세틸미리스톨레이트

Osteoarthritis and nutrition. From nutraceuticals to functional foods: a systematic review of the scientific evidence.

1. Arthritis Res Ther. 2006;8(4):R127. doi: 10.1186/ar2016. Osteoarthritis and nutrition. From nutraceuticals to functional foods: a systematic review of the scientific evidence. Ameye LG(1), Chee WS. Author information: (1)Nutrition and Health Department, Nestlé Research Center, Vers-chez-les-B

The minimal effective dose of cis-9-cetylmyristoleate (CMO) in persons presenting with knee joint pain: A double-blind, randomized, placebo-controlled trial.

1. Medicine (Baltimore). 2017 Mar;96(9):e6149. doi: 10.1097/MD.0000000000006149. The minimal effective dose of cis-9-cetylmyristoleate (CMO) in persons presenting with knee joint pain: A double-blind, randomized, placebo-controlled trial. Lee SC(1), Jin HS, Joo Y, Kim YC, Moon JY. Author information: (1)Department of Anesthesiology and Pain Medicine, Seoul National University Hospital Department of Anesthesiology and Pain Medicine, Samsung Medical Center Department of Anesthesiology and Pain Medicine, Integrated Cancer Management Center, Seoul National University Cancer Hospital, Seoul, Republic of Korea. BACKGROUND: Nutraceuticals containing cis-9-cetylmyristoleate (CMO) are used to improve knee pain despite the lack of placebo-controlled studies in humans. The aim of the study was to explore the minimal effective dose of CMO for relieving knee joint pain. METHODS: Twenty-eight subjects with mild degree arthritic knee joint pain were randomized into 4 groups; groups A, B, and C that contained 100%, 80%, and 62.4% of fatty acid component with 12.5% of CMO, and control group D (starch 100%). The pain intensity, functional disability, and the Patient Global Impression of Change (PGIC) were assessed for a 12-week ingestion period. RESULTS: Compared to group D (n = 6), there were significant differences in pain score in group A (n = 7, P = 0.005) and group C (n = 7, P = 0.012), but not significant in group B (n = 6, P = 0.180). Western Ontario and McMaster Universities Arthritis (WOMAC) score decreased significantly in groups A and C. The PGIC was positive in the majority (>50%) in groups A, B, and C, whereas negative in 83.3% in group D (control). CONCLUSION: CMO is effective in alleviating knee pain in persons with mild degree arthritis of the knee joint, at an effective dose of 62.4%. DOI: 10.1097/MD.0000000000006149 PMCID: PMC5340442 PMID: 28248869 [Indexed for MEDLINE] Conflict of interest statement: The authors have no conflicts of interest to disclose.

Effect of a cetylated fatty acid topical cream on functional mobility and quality of life of patients with osteoarthritis.

2. J Rheumatol. 2004 Apr;31(4):767-74. Effect of a cetylated fatty acid topical cream on functional mobility and quality of life of patients with osteoarthritis. Kraemer WJ(1), Ratamess NA, Anderson JM, Maresh CM, Tiberio DP, Joyce ME, Messinger BN, French DN, Rubin MR, Gómez AL, Volek JS, Hesslink R Jr. Author information: (1)Human Performance Laboratory, School of Medicine, University of Connecticut, Storrs, Connecticut 06269-1110, USA. William.Kraemer@uconn.edu OBJECTIVE: To examine the effect of a topical cream consisting of cetylated fatty acids on functional performance in patients diagnosed with osteoarthritis (OA) of one or both knees. METHODS: Forty patients diagnosed with knee OA were randomly assigned to one of 2 topical treatment groups: (1) cetylated fatty acid (CFA) (n = 20; age 62.7 +/- 11.7 yrs); or (2) placebo group (n = 20; age 64.6 +/- 10.5 yrs). Patients were tested on 3 occasions: (1) baseline (T1), (2) 30 min after initial treatment (T2), and (3) after 30-day treatment of cream application twice per day (T3). Assessments included knee range of motion (ROM), timed "up-and-go" from a chair and stair climbing, medial step-down test, and the unilateral anterior reach. RESULTS: For stair climbing ability and the up-and-go test, significant decreases in time were observed at T2 and T3 compared to T1 in the CFA group only. These differences were significant between groups. Supine ROM of the knees increased at T2 and T3 in CFA group, whereas no difference was observed in the placebo group. For the medial step-down test, significant improvement was observed at T2 and T3 compared to T1 in CFA group. For the unilateral anterior reach, significant improvement was observed for both legs in CFA group and in only the left leg in the placebo group. However, the improvements observed in CFA group were significantly greater than placebo group for both legs. CONCLUSION: Use of a CFA topical cream is an effective treatment for improving knee ROM, ability to ascend/descend stairs, ability to rise from sitting, walk and sit down, and unilateral balance. PMID: 15088305 [Indexed for MEDLINE]

Cetylated fatty acids improve knee function in patients with osteoarthritis.

3. J Rheumatol. 2002 Aug;29(8):1708-12. Cetylated fatty acids improve knee function in patients with osteoarthritis. Hesslink R Jr(1), Armstrong D 3rd, Nagendran MV, Sreevatsan S, Barathur R. Author information: (1)Hesslink Ventures, San Diego, California, USA. OBJECTIVE: To determine the benefit of cetylated fatty acids (CFA) on knee range of motion and function in patients with osteoarthritis (OA). METHODS: Sixty-four patients with chronic knee OA were evaluated at baseline and at 30 and 68 days after consuming either placebo (vegetable oil; n = 31) or CFA (Celadrin; n = 33). Evaluations included physician assessment, knee range of motion with goniometry, and the Lequesne Algofunctional Index (LAI). RESULTS: After 68 days, patients treated with CFA exhibited significant (p < 0.001) increase in knee flexion (10.1 degrees) compared to patients given placebo (1.1 degrees). Neither group reported improvement in knee extension. Patient responses to the LAI indicated a significant (p < 0.001) shift towards functional improvement for the CFA group (-5.4 points) after 68 days compared to a modest improvement in the placebo group (-2.1 points). CONCLUSION: Compared to placebo, CFA provides an improvement in knee range of motion and overall function in patients with OA of the knee. CFA may be an alternative to the use of nonsteroidal antiinflammatory drugs for the treatment of OA. PMID: 12180734 [Indexed for MEDLINE]

In Vitro Effects of Cetylated Fatty Acids Mixture from Celadrin on Chondrogenesis and Inflammation with Impact on Osteoarthritis.

1. Cartilage. 2020 Jan;11(1):88-97. doi: 10.1177/1947603518775798. Epub 2018 May 29. In Vitro Effects of Cetylated Fatty Acids Mixture from Celadrin on Chondrogenesis and Inflammation with Impact on Osteoarthritis. Hudita A(1), Galateanu B(1), Dinescu S(1), Costache M(1), Dinischiotu A(1), Negrei C(2), Stan M(2), Tsatsakis A(3), Nikitovic D(4), Lupuliasa D(5), Balanescu A(6). Author information: (1)Department of Biochemistry and Molecular Biology, University of Bucharest, Bucharest, Romania. (2)Departament of Toxicology, Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania. (3)Laboratory of Toxicology, School of Medicine, University of Crete, Heraklion, Greece. (4)Laboratory of Anatomy-Histology-Embryology, School of Medicine, University of Crete, Heraklion, Greece. (5)Department of Pharmaceutical Technology, Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania. (6)"Sfanta Maria" Clinical Hospital, "Carol Davila" University, Medicine and Pharmacy Faculty, Internal and Rheumatology Department, Bucharest, Romania. OBJECTIVE: Cetylated fatty acids are a group of naturally occurring fats of plant and/or animal origin. Cetyl myristoleate, in particular, was initially involved in osteoarthritis related research as its therapeutic administration prevented experimentally induced arthritis in Swiss Albino mice. In this context, the aim of our study was to investigate the possible mechanisms of Celadrin cetylated fatty acids action at the cellular level inflammation related pain relief and chondrogenesis. DESIGN: For this, we tested the effects of the cetylated fatty acids mixture from Celadrin on an in vitro scaffold-free 3-dimensional mesenchymal stem cells culture model of chondrogenesis. Furthermore, we treated stimulated mouse macrophage cells with the cetylated fatty acids mixture to investigate the expression profile of secreted inflammatory cytokines. RESULTS: The cetylated fatty acids mixture from Celadrin significantly decreased the production of IL-6, MCP-1, and TNF, key regulators of the inflammatory process, in stimulated RAW264.7 mouse macrophage cells. The treatment with cetylated fatty acids mixture initiated and propagated the process of chondrogenesis as demonstrated by the increased expression and deposition of chondrogenic markers by the differentiating mesenchymal cells. CONCLUSION: The cetylated fatty acids mixture from Celadrin reduces inflammation in vitro by significantly decreasing the expression of IL-6, MCP-1, and TNF in stimulated RAW264.7 mouse macrophage cells. These compounds facilitate the chondrogenic differentiation process of human adipose-derived stem cells by stimulating the expression of chondrogenic markers under chondrogenic induction conditions. DOI: 10.1177/1947603518775798 PMCID: PMC6921950 PMID: 29808705 [Indexed for MEDLINE] Conflict of interest statement: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Alternative therapies for traditional disease states: osteoarthritis.

2. Am Fam Physician. 2003 Jan 15;67(2):339-44. Alternative therapies for traditional disease states: osteoarthritis. Morelli V(1), Naquin C, Weaver V. Author information: (1)Family Practice Residency Program, Louisiana State University Health Sciences Center, Kenner, Louisiana 70065, USA. Comment in Am Fam Physician. 2003 Nov 1;68(9):1713; author reply 1713. Americans spend more on natural remedies for osteoarthritis than for any other medical condition. In treating osteoarthritis, glucosamine and chondroitin sulfate, two of the molecular building blocks found in articular cartilage, are the most commonly used alternative supplements. In randomized trials of variable quality, these compounds show efficacy in reducing symptoms, but neither has been shown to arrest progression of the disease or regenerate damaged cartilage. Although few clinical trials on S-adenosylmethionine exist, preliminary evidence indicates that it relieves pain to a degree similar to that of nonsteroidal anti-inflammatory drugs but with fewer side effects. Clinical trials of dimethyl sulfoxide offer conflicting results. Neither ginger nor cetyl myristoleate has proven clinical usefulness. PMID: 12562155 [Indexed for MEDLINE]

Synthesis of cetyl myristoleate and evaluation of its therapeutic efficacy in a murine model of collagen-induced arthritis.

3. Pharmacol Res. 2003 Jan;47(1):43-7. doi: 10.1016/s1043-6618(02)00239-6. Synthesis of cetyl myristoleate and evaluation of its therapeutic efficacy in a murine model of collagen-induced arthritis. Hunter KW Jr(1), Gault RA, Stehouwer JS, Tam-Chang SW. Author information: (1)Department of Microbiology, University of Nevada School of Medicine, Reno, NV 89557, USA. khunter@unr.edu Cetyl myristoleate (CM) was reported by Diehl and May [J Pharm Sci 83 (1994) 296] to block inflammation and prevent adjuvant-induced arthritis in rats. To verify this earlier work, we have synthesized pure CM and tested its anti-arthritic properties in a collagen-induced arthritis model in DBA/1LacJ mice. Multiple intraperitoneal injections of CM in 450 and 900 mg kg(-1) doses resulted in a significantly lower incidence of disease and caused a modest but significant diminution in clinical signs in those mice that developed arthritis. CM administered in daily oral doses of 20 mg kg(-1) also reduced the incidence of arthritis and caused a small reduction in the clinical signs in mice that developed arthritis. Although the protective effect of CM in collagen-induced arthritis observed in the present study was less dramatic than that reported earlier, our results confirm the anti-arthritic properties of pure CM. DOI: 10.1016/s1043-6618(02)00239-6 PMID: 12526860 [Indexed for MEDLINE]

Surfing the Net--information on the World Wide Web for persons with arthritis: patient empowerment or patient deceit?

4. J Rheumatol. 2001 Jan;28(1):185-91. Surfing the Net--information on the World Wide Web for persons with arthritis: patient empowerment or patient deceit? Suarez-Almazor ME(1), Kendall CJ, Dorgan M. Author information: (1)Veteran Affairs Medical Center, Health Services, Research, Baylor College of Medicine, Houston, Texas 77030, USA. mes@bcm.tmc.edu Comment in J Rheumatol. 2001 Jan;28(1):1-2. OBJECTIVE: In the past few years access to the Internet has become readily available. Patients are increasingly seeking and obtaining health information through the Internet, most often the World Wide Web (WWW). We assessed the content, authorship, and scope of the information available on WWW in relation to rheumatoid arthritis. METHODS: In an attempt to replicate use by the average person, a broad search of the Internet was conducted for the phrase "rheumatoid arthritis" using WebCrawler, a commonly used search engine. All the "hits" were critically assessed after visiting and collecting information from the respective Web sites in relation to relevance, scope, authorship, type of publication, and financial objectives. RESULTS: The search returned 537 hits. We evaluated 531-2 did not exist, 2 could not be contacted, one was not in English, and one required a membership to access. The 531 hits originated from 388 Web sites. Only 198 (51%) were considered to be relevant and 7 (2%) were of doubtful relevance. Thirty-four (17%) were posted by an individual, 57 (28%) by a nonprofit organization, 104 (51%) by a profit industry, and 10 (5%) by universities. Ninety-one (44%) promoted alternative therapies, the most common including cetyl-myristoleate, colloidal minerals, Pycnogenol, shark cartilage, and Tahitian Noni. Of the 107 sites with financial interests, 76 (71%) promoted alternative medicine. The first 100 hits only identified about a third of the nonprofit organizations or university owned Web pages. CONCLUSION: Many sites easily accessed by consumers appear to be profit based companies advertising an alternative product claimed to be effective for many conditions. These findings emphasize the need for critical evaluation of Web site contents. PMID: 11196523 [Indexed for MEDLINE]

Cetyl myristoleate isolated from Swiss albino mice: an apparent protective agent against adjuvant arthritis in rats.

