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Biomedicine & Pharmacotherapy =... May 2022Patients with ischemic heart disease receiving reperfusion therapy still need to face left ventricular remodeling and heart failure after myocardial infarction.... (Review)
Review
Patients with ischemic heart disease receiving reperfusion therapy still need to face left ventricular remodeling and heart failure after myocardial infarction. Reperfusion itself paradoxically leads to further cardiomyocyte death and systolic dysfunction. Ischemia/reperfusion (I/R) injury can eliminate the benefits of reperfusion therapy in patients and causes secondary myocardial injury. Mitochondrial dysfunction and structural disorder are the basic driving force of I/R injury. We summarized the basic relationship and potential mechanisms of mitochondrial injury in the development of I/R injury. Subsequently, this review summarized the natural products (NPs) that have been proven to targeting mitochondrial therapeutic effects during I/R injury in recent years and related cellular signal transduction pathways. We found that these NPs mainly protected the structural integrity of mitochondria and improve dysfunction, such as reducing mitochondrial division and fusion abnormalities, improving mitochondrial Ca overload and inhibiting reactive oxygen species overproduction, thereby playing a role in protecting cardiomyocytes during I/R injury. This data would deepen the understanding of I/R-induced mitochondrial pathological process and suggested that NPs are expected to be transformed into potential therapies targeting mitochondria.
Topics: Biological Products; Humans; Mitochondria; Myocardial Infarction; Myocardial Reperfusion Injury; Myocytes, Cardiac; Reactive Oxygen Species; Reperfusion
PubMed: 35366532
DOI: 10.1016/j.biopha.2022.112893 -
Neurological Sciences : Official... Jul 2022Intravenous thrombolysis (IT) and mechanical thrombectomy (MT) have significantly changed the clinical outcome of acute ischaemic stroke (AIS). Concerns about possible...
INTRODUCTION
Intravenous thrombolysis (IT) and mechanical thrombectomy (MT) have significantly changed the clinical outcome of acute ischaemic stroke (AIS). Concerns about possible complications often reduce the use of these treatment options for older patients, preferentially managed with antiplatelet therapy (AT). Aim of this study was to evaluate, in a population of middle-old (75-84 years) and oldest-old (≥ 85 years) subjects, the efficacy and safety of different treatments for AIS (IT, IT + MT, MT or AT), mortality and incidence of serious complications.
PATIENTS AND METHODS
All patients aged over 75 years admitted for AIS in two Stroke Units were enrolled. The physician in each case considered all treatment options and chose the best approach. NIHSS and modified Rankin Scale (mRS) were obtained and differences between admission and discharge scores, defined as delta(NIHSS) and delta(mRS), were calculated. The relationship between delta(NIHSS), delta(mRS) and type of procedure was analysed with a GLM/Multivariate model. Differences in mortality and incidence of serious complications were analysed with the chi-square test.
RESULTS
A total of 273 patients, mean age 84.07 (± 5.47) years, were included. The Delta(NIHSS) was significantly lower in patients treated with AT than in those treated with IT and MT (p < 0.009 and p < 0.005, respectively). Haemorrhagic infarction occurrence was significantly lower (p < 0.0001) among patients treated with AT (10.6%) or IT (16.7%) compared to MT (34.9%) or MT + IT (37.0%). No significant difference was observed for in-hospital mortality. Age did not influence the outcome.
CONCLUSIONS
Our results suggest that IT and AT are effective and relatively safe approaches in middle-aged and older patients.
Topics: Aged; Aged, 80 and over; Brain Ischemia; Humans; Middle Aged; Reperfusion; Retrospective Studies; Stroke; Thrombectomy; Treatment Outcome
PubMed: 35211810
DOI: 10.1007/s10072-022-05958-4 -
Cerebrovascular Diseases (Basel,... 2023We aimed to determine the treatment delay for ischemic stroke patients in Denmark.
INTRODUCTION
We aimed to determine the treatment delay for ischemic stroke patients in Denmark.
METHODS
A nationwide register-based study on acute ischemic stroke patients admitted through emergency medical services. Treatment delay comprised patient, prehospital, and in-hospital delay. Analyses were stratified according to length of prehospital delay (<3 vs. ≥3 h).
