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We tested five chemically and metabolically stable prostaglandin (PG) receptor agonists in a mouse model of dexamethasone-induced ocular hypertension (OHT). Whilst all compounds significantly (p < 0.05, ANOVA) lowered intraocular pressure (IOP) after twice-daily bilateral topical ocular dosing (5 µg/dose) over three weeks, the time course and magnitude of the responses varied. The onset of action of NS-304 (IP-PG receptor agonist) and rivenprost (EP4-PG receptor agonist) was slower than that of misoprostol (mixed EP2/EP3/EP4-PG receptor agonist), PF-04217329 (EP2-PG receptor agonist), and butaprost (EP2-PG receptor agonist). The rank order of IOP-lowering efficacies aligned with the onset of actions of these compounds. Peak IOP reductions relative to vehicle controls were as follows: misoprostol (74.52%) = PF-04217329 (74.32%) > butaprost (65.2%) > rivenprost (58.4%) > NS-304 (55.3%). A literature survey indicated that few previously evaluated compounds (e.g., latanoprost, timolol, pilocarpine, brimonidine, dorzolamide, cromakalim analog (CKLP1), losartan, tissue plasminogen activator, trans-resveratrol, sodium 4-phenyl acetic acid, etc.) in various animal models of steroid-induced OHT were able to match the effectiveness of misoprostol, PF-04217329 or butaprost. Since a common feature of the latter compounds is their relatively high affinity and potency at the EP2-PG receptor sub-type, which activates the production of intracellular cAMP in target cells, our studies suggest that drugs selective for the EP2-PG receptor may be suited to treat corticosteroid-induced OHT.

Background: The definition of minor ischemic stroke (MIS) is a topic of debate, however, the most accepted definition is a stroke with National Institutes of Health Stroke Scale (NIHSS) ≤ 5. Intravenous thrombolysis (IVT) is a crucial treatment option for acute ischemic stroke (AIS) including: alteplase, recombinant human tissue-type plasminogen activator (r-tPA), and the recently approved tenecteplase. However, there is a debate regarding its safety and efficacy. Therefore, our objective was to determine the safety and efficacy of IVT in treating minor stroke patients (NIHSS ≤ 5). Methods: Using the search strategy assigned which was based on three keywords: "mild" or "minor", "stroke", and "intravenous thrombolysis", we searched for eligible articles on PubMed, Web of Science, Embase, and Scopus from inception till 10th January 2024. We conducted this meta-analysis using the random effect model to account for the heterogeneity among the studies. For the dichotomous variables, we calculated the odds ratio (OR) from the event and total of these variables. While for the continuous variables, we calculated the mean difference (MD) of these variables. Pooling of OR for the occurrence of events was also conducted. Results: A total of 21 articles with 93,057 patients with MIS were included. The mean age of the participants ranged from 62.3 to 79.6. Most of the included patients had comorbidities such as hypertension, diabetes, previous stroke, smoking, atrial fibrillation, and hyperlipidemia. Of these, 10,850 received IVT while 82,207 did not. The use of IVT was statistically significant associated with 90-day modified Rankin score (mRs) 0–1 when compared with control with OR of 1.67 (95%CI: 1.46, 1.91, p < 0.00001) and was statistically significantly associated with improvement of NIHSS on discharge with OR of 2.19 (95%CI: 1.56, 3.08, p < 0.00001). In terms of safety outcomes, IVT has proven a safe profile, as there was no significant difference in intracranial hemorrhage (ICH) and mortality rates between the IVT and control groups with OR of 1.75 (95CI: 0.95, 3.23, p = 0.07) and 0.93 (95%CI: 0.77, 1.11, p = 0.41), respectively. Conclusion: Although some studies have not found any benefits of IVT in MIS patients, a substantial body of literature strongly endorses IVT as an effective and safe treatment for MIS. IVT has been shown to improve the mRs and NIHSS scores at the 90-day mark without an increased risk of ICH or mortality. [ABSTRACT FROM AUTHOR]

