THROMBOLYSIS IN PULMONARY EMBOLISM TREATMENT.

OBJECTIVE: The aim: To assess the effectiveness of thrombolytic therapy in treatment pulmonary embolism. PATIENTS AND METHODS: Materials and methods: The work analyzed the results of the survey and conservative treatment of 284 patients with pulmonary embolism treated in cardiological department in «Uzhgorod Central City Clinical Hospital¼ during 2019-2022. Patients were divided into two groups: group I - 250 (88%) patients received anticoagulant therapy; group II - 34 (12%) patients received thrombolytic therapy that was then switched to new oral anticoagulants. RESULTS: Results: In I group, the first three days were carried out continuously intravenous infusion of heparin in a dose of 25-30 thousand units per day, on the fourth day switched to subcutaneous injection for 10-14 days with subsequent switching to rivaroxaban. 34 (12.0%) patients of the II group, was started with thrombolytic therapy. 32 (94.1%) patients were prescribed alteplase 100 mg/day, and 2 (5.9%) patients - streptokinase 1.5 million units/day. After thrombolysis, patients were prescribed rivaroxaban for prolonged period. Thrombolytic therapy made it possible to prevent fatal cases, and in monotherapy with anticoagulants - mortality was 4.8%. Minor hemorrhagic complications like hematuria, local hematomas at the injection site, bleeding gums were observed in 7.6% of patients during thrombolytic therapy. No cases of large hemorrhages were observed. Manifestations of chronic postembolic pulmonary hypertension in the distant period were found in 97.1% and 6.9% of patients of the I and II groups, respectively. Lethality in the remote period was 5.3% - all in the 1st group of patients due to PE recurrence and acute myocardial infarction. CONCLUSION: Conclusions: Implementation of thrombolytic therapy in patients with thromboembolism of the pulmonary artery allows effectively prevent recurrence with a fatal outcome, restore the lumen of the pulmonary arteries and prevent the development of chronic postembolic pulmonary hypertension in the immediate and remote period of observation compared to isolated anticoagulant therapy.

Evolution of deep vein thrombosis treatment from leeches to mechanical thrombectomy.

Deep vein thrombosis (DVT) is one of the most common diseases in developed countries with significant socioeconomic consequences. The severity of DVT lies in the potential for life-threatening pulmonary embolism and the development of chronic venous insufficiency, referred to as post-thrombotic syndrome. Virchow contributed to the understanding of the pathophysiological events that lead to thrombosis by describing three basic risk mechanisms. The first therapeutic attempts in the 17th century included venepuncture and the application of leeches. The first anticoagulant drug was heparin, which entered clinical practice after 1935. Subsequent commercialization of oral vitamin K antagonists (warfarin) and the advent of low molecular weight heparin along with compression therapy allowed the expansion of outpatient treatment of DVT. Recently, new oral anticoagulants have been introduced, leading to improved safety due to lower risk of bleeding complications and simplification of the treatment process. The next step in the development of therapeutic options are invasive methods of early thrombus removal, which significantly shorten the process and aim to reduce the occurrence of late complications. These methods include local catheter-directed thrombolysis using tissue plasminogen activator, mechanical thrombectomy and their combination called pharmaco-mechanical thrombectomy. The latter is currently used in patients with acute ilio-femoral DVT.

Clot-targeted magnetic hyperthermia permeabilizes blood clots to make them more susceptible to thrombolysis.

