Corrigendum to "Study protocol for the follow-up examination of the Nor-Hand study: A hospital-based observational cohort study exploring pain and biomarkers in people with hand osteoarthritis" [Osteoarthr. Cartil. Open 3 (2021) 100198].

[This corrects the article DOI: 10.1016/j.ocarto.2021.100198.].

Associations of inflammatory and metabolic biomarkers with incident erosive hand osteoarthritis in the osteoarthritis initiative cohort.

OBJECTIVE: Erosive hand osteoarthritis (eHOA) is a subtype of hand osteoarthritis (OA) that develops in finger joints with pre-existing OA and is differentiated by clinical characteristics (hand pain/disability, inflammation, and erosions) that suggest inflammatory or metabolic processes. METHOD: This was a longitudinal nested case-cohort design among Osteoarthritis Initiative participants who had hand radiographs at baseline and 48-months, and biospecimens collected at baseline. We classified incident radiographic eHOA in individuals with ≥1 joint with Kellgren-Lawrence ≥2 and a central erosion present at 48-months but not at baseline. We used a random representative sample (n = 1282) for comparison. We measured serum biomarkers of inflammation, insulin resistance and dysglycemia, and adipokines using immunoassays and enzymatic colorimetric procedures, blinded to case status. RESULTS: Eighty-six participants developed incident radiographic eHOA. In the multivariate analyses adjusted for age, gender, race, smoking, and body mass index, and after adjustment for multiple analyses, incident radiographic eHOA was associated with elevated levels of interleukin-7 (risk ratio (RR) per SD = 1.30 [95% confidence interval (CI) 1.09, 1.55] p trend 0.01). CONCLUSION: This exploratory study suggests an association of elevated interleukin-7, an inflammatory cytokine, with incident eHOA, while other cytokines or biomarkers of metabolic inflammation were not associated. Interleukin-7 may mediate inflammation and tissue damage in susceptible osteoarthritic finger joints and participate in erosive progression.

Coagulopathy and adverse outcomes in hospitalized patients with COVID-19: results from the NOR-Solidarity trial.

Background: Several studies have examined parameters of increased thrombogenicity in COVID-19, but studies examining their association with long-term outcome and potential effects of antiviral agents in hospitalized patients with COVID-19 are scarce. Objectives: To evaluate plasma levels of hemostatic proteins during hospitalization in relation to disease severity, treatment modalities, and persistent pulmonary pathology after 3 months. Methods: In 165 patients with COVID-19 recruited into the NOR-Solidarity trial (NCT04321616) and randomized to treatment with hydroxychloroquine, remdesivir, or standard of care, we analyzed plasma levels of hemostatic proteins during the first 10 days of hospitalization (n = 160) and at 3 months of follow-up (n = 100) by enzyme immunoassay. Results: Our main findings were as follows: (i) tissue plasminogen activator (tPA) and tissue factor pathway inhibitor (TFPI) were increased in patients with severe disease (ie, the combined endpoint of respiratory failure [Po2-to-FiO2 ratio, <26.6 kPa] or need for treatment at an intensive care unit) during hospitalization. Compared to patients without severe disease, tPA levels were a median of 42% (P < .001), 29% (P = .002), and 36% (P = .015) higher at baseline, 3 to 5 days, and 7 to 10 days, respectively. For TFPI, median levels were 37% (P = .003), 25% (P < .001), and 10% (P = .13) higher in patients with severe disease at these time points, respectively. No changes in thrombin-antithrombin complex; alpha 2-antiplasmin; a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; or antithrombin were observed in relation to severe disease. (ii) Patients treated with remdesivir had lower levels of TFPI than those in patients treated with standard of care alone. (iii) TFPI levels during hospitalization, but not at 3 months of follow-up, were higher in those with persistent pathology on chest computed tomography imaging 3 months after hospital admission than in those without such pathology. No consistent changes in thrombin-antithrombin complex, alpha 2-antiplasmin, ADAMTS-13, tPA, or antithrombin were observed in relation to pulmonary pathology at 3 months of follow-up. Conclusion: TFPI and tPA are associated with severe disease in hospitalized patients with COVID-19. For TFPI, high levels measured during the first 10 days of hospitalization were also associated with persistent pulmonary pathology even 3 months after hospital admittance.

