ between Group B2 and Group B1.Conclusions:Optimizing IVT therapy for ischemic stroke is a feasible approach to limit the DNT to 30 min in ischemic stroke,significantly reducing delays within the therapeutic window and increasing the number of patients meeting target time segments.Additionally,generating a timeline for the IVT therapy process by scanning positioning quick response codes was a significant breakthrough in achieving the informatization of IVT quality management for stroke.展开更多
In this editorial,we comment on a recent article which addressed the therapeutic effect of aspirin plus edaravone in patients with cerebral infarction(CI).Herein,we outline the progress in therapy of CI.Apart from thr...In this editorial,we comment on a recent article which addressed the therapeutic effect of aspirin plus edaravone in patients with cerebral infarction(CI).Herein,we outline the progress in therapy of CI.Apart from thrombolysis,aspirin is the most effective treatment for CI.Edaravone,a free radical scavenger,reduces endothelial cell damage and delays neuronal cell death.Aspirin plus edaravone mitigates damage to brain tissue by different mechanisms,thereby expediting the reinstation of neurological function.However,the nephrotoxic effect of edaravone,along with gastrointestinal bleeding associated with aspirin,may restrict this combination therapy.Although clinical studies have demonstrated the efficacy of thrombolytic therapy and mechanical thrombectomy,patients receiving these treatments experience modest efficacy and many adverse events.Moreover,interest in exploring natural medicines for CI is increasing,and they appear to have a high potential to protect against CI.The evolution of therapeutic strategies is expected to improve clinical outcomes of patients with CI.展开更多
Acute ischemic stroke is one of the leading causes of morbidity and mortality worldwide.Restoration of cerebral blood flow to affected ischemic areas has been the cornerstone of therapy for patients for eligible patie...Acute ischemic stroke is one of the leading causes of morbidity and mortality worldwide.Restoration of cerebral blood flow to affected ischemic areas has been the cornerstone of therapy for patients for eligible patients as early diagnosis and treatment have shown improved outcomes.However,there has been a paradigm shift in the management approach over the last decade,and with the emphasis currently directed toward including newer modalities such as neuroprotection,stem cell treatment,magnetic stimulation,anti-apoptotic drugs,delayed recanali-zation,and utilization of artificial intelligence for early diagnosis and suggesting algorithm-based management protocols.展开更多
Compared with traditional piezoelectric ultrasonic devices,optoacoustic devices have unique advantages such as a simple preparation process,anti-electromagnetic interference,and wireless long-distance power supply.How...Compared with traditional piezoelectric ultrasonic devices,optoacoustic devices have unique advantages such as a simple preparation process,anti-electromagnetic interference,and wireless long-distance power supply.However,current optoacoustic devices remain limited due to a low damage threshold and energy conversion efficiency,which seriously hinder their widespread applications.In this study,using a self-healing polydimethylsiloxane(PDMS,Fe-Hpdca-PDMS)and carbon nanotube composite,a flexible optoacoustic patch is developed,which possesses the self-healing capability at room temperature,and can even recover from damage induced by cutting or laser irradiation.Moreover,this patch can generate high-intensity ultrasound(>25 MPa)without the focusing structure.The laser damage threshold is greater than 183.44 mJ cm^(-2),and the optoacoustic energy conversion efficiency reaches a major achievement at 10.66×10^(-3),compared with other carbon-based nanomaterials and PDMS composites.This patch is also been successfully examined in the application of acoustic flow,thrombolysis,and wireless energy harvesting.All findings in this study provides new insight into designing and fabricating of novel ultrasound devices for biomedical applications.展开更多
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
Thrombolytic therapy has been the mainstay for patients with pulmonary embolism(PE).Despite being linked to a higher risk of significant bleeding,clinical trials demonstrate that thrombolytic therapy should be used in...Thrombolytic therapy has been the mainstay for patients with pulmonary embolism(PE).Despite being linked to a higher risk of significant bleeding,clinical trials demonstrate that thrombolytic therapy should be used in patients with moderate to high-risk PE,in addition to hemodynamic instability symptoms.This prevents the progression of right heart failure and impending hemodynamic collapse.Diagnosing PE can be challenging due to the variety of presentations;therefore,guidelines and scoring systems have been established to guide physicians to correctly identify and manage the condition.Traditionally,systemic thrombolysis has been utilized to lyse the emboli in PE.However,newer techniques for thrombolysis have been developed,such as endovascular ultrasound-assisted catheter-directed thrombolysis for massive and intermediatehigh submassive risk groups.Additional newer techniques explored are the use of extracorporeal membrane oxygenation,direct aspiration,or fragmentation with aspiration.Because of the constantly changing therapeutic options and the scarcity of randomized controlled trials,choosing the best course of treatment for a given patient may be difficult.To help,the Pulmonary Embolism Reaction Team is a multidisciplinary,rapid response team that has been developed and is used at many institutions.Hence to bridge the knowledge gap,our review highlights various indications of thrombolysis in addition to the recent advances and management guidelines.展开更多
BACKGROUND Acute ischemic stroke(AIS)is mainly caused by cerebral blood flow disorders,which further leads to ischemic brain necrosis or encephalomalacia.The role of homocysteine(Hcy),an independent risk factor for ca...BACKGROUND Acute ischemic stroke(AIS)is mainly caused by cerebral blood flow disorders,which further leads to ischemic brain necrosis or encephalomalacia.The role of homocysteine(Hcy),an independent risk factor for cardiovascular disease,in the development of atherosclerosis is gradually revealed.However,studies are still rare and little is known about the relationship of Hcy level with the prognosis.AIM To explore the relationship between Hcy level and prognosis in elderly patients with AIS after thrombolytic therapy with recombinant tissue plasminogen activator(rtPA).METHODS A total of 120 patients with acute ischemic stroke who were admitted to Jingzhou Central Hospital and underwent recombinant tissue plasminogen activator treatment were randomly selected from January 2017 to December 2018.They were divided into two groups according to the level of Hcy,with 60 patients in each group.Patients with Hcy≥18.54 umol/L were included into a high-level group and those with Hcy<18.54 umol/L were included into a low-level group.The outcomes were analyzed in the two groups after the treatment.RESULTS The National institute of Health Stroke Scale(NIHSS)scores were significantly higher in the high-level group than in the low-level group before and 1 h after the treatment(P<0.05).There was no significant difference in NIHSS scores between the two groups at 12 and 24 h after the treatment(P>0.05).The Modified Rankin scale(MRS)scores were significantly higher in the high-level group than in the low-level group before and 1 h after the treatment(P<0.05).There was no significant difference in MRS scores between the two groups at 12 and 24 h after the treatment(P>0.05).NIHSS and MRS scores were positively correlated with the prognosis after thrombolytic therapy(P<0.05).CONCLUSION The level of Hcy is closely related to the prognosis of elderly patients with acute ischemic stroke,and after rtPA treatment,the prognosis of elderly patients is improved significantly.展开更多
