Effect of Cangrelor on Infarct Size in ST-Segment-Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial (The PITRI Trial).

BACKGROUND: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention. METHODS: This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore. Patients were randomized to receive either cangrelor or placebo initiated before the primary percutaneous coronary intervention procedure on top of oral ticagrelor. The key exclusion criteria included presenting <6 hours of symptom onset; previous MI and stroke or transient ischemic attack; on concomitant oral anticoagulants; and a contraindication for cardiovascular magnetic resonance. The primary efficacy end point was acute MI size by cardiovascular magnetic resonance within the first week expressed as percentage of the left ventricle mass (%LVmass). Microvascular obstruction was identified as areas of dark core of hypoenhancement within areas of late gadolinium enhancement. The primary safety end point was Bleeding Academic Research Consortium-defined major bleeding in the first 48 hours. Continuous variables were compared by Mann-Whitney U test (reported as median [first quartile-third quartile]), and categorical variables were compared by Fisher exact test. A 2-sided P<0.05 was considered statistically significant. RESULTS: Of 209 recruited patients, 164 patients (78%) completed the acute cardiovascular magnetic resonance scan. There were no significant differences in acute MI size (placebo, 14.9% [7.3-22.6] %LVmass versus cangrelor, 16.3 [9.9-24.4] %LVmass; P=0.40) or the incidence (placebo, 48% versus cangrelor, 47%; P=0.99) and extent of microvascular obstruction (placebo, 1.63 [0.60-4.65] %LVmass versus cangrelor, 1.18 [0.53-3.37] %LVmass; P=0.46) between placebo and cangrelor despite a 2-fold decrease in platelet reactivity with cangrelor. There were no Bleeding Academic Research Consortium-defined major bleeding events in either group in the first 48 hours. CONCLUSIONS: Cangrelor administered at the time of primary percutaneous coronary intervention did not reduce acute MI size or prevent microvascular obstruction in patients with ST-segment-elevation MI given oral ticagrelor despite a significant reduction of platelet reactivity during the percutaneous coronary intervention procedure. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03102723.

The Effect of Building-Level Socioeconomic Status on Bystander Cardiopulmonary Resuscitation: A Retrospective Cohort Study.

OBJECTIVE: Understanding the social determinants of bystander cardiopulmonary resuscitation (CPR) receipt can inform the design of public health interventions to increase bystander CPR. The association of socioeconomic status with bystander CPR is generally poorly understood. We evaluated the relationship between socioeconomic status and bystander CPR in cases of out-of-hospital cardiac arrest (OHCA). METHODS: This was a retrospective cohort study based on the Singapore cohort of the Pan-Asian Resuscitation Outcomes Study registry between 2010 and 2018. We categorized patients into low, medium, and high Singapore Housing Index (SHI) levels-a building-level index of socioeconomic status. The primary outcome was receipt of bystander CPR. The secondary outcomes were prehospital return of spontaneous circulation and survival to discharge. RESULTS: A total of 12,730 OHCA cases were included, the median age was 71 years, and 58.9% were male. The bystander CPR rate was 56.7%. Compared to patients in the low SHI category, those in the medium and high SHI categories were more likely to receive bystander CPR (medium SHI: adjusted odds ratio [aOR] 1.48, 95% CI 1.30-1.69; high SHI: aOR 1.93, 95% CI 1.67-2.24). High SHI patients had higher survival compared to low SHI patients on unadjusted analysis (OR 1.79, 95% CI 1.08-2.96), but not adjusted analysis (adjusted for age, sex, race, witness status, arrest time, past medical history of cancer, and first arrest rhythm). When comparing high with low SHI, females had larger increases in bystander CPR rates than males. CONCLUSIONS: Lower building-level socioeconomic status was independently associated with lower rate of bystander CPR, and females were more susceptible to the effect of low socioeconomic status on lower rate of bystander CPR.

Endovascular therapy for acute ischemic stroke with distal medium vessel occlusion: a systematic review and meta-analysis.