Radiographic joint space width in individuals with hand osteoarthritis: Are their "healthy" joints really healthy?

OBJECTIVES: We aimed to investigate the systemic nature of hand osteoarthritis (OA). We hypothesized that people who suffer from hand OA would display narrower radiographic joint space width (JSW) - not only in joints with apparent radiographic OA but also in their unaffected "healthy" joints. METHOD: We examined 3394 participants from the Osteoarthritis Initiative with available dominant hand radiographs at baseline. Cases were defined as having interphalangeal OA (IPOA) based on a Kellgren and Lawrence (KL) score of ≥2 in two or more finger joints, whereas controls did not have IPOA. We used custom software to make JSW measurements of the metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints in fingers 2-5 per hand. In joint-level analyses, we included only KL score=0, allowing us to compare all joints without IPOA in cases and controls. We used generalized estimating equation models to compare JSW between both groups, adjusted for age, gender, metacarpal length, and joint type. RESULTS: Finger joints without radiographic OA had significantly narrower JSW in the IPOA group compared to finger joints in the control group (p < 0.001). The differences were significant across all joint types and for both total JSW measurements as well as for central and lateral sub-regions within each joint group (p < 0.001). CONCLUSION: Unaffected finger joints in people with IPOA had narrower joint space than joints of healthy controls. This implies a systemic nature of hand OA, in which people may have a predisposition for general cartilage deterioration.

Predicting total knee arthroplasty from ultrasonography using machine learning.

Objective: To investigate the value of ultrasonographic data in predicting total knee replacement (TKR). Design: Data from the Musculoskeletal Pain in Ullensaker study (MUST) was linked to the Norwegian Arthroplasty Register to form a 5-7 year prospective cohort study of 630 persons (69% women, mean (SD) age 64 (8.7) years). We examined the predictive power of ultrasound (US) features, i.e. osteophytes, meniscal extrusion, synovitis in the suprapatellar recess, femoral cartilage thickness, and quality for future knee osteoarthritis (OA) surgery. We investigated 4 main settings for multivariate predictive modeling: 1) clinical predictors (age, sex, body mass index, knee injury, familial OA and workload), 2) radiographic data (assessed by the Kellgren Lawrence grade, KL) with clinical predictors, 3) US features and clinical predictors. Finally, we also considered an ensemble of models 2) and 3) and used it as our fifth model. All models were compared using the Average Precision (AP) and the Area Under Receiver Operating Characteristic Curve (AUC) metrics. Results: Clinical predictors yielded AP of 0.11 (95% confidence interval [CI] 0.05-0.23) and AUC of 0.69 (0.58-0.79). Clinical predictors with KL grade yielded AP of 0.20 (0.12-0.33) and AUC of 0.81 (0.67-0.90). The clinical variables with ultrasound yielded AP of 0.17 (0.08-0.30) and AUC of 0.79 (0.69-0.86). Conclusion: Ultrasonographic examination of the knee may provide added value to basic clinical and demographic descriptors when predicting TKR. While it does not achieve the same predictive performance as radiography, it can provide additional value to the radiographic examination.

Persistent T-cell exhaustion in relation to prolonged pulmonary pathology and death after severe COVID-19: Results from two Norwegian cohort studies.

BACKGROUND: T-cell activation is associated with an adverse outcome in COVID-19, but whether T-cell activation and exhaustion relate to persistent respiratory dysfunction and death is unknown. OBJECTIVES: To investigate whether T-cell activation and exhaustion persist and are associated with prolonged respiratory dysfunction and death after hospitalization for COVID-19. METHODS: Plasma and serum from two Norwegian cohorts of hospitalized patients with COVID-19 (n = 414) were analyzed for soluble (s) markers of T-cell activation (sCD25) and exhaustion (sTim-3) during hospitalization and follow-up. RESULTS: Both markers were strongly associated with acute respiratory failure, but only sTim-3 was independently associated with 60-day mortality. Levels of sTim-3 remained elevated 3 and 12 months after hospitalization and were associated with pulmonary radiological pathology after 3 months. CONCLUSION: Our findings suggest prolonged T-cell exhaustion is an important immunological sequela, potentially related to long-term outcomes after severe COVID-19.

