RESUMEN

Venous thrombosis and pulmonary embolism (venous thromboembolism) are important causes of morbidity and mortality worldwide. In patients with venous thromboembolism, thrombi obstruct blood vessels and resist physiological dissolution (fibrinolysis), which can be life threatening and cause chronic complications. Plasminogen activator therapy, which was developed >50 years ago, is effective in dissolving thrombi but has unacceptable bleeding risks. Safe dissolution of thrombi in patients with venous thromboembolism has been elusive despite multiple innovations in plasminogen activator design and catheter-based therapy. Evidence now suggests that fibrinolysis is rigidly controlled by endogenous fibrinolysis inhibitors, including α2-antiplasmin, plasminogen activator inhibitor-1, and thrombin-activable fibrinolysis inhibitor. Elevated levels of these fibrinolysis inhibitors are associated with an increased risk of venous thromboembolism in humans. New therapeutic paradigms suggest that accelerated and effective fibrinolysis may be achieved safely by therapeutically targeting these fibrinolytic inhibitors in venous thromboembolism. In this article, we discuss the role of fibrinolytic components in venous thromboembolism and the current status of research and development targeting fibrinolysis inhibitors.

Asunto(s)

Fibrinólisis , Fibrinolíticos , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/tratamiento farmacológico , Fibrinólisis/efectos de los fármacos , Fibrinolíticos/uso terapéutico , Fibrinolíticos/efectos adversos , Terapia Trombolítica/métodos , Animales , Inhibidor 1 de Activador Plasminogénico/metabolismo , Inhibidor 1 de Activador Plasminogénico/uso terapéutico

RESUMEN

Catheter-based interventions and surgical embolectomy represent alternatives to systemic fibrinolysis for patients with high-risk pulmonary embolism (PE) or those with intermediate-high-risk PE who deteriorate hemodynamically. They are indicated when systemic fibrinolysis is contraindicated or ineffective, or if obstructive shock is imminent. Extracorporeal membrane oxygenation can be added to reperfusion therapies or used alone for severe right ventricular dysfunction and cardiogenic shock. These advanced therapies complement but do not replace anticoagulation, which remains the cornerstone in PE management. This review summarizes the evidence and shares practical recommendations for the use of anticoagulant therapy before, during, and after acute PE interventions.

Asunto(s)

Anticoagulantes , Embolectomía , Embolia Pulmonar , Humanos , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Enfermedad Aguda , Embolectomía/métodos , Oxigenación por Membrana Extracorpórea/métodos , Terapia Trombolítica/métodos

RESUMEN

BACKGROUND: Intravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear. METHODS: We conducted a phase 3, three-group, adaptive, single-blind, randomized, controlled clinical trial at 57 sites in the United States. Patients with acute ischemic stroke who had received intravenous thrombolysis within 3 hours after symptom onset were assigned to receive intravenous argatroban, eptifibatide, or placebo within 75 minutes after the initiation of thrombolysis. The primary efficacy outcome, the utility-weighted 90-day modified Rankin scale score (range, 0 to 10, with higher scores reflecting better outcomes), was assessed by means of centralized adjudication. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after randomization. RESULTS: A total of 514 patients were assigned to receive argatroban (59 patients), eptifibatide (227 patients), or placebo (228 patients). All the patients received intravenous thrombolysis (70% received alteplase, and 30% received tenecteplase), and 225 patients (44%) underwent endovascular thrombectomy. At 90 days, the mean (±SD) utility-weighted modified Rankin scale scores were 5.2±3.7 with argatroban, 6.3±3.2 with eptifibatide, and 6.8±3.0 with placebo. The posterior probability that argatroban was better than placebo was 0.002 (posterior mean difference in utility-weighted modified Rankin scale score, -1.51±0.51) and that eptifibatide was better than placebo was 0.041 (posterior mean difference, -0.50±0.29). The incidence of symptomatic intracranial hemorrhage was similar in the three groups (4% with argatroban, 3% with eptifibatide, and 2% with placebo). Mortality at 90 days was higher in the argatroban group (24%) and the eptifibatide group (12%) than in the placebo group (8%). CONCLUSIONS: In patients with acute ischemic stroke treated with intravenous thrombolysis within 3 hours after symptom onset, adjunctive treatment with intravenous argatroban or eptifibatide did not reduce poststroke disability and was associated with increased mortality. (Funded by the National Institute of Neurological Disorders and Stroke; MOST ClinicalTrials.gov number, NCT03735979.).

Asunto(s)

Eptifibatida , Hemorragias Intracraneales , Accidente Cerebrovascular Isquémico , Péptidos , Ácidos Pipecólicos , Sulfonamidas , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arginina/administración & dosificación , Arginina/efectos adversos , Arginina/análogos & derivados , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Eptifibatida/administración & dosificación , Eptifibatida/efectos adversos , Fibrinolíticos/administración & dosificación , Fibrinolíticos/efectos adversos , Infusiones Intravenosas , Hemorragias Intracraneales/inducido químicamente , Hemorragias Intracraneales/epidemiología , Accidente Cerebrovascular Isquémico/mortalidad , Accidente Cerebrovascular Isquémico/terapia , Péptidos/administración & dosificación , Péptidos/efectos adversos , Péptidos/uso terapéutico , Ácidos Pipecólicos/administración & dosificación , Ácidos Pipecólicos/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Método Simple Ciego , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Terapia Trombolítica/efectos adversos , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Trombectomía/efectos adversos , Trombectomía/métodos , Resultado del Tratamiento , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Incidencia , Adulto

