Faculty Bibliography

OBJECTIVE:Knee osteoarthritis (KOA) causes pain and progressive disability, but pharmacologic treatments are limited. Colchicine inhibits inflammation that might modulate KOA, but efficacy trials have yielded mixed results. We tested whether colchicine, without concurrent NSAIDs, improved KOA pain, function, synovial effusion size, and OA-associated inflammatory serum biomarkers. METHODS:Participants with symptomatic KOA and radiographic Kellgren-Lawrence grades 2/3 were randomized to receive three months of daily colchicine or placebo in a double-blind manner, with no concurrent NSAID use. The primary outcome was between-group change in visual analog score (VAS) for index knee pain. Secondary outcomes included changes in Knee Osteoarthritis Outcome Scores (KOOS), size (depth in millimeters) of sonographically-identified effusions, acetaminophen use, and changes in OA-related serum biomarkers. RESULTS:, IL-1ra, IL-8, and VEGF (p < 0.16). CONCLUSION/CONCLUSIONS:This double-blind placebo-controlled trial of colchicine for KOA failed to demonstrate improvement in pain, function, or synovial effusion size in comparison to placebo at three months. Early improvement in OA-associated inflammatory biomarkers suggests a possible longer-term clinical benefit. Clinical Trials Registration No NCT03913442.

OBJECTIVE:To quantify general population prevalence, and differences by sex and BMI, in ultrasound (US) features of knee osteoarthritis (KOA), patient-reported knee symptoms (Ksx), radiographic KOA (rKOA), and symptomatic KOA (sxKOA). METHODS:Participants from the Johnston County Health Study (2019-2024; n=902) provided demographic, clinical, and imaging data. Ksx was defined as self-reported pain, aching or stiffness on most days of any one month in the past 12 months. rKOA was defined as Kellgren-Lawrence grade ≥2 (or total knee replacement (TKR)), severe rKOA as grades 3-4 (or TKR), and sxKOA as rKOA and Ksx in the same knee. Standardized US scoring was performed as previously reported. Weighted prevalence estimates and 95% confidence intervals (CI) for Ksx, rKOA, sxKOA, severe rKOA, and US features were calculated overall and by sex and BMI category. RESULTS:Among 902 participants (67% female; 66% non-Hispanic white, mean age 55 years, and BMI 33 kg/m²), the weighted prevalence of Ksx, rKOA, sxKOA, and severe rKOA were 61%, 36%, 27%, and 21%, respectively, all higher (based on non-overlapping CIs) than baseline estimates from the Johnston County Osteoarthritis Project and other cohorts. Ksx, rKOA, sxKOA, and severe rKOA were higher among females and those with obesity. Compared to females with obesity, those with severe obesity had higher prevalence of all radiographic outcomes at moderate and severe grades with non-overlapping CI. US effusion and synovitis were more prevalent in males, whereas medial and lateral cartilage damage were more common in females. With increasing obesity, osteophytes and medial cartilage damage were more prevalent, while gryescale effusion was actually less frequent. CONCLUSION/CONCLUSIONS:KOA prevalence continues to increase in the population. Sex and BMI differences in KOA prevalence and US features were most pronounced among females with severe obesity. Distinguishing between sexes and by obesity levels may improve understanding of KOA mechanisms and guide tailored prevention and treatment strategies.

PURPOSE/OBJECTIVE:mapping of the knee in vivo. METHODS:imaging was performed at 3 T. A bovine tendon was imaged at 0°, 55°, and 90° using CW, HS4 (3/6 ms), and TAN (3/6 ms) preparations at spin-lock amplitudes of 500-1000 Hz. Five healthy volunteers and five patients with knee osteoarthritis were scanned. Data were fit with mono-exponential (ME) and stretched-exponential (SE) models. Intrasubject repeatability was assessed in healthy volunteers. RESULTS:values most consistent with CW, while HS4-6 ms produced substantially higher values in the knee joint. TAN-6 ms (CV = 3.47%) and HS4-6 ms (CV = 4.24%) demonstrated better repeatability than CW (CV = 7.24%). CONCLUSION/CONCLUSIONS:contamination and high repeatability. The near orientation-independence of the SE parameter α suggests that it may serve as a more robust biomarker for highly ordered tissues.

