Whether to use total or unicompartmental knee replacement (TKA/UKA) for end-stage knee osteoarthritis remains controversial. Although UKA results in a faster recovery, lower rates of morbidity and ...mortality and fewer complications, the long-term revision rate is substantially higher than that for TKA. The effect of each intervention on patient-reported outcome remains unclear. The aim of this study was to determine whether six-month patient-reported outcome measures (PROMs) are better in patients after TKA or UKA, using data from a large national joint registry (NJR). We carried out a propensity score-matched cohort study which compared six-month PROMs after TKA and UKA in patients enrolled in the NJR for England and Wales, and the English national PROM collection programme. A total of 3519 UKA patients were matched to 10 557 TKAs. The mean six-month PROMs favoured UKA: the Oxford Knee Score was 37.7 (95% confidence interval (CI) 37.4 to 38.0) for UKA and 36.1 (95% CI 35.9 to 36.3) for TKA; the mean EuroQol EQ-5D index was 0.772 (95% CI 0.764 to 0.780) for UKA and 0.751 (95% CI 0.747 to 0.756) for TKA. UKA patients were more likely to achieve excellent results (odds ratio (OR) 1.59, 95% CI 1.47 to 1.72, p < 0.001) and to be highly satisfied (OR 1.27, 95% CI 1.17 to 1.39, p < 0.001), and were less likely to report complications than those who had undergone TKA. UKA gives better early patient-reported outcomes than TKA; these differences are most marked for the very best outcomes. Complications and readmission are more likely after TKA. Although the data presented reflect the short-term outcome, they suggest that the high revision rate for UKA may not be because of poorer clinical outcomes. These factors should inform decision-making in patients eligible for either procedure.
Neurofibrillary tangles (NFTs), composed of hyperphosphorylated tau proteins, are one of the pathologic hallmarks of Alzheimer disease (AD). We aimed to determine whether patterns of gray matter ...atrophy from antemortem MRI correlate with Braak staging of NFT pathology.
Eighty-three subjects with Braak stage III through VI, a pathologic diagnosis of low- to high-probability AD, and MRI within 4 years of death were identified. Voxel-based morphometry assessed gray matter atrophy in each Braak stage compared with 20 pathologic control subjects (Braak stages 0 through II).
In pairwise comparisons with Braak stages 0 through II, a graded response was observed across Braak stages V and VI, with more severe and widespread loss identified at Braak stage VI. No regions of loss were identified in Braak stage III or IV compared with Braak stages 0 through II. The lack of findings in Braak stages III and IV could be because Braak stage is based on the presence of any NFT pathology regardless of severity. Actual NFT burden may vary by Braak stage. Therefore, tau burden was assessed in subjects with Braak stages 0 through IV. Those with high tau burden showed greater gray matter loss in medial and lateral temporal lobes than those with low tau burden.
Patterns of gray matter loss are associated with neurofibrillary tangle (NFT) pathology, specifically with NFT burden at Braak stages III and IV and with Braak stage itself at higher stages. This validates three-dimensional patterns of atrophy on MRI as an approximate in vivo surrogate indicator of the full brain topographic representation of the neurodegenerative aspect of Alzheimer disease pathology.
•Early, acute PJI was rare following primary UKR, with an incidence of DAIR around 0.3% in this first 3 months.•The Kaplan-Meier survivor estimate for revision for any reason after DAIR was 52% at ...5 years.•Infection-free survivorship after DAIR was 57% at 5 years.•Patients with a viable implant at final follow-up had excellent functional outcomes.•DAIR can be considered to be the treatment of choice for an early acute PJI following UKR.
Periprosthetic joint infection (PJI) following unicompartmental knee replacement (UKR) is an uncommon, yet serious, complication. There is a paucity of evidence regarding the effectiveness of Debridement-Antibiotics-and-Implant-Retention (DAIR) in this setting. The aim of this study is to investigate the effectiveness of DAIR for acute UKR PJI.