5. J Pharm Sci. 1994 Mar;83(3):296-9. doi: 10.1002/jps.2600830307. Cetyl myristoleate isolated from Swiss albino mice: an apparent protective agent against adjuvant arthritis in rats. Diehl HW(1), May EL. Author information: (1)Department of Pharmacology, Medical College of Virginia, Richmond 23298. Cetyl myristoleate was isolated from National Institutes of Health, general purpose, Swiss albino mice that were immune to the polyarthritis induced in rats with Freund's adjuvant. This substance, or material synthesized from cetyl alcohol and myristoleic acid, afforded good protection against adjuvant-induced arthritic states in rats. In limited comparisons, cetyl oleate, also found in Swiss albino mice, gave lesser protection, whereas cetyl myristate and cetyl elaidate, the trans-isomer of cetyl oleate, appeared to be virtually ineffective. Dosage of the protective compound as well as the site of injection of Freund's adjuvant was important. DOI: 10.1002/jps.2600830307 PMID: 8207671 [Indexed for MEDLINE]

How are patient-reported pain outcomes associated with biomarker and structural pathology subtypes in knee osteoarthritis? An explorative evaluation in the IMI-APPROACH cohort.

6. Osteoarthr Cartil Open. 2025 Dec 11;8(1):100726. doi: 10.1016/j.ocarto.2025.100726. eCollection 2026 Mar. How are patient-reported pain outcomes associated with biomarker and structural pathology subtypes in knee osteoarthritis? An explorative evaluation in the IMI-APPROACH cohort. Jansen MP(1), Mastbergen SC(1), Wirth W(2)(3), Roemer FW(4)(5), Bacardit J(6), Bay-Jensen AC(7), Kloppenburg M(8)(9), Blanco FJ(10), Haugen IK(11), Berenbaum F(12)(13), Eijkelkamp N(14), Jarraya M(15). Author information: (1)Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. (2)Research Program for Musculoskeletal Imaging, Center for Anatomy and Cell Biology & Ludwig Boltzmann Institute for Arthritis and Rehabilitation (LBIAR), Paracelsus Medical University, Salzburg, Austria. (3)Chondrometrics GmbH, Freilassing, Germany. (4)Quantitative Imaging Center, Department of Radiology, Boston University School of Medicine, Boston, MA, USA. (5)Department of Radiology, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany. (6)Interdisciplinary Computing and Complex BioSystems (ICOS) Research Group, School of Computing, Newcastle University, Newcastle upon Tyne, United Kingdom. (7)ImmunoScience, Nordic Bioscience, Herlev, Denmark. (8)Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands. (9)Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands. (10)Grupo de Investigación de Reumatología (GIR), INIBIC - Complejo Hospitalario Universitario de A Coruña, SERGAS, Centro de Investigación CICA, Departamento de Fisioterapia y Medicina, Universidad de A Coruña, A Coruña, Spain. (11)Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway. (12)Department of Rheumatology, AP-HP Saint-Antoine Hospital, Paris, France. (13)Sorbonne University, INSERM CRSA, Paris, France. (14)Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. (15)Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. OBJECTIVE: To explore associations between patient-reported pain outcomes and knee osteoarthritis (OA) subtypes based on systemic biochemical markers and joint structural pathology as defined by MRI. METHODS: Data were obtained from 297 knee OA patients from the IMI-APPROACH study. Pain outcomes were assessed using the KOOS, WOMAC, ICOAP, NRS, PainDETECT, and a pain diary. Biochemical markers in serum and urine were used to classify patients into systemic biomarker subtypes (low tissue turnover, structural damage, and systemic inflammation) via k-means clustering. Structural pathology subtypes were determined using MRI into an inflammatory, meniscus/cartilage damage, and subchondral bone pathology subtype. Associations between pain measures and subtypes were analyzed using multivariable regression models adjusted for age, sex, and BMI. RESULTS: The systemic inflammation biomarker subtype was significantly associated with higher KOOS pain, WOMAC weight-bearing pain, NRS knee pain, and PainDETECT scores (all p ​≤ ​0.042 and β ​≥ ​0.12). The low tissue turnover subtype negatively associated with lower KOOS, WOMAC, and ICOAP constant pain (all p ​≤ ​0.22 and β ​≤ ​-0.13), and the structural damage subtype with lower PainDETECT scores (more nociceptive-like pain; p ​= ​0.046 and β ​= ​-0.12). Among MRI subtypes, meniscus/cartilage damage was significantly associated with lower PainDETECT scores (p ​= ​0.005 and β ​= ​-0.16). No significant associations were found for the subchondral bone subtype or pain diary outcomes. CONCLUSION: For commonly used pain questionnaires, pain severity seems linked with inflammatory activity more than structural damage. Structural damage is primarily associated with nociceptive-like pain according to PainDETECT, which might be valuable for patient selection to clinical trials and observational studies. © 2025 The Author(s). DOI: 10.1016/j.ocarto.2025.100726 PMCID: PMC12794487 PMID: 41531867 Conflict of interest statement: WW: Employee and shareholder of Chondrometrics GmbH. FWR: Shareholder of Boston Imaging Core Lab, LLC and consultant to Grünenthal GmbH. Editor in Chief Osteoarthritis Imaging. MK: Consulting fees from Pfizer, CHDR, Novartis, UCB, GSK, and Peptinov, all paid to institution. Royalties from Wolters-Kluwer and Springer Verlag, all paid to institution. FJB: Funding from Gedeon Richter Plc., Bristol-Myers Squibb International Corporation, Sun Pharma Global FZE, Celgene Corporation, Janssen Cilag International N.V, Janssen Research & Development, Viela Bio, Inc., Astrazeneca AB, UCB BIOSCIENCES GMBH, UCB BIOPHARMA SPRL, AbbVie Deutschland GmbH & Co.KG, Merck KGaA, Amgen, Inc., Novartis Farmacéutica, S.A., Boehringer Ingelheim España, S.A, CSL Behring, LLC, Glaxosmithkline Research & Development Limited, Pfizer Inc, Lilly S.A., Corbus Pharmaceuticals Inc., Biohope Scientific Solutions for Human Health S.L., Centrexion Therapeutics Corp., Sanofi, TEDEC-MEIJI FARMA S.A., KiniksaPharmaceuticals, Ltd. Grunenthal. IKH: Research grant (ADVANCE) from Pfizer (payment to institution) and personal fees from Abbvie, Novartis, Grünenthal and GSK, outside of the submitted work. FB: consulting fees from Grunenthal, GSK, Eli Lilly, Novartis, Pfizer, Servier, and 4P Pharma; honoraria from Viatris, Pfizer, and Zoetis; travel support from Nordic Pharma; holds patents related to 4Moving Biotech; serves on advisory boards for AstraZeneca, Sun Pharma, and Nordic Bioscience; and holds stock in 4P Pharma and 4Moving Biotech. CMO and co-founder of 4Moving Biotech. The other authors report no conflict of interest.

Clinical features and subgroup patterns in elderly and super-elderly TMD patients.

7. Sci Rep. 2025 Dec 13;16(1):371. doi: 10.1038/s41598-025-29749-x. Clinical features and subgroup patterns in elderly and super-elderly TMD patients. Lee YH(1)(2)(3), Jeon S(4), Kim TS(5), Kim HS(4), Auh QS(5), Noh YK(6)(7). Author information: (1)Department of Orofacial Pain and Oral Medicine, Dental Hospital, Kyung Hee University, Kyung Hee University School of Dentistry, #613 Hoegi-dong, Dongdaemun-gu, Seoul, 02447, South Korea. omod0209@gmail.com. (2)Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA, 02114, USA. omod0209@gmail.com. (3)Department of Orofacial Pain and Oral Medicine, Kyung Hee University Dental Hospital, #613 Hoegi-dong, Dongdaemun-gu, Seoul, 02447, South Korea. omod0209@gmail.com. (4)Department of Computer Science, Hanyang University, Seoul, 04763, South Korea. (5)Department of Orofacial Pain and Oral Medicine, Dental Hospital, Kyung Hee University, Kyung Hee University School of Dentistry, #613 Hoegi-dong, Dongdaemun-gu, Seoul, 02447, South Korea. (6)Department of Computer Science, Hanyang University, Seoul, 04763, South Korea. nohyung@hanyang.ac.kr. (7)School of Computational Sciences, Korea Institute for Advanced Study (KIAS), Seoul, 02455, South Korea. nohyung@hanyang.ac.kr. This cross-sectional study compares TMD signs and symptoms in patients aged ≥ 65 (elderly) and ≥ 85 (super-elderly) with younger age groups. Additionally, this study sought to identify the key factors contributing to increased pain intensity in elderly and super-elderly patients with TMD. A total of 4,661 patients with TMD (mean age = 42.22 ± 20.08 years, 3069 women and 1592 men) were analyzed, categorized into six age groups, including those aged 65–74, 75–84, and 85 + years. The clinical characteristics, pain intensity (VAS), and TMD subgroup distribution were examined. Generalized linear models and 2D/3D visualizations were used to explore the correlations and multivariable relationships. Of the 4,661 patients aged 7–113 years, 16.8% were elderly and 1.1% were super-elderly. The female-to-male ratios in the elderly group were 1.93:1 and 1.78:1, with females being predominant across all age groups. Elderly groups, including those aged 65–74 (3.92 ± 2.49), 75–84 (3.94 ± 2.73), and 85 + years (3.92 ± 2.49), had significantly higher VAS scores compared to younger age groups (p < 0.001), indicating moderate pain levels. Maximum mouth opening values were significantly smaller in the 75–84 (38.81 ± 10.79 mm) and 85 + groups (38.08 ± 12.79 mm) compared to younger groups (p < 0.001). Arthralgia was one of the most prevalent TMD subgroups in both elderly (58.2%) and super-elderly (50.0%) patients. Degenerative joint disease was more prevalent in the super-elderly group (48.0%) than in the elderly group (37.9%) (P < 0.05). Chronic TMD was most prevalent in the 0–19 years group (50.3%), followed by the super-elderly group (44.0%) (p < 0.001). GLM analysis showed that TMJ pain (B = 1.324, p < 0.001), TMJ noise (B = 0.757, p < 0.001), and age (B = 0.014, p < 0.001) were significantly associated with higher VAS scores, whereas increases in CMO (B = -0.011, p < 0.001) were associated with lower VAS scores. In the super-elderly group, the VAS score was also significantly associated with degenerative joint disease. The 2D and 3D visualizations revealed a tangled web of relationships among these clinical and diagnostic variables, showing how intricately they are intertwined and how they influence each other in complex patterns. This study provides valuable insights into the clinical patterns of TMD in elderly and super-elderly patients, emphasizing the need for tailored TMD management as this population grows. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-025-29749-x. DOI: 10.1038/s41598-025-29749-x PMCID: PMC12770324 PMID: 41390564 Conflict of interest statement: Declarations. Competing interests: The authors declare no competing interests. Approval for human experiments: The research protocol complied with the Declaration of Helsinki and was approved by the Institutional Review Board of Kyung Hee University Dental Hospital in Seoul, South Korea (IRB No.: KH-DT23-048-001). Consent to participate/consent to publish: Informed consent was obtained from all the participants involved in the study. For participants under the age of 18 years, informed consent for study participation was obtained from their parents or legal guardians. Written informed consent was obtained from all the participants.

Review of Safety and Efficacy of Polmacoxib: A Novel Dual Inhibitor of Cyclo-oxygenase 2 and Carbonic Anhydrase in Osteoarthritis and Acute Painful Conditions.