BACKGROUND: Thrombolysis is a frontline treatment for stroke, which involves the application of tissue plasminogen activator (tPA) to trigger endogenous clot-degradation pathways. However, it is only effective within 4.5 h of symptom onset because of clot contraction preventing tPA permeation into the clot. Magnetic hyperthermia (MH) mediated by tumor-targeted magnetic nanoparticles is used to treat cancer by using local heat generation to trigger apoptosis of cancer cells. OBJECTIVES: To develop clot-targeting magnetic nanoparticles to deliver MH to the surface of human blood clots, and to assess whether this can improve the efficacy of thrombolysis of contracted blood clots. METHODS: Clot-targeting magnetic nanoparticles were developed by functionalizing iron oxide nanoparticles with an antibody recognizing activated integrin αIIbß3 (PAC-1). The magnetic properties of the PAC-1-tagged magnetic nanoparticles were characterized and optimized to deliver clot-targeted MH. RESULTS: Clot-targeted MH increases the efficacy of tPA-mediated thrombolysis in contracted human blood clots, leading to a reduction in clot weight. MH increases the permeability of the clots to tPA, facilitating their breakdown. Scanning electron microscopy reveals that this effect is elicited through enhanced fibrin breakdown and triggering the disruption of red blood cells on the surface of the clot. Importantly, endothelial cells viability in a three-dimensional blood vessel model is unaffected by exposure to MH. CONCLUSIONS: This study demonstrates that clot-targeted MH can enhance the thrombolysis of contracted human blood clots and can be safely applied to enhance the timeframe in which thrombolysis is effective.

Efficacy of Chinese herbal medicine for tPA thrombolysis in experimental stroke: A systematic review and meta-analysis.

BACKGROUND: Tissue-type plasminogen activator (tPA) remains the sole FDA approved thrombolytic drug for ischemic stroke. But delayed thrombolytic therapy with tPA may increase the risk of hemorrhagic transformation. Many Chinese herbal medicines have been used as tPA helpers to enhance the capacity of tPA and minimize the risk of hemorrhagic transformation. The efficacy of Chinese herbal medicines on tPA thrombolysis is not systematically analyzed. METHODS: We searched the following three databases up to January 2022: Web of Science, PubMed, and Scopus. Studies that reported the efficacy and safety of Chinese herbal medicines on tPA thrombolysis in experimental stroke were included. The efficacy outcomes were neurological score and infarct volume, the safety outcomes were cerebral hemorrhage and blood brain barrier (BBB) damage. We used the checklist of CAMARADES to assess the quality of included studies. Standardized mean difference (SMD) with 95% confidence intervals were used to assess all the outcomes. Subgroup analyses were performed to explore the sources of heterogeneity. Trim and fill method and Egger's test were used to assess the potential publication bias. Sensitivity analyses were used to identify the stability of the results. RESULTS: A total of nine studies including 11 Chinese herbal medicines fulfilled the inclusion criteria and were subsequently analyzed. The pooled data demonstrated that Chinese herbal medicines improved neurological score (2.23 SMD, 1.42-3.04), infarct volume (1.08 SMD, 0.62-1.54), attenuated cerebral hemorrhage (1.87 SMD, 1.34-2.4), and BBB dysfunction (1.9 SMD, 1.35-2.45) following tPA thrombolysis in experimental stroke. Subgroup analysis indicated that the route of drug delivery, dosage of tPA, and stroke model used may be factors inducing heterogeneity and influencing the efficacy. CONCLUSION: Treatment with Chinese herbal medicines significantly improved neurological score and infarct volume, reduced cerebral hemorrhage and BBB damage after tPA thrombolysis. This study supports Chinese herbal medicine as an adjuvant therapy in reducing the side effects of tPA thrombolysis after acute ischemic stroke. The results should be interpreted with more caution since this article was based on animal studies.

Chinese herbal injections combined with rt-PA intravenous thrombolysis for acute ischemic stroke: A systematic review and meta-analysis protocol.

