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Limitations of plain radiographs may contribute to poor sensitivity in the detection of knee osteoarthritis and poor correlation with pain and physical function. 3D joint space width, measured from weight bearing CT images, may yield a more accurate correlation with patients' symptoms. We assessed the cross-sectional association between 3D joint space width and self-reported pain and physical function. 528 knees (57% women) were analyzed from Multicenter Osteoarthritis Study participants. An upright weight bearing CT scanner was used to acquire bilateral, weight-bearing fixed-flexion images of the knees. A 3D dataset was reconstructed from cone beam projections and joint space width was calculated across the joint surface. The percentages of the apposed medial tibiofemoral joint surface with joint space width

Simple Summary: Research increasingly shows that bacteria, the largest part of the gut microbiome, may play a significant role in cancer. These microorganisms produce metabolites that can travel through the body and interact with host cells via microbial metabolite receptors, potentially affecting cancer development. This study investigates the involvement of these receptors in human cells across twenty-three types of cancer. By analyzing data from both cancer cell lines and human tumor samples, we examined how these interactions may impact key cancer-related processes, such as immune response, tumor growth, and spread. Notably, we identified several receptors that are consistently altered in cancer, which might serve as helpful biomarkers for diagnosis or treatment. This research highlights the potential of targeting the gut microbiome in cancer therapy and provides valuable insights for developing new cancer treatments based on microbiome interactions. Background/Objectives: The role of the gut microbiome in cancer biology has become an increasingly prominent area of research, particularly regarding the role of microbial metabolites and their receptors (MMRs). These metabolites, through the various gut–organ axes, have been proven to influence several pathogenetic mechanisms. This study conducted a comprehensive pan-cancer analysis of MMR transcriptomic profiles across twenty-three cancer types, exploring the mechanisms through which they can influence cancer development and progression. Methods: Utilizing both cancer cell lines from CCLE (Cancer Cell Line Encyclopedia) and human tumor samples from TCGA (The Cancer Gene Atlas), we analyzed 107 MMRs interacting with microbial metabolites such as short-chain fatty acids, bile acids, indole derivatives, and others while studying their interactions with key known cancer genes. Results: Our results revealed that certain MMRs, such as GPR84 and serotonin receptors, are consistently upregulated in various malignancies, while others, like ADRA1A, are frequently downregulated, suggesting diverse roles in cancer pathophysiology. Furthermore, we identified significant correlations between MMR expression and cancer hallmark genes and pathways, including immune evasion, proliferation, and metastasis. Conclusions: These findings suggest that the interactions between microbial metabolites and MMRs may serve as potential biomarkers for cancer diagnosis, prognosis, and therapy, highlighting their therapeutic potential. This study underscores the significance of the microbiota–cancer axis and provides novel insights into microbiome-based strategies for cancer treatment. [ABSTRACT FROM AUTHOR]

The ankle infrequently develops primary osteoarthritis (OA), especially when compared to the hip and the knee. Ankle OA instead generally develops only after trauma. The consequences of end‐stage ankle OA can nonetheless be extremely debilitating, with impairment comparable to that of end‐stage kidney disease or congestive heart failure. Disconcertingly, evidence suggests that ankle OA can develop more often than is generally appreciated after even low‐energy rotational ankle fractures and chronic instability associated with recurrent ankle sprains, albeit at a slower rate than after more severe trauma. The mechanisms whereby ankle OA develops after trauma are poorly understood, but mechanical factors are implicated. A better understanding of the prevalence and mechanical etiology of post‐traumatic ankle OA can lead to better prevention and mitigation. New surgical and conservative interventions, including improved ligamentous repair strategies and custom carbon fiber bracing, hold promise for advancing treatment that may prevent residual ankle instability and the development of ankle OA. Studies are needed to fill in key knowledge gaps here related to etiology so that the interventions can target key factors. New technologies, including weight bearing CT and biplane fluoroscopy, offer fresh opportunities to better understand the relationships between trauma, ankle alignment, residual ankle instability, OA development, and foot/ankle function. This paper begins by reviewing the epidemiology of post‐traumatic ankle OA, presents evidence suggesting that new treatment options might be successful at preventing ankle OA, and then highlights recent technical advances in understanding of the origins of ankle OA to identify directions for future research. [ABSTRACT FROM AUTHOR]

