Retinal metabolism displays evidence for uncoupling of glycolysis and oxidative phosphorylation via Cori-, Cahill-, and mini-Krebs-cycle.

The retina consumes massive amounts of energy, yet its metabolism and substrate exploitation remain poorly understood. Here, we used a murine explant model to manipulate retinal energy metabolism under entirely controlled conditions and utilised 1H-NMR spectroscopy-based metabolomics, in situ enzyme detection, and cell viability readouts to uncover the pathways of retinal energy production. Our experimental manipulations resulted in varying degrees of photoreceptor degeneration, while the inner retina and retinal pigment epithelium were essentially unaffected. This selective vulnerability of photoreceptors suggested very specific adaptations in their energy metabolism. Rod photoreceptors were found to rely strongly on oxidative phosphorylation, but only mildly on glycolysis. Conversely, cone photoreceptors were dependent on glycolysis but insensitive to electron transport chain decoupling. Importantly, photoreceptors appeared to uncouple glycolytic and Krebs-cycle metabolism via three different pathways: (1) the mini-Krebs-cycle, fuelled by glutamine and branched chain amino acids, generating N-acetylaspartate; (2) the alanine-generating Cahill-cycle; (3) the lactate-releasing Cori-cycle. Moreover, the metabolomics data indicated a shuttling of taurine and hypotaurine between the retinal pigment epithelium and photoreceptors, likely resulting in an additional net transfer of reducing power to photoreceptors. These findings expand our understanding of retinal physiology and pathology and shed new light on neuronal energy homeostasis and the pathogenesis of neurodegenerative diseases.

Association of biochemical markers with bone marrow lesion changes on imaging-data from the Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium.

BACKGROUND: To assess the prognostic value of short-term change in biochemical markers as it relates to bone marrow lesions (BMLs) on MRI in knee osteoarthritis (OA) over 24 months and, furthermore, to assess the relationship between biochemical markers involved with tissue turnover and inflammation and BMLs on MRI. METHODS: Data from the Foundation for the National Institutes of Health OA Biomarkers Consortium within the Osteoarthritis Initiative (n = 600) was analyzed. BMLs were measured according to the MRI Osteoarthritis Knee Score (MOAKS) system (0-3), in 15 knee subregions. Serum and urinary biochemical markers assessed were as follows: serum C-terminal crosslinked telopeptide of type I collagen (CTX-I), serum crosslinked N-telopeptide of type I collagen (NTX-I), urinary CTX-Iα and CTX-Iß, urinary NTX-I, urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II), serum matrix metalloproteinase (MMP)-degraded type I, II, and III collagen (C1M, C2M, C3M), serum high sensitivity propeptide of type IIb collagen (hsPRO-C2), and matrix metalloproteinase-generated neoepitope of C-reactive protein (CRPM). The association between change in biochemical markers over 12 months and BMLs over 24 months was examined using regression models adjusted for covariates. The relationship between C1M, C2M, C3M, hsPRO-C2, and CRPM and BMLs at baseline and over 24 months was examined. RESULTS: Increases in serum CTX-I and urinary CTX-Iß over 12 months were associated with increased odds of changes in the number of subregions affected by any BML at 24 months. Increase in hsPRO-C2 was associated with decreased odds of worsening in the number of subregions affected by any BML over 24 months. C1M and C3M were associated with BMLs affected at baseline. CONCLUSIONS: Short-term changes in serum CTX-I, hsPRO-C2, and urinary CTX-Iß hold the potential to be prognostic of BML progression on MRI. The association of C1M and C3M with baseline BMLs on MRI warrants further investigation.

Predictors of Placebo Response to Local (Intra-Articular) Therapy In Osteoarthritis: An Individual Participant Data Meta-Analysis.