BACKGROUND Hemorrhagic transformation(HT)is a common complication in patients with cerebral infarction.However,its pathogenesis is poorly understood.The knowledge of factors that may increase risk for HT may help in i...BACKGROUND Hemorrhagic transformation(HT)is a common complication in patients with cerebral infarction.However,its pathogenesis is poorly understood.The knowledge of factors that may increase risk for HT may help in improving the safety of thrombolytic therapy.AIM To investigate the predictive value of serum calcium,albumin,globulin and matrix metalloproteinase-9(MMP-9)levels for HT after intravenous thrombolysis(IVT)in patients with acute cerebral infarction.METHODS Five hundred patients with acute cerebral infarction who received IVT with alteplase within 4.5 h after the onset of disease between January 2018 and January 2021 at our hospital were selected as the study subjects.They were divided into groups based on computed tomography scan results of the brain made within 36 h after thrombolysis.Forty patients with HT were enrolled in an observation group and 460 patients without HT were enrolled in a control group.Serum calcium,albumin,globulin and MMP-9 levels were compared between the two groups.Regression analysis was used to discuss the relationship between these indices and HT.RESULTS The previous history of hypertension,diabetes,atrial fibrillation,cerebrovascular diseases,smoking and alcohol intake were not associated with HT after IVT in patients with acute cerebral infarction(all P>0.05).The National Institutes of Health stroke scale(NHISS)score was associated with HT after IVT in patients with acute cerebral infarction(P<0.05).The serum calcium and albumin levels were lower in the observation group than in the control group(all P<0.05).The levels of globulin and MMP-9 were significantly higher in the observation group than in the control group(all P<0.05).Logistic regression analysis showed that NHISS score,serum calcium,albumin,globulins and MMP-9 were independent factors influencing the occurrence of HT following IVT in patients with cerebral infarction(P<0.05).CONCLUSION Serum calcium,albumin,globulin and MMP-9 levels are risk factors for HT after IVT in patients with acute cerebral infarction.Moreover,NHISS score can be used as a predictor of post-thrombolytic HT.展开更多
A strong fibrinolytic activity was demonstrated in the Semen Sojae Praeparatum(SSP), which is a famous traditional Chinese medicine. To study the activities and dynamic changes of fibrinolytic enzyme, standard fibrin ...A strong fibrinolytic activity was demonstrated in the Semen Sojae Praeparatum(SSP), which is a famous traditional Chinese medicine. To study the activities and dynamic changes of fibrinolytic enzyme, standard fibrin plate was used to determine the fibrinolytic activity. For the first time fibrinolytic enzyme was found during the fermentation of SSP and the fibrinolytic activities of samples were shown to increase significantly over time. In the "yellow cladding" stage, the fibrinolytic activity was 619.75 IU/g. On day 6, 12 and 15 of the "secondary fermentation" stage, the fibrinolytic activity was 711.49 IU/g, 866.67 IU/g, 1 022.31 IU/g, respectively. The results indicate that fibrinolytic enzyme was generated during the fermentation of SSP and it displayed increasing activity which peaked at the "secondary fermentation" stage. The fibrinolytic enzyme was found to not only degrades fibrin directly, but also activate plasminogen to do so.展开更多
AIM: To use perfusion-derived permeability-surface area product maps to predict hemorrhagic transformation following thrombolytic treatment for acute ischemic stroke.METHODS: We retrospectively analyzed our prospectiv...AIM: To use perfusion-derived permeability-surface area product maps to predict hemorrhagic transformation following thrombolytic treatment for acute ischemic stroke.METHODS: We retrospectively analyzed our prospectively kept acute stroke database over five consecutive months for patients with symptoms of acute ischemic stroke(AIS) who had computed tomography(CT) perfusion(CTP) done at arrival. Patients included in the analyses also had to have a follow-up CT. The permeability-surface area product maps(PS) was calculated for the side of the ischemia and/or infarction and for the contralateral unaffected side at the same level. The cerebral blood flow map was used to delineate the ischemic territory. Next, a region of interest was drawn at the centre of this territory on the PS parametric map. Finally, a mirror region of interest was created on the contralateral side at the same level. The relative permeability-surface area product maps(r PS) provided an internal control and was calculated as the ratio of the PS on the side of the AIS to the PS on the contralateral side. A student t-test was performed after log conversion of r PS between patients with and without hemorrhagic transformation. Log conversion was used to convert the data into normal distribution to use t-test. For the group of patients who experienced intracranial bleed, a student t-test was performed between those with only petechial hemorrhage and those with more severe parenchymal hematoma with subarachnoid haemorrhage.RESULTS: Of 84 patients with AIS and CTP at admission, only 42 patients had a follow-up CT. The r PSderived using the normal side as the internal control was significantly higher(P = 0.003) for the 15 cases of hemorrhagic transformation(1.71 + 1.64) compared to 27 cases that did not have any(1.07 + 1.30). Patients with values above the overall mean r PS of 1.3 had an increased likelihood of subsequent hemorrhagic transformation. The sensitivity of using this score to predict hemorrhagic transformation was 71.4, the specificity was 78.6, with a positive predictive value of 62.5 and negative predictive value of 84.6. The accuracy was 76.2. The odds ratio of an event occurring with such an r PS was 9.2. Of the 15 cases of hemorrhagic transformation, there was no difference(P = 0.35) in the r PS between the eight cases of petechial and the seven cases of more severe hemorrhagic events.CONCLUSION: Pretreatment PS can predict the occurrence of hemorrhagic transformation on follow-up of AIS patients with relatively high sensitivity, specificity, positive and negative predictive value.展开更多