Markers of cellular senescence is associated with persistent pulmonary pathology after COVID-19 infection.

BACKGROUND: The lungs are the organ most likely to sustain serious injury from coronavirus disease 2019 (COVID-19). However, the mechanisms for long-term complications are not clear. Patients with severe COVID-19 have shorter telomere lengths and higher levels of cellular senescence, and we hypothesized that circulating levels of the telomere-associated senescence markers chitotriosidase, ß-galactosidase, cathelicidin antimicrobial peptide and stathmin 1 (STMN1) were elevated in hospitalized COVID-19 patients compared to controls and could be associated with pulmonary sequelae following hospitalization. METHODS: Ninety-seven hospitalized patients with COVID-19 who underwent assessment for pulmonary sequelae at three-month follow-up were included in the study. ß-Galactosidase and chitotriosidase were analysed by fluorescence; stathmin 1 and cathelicidin antimicrobial peptide were analysed by enzyme immuno-assay in plasma samples from the acute phase and after three-months. In addition, the classical senescence markers cyclin-dependent kinase inhibitor 1A and 2A were analysed by enzyme immuno-assay in peripheral blood mononuclear cell lysate after three months. RESULTS: We found elevated plasma levels of the senescence markers chitotriosidase and stathmin 1 in patients three months after hospitalization with COVID-19, and these markers in addition to protein levels of cyclin-dependent kinase inhibitor 2A in cell lysate, were associated with pulmonary pathology. The elevated levels of these markers seem to reflect both age-dependent (chitotriosidase) and age-independent (stathmin 1, cyclin-dependent kinase inhibitor 2A) processes. CONCLUSIONS: We suggest that accelerated ageing or senescence could be important for long-term pulmonary complications of COVID-19, and our findings may be relevant for future research exploring the pathophysiology and management of these patients.

High Circulating Levels of the Homeostatic Chemokines CCL19 and CCL21 Predict Mortality and Disease Severity in COVID-19.

BACKGROUND: Immune dysregulation is a major factor in the development of severe coronavirus disease 2019 (COVID-19). The homeostatic chemokines CCL19 and CCL21 have been implicated as mediators of tissue inflammation, but data on their regulation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is limited. We thus investigated the levels of these chemokines in COVID-19 patients. METHODS: Serial blood samples were obtained from patients hospitalized with COVID-19 (n = 414). Circulating CCL19 and CCL21 levels during hospitalization and 3-month follow-up were analyzed. In vitro assays and analysis of RNAseq data from public repositories were performed to further explore possible regulatory mechanisms. RESULTS: A consistent increase in circulating levels of CCL19 and CCL21 was observed, with high levels correlating with disease severity measures, including respiratory failure, need for intensive care, and 60-day all-cause mortality. High levels of CCL21 at admission were associated with persisting impairment of pulmonary function at the 3-month follow-up. CONCLUSIONS: Our findings highlight CCL19 and CCL21 as markers of immune dysregulation in COVID-19. This may reflect aberrant regulation triggered by tissue inflammation, as observed in other chronic inflammatory and autoimmune conditions. Determination of the source and regulation of these chemokines and their effects on lung tissue is warranted to further clarify their role in COVID-19. CLINICAL TRIALS REGISTRATION: NCT04321616 and NCT04381819.

Cartilage Topography Assessment With Local-Area Cartilage Segmentation for Knee Magnetic Resonance Imaging.

