• Journal of Yeungnam Medical Science
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• v.38 no.4
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• pp.318-325
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• 2021

Background: The diagnosis and prediction of prognosis are important in patients with sepsis, and presepsin is helpful. In this study, we aimed to examine the usefulness of presepsin in predicting the prognosis of sepsis in Korea. Methods: Patients diagnosed with sepsis according to the sepsis-3 criteria were recruited into the study and classified into surviving and non-surviving groups based on in-hospital mortality. A total of 153 patients (32 and 121 patients with sepsis and septic shock, respectively) were included from July 2019 to August 2020. Results: Among the 153 patients with sepsis, 91 and 62 were in the survivor and non-survivor groups, respectively. Presepsin (p=0.004) and lactate (p=0.003) levels and the sequential organ failure assessment (SOFA) score (p<0.001) were higher in the non-survivor group. Receiver operating characteristic curve analysis revealed poor performances of presepsin and lactate in predicting the prognosis of sepsis (presepsin: area under the curve [AUC]=0.656, p=0.001; lactate: AUC=0.646, p=0.003). The SOFA score showed the best performance, with the highest AUC value (AUC=0.751, p<0.001). The prognostic cutoff point for presepsin was 1,176 pg/mL. Presepsin levels higher than 1,176 pg/mL (odds ratio [OR], 3.352; p<0.001), higher lactate levels (OR, 1.203; p=0.003), and higher SOFA score (OR, 1.249; p<0.001) were risk factors for in-hospital mortality. Conclusion: Presepsin levels were higher in non-survivors than in survivors. Thus, presepsin may be a valuable biomarker in predicting the prognosis of sepsis.

• Journal of The Korean Society of Emergency Medicine
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• v.29 no.5
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• pp.474-484
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• 2018

Objective: The time to positivity (TTP) of blood culture reflects bacterial load and has been reported to be associated with outcome in bloodstream infections. This study was performed to evaluate the relationship between the TTP of blood culture and the mortality rates associated with sepsis and septic shock according to the site of infection. Methods: We performed a retrospective cohort study on patients with sepsis and septic shock. The rates of blood culture positivity and mortality as well as the relationship between the TTP and 28-day mortality rate were compared among patients with different sites of infection, such as the lungs, abdomen, urogenital tract, and other sites. Results: A total of 2,668 patients were included, and the overall mortality rate was 21.6%. The rates of blood culture positivity and mortality were different among the different infection sites. There was no relationship between the TTP and mortality rates of total, lung, and urogenital infections. Patients with abdominal infections showed a negative correlation between the TTP and 28-day mortality rate. In patients with abdominal infections, a TTP<20 hours was independently associated with 28-day mortality compared with patients with negative blood culture (hazard ratio, 1.73; 95% confidence interval, 1.16-2.58). However, there was no difference in mortality rates of patients with a $TTP{\geq}20$ hours and a negative blood culture. Conclusion: The shorter TTP in patients with abdominal infections in sepsis and septic shock was associated with a higher 28-day mortality rate.

• BMB Reports
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• v.49 no.4
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• pp.214-219
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• 2016

A nucleosomal protein, high mobility group box 1 (HMGB1) is known to be a late mediator of sepsis. Dabrafenib is a B-Raf inhibitor and initially used for the treatment of metastatic melanoma therapy. Inhibition of HMGB1 and renewal of vascular integrity is appearing as an engaging therapeutic strategy in the administration of severe sepsis or septic shock. Here, we examined the effects of dabrafenib (DAB) on the modulation of HMGB1-mediated septic responses. DAB inhibited the release of HMGB1 and downregulated HMGB1-dependent inflammatory responses by enhancing the expressions of cell adhesion molecules (CAMs) in human endothelial cells. In addition, treatment with DAB inhibited the HMGB1 secretion by CLP and sepsis-related mortality and pulmonary injury. This study demonstrated that DAB could be alternative therapeutic options for sepsis or septic shock via the inhibition of the HMGB1 signaling pathway.

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.262.3-263
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• 2001

• IMMUNE NETWORK
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• v.10 no.3
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• pp.99-103
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• 2010

Background: Glycogen synthase kinase $3{\beta}$ ($GSK3{\beta}$) is a ubiquitous serine/threonine kinase that is regulated by serine phosphorylation at 9. Recent studies have reported the beneficial effects of a number of the pharmacological $GSK3{\beta}$ inhibitors in rodent models of septic shock. Since most of the $GSK3{\beta}$ inhibitors are targeted at the ATP-binding site, which is highly conserved among diverse protein kinases, the development of novel non-ATP competitive $GSK3{\beta}$ inhibitors is needed. Methods: Based on the unique phosphorylation motif of $GSK3{\beta}$, we designed and generated a novel class of $GSK3{\beta}$ inhibitor (GSK3i) peptides. In addition, we investigated the effects of a GSK3i peptide on lipopolysaccharide (LPS)-stimulated cytokine production and septic shock. Mice were intraperitoneally injected with GSK3i peptide and monitored over a 7-day period for survival. Results: We first demonstrate its effects on LPS-stimulated pro-inflammatory cytokine production including interleukin (IL)-6 and IL-12p40. LPS-induced IL-6 and IL-12p40 production in macrophages was suppressed when macrophages were treated with the GSKi peptide. Administration of the GSK3i peptide potently suppressed LPS-mediated endotoxin shock. Conclusion: Collectively, we present a rational strategy for the development of a therapeutic GSK3i peptide. This peptide may serve as a novel template for the design of non-ATP competitive GSK3 inhibitors.