OBJECTIVE: We undertook this study to evaluate potential predictors of placebo response with intra-articular (IA) injections for knee/hip osteoarthritis (OA) using individual participant data (IPD) from existing trials. METHODS: Randomized placebo-controlled trials evaluating IA glucocorticoid or hyaluronic acid published to September 2018 were selected. IPD for disease characteristics and outcome measures were acquired. Potential predictors of placebo response included participant characteristics, pain severity, intervention, and trial design. Placebo response was defined as at least a 20% reduction in baseline pain. Logistic regression models and odds ratios were computed as effect measures to evaluate patient and pain mechanisms and then pooled using a random effects model. Generalized mixed-effect models were applied to intervention and trial characteristics. RESULTS: Of 56 eligible trials, 6 shared data, and these were combined with the existing 4 OA Trial Bank studies, yielding 10 studies with IPD of 621 placebo participants for analysis. In the total placebo population, at short-term follow-up, the use of local anesthetic and ultrasound guidance were associated with reduced odds of placebo response. At midterm follow-up, mid- to long-term trial duration was associated with increased odds of placebo response, and worse baseline function scores were associated with reduced odds of a placebo response. CONCLUSION: The administration of local anesthetics or ultrasound guidance may reduce IA placebo response at short-term follow-up. At midterm follow-up, participants with worse baseline function scores may be less likely to respond to IA placebo, and mid- to long-term trial duration may enhance the placebo response. Further studies are required to corroborate these potential predictors of IA placebo response.

The OA Trial Bank: Update of individual patient data meta-analysis of intra-articular glucocorticoids in persons with knee and hip osteoarthritis.

Objective: To evaluate the efficacy of intra--articular (IA) glucocorticoid for knee or hip osteoarthritis (OA) in specific subgroups of patients according to the baseline severity of pain and inflammatory signs using individual patient data (IPD) from existing trials. Furthermore, this study aims to assess if a baseline pain cut-off was associated with clinically important effectiveness of IA glucocorticoid. This is an update of an IA glucocorticoid IPD meta-analysis by the OA Trial Bank. Method: Randomized trials evaluating one or more IA glucocorticoid preparations in hip and knee OA, published to May 2018 were selected. IPD of patient and disease characteristics and outcome measures were acquired. The primary outcome was pain severity at short-term follow-up (up to 4 weeks). Potential interaction effect of severe pain (≥70 points, 0-100 scale) and signs of inflammation at baseline were studied using a two-stage approach with general liner model followed by random effects model. Analysis of trend was conducted, assessing if a baseline pain cut-off was associated with the threshold for clinically important treatment effect of IA glucocorticoid compared to placebo. Results: Four out of 16 eligible randomized clinical trials (n â€‹= â€‹641) were combined with the existing OA Trial Bank studies (n â€‹= â€‹620), yielding 1261 participants from eleven studies. Participants with severe baseline pain compared to those with less severe pain had greater pain reduction at mid-term (around 12 weeks) (mean reduction: -6.90 (95%CI -10.91; -2.90)), but not at short- and long-term. No interaction effects were found between inflammatory signs and IA glucocorticoid injections compared to placebo at all follow-up time-points. Analysis of trend demonstrated treatment response to IA glucocorticoid from baseline pain levels >50 (0-100 scale) and above. Conclusion: This updated IPD meta-analysis demonstrated that participants with severe pain compared to those with less severe pain at baseline experienced significantly more pain relief with IA glucocorticoid compared with placebo at mid-term.

Inflammatory ultrasound features as prognostic factors of pain and functional outcomes following intra-articular platelet-rich plasma in knee osteoarthritis.

