Microbiological profile and risk factors for in-hospital mortality of infective endocarditis in tertiary care hospitals of south Vietnam.

OBJECTIVES: We aimed to evaluate the microbiological characteristics and risk factors for mortality of infective endocarditis in two tertiary hospitals in Ho Chi Minh City, south Vietnam. MATERIALS AND METHODS: A retrospective study of 189 patients (120 men, 69 women; mean age 38 ± 18 years) with the diagnosis of probable or definite infective endocarditis (IE) according to the modified Duke Criteria admitted to The Heart Institute or Tam Duc Hospital between January 2005 and December 2014. RESULTS: IE was related to a native valve in 165 patients (87.3%), and prosthetic valve in 24 (12.7%). Of the 189 patients in our series, the culture positive rate was 70.4%. The most common isolated pathogens were Streptococci (75.2%), Staphylococci (9.8%) followed by gram negative organism (4.5%). The sensitivity rate of Streptococci to ampicillin, ceftriaxone or vancomycin was 100%. The rate of methicillin resistant Staphylococcus aureus was 40%. There was a decrease in penicillin sensitivity for Streptococci over three eras: 2005-2007 (100%), 2008-2010 (94%) and 2010-2014 (84%). The in-hospital mortality rate was 6.9%. Logistic regression analysis found prosthetic valve and NYHA grade 3 or 4 heart failure and vegetation size of more than 15 mm as strong predictors of in-hospital mortality. CONCLUSION: Streptococcal species were the major pathogen of IE in the recent years with low rates of antimicrobial resistance. Prosthetic valve involvement, moderate or severe heart failure and vegetation size of more than 15 mm were independent predictors for in-hospital mortality in IE.

Occult RV systolic dysfunction detected by CMR derived RV circumferential strain in patients with pectus excavatum.

AIMS: To investigate the right ventricular (RV) strain in pectus excavatum (PE) patients using cardiac magnetic resonance tissue tracking (CMR TT). MATERIALS AND METHODS: Fifty consecutive pectus excavatum patients, 10 to 32 years of age (mean age 15 ± 4 years), underwent routine cardiac magnetic resonance imaging (CMR) including standard measures of chest geometry and cardiac size and function. The control group consisted of 20 healthy patients with a mean age of 17 ± 5 years. RV longitudinal and circumferential strain magnitude was assessed by a dedicated RV tissue tracking software. RESULTS: Fifty patients with images of sufficient quality were included in the analysis. The mean right and left ventricular ejection fractions were 55 ± 5% and 59 ± 4%. The RV global longitudinal strain was -21.88 ± 4.63%. The RV circumferential strain at base, mid-cavity and apex were -13.66 ± 3.09%, -11.31 ± 2.79%, -20.73 ± 3.45%, respectively. There was no statistically significant decrease in right ventricular or left ventricular ejection fraction between patients and controls (p > 0.05 for each). There was no significant difference in RV global longitudinal strain between two groups (-21.88 ± 4.63 versus -21.99 ± 3.58; p = 0.93). However, there was significant decrease in mid-cavity circumferential strain magnitude in pectus patients compared with controls (-11.31 ± 2.79 versus -16.19 ± 2.86; p < 0.001). PE patients had a significantly higher basal circumferential strain (-13.66 ± 3.09% versus -9.76 ± 1.79; p < 0.001) as well as apical circumferential strain (-20.73 ± 3.45% versus -12.07 ± 3.38) than control group. CONCLUSION: Mid-cavity circumferential strain but not longitudinal strain is reduced in pectus excavatum patients. Basal circumferential strain as well as apical circumferential strain were increased as compensatory mechanism for reduced mid-cavity circumferential strain. Further studies are needed to establish clinical significance of this finding.

2-(1 -hydroxyiminoalkyl)-1 ,4-dimethoxy-9,10-anthraquinones: synthesis and evaluation of cytotoxicity.

A series of 2-(1-hydroxyiminoalkyl)-1,4-dimethoxy-9,10-anthraquinones (oximes) was synthesized and evaluated for cytotoxicity against L1210 cells and A549 cells. These oximes showed a greater cytotoxic activity compared to those of 2-(1-hydroxyalkyl)-1,4-dimethoxy-9,10-anthraquinones as the hydroxyalkyl bioisosteres. The enhanced cytotoxicity assumed to be due to the improved water solubility of the hydroxyimino group. Moreover, it was found that the cytotoxicity of the oximes decreased with elongation of alkyl groups at the side chain. All of the synthesized compounds showed higher cytotoxicity against L1210 cells than A549 cells.