8. J Assoc Physicians India. 2025 Oct;73(10):88-92. doi: 10.59556/japi.73.1180. Review of Safety and Efficacy of Polmacoxib: A Novel Dual Inhibitor of Cyclo-oxygenase 2 and Carbonic Anhydrase in Osteoarthritis and Acute Painful Conditions. Gunjal VS(1), Pawar RR(2), Sharma AD(3). Author information: (1)Senior Medical Advisor, Department of Medical Affairs, Alkem Laboratories, Mumbai, Maharashtra, India, Corresponding Author, Orcid: https://orcid.org/0009-0001-5800-7008. (2)Head, Department of Medical Affairs, Alkem Laboratories, Mumbai, Maharashtra, India. (3)President and CMO, Department of Medical Affairs, Alkem Laboratories, Mumbai, Maharashtra, India, Orcid: https://orcid.org/0000-0001-6863-4729. Osteoarthritis (OA) is a chronic degenerative joint disorder and a leading cause of pain and disability among the elderly. Traditional nonsteroidal anti-inflammatory drugs (NSAIDs), though effective in symptom relief, pose significant risks of gastrointestinal, cardiovascular, and renal complications, especially in long-term use. Polmacoxib (CG100649) is a newer NSAID with its dual inhibitory role on cyclooxygenase-2 (COX-2) and carbonic anhydrase (CA), planned to offer higher therapeutic efficacy and safety. This review critically examines the pharmacodynamic and pharmacokinetic properties of polmacoxib, along with its clinical efficacy and safety in OA and acute pain conditions. Clinical trials across phases I-III consistently show polmacoxib to be well tolerated and effective in pain relief and efficient improvement of the joint, with a safety profile comparable to or better than traditional COX-2 inhibitors like celecoxib. Recent trials also explore its role in combination therapies for acute pain management, including dental and postoperative settings, showing noninferiority to standard regimens and fewer adverse events. Its innovative mechanism and pharmacological profile support its potential as a next-generation NSAID for OA and pain management, particularly in populations at high risk for NSAID-induced adverse effects. Further larger long-term studies are warranted to confirm its medical benefits and broader therapeutic applications. © Journal of The Association of Physicians of India 2025. DOI: 10.59556/japi.73.1180 PMID: 41100334 [Indexed for MEDLINE]

Cartilage loss is greater in knees with virtual joint replacement status than in matched controls without.

9. Osteoarthr Cartil Open. 2025 Aug 5;7(4):100658. doi: 10.1016/j.ocarto.2025.100658. eCollection 2025 Dec. Cartilage loss is greater in knees with virtual joint replacement status than in matched controls without. Eckstein F(1)(2), Wirth W(1)(2), Guermazi A(3), Roemer F(3)(4), Nevitt M(5), Ladel C(6), Sharma L(7), Hunter DJ(8), Kwoh CK(9)(10)(11). Author information: (1)Research Program for Musculoskeletal Imaging, Center for Anatomy and Cell Biology, and Ludwig Boltzmann Institute of Arthritis and Rehabilitation (LBIAR), Paracelsus Medical University (PMU) Salzburg, Austria. (2)Chondrometrics GmbH, Freilassing, Germany. (3)Department of Radiology, Chobanian & Avedisian Boston University School of Medicine, Boston, MA, USA. (4)Department of Radiology, Universitätsklinikum Erlangen & Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany. (5)Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA. (6)CHL4special Consultancy, Darmstadt, Germany. (7)Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago IL, USA. (8)Rheumatology Department, Royal North Shore Hospital. & Sydney Musculoskeletal Health, Kolling Institute, University Sydney, Sydney, Australia. (9)Department of Epidemiology, Grad. Sch. of Public Health, University of Pittsburgh, Pittsburgh, PA, USA. (10)Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. (11)Division of Rheumatology and University of Arizona Arthritis Center, University of Arizona College of Medicine, Tucson, AZ, USA. OBJECTIVE: We examined whether the trajectory of femorotibial cartilage loss differs between knees meeting a clinically defined virtual knee replacement (vKR) status based on patient-reported outcomes vs. those with low probability. DESIGN: vKR cases (highest 10 ​% of probabilities for having surgical KR) were selected using knee pain and quality of life criteria, developed from knees with actual KR. Knees reaching such symptom state at 48 months (M) follow-up (vKR case 60 ​M) were matched 1:1 with vKR controls (lowest 20 ​% probability) by sex, age, and baseline radiographic status. Of 65 knees displaying vKR case status at 60 ​M; 33 maintained or increased pain and QOL levels at 72 ​M (vKR+/+); 32 did not (vKR+/-). The thickness of medial and lateral tibial and femoral cartilages was determined from MRI, at up to five annual visits prior to 60 ​M. RESULTS: vKR case knees displayed substantially greater central medial femorotibial compartment cartilage thickness loss 2 years prior to reaching case status (-151 ​± ​337 [mean ​± ​SD] vs. -38 ​± ​249 ​μm; odds ratio [OR] 1.95 (95 ​% confidence interval: 1.23-3.08). Cartilage loss did not apparently differ between vKR+/+ and vKR +/- knees (p ​= ​0.73). CONCLUSIONS: Substantially greater cartilage thickness loss was detected in knees reaching vKR case status defined by patient-reported clinical criteria vs. vKR controls. This was found independently of whether this status was maintained at a later annual visit. The observed association suggests greater knee cartilage loss to be prospectively related to worse clinical outcome. It indicates further that the vKR criterion used here may be useful to explore relationships with other structural (imaging) assessments. © 2025 The Author(s). DOI: 10.1016/j.ocarto.2025.100658 PMCID: PMC12395530 PMID: 40893583 Conflict of interest statement: Felix Eckstein is co-owner and CEO of Chondrometrics GmbH, a company providing MR image analysis services to academic researchers and to the pharmaceutical industry. He has provided consulting services to MerckSerono, Galapagos/Servier, Kolon Tissue Gene, Novartis, Peptinov, Formation Bio, 4P Pharma, Sanofi, and Artialis. Wolfgang Wirth has a part time employment with Chondrometrics GmbH and is a co-owner of Chondrometrics GmbH. Ali Guermazi is President and co-owner of the Boston Core Imaging Lab (BICL). He has provided consulting services to TissueGene, Novartis, ICM, Paradigm, Formation Bio, 4Moving, Scarcell Therapeutics, Pacira, Coval, Medipost, Levicept and Peptinov. He is a Co-Editor-in-Chief of Skeletal Radiology. Frank Roemer is shareholder and CMO of Boston Core Imaging Lab (BICL), LLC. He received an institutional grant from the Else Kröner-Fresenius-Stiftung. He has provided consulting services to Grünenthal. He is Editor-in-Chief of the journal Osteoarthritis Imaging. Christoph Ladel was an employee of MerckKGaA and has provided consulting services to ReumaNederland, Charité, Formation Bio, Gordian Bio, Integra Holdings, CurNova and Regenosine. Travel support was received by netwOArk (COST action). C. Kent Kwoh Manuscript funding: NIH; Grants or contracts: AbbVie, Artiva, Lilly, BMS, Cumberland, Pfizer, GSK, Galapagos; Consulting fees: Trial Spark, Express Scripts, GSK, TLC Biosciences, AposHealth; Payment or honoraria for lectures: Focus Medical Communications, Participation on Data Safety; Monitoring or Advisory Board: Moebius Sun, Novartis, Xalud, Kolon Tissue Gene; Leadership or fiduciary role on a board: International Chinese Osteoarthritis Research Society (ICOARS). DJH is the Editor of the osteoarthritis section for UpToDate and co-Editor-in-Chief of Osteoarthritis and Cartilage. He provides consulting advice on scientific advisory boards for Haleon, TLCBio, Novartis, TissueGene, Sanofi, and Enlivex. Neither Michael Nevitt nor Leena Sharma have conflicts of interest to declare.

Platelet Rich Plasma for the Therapy of the Lumbar Facet Joint Syndrome: A Prospective Study About CT-Guided Facet Joint Injections With PRP Compared to Local Anesthetics.

10. Orthop Rev (Pavia). 2025 Aug 6;17:141416. doi: 10.52965/001c.141416. eCollection 2025. Platelet Rich Plasma for the Therapy of the Lumbar Facet Joint Syndrome: A Prospective Study About CT-Guided Facet Joint Injections With PRP Compared to Local Anesthetics. Baltzer AW(1), Enneper J(2), Baltzer LM(3), Godde G(4). Author information: (1)Orthopedic Surgery Center for Molecular Orthopedics. (2)Orthopedics Practice for Orthopedics and Sport. (3)Dentistry RWTH Aachen University. (4)Neurosurgery Center for Molecular Orthopedics. OBJECTIVE: To investigate the clinical effects of Leukocyte-poor-Platelet-Rich-Plasma (LpPRP) injections to treat chronic facet joint syndrome. METHODS: 78 patients suffering from chronic facet joint syndrome at the Center for Molecular Orthopedics (CMO) agreed to participate to this prospective controlled study to receiving a series of CT-guided PAT-injections (periarticular therapy) to lumbar facet joints. The patients were free to decide to receive either injections based on Platelet-Rich-Plasma (PRP) or local anesthetics (LA/bupivacaine). In this study leucocyte-poor PRP (LpPRP) was used for all patients of the verum group, namely autologous conditioned plasma (Arthrex ACP® / Arthrex Inc., Naples, FL, USA) as the verum group. 59 patients were treated 3-5 times in at least two levels of facet joints in the PRP group, 19 patients decided to join the LA group receiving local anesthetics (LA group) each in a weekly interval. All patients agreed to answer an automated email questionnaire for up to one year starting at baseline before receiving the first injections. The follow up protocol was based on a pain scale, and the Oswestry disability score. Data analysis was evaluated using the Excel analysis tools. RESULTS: Data analysis revealed that both, PRP and local anesthetics had a pain reducing effect initially at week 2 after receiving the first PAT, but from week six on up to one year post injection, PRP infiltrations were superior with a significantly reduced pain score compared to baseline up to one year (p<0.001). Oswestry score showed similar results with a significant improvement to about one half compared to baseline (p<0.001) up to six months, still being significantly better at one year (p<0.01). The comparison of the PRP group to the LA group showed a better pain relief and better values at the Oswestry disability score between three and six months and one year. CONCLUSIONS: We show that a CT-guided injection therapy (PAT) based on LpPRP addressing the facet joint mediated low back pain syndrome leads to a significant long term pain reduction, and to a significant improvement in the Oswestry disability score for at least one year. DOI: 10.52965/001c.141416 PMCID: PMC12352341 PMID: 40823278

A virtual knee replacement (vKR) multi-component endpoint for knee osteoarthritis based on patient-reported PROs: Data from the Osteoarthritis Initiative.

11. Osteoarthritis Cartilage. 2025 Nov;33(11):1372-1381. doi: 10.1016/j.joca.2025.08.001. Epub 2025 Aug 6. A virtual knee replacement (vKR) multi-component endpoint for knee osteoarthritis based on patient-reported PROs: Data from the Osteoarthritis Initiative. Kwoh CK(1), Boudreau RM(2), Eckstein F(3), Roemer FW(4), Hannon MJ(5), Guermazi A(6), Hunter DJ(7). Author information: (1)University of Arizona Arthritis Center and the Division of Rheumatology, University of Arizona College of Medicine-Tucson, Tucson, AZ, United States. Electronic address: Kwoh@arthritis.arizona.edu. (2)Department of Epidemiology, University of Pittsburgh School of Public Health, Pittsburgh, PA, United States. Electronic address: boudreaur@edc.pitt.edu. (3)Research Program for Musculoskeletal Imaging, Center for Anatomy and Cell Biology & Ludwig Boltzmann Institute for Arthritis and Rehabilitation (LBIAR), Paracelsus Medical University, Salzburg, Austria; Chondrometrics GmbH, Freilassing, Germany. Electronic address: felix.eckstein@pmu.ac.at. (4)Department of Radiology, Universitätsklinikum Erlangen & Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; Boston University School of Medicine, Boston, MA, United States. Electronic address: Frank.Roemer@uk-erlangen.de. (5)Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States. (6)Department of Radiology, Boston University School of Medicine, Boston, MA, United States. Electronic address: guermazi@bu.edu. (7)Royal North Shore Hospital, Rheumatology Department, and Sydney Musculoskeletal Health, Kolling Institute, University of Sydney, Sydney, NSW, Australia. Electronic address: david.hunter@sydney.edu.au. OBJECTIVE: To use patient-reported outcomes (PROs) and performance measures to develop a multi-component outcome (virtual knee replacement [vKR]) that predicts knee replacement (KR). METHODS: Osteoarthritis Initiative (OAI) participants with baseline radiographs, clinical assessments and health insurance were followed for 60 months. Of 8205 knees (4143 participants), 206 knees (187 participants) had KR. Eighteen clinical measures available at annual visits were considered, (e.g., Knee injury and Osteoarthritis Outcome Score knee pain (KOOS KP), frequency, severity, and Quality of Life (QoL), frequent knee pain, knee pain severity, SF12 Mental Health and Physical Health subscales, physical activity, depression, 20-meter walk and chair stands). Combinations of these were evaluated utilizing logistic regression to predict KRs in the next year. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were assessed. RESULTS: The most accurate models for predicting KR incorporated KOOS KP and KOOS QoL at a specific annual visit, and KOOS KP worsening over the previous year combined as weighted sums. Per 10 points of these assessments the odds of vKR increased by 30 % to 65 %. AUCs ranged from 0.87 to 0.92 (vKR1). Constraining KOOS KP and KOOS QoL to be worse at follow-up than at baseline, AUCs exceeded 0.85 (vKR2). When KOOS KP and KOOS QoL remained unchanged or worsened over one year, AUCs were >0.80 (vKR3). CONCLUSION: The three vKR criteria represent potential clinical multi-component outcomes for clinical trials of knee OA. After further validation, any of them may serve as a standalone clinical outcome or in combination with actual knee replacement. Copyright © 2025 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. DOI: 10.1016/j.joca.2025.08.001 PMCID: PMC12448240 PMID: 40780453 [Indexed for MEDLINE] Conflict of interest statement: Declaration of Competing Interest C. Kent Kwoh - Manuscript funding: NIH Grants or contracts: AbbVie, Artiva, Lilly, BMS, Cumberland, Pfizer, GSK, Galapagos Consulting fees: Trial Spark, Express Scripts, GSK, TLC Biosciences, AposHealth Payment or honoraria for lectures: Focus Medical Communications Participation on Data Safety Monitoring or Advisory Board: Moebius Sun, Novartis, Xalud, Kolon Tissue Gene Leadership or fiduciary role on a board: International Chinese Osteoarthritis Research Society (ICOARS). Robert M. Boudreau - Manuscript funding: NIH. Felix Eckstein - Co-owner/CEO of Chondrometrics GmbH, a company providing MR image analysis services to academic researchers and to the pharmaceutical industry Consulting fees: MerckSerono, Galapagos/Servier, Kolon Tissue Gene, Novartis, Peptinov, Formation Bio, 4P Pharma, Sanofi, Artialis. Frank W. Roemer - Shareholder/CMO of Boston Core Imaging Lab (BICL), LLC. Institutional grant: Else Kröner-Fresenius-Stiftung Consulting fees: Grünenthal. Editor-in-Chief of Osteoarthritis Imaging. Michael J. Hannon - Manuscript funding: NIH. Ali Guermazi - President/Co-owner of the Boston Core Imaging Lab (BICL), LLC. Consulting fees: TissueGene, Novartis, ICM, Paradigm, Formation Bio, 4Moving, Scarcell Therapeutics, Pacira, Coval, Medipost, Levicept, Peptinov. Co-Editor-in-Chief of Skeletal Radiology.