AbstractChinese hamster ovary (CHO) cells represent the most common host system for the expression of high-quality recombinant proteins. The development of stable CHO cell lines used in industrial recombinant protein production often relies on dihydrofolate reductase (DHFR) and glutamine synthetase (GS) amplification systems. Conventional approaches to develop stable cell lines lead to heterogeneous cell populations. Consequently, it is desirable to adopt innovative strategies to increase the efficiency of clone selection to reduce the time and effort invested in the cell line development process. Attenuating the selection marker gene is an effective strategy for isolating high-producing cells. In this study, we evaluated the efficiency of an attenuated glutamine synthetase selection system for the expression of human tissue plasminogen activator (t-PA) in CHO cells. We introduced an AU-rich element (ARE) at the 3’UTR of the glutamine synthetase coding sequence and employed a weak promoter (mSV40) for the expression of this gene. Subsequently, we analyzed the effect of ARE on the GS RNA levels, and recombinant t-PA expression. Our results demonstrate that the use of ARE significantly enhances the detection of high expressing cells compared to the control. Additionally, the t-PA expression level in GS-ARE clones was approximately 900-fold greater than those without the ARE. [ABSTRACT FROM AUTHOR]

Introduction: Hemorrhagic transformation (HT) is a severe complication in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO) after endovascular treatment (EVT). We hypothesize that asymmetry of the internal cerebral veins (ICVs) on baseline CT angiogram (CTA) may serve as an adjunctive predictor of HT. Methods: We conducted a study on consecutive AIS-LVO patients from November 2020 to April 2022. These patients had anterior circulation occlusions and were treated with EVT. Asymmetrical ICVs were assessed using CTA and defined as hypodensity (reduced opacification) on the ipsilateral side of occlusion compared to the contralateral side. The primary outcome was HT, defined as hemorrhage within the ischemic territory. This was evaluated using follow-up imaging (CT scan or magnetic resonance imaging) performed 48 h post-EVT. HT was classified into four subtypes based on the European Cooperative Acute Stroke Study-II criteria. Results: A total of 126 patients were included, with an HT rate of 49.2% (62/126). ICV asymmetry was observed in 54.0% (68/126) of patients. The ICV asymmetry group exhibited a significantly higher risk of parenchymatous hematoma-type HT (33.8% vs. 15.5%, p = 0.019) and symptomatic intracerebral hemorrhage (sICH) (23.5% vs. 5.2%, p = 0.004). In multivariate logistic regression, ICV asymmetry (OR 3.809, 95% CI 1.582–9.171), baseline Alberta Stroke Program Early CT Score (OR 0.771, 95% CI 0.608–0.978), intravenous recombinant tissue plasminogen activator (OR 2.847, 95% CI 1.098–2.7.385), and poor collateral circulation (OR 3.998, 95% CI 1.572–10.169) were identified as independent risk factors of HT. Conclusion: ICV asymmetry, likely resulting from impaired autoregulation or tissue micro-perfusion hampering cerebral blood flow (CBF), is a novel radiological sign that independently predicts HT. It is associated with a higher risk of sICH in AIS-LVO patients after EVT. Further research is warranted to validate these findings. [ABSTRACT FROM AUTHOR]

