Reperfusion Time Research Articles

Donor Time to Death and Kidney Transplant Outcomes in the Setting of a 3-Hour Minimum Wait Policy

ImportanceLengthening waiting lists for organ transplant mandates the development of strategies to expand the deceased donor pool. Due to concerns regarding organ viability, most organ donation organizations internationally wait no longer than 1 to 2 hours for potential donation after circulatory death (DCD), possibly underutilizing an important organ source; UK policy mandates a minimum 3-hour wait time.ObjectiveTo assess whether time to death (TTD) from withdrawal of life-sustaining treatment (WLST) is associated with kidney transplant outcomes.Design, Setting, and ParticipantsThis population-based cohort study used data from the prospectively maintained UK Transplant Registry from all 23 UK kidney transplant centers from January 1, 2013, to December 31, 2021; follow-up was until the date of data extraction (October 2023). Participants comprised 7183 adult recipients of DCD kidney-alone transplants.ExposureDuration of TTD, defined as time from WLST to donor mechanical asystole.Main Outcomes and MeasuresPrimary outcome was 12-month estimated glomerular filtration rate (eGFR; for the main eGFR model, variables with significant right skew [histogram visual assessment] were analyzed on the log2 scale), with secondary outcomes of delayed graft function and graft survival (censored at death or 5 years).ResultsThis study included 7183 kidney transplant recipients (median age, 56 years [IQR, 47-64 years]; 4666 men [65.0%]). Median donor age was 55 years (IQR, 44-63 years). Median TTD was 15 minutes (range, 0-407 minutes), with 885 kidneys transplanted from donors with TTD over 1 hour and 303 kidneys transplanted from donors with TTD over 2 hours. Donor TTD was not associated with recipient 12-month eGFR on adjusted linear regression (change per doubling of TTD, −0.25; 95% CI, −0.68 to 0.19; P = .27), nor with delayed graft function (adjusted odds ratio, 1.01; 95% CI, 0.97-1.06; P = .65) or graft survival (adjusted hazard ratio, 1.00; 95% CI, 0.95-1.07; P = .92). These findings were confirmed with restricted cubic spline models (assessing nonlinear associations) and tests of interaction (including normothermic regional perfusion). In contrast, donor asystolic time, cold ischemic time, and reperfusion time were independently associated with outcomes. Compared with a theoretical 1-hour maximum wait time, the UK policy (minimum 3-hour wait time) has been associated with 885 extra DCD transplants compared with 6298 transplants (14.1% increase).Conclusions and RelevanceIn this cohort study of DCD kidney recipients, donor TTD was not associated with posttransplant outcomes, in contrast to subsequent ischemic times. Altering international transplant practice to mandate minimum 3-hour donor wait times could substantially increase numbers of kidney transplants performed without prejudicing outcomes.

Abstract 4119303: The New Strait-Jacket Designed for Endovascular Therapy Reduces the First Reperfusion Time of Emergency Thrombectomy for Stroke

Introduction: Conscious sedation during cerebrovascular interventional surgery can shorten the time of vascular recanalization and bring significant benefits to patients, but patients are often difficult to cooperate, which affects the operation of interventional surgery. This study aims to develop a novel cerebral vascular intervention strait-jacket and explore its safety and effectiveness in emergency cerebral vascular intervention surgery. Methods: Using the convenient sampling method, patients with acute large artery occlusion stroke who underwent emergency mechanical thrombectomy in Zhongnan Hospital of Wuhan University from September 2018 to March 2021 were selected as the research objects. The control group was treated with conventional restraint belt, and the experimental group was treated with new cerebrovascular interventional surgery strait-jacket. The first reperfusion time, total operation time, modified Rankin score (mRS) at 30 days, intraoperative limb prolapse rate, average surgical cost, and safety indicators were compared between the two groups. The t test, Mann-Whitney U test or Fisher exact test were used for comparison between groups according to the data type. A p<0.05 indicated statistical significance. Results: The new type of cerebrovascular interventional surgical strait-jacket developed in this study are shown in Figure 1, which have been patented and transformed into products. A total of 140 patients were included for mechanical thrombectomy, randomly divided into an experimental group (n=69) and a control group (n=71). Using the new strait-jacket significantly shortened the first reperfusion time (43.5±13.7 vs 50.7±15.7, P=0.039) and the total operation time (81.1±12.6 vs 93.2±21.1, P=0.027). There was a significant decrease in limb dislodgement rate (0% vs 35.2%, P<0.001) and a noticeable reduction in average surgical cost (76315±12400 vs 81462±14142 P=0.040) by using the strait-jacket. In terms of safety performance, using the strait-jacket significantly lower rates of skin redness than the control group (8.7% vs 42.3%, P<0.001). Conclusion: The new type of cerebrovascular interventional surgical strait-jacket is safe, which can effectively shorten the operation time, reduce the rate of intraoperative limb prolapse and the average operation cost, and can bring good social benefits.