Plasmodium knowlesi (Pk) Malaria: A Review & Proposal of Therapeutically Rational Exchange (T-REX) of Pk-Resistant Red Blood Cells.

12. Trop Med Infect Dis. 2023 Oct 20;8(10):478. doi: 10.3390/tropicalmed8100478. Plasmodium knowlesi (Pk) Malaria: A Review & Proposal of Therapeutically Rational Exchange (T-REX) of Pk-Resistant Red Blood Cells. Jajosky RP(1)(2), Wu SC(1), Jajosky PG(2), Stowell SR(1). Author information: (1)Joint Program in Transfusion Medicine, Brigham and Women's Hospital, Harvard Medical School, 630E New Research Building, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. (2)Biconcavity Inc., Lilburn, GA 30047, USA. Plasmodium knowlesi (Pk) causes zoonotic malaria and is known as the "fifth human malaria parasite". Pk malaria is an emerging threat because infections are increasing and can be fatal. While most infections are in Southeast Asia (SEA), especially Malaysia, travelers frequently visit this region and can present with Pk malaria around the world. So, clinicians need to know (1) patients who present with fever after recent travel to SEA might be infected with Pk and (2) Pk is often misdiagnosed as P. malariae (which typically causes less severe malaria). Here we review the history, pathophysiology, clinical features, diagnosis, and treatment of Pk malaria. Severe disease is most common in adults. Signs and symptoms can include fever, abdominal pain, jaundice, acute kidney injury, acute respiratory distress syndrome, hyponatremia, hyperparasitemia, and thrombocytopenia. Dengue is one of the diseases to be considered in the differential. Regarding pathophysiologic mechanisms, when Pk parasites invade mature red blood cells (RBCs, i.e., normocytes) and reticulocytes, changes in the red blood cell (RBC) surface can result in life-threatening cytoadherence, sequestration, and reduced RBC deformability. Since molecular mechanisms involving the erythrocytic stage are responsible for onset of severe disease and lethal outcomes, it is biologically plausible that manual exchange transfusion (ET) or automated RBC exchange (RBCX) could be highly beneficial by replacing "sticky" parasitized RBCs with uninfected, deformable, healthy donor RBCs. Here we suggest use of special Pk-resistant donor RBCs to optimize adjunctive manual ET/RBCX for malaria. "Therapeutically-rational exchange transfusion" (T-REX) is proposed in which Pk-resistant RBCs are transfused (instead of disease-promoting RBCs). Because expression of the Duffy antigen on the surface of human RBCs is essential for parasite invasion, T-REX of Duffy-negative RBCs-also known as Fy(a-b-) RBCs-could replace the majority of the patient's circulating normocytes with Pk invasion-resistant RBCs (in a single procedure lasting about 2 h). When sequestered or non-sequestered iRBCs rupture-in a 24 h Pk asexual life cycle-the released merozoites cannot invade Fy(a-b-) RBCs. When Fy(a-b-) RBC units are scarce (e.g., in Malaysia), clinicians can consider the risks and benefits of transfusing plausibly Pk-resistant RBCs, such as glucose-6-phosphate dehydrogenase deficient (G6PDd) RBCs and Southeast Asian ovalocytes (SAO). Patients typically require a very short recovery time (<1 h) after the procedure. Fy(a-b-) RBCs should have a normal lifespan, while SAO and G6PDd RBCs may have mildly reduced half-lives. Because SAO and G6PDd RBCs come from screened blood donors who are healthy and not anemic, these RBCs have a low-risk for hemolysis and do not need to be removed after the patient recovers from malaria. T-REX could be especially useful if (1) antimalarial medications are not readily available, (2) patients are likely to progress to severe disease, or (3) drug-resistant strains emerge. In conclusion, T-REX is a proposed optimization of manual ET/RBCX that has not yet been utilized but can be considered by physicians to treat Pk malaria patients. DOI: 10.3390/tropicalmed8100478 PMCID: PMC10610852 PMID: 37888606 Conflict of interest statement: Ryan Jajosky is CEO of Biconcavity Inc. Philip Jajosky is CMO of Biconcavity Inc.

Amsterdam 2022 process: A summary of the methodology for the Amsterdam International Consensus on Concussion in Sport.

