جستجوی مقالات مرتبط با کلیدواژه « Tissue Plasminogen Activator » در نشریات گروه « پزشکی »

Intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) has been considered as primary therapy in ischemic stroke patients. Alteplase is prescripted as the thrombolytic therapy for more than two decades. Tenecteplase is a new type of tPA that is reported to have beneficial effects in recent years. The present research focused on the effectiveness and the side effects of tenecteplase in the ischemic stroke.

Here we administrated 0.25 mg/kg tenecteplase in 36 individuals with acute ischemic stroke in the first 4.5 hours of stroke occurrence. The NIHSS in baseline, 24 hours, 7 days after and the modified Rankin scale (mRS) at 90 days were assessed. The primary efficacy outcome was reduction of at least 4 points in the NIHSS during 7 days and the secondary efficacy outcome was defined as mRS 0 and 1 at 90 days. The safety outcome was evaluated based on the symptomatic intracranial hemorrhage (ICH) and death occurance during 90 days.

The mean NIHSS at baseline was 12.7±4.6, and the mean NIHSS corresponding to 24 hours after admission was 9.6±4.8. The mean 7-day NIHSS was 7.6±4.4. The primary and secondary efficacy outcomes were met in 18 (50%) and 22 (61.1 %) of the patients respectively. Symptomatic ICH was observed in one patient with lung cancer who died of respiratory failure.

This study confirmed the efficacy and safety of tenecteplase in thrombolysis for acute ischemic stroke treatment. Tenecteplase appears to be an appropriate therapy as thrombolytic agent against ischemic stroke.

Strokes rank among the leading causes of death and disability worldwide, with acute ischemic stroke (AIS) on the rise in Iran. Thrombolytic drugs constitute a primary treatment for ischemic stroke. However, due to limited studies in Iran, there exists hesitation among physicians regarding their administration. This study aims to assess the efficacy of these drugs on AIS patients.

In a clinical trial, 80 patients with ischemic stroke were divided into treatment and control groups. Both groups were assessed upon admission and 72 hours later using the National Institutes of Health Stroke Scale (NIHSS) and the Modified Rankin Scale (mRS) scores at discharge. The treatment group received Alteplase (0.9mg/kg), while the control group received standard care. Statistical analysis was performed using SPSS 20.

The mean NIHSS ± SD scores at admission and 72 hours later in the treatment group were 10.0±3.51 and 4.55±8.75, respectively, compared to 8.53±3.52 and 7.88±9.21 in the control group, showing a significant difference in favor of the treatment group (P < 0.001). Similarly, the mean mRS± SD score in the treatment group was 1.68±1.79, significantly lower than the control group's 3.15±1.61 (P < 0.001).

 Intravenous Alteplase administration proved effective in treating patients with ischemic stroke, significantly reducing neurological complications and disabilities compared to standard medical care.

Intrapleural instillation of fibrinolytic agents is novel in treating empyema. Although the efficacy of this method for treating empyema remains a topic of debate among experts, several studies have shown that the results of this technique are almost equivalent to surgical operations in the lower stages of the disease. However, in more advanced stages of empyema, surgery may be required. Despite the worldwide use of fibrinolytic agents instead of surgical procedures, the benefits of using these agents postoperatively still need to be defined.

In this prospective study, we aimed to compare the effects of streptokinase and alteplase in managing empyema in patients who underwent any surgical operations.

We prospectively compared the outcomes of using alteplase and streptokinase in children who underwent surgical operations for empyema between 2015 and 2022. Following the surgery, fibrinolytic agents were instilled through thoracostomy tubes according to a specific protocol. The length of stay, frequency of complications, need for another surgery, and mortality were measured in each group.

Among 53 patients who met the inclusion criteria, 31 (58.5%) patients received streptokinase postoperatively, while the others were treated using alteplase. The length of stay after the surgery, wound infection, and mortality rate did not differ significantly between the groups (P-value = 0.394, 0.080, 0.767, respectively). However, the need for another surgery due to unexpanded lungs was significantly lower in the alteplase group (0% vs. 19.4%, P = 0.028).