Direct Aspiration Versus Combined Technique for Anterior Distal, Medium Vessel Occlusions Stroke: The JET Distal Vessel Occlusion Study

BACKGROUND AND OBJECTIVES: The optimal mechanical thrombectomy technique for distal, medium vessel occlusion (DMVO) stroke remains unknown. We aimed to compare the safety and efficacy of 2 thrombectomy first-line approaches, direct aspiration (DA), and combined technique (CT) in patients with DMVOs. METHODS: We conducted a retrospective review of a prospectively collected multicenter database of patients with DMVOs (at or distal to M2 and A1), who underwent mechanical thrombectomy with JET D reperfusion catheters between January 2020 and December 2021. The primary end point was the rate of first-pass complete recanalization, defined as modified treatment in cerebral infarction (mTICI) 3. The hemorrhagic complications, the 90 days functional independence rate (modified Rankin Scale 0-2), and mortality were also evaluated. RESULTS: A total of 171 consecutive patients were enrolled (95 in DA and 76 in CT cohort). The 2 groups had comparable demographics and baseline characteristics. The DA group had a higher rate of first-pass effect (40.0% vs 10.5%, P < .001), final mTICI 2b-3 (89.5% vs 71.1%, P = .003) and final mTICI 3 (58.9% vs 28.9%, P < .001), shorter groin to reperfusion time (65 ± 43 min vs 101 ± 60 min, P < .001), and higher rate of 90-day functional independence (63.7% vs 36.1%; P = .001) compared with the CT group. There were no significant differences in hemorrhagic complications between the 2 groups. The DA group showed a lower rate of 90-day mortality (9.9% vs 27.8%; P = .004). CONCLUSION: In patients with DMVOs, DA with a distal dedicated reperfusion catheter appears to demonstrate better safety and efficacy when compared with the CT using the same catheter.

Abstract 4119613: Evaluation of Gender, Racial and Ethnic Differences in Time to PCI in the Pre and Post Covid-19 Era

Introduction: Percutaneous Coronary Intervention (PCI) is recommended for reperfusion of patients presenting with ST-segment myocardial infarction (STEMI) within 90 minutes. In this study, we sought to identify differences in PCI timing based on gender, race and ethnicity in the pre- and post-COVID era. Methods: We collected retrospective data on 760 patients admitted with STEMI at our quaternary academic medical center from 2018-2022. We defined our binary outcome as time to PCI less than 90 minutes, and adjusted for transfers from outside hospitals. We utilized univariate logistic regression analysis to analyze the association of demographic, clinical, and cardiac catheterization details on our outcome. We then utilized multivariate logistic regression analysis to determine the association of our covariates of interests with time to PCI. The logistic regression model was adjusted for collinearity which were deemed not significant. Results: Among our study population, COVID did not significantly impact whether or not a patient had a diagnostic cardiac catheterization on univariate analysis (OR 2.68, 95% CI 0.61-18.40, p=0.23). However, the post-COVID era was significantly associated with a delayed time to PCI on multivariate analysis [OR 1.62, 95% CI 1.04-2.55, p=0.035) [Figure 1]. In addition, females were 1.8x more likely to have a delayed PCI than males on multivariate regression [OR 1.80, 95% CI 1.10-2.95, p= 0.019) [Figure 1]. Interestingly, on multivariate analysis, females were more likely to have delayed reperfusion in the pre-COVID era (OR 2.92, 1.29-6.77,p= 0.01) but not the post-COVID era (OR 1.54, 0.78-3.06,p=0.2134). Patients in the post-COVID era had increased risk of having their culprit coronary not revascularized on multivariate analysis (OR 2.85, 1.2-8.03, p= 0.03). Conclusions: At our center, COVID did not significantly impact cardiac catheterization rates. However, COVID was significantly associated with delayed reperfusion timing and not revascularizing culprit vessels. Females were much more likely to have a delayed PCI than males in the pre-COVID era which was not seen following COVID-19.

Investigation of stent retriever removal forces in an experimental model of acute ischemic stroke

