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Caspian Journal of Internal Medicine 2024One of the most effective treatments for patients with acute ischemic stroke (AIS) is intravenous recombinant tissue plasminogen activator (rtPA) which can minimize...
Factors affecting improvement after intravenous administration of recombinant tissue plasminogen activator (rtPA) among patients with acute ischemic stroke: A historical cohort study.
BACKGROUND
One of the most effective treatments for patients with acute ischemic stroke (AIS) is intravenous recombinant tissue plasminogen activator (rtPA) which can minimize mortality and morbidities. In this historical cohort study, we investigate the factors affecting clinical outcomes after IV thrombolysis for AIS.
METHODS
We included 87 patients with acute ischemic stroke who were treated with rtPA between 2015 and 2019. Demographic and clinical data were recorded. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the clinical outcomes.
RESULTS
36 patients showed lack of improvement at discharge. In unadjusted model, hypercholesterolemia was the only predictor of lack of improvement (P= 0.043; OR=0.304; CI= 0.096-0.963). After adjusting, hypertension (P= 0.018; OR= 0.18; CI= 0.043-0.749) and hypercholesterolemia (P= 0.008; OR= 8.68; CI= 1.773-42.54) were independent determinants of lack of clinical response. To evaluate risk factors in association with the duration of hospitalization, we found variables which lengthened hospitalization span including; age over 60 years (HR= 0.42 P= 0.002), hypercholesterolemia (HR= 2.19 P= 0.031), Angiotensin-converting enzyme (ACE) Inhibitors consumption (HR= 1.87 P= 0.022), and type of infarction (non-lacunar) (HR= 0.51 P= 0.026). Results indicated no considerable relationship between dose of rtPA and the appropriate response to treatment (OR=8.686 P= 0.324).
CONCLUSION
The closer dose of rtPA goes up to standard range, the more chance of improvement will gain without increasing the risk of symptomatic intra-cerebral hemorrhage (SICH). Determining factors involved in intravenous reperfusion outcomes help physicians to identify the patients who benefit the most from rtPA.
PubMed: 38807733
DOI: 10.22088/cjim.15.2.251 -
Indian Journal of Ophthalmology Jun 2024Submacular hemorrhage (SMH) is a sight-threatening disorder. Choroidal neovascularization secondary to age-related macular degeneration, polypoidal choroidal...
BACKGROUND
Submacular hemorrhage (SMH) is a sight-threatening disorder. Choroidal neovascularization secondary to age-related macular degeneration, polypoidal choroidal vasculopathy, trauma, angioid streaks, and pathological myopia are a few important causes. The conventional treatment of massive SMH is vitrectomy with manual removal of the clot with extensive retinectomy with/without tissue plasminogen activator (tPA). The usual dose of subretinal tPA is 10-25 µg.
PURPOSE
To describe a new surgical approach in a case of massive SMH with retinal detachment without retinectomy.
SYNOPSIS
In our case of near total hemorrhagic retinal detachment due to subretinal hemorrhage caused by trauma (road traffic accident), the patient presented with a visual acuity of counting fingers. Core vitrectomy was performed and posterior vitreous detachment was induced. The locations for retinotomy to inject and aspirate subretinal blood were selected at the maximum height of retinal elevation near the arcades. Recombinant tPA (10 µg/0.1 ml concentration; 0.3 ml injected in two locations) was injected subretinally with a 23-G soft tip cannula in the superotemporal and inferonasal quadrant causing subretinal bleb formation. Subsequently, the surgeon waited for approximately 20 min on the table for the liquefaction of the clot. The liquefied blood and tPA were drained with a silicone soft tip. Endolaser was performed at the retinotomy site and 1000cs silicone oil was injected. No signs of toxicity such as vitritis, vasculitis, or retinal necrosis were noted.
HIGHLIGHTS
Our unique technique of high-dose intraoperative subretinal tPA (60 µg) is safe and helpful in rapid clot lysis and recovery of visual acuity. The patient gained a visual acuity of 20/80 from counting fingers after 1 month of surgery and 20/60 after silicone oil removal. A high dose of tPA aids in the immediate aspiration of blood from a small retinotomy. A 23-G soft tip was used instead of a 41-G subretinal cannula to inject a large quantity of subretinal tPA.