RESUMEN

BACKGROUND: Coronary artery thrombosis and myocardial ischemia caused by giant coronary aneurysms are the main causes of death in children with Kawasaki disease. The use of thrombolytic therapy in children with Kawasaki disease who have coronary thrombosis is a controversial topic, especially with respect to the timing of treatment. CASE PRESENTATION: In this article, we report a case of a child aged two years and nine months with Kawasaki disease whose coronary arteries had no involvement in the acute phase. However, by only one week after discharge, the patient returned because we found giant coronary aneurysms complicated by thrombosis via echocardiography. Despite aggressive thrombolytic therapy, the child developed myocardial ischemia during thrombolytic therapy. Fortunately, because of timely treatment, the child's thrombus has dissolved, and the myocardial ischemia has resolved. CONCLUSIONS: This case suggests that for patients at high risk of coronary artery aneurysms, echocardiography may need to be reviewed earlier. Low-molecular-weight heparin should be added to antagonize the early procoagulant effects of warfarin when warfarin therapy is initiated. In the case of first-detected coronary thrombosis, aggressive thrombolytic therapy may be justified, particularly during the acute and subacute phases of the disease course.

Asunto(s)

Aneurisma Coronario , Trombosis Coronaria , Síndrome Mucocutáneo Linfonodular , Isquemia Miocárdica , Terapia Trombolítica , Humanos , Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome Mucocutáneo Linfonodular/diagnóstico , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Trombosis Coronaria/diagnóstico por imagen , Trombosis Coronaria/etiología , Aneurisma Coronario/diagnóstico por imagen , Aneurisma Coronario/etiología , Resultado del Tratamiento , Preescolar , Isquemia Miocárdica/etiología , Isquemia Miocárdica/tratamiento farmacológico , Isquemia Miocárdica/diagnóstico por imagen , Masculino , Anticoagulantes/uso terapéutico , Fibrinolíticos/uso terapéutico , Angiografía Coronaria

RESUMEN

We present two clinical cases of successful endovascular treatment of proximal deep vein thrombosis following May-Thurner syndrome. In the first case, 2-day regional catheter thrombolysis, percutaneous mechanical thrombectomy and venous stenting were required to restore hemodynamics in the left lower limb. In the second case, regional catheter thrombolysis continued for 3 days with subsequent thrombotic mass lysis. However, iliac vein was severely narrowed that required venous stenting. Long-term results were favorable in both cases. Venous outflow has become almost normal after endovascular treatment. The patients' ability to work has been restored.

Asunto(s)

Procedimientos Endovasculares , Vena Ilíaca , Síndrome de May-Thurner , Stents , Trombectomía , Trombosis de la Vena , Humanos , Síndrome de May-Thurner/complicaciones , Síndrome de May-Thurner/terapia , Síndrome de May-Thurner/diagnóstico , Síndrome de May-Thurner/cirugía , Trombosis de la Vena/etiología , Trombosis de la Vena/terapia , Trombosis de la Vena/cirugía , Trombosis de la Vena/diagnóstico , Procedimientos Endovasculares/métodos , Resultado del Tratamiento , Vena Ilíaca/cirugía , Trombectomía/métodos , Femenino , Masculino , Terapia Trombolítica/métodos , Persona de Mediana Edad , Adulto , Extremidad Inferior/irrigación sanguínea

RESUMEN

BACKGROUND: Pulmonary embolism (PE) is a critical condition requiring effective management strategies. Several options are available, including thrombolytic therapy and anticoagulants. OBJECTIVES: To assess the impact of thrombolytic therapy either combined with anticoagulant (AC) or alone versus AC alone on mortality, recurrence, clinical deterioration, bleeding, and hospital stay. METHOD: This study included 25 previously published studies from 1990 to 2023, with a total of 12 836 participants. Dichotomous and continuous analysis models were used to evaluate outcomes, with heterogeneity and publication bias tests applied. A random model was used for data analysis. Several databases were searched for the identification and inclusion of studies, such as Ovid, PubMed, Cochrane Library, Google Scholar, and Embase. RESULTS: For sub-massive PE, CDT plus AC significantly reduced in-hospital, 30-day, and 12-month mortality compared to AC alone, odds ratio (OR) of -0.99 (95% CI [-1.32 to -0.66]), with increased major bleeding risk but no difference in minor bleeding or hospital stay, OR = 0.46, 95% CI [-0.03 to 0.96]). For acute intermediate PE, systemic thrombolytic therapy did not affect all-cause or in-hospital mortality but increased minor bleeding, reduced recurrent PE, and prevented clinical deterioration. The heterogeneity of different models in the current study varied from 0% to 37.9%. CONCLUSION: The addition of CDT to AC improves mortality outcomes for sub-massive PE but raises the risk of major bleeding. Systemic thrombolytic therapy reduces recurrence and clinical decline in acute intermediate PE despite increasing minor bleeding. Individualized patient assessment is essential for optimizing PE management strategies.

