| 1. |
- Winkler, TW, et al.
(författare)
-
Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
- 2022
-
Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 580-
-
Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Dale, H., et al.
(författare)
-
Increasing risk of revision due to infection after primary total hip arthroplasty: results from the Nordic Arthro- plasty Register Association
- 2023
-
Ingår i: Acta orthopaedica. - : Medical Journals Sweden. - 1745-3674 .- 1745-3682. ; 94, s. 307-315
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose - The incidence of peripros-thetic joint infection after total hip arthroplasty (THA) may be increasing. We performed time-trend analyses of risk, rates, and timing of revision due to infection after primary THAs in the Nordic countries from the period 2004-2018. Patients and methods - 569,463 primary THAs reported to the Nordic Arthroplasty Register Association from 2004 to 2018 were studied. Absolute risk estimates were calculated by Kaplan-Meier and cumulative incidence function methods, whereas adjusted hazard ratios (aHR) were assessed by Cox regression with the first revision due to infection after primary THA as primary endpoint. In addi-tion, we explored changes in the time span from primary THA to revision due to infection. Results - 5,653 (1.0%) primary THAs were revised due to infection during a median follow-up time of 5.4 (IQR 2.5-8.9) years after surgery. Compared with the period 2004-2008, the aHRs for revision were 1.4 (95% confidence interval [CI] 1.3-1.5) for 2009-2013, and 1.9 (CI 1.7-2.0) for 2014-2018. The absolute 5-year rates of revision due to infection were 0.7% (CI 0.7-0.7), 1.0% (CI 0.9-1.0), and 1.2% (CI 1.2-1.3) for the 3 time periods respectively. We found changes in the time span from primary THA to revi-sion due to infection. Compared with 2004-2008, the aHR for revision within 30 days after THA was 2.5 (CI 2.1-2.9) for 2009-2013, and 3.4 (CI 3.0-3.9) for 2013-2018. The aHR for revision within 31-90 days after THA was 1.5 (CI 1.3-1.9) for 2009-2013, and 2.5 (CI 2.1-3.0) for 2013-2018, compared with 2004-2008.Conclusion - The risk of revision due to infection after primary THA almost doubled, both in absolute cumulative incidence and in relative risk, throughout the period 2004- 2018. This increase was mainly due to an increased risk of revision within 90 days of THA. This may reflect a "true" increase (i.e., frailer patients or more use of uncemented implants) and/or an "apparent" increase (i.e., improved diagnostics, changed revision strategy, or completeness of reporting) in incidence of periprosthetic joint infection. It is not possible to disclose such changes in the present study, and this warrants further research.
|
|
| 6. |
- Gorski, Mathias, et al.
(författare)
-
Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies
- 2022
-
Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 102:3, s. 624-639
-
Tidskriftsartikel (refereegranskat)abstract
- Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
|
|
| 7. |
- Leta, Tesfaye H., et al.
(författare)
-
Periprosthetic Joint Infection After Total Knee Arthroplasty With or Without Antibiotic Bone Cement
- 2024
-
Ingår i: JAMA Network Open. - 2574-3805. ; 7:5, s. 2412898-2412898
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: Despite increased use of antibiotic-loaded bone cement (ALBC) in joint arthroplasty over recent decades, current evidence for prophylactic use of ALBC to reduce risk of periprosthetic joint infection (PJI) is insufficient. Objective: To compare the rate of revision attributed to PJI following primary total knee arthroplasty (TKA) using ALBC vs plain bone cement. Design, Setting, and Participants: This international cohort study used data from 14 national or regional joint arthroplasty registries in Australia, Denmark, Finland, Germany, Italy, New Zealand, Norway, Romania, Sweden, Switzerland, the Netherlands, the UK, and the US. The study included primary TKAs for osteoarthritis registered from January 1, 2010, to December 31, 2020, and followed-up until December 31, 2021. Data analysis was performed from April to September 2023. Exposure: Primary TKA with ALBC vs plain bone cement. Main Outcomes and Measures: The primary outcome was risk of 1-year revision for PJI. Using a distributed data network analysis method, data were harmonized, and a cumulative revision rate was calculated (1 - Kaplan-Meier), and Cox regression analyses were performed within the 10 registries using both cement types. A meta-analysis was then performed to combine all aggregated data and evaluate the risk of 1-year revision for PJI and all causes. Results: Among 2 168 924 TKAs included, 93% were performed with ALBC. Most TKAs were performed in female patients (59.5%) and patients aged 65 to 74 years (39.9%), fully cemented (92.2%), and in the 2015 to 2020 period (62.5%). All participating registries reported a cumulative 1-year revision rate for PJI of less than 1% following primary TKA with ALBC (range, 0.21%-0.80%) and with plain bone cement (range, 0.23%-0.70%). The meta-analyses based on adjusted Cox regression for 1 917 190 TKAs showed no statistically significant difference at 1 year in risk of revision for PJI (hazard rate ratio, 1.16; 95% CI, 0.89-1.52) or for all causes (hazard rate ratio, 1.12; 95% CI, 0.89-1.40) among TKAs performed with ALBC vs plain bone cement. Conclusions and Relevance: In this study, the risk of revision for PJI was similar between ALBC and plain bone cement following primary TKA. Any additional costs of ALBC and its relative value in reducing revision risk should be considered in the context of the overall health care delivery system.
|
|
| 8. |
- Mikkelsen, R. T., et al.