AIM: To explore inflammatory ultrasound predictors of improvements in pain and function over 2, 6, and 12 months following administration of intra-articular platelet-rich plasma (PRP) in knee osteoarthritis (OA). METHOD: Patients with painful mild-moderate radiographic knee OA from a subset of the RESTORE RCT underwent ultrasound assessment according to the standardized OMERACT scanning protocol to detect inflammatory features such as synovitis, synovial hypertrophy, and effusion with power Doppler. The study knee was treated with 3 once-weekly PRP injections obtained after centrifugation at 1500 g for 5 min. Numerical Rating Score (NRS), Intermittent and Constant Osteoarthritis Pain (ICOAP) questionnaire, and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) function sub-score were used to measure pain and functional severity. Separate linear regression models were performed to determine whether baseline ultrasound-detected features of inflammation predicted the improvement in pain and function following PRP injection in both unadjusted and adjusted models for confounders. RESULTS: Forty-four participants were included, with 25 (56.8%) being female. In an unadjusted model, higher OMERACT scores for inflammatory features such as global synovitis and/or effusion were significantly associated with greater improvement in all outcomes measured at 2 months but not at 6 and 12 months for pain measures. Only global synovitis showed significant association with functional improvement at 2 and 12 months. Similar findings were observed in the adjusted model. CONCLUSION: Ultrasound indices of knee inflammation predicted short-term improvements in pain severity and both short- and longer-term improvements in function following intra-articular PRP injection.

A rare case of histiocytic proliferative disease in a cat.

A 7-year-old intact female domestic medium hair cat was examined at a veterinary clinic for a scabbed nodule over the right shoulder. Multiple nodules recurred at the same site after the first surgical excision, and a second surgical excision was performed. Histopathology demonstrated high-mitotic-rate neoplastic cells and therefore a histiocytic proliferative disease was initially suspected. The condition progressed rapidly within a 5-month period and the cat was euthanized due to sudden onset of severe dyspnea. Necropsy showed diffuse metastatic nodules in the lungs, confirming a histiocytic proliferative disease, with histiocytic sarcoma being the most likely differential diagnosis.

Un cas rare de maladie histiocytaire proliférative chez un chat. Une chatte domestique á poil moyen intacte de 7 ans a été examinée dans une clinique vétérinaire pour un nodule croûteux sur l'épaule droite. Plusieurs nodules sont réapparus au même site après la première excision chirurgicale, et une deuxième excision chirurgicale a été réalisée. L'histopathologie a mis en évidence des cellules néoplasiques á taux mitotique élevé et, par conséquent, une maladie proliférative histiocytaire a été initialement suspectée. L'état a progressé rapidement en l'espace de 5 mois et le chat a été euthanasié en raison de l'apparition soudaine d'une dyspnée sévère. L'autopsie a montré des nodules métastatiques diffus dans les poumons, confirmant une maladie proliférative histiocytaire, le sarcome histiocytaire étant le diagnostic différentiel le plus probable.(Traduit par Dr Serge Messier).

Self-regulation of time: The importance of time estimation accuracy.

Time management is one central aspect of students' self-regulated learning. In addition, biased time estimation seems to be central to students' self-regulation of their time. In this study, we explored college students' time estimation bias. In addition, we were interested in whether the activation of task beliefs influenced students' time estimation bias and how specific beliefs about task difficulty influence time estimation bias. Findings suggested that students tended to demonstrate bias in their estimations of the time their academic tasks would take. Additionally, the activation of task beliefs did not influence students' time estimation accuracy. Finally, both prior task difficulty and anticipated difficulty influenced students' time estimation bias. These findings highlight the complexity of students' time estimation bias and point to the opportunities for future directions.

Single-Cell Transcriptomic Profiling in Inherited Retinal Degeneration Reveals Distinct Metabolic Pathways in Rod and Cone Photoreceptors.

The cellular mechanisms underlying hereditary photoreceptor degeneration are still poorly understood. The aim of this study was to systematically map the transcriptional changes that occur in the degenerating mouse retina at the single cell level. To this end, we employed single-cell RNA-sequencing (scRNA-seq) and retinal degeneration-1 (rd1) mice to profile the impact of the disease mutation on the diverse retinal cell types during early post-natal development. The transcriptome data allowed to annotate 43,979 individual cells grouped into 20 distinct clusters. We further characterized cluster-specific metabolic and biological changes in individual cell types. Our results highlight Ca2+-signaling as relevant to hereditary photoreceptor degeneration. Although metabolic reprogramming in retina, known as the 'Warburg effect', has been documented, further metabolic changes were noticed in rd1 mice. Such metabolic changes in rd1 mutation was likely regulated through mitogen-activated protein kinase (MAPK) pathway. By combining single-cell transcriptomes and immunofluorescence staining, our study revealed cell type-specific changes in gene expression, as well as interplay between Ca2+-induced cell death and metabolic pathways.