IntroductionMechanical thrombectomy becomes more complex when the occlusion occurs in a tortuous cerebral anatomy, increasing the puncture to reperfusion time and the number of attempts for clot removal. Therefore, an understanding of stent retriever performance in these locations is necessary to increase the efficiency and safety of the procedure. An in vitro investigation into the effects of occlusion site tortuosity, blood clot hematocrit, and device geometry was conducted to identify their individual influence on stent retriever removal forces.MethodsEmbolus analogs were used to create occlusions in a mock circulatory flow loop, and in vitro mechanical thrombectomies were performed in arterial models of increasing tortuosity. The stent retriever removal forces of Solitaire Platinum and EmboTrap II devices were recorded through each geometry with and without embolus analogs present. Similar experiments were also conducted with Solitaire stent retrievers of varying lengths and diameters and 0, 25, and 50% hematocrit embolus analogs.ResultsThe removal force increased as model tortuosity increased for both the Solitaire Platinum and EmboTrap II stent retriever devices. The average removal forces in the simplest geometry with the Solitaire Platinum and EmboTrap II were 0.24 ± 0.01 N and 0.37 ± 0.02 N, respectively, and increased to 1.2 ± 0.08 N and 1.6 ± 0.17 N, respectively, in the most complex geometry. Slight increases in removal force were found with 0% hematocrit embolus analogs, however, no statistical significance between removal force and EA hematocrit was observed. A comparison between stent retriever removal forces between devices of different diameters also proved to be significant (p < 0.01), while forces between devices of varying lengths were not (p > 0.05).ConclusionBenchtop mechanical thrombectomies performed with commercial stent retrievers of varying geometry showed that device removal forces increase with increasing model tortuosity, clot hematocrit does not play a significant role in device removal force, and that a stent retriever’s diameter has a greater impact on removal forces compared to its length. These results provide an improved understanding of the overall forces involved in mechanical thrombectomy and can be used to develop safer and more effective stent retrievers for the most difficult cases.

Culprit vessel revascularization prior to complete angiography as a strategy to minimize delays in primary percutaneous coronary intervention for patients with ST-elevation myocardial infarction: a systematic review and meta-analysis.

The rapid restoration of blood flow in patients with acute myocardial infarction with ST elevation through percutaneous coronary intervention (PCI) is crucial for the survival of this population. Attempts to decrease the time from diagnosis of ST-segment elevation myocardial infarction (STEMI) to arrival at the catheterization laboratory have been extensively investigated. However, strategies during the procedure aiming to reduce the time to reperfusion are lacking. We conducted a meta-analysis to evaluate culprit vessel revascularization prior to complete angiography as a strategy to minimize delays in primary PCI for patients with STEMI. We searched PubMed, Embase, and Cochrane Central. Outcomes: vascular access-to-balloon, door-to-balloon, and first medical contact-to-balloon times; death, reinfarction in 30 days, Bleeding Academic Research Consortium ≥3 type, coronary artery bypass grafting referral, and left ventricular ejection fraction %. Statistical analysis was performed using the R program (version 4.3.2). Heterogeneity was assessed with I2 statistics. We included 2050 patients from six studies, of which two were randomized controlled trials and four were observational studies. Culprit vessel revascularization prior to complete angiography was associated with a statistically significant decrease of times: vascular access-to-balloon time (mean difference -6.79 min; 95% CI: -8.00 to -5.58; P < 0.01; I2 = 82%) and door-to-balloon time (mean difference -9.02 min; 95% CI: -12.83 to -5.22; P < 0.01; I2 = 93%). In this meta-analysis, performing PCI on the culprit lesion prior to complete coronary angiography led to significantly shorter reperfusion times, with no discernible differences in complication rates.

Simulated ischaemia/reperfusion impairs trophoblast function through divergent oxidative stress- and MMP-9-dependent mechanisms.

Early-onset pre-eclampsia is believed to arise from defective placentation in the 1st trimester, leading to placental ischaemia/reperfusion (I/R) and oxidative stress. However, our current understanding of the effects of I/R and oxidative stress on trophoblast function is ambiguous in part due to studies exposing trophoblasts to hypoxia instead of I/R, and which report conflicting results. Here we present a model of simulated ischaemia/reperfusion (SI/R) to recapitulate the pathophysiological events of early-onset PE, by exposing 1st trimester cytotrophoblast HTR-8/SVneo cells to a simulated ischaemia buffer followed by reperfusion. We examined different ischaemia and reperfusion times and observed that 1h ischaemia and 24h reperfusion induced an increase in reactive oxygen species (ROS) production (p < 0.0001) and oxygen consumption rate (p < 0.01). SI/R-exposed trophoblast cells exhibited deficits in migration, proliferation and invasion (p < 0.01). While the deficits in migration and proliferation were rescued by antioxidants, suggesting a ROS-dependent mechanism, the loss of invasion was not affected by antioxidants, which suggests a divergent ROS-independent pathway. In line with this, we observed a decrease in MMP-9, the key regulatory enzyme necessary for trophoblast invasion (p < 0.01), which was similarly unaffected by antioxidants, and pharmacological inhibition of MMP-9 replicated the phenotype of deficient invasion (p < 0.01). Collectively, these data demonstrate that I/R impairs trophoblast migration and proliferation via a ROS-dependent mechanism, and invasion via a ROS-independent loss of MMP-9, disambiguating the role of oxidative stress and providing insights into the response of trophoblasts to I/R in the context of early-onset PE.