Nattokinase(NK), which has been identified as a potent fibrinolytic protease, has remarkable potential in treatment of thrombolysis, and even has the ability to ameliorate chronic vein thrombosis. To reduce the hemorr...Nattokinase(NK), which has been identified as a potent fibrinolytic protease, has remarkable potential in treatment of thrombolysis, and even has the ability to ameliorate chronic vein thrombosis. To reduce the hemorrhagic risk from an intravenous injection of NK,nattokinase-tauroursodeoxycholate(NK-TUDCA) complex was prepared at different pH values and with different ratios of NK and TUDCA. When assessing survival time, survival state,tail injury, and the body weight of mice, it was found that the NK-TUDCA complex(NK: 10 k IU/ml; TUDCA: 10 mg/ml; pH 5.0) had a lower toxicity when administered at an NK dosage of 130 kIU/kg in the acute toxicity test and 13 kIU/kg in the repeated low-dose challenge. From the results of the in vitro thrombolytic test and characterization of NKTUDCA, we speculated that the delayed release of NK-TUDCA might be the main cause of toxicity reduction by the complex. This study described the preparation of an NK complex with low toxicity following intravenous administration, which could be utilized for further clinical study of NK.展开更多
Recombinant tissue plasminogen activator （rPA） has been used as a thrombolytic agent. However, considerable improvements have been done to prolong its plasma half-life （tl/2） and reduce its side effects, such as i...Recombinant tissue plasminogen activator （rPA） has been used as a thrombolytic agent. However, considerable improvements have been done to prolong its plasma half-life （tl/2） and reduce its side effects, such as intracranial hemorrhage. Based on these improvements, a mutant ofrPA, mrPA, was designed by mutating its PAI-1 binding site to extend its tl/2. Furthermore, a fusion protein conjugating mrPA with NR3 was designed, which was a rAcAp5 mutant with a platelet GPIIb/IIIa-binding RGD motif, to enhance the ability of targeted-thrombus and thrombolysis. The synthesized DNA sequences coding the two proteins were amplified by PCR, cloned into pET30a to construct recombinant plasmids pET30a-mrPA and pET30a-mrPA-NR3, and transformed into E. coli BL21 （DE3）. The two proteins were expressed in inclusion bodies induced by isopropy113-D-1-thiogalactopyranoside. After purified to qualified purity using one-step Ni affinity chromatography, the denatured proteins were refolded by dialysis. Their thrombolytic effects in vitro and in vivo were evaluated. In vitro 3.5 and 7 pmol/L of mrPA significantly reduced thrombus weight; 1.75, 3.5 and 7 ~tmol/L of mrPA-NR3 also significantly reduced the thrombus weight, and mrPA-NR3 displayed stronger thrombolytic effects than mrPA at 7 lamol/L. In vivo both mrPA and mrPA-NR3 showed significantly thrombolytic effect at 60-240 ktmol/kg in thrombolytic model of inferior vena cava. Importantly, mrPA-NR3 exhibited more potent thrombolytic effect than both mrPA and rhM-tPA （positive control） at 240 p.mol/kg. In addition, these two novel proteins did not increase bleeding time while they exerted thrombolytic effect. In conclusion, we engineered two novel proteins and proved that fusion protein had better thrombolytic effect than non-fusion protein, and the results suggest that dual thrombolytic mechanism or thrombus-target potentiated the thrombolytic effect ofrPA and alleviated hemorrhage side reaction. This study may shed light on the development of novel thrombolytic agents with targeted thrombolysis and reduced side effects.展开更多
A 31-year-old female who had well-established polycythemia vera one year before, presented with the sudden onset. She had severe ascites and hepatic encephalopathy 12 d prior to admission. Real-time ultrasonography re...A 31-year-old female who had well-established polycythemia vera one year before, presented with the sudden onset. She had severe ascites and hepatic encephalopathy 12 d prior to admission. Real-time ultrasonography revealed a supra hepatic thrombosis extending toward the inferior vena cava （IVC）. Thrombolytic therapy with systemic streptokinase （250000 IU loading ＋ 100000 IU/h infusion） was started. At the end of 72 h infusion, the patient＇s general condition improved. A color Doppler ultrasonography then showed complete and partial resolution of the thrombosis in the supra hepatic vein and IVC, respectively. Despite this good response, 12 d later, the symptoms recurred. Venography detected complete obstruction of the IVC. Percutanous balloon angioplasty with stent insertion was performed successfully and the patient was discharged without any evidence of liver disease. A combination of systemic streptokinase and radiological intervention was effective in our patient.展开更多
Intravascular thrombosis, a critical pathophysiological feature of many cardiovascular disorders, leads to the formation of life-threatening obstructive blood clots within the vessels. Rapid recanalization of occluded...Intravascular thrombosis, a critical pathophysiological feature of many cardiovascular disorders, leads to the formation of life-threatening obstructive blood clots within the vessels. Rapid recanalization of occluded vessels is essential for the patients' outcome, but the currently available systemic fibrinolytic therapy is associated with low efficacy and tremendous side effects. Additionally, many patients are ineligible for systemic thrombolytic therapy, either due to delayed admission to the hospital after symptom onset, or because of recent surgery, or bleeding. In order to improve the treatment efficacy and to limit the risk of hemorrhagic complications, both precise imaging of the affected vascular regions, and the localized application of fibrinolytic agents, are required. Recent years have brought about considerable advances in nanomedical approaches to thrombosis. Although these thrombustargeting imaging agents and nanotherapies are not yet implemented in humans, substantial amount of successful in vivo applications have been reported, including animal models of stroke, acute arterial thrombosis, and pulmonary embolism. It is evident that the future progress in diagnosis and treatment of thrombosis will be closely bound with the development of novel nanotechnology-based strategies. This Editorial focuses on the recently reported approaches, which hold a great promise for personalized, disease-targeted treatment and reduced side effects in the patients suffering from this life-threatening condition.展开更多