This study investigates whether multi-component T₂ mapping, using bi-exponential (BE) and stretched-exponential (SE) models, enhances the early detection of knee osteoarthritis (OA) compared with the conventional mono-exponential (ME) approach. T₂ relaxation maps were derived from 26 patients with early-stage OA and 26 healthy controls. To minimize the influence of age-related cartilage changes, all model-derived parameters were adjusted for age prior to analysis. Quantitative T₂ parameters were extracted from six anatomically defined cartilage sub-regions to capture spatially heterogeneous tissue alterations characteristic of early OA. These parameters were then integrated using linear discriminant analysis to assess combined diagnostic performance. Global whole-cartilage analyses demonstrated limited discriminatory power across all models, with area under the receiver operating characteristic curve (AUC) values not exceeding 0.65, indicating that diffuse averaging obscures subtle, localized degeneration. In contrast, sub-regional analysis improved classification accuracy, highlighting the importance of regional assessment in early disease. Among the evaluated models, the BE-T₂ model showed the highest performance, achieving an AUC of 0.68, and marginally outperforming both the SE model (AUC = 0.60) and the ME model (AUC = 0.51). These findings suggest that multi-component T₂ mapping, particularly when applied at a sub-regional level, may offer improved sensitivity to early cartilage compositional changes. Overall, this approach shows strong potential as a noninvasive imaging biomarker for the early detection of knee OA.

BACKGROUND:) mapping is sensitive to early cartilage changes, but the mono-exponential (ME) model may be limited. Multi-component models can capture more tissue complexity, but their diagnostic advantage has not been validated. PURPOSE/OBJECTIVE:models can improve early knee OA detection over the ME model. STUDY TYPE/METHODS:Case-control study. POPULATION/METHODS:Twenty-six healthy subjects (mean age 51.5) and 26 early knee OA patients (mean age 61.8). FIELD STRENGTH/SEQUENCE/UNASSIGNED:-prepared Turbo FLASH sequence at 3 T field strength. ASSESSMENT/RESULTS:parameters from three exponential models were adjusted for age. To maximize group separability, the parameters were combined into single discriminators for both global knee cartilage and six anatomical sub-regions. Diagnostic performance was assessed based on the ability of these combined models to distinguish early OA. STATISTICAL TESTS/METHODS:Parameters were adjusted for age. Mann-Whitney U-test (group comparisons), linear discriminant analysis (LDA), and area under the receiver operating characteristic (ROC) curve (AUC) with bootstrapped 95% confidence intervals (CI). Significance level set at p < 0.05, using the false discovery rate (FDR) to correct for multiple comparisons. RESULTS:In the global analysis, no model demonstrated significant diagnostic performance (p-values of 0.63, 0.96, 0.63 for ME, SE, and BE). Multi-regional SE model (AUC = 0.83, CI: 0.72, 0.93) significantly distinguished OA and healthy groups. Calibration analysis showed the SE model had the lowest Brier score (0.17), significantly better than the ME model (0.26). DATA CONCLUSION/CONCLUSIONS:parameter maps suggests an improvement in diagnostic performance for early knee OA compared to globally averaged measurements. The stretched-exponential model showed the most promise. However, small sample size and wide confidence intervals highlight the need for further validation with a larger cohort before clinical utility claims can be made. EVIDENCE LEVEL/METHODS:4. TECHNICAL EFFICACY/UNASSIGNED:Stage 2.

Osteoarthritis, especially knee osteoarthritis, is a leading cause of disability and reduced quality of life. The etiology of pain in osteoarthritis is multifactorial, and one promising potential treatment approach involves targeting chemokine systems. The present study was a phase 2, multisite, multiperiod randomized crossover trial of CNTX-6970, a small molecule and selective oral cytokine chemokine receptor type 2 (CCR2) and CCR5 antagonist, in patients with painful knee osteoarthritis (OA). It represents the first trial performed within the National Institutes of Health's Early Phase Pain Investigation Clinical Network. The primary objectives were to evaluate the safety and efficacy of CNTX-6970, relative to placebo, for the treatment of moderate to severe pain related to knee OA. A total of 55 participants were randomized in this multiperiod crossover trial. Linear mixed effects models revealed no significant pain-related benefits of active medication; indeed, trial participants reported slightly higher knee pain intensity when taking the novel chemokine antagonist CNTX-6970 than when taking placebo. In addition, biomarker analysis revealed notably higher level of serum monocyte chemoattractant protein 1 levels when patients were on CNTX-6970 compared to placebo. Overall, although CNTX-6970 was safe and relatively well-tolerated, pharmacologic blockade of specific chemokine receptors with this compound was not effective in reducing moderate-to-severe knee osteoarthritis pain.