Responsiveness of an activity tracker as a measurement tool in a knee osteoarthritis clinical trial (ACTIVe-OA study).

BACKGROUND: In osteoarthritis (OA) clinical trials, reliable and responsive outcome measures to document physical and functional improvements are limited. OBJECTIVE: This study aimed to assess whether the use of an activity tracker in an OA clinical trial is a responsive measurement tool. Secondary objectives assessed feasibility and validity. METHODS: We recruited 65 participants in a prospective cohort study nested in a placebo-controlled clinical trial of platelet-rich plasma injection in knee OA. Participants wore an activity tracker (Fitbit Flex 2), and a smartphone was preloaded with a mobile application (OApp) designed to monitor load rates as a surrogate of knee loading. Participants used the systems for 7 days at baseline and for 7 days before the 2-month follow-up assessment. Effect size (ES) and standardised response mean (SRM) were calculated for change in step count and knee loading rate and regularly used knee OA outcome measures. Correlation coefficients (r) were calculated to examine the strength of the association between outcome measures. RESULTS: . Step count showed a trivial ES and SRM and mean knee loading rate measurements a moderate ES and SRM. We found a weak but significant correlation between change in mean steps per day and global improvement overall (r= 0.28) and Western Ontario and McMaster Universities Osteoarthritis Index function (r = -0.28). Compliance was high with the activity trackers. CONCLUSIONS: Despite good feasibility, this study did not show significant responsiveness or validity of the activity trackers as compared with currently recommended outcome measures in OA clinical trials. The main challenge is the lack of a gold standard outcome measure to validate against, and because of the complex interplay between pain and measured function, a lack of correlation does not necessarily represent a failed validation in this context. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY: ACTRN12617000853347. This trial is a substudy of the "Platelet-rich plasma as a symptom-and disease-modifying treatment for knee osteoarthritis - the RESTORE trial".

Reliability and Convergent Construct Validity of Quantitative Ultrasound for Synovitis, Meniscal Extrusion, and Osteophyte in Knee Osteoarthritis With MRI.

AIMS: To determine: 1) inter-rater reliability of quantitative measurements of ultrasound-detected synovitis, meniscal extrusion, and osteophytes; and 2) construct (convergent) validity via correlations and absolute agreements between ultrasound- and gold-standard magnetic resonance imaging (MRI)-outcomes in knee osteoarthritis. METHODS: Dynamic ultrasound images for supra-patellar synovitis, meniscal extrusion, and osteophytes were acquired and quantified by a physician operator, musculoskeletal ultrasonographer, and medical student independently. On the same day, 3T MRI images were acquired. Effusion-synovitis, meniscal extrusion, and osteophytes were quantified on sagittal or coronal proton-density-weighted fat-suppressed noncontrast TSE sequences, respectively. Intra-class correlation coefficients (ICCs), Pearson's correlations (r), and Bland-Altman plots were used to analyze inter-rater reliability, and correlations, and agreements between the two imaging modalities. RESULTS: Eighty-nine participants [48 females (53.9%)] with mean (standard deviation) age of 61.5 ± 6.9 years were included. The inter-rater reliability was excellent for osteophytes (ICC range = 0.90-0.96), meniscal extrusion (ICC range = 0.90-0.93), and synovitis (ICC range = 0.86-0.88). The correlations between ultrasound pathologies and their MRI counterparts were very strong (ICC range = 0.85-0.98) except for lateral meniscal extrusion [0.66 (95% CI, 0.52-0.76)]. Bland-Altman plots showed 0.01, 0.05, 0.10, 0.53, and 0.60 mm larger size in ultrasound medial tibial and medial femoral osteophytes, medial meniscal extrusions, synovitis, and lateral meniscal extrusions with 95% limits of agreements [±0.39, ±0.44, ±0.85, ±0.70, and ±0.90 (SDs)] than MRI measures, respectively. The lines of equality were within 95% CI of the mean differences (bias) only for medial osteophytes and medial meniscal extrusion. CONCLUSION: The quantitative assessment of synovitis, meniscal extrusion, and osteophytes generally showed excellent inter-rater reliability and strong correlations with MRI-based measurements. Absolute agreement was strong for medial tibiofemoral pathologies.