The thrombolytic protease tissue plasminogen activator (tPA) is expressed in the CNS, where it regulates diverse functions including neuronal plasticity, neuroinflammation, and blood-brain-barrier integrity. However, its role in different brain regions such as the substantia nigra (SN) is largely unexplored. In this study, we characterize tPA expression, activity, and localization in the SN using a combination of retrograde tracing and β-galactosidase tPA reporter mice. We further investigate tPA's potential role in SN pathology in an α-synuclein mouse model of Parkinson's disease (PD). To characterize the mechanism of tPA action in α-synuclein-mediated pathology in the SN and to identify possible therapeutic pathways, we performed RNA-seq analysis of the SN and used multiple transgenic mouse models. These included tPA deficient mice and two newly developed transgenic mice, a knock-in model expressing endogenous levels of proteolytically inactive tPA (tPA Ala-KI) and a second model overexpressing proteolytically inactive tPA (tPA Ala-BAC). Our findings show that striatal GABAergic neurons send tPA+ projections to dopaminergic (DA)-neurons in the SN and that tPA is released from SN-derived synaptosomes upon stimulation. We also found that tPA levels in the SN increased following α-synuclein overexpression. Importantly, tPA deficiency protects DA-neurons from degeneration, prevents behavioral deficits, and reduces microglia activation and T-cell infiltration induced by α-synuclein overexpression. RNA-seq analysis indicates that tPA in the SN is required for the upregulation of genes involved in the innate and adaptive immune responses induced by α-synuclein overexpression. Overexpression of α-synuclein in tPA Ala-KI mice, expressing only proteolytically inactive tPA, confirms that tPA-mediated neuroinflammation and neurodegeneration is independent of its proteolytic activity. Moreover, overexpression of proteolytically inactive tPA in tPA Ala-BAC mice leads to increased neuroinflammation and neurodegeneration compared to mice expressing normal levels of tPA, suggesting a tPA dose response. Finally, treatment of mice with glunomab, a neutralizing antibody that selectively blocks tPA binding to the N-methyl-D-aspartate receptor-1 (NMDAR1) without affecting NMDAR1 ion channel function, identifies the tPA interaction with NMDAR1 as necessary for tPA-mediated neuroinflammation and neurodegeneration in response to α-synuclein-mediated neurotoxicity. Thus, our data identifies a novel pathway that promotes DA-neuron degeneration and suggests a potential therapeutic intervention for PD targeting the tPA-NMDAR1 interaction. [ABSTRACT FROM AUTHOR]

The article discusses the 40th anniversary of the TIMI Study Group, which began in 1955 with a focus on identifying determinants of myocardial oxygen supply and demand. Over the years, the TIMI trials have made significant contributions to cardiovascular care, including advancements in antithrombotic therapy, lipid-lowering therapy, and antiplatelet therapy. The TIMI trials have enrolled over 400,000 patients and have been instrumental in developing evidence-based medicine practices in cardiovascular care. [Extracted from the article]

Objective: To investigate the screening efficacy of six thrombotic markers for hypercoagulable state (HCS) in pregnant women, including thrombin-antithrombin III complex (TAT), plasmin-alpha-2 plasmin inhibitor complex (PIC), thrombomodulin (TM), tissue-type plasminogen activator inhibitor complex(t-PAI-C), D-dimer(D-D), and fibrinogen degradation products (FDP). Methods: This was a retrospective study. Eighty-five high-risk pregnant women who underwent antenatal examination at Baoding maternal and Child Health Hospital from December 2022 to September 2023 were included as the observation group, while 85 healthy pregnant women without complications or comorbidities who underwent routine antenatal examinations at our hospital were randomly enrolled as the control group. Analyzed the screening value of these six thrombotic markers in pregnant women at risk of HCS. Results: The levels of TAT, PIC, TM, FDP, and D-D in the observation group were significantly higher than in the control group ( P < 0.05 respectively). Pearson correlation analysis showed a weak correlation between maternal age and TAT levels ( r = - 0.179 P < 0.05 ) as well as between BMI and FDP and D-D ( r = 0.214, 0.232 P < 0.05 respectively). Binary logistic regression analysis revealed that abnormal D-D levels were a risk factor for HCS in pregnant women (OR = 0.117, 95% CI: 0.621-0.639, P < 0.05 ) . The area under the joint curve was 0.757, indicating that the model is of certain predictive value for HCS in pregnant women. Conclusion: TAT, PIC, TM, t-PAI-C, D-D, and FDP can used for the screening of HCS in pregnant women and have a certain predictive value for high-risk pregnant women. [ABSTRACT FROM AUTHOR]