OBJECTIVE/UNASSIGNED:To identify phenotypes of knee osteoarthritis (KOA) based on demographic and clinical variables, symptoms, and ultrasound (US) features using a novel machine learning approach. DESIGN/UNASSIGNED:Johnston County Health Study participants provided demographics, symptomatic and functional assessments, and joint radiographs, which were transformed into the clinical data block. Standardized knee US were obtained, and US features composed the second data block. The Angle-based Joint and Individual Variation Explained (AJIVE) algorithm was used to identify shared and individual modes of variation. We focused on shared structure to explore how US features and non-US clinical data vary together overall, and in the subset with radiographic KOA (rKOA). RESULTS/UNASSIGNED:); 335 (39%) had rKOA. AJIVE identified two components of shared variation (SC1 and SC2). SC1 associated osteophytes and cartilage damage on US with higher BMI, older age, and worse symptoms and outcome scores. SC2 correlated the presence of effusion and synovitis but less cartilage damage on US with better physical function and lower BMI. A similar pattern was seen in those with rKOA. CONCLUSIONS/UNASSIGNED:We identified two shared directions of variation which may represent distinct phenotypes of KOA. The first fits with prior KOA studies linking presence of osteophytes and cartilage damage to worse symptoms and function. The second may represent an inflammatory subtype of KOA, with greater effusion and synovitis but less osteophytosis and cartilage damage. These clinically feasible phenotypes should be confirmed in future studies.

PURPOSE/OBJECTIVE:To evaluate the safety and efficacy of genicular artery embolization and its longitudinal effects on biomarkers implicated in knee osteoarthritis (KOA) pathogenesis.. MATERIALS AND METHODS/METHODS:This is a prospective, single-arm clinical trial of patients with symptomatic KOA resistant to conservative therapy for greater than 3 months. Twenty-five patients who underwent GAE using 250-μm microspheres were included. Patient reported outcome measures were evaluated at baseline and 1-, 3-, and 12-months following GAE. Blood samples were collected for biomarker analysis. Magnetic resonance imaging was obtained at baseline and 3 months post GAE. The primary endpoint was the clinical success rate at 12 months. Baseline and follow-up outcomes were analyzed using the Wilcoxon matched-pairs signed-rank test. RESULTS:The technical success was 100%, with no significant adverse events. The clinical success rate was 62%. The mean VAS pain score for the target knee decreased by 48.5% at 1 month, 50.8% at 3 months, and 55.4% at 12 months (p < .001). WOMAC pain scores improved by 39.6% at 1 month, 50.1% at 3 months, and 43.7% at 12 months (p < .001). There was a statistically significant decrease in the serum levels of vascular endothelial growth factor (VEGF) and Interleukin-1 receptor antagonist (IL-1Ra) at 12 months. The remaining biomarkers showed no significant change. CONCLUSIONS:GAE is a safe treatment for symptomatic KOA, providing clinically significant pain relief for a subset of patients. The observed reductions in serum VEGF and IL-1Ra levels following GAE may contribute to local pain relief and decreased inflammation in the knee joints.

Adult-onset Still's disease is a rare systemic autoinflammatory condition of unknown aetiology. It is a diagnosis of exclusion based primarily on clinical features and non-specific laboratory findings using either the Yamaguchi or Fautrel criteria. Here, we present a case of atypical adult-onset Still's disease in a young man with twice-daily fevers, night sweats and evanescent rash on his face but not enough features to meet the Yamaguchi or Fautrel criteria after extensive (but unrevealing) infectious, autoimmune and malignancy workups. He responded well to corticosteroid therapy with periodic relapses while transitioning to anti-IL1 therapy for 8 months. At a 2-year follow-up, he now remains symptom-free after stopping anti-IL1 therapy for over a year.