| 1. |
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| 2. |
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| 3. |
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- 2019
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Journal article (peer-reviewed)
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| 4. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 5. |
- Thomas, H. J. D., et al.
(author)
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Global plant trait relationships extend to the climatic extremes of the tundra biome
- 2020
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In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- The majority of variation in six traits critical to the growth, survival and reproduction of plant species is thought to be organised along just two dimensions, corresponding to strategies of plant size and resource acquisition. However, it is unknown whether global plant trait relationships extend to climatic extremes, and if these interspecific relationships are confounded by trait variation within species. We test whether trait relationships extend to the cold extremes of life on Earth using the largest database of tundra plant traits yet compiled. We show that tundra plants demonstrate remarkably similar resource economic traits, but not size traits, compared to global distributions, and exhibit the same two dimensions of trait variation. Three quarters of trait variation occurs among species, mirroring global estimates of interspecific trait variation. Plant trait relationships are thus generalizable to the edge of global trait-space, informing prediction of plant community change in a warming world.
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| 6. |
- Thomas, H. J.D., et al.
(author)
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Traditional plant functional groups explain variation in economic but not size-related traits across the tundra biome
- 2019
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In: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 28:2, s. 78-95
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Journal article (peer-reviewed)abstract
- © 2018 The Authors Global Ecology and Biogeography Published by John Wiley & Sons Ltd Aim: Plant functional groups are widely used in community ecology and earth system modelling to describe trait variation within and across plant communities. However, this approach rests on the assumption that functional groups explain a large proportion of trait variation among species. We test whether four commonly used plant functional groups represent variation in six ecologically important plant traits. Location: Tundra biome. Time period: Data collected between 1964 and 2016. Major taxa studied: 295 tundra vascular plant species. Methods: We compiled a database of six plant traits (plant height, leaf area, specific leaf area, leaf dry matter content, leaf nitrogen, seed mass) for tundra species. We examined the variation in species-level trait expression explained by four traditional functional groups (evergreen shrubs, deciduous shrubs, graminoids, forbs), and whether variation explained was dependent upon the traits included in analysis. We further compared the explanatory power and species composition of functional groups to alternative classifications generated using post hoc clustering of species-level traits. Results: Traditional functional groups explained significant differences in trait expression, particularly amongst traits associated with resource economics, which were consistent across sites and at the biome scale. However, functional groups explained 19% of overall trait variation and poorly represented differences in traits associated with plant size. Post hoc classification of species did not correspond well with traditional functional groups, and explained twice as much variation in species-level trait expression. Main conclusions: Traditional functional groups only coarsely represent variation in well-measured traits within tundra plant communities, and better explain resource economic traits than size-related traits. We recommend caution when using functional group approaches to predict tundra ecosystem change, or ecosystem functions relating to plant size, such as albedo or carbon storage. We argue that alternative classifications or direct use of specific plant traits could provide new insight into ecological prediction and modelling.
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| 7. |
- Criado, M. G., et al.
(author)
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Plant traits poorly predict winner and loser shrub species in a warming tundra biome
- 2023
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In: Nature Communications. - 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- Climate change is leading to species redistributions. In the tundra biome, shrubs are generally expanding, but not all tundra shrub species will benefit from warming. Winner and loser species, and the characteristics that may determine success or failure, have not yet been fully identified. Here, we investigate whether past abundance changes, current range sizes and projected range shifts derived from species distribution models are related to plant trait values and intraspecific trait variation. We combined 17,921 trait records with observed past and modelled future distributions from 62 tundra shrub species across three continents. We found that species with greater variation in seed mass and specific leaf area had larger projected range shifts, and projected winner species had greater seed mass values. However, trait values and variation were not consistently related to current and projected ranges, nor to past abundance change. Overall, our findings indicate that abundance change and range shifts will not lead to directional modifications in shrub trait composition, since winner and loser species share relatively similar trait spaces. Functional trait data could guide predictions of species responses to environmental change. Here, the authors show that winner and loser shrub species in the warming tundra biome overlap in trait space and may therefore be difficult to predict based on commonly measured traits.
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| 8. |
- Björkman, Anne, 1981, et al.
(author)
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Plant functional trait change across a warming tundra biome
- 2018
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 562:7725, s. 57-62
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Journal article (peer-reviewed)abstract
- The tundra is warming more rapidly than any other biome on Earth, and the potential ramifications are far-reaching because of global feedback effects between vegetation and climate. A better understanding of how environmental factors shape plant structure and function is crucial for predicting the consequences of environmental change for ecosystem functioning. Here we explore the biome-wide relationships between temperature, moisture and seven key plant functional traits both across space and over three decades of warming at 117 tundra locations. Spatial temperature–trait relationships were generally strong but soil moisture had a marked influence on the strength and direction of these relationships, highlighting the potentially important influence of changes in water availability on future trait shifts in tundra plant communities. Community height increased with warming across all sites over the past three decades, but other traits lagged far behind predicted rates of change. Our findings highlight the challenge of using space-for-time substitution to predict the functional consequences of future warming and suggest that functions that are tied closely to plant height will experience the most rapid change. They also reveal the strength with which environmental factors shape biotic communities at the coldest extremes of the planet and will help to improve projections of functional changes in tundra ecosystems with climate warming.