OBJECTIVE: Local-area cartilage segmentation (LACS) software was developed to segment medial femur (MF) cartilage on magnetic resonance imaging (MRI). Our objectives were 1) to extend LACS to the lateral femur (LF), medial tibia (MT), and lateral tibia (LT), 2) to compare LACS to an established manual segmentation method, and 3) to visualize cartilage responsiveness over each cartilage plate. METHODS: Osteoarthritis Initiative participants with symptomatic knee osteoarthritis (OA) were selected, including knees selected at random (n = 40) and knees identified with loss of cartilage based on manual segmentation (Chondrometrics GmbH), an enriched sample of 126 knees. LACS was used to segment cartilage in the MF, LF, MT, and LT on sagittal 3D double-echo steady-state MRI scans at baseline and at 2-year follow-up. We compared LACS and Chondrometrics average thickness measures by estimating the correlation in each cartilage plate and estimating the standardized response mean (SRM) for 2-year cartilage change. We illustrated cartilage loss topographically with SRM heatmaps. RESULTS: The estimated correlation between LACS and Chondrometrics measures was r = 0.91 (95% confidence interval [95% CI] 0.86, 0.94) for LF, r = 0.93 (95% CI 0.89, 0.95) for MF, r = 0.97 (95% CI 0.96, 0.98) for LT, and r = 0.87 (95% CI 0.81, 0.91) for MT. Estimated SRMs for LACS and Chondrometrics measures were similar in the random sample, and SRM heatmaps identified subregions of LACS-measured cartilage loss. CONCLUSION: LACS cartilage thickness measurement in the MF and LF and tibia correlated well with established manual segmentation-based measurement, with similar responsiveness to change, among knees with symptomatic knee OA. LACS measurement of cartilage plate topography enables spatiotemporal analysis of cartilage loss in future knee OA studies.

Ultrasonography of Inflammatory and Structural Lesions in Hand Osteoarthritis: An Outcome Measures in Rheumatology Agreement and Reliability Study.

OBJECTIVE: To standardize and assess the reliability of ultrasonographic assessment of inflammatory and structural lesions in patients with hand osteoarthritis (OA). METHODS: The Outcome Measures in Rheumatology Ultrasound Working Group selected synovial hypertrophy (SH), joint effusion (JE), and power Doppler (PD) signals as the main inflammatory lesions in hand OA, and suggested osteophytes in the scapho-trapezio-trapezoid (STT) and cartilage defects in the proximal interphalangeal (PIP) joints as novel additions to previous structural scoring systems. A complementary imaging atlas provided detailed examples of the scores. A reliability exercise of static images was performed for the inflammatory features, followed by a patient-based exercise with 6 sonographers testing inflammatory and structural features in 12 hand OA patients. We used Cohen's kappa for intrareader and Light's kappa for interreader reliability for all features except PD, in which prevalence-adjusted bias-adjusted kappa (PABAK) was applied. Percentage agreement was also assessed. RESULTS: The web-based reliability exercise demonstrated substantial intra- and interreader reliability for all inflammatory features (κ > 0.64). In the patient-based exercise, intra- and interreader reliability, respectively, varied: SH κ = 0.73 and 0.45; JE κ = 0.70 and 0.55; PD PABAK = 0.90 and 0.88; PIP joint cartilage κ = 0.56 and 0.45; and STT osteophytes κ = 0.62 and 0.36. Percentage close agreement was high for all features (>85%). CONCLUSION: With ultrasound, substantial to excellent intrareader reliability was found for inflammatory features of hand OA. Interreader reliability was moderate, but overall high close agreement between readers suggests that better reliability is achievable after further training. Assessment of osteophytes in the STT joint and cartilage in the PIP joints achieved less reliability and the latter is not endorsed.

Associations between joint pathologies and central sensitization in persons with hand osteoarthritis: results from the Nor-Hand study.

OBJECTIVE: Pain sensitization is associated with pain severity in persons with hand OA. What contributes to pain sensitization is unclear. This study explores whether hand OA pathologies and symptom duration are related to central sensitization. METHOD: Participants with hand OA in the Nor-Hand study underwent bilateral hand radiography and US examination. Central sensitization was assessed with pressure pain thresholds (PPT) at remote sites (wrist, trapezius and tibialis anterior muscles) and temporal summation. We examined whether hand OA pathologies, independent of each other, including structural severity (Kellgren-Lawrence sum score, presence of erosive hand OA), inflammatory severity (greyscale synovitis and power Doppler activity sum scores) and symptom duration, were related to central sensitization, adjusting for age, sex, BMI, comorbidities and OA-severity of knee/hip. RESULTS: In 291 participants (88% women, median age 61 years, interquartile range 57-66 years) Kellgren-Lawrence, greyscale synovitis and power Doppler activity sum scores were not associated with lower PPTs at remote sites. Persons with erosive hand OA had lower PPTs at the wrist (adjusted beta -0.75, 95% CI -1.32, -0.19) and tibialis anterior (adjusted beta -0.82, 95% CI -1.54, -0.09) and had greater temporal summation (adjusted beta 0.56, 95% CI 0.12, 1.01) compared with persons with non-erosive disease. No associations were found for symptom duration. CONCLUSIONS: A person's overall amount of structural or inflammatory hand OA pathologies was not associated with central sensitization. Although persons with erosive hand OA showed greater signs of central sensitization, the small differences suggest that central sensitization is mainly explained by factors other than joint pathologies.