Between 2006 and 2019, 5195 UKR were performed at our institution. Over this period, sixteen patients underwent DAIR for early, acute PJI. All patients met MSIS PJI diagnostic criteria. The median age at DAIR was 67 years (range 40–73) and 12 patients were male (75.0%). The median time to DAIR was 24 days (range 6–60). Patients were followed up for a median of 6.5 years (range1.4–10.5) following DAIR.
0.3% (16/5195) of UKR in our institution had a DAIR within 3 months. 15 of 16 patients (93.8%) were culture positive, with the most common organism MSSA (n = 8, 50.0%). Patients were treated with an organism-specific intravenous antibiotic regime for a median of 6 weeks, followed by oral antibiotics for a median duration of 6 months. The Kaplan-Meier survivor estimate for revision for PJI was 57% (95%CI: 28–78%) at five years, and survivor estimate for all cause revision 52% (95%CI: 25–74%).The median Oxford Knee Score for patients with a viable implant at final follow-up was 45 points (range 39–46).
Early, acute PJI after UKR is rare. DAIR had a moderate success rate, with infection-free survivorship of 57% at 5 years. Those successfully treated with DAIR had excellent functional outcome and implant survival.
There have been concerns about the long-term survival of unicompartmental knee arthroplasty (UKA). This prospective study reports the 15-year survival and ten-year functional outcome of a consecutive ...series of 1000 minimally invasive Phase 3 Oxford medial UKAs (818 patients, 393 men, 48%, 425 women, 52%, mean age 66 years; 32 to 88). These were implanted by two surgeons involved with the design of the prosthesis to treat anteromedial osteoarthritis and spontaneous osteonecrosis of the knee, which are recommended indications. Patients were prospectively identified and followed up independently for a mean of 10.3 years (5.3 to 16.6). At ten years, the mean Oxford Knee Score was 40 (standard deviation (sd) 9; 2 to 48): 79% of knees (349) had an excellent or good outcome. There were 52 implant-related re-operations at a mean of 5.5 years (0.2 to 14.7). The most common reasons for re-operation were arthritis in the lateral compartment (2.5%, 25 knees), bearing dislocation (0.7%, seven knees) and unexplained pain (0.7%, seven knees). When all implant-related re-operations were considered as failures, the ten-year rate of survival was 94% (95% confidence interval (CI) 92 to 96) and the 15-year survival rate 91% (CI 83 to 98). When failure of the implant was the endpoint the 15-year survival was 99% (CI 96 to 100). This is the only large series of minimally invasive UKAs with 15-year survival data. The results support the continued use of minimally invasive UKA for the recommended indications.
We assess the impact of transport of pollution from midlatitudes on the abundance of ozone in the Arctic in summer 2006 using the GEOS‐Chem global chemical transport model and its adjoint. We find ...that although the impact of midlatitude emissions on ozone abundances in the Arctic is at a maximum in fall and winter, in July transport from North America, Asia, and Europe together contributed about 25% of surface ozone abundances in the Arctic. Throughout the summer, the dominant source of ozone in the Arctic troposphere was photochemical production within the Arctic, which accounted for more than 50% of the ozone in the Arctic boundary layer and as much as 30%–40% of the ozone in the middle troposphere. An adjoint sensitivity analysis of the impact of NOx emissions on ozone at Alert shows that on synoptic time scales in both the lower and middle troposphere, ozone abundances are more sensitive to emissions between 50°N and 70°N, with important influences from anthropogenic, biomass burning, soil, and lightning sources. Although local surface NOx emissions contribute to ozone formation, transport of NOx in the form of peroxyacetyl nitrate (PAN) from outside the Arctic and from the upper troposphere also contributed to ozone production in the lower troposphere. We find that in late May and June the release of NOx from PAN decomposition accounted for 93% and 55% of ozone production at the Arctic surface, respectively.
