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Keywords = rt-PA thrombolysis

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18 pages, 1406 KiB  
Systematic Review
Treatment Strategies and Prognostic Outcomes in Acute Limb Ischemia: A Systematic Review and Meta-Analysis Comparing Thrombolytic Therapy and Open Surgical Interventions
by Mircea Cătălin Coșarcă, Nicolae Alexandru Lazăr, Suzana Vasilica Șincaru, Bogdan Corneliu Bandici, Eduard Costin Argatu, Cosmin Carașca, Ráduly Gergő, Dorin Constantin Dorobanțu, Cristian Trâmbițaș and Adrian Vasile Mureșan
Medicina 2025, 61(5), 828; https://doi.org/10.3390/medicina61050828 - 30 Apr 2025
Viewed by 1110
Abstract
Background and Objectives: Acute limb ischemia (ALI) is a life-threatening vascular emergency that requires immediate intervention to restore perfusion and prevent limb loss or mortality. Management strategies primarily include thrombolysis and surgical revascularization, each with distinct risks and benefits. This review evaluates [...] Read more.
Background and Objectives: Acute limb ischemia (ALI) is a life-threatening vascular emergency that requires immediate intervention to restore perfusion and prevent limb loss or mortality. Management strategies primarily include thrombolysis and surgical revascularization, each with distinct risks and benefits. This review evaluates and compares the outcomes of thrombolysis and surgical revascularization in ALI management, emphasizing their efficacy, safety, and patient selection criteria. Materials and Methods: A systematic review was conducted in adherence to PRISMA guidelines, analyzing data from 15 studies, including randomized controlled trials and large retrospective analyses, encompassing over 3500 patients with varying demographics and clinical presentations. Study quality was assessed using the Cochrane risk of bias tool and the Newcastle–Ottawa Scale. Results: Thrombolysis, utilizing agents such as urokinase or recombinant tissue plasminogen activator (rt-PA), demonstrated limb salvage rates up to 90% in acute cases, with 30-day mortality rates of 4–6%. It was particularly effective in patients with embolic occlusions or short symptom durations. However, bleeding complications associated with thrombolysis were reported in up to 47% of cases. Conversely, surgical revascularization remains crucial for those with advanced ischemia or contraindications to thrombolysis, offering reliable perfusion restoration but with higher perioperative morbidity, especially in older patients with significant comorbidities. Recent advancements, including hybrid approaches combining catheter-directed thrombolysis with percutaneous mechanical thrombectomy, have shown promise in improving outcomes by reducing procedure times and enhancing clot resolution. Conclusions: While thrombolysis and surgical revascularization are effective, optimizing patient selection remains a key challenge. Future research should focus on refining treatment algorithms, investigating novel thrombolytic agents, and expanding the role of minimally invasive techniques to improve long-term outcomes while mitigating complications such as bleeding and reperfusion injuries. Full article
(This article belongs to the Section Surgery)
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16 pages, 3484 KiB  
Article
Risk Factors and Outcomes of Hemorrhagic Transformation in Acute Ischemic Stroke Following Thrombolysis: Analysis of a Single-Center Experience and Review of the Literature
by Ileana Neacă, Cristina Elena Negroiu, Iulia Tudorașcu, Raluca Dănoiu, Cristiana Gianina Moise, Despina Manuela Toader and Suzana Dănoiu
Medicina 2025, 61(4), 722; https://doi.org/10.3390/medicina61040722 - 14 Apr 2025
Cited by 2 | Viewed by 1477
Abstract
Background and Objectives: This is a retrospective study conducted at the Clinical County Hospital of Craiova, Romania, providing valuable insights into hemorrhagic transformation (HT) in thrombolyzed patients with acute ischemic stroke (AIS). Hemorrhagic complications remain a significant concern after intravenous thrombolysis with [...] Read more.