Urbanization and Knee Cartilage Growth Among Children and Adolescents in Western Kenya.

OBJECTIVE: Previous studies have demonstrated that low physical activity levels during youth are associated with the development of thin knee cartilage, which may increase susceptibility to osteoarthritis later in life. Here, we propose and test the hypothesis that reductions in physical activity impair knee cartilage growth among people in developing countries experiencing urbanization and increased market integration. METHODS: Ultrasonography was used to measure knee cartilage thickness in 168 children and adolescents (aged 8-17 years) from two groups in western Kenya: a rural, physically active group from a small-scale farming community and an urban, less physically active group from the nearby city of Eldoret. We used general linear models to assess the relative effects of age on cartilage thickness in these two groups, controlling for sex and leg length. RESULTS: Both groups exhibited significant reductions in knee cartilage thickness with increasing age (P < 0.0001; 95% confidence interval [CI] 0.15-0.06 mm), yet the rate of reduction was significantly less in the rural than in the urban group (P = 0.012; 95% CI 0.01-0.10 mm). CONCLUSION: The results support our hypothesis by showing that individuals from the more physically active rural group exhibited less knee cartilage loss during youth than the more sedentary urban group. Our findings suggest that reduced physical activity associated with urbanization in developing nations may affect adult knee cartilage thickness and thus could be a factor that increases susceptibility to osteoarthritis.

Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 : A Randomized Trial.

BACKGROUND: New treatment modalities are urgently needed for patients with COVID-19. The World Health Organization (WHO) Solidarity trial showed no effect of remdesivir or hydroxychloroquine (HCQ) on mortality, but the antiviral effects of these drugs are not known. OBJECTIVE: To evaluate the effects of remdesivir and HCQ on all-cause, in-hospital mortality; the degree of respiratory failure and inflammation; and viral clearance in the oropharynx. DESIGN: NOR-Solidarity is an independent, add-on, randomized controlled trial to the WHO Solidarity trial that included biobanking and 3 months of clinical follow-up (ClinicalTrials.gov: NCT04321616). SETTING: 23 hospitals in Norway. PATIENTS: Eligible patients were adults hospitalized with confirmed SARS-CoV-2 infection. INTERVENTION: Between 28 March and 4 October 2020, a total of 185 patients were randomly assigned and 181 were included in the full analysis set. Patients received remdesivir (n = 42), HCQ (n = 52), or standard of care (SoC) (n = 87). MEASUREMENTS: In addition to the primary end point of WHO Solidarity, study-specific outcomes were viral clearance in oropharyngeal specimens, the degree of respiratory failure, and inflammatory variables. RESULTS: No significant differences were seen between treatment groups in mortality during hospitalization. There was a marked decrease in SARS-CoV-2 load in the oropharynx during the first week overall, with similar decreases and 10-day viral loads among the remdesivir, HCQ, and SoC groups. Remdesivir and HCQ did not affect the degree of respiratory failure or inflammatory variables in plasma or serum. The lack of antiviral effect was not associated with symptom duration, level of viral load, degree of inflammation, or presence of antibodies against SARS-CoV-2 at hospital admittance. LIMITATION: The trial had no placebo group. CONCLUSION: Neither remdesivir nor HCQ affected viral clearance in hospitalized patients with COVID-19. PRIMARY FUNDING SOURCE: National Clinical Therapy Research in the Specialist Health Services, Norway.

Erosive Hand Osteoarthritis: Incidence and Predictive Characteristics Among Participants in the Osteoarthritis Initiative.