Background: Implant survivorship in uncemented total ankle replacement (TAR) is dependent on achieving initial stability. This is because early micromotion between the implant and bone can disrupt the process of osseointegration, leading to poor long-term outcomes. Tibial implant fixation features are designed to resist micromotion, aided by bony sidewall retention and interference fit. The goal of this study was to investigate design-specific factors influencing implant-bone micromotion in TAR tibial components with interference fit. Methods: Three implant designs with fixation features representative of current TAR tibial components (ARC, SPIKES, KEEL) were virtually inserted into models of the distal tibias of 2 patients with end-stage ankle arthritis. Tibia models were generated from deidentified patient computed tomography scans, with material properties for modeling bone behavior and compaction during press-fit. Finite element analysis (FEA) was used to simulate 2 fixation configurations: (1) no sidewalls or interference fit, and (2) sidewalls with interference fit. Load profiles representing the stance phase of gait were applied to the models, and implant-bone micromotions were computed from FEA output. Results: Sidewalls and interference fit substantially influenced implant-bone micromotions across all designs studied. When sidewalls and interference fit were modeled, average micromotions were less than 11 µm, consistent across the stance phase of gait. Without sidewalls or interference fit, micromotions were largest near either heel strike or toe-off. In the absence of sidewalls and interference fit, the amount of micromotion generally aligned inversely with the size of implant fixation features; the ARC design had the largest micromotion (~540 µm average), whereas the KEEL design had the smallest micromotion (~15 µm). Conclusion: This study presents new insights into the effect of TAR fixation features on implant-bone micromotion. With sidewalls and interference fit, micromotion is predicted to be minimal for implants, whereas with no sidewalls and no interference fit, micromotion depended primarily on the implant design. Clinical Relevance: This study presents new insights into the effect of TAR primary fixation features on implant-bone micromotion. Although design features heavily influenced implant stability in the model, their influence was greatly diminished when interference fit was introduced. The results of this study show the relative importance of design features and interference fit in the predicted initial stability of uncemented TAR, potentially a key factor in implant survivorship. [ABSTRACT FROM AUTHOR]

The objective of this project was to determine the relationship between medial tibiofemoral joint space width measured on fixed-flexion radiographs and the three-dimensional joint space width distribution on low-dose, standing CT (SCT) imaging. At the 84-month visit of the Multicenter Osteoarthritis Study, 20 participants were recruited. A commercial SCT scanner for the foot and ankle was modified to image knees while standing. Medial tibiofemoral joint space width was assessed on radiographs at fixed locations from 15% to 30% of compartment width using validated software and on SCT by mapping the distances between three-dimensional subchondral bone surfaces. Individual joint space width values from radiographs were compared with three-dimensional joint space width values from corresponding sagittal plane locations using paired t-tests and correlation coefficients. For the four medial-most tibiofemoral locations, radiographic joint space width values exceeded the minimal joint space width on SCT by a mean of 2.0 mm and were approximately equal to the 61st percentile value of the joint space width distribution at each respective sagittal-plane location. Correlation coefficients at these locations were 0.91-0.97 and the offsets between joint space width values from radiographs and SCT measurements were consistent. There were greater offsets and variability in the offsets between modalities closer to the tibial spine. Joint space width measurements on fixed-flexion radiographs are highly correlated with three-dimensional joint space width from SCT. In addition to avoiding bony overlap obscuring the joint, a limitation of radiographs, the current study supports a role for SCT in the evaluation of tibiofemoral OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1388-1395, 2017.

Patients with tibial pilon fractures have a higher incidence of post-traumatic osteoarthritis than those with fractures of the tibial plateau. This may indicate that pilon fractures present a greater mechanical insult to the joint than do plateau fractures. We tested the hypothesis that fracture energy and articular fracture edge length, two independent indicators of severity, are higher in pilon than plateau fractures. We also evaluated whether clinical fracture classification systems accurately reflect severity. Seventy-five tibial plateau fractures and 52 tibial pilon fractures from a multi-institutional study were selected to span the spectrum of severity. Fracture severity measures were calculated using objective CT-based image analysis methods. The ranges of fracture energies measured for tibial plateau and pilon fractures were 3.2-33.2 Joules (J) and 3.6-32.2 J, respectively, and articular fracture edge lengths were 68.0-493.0 mm and 56.1-288.6 mm, respectively. There were no differences in the fracture energies between the two fracture types, but plateau fractures had greater articular fracture edge lengths (p

