Population genetics meets ecology: a guide to individual-based simulations in continuous landscapes.

Individual-based simulation has become an increasingly crucial tool for many fields of population biology. However, implementing realistic and stable simulations in continuous space presents a variety of difficulties, from modeling choices to computational efficiency. This paper aims to be a practical guide to spatial simulation, helping researchers to implement realistic and efficient spatial, individual-based simulations and avoid common pitfalls. To do this, we delve into mechanisms of mating, reproduction, density-dependent feedback, and dispersal, all of which may vary across the landscape, discuss how these affect population dynamics, and describe how to parameterize simulations in convenient ways (for instance, to achieve a desired population density). We also demonstrate how to implement these models using the current version of the individual-based simulator, SLiM. Since SLiM has the capacity to simulate genomes, we also discuss natural selection - in particular, how genetic variation can affect demographic processes. Finally, we provide four short vignettes: simulations of pikas that shift their range up a mountain as temperatures rise; mosquitoes that live in rivers as juveniles and experience seasonally changing habitat; cane toads that expand across Australia, reaching 120 million individuals; and monarch butterflies whose populations are regulated by an explicitly modeled resource (milkweed).

Population dynamics in spatial suppression gene drive models and the effect of resistance, density dependence, and life history.

Due to their super-Mendelian inheritance, gene drive systems have the potential to provide revolutionary solutions to critical public health and environmental problems. For suppression drives, however, spatial structure can cause "chasing" population dynamics that may postpone target population elimination or even cause the drive to fail. In chasing, wild-type individuals elude the drive and recolonize previously suppressed areas. The drive can re-enter these recolonized areas, but often is not able to catch up to wild-type and finally eliminate it. Previous methods for chasing detection are only suitable to limited parameter ranges. In this study with expanded parameter ranges, we found that the shift from chasing dynamics to static equilibrium outcomes is continuous as drive performance is reduced. To quantify this, we defined a Weighted Average Nearest Neighbor statistic to assess the clustering degree during chasing, while also characterizing chasing by the per-generation chance of population elimination and drive loss. To detect chasing dynamics in local areas and to detect the start of chasing, we implemented Density-Based Spatial Clustering of Applications with Noise. Using these techniques, we determined the effect of arena size, resistance allele formation rate in both the germline and in the early embryo from maternally deposited Cas9, life history and reproduction strategies, and density-dependent growth curve shape on chasing outcomes. We found that larger real-world areas will be much more vulnerable to chasing and that species with overlapping generations, fecundity-based density dependence, and concave density-dependent growth curves have smaller and more clustered local chasing with a greater chance of eventual population elimination. We also found that embryo resistance and germline resistance hinder drive performance in different ways. These considerations will be important for determining the necessary drive performance parameters needed for success in different species, and whether future drives could potentially be considered as release candidates.

Signatures of selective sweeps in continuous-space populations.

Selective sweeps describe the process by which an adaptive mutation arises and rapidly fixes in the population, thereby removing genetic variation in its genomic vicinity. The expected signatures of selective sweeps are relatively well understood in panmictic population models, yet natural populations often extend across larger geographic ranges where individuals are more likely to mate with those born nearby. To investigate how such spatial population structure can affect sweep dynamics and signatures, we simulated selective sweeps in populations inhabiting a two-dimensional continuous landscape. The maximum dispersal distance of offspring from their parents can be varied in our simulations from an essentially panmictic population to scenarios with increasingly limited dispersal. We find that in low-dispersal populations, adaptive mutations spread more slowly than in panmictic ones, while recombination becomes less effective at breaking up genetic linkage around the sweep locus. Together, these factors result in a trough of reduced genetic diversity around the sweep locus that looks very similar across dispersal rates. We also find that the site frequency spectrum around hard sweeps in low-dispersal populations becomes enriched for intermediate-frequency variants, making these sweeps appear softer than they are. Furthermore, haplotype heterozygosity at the sweep locus tends to be elevated in low-dispersal scenarios as compared to panmixia, contrary to what we observe in neutral scenarios without sweeps. The haplotype patterns generated by these hard sweeps in low-dispersal populations can resemble soft sweeps from standing genetic variation that arose from substantially older alleles. Our results highlight the need for better accounting for spatial population structure when making inferences about selective sweeps.