Background and Objectives: This is a retrospective study conducted at the Clinical County Hospital of Craiova, Romania, providing valuable insights into hemorrhagic transformation (HT) in thrombolyzed patients with acute ischemic stroke (AIS). Hemorrhagic complications remain a significant concern after intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA). This study aims to analyze clinical and biological factors associated with HT following thrombolysis. Materials and Methods: A retrospective analysis was conducted on 356 patients who received rt-PA at the Clinical County Hospital of Craiova between January 2020 and December 2024. Patients were divided into three groups based on CT findings at 24 h post-thrombolysis: no HT, minimal HT, and massive HT. Baseline characteristics were analyzed, including demographics, medical history, NIHSS scores, imaging findings, and laboratory parameters. Statistical analysis was performed using ANOVA and chi-square tests, with a significance threshold of p < 0.05. Results: HT occurred in 12.08% of patients (minimal HT: 8.15%, massive HT: 3.93%). Mortality was significantly higher in the massive HT group (71.43%) compared to minimal HT (41.38%) and non-HT (13.42%) (p < 0.001). Lower platelet count (p = 0.003), elevated blood glucose (p = 0.004), prolonged QT interval (p = 0.004), and reduced fibrinogen levels (p = 0.005) were significantly associated with HT. Other risk factors included atrial fibrillation (p = 0.001), hypertension (p = 0.005), delayed door-to-needle time (p < 0.001), diabetes mellitus (p = 0.007), dense ACM sign on CT (p = 0.003), older age (p < 0.001), obesity (p = 0.001), early neurological deterioration at 2 h/24 h (p < 0.001), elevated GOT (p < 0.001), elevated GPT (p = 0.002), lower LDL cholesterol (p < 0.001), lower total cholesterol (p = 0.001), and lower triglycerides (p < 0.001). Conclusions: Patients with HT had worse clinical outcomes, with massive HT associated with the highest mortality. Risk factors include age, nutritional status, hyperglycemia, and low platelet and fibrinogen levels, among others. Full article
(This article belongs to the Section Neurology)
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20 pages, 4176 KiB  
Systematic Review
Nanoparticles for Thrombolytic Therapy in Ischemic Stroke: A Systematic Review and Meta-Analysis of Preclinical Studies
by Jesús Prego-Domínguez, Fernando Laso-García, Nuria Palomar-Alonso, María Pérez-Mato, Esteban López-Arias, Antonio Dopico-López, Pablo Hervella, María Gutiérrez-Fernández, María Alonso de Leciñana, Ester Polo, Beatriz Pelaz, Pablo del Pino, Francisco Campos and Clara Correa-Paz
Pharmaceutics 2025, 17(2), 208; https://doi.org/10.3390/pharmaceutics17020208 - 6 Feb 2025
Viewed by 2489
Abstract
Background: Recombinant tissue plasminogen activator (rtPA) remains the standard thrombolytic treatment for ischemic stroke. Different types of nanoparticles have emerged as promising tools to improve the benefits and decrease the drawbacks of this therapy. Among them, cell membrane-derived (CMD) nanomedicines have gained special [...] Read more.
Background: Recombinant tissue plasminogen activator (rtPA) remains the standard thrombolytic treatment for ischemic stroke. Different types of nanoparticles have emerged as promising tools to improve the benefits and decrease the drawbacks of this therapy. Among them, cell membrane-derived (CMD) nanomedicines have gained special interest due to their capability to increase the half-life of particles in blood, biocompatibility, and thrombus targeting. In order to update and evaluate the efficacy of these nanosystems, we performed a meta-analysis of the selected in vivo preclinical studies. Methods: Preclinical in vivo studies in ischemic stroke models have been identified through a search in the Pubmed database. We included studies of rtPA-nanoparticles, which assessed infarct volume and/or neurological improvement. Nanosystems were compared with free (non-encapsulated) rtPA treatment. Standardized mean differences were computed and pooled to estimate effect sizes for lesion volumes and neurological scores. Subgroup analyses by the risk of bias, type of nanoparticle, and time of administration were also performed. Results: A total of 18 publications were included in the meta-analysis. This was based on defined search inclusion criteria. Our analysis revealed that rtPA-nanoparticles improved both lesion volume and neurological scores compared with the free rtPA treatment. Moreover, CMD nanomedicines showed better evolution of infarct volume compared to the other nanoparticles. Funnel plots of lesion volume exhibited asymmetry and publication bias. Heterogeneity was generally high, and the funnel plot and Egger test showed some evidence of publication bias that did not achieve statistical significance in the trim-and-fill analysis. Conclusions: rtPA-encapsulating nanosystems were shown to decrease infarct volume and improve neurological scales compared to the standard treatment, and CMD nanomedicines had the greatest beneficial effect. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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11 pages, 2643 KiB  
Article
Clinicopathological Observations in Acute Stroke Patients Treated with Intravenous Thrombolysis
by Lilla Hudák, Kitti Bernadett Kovács, Zsuzsa Bagoly, István Szegedi, Viktor Bencs, Linda Lóczi, Rita Orbán-Kálmándi, Henrietta Péter-Pakó, Zsófia Fülesdi, Blanka Busi, Attila Nagy, Beáta Perjési-Kiss, László Oláh and László Csiba
J. Clin. Med. 2024, 13(19), 6012; https://doi.org/10.3390/jcm13196012 - 9 Oct 2024
Viewed by 1539
Abstract
Background: Ischemic stroke is a leading cause of mortality worldwide, and intravenous thrombolysis, while improving functional outcomes, still leaves a significant mortality rate. This study aimed to investigate the clinical and pathological data of thrombolysed stroke patients who subsequently died and underwent [...] Read more.