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| 9. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
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In: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
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Research review (peer-reviewed)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.
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| 10. |
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| 11. |
- Björkman, Anne, 1981, et al.
(author)
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Tundra Trait Team: A database of plant traits spanning the tundra biome
- 2018
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In: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 27:12, s. 1402-1411
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Journal article (peer-reviewed)abstract
- © 2018 The Authors Global Ecology and Biogeography Published by John Wiley & Sons Ltd Motivation: The Tundra Trait Team (TTT) database includes field-based measurements of key traits related to plant form and function at multiple sites across the tundra biome. This dataset can be used to address theoretical questions about plant strategy and trade-offs, trait–environment relationships and environmental filtering, and trait variation across spatial scales, to validate satellite data, and to inform Earth system model parameters. Main types of variable contained: The database contains 91,970 measurements of 18 plant traits. The most frequently measured traits (>1,000 observations each) include plant height, leaf area, specific leaf area, leaf fresh and dry mass, leaf dry matter content, leaf nitrogen, carbon and phosphorus content, leaf C:N and N:P, seed mass, and stem specific density. Spatial location and grain: Measurements were collected in tundra habitats in both the Northern and Southern Hemispheres, including Arctic sites in Alaska, Canada, Greenland, Fennoscandia and Siberia, alpine sites in the European Alps, Colorado Rockies, Caucasus, Ural Mountains, Pyrenees, Australian Alps, and Central Otago Mountains (New Zealand), and sub-Antarctic Marion Island. More than 99% of observations are georeferenced. Time period and grain: All data were collected between 1964 and 2018. A small number of sites have repeated trait measurements at two or more time periods. Major taxa and level of measurement: Trait measurements were made on 978 terrestrial vascular plant species growing in tundra habitats. Most observations are on individuals (86%), while the remainder represent plot or site means or maximums per species. Software format: csv file and GitHub repository with data cleaning scripts in R; contribution to TRY plant trait database (www.try-db.org) to be included in the next version release.
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| 12. |
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Klionsky, DJ, et al.
(author)
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Autophagy in major human diseases
- 2021
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In: The EMBO journal. - : EMBO. - 1460-2075 .- 0261-4189. ; 40:19, s. e108863-
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Journal article (peer-reviewed)
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| 17. |
- Komatsu, Kimberly J., et al.
(author)
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Global change effects on plant communities are magnified by time and the number of global change factors imposed
- 2019
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In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:36, s. 17867-17873
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Journal article (peer-reviewed)abstract
- Accurate prediction of community responses to global change drivers (GCDs) is critical given the effects of biodiversity on ecosystem services. There is consensus that human activities are driving species extinctions at the global scale, but debate remains over whether GCDs are systematically altering local communities worldwide. Across 105 experiments that included over 400 experimental manipulations, we found evidence for a lagged response of herbaceous plant communities to GCDs caused by shifts in the identities and relative abundances of species, often without a corresponding difference in species richness. These results provide evidence that community responses are pervasive across a wide variety of GCDs on long-term temporal scales and that these responses increase in strength when multiple GCDs are simultaneously imposed.Global change drivers (GCDs) are expected to alter community structure and consequently, the services that ecosystems provide. Yet, few experimental investigations have examined effects of GCDs on plant community structure across multiple ecosystem types, and those that do exist present conflicting patterns. In an unprecedented global synthesis of over 100 experiments that manipulated factors linked to GCDs, we show that herbaceous plant community responses depend on experimental manipulation length and number of factors manipulated. We found that plant communities are fairly resistant to experimentally manipulated GCDs in the short term (<10 y). In contrast, long-term (≥10 y) experiments show increasing community divergence of treatments from control conditions. Surprisingly, these community responses occurred with similar frequency across the GCD types manipulated in our database. However, community responses were more common when 3 or more GCDs were simultaneously manipulated, suggesting the emergence of additive or synergistic effects of multiple drivers, particularly over long time periods. In half of the cases, GCD manipulations caused a difference in community composition without a corresponding species richness difference, indicating that species reordering or replacement is an important mechanism of community responses to GCDs and should be given greater consideration when examining consequences of GCDs for the biodiversity–ecosystem function relationship. Human activities are currently driving unparalleled global changes worldwide. Our analyses provide the most comprehensive evidence to date that these human activities may have widespread impacts on plant community composition globally, which will increase in frequency over time and be greater in areas where communities face multiple GCDs simultaneously.
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| 18. |
- MacDougall, Andrew S., et al.
(author)
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Widening global variability in grassland biomass since the 1980s
- 2024
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In: Nature Ecology & Evolution. - : Springer Nature. - 2397-334X.
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Journal article (peer-reviewed)abstract
- Global change is associated with variable shifts in the annual production of aboveground plant biomass, suggesting localized sensitivities with unclear causal origins. Combining remotely sensed normalized difference vegetation index data since the 1980s with contemporary field data from 84 grasslands on 6 continents, we show a widening divergence in site-level biomass ranging from +51% to −34% globally. Biomass generally increased in warmer, wetter and species-rich sites with longer growing seasons and declined in species-poor arid areas. Phenological changes were widespread, revealing substantive transitions in grassland seasonal cycling. Grazing, nitrogen deposition and plant invasion were prevalent in some regions but did not predict overall trends. Grasslands are undergoing sizable changes in production, with implications for food security, biodiversity and carbon storage especially in arid regions where declines are accelerating.