Corrigendum: Self-regulation of time: The importance of time estimation accuracy.

[This corrects the article DOI: 10.3389/fpsyg.2022.925812.].

Effect of Intra-articular Platelet-Rich Plasma vs Placebo Injection on Pain and Medial Tibial Cartilage Volume in Patients With Knee Osteoarthritis: The RESTORE Randomized Clinical Trial.

Importance: Most clinical guidelines do not recommend platelet-rich plasma (PRP) for knee osteoarthritis (OA) because of lack of high-quality evidence on efficacy for symptoms and joint structure, but the guidelines emphasize the need for rigorous studies. Despite this, use of PRP in knee OA is increasing. Objective: To evaluate the effects of intra-articular PRP injections on symptoms and joint structure in patients with symptomatic mild to moderate radiographic medial knee OA. Design, Setting, and Participants: This randomized, 2-group, placebo-controlled, participant-, injector-, and assessor-blinded clinical trial enrolled community-based participants (n = 288) aged 50 years or older with symptomatic medial knee OA (Kellgren and Lawrence grade 2 or 3) in Sydney and Melbourne, Australia, from August 24, 2017, to July 5, 2019. The 12-month follow-up was completed on July 22, 2020. Interventions: Interventions involved 3 intra-articular injections at weekly intervals of either leukocyte-poor PRP using a commercially available product (n = 144 participants) or saline placebo (n = 144 participants). Main Outcomes and Measures: The 2 primary outcomes were 12-month change in overall average knee pain scores (11-point scale; range, 0-10, with higher scores indicating worse pain; minimum clinically important difference of 1.8) and percentage change in medial tibial cartilage volume as assessed by magnetic resonance imaging (MRI). Thirty-one secondary outcomes (25 symptom related and 6 MRI assessed; minimum clinically important difference not known) evaluated pain, function, quality of life, global change, and joint structures at 2-month and/or 12-month follow-up. Results: Among 288 patients who were randomized (mean age, 61.9 [SD, 6.5] years; 169 [59%] women), 269 (93%) completed the trial. In both groups, 140 participants (97%) received all 3 injections. After 12 months, treatment with PRP vs placebo injection resulted in a mean change in knee pain scores of -2.1 vs -1.8 points, respectively (difference, -0.4 [95% CI, -0.9 to 0.2] points; P = .17). The mean change in medial tibial cartilage volume was -1.4% vs -1.2%, respectively (difference, -0.2% [95% CI, -1.9% to 1.5%]; P = .81). Of 31 prespecified secondary outcomes, 29 showed no significant between-group differences. Conclusions and Relevance: Among patients with symptomatic mild to moderate radiographic knee OA, intra-articular injection of PRP, compared with injection of saline placebo, did not result in a significant difference in symptoms or joint structure at 12 months. These findings do not support use of PRP for the management of knee OA. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12617000853347.

TEXT4myBACK - The Development Process of a Self-Management Intervention Delivered Via Text Message for Low Back Pain.

