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Choi W, Jeong H, Oh S, Jung TD. Instant gait classification for hip osteoarthritis patients: a non-wearable sensor approach utilizing Pearson correlation, SMAPE, and GMM. Biomed Eng Lett 2025; 15:301-310. [PMID: 40026883 PMCID: PMC11871253 DOI: 10.1007/s13534-024-00448-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 10/23/2024] [Accepted: 11/15/2024] [Indexed: 03/05/2025] Open
Abstract
This study aims to establish a methodology for classifying gait patterns in patients with hip osteoarthritis without the use of wearable sensors. Although patients with the same pathological condition may exhibit significantly different gait patterns, an accurate and efficient classification system is needed: one that reduces the effort and preparation time for both patients and clinicians, allowing gait analysis and classification without the need for cumbersome sensors like EMG or camera-based systems. The proposed methodology follows three key steps. First, ground reaction forces are measured in three directions-anterior-posterior, medial-lateral, and vertical-using a force plate during gait analysis. These force data are then evaluated through two approaches: trend similarity is assessed using the Pearson correlation coefficient, while scale similarity is measured with the Symmetric Mean Absolute Percentage Error (SMAPE), comparing results with healthy controls. Finally, Gaussian Mixture Models (GMM) are applied to cluster both healthy controls and patients, grouping the patients into distinct categories based on six quantified metrics derived from the correlation and SMAPE. Using the proposed methodology, 16 patients with hip osteoarthritis were successfully categorized into two distinct gait groups (Group 1 and Group 2). The gait patterns of these groups were further analyzed by comparing joint moments and angles in the lower limbs among healthy individuals and the classified patient groups. This study demonstrates that gait pattern classification can be reliably achieved using only force-plate data, offering a practical tool for personalized rehabilitation in hip osteoarthritis patients. By incorporating quantitative variables that capture both gait trends and scale, the methodology efficiently classifies patients with just 2-3 ms of natural walking. This minimizes the burden on patients while delivering a more accurate and realistic assessment. The proposed approach maintains a level of accuracy comparable to more complex methods, while being easier to implement and more accessible in clinical settings.
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Affiliation(s)
- Wiha Choi
- Department of Robotics and Mechatronics Engineering, DGIST, Daegu, 711-785 Republic of Korea
| | - Hieyong Jeong
- Department of Artificial Intelligence Convergence, Chonnam National University, 77 Yongbongro, Bukgu, Gwangju, 61186 Republic of Korea
| | - Sehoon Oh
- Department of Robotics and Mechatronics Engineering, DGIST, Daegu, 711-785 Republic of Korea
| | - Tae-Du Jung
- School of Medicine, Kyungpook National University Hospital, 680 Gukchaebosang-ro, Jung-gu, Daegu, 41404 Republic of Korea
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2
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Wier J, Jones IA, Palmer R, Mayfield CK, Kassebaum NJ, Lieberman JR, Heckmann ND. Complete Blood Cell Count-Based Ratios Identify Total Joint Arthroplasty Patients Likely to Benefit from Perioperative Dexamethasone. J Bone Joint Surg Am 2025; 107:163-173. [PMID: 39812724 DOI: 10.2106/jbjs.24.00184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2025]
Abstract
BACKGROUND Complete blood cell count-based ratios (CBRs), including the neutrophil-lymphocyte ratio (NLR) and monocyte-lymphocyte ratio (MLR), are inflammatory markers associated with postoperative morbidity. Given the link between the surgical stress response and complications after total joint arthroplasty (TJA), this study aimed to evaluate whether higher preoperative CBR values predict greater postoperative benefits associated with dexamethasone utilization. METHODS The Premier Healthcare Database was queried for adult patients who underwent primary, elective total hip or knee arthroplasty (THA or TKA). Multivariable logistic regression models using dexamethasone exposure and CBRs as independent variables assessed primary end points of 90-day postoperative complications and length of stay (LOS) of ≥3 days. The probability difference between the dexamethasone and non-dexamethasone groups for each primary end point was determined across all values of each CBR. Probability differences were compared across CBR quartiles. RESULTS