Background: Ischemic stroke is a leading cause of mortality worldwide, and intravenous thrombolysis, while improving functional outcomes, still leaves a significant mortality rate. This study aimed to investigate the clinical and pathological data of thrombolysed stroke patients who subsequently died and underwent autopsy, focusing on hemorrhagic transformation (HT). Methods: Over a 10-year period, 1426 acute ischemic stroke patients received thrombolysis at our center, with an in-hospital mortality rate of 11.7%. Autopsies were performed on 98 of the 167 deceased patients. Results: HT was found in 47% of these cases, only less than half occurring within a day of thrombolysis. Significant independent predictors of HT included higher lactate dehydrogenase (LD) levels and higher INR values at admission. HT directly caused death in 30% of cases, often through herniation, while other complications (pulmonary embolism, pneumonia) were also common. Conclusions: These findings highlight the importance of postmortem investigations to accurately determine the incidence of HT and contributing factors. Our data indicate that in the vast majority of HT cases, the role of contributing factors other than rt-PA may be important. Of the routinely assessed clinical and laboratory parameters at admission, only LD and INR were found to be independent predictors of HT in the autopsied studied cohort. Full article
(This article belongs to the Special Issue Cerebrovascular Disease: Symptoms, Diagnosis and Current Treatment)
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13 pages, 388 KiB  
Article
Catheter-Directed Thrombolysis in the Management of Thrombotic Peripheral Artery Occlusions—Acute and Mid-Term Clinical Outcomes
by Ulrich Beschorner, Tanja Boehme, Elias Noory, Roaa Bollenbacher, Jonas Salm, Kambis Mashayekhi, Dirk Westermann and Thomas Zeller
J. Clin. Med. 2024, 13(19), 5732; https://doi.org/10.3390/jcm13195732 - 26 Sep 2024
Cited by 2 | Viewed by 1570
Abstract
Objectives: To evaluate the safety and efficacy of catheter-directed thrombolysis (CDT) with the recombinant tissue plasminogen activator (rt-PA) in all patients with symptomatic peripheral artery disease in real world practice. Methods: Consecutive patients treated with CDT between January 2013 and December 2020 [...] Read more.
Objectives: To evaluate the safety and efficacy of catheter-directed thrombolysis (CDT) with the recombinant tissue plasminogen activator (rt-PA) in all patients with symptomatic peripheral artery disease in real world practice. Methods: Consecutive patients treated with CDT between January 2013 and December 2020 were included in this retrospective analysis. The primary endpoint was the rate of serious adverse events (SAEs) until discharge. Secondary endpoints included interventional success, predictors for SAEs, bleeding and reperfusion edema/compartment syndrome, limb salvage, and clinical outcomes including target lesion revascularization rate (TLR). Results: Overall, 1238 patients were treated with CDT. SAEs occurred in 511 (41.3%) of the patients, 314 (25.4%) being bleeding complications. There were 95 cases of reperfusion edema/compartment syndrome. Forty-two patients underwent amputation and 33 patients (2.7%) died. CDT was successful in 1177 cases (95.1%). Multivariate logistic regression analysis identified age, abciximab and alprostadil usage, and lysis duration as predictors for SAEs and the use of abciximab as a predictor of reperfusion edema/compartment syndrome. Predictors for bleeding were age, alprostadil usage, and lysis duration. At 12 and 24 months, the limb salvage rate was 91.6% and 88.8%, and TLR rate was 46% and 57.2%, respectively. Conclusions: CDT is an effective endovascular method for the treatment of thrombotic peripheral artery occlusions but is associated with a high complication rate. For SAEs in general and bleeding specifically, increasing age, alprostadil use, and lysis duration were independent risk factors. Full article
(This article belongs to the Section Vascular Medicine)
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16 pages, 1463 KiB  
Article
Evaluating Thrombolysis Rates and Emergency Department Time Targets in Acute Ischemic Stroke: Need for Personalized Medicine
by Daian Ionel Popa, Florina Buleu, Carmen Williams, Anca Tudor, Dumitru Sutoi, Cosmin Iosif Trebuian, Covasala Constantin Ioan, Dragoș Forțofoiu, Marius Badalica-Petrescu, Ion Petre, Aida Iancu and Ovidiu Alexandru Mederle
J. Pers. Med. 2024, 14(9), 955; https://doi.org/10.3390/jpm14090955 - 9 Sep 2024
Cited by 1 | Viewed by 1478
Abstract
Background and objectives: In the era of personalized medicine, standard protocols regarding the management of acute ischemic stroke (AIS) focus on time targets alone without tailoring the protocol to the specific patient and hospital characteristics to increase IV thrombolysis rates and improve outcomes [...] Read more.
