Citicoline for treating people with acute ischemic stroke.
Ontology highlight
ABSTRACT:
SUBMITTER: Marti-Carvajal AJ
PROVIDER: S-EPMC8406786 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Citicoline (CDPC) is a natural supplement with well-documented neuroprotective effects in the treatment of neurodegenerative diseases. In the present study, we sought to exploit citicoline as a theranostic agent with its inherent chemical exchange saturation transfer (CEST) MRI signal, which can be directly used as an MRI guidance in the citicoline drug delivery. Our in vitro CEST MRI results showed citicoline has two inherent CEST signals at +1 and +2 ppm, attributed to exchangeable hydroxyl and amine protons, respectively. To facilitate the targeted drug delivery of citicoline to ischemic regions, we prepared liposomes encapsulating citicoline (CDPC-lipo) and characterized the particle properties and CEST MRI properties. The in vivo CEST MRI detection of liposomal citicoline was then examined in a rat brain model of unilateral transient ischemia induced by a two-hour middle cerebral artery occlusion. The results showed that the delivery of CPDC-lipo to the brain ischemic areas could be monitored and quantified by CEST MRI. When administered intra-arterially, CDPC-lipo clearly demonstrated a detectable CEST MRI contrast at 2 ppm. CEST MRI revealed that liposomes preferentially accumulated in the areas of ischemia with a disrupted blood-brain-barrier. We furthermore used CEST MRI to detect the improvement in drug delivery using CDPC-lipo targeted against vascular cell adhesion molecule (VCAM)-1 in the same animal model. The MRI findings were validated using fluorescence microscopy. Hence, liposomal citicoline represents a prototype theranostic system, where the therapeutic agent can be detected directly by CEST MRI in a label-free fashion.
| S-EPMC4955057 | biostudies-literature
Project description:Transcranial near-infrared laser therapy (NILT) has been investigated as a novel neuroprotective treatment for acute ischemic stroke (AIS), for approximately 10 years. Two clinical trials, NeuroThera Effectiveness and Safety Trial (NEST)-1 and NEST-2, have evaluated the use of NILT to promote clinical recovery in patients with AIS. This review covers preclinical, translational, and clinical studies documented during the period 1997-2010. The primary aim of this article is to detail the development profile of NILT to treat AIS. Secondly, insight into possible mechanisms involved in light therapy will be presented. Lastly, possible new directions that should be considered to improve the efficacy profile of NILT in AIS patients will be discussed. The use of NILT was advanced to clinical trials based upon extensive translational research using multiple species. NILT, which may promote functional and behavioral recovery via a mitochondrial mechanism and by enhancing cerebral blood flow, may eventually be established as an Food and Drug Administration (FDA)-approved treatment for stroke. The NEST-3 trial, which is the pivotal trial for FDA approval, should incorporate hypotheses derived from translational studies to ensure efficacy in patients. Future NILT studies should consider administration of a thrombolytic to enhance cerebral reperfusion alongside NILT neuroprotection.
| S-EPMC3059546 | biostudies-other
Project description:Studies have demonstrated that intravenous recombinant tissue plasminogen activator (IV rtPA) is a cost-effective treatment for acute ischemic stroke. Age-specific cost effectiveness has not been well examined. This study estimated age-specific incremental cost-effectiveness ratios (ICERs) of IV rtPA treatment versus no IV rtPA.A Markov model was developed to examine the economic impact of IV rtPA over a 20-year time horizon on four age groups (18-44, 45-64, 65-80, and ?81 years) from the U.S. healthcare sector perspective. The model used health outcomes from a national stroke registry adjusted by parameters from previous literature and current hospitalization costs in 2013 U.S. dollars. Long-term annual costs and quality-adjusted life years (QALYs) in the years after a stroke were discounted at 3% per year. Incremental costs, incremental QALYs, and ICERs were estimated and sensitivity analyses were conducted between 2015 and 2017.Use of IV rtPA gained 0.55 QALYs and cost $3,941 more than no IV rtPA for stroke patients aged ?18 years over a 20-year time horizon. IV rtPA was a dominant strategy compared to no IV rtPA for patients aged 18-44 and 45-64 years. For patients aged 65-80 years, IV rtPA gained 0.44 QALYs and cost $4,872 more than no IV rtPA (ICER=$11,132/QALY). For patients aged ?81 years, ICER was estimated at $48,676/QALY.IV rtPA saved costs and improved health outcomes for patients aged 18-64 years and was cost effective for those aged ?65 years. These findings support the use of IV rtPA.