Alteplase as an intrapleural fibrinolytic is more effective than streptokinase in patients who underwent surgical operations due to empyema. The need for another surgery following the instillation of alteplase through chest tubes postoperatively may be decreased.

According to the American Heart Association and American Stroke Association (AHA/ASA) guidelines, in acute stroke, the door-to-computed tomography (CT) scan (DTC) time should be less than 25 minutes, and time to injection of recombinant tissue-type plasminogen activator (r-tPA) [door-to-needle (DTN) time] should be less than 60 minutes.

We had a tendency to prospectively collect the clinical and time information of patients who received r-tPA during one year after the initiation of prehospital notification (PN). Patients were divided into three groups, covering patients transferred by Emergency Medical Service (EMS) with and without PN, and non-EMS. We then contrasted the impact of EMS with PN and EMS use on onset-to-needle time (ONT), and the neurological outcome. Good outcome was determined as Modified Rankin Scale (MRS) ≤ 2 at 3-month follow-up.

Among 102 studied patients, 64% were transferred by EMS, of whom 53.9% entered PN. Compared with non-PN groups, EMS with PN group showed significantly shorter DTN and DTC time, as well as ONT.

Our study showed that EMS with PN, rather than EMS, significantly improved stroke outcome by shortening of ONT.

Severe hyperkalemia usually presents as cardiac or neurologic manifestations. We report a case of a 63-year-old Caucasian woman, who was admitted to Namazi Hospital, affiliated with Shiraz University of Medical Sciences (Shiraz, Iran) in August 2019. The patient suffered from left-sided weakness and slurred speech for one hour prior to admission. Initially, the patient was treated for acute ischemic stroke, and an intravenous recombinant tissue plasminogen activator (IV-rTPA) was prescribed. However, further investigations showed severe hyperkalemia. Hemiparesis and slurred speech improved significantly with appropriate management of hyperkalemia. To the best of our knowledge, this is the first case of hyperkalemia masquerading as acute ischemic stroke without evidence of concomitant central nervous system malignancies, large vessel atherosclerosis, or recreational drug abuse. Stroke mimics due to hyperkalemia should be considered in any patient with simultaneous sudden onset of focal neurologic deficits and tall peaked T waves, particularly in the context of renal failure and a history of potassium-sparing drug use.

One of the main parts of the early treatment of Acute Ischemic Stroke (AIS) is the attitude and knowledge of Emergency Medicine (EM) specialists. This study aimed to investigate the knowledge and attitude of emergency physicians working in Iran about the prescription of tissue Plasminogen Activator (tPA) in AIS. This was a cross-sectional questionnaire-based study including EM physicians working in different cities of Iran in 2020. A previously used English questionnaire was translated into Persian. After face validity and reliability assessment, the final questionnaire was designed as a Google form and sent to 400 EM professionals. 128 physicians filled in the forms. 64.8% of participants had sufficient attitude and 68% had sufficient knowledge about tPA treatment in AIS. The knowledge regarding tPA treatment was higher in the age>40 years, male gender and physicians with up-to-date information (P<0.05), but no significant association was found for the attitude. Logistic regression analysis showed that the amount of information about tPA administration in AIS (OR=3.475, 95% CI =1.242-9.723, p=0.018) and age (OR=0.336, 95% CI = 0.130-0.865, p=0.024) had the greatest impact on the level of knowledge for tPA treatment. About two-thirds of EM professionals in Iran had sufficient knowledge and attitude about tPA administration in AIS. Having up-to-date information and age>40 years were the major predictors of higher knowledge of AIS treatment. Holding some training workshops together with strengthening infrastructures such as establishing intensive stroke units would help to increase the use of tPA in AIS in Iran.

