Implementation of Ireland's first state-funded day-case total hip arthroplasty programme.

BACKGROUND: Over the last two decades, many elective procedures have transitioned to day-case surgery thanks to the introduction of 'enhanced recovery' protocols. Only recently has total hip arthroplasty been considered a candidate for day-case surgery, as it was once associated with significant pain, mobility impairment and prolonged postoperative recovery. The National Orthopaedic Hospital Cappagh became the first public hospital in Ireland to set up a day-case total hip arthroplasty service in June 2018, and since then has performed over 109 such cases. AIMS: We outline our day-case total hip arthroplasty pathway, with specific focus on anaesthetic considerations. We report rates of failed discharge and readmission. RESULTS: We achieved successful same-day discharge in 90.8% of our first 109 cases. Readmission rate was 4.6%. CONCLUSION: Our experience of implementing a day-case total hip arthroplasty pathway was highly positive and congruent with expectations from the literature. With appropriate patient selection and education, day-case total hip arthroplasty is not just safe, but of benefit to both patients and healthcare systems.

Centriole splitting caused by loss of the centrosomal linker protein C-NAP1 reduces centriolar satellite density and impedes centrosome amplification.

Duplication of the centrosomes is a tightly regulated process. Abnormal centrosome numbers can impair cell division and cause changes in how cells migrate. Duplicated centrosomes are held together by a proteinaceous linker made up of rootletin filaments anchored to the centrioles by C-NAP1. This linker is removed in a NEK2A kinase-dependent manner as mitosis begins. To explore C-NAP1 activities in regulating centrosome activities, we used genome editing to ablate it. C-NAP1-null cells were viable and had an increased frequency of premature centriole separation, accompanied by reduced density of the centriolar satellites, with reexpression of C-NAP1 rescuing both phenotypes. We found that the primary cilium, a signaling structure that arises from the mother centriole docked to the cell membrane, was intact in the absence of C-NAP1, although components of the ciliary rootlet were aberrantly localized away from the base of the cilium. C-NAP1-deficient cells were capable of signaling through the cilium, as determined by gene expression analysis after fluid flow-induced shear stress and the relocalization of components of the Hedgehog pathway. Centrosome amplification induced by DNA damage or by PLK4 or CDK2 overexpression was markedly reduced in the absence of C-NAP1. We conclude that centriole splitting reduces the local density of key centriolar precursors to impede overduplication.

SUMO ligase activity of vertebrate Mms21/Nse2 is required for efficient DNA repair but not for Smc5/6 complex stability.

Nse2/Mms21 is an E3 SUMO ligase component of the Smc5/6 complex, which plays multiple roles in maintaining genome stability. To study the functions of the vertebrate Nse2 orthologue, we generated Nse2-deficient chicken DT40 cells. Nse2 was dispensable for DT40 cell viability and required for efficient repair of bulky DNA lesions, although Nse2-deficient cells showed normal sensitivity to ionising radiation-induced DNA damage. Homologous recombination activities were reduced in Nse2(-/-/-) cells. Nse2 deficiency destabilised Smc5, but not Smc6. In rescue experiments, we found that the SUMO ligase activity of Nse2 was required for an efficient response to MMS- or cis-platin-induced DNA damage, and for homologous recombination, but not for Smc5 stability. Gel filtration analysis indicated that Smc5 and Nse2 remain associated during the cell cycle and after DNA damage and Smc5/Smc6 association is independent of Nse2. Analysis of Nse2(-/-/-)Smc5(-) clones, which were viable although slow-growing, showed no significant increase in DNA damage sensitivity. We propose that Nse2 determines the activity, but not the assembly, of the Smc5/6 complex in vertebrate cells, and this activity requires the Nse2 SUMO ligase function.