RESULTS
A total of 5,356 ischemic stroke episodes were included. The median onset-to-door time was 187 min, and 2,405 (43%) arrived at the stroke unit within 3 h. Overall, the median patient delay was 115 min. For early arrival (n = 2,280), patient delay was 27 min compared to 437 min for late arrivals (n = 2,448). Median prehospital delay varied by 9 min between early- and late-arriving patients. Approximately 48% of the early-arriving patients compared to 9% of the late-arriving patients received i.v. thrombolysis. For thrombectomy, the numbers were 10% and 3%, respectively. This corresponded to an unadjusted relative risk (RR) of 0.18 (95% CI: 0.16-0.21) and adjusted (age, sex, cohabitation status, and stroke severity) RR of 0.20 (95% CI: 0.18-0.23) for i.v. thrombolysis when comparing patients arriving later than 3 h with patients arriving earlier. For thrombectomy, the unadjusted and adjusted RRs were 0.30 (95% CI: 0.23-0.39) and 0.40 (95% CI: 0.31-0.52), respectively.
CONCLUSIONS
Patient delay remains the most important barrier for use of reperfusion therapy among acute ischemic stroke patients calling 1-1-2, whereas system delay seems independent of patient delay.
Topics: Humans; Ischemic Stroke; Time-to-Treatment; Thrombolytic Therapy; Stroke; Emergency Medical Services; Reperfusion; Denmark; Treatment Outcome
PubMed: 36315990
DOI: 10.1159/000526733 -
Journal of Atherosclerosis and... Jul 2022We evaluated the delay in stroke reperfusion therapy between the pre-coronavirus disease 2019 (COVID-19) period and the with-COVID-19 period, and compared this delay... (Comparative Study)
Comparative Study
AIM
We evaluated the delay in stroke reperfusion therapy between the pre-coronavirus disease 2019 (COVID-19) period and the with-COVID-19 period, and compared this delay between each phase of the with-COVID-19 period.
METHODS
Patients with acute ischemic stroke (AIS) undergoing intravenous thrombolysis and/or mechanical thrombectomy were selected from our single-center prospective registry. The time to perform reperfusion therapy were compared between patients admitted from March 2019 to February 2020 (pre-COVID-19 group) and those from March 2020 to February 2021 (with-COVID-19 group). Patients in the with-COVID-19 group were further divided into three 4-month-long subgroups (first-phase: March to June 2020; second-phase: July to October 2020; third-phase: November 2020 to February 2021), and the time delay of reperfusion therapy were compared between these subgroups.
RESULTS
Of 1,260 patients with AIS hospitalized in the study period, 265 patients were examined. Compared with the pre-COVID-19 group (133 patients; median age, 79 years), the with-COVID-19 group (132 patients; median age, 79 years) had a longer median door-to-imaging time (25 min vs. 27 min, P=0.04), and a longer door-to-groin puncture time (65 min vs. 72 min, P=0.02). In the three 4-month-long subgroups, the median door-to-needle time (49 min, 43 min, and 38 min, respectively; P=0.04) and door-to-groin puncture time (83 min, 70 min, and 61 min, P<0.01, respectively) decreased significantly during the with-COVID-19 period.
CONCLUSIONS
The delay in reperfusion therapy increased during the with-COVID-19 period compared with the pre-COVID-19 period. However, the door-to-needle time and door-to-groin puncture time decreased as time elapsed during the with-COVID-19 period.
CLINICALTRIALS
gov Identifier: NCT02251665.
Topics: Aged; COVID-19; Humans; Ischemic Stroke; Reperfusion; Stroke; Thrombectomy; Thrombolytic Therapy; Time-to-Treatment; Workflow
PubMed: 34393139
DOI: 10.5551/jat.63090 -
Advances in Clinical and Experimental... Jun 2022Patients with diabetes are known to have worse outcomes after an acute ischemic stroke (AIS) relative to those without diabetes. However, the impact of diabetes on the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with diabetes are known to have worse outcomes after an acute ischemic stroke (AIS) relative to those without diabetes. However, the impact of diabetes on the outcomes after the reperfusion therapy is poorly understood.
OBJECTIVES
This study investigated prognostic accuracy of diabetes and its association with clinical and safety outcomes in AIS patients receiving intravenous thrombolysis (IVT), endovascular thrombectomy (EVT), or both.
MATERIAL AND METHODS
Studies were identified from PubMed, Embase and Cochrane databases, using the following inclusion criteria: (a) AIS patients receiving reperfusion therapy, (b) age ≥ 18 years, (c) hemispheric stroke, and (d) the availability of comparative data between diabetic and nondiabetic groups and relevant poststroke outcomes. Random effects modelling was used to study the association of diabetes with functional outcome at discharge and at 90 days, mortality at 90 days, recanalization status, and postreperfusion safety outcomes, including rates of symptomatic intracerebral hemorrhage (sICH) and hemorrhagic transformation (HT). Forest plots of odds ratios (ORs) were generated.