Thrombosis is a global health issue and one of the leading factors of death.However,its diagnosis has been limited to the late stages,and its therapeutic window is too narrow to provide reasonable and effective treatm...Thrombosis is a global health issue and one of the leading factors of death.However,its diagnosis has been limited to the late stages,and its therapeutic window is too narrow to provide reasonable and effective treatment.In addition,clinical thrombolytics suffer from a short half-life,allergic reactions,inactivation,and unwanted tissue hemorrhage.Nano-medicines have gained extensive attention in diagnosis,drug delivery,and photo/sound/magnetic-theranostics due to their convertible properties.Furthermore,diagnosis and treatment of thrombosis using nano-medicines have also been widely studied.This review summarizes the recent advances in this area,which revealed six types of nanoparticle approaches:(1)in vitro diagnostic kits using“synthetic biomarkers”;(2)in vivo imaging using nano-contrast agents;(3)targeted drug delivery systems using artificial nanoparticles;(4)microenvironment responsive drug delivery systems;(5)drug delivery systems using biological nanostructures;and(6)treatments with external irradiation.The investigations of nano-medicines are believed to be of great significance,and some of the advanced drug delivery systems show potential applications in clinical theranotics.展开更多
AIM To evaluate reproducibility of pulmonary embolism(PE) clot volume quantification using computed tomography pulmonary angiogram(CTPA) in a multicenter setting.METHODS This study was performed using anonymized data ...AIM To evaluate reproducibility of pulmonary embolism(PE) clot volume quantification using computed tomography pulmonary angiogram(CTPA) in a multicenter setting.METHODS This study was performed using anonymized data in conformance with HIPAA and IRB Regulations(March 2015-November 2016). Anonymized CTPA data was acquired from 23 scanners from 18 imaging centers using each site's standard PE protocol. Two independent analysts measured PE volumes using a semi-automated region-growing algorithm on an FDA-approved image analysis platform. Total thrombus volume(TTV) was calculated per patient as the primary endpoint. Secondary endpoints were individual thrombus volume(ITV), Qanadli score and modified Qanadli score per patient. Inter-and intra-observer reproducibility were assessed using intra-class correlation coefficient(ICC) and BlandAltman analysis. RESULTS Analyst 1 found 72 emboli in the 23 patients with a mean number of emboli of 3.13 per patient with a range of 0-11 emboli per patient. The clot volumes ranged from 0.0041-47.34 cm3(mean +/-SD, 5.93 +/-10.15 cm3). On the second read, analyst 1 found the same number and distribution of emboli with a range of volumes for read 2 from 0.0041 – 45.52 cm3(mean +/-SD, 5.42 +/-9.53 cm3). Analyst 2 found 73 emboli in the 23 patients with a mean number of emboli of 3.17 per patient with a range of 0-11 emboli per patient. The clot volumes ranged from 0.00459-46.29 cm3(mean +/-SD, 5.91 +/-10.06 cm3). Inter-and intraobserver variability measurements indicated excellent reproducibility of the semi-automated method for quantifying PE volume burden. ICC for all endpoints was greater than 0.95 for inter-and intra-observer analysis. Bland-Altman analysis indicated no significant biases.CONCLUSION Semi-automated region growing algorithm for quantifying PE is reproducible using data from multiple scanners and is a suitable method for image analysis in multicenter clinical trials.展开更多
AIM To examine effects of computed tomography(CT)image acquisition/reconstruction parameters on clot volume quantification in vitro for research method validation purposes.METHODS This study was performed in conforman...AIM To examine effects of computed tomography(CT)image acquisition/reconstruction parameters on clot volume quantification in vitro for research method validation purposes.METHODS This study was performed in conformance with HIPAA and IRB Regulations(March 2015-November 2016).A ten blood clot phantom was designed and scanned on a dual-energy CT scanner(SOMATOM Force,Siemens Healthcare Gm BH,Erlangen,Germany)with varying pitch,iterative reconstruction,energy level and slicethickness.A range of clot and tube sizes were used in an attempt to replicate in vivo emboli found within central and segmental branches of the pulmonary arteries in patients with pulmonary emboli.Clot volume was the measured parameter and was analyzed by a single image analyst using a semi-automated region growing algorithm implemented in the FDA-approved Siemens syngo.via image analysis platform.Mixed model analysis was performed on the data.RESULTS On the acquisition side,the continuous factor of energy showed no statistically significant effect on absolute clot volume quantification(P=0.9898).On the other hand,when considering the fixed factor of pitch,there were statistically significant differences in clot volume quantification(P<0.0001).On the reconstruction side,with the continuous factor of reconstruction slice thickness no statistically significant effect on absolute clot volume quantification was demonstrated(P=0.4500).Also on the reconstruction side,with the fixed factor of using iterative reconstructions there was also no statistically significant effect on absolute clot volume quantification(P=0.3011).In addition,there was excellent R^2 correlation between the scale-measured mass of the clots both with respect to the CT measured volumes and with respect to volumes measure by the water displacement method.CONCLUSION Aside from varying pitch,changing CT acquisition parameters and using iterative reconstructions had no significant impact on clot volume quantification with a semi-automated region growing algorithm.展开更多
基金Supported by Scientific Research Projects from Wuhan Municipal Health Commission of China,No.WX23B42.
文摘BACKGROUND Cardiac arrest caused by acute pulmonary embolism(PE)is the most serious clinical circumstance,necessitating rapid identification,immediate cardiopulmonary resuscitation(CPR),and systemic thrombolytic therapy.Extracorporeal CPR(ECPR)is typically employed as a rescue therapy for selected patients when conventional CPR is failing in settings where it can be implemented.CASE SUMMARY We present a case of a 69-year-old male who experienced a prolonged cardiac arrest in an ambulance with pulseless electrical activity.Upon arrival at the emergency department with ongoing manual chest compressions,bedside pointof-care ultrasound revealed an enlarged right ventricle without contractility.Acute PE was suspected as the cause of cardiac arrest,and intravenous thrombolytic therapy with 50 mg tissue plasminogen activator was administered during mechanical chest compressions.Despite 31 minutes of CPR,return of spontaneous circulation was not achieved until 8 minutes after initiation of Veno-arterial extracorporeal membrane oxygenation(ECMO)support.Under ECMO support,the hemodynamic status and myocardial contractility significantly improved.However,the patient ultimately did not survive due to intracerebral hemorrhagic complications,leading to death a few days later in the hospital.CONCLUSION This case illustrates the potential of combining systemic thrombolysis with ECPR for refractory cardiac arrest caused by acute PE,but it also highlights the increased risk of significant bleeding complications,including fatal intracranial hemorrhage.
基金Agency for Healthcare Research and Quality(PI Zachrison,K08HS024561)National Institutes of Health(PI Hsia R01HL134182,R01HL114822).