Ischemic stroke is responsible for significant morbidity and mortality in the United States and worldwide. Stroke treatment optimization requires emergency medical personnel to make rapid triage decisions concerning destination hospitals that may differ in their ability to provide highly time-sensitive pharmaceutical and surgical interventions. These decisions are particularly crucial in rural areas, where transport decisions can have a large impact on treatment times – often involving a trade-off between delay in pharmaceutical therapy or a delay in endovascular thrombectomy. In this work, we explore a Bayesian modeling framework to address this decision-making process, showing how these techniques may be used to fully account for diagnostic and therapeutic uncertainty. We demonstrate how these techniques can contextualize triage decision at a fine-grained spatial scale. We further show the application of this modeling approach in the US State of Iowa, using data from the Virtual International Stroke Trials Archive (VISTA), and describe potential next steps for improved triage. ABBREVIATION LVO: large vessel occlusion; non-LVO, non-large vessel occlusion; IVT: intravenous tissue plasminogen activator; EVT: endovascular thrombectomy; CSC: comprehensive stroke centers; PSC: primary stroke centers; DS: drip and ship; MS, mothership; EMS: Emergency Medical Service; BGLM: Bayesian Generalized Linear Model; BGAM: Bayesian Generalized Additive Model; BART: Bayesian Additive Regression Trees; VISTA: Virtual International Stroke Trials Archive; NIHSS: National Institute of Health Stroke Severity Scale; ASPECTS: Alberta Stroke Programme Early CT Score; mRS, modified Rankin score; ROCAUC: Area under the receiver operating characteristic curve; ELPD: Expected Log pointwise Predictive Density; SE: Standard Error; ICA: Internal Carotid Artery; M1: Middle Cerebral Artery segment 1; M2: Middle Cerebral Artery segment 2; TIA: Transient Ischemic Attack; Cr-I: Credible Intervals; LKW: Last Known Well [ABSTRACT FROM AUTHOR]

Background: Efforts to improve rural stroke care have intensified in China. However, high-quality comprehensive data on the differences in care and outcomes between rural and urban hospitals are limited. Methods: We analyzed data on patients with acute ischemic stroke hospitalized in the China Stroke Center Alliance hospitals from 2015 to 2022. The in-hospital management measures assessed included nine acute and five discharge management measures. Outcomes evaluated included death or discharge against medical advice (DAMA), major adverse cardiovascular events (MACE), disability at discharge, and in-hospital complications. Results: We enrolled 1,583,271 patients with acute ischemic stroke from 1930 hospitals, comprising 1086 (56.3%) rural sites with 735,452 patients and 844 (43.7%) urban sites with 847,891 patients. Patients in rural hospitals demonstrate suboptimal management measures compared to those in urban hospitals, including lower rates of intravenous recombinant tissue plasminogen activator within 4.5 h (26.0% vs 28.3%; difference: –2.3% (–2.5% to −2.0%)), endovascular treatment (0.6% vs 1.9%; difference: –1.3% (–1.3% to −1.2%)), vessel assessment (88.5% vs 92.0%; difference: –3.5% (95% confidence interval (CI): –3.6% to −3.4%)), and anticoagulants for atrial fibrillation at discharge (42.9% vs 47.7%; difference: –4.8% (95% CI: –5.4% to −4.2%)). Overall, the rural-urban disparity in in-hospital outcomes was small. Rural patients had a slightly higher rate of in-hospital death/DAMA (9.0% vs 8.0%; adjusted odds ratio (OR): 1.22 (95% CI: 1.20–1.23); adjusted risk difference (aRD): 1.3% (95% CI: 1.2%–1.4%)) and a slightly lower rate of complications (10.9% vs 13.0%; aOR: 0.83 (95% CI: 0.82–0.84); aRD: –1.3% (95% CI: –1.3% to –1.3%)). No notable rural-urban differences were observed in MACE and disability at discharge. Conclusion: Patients in rural hospitals demonstrated suboptimal management measures and had higher rates of in-hospital death/DAMA compared to those in urban hospitals. Prioritizing the allocation of health resources to rural hospitals is essential to improve healthcare quality and outcomes. Data access statement: The data supporting the findings of this study are available from the corresponding author upon reasonable request. [ABSTRACT FROM AUTHOR]