BACKGROUND: Acute ischemic stroke (AIS) is an important factor leading to adult death and disability globally. For AIS patients who meet certain conditions, recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis is an important method recommended by national guidelines to achieve vascular recanalization. However, complications such as hemorrhagic transformation and vascular reocclusion after thrombolysis are still unsolved problems in clinical. Several systematic reviews of clinical randomized controlled trials (RCTs) in the past have shown that Chinese herbal injections (CHIs) can improve the neurological function of patients, increase the tolerance of ischemic tissues to hypoxia, and inhibit platelet aggregation. Therefore, this study conducted a meta-analysis of AIS treatment with intravenous thrombolysis alone and compared it with the combined application of CHIs. To evaluate whether CHIs have a synergistic effect on thrombolytic therapy and provide a basis for clinical application. METHODS: The following databases will be searched until September 2020: ①English databases: PubMed, Cochrane Library, Embase; ②Chinese databases: CNKI, Wanfang database, Weipu database, SinoMed. RCTs will be included to compare the efficacy of thrombolysis combined with CHIs and thrombolysis alone in the treatment of AIS. Data extraction and risk of bias assessments will be carried out by 2 verifiers independently. The risk of bias will be evaluated through the Cochrane risk of bias tool. Review Manager software 5.3 will be used for statistical analysis. RESULTS: This study will provide comprehensive evidence for the treatment of AIS by CHIs combined with intravenous thrombolysis from multiple aspects. CONCLUSION: The conclusion of the meta-analysis will provide a basis for judging whether CHIs combined with intravenous thrombolysis is an effective measure for the treatment of AIS. ETHICS AND DISSEMINATION: Ethical approval is not needed because this study will be based on data that already published. We will publish the findings of this study in a peer-reviewed journal and related conferences. PROSPERO REGISTRATION NUMBER: CRD42020215546.

Dual-Targeting Glycol Chitosan/Heparin-Decorated Polypyrrole Nanoparticle for Augmented Photothermal Thrombolytic Therapy.

Near-infrared (NIR)-light-modulated photothermal thrombolysis has been investigated to overcome the hemorrhage danger posed by clinical clot-busting substances. A long-standing issue in thrombosis fibrinolytics is the lack of lesion-specific therapy, which should not be ignored. Herein, a novel thrombolysis therapy using photothermal disintegration of a fibrin clot was explored through dual-targeting glycol chitosan/heparin-decorated polypyrrole nanoparticles (GCS-PPY-H NPs) to enhance thrombus delivery and thrombolytic therapeutic efficacy. GCS-PPY-H NPs can target acidic/P-selectin high-expression inflammatory endothelial cells/thrombus sites for initiating lesion-site-specific thrombolysis by hyperthermia using NIR irradiation. A significant fibrin clot-clearance rate was achieved with thrombolysis using dual-targeting/modality photothermal clot disintegration in vivo. The molecular level mechanisms of the developed nanoformulations and interface properties were determined using multiple surface specific analytical techniques, such as particle size distribution, zeta potential, electron microscopy, Fourier-transform infrared spectroscopy (FTIR), wavelength absorbance, photothermal, immunofluorescence, and histology. Owing to the augmented thrombus delivery of GCS-PPY-H NPs and swift treatment time, dual-targeting photothermal clot disintegration as a systematic treatment using GCS-PPY-H NPs can be effectively applied in thrombolysis. This novel approach possesses a promising future for thrombolytic treatment.

Frostbite: Current status and advancements in therapeutics.

Frostbite is a severe ischemic injury which occurs due to the tissue vascular damage after sub-zero temperature tissue exposure. Deep frostbite can result in necrosis and may need amputation of affected tissue. Though a serious injury, it is not very well understood, and further scientific exploration is needed. This work explores the current understanding of the pathophysiology of frostbite. We reviewed the current status of the diagnostics, the drugs, the therapies and the surgical practices for prevention and management of frostbite. Advances in nanotechnology and drug delivery had improved the therapeutic outcomes significantly. This review also explored the latest advancements and researches done for development of newer therapeutics and diagnostics for frostbite care.

Viral Coagulopathy in Patients With COVID-19: Treatment and Care.