Rates of intracranial hemorrhage (ICH) after intravenous thrombolysis (IVT) differ depending on ethnicity, one reason that few Eastern countries have approved a lower dose of alteplase. Data in this regard are scarce in the Middle Eastern region.

The present retrospective study was performed on data extracted from the Safe Implementation of Treatments in Stroke (SITS) registry. Computed tomography (CT) image analysis was based on the SITS-Monitoring Study (SITS-MOST) definition for symptomatic ICH (SICH). Functional outcome at 3 months was assessed using the modified Rankin Scale (mRS). Multivariate logistic regression including adjusted analysis was used for comparison between groups.

Of 6615 patients, 1055 were enrolled. A total of 86% (n = 906) received a standard dose and 14% (n = 149) received a low dose of alteplase. Favorable 3-month outcome was achieved in 481 (53%) patients in the standard group and 71 (48%) patients in the low-dose group [adjusted odds ratio (AOR) = 1.24, 95% confidence interval (CI): 0.87-1.75, P = 0.218]. SICH occurred in 14 (1.5%) patients in the standard group and 3 (2%) patients in the low-dose group [odds ratio (OR) = 2.77, 95% CI: 0.36-21.04, P = 0.120]. At 3 months, mortality occurred in 145 (16.0%) patients in the standard group and 29 (19.4%) patients in the low-dose group (OR = 1.22, 95% CI: 0.78-1.91, P = 0.346).

Low-dose compared to standard-dose alteplase for patients with acute ischemic stroke (AIS) was not associated with fewer hemorrhagic events and there was no significant difference in the favorable 3-month outcome (mRS: 0-2) or mortality rate.

Delayed tissue plasminogen activator (tPA) thrombolysis is accompanied by different complications in stroke patients. Studies reported sex differences in stroke therapy. Ischemic postconditioning (PC) unveils neuroprotection in stroke models. In this study, we investigate the combined effect of delayed tPA therapy and PC procedure during an embolic stroke experimental model in female rats.  Female Wistar rats were randomly divided into control (saline), tPA, PC, and tPA+PC groups after stroke induction via clot injection to the middle cerebral artery. tPA treatment was initiated 6 hr after stroke, and PC procedure was performed 6.5 hr post-ischemia induction (occlusion: 10 sec; reopening: 30 sec; 5 cycles). The cerebral blood flow (CBF) was recorded up to 60 min from IV tPA injection time. The parameters of brain edema, infarct volume, disruption of the blood-brain barrier (BBB), behavioral tests, and matrix metalloproteinases-9 (MMP-9) were evaluated. This study revealed that PC conduction prevents excessive CBF increase by tPA and played a protective role in infarct volume reduction (P<0.05). The combination of PC and tPA reduced the infarct volume, brain edema, and protected BBB. tPA+PC could alleviate neurobehavioral disorders compared with control or tPA. Moreover, PC had the capability of MMP-9 reduction when combined with delayed tPA (P<0.05). Conduction of PC not only alleviated some stroke complications but also enhanced the therapeutic time window of tPA in female rats under embolic stroke.

Thrombolytic therapy is the recommended treatment of acute ischemic stroke. It is crucial to evaluate the treatment results with recombinant Tissue Plasminogen Activator (r-TPA) in patients with acute stroke.

This study aimed to evaluate treatment outcomes with r-TPA in patients with acute stroke in a referral stroke center in Iran.

In this retrospective study, 87 patients with symptoms of acute stroke were examined. They were referred to a stroke center in Gilan Province, Iran, from June 2016 to April 2020 and received r-TPA (0.9 mg/kg). Demographic information, the time interval between the onset of symptoms and r-TPA administration, complications, and National Institutes of Health Stroke Scale (NIHSS) upon arrival and discharge and death of patients were extracted from their hospital files. The paired t-test, independent t-test, and Pearson correlation test were used to compare variables using IBM SPSS for Windows version 20.0 (IBM Corp., Armonk, NY, USA).

