Background To evaluate the effect of recombinant human thrombopoietin(rhTPO)on clinical prognosis by exploring changes in endothelial cell injury markers and inflammatory factors in patients with sepsis after treatmen...Background To evaluate the effect of recombinant human thrombopoietin(rhTPO)on clinical prognosis by exploring changes in endothelial cell injury markers and inflammatory factors in patients with sepsis after treatment with rhTPO.Methods This retrospective observational study involved patients with sepsis(diagnosed according to Sepsis 3.0)admitted to Shanghai General Hospital intensive care unit from January 1,2019 to December 31,2022.Patients were divided into two groups(control and rhTPO)according to whether they received rhTPO.Baseline information,clinical data,prognosis,and survival status of the patients,as well as inflammatory factors and immune function indicators were collected.The main monitoring indicators were endothelial cell-specific molecule(ESM-1),human heparin-binding protein(HBP),and CD31;secondary monitoring indicators were interleukin(IL)-6,tumor necrosis factor(TNF)-α,extravascular lung water index,platelet,antithrombin III,fibrinogen,and international normalized ratio.We used intraperitoneal injection of lipopolysaccharide(LPS)to establish a mouse model of sepsis.Mice were randomly divided into four groups:normal saline,LPS,LPS+rhTPO,and LPS+rhTPO+LY294002.Plasma indicators in mice were measured by enzyme-linked immunosorbent assay.Results A total of 84 patients were included in the study.After 7 days of treatment,ESM-1 decreased more significantly in the rhTPO group than in the control group compared with day 1(median=38.6[interquartile range,IQR:7.2 to 67.8]pg/mL vs.median=23.0[IQR:−15.7 to 51.5]pg/mL,P=0.008).HBP and CD31 also decreased significantly in the rhTPO group compared with the control group(median=59.6[IQR:−1.9 to 91.9]pg/mL vs.median=2.4[IQR:−23.2 to 43.2]pg/mL;median=2.4[IQR:0.4 to 3.5]pg/mL vs.median=−0.6[IQR:−2.2 to 0.8]pg/mL,P<0.001).Inflammatory markers IL-6 and TNF-αdecreased more significantly in the rhTPO group than in the control group compared with day 1(median=46.0[IQR:15.8 to 99.1]pg/mL vs.median=31.2[IQR:19.7 to 171.0]pg/mL,P<0.001;median=17.2[IQR:6.4 to 23.2]pg/mL vs.median=0.0[IQR:0.0 to 13.8]pg/mL,P=0.010).LPS+rhTPO-treated mice showed significantly lower vascular von Willebrand factor(P=0.003),vascular endothelial growth factor(P=0.002),IL-6(P<0.001),and TNF-α(P<0.001)than mice in the LPS group.Endothelial cell damage factors vascular von Willebrand factor(P=0.012),vascular endothelial growth factor(P=0.001),IL-6(P<0.001),and TNF-α(P=0.001)were significantly elevated by inhibiting the PI3K/Akt pathway.Conclusion rhTPO alleviates endothelial injury and inflammatory indices in sepsis,and may regulate septic endothelial cell injury through the PI3K/Akt pathway.展开更多
Background Since the beginning of the coronavirus disease 2019(COVID-19)pandemic,prone positioning has been widely applied for non-intubated,spontaneously breathing patients.However,the efficacy and safety of prone po...Background Since the beginning of the coronavirus disease 2019(COVID-19)pandemic,prone positioning has been widely applied for non-intubated,spontaneously breathing patients.However,the efficacy and safety of prone positioning in non-intubated patients with COVID-19-related acute hypoxemic respiratory failure remain unclear.We aimed to systematically analyze the outcomes associated with awake prone positioning(APP).Methods We conducted a systematic literature search of PubMed/MEDLINE,Cochrane Library,Embase,and Web of Science from January 1,2020,to June 3,2022.This study included adult patients with acute respiratory failure caused by COVID-19.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines were followed,and the study quality was assessed using the Cochrane risk-of-bias tool.The primary outcome was the reported cumulative intubation risk across randomized controlled trials(RCTs),and the effect estimates were calculated as risk ratios(RRs;95%confidence interval[CI]).Results A total of 495 studies were identified,of which 10 fulfilled the selection criteria,and 2294 patients were included.In comparison to supine positioning,APP significantly reduced the need for intubation in the overall population(RR=0.84,95%CI:0.74–0.95).The two groups showed no significant differences in the incidence of adverse events(RR=1.16,95%CI:0.48–2.76).The meta-analysis revealed no difference in mortality between the groups(RR=0.93,95%CI:0.77–1.11).Conclusions APP was safe and reduced the need for intubation in patients with respiratory failure associated with COVID-19.However,it did not significantly reduce mortality in comparison to usual care without prone positioning.展开更多
基金supported by grants from the Shenkang Municipal Hospital emerging Frontier technology joint project(grant no.SHDC12019131)the National Natural Science Foundation of China(grant no.82202423)+4 种基金the Clinical Research Innovation Plan of Shanghai General Hospital(grant no.CCTR-2022B04)the 3rd Sansheng TCP Young and Middleaged Scientific Research FundingShanghai Jiao Tong University“Medicine-Engineering Interdisciplinary Research Fund”(grant no.YG2021QN79)National Key Clinical Specialist Construction Project(grant no.Z155080000004)Shanghai Committee(grant no.23Y31900100).