13. Br J Sports Med. 2023 Jun;57(11):712-721. doi: 10.1136/bjsports-2022-106663. Amsterdam 2022 process: A summary of the methodology for the Amsterdam International Consensus on Concussion in Sport. Schneider KJ(1)(2)(3), Patricios JS(4), Meeuwisse W(5), Schneider GM(6), Hayden KA(7), Premji Z(8), Ahmed OH(9)(10)(11), Blauwet C(12)(13), Broglio S(14), Cantu RC(15)(16), Davis GA(17)(18), Dvorak J(19), Echemendia RJ(20), Emery CA(21), Iverson GL(22)(23), Leddy JJ(24), Makdissi M(25)(26), McCrea M(27), McNamee M(28)(29), Putukian M(30), Yeates KO(2)(3)(31), Black AM(21), Burma JS(21), Critchley M(32), Eliason PH(32), Räisänen AM(33), Tabor JB(32), Toomey C(21)(34), Ronksley PE(35), Cassidy JD(36). Author information: (1)Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada kjschnei@ucalgary.ca. (2)Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada. (3)Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada. (4)Wits Sport and Health (WiSH), School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. (5)National Hockey League, New York City, New York, USA. (6)Department of Radiology, University of Calgary, Calgary, Alberta, Canada. (7)Libraries and Cultural Resources, University of Calgary, Calgary, Alberta, Canada. (8)Libraries, University of Victoria, Victoria, British Columbia, Canada. (9)Physiotherapy Department, University Hospitals Dorset NHS Foundation Trust, Poole, UK. (10)The FA Centre for Para Football Research, The Football Association, Burton-Upon-Trent, UK. (11)School of Sport, Health and Exercise Science, University of Portsmouth, Portsmouth, UK. (12)Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation, Spaulding Hospital/Brigham and Women's Hospital, Harvard Medical School, Charlestown, Massachusetts, USA. (13)Kelley Adaptive Sports Research Institute, Boston, Massachusetts, USA. (14)Michigan Concussion Center, University of Michigan, Ann Arbor, Michigan, USA. (15)Centre for the Study of Traumatic Encephalopathy, Boston University School of Medicine, Boston, Massachusetts, USA. (16)Neurosurgery, Boston University School of Medicine, Boston, Massachusetts, USA. (17)Murdoch Children's Research Institute, Parkville, Victoria, Australia. (18)Cabrini Health, Malvern, Victoria, Australia. (19)Spine Unit, Schulthess Clinic Human Performance Lab, Zurich, Switzerland. (20)Psychology, University of Missouri Kansas City, Kansas City, Missouri, USA. (21)Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada. (22)Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts, USA. (23)Sports Concussion Program, MassGeneral Hospital for Children, Boston, Massachusetts, USA. (24)UBMD Orthopaedics and Sports Medicine, SUNY Buffalo, Buffalo, New York, USA. (25)Florey Institute of Neuroscience and Mental Health - Austin Campus, Heidelberg, Victoria, Australia. (26)La Trobe Sport and Exercise Medicine Research Centre, Melbourne, Victoria, Australia. (27)Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA. (28)Department of Movement Sciences, Katholieke Universiteit (KU) Leuven, Leuven, Belgium. (29)Swansea University, Swansea, UK. (30)Major League Soccer, Major League Soccer, New York, New York, USA. (31)Department of Psychology, University of Calgary, Calgary, Alberta, Canada. (32)University of Calgary, Calgary, Alberta, Canada. (33)Department of Physical Therapy Education - Oregon, Western University of Health Sciences College of Health Sciences - Northwest, Lebanon, Oregon, USA. (34)School of Allied Health, University of Limerick, Limerick, Ireland. (35)Community Health Sciences, University of Calgary, Calgary, Alberta, Canada. (36)Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada. The purpose of this paper is to summarise the consensus methodology that was used to inform the International Consensus Statement on Concussion in Sport (Amsterdam 2022). Building on a Delphi process to inform the questions and outcomes from the 5th International Conference on Concussion in Sport, the Scientific Committee identified key questions, the answers to which would help encapsulate the current science in sport-related concussion and help guide clinical practice. Over 3½ years, delayed by 2 years due to the pandemic, author groups conducted systematic reviews on each selected topic. The 6th International Conference on Concussion in Sport was held in Amsterdam (27-30 October 2022) and consisted of 2 days of systematic review presentations, panel discussions, question and answer engagement with the 600 attendees, and abstract presentations. This was followed by a closed third day of consensus deliberations by an expert panel of 29 with observers in attendance. The fourth day, also closed, was dedicated to a workshop to discuss and refine the sports concussion tools (Concussion Recognition Tool 6 (CRT6), Sport Concussion Assessment Tool 6 (SCAT6), Child SCAT6, Sport Concussion Office Assessment Tool 6 (SCOAT6) and Child SCOAT6). We include a summary of recommendations for methodological improvements for future research that grew out of the systematic reviews. © Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ. DOI: 10.1136/bjsports-2022-106663 PMID: 37316208 [Indexed for MEDLINE] Conflict of interest statement: a Competing interests: OHA is a Senior Physiotherapist at University Hospitals Dorset NHS Foundation Trust (England) and is Para Football Physiotherapy Lead/Para Football Classification Lead at the Football Association (England). He also works on a consultancy basis with the Football Association as the squad physiotherapist to the England Cerebral Palsy Football squad, and teaches on the Football Association’s Advanced Trauma and Medical Management in Football course on a consultancy basis. He has a Visiting Senior Lecturer position at the University of Portsmouth, England (unpaid). He sits on several disability sport committees including Para Football Foundation as Medical Unit Co-Lead (unpaid), the International Federation of Cerebral Palsy Football as Medical and Sports Science Director (unpaid), and the International Blind Sports Association as Medical Committee member (unpaid). He has Associate Editor positions at the British Journal of Sports Medicine (unpaid) and British Medical Journal (BMJ) Open Sports & Exercise Medicine (unpaid). He is also an Institutional Ethics Committee external member for World Rugby (unpaid), and co-chair of the Concussion in Para Sport Group (unpaid). AB has received peer-reviewed research funding from the Social Sciences and Humanities Research Council. She is also a Sport Information Resource Centre board member and Canadian Athletic Therapists Association committee member. She has received an honorarium for the administrative aspects of the reviews. CB is an Associate Professor of Physical Medicine & Rehabilitation (PM&R) at Spaulding Rehabilitation Hospital/Harvard Medical School and Chief Medical Officer at Spaulding Rehabilitation Hospital. She receives grant funding from the United States (US) Center for Disease Control (CDC) and Prevention and the U.S. National Institute on Disability, Independent Living, and Rehabilitation Research. She serves on the Board of Directors of the United States Olympic & Paralympic Committee (unpaid) as well as the International Paralympic Committee Medical Committee (unpaid) and the International Olympic Committee Medical & Scientific Commission (unpaid). She serves as an Associate Editor of the British Journal of Sports Medicine (unpaid) as well as the PM&R Journal (unpaid). SB current or past research funding from the National Institutes of Health; Centers for Disease Control and Prevention (CDC); Department of Defense - USA Medical Research Acquisition Activity, National Collegiate Athletic Association (NCAA); National Athletic Trainers’ Association Foundation; National Football League (NFL)/Under Armour/General Electric (GE); Simbex; and ElmindA. He has consulted for US Soccer (paid), US Cycling (unpaid), University of Calgary SHRed Concussions external advisory board (unpaid), medicolegal litigation, and received speaker honorarium and travel reimbursements (including Concussion in Sport Group -CISG) for talks given. He is coauthor of “Biomechanics of Injury (3rd edition)” and has a patent pending on “Brain Metabolism Monitoring Through CCO Measurements Using All-Fiber-Integrated Super-Continuum Source” (US Application No. 17/164,490). He is/was on the editorial boards (all unpaid) for Journal of Athletic Training (2015 to present), Concussion (2014 to present), Athletic Training & Sports Health Care (2008 to present), British Journal of Sport Medicine (2008 to 2019). JSB is supported by the University of Calgary, the Natural Sciences and Engineering Research Council [CGSD3-559333- 2021], and an honorarium for the methods author work associated with Reviews two and four. RCC is a Senior Advisor NFL Head Neck & Spine Committee VP NOCSAE and Chair Scientific Advisory CommitteeCo-Founder Medical Director Concussion Legacy FoundationRoyalties Houghton Mifflin Harcourt Legal Expert Opinion. JDC National Collegiate Athletic Association payments for expert testimony. National Hockey League (NHL) payments for expert testimony. GAD is a member of the Scientific Committee of the 6th International Conference on Concussion in Sport; anhonorary member of the Australian Football League (AFL) Concussion Scientific Committee; Section Editor, Sport and Rehabilitation, NEUROSURGERY; and has attended meetings organised by sporting organisations including the NFL, National Rugby League (NRL), International Ice Hockey Federation (IIHF), International Olympic Committee (IOC) and Federation International de Football Association (FIFA); however, has not received any payment, research funding or other monies from these groups other than for travel costs. JD has nothing to disclose. RJE is a paid consultant for the NHL and co-chair of the NHL/NHL Players Association (NHLPA) Concussion Subcommittee. He is also a paid consultant and chair of the Major League Soccer concussion committee, and a consultant to the US Soccer Federation. He previously served as a neuropsychology consultant to Princeton University Athletic Medicine and EyeGuide. He is currently a co-Primary Investigator (PI) for a grant funded by the NFL (NFL-Long) through Boston Children’s Hospital. He occasionally provides expert testimony in matters related to mTBI and sports concussion, and occasionally receives honoraria and travel support/reimbursement for professional meetings. PE is a data consultant to the National Hockey League; received an honorarium for the administrative aspects of the reviews. CAE has received external peer-reviewed research funding from Canadian Institutes of Health Research (CIHR), Canada Foundation for Innovation, International Olympic Committee Medical and Scientific Committee, NFL Play Smart Play Safe Program, and World Rugby. She is an Associate Editor of British Journal of Sport Medicine (BJSM) (unpaid) and has received travel and accommodation support for meetings where she has presented. She is an external advisory board member (unpaid) for HitIQ. KAH has nothing to disclose. GI, PhD serves as a scientific advisor for NanoDX®, Sway Operations, LLC, and Highmark, Inc. He has a clinical and consulting practice in forensic neuropsychology, including expert testimony, involving individuals who have sustained mTBIs (including former athletes). He has received research funding from several test publishing companies, including ImPACT Applications, Inc., CNS Vital Signs, and Psychological Assessment Resources (PAR, Inc.). He has received research funding as a principal investigator from the NFL, and subcontract grant funding as a collaborator from the Harvard Integrated Program to Protect and Improve the Health of NFL Players Association Members. He has received research funding from the Wounded Warrior Project™. He acknowledges unrestricted philanthropic support from ImPACT Applications, Inc., the Mooney-Reed Charitable Foundation, Boston Bolts, the National Rugby League, and the Schoen Adams Research Institute at Spaulding Rehabilitation. JJL receives grant/research support from National Institutes of Health (NIH), Department of Defence (DoD) and American Medical Society for Sports Medicine (AMSSM); is a member of the Scientific Advisory Board for Neuronasal, Highmark Innovations, and Quadrant Biosciences; minority stock options in Highmark Innovations and 360 Concussion Care; expert consultant to NCAA. Consults with NFL and NHL teams on athlete care but does not receive any compensation from these organisations; Editorial Board of Journal of Head Trauma Rehabilitation. MM is sport and exercise medicine physician working in private consulting practice. He is the Chief Medical Officer for the Australian Football League (AFL) and an independent consultant to World Rugby. He is a Shareholder of Olympic Park Sports Medicine Centre in Melbourne. He has previously held positions as the senior physician at the Hawthorn Hawks Football Club (AFL) and Chief Executive Officer of the AFL Doctors Association. He has received research grants from the Australian Football League, outside the submitted work. He has received travel support received from the Australian Football League, FIFA and the International Olympic Committee to attend and present at international conferences. Member of the Scientific Committee for the 6th International Conference on Concussion in Sport. Honorary member of the International CISG and an honorary member of the Australian Rugby Union Concussion Advisory Group. MMcC reports research grants from the US NIH, US Department of Defense, US CDC, US Department of Veterans Affairs, Abbott Laboratories, NFL, and NCAA, and consultancy with the Green Bay Packers and Neurotrauma Sciences, Inc. MMcN 1. Chair, Ethics Expert Group, World Antidoping Agency (WADA) (2021–23) (paid) 2. Member, International Boxing Association, Ethics and Integrity Committee, (2021–22; resigned Oct 2022) (paid) 3. Chair, Therapeutic Use Exemption Fairness Committee (2020–) (paid) 4. Member, Steering Group, Sex Segregation in Sport, International Association of Athletics Federations (IAAF)/World Athletics, (2019–20) (unpaid) 5. Member, International Ice Hockey Federation, Ethics and Integrity Committee (2019–21) (paid) 6. Member, International Olympic Committee Consensus Statement Expert Group on Injuries in Children and Adolescents (2017) (unpaid) 7. Member, Ethics Expert Group, WADA (2016–21) (unpaid) 8. Member, International Olympic Committee Consensus Statement Expert Group on Pain Management (2016)) (unpaid). WM is employed as the Chief Medical Officer of the National Hockey League. JP: Editor BJSM (honorarium); Member of World Rugby Concussion Advisory Group (unpaid); Independent Concussion Consultant for World Rugby (fee per consultation); Medical consultant to South African Rugby (unpaid); Co-chair of the Scientific Committee, 6th International Conference on Concussion in Sport (unpaid); Board member of the CISG (unpaid); Scientific Board member, EyeGuideTM (unpaid). ZP has no conflicts of interests to declare. MP declares the following: Consultant, Chief Medical Officer (CMO), Major League Soccer; Senior Advisor, NFL Head, Neck NCAA-CARE-DoD 2.0, ended 2020; Have received honoraria and reimbursement for travel for speaking and conferences attended; Have written chapters for UpToDate, and received royalties for the Netter’s Sports Medicine textbook; Have provided work as an expert for cases involving concussion, team physician and other sports medicine topics. AMR: Stipend for the clerical and administrative aspects of the systematic review. Tonal Strength Institute: Research grant (not specifically related to the present work). Alberta Bone and Joint Strategic Clinical Network: Research grant (not specifically related to the present work). PER has no conflicts of interest to declare. GMS is an owner of a multidisciplinary practice (managing patients with MSK pain disorders). He is a board member of Hockey Calgary (Calgary, AB, Canada) and Chair of the Alberta Association of Physiotherapy. He received funding for the administrative aspects of the writing of two of the systematic reviews that informed the consensus process. KJS has received grant funding from the CIHR, NFL Scientific Advisory Board, International Olympic Committee Medical and Scientific Research Fund, World Rugby, Mitacs Accelerate, University of Calgary, with funds paid to her institution and not to her personally. She is an Associate Editor of BJSM (unpaid), Independent consultant to World Rugby and has received travel and accommodation support for meetings where she has presented. She coordinated the writing of the systematic reviews that informed Amsterdam International Consensus on Concussion in Sport, for which she has received an educational grant to assist with the administrative costs associated with the writing of the reviews (with funds paid to her institution). She is a member of the AFL Concussion Scientific Committee (unpaid position), Brain Canada (unpaid positions) and Board member of the Concussion in Sport Group (CISG)(unpaid). She works as a physiotherapy consultant and treats athletes of all levels of sport from grass roots to professional. JT: Doctoral funding through the CIHR; Jason also received an honorarium for the administrative parts of the review. KOY holds the Ronald and Irene Ward Chair in Pediatric Brain Injury funded by the Alberta Children’s Hospital Foundation. He is a principal investigator on grants from the CIHR, and co-investigator on research grants from CIHR, Brain Canada Foundation, Social Science and Humanities Research Council (Canada), and NFL Scientific Advisory Board. He is the Editor of Neuropsychology, for which he receives an editorial stipend from the American Psychological Association. He chairs the Canadian Concussion Network, which is funded by CIHR. He is a member of the Scientific Advisory Committee for Brain Injury Canada and the National Research Advisory Council for the National Pediatric Rehabilitation Resource Center.

Which risk factors determine cartilage thickness and composition change in radiographically normal knees? - Data from the Osteoarthritis Initiative.

14. Osteoarthr Cartil Open. 2023 Apr 28;5(3):100365. doi: 10.1016/j.ocarto.2023.100365. eCollection 2023 Sep. Which risk factors determine cartilage thickness and composition change in radiographically normal knees? - Data from the Osteoarthritis Initiative. Eckstein F(1)(2), Maschek S(1)(2), Culvenor A(1)(3), Sharma L(4), Roemer FW(5)(6), Duda GN(7), Wirth W(1)(2). Author information: (1)Department of Imaging and Functional Musculoskeletal Research, Institute of Anatomy and Cell Biology & Ludwig Boltzmann Intitute of Arthritis & Rehabilitation (LBIAR), Paracelsus Medical University Salzburg & Nuremberg, Salzburg, Austria. (2)Chondrometrics GmbH, Ainring, Germany. (3)La Trobe Sport and Exercise Medicine Research Centre, School of Allied Health La Trobe University, Bundoora, Australia. (4)Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago IL, USA. (5)Department of Radiology, Friedrich-Alexander University Erlangen-Nürnberg & Universitätsklinikum Erlangen, Erlangen, Germany. (6)Department of Radiology, Boston University School of Medicine, Boston, MA, USA. (7)Julius Wolff Institute, Berlin-Brandenburg Institute of Health at Charité - Universitätsmedizin Berlin, Germany. OBJECTIVE: Therapy for osteoarthritis ideally aims at preserving structure before radiographic change occurs. This study tests: a) whether longitudinal deterioration in cartilage thickness and composition (transverse relaxation-time T2) are greater in radiographically normal knees "at risk" of incident osteoarthritis than in those without risk factors; and b) which risk factors may be associated with these deteriorations. DESIGN: 755 knees from the Osteoarthritis Initiative were studied; all were bilaterally Kellgren Lawrence grade [KLG] 0 initially, and had magnetic resonance images available at 12- and 48-month follow-up. 678 knees were "at risk", whereas 77 were not (i.e., non-exposed reference). Cartilage thickness and composition change was determined in 16 femorotibial subregions, with deep and superficial T2 being analyzed in a subset (n ​= ​59/52). Subregion values were used to compute location-independent change scores. RESULTS: In KLG0 knees "at risk", the femorotibial cartilage thinning score (-634 ​± ​516 ​μm) over 3 years exceeded the thickening score by approximately 20%, and was 27% greater (p ​< ​0.01; Cohen D -0.27) than the thinning score in "non-exposed" knees (-501 ​± ​319 ​μm). Superficial and deep cartilage T2 change, however, did not differ significantly between both groups (p ​≥ ​0.38). Age, sex, body mass index, knee trauma/surgery history, family history of joint replacement, presence of Heberden's nodes, repetitive knee bending were not significantly associated with cartilage thinning (r2<1%), with only knee pain reaching statistical significance. CONCLUSIONS: Knees "at risk" of incident knee OA displayed greater cartilage thinning scores than those "non-exposed". Except for knee pain, the greater cartilage loss was not significantly associated with demographic or clinical risk factors. © 2023 The Author(s). DOI: 10.1016/j.ocarto.2023.100365 PMCID: PMC10188628 PMID: 37207279 Conflict of interest statement: Dr. Maschek and Dr. Wirth are part time employees and co-owners of Chondrometrics GmbH. Dr. Roemer was a part time employee of Chondrometrics during the funding period of the grant by the Bundesministerium für Bildung und Forschung (BMBF – 01EC1408D OVERLOAD-PREVOP) from 10/2015 until 02/2019 and is shareholder, CMO and Director of Research of Boston Imaging Core Lab (BICL), LLC. Dr. Duda and Dr. Sharma have no conflicts to declare. Dr. Eckstein is CEO/CMO and co-owner of Chondrometrics GmbH, and he has provided consulting services to Merck KGaA, Samumed, Tissuegene, Servier, Galapagos and Roche. He also has received speaker honoraria from Medtronic.