Asunto(s)

Anticoagulantes , Embolia Pulmonar , Terapia Trombolítica , Humanos , Anticoagulantes/uso terapéutico , Fibrinolíticos/uso terapéutico , Fibrinolíticos/efectos adversos , Hemorragia/inducido químicamente , Mortalidad Hospitalaria , Embolia Pulmonar/tratamiento farmacológico , Embolia Pulmonar/mortalidad , Recurrencia , Factores de Riesgo , Terapia Trombolítica/métodos , Terapia Trombolítica/efectos adversos , Resultado del Tratamiento

RESUMEN

Importance: Stroke treatment is exquisitely time sensitive. The door-in-door-out (DIDO) time, defined as the total time spent in the emergency department (ED) at a transferring hospital, is an important quality metric for the care of acute stroke. However, little is known about the contributions of specific process steps to delays and disparities in DIDO time. Objective: To quantify process steps and their association with DIDO times at transferring hospitals among patients with acute ischemic stroke (AIS). Design, Setting, and Participants: This retrospective cohort study analyzed patients in the American Heart Association Get With the Guidelines-Stroke registry with AIS presenting between January 1, 2019, to December 31, 2021, and transferred from the presenting hospital ED to another acute care hospital for evaluation of thrombolytics, endovascular therapy, or postthrombolytic care. Data were analyzed from July 8 to October 13, 2023. Exposures: Intervals of ED care of ischemic stroke: door-to-imaging and imaging-to-door times. Main Outcomes and Measures: The primary outcome was DIDO time. Multivariate generalized estimating equations regression models were performed to compare contributions of interval process times to explain variation in DIDO time, controlling for patient- and hospital-level characteristics. Results: Among 28 887 patients (50.5% male; mean [SD] age, 68.3 [14.8] years; 5.5% Hispanic, 14.7% non-Hispanic Black, and 73.2% non-Hispanic White), mean (SD) DIDO time was 171.4 (149.5) minutes, mean (SD) door-to-imaging time was 18.3 (34.1) minutes, and mean (SD) imaging-to-door time was 153.1 (141.5) minutes. In the model adjusting for door-to-imaging time, the following were associated with longer DIDO time: age 80 years or older (compared with 18-59 years; 5.97 [95% CI, 1.02-10.92] minutes), female sex (5.21 [95% CI, 1.55-8.87] minutes), and non-Hispanic Black race (compared with non-Hispanic White 10.09 [95% CI, 4.21-15.96] minutes). In the model including imaging-to-door time as a covariate, disparities in DIDO by age and female sex became nonsignificant, and the disparity by Black race was attenuated (2.32 [95% CI, 1.09-3.56] minutes). Conclusions and Relevance: In this national cohort study of interhospital transfer of patients with AIS, delays in DIDO time by Black race, older age (≥80 years), and female sex were largely explained by the imaging-to-door period, suggesting that future systems interventions should target this interval to reduce these disparities. While existing guidelines and care resources heavily focus on reducing door-to-imaging times, further attention is warranted to reduce imaging-to-door times in the management of patients with AIS who require interhospital transfer.

Asunto(s)

Servicio de Urgencia en Hospital , Accidente Cerebrovascular Isquémico , Transferencia de Pacientes , Tiempo de Tratamiento , Humanos , Femenino , Masculino , Accidente Cerebrovascular Isquémico/terapia , Anciano , Servicio de Urgencia en Hospital/estadística & datos numéricos , Transferencia de Pacientes/estadística & datos numéricos , Estudios Retrospectivos , Tiempo de Tratamiento/estadística & datos numéricos , Persona de Mediana Edad , Anciano de 80 o más Años , Sistema de Registros , Factores de Tiempo , Terapia Trombolítica/estadística & datos numéricos , Terapia Trombolítica/métodos , Estados Unidos

RESUMEN

BACKGROUND: While surgery still remains the gold standard treatment for mechanical prosthetic valve thrombosis (MPVT) by many guidelines, the ultraslow low-dose thrombolytic regimen has been reported as a promising alternative. METHODS: In this prospective single-center cohort, patients with acute MPVT were treated with an ultraslow low-dose thrombolytic regimen consisting of 25 mg infusion of recombinant tissue-type plasminogen activator (rtPA) over 25 h. The regimen could be repeated in case of failure until resolution/occurrence of adverse events or a maximum cumulative dose of 150 mg. The primary outcome was the complete MPVT resolution rate; other outcomes included first-dose success rate, major bleeding, thromboembolic events, mortality, and total thrombolytic dose/duration. RESULTS: Between April 2018 to January 2024, 135 episodes of acute MPVT were treated with an ultraslow low-dose thrombolytic regimen in 118 patients. In 118/135 (87.4 %) episodes, right-sided prosthetic valve was involved. Complete success was achieved in 88.1 % of cases, with 39.5 % responding after the first dose. The median total dose was 50 mg over a median of 30 h. Only one fatal intracranial hemorrhage occurred (0.7 %), with no other bleeding or thromboembolic complications. CONCLUSION: The ultraslow low-dose thrombolytic regimen appears to exhibit high efficacy and acceptable safety in treating acute MPVT. Further large clinical trials are essential for validating these preliminary findings.