Background and objectives: In the era of personalized medicine, standard protocols regarding the management of acute ischemic stroke (AIS) focus on time targets alone without tailoring the protocol to the specific patient and hospital characteristics to increase IV thrombolysis rates and improve outcomes for these patients by considering organizational differences and patient-related factors that influence adherence to target times at the emergency department level. With this in mind, we evaluate the effect of achieving ED time targets from standard protocol and patient-related risk factors on the intravenous (IV) thrombolysis rate in patients with AIS in the therapeutic window. Materials and Methods: For our research, we enrolled people who arrived at the ED with signs of recent AIS with an onset of less than 4.5 h. Initially, 355 patients were included in the study, but through careful screening, only 258 were considered eligible to participate. Of the final group of 258 patients, only 46 received intravenous thrombolysis treatment. Results: In our study, when we are analyzing ED times in patients admitted with stroke symptoms in the therapeutic window, we found statistically significantly decreased ED times for patients that performed IV thrombolysis compared to patients not performing as follows: a median of 100 min in onset-to-ED door time (p < 0.001), a door-to-physician time (ED doctor) of 4 min (p = 0.009), door-to-blood-samples of 5 min (p = 0.026), a door-to-CT time of 15.5 min (p = 0.009), and door-to-CT results of 37 min (p < 0.001). In addition, patients who received intravenous thrombolysis were found to be significantly older (p < 0.001), with lower height and weight (p < 0.001 for both) and lower Glasgow Coma Scale (GCS) scores (9 ± 4.94 vs. 13.85 ± 2.41, p < 0.001). The logistic regression analysis indicated that the onset-to-ED time (p < 0.001) and the door-to-physician time (p = 0.014) for emergency medicine physicians are significant predictors of the likelihood of administering thrombolysis. By analyzing the impact of comorbidities, we observed that dyslipidemia, chronic arterial hypertension, and diabetes mellitus are significant predictive factors for performing IV thrombolysis (the presence of dyslipidemia and diabetes mellitus are predictive factors for performing IV thrombolysis, while the presence of arterial hypertension is not). Conclusions: The ED time targets that significantly influenced IV thrombolysis in our study were the onset-to-ED door time and the time it takes for the ED doctor to assess the AIS patient (door-to-physician time). The IV thrombolysis rate for these patients was 17.83%, lower than expected despite achieving most ED time targets, with the presence of chronic arterial hypertension as a significant predictive patient-related factor for not performing it. Even though our reported hospital’s thrombolysis rate is favorable compared to international reports, there is always room for improvement. Based on our study results, it is necessary that new protocols to customized standard protocols and ED time targets for increasing IV thrombolysis rate in patients with AIS in the therapeutic window, focusing more on patient-related factors and type of hospitals, granting personalized medicine its right. Based on our study results, it is necessary that new protocols customize standard protocols and ED time targets for increasing IV thrombolysis rate in patients with AIS in the therapeutic window, focusing more on patient-related factors and type of hospitals, granting personalized medicine its right. Full article
(This article belongs to the Special Issue Emergency and Critical Care in the Context of Personalized Medicine)
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9 pages, 1111 KiB  
Article
Analysis of Safety and Efficacy of the Early Initiation of Antithrombotic Secondary Prevention in Patients Treated with Intravenous Thrombolysis for Acute Ischemic Stroke
by Georgi Krastev, Miroslav Mako, Zuzana Števková, Romana Havranová and Kristína Andrášiková
J. Clin. Med. 2024, 13(9), 2710; https://doi.org/10.3390/jcm13092710 - 5 May 2024
Cited by 1 | Viewed by 1343
Abstract
Background and Objectives: Current guidelines and the alteplase product insert recommend that antithrombotic therapy be avoided within 24 h of intravenous thrombolytic therapy with rt-PA in acute ischemic stroke. Therefore, the rate of stroke recurrence is unclear in terms of early neurological [...] Read more.
Background and Objectives: Current guidelines and the alteplase product insert recommend that antithrombotic therapy be avoided within 24 h of intravenous thrombolytic therapy with rt-PA in acute ischemic stroke. Therefore, the rate of stroke recurrence is unclear in terms of early neurological deterioration, which we could prevent with the early administration of antithrombotic therapy. We do not know the effect of early antithrombotic therapy after intravenous thrombolysis with rt-PA in acute stroke on the outcome in patients after 90 days either. Design: Prospective monocentric observational cohort study. Methods: Data were collected from consecutive patients treated with alteplase for acute ischemic stroke between January 2015 and January 2023. We examined functional outcome at 90 days, including the risk of symptomatic intracranial hemorrhage and mortality rate as safety indicators and stroke recurrence events in both early and standard antithrombotic therapy at 24 h after intravenous thrombolysis. Results: A total of 489 patients were included, of which 278 (56.9%) were men. Of these, 407 (83.2%) patients received early antithrombotic therapy. No symptomatic intracranial hemorrhage occurred in any participants. There was a significantly higher number of patients with an excellent outcome (mRS 0-1) in early antithrombotic treatment (211 (53.1%) versus 28 (34.6%) in standard antithrombotic treatment (p = 0.002, OR 0.47, 95% CI: 0.28–0.76). Conclusions: Early antithrombotic treatment after intravenous therapy in patients with acute ischemic stroke revealed no safety concerns compared with standard antithrombotic therapy and resulted in a significantly higher proportion of patients with an excellent functional outcome. Full article
(This article belongs to the Special Issue Advances in the Diagnosis, Treatment, and Prognosis of Acute Stroke)
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21 pages, 27681 KiB  
Article
Acupuncture Extended the Thrombolysis Window by Suppressing Blood–Brain Barrier Disruption and Regulating Autophagy–Apoptosis Balance after Ischemic Stroke
by Zhihui Zhang, Tianliang Lu, Shanshan Li, Ruyu Zhao, Honglei Li, Xinchang Zhang, Yiyang Li, Yawen Xia and Guangxia Ni
Brain Sci. 2024, 14(4), 399; https://doi.org/10.3390/brainsci14040399 - 19 Apr 2024
Cited by 11 | Viewed by 3036
Abstract
Background: Ischemic stroke (IS) is one of the leading causes of death and disability worldwide. The narrow therapeutic window (within 4.5 h) and severe hemorrhagic potential limits therapeutic efficacy of recombinant tissue type plasminogen activator (rt-PA) intravenous thrombolysis for patients. Xingnao Kaiqiao (XNKQ) [...] Read more.