Effectiveness of Vitamin D along with Splint therapy in the Vit D deficient patients with Temporomandibular disorder-A Randomized, double-blind, placebo-controlled clinical trial.

15. J Indian Prosthodont Soc. 2022 Jan-Mar;22(1):65-73. doi: 10.4103/jips.jips_334_21. Effectiveness of Vitamin D along with Splint therapy in the Vit D deficient patients with Temporomandibular disorder-A Randomized, double-blind, placebo-controlled clinical trial. Gupta AK(1), Gupta R(1), Gill S(1). Author information: (1)Department of Prosthodontics, Maulana Azad Institute of Dental Sciences, New Delhi, India. AIM: The purpose of this study is to comparatively evaluate the Vitamin D supplementation and stabilization splint therapy in patients exhibiting temporomandibular disorders (TMD). SETTINGS AND DESIGN: The study design was double-blinded, parallel-group, randomized and placebo-controlled trial conducted in patients with low Vitamin D and TMDs, which were allocated to two groups, Study group S + D (Stabilization splint with Vitamin D supplementation) and Control Group S (Stabilization Splint with placebo drug). SUBJECTS AND METHODS: Thirty-six participants of 18-45 years of age gap with Vitamin D deficiency and TMD were included in the study. Preoperative values of Vitamin D levels in ng/ml, comfort mouth opening (CMO) in mm, maximum mouth opening (MMO) in mm, temporomandibular joint (TMJ) tenderness (grading 0-3), Visual analog scale score (VAS Score 0-10 cm), and total energy (TE) integral values of both left and right TMJ's in Hertz (Hz) were recorded using joint vibration analysis All the values of CMO, MMO, TMJ Tenderness and VAS were recorded at each follow-up at 1st week, 1st month, 2nd month, and 3rd month, respectively. Postoperative Vitamin D levels and TE of both TMJs were recorded at end of 3 months. STATISTICAL ANALYSIS USED: For intergroup comparison, Mann-Whitney U-test and Pearson Chi-square tests were done. For Intragroup comparison, Wilcoxon signed rank test was used for comparison. RESULTS: In Intergroup comparison, a significant difference was seen in CMO, VAS score and MMO (P < 0.05) but not among mean values of TE of right and left TMJ, and Vitamin D levels (P < 0.05). In both groups, there were significant statistical variations in CMO, VAS score, MMO, and TE integral before and after treatment in the right and left TMJs (P < 0.05). CONCLUSIONS: The study concludes centric stabilization splint helps in improving symptoms of TMD patients and Vitamin D supplementation provided faster relief in those cases. DOI: 10.4103/jips.jips_334_21 PMCID: PMC8884346 PMID: 36510949 [Indexed for MEDLINE] Conflict of interest statement: None

Efficacy and cost-effectiveness of Stem Cell injections for symptomatic relief and strUctural improvement in people with Tibiofemoral knee OsteoaRthritis: protocol for a randomised placebo-controlled trial (the SCUlpTOR trial).

16. BMJ Open. 2021 Nov 29;11(11):e056382. doi: 10.1136/bmjopen-2021-056382. Efficacy and cost-effectiveness of Stem Cell injections for symptomatic relief and strUctural improvement in people with Tibiofemoral knee OsteoaRthritis: protocol for a randomised placebo-controlled trial (the SCUlpTOR trial). Liu X(1)(2), Robbins S(1)(2), Wang X(1)(2), Virk S(1)(2), Schuck K(1)(2), Deveza LA(1)(2), Oo WM(1)(2), Carmichael K(3), Antony B(3), Eckstein F(4)(5), Wirth W(4)(5), Little C(6), Linklater J(7), Harris A(8), Humphries D(9), O'Connell R(10), Heller G(10), Buttel T(11), Lohmander S(12), Ding C(3)(13), Hunter DJ(14)(2)(13). Author information: (1)Department of Rheumatology, Royal North Shore Hospital, Northern Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia. (2)Institute of Bone and Joint Research, Kolling Institute of Medical Research, The University of Sydney, Sydney, New South Wales, Australia. (3)Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia. (4)Institute of Anatomy and Cell Biology and Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Paracelsus Medical University Salzburg, Salzburg, Austria. (5)Chondrometrics GmbH, Freilassing, Germany. (6)Raymond Purves Bone and Joint Research Labs, Kolling Institute of Medical Research, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia. (7)Castlereagh Imaging, St Leonards, Sydney, New South Wales, Australia. (8)Centre for Health Economics, Monash University, Clayton, Victoria, Australia. (9)School of Medicine, College of Health and Medicine, University of Tasmania Faculty of Health, Hobart, Tasmania, Australia. (10)NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia. (11)Representative of People with Knee Osteoarthritis, Sydney, New South Wales, Australia. (12)Department of Clinical Sciences Lund, Orthopaedics, Lund University, Lund, Sweden. (13)Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China. (14)Department of Rheumatology, Royal North Shore Hospital, Northern Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia david.hunter@sydney.edu.au. INTRODUCTION: Knee osteoarthritis (KOA) is a highly prevalent disabling joint disease. Intra-articular stem cell therapy is increasingly being used for treating KOA with little high-quality evidence to support its use. The aim of this study is to investigate the efficacy, safety and cost-effectiveness of allogeneic mesenchymal stem cells (Cymerus MSCs) for treating symptomatic tibiofemoral KOA and improving knee structure over 24 months. METHODS AND ANALYSIS: The Stem Cell injections for symptomatic relief and strUctural improvement in people with Tibiofemoral knee OsteoaRthritis study is a phase III, multi-centre, parallel, superiority, randomised, double-blind, placebo-controlled trial, which will be conducted in Sydney and Hobart, Australia. 440 participants (220 per arm) aged over 40 years with painful KOA and mild to moderate structural change on X-ray (Kellgren and Lawrence grade 2 or 3) with medial minimum joint space width between 1 and 4 mm in the study knee will be recruited from the community and randomly allocated to receive either intra-articular MSCs or saline at baseline, week 3 and week 52. The coprimary outcomes will be the proportion of participants achieving patient-acceptable symptom state for knee pain at 24 months and quantitative central medial femorotibial compartment cartilage thickness change from baseline to 24 months. Main secondary outcomes include change in knee pain, Patient Global Assessment, physical function, quality of life and other structural changes. Additional data for cost-effectiveness analysis will also be recorded. Adverse events will be monitored throughout the study. The primary analysis will be conducted using modified intention-to-treat. ETHICS AND DISSEMINATION: This protocol has been approved by The University of Sydney (USYD) Human Research Ethics Committee (HREC) #: 2020/119 and The University of Tasmania (UTAS) HREC #: H0021868. All participants will be required to provide informed consent. Dissemination will occur through conferences, social media, and scientific publications. TRIAL REGISTRATION NUMBERS: Australian New Zealand Clinical Trials Registry (ACTRN12620000870954); U1111-1234-4897. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. DOI: 10.1136/bmjopen-2021-056382 PMCID: PMC8633994 PMID: 34845081 [Indexed for MEDLINE] Conflict of interest statement: Competing interests: DJH is supported by an NHMRC Investigator Grant and provides consulting advice for Merck Serono, TLC Bio, Tissuegene and Pfizer. CL has provided consulting advice for Merck Serono and Galapagos Pharmaceuticals, and receives research funding from numerous pharmaceutical companies through specific services/testing contract research agreements between and managed by The University of Sydney or the NSLHD. SL provides consulting advice for Arthro Therapeutics, Pfizer and Synartro. LAD has received partial reimbursement of a conference registration by Pfizer. FE is CEO/CMO and co-owner of Chondrometrics GmbH, and he has provided consulting services to Merck KGaA, Abbvie, Samumed, Kolon-Tissuegene, Servier, Galapagos, Roche, Novartis, ICM and HealthLink. WW is co-owner of Chondrometrics GmbH, and has provided consulting services to Galapagos.

Discovery of bone morphogenetic protein 7-derived peptide sequences that attenuate the human osteoarthritic chondrocyte phenotype.

17. Mol Ther Methods Clin Dev. 2021 Mar 17;21:247-261. doi: 10.1016/j.omtm.2021.03.009. eCollection 2021 Jun 11. Discovery of bone morphogenetic protein 7-derived peptide sequences that attenuate the human osteoarthritic chondrocyte phenotype. Caron MMJ(1), Ripmeester EGJ(1), van den Akker G(1), Wijnands NKAP(1), Steijns J(1), Surtel DAM(1), Cremers A(1), Emans PJ(1)(2), van Rhijn LW(1)(2), Welting TJM(1)(2). Author information: (1)Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, the Netherlands. (2)Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, the Netherlands. Treatment of osteoarthritis (OA) is mainly symptomatic by alleviating pain to postpone total joint replacement. Bone morphogenetic protein 7 (BMP7) is a candidate morphogen for experimental OA treatment that favorably alters the chondrocyte and cartilage phenotype. Intra-articular delivery and sustained release of a recombinant growth factor for treating OA are challenging, whereas the use of peptide technology potentially circumvents many of these challenges. In this study, we screened a high-resolution BMP7 peptide library and discovered several overlapping peptide sequences from two regions in BMP7 with nanomolar bioactivity that attenuated the pathological OA chondrocyte phenotype. A single exposure of OA chondrocytes to peptides p[63-82] and p[113-132] ameliorated the OA chondrocyte phenotype for up to 8 days, and peptides were bioactive on chondrocytes in OA synovial fluid. Peptides p[63-82] and p[113-132] required NKX3-2 for their bioactivity on chondrocytes and provoke changes in SMAD signaling activity. The bioactivity of p[63-82] depended on specific evolutionary conserved sequence elements common to BMP family members. Intra-articular injection of a rat medial meniscal tear (MMT) model with peptide p[63-82] attenuated cartilage degeneration. Together, this study identified two regions in BMP7 from which bioactive peptides are able to attenuate the OA chondrocyte phenotype. These BMP7-derived peptides provide potential novel disease-modifying treatment options for OA. © 2021 The Authors. DOI: 10.1016/j.omtm.2021.03.009 PMCID: PMC8022858 PMID: 33850953 Conflict of interest statement: The study sponsors had no involvement in study design, collection, analysis, and interpretation of data; the writing of the manuscript; or the decision to submit the manuscript for publication. M.M.J.C. and T.J.M.W. are inventors on patents WO2017178251 and WO2017178253 (owned by Chondropeptix). P.J.E., L.W.v.R., and T.J.M.W. are shareholders in Chondropeptix and are CMO, CDO, and CSO of Chondropeptix, respectively. The other authors declare no competing interests.

Identifying rheumatic disease patients at high risk and requiring shielding during the COVID-19 pandemic.

18. Clin Med (Lond). 2020 May 15;20(3):256-261. doi: 10.7861/clinmed.2020-0149. Print 2020 May 5. Identifying rheumatic disease patients at high risk and requiring shielding during the COVID-19 pandemic. Price E(1), MacPhie E(2), Kay L(3), Lanyon P(4), Griffiths B(5), Holroyd C(6), Abhishek A(7), Youngstein T(8), Bailey K(9), Clinch J(10), Shaikh M(11), Rivett A(12). Author information: (1)Great Western Hospital, Swindon, UK and president, British Society for Rheumatology, London, UK. (2)Lancashire and South Cumbria NHS Foundation Trust, Preston, UK and chair of the Clinical Affairs Committee, British Society for Rheumatology, London, UK. (3)The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK and joint national clinical lead for rheumatology, NHS England and Improvement, London, UK. (4)Nottingham University Hospitals NHS Trust, Nottingham, UK and national clinical co-lead for rheumatology, NHS Improvement, London, UK. (5)Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK and chair of the Specialised Rheumatology Clinical Reference Group, NHS England, London, UK. (6)University Hospital Southampton, Southampton, UK. (7)The University of Nottingham, Nottingham, UK and Nottingham Biomedical Research Centre, Nottingham, UK. (8)Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK. (9)Oxford University Hospitals NHS Foundation Trust, Oxford, UK. (10)Bristol Royal Hospital for Children, Bristol, UK and medical lead, Bath Centre for Pain Services, Bath, UK. (11)James Cook University Hospital, Middlesbrough, UK. (12)British Society for Rheumatology, London, UK elizabeth.price5@nhs.net. Rheumatology teams care for patients with diverse, systemic autoimmune diseases who are often immunosuppressed and at high risk of infections. The current COVID-19 pandemic has presented particular challenges in caring for and managing this patient group. The office of the chief medical officer (CMO) for England contacted the rheumatology community to provide expert advice on the identification of extremely vulnerable patients at very high risk during the COVID-19 pandemic who should be 'shielded'. This involves the patients being asked to strictly self-isolate for at least 12 weeks with additional funded support provided for them to remain at home. A group of rheumatologists (the authors) have devised a pragmatic guide to identifying the very highest risk group using a rapidly developed scoring system which went live simultaneous with the Government announcement on shielding and was cascaded to all rheumatologists working in England. © Royal College of Physicians 2020. All rights reserved. DOI: 10.7861/clinmed.2020-0149 PMCID: PMC7354033 PMID: 32371418

Improving osteoarthritis care by digital means - Effects of a digital self-management program after 24- or 48-weeks of treatment.