Introduction: In the last decades, the recombinant tissue plasminogen activator alteplase has been the standard fibrinolytic treatment of acute myocardial infarction, pulmonary embolism, and acute ischemic stroke. An optimized version of alteplase, tenecteplase, has been developed by exchanging six amino acids to increase half-life, achieve higher fibrin selectivity and increase resistance to plasminogen activator inhibitor-1. Meanwhile, several products containing tenecteplase exist. The aim of this study was to compare the fibrinolytic activity and overall product quality of the 25 mg/vial presentation of tenecteplase originator Metalyse® (Boehringer Ingelheim Pharma GmbH and Co., KG, Ingelheim, Germany) to the 16 mg/vial formulation of the tenecteplase copy Mingfule® (CSPC Recomgen Pharmaceutical, Guangzhou, Co., Ltd.). Methods: We have systematically analyzed and evaluated the biochemical and fibrinolytic differences between Metalyse® and Mingfule® using a wide range of routine quality testing assays, supplemented by mass spectrometry analysis and surface plasmon resonance assays. Additional host cell protein quantification and clot lysis testing following plasmin incubation over time were performed. Results: Several key differences in biochemical composition and clot lysis activity were observed between the two tenecteplase variants. Versus Metalyse®, Mingfule® exhibited lower clot lysis activity and contained less of the two-chain form of tenecteplase. In addition, there were differences in sialic acid content, galactosylation, and fucosylation patterns, with Mingfule® exhibiting more bi- and less tri- and tetra-antennary glycosylation, leading to a different charge and size heterogeneity profile. Furthermore, Mingfule® displayed highly dissimilar binding to the three clearance receptors (LRP-1, ASGR, and mannose receptor) compared with Metalyse®. Purity analysis showed that Mingfule® contained a lower monomer content and, in contrast to Metalyse®, substantial amounts of host cell protein. Discussion: Taken together, these data demonstrate that the tenecteplase copy Mingfule® has several meaningful fibrinolytic and biochemical differences compared with Metalyse®. This raises the question of whether data from clinical studies with one of the products can be generalized for all tenecteplase variants. [ABSTRACT FROM AUTHOR]

Objective: Our study successfully developed an assay kit for thrombin-antithrombin complex (TAT) and demonstrated the predictive value of plasma TAT concentration in the development of venous thromboembolism (VTE) in patients with cervical cancer. Method: A retrospective analysis was conducted on 177 patients with cervical cancer who received treatment at the Affiliated Hospital of Jiangnan University in Wuxi City from July 1, 2023 to October 1, 2023. This study provides a comprehensive analysis of cervical cancer patients and their VTE risk factors. The patients were divided into two groups: 27 cases with VTE (Thrombosis group) and 150 cases without VTE (Non-thrombotic group). Additionally, the patients were classified into four stages based on tumor stage: 42 cases of stage I, 45 cases of stage II, 62 cases of stage III, and 28 cases of stage IV. The control group consisted of 80 healthy patients undergoing medical check-ups. Thrombin-antithrombin complex (TAT), fibrinolytic enzyme-α2-fibrinolytic inhibitor complex (PIC), thrombomodulin (TM), and tissue-type plasminogen activator inhibitor 1 complex (t-PAIC) were detected using quantitative chemiluminescence immunoassay. The study assessed the variations in thrombotic marker levels among cervical cancer patients of different stages through a receiver operating characteristic (ROC) curve. Result: The TAT reagent demonstrated a detection limit of 0.048 ng/mL, with a linear R value of 0.9997, indicating high accuracy and precision. The reagent's accelerated stability was also excellent, with deviations of less than 10%. Furthermore, the correlation coefficient of this method with Hyson Mecon was R2 = 0.9683. Notably, in patients with cervical cancer, TAT and PIC levels were found to be elevated compared to those of the healthy population. Cervical cancer patients who developed thrombosis had significantly elevated levels of TAT and fibrinogen degradation products (FDP) compared to those who did not. Furthermore, patients with stage III-IV cervical cancer exhibited higher levels of the six markers than those with stage I-II during staging. Notably, the combination of four or six markers significantly improved the sensitivity and specificity of the diagnosis, as demonstrated by the ROC curves. Conclusion: Our developed TAT test kit has excellent performance and low cost, making it a clinically valuable tool for widespread use. Elevated TAT levels have significant predictive value for thrombosis occurrence in cervical cancer patients. The combination of t-PAIC, TM, TAT, PIC, D-dimer(D-D), and FDP markers is superior to using a single marker for diagnosing VTE in patients with malignant tumors. Screening cervical cancer patients for the six markers is essential to aid in active prophylaxis, determine optimal treatment timing, and implement nursing interventions to improve prognosis, reduce venous thrombosis incidence and mortality, and prolong survival time. [ABSTRACT FROM AUTHOR]

