Functional results of total-knee arthroplasty versus medial unicompartmental arthroplasty:two-year results of a randomised, assessor-blinded multicentre trial

Abstract Objective:The primary objective of the trial was to assess the clinical effectiveness of medial unicompartmental knee arthroplasty versus total knee arthroplasty in patients with isolated medial osteoarthritis of the knee. Design: Prospective, randomised, 2 years, assessor-blind, multicentre, superiority trial. Setting: The patients were enrolled between December 2015 and May 2018 from the outpatient clinics of three public high-volume arthroplasty hospitals (Finland). Participants: We recruited 143 patients with symptomatic-isolated medial osteoarthritis of the knee needing an arthroplasty procedure. All the patients were suitable for both unicompartmental and total knee arthroplasties. Population was selected as the end-stage-isolated medial osteoarthritis. Interventions: All patients, randomized 1:1, received a medial unicompartmental arthroplasty or a total knee arthroplasty through a similar midline skin incision. Patients were blinded to the type of arthroplasty for the whole 2 years of follow-up. Main outcome measures: Primary outcome measure was between-group differences in the Oxford Knee Score (OKS) and secondary outcome Knee injury and Osteoarthritis Score (KOOS) at 2 years postoperatively. The changes within and between the groups were analysed with analysis of variance for repeated measurements. Results: The primary outcome was comparable for medial unicompartmental arthroplasty and total knee arthroplasty at 2 years. The mean difference in the OKS between the groups was 1.6 points (95% CI −0.7 to 3.9). In the KOOS subscales, the mean difference between the groups was 0.1 points (95% CI −4.8 to 5.0) for pain, 7.8 points (95% CI 1.5 to 14.0) for symptoms, 4.3 points (95% CI −0.6 to 9.2) for function in daily living, 4.3 points (95% CI −3.0 to 11.6) for function in sports, and 2.1 points (95% CI −4.8 to 9.1) for knee-related quality of life. Conclusions: The recovery after unicompartmental knee arthroplasty was faster compared with total knee arthroplasty, but unicompartmental arthroplasty did not provide a better patient-reported outcome at 2 years. Trial registration number: NCT02481427

Inflammation and neutrophil oxidative burst in a family with NFKB1 p.R157X LOF and sterile necrotizing fasciitis

Abstract Loss-of-function (LOF) mutations in NFKB1, coding for p105, may cause common variable immunodeficiency due to dysregulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κΒ) pathway. Monoallelic LOF variants of NFKB1 can predispose to uncontrolled inflammation including sterile necrotizing fasciitis or pyoderma gangrenosum. In this study, we explored the impact of a heterozygous NFKB1 c.C936T/p.R157X LOF variant on immunity in sterile fasciitis patients and their family members. The p50 or p105 protein levels were reduced in all variant carriers. Interleukin-1β (IL-1β) and interleukin-8 (IL-8) levels were elevated in vitro, potentially contributing to the very high neutrophil counts observed during fasciitis episodes. Phosphorylation of p65/RelA was reduced in p.R157X neutrophils suggesting defective activation of canonical NF-κB. Oxidative burst after NF-κB-independent phorbol 12-myristate 13-acetate (PMA) stimulation was similar in both p.R157X and control neutrophils. Comparable amounts of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex subunits were found in p.R157X and control neutrophils. However, a compromised oxidative burst was observed in p.R157X neutrophils following activation of NF-κB-dependent mechanisms following stimulation of toll-like receptor 2 (TLR2) and Dectin-1. Neutrophil extracellular trap formation was not affected by p.R157X. In summary, the NFKB1 c.C936T/p.R157X LOF variant has an impact on inflammation and neutrophil function and may play a role in the pathogenesis of sterile necrotizing fasciitis