Background:Severe burns induce volume shifts via capillary leaks,eventually requiring massive fluid resuscitation and promoting tissue edema.Albumin may help to mitigate the edema,thereby improving perfusion.This stud...Background:Severe burns induce volume shifts via capillary leaks,eventually requiring massive fluid resuscitation and promoting tissue edema.Albumin may help to mitigate the edema,thereby improving perfusion.This study shows that sublingual microcirculation measurements can quantify both tissue perfusion and edema.Methods:This prospective observational study was conducted between November 2018 and December 2019 in the intensive care unit of Maasstad Hospital Burn Center,Rotterdam,The Netherlands.Patients with severe burns affecting>15%of the total body surface area were included.Fluid management was conducted in accordance with the Parkland formula.Albumin(20%)was administered at a rate of 0.5 mL/(kg·h),starting 12 h after the burn incident.Alterations in the sublingual microcirculation,including capillary perfusion and density,were measured at admission(T0)and 4 h(T4)and 12 h(T12)after admission.Sublingual depth of focus(DOF)of the microcirculation was used to quantify the tissue edema.Results:Nine patients were recruited with a mean total body surface area of 36%±23%.By T12,a median of 4085 mL(interquartile range[IQR]:3714-6756 mL)of crystalloids and 446 mL(IQR:176-700 mL)of 20%albumin were administered.The DOF increased significantly after crystalloid administration(T4 vs.T0,mean difference[MD]=27.4μm,95%confidence interval[CI]:3.4 to 50.9,P=0.040).Following albumin administration,DOF significantly decreased(T12 vs.T4,MD=-76.4μm,95%CI:-116.6 to-36.1,P=0.002).Total vessel density decreased significantly with crystalloid administration(T4 vs.T0,MD=-3.5 mm/mm2,95%CI:-5.7 to-1.4,P=0.004)but increased after albumin administration(T12 vs.T4,MD=6.2 mm/mm2,95%CI:3.2 to 9.3,P=0.001).Conclusion:Sublingual microcirculation measurement of DOF and other parameters provide a valuable tool for the assessment of tissue perfusion and edema in patients with severe burns.Further investigation is required to evaluate the role of albumin in increasing microcirculatory convection and reducing tissue edema.展开更多
Background and Aims:Liver failure syndromes are characterised by a dysregulated immune response leading to immune paralysis.Adrenomedullin(ADM)is a potent vasodilator and immunoregulator.This study aimed to explore th...Background and Aims:Liver failure syndromes are characterised by a dysregulated immune response leading to immune paralysis.Adrenomedullin(ADM)is a potent vasodilator and immunoregulator.This study aimed to explore the role of ADM in liver failure,hypothesising that there is a detrimental imbalance between ADM and adrenomedullin binding protein(AMBP)1 that promotes a switch of monocytes/macrophages towards a pro-restorative phenotype and function.Methods:Consecutive patients with acute liver failure(ALF),acute-on-chronic liver failure(ACLF),and decompensated cirrhosis,as well as healthy controls(HC)were included between April 2020 and June 2024.Peripheral blood mononuclear cells/monocytes were isolated and used for RNA sequencing and cell culture.ADM and AMBP1 were measured by enzyme-linked immunosorbent assay.Results:Fifty-four patients with ALF,25 with ACLF,9 with decompensated cirrhosis,and 16 with HC were included.ADM expression in isolated monocytes was increased in ALF(log fold change=5.88,p=0.000216413)and ACLF(log fold change=4.62,p=0.00057122)compared to HC.Plasma ADM concentration was higher in ALF(1,684±1,156 pg/mL)vs.ACLF(836.1±765.2 pg/mL)and HC(164.8±62.73 pg/mL).AMBP1 was significantly reduced in ALF(59.27±44μg/mL)vs.ACLF(126.3±72.23μg/mL)and HC(252.8±159.7μg/mL)(p<0.0001,ALF vs.HC).Treatment with LPS increased ADM concentration in peripheral blood mononuclear cell supernatant(ALF n=6;561.4±1,038 pg/mL vs.259.2±213.7 pg/mL,ACLF n=4;3,202±491.2 vs.1,757±1,689 pg/mL).The percentage of CD14+cells expressing Mer tyrosine kinase was reduced after culture with LPS(2.077±0.87%);however,co-culture with ADM 100 nM restored the phenotype(3.852±1.063%).Conclusions:ADM is increased in liver failure,whereas AMBP1 is reduced.ADM affects monocyte function,increasing Mer Tyrosine Kinase and promoting a pro-restorative,anti-inflammatory phenotype.展开更多
基金project is co-funded by the PPP allowance to stimulate public-private partnership made available by Health~Holland,Top Sector Life Sciences&Health,as well as by a contribution from the Dutch Burns Foundation(grant number:nr LSHM 17077-SGF)www.health-holland.com.