Neurological diseases have consistently represented a significant challenge in both clinical treatment and scientific research. As research has progressed, the significance of mitochondria in the pathogenesis and progression of neurological diseases has become increasingly prominent. Mitochondria serve not only as a source of energy, but also as regulators of cellular growth and death. Both oxidative stress and mitophagy are intimately associated with mitochondria, and there is mounting evidence that mitophagy and oxidative stress exert a pivotal regulatory influence on the pathogenesis of neurological diseases. In recent years, there has been a notable rise in the prevalence of cerebral ischemia/reperfusion injury (CI/RI), vascular dementia (VaD), and Alzheimer's disease (AD), which collectively represent a significant public health concern. Reduced levels of mitophagy have been observed in CI/RI, VaD and AD. The improvement of associated pathology has been demonstrated through the increase of mitophagy levels. CI/RI results in cerebral tissue ischemia and hypoxia, which causes oxidative stress, disruption of the blood–brain barrier (BBB) and damage to the cerebral vasculature. The BBB disruption and cerebral vascular injury may induce or exacerbate VaD to some extent. In addition, inadequate cerebral perfusion due to vascular injury or altered function may exacerbate the accumulation of amyloid β (Aβ) thereby contributing to or exacerbating AD pathology. Intravenous tissue plasminogen activator (tPA; alteplase) and endovascular thrombectomy are effective treatments for stroke. However, there is a narrow window of opportunity for the administration of tPA and thrombectomy, which results in a markedly elevated incidence of disability among patients with CI/RI. It is regrettable that there are currently no there are still no specific drugs for VaD and AD. Despite the availability of the U.S. Food and Drug Administration (FDA)-approved clinical first-line drugs for AD, including memantine, donepezil hydrochloride, and galantamine, these agents do not fundamentally block the pathological process of AD. In this paper, we undertake a review of the mechanisms of mitophagy and oxidative stress in neurological disorders, a summary of the clinical trials conducted in recent years, and a proposal for a new strategy for targeted treatment of neurological disorders based on both mitophagy and oxidative stress. [ABSTRACT FROM AUTHOR]

OBJECTIVE To determine the causes, time to resolution, effect of therapeutics, and ocular sequelae of hyphema, fibrin, and/or vitreal hemorrhage in horses. ANIMALS 225 horses (219 eyes) who were diagnosed with hyphema, fibrin, and/or vitreal hemorrhage. METHODS Records were retrospectively reviewed for the horses. Signalment, ophthalmic examination findings, causes, treatments, and outcomes were evaluated. RESULTS Common causes of intraocular fibrin or hemorrhage were equine recurrent uveitis (42/219 horses), corneal stromal abscess (32/219 horses), corneal stromal ulcer (25/219 horses), and trauma (21/219 horses). Eyes with fibrin that were treated with intracameral tissue plasminogen activator (TPA; n = 18 eyes) had significantly lower days to resolution (8.9 + 12.6 days) compared to eyes not treated with TPA (28.3 + 46.7 days). Ocular sequelae in horses with fibrin, such as cataracts (18/120 eyes), synechiae (11/120 eyes), and vision loss (17/120 eyes), were significantly less common in eyes treated with TPA. Sequelae in eyes with hyphema included cataracts (9/36 eyes), synechiae (6/36 eyes), and vision loss (5/36 eyes). Although 41 horses had an enucleation at presentation because of severe disease, 14/144 (< 10%) of horses with follow-up required an enucleation. CLINICAL RELEVANCE The presence of blood products in the eyes of horses suggests severe ocular disease, but if the eye is not enucleated at presentation, the prognosis is good for maintaining the eye. Also, the use of intracameral TPA in horses with anterior chamber fibrin but not those with hyphema, results in less adverse ocular sequelae. [ABSTRACT FROM AUTHOR]