Background: Ischemic stroke (IS) is one of the leading causes of death and disability worldwide. The narrow therapeutic window (within 4.5 h) and severe hemorrhagic potential limits therapeutic efficacy of recombinant tissue type plasminogen activator (rt-PA) intravenous thrombolysis for patients. Xingnao Kaiqiao (XNKQ) acupuncture is an integral part of traditional Chinese medicine, specifically designed to address acute ischemic stroke by targeting key acupoints such as Shuigou (GV26) and Neiguan (PC6). In this study, we explored the therapeutic potential of XNKQ acupuncture in extending the time window for thrombolysis and interrogated the molecular mechanisms responsible for this effect. Methods: The effect of extending the thrombolysis window by acupuncture was evaluated via TTC staining, neuronal score evaluation, hemorrhagic transformation assay, and H&E staining. RNA sequencing (RNA-seq) technology was performed to identify the therapeutic targets and intervention mechanisms of acupuncture. Evans blue staining and transmission electron microscopy were used to assess blood–brain barrier (BBB) integrity. Immunofluorescence staining and co-immunoprecipitation were performed to evaluate the level of autophagy and apoptosis and validate their interactions with BBB endothelial cells. Results: Acupuncture alleviated infarction and neurological deficits and extended the thrombolysis window to 6 h. The RNA-seq revealed 16 potential therapeutic predictors for acupuncture intervention, which related to suppressing inflammation and restoring the function of BBB and blood vessels. Furthermore, acupuncture suppressed BBB leakage and preserved tight junction protein expression. The protective effect was associated with regulation of the autophagy–apoptosis balance in BBB endothelial cells. Acupuncture intervention dissociated the Beclin1/Bcl-2 complex, thereby promoting autophagy and reducing apoptosis. Conclusion: XNKQ acupuncture could serve as an adjunctive therapy for rt-PA thrombolysis, aiming to extend the therapeutic time window and mitigate ischemia–reperfusion injury. Acupuncture suppressed BBB disruption by regulating the autophagy–apoptosis balance, which in turn extended the therapeutic window of rt-PA in IS. These findings provide a rationale for further exploration of acupuncture as a complementary candidate co-administered with rt-PA. Full article
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15 pages, 1357 KiB  
Article
Emergency Department Time Targets for Interhospital Transfer of Patients with Acute Ischemic Stroke
by Daian Popa, Aida Iancu, Alina Petrica, Florina Buleu, Carmen Gabriela Williams, Dumitru Sutoi, Cosmin Trebuian, Anca Tudor and Ovidiu Alexandru Mederle
J. Pers. Med. 2024, 14(1), 13; https://doi.org/10.3390/jpm14010013 - 21 Dec 2023
Cited by 7 | Viewed by 2327
Abstract
Background and objectives: Although the intravenous tissue plasminogen activator (rt-PA) has been shown to be effective in the treatment of acute ischemic stroke (AIS), only a small proportion of stroke patients receive this drug. The low administration rate is mainly due to [...] Read more.
Background and objectives: Although the intravenous tissue plasminogen activator (rt-PA) has been shown to be effective in the treatment of acute ischemic stroke (AIS), only a small proportion of stroke patients receive this drug. The low administration rate is mainly due to the delayed presentation of patients to the emergency department (ED) or the lack of a stroke team/unit in most of the hospitals. Thus, the aim of this study is to analyze ED time targets and the rate of rt-PA intravenous administration after the initial admission of patients with AIS in an ED from a traditional healthcare center (without a neurologist or stroke team/unit). Methods: To analyze which factors influence the administration of rt-PA, we split the general sample (n = 202) into two groups: group No rt-PA (n = 137) and group rt-PA (n = 65). This is based on the performing or no intravenous thrombolysis. Results: Analyzing ED time targets for all samples, we found that the median onset-to-ED door time was 180 min (IQR, 120–217.5 min), door-to-physician time was 4 min (IQR, 3–7 min), door-to-CT time was 52 min (IQR, 48–55 min), and door-in-door-out time was 61 min (IQR, 59–65 min). ED time targets such as door-to-physician time (p = 0.245), door-to-CT time (p = 0.219), door-in-door-out time (p = 0.24), NIHSS at admission to the Neurology department (p = 0.405), or NIHSS after 24 h (p = 0.9) did not have a statistically significant effect on the administration or no rt-PA treatment in patients included in our study. Only the highest door-to-CT time was statistically significantly correlated with the death outcome. Conclusion: In our study, the iv rt-PA administration rate was 32.18%. A statistically significant correlation between the highest door-to-CT time and death outcome was found. Full article
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7 pages, 5008 KiB  
Case Report
Microcatheter-Directed Thrombolysis Using Recombinant Tissue Plasminogen Activator for the Treatment of Acute Superior Mesenteric Artery Embolism: A Case Report
by Yang-Won Kim, Ho-Cheol Choi, Won-Jeong Yang, Byeong-Ju Koo, Jae-Kyeong Ahn, Jeong-Pyo Lee, Jae-Bum Na, Sa-Hong Jo, Sung-Eun Park and Jung-Ho Won
Medicina 2023, 59(11), 1889; https://doi.org/10.3390/medicina59111889 - 24 Oct 2023
Cited by 2 | Viewed by 1670
Abstract
Background: Acute mesenteric ischemia (AMI) is a life-threatening condition, and in 50% of patients, AMI is caused by acute superior mesenteric artery (SMA) embolism. Endovascular treatment is increasingly being considered the primary modality in selected cases. Many studies have reported that percutaneous [...] Read more.