文摘Background:Severe burns induce volume shifts via capillary leaks,eventually requiring massive fluid resuscitation and promoting tissue edema.Albumin may help to mitigate the edema,thereby improving perfusion.This study shows that sublingual microcirculation measurements can quantify both tissue perfusion and edema.Methods:This prospective observational study was conducted between November 2018 and December 2019 in the intensive care unit of Maasstad Hospital Burn Center,Rotterdam,The Netherlands.Patients with severe burns affecting>15%of the total body surface area were included.Fluid management was conducted in accordance with the Parkland formula.Albumin(20%)was administered at a rate of 0.5 mL/(kg·h),starting 12 h after the burn incident.Alterations in the sublingual microcirculation,including capillary perfusion and density,were measured at admission(T0)and 4 h(T4)and 12 h(T12)after admission.Sublingual depth of focus(DOF)of the microcirculation was used to quantify the tissue edema.Results:Nine patients were recruited with a mean total body surface area of 36%±23%.By T12,a median of 4085 mL(interquartile range[IQR]:3714-6756 mL)of crystalloids and 446 mL(IQR:176-700 mL)of 20%albumin were administered.The DOF increased significantly after crystalloid administration(T4 vs.T0,mean difference[MD]=27.4μm,95%confidence interval[CI]:3.4 to 50.9,P=0.040).Following albumin administration,DOF significantly decreased(T12 vs.T4,MD=-76.4μm,95%CI:-116.6 to-36.1,P=0.002).Total vessel density decreased significantly with crystalloid administration(T4 vs.T0,MD=-3.5 mm/mm2,95%CI:-5.7 to-1.4,P=0.004)but increased after albumin administration(T12 vs.T4,MD=6.2 mm/mm2,95%CI:3.2 to 9.3,P=0.001).Conclusion:Sublingual microcirculation measurement of DOF and other parameters provide a valuable tool for the assessment of tissue perfusion and edema in patients with severe burns.Further investigation is required to evaluate the role of albumin in increasing microcirculatory convection and reducing tissue edema.
基金supported by the MRC IAA 2021 King’s College London(MR/X502923/1).
文摘Background and Aims:Liver failure syndromes are characterised by a dysregulated immune response leading to immune paralysis.Adrenomedullin(ADM)is a potent vasodilator and immunoregulator.This study aimed to explore the role of ADM in liver failure,hypothesising that there is a detrimental imbalance between ADM and adrenomedullin binding protein(AMBP)1 that promotes a switch of monocytes/macrophages towards a pro-restorative phenotype and function.Methods:Consecutive patients with acute liver failure(ALF),acute-on-chronic liver failure(ACLF),and decompensated cirrhosis,as well as healthy controls(HC)were included between April 2020 and June 2024.Peripheral blood mononuclear cells/monocytes were isolated and used for RNA sequencing and cell culture.ADM and AMBP1 were measured by enzyme-linked immunosorbent assay.Results:Fifty-four patients with ALF,25 with ACLF,9 with decompensated cirrhosis,and 16 with HC were included.ADM expression in isolated monocytes was increased in ALF(log fold change=5.88,p=0.000216413)and ACLF(log fold change=4.62,p=0.00057122)compared to HC.Plasma ADM concentration was higher in ALF(1,684±1,156 pg/mL)vs.ACLF(836.1±765.2 pg/mL)and HC(164.8±62.73 pg/mL).AMBP1 was significantly reduced in ALF(59.27±44μg/mL)vs.ACLF(126.3±72.23μg/mL)and HC(252.8±159.7μg/mL)(p<0.0001,ALF vs.HC).Treatment with LPS increased ADM concentration in peripheral blood mononuclear cell supernatant(ALF n=6;561.4±1,038 pg/mL vs.259.2±213.7 pg/mL,ACLF n=4;3,202±491.2 vs.1,757±1,689 pg/mL).The percentage of CD14+cells expressing Mer tyrosine kinase was reduced after culture with LPS(2.077±0.87%);however,co-culture with ADM 100 nM restored the phenotype(3.852±1.063%).Conclusions:ADM is increased in liver failure,whereas AMBP1 is reduced.ADM affects monocyte function,increasing Mer Tyrosine Kinase and promoting a pro-restorative,anti-inflammatory phenotype.