文摘Background To evaluate the effect of recombinant human thrombopoietin(rhTPO)on clinical prognosis by exploring changes in endothelial cell injury markers and inflammatory factors in patients with sepsis after treatment with rhTPO.Methods This retrospective observational study involved patients with sepsis(diagnosed according to Sepsis 3.0)admitted to Shanghai General Hospital intensive care unit from January 1,2019 to December 31,2022.Patients were divided into two groups(control and rhTPO)according to whether they received rhTPO.Baseline information,clinical data,prognosis,and survival status of the patients,as well as inflammatory factors and immune function indicators were collected.The main monitoring indicators were endothelial cell-specific molecule(ESM-1),human heparin-binding protein(HBP),and CD31;secondary monitoring indicators were interleukin(IL)-6,tumor necrosis factor(TNF)-α,extravascular lung water index,platelet,antithrombin III,fibrinogen,and international normalized ratio.We used intraperitoneal injection of lipopolysaccharide(LPS)to establish a mouse model of sepsis.Mice were randomly divided into four groups:normal saline,LPS,LPS+rhTPO,and LPS+rhTPO+LY294002.Plasma indicators in mice were measured by enzyme-linked immunosorbent assay.Results A total of 84 patients were included in the study.After 7 days of treatment,ESM-1 decreased more significantly in the rhTPO group than in the control group compared with day 1(median=38.6[interquartile range,IQR:7.2 to 67.8]pg/mL vs.median=23.0[IQR:−15.7 to 51.5]pg/mL,P=0.008).HBP and CD31 also decreased significantly in the rhTPO group compared with the control group(median=59.6[IQR:−1.9 to 91.9]pg/mL vs.median=2.4[IQR:−23.2 to 43.2]pg/mL;median=2.4[IQR:0.4 to 3.5]pg/mL vs.median=−0.6[IQR:−2.2 to 0.8]pg/mL,P<0.001).Inflammatory markers IL-6 and TNF-αdecreased more significantly in the rhTPO group than in the control group compared with day 1(median=46.0[IQR:15.8 to 99.1]pg/mL vs.median=31.2[IQR:19.7 to 171.0]pg/mL,P<0.001;median=17.2[IQR:6.4 to 23.2]pg/mL vs.median=0.0[IQR:0.0 to 13.8]pg/mL,P=0.010).LPS+rhTPO-treated mice showed significantly lower vascular von Willebrand factor(P=0.003),vascular endothelial growth factor(P=0.002),IL-6(P<0.001),and TNF-α(P<0.001)than mice in the LPS group.Endothelial cell damage factors vascular von Willebrand factor(P=0.012),vascular endothelial growth factor(P=0.001),IL-6(P<0.001),and TNF-α(P=0.001)were significantly elevated by inhibiting the PI3K/Akt pathway.Conclusion rhTPO alleviates endothelial injury and inflammatory indices in sepsis,and may regulate septic endothelial cell injury through the PI3K/Akt pathway.
基金supported by the Clinical Research Plan of SHDC (grant number:SHDC2020CR2013A)the Clinical Research Plan of SHDC (grant number:SHDC2020CR5010-003).
文摘Background Since the beginning of the coronavirus disease 2019(COVID-19)pandemic,prone positioning has been widely applied for non-intubated,spontaneously breathing patients.However,the efficacy and safety of prone positioning in non-intubated patients with COVID-19-related acute hypoxemic respiratory failure remain unclear.We aimed to systematically analyze the outcomes associated with awake prone positioning(APP).Methods We conducted a systematic literature search of PubMed/MEDLINE,Cochrane Library,Embase,and Web of Science from January 1,2020,to June 3,2022.This study included adult patients with acute respiratory failure caused by COVID-19.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines were followed,and the study quality was assessed using the Cochrane risk-of-bias tool.The primary outcome was the reported cumulative intubation risk across randomized controlled trials(RCTs),and the effect estimates were calculated as risk ratios(RRs;95%confidence interval[CI]).Results A total of 495 studies were identified,of which 10 fulfilled the selection criteria,and 2294 patients were included.In comparison to supine positioning,APP significantly reduced the need for intubation in the overall population(RR=0.84,95%CI:0.74–0.95).The two groups showed no significant differences in the incidence of adverse events(RR=1.16,95%CI:0.48–2.76).The meta-analysis revealed no difference in mortality between the groups(RR=0.93,95%CI:0.77–1.11).Conclusions APP was safe and reduced the need for intubation in patients with respiratory failure associated with COVID-19.However,it did not significantly reduce mortality in comparison to usual care without prone positioning.