Reconstructing dietary practices at Tell Kamid el-Loz (Lebanon) during the Bronze and Iron Age III / Persian to Hellenistic periods using plant micro-remains from dental calculus and stable isotope analysis of bone collagen.

Tell Kamid el-Loz (Lebanon) was an important Bronze Age urban center that dominated one of the central crossroads of the Ancient Near East, connecting Egypt and the Levant with northern Mesopotamia, Anatolia, and Syria, as well as the interior with the Mediterranean coast. However, by the early Iron Age, the site had shrunk to a small rural settlement. Later, in the Iron Age III / Persian-Hellenistic, only enigmatic pits and a large cemetery remained. In this paper, we analyzed plant micro-remains from the dental calculus of 15 individuals (3 from the Middle Bronze Age II and 12 from the Iron Age III / Persian-Hellenistic) and δ 13C and δ 15N stable isotope data from tbulk bone collagen of 74 individuals (10 from the Middle Bronze Age II and 64 from the Iron Age III / Persian-Hellenistic) and 13 Late Bronze Age animal bones (7 Ovis/Capra and 6 Bos). Our results indicate general stability of human diet throughout the Middle Bronze Age II and the Iron III / Persian-Hellenistic periods, with a reliance on C3 plant crops and terrestrial animals also consuming C3 plants. In the later period, the plant micro-remains indicate the consumption of C4 plants and sedges, and the stable isotope analysis indicates differences in diet between males and females. Supplementary Information: The online version contains supplementary material available at 10.1007/s12520-024-02000-w.

e3SIM: epidemiological-ecological-evolutionary simulation framework for genomic epidemiology.

Infectious disease dynamics are driven by the complex interplay of epidemiological, ecological, and evolutionary processes. Accurately modeling these interactions is crucial for understanding pathogen spread and informing public health strategies. However, existing simulators often fail to capture the dynamic interplay between these processes, resulting in oversimplified models that do not fully reflect real-world complexities in which the pathogen's genetic evolution dynamically influences disease transmission. We introduce the epidemiological-ecological-evolutionary simulator (e3SIM), an open-source framework that concurrently models the transmission dynamics and molecular evolution of pathogens within a host population while integrating environmental factors. Using an agent-based, discrete-generation, forward-in-time approach, e3SIM incorporates compartmental models, host-population contact networks, and quantitative-trait models for pathogens. This integration allows for realistic simulations of disease spread and pathogen evolution. Key features include a modular and scalable design, flexibility in modeling various epidemiological and population-genetic complexities, incorporation of time-varying environmental factors, and a user-friendly graphical interface. We demonstrate e3SIM's capabilities through simulations of realistic outbreak scenarios with SARS-CoV-2 and Mycobacterium tuberculosis, illustrating its flexibility for studying the genomic epidemiology of diverse pathogen types.

Scapular morphology does not predict supraspinatus tendon tear propagation following an individualised exercise therapy programme.