The Mean±SD of NIHSS reduced from 14.7±6.4 to 8.9±7.6 (P<0.001). The most common complication was Intracerebral Hemorrhage (ICH) (12.6%). The hospital mortality rate was 23%. ICH occurred among 40% (n=8) of those who expired, and 4.47% (n=3) of them survived, and this difference was significant (P<0.001).

The recovery with r-TPA administration in the stroke center was acceptable. Mortality and ICH occurrence rates were higher than other non-Iranian studies. It seems that we should change the case selection criteria and prescription dose to achieve better results of treatment with TPA.

Intravenous (IV) recombinant tissue Plasminogen Activator (rtPA) (IV-rtPA) is the only FDA-approved pharmacological therapy for treatment in acute ischemic stroke and the administration of IV-rtPA is crucially time-dependent.

This study aimed to evaluate symptom-to-needle time and factors associated with the prehospital delay in patients with acute ischemic stroke referred to Poursina Hospital, a referral hospital in the north of Iran.

In this cross-sectional study, all patients with acute stroke referred to Poursina Hospital from June to December 2016 were evaluated. The study data were extracted from the patients’ records. SPSS v. 21 was used to analyze the obtained data. The independent samples t-test and the Chi-square test were used to explore the appropriate relation of variables.

A total of 322 patients were included. Their mean age was 74.4 years and 55.6% were male. According to findings, only 74 patients (22.98%) were transferred to the hospital via Emergency Medical Service (EMS), most of them (64.86%) arrived at the right time. There is a significant relationship between EMS transfer use and arriving at the hospital at the right time. Overall, 13.9% of patients received IV rtPA, and 75.5% of the patients received rtPA in less than 60 minutes. Among the patients arrived in the golden time, the average times to treatment were as follows: onset-to-door (OTD), 105 min; door-to-admission, 3 min; admission-to-doctor, 7 min; doctor-to-Computed Tomography (CT), 15 min; CT-to-treatment, 26 min; symptom to needle time, 152 min; and door-to-needle time (DNT), 49 min.

According to this study, although the two-third of eligible patients were transferred to the hospital at the right time, the rate of using EMS for patient transportation is low.

Reperfusion and neuroprotection are 2 main treatment strategies exist for management of pa- tients with ischemic stroke. This study aimed to assess the 3-month outcome of patients who underwent throm- bolytic therapy following ischemic stroke.

In the present prospective cohort study, the 3-month out- come of patients (mortality, disability) with acute ischemic stroke admitted to neurology department an edu- cational hospital, Kermanshah, Iran, from 2016 to 2019, who had received thrombolytic therapy was assessed. National Institute of Health Stroke Scale (NIHSS) and Modified Rankin Score (MRS) were used for measuring the degree of disability (on admission, at the time of discharge and 3 months after thrombolytic therapy). Re- sults: 217 patients with the mean age of 66.40 ± 13.37 (27 – 97) years were studied (55.3% male). There was no significant correlation between decrease in NIHSS score and age (p = 0.44), sex (p = 0.082), time interval be- tween initiation of symptoms (p = 0.104), and blood pressure on admission (p = 0.156). However, patients with blood sugar lower than 144 had better 3-month outcome (p = 0.045). Additionally, there was no significant cor- relation between the rate of decrease in MRS score and age (p = 0.813), sex (p = 0.875), time interval between initiation of symptoms (p = 0.495), and blood pressure on admission (p = 0.264). However, patients with blood sugar lower than 144 had better 3-month outcome (p = 0.022). 47 (21.7%) patient died and 170 (78.3%) were discharged. Mean age of the patients who died (73.70 ± 11.85 versus 64.39 ± 13.09 years; p < 0.0001) and their NIHSS score on admission (13.22 ± 6.01 versus 11.28 ± 5.70; p = 0.045) were significantly higher. In other words, the odds of mortality was 3.19 times in patients over 60 years of age (95% confidence interval (CI): 1.18 – 8.62) and 1.83 times in patients with NIHSS score over 12 (95% CI: 0.92 – 3.61).