A total of 32,849 primary, elective TJAs (12,788 THAs [38.93%], 20,061 TKAs [61.07%]) performed between 2016 and 2021 were identified, and 22,282 (67.83%) of the patients received perioperative dexamethasone. Among patients with an NLR value of >1.00, those receiving dexamethasone had a lower probability of postoperative complications (all p < 0.05). Dexamethasone was associated with lower odds of an LOS of ≥3 days among patients in the highest NLR quartile (≥4.67) compared with the lowest quartile (NLR <1.84) (p = 0.002). Among patients with an MLR value of ≥0.36, those receiving dexamethasone had significantly lower odds of postoperative complications. Dexamethasone was associated with lower odds of an LOS of ≥3 days among patients with an MLR of ≥0.33 (the 2 highest quartiles) compared with an MLR of <0.24 (the lowest quartile) (p = 0.039). CONCLUSIONS Higher NLR and MLR values were associated with greater marginal benefit from perioperative dexamethasone treatment, establishing a modifiable link between adverse outcomes and perioperative inflammation in TJA. LEVEL OF EVIDENCE Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
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Affiliation(s)
- Julian Wier
- Department of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, California
| | - Ian A Jones
- Department of Anesthesiology & Pain Medicine, University of Washington, Seattle, Washington
| | - Ryan Palmer
- Department of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, California
| | - Cory K Mayfield
- Department of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, California
| | - Nicholas J Kassebaum
- Department of Anesthesiology & Pain Medicine, University of Washington, Seattle, Washington
| | - Jay R Lieberman
- Department of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, California
| | - Nathanael D Heckmann
- Department of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, California
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Sen S, Sharma A, Kriplani P, Malhotra H, Mittal V. Formulation and Evaluation of Microsponges-loaded Transdermal Gel for the Management of Osteoarthritis. RECENT ADVANCES IN INFLAMMATION & ALLERGY DRUG DISCOVERY 2025; 19:79-99. [PMID: 40195704 DOI: 10.2174/0127722708297654240718053117] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Revised: 05/02/2024] [Accepted: 05/27/2024] [Indexed: 04/09/2025]
Abstract
BACKGROUND Osteoarthritis (OA) stands as the most widespread form of arthritis, representing a primary source of pain and functional impairment among the elderly. It is often referred to as a degenerative joint disease. OA is more than just wear and tear; it is an aberrant remodelling of joint tissues prompted by a deluge of inflammatory mediators released within the compromised joint. This disease affects 15 million people in India annually. OBJECTIVE Aceclofenac is a COX-2 inhibitor that has anti-inflammatory activity. However, aceclofenac has a short mean plasma elimination half-life and poor water solubility. It requires frequent dosing, which has been linked to a number of negative side effects, including bleeding and gastrointestinal irritation. A potential solution to this problem is the transdermal administration of aceclofenac using microsponges. In order to have a synergistic effect along with the bioenhancer effects, piperine was incorporated into the formulation. METHODS Microsponges were created using the quasi-emulsion solvent diffusion method. After characterization, the prepared microsponges were incorporated into the Carbopol gel. The in vivo study focused on evaluating the optimized formulation, F1. RESULTS All the prepared microsponge formulations underwent assessment based on parameters including yield of production, entrapment efficiency, and in vitro drug release. The outcomes indicated that batches ranging from F1 to F9 showed positive entrapment efficiency and in vitro drug release. From 50.37% to 80.76 % and 71.18% to 91.8% and in vivo studies the results reveal that the inflammatory cells in the best formulation Ace(B) group were reduced hence the formulation's anti-inflammatory impact was achieved. CONCLUSION The findings indicate that Formulation F1 exhibits superior entrapment and enhanced drug release. The kinetics study suggests that the optimized formulation aligns well with the Higuchi model and adheres to the Fickian transport drug release mechanism. Animal study findings suggest that optimized formulation Ace(B) may possess ideal -anti-osteoarthritic activity for osteoarthritic disease. Further clinical trials on humans may be conducted in order to make the research fruitful for society.