Purpose: To determine whether scapular morphology could predict isolated supraspinatus tendon tear propagation after exercise therapy. We hypothesised that a larger critical shoulder angle (CSA) and type III acromial morphology predict a positive change in tear size. Methods: Fifty-nine individuals aged 40-70 years with isolated symptomatic high-grade partial or full-thickness supraspinatus tendon tears were included. Individuals participated in a structured, individualised 12-week exercise therapy programme and underwent ultrasound to measure tear size at baseline and 12 months following therapy. Computed tomography images were segmented to create three-dimensional subject-specific bone models and reviewed by three trained clinicians to measure CSA and to determine acromion morphology based on the Bigliani classification. A binary logistic regression was performed to determine the predictive value of CSA and acromion morphology on tear propagation. Results: The CSA was 30.0 ± 5.4°. Thirty-one individuals (52.5%) had type II acromial morphology, followed by type III and type I morphologies (25.4% and 22.0%, respectively); 81.4% experienced no change in tear size, four (6.8%) individuals experienced tear propagation and seven (11.9%) individuals had a negative change in tear size. No significant difference in tear propagation rates based on CSA or acromion morphology (not significant [NS]) was observed. The model predicted tear size status in 81.4% of cases but only predicted tear propagation 8.3% of the time. Overall, CSA and acromion morphology only predicted 24.3% (R 2 = 0.243) of variance in tear propagation (NS). Conclusions: CSA and acromion morphology were NS predictors of tear propagation of the supraspinatus tendon 12 months following an individualised exercise therapy programme. Level of Evidence: II.

Modulation of Alzheimer's Disease Aß40 Fibril Polymorphism by the Small Heat Shock Protein αB-Crystallin.

Deposition of amyloid plaques in the brains of Alzheimer's disease (AD) patients is a hallmark of the disease. AD plaques consist primarily of the beta-amyloid (Aß) peptide but can contain other factors such as lipids, proteoglycans, and chaperones. So far, it is unclear how the cellular environment modulates fibril polymorphism and how differences in fibril structure affect cell viability. The small heat-shock protein (sHSP) alpha-B-Crystallin (αBC) is abundant in brains of AD patients, and colocalizes with Aß amyloid plaques. Using solid-state NMR spectroscopy, we show that the Aß40 fibril seed structure is not replicated in the presence of the sHSP. αBC prevents the generation of a compact fibril structure and leads to the formation of a new polymorph with a dynamic N-terminus. We find that the N-terminal fuzzy coat and the stability of the C-terminal residues in the Aß40 fibril core affect the chemical and thermodynamic stability of the fibrils and influence their seeding capacity. We believe that our results yield a better understanding of how sHSP, such as αBC, that are part of the cellular environment, can affect fibril structures related to cell degeneration in amyloid diseases.

Performance Evaluation of a Novel Artificial Intelligence-Assisted Digital Microscopy System for the Routine Analysis of Bone Marrow Aspirates.

Bone marrow aspiration (BMA) smear analysis is essential for diagnosis, treatment, and monitoring of a variety of benign and neoplastic hematological conditions. Currently, this analysis is performed by manual microscopy. We conducted a multicenter study to validate a computational microscopy approach with an artificial intelligence-driven decision support system. A total of 795 BMA specimens (615 Romanowsky-stained and 180 Prussian blue-stained) from patients with neoplastic and other clinical conditions were analyzed, comparing the performance of the Scopio Labs X100 Full Field BMA system (test method) with manual microscopy (reference method). The system provided an average of 1,385 ± 536 (range, 0-3,131) cells per specimen for analysis. An average of 39.98 ± 19.64 fields of view (range, 0-140) per specimen were selected by the system for analysis, of them 87% ± 21% (range, 0%-100%) were accepted by the qualified operators. These regions were included in an average of 17.62 ± 7.24 regions of interest (range, 1-50) per specimen. The efficiency, sensitivity, and specificity for primary and secondary marrow aspirate characteristics (maturation, morphology, and count assessment), as well as overall interuser agreement, were evaluated. The test method showed a high correlation with the reference method for comprehensive BMA evaluation, both on Romanowsky- (90.85% efficiency, 81.61% sensitivity, and 92.88% specificity) and Prussian blue-stained samples (90.0% efficiency, 81.94% sensitivity, and 93.38% specificity). The overall agreement between the test and reference methods for BMA assessment was 91.1%. For repeatability and reproducibility, all standard deviations and coefficients of variation values were below the predefined acceptance criteria both for discrete measurements (coefficient of variation below 20%) and differential measurements (SD below 5%). The high degree of correlation between the digital decision support system and manual microscopy demonstrates the potential of this system to provide a high-quality, accurate digital BMA analysis, expediting expert review and diagnosis of BMA specimens, with practical applications including remote BMA evaluation and possibly new opportunities for the research of normal and neoplastic hematopoiesis.

