Nomogram for the prediction of tigecycline-induced hypofibrinogenaemia in a Chinese population.

BACKGROUND: Tigecycline has been widely used for multi-drug-resistant bacterial infections in China. Although many studies have reported the risk factors for tigecycline-induced hypofibrinogenaemia, it remains unknown whether valproic acid or voriconazole in combination with tigecycline is associated with the decrease in fibrinogen, as both drugs could lead to coagulation disorders. The aim of this study was to develop a nomogram for the prediction of tigecycline-induced hypofibrinogenaemia. METHODS: This was a multi-centre retrospective case-control study. The primary outcome was the accurate prediction of tigecycline-induced hypofibrinogenaemia. Nomograms were developed from logistic regression models with least absolute shrinkage and selection operator regression for variable selection. Model performance was assessed via calibration plots, and models were validated internally using bootstrapping on a validation cohort. RESULTS: In total, 2362 patients were screened, of which 611 were eligible for inclusion in this study. These 611 patients were divided into the training cohort (n=488) and the validation cohort (n=123). Predictors included in the nomogram for the total population were total dose, age, fibrinogen, prothrombin time (PT), comorbidity, and concomitant use of voriconazole. Total dose, fibrinogen, PT, activated partial thromboplastin time, white blood cell count, and concomitant use of voriconazole were selected to predict hypofibrinogenaemia in patients with malignant haematologic diseases. Both models were calibrated adequately, and their predictions were correlated with the observed outcome. The cut-offs for treatment duration in the total population and the subgroup were 10 and 6 days, respectively. CONCLUSIONS: Tigecycline in combination with voriconazole could increase the risk of hypofibrinogenaemia, and tigecycline-induced hypofibrinogenaemia is more likely to occur in patients with malignant haematologic diseases.

LncRNA CASC2 Alleviates Sepsis-induced Acute Lung Injury by Regulating the miR-152-3p/PDK4 Axis.

BACKGROUND: Acute lung injury (ALI) is an early complication of sepsis and it is also considered as an important cause of high mortality in sepsis patients. This research aimed to explore the potential role and mechanism of long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) in sepsis-induced ALI. METHODS: The levels of CASC2, microRNA-152-3p (miR-152-3p) and pyruvate dehydrogenase kinase 4 (PDK4) in sepsis patients and LPS-treated HPAEpiC were detected by quantitative real-time PCR and western blot. Cell viability and apoptosis were assessed by Counting Kit-8 (CCK-8) assay and flow cytometry. The concentrations of inflammatory factors were tested by Enzyme-linked immunosorbent assay. Oxidative stress was evaluated by the levels of reactive oxygen species and superoxide dismutase using corresponding commercial kits. The targeting relationship between miR-152-3p and CASC2 or PDK4 was verified by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. RESULTS: CASC2 and PDK4 were down-regulated, while miR-152-3p was up-regulated in sepsis patients and LPS-stimulated HPAEpiC. Overexpression of CASC2 relieved the LPS-resulted cell viability inhibition, apoptosis promotion, inflammatory and oxidative damages in HPAEpiC. In addition, miR-152-3p was a miRNA target of CASC2 and CASC2 alleviated cell injury in LPS-disposed HPAEpiC by sponging miR-152-3p. Moreover, miR-152-3p directly targeted PDK4 and CASC2 increased the PDK4 expression by depending on the sponge effect on miR-152-3p. Meanwhile, inhibition of miR-152-3p attenuated LPS-triggered HPAEpiC injury by upregulating the level of PDK4. CONCLUSION: These results suggested that CASC2 ameliorated the LPS-induced injury in HPAEpiC via regulating miR-152-3p/PDK4 pathway.