RESULTS
Of a total cohort of 82,764 patients who received reperfusion therapy, 16,877 had diabetes. Diabetes significantly increased the odds of poor functional outcome at discharge (OR 1.310; 95% confidence interval (95% CI): [1.091; 1.574]; p = 0.0037) and at 90 days (OR 1.487; 95% CI: [1.335; 1.656]; p < 0.00010), mortality at 90 days (OR 1.709; 95% CI: [1.633; 1.788]; p < 0.0001), sICH (OR 1.595; 95% CI: [1.301; 1.956]; p < 0.0001), and HT (OR 1.276; 95% CI: [1.055; 1.543]; p = 0.0118).
CONCLUSION
Our meta-analysis demonstrates that diabetes is significantly associated with poor functional outcome, increased mortality and poor postprocedural safety outcomes, including sICH and HT.
Topics: Adolescent; Adult; Cerebral Hemorrhage; Diabetes Mellitus; Humans; Ischemic Stroke; Reperfusion; Treatment Outcome
PubMed: 35212489
DOI: 10.17219/acem/146273 -
EuroIntervention : Journal of EuroPCR... Nov 2023Reperfusion therapy is challenging in the elderly. Catheter-directed therapies are an alternative for higher-risk pulmonary embolism (PE) patients if systemic...
BACKGROUND
Reperfusion therapy is challenging in the elderly. Catheter-directed therapies are an alternative for higher-risk pulmonary embolism (PE) patients if systemic thrombolysis (ST) is contraindicated or has failed. Their safety has not been evaluated in specific vulnerable populations.
AIMS
We aimed to assess the safety of reperfusion therapies in elderly and frail patients in the real world.
METHODS
In the US Nationwide Inpatient Sample from 2016 to 2020, we identified hospitalisations of patients ≥65 years with PE and defined a frailty subgroup using the Johns Hopkins Adjusted Clinical Groups frailty-defining diagnosis indicator. We investigated reperfusion therapies (ST, catheter-directed thrombolysis [CDT], catheter-based thrombectomy [CBT], surgical embolectomy [SE]) and their associated safety outcomes (overall and major bleeding).
RESULTS
Among 980,245 hospitalisations of patients ≥65 years with PE (28.0% frail), reperfusion therapies were used in 4.9% (17.6% among high-risk PE). ST utilisation remained stable, while the use of catheter-directed therapies increased from 1.7% in 2016 to 3.2% in 2020. Among all hospitalisations with reperfusion, CDT, compared to ST, was associated with reduced major bleeding (5.8% vs 12.2%, odds ratio [OR] 0.58, 95% confidence interval [CI]: 0.49-0.70); these results also applied to frail patients. CBT, compared to SE, was also associated with reduced major bleeding (11.0% vs 22.4%, OR 0.63, 95% CI: 0.43-0.91), but not among frail patients. These differences were particularly significant in patients with non-high-risk PE. Differences persisted for overall bleeding as well.
CONCLUSIONS
Catheter-directed therapies may be a safer alternative to classical reperfusion therapies for elderly and frail patients with PE requiring reperfusion treatment.
Topics: Humans; Aged; Thrombolytic Therapy; Fibrinolytic Agents; Frailty; Treatment Outcome; Pulmonary Embolism; Hemorrhage; Reperfusion
PubMed: 37767997
DOI: 10.4244/EIJ-D-23-00399 -
Acta Neurologica Belgica Apr 2022Pre-intervention CT imaging-based biomarkers, such as hyperdense middle cerebral artery sign (HMCAS) may have a role in acute ischaemic stroke prognostication. However,... (Meta-Analysis)
Meta-Analysis
Prognostic capacity of hyperdense middle cerebral artery sign in anterior circulation acute ischaemic stroke patients receiving reperfusion therapy: a systematic review and meta-analysis.