COVID-19 has proven to be particularly challenging given the complex pathogenesis of SARS-CoV-2. Early data have demonstrated how the host response to this novel coronavirus leads to the proliferation of pro-inflammatory cytokines, massive endothelial damage, and generalized vascular manifestations. While SARS-CoV-2 primarily targets the upper and lower respiratory tract, other organ systems are also affected. SARS-CoV-2 relies on 2 host cell receptors for successful attachment: angiotensin-converting enzyme 2 and transmembrane protease serine 2. Clinicopathologic reports have demonstrated associations between severe COVID-19 and viral coagulopathy, resulting in pulmonary embolism; venous, arterial, and microvascular thrombosis; lung endothelial injury; and associated thrombotic complications leading to acute respiratory distress syndrome. Viral coagulopathy is not novel given similar observations with SARS classic, including the consumption of platelets, generation of thrombin, and increased fibrin degradation product exhibiting overt disseminated intravascular coagulation-like syndrome. The specific mechanism(s) behind the thrombotic complications in COVID-19 patients has yet to be fully understood. Parenteral anticoagulants, such as heparin and low-molecular-weights heparins, are widely used in the management of COVID-19 patients. Beyond the primary (anticoagulant) effects of these agents, they may exhibit antiviral, anti-inflammatory, and cytoprotective effects. Direct oral anticoagulants and antiplatelet agents are also useful in the management of these patients. Tissue plasminogen activator and other fibrinolytic modalities may also be helpful in the overall management. Catheter-directed thrombolysis can be used in patients developing pulmonary embolism. Further investigations are required to understand the molecular and cellular mechanisms involved in the pathogenesis of COVID-19-associated thrombotic complications.

Evidence-based practice guideline on integrative medicine for stroke 2019.

OBJECTIVE: Stroke is the leading cause of death and disability in China. Chinese medicine integrated with conventional medicine is now widely used in the prevention and treatment of stroke. A clinical practice guideline for the application of integrative medicine in stroke is urgently needed. METHODS: This guideline was developed following the methodology and procedures recommended in the World Health Organization Handbook for Guideline Development and the Guideline Development Handbook for Diagnosis and Therapy of Integrative Medicine. The quality of evidence and strength of recommendations were evaluated using the GRADE approach. The guideline followed the RIGHT statement and AGREE II was consulted to ensure its quality. RESULTS: A multidisciplinary working team was established. Eleven research questions from 15 clinical questions were identified by questionnaire surveys, face-to-face meetings, and analyzed by the working team. Fourteen recommendations regarding integrative medicine for ischemic stroke, hemorrhagic stroke, and complications of stroke were formulated from systematic reviews of the benefits, harms, cost-effectiveness, quality of evidence, the values and preferences of patients and their family members, feedback on proposed recommendations from medical practitioners from a variety of disciplines, and a face-to-face consensus meeting. CONCLUSIONS: This guideline focuses on clinical treatments that are specific to integrative medicine for stroke and can be used at all levels in medical institutions and rehabilitation facilities. The end-users of the guideline are most likely to be medical practitioners, including Chinese herbal medicine specialists, acupuncturists, integrative medicine practitioners, physicians, physical therapists, and clinical pharmacists.

Preparation of Peptide and Recombinant Tissue Plasminogen Activator Conjugated Poly(Lactic-Co-Glycolic Acid) (PLGA) Magnetic Nanoparticles for Dual Targeted Thrombolytic Therapy.