19. PLoS One. 2020 Mar 4;15(3):e0229783. doi: 10.1371/journal.pone.0229783. eCollection 2020. Improving osteoarthritis care by digital means - Effects of a digital self-management program after 24- or 48-weeks of treatment. Dahlberg LE(1)(2), Dell'Isola A(1), Lohmander LS(1)(2), Nero H(1)(2). Author information: (1)Department of Clinical Sciences Lund, Orthopaedics, Lund University, Lund, Sweden. (2)Arthro Therapeutics, Malmö, Sweden. BACKGROUND: Osteoarthritis (OA) is highly prevalent in older adults and a growing cause of disability. Easily accessible first-line treatment of OA is increasingly important. Digital self-management programs have in recent years become available. Evidence of short-term effects of such programs are abundant, yet reports on long-term benefits and adherence to treatment are scarce. The current study's objective was to investigate the long-term pain and function outcomes of people with hip or knee OA participating in a digital self-management programme. METHODS AND FINDINGS: In this longitudinal cohort study, individuals with hip and knee OA, from the register of a digital self-management program and with 0-24-week (n = 499) or 0-48-week adherence (n = 138), were included. The treatment effect in terms of monthly pain (NRS, 0-10 worst to best) and physical function (30-second chair stand test (30CST), number of repetitions) change were investigated using a mixed model, controlling for the effect of age, body mass index (BMI), gender and index joint. For the 24-week sub-sample, pain NRS decreased monthly by -0.43 units (95% CI -0.51, -0.35, mean knee pain from 5.6 to 3.1, and hip pain from 5.9 to 3.8) and 30CST repetitions increased monthly by 0.76 repetitions (95% CI 0.64, 0.89 mean for knee from 10.0 to 14.3, and for hip from 10.9 to 14.8). For the 48-week sub-sample, pain decreased monthly by -0.39 units (95% CI -0.43, -0.36, mean knee pain from 5.7 to 3.2, and hip pain from 5.8 to 3.8), and repetitions increased by 0.72 repetitions (95% CI 0.65, 0.79, mean repetitions for knee from 10.3 to 14.4, and for hip from 11.1 to 14.9). There were no clinically relevant effects on the improvement of pain or function by any covariate (age, sex, index joint). The lack of a control group and randomization limit our ability to explain the mechanisms of the observed results. CONCLUSIONS: Continuously participating in a digital OA treatment program for 6 or 12 months was associated with a clinically important decrease in joint pain and increased physical function, in hip and knee OA. Future research should follow OA-related outcomes in participants that end their treatment to explore when and why that decision was made. DOI: 10.1371/journal.pone.0229783 PMCID: PMC7056265 PMID: 32130276 [Indexed for MEDLINE] Conflict of interest statement: Joint Academy® is a product of Arthro Therapeutics® (AT), a Swedish e-health company. Håkan Nero and Stefan Lohmander are part-time consultants for AT, and Leif Dahlberg is CMO of AT. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no other competing interests to report.

Psychological and Pain Sensitization Characteristics Are Associated With Patellofemoral Osteoarthritis Symptoms: The Multicenter Osteoarthritis Study.

20. J Rheumatol. 2020 Nov 1;47(11):1696-1703. doi: 10.3899/jrheum.190981. Epub 2020 Mar 1. Psychological and Pain Sensitization Characteristics Are Associated With Patellofemoral Osteoarthritis Symptoms: The Multicenter Osteoarthritis Study. Collins NJ(1), Neogi T(2), Vicenzino B(3), Guermazi A(2), Roemer FW(4), Lewis CE(5), Torner JC(6), Nevitt MC(7), Stefanik JJ(8). Author information: (1)N. Collins, PT, PhD, B. Vicenzino, PT, PhD, School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane, Australia; n.collins1@uq.edu.au. (2)T. Neogi, MD, PhD, A. Guermazi, MD, PhD, School of Medicine, Boston University, Boston Massachusetts, USA. (3)N. Collins, PT, PhD, B. Vicenzino, PT, PhD, School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane, Australia. (4)F.W. Roemer, MD, Department of Radiology, University of Erlangen-Nuremberg, Erlangen, Germany. (5)C.E. Lewis, MD, MSPH, Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA. (6)J.C. Torner, PhD, Department of Epidemiology, The University of Iowa, Iowa City, Iowa, USA. (7)M.C. Nevitt, MPH, PhD, Department of Epidemiology and Biostatistics, University of California San Francisco, California, USA. (8)J.J. Stefanik, PT, PhD, Department of Physical Therapy, Movement and Rehabilitation Sciences, Northeastern University, Boston, Massachusetts, USA. OBJECTIVE: Determine the relation of symptomatic and structural features of patellofemoral osteoarthritis (PFOA) to psychological characteristics and measures of pain sensitization, in older adults with or at risk of knee osteoarthritis (OA). METHODS: This study included 1112 participants from the Multicenter Osteoarthritis Study (713 females, mean age 66.8 ± SD 7.6 yrs, body mass index 29.5 ± 4.8 kg/m2). Participants were grouped based on the presence of PFOA symptoms (anterior knee pain and pain on stairs) and magnetic resonance imaging (MRI) PFOA (full-thickness cartilage lesion with bone marrow lesion): (1) patellofemoral (PF) symptoms with MRI PFOA; (2) PF symptoms without MRI PFOA; (3) MRI PFOA without PF symptoms; and (4) no PF symptoms or MRI PFOA (no PFOA). Relation of PFOA classification to depressive symptoms, catastrophizing, temporal summation (TS) and pressure pain thresholds (PPT) was evaluated using logistic (categorical variables) and linear regression (continuous variables). RESULTS: Compared with no PFOA, those with PF symptoms with or without MRI PFOA had significantly greater odds of depressive symptoms, catastrophizing, and patellar TS (OR range 1.5-2.01), and those with PF symptoms without MRI PFOA had significantly greater odds of wrist TS (OR 1.66). Males with PF symptoms without MRI PFOA had significantly lower pressure PPT at the patella compared with no PFOA and those with MRI PFOA only (no symptoms). There were no significant differences at the wrist for males, or the patella or wrist for females. CONCLUSION: Persons with PFOA symptoms, regardless of MRI PFOA status, are more likely to demonstrate depressive symptoms, catastrophizing, and TS. Males with PFOA symptoms without MRI PFOA demonstrate local hyperalgesia. DOI: 10.3899/jrheum.190981 PMCID: PMC8005266 PMID: 32115429 [Indexed for MEDLINE] Conflict of interest statement: CONFLICTS OF INTEREST A. Guermazi is the President and shareholder of Boston Imaging Core Lab (BICL), LLC, and consultant to Pfizer, MerckSerono, GE, TissueGene, OrthoTrophix, AstraZeneca and Sanofi. F. Roemer is a CMO and shareholder of BICL, LLC.

The association of frontal plane alignment to MRI-defined worsening of patellofemoral osteoarthritis: the MOST study.

21. Osteoarthritis Cartilage. 2019 Mar;27(3):459-467. doi: 10.1016/j.joca.2018.11.004. Epub 2018 Nov 28. The association of frontal plane alignment to MRI-defined worsening of patellofemoral osteoarthritis: the MOST study. Macri EM(1), Felson DT(2), Ziegler ML(3), Cooke TDV(4), Guermazi A(5), Roemer FW(6), Neogi T(7), Torner J(8), Lewis CE(9), Nevitt MC(10), Stefanik JJ(11). Author information: (1)Department of Physical Therapy, University of Delaware, Newark, DE, USA; Department of General Practice, Erasmus MC, Rotterdam, NL. Electronic address: e.macri@erasmusmc.nl. (2)Clinical Epidemiology Research and Training Unit, School of Medicine, Boston University, Boston, MA, USA; Division of Musculoskeletal & Dermatological Sciences, University of Manchester, Manchester, UK. Electronic address: dfelson@bu.edu. (3)Biostatistics Core, College of Health Sciences, University of Delaware, Newark, DE, USA. Electronic address: mlz@udel.edu. (4)School of Rehabilitation Therapy, Queen's University, Kingston, ON, Canada. Electronic address: derek@cookes.ca. (5)Quantitative Imaging Center, Department of Radiology, School of Medicine, Boston University, Boston, MA, USA. Electronic address: Ali.Guermazi@bmc.org. (6)Quantitative Imaging Center, Department of Radiology, School of Medicine, Boston University, Boston, MA, USA; Department of Radiology, University of Erlangen-Nuremberg, Erlangen, Germany. Electronic address: Frank.Roemer@uk-erlangen.de. (7)Clinical Epidemiology Research and Training Unit, School of Medicine, Boston University, Boston, MA, USA. Electronic address: tneogi@bu.edu. (8)Department of Epidemiology, University of Iowa, Iowa City, IA, USA. Electronic address: james-torner@uiowa.edu. (9)Division of Preventive Medicine, University of Alabama, Birmingham, AL, USA. Electronic address: celewis@uabmc.edu. (10)Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA. Electronic address: MNevitt@psg.ucsf.edu. (11)Department of Physical Therapy, Movement and Rehabilitation Sciences, Northeastern University, Boston, MA, USA; Department of Physical Therapy, University of Delaware, Newark, USA. Electronic address: j.stefanik@northeastern.edu. OBJECTIVE: To determine the sex-specific relation of frontal plane alignment (FPA) to magnetic resonance imaging (MRI)-defined features of patellofemoral osteoarthritis, and also to tibiofemoral osteoarthritis and knee pain. METHOD: The Multicenter Osteoarthritis Study is cohort study comprised of individuals with or at risk of knee osteoarthritis. We determined the sex-specific dose-response relation of baseline FPA to MRI-defined patellofemoral and tibiofemoral structural worsening, and incident knee pain, over 7 years. RESULTS: In women only, greater varus alignment was associated with medial patellofemoral osteophytes (risk ratio [RR] 1.7 [95% CI 1.2, 2.6]) and valgus with lateral patellofemoral osteophytes (RR 1.9 [1.0, 3.6]). In men, greater varus increased risk for medial tibiofemoral cartilage worsening (RR 1.7 [1.1, 2.6]), and valgus for lateral tibiofemoral cartilage worsening (RR 1.8 [1.6, 2.2]). In women, findings were similar for tibiofemoral cartilage, but varus also increased risk for medial bone marrow lesions [BMLs] (RR 2.2 [1.6, 3.1]) and medial osteophytes (RR 1.8 [1.3, 2.5]), and valgus for lateral BMLs (RR 3.3 [2.2, 4.5]) and osteophytes (RR 2.0 [1.2, 3.2]). Varus increased risk of incident pain in men (RR 1.7 [1.4, 2.2]) and women (RR 1.3 [1.0, 1.6]), valgus did so in men only (RR 1.5 [1.1, 1.9]). CONCLUSION: FPA was associated with patellofemoral osteophyte worsening in women, though overall was more strongly associated with tibiofemoral than patellofemoral osteoarthritis feature worsening. FPA in women was more consistently associated with structural worsening, yet men had higher associations with incident pain. Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. DOI: 10.1016/j.joca.2018.11.004 PMCID: PMC6391198 PMID: 30500383 [Indexed for MEDLINE] Conflict of interest statement: Conflict of interest: A Guermazi is the president of Boston Imaging Core Lab (BICL), LLC, and a consultant to Merck Serono, TissueGene, Genzyme, AstraZeneca, OrthoTrophixs, Pfizer and GE Healthcare. F Roemer is CMO and shareholder of BICL. TDV Cooke is the president of OAISYS Inc.

Antinuclear antibody and rheumatoid factor positivity in temporomandibular disorders.