文摘Background Administrative data are frequently used in stroke research.Ensuring accurate identification of patients who had an ischaemic stroke,and those receiving thrombolysis and endovascular thrombectomy(EVT)is critical to ensure representativeness and generalisability.We examined differences in patient samples based on mode of identification,and propose a strategy for future patient and procedure identification in large administrative databases.Methods We used non-public administrative data from the state of California to identify all patients who had an ischaemic stroke discharged from an emergency department(ED)or inpatient hospitalisation from 2010 to 2017 based on International Classification of Disease(ICD-9)(2010-2015),ICD-10(2015-2017)and Medicare Severity-Diagnosis-related Group(MS-DRG)discharge codes.We identified patients with interhospital transfers,patients receiving thrombolytics and patients treated with EVT based on ICD,Current Procedural Terminology(CPT)and MS-DRG codes.We determined what proportion of these transfers and procedures would have been identified with ICD versus MS-DRG discharge codes.Results Of 365099 ischaemic stroke encounters,most(87.70%)had both a stroke-related ICD-9 or ICD-10 code and stroke-related MS-DRG code;12.28% had only an ICD-9 or ICD-10 code and 0.02% had only an MS-DRG code.Nearly all transfers(99.99%)were identified using ICD codes.We identified 32433 thrombolytic-treated patients(8.9% of total)using ICD,CPT and MS-DRG codes;the combination of ICD and CPT codes identified nearly all(98%).We identified 7691 patients treated with EVT(2.1%of total)using ICD and MS-DRG codes;both MS-DRG and ICD-9/ICD-10 codes were necessary because ICD codes alone missed 13.2%of EVTs.CPT codes only pertain to outpatient/ED patients and are not useful for EVT identification.Conclusions ICD-9/ICD-10 diagnosis codes capture nearly all ischaemic stroke encounters and transfers,while the combination of ICD-9/ICD-10 and CPT codes are adequate for identifying thrombolytic treatment in administrative datasets.However,MS-DRG codes are necessary in addition to ICD codes for identifying EVT,likely due to favourable reimbursement for EVT-related MS-DRG codes incentivising accurate coding.
文摘Based on the mobile Internet, Internet of Things, big data, cloud computing,“intelligentization” and other technologies, a safe and reliable management platform for integrating information about acute ischemic stroke (AIS) thrombolysis with unified standards should be established. The management platform should include intelligent screening of high-risk groups and servers for monitoring them, server analysis of patient medical records, a server for supervision and integrated management of patient education, an integrated system of healthcare records, and a clinical decision-support system for AIS emergencies. Such a system would constitute a standardized data capture and integrated intelligent analysis system for the key information necessary in thrombolytics. In this way a human-oriented prevention and intervention mechanism for continuous care and prevention of stroke would be formed to achieve the collection and intelligent analysis of key information in drug thrombolysis. It would provide data support for AIS thrombolytics management strategies that would improve the coverage of drug thrombolysis in primary hospitals, and also optimize AIS emergency processes to increase the success rate of thrombolysis.
基金supported by Zhejiang Provincial Medical and Health Science and Technology Plan Project(2023KY448).
文摘Objective:Early thrombolytic therapy for ischemic stroke within the therapeutic window is associated with improved clinical outcomes.This study investigated whether optimizing intravenous thrombolytic(IVT)therapy strategies for stroke could reduce treatment delays.Methods:To reduce delays in IVT therapy for ischemic stroke,a series of quality improvement measures were implemented at a tertiary hospital in Hangzhou,Zhejiang Province,from June 2021 to August 2023,which included developing a timeline process management system,forming a nurse-led stroke process management team,providing homogeneous training,standardizing the IVT therapy process for ischemic stroke,and introducing an incentive policy.During the pre-(from June 2021 to February 2022,group A)and post-(from March to November 2022,group B1;from December 2022 to August 2023,group B2[implementation of an additional incentive policy])of the implementation the strategy,the door-tocomputed tomographic angiography(CTA)time(DCT),CTA time,neurology consultation to consent for IVT,CTA-to-needle time(CNT),and door-to-needle time(DNT),the percentage of people who underwent CTA within 20 min,15 min,and 10 min and DNT within 60 min,45 min,and 30 min were collected and compared.Results:Following the implementation of the standardized IVT process management strategy for stroke,the DNT for group B1 and group B2 were 30(24,44)min and 31(24,41)min,respectively,both significantly lower than the 46(38,58)min in group A(P<0.001);the median DCT were both 13 min in group B1 and B2 lower than 17min in group A(P<0.001);the median CTA were 12 min in Group B1 and 9 min in Group B2 lower than 14 min in group A(P<0.001);similar results were observed during the neurology consultation to obtain consent for IVT and CNT.Compared with group A,the proportion of DCT20 min,15 min,and 10 min was higher in groups B1 and B2(P<0.05),and the same result was observed at DNT60 min,45 min,and 30 min(P<0.05).However,the additional incentive policy did not significantly differ between Group B2 and Group B1.Conclusions:Optimizing IVT therapy for ischemic stroke is a feasible approach to limit the DNT to 30 min in ischemic stroke,significantly reducing delays within the therapeutic window and increasing the number of patients meeting target time segments.Additionally,generating a timeline for the IVT therapy process by scanning positioning quick response codes was a significant breakthrough in achieving the informatization of IVT quality management for stroke.
文摘In this editorial,we comment on a recent article which addressed the therapeutic effect of aspirin plus edaravone in patients with cerebral infarction(CI).Herein,we outline the progress in therapy of CI.Apart from thrombolysis,aspirin is the most effective treatment for CI.Edaravone,a free radical scavenger,reduces endothelial cell damage and delays neuronal cell death.Aspirin plus edaravone mitigates damage to brain tissue by different mechanisms,thereby expediting the reinstation of neurological function.However,the nephrotoxic effect of edaravone,along with gastrointestinal bleeding associated with aspirin,may restrict this combination therapy.Although clinical studies have demonstrated the efficacy of thrombolytic therapy and mechanical thrombectomy,patients receiving these treatments experience modest efficacy and many adverse events.Moreover,interest in exploring natural medicines for CI is increasing,and they appear to have a high potential to protect against CI.The evolution of therapeutic strategies is expected to improve clinical outcomes of patients with CI.
文摘Acute ischemic stroke is one of the leading causes of morbidity and mortality worldwide.Restoration of cerebral blood flow to affected ischemic areas has been the cornerstone of therapy for patients for eligible patients as early diagnosis and treatment have shown improved outcomes.However,there has been a paradigm shift in the management approach over the last decade,and with the emphasis currently directed toward including newer modalities such as neuroprotection,stem cell treatment,magnetic stimulation,anti-apoptotic drugs,delayed recanali-zation,and utilization of artificial intelligence for early diagnosis and suggesting algorithm-based management protocols.
基金This work was supported by the Natural Science Foundation of China(Grant no.U22A20259,12102140)the Shenzhen Basic Science Research(No.JCYJ20200109110006136)the China Postdoctoral Science Foundation(No.2022M721258).We also thank the Analytical and Testing Center of Huazhong University of Science&Technology.
