Advances in Dyslipidaemia Treatments: Focusing on ApoC3 and ANGPTL3 Inhibitors

Apolipoprotein C3 (apoC3) and angiopoietin-like protein 3 (ANGPTL3) inhibit lipolysis by lipoprotein lipase and may influence the secretion and uptake of various lipoproteins.Genetic studies show that depletion of these proteins is associated with improved lipid profiles and reduced cardiovascular events so it was anticipated that drugs which mimic the effects of loss-of-function mutations would be useful lipid treatments. ANGPTL3 inhibitors were initially developed as a treatment for severe hypertriglyceridaemia including familial chylomicronaemia syndrome (FCS), which is usually not adequately controlled with currently available drugs. However, it was found ANGPTL3 inhibitors were also effective in reducing low-density lipoprotein cholesterol (LDL-C) and they were studied in patients with homozygous familial hypercholesterolaemia (FH). Evinacumab targets ANGPTL3 and reduced LDL-C by about 50% in patients with homozygous FH and it has been approved for that indication. The antisense oligonucleotide (ASO) vupanorsen targeting ANGPTL3 was less effective in reducing LDL-C in patients with moderate hypertriglyceridaemia and its development has been discontinued but the small interfering RNA (siRNA) ARO-ANG3 is being investigated in Phase 2 studies. ApoC3 can be inhibited by the ASO volanesorsen, which reduced triglycerides by >70% in patients with FCS and it was approved for FCS in Europe but not in the United States because of concerns about thrombocytopaenia. Olezarsen is an N-acetylgalactosamine-conjugated ASO targeting apoC3 which appears as effective as volanesorsen without the risk of thrombocytopaenia and is undergoing Phase 3 trials. AROAPOC3 is an siRNA targeting apoC3 that is currently being investigated in Phase 3 studies.

Distribution,antimicrobial resistance of pathogens from blood culture,and risk factors for death of children with leukemia / 中国感染控制杂志

Objective To observe distribution and antimicrobial resistance of pathogens from blood culture of chil-dren with leukemia,and study risk factors.Methods From September 2013 to November 2016,species and antimi-crobial resistance types of 131 strains of pathogens isolated from blood culture of 110 children in a pediatric hemato-logy ward were analyzed,childrens'clinical data were also analyzed statistically.Results 131 strains(5.23%)of pathogens were isolated from 2 505 blood culture specimens,gram-negative bacilli and gram-positive cocci accounted for 52.67% and 43.51% respectively,the top 3 pathogens were Escherichia coli(15.27%),Klebsiella pneumoniae (15.27%),and Staphylococcus hominis(12.98%). Gram-negative bacilli were highly resistant to ampicillin,ce-fazolin,ceftriaxone,and ampicillin/sulbactam,but sensitive to amikacin,cefoperazone/sulbactam,piperacillin/tazobactam,and carbapenems;gram-positive cocci had higher resistance to penicillin,oxacillin,erythromycin,and clindamycin,but were sensitive to tigecycline,linezolid,vancomycin,and quinupristin/dalfopristin. Univariate analysis showed that mixed infection,diarrhea,Pseudomonasaeruginosa infection,and Acinetobacterbaumannii in-fection were related to mortality due to bloodstream infection in children with leukemia.Conclusion Pathogens cau-sing bloodstream infection in children with leukemia is widely distributed,antimicrobial resistance rate is high,it is very im-portant to take active precaution and rational treatment according to antimicrobial susceptibility testing result.

Emergence of methicillin-resistant Staphylococcus aureus SCCmec type IV/V epidemic clones in a large teaching hospital in China / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the staphylococcal cassette chromosome mec (SCCmec) genotype and molecular epidemiological characteristics of healthcare-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) in a large teaching hospital in China.</p><p><b>METHDOS</b>From January 2012 to December 2012, a total of 71 nonduplicate HA-MRSA were collected in a teaching hospital in Changsha, China. SCCmec types were determined by multiplex PCR, and Panton-Valentine leukocidin (PVL) gene was detected by PCR. The homology among the tested isolates was determined using pulsed-field gel electrophoresis (PFGE).</p><p><b>RESULTS</b>Of the 71 HA-MRSA isolates, 49 (69.0%) carried SCCmec III, 10 (14.1%) carried SCCmec IV, 3 (4.2%) carried SCCmec V and 3 (4.2%) carried SCCmec II; the remaining 6 isolates were not typeable by PCR. Compared with patients having SCCmec I/II/III MRSA infections, those with SCCmec IV/V MRSA infections had a significantly younger age and a similar duration of hospital stay before the first MRSA-positive culture and total hospital stay. PVL genes were strongly associated with SCCmec type IV/V MRSA infections. HA-SCCmec IV/V MRSA strains showed a greater susceptibility to rifampicin, gentamicin, levofloxacin, ciprofloxacin, and tetracycline than HA-SCCmec I/II/III MRSA strains. The 13 HA-SCCmec IV/V MRSA isolates formed one large group at the 55% similarity level. Three PFGE clusters with a similarity index of 85% or more were identified, and unique PFGE profiles were observed in 4 isolates.</p><p><b>CONCLUSION</b>This is the first report of HA-MRSA isolates carrying SCCmec V in Chinese hospitals. SCCmec types IV and V MRSA clones have emerged in Chinese hospitals, which urges more rigorous surveillance of their spread in healthcare facilities in China.</p>