Influence of social factors on prompt reperfusion in patients with ST-segment elevation myocardial infarction: results from the KRAMI multicenter registry

Abstract Background The time from symptom onset to reperfusion therapy was particularly important for ST-segment elevation myocardial infarction (STEMI) patients. We sought to investigate the impact of social factors on prompt reperfusion in STEMI patients. Methods A total of 5,264 patients with a diagnosis of STEMI from Korean Registry of Acute Myocardial Infarction (KRAMI) was participated in present study. The association between social factors and process of symptom onset-to-timely reperfusion was evaluated. Process of symptom-to-reperfusion time was included door-to-balloon (DTB) time, symptom-to-door (STD) time and symptom-to-balloon (STB) time. Results In the entire study population, the median times of DTB, STD and STB were 55 min, 117 min and 175 min, respectively. With 3 parameters, only DTB was associated with in-hospital mortality (Fig. 1 and 2). Old age and male were more likely to delay treatment (p for age=0.000; p for gender &amp;lt;0.0001). Moreover, higher education was linked to reduction of STD and STB time (p&amp;lt;0.05). Living alone was associated with prolonged STB time, and symptom appearing outside was linked to delay medical care. Transportation with ambulance was significantly associated with reduction of reperfusion time, and inter-hospital transportation was particularly prominent (STD: OR 5.450, 95% CI 4.796 - 6.193, p&amp;lt;0.0001; STB: OR 4.593, 95% CI 4.038 - 5.225, p&amp;lt;0.0001). In addition, treatment time during off-hours was relatively delayed DTB time. Conclusions Door to balloon time is directy related to in-hospital mortality. Social factors, such as age, gender, and education level, and transportation with ambulance were related to timely reperfusion in STEMI patients.

Thrombolysis versus primary percutaneous coronary intervention in patients with suspected ST-elevation myocardial infarction - a SWEDEHEART observational study

Abstract Background Primary percutaneous coronary intervention (PCI) is the recommended reperfusion strategy in ST-elevation myocardial infarction (STEMI) patients provided time to reperfusion is ≤120 minutes. In patients presenting early with an estimated time to reperfusion &amp;gt;120 minutes, thrombolytic therapy should be considered according to European Society of Cardiology guidelines. However, there is a lack of contemporary data on patients treated with thrombolysis. Aims Our aim was to determine how often thrombolysis was administered in STEMI patients having an estimated time to reperfusion of &amp;gt;120 minutes and to study outcome differences between patients treated with thrombolysis compared to those treated with primary PCI. Methods We calculated transport times to nearest primary PCI centre using three-digit zip codes for each patient enrolled in the SWEDEHEART registry from 2008–2021 in the five geographic areas in Sweden routinely using thrombolysis and included those with &amp;gt;120 min estimated transportation time to reperfusion time. Patients without ST-elevations on prehospital ECG and ongoing chest pain as well as patients with left bundle branch block, pacemaker rhythm and patients with contraindications to thrombolysis were excluded. Patients were grouped by received reperfusion therapy with prehospital thrombolysis or no prehospital thrombolysis and studied with regard to 1- and 3-year mortality using Kaplan-Meier failure estimates and Cox regression adjusted for difference in baseline characteristics. Results A total of 1,840 patients were included of whom 1,381 (75.1%) received thrombolysis. A final diagnosis of STEMI was observed in 92.6% of patients receiving thrombolysis and 80.2% of patients treated with primary PCI. The median transport time estimate to a PCI centre was 153 minutes in both groups. Median time from onset of symptoms to reperfusion therapy was 131 minutes for the thrombolysis group and 255 minutes for the PCI group. Patients who received thrombolysis were on average 2 years younger and had fewer comorbidities such as diabetes, cancer and heart failure. Among patients treated with thrombolysis, a total of 42.7% of patients underwent rescue PCI. There was no significant difference in 365-day mortality (6.7% vs 11.8%, adjusted HR 0.84, 95% CI: 0.59-1.19, p=0.33) or 3-year mortality rates (10.3% vs 16.6%, adjusted HR 0.89, 95% CI: 0.66-1.19, p=0.44) between patients treated with thrombolysis and primary PCI groups. Conclusions In this population-based study of patients where primary PCI cannot be expeditiously used, we observed a commendable adherence rate of 75% to the ESC guidelines for thrombolysis treatment. Moreover, our findings revealed that the administration of thrombolysis was not associated with any discernible benefits or harm.Unadjusted and adjusted Cox-modelKaplan-Meier survival analysis

Platelet membrane coated r-SAK to improve thrombolytic efficacy by targeting thrombus