OBJECTIVE: To evaluate age, sex, race, osteoarthritis (OA) severity, metabolic factors, and bone health as risk factors for erosive hand OA at baseline and its incidence over a 48-month period. METHODS: This was a longitudinal cohort study that included participants from the Osteoarthritis Initiative (OAI) with complete hand radiographs from baseline and 48-month visits who were eligible at baseline for incident erosive hand OA (i.e., had or were at risk for knee OA [criterion for OAI inclusion] and did not currently have erosive hand OA). Individuals were classified as having erosive hand OA if the Kellgren/Lawrence (K/L) grade was ≥2 in at least 1 interphalangeal joint on 2 different fingers and central erosion was present in at least 1 joint. RESULTS: Of the 3,365 individuals without prevalent erosive hand OA at baseline, 86 (2.6%) developed erosive hand OA during the 48-month period. Risk factors included older age (relative risk [RR] per SD 1.63 [95% confidence interval 1.35-1.97]), female sex (RR 2.47 [95% confidence interval 1.52-4.02]), greater OA severity (sum K/L grade 13.9 versus 5.3; P < 0.001), and less cortical width (1.38 mm versus 1.52 mm; P < 0.001). After 48 months, subjects who had developed erosive hand OA were characterized by greater progression of radiographic OA (i.e., joint space narrowing, K/L grade progression [RR 1.35], and loss of cortical thickness [RR 1.23]), adjusted for age, sex, race, body mass index, and baseline OA severity (sum K/L grade). CONCLUSION: These findings demonstrate that erosive hand OA is more common in older women and is strongly associated with severity of articular structural damage and its progression. Individuals who develop erosive hand OA have thinner bones prior to erosive hand OA development and as it progresses, suggesting that erosive hand OA is a disorder of skeletal frailty.

Study protocol for the follow-up examination of the Nor-Hand study: A hospital-based observational cohort study exploring pain and biomarkers in people with hand osteoarthritis.

Objective: This study aims to increase the understanding of pain mechanisms in hand OA and explore potential risk factors for pain development or worsening in a biopsychosocial framework. Another important aim is to validate potential soluble and imaging OA biomarkers. Design: The follow-up examination of the Nor-Hand hospital-based observational cohort study started in October 2019 and was completed in May 2021. In total, 212 of the 300 participants with hand OA who were examined at baseline attended the follow-up study. The participants underwent clinical joint examinations, medical and functional assessments, quantitative sensory testing, fluorescence optical imaging, ultrasound of the hands, acromioclavicular joints, feet, knees and hips, conventional radiographs of the hands and feet and magnetic resonance imaging of the dominant hand. Blood and urine samples were collected, and all participants answered questions about demographic factors and OA-related questionnaires. Associations between disease variables and symptoms will be examined in cross-sectional and longitudinal analyses. Longitudinal analyses will be performed to assess the predictive value of baseline variables on hand OA outcomes. Conclusion: Current knowledge about predictors for disease progression in hand OA is limited, but with longitudinal data we will be able to explore the predictive value of baseline variables on hand OA outcomes, such as changes in patient-reported outcomes or changes in soluble and imaging biomarkers. This provides a unique opportunity to gain more knowledge about the natural disease course of hand OA.

Relationship between cam morphology, hip symptoms, and hip osteoarthritis: the Musculoskeletal pain in Ullersaker STudy (MUST) cohort.

BACKGROUND: The primary aim of this study was to determine the prevalence of cam morphology in a cohort of people aged 40-55 years. Secondary aims were to: (1) determine differences in participant characteristics, physical impairments, radiographic and ultrasound appearances of people with and without cam morphology; and (2) explore associations between cam morphology and radiographic measures of hip osteoarthritis (OA). METHODS: 107 people (68% women; 49 ± 4 years) from the Musculoskeletal pain in Ullensaker (MUST) Study underwent the clinical and imaging examinations. Examinations included questionnaires, hip range, functional task performance, pelvic radiographs and ultrasound. Alpha angle and radiographic hip OA (Kellgren Lawrence (KL) and minimal joint space (MJS)) were determined. RESULTS: The prevalence of cam morphology was 42% and was bilateral in 47%. People with cam morphology were 6 times more likely to have a KL score ⩾2 (adjusted odds ratio [95% confidence intervals, p-value]) 6.386 [1.582-37.646, p = 0.012]) and 4 times more likely to have MJS <2.0 mm (adjusted odds ratio 4.032 [1.031-12.639, p = 0.045]). The prevalence of radiographic OA features ranged from 4-13% in people with cam morphology, and 0-3% in those without. Those with cam morphology also demonstrated reduced hip flexion and rotation range (p = 0.018-0.036) compared with those without. There was no association between ultrasonic features and patient reported outcomes, and cam morphology. CONCLUSIONS: In a cohort aged 40-55 years, the prevalence of cam morphology was high (42%), with a significant relationship between cam morphology and radiographic measures of hip OA. Further longitudinal studies should explore the relationship between cam morphology and hip OA in younger people.

