Chest pain symptoms during myocardial infarction in patients with and without diabetes: a systematic review and meta-analysis.

OBJECTIVE: Chest pain (CP) is key in diagnosing myocardial infarction (MI). Patients with diabetes mellitus (DM) are at increased risk of an MI but may experience less CP, leading to delayed treatment and worse outcomes. We compared the prevalence of CP in those with and without DM who had an MI. METHODS: The study population was people with MI presenting to healthcare services. The outcome measure was the absence of CP during MI, comparing those with and without DM. Medline and Embase databases were searched to 18 October 2021, identifying 9272 records. After initial independent screening, 87 reports were assessed for eligibility against the inclusion criteria, quality and risk of bias assessment (Strengthening the Reporting of Observational Studies in Epidemiology and Newcastle-Ottawa criteria), leaving 22 studies. The meta-analysis followed Meta-analysis Of Observational Studies in Epidemiology criteria and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled ORs, weights and 95% CIs were calculated using a random-effects model. RESULTS: This meta-analysis included 232 519 participants from 22 studies and showed an increased likelihood of no CP during an MI for those with DM, compared with those without. This was 43% higher in patients with DM in the cohort and cross-sectional studies (OR: 1.43; 95% CI: 1.26 to 1.62), and 44% higher in case-control studies (OR: 1.44; 95% CI: 1.11 to 1.87). CONCLUSION: In patients with an MI, patients with DM are less likely than those without to have presentations with CP recorded. Clinicians should consider an MI diagnosis when patients with DM present with atypical symptoms and treatment protocols should reflect this, alongside an increased patient awareness on this issue. PROSPERO REGISTRATION NUMBER: CRD42017058223.

Properdin: A Novel Target for Neuroprotection in Neonatal Hypoxic-Ischemic Brain Injury.

Background: Hypoxic-ischemic (HI) encephalopathy is a major cause of neonatal mortality and morbidity, with a global incidence of 3 per 1,000 live births. Intrauterine or perinatal complications, including maternal infection, constitute a major risk for the development of neonatal HI brain damage. During HI, inflammatory response and oxidative stress occur, causing subsequent cell death. The presence of an infection sensitizes the neonatal brain, making it more vulnerable to the HI damage. Currently, therapeutic hypothermia is the only clinically approved treatment available for HI encephalopathy, however it is only partially effective in HI alone and its application in infection-sensitized HI is debatable. Therefore, there is an unmet clinical need for the development of novel therapeutic interventions for the treatment of HI. Such an alternative is targeting the complement system. Properdin, which is involved in stabilization of the alternative pathway convertases, is the only known positive regulator of alternative complement activation. Absence of the classical pathway in the neonatal HI brain is neuroprotective. However, there is a paucity of data on the participation of the alternative pathway and in particular the role of properdin in HI brain damage. Objectives: Our study aimed to validate the effect of global properdin deletion in two mouse models: HI alone and LPS-sensitized HI, thus addressing two different clinical scenarios. Results: Our results indicate that global properdin deletion in a Rice-Vannucci model of neonatal HI and LPS-sensitized HI brain damage, in the short term, clearly reduced forebrain cell death and microglial activation, as well as tissue loss. In HI alone, deletion of properdin reduced TUNEL+ cell death and microglial post-HI response at 48 h post insult. Under the conditions of LPS-sensitized HI, properdin deletion diminished TUNEL+ cell death, tissue loss and microglial activation at 48 h post-HI. Conclusion: Overall, our data suggests a critical role for properdin, and possibly also a contribution in neonatal HI alone and in infection-sensitized HI brain damage. Thus, properdin can be considered a novel target for treatment of neonatal HI brain damage.