Abstract Background Thrombolytic therapy is one of the most effective treatments to achieve rapid thrombus clearance and recanalization of blocked vessels in thrombotic diseases. However, the application of thrombolytic strategy has been limited due to unsatisfied thrombolytic efficacy, relatively higher bleeding complications, and consequently restricted indications.[1] With the development of nanotechnology and biotechnology, platelet membrane nanoparticles have been developed to enable the targeted delivery of thrombolytic agents to local thrombus sites.[2] Recombinant staphylokinase (r-SAK) is a third-generation thrombolytic agent produced by genetic engineering technology. In this study, platelet membrane coated r-SAK (PLT-r-SAK) was constructed, and its thrombolytic efficacy was evaluated in in-vitro and in-vivo experiments. Purpose We aimed to construct a thrombus-targeting agent of PLT-r-SAK and investigate its thrombolytic efficacy. Methods PLT-r-SAK was prepared by encapsulating r-SAK into platelet membrane vesicles using a membrane extrusion method. An in-vitro thrombolytic experiment was performed to examine the thrombolytic efficacy of PLT-r-SAK, and a totally occluded femoral artery thrombosis model of rabbit was developed to evaluate the in-vivo thrombolytic efficacy of PLT-r-SAK. The changes in femoral artery pressure were adopted to assess the vessel opening status. Besides, the effect of the antiplatelet drugs on the thrombolytic efficacy of PLT-r-SAK was explored. Finally, near-infrared fluorescence imaging system was used to verify the thrombus-targeting effect of PLT-r-SAK. Results PLT-r-SAK was firstly constructed, which exhibited a uniformly dispersed spherical morphology with a diameter of 185.8 ± 1.5 nm and a zeta potential of -26.1 ± 0.8 mV. In the in-vitro animal experiment, the thrombolysis rate of PLT-r-SAK was significantly higher than that of the same (low) dose and 4-fold (high) dose r-SAK (Figure 1a, 1b). In the in-vivo experiment, the initial recanalization time of PLT-r-SAK was significantly shorter than that of the low dose and high dose r-SAK, and the duration of the reperfusion time of PLT-r-SAK was prolonged compared to low dose and high dose r-SAK (Figure 1c). Another in-vitro experiment showed that the increased thrombolysis rate of PLT-r-SAK could be inhibited by platelet poor plasma (PPP) from aspirin- and ticagrelor-treated patients. Finally, both the in-vitro and in-vivo near-infrared fluorescence imaging showed significantly higher radiant efficiency in the PLT-r-SAK group as compared to the NS group (Figure 2). Conclusions Platelet membrane coating significantly improves the thrombolytic efficacy of r-SAK, which is related to the thrombus-targeting activity of the platelet membrane and can be inhibited by aspirin- and ticagrelor-treated plasma.Thrombolytic efficacy of PLT-r-SAKThrombus-targeting evidence of PLT-r-SAK

Time-dependent networks for the treatment of acute coronary syndrome in South East Tuscany

Abstract Introduction The importance of timely reperfusion therapy in Cardiovascular diseases is crucial, leading to the creation of time-dependent networks for Acute Coronary Syndrome treatment. The ACS-STEMI treatment network in Tuscany operates across three health authorities (LHAs),including South-East Tuscany. The network ensures ACS-STEMI treatment in 12 hospitals integrating new territories such as Piombino and Elba into the network. Aim of the study is to assess the impact of an analytical monitoring system of the times to reperfusion treatment and the actions to improve the performance of the network. Methods In this retrospective study an analytical evaluation of the network’s performance was conducted. We utilized data on patient transport, symptom onset to medical contact times, and outcomes from the National Outcomes Program (PNE).Analytical evaluations in 2021 measured the network’s performance, identifying main delay causes. The treatment process is divided into periods from symptom onset to coronary reperfusion, and interventions like public campaigns, ECG transmission and fast-track transfers have been implemented. Results South East Tuscany LHU had the lowest 30-day mortality rate for ACS patients in Italian hospitals with 300 cases annually in 2020 and 2021.Improvements continued into 2022 and 2023, further reducing mortality rates in patients initially admitted to SPOKE hospitals. For Piombino and Island of Elba residents,30-day mortality decreased from 8.8% (2017-2020) to 5.7% in 2022. The Grosseto hub treated 80% of STEMI patients within 90 minutes in 2022. Conclusions The establishment of a well-organized time-dependent network for ACS-STEMI treatment in Tuscany has significantly improved patient outcomes, demonstrating the critical role of timely and efficient care pathways. The network’s success is attributed to several factors, including improved accessibility, enhanced coordination among healthcare facilities, and effective use of technology and resources. Key messages • Treatment networks for ACS/STEMI can improve health outcomes in peripheral areas. • Structured clinical-care pathways in delivering high-quality care for ACS patients reduces ACS mortality.

Artesunate-driven autophagy: a shield against liver hypoxia/reoxygenation insult in rats via modulation of GLP1R, the chief metabolic kinase AMPK, mTOR, ULK1, P70S6K, cyclin D1, Akt, and GSK3β