文摘Compared with traditional piezoelectric ultrasonic devices,optoacoustic devices have unique advantages such as a simple preparation process,anti-electromagnetic interference,and wireless long-distance power supply.However,current optoacoustic devices remain limited due to a low damage threshold and energy conversion efficiency,which seriously hinder their widespread applications.In this study,using a self-healing polydimethylsiloxane(PDMS,Fe-Hpdca-PDMS)and carbon nanotube composite,a flexible optoacoustic patch is developed,which possesses the self-healing capability at room temperature,and can even recover from damage induced by cutting or laser irradiation.Moreover,this patch can generate high-intensity ultrasound(>25 MPa)without the focusing structure.The laser damage threshold is greater than 183.44 mJ cm^(-2),and the optoacoustic energy conversion efficiency reaches a major achievement at 10.66×10^(-3),compared with other carbon-based nanomaterials and PDMS composites.This patch is also been successfully examined in the application of acoustic flow,thrombolysis,and wireless energy harvesting.All findings in this study provides new insight into designing and fabricating of novel ultrasound devices for biomedical applications.
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Thrombolytic therapy has been the mainstay for patients with pulmonary embolism(PE).Despite being linked to a higher risk of significant bleeding,clinical trials demonstrate that thrombolytic therapy should be used in patients with moderate to high-risk PE,in addition to hemodynamic instability symptoms.This prevents the progression of right heart failure and impending hemodynamic collapse.Diagnosing PE can be challenging due to the variety of presentations;therefore,guidelines and scoring systems have been established to guide physicians to correctly identify and manage the condition.Traditionally,systemic thrombolysis has been utilized to lyse the emboli in PE.However,newer techniques for thrombolysis have been developed,such as endovascular ultrasound-assisted catheter-directed thrombolysis for massive and intermediatehigh submassive risk groups.Additional newer techniques explored are the use of extracorporeal membrane oxygenation,direct aspiration,or fragmentation with aspiration.Because of the constantly changing therapeutic options and the scarcity of randomized controlled trials,choosing the best course of treatment for a given patient may be difficult.To help,the Pulmonary Embolism Reaction Team is a multidisciplinary,rapid response team that has been developed and is used at many institutions.Hence to bridge the knowledge gap,our review highlights various indications of thrombolysis in addition to the recent advances and management guidelines.
文摘BACKGROUND Acute ischemic stroke(AIS)is mainly caused by cerebral blood flow disorders,which further leads to ischemic brain necrosis or encephalomalacia.The role of homocysteine(Hcy),an independent risk factor for cardiovascular disease,in the development of atherosclerosis is gradually revealed.However,studies are still rare and little is known about the relationship of Hcy level with the prognosis.AIM To explore the relationship between Hcy level and prognosis in elderly patients with AIS after thrombolytic therapy with recombinant tissue plasminogen activator(rtPA).METHODS A total of 120 patients with acute ischemic stroke who were admitted to Jingzhou Central Hospital and underwent recombinant tissue plasminogen activator treatment were randomly selected from January 2017 to December 2018.They were divided into two groups according to the level of Hcy,with 60 patients in each group.Patients with Hcy≥18.54 umol/L were included into a high-level group and those with Hcy<18.54 umol/L were included into a low-level group.The outcomes were analyzed in the two groups after the treatment.RESULTS The National institute of Health Stroke Scale(NIHSS)scores were significantly higher in the high-level group than in the low-level group before and 1 h after the treatment(P<0.05).There was no significant difference in NIHSS scores between the two groups at 12 and 24 h after the treatment(P>0.05).The Modified Rankin scale(MRS)scores were significantly higher in the high-level group than in the low-level group before and 1 h after the treatment(P<0.05).There was no significant difference in MRS scores between the two groups at 12 and 24 h after the treatment(P>0.05).NIHSS and MRS scores were positively correlated with the prognosis after thrombolytic therapy(P<0.05).CONCLUSION The level of Hcy is closely related to the prognosis of elderly patients with acute ischemic stroke,and after rtPA treatment,the prognosis of elderly patients is improved significantly.
基金Supported by Scientific Research Fund of Hebei Health Commission,No.20210197.
文摘BACKGROUND Hemorrhagic transformation(HT)is a common complication in patients with cerebral infarction.However,its pathogenesis is poorly understood.The knowledge of factors that may increase risk for HT may help in improving the safety of thrombolytic therapy.AIM To investigate the predictive value of serum calcium,albumin,globulin and matrix metalloproteinase-9(MMP-9)levels for HT after intravenous thrombolysis(IVT)in patients with acute cerebral infarction.METHODS Five hundred patients with acute cerebral infarction who received IVT with alteplase within 4.5 h after the onset of disease between January 2018 and January 2021 at our hospital were selected as the study subjects.They were divided into groups based on computed tomography scan results of the brain made within 36 h after thrombolysis.Forty patients with HT were enrolled in an observation group and 460 patients without HT were enrolled in a control group.Serum calcium,albumin,globulin and MMP-9 levels were compared between the two groups.Regression analysis was used to discuss the relationship between these indices and HT.RESULTS The previous history of hypertension,diabetes,atrial fibrillation,cerebrovascular diseases,smoking and alcohol intake were not associated with HT after IVT in patients with acute cerebral infarction(all P>0.05).The National Institutes of Health stroke scale(NHISS)score was associated with HT after IVT in patients with acute cerebral infarction(P<0.05).The serum calcium and albumin levels were lower in the observation group than in the control group(all P<0.05).The levels of globulin and MMP-9 were significantly higher in the observation group than in the control group(all P<0.05).Logistic regression analysis showed that NHISS score,serum calcium,albumin,globulins and MMP-9 were independent factors influencing the occurrence of HT following IVT in patients with cerebral infarction(P<0.05).CONCLUSION Serum calcium,albumin,globulin and MMP-9 levels are risk factors for HT after IVT in patients with acute cerebral infarction.Moreover,NHISS score can be used as a predictor of post-thrombolytic HT.
基金Supported by the National Natural Science Foundation of China(81660664)the Natural Science Foundation of Jiangxi Province(20192ACBL21032,20192BBGL70051,20192BAB205098,20171BAB21 5061,GJJ150844,GJJ160858)+1 种基金Jiangxi Provincial Health and Family Planning Commission(2017Z016)the Natural Science Foundation of Jiangxi University of Traditional Chinese Medicine(2014BS013).