OBJECTIVE: To develop a bank of text messages for a lifestyle-based self-management intervention for people with low back pain (LBP). DESIGN: Iterative development process. SETTING: Community and primary care. PARTICIPANTS: Fifteen researchers, clinicians, and consumer representatives participated in the concept and initial content development phase. Twelve experts (researchers and clinicians) and 12 consumers participated in the experts and consumers review phase. Full study sample of participants was N=39. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We first conducted two 2-hour workshops to identify important domains for people with LBP, sources of content, appropriate volume, and timing of the messages. The messages were then drafted by a team of writers. Second, we invited expert researchers and clinicians to review and score the messages using a 5-item psychometric scale according to (1) the appropriateness of the content and (2) the likelihood of clinical effectiveness and to provide written feedback. Messages scoring ≤8 out of 10 points would be modified accordingly. Consumers were invited to review the messages and score them using a 5-item psychometric scale according to the utility of the content, the understanding of the content, and language acceptability and to provide feedback. Messages scoring ≤12 out of 15 points would be improved. RESULTS: Exercise, education, mood, sleep, use of care, and medication domains were identified and 82 domain-specific evidence-based messages were written. Messages received a mean score of 8.3 out of 10 points by experts. Twenty-nine messages were modified accordingly. The mean score of the messages based on consumers feedback was of 12.5 out of 15 points. Thirty-six messages were improved. CONCLUSIONS: We developed a bank of text messages for an evidence-based self-management intervention using a theory-based, iterative, codesign process with researchers, consumers, and clinicians. This article provides scientific support for future development of text message interventions within the pain field.

Are OMERACT Knee Osteoarthritis Ultrasound Scores Associated With Pain Severity, Other Symptoms, and Radiographic and Magnetic Resonance Imaging Findings?

OBJECTIVE: To investigate the associations of Outcome Measures in Rheumatology (OMERACT) ultrasound scores for knee osteoarthritis (OA) with pain severity, other symptoms, and OA severity on radiographs and magnetic resonance imaging (MRI). METHODS: Participants with symptomatic and mild to moderate radiographic knee OA underwent baseline dynamic ultrasound (US) assessment according to standardized OMERACT scanning protocol. Using the published US image atlas, a physician operator obtained semiquantitative or binary scores for US pathologies. Clinical severity was measured on numerical rating scale (NRS) and Knee Injury and Osteoarthritis Outcome Score (KOOS) symptoms and pain subscores. OA severity was assessed using the Kellgren-Lawrence (KL) grade on radiographs and MRI Osteoarthritis Knee Score (MOAKS) on noncontrast-enhanced MRI. Separate linear regression models were used to determine associations of US OA pathologies with pain and KOOS subscores, and Spearman correlations were used for US scores with KL grade and MOAKS. RESULTS: Eighty-nine participants were included. Greater synovial hypertrophy, power Doppler (PD), and meniscal extrusion scores were associated with worse NRS pain [ß 0.92 (95% CI 0.25-1.58), ß 0.73 (95% CI 0.11-1.35), and ß 1.01 (95% CI 0.22-1.80), respectively]. All greater US scores, except for cartilage grade, demonstrated significant associations with worse KOOS symptoms, whereas only PD and meniscal extrusion were associated with worse KOOS pain. All US scores, except for PD, were significantly correlated with KL grade. US pathologies, except for cartilage, revealed moderate to good correlation with their MOAKS counterparts, with US synovitis having the greatest correlation (0.69, 95% CI 0.60-0.78). CONCLUSION: OMERACT US scores revealed significant associations with pain severity, KL grade, and MOAKS.

Exploring translational gaps between basic scientists, clinical researchers, clinicians, and consumers: Proceedings and recommendations arising from the 2020 mine the gap online workshop.

Objective: To provide a summary of the translational gaps in musculoskeletal research as identified in the Mine the Gap workshop and propose possible solutions. Methods: The Mine the Gap online workshop was hosted on October 14th and 15th, 2020. Five international panels, each comprised of a clinician, clinical researcher and basic scientist, presented gaps and proposed solutions for the themes of biomechanics, pain, biological measurements, phenotypes and imaging. This was followed by an interactive panel discussion with consumer insights. Results: A number of translational gaps and proposed solutions across each of the five themes were identified. A consumer panel provided constructive feedback highlighting the need for improved resources, communication and shared decision making, and treatment individualisation. Conclusion: This brief report provides a greater understanding of the diverse work and gaps relevant to fundamental/discovery scientists, clinical researchers and clinicians working across the musculoskeletal field. The numerous translational gaps highlight the need to improve communication and collaboration across the musculoskeletal field.

