Jamie Sin Ying Ho

Background: Ischemic stroke incidence in young adults is increasing globally, with return to work (RTW) a key rehabilitation goal. We aimed to assess the overall proportions of and factors associated with RTW following young adult ischemic stroke. Methods and Results: We performed a retrospective cohort study of all patients with ischemic stroke aged 18 to 50 years at 2 tertiary hospitals in Singapore from 2020 to 2022. We evaluated associations between patient characteristics and 3‐month RTW status, augmenting these findings with a systematic review and meta‐analysis of PubMed, Embase, Scopus, and Cochrane databases from January 2000 to November 2023. We pooled proportions for RTW and functional recovery (defined as a 90‐day modified Rankin Scale score of 0–2) and meta‐analyzed associations between patient characteristics and RTW using random‐effects models. In this multicenter cohort, 68.8% (249/362) of young patients with ischemic stroke returned to work, while 87.8% (318/362) achieved functional recovery. Multivariable logistic regression showed that patients with large‐artery atherosclerosis pathogenesis, diabetes, higher admission National Institutes of Health Stroke Scale scores, and higher 90‐day modified Rankin Scale had significantly lower odds of RTW. The systematic review and meta‐analyses of 1914 patients across 6 cohort studies identified significantly lower odds of RTW in patients with large‐artery atherosclerosis, diabetes, and admission National Institutes of Health Stroke Scale SCORE >15. The pooled proportion of RTW was 63.2% (984/1574 [95% CI, 56.0–69.9]) and functional recovery 84.7% (719/846 [95% CI, 81.1–87.8]). Conclusions: Patients with large‐artery atherosclerosis, diabetes, and higher admission National Institutes of Health Stroke Scale score at baseline are less likely to RTW. While lower 90‐day modified Rankin Scale is significantly associated with RTW, many patients achieving functional recovery do not RTW. Well‐designed cohort studies are warranted to explore this disparity.

Background: Left atrial (LA) fibrosis is a marker of atrial cardiomyopathy and has been reported to be associated with both atrial fibrillation and ischemic stroke. Elucidating this relationship is clinically important as LA fibrosis could serve as a surrogate biomarker of LA cardiomyopathy. The objective of this study is to investigate the association of LA fibrosis and embolic stroke of undetermined source (ESUS) using cardiac magnetic resonance imaging. Methods and Results: Following an International Prospective Register of Systematic Reviews‐registered protocol, 3 blinded reviewers performed a systematic review for studies that quantified the degree of LA fibrosis in patients with ESUS as compared with healthy patients from inception to February 2024. A meta‐analysis was conducted in the mean difference. From 7 studies (705 patients), there was a significantly higher degree of LA fibrosis in patients with ESUS compared with healthy controls (MD, 5.71% [95% CI, 3.55%–7.87%], P P P =0.35). Conclusions: A significantly higher degree of LA fibrosis was found in patients with ESUS as compared with healthy controls. This suggests that LA fibrosis may play a significant role in the pathogenesis of ESUS. Further research is warranted to investigate LA fibrosis as a surrogate biomarker of atrial cardiomyopathy and recurrent stroke risk in patients with ESUS.

BACKGROUND: Cardiocerebral infarction (CCI), which is concomitant with acute myocardial infarction (AMI) and acute ischemic stroke (AIS), is a rare but severe presentation. However, there are few data on CCI, and the treatment options are uncertain. We investigated the characteristics and outcomes of CCI compared with AMI or AIS alone. METHODS: We performed a retrospective cohort study of 120 531 patients with AMI and AIS from the national stroke and AMI registries in Singapore. Patients were categorized into AMI only, AIS only, synchronous CCI (same-day), and metachronous CCI (within 1 week). The primary outcome was all-cause mortality, and the secondary outcome was cardiovascular mortality. The mortality risks were compared using Cox regression. Multivariable models were adjusted for baseline demographics, clinical variables, and treatment for AMI or AIS. RESULTS: Of 127 919 patients identified, 120 531 (94.2%) were included; 74 219 (61.6%) patients had AMI only, 44 721 (37.1%) had AIS only, 625 (0.5%) had synchronous CCI, and 966 (0.8%) had metachronous CCI. The mean age was 67.7 (SD, 14.0) years. Synchronous and metachronous CCI had a higher risk of 30-day mortality (synchronous: adjusted HR [aHR], 2.41 [95% CI, 1.77–3.28]; metachronous: aHR, 2.80 [95% CI, 2.11–3.73]) than AMI only and AIS only (synchronous: aHR, 2.90 [95% CI, 1.87–4.51]; metachronous: aHR, 4.36 [95% CI, 3.03–6.27]). The risk of cardiovascular mortality was higher in synchronous and metachronous CCI than AMI (synchronous: aHR, 3.03 [95% CI, 2.15–4.28]; metachronous: aHR, 3.41 [95% CI, 2.50–4.65]) or AIS only (synchronous: aHR, 2.58 [95% CI, 1.52–4.36]; metachronous: aHR, 4.52 [95% CI, 2.95–6.92]). In synchronous CCI, AMI was less likely to be managed with PCI and secondary prevention medications ( P <0.001) compared with AMI only. CONCLUSIONS: Synchronous CCI occurred in 1 in 200 cases of AIS and AMI. Synchronous and metachronous CCI had higher mortality than AMI or AIS alone.