22. Head Face Med. 2018 Nov 22;14(1):26. doi: 10.1186/s13005-018-0183-3. Antinuclear antibody and rheumatoid factor positivity in temporomandibular disorders. Kim JR(1), Jo JH(2), Chung JW(3), Park JW(4). Author information: (1)Department of Dentistry and Oral Medicine, School of Medicine, Catholic University of Daegu, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu, 42472, Republic of Korea. (2)Department of Oral Medicine, Seoul National University Dental Hospital, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. (3)Department of Oral Medicine and Oral Diagnosis, School of Dentistry and Dental Research Institute, Seoul National University, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. (4)Department of Oral Medicine and Oral Diagnosis, School of Dentistry and Dental Research Institute, Seoul National University, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. ankara01@snu.ac.kr. BACKGROUND: To investigate the differences in clinical characteristics and long-term treatment outcomes according to antinuclear antibody(ANA) and rheumatoid factor(RF) positivity and the correlation between pain-related and hematological indices in temporomandibular disorders(TMD) patients. METHODS: Clinical examinations were done following the Research Diagnostic Criteria for TMD in 257 patients. Comprehensive screening along with psychological and hematological evaluations (ANA, RF, complete blood cell count, C-reactive protein[CRP] and erythrocyte sedimentation rate[ESR]) were conducted. Clinical characteristics and treatment outcomes were statistically compared between ANA/RF positive and negative groups. RESULTS: Thirty-nine patients showed ANA/RF positivity. Male patients had smaller comfortable mouth opening(CMO)(p = 0.033) and maximum mouth opening(MMO)(p = 0.016) ranges with more painful neck muscles on palpation when RF/ANA positive. Pain duration, intensity, disability days and psychological distress levels were also higher in RF/ANA positive male patients. Significant correlation was shown in ESR with pain duration(p < 0.05) and numeric rating scale(NRS) before treatment(p < 0.05), CRP with NRS before treatment(p < 0.01), and red blood cell (RBC) with pain intensity(p < 0.05), NRS before treatment(p < 0.01), CMO(p < 0.01), pain on palpation of cervical muscles(p < 0.01), CMO(p < 0.05), and MMO(p < 0.05) 6 months after treatment. CONCLUSIONS: These results may point towards a nonspecific autoimmune disposition in a subgroup of TMD patients. RF and ANA could be considered as a screening test for the detection of autoimmune phenomena in TMD. DOI: 10.1186/s13005-018-0183-3 PMCID: PMC6249715 PMID: 30466447 [Indexed for MEDLINE] Conflict of interest statement: ETHICS APPROVAL AND CONSENT TO PARTICIPATE: This study was approved by the Institutional Review Board (IRB) of Seoul National University Dental Hospital (CRI #15018). The IRB authorized the exemption of informed consent from the subjects. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER’S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Evaluation of a digital platform for osteoarthritis treatment: study protocol for a randomised clinical study.

23. BMJ Open. 2018 Nov 8;8(11):e022925. doi: 10.1136/bmjopen-2018-022925. Evaluation of a digital platform for osteoarthritis treatment: study protocol for a randomised clinical study. Nero H(1)(2), Ranstam J(1), Kiadaliri AA(3), Dahlberg LE(2)(4). Author information: (1)Orthopedics, Department of Clinical Sciences Lund, Lund University, Lund, Sweden. (2)Joint Academy, Malmö, Sweden. (3)Clinical Epidemiology Unit, Department of Clinical Sciences Lund, Lund University, Lund, Sweden. (4)Orthopedics, Department of Clinical Sciences Lund, Lund University, Skane University Hospital, Lund, Sweden. INTRODUCTION: Despite favourable results from structured face-to-face treatment of osteoarthritis (OA) in Sweden through the Better management of patients with OsteoArthritis (BOA) initiative, only around 20% of people with knee or hip OA receive the primary treatment recommended by international guidelines (ie, information, exercise, weight management). In 2014, a digital treatment programme named Joint Academy was introduced in Sweden, based on the same concept as the face-to-face BOA programme. In line with BOA, Joint Academy follows national and international guidelines and best practice for OA treatment. Results from observational studies suggest that this digital treatment is a valuable alternative to the traditional treatment approach and can positively impact patients' function and pain. However, conclusions from such studies commonly suggest that more rigorous testing is necessary to ascertain the benefits of digital treatment delivery for people with OA. METHODS AND ANALYSIS: A randomised clinical trial will be performed, comparing regular face-to-face care according to BOA with the digital version, Joint Academy. A total of 270 participants with clinically diagnosed knee OA will be recruited at primary care centres and randomised to either standard treatment (BOA) for 3 months, or the experimental group (digital intervention programme). Both groups will receive educational sessions and exercises yet with a difference in programme deliverance. The objective of the trial is to evaluate the effectiveness of the online treatment programme, in comparison with BOA. The two treatment groups will be compared with respect to the number of repetitions of the 30 s chair stand test at 3, 6 and 12 months, using a mixed model repeated measures analysis of variance. ETHICS AND DISSEMINATION: Ethical approval has been attained from the Regional Board of Ethics in Lund, Sweden (Dnr 2017/719). Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03328741. © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. DOI: 10.1136/bmjopen-2018-022925 PMCID: PMC6231565 PMID: 30413507 [Indexed for MEDLINE] Conflict of interest statement: Competing interests: HN is hired as a part-time consultant for Arthro, the corporation behind JA, and LED is the unemployed CMO of Arthro.

From Early Radiographic Knee Osteoarthritis to Joint Arthroplasty: Determinants of Structural Progression and Symptoms.

24. Arthritis Care Res (Hoboken). 2018 Dec;70(12):1778-1786. doi: 10.1002/acr.23545. From Early Radiographic Knee Osteoarthritis to Joint Arthroplasty: Determinants of Structural Progression and Symptoms. Roemer FW(1), Kwoh CK(2), Fujii T(3), Hannon MJ(4), Boudreau RM(3), Hunter DJ(5), Eckstein F(6), John MR(7), Guermazi A(8). Author information: (1)Boston University School of Medicine, Boston, Massachusetts, and University of Erlangen-Nuremberg, Erlangen, Germany. (2)University of Arizona College of Medicine, Tucson. (3)Paracelsus Medical University Salzburg and Nuremberg, Salzburg, Austria, and University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania. (4)University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. (5)Royal North Shore Hospital and University of Sydney, Sydney, New South Wales, Australia. (6)Paracelsus Medical University, Salzburg, Austria. (7)Novartis Pharma AG, Basel, Switzerland. (8)Boston University School of Medicine, Boston, Massachusetts. OBJECTIVE: To assess structural progression in knees with no/mild radiographic osteoarthritis (OA) (i.e., Kellgren/Lawrence [K/L] grades 0-2) that will undergo knee replacement during a 5-year period; to assess differences in structural damage on magnetic resonance imaging (MRI) in knees with no/mild radiographic OA versus those with severe radiographic OA (i.e., K/L grades 3 and 4) at baseline; and to assess differences in pain levels between those groups. METHODS: All participants who underwent knee replacement from baseline to 60 months were drawn from the Osteoarthritis Initiative. MRIs were assessed for bone marrow lesions (BMLs), Hoffa synovitis, and effusion synovitis (i.e., hyperintensity signal changes in the fat pad and abnormal amount of capsular distension due to intraarticular joint fluid and/or synovial thickening) at baseline and at the time point before knee replacement (T0). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Injury and Osteoarthritis Outcome Score (KOOS) pain were used for pain characterization. WOMAC activities of daily living and KOOS quality of life were applied to characterize functional status of the included participants. Logistic regression was used to assess the association of no/mild radiographic OA with these MRI features and pain. RESULTS: Based on inclusion criteria, 181 knees were selected. Participants were predominantly female (57.8%) with a mean age of 64.4 years. A total of 51 knees (28.2%) had no/mild radiographic OA at baseline. Of these, 51.0% progressed to severe radiographic OA. No/mild radiographic OA knees showed higher odds of BMLs in the patellofemoral joint at baseline (odds ratio [OR] 7.92 [95% confidence interval (95% CI) 3.45-18.16]) and T0 (OR 9.44 [95% CI 4.00-22.28]) compared to severe radiographic OA knees. In addition, no/mild radiographic OA knees were associated with change from no pain to pain from baseline to T0 (adjusted OR 5.48 [95% CI 1.25-24.00]). CONCLUSION: More than half of the knees with no/mild radiographic OA before knee replacement progressed to severe radiographic OA during 4 years of follow-up. BMLs in the patellofemoral joint were more often seen among knees that had no/mild radiographic OA. Worsening pain status may contribute to knee replacement in knees with no/mild radiographic OA. © 2018, American College of Rheumatology. DOI: 10.1002/acr.23545 PMCID: PMC6089673 PMID: 29438603 [Indexed for MEDLINE] Conflict of interest statement: Conflict of Interest Statement Frank W. Roemer: CMO and Shareholder Boston Imaging Core Lab. (BICL), LLC. C. Kent Kwoh: Research grants to the University of Arizona by Abbvie and EMD Serono (>$10,000). Consultant for Thusane, EMD Serono, Astellas (all < $10,000) Tomoko Fujii: No financial disclosures. Michael J. Hannon: Consultant to EMD Serono (> $10,000) Robert M. Boudreau: No financial disclosures. David J. Hunter: Consultant to Merck Serono, TissueGene and Flexion (all < $10,000) Felix Eckstein: CEO and shareholder of Chondrometrics GmbH and consultant to Merck Serono, Samumed, Abbvie, Bioclinica and Servier (all < $10,000) Markus R. John: full time employee by F. Hoffmann-La Roche Ltd, Basel, Switzerland Ali Guermazi: President of Boston Imaging Core Lab, LLC, and consultant to Merck Serono and Pfizer (>$10,000), Tissue Gene, OrthoTrophix, GE, Sanofi and Astra Zeneca (<$10,000)

Predictive and concurrent validity of cartilage thickness change as a marker of knee osteoarthritis progression: data from the Osteoarthritis Initiative.

25. Osteoarthritis Cartilage. 2017 Dec;25(12):2063-2071. doi: 10.1016/j.joca.2017.08.005. Epub 2017 Aug 31. Predictive and concurrent validity of cartilage thickness change as a marker of knee osteoarthritis progression: data from the Osteoarthritis Initiative. Wirth W(1), Hunter DJ(2), Nevitt MC(3), Sharma L(4), Kwoh CK(5), Ladel C(6), Eckstein F(7). Author information: (1)Institute of Anatomy, Paracelsus Medical University Salzburg & Nuremberg, Salzburg, Austria & Chondrometrics GmbH, Ainring, Germany. Electronic address: wolfgang.wirth@pmu.ac.at. (2)Rheumatology Department, Royal North Shore Hospital and Institute of Bone and Joint Research, Kolling Institute, University of Sydney, Sydney, NSW, Australia. (3)Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA. (4)Northwestern University, Chicago IL, USA. (5)Division of Rheumatology, University of Arizona Arthritis Center, University of Arizona, Tucson, AZ, USA. (6)Merck KGaA, Darmstadt, Germany. (7)Institute of Anatomy, Paracelsus Medical University Salzburg & Nuremberg, Salzburg, Austria & Chondrometrics GmbH, Ainring, Germany. OBJECTIVE: To investigate the predictive and concurrent validity of magnetic resonance imaging (MRI)-based cartilage thickness change between baseline (BL) and year-two (Y2) follow-up (predictive validity) and between Y2 and Y4 follow-up (concurrent validity) for symptomatic and radiographic knee osteoarthritis (OA) progression during Y2→Y4. METHODS: 777 knees from 777 Osteoarthritis Initiative (OAI) participants (age: 61.3 ± 9.0 years, BMI: 30.1 ± 4.8 kg/m2) with Kellgren Lawrence (KL) grade 1-3 at Y2 (visit before progression interval) had cartilage thickness measurements from 3T MRI at BL, Y2 (n = 777), and Y4 (n = 708). Analysis of covariance and logistic regression were used to assess the association of pain progression (≥9 WOMAC units [scale 0-100], n = 205/572 with/without progression) and radiographic progression (≥0.7 mm minimum joint space width (mJSW) loss, n = 166/611 with/without progression) between Y2 and Y4 with preceding (BL→Y2) and concurrent (Y2→Y4) change in central medial femorotibial (cMFTC) compartment cartilage thickness. RESULTS: Symptomatic progression was associated with concurrent (Y2→Y4: -305 ± 470 μm vs -155 ± 346 μm, Odds ratios (OR) = 1.5 [1.2, 1.7]) but not with preceding cartilage thickness loss in cMFTC (-150 ± 276 μm vs -151 ± 299 μm, OR = 0.9 95% CI: [0.8, 1.1]). Radiographic progression, in contrast, was significantly associated with both concurrent (-542 ± 550 μm vs -98 ± 255 μm, OR = 3.4 [2.6, 4.3]) and preceding cMFTC thickness loss (-229 ± 355 μm vs -130 ± 270 μm, OR = 1.3 [1.1, 1.5]). CONCLUSIONS: These results extend previous reports that did not discern predictive vs concurrent associations of cartilage thickness loss with OA progression. The observed predictive and concurrent validity of cartilage thickness loss for radiographic progression and observed concurrent validity for symptomatic progression provide an important step in qualifying cartilage thickness loss as a biomarker of knee OA progression. CLINICALTRIALS. GOV IDENTIFICATION: NCT00080171. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. DOI: 10.1016/j.joca.2017.08.005 PMCID: PMC5688009 PMID: 28838858 [Indexed for MEDLINE] Conflict of interest statement: CONFLICTS OF INTEREST W. Wirth is a part time employee and co-owner of Chondrometrics GmbH. D.J. Hunter is a consultant for Flexion and Merck KGaA. C.K. Kwoh has received research support from Merck Serono and Abbvie. C. Ladel is an employee of Merck KGaA. F. Eckstein is CEO/CMO and co-owner of Chondrometrics GmbH, which has received funding from the FNIH OA Biomarker Consortium for the quantitative analysis of cartilage data in this study. He has received consulting fees from Merck KGaA as well as honoraria from Medtronic (less than $10,000 each). M. C. Nevitt and L. Sharma have no conflicts of interest.