AIMS: Endovascular therapy (EVT) for distal medium vessel occlusions (DMVOs) is a potential frontier of acute ischemic stroke (AIS) treatment, but its efficacy against best medical therapy (BMT) remains unknown. We performed a systematic review and meta-analysis evaluating the efficacy and safety of EVT versus BMT in primary DMVO. METHODS: We systematically searched PubMed, Cochrane Library and Embase, from inception to August 14, 2022, for studies comparing EVT with BMT in DMVO-AIS. We adopted the Distal Thrombectomy Summit Group's definition of DMVO. Efficacy outcomes were functional independence (90-day modified Rankin Scale (mRS) 0-2) and excellent functional outcomes (90-day mRS 0-1). Safety outcomes were symptomatic intracranial hemorrhage (sICH) and 90-day mortality. RESULTS: Fourteen observational and two randomized-controlled studies were included, with 1202 patients receiving EVT and 1267 receiving BMT. After trim-and-fill correction, EVT achieved significantly better odds of functional independence than BMT (adjusted OR 1.61, 95% CI 1.06 to 2.43). There were no significant differences in overall excellent functional outcomes (OR 1.23, 95% CI 0.88 to 1.71), sICH (OR 1.44, 95% CI 0.78 to 2.66), and mortality (OR 1.03, 95% CI 0.73 to 1.45). Stratified by EVT method, mechanical thrombectomy±intra-arterial thrombolysis achieved more excellent functional outcomes than BMT (OR 1.59, 95% CI 1.13 to 2.23). In mild strokes (National Institutes of Health Stroke Scale score <6), EVT caused significantly more sICH (OR 6.30, 95% CI 1.55 to 25.64). CONCLUSIONS: EVT shows promising efficacy benefit over BMT for primary DMVO-AIS. Further randomized controlled trials are necessary to evaluate the efficacy and safety of EVT in DMVO-AIS.

Negative interaction between nitrates and remote ischemic preconditioning in patients undergoing cardiac surgery: the ERIC-GTN and ERICCA studies.

Remote ischaemic preconditioning (RIPC) using transient limb ischaemia failed to improve clinical outcomes following cardiac surgery and the reasons for this remain unclear. In the ERIC-GTN study, we evaluated whether concomitant nitrate therapy abrogated RIPC cardioprotection. We also undertook a post-hoc analysis of the ERICCA study, to investigate a potential negative interaction between RIPC and nitrates on clinical outcomes following cardiac surgery. In ERIC-GTN, 185 patients undergoing cardiac surgery were randomized to: (1) Control (no RIPC or nitrates); (2) RIPC alone; (3); Nitrates alone; and (4) RIPC + Nitrates. An intravenous infusion of nitrates (glyceryl trinitrate 1 mg/mL solution) was commenced on arrival at the operating theatre at a rate of 2-5 mL/h to maintain a mean arterial pressure between 60 and 70 mmHg and was stopped when the patient was taken off cardiopulmonary bypass. The primary endpoint was peri-operative myocardial injury (PMI) quantified by a 48-h area-under-the-curve high-sensitivity Troponin-T (48 h-AUC-hs-cTnT). In ERICCA, we analysed data for 1502 patients undergoing cardiac surgery to investigate for a potential negative interaction between RIPC and nitrates on clinical outcomes at 12-months. In ERIC-GTN, RIPC alone reduced 48 h-AUC-hs-cTnT by 37.1%, when compared to control (ratio of AUC 0.629 [95% CI 0.413-0.957], p = 0.031), and this cardioprotective effect was abrogated in the presence of nitrates. Treatment with nitrates alone did not reduce 48 h-AUC-hs-cTnT, when compared to control. In ERICCA there was a negative interaction between nitrate use and RIPC for all-cause and cardiovascular mortality at 12-months, and for risk of peri-operative myocardial infarction. RIPC alone reduced the risk of peri-operative myocardial infarction, compared to control, but no significant effect of RIPC was demonstrated for the other outcomes. When RIPC and nitrates were used together they had an adverse impact in patients undergoing cardiac surgery with the presence of nitrates abrogating RIPC-induced cardioprotection and increasing the risk of mortality at 12-months post-cardiac surgery in patients receiving RIPC.

Intravenous thrombolysis and endovascular thrombectomy for acute ischaemic stroke in patients with Moyamoya disease - a systematic review and meta-summary of case reports.