A practical guide to the implementation of AI in orthopaedic research, Part 6: How to evaluate the performance of AI research?

Artificial intelligence's (AI) accelerating progress demands rigorous evaluation standards to ensure safe, effective integration into healthcare's high-stakes decisions. As AI increasingly enables prediction, analysis and judgement capabilities relevant to medicine, proper evaluation and interpretation are indispensable. Erroneous AI could endanger patients; thus, developing, validating and deploying medical AI demands adhering to strict, transparent standards centred on safety, ethics and responsible oversight. Core considerations include assessing performance on diverse real-world data, collaborating with domain experts, confirming model reliability and limitations, and advancing interpretability. Thoughtful selection of evaluation metrics suited to the clinical context along with testing on diverse data sets representing different populations improves generalisability. Partnering software engineers, data scientists and medical practitioners ground assessment in real needs. Journals must uphold reporting standards matching AI's societal impacts. With rigorous, holistic evaluation frameworks, AI can progress towards expanding healthcare access and quality. Level of Evidence: Level V.

Germline Cas9 promoters with improved performance for homing gene drive.

Gene drive systems could be a viable strategy to prevent pathogen transmission or suppress vector populations by propagating drive alleles with super-Mendelian inheritance. CRISPR-based homing gene drives convert wild type alleles into drive alleles in heterozygotes with Cas9 and gRNA. It is thus desirable to identify Cas9 promoters that yield high drive conversion rates, minimize the formation rate of resistance alleles in both the germline and the early embryo, and limit somatic Cas9 expression. In Drosophila, the nanos promoter avoids leaky somatic expression, but at the cost of high embryo resistance from maternally deposited Cas9. To improve drive efficiency, we test eleven Drosophila melanogaster germline promoters. Some achieve higher drive conversion efficiency with minimal embryo resistance, but none completely avoid somatic expression. However, such somatic expression often does not carry detectable fitness costs for a rescue homing drive targeting a haplolethal gene, suggesting somatic drive conversion. Supporting a 4-gRNA suppression drive, one promoter leads to a low drive equilibrium frequency due to fitness costs from somatic expression, but the other outperforms nanos, resulting in successful suppression of the cage population. Overall, these Cas9 promoters hold advantages for homing drives in Drosophila species and may possess valuable homologs in other organisms.

Motive and opportunity: MYC rearrangements in high-grade B-cell lymphoma with MYC and BCL2 rearrangements (an LLMPP study).

ABSTRACT: Rearrangements that place the oncogenes MYC, BCL2, or BCL6 adjacent to superenhancers are common in mature B-cell lymphomas. Lymphomas with diffuse large B-cell lymphoma (DLBCL) or high-grade morphology with both MYC and BCL2 rearrangements are classified as high-grade B-cell lymphoma with MYC and BCL2 rearrangements ("double hit"; HGBCL-DH-BCL2) and are associated with aggressive disease and poor outcomes. Although it is established that MYC rearrangements involving immunoglobulin (IG) loci are associated with inferior outcomes relative to those involving other non-IG superenhancers, the frequency of and mechanisms driving IG vs non-IG MYC rearrangements have not been elucidated. Here, we used custom targeted capture and/or whole-genome sequencing to characterize oncogene rearrangements across 883 mature B-cell lymphomas including Burkitt lymphoma, follicular lymphoma, DLBCL, and HGBCL-DH-BCL2 tumors. We demonstrate that, although BCL2 rearrangement topology is consistent across entities, HGBCL-DH-BCL2 have distinct MYC rearrangement architecture relative to tumors with single MYC rearrangements or with both MYC and BCL6 rearrangements (HGBCL-DH-BCL6), including both a higher frequency of non-IG rearrangements and different architecture of MYC::IGH rearrangements. The distinct MYC rearrangement patterns in HGBCL-DH-BCL2 occur on the background of high levels of somatic hypermutation across MYC partner loci in HGBCL-DH-BCL2, creating more opportunity to form these rearrangements. Furthermore, because 1 IGH allele is already disrupted by the existing BCL2 rearrangement, the MYC rearrangement architecture in HGBCL-DH-BCL2 likely reflects selective pressure to preserve both BCL2 and B-cell receptor expression. These data provide new mechanistic explanations for the distinct patterns of MYC rearrangements observed across different lymphoma entities.