Background: Acute mesenteric ischemia (AMI) is a life-threatening condition, and in 50% of patients, AMI is caused by acute superior mesenteric artery (SMA) embolism. Endovascular treatment is increasingly being considered the primary modality in selected cases. Many studies have reported that percutaneous aspiration embolectomy using a guiding catheter and thrombolysis with recombinant tissue plasminogen activator (rtPA) are effective in treating SMA embolism. However, no reports on treating SMA embolism using rtPA administered via a microcatheter exist. Case presentation: A 64-year-old man with underlying atrial fibrillation presented with acute SMA embolism revealed using computed tomography (CT). rtPA (total 3 mg) was carefully administered into the occluded SMA through a microcatheter. No complications occurred, and complete revascularization of the SMA was revealed on follow-up CT. Conclusions: Compared with previous reports, this case report reveals that successful revascularization can be achieved using rtPA administered via a microcatheter, with a low dose of rtPA and a short duration of thrombolysis. Full article
(This article belongs to the Section Gastroenterology & Hepatology)
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17 pages, 1538 KiB  
Article
Nebulized Recombinant Tissue Plasminogen Activator (rt-PA) for Acute COVID-19-Induced Respiratory Failure: An Exploratory Proof-of-Concept Trial
by Pratima Chowdary, Banwari Agarwal, Maria Rita Peralta, Sanjay Bhagani, Simon Lee, James Goldring, Marc Lipman, Emal Waqif, Mark Phillips, Helen Philippou, Jonathan H. Foley, Nicola J. Mutch, Robert A. S. Ariëns, Kathleen A. Stringer, Federico Ricciardi, Marie Watissée, Derralynn Hughes, Amit Nathwani, Anne Riddell, David Patch, Jim Buckley, Mark De Neef, Rahul Dimber, Cecilia Diaz-Garcia, Honey Patel, Aarti Nandani, Upuli Dissanayake, Nick Chadwick, Ahmed A. A. M. M. Alkhatip, Peter Watkinson, Eamon Raith, Suveer Singh, Tony Wolff, Rajeev Jha, Simon E. Brill, Ameet Bakhai, Alison Evans, Farhat Gilani and Keith Gomezadd Show full author list remove Hide full author list
J. Clin. Med. 2023, 12(18), 5848; https://doi.org/10.3390/jcm12185848 - 8 Sep 2023
Cited by 1 | Viewed by 2380
Abstract
Acute lung injury in COVID-19 results in diffuse alveolar damage with disruption of the alveolar-capillary barrier, coagulation activation, alveolar fibrin deposition and pulmonary capillary thrombi. Nebulized recombinant tissue plasminogen activator (rt-PA) has the potential to facilitate localized thrombolysis in the alveolar compartment and [...] Read more.
Acute lung injury in COVID-19 results in diffuse alveolar damage with disruption of the alveolar-capillary barrier, coagulation activation, alveolar fibrin deposition and pulmonary capillary thrombi. Nebulized recombinant tissue plasminogen activator (rt-PA) has the potential to facilitate localized thrombolysis in the alveolar compartment and improve oxygenation. In this proof-of-concept safety study, adults with COVID-19-induced respiratory failure and a <300 mmHg PaO2/FiO2 (P/F) ratio requiring invasive mechanical ventilation (IMV) or non-invasive respiratory support (NIRS) received nebulized rt-PA in two cohorts (C1 and C2), alongside standard of care, between 23 April–30 July 2020 and 21 January–19 February 2021, respectively. Matched historical controls (MHC; n = 18) were used in C1 to explore efficacy. Safety co-primary endpoints were treatment-related bleeds and <1.0–1.5 g/L fibrinogen reduction. A variable dosing strategy with clinical efficacy endpoint and minimal safety concerns was determined in C1 for use in C2; patients were stratified by ventilation type to receive 40–60 mg rt-PA daily for ≤14 days. Nine patients in C1 (IMV, 6/9; NIRS, 3/9) and 26 in C2 (IMV, 12/26; NIRS, 14/26) received nebulized rt-PA for a mean (SD) of 6.7 (4.6) and 9.1(4.6) days, respectively. Four bleeds (one severe, three mild) in three patients were considered treatment related. There were no significant fibrinogen reductions. Greater improvements in mean P/F ratio from baseline to study end were observed in C1 compared with MHC (C1; 154 to 299 vs. MHC; 154 to 212). In C2, there was no difference in the baseline P/F ratio of NIRS and IMV patients. However, a larger improvement in the P/F ratio occurred in NIRS patients (NIRS; 126 to 240 vs. IMV; 120 to 188) and fewer treatment days were required (NIRS; 7.86 vs. IMV; 10.5). Nebulized rt-PA appears to be well-tolerated, with a trend towards improved oxygenation, particularly in the NIRS group. Randomized clinical trials are required to demonstrate the clinical effect significance and magnitude. Full article
(This article belongs to the Special Issue Update on Acute Severe Respiratory Infections)
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17 pages, 1925 KiB  
Article
Enhanced Cerebroprotection of Xenon-Loaded Liposomes in Combination with rtPA Thrombolysis for Embolic Ischemic Stroke
by Tao Peng, Keith Booher, Melanie R. Moody, Xing Yin, Jaroslaw Aronowski, David D. McPherson, Sean I. Savitz, Hyunggun Kim and Shao-Ling Huang
Biomolecules 2023, 13(8), 1256; https://doi.org/10.3390/biom13081256 - 16 Aug 2023
Cited by 8 | Viewed by 2183
Abstract
Xenon (Xe) has shown great potential as a stroke treatment due to its exceptional ability to protect brain tissue without inducing side effects. We have previously developed Xe-loaded liposomes for the ultrasound-activated delivery of Xe into the cerebral region and demonstrated their therapeutic [...] Read more.