There was no significant correlation between 3-month disabilities of stroke patients underwent thrombolytic therapy and age, sex, time from initiation of symptoms, or vital signs on admission. Patients with a blood sugar lower than 144 had better 3-month outcome.

Currently, the most available treatment for acute ischemic stroke (AIS) is thrombolytic therapy with recombinant tissue plasminogen activator (r-TPA). A challenge in r-TPA therapy is the prediction of recovery in each case.

The aim was to find a possible relationship between the cerebral oximetry indexes and the clinical outcome of r-TPA therapy to assess the cerebral oximetry as a non-invasive monitoring agent for therapy.

The inclusion criteria were all patients with AIS who received r-TPA. The neurologic status was evaluated based on the national institutes of health stroke scale (NIHSS) score at arrival, and after a period of 24 hours. In addition, the levels of brain oxygenation in both hemispheres were measured before and continuously over the first 24 hours after r-TPA injection, using an oximetric sensor in the frontal lobes. The clinical success was defined as a 4-point improvement from the baseline NIHSS.

Total 44 patients with the mean age of 58.2 ± 2.18 years were enrolled, of whom 68.18% were male. Twenty-eight patients remained clinically unimproved and 16 patients were improved. A significant difference was found in the mean surface area under the brain oximetric curve in the 24 hour, in the affected hemisphere in the improved group, compared to the unimproved group (P = 0.007). There was a significant difference between the mean increase in brain oxygenation within 24 hours in the improved and unimproved groups (P = 0.002).

It is likely that, The cerebral oximetry could contribute to predict the likelihood of r-TPA prognosis in patients with AIS.

The expression of bio-therapeutic proteins in mammalian cells, such as CHO, attains high homogeneity related to post-translational modifications. Although CHO remains the most popular cell line for bestselling biotherapeutic proteins on the market, there are still drawbacks such as expensive culture media, long time line, and high drug cost. Recently, researches on a novel Leishmania protozoan system have confirmed that this low level eukaryote could represent a competitive alternative to the mammalian cell lines. The full length of coding sequence of modified tPA TNKase tenecteplase) was synthesized and cloned into an inducible expression vector of L. tarentolae T7-TR cells. The expression of the construct was driven by a Tet-inducible promoter. A Leishmania secretory signal sequence was also added to the expression cassette to facilitate the release of the recombinant protein into the medium. The secretory recombinant protein was analyzed and confirmed by SDS-PAGE and Western blot analyses. The expression level of TNKase in this novel system of L. tarentolae was 810 IU/mL after induction, which means that the percentage of expression increases two times compared to previous models in L. tarentolae. The TNKase activity was comparable with Activase. Our results suggested that expressed TNK (modified tPA) is functionally compatible with Activase regarding their effect on fibrinolysis. Given the post-translational modification similarities between mammalian and L. tarentolae, it is speculated that this system is capable of producing complex proteins such as tPA similar to mammalian system, with easier manipulation and non-expensive method.

Despite the development of Intravenous thrombolysis with tissue Plasminogen Activator (IVtPA) guidelines in each affiliated stroke center, protocol violations may be observed in each hospital with IVtPA facilities. An extensive search of scientific electronic databases including PubMed, OVID, Index Medicus, Index Copernicus, Google, ISI, and Scopus was performed with keywords of Thrombolysis, Off-label, Out of Protocol, Violation, Time Window, Dose, tPA, and Stroke terminated on 01 May 2018. Safety and functional outcomes are less favorable beyond three hours; however, the wider time window until 4.5 hours is recommended. Lower dose of alteplase (0.6 mg/kg) is approved in Japan. The proposed dose of tPA in Iranian population is similar to that of the Japanese. Overall, the outcomes in patients treated with off-label IVtPA or protocol violation were better than those of the controls based on registry data. There is little disagreement about time window of IVtPA. The dose of 0.6 mg/kg is used in some Asian countries with similar therapeutic results.