Neuroprotective drugs as adjunctive therapy for adults with acute ischemic stroke (AIS) remains contentious. This study summarizes the latest evidence regarding the benefits of neuroprotective agents combined with intravenous recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis. This study conducted a structured search of PubMed, the Cochrane Library, EMBASE, Wanfang Data, and CNKI databases from their inception to March 2024. Grey literature was also searched. The outcomes included efficacy (National Institutes of Health Stroke Scale (NIHSS) score and Barthel Index (BI) score) and safety (rate of adverse reactions). A total of 70 randomized controlled trials were selected for this network meta-analysis (NMA), encompassing 4,140 patients with AIS treated using different neuroprotective agents plus RT-PA, while 4,012 patients with AIS were in control groups. The top three treatments for NIHSS scores at the 2-week follow-up were Edaravone Dexborneo with 0.9 mg/kg rt-PA, Edaravone with 0.9 mg/kg rt-PA, and HUK with 0.9 mg/kg rt-PA. HUK with 0.9 mg/kg rt-PA, Dl-3n-butylphthalide with 0.9 mg/kg rt-PA, and Edaravone Dexborneo with 0.9 mg/kg rt-PA were ranked the top three for BI scores at the 2-week follow-up. The top three treatments with the lowest adverse effect rates were 0.6 mg/kg rt-PA, HUK with 0.9 mg/kg rt-PA, and Edaravone Dexborneo with 0.9 mg/kg rt-PA due to their excellent safety profiles. Compared to rt-PA alone, the combination treatments of Edaravone+rt-PA, Edaravone Dexborneol+rt-PA, HUK+rt-PA, Dl-3n-butylphthalide+rt-PA, and Ganglioside GM1+rt-PA have shown superior efficacy. This NMA suggest that combination therapies of neuroprotective agents and rt-PA can offer better outcomes for patients with AIS. The results support the potential integration of these combination therapies into standard AIS treatment, aiming for improved patient outcomes and personalized therapeutic approaches. [ABSTRACT FROM AUTHOR]