BACKGROUND AND AIMS: Patients with Moyamoya disease (MMD) can present with ischaemic or haemorrhagic stroke. There is no good evidence for treatment strategies in MMD-associated acute ischaemic stroke (AIS), particularly for treatments like intravenous thrombolysis (IVT) and endovascular thrombectomy (ET). As the intracranial vessels are friable in MMD, and the risk of bleeding is high, the use of IVT and ET is controversial. To clarify the safety and efficacy of IVT/ET in the treatment of MMD-associated AIS, we performed a systematic review and meta-summary to examine this issue. METHODS: A systematic search was performed from four electronic databases: PubMed (MEDLINE), Cochrane Library, EMBASE and Scopus, profiling data from inception till 21 November 2021, as well as, manually on Google Scholar. RESULTS: Ten case reports detailing 10 MMD patients presenting with AIS and undergoing IVT or ET, or both, were included in the analysis. The median National Institute of Health Stroke Scale score at presentation was 10 (Interquartile Range [IQR] = 6.0-16.5). IVT alone was instituted in 6 patients, primary ET was attempted in 2, and 2 had received bridging IVT with ET. Of the 4 patients who underwent ET, 2 patients achieved successful reperfusion (modified Thrombolysis In Cerebral Infarction scale [mTICI] ≥ 2b). In terms of functional outcomes, One patient achieved complete recovery (modified Rankin Scale 0), 4 patients attained improvement in neurological status, and 4 had no improvement, whilst functional outcome was unreported in 1 patient. No patient experienced symptomatic intracranial haemorrhage. CONCLUSIONS: In this systematic review and meta-summary, the utility of IVT and ET in MMD-associated AIS appears feasible in selected cases. Further larger cohort studies are required to evaluate these treatment approaches. HIGHLIGHTS: · AIS in MMD was typically managed with bypass surgery but not via thrombolysis or thrombectomy. · In this meta-summary, all patients treated with thrombolysis and/or thrombectomy survived and some experienced symptomatic and/or functional improvement. · Further larger cohort studies are necessary for investigating the role of thrombolysis and/or thrombectomy as treatment of AIS in MMD.

Development and validation of an interpretable machine learning scoring tool for estimating time to emergency readmissions.

Background: Emergency readmission poses an additional burden on both patients and healthcare systems. Risk stratification is the first step of transitional care interventions targeted at reducing readmission. To accurately predict the short- and intermediate-term risks of readmission and provide information for further temporal risk stratification, we developed and validated an interpretable machine learning risk scoring system. Methods: In this retrospective study, all emergency admission episodes from January 1st 2009 to December 31st 2016 at a tertiary hospital in Singapore were assessed. The primary outcome was time to emergency readmission within 90 days post discharge. The Score for Emergency ReAdmission Prediction (SERAP) tool was derived via an interpretable machine learning-based system for time-to-event outcomes. SERAP is six-variable survival score, and takes the number of emergency admissions last year, age, history of malignancy, history of renal diseases, serum creatinine level, and serum albumin level during index admission into consideration. Findings: A total of 293,589 ED admission episodes were finally included in the whole cohort. Among them, 203,748 episodes were included in the training cohort, 50,937 episodes in the validation cohort, and 38,904 in the testing cohort. Readmission within 90 days was documented in 80,213 (27.3%) episodes, with a median time to emergency readmission of 22 days (Interquartile range: 8-47). For different time points, the readmission rates observed in the whole cohort were 6.7% at 7 days, 10.6% at 14 days, 13.6% at 21 days, 16.4% at 30 days, and 23.0% at 60 days. In the testing cohort, the SERAP achieved an integrated area under the curve of 0.737 (95% confidence interval: 0.730-0.743). For a specific 30-day readmission prediction, SERAP outperformed the LACE index (Length of stay, Acuity of admission, Charlson comorbidity index, and Emergency department visits in past six months) and the HOSPITAL score (Hemoglobin at discharge, discharge from an Oncology service, Sodium level at discharge, Procedure during the index admission, Index Type of admission, number of Admissions during the last 12 months, and Length of stay). Besides 30-day readmission, SERAP can predict readmission rates at any time point during the 90-day period. Interpretation: Better performance in risk prediction was achieved by the SERAP than other existing scores, and accurate information about time to emergency readmission was generated for further temporal risk stratification and clinical decision-making. In the future, external validation studies are needed to evaluate the SERAP at different settings and assess their real-world performance. Funding: This study was supported by the Singapore National Medical Research Council under the PULSES Center Grant, and Duke-NUS Medical School.

Association of ambient air pollution with risk of hemorrhagic stroke: A time-stratified case crossover analysis of the Singapore stroke registry.

