Are prognostic scores and biomarkers such as procalcitonin the appropriate prognostic precursors for elderly patients with sepsis in the emergency department?

BACKGROUND: The mortality of patients with severe sepsis and septic shock is still high, and the prognosis of elderly patients tends to be particularly poor. Therefore, this study sought to conduct a comparative analysis of the abbreviated mortality in emergency department sepsis (abbMEDS) score, sequential organ failure assessment (SOFA) score, infection probability score (IPS), initial procalcitonin (PCT), and cytokine levels to investigate the effectiveness of each index in predicting the prognosis of elderly patients with sepsis in the emergency department (ED). METHODS: This was a single-center prospective study, and classified 55 patients (≥65 years of age) with systemic inflammatory response syndrome (SIRS) from January 2013 to December 2013 in the ED. A total of 36 elderly patients were diagnosed with sepsis. The prediction of prognosis using the prognostic scores (abbMEDS, SOFA, IPS) was analyzed. An early blood examination (WBC count, C-reactive protein, PCT, and cytokines) was conducted within the first 2 h of the patient's arrival at the ED. RESULTS: The median (IQR) age of subjects was 76.5 (70.5-81.5). After 28 days, 27 subjects (75 %) had survived, and 9 (25 %) had died. Fifteen (41.7 %) were sent to intensive care units (ICUs). The SOFA score and abbMEDS showed higher median (IQR) values of 9.5 (7.0-11.0) and 13.5 (12.0-15.0), respectively, in the ICU group than in the general ward group (p < 0.001). Analysis of the levels of PCT, IL-10, IL-6, and IL-5 had a significantly better ability to predict ICU admission (p = 0.001, p = 0.023, p = 0.030, p = 0.001). The prediction of mortality in the first 28 days via SOFA and the abbMEDS resulted in scores of 11.0 (8.0-11.0) and 14.0 (12.5-15.5) (p = 0.004, p = 0.003), respectively. However, levels of IPS, PCT, and cytokines did not show significant differences. CONCLUSIONS: In predicting ICU admission and the death of elderly sepsis patients in ED, SOFA and abbMEDS scores were effective. Of the various biomarkers, PCT, IL-10, IL-6, and IL-5 were effective in predicting ICU admission, but were not effective in predicting the death of elderly sepsis patients.

Anti-angiogenic and anti-tumor apoptotic activities of a topoisomerase II inhibiting agent SJ-8026.

A new piperazine derivative, SJ-8026, is a synthetic anti-cancer agent which exhibits topoisomerase II-inhibiting activities. In this study, we investigated the possibility that this compound inhibits angiogenesis and induces tumor-cell apoptosis using bovine aortic endothelial cells (BAECs) and human hepatocellular carcinoma cells (HepG2) as a model system. in vivo, SJ-8026 decreased the neovascularization of chick embryos and the basic fibroblast growth factor-induced angiogenesis in the chorioallantoic membrane and the mouse Matrigel implants. in vitro, SJ-8026 treatment resulted in the inhibition of proliferation, migration, invasion and tube formation in BAECs. In addition, the treatment of SJ-8026 in HepG2 cells reduced the cell viability, and caused the production of fragmented DNA and the morphological changes corresponding to apoptosis including condensed and fragmented DNA. SJ-8026 also elicited the release of cytochrome c and the activation of caspase-3. Therefore, it is possible that SJ-8026 functions as both angiogenesis inhibitor and apoptosis inducer. Taken together, these results suggest that SJ-8026 may be a candidate for strong anti-cancer agent with the ability to inhibit the angiogenesis of endothelial cells and to induce the apoptosis of tumor cells.

Anti-angiogenic and anti-tumor apoptotic activities of SJ-8002, a new piperazine derivative.

A new piperazine derivative, SJ-8002, is a synthetic anti-cancer agent which exhibits microtubule-inhibiting activities. In this study, we investigated the possibility that this compound inhibits angiogenesis and induces tumor-cell apoptosis using bovine aortic endothelial cells (BAECs) and human hepatocellular carcinoma cells (HepG2) as a model system, respectively. In vivo, SJ-8002 decreased the neovascularization of chick embryos and the basic fibroblast growth factor (bFGF)-induced angiogenesis in the chorioallantoic membrane (CAM) and the mouse Matrigel implants, respectively. In vitro, SJ-8002 treatment resulted in the inhibition of proliferation, migration, invasion and tube formation, and of matrix metalloproteinase-2 (MMP-2) expression in BAECs. In addition, the SJ-8002 treatment in HepG2 cells reduced cell viability, and caused the production of fragmented DNA and the morphological changes corresponding to apoptosis including condensed and fragmented DNA in a concentration-dependent manner. SJ-8002 also elicited the release of cytochrome c and the activation of caspase-3. Therefore, it is possible that SJ-8002 functions as both angiogenesis inhibitor and apoptosis inducer. Taken together, these results suggest that SJ-8002 may be a candidate for strong anti-cancer agent with the ability to inhibit the angiogenesis of endothelial cells and to induce the apoptosis of tumor cells.

Microtubule inhibitory effects of various SJ compounds on tissue culture cells.

SJ compounds (SJ8002 and related compounds) are a group of novel anticancer agents (Cho, Chung, Lee, Kwon, Kang, Joo, and Oh. PCT/KR02/00392). To explore the anticancer mechanism of these compounds, we examined the effect of SJ8002 on microtubules of six human cell lines. At a high concentration (2 microg/mL), SJ8002 effectively disrupted microtubules of the six cell lines within 1 h. At lower concentrations (0.05 to approximately 1.0 microg/mL), the antimicrotubule activity of SJ8002 varied defending on cell lines. The inhibition of in vitro polymerization of pure tubulin by SJ8002 suggested that SJ8002 acts on free tubulin, inhibits the polymerization of tubulin dimer into microtubules, and hence induces the depolymerization of microtubules.