Reperfusion Time Research Articles

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 <0.0001). Moreover, higher education was linked to reduction of STD and STB time (p<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<0.0001; STB: OR 4.593, 95% CI 4.038 - 5.225, p<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 >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 >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 >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.

Glycaemia and ischaemia-reperfusion brain injury in patients with ischaemic stroke treated with mechanical thrombectomy (GLIAS-MT): an observational, unicentric, prospective study protocol

IntroductionPoststroke hyperglycaemia is an independent risk factor for poorer outcomes in patients treated with mechanical thrombectomy (MT) and is associated with a lower probability of functional recovery and higher mortality...

Impact of Time of Day on Surgical Outcomes After Lung Transplantation (Night-Time Lung Transplant)

BackgroundSurgical outcomes have been linked to the technical and cognitive abilities of an exhausted surgical team. In parallel, advancements in preservation have led to the proposal of daytime lung transplants. We sought to investigate whether time of day is associated with outcomes in lung transplants. MethodsData on 30,404 lung transplants from 2005 to 2021 were obtained from the United Network for Organ Sharing database. Patients were categorized based on the time of surgery with early-hours defined as donor cross-clamp between 10 pm and 3 am, and Cox regression models for 90-day and long-term mortality were made to assess the risk according to time of transplant and covariates. Additionally, the Cox modeling was repeated with donor cross-clamp and the estimated reperfusion time of day as continuous functions. ResultsAmong 30,404 transplants, 20.7% (6295) were performed during early hours. No significant difference was found between the 2 groups in unadjusted 90-day and long-term mortality (log-rank, P = .176 and .363, respectively), and results were unchanged when adjusting for covariates (P = .233 and .738, respectively). However, when examining donor cross-clamp time and reperfusion time as continuous variables in separate multivariable analyses, we observed significant associations with 90-day mortality (P = .002 and .022, respectively). Notably, lower mortality rates were observed for donor clamp-times between 8 am and 1 pm and estimated reperfusion times between 1 pm and 6 pm. ConclusionsAlthough binary categorizations of the time of day of lung transplants did not show a significant impact on short- or long-term survival, continuous-time analyses demonstrated that certain times during the day were associated with favorable short-term survival.

Sex differences in delay times in ST-segment elevation myocardial infarction: A cohort study

BackgroundThe present study analyzes a cohort of consecutive patients with ST-segment elevation acute myocardial infarction (STEMI), evaluating the ischemia–reperfusion times from the perspective of gender differences (females versus males), with a long-term follow-up. MethodsSingle-center analytical cohort study of patients with STEMI in a tertiary hospital, between January 2015 and December 2020. ResultsA total of 2668 patients were included, 2002 (75%) men and 666 (25%) women. The time elapsed from the onset of symptoms to the opening of the artery was 197min (IQR 140–300) vs 220min (IQR 152–340), p=0.004 in men and women respectively. A delay in health care significantly impacts the occurrence of cardiovascular adverse events at follow-up, HR 1.34 [95%CI 1.06–1.70]; p=0.015. ConclusionsWomen took longer to go to health care services and had a longer delay both in the diagnosis of STEMI and in coronary reperfusion. It is imperative to emphasize the necessity of educating women about the recognition of ischemic heart disease symptoms, empowering them to raise early alarms and seek timely medical attention.

Prognostic indicators for canine parvoviral enteritis in a Teaching Hospital in Italy: a retrospective study of 76 cases.

Potential prognostic indicators have been associated with decreased survival during canine parvoviral enteritis (CPE), such as body weight, sex, and clinicopathological parameters. Few studies reported the prognostic factors for CPE in Italy; therefore, the aim of this study was to identify prognostic factors associated with the survival of dogs admitted to the Veterinary Teaching Hospital of Perugia University, naturally infected with canine parvovirus. Seventy-six medical records of dogs with a definitive diagnosis of parvoviral infection admitted from 2017 to 2021 have been reviewed and included in the study. From medical records were extracted data on signalment, history, clinical examination, hematology, serum biochemistry, treatments, progression of clinical signs during hospitalization and outcome. The data have been subjected to univariate and multivariate statistical analysis. Our results showed winter season, male sex, dog ownership, small breed, normal sensory status, normal heart rate, normal hydration status, abdominal pain, increased capillary reperfusion time, and normal white blood cell count as positive prognostic factors. The survival model confirmed that parameters such as male sex, small breed, and ownership increased the survival rate during hospitalization. Data reported in the present study are partially in agreement with previous studies and added new information on the possible prognostic factors in dogs affected by CPE in Italy.