Validity and diagnostic performance of fluorescence optical imaging measuring synovitis in hand osteoarthritis: baseline results from the Nor-Hand cohort.

OBJECTIVE: Fluorescence optical imaging (FOI) demonstrates enhanced microcirculation in finger joints as a sign of inflammation. We wanted to assess the validity and diagnostic performance of FOI measuring synovitis in persons with hand OA, comparing it with magnetic resonance imaging (MRI)- and ultrasound-detected synovitis. METHODS: Two hundred and twenty-one participants with hand OA underwent FOI and ultrasound (gray-scale synovitis and power Doppler activity) of the bilateral hands and contrast-enhanced MRI examination of the dominant hand. Fifteen joints in each hand were scored on semi-quantitative scales (grade 0-3) for all modalities. Four FOI images were evaluated: one composite image (Prima Vista Mode (PVM)) and three images representing phases of fluorescent dye distribution. Spearman's correlation coefficients were calculated between sum scores of FOI, MRI, and ultrasound. Sensitivity, specificity, and area under the curve (AUC) were calculated for FOI using MRI or ultrasound as reference. RESULTS: FOI did not demonstrate enhancement in the thumb base, and the joint was excluded from further analyses. FOI sum scores showed poor to fair correlations with MRI (rho 0.01-0.24) and GS synovitis sum scores (rho 0.12-0.25). None of the FOI images demonstrated both good sensitivity and specificity, and the AUC ranged from 0.50-0.61 and 0.51-0.63 with MRI and GS synovitis as reference, respectively. FOI demonstrated similar diagnostic performance with PD activity and GS synovitis as reference. CONCLUSION: FOI enhancement correlated poorly with synovitis assessed by more established imaging modalities, questioning the value of FOI for the evaluation of synovitis in hand OA.

Associations Between Ultrasound-Detected Synovitis, Pain, and Function in Interphalangeal and Thumb Base Osteoarthritis: Data From the Nor-Hand Cohort.

OBJECTIVE: To explore whether ultrasound-detected gray-scale synovitis and power Doppler activity in the interphalangeal and first carpometacarpal (CMC1) joints are associated with pain and physical function in patients with hand osteoarthritis (OA). METHODS: A total of 290 patients with hand OA underwent an ultrasound examination of the bilateral interphalangeal and CMC1 joints. Using logistic regression analyses with generalized estimating equations, we examined whether grade 0-3 gray-scale synovitis and power Doppler activity were associated with pain in the same joint. Using linear regression analyses, we examined whether the degree of inflammation was associated with numeric rating scale and Australian/Canadian (AUSCAN) Osteoarthritis Hand Index hand pain, AUSCAN physical function, and grip strength scores. Analyses were made separately for interphalangeal and CMC1 joints, and adjusted for age, sex, body mass index, psychosocial factors, use of analgesics, and presence of osteophytes. RESULTS: At joint level, increasing gray-scale synovitis severity was associated with higher odds of pain upon palpation in both the interphalangeal (grade 2-3; odds ratio [OR] 3.17 [95% confidence interval (95% CI) 2.35, 4.28]) and CMC1 joints (grade 2-3; OR 4.40 [95% CI 2.10, 9.24]). Similar associations were found for power Doppler activity and joint pain in the previous 24 hours and 6 weeks. Power Doppler activity in CMC1 was also related to overall hand pain/physical function and lower grip strength. CONCLUSION: Inflammation in both the interphalangeal and CMC1 joints was associated with pain in the same joint. However, associations with hand pain, reduced physical function, and lower grip strength were only present for inflammation in the CMC1 joints, suggesting that lowering CMC1 inflammation is an important treatment target.