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| 19. |
- Ochoa-Hueso, Raúl, et al.
(author)
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Microbial processing of plant remains is co-limited by multiple nutrients in global grasslands
- 2020
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In: Global Change Biology. - : John Wiley & Sons. - 1354-1013 .- 1365-2486. ; 26:8, s. 4572-4582
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Journal article (peer-reviewed)abstract
- Microbial processing of aggregate-unprotected organic matter inputs is key for soil fertility, long-term ecosystem carbon and nutrient sequestration and sustainable agriculture. We investigated the effects of adding multiple nutrients (nitrogen, phosphorus and potassium plus nine essential macro- and micro-nutrients) on decomposition and biochemical transformation of standard plant materials buried in 21 grasslands from four continents. Addition of multiple nutrients weakly but consistently increased decomposition and biochemical transformation of plant remains during the peak-season, concurrent with changes in microbial exoenzymatic activity. Higher mean annual precipitation and lower mean annual temperature were the main climatic drivers of higher decomposition rates, while biochemical transformation of plant remains was negatively related to temperature of the wettest quarter. Nutrients enhanced decomposition most at cool, high rainfall sites, indicating that in a warmer and drier future fertilized grassland soils will have an even more limited potential for microbial processing of plant remains.
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| 20. |
- Ackerman, I. N., et al.
(author)
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Lifetime Risk of Primary Total Hip Replacement Surgery for Osteoarthritis From 2003 to 2013: A Multinational Analysis Using National Registry Data
- 2017
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In: Arthritis Care Res (Hoboken). - : Wiley. - 2151-464X. ; 69:11, s. 1659-1667
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To compare the lifetime risk of total hip replacement (THR) surgery for osteoarthritis (OA) between countries, and over time. METHODS: Data on primary THR procedures performed for OA in 2003 and 2013 were extracted from national arthroplasty registries in Australia, Denmark, Finland, Norway, and Sweden. Life tables and population data were also obtained for each country. Lifetime risk of THR was calculated for 2003 and 2013 using registry, life table, and population data. RESULTS: In 2003, lifetime risk of THR ranged from 8.7% (Denmark) to 15.9% (Norway) for females, and from 6.3% (Denmark) to 8.6% (Finland) for males. With the exception of females in Norway (where lifetime risk started and remained high), lifetime risk of THR increased significantly for both sexes in all countries from 2003 to 2013. In 2013, lifetime risk of THR was as high as 1 in 7 women in Norway, and 1 in 10 men in Finland. Females consistently demonstrated the highest lifetime risk of THR at both time points. Notably, lifetime risk for females in Norway was approximately double the risk for males in 2003 (females 15.9% [95% confidence interval (95% CI) 15.6-16.1], males 6.9% [95% CI 6.7-7.1]), and 2013 (females 16.0% [95% CI 15.8-16.3], males 8.3% [95% CI 8.1-8.5]). CONCLUSION: Using representative, population-based data, this study found statistically significant increases in the lifetime risk of THR in 5 countries over a 10-year period, and substantial between-sex differences. These multinational risk estimates can inform resource planning for OA service delivery.
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| 21. |
- Ackerman, I. N., et al.
(author)
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Substantial rise in the lifetime risk of primary total knee replacement surgery for osteoarthritis from 2003 to 2013: an international, population-level analysis
- 2017
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In: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 25:4, s. 455-461
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Journal article (peer-reviewed)abstract
- Objective: To estimate and compare the lifetime risk of total knee replacement surgery (TKR) for osteoarthritis (OA) between countries, and over time. Method: Data on primary TKR procedures performed for OA in 2003 and 2013 were extracted from national arthroplasty registries in Australia, Denmark, Finland, Norway and Sweden. Life tables and population data were also obtained for each country. Lifetime risk of TKR was calculated for 2003 and 2013 using registry, life table and population data. Results: Marked international variation in lifetime risk of TKR was evident, with females consistently demonstrating the greatest risk. In 2013, Finland had the highest lifetime risk for females (22.8%, 95% CI 22.5-23.1%) and Australia had the highest risk for males (15.4%, 95% CI 15.1-15.6%). Norway had the lowest lifetime risk for females (9.7%, 95% CI 9.5-9.9%) and males (5.8%, 95% CI 5.6-5.9%) in 2013. All countries showed a significant rise in lifetime risk of TKR for both sexes over the 10-year study period, with the largest increases observed in Australia (females: from 13.6% to 21.1%; males: from 9.8% to 15.4%). Conclusions: Using population-based data, this study identified significant increases in the lifetime risk of TKR in all five countries from 2003 to 2013. Lifetime risk of TKR was as high as 1 in 5 women in Finland, and 1 in 7 males in Australia. These risk estimates quantify the healthcare resource burden of knee OA at the population level, providing an important resource for public health policy development and healthcare planning. (C) 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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| 22. |
- Badawy, Mona, et al.