Evaluation of shoot-growth variation in diverse carrot (Daucus carota L.) germplasm for genetic improvement of stand establishment.

Carrot (Daucus carota L.) is a high value, nutritious, and colorful crop, but delivering carrots from seed to table can be a struggle for carrot growers. Weed competitive ability is a critical trait for crop success that carrot and its apiaceous relatives often lack owing to their characteristic slow shoot growth and erratic seedling emergence, even among genetically uniform lines. This study is the first field-based, multi-year experiment to evaluate shoot-growth trait variation over a 100-day growing season in a carrot diversity panel (N=695) that includes genetically diverse carrot accessions from the United States Department of Agriculture National Plant Germplasm System. We report phenotypic variability for shoot-growth characteristics, the first broad-sense heritability estimates for seedling emergence (0.68 < H2 < 0.80) and early-season canopy coverage ( 0.61 < H2 < 0.65), and consistent broad-sense heritability for late-season canopy height (0.76 < H2 < 0.82), indicating quantitative inheritance and potential for improvement through plant breeding. Strong correlation between emergence and canopy coverage (0.62 < r < 0.72) suggests that improvement of seedling emergence has great potential to increase yield and weed competitive ability. Accessions with high emergence and vigorous canopy growth are of immediate use to breeders targeting stand establishment, weed-tolerance, or weed-suppressant carrots, which is of particular advantage to the organic carrot production sector, reducing the costs and labor associated with herbicide application and weeding. We developed a standardized vocabulary and protocol to describe shoot-growth and facilitate collaboration and communication across carrot research groups. Our study facilitates identification and utilization of carrot genetic resources, conservation of agrobiodiversity, and development of breeding stocks for weed-competitive ability, with the long-term goal of delivering improved carrot cultivars to breeders, growers, and consumers. Accession selection can be further optimized for efficient breeding by combining shoot growth data with phenological data in this study's companion paper to identify ideotypes based on global market needs.

Formation of Key Aroma Compounds During 30 Weeks of Ripening in Gouda-Type Cheese Produced from Pasteurized and Raw Milk.

Gouda-type cheeses were produced on a pilot-scale from raw milk (RM-G) and pasteurized milk (PM-G). Sixteen key aroma compounds previously characterized by the sensomics approach were quantitated in the unripened cheeses and at five different ripening stages (4, 7, 11, 19, and 30 weeks) by means of stable isotope dilution assays. Different trends were observed in the formation of the key aroma compounds. Short-chain free fatty acids and ethyl butanoate as well as ethyl hexanoate continuously increased during ripening but to a greater extent in RM-G. Branched-chain fatty acids such as 3-methylbutanoic acid were also continuously formed and reached a 60-fold concentration after 30 weeks, in particular in PM-G. 3-Methylbutanal and butane-2,3-dione reached a maximum concentration after 7 weeks and decreased with longer ripening. Lactones were high in the unripened cheeses and increased only slightly during ripening. Recent results have shown that free amino acids were released during ripening. The aroma compounds 3-methylbutanal, 3-methyl-1-butanol, and 3-methylbutanoic acid are suggested to be formed by microbial enzymes degrading the amino acid l-leucine following the Ehrlich pathway. To gain insight into the quantitative formation of each of the three aroma compounds, the conversion of the labeled precursors (13C6)-l-leucine and (2H3)-2-keto-4-methylpentanoic acid into the isotopically labeled aroma compounds was studied. By applying the CAMOLA approach (defined mixture of labeled and unlabeled precursor), l-leucine was confirmed as the only precursor of the three aroma compounds in the cheese with the preferential formation of 3-methylbutanoic acid.

