Outcomes of thrombus aspiration during primary percutaneous coronary intervention for ST-elevation myocardial infarction.

BACKGROUND: Previous large multi-centre randomised controlled trials have not provided clear benefit with routine intracoronary thrombus aspiration (TA) as an adjunct to primary percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI). AIM: To determine whether there is a difference in outcomes with the use of manual TA prior to PCI, compared with PCI alone in a cohort of patients with STEMI. METHODS: We analysed data from 6270 consecutive patients undergoing primary PCI for STEMI prospectively enrolled in the Melbourne Interventional Group registry between 2007 and 2018. Multivariable analysis was performed to determine predictors of 30-day major adverse cardiovascular and cerebrovascular events (MACCE) and long-term mortality. RESULTS: We compared 1621 (26%) patients undergoing primary PCI with TA to 4649 (74%) patients undergoing PCI alone. Male gender (81% vs 78%; P < 0.01), younger age (61 vs 63 years; P = 0.03), GP-IIb/IIIa use (76% vs 58%, P < 0.01), and current smoking (40% vs 36%; P < 0.01) were more common in the TA group. TA was more likely to be used in patients with complex lesions (83% vs 66%; P < 0.01) with TIMI 0 flow (77% vs 56%; P < 0.01). No significant difference in post-procedural TIMI flow, stroke, 30-day mortality, or long-term mortality were identified. Multivariable analysis demonstrated a reduction in 30-day MACCE (hazard ratio (HR) 0.75; confidence interval (CI) 0.63-0.89; P < 0.01) in the TA group, but was not associated with long-term mortality (HR 0.98; CI 0.85-1.1; P = 0.73). CONCLUSION: The use of TA in patients undergoing primary PCI for STEMI was not associated with improved short or long-term mortality when compared with PCI alone.

METTL3 promotes colorectal cancer metastasis by promoting the maturation of pri-microRNA-196b.

PURPOSE: Methyltransferase-like 3 (METTL3), a key member of the m6A methyltransferase complex, is upregulated in multiple human malignancies and plays a role in regulating tumor migration. This study aimed to reveal the underlying mechanism by which METTL3 in regulates the metastasis of colorectal cancer (CRC). METHODS: We compared METTL3 expression levels in CRC tumor tissues and adjacent nontumor tissues by immunohistochemistry (IHC). The functional roles of METTL3 in CRC were assessed by real-time cell migration assays, wound-healing assays and Transwell assays. miRNA sequencing (miRNA-seq), RNA-binding protein immunoprecipitation (RIP) assays and N6-methyladenosine immunoprecipitation (MeRIP) assays were performed to confirm the molecular mechanism underlying the involvement of METTL3 in CRC cell metastasis. RESULTS: We found that METTL3 was overexpressed in CRC tissues. METTL3 knockdown significantly inhibited CRC cell migration and invasion, while METTL3 overexpression had the opposite effects. Furthermore, we demonstrated that METTL3 regulates miR-196b expression via an N6-methyladenosine (m6A)-pri-miR-196b-dependent mechanism and thereby promotes CRC metastasis. CONCLUSION: This study shows the important role of METTL3 in CRC metastasis and provides novel insight into m6A modification in CRC metastasis.

Arrhythmogenic Right Ventricular Cardiomyopathy: A Review of Living and Deceased Probands.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a potentially life-threatening genetic cardiomyopathy with a spectrum of clinical presentations including sudden cardiac death (SCD). METHODS: Clinical and genetic data of 44 probands referred to a cardiac genetics clinic (2007-2017) who met 2010 Task Force Criteria (TFC) for ARVC diagnosis were included. RESULTS: Thirty-three (33) (75%) male, 20 (45%) were referred by the Victorian Institute of Forensic Medicine. Presentation that lead to diagnosis included ARVC-related SCD (n=19), SCD due to alternate cause of death (n=1), aborted cardiac arrest (n=6), stable symptomatic ventricular tachycardia (n=14), palpitations (n=3) and presyncope (n=1). Left ventricular involvement (50%) was more common in the SCD subgroup (84% vs 21%, p<0.001). Genetic testing (n=39) revealed a pathogenic mutation in 16 (commonest: plakophillin-2 (n=9)), a variant of uncertain significance (VUS) in 15, with no abnormality in eight. In the SCD subgroup, median age at death was 44.7 years and 74% were male. Genetic testing (n=16) in this subgroup revealed a pathogenic mutation in six patients (commonest: desmoplakin (n=4)). Comparison of the two commonest mutations (PKP2 and desmoplakin [DSP]) showed DSP mutation was more frequently associated with SCD (p<0.01) and LV involvement (p<0.001). Screening of 117 relatives has lead to ARVC diagnosis in 29 patients. CONCLUSIONS: Arrhythmogenic right ventricular cardiomyopathy has a heterogeneous and often severe clinical presentation. Sudden cardiac death and aborted cardiac arrest (ACA) are common, demonstrating electrical abnormalities appear early in the ARVC phenotype. Left ventricular involvement was common and may reflect a worse prognosis. Genetic testing is essential in family screening and may be helpful in risk assessment. Desmoplakin mutation is associated with LV involvement and may be indicative of worse prognosis and increased risk of SCD. Genetic screening of proband family members in a specialised multidisciplinary clinic is essential in early diagnosis of affected family members.