The purpose of this meta-analysis was to compare the ability of the qSOFA in predicting short- (≤30 days or in-hospital mortality) and long-term (>30 days) mortality among patients outside the intensive care unit setting. Studies reporting on the qSOFA and mortality were searched using MEDLINE and SCOPUS. Studies were included if they involved patients presenting to the ED with suspected infection and usage of qSOFA score for mortality prognostication. Data on qSOFA scores and mortality rates were extracted from 36 studies. The overall pooled sensitivity and specificity for the qSOFA were 48% and 86% for short-term mortality and 32% and 92% for long-term mortality, respectively. Studies reporting on short-term mortality were heterogeneous (Odd ratio, OR = 5.6; 95% CI = 4.6-6.8; Higgins's I2 = 94%), while long-term mortality studies were homogenous (OR = 4.7; 95% CI = 3.5-6.1; Higgins's I2 = 0%). There was no publication bias for short-term mortality analysis. The qSOFA score showed poor sensitivity but moderate specificity for both short and long-term mortality, with similar performance in predicting both short- and long- term mortality. Geographical region was shown to have nominal significant (p = 0.05) influence on qSOFA short-term mortality prediction.
Non-viral gene delivery holds promises for treating inherited diseases. However, the limited cloning capacity of plasmids may hinder the co-delivery of distinct genes to the transfected cells. Previously, the conjugation of maleimide-functionalized polyurethane grafted with small molecular weight polyethylenimine (PU-PEI600-Mal) using 1,6-hexanedithiol (HDT) could promote the co-delivery and extensive co-expression of two different plasmids in target cells. Herein, we designed HDT-conjugated PU-PEI600-Mal for the simultaneous delivery of CRISPR/Cas9 components to achieve efficient gene correction in the induced pluripotent stem cell (iPSC)-derived model of Fabry cardiomyopathy (FC) harboring GLA IVS4 + 919 G > A mutation. This FC in vitro model recapitulated several clinical FC features, including cardiomyocyte hypertrophy and lysosomal globotriaosylceramide (Gb3) deposition. As evidenced by the expression of two reporter genes, GFP and mCherry, the addition of HDT conjugated two distinct PU-PEI600-Mal/DNA complexes and promoted the co-delivery of sgRNA/Cas9 and homology-directed repair DNA template into target cells to achieve an effective gene correction of IVS4 + 919 G > A mutation. PU-PEI600-Mal/DNA with or without HDT-mediated conjugation consistently showed neither the cytotoxicity nor an adverse effect on cardiac induction of transfected FC-iPSCs. After the gene correction and cardiac induction, disease features, including cardiomyocyte hypertrophy, the mis-regulated gene expressions, and Gb3 deposition, were remarkably rescued in the FC-iPSC-differentiated cardiomyocytes. Collectively, HDT-conjugated PU-PEI600-Mal-mediated dual DNA transfection system can be an ideal approach to improve the concurrent transfection of non-viral-based gene editing system in inherited diseases with specific mutations.