Influence of Milk Pasteurization on the Key Aroma Compounds in a 30 Weeks Ripened Pilot-Scale Gouda Cheese Elucidated by the Sensomics Approach.

Gouda cheese was produced from pasteurized milk and ripened for 30 weeks (PM-G). By application of gas chromatography/olfactometry and an aroma extract dilution analysis on the volatiles isolated by extraction/SAFE distillation, 25 odor-active compounds in the flavor dilution (FD) factor range from 16 to 4096 were identified. Butanoic acid, 2- and 3-methylbutanoic acid, and acetic acid showed the highest FD factors, and 2-phenylethanol, δ-decalactone, and δ-dodecalactone were most odor-active in the neutral-basic fraction. Quantitations by stable isotope dilution assays followed by a calculation of odor activity values (OAVs) revealed acetic acid, 3-methylbutanoic acid, butanoic acid, and butane-2,3-dione with the highest OAVs. Finally, an aroma recombinate prepared based on the quantitative data well agreed with the aroma profile of the PM-G. In Gouda cheese produced from raw (nonpasteurized) milk (RM-G), qualitatively the same set of odor-active compounds was identified. However, higher OAVs of butanoic acid, hexanoic acid, and their corresponding ethyl esters were found. On the other hand, in the PM-G, higher OAVs for 3-methylbutanoic acid, 3-methylbutanol, 3-methylbutanal, and butane-2,3-dione were determined. The different rankings of these key aroma compounds clearly reflect the aroma differences of the two Gouda-type cheeses. A higher activity of lipase in the RM-G and higher amounts of free l-leucine in PM-G on the other side were responsible for the differences in the concentrations of some key aroma compounds.

Advancing utilization of diverse global carrot (Daucus carota L.) germplasm with flowering habit trait ontology.

Biennial vegetable crops are challenging to breed due to long breeding cycle times. At the same time, it is important to preserve a strong biennial growth habit, avoiding premature flowering that renders the crop unmarketable. Gene banks carry important genetic variation which may be essential to improve crop resilience, but these collections are underutilized due to lack of characterization for key traits like bolting tendency for biennial vegetable crops. Due to concerns about introducing undesirable traits such as premature flowering into elite germplasm, many accessions may not be considered for other key traits that benefit growers, leaving crops more vulnerable to pests, diseases, and abiotic stresses. In this study, we develop a method for characterizing flowering to identify accessions that are predominantly biennial, which could be incorporated into biennial breeding programs without substantially increasing the risk of annual growth habits. This should increase the use of these accessions if they are also sources of other important traits such as disease resistance. We developed the CarrotOmics flowering habit trait ontology and evaluated flowering habit in the largest (N=695), and most diverse collection of cultivated carrots studied to date. Over 80% of accessions were collected from the Eurasian supercontinent, which includes the primary and secondary centers of carrot diversity. We successfully identified untapped genetic diversity in biennial carrot germplasm (n=197 with 0% plants flowering) and predominantly-biennial germplasm (n=357 with <15% plants flowering). High broad-sense heritability for flowering habit (0.81 < H2< 0.93) indicates a strong genetic component of this trait, suggesting that these carrot accessions should be consistently biennial. Breeders can select biennial plants and eliminate annual plants from a predominantly biennial population. The establishment of the predominantly biennial subcategory nearly doubles the availability of germplasm with commercial potential and accounts for 54% of the germplasm collection we evaluated. This subcollection is a useful source of genetic diversity for breeders. This method could also be applied to other biennial vegetable genetic resources and to introduce higher levels of genetic diversity into commercial cultivars, to reduce crop genetic vulnerability. We encourage breeders and researchers of biennial crops to optimize this strategy for their particular crop.