• Journal of Ginseng Research
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• v.32 no.4
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• pp.315-323
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• 2008

In the previous studies, we isolated the compound K rich fractions (CKRF) and showed that CKRF inhibited Toll-like receptor (TLR) 4- or TLR9-induced inflammatory signaling. To extend our previous studies,1) we investigated the molecular mechanisms of CKRF in the TLR4-associated signaling via nuclear factor (NF)-${\kappa}B$, and in vivo role of CKRF for induction of tolerance in lipopolysaccharide (LPS)-induced septic shock. In murine bone marrow-dervied macrophages, CKRF significantly inhibited the induction of mRNA expression of proinflammatory mediators such as tumor necrosis factor-${\alpha}$, interleukin-6, cyclooxygenase-2, and inducible nitric oxide synthase. In addition, CKRF significantly attenuated the transcriptional activities of TLR4/LPS-induced NF-${\kappa}B$. Nuclear translocation of NF-${\kappa}B$ in response to LPS stimulation was significantly abrogated by pre-treatment with CKRF. Furthermore, CKRF inhibited the recruitment of p65 to the interferon-sensitive response element flanking region in response to LPS. Finally, oral administration of CKRF significantly protected mice from Gram-negative bacterial LPS-induced lethal shock and inhibited systemic inflammatory cytokine levels. Together, these results demonstrate that CKRF modulates the TLR4-dependent NF-${\kappa}B$ activation, and suggest a therapeutic role for Gram-negative septic shock.

• Journal of Sasang Constitutional Medicine
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• v.25 no.4
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• pp.432-441
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• 2013

Objectives Despite the treatment with antibiotics, patients with sepsis has a high mortality (80%) in the underlying disease group. The aim of this study was to report the improvement of septic condition of the cholangiocarcinoma patient after the treatment with Handayeolso-tang, Fel Tauri, and antibiotics. Methods We retrospectively reviewed the medical records. The patient's subjective symptoms such as chilling and abdominal pain were evaluated by NRS and the performance status was evaluated by ECOG. This case was literally compared with relevant published studies on prognosis of sepsis. Results Despite poor prognostic factor(MEDS score 18), the patient's symptoms such as fever, chilling, abdominal pain, and diarrhea and ECOG(Eastern Cooperative Oncology Group) improved. The patient was hemodynamically stabilized on 3rd day from the treatment, and her laboratory test results were normalized on 7th day. Conclusions A female patient of metastatic cholangiocarcinoma came to the hospital for cholangitis, later causing septic shock. Both her symptoms and laboratory tests showed significant improvement after the treatment of antibiotics, Handayeolso-tang and Fel Tauri. To our knowledge, this is the first case reporting the synergistic combination of Korean oriental medicine and Western medicine approaching to sepsis.

• Journal of The Korean Society of Emergency Medicine
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• v.29 no.5
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• pp.465-473
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• 2018

Objective: We evaluated the clinical characteristics and prognoses of patients with septic shock who transferred to the emergency department (ED) in a tertiary referral center. Methods: This study was performed using a prospective, multi-center registry of septic shock, with the participation of 11 tertiary referral centers in the Korean Shock Society between October 2015 and February 2017. We classified the patients as a transferred group who transferred from other hospitals after meeting the inclusion criteria upon ED arrival and a non-transferred group who presented directly to the ED. Primary outcome was hospital mortality. We conducted multiple logistic regression analysis to assess variables related to in-hospital mortality. Results: A total of 2,098 patients were included, and we assigned 717 patients to the transferred group and 1,381 patients to the non-transferred group. The initial Sequential Organ Failure Assessment score was higher in the transferred group than the non-transferred group (6; interquartile range [IQR], 4-9 vs. 6; IQR, 4-8; P<0.001). Mechanical ventilator (29% vs. 21%, P<0.001) and renal replacement therapy (12% vs. 9%, P=0.034) within 24 hours after ED arrival were more frequently applied in the transferred group than the non-transferred group. Overall hospital mortality was 22% and there was no significant difference between transferred and non-transferred groups (23% vs. 22%, P=0.820). Multivariable analysis showed an odds ratio for in-hospital mortality of 1.00 (95% confidence interval, 0.78-1.28; P=0.999) for the transferred group compared with the non-transferred group. Conclusion: The transferred group showed higher severity and needed more organ support procedures than the non-transferred group. However, inter-hospital transfer did not affect in-hospital mortality.

• YAKHAK HOEJI
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• v.45 no.1
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• pp.16-22
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• 2001

Novel yakuchinone derivatives have been designed, synthesized and evaluated their inhibitory activity of NO production in lipopolysaccharide (LPS)-activated macrophages. From this study, some enone compounds have been found to be highly active in the assay. In view of the importance of NO in septic shock and inflammation, these compounds may be useful candidates for the development of new drug to treat endotoxemia and inflammation accompanying overproduction of NO.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.203.2-204
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• 2003

Nitric oxide (NO) produced in large amounts by inducible nitric oxide synthase (iNOS) is known to be responsible for the vasodilation and hypotension observed in septic shock and inflammation. Inhibitors of iNOS, thus, may be useful candidate for the treatment of inflammatory diseases accompanied by the overproduction of NO. We prepared alcoholic extracts of woody plants and screened the inhibitory activity of NO production in lipopolysaccharide (LPS)-activated macrophages after the treatment of these extracts. (omitted)