(author)
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Hospital volume and the risk of revision in Oxford unicompartmental knee arthroplasty in the Nordic countries -an observational study of 14,496 cases
- 2017
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In: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 18:1
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Journal article (peer-reviewed)abstract
- Background: High procedure volume and dedication to unicompartmental knee arthroplasty (UKA) has been suggested to improve revision rates. This study aimed to quantify the annual hospital volume effect on revision risk in Oxfordu? nicompartmental knee arthroplasty in the Nordic countries. Methods: 14,496 cases of cemented medial Oxford III UKA were identified in 126 hospitals in the four countries included in the Nordic Arthroplasty Register Association (NARA) database from 2000 to 2012. Hospitals were divided by quartiles into 4 annual procedure volume groups (≤11, 12-23, 24-43 and ≥44). The outcome was revision risk after 2 and 10 years calculated using Kaplan Meier method. Multivariate Cox regression analysis was used to assess the Hazard Ratio (HR) of any revision due to specific reasons with 95% confidence intervals (CI). Results: The implant survival was 80% at 10 years in the volume group ≤11 procedures per year compared to 83% in other volume groups. The HR adjusted for age category, sex, year of surgery and nation was 0.87 (95% CI: 0.76-0.99, p = 0.036) for the group 12-23 procedures per year, 0.78 (95% CI: 0.68-0.91, p = 0.002) for the group 24-43 procedures per year and 0.82 (95% CI: 0.70-0.94, p = 0.006) for the group ≥44 procedures per year compared to the low volume group. Log-rank test was p = 0.003. The risk of revision for unexplained pain was 40-50% higher in the low compared with other volume groups. Conclusion: Low volume hospitals performing ≤11 Oxford III UKAs per year were associated with an increased risk of revision compared to higher volume hospitals, and unexplained pain as revision cause was more common in low volume hospitals.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Garcia-Closas, Montserrat, et al.
(author)
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Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics
- 2008
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In: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 4:4, s. e1000054-
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Journal article (peer-reviewed)abstract
- A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific protein 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER-positive (per-allele OR (95%CI) = 1.31 (1.27-1.36)) than ER-negative (1.08 (1.03-1.14)) disease (P for heterogeneity = 10(-13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER-positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs (rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER-negative disease, the strongest association being for rs3803662 in TNRC9 (1.14 (1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis (per-allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER-positive and ER-negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment.
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| 27. |
- Halvorsen, V., et al.
(author)
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Outcome of 881 total hip arthroplasties in 747 patients 21 years or younger: data from the Nordic Arthroplasty Register Association (NARA) 1995-2016
- 2019
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In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 90:4, s. 331-337
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Journal article (peer-reviewed)abstract
- Background and purpose - The literature is scarce on the outcome of the youngest patients with total hip arthroplasties (THAs). We analyzed register data, revision risk, and related factors in patients 21 years or younger with THAs in the Nordic Arthroplasty Register Association (NARA). Patients and methods - We included all THA patients 21 years or younger reported during 1995 through 2016 to the Danish, Finnish, Norwegian, and Swedish hip arthroplasty registers and merged these into the NARA dataset. Primary outcome was any implant revision. Results - We identified 881 THAs in 747 patients. Mean age at primary surgery was 18 years (9-21). The indications for THA were pediatric hip diseases (33%), systemic inflammatory disease (23%), osteoarthritis (4%), avascular necrosis (12%), hip fracture sequelae (7%), and other diagnoses (21%). Unadjusted 10-year survival for all THAs was 86%. Comparison between indications showed no differences in survival. Uncemented implants were used most frequently. Survival for uncemented and cemented implants was the same adjusted for sex, indication, head size, and time period for primary surgery. Aseptic loosening was the main cause of revision. Interpretation - Both cemented and uncemented fixations seem to be a viable option in this age group, but with a lower implant survival than in older patient groups.
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| 28. |
- Irmola, Tero, et al.
(author)
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Association between fixation type and revision risk in total knee arthroplasty patients aged 65 years and older : a cohort study of 265,877 patients from the Nordic Arthroplasty Register Association 2000–2016
- 2021
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In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 92:1, s. 91-96
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Journal article (peer-reviewed)abstract
- Background and purpose — The population of the Nordic countries is aging and the number of elderly patients undergoing total knee arthroplasty (TKA) is also expected to increase. Reliable fixation methods are essential to avoid revisions. We compared the survival of different TKA fixation concepts with cemented fixation as the gold standard. Patients and methods — We used data from the Nordic Arthroplasty Register Association (NARA) database of 265,877 unconstrained TKAs performed for patients aged ≥ 65 years with primary knee osteoarthritis between 2000 and 2016. Kaplan–Meier (KM) survival analysis with 95% confidence intervals (CI) and the Cox multiple-regression model were used to compare the revision risk of the fixation methods. Results — Cemented fixation was used in 243,166 cases, uncemented in 8,000, hybrid (uncemented femur with cemented tibia) in 14,248, and inverse hybrid (cemented femur with uncemented tibia) fixation in 463 cases. The 10-year KM survivorship (95% CI) of cemented TKAs was 96% (96 − 97), uncemented 94% (94 − 95), hybrid 96% (96 − 96), and inverse hybrid 96% (94 − 99), respectively. Uncemented TKA was associated with increased risk of revision compared with the cemented TKA; the adjusted hazard ratio was 1.3 (95% CI 1.1 − 1.4). Interpretation — Cemented, hybrid, and inverse hybrid TKAs showed 10-year survival rates exceeding 95%. Uncemented fixation was associated with an increased risk of revision in comparison with cemented fixation. As both hybrid and inverse hybrid fixation were used in only a limited number of TKAs, indicating possibility of selection bias in their favor, cemented TKA still remains the gold standard, as it works reliably in the hands of many.