文摘A strong fibrinolytic activity was demonstrated in the Semen Sojae Praeparatum(SSP), which is a famous traditional Chinese medicine. To study the activities and dynamic changes of fibrinolytic enzyme, standard fibrin plate was used to determine the fibrinolytic activity. For the first time fibrinolytic enzyme was found during the fermentation of SSP and the fibrinolytic activities of samples were shown to increase significantly over time. In the "yellow cladding" stage, the fibrinolytic activity was 619.75 IU/g. On day 6, 12 and 15 of the "secondary fermentation" stage, the fibrinolytic activity was 711.49 IU/g, 866.67 IU/g, 1 022.31 IU/g, respectively. The results indicate that fibrinolytic enzyme was generated during the fermentation of SSP and it displayed increasing activity which peaked at the "secondary fermentation" stage. The fibrinolytic enzyme was found to not only degrades fibrin directly, but also activate plasminogen to do so.
文摘AIM: To use perfusion-derived permeability-surface area product maps to predict hemorrhagic transformation following thrombolytic treatment for acute ischemic stroke.METHODS: We retrospectively analyzed our prospectively kept acute stroke database over five consecutive months for patients with symptoms of acute ischemic stroke(AIS) who had computed tomography(CT) perfusion(CTP) done at arrival. Patients included in the analyses also had to have a follow-up CT. The permeability-surface area product maps(PS) was calculated for the side of the ischemia and/or infarction and for the contralateral unaffected side at the same level. The cerebral blood flow map was used to delineate the ischemic territory. Next, a region of interest was drawn at the centre of this territory on the PS parametric map. Finally, a mirror region of interest was created on the contralateral side at the same level. The relative permeability-surface area product maps(r PS) provided an internal control and was calculated as the ratio of the PS on the side of the AIS to the PS on the contralateral side. A student t-test was performed after log conversion of r PS between patients with and without hemorrhagic transformation. Log conversion was used to convert the data into normal distribution to use t-test. For the group of patients who experienced intracranial bleed, a student t-test was performed between those with only petechial hemorrhage and those with more severe parenchymal hematoma with subarachnoid haemorrhage.RESULTS: Of 84 patients with AIS and CTP at admission, only 42 patients had a follow-up CT. The r PSderived using the normal side as the internal control was significantly higher(P = 0.003) for the 15 cases of hemorrhagic transformation(1.71 + 1.64) compared to 27 cases that did not have any(1.07 + 1.30). Patients with values above the overall mean r PS of 1.3 had an increased likelihood of subsequent hemorrhagic transformation. The sensitivity of using this score to predict hemorrhagic transformation was 71.4, the specificity was 78.6, with a positive predictive value of 62.5 and negative predictive value of 84.6. The accuracy was 76.2. The odds ratio of an event occurring with such an r PS was 9.2. Of the 15 cases of hemorrhagic transformation, there was no difference(P = 0.35) in the r PS between the eight cases of petechial and the seven cases of more severe hemorrhagic events.CONCLUSION: Pretreatment PS can predict the occurrence of hemorrhagic transformation on follow-up of AIS patients with relatively high sensitivity, specificity, positive and negative predictive value.
文摘Nattokinase(NK), which has been identified as a potent fibrinolytic protease, has remarkable potential in treatment of thrombolysis, and even has the ability to ameliorate chronic vein thrombosis. To reduce the hemorrhagic risk from an intravenous injection of NK,nattokinase-tauroursodeoxycholate(NK-TUDCA) complex was prepared at different pH values and with different ratios of NK and TUDCA. When assessing survival time, survival state,tail injury, and the body weight of mice, it was found that the NK-TUDCA complex(NK: 10 k IU/ml; TUDCA: 10 mg/ml; pH 5.0) had a lower toxicity when administered at an NK dosage of 130 kIU/kg in the acute toxicity test and 13 kIU/kg in the repeated low-dose challenge. From the results of the in vitro thrombolytic test and characterization of NKTUDCA, we speculated that the delayed release of NK-TUDCA might be the main cause of toxicity reduction by the complex. This study described the preparation of an NK complex with low toxicity following intravenous administration, which could be utilized for further clinical study of NK.
基金National Natural Science Foundation of China(Grant No.81573333 and 81503060)
文摘Recombinant tissue plasminogen activator （rPA） has been used as a thrombolytic agent. However, considerable improvements have been done to prolong its plasma half-life （tl/2） and reduce its side effects, such as intracranial hemorrhage. Based on these improvements, a mutant ofrPA, mrPA, was designed by mutating its PAI-1 binding site to extend its tl/2. Furthermore, a fusion protein conjugating mrPA with NR3 was designed, which was a rAcAp5 mutant with a platelet GPIIb/IIIa-binding RGD motif, to enhance the ability of targeted-thrombus and thrombolysis. The synthesized DNA sequences coding the two proteins were amplified by PCR, cloned into pET30a to construct recombinant plasmids pET30a-mrPA and pET30a-mrPA-NR3, and transformed into E. coli BL21 （DE3）. The two proteins were expressed in inclusion bodies induced by isopropy113-D-1-thiogalactopyranoside. After purified to qualified purity using one-step Ni affinity chromatography, the denatured proteins were refolded by dialysis. Their thrombolytic effects in vitro and in vivo were evaluated. In vitro 3.5 and 7 pmol/L of mrPA significantly reduced thrombus weight; 1.75, 3.5 and 7 ~tmol/L of mrPA-NR3 also significantly reduced the thrombus weight, and mrPA-NR3 displayed stronger thrombolytic effects than mrPA at 7 lamol/L. In vivo both mrPA and mrPA-NR3 showed significantly thrombolytic effect at 60-240 ktmol/kg in thrombolytic model of inferior vena cava. Importantly, mrPA-NR3 exhibited more potent thrombolytic effect than both mrPA and rhM-tPA （positive control） at 240 p.mol/kg. In addition, these two novel proteins did not increase bleeding time while they exerted thrombolytic effect. In conclusion, we engineered two novel proteins and proved that fusion protein had better thrombolytic effect than non-fusion protein, and the results suggest that dual thrombolytic mechanism or thrombus-target potentiated the thrombolytic effect ofrPA and alleviated hemorrhage side reaction. This study may shed light on the development of novel thrombolytic agents with targeted thrombolysis and reduced side effects.
文摘A 31-year-old female who had well-established polycythemia vera one year before, presented with the sudden onset. She had severe ascites and hepatic encephalopathy 12 d prior to admission. Real-time ultrasonography revealed a supra hepatic thrombosis extending toward the inferior vena cava （IVC）. Thrombolytic therapy with systemic streptokinase （250000 IU loading ＋ 100000 IU/h infusion） was started. At the end of 72 h infusion, the patient＇s general condition improved. A color Doppler ultrasonography then showed complete and partial resolution of the thrombosis in the supra hepatic vein and IVC, respectively. Despite this good response, 12 d later, the symptoms recurred. Venography detected complete obstruction of the IVC. Percutanous balloon angioplasty with stent insertion was performed successfully and the patient was discharged without any evidence of liver disease. A combination of systemic streptokinase and radiological intervention was effective in our patient.