VIDEO LINK
https://youtu.be/JzZBDUfa3NA.
Topics: Humans; Tissue Plasminogen Activator; Retinal Hemorrhage; Vitrectomy; Fibrinolytic Agents; Visual Acuity; Tomography, Optical Coherence; Male; Fundus Oculi; Fluorescein Angiography; Dose-Response Relationship, Drug
PubMed: 38804808
DOI: 10.4103/IJO.IJO_2295_23 -
Neurology International May 2024In recent years, there has been a growing interest in factor XIII in ischaemic stroke. The study's main aim was to assess the usefulness of factor XIII concentration...
BACKGROUND AND AIMS
In recent years, there has been a growing interest in factor XIII in ischaemic stroke. The study's main aim was to assess the usefulness of factor XIII concentration determination in patients with acute ischaemic stroke (AIS) treated with thrombolysis with recombinant tissue plasminogen activator (t-PA).
METHODS
The study was conducted in two groups of 84 patients with AIS: group I-with thrombolytic therapy and group II-without thrombolysis. A physical examination, neurological status (using the National Institutes of Health Stroke Scale, NIHSS), daily patients' activities measured with the Barthel Index and Modified Rankin Scale (mRS), and blood parameters were conducted on day 1 and day 7. The following parameters were assessed: highly sensitive C-reaction protein (CRP), fibrinogen, D-dimers (DD), neutrophil-lymphocyte ratio (NLR index), and the concentration of factor XIII-A.
RESULTS
In group I, the concentration of XIII-A decreased significantly between day 1 and 7 ( < 0.001). In group I, the concentration of XIII-A on day 7 in Total Anterior Circulation Infarct (TACI) was significantly lower than in non-TACI stroke. XIII-A concentration in group I was significantly lower in patients < 31 points with Acute Stroke Registry and Analysis of Lausanne (ASTRAL). A greater decrease in XIII-A between the first sampling on day 1 and the second sampling on day 7 was associated with a worse patient neurological state in group I.
CONCLUSIONS
In patients with AIS treated with t-PA, factor XIII concentrations decrease in the acute phase of stroke, and the largest decrease occurs in the TACI stroke. Determination of factor XIII concentration in patients with AIS can be used in clinical practice as an additional parameter supporting the assessment of stroke severity and may play a role in the prognosis; lower factor XIII-A activity may be a predictor of a worse prognosis.
PubMed: 38804480
DOI: 10.3390/neurolint16030041 -
The Western Journal of Emergency... May 2024Alteplase (tPA) is the initial treatment for acute ischemic stroke. Current tPA guidelines exclude patients who took direct oral anticoagulants (DOAC) within the prior...
BACKGROUND
Alteplase (tPA) is the initial treatment for acute ischemic stroke. Current tPA guidelines exclude patients who took direct oral anticoagulants (DOAC) within the prior 48 hours. In this propensity-matched retrospective study we compared acute ischemic stroke patients treated with tPA who had received DOACs within 48 hours of thrombolysis to those not previously treated with DOACs, regarding three outcomes: mortality; intracranial hemorrhage (ICH); and need for acute blood transfusions (as a marker of significant blood loss).
METHODS
Using the United States cohort of 54 healthcare organizations in the TriNetx database, we identified 8,582 stroke patients treated with tPA on DOACs within 48 hours of thrombolysis and 46,703 stroke patients treated with tPA not on DOACs since January 1, 2012. We performed propensity score matching on demographic information and seven prior clinical diagnostic groups, resulting in a total of 17,164 acute stroke patients evenly matched between groups. We recorded mortality rates, frequency of ICH, and need for blood transfusions for each group over the ensuing 7- and 30-day periods.
RESULTS
Patients treated with tPA on DOACs had reduced mortality (3.3% vs 7.3%; risk ratio [RR] 0.456; < 0.001), fewer ICHs (6.8% vs 10.1%; RR 0.678; < 0.001), and less risk of major bleeding as measured by frequency of blood transfusions (0.5% vs 1.5%; RR 0.317; < 0.001) at 7 days post thrombolytic, than the tPA patients not on DOACS. Findings for 30 days post-thrombolytics were similar/statistically significant with lower mortality rate (7.2% vs 13.1%; RR 0.550; < 0.001), fewer ICHs (7.6% vs 10.8%; RR 0.705; < 0.001), and fewer blood transfusions (0.9% vs 2.0%; RR 0.448; < 0.001).