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| 29. |
- Irmola, Tero, et al.
(author)
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Impact of the Nordic Arthroplasty Register Association (NARA) collaboration on demographics, methods and revision rates in knee arthroplasty : a register-based study from NARA 2000–2017
- 2022
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In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 93, s. 866-873
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Journal article (peer-reviewed)abstract
- Background and purpose — We have previously observed differences in treatment and outcome of knee arthroplasties in the Nordic countries. To evaluate the impact of Nordic collaboration in the last 15 years we aimed to compare patient demographics, methods, and revision rates in primary knee arthroplasties among the 4 Nordic countries. Patients and methods — We included 535,051 primary knee arthroplasties reported 2000–2017 from the Nordic Arthroplasty Register Association (NARA) database. Kaplan–Meier analysis (KM) and restricted mean survival time (RMST) analysis were used to evaluate the cumulative revision rate (CRR) and RMST estimates with 95% confidence intervals (CI) and to compare countries in relation to risk of revision for any reason. Results — After 2010, the increase in incidence of knee arthroplasty plateaued in Sweden and Denmark but contin-ued to increase in Finland and Norway. In 2017 the incidence was highest in Finland with 226 per 105 person-years, while it was less than 150 per 105 in the 3 other Nordic coun-tries. In total knee arthroplasties performed for osteoarthri-tis (OA), overall CRR at 15 years for revision due to any reason was higher in Denmark (CRR 9.6%, 95% CI 9.2−10), Norway (CRR 9.1%, CI 8.7−9.5), and Finland (CRR 7.0%, CI 6.8−7.3) compared with Sweden (CRR 6.6%, CI 6.4−6.8). There were differences among the countries in use of implant brand and type, fixation, patellar component, and use of unicompartmental knee arthroplasty. Interpretation — We evinced a slowing growth of incidence of knee arthroplasties in the Nordic countries after 2010 with Finland having the highest incidence. We also noted substantial differences among the 4 Nordic countries, with Sweden having a lower risk of revision than the other countries. No impact of NARA could be demonstrated and CRR did not improve over time.
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| 30. |
- Makela, K. T., et al.
(author)
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Countrywise results of total hip replacement An analysis of 438,733 hips based on the Nordic Arthroplasty Register Association database
- 2014
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In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 85:2, s. 107-116
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Journal article (peer-reviewed)abstract
- Background and purpose An earlier Nordic Arthroplasty Register Association (NARA) report on 280,201 total hip replacements (THRs) based on data from 1995-2006, from Sweden, Norway, and Denmark, was published in 2009. The present study assessed THR survival according to country, based on the NARA database with the Finnish data included. Material and methods 438,733 THRs performed during the period 1995-2011 in Sweden, Denmark, Norway, and Finland were included. Kaplan-Meier survival analysis was used to calculate survival probabilities with 95% confidence interval (CI). Cox multiple regression, with adjustment for age, sex, and diagnosis, was used to analyze implant survival with revision for any reason as endpoint. Results The 15-year survival, with any revision as an endpoint, for all THRs was 86% (CI: 85.7-86.9) in Denmark, 88% (CI: 87.6-88.3) in Sweden, 87% (CI: 86.4-87.4) in Norway, and 84% (CI: 82.9-84.1) in Finland. Revision risk for all THRs was less in Sweden than in the 3 other countries during the first 5 years. However, revision risk for uncemented THR was less in Denmark than in Sweden during the sixth (HR = 0.53, CI: 0.34-0.82), seventh (HR = 0.60, CI: 0.37-0.97), and ninth (HR = 0.59, CI: 0.36-0.98) year of follow-up. Interpretation The differences in THR survival rates were considerable, with inferior results in Finland. Brand-level comparison of THRs in Nordic countries will be required.
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| 31. |
- Makela, K. T., et al.