Key Points
Midlatitude source regions contribute 10‐25% of Arctic ozone in summer
On short time scales, Arctic O3 is most sensitive to NOx emissions at 50‐70N
NOx transported as PAN constitutes most of O3 produced in the Arctic spring
Jun N-terminal kinase (JNK) is a stress-activated protein kinase that can be induced by inflammatory cytokines, bacterial endotoxin, osmotic shock, UV radiation, and hypoxia. We report the ...identification of an anthrapyrazolone series with significant inhibition of JNK1, -2, and -3 (Ki= 0.19 µM). SP600125 is a reversible ATP-competitive inhibitor with >20-fold selectivity vs. a range of kinases and enzymes tested. In cells, SP600125 dose dependently inhibited the phosphorylation of c-Jun, the expression of inflammatory genes COX-2, IL-2, IFN-γ, TNF-α, and prevented the activation and differentiation of primary human CD4 cell cultures. In animal studies, SP600125 blocked (bacterial) lipopolysaccharide-induced expression of tumor necrosis factor-α and inhibited anti-CD3-induced apoptosis of CD4+CD8+thymocytes. Our study supports targeting JNK as an important strategy in inflammatory disease, apoptotic cell death, and cancer.
Unicompartmental knee arthroplasty (UKA) has advantages over total knee arthroplasty but national joint registries report a significantly higher revision rate for UKA. As a result, most surgeons are ...highly selective, offering UKA only to a small proportion (up to 5%) of patients requiring arthroplasty of the knee, and consequently performing few each year. However, surgeons with large UKA practices have the lowest rates of revision. The overall size of the practice is often beyond the surgeon's control, therefore case volume may only be increased by broadening the indications for surgery, and offering UKA to a greater proportion of patients requiring arthroplasty of the knee. The aim of this study was to determine the optimal UKA usage (defined as the percentage of knee arthroplasty practice comprised by UKA) to minimise the rate of revision in a sample of 41 986 records from the for National Joint Registry for England and Wales (NJR). UKA usage has a complex, non-linear relationship with the rate of revision. Acceptable results are achieved with the use of 20% or more. Optimal results are achieved with usage between 40% and 60%. Surgeons with the lowest usage (up to 5%) have the highest rates of revision. With optimal usage, using the most commonly used implant, five-year survival is 96% (95% confidence interval (CI) 94.9 to 96.0), compared with 90% (95% CI 88.4 to 91.6) with low usage (5%) previously considered ideal. The rate of revision of UKA is highest with low usage, implying the use of narrow, and perhaps inappropriate, indications. The widespread use of broad indications, using appropriate implants, would give patients the advantages of UKA, without the high rate of revision.
Non-epithelial gonadal tumours largely comprise sex cord-stromal tumours (SCSTs) and germ cell tumours (GCTs). Specific somatic mutations in DICER1, a microRNA maturation pathway gene, have been ...identified in these tumours. We conducted a study that aimed to confirm, refine and extend the previous observations.
We used Sanger sequencing to sequence the RNase IIIa and IIIb domains of DICER1 in 154 gonadal tumours from 135 females and 19 males, as well as 43 extra-gonadal GCTs from 26 females and 17 males.
We identified heterozygous non-synonymous mutations in the RNase IIIb domain of DICER1 in 14/197 non-epithelial tumours (7.1%). Mutations were found in 9/28 SCSTs (32%), 5/118 gonadal GCTs (4.2%), 0/43 extra-gonadal GCTs and 0/8 miscellaneous tumours. The 14 mutations affected only five residues: E1705, D1709, E1788, D1810 and E1813. In all five patients where matched and constitutional DNA was available, the mutations were only somatic. There were no mutations found in the RNase IIIa domain.
More than half (8/15) of Sertoli-Leydig cell tumours (SLCTs) harbour DICER1 mutations in the RNase IIIb domain, while mutations are rarely found in GCTs. Genetic alterations in SLCTs may aid in classification and provide new approaches to therapy.
There is a North Atlantic divide, with cementless femoral stems being used more frequently in the USA and cemented stems being used more frequently in many countries in Europe. This is primarily ...because different cemented stems have been used on different sides of the Atlantic and the results of the cemented stems in the US have often been poor, whereas the results of the stems used in Europe have been good. In the National registers in Europe, cemented stems have tended to achieve better results than cementless.
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