Prediction of 28-days mortality with sequential organ failure assessment (SOFA), quick SOFA (qSOFA) and systemic inflammatory response syndrome (SIRS) — A retrospective study of medical patients with acute infectious disease

Aims: Evaluating the use of sequential organ failure assessment (SOFA) ≥ 2 compared to quick SOFA (qSOFA) and to systemic inflammatory response syndrome (SIRS) in assessing 28-days mortality in medical patients with acute infection. Methods: In total, 323 patients with verified infection were stratified in accordance to Sepsis-3. SOFA, qSOFA and SIRS were calculated using registered variables. Adverse outcome was death within 28-days of admission. Results: In total, 190 (59%) patients had a SOFA score ≥ 2 and the overall in-hospital mortality was 21 (6%). Scores of SOFA and qSOFA were both significantly elevated in non-survivors. SOFA showed good accuracy (Area under the receiver operating characteristic (AUROC) = 0.83, 95% CI, 0.76 - 0.90) for 28-days mortality compared with qSOFA (AUROC = 0.67, 95% CI, 0.54 - 0.80) and SIRS (AUROC = 0.62, 95% Cl 0.49 - 0.74). SOFA was ≥ 2 in all patients who died, while qSOFA and SIRS was ≥ 2 in 8 (38%) and 17 (81%) of the patients who died, respectively. Conclusion: SOFA score ≥ 2 was better than SIRS and qSOFA to predict mortality within 28-days of admission among patients with acute infectious disease. Keywords: Sepsis, qSOFA, SOFA, SIRS, Non-IC

The macrophage activation marker sMR as a diagnostic and prognostic marker in patients with acute infectious disease with or without sepsis

<p>Sepsis is a leading cause of mortality. This study aims to assess the utility of the soluble mannose receptor (sMR) as a biomarker of sepsis and mortality in patients hospitalized with suspected infection. Using an in-house ELISA assay the concentration of sMR was analyzed in the serum of patients from three prospective studies. Using Sepsis-3 guidelines, patients were stratified as no infection (NI, <i>n</i> = 68), verified infection without sepsis (NSEP, <i>n</i> = 133) and verified infection with sepsis (SEP, <i>n</i> = 190). Adverse outcome was assessed as death before 28 days. We show that the sensitivity of sMR to predict mortality [area under curve (AUC) = 0.77] exceeded the sensitivity of procalcitonin (PCT, AUC = 0.63), C-reactive protein (CRP, AUC = 0.61) and the macrophage soluble receptor, CD163 (sCD163, AUC = 0.74), while it was less accurate to predict diagnosis of sepsis [AUC(sMR) = 0.69 vs. AUC(PCT) = 0.79, AUC(CRP) = 0.71 and AUC(sCD163) = 0.66]. Median sMR was significantly higher in the group with SEP (0.55 mg/L), compared with the groups without sepsis (NI and NSEP) (0.39 mg/L, <i>p</i> < .0001), and among those who died compared to those who survived (0.89 mg/L vs. 0.44 mg/L, <i>p</i> < .0001). Our results, and the current literature, support further evaluation of sMR as a biomarker of sepsis and mortality among patients hospitalized with suspected infection.</p

SSX2 is a novel DNA-binding protein that antagonizes polycomb group body formation and gene repression

Polycomb group (PcG) complexes regulate cellular identity through epigenetic programming of chromatin. Here, we show that SSX2, a germline-specific protein ectopically expressed in melanoma and other types of human cancers, is a chromatin-associated protein that antagonizes BMI1 and EZH2 PcG body formation and derepresses PcG target genes. SSX2 further negatively regulates the level of the PcG-associated histone mark H3K27me3 in melanoma cells, and there is a clear inverse correlation between SSX2/3 expression and H3K27me3 in spermatogenesis. However, SSX2 does not affect the overall composition and stability of PcG complexes, and there is no direct concordance between SSX2 and BMI1/H3K27me3 presence at regulated genes. This suggests that SSX2 antagonizes PcG function through an indirect mechanism, such as modulation of chromatin structure. SSX2 binds double-stranded DNA in a sequence non-specific manner in agreement with the observed widespread association with chromatin. Our results implicate SSX2 in regulation of chromatin structure and function