Xenon (Xe) has shown great potential as a stroke treatment due to its exceptional ability to protect brain tissue without inducing side effects. We have previously developed Xe-loaded liposomes for the ultrasound-activated delivery of Xe into the cerebral region and demonstrated their therapeutic efficacy. At present, the sole FDA-approved thrombolytic agent for stroke treatment is recombinant tissue plasminogen activator (rtPA). In this study, we aimed to investigate the potential of combining Xe-liposomes with an intravenous rtPA treatment in a clinically relevant embolic rat stroke model. We evaluated the combinational effect using an in vitro clot lysis model and an in vivo embolic middle cerebral artery occlusion (eMCAO) rat model. The treatment groups received intravenous administration of Xe-liposomes (20 mg/kg) at 2 h post-stroke onset, followed by the administration of rtPA (10 mg/kg) at either 2 or 4 h after the onset. Three days after the stroke, behavioral tests were conducted, and brain sections were collected for triphenyltetrazolium chloride (TTC) and TUNEL staining. Infarct size was determined as normalized infarct volume (%). Both in vitro and in vivo clot lysis experiments demonstrated that Xe-liposomes in combination with rtPA resulted in effective clot lysis comparable to the treatment with free rtPA alone. Animals treated with Xe-liposomes in combination with rtPA showed reduced TUNEL-positive cells and demonstrated improved neurological recovery. Importantly, Xe-liposomes in combination with late rtPA treatment reduced rtPA-induced hemorrhage, attributing to the reduction of MMP9 immunoreactivity. This study demonstrates that the combined therapy of Xe-liposomes and rtPA provides enhanced therapeutic efficacy, leading to decreased neuronal cell death and a potential to mitigate hemorrhagic side effects associated with late rtPA treatment. Full article
(This article belongs to the Section Molecular Medicine)
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8 pages, 240 KiB  
Brief Report
Urokinase versus Alteplase in Patients with Intermediate–High-Risk Pulmonary Embolism Treated with Ultrasound-Accelerated Endovascular Thrombolysis
by Hani Al-Terki, Michael Gotzmann, Felix Mahfoud, Lucas Lauder and Andreas Mügge
J. Clin. Med. 2023, 12(12), 4006; https://doi.org/10.3390/jcm12124006 - 12 Jun 2023
Cited by 1 | Viewed by 1641
Abstract
Background. Ultrasound-accelerated thrombolysis (USAT) is a safe and effective treatment for patients with intermediate–high-risk pulmonary embolism (PE). In all studies investigating USAT in the setting of PE, the recombinant tissue-plasminogen activator (rt-PA) alteplase or actilyse was used. Currently, there is a shortage of [...] Read more.
Background. Ultrasound-accelerated thrombolysis (USAT) is a safe and effective treatment for patients with intermediate–high-risk pulmonary embolism (PE). In all studies investigating USAT in the setting of PE, the recombinant tissue-plasminogen activator (rt-PA) alteplase or actilyse was used. Currently, there is a shortage of alteplase (Alteplase, Boehringer Ingelheim) in Europe. It is unknown whether the efficacy of urokinase (UK) is comparable with alteplase for USAT in patients with PE. Methods. Patients with intermediate–high-risk PE undergoing USAT with urokinase and alteplase were included in this study. One-to-one nearest neighbour matching was performed to account for baseline differences. We identified one patient treated with USAT and UK (n = 9) for each patient treated with USAT and alteplase (n = 9). Results. A total of 56 patients underwent USAT. The treatment was successful in all patients. The propensity score matched the identified nine pairs of patients. There were no statistically significant differences in the change in right ventricle-to-left ventricle (RV/LV) ratio (0.4 ± 0.3 versus 0.5 ± 0.4, p = 0.54), systolic pulmonary artery pressure (17.3 ± 8.0 versus 18.1 ± 8.1, p = 0.17), or improvement of RV function (5.8 ± 3.8 versus 5.1 ± 2.6, p = 1.0). The complication rates were comparable (11% in both groups, p = 0.55). There were no deaths in hospital or during 90 days in either group. Conclusions. In this case-matched comparison, the short-term clinical and echocardiographic outcomes showed comparable results between USAT–UK and USAT–rt-PA. Full article
(This article belongs to the Section Cardiovascular Medicine)
15 pages, 2126 KiB  
Article
Early Hemorrhagic Transformation after Reperfusion Therapy in Patients with Acute Ischemic Stroke: Analysis of Risk Factors and Predictors
by Aida Iancu, Florina Buleu, Dana Simona Chita, Adrian Tutelca, Raluca Tudor and Silviu Brad
Brain Sci. 2023, 13(5), 840; https://doi.org/10.3390/brainsci13050840 - 22 May 2023
Cited by 18 | Viewed by 6191
Abstract
Background: The standard reperfusion therapy for acute ischemic stroke (AIS) is considered to be thrombolysis, but its application is limited by the high risk of hemorrhagic transformation (HT). This study aimed to analyze risk factors and predictors of early HT after reperfusion [...] Read more.