Asunto(s)

Fibrinolíticos , Prótesis Valvulares Cardíacas , Terapia Trombolítica , Trombosis , Humanos , Femenino , Masculino , Estudios Prospectivos , Terapia Trombolítica/métodos , Prótesis Valvulares Cardíacas/efectos adversos , Persona de Mediana Edad , Trombosis/tratamiento farmacológico , Trombosis/etiología , Fibrinolíticos/administración & dosificación , Fibrinolíticos/uso terapéutico , Anciano , Estudios de Cohortes , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/uso terapéutico , Adulto , Relación Dosis-Respuesta a Droga , Resultado del Tratamiento , Enfermedad Aguda

RESUMEN

Venous thromboembolism (VTE) has been occurring frequently in human society. There is an urgent need to study the influence of several factors on thrombolytic therapy, such as the effects of vascular pressure levels (VPL) and the drug injection time (DIT). Considering blood as a non-Newtonian fluid, valve as a hyperelastic material, and thrombus as a porous medium, a new numerical simulation model of biofluid mechanics incorporating fluid-solid coupling phenomena and biochemical substance reactions is established based on the N-S equations and the convection-diffusion reaction equations. Then, a unique in vitro experimental platform is established to verify the correctness of the constructed mathematical model. The results showed that vascular compression resulted in significant differences in blood flow status localized within the vessel. Vascular compression causes the blood boosting index to fluctuate and the valve displacement values are 135% and 158% greater than the lower VPL, respectively. At the same time, vascular compression weakened vortex intensity, accelerated material transport and response, and improved the treatment. Compared with low VPL, the therapeutic efficacy increased by 7% and 15%, respectively. In addition, when the dose of the drug is high, different injection times can increase the therapeutic effect to different degrees, with a maximum difference of 12%. Our in vitro experiments are similar to the results obtained by numerical simulation, which can verify the reliability of numerical simulation. The computational model proposed and the experimental platform designed in this study have the potential to assist in clinical medication prediction in different venous thromboembolism patients.

Asunto(s)

Simulación por Computador , Modelos Cardiovasculares , Terapia Trombolítica , Humanos , Terapia Trombolítica/métodos , Tromboembolia Venosa/tratamiento farmacológico , Fibrinolíticos/administración & dosificación , Presión Sanguínea/efectos de los fármacos

RESUMEN

Background: Thrombolytic therapy is essential for acute ischemic stroke (AIS) management but poses a risk of hemorrhagic transformation (HT), necessitating accurate prediction to optimize patient care. Methods: A comprehensive search was conducted across PubMed, Web of Science, Scopus, Embase, and Google Scholar, covering studies from inception until July 10, 2024. Studies were included if they used machine learning (ML) or deep learning algorithms to predict HT in AIS patients treated with thrombolysis. Exclusion criteria included studies involving endovascular treatments and those not evaluating model effectiveness. Data extraction and quality assessment were performed following PRISMA guidelines and using the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) and Prediction Model Risk of Bias Assessment Tool (PROBAST) tools. Results: Out of 1943 identified records, 12 studies were included in the final analysis, encompassing 18 007 AIS patients who received thrombolytic therapy. The ML models demonstrated high predictive performance, with pooled area under the curve (AUC) values ranging from 0.79 to 0.95. Specifically, XGBoost models achieved AUCs of up to 0.953 and Artificial Neural Network (ANN) models reached up to 0.942. Sensitivity and specificity varied significantly, with the highest sensitivity at 0.90 and specificity at 0.99. Significant predictors of HT included age, glucose levels, NIH Stroke Scale (NIHSS) score, systolic and diastolic blood pressure, and radiomic features. Despite these promising results, methodological disparities and limited external validation highlighted the need for standardized reporting and further rigorous testing. Conclusion: ML techniques, especially XGBoost and ANN, show great promise in predicting HT following thrombolysis in AIS patients, enhancing risk stratification and clinical decision-making. Future research should focus on prospective study designs, standardized reporting, and integrating ML assessments into clinical workflows to improve AIS management and patient outcomes.

Asunto(s)

Accidente Cerebrovascular Isquémico , Aprendizaje Automático , Terapia Trombolítica , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Terapia Trombolítica/métodos

RESUMEN

Pulmonary embolism is a manifestation of venous thromboembolic disease, characterized by thrombus formation within the pulmonary arteries. Symptoms and clinical signs are numerous and nonspecific. Diagnosis relies on medical imaging (thoracic CT angiography or ventilation/perfusion scintigraphy). This disease requires prompt management to reduce morbidity and mortality. Treatment strategies include anticoagulation, systemic or catheter-guided thrombolysis, mechanical thrombectomy or surgery. In our institution, we have a multidisciplinary team, called PERT (Pulmonary Embolism Response Team), responsible for guiding the management of pulmonary embolism and for facilitating the access to those emerging endovascular techniques.

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L'embolie pulmonaire est une manifestation de la maladie thromboembolique veineuse, caractérisée par la formation d'un ou plusieurs thrombi au sein des artères pulmonaires. Les symptômes et signes cliniques sont nombreux et non spécifiques. Le diagnostic repose sur l'imagerie médicale (angioscanner thoracique ou scintigraphie de ventilation/perfusion). Cette pathologie nécessite une prise en charge rapide pour en réduire la morbidité et la mortalité. Les stratégies de traitement incluent l'anticoagulation, la thrombolyse systémique ou guidée par cathéter, la thrombectomie mécanique ou la chirurgie. Au sein de notre institution, nous disposons d'une équipe multidisciplinaire, appelée PERT («Pulmonary Embolism Response Team¼), chargée d'orienter la prise en charge thérapeutique de l'embolie pulmonaire et de faciliter le recours aux nouvelles techniques endovasculaires disponibles.