(författare)
-
Does choice of bearings influence the survival of cement-less total hip arthroplasty in patients aged 20-55 years? Comparison of 21,594 patients reported to the Nordic Arthroplasty Register Association dataset 2005-2017
- 2023
-
Ingår i: Acta Orthopaedica. - 1745-3674. ; 94, s. 266-273
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose - The bearings with the best survivorship for young patients with total hip arthroplasty (THA) should be identified. We compared hazard ratios (HR) of revision of primary stemmed cementless THAs with metal-on-metal (MoM), ceramic-on-ceramic (CoC), and ceramic-on-highly-crosslinked-polyethylene (CoXLP) with that of metal-on-highly-crosslinked-polyethylene (MoXLP) bearings in patients aged 20-55 years with primary osteoar-thritis or childhood hip disorders. Patients and methods - From the Nordic Arthroplasty Register Association dataset we included 1,813 MoM, 3,615 CoC, 5,947 CoXLP, and 10,219 MoXLP THA in patients operated on between 2005 and 2017 in a prospective cohort study. We used the Kaplan-Meier estimator for THA sur-vivorship and Cox regression to estimate HR of revision adjusted for confounders (including 95% confidence inter-vals [CI]). MoXLP was used as reference. HRs were calcu-lated during 3 intervals (0-2, 2-7, and 7-13 years) to meet the assumption of proportional hazards. Results - Median follow-up was 5 years for MoXLP, 10 years for MoM, 6 years for CoC, and 4 years for CoXLP. 13-year Kaplan-Meier survival estimates were 95% (CI 94-95) for MoXLP, 82% (CI 80-84) for MoM, 93% (CI 92-95) for CoC, and 93% (CI 92-94) for CoXLP bearings. MoM had higher 2-7 and 7-13 years' adjusted HRs of revi-sion (3.6, CI 2.3-5.7 and 4.1, CI 1.7-10). MoXLP, CoC, and CoXLP had similar HRs in all 3 periods. The 7-13-year adjusted HRs of revision of CoC and CoXLP were statisti-cally non-significantly higher. Conclusion - In young patients, MoXLP for primary cementless THA had higher revision-free survival and lower HR for revision than MoM bearings. Longer follow-up is needed to compare MoXLP, CoC, and CoXLP.
|
|
| 9. |
- Tsikandylakis, Georgios, et al.
(författare)
-
Is there a reduction in risk of revision when 36-mm heads instead of 32 mm are used in total hip arthroplasty for patients with proximal femur fractures?: A matched analysis of 5,030 patients with a median of 2.5 years’ follow-up between 2006 and 2016 in the Nordic Arthroplasty Register Association
- 2020
-
Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 91:4, s. 401-407
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose — 32-mm heads are widely used in total hip arthroplasty (THA) in Scandinavia, while the proportion of 36-mm heads is increasing as they are expected to increase THA stability. We investigated whether the use of 36-mm heads in THA after proximal femur fracture (PFF) is associated with a lower risk of revision compared with 32-mm heads. Patients and methods — We included 5,030 patients operated with THA due to PFF with 32- or 36-mm heads from the Nordic Arthroplasty Register Association database. Each patient with a 36-mm head was matched with a patient with a 32-mm head, using propensity score. The patients were operated between 2006 and 2016, with a metal or ceramic head on a polyethylene bearing. Cox proportional hazards models were fitted to estimate the unadjusted and adjusted hazard ratio (HR) with 95% confidence intervals (CI) for revision for any reason and revision due to dislocation for 36-mm heads compared with 32-mm heads. Results — 36-mm heads had an HR of 0.9 (CI 0.7–1.2) for revision for any reason and 0.8 (CI 0.5–1.3) for revision due to dislocation compared with 32-mm heads at a median follow-up of 2.5 years (interquartile range 1–4.4). Interpretation — We were not able to demonstrate any clinically relevant reduction of the risk of THA revision for any reason or due to dislocation when 36-mm heads were used versus 32-mm. Residual confounding due to lack of data on patient comorbidities and body mass index could bias our results. © 2020, © 2020 The Author(s). Published by Taylor & Francis on behalf of the Nordic Orthopedic Federation.
|
|