(author)
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The benefits of collaboration: the Nordic Arthroplasty Register Association
- 2019
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In: Efort Open Reviews. - : Bioscientifica. - 2058-5241 .- 2396-7544. ; 4:6, s. 391-400
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Journal article (peer-reviewed)abstract
- The Nordic Arthroplasty Register Association (NARA) was established in 2007 by arthroplasty register representatives from Sweden, Norway and Denmark with the overall aim to improve the quality of research and thereby enhance the possibility for quality improvement with arthroplasty surgery. Finland joined the NARA collaboration in 2010. NARA minimal hip, knee and shoulder datasets were created with variables that all countries can deliver. They are dynamic datasets, currently with 25 variables for hip arthroplasty, 20 for knee arthroplasty and 20 for shoulder arthroplasty. NARA has published statistical guidelines for the analysis of arthroplasty register data. The association is continuously working on the improvement of statistical methods and the application of new ones. There are 31 published peer-reviewed papers based on the NARA databases and 20 ongoing projects in different phases. Several NARA publications have significantly affected clinical practice. For example, metal-on-metal total hip arthroplasty and resurfacing arthroplasty have been abandoned due to increased revision risk based on i.a. NARA reports. Further, the use of uncemented total hip arthroplasty in elderly patients has decreased significantly, especially in Finland, based on the NARA data. The NARA collaboration has been successful because the countries were able to agree on a common dataset and variable definitions. The collaboration was also successful because the group was able to initiate a number of research projects and provide answers to clinically relevant questions. A number of specific goals, set up in 2007, have been achieved and new one has emerged in the process.
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| 32. |
- NiemeläInen, Mika J., et al.
(author)
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Different incidences of knee arthroplasty in the Nordic countries : A population-based study from the Nordic Arthroplasty Register Association
- 2017
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In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 88:2, s. 173-178
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Journal article (peer-reviewed)abstract
- Background and purpose — The annual number of total knee arthroplasties (TKAs) has increased worldwide in recent years. To make projections regarding future needs for primaries and revisions, additional knowledge is important. We analyzed and compared the incidences among 4 Nordic countries Patients and methods — Using Nordic Arthroplasty Register Association (NARA) data from 4 countries, we analyzed differences between age and sex groups. We included patients over 30 years of age who were operated with TKA or unicompartmental knee arthroplasty (UKA) during the period 1997–2012. The negative binomial regression model was used to analyze changes in general trends and in sex and age groups. Results — The average annual increase in the incidence of TKA was statistically significant in all countries. The incidence of TKA was higher in women than in men in all 4 countries. It was highest in Finland in patients aged 65 years or more. At the end of the study period in 2012, Finland’s total incidence was double that of Norway, 1.3 times that of Sweden and 1.4 times that of Denmark. The incidence was lowest in the youngest age groups (< 65 years) in all 4 countries. The proportional increase in incidence was highest in patients who were younger than 65 years. Interpretation — The incidence of knee arthroplasty steadily increased in the 4 countries over the study period. The differences between the countries were considerable, with the highest incidence in Finland. Patients aged 65 years or more contributed to most of the total incidence of knee arthroplasty.
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| 33. |
- Niemeläinen, Mika J., et al.
(author)
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The effect of fixation type on the survivorship of contemporary total knee arthroplasty in patients younger than 65 years of age : a register-based study of 115,177 knees in the Nordic Arthroplasty Register Association (NARA) 2000–2016
- 2020
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In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 91:2, s. 184-190
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Journal article (peer-reviewed)abstract
- Background and purpose — Cemented fixation is regarded as the gold standard in total knee arthroplasty (TKA). Among working-age patients, there has been controversy regarding the optimal fixation method in TKA. To address this issue, we conducted a register-based study to assess the survivorship of cemented, uncemented, hybrid, and inverse hybrid TKAs in patients aged < 65 years. Patients and methods — We used the Nordic Arthroplasty Register Association data of 115,177 unconstrained TKAs performed for patients aged < 65 years with primary knee osteoarthritis over 2000–2016. Kaplan–Meier (KM) survival analysis with 95% confidence intervals (CI) and Cox multiple-regression model with adjustment for age, sex, and nation were used to compare fixation methods in relation to revision for any reason. Results — The 10-year KM survivorship of cemented TKAs was 93.6% (95% CI 93.4–93.8), uncemented 91.2% (CI 90.1–92.2), hybrid 93.0% (Cl 92.2–93.8), and inverse hybrid 96.0% (CI 94.1–98.1). In the Cox model, hybrid TKA showed decreased risk of revision after 6 years’ follow-up compared with the reference group (cemented) (hazard ratio [HR] 0.5 [CI 0.4–0.8]), while uncemented TKAs showed increased risk of revision both < 1 year (HR 1.4 [1.1–1.7]) and > 6 years’ (HR 1.3 [1.0–1.7]) follow-up compared to the reference. Interpretation — Both cemented and hybrid TKAs had 10-year survival rates exceeding 92–>93% in patients aged < 65 years. Cemented TKA, however, was used in the vast majority (89%) of the operations in the current study. As it performs reliably in the hands of many, it still deserves the status of gold standard for TKA in working-age patients.
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| 34. |
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| 35. |
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| 36. |
- Dale, Håvard, et al.
(author)
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Increasing risk of prosthetic joint infection after total hip arthroplasty.