Asunto(s)

Embolia Pulmonar , Humanos , Embolia Pulmonar/terapia , Embolia Pulmonar/diagnóstico , Trombectomía/métodos , Terapia Trombolítica/métodos , Masculino , Anticoagulantes/uso terapéutico , Femenino

RESUMEN

BACKGROUND AND OBJECTIVES: Limited data exist on the safety of IV thrombolysis (IVT) for acute ischemic stroke (AIS) after dabigatran reversal with idarucizumab. We sought to evaluate the safety and efficacy of idarucizumab pretreatment in patients with AIS receiving IVT. METHODS: A national registry-based study evaluated the safety and efficacy of IVT in this specific subgroup. We also conducted a systematic review and meta-analysis of cohort studies and case series, aiming to document the pooled rates of (1) symptomatic intracranial hemorrhage (sICH), (2) any intracranial hemorrhage, (3) 3-month mortality, and (4) the proportion of excellent (modified Rankin Scale [mRS] scores 0-1) and (5) good (mRS scores 0-2) functional outcome at 3 months among patients with AIS, who received IVT after dabigatran reversal with idarucizumab. Moreover, we sought to compare these outcomes between IVT-treated patients after dabigatran reversal with idarucizumab and IVT-treated patients without dabigatran pretreatment. RESULTS: Thirteen cohorts including our nation-wide registry-based cohort and 1 case series comprising 553 patients with AIS (mean age: 75 years; male sex: 65%; median baseline NIH Stroke Scale score: 11 points) receiving idarucizumab before IVT were included in this meta-analysis. The pooled rate of sICH after IVT after idarucizumab administration was 4% (95% CI 1-9; I2 = 26%), while the pooled rates of any intracranial hemorrhage and 3-month mortality were 10% (95% CI 5-16; I2 = 24%) and 18% (95% CI 10-27; I2 = 0%), respectively. The pooled rates of excellent and good functional outcomes at 3 months were 56% (95% CI 27-83; I2 = 69%) and 70% (95% CI 57-81; I2 = 40%), respectively. The risk of sICH (risk ratio [RR] 1.86; 95% CI 0.91-3.80; I2 = 0%), any intracranial hemorrhage (RR 1.76; 95% CI 0.99-3.11; I2 = 8%), and 3-month mortality (RR 1.50; 95% CI 0.91-2.48; I2 = 0%) did not differ between patients with AIS receiving IVT with and without idarucizumab. Moreover, idarucizumab administration was associated with higher likelihood of achieving a 3-month good functional outcome (RR 1.35; 95% CI 1.11-1.65; I2 = 27%). DISCUSSION: IVT for AIS after dabigatran reversal with idarucizumab seems to be safe and effective in observational studies with limited number of patients. Randomized-controlled clinical trials are warranted to provide robust evidence on the safety and efficacy of IVT in this specific AIS subgroup.

Asunto(s)

Anticuerpos Monoclonales Humanizados , Antitrombinas , Dabigatrán , Accidente Cerebrovascular Isquémico , Sistema de Registros , Terapia Trombolítica , Humanos , Dabigatrán/uso terapéutico , Dabigatrán/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Antitrombinas/uso terapéutico , Antitrombinas/efectos adversos , Terapia Trombolítica/métodos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Anciano , Masculino , Femenino , Hemorragias Intracraneales/inducido químicamente , Hemorragias Intracraneales/tratamiento farmacológico , Resultado del Tratamiento

RESUMEN

INTRODUCTION: Hospital overcrowding where patient admissions exceed capacity is associated with worse outcomes in Emergency Department. Developments in emergency stroke care have been associated with improvements in stroke outcome but are dependent on effective, organised care. We examined if overcrowding in the hospital system was associated with negative changes in stroke outcome. METHODS: Data on overcrowding were obtained from the Irish Nurses and Midwives Organisation (INMO) 'Trolley Count' database recording the number of patients cared for on trolleys/chairs in all acute hospitals each midnight. These were compared with quarterly data from the Irish National Audit of Stroke from 2013 to 2021 inclusive. Variables analysed were inpatient mortality rate, thrombolysis rate for ischaemic stroke, median door to needle time and median length of stay. RESULTS: 579449 patient episodes were recorded by Trolley Watch over the period, (Quarterly Median 16719.5, range 3389-27015). Average Quarterly Thrombolysis rate was 11.3% (sd 1.3%) Median Quarterly Inpatient Mortality rate was 11.8% (Range 8.9-14.0%). Median Quarterly Length of stay was 9 days (8-11 days). Median quarterly door to needle was 65 min (45-80 min). Q1 was typically the worst for overcrowding with on average 19777 incidences (sd 4786). This was significantly higher than for Q2 (mean 13540 (sd 4785) p = 0.005 t-test) and for Q3 (mean 14542 (sd 4753) p = 0.03). No significant correlation was found between quarterly Trolley watch episodes and inpatient mortality (r = 0.084, p = 0.63), median length of stay r=-0.15, p = 0.37) or thrombolysis rate (r = 0.089 p = 0.61). There was an unexpected significant negative correlation between trolley watch data and median door to needle time (r=-0.36, p = 0.03). CONCLUSION: Despite increasing hospital overcrowding, stroke services still managed to preserve standard of care. We could find no association between levels of overcrowding and deterioration in selected indices of patient care.

