Given the higher likelihood of ACS and respiratory complications amongst SCD patients during the H1N1 outbreak, it is possible that SCD patients are also at higher risk of such complications from COVID-19, particularly those with a history of pulmonary comorbidities. However, it is unclear if the SARS-CoV-2 pandemic will lead to increased rates of ACS for sickle cell patients. Still, hospitalized sickle cell patients should be monitored closely for development of ACS and if this occurs, exchange transfusion should be promptly initiated.
Introduction
Thymic epithelial tumors (TETs) are rare tumors originating from the epithelia of the thymus, and therapeutic options beyond surgery are limited. Pathogenesis of TETs is poorly understood, and the scarcity of model systems for these rare tumors makes the study of their biology very challenging.
Methods
A new cell line (MP57) was established from a thymic carcinoma specimen and characterized using standard biomarker analysis, as well as next generation sequencing (NGS), and functional assays. Sanger sequencing was used to confirm the mutations identified by NGS.
Results
MP57 possesses all the tested thymic epithelial markers and is deemed to be a bona fide thymic carcinoma cell line. NGS analysis of MP57 identified a mutation in PIK3R2, a regulatory subunit of PI3K. Further analysis identified different mutations in multiple PI3K subunits in another cell line and several primary thymic carcinoma samples, including two catalytic subunits (PIK3CA and PIK3CG) and another regulatory subunit (PIK3R4). Inhibiting PI3K with GDC0941 resulted in in vitro antitumor activities in TET cells carrying mutant PI3K subunits.
Conclusions
Alterations of PI3K, due to mutations in its catalytic or regulatory subunits, is observed in a subgroup of TETs, in particular thymic carcinomas. Targeting PI3K may be an effective strategy to treat these tumors.
Aim
Optimal dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) intends to balance ischemic and bleeding risks. Various DAPT de-escalation strategies, defined as switching from a full-dose potent to a reduced dose or less potent P2Y12 inhibitor, have been evaluated in several ACS-PCI trials. We aimed to compare DAPT de-escalation to standard DAPT with full dose potent P2Y12 inhibitors in ACS patients who underwent PCI.
Methods & results
PubMed, Google Scholar and Cochrane Central Register of Controlled Trials were searched for eligible randomised controlled trials. Aspirin monotherapy trials were excluded. Five randomised trials (n = 10,779 patients) that assigned DAPT de-escalation (genetically guided to clopidogrel n = 1,242; platelet function guided to clopidogrel n = 1,304; unguided to clopidogrel n = 1,672; unguided to lower dose n = 1,170) versus standard DAPT (control group n = 5,391) were included in this analysis. DAPT de-escalation was associated with a significant reduction in Bleeding Academic Research Consortium ≥ 2 bleeding (HR 0.57, 95% CI 0.42–0.78; I2 = 77%) as well as major adverse cardiac events, represented in most trials by the composite of cardiovascular mortality, myocardial infarction, stent thrombosis and stroke (HR 0.77, 95% CI 0.62–0.96; I2 = 0%). Notwithstanding the limited power, consistency was noted across various de-escalation strategies.
Conclusion
De-escalation of DAPT after PCI for ACS, both unguided and guided by genetic or platelet function testing, was associated with lower rates of clinically relevant bleeding and ischemic events as compared to standard DAPT with potent P2Y12 inhibitors based on five open-label RCTs reviewed.
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