Synthesis and evaluation of the antitumor activity of 2-substituted 1,4-dihydroxy-9,10-anthraquinones.

2-(1-Hydroxyiminoalkyl)-1,4-dimethoxy-9,10-anthraquinones were demethylated to produce 2-(1-hydroxyiminoalkyl)-1,4-dihydroxy-9,10-anthraquinones (1,4-dihydroxy-9,10-anthraquinone, DHAQ), oxime hydroxyl groups were in turn acylated to give the corresponding 2-(1-acyloxyiminoalkyl)-DHAQ derivatives. The anti-proliferative activity of 2-(1-hydroxyiminoalkyl)-DHAQ derivatives was found to be dependent on the size of an alkyl chain. Thus, DHAQ analogues with alkyl chains longer than heptyl had negligible anti-proliferative activity, whilst those compounds possessing shorter chains demonstrated moderate anti-proliferative activity (ED50, 2.73-19.21 microM). However, the antitumor activity as expressed by T/C values did not correlate with the anti-proliferative activity; 2-(1-hydroxyiminononyl)-DHAQ with an ED50 value of more than 20 microM exhibited potent antitumor activity (T/C, 166%). Only four of the 2-(1-hydroxyiminoalkyl)-DHAQ analogues showed good antitumor activity (T/C, > 150%); 2-(1-hydroxyiminobutyl)-DHAQ (T/C, 163%), 2-(1-hydroxyiminopentyl)-DHAQ (T/C, 180%) and 2-(1-hydroxyiminononyl)-DHAQ (T/C, 166%). Acylation of the hydroxyl group of these oximes enhanced the anti-proliferative activity and antitumor effects; 2-(1-propanoyloxyiminopropyl)-DHAQ (ED50, 4.41 microM; T/C, 221%) vs. 2-(1-hydroxyiminopropyl)-DHAQ (ED50, 14.64 microM; T/C, 100%) and 2-(1-propanoyloxyiminobutyl)-DHAQ (ED50, 2.65 microM; T/C, 202%) vs. 2-(1-hydroxyiminobutyl)-DHAQ (ED50, 16.43 microM; T/C, 163%).

Effect of the aryl substituent on antitumor activity of 2-substituted-1,4-dihydroxy-9,10-anthraquinones and 2-substituted-anthracene-1,4,9,10-tetraones.

2-(1-Aryl-1-hydroxymethyl)- and 2-aroyl-DHAQ derivatives (DHAQ, 1,4-dihydroxy-9,10-anthraquinone), and 2-(1-aryl-1-hydroxymethyl)-ATO derivatives (ATO, anthracene-1,4,9,10-tetraone) were synthesized and their antitumor activities were determined. 2-(1-Aryl-1-hydroxymethyl)-DHAQ derivatives showed a stronger cytotoxicity compared to the series of 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10-anthraquinone derivatives. It was suggested that the presence of aryl group at the side chain accelerated the bioreductive activation leading to cell death. 2-Aroyl-DHAQ derivatives, despite their higher electrophilicity, revealed smaller cytotoxicity and antitumor activity (expressed by T/C value) than 2-(1-aryl-1-hydroxymethyl)-DHAQ derivatives. Thus, no consistent relationship between the electronic effect on aromatic side chain and the cytotoxicity was observed. ATO series exhibited a higher antitumor activity (T/C, 125 to approximately 218%), though their cytotoxicity was not further improved compared to that of 2-(1-aryl-1-hydroxymethyl)-1,4-dihydroxy-9,10-anthraquinones. They manifested no correlation between the cytotoxicity and the antitumor activity. In case of 2-[1-hydroxy-1-(4-propylphenyl)-methyl]-ATO, the most bioactive one in vivo among the same series, it showed an ED50 value of 10.2 mg/mL and a T/C value of 218%. It is assumed that the anthracene-1,4,9,10-tetraones after uptake into cellular tissues might be transformed to a cytotoxic metabolite(s).