| S-EPMC5819005 | biostudies-literature
Project description:Background and purposeThrombolysis is underused in acute ischemic stroke, mainly due to the reluctance of physicians to treat thrombolysis patients. However, a computerized clinical decision support system can help physicians to develop individualized stroke treatments.MethodsA consecutive series of 958 patients, hospitalized within 12 hours of ischemic stroke onset from a representative clinical center in Korea, was used to establish a prognostic model. Multivariable logistic regression was used to develop the model for global and safety outcomes. An external validation of developed model was performed using 954 patients data obtained from 5 university hospitals or regional stroke centers.ResultsFinal global outcome predictors were age; previous modified Rankin scale score; initial National Institutes of Health Stroke Scale (NIHSS) score; previous stroke; diabetes; prior use of antiplatelet treatment, antihypertensive drugs, and statins; lacunae; thrombolysis; onset to treatment time; and systolic blood pressure. Final safety outcome predictors were age, initial NIHSS score, thrombolysis, onset to treatment time, systolic blood pressure, and glucose level. The discriminative ability of the prognostic model showed a C-statistic of 0.89 and 0.84 for the global and safety outcomes, respectively. Internal and external validation showed similar C-statistic results. After updating the model, calibration slopes were corrected from 0.68 to 1.0 and from 0.96 to 1.0 for the global and safety outcome models, respectively.ConclusionsA novel computerized outcome prediction model for thrombolysis after ischemic stroke was developed using large amounts of clinical information. After external validation and updating, the model's performance was deemed clinically satisfactory.
| S-EPMC4460339 | biostudies-literature
Project description:ObjectivesConcise "synthetic" review of the state of the art of management of acute ischemic stroke.Data sourcesAvailable literature on PubMed.Study selectionWe selected landmark studies, recent clinical trials, observational studies, and professional guidelines on the management of stroke including the last 10 years.Data extractionEligible studies were identified and results leading to guideline recommendations were summarized.Data synthesisStroke mortality has been declining over the past 6 decades, and as a result, stroke has fallen from the second to the fifth leading cause of death in the United States. This trend may follow recent advances in the management of stroke, which highlight the importance of early recognition and early revascularization. Recent studies have shown that early recognition, emergency interventional treatment of acute ischemic stroke, and treatment in dedicated stroke centers can significantly reduce stroke-related morbidity and mortality. However, stroke remains the second leading cause of death worldwide and the number one cause for acquired long-term disability, resulting in a global annual economic burden.ConclusionsAppropriate treatment of ischemic stroke is essential in the reduction of mortality and morbidity. Management of stroke involves a multidisciplinary approach that starts and extends beyond hospital admission.
| S-EPMC7540624 | biostudies-literature
Project description:Intra-arterial therapy (IAT) for acute ischemic stroke refers to endovascular catheter-based approaches to achieve recanalization using mechanical clot disruption, locally injected thrombolytic agents or both. IAT may be used in addition to intravenous tissue plasminogen activator (tPA) or in patients who do not qualify for tPA, usually because they are outside the approved 3-h timeframe window or have contraindications, such as elevated international normalized ratio or partial thromboplastin time. Recanalization rates correlate with clinical improvement, and with the newest catheters it is possible to achieve recanalization in roughly 80% of patients treated. However, while the catheters are approved by the Food and Drug Administration, there are still no randomized trial data demonstrating the role of current IAT therapy vs either tPA or standard management. IAT is reserved for patients with large artery occlusions in the basilar, distal carotid, or proximal middle cerebral arteries. Imaging the penumbra using magnetic resonance imaging or computed tomographic perfusion is currently the most frequently used way to identify patients who might benefit. However, the imaging and clinical criteria for identifying which patients benefit, and perhaps more importantly those who will do poorly despite IAT, remain unclear.
| S-EPMC3250276 | biostudies-other
Project description:The most important service that imaging provides to patients with ischemic stroke is to rapidly identify those patients who are most likely to benefit from immediate treatment. This group includes patients who have severe neurological symptoms due to an occlusion of a major artery, and who are candidates for recanalization using intravenous thrombolysis or intra-arterial intervention to remove the occlusion. Outcomes for these patients are determined by symptom severity, the artery that is occluded, the size of the infarct at the time of presentation, and the effect of treatment. MRI provides key physiological information through MR angiography and diffusion MRI that has been proven to be of high clinical value in identify patients who are in need of immediate treatment. Perfusion MRI provides information about the ischemic penumbra, but its clinical value is unproven. In current clinical practice, the time since stroke onset is dominant over physiologic information provided by MRI in treatment decisions. This will change only when clinical trials prove that stroke physiology as revealed by MRI is superior to time from stroke onset in promoting good clinical outcomes.