- 2012
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In: Acta orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 83:5, s. 449-58
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Journal article (peer-reviewed)abstract
- Background and purpose The risk of revision due to infection after primary total hip arthroplasty (THA) has been reported to be increasing in Norway. We investigated whether this increase is a common feature in the Nordic countries (Denmark, Finland, Norway, and Sweden). Materials and methods The study was based on the Nordic Arthroplasty Register Association (NARA) dataset. 432,168 primary THAs from 1995 to 2009 were included (Denmark: 83,853, Finland 78,106, Norway 88,455, and Sweden 181,754). Adjusted survival analyses were performed using Cox regression models with revision due to infection as the endpoint. The effect of risk factors such as the year of surgery, age, sex, diagnosis, type of prosthesis, and fixation were assessed. Results 2,778 (0.6%) of the primary THAs were revised due to infection. Compared to the period 1995-1999, the relative risk (with 95% CI) of revision due to infection was 1.1 (1.0-1.2) in 2000-2004 and 1.6 (1.4-1.7) in 2005-2009. Adjusted cumulative 5-year revision rates due to infection were 0.46% (0.42-0.50) in 1995-1999, 0.54% (0.50-0.58) in 2000-2004, and 0.71% (0.66-0.76) in 2005-2009. The entire increase in risk of revision due to infection was within 1 year of primary surgery, and most notably in the first 3 months. The risk of revision due to infection increased in all 4 countries. Risk factors for revision due to infection were male sex, hybrid fixation, cement without antibiotics, and THA performed due to inflammatory disease, hip fracture, or femoral head necrosis. None of these risk factors increased in incidence during the study period. Interpretation We found increased relative risk of revision and increased cumulative 5-year revision rates due to infection after primary THA during the period 1995-2009. No change in risk factors in the NARA dataset could explain this increase. We believe that there has been an actual increase in the incidence of prosthetic joint infections after THA.
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| 37. |
- Dale, H., et al.
(author)
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Increasing risk of revision due to infection after primary total hip arthroplasty: results from the Nordic Arthro- plasty Register Association
- 2023
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In: Acta orthopaedica. - : Medical Journals Sweden. - 1745-3674 .- 1745-3682. ; 94, s. 307-315
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Journal article (peer-reviewed)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.
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| 38. |
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| 39. |
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| 40. |
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| 41. |
- Eskelinen, M., et al.
(author)
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Preoperative serum levels of follicle stimulating hormone (FSH) and prognosis in invasive breast cancer
- 2004
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In: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 30:5, s. 495-500
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Journal article (peer-reviewed)abstract
- AIMS: We investigated the association between preoperative serum levels of follicle stimulating hormone (FSH) and the prognosis in women with invasive breast cancer. METHODS: Serum levels of FSH were measured in 182 premenopausal and 581 peri- or postmenopausal women with invasive breast cancer. They were followed for a mean time of 84 months. The study endpoint was death from breast cancer (182 events). Analyses were stratified on menopausal status. RESULTS: None of the estimates showed a statistically significant result. In both pre- and postmenopausal women there was a nominally higher probability of survival with a higher FSH level. Point estimates in multivariate analysis incorporating age, tumour diameter, axillary lymph status, estrogen and progesterone receptor content and year of treatment indicated a stronger association with FSH levels in premenopausal than postmenopausal women (relative hazard 0.63 or 0.85, respectively in the highest compared with the lowest quartile). CONCLUSION: We did not find any statistically significant association between preoperative serum level of FSH and prognosis. Today, FSH is not a clinical target for intervention or a clinically useful prognostic factor and the results of clinical studies up to date can only be used for motivation of further experimental laboratory research.
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| 42. |
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| 43. |
- Hailer, Nils P, et al.
(author)
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Hydroxyapatite coating does not improve uncemented stem survival after total hip arthroplasty!
- 2015
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In: Acta orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 86:1, s. 18-25
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Journal article (peer-reviewed)abstract
- Background and purpose - It is still being debated whether HA coating of uncemented stems used in total hip arthroplasty (THA) improves implant survival. We therefore investigated different uncemented stem brands, with and without HA coating, regarding early and long-term survival. Patients and methods - We identified 152,410 THA procedures using uncemented stems that were performed between 1995 and 2011 and registered in the Nordic Arthroplasty Register Association (NARA) database. We excluded 19,446 procedures that used stem brands less than 500 times in each country, procedures performed due to diagnoses other than osteoarthritis or pediatric hip disease, and procedures with missing information on the type of coating. 22 stem brands remained (which were used in 116,069 procedures) for analysis of revision of any component. 79,192 procedures from Denmark, Norway, and Sweden were analyzed for the endpoint stem revision. Unadjusted survival rates were calculated according to Kaplan-Meier, and Cox proportional hazards models were fitted in order to calculate hazard ratios (HRs) for the risk of revision with 95% confidence intervals (CIs). Results - Unadjusted 10-year survival with the endpoint revision of any component for any reason was 92.1% (CI: 91.8-92.4). Unadjusted 10-year survival with the endpoint stem revision due to aseptic loosening varied between the stem brands investigated and ranged from 96.7% (CI: 94.4-99.0) to 99.9% (CI: 99.6-100). Of the stem brands with the best survival, stems with and without HA coating were found. The presence of HA coating was not associated with statistically significant effects on the adjusted risk of stem revision due to aseptic loosening, with an HR of 0.8 (CI: 0.5-1.3; p = 0.4). The adjusted risk of revision due to infection was similar in the groups of THAs using HA-coated and non-HA-coated stems, with an HR of 0.9 (CI: 0.8-1.1; p = 0.6) for the presence of HA coating. The commonly used Bimetric stem (n = 25,329) was available both with and without HA coating, and the adjusted risk of stem revision due to aseptic loosening was similar for the 2 variants, with an HR of 0.9 (CI: 0.5-1.4; p = 0.5) for the HA-coated Bimetric stem. Interpretation - Uncemented HA-coated stems had similar results to those of uncemented stems with porous coating or rough sand-blasted stems. The use of HA coating on stems available both with and without this surface treatment had no clinically relevant effect on their outcome, and we thus question whether HA coating adds any value to well-functioning stem designs.