Rational design of an activatable dual-color fluorogenic probe for revealing the interaction of adenosine-5′-triphosphate and peroxynitrite in pyroptosis associated with acute kidney injury

ATP and ONOO- play unique roles in various biological events and exhibit notable interactions. To date, there is no available chemical tool for investigating the correlation between ATP and ONOO- concentrations in pyroptosis associated with acute kidney injury (AKI). Herein, we designed a novel dual-color near-infrared fluorescent (NIRF) probe P2 for simultaneous visualization of ATP and ONOO- both in vitro and in vivo. Unlike previously reported single-site fluorescent probes, P2 enabled concurrent imaging of ATP and ONOO- in two distinct fluorescence channels, with emission wavelengths centered at 585 and 690 nm, which greatly reduced spectral cross-talk. Employing a HK-2 pyroptosis model, a significant interaction between ATP and ONOO- was unveiled. Elevated ONOO- production was found to correlate with decreased ATP levels; conversely, an increase in ATP levels was associated with rapid ONOO- scavenging. Remarkably, P2 allowed the assessment of cellular hypoxia by monitoring ATP and ONOO- concentrations. The commercial ONOO--scavenger uric acid showcased a protective effect on HK-2 cells via inhibition of the cellular pyroptosis pathway. Furthermore, P2 was successfully employed for imaging of ATP and ONOO- in the AKI mice model. Our findings confirmed that renal ischemia-reperfusion triggered a rise in ONOO- levels, concurrent with a decline in ATP levels. Surprisingly, the cells exhibited a compensatory recovery of ATP levels as the reperfusion time was prolonged. These results suggested the newly devised P2, as a pivotal chemical tool for the simultaneous monitoring of ATP and ONOO-, might open new avenues for disease diagnosis and treatment.

Usefulness of Prehospital 12-Lead Electrocardiography System in ST-Segment Elevation Myocardial Infarction Patients in Oita - Comparison Between Urban and Rural Areas, Weekday Daytime and Weekday Nighttime/Holidays.

We have reported that a prehospital 12-lead electrocardiography system (P-ECG) contributed to transport of suspected acute coronary syndrome (ACS) patients to appropriate institutes and in this study, we compared its usefulness between urban and rural areas, and between weekday daytime and weekday nighttime/holiday.Methods and Results: Consecutive STEMI patients who underwent successful primary percutaneous coronary intervention after using P-ECG were assigned to the P-ECG group (n=123; 29 female, 70±13 years), and comparable STEMI patients without using P-ECG were assigned to the conventional group (n=117; 33 females, mean age 70±13 years). There was no significant difference in door-to-reperfusion times between the rural and urban cases (70±32 vs. 69±29 min, P=0.73). Door-to-reperfusion times in the urban P-ECG group were shorter than those in the urban conventional group for weekday nighttime/holiday (65±21 vs. 83±32 min, P=0.0005). However, there was no significance different between groups for weekday daytime. First medical contact to reperfusion time (90±22 vs. 105±37 min, P=0.0091) in the urban P-ECG group were significantly shorter than in the urban conventional groups for weekday nighttime/holiday, but were not significantly different between the groups for weekday daytime. P-ECG is useful even in urban areas, especially for patients who develop STEMI during weekday nighttime or while on a holiday.

Impact of post-thrombectomy isolated subarachnoid hemorrhage on neurological outcomes in patients with anterior ischemic stroke – a retrospective single-center observational study

PurposeWe aimed to investigate the impact of post-thrombectomy isolated subarachnoid hemorrhage (i-SAH) and other types of intracranial hemorrhage (o-ICH) on patient’s neurological outcomes.MethodsStroke data from 2018 to 2022 in a tertiary care center were retrospectively analyzed. Patients with large vessel occlusion from ICA to M2 branch were included. Post-thrombectomy intracranial hemorrhages at 24 h were categorized with Heidelberg Bleeding Classification. Neurological impairment of patients was continuously assessed at admission, at 24 h, 48 h and 72 h, and at discharge. Predictors of i-SAH and o-ICH were assessed.Results297 patients were included. i-SAH and o-ICH were found in 12.1% (36/297) and 11.4% (34/297) of patients. Overall, NIHSS of i-SAH patients at discharge were comparable to o-ICH patients (median 22 vs. 21, p = 0.889) and were significantly higher than in non-ICH patients (22 vs. 7, p < 0.001). i-SAH often resulted in abrupt deterioration of patient’s neurological symptoms at 24 h after thrombectomy. Compared to non-ICH patients, the occurrence of i-SAH was frequently associated with worse neurological outcome at discharge (median NIHSS increase of 4 vs. decrease of 4, p < 0.001) and higher in-hospital mortality (41.7% vs. 23.8%, p = 0.022). Regardless of successful reperfusion (TICI 2b/3), the beneficial impact of thrombectomy appeared to be outweighed by the adverse effect of i-SAH. Incomplete reperfusion and shorter time from symptom onset to admission were associated with higher probability of i-SAH, whereas longer procedure time and lower baseline ASPECTS were predictive for o-ICH occurrence.ConclusionPost-thrombectomy isolated subarachnoid hemorrhage is a common complication with significant negative impact on neurological outcome.