Background: Primary implant stability is important for successful outcomes after uncemented total ankle replacement (TAR). However, the influence of patient-specific bone density on TAR performance is poorly understood, especially for implants that rely on press-fit for stable primary fixation. Our goal was to evaluate how bone density influences implant-bone interfacial micromotions in 3 press-fit tibial component designs by sampling from a TAR preoperative planning database using finite element analysis (FEA). Methods: FEA was conducted in 4 TAR patients with relatively low-density (n = 2, lowest 10% of a sample including 58 patients) and average-density (n = 2, midrange of sample) bone as assessed from deidentified patient CT scans. Three tibial implant designs were evaluated: a bone-sparing resurfacing implant, a cortex-sparing anterior approach monoblock stemmed implant, and a distal-reaming modular stemmed implant. Implants were inserted into tibia geometries obtained from the CT scans. Press-fit implantation was modeled first, followed by loadings from the stance phase of gait, and the associated micromotions were computed from the FEA output. Results: In general, patients with average-density bone had FEA predicted lower micromotions than patients with low-density bone. FEA suggests that implant fixation features had less influence on micromotions in patients with average-density bone, with peak micromotions ranging from 2 to 23 µm (3.1 ± 1.3 µm average micromotion). For patients with low-density bone, interfacial regions are predicted to experience micromotions exceeding the bony ingrowth threshold of 50 µm only for the resurfacing implant. Conclusion: We investigated the influence of bone density on implant-bone micromotions with varying primary fixation features using FEA. The model predicts that micromotions are less in average-density bone, regardless of implant fixation features. However, both stemmed devices showed lower micromotions in less-dense bone, albeit with the corresponding clinical trade-off of requiring more tibial bone removal. Clinical Relevance: The results presented here implicate the complementary role that local bone density plays in the primary fixation stability of uncemented TAR. [ABSTRACT FROM AUTHOR]

ObjectivesDetermine the agreement between subjective assessments of fracture severity and an objective computed tomography (CT)-based metric of fracture energy in tibial plateau fractures.MethodsSix fellowship-trained orthopaedic trauma surgeons independently rank-ordered 20 tibial plateau fractures in terms of severity based on anteroposterior and lateral knee radiographs. A CT-based image analysis methodology was used to quantify the fracture energy, and agreement between the surgeons' severity rankings and the fracture energy metric was tested by computing their concordance, a statistical measure that estimates the probability that any 2 cases would be ranked with the same ordering by 2 different raters or methods.ResultsConcordance between the 6 orthopaedic surgeons ranged from 82% to 93%, and concordance between surgeon severity rankings and the computed fracture energy ranged from 73% to 78%.ConclusionsThere is a high level of agreement between experienced surgeons in their assessments of tibial plateau fracture severity, and a slightly lower agreement between the surgeon assessments and an objective CT-based metric of fracture energy. Taken together, these results suggest that experienced surgeons share a similar understanding of what makes a tibial plateau fracture more or less severe, and an objective CT-based metric of fracture energy captures much but not all of that information. Further research is ongoing to characterize the relationship between surgeon assessments of severity, fracture energy, and the eventual clinical outcomes for patients with fractures of the tibial plateau.

The success of uncemented total ankle replacement (TAR) is linked to initial stability because bony ingrowth depends upon limited early micromotion. Tibial implant design fixation features resist micromotion aided by bony sidewall retention and interference fit. Our goal was to investigate factors influencing implant‐bone micromotion in TAR. Two TAR tibial components were virtually inserted into CT‐derived computer models of two distal tibias from patients with end‐stage ankle arthritis. Density‐based inhomogeneous material assignment was used to model bone compaction during press‐fit. Finite element analysis (FEA) was used to simulate three fixation cases: (1) no sidewalls + line‐to‐line fit, (2) sidewalls + line‐to‐line fit, and (3) sidewalls + 50, 100, or 200 µm interference fit. Kinetic profiles from the stance phase of gait were simulated and micromotions computed from FEA output. Without sidewalls or interference fit, micromotions were largest in early and late stance, with largest micromotions (averaging ~150–250 µm) observed near heel strike. Micromotions decreased 39%–62% when sidewalls were retained. When interference fit was also modeled, micromotions decreased another 37%–61% to ~10 µm. Micromotion differences between patients persisted with sidewall retention but largely disappeared with interference fit. This study presents new insights into the effects of TAR fixation features on implant‐bone micromotion. Stability appeared to be influenced by surrounding bone quality, but this influence was greatly diminished when interference fit was introduced. More complete understanding of TAR implant features and performance is needed, but our results show the importance of bone quality and interference fit in the stability of uncemented TAR. [ABSTRACT FROM AUTHOR]