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| 44. |
- Hailer, Nils P, et al.
(author)
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Hydroxyapatite coating does not improve uncemented stem survival after total hip arthroplasty! : An analysis of 116,069 THAs in the Nordic Arthroplasty Register Association (NARA) database
- 2015
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In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 86:1, s. 18-25
-
Journal article (peer-reviewed)abstract
- Background and purposeIt is still being debated whether HA coating of uncemented stems used in total hip arthroplasty (THA) improves implant survival. We therefore investigated different uncemented stem brands, with and without HA coating, regarding early and long-term survival.Patients and methods We identified 152,410 THA procedures using uncemented stems that were performed between 1995 and 2011 and registered in the Nordic Arthroplasty Register Association (NARA) database. We excluded 19,446 procedures that used stem brands less than 500 times in each country, procedures performed due to diagnoses other than osteoarthritis or pediatric hip disease, and procedures with missing information on the type of coating. 22 stem brands remained (which were used in 116,069 procedures) for analysis of revision of any component. 79,192 procedures from Denmark, Norway, and Sweden were analyzed for the endpoint stem revision. Unadjusted survival rates were calculated according to Kaplan-Meier, and Cox proportional hazards models were fitted in order to calculate hazard ratios (HRs) for the risk of revision with 95% confidence intervals (CIs).ResultsUnadjusted 10-year survival with the endpoint revision of any component for any reason was 92.1% (CI: 91.8-92.4). Unadjusted 10-year survival with the endpoint stem revision due to aseptic loosening varied between the stem brands investigated and ranged from 96.7% (CI: 94.4-99.0) to 99.9% (CI: 99.6-100). Of the stem brands with the best survival, stems with and without HA coating were found. The presence of HA coating was not associated with statistically significant effects on the adjusted risk of stem revision due to aseptic loosening, with an HR of 0.8 (CI: 0.5-1.3; p = 0.4). The adjusted risk of revision due to infection was similar in the groups of THAs using HA-coated and non-HA-coated stems, with an HR of 0.9 (CI: 0.8-1.1; p = 0.6) for the presence of HA coating. The commonly used Bimetric stem (n = 25,329) was available both with and without HA coating, and the adjusted risk of stem revision due to aseptic loosening was similar for the 2 variants, with an HR of 0.9 (CI: 0.5-1.4; p = 0.5) for the HA-coated Bimetric stem.Interpretation Uncemented HA-coated stems had similar results to those of uncemented stems with porous coating or rough sand-blasted stems. The use of HA coating on stems available both with and without this surface treatment had no clinically relevant effect on their outcome, and we thus question whether HA coating adds any value to well-functioning stem designs.
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| 45. |
- Mikkelsen, R. T., et al.
(author)
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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
-
In: Acta Orthopaedica. - 1745-3674. ; 94, s. 266-273
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Journal article (peer-reviewed)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.
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| 46. |
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| 47. |
- Orozco, Gustavo A., et al.
(author)
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Shear strain and inflammation-induced fixed charge density loss in the knee joint cartilage following ACL injury and reconstruction : A computational study
- 2022
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In: Journal of Orthopaedic Research. - : Wiley. - 0736-0266 .- 1554-527X. ; 40:7, s. 1505-1522
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Journal article (peer-reviewed)abstract
- Excessive tissue deformation near cartilage lesions and acute inflammation within the knee joint after anterior cruciate ligament (ACL) rupture and reconstruction surgery accelerate the loss of fixed charge density (FCD) and subsequent cartilage tissue degeneration. Here, we show how biomechanical and biochemical degradation pathways can predict FCD loss using a patient-specific finite element model of an ACL reconstructed knee joint exhibiting a chondral lesion. Biomechanical degradation was based on the excessive maximum shear strains that may result in cell apoptosis, while biochemical degradation was driven by the diffusion of pro-inflammatory cytokines. We found that the biomechanical model was able to predict substantial localized FCD loss near the lesion and on the medial areas of the lateral tibial cartilage. In turn, the biochemical model predicted FCD loss all around the lesion and at intact areas; the highest FCD loss was at the cartilage–synovial fluid-interface and decreased toward the deeper zones. Interestingly, simulating a downturn of an acute inflammatory response by reducing the cytokine concentration exponentially over time in synovial fluid led to a partial recovery of FCD content in the cartilage. Our novel numerical approach suggests that in vivo FCD loss can be estimated in injured cartilage following ACL injury and reconstruction. Our novel modeling platform can benefit the prediction of PTOA progression and the development of treatment interventions such as disease-modifying drug testing and rehabilitation strategies.
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