BackgroundHepatic hypoxia/reoxygenation (H/R) insult is a critical issue in hepatic transplant and surgeries, profoundly influencing postoperative prognosis. One crucial pathomechanism in this condition is impaired autophagy flux, which disrupts liver homeostasis. Artesunate, an antimalarial drug, has shown potential in providing hepatoprotection against H/R injury; however, whether it can modulate disrupted autophagy to enhance hepatoprotection remains unclear.Purpose of the studyAccordingly, we delved into the potential mechanism(s) through which artesunate modulates the autophagy process in a hepatic H/R injury model.Methods and resultsRats were categorized into three groups, viz. sham operated, H/R, and artesunate-treated (50 mg/kg, i.p). Disease regression was evaluated microscopically, and molecular alternations were assessed biochemically using ELISA and western blotting techniques. Mechanistic analysis revealed that artesunate administration at reperfusion time significantly upregulated the gene expression of GLP1R protein expression of p-AMPK, accompanied by a downregulation in those of p-mTOR, and its target molecule p-ULK1, presenting the first trail to initiate autophagy. Additionally, artesunate reduced H/R-induced hepatic upregulated protein expression of p-mTOR/P70S6K cue, and cyclin D1 content, which positively correlated with the mTOR/P70S6K axis. Moreover, artesunate sharply upregulated active p-Akt, which in turn phosphorylated/inactivated GSK3β, a cascade that indirectly promotes autophagy. Consequently, artesunate increased the hepatic beclin-1 and LC3-II to further uphold its autophagic capacity. The hepato-therapeutic effectiveness of artesunate was further evidenced by reduced serum ALT and AST levels, along with diminished hepatic histopathological alterations.ConclusionArtesunate protected liver by triggering autophagy partly by modulating the GLP1R/AMPK/mTOR/ULK1, GLP1R/AMPK/mTOR/P70S6K, cyclin D1, and Akt/GSK3β trajectories providing a significant therapeutic potential in managing hepatic H/R insult.

Timeliness of reperfusion in ST-segment elevation myocardial infarction and outcomes in Kerala, India: results of the TRUST outcomes registry.

Transatlantic guidelines endorse quality metrics for timely reperfusion in patients with ST-elevation myocardial infarction (STEMI). Compliance in low- and middle-income countries (LMICs) is largely unknown. We prospectively evaluated 2928 STEMI patients in Kerala, India, across 16 PCI-capable hospitals who received reperfusion with either primary percutaneous coronary intervention (PPCI) or fibrinolysis. Primary endpoint was a major adverse cardiovascular event (MACE) composite of death, non-fatal myocardial infarction, stroke or readmission for heart failure at 1-year. Among reperfused STEMI patients, 320 (10.9%) received timely reperfusion with either PPCI or fibrinolysis, 1985 (67.8%) received delayed PPCI, and 623 (21.3%) received delayed fibrinolysis. Timely reperfusion had lower unadjusted MACE rates than delayed PCI or fibrinolysis (timely reperfusion: 11.9%, delayed PPCI: 13.6%, delayed fibrinolysis: 23.9%, P < 0.001). Mortality was lowest in the timely reperfusion group (timely reperfusion: 6.3%, delayed PPCI: 7.8%, delayed fibrinolysis 18.8%, P < 0.001). After multivariate analysis, delayed fibrinolysis had a higher MACE rate (HR 1.52 95% CI 1.04-2.21) and mortality (HR 1.97, 95% CI 1.18-3.25) compared to timely reperfusion. Total ischemic time > 3h and delayed first medical contact-to-needle time predicted MACE at 1 year. Among STEMI patients in Kerala, India, only one in 10 eligible patients received timely reperfusion. Longer total ischemic times and delayed fibrinolysis were associated with 1-year MACE. Improving timely reperfusion is critical to enhancing STEMI outcomes in LMICs. What is already known on this topic Given the established link between delay to reperfusion and worse major adverse cardiac events (MACE), global efforts have concentrated on minimizing different components of the total ischemic time to improve ST-elevation myocardial infarction (STEMI) outcomes. Compliance in low- and middle-income countries (LMICs) is largely unknown. What this study adds In this cohort of STEMI patients in Kerala, India, total ischemic time and first medical contact-to-needle time correlated with long-term MACE rates, whereas other timeliness indicators did not. How this study might affect research, practice or policy Our study highlights the significant barriers to accessing STEMI care that are prevalent in LMICs despite incremental growth in the number of PCI-capable hospitals. The pre-hospital phase within total ischemic time is the most important quality improvement metric of STEMI care in LMICs, especially for patients chosen for fibrinolysis.

Feasibility of 10-Minute Arrival Time to Departure Time Metric for STEMI Patients

Objectives Delays in reperfusion treatment in ST-elevation myocardial infarction (STEMI) patients leads to higher morbidity and mortality. Previous reports for Helicopter Emergency Medical Services (HEMS) suggests a 10-minute skid-to-skid (arrival to departure) time to achieve appropriate reperfusion times. However, there is no published data on whether this goal is achievable for a HEMS service. This study aims to see if a midwestern critical care service can consistently achieve a 10-minute helicopter skid-to-skid time or ground critical care service arrival to departure time. Further, comparing this metric between ground and helicopter transportations will help evaluate the ideal transportation method to optimize time to percutaneous intervention (PCI). Methods This was a retrospective chart review utilizing 10 years of data from our ground and HEMS program to assess whether a 10-minute arrival to departure time for STEMI patients could be achieved. Patients included were at least 18 years of age and were transported from the referring facility for further STEMI management. Wilcoxon rank sum test and Chi-square tests were used to evaluate data between helicopter and ground services. Results Included in the study were 686 patients, 608 by helicopter transport and 78 by ground transport. The median arrival to departure time was 14 min (IQR = 5) for helicopter patients and 13 min (IQR = 6) for ground patients. There was not a statistically significant difference in this metric for STEMI patients transported by helicopter versus ground. A statistically significant difference, though, existed between helicopter and ground transports among percent with times less than or equal to 10 min versus percent times greater than 10 min, X2 = 5.46, df = 1, p = 0.02. Two referring facilities had statistically significant differences in median arrival to departure times. Conclusions Our study found that a median EMS arrival to departure time of 10 min to transport STEMI patients was not consistently achieved via either helicopter or ground transportation.