Editorial Commentary: Early Outcomes of Suture Tape Augmentation in Quadriceps Tendon Autograft Anterior Cruciate Ligament Reconstruction Are Promising but Require Long-term Proof.

The management of anterior cruciate ligament (ACL) injuries continually evolves, with new interest in all-soft tissue quadriceps tendon autograft, as well as new interest in suture tape augmentation of the graft, particularly in high-risk patients with young age; female sex; lower-limb alignment, tibial, or femoral abnormalities; hyperlaxity; concomitant meniscal and/or additional ligamentous injuries; or participation in high-risk sports. Load-sharing suture tape enhances the biomechanical stability of the reconstructed ACL, especially during the initial ingrowth and ligamentization phase, and biomechanical evidence highlights a reduced risk of graft elongation and failure under the loads encountered during daily physical activities and sport. Optimal tape tensioning could be achieved in knee hyperextension, when the ACL is at maximal length, to avoid overconstraint. The published 2-year outcomes of this technique are excellent. Current comparative studies, however, have not shown superiority. Additional controlled studies and studies with longer-term follow-up are needed, as well as comparison to extra-articular tenodesis augmentation.

The Celiac-Disease Superantigen Oligomerizes and Increases Permeability in an Enterocyte Cell Model.

Celiac disease (CeD) is an autoimmune disorder triggered by gluten proteins, affecting approximately 1 % of the global population. The 33-mer deamidated gliadin peptide (DGP) is a metabolically modified wheat-gluten superantigen for CeD. Here, we demonstrate that the 33-mer DGP spontaneously assembles into oligomers with a diameter of approximately 24 nm. The 33-mer DGP oligomers present two main secondary structural motifs-a major polyproline II helix and a minor ß-sheet structure. Importantly, in the presence of 33-mer DGP oligomers, there is a statistically significant increase in the permeability in the gut epithelial cell model Caco-2, accompanied by the redistribution of zonula occludens-1, a master tight junction protein. These findings provide novel molecular and supramolecular insights into the impact of 33-mer DGP in CeD and highlight the relevance of gliadin peptide oligomerization.

Tibial plateau fractures are associated with poor functional outcomes and a low conversion rate to total knee arthroplasty.

PURPOSE: The aim of this study was to analyse the functional outcome and the conversion rate to total knee arthroplasty (TKA) after surgically treated tibial plateau fractures (TPF). METHODS: All patients undergoing surgical treatment of TPF at a single institution between January 2003 and December 2019 were retrospectively reviewed. The Knee injury and Osteoarthritis Outcome Score (KOOS) and Tegner activity scale (TAS) were collected. The conversion rate to TKA was examined 2, 5, 7 and 10 years after surgical treatment of TPF. RESULTS: Ninety-four patients, with a mean follow-up of 110.6 months (±60.0), were included in the functional outcome assessment. Mean KOOS scores were 75.4 for symptoms, 80.6 for pain, 84.3 for activities of daily living (ADL), 59.5 for sports and 61.3 for QOL. All subscales were significantly lower on the injured side compared with the contralateral leg. Lower KOOS was observed in patients with hardware removal and Schatzker type 5 and 6 injuries. Median TAS was postinjury (4) significantly lower than preinjury (5) (p < 0.001). The conversion rate to TKA was 6.3%, 10.9%, 11.7% and 12.2% after 2,5,7 and 10 years of follow-up, respectively. Patients undergoing TKA were older than patients with no conversion to TKA (2 years follow-up 53.8 vs. 64.5 years, p = 0.026). CONCLUSION: TPFs decrease the function of the knee when compared with the contralateral side and to the preoperative condition. Bicondylar fractures are associated with worse functional outcomes. A conversion rate to TKA of 12.2% was found at 10 years follow-up. LEVEL OF EVIDENCE: Level III.