Recombinant tissue plasminogen activator (rtPA) is the only thrombolytic agent that has been approved by the FDA for treatment of ischemic stroke. However, a high dose intravenous infusion is required to maintain effective drug concentration, owing to the short half-life of the thrombolytic drug, whereas a momentous limitation is the risk of bleeding. We envision a dual targeted strategy for rtPA delivery will be feasible to minimize the required dose of rtPA for treatment. For this purpose, rtPA and fibrin-avid peptide were co-immobilized to poly(lactic-co-glycolic acid) (PLGA) magnetic nanoparticles (PMNP) to prepare peptide/rtPA conjugated PMNPs (pPMNP-rtPA). During preparation, PMNP was first surface modified with avidin, which could interact with biotin. This is followed by binding PMNP-avidin with biotin-PEG-rtPA (or biotin-PEG-peptide), which was prepared beforehand by binding rtPA (or peptide) to biotin-PEG-maleimide while using click chemistry between maleimide and the single -SH group in rtPA (or peptide). The physicochemical property characterization indicated the successful preparation of the magnetic nanoparticles with full retention of rtPA fibrinolysis activity, while biological response studies underlined the high biocompatibility of all magnetic nanoparticles from cytotoxicity and hemolysis assays in vitro. The magnetic guidance and fibrin binding effects were also confirmed, which led to a higher thrombolysis rate in vitro using PMNP-rtPA or pPMNP-rtPA when compared to free rtPA after static or dynamic incubation with blood clots. Using pressure-dependent clot lysis model in a flow system, dual targeted pPMNP-rtPA could reduce the clot lysis time for reperfusion by 40% when compared to free rtPA at the same drug dosage. From in vivo targeted thrombolysis in a rat embolic model, pPMNP-rtPA was used at 20% of free rtPA dosage to restore the iliac blood flow in vascular thrombus that was created by injecting a blood clot to the hind limb area.

Acute phase treatment in central retinal artery occlusion: thrombolysis, hyperbaric oxygen therapy or both?

Central retinal artery occlusion (CRAO) is a neuro-ophthalmological emergency. There is a finite time window for acute interventions such as revascularization (e.g. intravenous thrombolysis-IVT) and retinal oxygenation (e.g. hyperbaric oxygen therapy-HBOT) therapies. Case 1: A 35-year-old female presented with CRAO in the right eye (OD) confirmed by fluorescein angiography (FA) and optical coherence tomography (OCT). She underwent 4 sessions of HBOT (100% O2 at 2.4 atmosphere absolute for 90 min). Afterwards, visual defect on the nasal field was kept but visual acuity (VA) improved from counting fingers to 1.0. Case 2: A 65-year-old male presented with CRAO in his left eye (OS) with 1.5 h of evolution. Orbital sonography and OCT confirmed the presence of an embolus and he underwent IVT with rTPA (0.9 mg/kg). VA improved from light perception to 0.1. Case 3: A 21-year-old male presented acute visual loss in his OD with 2.5 h of evolution. OCT and retinography identified CRAO. He was submitted to IVT (rTPA-0.9 mg/kg) followed by 12 sessions of HBOT. VA improved from hand motion to 1.0. Our case series depicts the approaches and possible outcomes in acute management of an infrequent, but highly morbid, cerebroretinovascular disorder. Future clinical trials are warranted to tackle current difficulties in CRAO treatment.

Comparative outcomes of catheter-directed thrombolysis plus rivaroxaban vs rivaroxaban alone in patients with acute iliofemoral deep vein thrombosis.

BACKGROUND: Since novel oral anticoagulants (NOACs) have been introduced in the past decade, the first option of deep vein thrombosis (DVT) treatment is toward NOACs. However, aggressive and early thrombus removal strategy is widely used for treating acute iliofemoral DVT. Consequently, optimal treatment duration, efficacy, and safety of rivaroxaban alone or in combination with catheter-directed intrathrombus thrombolysis (CDT) in acute iliofemoral DVT patients should be investigated. METHODS: Patients with recent acute iliofemoral DVT treated with combined CDT-rivaroxaban (CDT) or rivaroxaban alone (control) were followed for mean (standard deviation) of 25.7 (2.5) months. DVT evolution, treatment efficacy and safety, and predisposing factors for patency and postthrombotic syndrome (PTS) development were analyzed through duplex ultrasonography, plethysmography, venography, and computed tomographic venography. RESULTS: 43.2%, 64.9%, 75.7%, and 72.2% of the CDT patients showed complete patency at 3, 6, 12, and 24 months of treatment compared with the control patients having 8.5%, 36.2%, 55.3%, and 57.4% of cumulative patency at 3, 6, 12, and 24 months, respectively (p = 0.001, 0.017, 0.088, and 0.081, respectively). The p value of the log-rank test comparing patency rates of the two groups was 0.009. The median (interquartile range, IQR) Villalta scores at 24 months were 3 (2-5) and 6 (4-8) in CDT and control patients, respectively (p = 0·001). PTS and bleeding events during therapy were, respectively, found in 35.1% and 63.8% (p = 0.017) and in 27% and 17% of CDT and control patients (p = 0.4). The Kaplan-Meier curve analysis of cumulative patency at 24 months for 6 months of rivaroxaban treatment was significant (p = 0.016). CONCLUSION: Treatment therapy and treatment duration with rivaroxaban alone or in combination with CDT are potentially associated with vein patency at 24 months, and a 6-month lysis rate and obstructive vein can influence PTS development. A larger randomized trial is warranted to confirm these findings.