| S-EPMC3400122 | biostudies-literature
Project description:Malignant stroke occurs in a subgroup of patients suffering from ischemic cerebral infarction and is characterized by neurological deterioration due to progressive edema, raised intracranial pressure, and cerebral herniation. Decompressive craniectomy (DC) is a surgical technique aiming to open the "closed box" represented by the non-expandable skull in cases of refractory intracranial hypertension. It is a valuable modality in the armamentarium to treat patients with malignant stroke: the life-saving effect has been proven for both supratentorial and infratentorial DC in virtually all age groups. This leaves physicians with the difficult task to decide who will require early or preemptive surgery and who might benefit from postponing surgery until clear evidence of deterioration evolves. Together with the patient's relatives, physicians also have to ascertain whether the patient will have acceptable disability and quality of life in his or her presumed perception, based on preoperative predictions. This complex decision-making process can only be managed with interdisciplinary efforts and should be supported by continued research in the age of personalized medicine.
| S-EPMC6556035 | biostudies-literature
Project description:Tenecteplase is a fibrinolytic drug with higher fibrin specificity and longer half-life than the standard stroke thrombolytic, alteplase, permitting the convenience of single bolus administration. Tenecteplase, at 0.5 mg/kg, has regulatory approval to treat ST-segment-elevation myocardial infarction, for which it has equivalent 30-day mortality and fewer systemic hemorrhages. Investigated as a thrombolytic for ischemic stroke over the past 15 years, tenecteplase is currently being studied in several phase 3 trials. Based on a systematic literature search, we provide a qualitative synthesis of published stroke clinical trials of tenecteplase that (1) performed randomized comparisons with alteplase, (2) compared different doses of tenecteplase, or (3) provided unique quantitative meta-analyses. Four phase 2 and one phase 3 study performed randomized comparisons with alteplase. These and other phase 2 studies compared different tenecteplase doses and effects on early outcomes of recanalization, reperfusion, and substantial neurological improvement, as well as symptomatic intracranial hemorrhage and 3-month disability on the modified Rankin Scale. Although no single trial prospectively demonstrated superiority or noninferiority of tenecteplase on clinical outcome, meta-analyses of these trials (1585 patients randomized) point to tenecteplase superiority in recanalization of large vessel occlusions and noninferiority in disability-free 3-month outcome, without increases in symptomatic intracranial hemorrhage or mortality. Doses of 0.25 and 0.4 mg/kg have been tested, but no advantage of the higher dose has been suggested by the results. Current clinical practice guidelines for stroke include intravenous tenecteplase at either dose as a second-tier option, with the 0.25 mg/kg dose recommended for large vessel occlusions, based on a phase 2 trial that demonstrated superior recanalization and improved 3-month outcome relative to alteplase. Ongoing randomized phase 3 trials may better define the comparative risks and benefits of tenecteplase and alteplase for stroke thrombolysis and answer questions of tenecteplase efficacy in the >4.5-hour time window, in wake-up stroke, and in combination with endovascular thrombectomy.
| S-EPMC7606819 | biostudies-literature
Project description:BackgroundIn patients with ischemic stroke, endovascular treatment results in a higher rate of recanalization of the affected cerebral artery than systemic intravenous thrombolytic therapy. However, comparison of the clinical efficacy of the two approaches is needed.MethodsWe randomly assigned 362 patients with acute ischemic stroke, within 4.5 hours after onset, to endovascular therapy (intraarterial thrombolysis with recombinant tissue plasminogen activator [t-PA], mechanical clot disruption or retrieval, or a combination of these approaches) or intravenous t-PA. Treatments were to be given as soon as possible after randomization. The primary outcome was survival free of disability (defined as a modified Rankin score of 0 or 1 on a scale of 0 to 6, with 0 indicating no symptoms, 1 no clinically significant disability despite symptoms, and 6 death) at 3 months.ResultsA total of 181 patients were assigned to receive endovascular therapy, and 181 intravenous t-PA. The median time from stroke onset to the start of treatment was 3.75 hours for endovascular therapy and 2.75 hours for intravenous t-PA (P<0.001). At 3 months, 55 patients in the endovascular-therapy group (30.4%) and 63 in the intravenous t-PA group (34.8%) were alive without disability (odds ratio adjusted for age, sex, stroke severity, and atrial fibrillation status at baseline, 0.71; 95% confidence interval, 0.44 to 1.14; P=0.16). Fatal or nonfatal symptomatic intracranial hemorrhage within 7 days occurred in 6% of the patients in each group, and there were no significant differences between groups in the rates of other serious adverse events or the case fatality rate.ConclusionsThe results of this trial in patients with acute ischemic stroke indicate that endovascular therapy is not superior to standard treatment with intravenous t-PA. (Funded by the Italian Medicines Agency, ClinicalTrials.gov number, NCT00640367.).
| S-EPMC3708480 | biostudies-literature