Background/introduction: Type 2 myocardial infarction (T2MI), caused by myocardial oxygen supply/demand mismatch without acute thrombotic plaque disruption, makes up 2-25% of reported MI. T2MI may be triggered by conditions such as arrhythmias, anaemia, sepsis, heart failure, but the incidence, outcomes and predictors of poor outcomes post-T2MI requires further study. Aims: In this study, we characterised the incidence, outcomes and predictors of poor outcomes in T2MI in Singapore. Methods: We performed an ambidirectional cohort study of 10720 consecutive T2MI patients from January 2012 to December 2018 from the national Singapore MI Registry (SMIR). The primary outcome was major adverse cardiovascular events (MACE; composite of MI, stroke and mortality) within 30 days and 1 year. The secondary outcomes were all-cause mortality, cardiovascular death and stroke. Results: Of 10,724 patients with T2MI, 3852 (35.9%) had MACE within 30 days and 5947 (51.4%) had MACE within 1 year (Table 1). The incidence of T2MI increased from 20 per 100,000 residents in 2012 to 80 per 100,000 residents in 2017 (Figure 1A). Significant independent predictors of MACE at 30 days on multivariable analysis include age (hazard ratio [HR] 1.01, 95% confidence interval (CI) 1.00-1.01), history of hypertension (HR 1.23, 95% CI 1.06-1.42) or diabetes mellitus (HR 1.32, 95% CI 1.17-1.48), Killip classes 2-4 and left ventricular ejection fraction <50% during hospitalization. Low hemoglobin (Hb) 8-9 (HR 1.42, 95% CI 1.07-1.88) and 10-11 (HR 1.36, 95% CI 1.05-1.76) compared to Hb 14-15, were predictors of MACE at 30 days and Hb <13 showed significant associated with MACE at 1 year. Hb <12 was also significantly associated with all-cause mortality at 1 year, but not cardiovascular death or stroke. Significant predictors of stroke at 1 year included current smoking (HR 1.53, 95% CI 1.04-2.23) and atrial fibrillation (AF) (HR 1.54, 95% CI 1.21-1.97). Troponin levels were not significantly associated with MACE at 30 days or 1 year. Conclusions: The incidence of T2MI has been increasing since 2012, with generally poor outcomes within 1 year. Predictors of poor outcomes include age, history of cardiovascular risk factors, AF, reduced LVEF during hospitalization, and low hemoglobin. A higher target Hb may be needed post-T2MI, and further research is needed to establish this.