In vitro examination of the thrombolytic efficacy of tenecteplase and therapeutic ultrasound compared to rt-PA.

BACKGROUND: Optimizing thrombolytic therapy is vital for improving stroke outcomes. We aimed to develop standardized thrombolysis conditions to evaluate the efficacy of tenecteplase (TNK) compared to the current gold standard rt-PA (alteplase), with and without additional ultrasound treatment. We also wanted to introduce a new analytical approach to quantify fibrin fiber density in transmission electron microscopy (TEM). METHODS: In vitro clots that are similar to ex vivo clots concerning their histological condition and their durability were generated from whole blood. For five treatment groups we compared relative clot weight loss (each n = 60) and fibrin fiber density in TEM (each n = 5). The control group (A) was treated only with plasma. Two groups were designated for each rt-PA (B + C) and TNK (D + E). Groups C and E were additionally treated with ultrasound. Dosages were 50 µg/ml for rt-PA and 30 µg/ml for TNK. Results were evaluated by using analyses of variance (ANOVA) and post-hoc t-tests. RESULTS: Weight loss was increased significantly for all groups compared to the control group. Both TNK groups showed significantly increased weight loss compared to their counterpart rt-PA group (p ≤ 0.001). For TEM only group D showed significantly decreased fibrin fiber density (p < 0.05) compared to both rt-PA groups. Ultrasound did not significantly increase dissolution of clots with either method (best p = 0.16). CONCLUSIONS: Tenecteplase dissolved clots more effectively than rt-PA with and without ultrasound. A higher sample size could provide more convincing results for TEM.

Identification, diagnosis, treatment, and in-hospital outcomes of acute pulmonary embolism: Results from a single integrated health system.

BACKGROUND: Although the high-risk acute pulmonary embolism (PE) population has been described, little is known about the contemporary inpatient experience and practice patterns of the PE population as a whole. METHODS: All patients with a diagnosis of acute PE from January 1, 2016, to June 30, 2017 within our academic, multihospital health system were retrospectively identified using International Classification of Diseases, 10th Revision, codes, and data were manually abstracted by 2 clinical investigators. Descriptive analyses were performed according to clinical risk stratification categories from the European Society of Cardiology. RESULTS: Of 829 total patients, 372 (44.8%) patients had intermediate or high-risk PE. Mean age was 62.1 years old, and 42.1% of patients had a history of malignancy. One hundred fifty-three (18.5%) patients had an acute PE during a hospitalization for another indication. A total of 6.0% underwent invasive PE therapies, 26.1% required intensive care unit admission, and 9.0% experienced in-hospital death or hospice discharge. In a subgroup description, patients who developed acute PE during a hospitalization for another indication had a higher incidence of incomplete risk stratification and a higher mortality (9.8%) than the primary cohort. Mortality was attributed to PE in 48.4% of cases. CONCLUSIONS: This contemporary description of acute PE managed at a single large, multihospital academic health system highlights substantial health care utilization and high mortality despite the available of advanced therapeutics. Additional work is needed to standardize care for the heterogeneous PE population to ensure appropriate allocation of resources and improved outcomes for all PE patients.