CONCLUSION
Acute ischemic stroke patients treated with tPA who received DOACs within 48 hours of thrombolysis had lower mortality rates, reduced incidence of ICH, and less blood loss than those not on DOACs. Our study suggests that prior use of DOACs should not be a contraindication to thrombolysis for ischemic stroke.
Topics: Humans; Retrospective Studies; Female; Male; Aged; Thrombolytic Therapy; Tissue Plasminogen Activator; Fibrinolytic Agents; Anticoagulants; United States; Propensity Score; Administration, Oral; Ischemic Stroke; Middle Aged; Intracranial Hemorrhages; Stroke; Aged, 80 and over; Blood Transfusion
PubMed: 38801047
DOI: 10.5811/westjem.18063 -
Pharmaceutics Apr 2024Plasminogen activators, such as recombinant tissue-type plasminogen activators (rtPAs), while effective in treating thromboembolic diseases, often induce hemorrhagic...
Plasminogen activators, such as recombinant tissue-type plasminogen activators (rtPAs), while effective in treating thromboembolic diseases, often induce hemorrhagic complications due to non-specific enzyme activities in the systemic circulation. This study evaluated the targeting efficiency, efficacy, biodistribution, and potential toxicity of a rtPA covalently attached to chitosan-coated magnetic nanoparticles (chitosan-MNP-rtPA). The thrombolytic activity of a chitosan-MNP-rtPA was preserved by protection from an endogenous plasminogen activator inhibitor-1 (PAI-1) in whole blood and after circulation in vivo, as examined by thromboelastometry. Single-photon emission computed tomography (SPECT) demonstrated real-time retention of a Tc-MNP-rtPA induced by magnet application in a rat embolic model; an 80% reduction in rtPA dosage for a chitosan-MNP-rtPA with magnetic guidance was shown to restore blood flow. After treatment, iron deposition was observed in the reticuloendothelial systems, with portal edema and neutrophil infiltration in the liver at a ten-fold higher dose but not the regular dose. Nevertheless, no liver or renal toxicity was observed at this higher dose. In conclusion, the liver may still be the major deposit site of rtPA nanocomposites after targeted delivery; chitosan-coated MNPs are potentially amenable to target therapeutics with parenteral administration.
PubMed: 38794257
DOI: 10.3390/pharmaceutics16050596 -
Journal of Personalized Medicine May 2024Inflammation during the perioperative period of joint arthroplasty is a critical aspect of patient outcomes, influencing both the pathophysiology of pain and the healing... (Review)
Review
Interactions and Trends of Interleukins, PAI-1, CRP, and TNF-α in Inflammatory Responses during the Perioperative Period of Joint Arthroplasty: Implications for Pain Management-A Narrative Review.
Inflammation during the perioperative period of joint arthroplasty is a critical aspect of patient outcomes, influencing both the pathophysiology of pain and the healing process. This narrative review comprehensively evaluates the roles of specific cytokines and inflammatory biomarkers in this context and their implications for pain management. Inflammatory responses are initiated and propagated by cytokines, which are pivotal in the development of both acute and chronic postoperative pain. Pro-inflammatory cytokines play essential roles in up-regulating the inflammatory response, which, if not adequately controlled, leads to sustained pain and impaired tissue healing. Anti-inflammatory cytokines work to dampen inflammatory responses and promote resolution. Our discussion extends to the genetic and molecular influences on cytokine production, which influence pain perception and recovery rates post-surgery. Furthermore, the role of PAI-1 in modulating inflammation through its impact on the fibrinolytic system highlights its potential as a therapeutic target. The perioperative modulation of these cytokines through various analgesic and anesthetic techniques, including the fascia iliac compartment block, demonstrates a significant reduction in pain and inflammatory markers, thus underscoring the importance of targeted therapeutic strategies. Our analysis suggests that a nuanced understanding of the interplay between pro-inflammatory and anti-inflammatory cytokines is required. Future research should focus on individualized pain management strategies.