Category: Other; Midfoot/Forefoot Introduction/Purpose: Charcot-Marie-Tooth (CMT) disease is an inherited peripheral neuropathy known to cause progressive sensory and motor impairment. Patients often develop foot structure abnormalities, including pes cavus, due to intrinsic muscle weakness. These deformities, paired with the disease's typical sensory and motor symptoms, can increase the risk of falls. Ankle foot orthoses (AFOs) are commonly used with the intent of reducing fall risk and restoring a more normal gait. The Timed Up and Go (TUG) test is widely used as a clinical screening tool to identify patients at risk of falling. No previous study has applied the TUG test in the setting of CMT fall risk assessment. The purpose of this study was to assess the overall predictive value of TUG on fall risk in CMT. Methods: Existing data from patients seen at the at the University of Iowa Hospitals and Clinics, as part of research with the Inherited Neuropathy Consortium (INC), were used for this investigation. Patients in the INC return to clinic on an annual basis and data from each patient's most recent evaluation were included for analysis. All CMT sub-types were included. Clinical outcome measures were taken from the CMT Functional Outcome Measure (CMT-FOM) and the CMT Health Index (CMT-HI). Timed up and go (TUG) and patient reported ankle-foot orthoses (AFO) use was recorded as part of the CMT-FOM. The CMT-HI provides patient perspective on the impact of various health related topics, including difficulty getting up from the floor or ground, falling, and difficulty rising from a seated position. Kruskal-Wallis and Wilcoxon Rank Sum tests were utilized for statistical analysis and pair-wise group comparisons. Results: In total, 126 patients of 4,971 available records were included for analysis. The remainder were excluded due to missing data, unconfirmed CMT diagnosis, or statistical outliers. TUG scores ranged from 3.4s to 26.0s (mean 9.70s). Responses to the CMT-HI Falls question included no effect, little effect, moderate effect, and severely effecting, and poorer responses were correlated with a slower average TUG (p< 0.0001). Participants who reported AFO use had a average TUG score of 11.29 seconds while non-users averaged 10.0 seconds (p=0.0015). 117/126 (93%) patients reported foot deformity: 106 pes cavus, 6 pes planus, 5 "other", 7 reported none, and 2 unreported. Of the 117 with reported deformities, those with pes planus averaged a TUG of 9.76 seconds compared to 9.45 seconds with pes cavus. Conclusion: This is the first study to identify a significant correlation between patient-reported fall risk and average TUG in CMT patients. This observation of slower TUG times in individuals with greater fall risk is consistent with findings available for other at-risk falls populations, such as stroke patients. The most predominant deformity was pes cavus. However, neither the presence nor absence of foot deformities showed a substantial difference in TUG results. Patients who wore Ankle-foot orthoses had, on average, slower times in the TUG test than non-users. This is likely due to greater a dependency on AFOs with increased disease progression. [ABSTRACT FROM AUTHOR]

Psychomotor skill and decision‐making efficiency in surgical wire navigation can be objectively evaluated by analysis of intraoperative fluoroscopic image sequences. Prior work suggests that such image‐based behavior analysis of operating room (OR) performance can predict performer experience level (R2 = 0.62) and agree with expert opinion (the current standard) on the quality of a final implant construct (R2 = 0.59). However, it is unclear how objective image‐based evaluation compares with expert assessments for entire technical OR performances. This study examines the relationships between three key variables: (1) objective image‐based criteria, (2) expert opinions, and (3) performing surgeon experience level. A paired‐comparison survey of seven experts, based upon eight OR fluoroscopic wire navigation image sequences, shows that the experts' preferences are best explained by objective metrics that reflect psychomotor and decision‐making behaviors which are counter‐productive to successful implant placement, like image count (R2 = 0.83) and behavior tally (R2 = 0.74). One such behavior, adjustments away from goal, uniquely correlated well with all three key variables: a fluoroscopic image‐based analysis composite score (R2 = 0.40), expert consensus (R2 = 0.76), and performer experience (R2 = 0.41). These results confirm that experts view less efficient technical behavior as indicative of lesser technical proficiency. While expert assessments of technical skill were reliable and consistent, neither individual nor consensus expert opinion appears to correlate with performer experience (R2 = 0.11). [ABSTRACT FROM AUTHOR]