Higher intracranial positioning of an 8 Fr guide catheter improves efficacy of aspiration thrombectomy in large vessel occlusion stroke

BackgroundHigher positioning of a large bore guide catheter during endovascular thrombectomy (EVT) is hypothesized to potentially improve thrombectomy success.ObjectiveTo evaluate the safety and efficacy of intracranial guide catheter placement during...

Current and Future Roles of Glycoprotein IIb-IIIa Inhibitors in Primary Angioplasty for ST-Segment Elevation Myocardial Infarction.

Acute myocardial infarction still represents the major cause of mortality in high-income countries. Therefore, considerable efforts have been focused on the treatment of myocardial infarctions in the acute and long-term phase, with special attention being paid to reperfusion strategies and adjunctive antithrombotic therapies. In fact, despite the successful mechanical recanalization of the epicardial conduit, a substantial percentage of patients still experience poor myocardial reperfusion or acute/subacute in-stent thrombosis. Due the delayed onset of action of currently available oral antiplatelet therapies, glycoprotein (GP) IIb-IIIa inhibitors could be expected to improve clinical outcomes, especially when administrated in the early phase of the infarction, due to the larger platelet composition of fresh thrombi, the dynamic nature of early thrombi, and the larger amount of viable myocardium existing in the early, as compared to a delayed, phase. Considerable evidence has accumulated regarding the benefits from GP IIb-IIIa inhibitors on mortality, especially among high-risk patients and when administered as an upstream strategy. Therefore, based on currently available data, GP IIb-IIIa inhibitors can be considered when the drug can be administered within the first 3 h of symptom onset and among high-risk patients (e.g., those with advanced Killip class or an anterior myocardial infarction). Even though it is not universally accepted, in our opinion, this strategy should be implemented in a pre-hospital setting (in an ambulance) or as soon as possible when arriving at the hospital (at the Emergency Room or Coronary Care Unit, irrespective of whether they are in spoke or hub hospitals). A new, second-generation GP IIb-IIIa inhibitor (zalunfiban) appears to be highly suitable as a pre-hospital pharmacological facilitation strategy at the time of first medical contact due to its favourable features, including its simple subcutaneous administration, rapid onset of action (15 min), and limited time of action (with a half-life of ~1 h), which is likely to minimize the risk of bleeding. The ongoing CELEBRATE trial, including 2499 STEMI patients, may potentially provide compelling data to support the upstream treatment of STEMI patients undergoing mechanical reperfusion. In fact, although the current therapeutic target of increased rates of timely reperfusion has been achieved, the future goal in myocardial infarction treatment should be to achieve the most rapid reperfusion prior to primary percutaneous coronary intervention, thus further minimizing myocardial damage, or, in some cases, even preventing it completely, and improving survival.

Differences between sexes in STEMI treatment and outcomes with contemporary primary PCI.

Historically, differences in timely reperfusion and outcomes have been described in females who suffer ST-segment elevation myocardial infarction (STEMI). However, there have been improvements in the treatment of STEMI patients with contemporary Percutaneous Coronary Intervention (PCI) strategies. Comparisons between sexes were performed on STEMI patients treated with primary PCI over a 4-year period (January 1, 2017-December 31, 2020) from the Queensland Cardiac Outcomes Registry. Primary outcomes were 30-day and 1-year cardiovascular mortality. Secondary outcomes were STEMI performance measures. The total and direct effects of gender on mortality outcomes were estimated using logistic and multinomial logistic regression models. Overall, 2747 (76% male) were included. Females were on average older (65.9 vs. 61.9 years; p < 0.001), had longer total ischemic time (69 min vs. 52 min; p < 0.001) and less achievement of STEMI performance targets (<90 min) (50% vs. 58%; p < 0.001). There was no evidence for a total (odds ratio [OR] 1.3 (95% confidence interval [CI]: 0.8-2.2; p = 0.35) or direct (adjusted OR 1.2 (95% CI: 0.7-2.1; p = 0.58) effect of female sex on 30-day mortality. One-year mortality was higher in females (6.9% vs. 4.4%; p = 0.014) with total effect estimates consistent with increased risk of cardiovascular mortality (Incidence rate ratio [IRR]: 1.5; 95% CI: 1.0-2.3; p = 0.059) and noncardiovascular mortality (IRR: 2.1; 95% CI: 0.9-4.7; p = 0.077) in females. However, direct (adjusted) effect estimates of cardiovascular mortality (IRR: 1.0; 95% CI: 0.6-1.6; p = 0.94) indicated sex differences were explained by confounders and mediators. Small sex differences in STEMI performance measures still exist; however, with contemporary primary PCI strategies, sex is not associated with cardiovascular mortality at 30 days or 1 year.