PubMed: 38793119
DOI: 10.3390/jpm14050537 -
Journal of Education and Health... 2024The benefits of using Alteplase are time-dependent. This study aimed to evaluate delays between the onset of symptoms and the administration of Alteplase and related...
BACKGROUND
The benefits of using Alteplase are time-dependent. This study aimed to evaluate delays between the onset of symptoms and the administration of Alteplase and related factors in patients with acute ischemic stroke (AIS).
MATERIALS AND METHODS
In this cross-sectional study, 60 AIS patients receiving Alteplase were selected by census sampling from July 2020 to July 2021 from the eligible patients referred to Shahid Beheshti Hospital in Kashan, Iran. The data collection tool was a researcher-made questionnaire containing demographic information, time periods from the onset of symptoms to the injection of Alteplase, and associated factors. The required information was collected from the patients, their relatives, their health records, and Kashan Emergency Medical Service (EMS) information system. Data were analyzed in SPSS-16.
RESULTS
Eighty-five percent of the 60 patients participating in the study were transferred to the hospital by EMS ambulances. The mean time intervals between different phases were as follows: Onset-To-Door (OTD) time 81.35 ± 33.76 minutes; Door-To-CT (DTC) scan time 16.12 ± 17.46 minutes; Door-To-Needle (DNT) time 51.30 ± 26.14 minutes; and the overall Onset-To-Needle (ONT) time 133.75 ± 39.17 minutes. Also, the mean ONT in people transferred by EMS was about 129 minutes, and the longest prehospital delay in these patients was related to the time between the arrival of the EMS ambulance to the hospital. Marital status and geographical location where the stroke had occurred showed a significant relationship with prehospital delay and pre-hospital notification (PHN) by EMS But there was no relationship between underlying diseases or economic status and prehospital delays; also, the patient's diastolic blood pressure at the time of receiving Alteplase showed a significant relationship with in-hospital delay.
CONCLUSION
The findings of the study showed that the majority of people trust and use EMS ambulances to transfer to the hospital and the time spent in different stages, from the onset of symptoms to the injection of the thrombolytic drug, was in an acceptable range in the patients.
PubMed: 38784291
DOI: 10.4103/jehp.jehp_1685_22 -
Implementation of a Tenecteplase Protocol for Treatment of Acute Ischemic Stroke in a Health System.Innovations in Pharmacy 2024. Alteplase is the standard of care for intravenous thrombolytic treatment of acute ischemic stroke, but recent evidence suggests that tenecteplase may be as safe and...
. Alteplase is the standard of care for intravenous thrombolytic treatment of acute ischemic stroke, but recent evidence suggests that tenecteplase may be as safe and efficacious. The purpose of this study was to evaluate the direct cost savings, safety, and efficacy outcomes following the implementation of a tenecteplase protocol for acute ischemic stroke in the emergency departments within a health system. . A multicenter retrospective medical record review was performed for 4 months prior to protocol implementation on patients who received alteplase and for 4 months post-implementation on patients who received tenecteplase. The primary outcome was the direct cost difference associated with tenecteplase. Secondary outcomes included reduction in National Institutes of Health Stroke Scale 24 hours after thrombolytic therapy, door-to-needle time, symptom onset to intravenous thrombolysis time, incidence of adverse effects, and death. . Pre-implementation, 102 received alteplase and post-implementation, 117 received tenecteplase. Four months of utilization of tenecteplase resulted in direct cost savings of $209,476.80 for the health system, which translates to roughly $2,000 per patient. Reduction in the National Institutes for Health Stroke Scale were similar between the two groups with -3.96 in alteplase and -3.18 in tenecteplase (p = 0.952). Median door-to-needle time was 44.5 minutes in alteplase and 49 minutes in tenecteplase. Adverse events occurred in 19 patients in alteplase and 19 in tenecteplase (p = 0.573). Death occurred in 9 patients in alteplase and 14 patients in tenecteplase (p = 0.376). . A tenecteplase protocol was successfully implemented in the healthcare system resulting in direct cost savings with no significant differences in adverse events.
PubMed: 38779109
DOI: 10.24926/iip.v15i1.5801 -
Ultrasound in Medicine & Biology May 2024Standard treatment for deep vein thrombosis (DVT) involves catheter-directed anticoagulants or thrombolytics, but the chronic thrombi present in many DVT cases are often...