Pre-intervention CT imaging-based biomarkers, such as hyperdense middle cerebral artery sign (HMCAS) may have a role in acute ischaemic stroke prognostication. However, the clinical utility of HMCAS in settings of reperfusion therapy and the level of prognostic association is still unclear. This systematic review and meta-analysis investigated the association of HMCAS sign with clinical outcomes and its prognostic capacity in acute ischaemic stroke patients treated with reperfusion therapy. Prospective and retrospective studies from the following databases were retrieved from EMBASE, MEDLINE and Cochrane. Association of HMCAS with functional outcome, symptomatic intracerebral haemorrhage (sICH) and mortality were investigated. The random effect model was used to calculate the risk ratio (RR). Subgroup analyses were performed for subgroups of patients receiving thrombolysis (tPA), mechanical thrombectomy (EVT) and/or combined therapy (tPA + EVT). HMCAS significantly increased the rate of poor functional outcome by 1.43-fold in patients (RR 1.43; 95% CI 1.30-1.57; p < 0.0001) without any significant differences in sICH rates (RR 0.91; 95% CI 0.68-1.23; p = 0.546) and mortality (RR 1.34; 95% CI 0.72-2.51; p = 354) in patients with positive HMCAS as compared to negative HMCAS. In subgroup analyses, significant association between HMCAS and 90 days functional outcome was observed in patients receiving tPA (RR 1.53; 95% CI 1.40-1.67; p < 0.0001) or both therapies (RR 1.40; 95% CI 1.08-1.80; p = 0.010). This meta-analysis demonstrated that pre-treatment HMCAS increases risk of poor functional outcomes. However, its prognostic sensitivity and specificity in predicting long-term functional outcome, mortality and sICH after reperfusion therapy is poor.
Topics: Brain Ischemia; Cerebral Hemorrhage; Fibrinolytic Agents; Humans; Ischemic Stroke; Middle Cerebral Artery; Prognosis; Prospective Studies; Reperfusion; Retrospective Studies; Stroke; Thrombolytic Therapy; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 34095978
DOI: 10.1007/s13760-021-01720-3 -
Brain and Behavior Oct 2019Approximately, half of the acute stroke patients with minor symptoms were excluded from thrombolysis in some randomized controlled trials (RCTs). There is little... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Approximately, half of the acute stroke patients with minor symptoms were excluded from thrombolysis in some randomized controlled trials (RCTs). There is little evidence on treating minor strokes with rt-PA. Here, we performed a systematic review and meta-analysis to assess the safety and efficacy of thrombolysis in these patients.
METHODS
PubMed, Embase, Web of Science, and Cochrane Library were searched in July 2018. All available RCTs and retrospective comparative studies that compared thrombolysis with nonthrombolysis' for acute minor stroke (NIHSS ≤ 5) with quantitative outcomes were included.
RESULTS
Ten studies, including a total of 4,333 patients, were identified. The risk of intracranial hemorrhage (ICH) was higher in the rt-PA group as compared with that in the non-rt-PA group (3.8% vs. 0.6%; p = .0001). However, there is no significant difference in the rate of mortality between the two groups (p = .96). The pooled rate of a good outcome in 90 days was 67.8% in those with rt-PA and 63.3% in those without rt-PA (p = .07). Heterogeneity was 43% between the studies (p = .08). After adjusting for the heterogeneity, thrombolysis was associated with good outcome (68.3% vs. 63.0%, OR 1.47; 95% CI 1.14-1.89; p = .003). In post hoc analyses, including only RCTs, the pooled rate of good outcome had no significant differences between the two groups (86.6% vs. 85.7%, 95% CI 0.44-3.17, p = .74; 87.4% vs. 91.9%, 95% CI 0.35-1.41, p = .32; before and after adjusting separately).
CONCLUSIONS
Although thrombolysis might increase the risk of ICH based on existing studies, patients with acute minor ischemic stroke could still benefit from thrombolysis at 3 months from the onset.
Topics: Fibrinolytic Agents; Humans; Male; Reperfusion; Retrospective Studies; Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 31532082
DOI: 10.1002/brb3.1398 -
JAMA Neurology Dec 2020A significant proportion of acute ischemic strokes occur while patients are hospitalized. Limited contemporary data exist on the utilization rates of intravenous...
IMPORTANCE
A significant proportion of acute ischemic strokes occur while patients are hospitalized. Limited contemporary data exist on the utilization rates of intravenous thrombolysis or endovascular therapy for in-hospital stroke.
OBJECTIVE
To use a national registry to examine temporal trends in the use of intravenous and endovascular reperfusion therapies for treatment of in-hospital stroke.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study analyzed data from 267 956 patients who underwent reperfusion therapy for stroke with in-hospital or out-of-hospital onset reported in the Get With the Guidelines-Stroke national registry from January 2008 to September 2018.