Asunto(s)

Aglomeración , Mortalidad Hospitalaria , Accidente Cerebrovascular , Humanos , Irlanda , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/mortalidad , Tiempo de Internación/estadística & datos numéricos , Femenino , Servicio de Urgencia en Hospital/estadística & datos numéricos , Masculino , Terapia Trombolítica/estadística & datos numéricos , Anciano , Auditoría Médica , Tiempo de Tratamiento/estadística & datos numéricos , Persona de Mediana Edad

RESUMEN

BACKGROUND: This study was conducted to determine optimal predictive ability of National Institutes of Health Stroke Scale (NIHSS) measurements at baseline, 24 hours, and change from baseline to 24 hours after thrombolysis on functional recovery in patients with acute ischemic stroke who participated in the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study). METHODS AND RESULTS: ENCHANTED was an international, multicenter, 2×2 quasifactorial, prospective, randomized open trial of low-dose versus standard-dose intravenous alteplase and intensive versus guideline-recommended blood pressure lowering in thrombolysis-eligible patients with acute ischemic stroke. Absolute (baseline minus 24 hours) and percentage (absolute change/baseline × 100) changes in NIHSS scores were calculated. Receiver operating characteristic curve analyses assessed performance of different NIHSS measurements on 90-day favorable functional recovery (modified Rankin Scale [mRS] score 0-2) and excellent functional recovery (mRS score 0-1). Youden index was used to identify optimal predictor cutoff points. A total of 4410 patients in the ENCHANTED trial were enrolled. The 24-hour NIHSS score had the highest discriminative ability for predicting favorable 90-day functional recovery (mRS score 0-2; area under the curve 0.866 versus 0.755, 0.689, 0.764; P<0.001) than baseline, absolute, and percentage change of NIHSS score, respectively. The optimal cutoff point of 24-hour NIHSS score for predicting favorable functional recovery was ≤4 (sensitivity 66.5%, specificity 87.1%, adjusted odds ratio, 9.44 [95% CI, 7.77-11.48]). The 24-hour NIHSS score (≤3) was the best predictor of 90-day excellent functional recovery (mRS score 0-1). Findings were consistent across subgroups, including sex, race, baseline NIHSS score, stroke subtype, and age. CONCLUSIONS: In thrombolysis-eligible patients with acute ischemic stroke, 24-hour NIHSS score (optimal cutpoint of 4) is the strongest predictor of 90-day functional recovery over baseline and early change of NIHSS score. REGISTRATION: URL: https://clinicaltrials.gov. Unique Identifier: NCT01422616.

Asunto(s)

Fibrinolíticos , Accidente Cerebrovascular Isquémico , Recuperación de la Función , Terapia Trombolítica , Activador de Tejido Plasminógeno , Humanos , Masculino , Femenino , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/fisiopatología , Accidente Cerebrovascular Isquémico/diagnóstico , Anciano , Terapia Trombolítica/métodos , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/uso terapéutico , Fibrinolíticos/uso terapéutico , Fibrinolíticos/administración & dosificación , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , Valor Predictivo de las Pruebas , Resultado del Tratamiento , Pronóstico , Índice de Severidad de la Enfermedad , Estado Funcional , Evaluación de la Discapacidad , Anciano de 80 o más Años

RESUMEN

OBJECTIVE: This study aimed to externally validate different predictive scores for symptomatic intracranial hemorrhage (SICH) after intravenous thrombolysis (IVT), with a particular focus on their predictive abilities in Asian stroke patients. METHODS: We retrospectively enrolled stroke patients who received a standard dose of alteplase within 4.5 hours from symptom onset at the First Affiliated Hospital of Dalian Medical University from July 2010 to August 2023. SICH was defined as the hemorrhagic transformation detected on the head CT scan completed within 48 h post-IVT, accompanied by a clinical deterioration of at least a 4-point increase in NIHSS score. Predictive abilities of the HAT, MSS, SEDAN, SPAN-100, and GRASPS scores were tested. Discrimination and calibration were performed using the area under the receiver operating characteristic curve (ROC-AUC), DeLong test, and Hosmer-Lemeshow (H-L) goodness-of-fit test. RESULTS: The study included 1007 stroke patients, of whom 31 (3.08 %) developed SICH. ROC-AUCs for predicting SICH were: 0.796 (95 %CI: 0.726-0.866) for the GRASPS score, 0.724 (95 %CI: 0.644-0.804) for the MSS score, 0.715 (95 %CI: 0.619-0.811) for the SEDAN score, 0.714 (95 %CI: 0.611-0.817) for the HAT score, and 0.605 (95 %CI: 0.491-0.720) for the SPAN-100 score (all P < 0.05). DeLong tests showed that the GRASPS score demonstrated significantly better discrimination than the MSS score (P = 0.010), the SEDAN score (P = 0.009), the HAT score (P = 0.049), and the SPAN-100 score (P = 0.000). H-L tests indicated good calibrations which were ranked HAT > SEDAN > MSS > SPAN-100 > GRASPS scores. CONCLUSION: The GRASPS score showed reasonable predictive ability for SICH, indicating its potential utility for Asian stroke patients receiving IVT.

