Objective:This study examines the outcome of augmentation cystoplasty(AC)in children with stages III and IV chronic kidney disease(CKD)secondary to neurogenic bladder in which transplantation was not imminent.Methods:...Objective:This study examines the outcome of augmentation cystoplasty(AC)in children with stages III and IV chronic kidney disease(CKD)secondary to neurogenic bladder in which transplantation was not imminent.Methods:Hospital records of all children with CKD stages III and IV who underwent AC between 2008 and 2017 were retrieved to study outcome and complications including estimated glomerular filtration rate(eGFR,National Kidney Foundation Calculator),somatic growth(percentiles,compared with population data),and febrile urinary tract infections(fUTIs)requiring admission.Statistical analysis was performed using R.Results:AC was performed in 13 children with CKD stages III and IV(10 girls;median 8.0 years)with median follow-up of 51 months.Patients had incontinence(10/13),reflux(7/13),and hydronephrosis(13/13)despite antimuscarinics and intermittent catheterization.Bladder capacity was 74%of expected and median compliance was 5 mL/cm H20(inter-quartile range 4 mL/cm H20).All underwent ileocystoplasty(25 cm bowel).One each had nephrectomy and mitrofanoff conduit.All had resolution of incontinence.One had acute kidney injury that recovered.Initial eGFR at presentation(24 mL/min/1.73 m2)improved with conservative management alone(52 mL/min/1.73 m2,p=0.004).This improved further 1 year following AC(61 mL/min/1.73 m2,p=0.036)with stable function at 7 years.There was improvement in somatic growth,hydronephrosis,and fUTI despite no ureteric re-implantation.Conclusion:AC carries acceptable morbidity in children with CKD stages III and IV secondary to neurogenic bladder.Surgery is effective with improvements in continence,eGFR,somatic growth,and propensity for fUTIs.Ureteric re-implantation might not be necessary.展开更多
Porous biomaterials which provide a structural and biological support for cells have immense potential in tissue engineering and cell-based therapies for tissue repair.Collagen biomaterials that can host endothelial c...Porous biomaterials which provide a structural and biological support for cells have immense potential in tissue engineering and cell-based therapies for tissue repair.Collagen biomaterials that can host endothelial cells represent promising tools for the vascularization of engineered tissues.Three-dimensional collagen scaffolds possessing controlled architecture and mechanical stiffness are obtained through freeze–drying of collagen suspensions,followed by chemical cross-linking which maintains their stability.However,cross-linking scaffolds renders their biological activity suboptimal for many cell types,including human umbilical vein endothelial cells(HUVECs),by inhibiting cell–collagen interactions.Here,we have improved crucial HUVEC interactions with such cross-linked collagen biomaterials by covalently coupling combinations of triple-helical peptides(THPs).These are ligands for collagen-binding cell-surface receptors(integrins or discoidin domain receptors)or secreted proteins(SPARC and von Willebrand factor).THPs enhanced HUVEC adhesion,spreading and proliferation on 2D collagen films.THPs grafted to 3D-cross-linked collagen scaffolds promoted cell survival over seven days.This study demonstrates that THP-functionalized collagen scaffolds are promising candidates for hosting endothelial cells with potential for the production of vascularized engineered tissues in regenerative medicine applications.展开更多
文摘Objective:This study examines the outcome of augmentation cystoplasty(AC)in children with stages III and IV chronic kidney disease(CKD)secondary to neurogenic bladder in which transplantation was not imminent.Methods:Hospital records of all children with CKD stages III and IV who underwent AC between 2008 and 2017 were retrieved to study outcome and complications including estimated glomerular filtration rate(eGFR,National Kidney Foundation Calculator),somatic growth(percentiles,compared with population data),and febrile urinary tract infections(fUTIs)requiring admission.Statistical analysis was performed using R.Results:AC was performed in 13 children with CKD stages III and IV(10 girls;median 8.0 years)with median follow-up of 51 months.Patients had incontinence(10/13),reflux(7/13),and hydronephrosis(13/13)despite antimuscarinics and intermittent catheterization.Bladder capacity was 74%of expected and median compliance was 5 mL/cm H20(inter-quartile range 4 mL/cm H20).All underwent ileocystoplasty(25 cm bowel).One each had nephrectomy and mitrofanoff conduit.All had resolution of incontinence.One had acute kidney injury that recovered.Initial eGFR at presentation(24 mL/min/1.73 m2)improved with conservative management alone(52 mL/min/1.73 m2,p=0.004).This improved further 1 year following AC(61 mL/min/1.73 m2,p=0.036)with stable function at 7 years.There was improvement in somatic growth,hydronephrosis,and fUTI despite no ureteric re-implantation.Conclusion:AC carries acceptable morbidity in children with CKD stages III and IV secondary to neurogenic bladder.Surgery is effective with improvements in continence,eGFR,somatic growth,and propensity for fUTIs.Ureteric re-implantation might not be necessary.
基金supported in the Department of Biochemistry by grants from British Heart Foundation(SP/15/7/31561,FS/15/20/31335 , RG/15/4/31268)funded by EPSRC fellowship(EP/N019938/1)+2 种基金supported by BHF grants FS/18/46/33663 , RM/17/2/33380funding from the Wellcome Trust and MRC to the Wellcome-Medical Research Council Cambridge Stem Cell InstituteConfocal imaging of scaffolds was performed at the Microscopy Core facility at the Sainsbury Laboratory,Cambridge,UK and was supported by the Gatsby Charitable Foundation.
文摘Porous biomaterials which provide a structural and biological support for cells have immense potential in tissue engineering and cell-based therapies for tissue repair.Collagen biomaterials that can host endothelial cells represent promising tools for the vascularization of engineered tissues.Three-dimensional collagen scaffolds possessing controlled architecture and mechanical stiffness are obtained through freeze–drying of collagen suspensions,followed by chemical cross-linking which maintains their stability.However,cross-linking scaffolds renders their biological activity suboptimal for many cell types,including human umbilical vein endothelial cells(HUVECs),by inhibiting cell–collagen interactions.Here,we have improved crucial HUVEC interactions with such cross-linked collagen biomaterials by covalently coupling combinations of triple-helical peptides(THPs).These are ligands for collagen-binding cell-surface receptors(integrins or discoidin domain receptors)or secreted proteins(SPARC and von Willebrand factor).THPs enhanced HUVEC adhesion,spreading and proliferation on 2D collagen films.THPs grafted to 3D-cross-linked collagen scaffolds promoted cell survival over seven days.This study demonstrates that THP-functionalized collagen scaffolds are promising candidates for hosting endothelial cells with potential for the production of vascularized engineered tissues in regenerative medicine applications.