Objective Methods Results Interpretation Given the high disease and cost burden of ischemic stroke, evaluating the clinical efficacy and cost‐effectiveness of new approaches to prevent and treat ischemic stroke is critical. Effective ischemic stroke management depends on timely administration of thrombolytics after stroke onset. This study evaluates the cost‐effectiveness associated with the use of mobile stroke units (MSUs) to expedite tissue plasminogen activator (tPA) administration, as compared with standard management through emergency medical services (EMS).This study is a prospective, multicenter, alternating‐week, cluster‐controlled trial of MSU versus EMS. One‐year and life‐time cost‐effectiveness analyses, using the incremental cost‐effectiveness ratio (ICER) method, were performed from the perspective of CMS's Medicare. Quality‐adjusted life years (QALYs) estimated using patient‐reported EQ‐5D‐5L data were used as the effectiveness measure. Health care utilizations were converted to costs using average national Medicare reimbursements. ICERs excluding patients with pre‐existing disability, and limited to stroke‐related costs were also calculated.The first‐year ICER for all tPA‐eligible patients using total cost differences between MSU and EMS groups was $238,873/QALY; for patients without pre‐existing disability was $61,199/QALY. The lifetime ICERs for all tPA‐eligible patients and for those without pre‐existing disability were $94,710 and $31,259/QALY, respectively. All ICERs were lower when restricted to stroke‐related costs and were highly dependent on the number of patients treated per year in an MSU.MSUs' cost‐effectiveness is borderline if we consider total first‐year costs and outcomes in all tPA‐eligible patients. MSUs are cost‐effective to highly cost‐effective when calculations are based on patients without pre‐existing disability, patients' lifetime horizon, stroke‐related costs, and more patients treated per year in an MSU. ANN NEUROL 2024 [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aim Methods Results Conclusion The efficacy of intravenous alteplase therapy for acute cerebral infarction is well established, regardless of the ischemic stroke subtype. However, its effectiveness in patients with mild cerebral infarction remains controversial, raising concerns about the significance of the treatment.To retrospectively evaluate the efficacy of intravenous alteplase in patients with mild cerebral infarction and other factors affecting the outcome.A total of 527 patients received intravenous alteplase (0.6 mg/kg) at our hospital between October 2012 and March 2023. Of these, 118 patients with mild cerebral infarction (National Institutes of Health Stroke Scale [NIHSS] ≤ 5) who were treated with intravenous alteplase without mechanical thrombectomy were retrospectively evaluated for treatment efficacy and the factors affecting the efficacy.The modified Rankin scale (mRS) outcome at 90 days was good (mRS: 0–1) in 85 (72%) patients and poor (mRS: 2–5) in 33 (28%) patients. Branch atheromatous disease (BAD) and proximal anterior circulation large vessel occlusion (proximal LVO: internal carotid artery and M1 segment of middle cerebral artery) were observed more frequently in the poor outcome group than in the good outcome group. Multivariate analysis, adjusted for age and sex, identified BAD and proximal LVO as factors associated with poor outcomes after intravenous alteplase treatment for mild cerebral infarction. Symptomatic intracranial hemorrhage was observed in one patient with BAD.Most patients with mild cerebral infarction who were treated with intravenous alteplase alone had good outcomes. BAD and proximal LVO were other factors influencing poor outcomes. [ABSTRACT FROM AUTHOR]

Objective: To investigate the risk factors for the recurrence of acute cerebral infarction (ACI) within half a year after treatment with recombinant human TNK tissue-type plasminogen activator (rhTNKtPA) and secondary prevention. Methods: A total of 84 patients with ACI treated with rhTNK-tPA in our hospital from March 2023 to April 2024 were selected for the study. The patients were divided into a recurrence group and a non-recurrence group according to whether they recurred within half a year after treatment. The clinical data of the two groups of patients were compared, and the risk factors of recurrent cerebral infarction were analyzed. The risk prediction model of the nomogram was constructed by incorporating the risk factors and its effectiveness was verified. Model discrimination was assessed by using the receiver operating characteristic curve (ROC). Model fit was evaluated with calibration curves. Hosmer-Lemeshow (HL) analysis was applied to assess model consistency. At the same time, the effect of secondary prevention on the recurrence rate was explored. Results: There were 20 patients with a recurrence of ACI, and the recurrence rate was 23.81%. Multivariate Logistic regression analysis showed that the risk factors of recurrence in patients with ACI included age = 70 years, smoking, hypertension, diabetes, irregular or never using antiplatelet drugs (P<0.05). The prediction model of the nomogram was constructed according to the above indexes. The area under the curve (AUC) of the model's training and test sets for predicting recurrence within six months in patients with acute cerebral infarction was 0.918 (95%CI: 0.848-0.988) and 0.850 (95%CI: 0.703-0.997). At the same time, the HL test showed good goodness of fit (χ2 =1.684, P = 0.989). The calibration curves indicated good agreement between the predicted values of the nomograms and the actual observed values. The recurrence rate of ACI patients who took secondary prevention measures was lower than that of patients who did not take corresponding measures (P<0.05). Conclusions: Patients with ACI have a high recurrence rate within half a year. Age =70 years, smoking, hypertension, diabetes, irregular or never use of antiplatelet drugs are risk factors for recurrence. The prediction model of nomogram combined with 5 indicators can be used as an accurate and rapid clinical evaluation tool. The recurrence rate can be reduced by taking corresponding secondary prevention interventions for patients. [ABSTRACT FROM AUTHOR]