Asunto(s)

Fibrinolíticos , Hemorragias Intracraneales , Accidente Cerebrovascular , Terapia Trombolítica , Activador de Tejido Plasminógeno , Humanos , Masculino , Femenino , Hemorragias Intracraneales/diagnóstico por imagen , Persona de Mediana Edad , Anciano , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/métodos , Fibrinolíticos/administración & dosificación , Fibrinolíticos/efectos adversos , Fibrinolíticos/uso terapéutico , Estudios Retrospectivos , Activador de Tejido Plasminógeno/efectos adversos , Activador de Tejido Plasminógeno/uso terapéutico , Activador de Tejido Plasminógeno/administración & dosificación , Pueblo Asiatico , Valor Predictivo de las Pruebas , Anciano de 80 o más Años , Administración Intravenosa

RESUMEN

Near-infrared II (NIR-II) imaging and photothermal therapy hold tremendous potential in precision diagnosis and treatment within biological organisms. However, a significant challenge is the shortage of NIR-II fluorescent probes with both high photothermal conversion coefficient (PCE) and fluorescence quantum yield (ΦF). Herein, we address this issue by integrating a large conjugated electron-withdrawing core, multiple rotors, and multiple alkyl chains into a molecule to successfully generate a NIR-II agent 4THTPB with excellent PCE (87.6%) and high ΦF (3.2%). 4THTPB shows a maximum emission peak at 1058 nm, and the emission tail could extend to as long as 1700 nm. These characteristics make its nanoparticles (NPs) perform well in NIR-II high-resolution angiography, thereby allowing for precise diagnosis of thrombus through NIR-II imaging and enabling efficient photothermal thrombolysis. This work not only furnishes a NIR-II agent with excellent overall performance but also provides valuable guidance for the design of high-performance NIR-II agents.

Asunto(s)

Colorantes Fluorescentes , Rayos Infrarrojos , Colorantes Fluorescentes/química , Humanos , Nanopartículas/química , Terapia Fototérmica , Animales , Imagen Óptica , Ratones , Trombosis/diagnóstico por imagen , Terapia Trombolítica , Fototerapia

RESUMEN

BACKGROUND: Endovascular treatment (EVT) has been demonstrated to be effective for patients with tandem occlusion. The efficacy and safety of intravenous thrombolysis before EVT in patients with tandem occlusion remain debatable. METHODS AND RESULTS: We conducted a systematic review and meta-analysis with PubMed, EMBASE, and the Cochrane Library from inception to September 2023. The primary outcome was functional independence, defined as a modified Rankin Scale score of 0 to 2 at 90 days. The secondary outcomes included the successful recanalization rate, symptomatic intracerebral hemorrhage, and mortality at 90 days. In total, 9 studies with 1838 enrolled participants were identified. Our results showed that, compared with treatment with EVT alone, intravenous thrombolysis before EVT was associated with a greater proportion of functional independence at 90 days (odds ratio [OR], 1.39 [95% CI, 1.14-1.69]; P=0.001), a greater rate of successful recanalization (OR, 1.45 [95% CI, 1.11-1.89]; P=0.007) and decreased mortality (OR, 0.68 [95% CI, 0.50-0.93]; P=0.02). Furthermore, there was no significant difference in symptomatic intracerebral hemorrhage between the intravenous thrombolysis plus EVT group and the EVT alone group (OR, 1.16 [95% CI, 0.79-1.70]; P=0.45). CONCLUSIONS: In patients with acute ischemic stroke and tandem occlusion, intravenous thrombolysis before EVT was associated with a greater rate of favorable functional outcomes and successful recanalization and a lower mortality rate without an increased risk of symptomatic intracerebral hemorrhage compared with patients receiving EVT alone.

Asunto(s)

Procedimientos Endovasculares , Fibrinolíticos , Accidente Cerebrovascular Isquémico , Terapia Trombolítica , Humanos , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/métodos , Accidente Cerebrovascular Isquémico/mortalidad , Accidente Cerebrovascular Isquémico/terapia , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/métodos , Fibrinolíticos/efectos adversos , Fibrinolíticos/administración & dosificación , Fibrinolíticos/uso terapéutico , Resultado del Tratamiento , Administración Intravenosa

RESUMEN

Background The combination of intravenous thrombolysis (IVT) with mechanical thrombectomy (MT) may have clinical benefits for patients with medium vessel occlusion. Purpose To examine whether MT combined with IVT is associated with different outcomes than MT alone in patients with acute ischemic stroke (AIS) and medium vessel occlusion. Materials and Methods This retrospective study included consecutive adult patients with AIS and medium vessel occlusion treated with MT or MT with IVT at 37 academic centers in North America, Asia, and Europe. Data were collected from September 2017 to July 2021. Propensity score matching was performed to reduce confounding. Univariable and multivariable logistic regression analyses were performed to test the association between the addition of IVT treatment and different functional and safety outcomes. Results After propensity score matching, 670 patients (median age, 75 years [IQR, 64-82 years]; 356 female) were included in the analysis; 335 underwent MT alone and 335 underwent MT with IVT. Median onset to puncture (350 vs 210 minutes, P < .001) and onset to recanalization (397 vs 273 minutes, P < .001) times were higher in the MT group than the MT with IVT group, respectively. In the univariable regression analysis, the addition of IVT was associated with higher odds of a modified Rankin Scale (mRS) score 0-2 (odds ratio [OR], 1.44; 95% CI: 1.06, 1.96; P = .019); however, this association was not observed in the multivariable analysis (OR, 1.37; 95% CI: 0.99, 1.89; P = .054). In the multivariable analysis, the addition of IVT also showed no evidence of an association with the odds of first-pass effect (OR, 1.27; 95% CI: 0.9, 1.79; P = .17), Thrombolysis in Cerebral Infarction grades 2b-3 (OR, 1.64; 95% CI: 0.99, 2.73; P = .055), mRS scores 0-1 (OR, 1.27; 95% CI: 0.91, 1.76; P = .16), mortality (OR, 0.78; 95% CI: 0.49, 1.24; P = .29), or intracranial hemorrhage (OR, 1.25; 95% CI: 0.88, 1.76; P = .21). Conclusion Adjunctive IVT may not provide benefit to MT in patients with AIS caused by distal and medium vessel occlusion. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Wojak in this issue.