BACKGROUND: Haemorrhagic stroke (HS) is a major cause of mortality and disability. Previous studies reported inconsistent associations between ambient air pollutants and HS risk. OBJECTIVE: We evaluated the association between air pollutant exposure and the risk of HS in a cosmopolitan city in the tropics. METHODS: We performed a nationwide, population-based, time-stratified case-crossover analysis on all HS cases reported to the Singapore Stroke Registry from 2009 to 2018 (n = 12,636). We estimated the risk of HS across tertiles of air pollutant concentrations in conditional Poisson models, adjusting for meteorological confounders. We stratified our analysis by age, atrial fibrillation and smoking status, and investigated the lagged effects of each pollutant on the risk of HS up to 5 days. RESULTS: All 12,636 episodes of HS were included. The median (1st-to 3rd-quartile) daily pollutant levels from 22 remote stations deployed across the island were as follows: (PM2.5 = 15.9 (12.7-20.5), PM10 = 27.3 (22.7-33.4), O3 = 22.5 (17.3-29.8), NO2 = 23.3 (18.8-28.4), SO2 = 10.2 (5.6-14.4), CO = 0.5 (0.5-0.6). The median (1st-to 3rd-quartile) temperature (°C) was 27.9 (27.1-28.7), that of relative humidity (%) was 79.4 (75.6-83.2), and that of total rainfall (mm) was 0.0 (0.0-4.2). Higher levels of CO were significantly associated with an increased risk of HS (3rd tertile vs 1st tertile: Incidence Rate Ratio (IRR) = 1.06, 95% CI = 1.01-1.12). The increased risk of HS due to CO persisted for at least 5 days after exposure. Individuals under 65 years old and non-smokers had a higher risk of HS when exposed to CO. O3 was associated with increased risk of HS up to 5 days (3rd tertile vs 1st tertile: IRRday 1 = 1.07, 95% CI = 1.02-1.12; IRRday 5 = 1.07, 95% CI = 1.02-1.13). CONCLUSION: Short-term exposure to ambient CO levels was associated with an increased risk of HS. A reduction in CO emissions may reduce the burden of HS in the population.

Association between smoking status and outcomes in myocardial infarction patients undergoing percutaneous coronary intervention.

Smoking is one of the leading risk factors for cardiovascular diseases, including ischemic heart disease and hypertension. However, in acute myocardial infarction (AMI) patients, smoking has been associated with better clinical outcomes, a phenomenon termed the "smoker's paradox." Given the known detrimental effects of smoking on the cardiovascular system, it has been proposed that the beneficial effect of smoking on outcomes is due to age differences between smokers and non-smokers and is therefore a smoker's pseudoparadox. The aim of this study was to evaluate the association between smoking status and clinical outcomes in ST-segment elevation (STEMI) and non-STEMI (NSTEMI) patients treated by percutaneous coronary intervention (PCI), using a national multi-ethnic Asian registry. In unadjusted analyses, current smokers had better clinical outcomes following STEMI and NSTEMI. However, after adjusting for age, the protective effect of smoking was lost, confirming a smoker's pseudoparadox. Interestingly, although current smokers had increased risk for recurrent MI within 1 year after PCI in both STEMI and NSTEMI patients, there was no increase in mortality. In summary, we confirm the existence of a smoker's pseudoparadox in a multi-ethnic Asian cohort of STEMI and NSTEMI patients and report increased risk of recurrent MI, but not mortality, in smokers.

Electric bicycle-related injuries presenting to a provincial hospital in China: A retrospective study.

The use of electric bicycles (EBs) in China is growing. In the present study, we aimed to characterize the pattern and outcomes of EB-related injuries presenting to a major general hospital in China.This was a retrospective review of EB-related injuries presenting to Zhejiang Provincial People's Hospital from 2008 to 2011. Cases were identified from medical records according to diagnosis codes. Data captured included demographics, injury characteristics, and outcomes.A total of 3156 cases were reviewed in the present study. There were 1460 cases of traffic accidents, of which 482 cases were EB-related (32.7%). In addition, most of EB-related cases (44.6%) belonged to the 41- to 60-year-old age group. Median injury severity score was 10. Moreover, 34.9% underwent surgery and 24.7% were admitted to intensive care unit. The median hospitalization cost was 14,269 USD. Fracture (56.5%) was the most frequently diagnosed injury type, and head was the most commonly injured body region (31.1%).EB-related injuries have become a major health concern, making up a sizeable proportion of injuries presenting to the emergency department. Therefore, it is necessary to establish injury prevention and strategies for EB road safety. Implementation of policy such as compulsory helmet use, as well as popularization of EB road safety education should be considered to improve the current situation of EB-related injuries in China.