Corrigendum to "Exploring translational gaps between basic scientists, clinical researchers, clinicians, and consumers: Proceedings and recommendations arising from the 2020 mine the gap online workshop" [Osteoarthritis Cartilage Open 29 (2021) 100163].

[This corrects the article DOI: 10.1016/j.ocarto.2021.100163.].

Effects of Knowledge and Value on Quality of Supportive Peer Feedback.

BACKGROUND: Motivational barriers and lack of knowledge about peer review inhibit creation of supportive peer feedback between nursing students. PURPOSE: The purpose of this study was to examine the effects of knowledge of peer-review practices and value for the process of creating supportive peer feedback on the quality of feedback nursing students create for their peers. METHOD: Data from 155 graduate nursing students were analyzed in this quasi-experimental, repeated-measures design, using analysis of covariance and conditional process analysis. RESULTS: Students who had high levels of knowledge and a strong sense of value for providing feedback to peers produced higher-quality supportive peer feedback. CONCLUSION: Even when a student has sufficient knowledge and skills to produce supportive peer feedback, their ability may not transfer to real peer-review contexts if they do not also have a strong sense of value for providing high-quality feedback to peers.

What is the selection process for osteoarthritis pharmacotherapy?

Osteoarthritis is the most prevalent joint condition that continues to increase with an ever-aging population and the rising tide of obesity. There are multiple recommendations/guidelines for the management of osteoarthritis. The basis of management should focus on self-management and education, lifestyle modifications, exercise and when appropriate, weight loss. Pharmacotherapy is targeted toward pain palliation with no agents available presently to target prevention and disease modification. The selection of pharmacotherapy should be tailored to the individual, taking into account of personal preferences and interactions with underlying co-morbidities. This editorial provides a guide to the selection process of presently available pharmacotherapy in osteoarthritis.

Superb Microvascular Imaging in Low-Grade Inflammation of Knee Osteoarthritis Compared With Power Doppler: Clinical, Radiographic and MRI Relationship.

We compared the assessment of active synovitis in knee osteoarthritis (OA) by utilising superb microvascular imaging (SMI) and conventional power Doppler (cPD) techniques, and then correlated each technique with paients' symptoms, radiographic features and magnetic resonance imaging (MRI)-detected synovitis. A subgroup of participants with symptomatic knee OA underwent dynamic ultrasound assessment for semi-quantitative scores for SMI and cPD in the suprapatellar, medial and lateral parapatellar knee recesses. Knee pain and other symptoms were evaluated with the knee injury and osteoarthritis outcome score (KOOS). OA severity was assessed using the Kellgren and Lawrence grade (KLG) on radiograph and effusion-synovitis and Hoffa's synovitis score of MRI osteoarthritis knee score on non-contrast-enhanced MRI sequences. The χ2 test and κ statistics were conducted to compare detectability of SMI and cPD for low-grade inflammation, and the Spearman's correlation and Fisher's r to z transformation were conducted to compare correlations of both techniques with symptoms and imaging severity. A total of 89 participants were included in the analyses. SMI increased the detection rate by 25.5% for grade 0 cPD, by 35.4% for grade 1 cPD and by 9% for grade 2 cPD. SMI showed significant correlations with KOOS symptoms, KLG, MRI effusion-synovitis and Hoffa's synovitis scores (r = -0.24 [-0.45, -0.01]; r = 0.31 [0.10, 0.50]; r = 0.49 [0.33, 0.63]; and r = 0.54 [0.37, 0.68]). The cPD was significantly correlated with KOOS pain, other symptoms, MRI effusion-synovitis and Hoffa's synovitis (r = -0.23 [-0.44, -0.01]; r = -0.29 [-0.49, -0.06]; r = 0.46 [0.28, 61], r = 0.46 [0.25, 0.63]). However, no significant differences were detected in their extent of correlations. SMI can detect low-grade inflammation implicated in OA disease better than cPD and reveal a significant correlation with symptoms, radiographic features and MRI synovitis. The added clinical value of SMI over cPD is still not clear.