Asunto(s)

Accidente Cerebrovascular Isquémico , Trombectomía , Terapia Trombolítica , Humanos , Femenino , Masculino , Anciano , Estudios Retrospectivos , Trombectomía/métodos , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/cirugía , Accidente Cerebrovascular Isquémico/terapia , Persona de Mediana Edad , Anciano de 80 o más Años , Terapia Trombolítica/métodos , Terapia Combinada , Resultado del Tratamiento , Fibrinolíticos/uso terapéutico , Fibrinolíticos/administración & dosificación , Puntaje de Propensión

RESUMEN

Bleeding within the pleural space may result in persistent clot formation called retained hemothorax (RH). RH is prone to organization, which compromises effective drainage, leading to lung restriction and dyspnea. Intrapleural fibrinolytic therapy is used to clear the persistent organizing clot in lieu of surgery, but fibrinolysin selection, delivery strategies, and dosing have yet to be identified. We used a recently established rabbit model of RH to test whether intrapleural delivery of single-chain urokinase (scuPA) can most effectively clear RH. scuPA, or single-chain tissue plasminogen activator (sctPA), was delivered via thoracostomy tube on day 7 as either one or two doses 8 h apart. Pleural clot dissolution was assessed using transthoracic ultrasonography, chest computed tomography, two-dimensional and clot displacement measurements, and gross analysis. Two doses of scuPA (1 mg/kg) were more effective than a bolus dose of 2 mg/kg in resolving RH and facilitating drainage of pleural fluids (PF). Red blood cell counts in the PF of scuPA, or sctPA-treated rabbits were comparable, and no gross intrapleural hemorrhage was observed. Both fibrinolysins were equally effective in clearing clots and promoting pleural drainage. Biomarkers of inflammation and organization were likewise comparable in PF from both groups. The findings suggest that single-agent therapy may be effective in clearing RH; however, the clinical advantage of intrapleural scuPA remains to be established by future clinical trials.

Asunto(s)

Fibrinolíticos , Hemotórax , Terapia Trombolítica , Activador de Tejido Plasminógeno , Activador de Plasminógeno de Tipo Uroquinasa , Animales , Conejos , Hemotórax/etiología , Hemotórax/terapia , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/uso terapéutico , Fibrinolíticos/administración & dosificación , Fibrinolíticos/farmacología , Fibrinolíticos/uso terapéutico , Terapia Trombolítica/métodos , Modelos Animales de Enfermedad , Pleura/efectos de los fármacos

RESUMEN

BACKGROUND: Complicated pleural infection comprises of complex effusions and empyema. When tube thoracostomy is ineffective, treatment options include surgical drainage, deloculation and decortication or intrapleural fibrinolysis. We performed a systematic review and meta-analysis to examine which technique is superior in treating complicated pleural infections. METHODS: PubMed, MEDLINE and EMBASE databases were searched for studies published between January 2000 to July 2023 comparing surgery and intrapleural fibrinolysis for treatment of complicated pleural infection. The primary outcome was treatment success. Secondary outcomes included hospital length of stay, chest drain duration and in-hospital mortality. RESULTS: Surgical management of complicated pleural infections was more likely to be successful than intrapleural fibrinolysis (RR 1.18; 95% CI 1.02, 1.38). Surgical intervention group benefited from statistically significant shorter hospital length of stay (MD: 3.85; 95% CI 1.09, 6.62) and chest drain duration (MD: 3.42; 95% CI 1.36, 5.48). There was no observed difference between in-hospital mortality (RR: 1.00; 95% CI 0.99, 1.02). CONCLUSION: Surgical management of complicated pleural infections results in increased likelihood of treatment success, shorter chest drain duration and hospital length of stay in the adult population compared with intrapleural fibrinolysis. In-hospital mortality did not differ. Large cohort and randomized research need to be conducted to confirm these findings.

Asunto(s)

Terapia Trombolítica , Humanos , Terapia Trombolítica/métodos , Empiema Pleural/cirugía , Empiema Pleural/mortalidad , Empiema Pleural/diagnóstico , Resultado del Tratamiento , Mortalidad Hospitalaria , Drenaje/métodos , Tiempo de Internación , Fibrinolíticos/administración & dosificación , Fibrinolíticos/uso terapéutico , Fibrinólisis/efectos de los fármacos , Derrame Pleural/cirugía , Derrame Pleural/terapia