EXPOSURES
In-hospital onset vs out-of-hospital onset of stroke symptoms.
MAIN OUTCOMES AND MEASURES
Temporal trends in the use of reperfusion therapy, process measures of quality, and the association between functional outcomes and key patient characteristics, comorbidities, and treatments.
RESULTS
Of 67 493 patients with in-hospital stroke onset, this study observed increased rates of vascular risk factors (standardized mean difference >10%) but no significant differences in age or sex in patients undergoing intravenous thrombolysis only (mean [interquartile range {IQR}] age, 72 [80-62] y; 53.2% female) or those undergoing endovascular therapy (mean [IQR] age, 69 [59-79] y; 49.8% female). Of these patients, 10 481 (15.5%) received intravenous thrombolysis and 2494 (3.7%) underwent endovascular therapy. Compared with 2008, in 2018 the proportion of in-hospital stroke among all stroke hospital discharges was higher (3.5% vs 2.7%; P < .001), as was use of intravenous thrombolysis (19.1% vs 9.1%; P < .001) and endovascular therapy (6.4% vs 2.5%; P < .001) in patients with in-hospital stroke, with a significant increase in endovascular therapy in mid-2015 (P < .001). Compared with patients who received intravenous thrombolysis for out-of-hospital stroke onset, those with in-hospital onset were associated with longer median (IQR) times from stroke recognition to cranial imaging (33 [18-60] vs 16 [9-26] minutes; P < .001) and to thrombolysis bolus (81 [52-125] vs 60 [45-84] minutes; P < .001). In adjusted analyses, patients with in-hospital stroke onset who were treated with intravenous thrombolysis were less likely to ambulate independently at discharge (adjusted odds ratio, 0.78; 95% CI, 0.74-0.82; P < .001) and were more likely to die or to be discharged to hospice (adjusted odds ratio, 1.39; 95% CI, 1.29-1.50; P < .001) than patients with out-of-hospital onset who also received intravenous thrombolysis treatment. Comparisons among patients treated with endovascular therapy yielded similar findings.
CONCLUSIONS AND RELEVANCE
In this cohort study, in-hospital stroke onset was increasingly reported and treated with reperfusion therapy. Compared with out-of-hospital stroke onset, in-hospital onset was associated with longer delays to reperfusion and worse functional outcomes, highlighting opportunities to further care for patients with in-hospital stroke onset.
Topics: Aged; Aged, 80 and over; Cohort Studies; Endovascular Procedures; Female; Hospitalization; Humans; Ischemic Stroke; Male; Middle Aged; Reperfusion; Retrospective Studies; Thrombolytic Therapy
PubMed: 32955582
DOI: 10.1001/jamaneurol.2020.3362 -
International Journal of Molecular... Feb 2024Reperfusion stroke therapy is a modern treatment that involves thrombolysis and the mechanical removal of thrombus from the extracranial and/or cerebral arteries,...
Reperfusion stroke therapy is a modern treatment that involves thrombolysis and the mechanical removal of thrombus from the extracranial and/or cerebral arteries, thereby increasing penumbra reperfusion. After reperfusion therapy, 46% of patients are able to live independently 3 months after stroke onset. MicroRNAs (miRNAs) are essential regulators in the development of cerebral ischemia/reperfusion injury and the efficacy of the applied treatment. The first aim of this study was to examine the change in serum miRNA levels via next-generation sequencing (NGS) 10 days after the onset of acute stroke and reperfusion treatment. Next, the predictive values of the bioinformatics analysis of miRNA gene targets for the assessment of brain ischemic response to reperfusion treatment were explored. Human serum samples were collected from patients on days 1 and 10 after stroke onset and reperfusion treatment. The samples were subjected to NGS and then validated using qRT-PCR. Differentially expressed miRNAs (DEmiRNAs) were used for enrichment analysis. Hsa-miR-9-3p and hsa-miR-9-5p expression were downregulated on day 10 compared to reperfusion treatment on day 1 after stroke. The functional analysis of miRNA target genes revealed a strong association between the identified miRNA and stroke-related biological processes related to neuroregeneration signaling pathways. Hsa-miR-9-3p and hsa-miR-9-5p are potential candidates for the further exploration of reperfusion treatment efficacy in stroke patients.
Topics: Humans; MicroRNAs; Signal Transduction; Stroke; Reperfusion
PubMed: 38474013
DOI: 10.3390/ijms25052766