Background: A tourniquet is often used to create a bloodless surgical field during total knee arthroplasty (TKA). It is still debated whether tourniquet use improves durability of cemented implant... Show moreBackground: A tourniquet is often used to create a bloodless surgical field during total knee arthroplasty (TKA). It is still debated whether tourniquet use improves durability of cemented implant fixation and thereby prosthesis survival. Some studies showed tourniquet application has a negative impact on post-operative wound healing, pain and function, whilst other publications contradict this. However, no previous studies evaluated the effect of tourniquet use on prosthesis survival and mid-term functional outcome specifically. Methods: In this longitudinal observational cohort study 115 patients (116 knees) undergoing TKA without tourniquet use were compared with 374 patients (395 knees) with a tourniquet. Prosthesis survival, revision risks and complications were analysed through chart review after a mean follow-up period of 5.3 years. Additionally, patient reported outcome measures regarding knee functionality and health status (PROMs; KOOS, OKS, EQ-5D, SF-12) were collected prospectively. Results: Both groups had an equal overall re-operation rate of 4.3% and showed similar revision rates for aseptic loosening as well as for other causes. In the tourniquet group a higher complication rate (14.7% vs 10.3%) was observed. The majority was urinary retention requiring bladder catheterization. Both groups showed comparable, improved post-operative functional results compared to the pre-operative state for all PROMs at all time points. Conclusions: In this study TKA without tourniquet use yielded similar mid-term results as TKA with tourniquet use with regard to prosthesis survival, reoperations, complications, knee functionality and health status.(c) 2022 Elsevier B.V. All rights reserved. Show less
Background and Aims: In hereditary hemorrhagic telangiectasia (HHT), severe liver vascular malformations are associated with mutations in the Activin A Receptor-Like Type 1 (ACVRL1) gene encoding... Show moreBackground and Aims: In hereditary hemorrhagic telangiectasia (HHT), severe liver vascular malformations are associated with mutations in the Activin A Receptor-Like Type 1 (ACVRL1) gene encoding ALK1, the receptor for bone morphogenetic protein (BMP) 9/BMP10, which regulates blood vessel development. Here, we established an HHT mouse model with exclusive liver involvement and adequate life expectancy to investigate ALK1 signaling in liver vessel formation and metabolic function. Approach and Results: Liver sinusoidal endothelial cell (LSEC)-selective Cre deleter line, Stab2-iCreF3, was crossed with Acvrl1-floxed mice to generate LSEC-specific Acvrl1-deficient mice (Alk1(HEC-KO)). Alk1(HEC-KO) mice revealed hepatic vascular malformations and increased posthepatic flow, causing right ventricular volume overload. Transcriptomic analyses demonstrated induction of proangiogenic/tip cell gene sets and arterialization of hepatic vessels at the expense of LSEC and central venous identities. Loss of LSEC angiokines Wnt2, Wnt9b, and R-spondin-3 (Rspo3) led to disruption of metabolic liver zonation in Alk1(HEC-KO) mice and in liver specimens of patients with HHT. Furthermore, prion-like protein doppel (Prnd) and placental growth factor (Pgf) were upregulated in Alk1(HEC-KO) hepatic endothelial cells, representing candidates driving the organ-specific pathogenesis of HHT. In LSEC in vitro, stimulation or inhibition of ALK1 signaling counter-regulated Inhibitors of DNA binding (ID)1-3, known Alk1 transcriptional targets. Stimulation of ALK1 signaling and inhibition of ID1-3 function confirmed regulation of Wnt2 and Rspo3 by the BMP9/ALK1/ID axis. Conclusions: Hepatic endothelial ALK1 signaling protects from development of vascular malformations preserving organ-specific endothelial differentiation and angiocrine signaling. The long-term surviving Alk1(HEC-KO) HHT model offers opportunities to develop targeted therapies for this severe disease. Show less
Goodwin, A.J.; Velzen, S. van; Miller-Jones, J.C.A.; Mummery, A.; Bietenholz, M.F.; Wederfoort, A.; ... ; Yan, L. 2022