Objectives: Infective endocarditis (IE) is a devastating disease with a 50% 1-year mortality rate. In recent years, medical authorities across the globe advised stricter criteria for antibiotic prophylaxis in patients with high risk of IE undergoing dental procedures. Whether such recommendations may increase the risk of IE in at-risk patients must be investigated. Design: Prospectively registered systematic review and meta-analysis. Data sources: Medline, Embase, Scopus and ClinicalTrials.gov were searched through 23 May 2022, together with an updated search on 5 August 2023. Eligibility criteria: All primary studies reporting IE within 3 months of dental procedures in adults >18 years of age were included, while conference abstracts, reviews, case reports and case series involving fewer than 10 cases were excluded. Data extraction and synthesis: All studies were assessed by two reviewers independently, and any discrepancies were further resolved through a third researcher. Results: Of the 3771 articles screened, 38 observational studies fit the inclusion criteria and were included in the study for subsequent analysis. Overall, 11% (95% CI 0.08 to 0.16, I ² =100%) of IE are associated with recent dental procedures. Streptococcus viridans accounted for 69% (95% CI 0.46 to 0.85) of IE in patients who had undergone recent dental procedures, compared with only 21% (95% CI 0.17 to 0.26) in controls (p=0.003). None of the high-risk patients developed IE across all studies where 100% of the patients were treated with prophylactic antibiotics, and IE patients are 12% more likely to have undergone recent dental manipulation compared with matched controls (95% CI 1.00 to 1.26, p=0.048). Conclusions: Although there is a lack of randomised control trials due to logistic difficulties in the literature on this topic, antibiotic prophylaxis are likely of benefit in reducing the incidence of IE in high-risk patients after dental procedures. Further well-designed high-quality case-control studies are required. Trial registration number: CRD42022326664.

Acute ischemic stroke (AIS) is the leading cause of disability and one of the top causes of mortality worldwide. The current standard of care is reperfusion therapy including intravenous thrombolysis (IVT) and thrombectomy. However, these treatments have limitations as they have a limited therapeutic window. Hence, there is a vital need to develop neuroprotective agents to prevent brain injury, extend the reperfusion window, improve mortality, and reduce disability in AIS patients. Neuroprotective agents work by counteracting the detrimental biochemical and molecular events that result in irreversible ischemic damage. Numerous preclinical studies and clinical trials have been done on different agents. Thus far, all have been definitively unsuccessful in large trials. Currently, there are several challenges in translation from animal studies to human trials. It is important to understand the current evidence as well as past challenges in the development of neuroprotective strategies in AIS in order for a more strategic selection of agents to be studied, improve study designs and thus contribute to the development of effective neuroprotective agents. Newer agents have shown promise in neuroprotection, and human trials are ongoing. In this review, the mechanisms of action of different families of neuroprotective agents were discussed. The evidence for the efficacy of different drugs in each family of neuroprotective agents was also evaluated and the current research landscape in neuroprotection for AIS was summarized. The past challenges and limitations in clinical trials and proposed possible ways to address these issues were highlighted.

We thank Dr Zhou Shunfeng for his kind comments on our study. ¹ Our study synthesized data from case reports regarding cardio-cerebral infarctions (CCI), to determine the characteristics of the patients and the available treatment modalities. Given the high mortality rate of CCI, and consequently a low number of recorded cases in literature, no relevant large-scale studies surfaced during our search, which was also commented on by the author. We appreciate the author for highlighting this need, as further research is needed to determine the best treatment for these patients. Another suggestion was including patient characteristics such as body mass index, occupation and diet. We agree that the description of the above parameters would better characterize the population of patients that experience CCI. We are unfortunately limited in the collection of such data due to the nature of the studies available for use in our analysis. Future large-scale studies would benefit by including the above parameters in their data collection and reporting.

Introduction: This study aimed to investigate the impact of anaemia on long-term clinical outcomes in patients who underwent semi-urgent and elective percutaneous coronary intervention (PCI) in an Asian population. Although the effects of anaemia on outcomes in Asian patients are well studied for acute coronary syndrome, its impact on Asian patients undergoing semi-urgent and elective PCI is unclear.Methods: This was a retrospective cohort study of patients who underwent semi-urgent and elective PCI from January 1, 2014, to December 31, 2015, at a tertiary academic centre. A total of 1,685 patients were included. They were stratified into three groups: normal (≥12 g/dL), intermediate (10–11.9 g/dL), and low (p = 0.004]. This was driven by the increased risk of target lesions revascularisation observed in the low haemoglobin level group compared to the normal haemoglobin level group (aHR 17.74, 95% CI: 1.74, 180.80; p = 0.015). The patients in the low haemoglobin level group were also associated with a higher risk of bleeding events compared to the normal haemoglobin level group (aHR 7.18, 95% CI: 1.13, 45.40; p = 0.036).Conclusion: In our Asian cohort, patients with anaemia undergoing PCI were associated with a higher comorbid burden. Despite adjustments for comorbidities, these patients had higher mortality and worse cardiovascular outcomes following contemporary PCI.