Assessment of patients with coronary artery disease who may benefit from the use of rivaroxaban in the real world: implementation of the COMPASS trial criteria in the TERCET registry population.

INTRODUCTION: The positive outcomes of the COMPASS trial raise questions about the proportion of patients who could benefit from additional therapy with rivaroxaban in real­world practice. OBJECTIVES: We aimed to identify the proportion of patients from the TERCET registry with significant coronary artery disease (TERCET­CAD) who could benefit from the use of rivaroxaban and to assess their clinical characteristics and long­term prognosis in comparison with the corresponding measures in the COMPASS trial. PATIENTS AND METHODS: The COMPASS criteria were applied in the TERCET­CAD population. Patients who met the criteria of the COMPASS trial were included in the COMPASS­like group. The baseline characteristics and long­term outcomes of the COMPASS­like group were compared with the corresponding measures in the acetylsalicylic acid (ASA)-alone arm from the COMPASS trial. RESULTS: The COMPASS­like group included 3884 patients (31.6%) out of the 12 286 patients constituting the TERCET­CAD population. Patients in the COMPASS­like group were characterized by older age (P <0.001) and a more frequent occurrence of risk factors for CAD than those in the ASA­alone arm of the COMPASS trial. The rate of a composite endpoint in the COMPASS­like group was 9%, and in the ASA­alone arm of the COMPASS trial, it was 6% (P <0.001). CONCLUSIONS: Less than one-third of the TERCET­CAD population met the COMPASS criteria and could potentially benefit from low­dose rivaroxaban therapy. Unfavorable clinical profiles and higher rates of adverse events in the TERCET registry compared with those in the COMPASS trial may predict greater benefits from the implementation of low­dose rivaroxaban in the real­world population.

New progress in the approaches for blood-brain barrier protection in acute ischemic stroke.

Ischemic stroke is a disease with high morbidity and mortality worldwide, which often places an additional strain on families and society due to the poor prognosis. Blood brain-barrier (BBB) damage is the critical pathological process, which contributes to hemorrhagic transformation (HT) and poor prognosis in cerebral ischemia. Thus, there is a pressing need to seek an approach to ameliorate BBB damage and reduce the HT that can be induced by fibrinolytic therapy involving recombinant tissue plasminogen activator (rtPA) in clinical practice. This review provides an overview of the recent scientific reports to improve our understanding of new approaches to ameliorating BBB damage in ischemic stroke, including physical approaches, chemical agents, traditional Chinese medicine and its extracts, neural stem cell therapy and microRNA intervention. Inhibiting matrix metalloproteinases (MMP) is possibly the main functional mechanism of these BBB protectants, along with anti-oxidative and anti-inflammatory effects. Other significant mechanisms for BBB protection have been studied recently, such as anti-apoptosis, extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)/ Akt pathways and so on. An in-depth understanding of the related mechanisms contributes to finding potential approaches for BBB protection, and a deeper understanding of the emerging BBB protectants offers opportunities to seek a promising adjuvant therapy to prevent HT in the post-stroke brain.

Transient Q-waves in an infant with asymptomatic myocardial infarction due to Kawasaki disease.

Giant coronary artery aneurysms are a complication of Kawasaki disease and can be fatal if associated with thrombosis. We describe the clinical outcome of a boy with Kawasaki disease who exhibited "supergiant" coronary artery aneurysms at the age of 14 months and, despite treatment with anticoagulant and antiplatelet medication, developed a left coronary artery thrombosis and presented following a myocardial infarction at 2 years old. Although his symptoms were minimal, the myocardial infarction was identified by abnormal Q-waves and giant negative T-waves in precordial leads of routine electrocardiography. Intensive anticoagulant therapy combining heparin injections and high-dose warfarin was successful. The abnormal Q-waves and negative T-waves had completely disappeared 2 weeks later, likely in association with confirmed reperfusion. On the basis of prompt identification of abnormal Q-waves by electrocardiography, the patient could avoid thrombolytic therapy and catheter or surgical intervention.