Background: The standard reperfusion therapy for acute ischemic stroke (AIS) is considered to be thrombolysis, but its application is limited by the high risk of hemorrhagic transformation (HT). This study aimed to analyze risk factors and predictors of early HT after reperfusion therapy (intravenous thrombolysis or mechanical thrombectomy). Material and methods: Patients with acute ischemic stroke who developed HT in the first 24 h after receiving rtPA thrombolysis or performing mechanical thrombectomy were retrospectively reviewed. They were divided into two groups, respectively, the early-HT group and the without-early-HT group based on cranial computed tomography performed at 24 h, regardless of the type of hemorrhagic transformation. Results: A total of 211 consecutive patients were enrolled in this study. Among these patients, 20.37% (n = 43; age: median 70.00 years; 51.2% males) had early HT. Multivariate analysis of independent risk factors associated with early HT found that male gender increased the risk by 2.7-fold, the presence of baseline high blood pressure by 2.4-fold, and high glycemic values by 1.2-fold. Higher values of NIHSS at 24 h increased the risk of hemorrhagic transformation by 1.18-fold, while higher values of ASPECTS at 24 h decreased the risk of hemorrhagic transformation by 0.6-fold. Conclusions: In our study, male gender, baseline high blood pressure, and high glycemic values, along with higher values of NIHSS were associated with the increased risk of early HT. Furthermore, the identification of early-HT predictors is critical in patients with AIS for the clinical outcome after reperfusion therapy. Predictive models to be used in the future to select more careful patients with a low risk of early HT need to be developed in order to minimize the impact of HT associated with reperfusion techniques. Full article
(This article belongs to the Section Neurorehabilitation)
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14 pages, 739 KiB  
Article
Elevated Blood Alcohol Concentration Is Associated with Improved Clinical Outcomes of Intravenous Thrombolysis Treatment in Acute Ischemic Stroke Patients—A Retrospective Study
by Tamás Árokszállási, Eszter Balogh, Rita Orbán-Kálmándi, Máté Pásztor, Anita Árokszállási, Edit Boglárka Nagy, Ivett Belán, Zsolt May, Tünde Csépány, László Csiba, Zsuzsa Bagoly and László Oláh
J. Clin. Med. 2023, 12(6), 2238; https://doi.org/10.3390/jcm12062238 - 14 Mar 2023
Cited by 1 | Viewed by 2551
Abstract
Background: Intravenous thrombolysis (IVT) improves acute ischemic stroke (AIS) outcomes, but with limited success. In addition, ethanol potentiates the effect of r-tPA in ischemia models. Methods: The effect of acute alcohol consumption on IVT outcomes was investigated in a retrospective cohort study. AIS [...] Read more.
Background: Intravenous thrombolysis (IVT) improves acute ischemic stroke (AIS) outcomes, but with limited success. In addition, ethanol potentiates the effect of r-tPA in ischemia models. Methods: The effect of acute alcohol consumption on IVT outcomes was investigated in a retrospective cohort study. AIS patients with detectable blood alcohol concentration (BAC) during IVT were included (alcohol group; n = 60). For each case, 3 control subjects who underwent IVT but denied alcohol consumption were matched in terms of age, sex, affected brain area, and stroke severity. Outcomes were determined using the NIHSS at 7 days and the modified Rankin scale (mRS) at 90 days. Results: Patients were younger and had a less severe stroke than in a standard stroke study. Favorable long-term outcomes (mRS 0–2) occurred significantly more frequently in the alcohol group compared to controls (90% vs. 63%, p < 0.001). However, the rates of hemorrhagic transformation were similar. Multiple logistic regression models identified elevated BAC as a significant protective factor against unfavorable short-term (OR: 0.091, 95% CI: 0.036–0.227, p < 0.001) and long-term outcomes (OR: 0.187, 95% CI: 0.066–0.535, p = 0.002). In patients with BAC > 0.2%, significantly lower NIHSS was observed at 3 and 7 days after IVT vs. in those with 0.01–0.2% ethanol levels. Conclusion: Elevated BAC is associated with improved outcomes in IVT-treated AIS without affecting safety. Full article
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