Ozone Administration Reduces Myocardial Ischemia Reperfusion Injury in Streptozotocin Induced Diabetes Mellitus Rat Model.

This study aimed to demonstrate whether ozone has cardioprotective effects on the myocardial ischemia-reperfusion injury (IRI) in rats with streptozotocin(STZ)-induced diabetes. A total of 38 male Wistar Albino rats were divided into five groups as follows: control group (group C,n=6), diabetic group (group D,n=6), diabetic ozone group (group DO,n=6), diabetic-ischemia/reperfusion (group DIR,n=6), diabetic-ischemia/reperfusion-ozone (group DIRO,n=6). Six rats died during this period and two died because of surgical complications. A myocardial ischemia-reperfusion model was created using a thoracotomy incision from 4th intercostal space. The LAD was ligated using an 8-0 prolene suture for 30min. Ozone was administered intraperitoneally(1mg/kg) 5min before reperfusion. The reperfusion time was 120min. At the end of the reperfusion procedure, myocardial tissue histopathological examinations, and serum biochemical analyses were performed. The percentage of TUNEL(+) cardiomyocytes/HPF was significantly higher in the DIR group than in the C, D, and DO groups. Conversely, TUNEL positivity was significantly lower in the DIRO group than in the DIR group. The IRI score was significantly higher in the DIR and DIRO groups than that in the C, D, and DO groups. In contrast, the IRI damage score in the DIRO group was significantly lower than that in the DIR group. Serum MDA levels were significantly higher in the DIR group than in the C, D, and DO groups. Similarly, MDA levels were significantly higher in the DIRO group than in the C and D groups. CAT activity was significantly higher in the DIR group than in the C and D groups. SOD activity was significantly higher in the DIR group than in the C and DO groups. Our study showed that ozone exerts cardioprotective effects in STZ-induced diabetic rats through its antioxidant role against oxidative stress. Both biochemical and histological analyses clearly revealed that ozone has beneficial effects against IRI in the diabetic rat myocardium.

Identification and validation of leukemia inhibitory factor as a protective factor in ischemic acute kidney injury

BackgroundIschemia-reperfusion injury (IRI) is a common pathophysiological mechanism of acute kidney injury (AKI). There is an urgent need for a more comprehensive analysis of its underlying mechanisms. Materials and methodsThe RNA-sequencing dataset GSE153625 was used to examine differentially expressed genes (DEGs) of kidney tissues in IRI-AKI mice compared with sham mice. We used 10 algorithms provided by cytohubba plugin and four external datasets (GSE192532, GSE52004, GSE98622, and GSE185383) to screen for hub genes. The IRI-AKI mouse model with different reperfusion times was established to validate the expression of hub gene in the kidneys. HK-2 cells were cultured in vitro under hypoxia/reoxygenation (H/R) conditions, via transfection with si-LIF or supplementation with the LIF protein to explore the function of the LIF gene. ResultsWe screened a total of 1,540 DEGs in the IRI group compared with the sham group and identified that the LIF hub gene may play potential roles in IRI-AKI. LIF was markedly upregulated in the kidney tissues of IRI-AKI mice, as well as in HK-2 cells grown under H/R conditions. The knockdown of LIF aggravated apoptosis and oxidative stress (OS) injury under H/R conditions. Administration of the LIF protein rescued the effects of si-LIF, alleviating cellular apoptosis and OS. ConclusionThese findings indicate an important role of the LIF gene in term of regulating apoptosis and OS in the early phases of IRI-AKI. Targeting LIF may therefore represent a promising therapeutic strategy for IRI-AKI.

Eastern Health, Box Hill Hospital and Maroondah Hospital. Melbourne, Australia.

Box Hill Hospital has approximately 750 stroke presentations per annum and in 2023, 99 patients received thrombolysis and 40 were transferred out for thrombectomy. Thrombolysis rates, for patients with ischaemic stroke that present within 4.5 hours of symptom onset, was at 37%, with a median door-to-needle (DNT) of 41 minutes, 86% of cases being treated under 60 minutes of arrival and our fastest DNT being 16 minutes. Meidan DIDO was 47 minutes with the fastest recorded 17 minutes. Reperfusion time metrics have improved significantly over the years with the biggest impact being from a direct to CT protocol, organisational coordination and the presence of an Acute Stroke Nurse (ASN) for patients receiving thrombolysis.