OBJECTIVE
Standard treatment for deep vein thrombosis (DVT) involves catheter-directed anticoagulants or thrombolytics, but the chronic thrombi present in many DVT cases are often resistant to this therapy. Histotripsy has been found to be a promising adjuvant treatment, using the mechanical action of cavitating bubble clouds to enhance thrombolytic activity. The objective of this study was to determine if histotripsy enhanced recombinant tissue plasminogen activator (rt-PA) thrombolysis in highly retracted porcine clots in vitro in a flow model of occlusive DVT.
METHODS
Highly retracted porcine whole blood clots were treated for 1 h with either catheter-directed saline (negative control), rt-PA (lytic control), histotripsy, DEFINITY and histotripsy or the combination of rt-PA and histotripsy with or without DEFINITY. Five-cycle, 1.5 MHz histotripsy pulses with a peak negative pressure of 33.2 MPa and pulse repetition frequency of 40 Hz were applied along the clot. B-Mode and passive cavitation images were acquired during histotripsy insonation to monitor bubble activity.
RESULTS
Clots subjected to histotripsy with and without rt-PA exhibited greater thrombolytic efficacy than controls (7.0% flow recovery or lower), and histotripsy with rt-PA was more efficacious than histotripsy with saline (86.1 ± 10.2% compared with 61.7 ± 19.8% flow recovery). The addition of DEFINITY to histotripsy with or without rt-PA did not enhance either thrombolytic efficacy or cavitation dose. Cavitation dose generally did not correlate with thrombolytic efficacy.
CONCLUSION
Enhancement of thrombolytic efficacy was achieved using histotripsy, with and without catheter-directed rt-PA, in the presence of physiologic flow. This suggests these treatments may be effective as therapy for DVT.
PubMed: 38777639
DOI: 10.1016/j.ultrasmedbio.2024.04.002 -
Stroke and Vascular Neurology May 2024Racism contributes to higher comorbid risk factors and barriers to preventive measures for black Americans. Advancements in systems of care, tissue plasminogen activator...
BACKGROUND
Racism contributes to higher comorbid risk factors and barriers to preventive measures for black Americans. Advancements in systems of care, tissue plasminogen activator (tPA) availability and endovascular thrombectomy (ET) have impacted practice and outcomes while outpacing contemporary investigation into acute ischaemic stroke (AIS) care disparities. We examined whether recent data suggest ongoing disparity in AIS interventions and outcomes, and if hospital characteristics affect disparities.
METHODS
We examined 2016-2019 fee-for-service Medicare inpatient data. We ran unadjusted logistic regression models to calculate ORs and 95% CI for two interventions (tPA and ET) and four outcomes (inpatient mortality, 30-day mortality, discharge home and outpatient visit within 30 days), with the main predictor black versus white race, additionally adjusting for demographics, hospital characteristics, stroke severity and comorbidities.
RESULTS
805 181 AIS admissions were analysed (12.4% black, 87.6% white). Compared with white patients, black patients had reduced odds of receiving tPA (OR 0.71, 95% CI 0.69 to 0.74, p<0.0001) and ET (0.69, 95% CI 0.65 to 0.72, p<0.0001). After tPA, black patients had reduced odds of 30-day mortality (0.77, 95% CI 0.72 to 0.82, p<0.0001), discharge home (0.72, 95% CI 0.68 to 0.77, p<0.0001) and outpatient visit within 30 days (0.89, 95% CI 0.84 to 0.95, p=0.0002). After ET, black patients had reduced odds of 30-day mortality (0.71, 95% CI 0.63 to 0.79, p<0.0001) and discharge home (0.75, 95% CI 0.64 to 0.88, p=0.0005). Adjusted models showed little difference in the magnitude, direction or significance of the main effects.
CONCLUSIONS
Black patients were less likely to receive AIS treatments, and if treated had lower likelihood of 30-day mortality, discharge home and outpatient visits. Despite advancements in practice and therapies, racial disparities remain in the modern era of AIS care and are consistent with inequalities previously identified over the last 20 years. The impact of hospital attributes on AIS care disparities warrants further investigation.
PubMed: 38777349
DOI: 10.1136/svn-2023-003051