基金Supported by The EU"Nano Athero"project FP7-NMP-2012-LARGE-6-309820the DFG(CI 162/2-1,SPP1681)
文摘Intravascular thrombosis, a critical pathophysiological feature of many cardiovascular disorders, leads to the formation of life-threatening obstructive blood clots within the vessels. Rapid recanalization of occluded vessels is essential for the patients' outcome, but the currently available systemic fibrinolytic therapy is associated with low efficacy and tremendous side effects. Additionally, many patients are ineligible for systemic thrombolytic therapy, either due to delayed admission to the hospital after symptom onset, or because of recent surgery, or bleeding. In order to improve the treatment efficacy and to limit the risk of hemorrhagic complications, both precise imaging of the affected vascular regions, and the localized application of fibrinolytic agents, are required. Recent years have brought about considerable advances in nanomedical approaches to thrombosis. Although these thrombustargeting imaging agents and nanotherapies are not yet implemented in humans, substantial amount of successful in vivo applications have been reported, including animal models of stroke, acute arterial thrombosis, and pulmonary embolism. It is evident that the future progress in diagnosis and treatment of thrombosis will be closely bound with the development of novel nanotechnology-based strategies. This Editorial focuses on the recently reported approaches, which hold a great promise for personalized, disease-targeted treatment and reduced side effects in the patients suffering from this life-threatening condition.
基金supported by the Major State Basic Research Development Program of China(2017YFA0205201 and 2018YFA0107301)the National Natural Science Foundation of China(81901876,81925019,81603015,81871404,81801817,and U1705281)+2 种基金Xiamen science and technology program(3502Z20173012)the Fundamental Research Funds for the Central Universities(20720190088 and 20720200019)the Program for New Century Excellent Talents in University,China(NCET-13-0502).
文摘Thrombosis is a global health issue and one of the leading factors of death.However,its diagnosis has been limited to the late stages,and its therapeutic window is too narrow to provide reasonable and effective treatment.In addition,clinical thrombolytics suffer from a short half-life,allergic reactions,inactivation,and unwanted tissue hemorrhage.Nano-medicines have gained extensive attention in diagnosis,drug delivery,and photo/sound/magnetic-theranostics due to their convertible properties.Furthermore,diagnosis and treatment of thrombosis using nano-medicines have also been widely studied.This review summarizes the recent advances in this area,which revealed six types of nanoparticle approaches:(1)in vitro diagnostic kits using“synthetic biomarkers”;(2)in vivo imaging using nano-contrast agents;(3)targeted drug delivery systems using artificial nanoparticles;(4)microenvironment responsive drug delivery systems;(5)drug delivery systems using biological nanostructures;and(6)treatments with external irradiation.The investigations of nano-medicines are believed to be of great significance,and some of the advanced drug delivery systems show potential applications in clinical theranotics.
文摘AIM To evaluate reproducibility of pulmonary embolism(PE) clot volume quantification using computed tomography pulmonary angiogram(CTPA) in a multicenter setting.METHODS This study was performed using anonymized data in conformance with HIPAA and IRB Regulations(March 2015-November 2016). Anonymized CTPA data was acquired from 23 scanners from 18 imaging centers using each site's standard PE protocol. Two independent analysts measured PE volumes using a semi-automated region-growing algorithm on an FDA-approved image analysis platform. Total thrombus volume(TTV) was calculated per patient as the primary endpoint. Secondary endpoints were individual thrombus volume(ITV), Qanadli score and modified Qanadli score per patient. Inter-and intra-observer reproducibility were assessed using intra-class correlation coefficient(ICC) and BlandAltman analysis. RESULTS Analyst 1 found 72 emboli in the 23 patients with a mean number of emboli of 3.13 per patient with a range of 0-11 emboli per patient. The clot volumes ranged from 0.0041-47.34 cm3(mean +/-SD, 5.93 +/-10.15 cm3). On the second read, analyst 1 found the same number and distribution of emboli with a range of volumes for read 2 from 0.0041 – 45.52 cm3(mean +/-SD, 5.42 +/-9.53 cm3). Analyst 2 found 73 emboli in the 23 patients with a mean number of emboli of 3.17 per patient with a range of 0-11 emboli per patient. The clot volumes ranged from 0.00459-46.29 cm3(mean +/-SD, 5.91 +/-10.06 cm3). Inter-and intraobserver variability measurements indicated excellent reproducibility of the semi-automated method for quantifying PE volume burden. ICC for all endpoints was greater than 0.95 for inter-and intra-observer analysis. Bland-Altman analysis indicated no significant biases.CONCLUSION Semi-automated region growing algorithm for quantifying PE is reproducible using data from multiple scanners and is a suitable method for image analysis in multicenter clinical trials.
文摘AIM To examine effects of computed tomography(CT)image acquisition/reconstruction parameters on clot volume quantification in vitro for research method validation purposes.METHODS This study was performed in conformance with HIPAA and IRB Regulations(March 2015-November 2016).A ten blood clot phantom was designed and scanned on a dual-energy CT scanner(SOMATOM Force,Siemens Healthcare Gm BH,Erlangen,Germany)with varying pitch,iterative reconstruction,energy level and slicethickness.A range of clot and tube sizes were used in an attempt to replicate in vivo emboli found within central and segmental branches of the pulmonary arteries in patients with pulmonary emboli.Clot volume was the measured parameter and was analyzed by a single image analyst using a semi-automated region growing algorithm implemented in the FDA-approved Siemens syngo.via image analysis platform.Mixed model analysis was performed on the data.RESULTS On the acquisition side,the continuous factor of energy showed no statistically significant effect on absolute clot volume quantification(P=0.9898).On the other hand,when considering the fixed factor of pitch,there were statistically significant differences in clot volume quantification(P<0.0001).On the reconstruction side,with the continuous factor of reconstruction slice thickness no statistically significant effect on absolute clot volume quantification was demonstrated(P=0.4500).Also on the reconstruction side,with the fixed factor of using iterative reconstructions there was also no statistically significant effect on absolute clot volume quantification(P=0.3011).In addition,there was excellent R^2 correlation between the scale-measured mass of the clots both with respect to the CT measured volumes and with respect to volumes measure by the water displacement method.CONCLUSION Aside from varying pitch,changing CT acquisition parameters and using iterative reconstructions had no significant impact on clot volume quantification with a semi-automated region growing algorithm.
