Data driven analysis reveals prognostic genes and immunological targets in human sepsis-associated acute kidney injury

BACKGROUND:The molecular mechanism of sepsis-associated acute kidney injury(SA-AKI)is unclear.We analyzed co-differentially expressed genes(co-DEGs)to elucidate the underlying mechanism and intervention targets of SA-AKI.METHODS:The microarray datasets GSE65682,GSE30718,and GSE174220 were downloaded from the Gene Expression Omnibus(GEO)database.We identified the co-DEGs and constructed a gene co-expression network to screen the hub genes.We analyzed immune correlations and disease correlations and performed functional annotation of the hub genes.We also performed single-cell and microenvironment analyses and investigated the enrichment pathways and the main transcription factors.Finally,we conducted a correlation analysis to evaluate the role of the hub genes.RESULTS:Interleukin 32(IL32)was identified as the hub gene in SA-AKI,and the main enriched signaling pathways were associated with hemopoiesis,cellular response to cytokine stimulus,inflammatory response,and regulation of kidney development.Additionally,IL32 was significantly associated with mortality in SA-AKI patients.Monocytes,macrophages,T cells,and NK cells were closely related to IL32 and were involved in the immune microenvironment in SA-AKI patients.IL32 expression increased significantly in the kidney of septic mouse.Toll-like receptor 2(TLR2)was significantly and negatively correlated with IL32.CONCLUSION:IL32 is the key gene involved in SA-AKI and is significantly associated with prognosis.TLR2 and relevant immune cells are closely related to key genes.

The Influencing Factors of Neutrophil-to-Lymphocyte Ratio as a Prognostic Marker for Sepsis:Analysis from a Large Database

The neutrophil-to-lymphocyte ratio (NLR) is an important predictive prognostic tool. However, its accuracy for predicting sepsis remains debatable. This study aimed to evaluate the factors influencing the ability of NLR to predict sepsis. Adult patients with sepsis or septic shock from the eICU database were enrolled in this study. Results showed that there was a significant difference in NLR between the survival and nonsurvival groups (median [lower quartile–upper quartile], 15.27 [7.92–26.28] vs. 17.97 [8.94–31.85], P = 0.008). Area under the curve (AUC) of NLR on the sixth day was the highest. AUC of NLR was significantly higher in the Simplified Acute Physiological Score (SAPS) 3 ≤52 group than that in the SAPS3 > 52 group (0.78 ± 0.05 vs. 0.69 ± 0.03, P = 0.007). AUC of NLR in the nonshock group was significantly higher than that in the shock group (0.72 ± 0.04 vs. 0.65 ± 0.05, P < 0.01). The ability of NLR as a prognosis predictor of sepsis was influenced by admission time, SAPS3, and shock.

Influence of positive end-expiratory pressure upregulation on the right ventricle in critical patients with acute respiratory distress syndrome:an observational cohort study

Background This study aimed to investigate the influence of positive end-expiratory pressure(PEEP)on the right ventricle(RV)of mechanical ventilation-assisted patients through echocardiography.Methods Seventy-six patients assisted with mechanical ventilation were enrolled in this study.Positive end-expiratory pressure was upregulated by 4 cm H_(2)O to treat acute respiratory distress syndrome,wherein echocardiography was performed before and after this process.Hemodynamic data were also recorded.All variables were compared before and after PEEP upregulation.The effect of PEEP was also evaluated in patients with and without decreased static lung compliance(SLC).Results Positive end-expiratory pressure upregulation significantly affected the RV function.Remarkable differences were observed in the following:Tei index(P=0.027),pulmonary artery pressure(P=0.039),tricuspid annular plane systolic excursion(P=0.014),early wave/atrial wave(P=0.002),diaphragm excursion(P<0.001),inferior vena cava collapsing index(P<0.001),and SLC(P<0.001).There were no significant changes in heart rate,respiratory rate,central venous pressure,mean arterial pressure,and base excess(P>0.05).Furthermore,the cardiac output of the RV was not significantly affected.In patients with decreased SLC(n=41),there were more significant changes in diaphragm excursion(P<0.001),inferior vena cava collapse index(P=0.025),pulmonary artery pressure(P<0.001),and tricuspid annular plane systolic excursion(P=0.007)than in those without decreased SLC(n=35).Conclusion Positive end-expiratory pressure upregulation significantly affected the RV function of critically ill patients with acute respiratory distress syndrome,especially in those with decreased SLC.

Hospital healthcare costs attributable to heat and future estimations in the context of climate change in Perth, Western Australia

Climate change with increasing temperature is making a significant impact on human health, including more heat-related diseases, and increasing the burden on the healthcare system. Although many studies have explored the association between increasing temperatures and negative health outcomes, research on the associated costs of heat-related diseases remains relatively sparse. Furthermore, estimations of future costs associated with heat-attributable hospital healthcare have not been well explored. This study used a distributed lag nonlinear model to estimate heat-attributable hospital healthcare costs in Perth, Western Australia. Using 2006–2012 as the baseline, future costings for 2026–2032 and 2046–2052 were estimated under RCP2.6, RCP4.5, and RCP8.5. Higher temperatures were found to be associated with increased hospital healthcare costs. The total hospital costs attributable to heat over the baseline period 2006–2012 was estimated to be 79.5 million AUD, with costs for mental health hospitalizations being the largest contributor of the heat-related conditions examined. Costs are estimated to increase substantially to 125.8–129.1 million AUD in 2026–2032, and 174.1–190.3 million AUD by midcentury under climate change scenarios. Our findings of a notable burden of heat-attributable healthcare costs now and in the future emphasize the importance of climate change adaptation measures to reduce the adverse health effects of increasing temperatures and heat exposure on the people of Perth.

No benefit of hydrocortisone,ascorbic acid,and thiamine in reducing mortality in adult sepsis patients:a systematic review and meta-analysis

Background:Supplementation of corticosteroid,ascorbic acid and thiamine in adult septic patients remains controversial.We aimed to evaluate the efficacy and safety of hydrocortisone,ascorbic acid and thiamine(HAT)in adult septic patients.Methods:Data search included Pumbed,EMBASE,and the Cochrane Library from inception to Sep,2021.Only studies with classifications of sepsis and intravenous HAT treatment were included.Adult patients with sepsis(aged≥18 years)were divided into 2 groups.The treatment group received HAT therapy,whereas the control group received standard care and/or intravenous hydrocortisone.The primary outcome was hospital mortality.Results:Eleven studies including 4579 patients who fulfilled the predefined criteria were analyzed(6 randomized controlled trials[RCTs]and 5 clinical cohort studies).No hospital mortality reduction was demonstrated in patients treated with HAT when compared to the reference(OR:0.99;95%CI:0.77 to 1.27;I^(2)=39%)group.Sequential organ failure assessment(SOFA)score decrement at 72hours was more significant in HAT-treated patients(mean difference[MD]:–1.23;95%CI:–1.94 to–0.53;I^(2)=81%).There was no difference in the duration of vasopressor use between HAT-treated patients and controls(MD:–4.92;95%CI:–24.38 to 14.53;I^(2)=97%).Statistical heterogeneity was noted with no sign of significant publication bias.Conclusion:In adult sepsis and septic shock patients,HAT treatment failed to reduce mortality or shorten vasopressor duration,but reduced SOFA scores.