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Affiliation(s)
- Shiwani Sen
- Guru Gobind Singh College of Pharmacy, Yamunanagar, Haryana, 135001, India
| | - Anjali Sharma
- Guru Gobind Singh College of Pharmacy, Yamunanagar, Haryana, 135001, India
| | - Priyanka Kriplani
- Guru Gobind Singh College of Pharmacy, Yamunanagar, Haryana, 135001, India
| | - Hitesh Malhotra
- Guru Gobind Singh College of Pharmacy, Yamunanagar, Haryana, 135001, India
| | - Vishnu Mittal
- Guru Gobind Singh College of Pharmacy, Yamunanagar, Haryana, 135001, India
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Luo X, Wang Q, Tan H, Zhao W, Yao Y, Lu S. Digital assessment of muscle adaptation in obese patients with osteoarthritis: Insights from surface electromyography (sEMG). Digit Health 2025; 11:20552076241311940. [PMID: 39758257 PMCID: PMC11696943 DOI: 10.1177/20552076241311940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Accepted: 12/18/2024] [Indexed: 01/07/2025] Open
Abstract
BACKGROUND Obesity and severe knee osteoarthritis (KOA) lead to significant gait and muscle adaptations. However, the relationship between core muscle strength and the severity of KOA in obese patients remains unclear. This study aimed to determine the association between muscle strength adaptation and the severity of KOA in obese individuals. METHODS We recruited 119 obese participants with unilateral KOA from January 2021 to December 2023, all classified with mild to moderate KOA grades. KOA severity was assessed using the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), which categorized participants into two groups based on disease severity. Electromyographic data from the psoas, gluteus medius, vastus lateralis, vastus medialis, rectus femoris, medial gastrocnemius, lateral gastrocnemius, tibialis anterior, and biceps femoris muscles were collected during isometric and dynamic knee extension. RESULTS Significant differences were observed in all selected muscles between the affected knee joint and the contralateral side during both dynamic and isometric knee extensions. The difference in electromyographic data-including mean absolute value (MAV), root mean square (RMS), and center frequency (CF)-was significantly different across groups categorized by KOA severity. Notably, the MAV values of the vastus medialis, lateral gastrocnemius, and biceps femoris, as well as the CF values of the medial and lateral gastrocnemius, showed no significant differences in some instances during both dynamic and isometric extensions. CONCLUSION This study indicates that obese individuals with KOA exhibit lower muscle intensity and higher fatigability in comparison to the contralateral side during both isometric and dynamic knee extensions. Furthermore, significant reductions in muscle intensity were observed in the psoas, gluteus medius, vastus lateralis, rectus femoris, medial gastrocnemius, and tibialis anterior muscles, correlating with the advanced severity of KOA.
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Affiliation(s)
- Xinran Luo
- School of Biomedical Engineering, Shanghai Tech University, Shanghai, China
| | - Qiaojie Wang
- Department of Joint Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hongyu Tan
- Jinzhou Medical University, Jinzhou, China
| | - Wenbo Zhao
- Jinzhou Medical University, Jinzhou, China
| | - Yifei Yao
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Shengdi Lu
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Noorwali A, Aljoud F, Alghamdi A, Sattami N, Bashah T, Noorwali A, Pushparaj PN, Gauthaman K. Evaluation of serum biomarkers after intra-articular injection of rat bone marrow-derived mesenchymal stem cells in a rat model of knee osteoarthritis. Heliyon 2024; 10:e39940. [PMID: 39553645 PMCID: PMC11565378 DOI: 10.1016/j.heliyon.2024.e39940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 10/27/2024] [Accepted: 10/28/2024] [Indexed: 11/19/2024] Open
Abstract
Background Osteoarthritis (OA) is a prevalent joint disorder characterized by joint pain, functional impairment, and disability. The current study investigated the therapeutic effects of intra-articular injection of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs) in rats with knee OA. Methods Fourty five male Wistar rats were randomly divided into three groups (A-C) and received either an intra-articular injection of normal saline (NS) or rBM-MSCs. The normal control group (A, n = 15) received NS, the OA control group (B, n = 15) received NS, and the OA treated group (C, n = 15) received rBM-MSCs (0.5 × 106 cells in 25 μL NS). Knee OA was induced using monosodium iodoacetate (MIA). rBM-MSCs were sourced from female Wistar rats and their stem cells were characterized using flow cytometry. Histomorphometric analyses were performed on knee sections from both normal and OA knee. Serum biomarkers, including hyaluronic acid (HA), cross-linked N-telopeptide of type I collagen-1 (NTX-1), NGF, calcitonin gene-related peptide (CGRP), matrix metalloproteinase-3 (MMP-3), oligomeric cartilage matrix protein COMP, interleukin-6 (IL-6), and soluble IL-6 receptor (sIL-6R), were analyzed using ELISA kits. Ingenuity Pathway Analysis (IPA) was used to determine the genes regulated by MSCs in OA, and the protective mechanisms were determined using the Molecular Activity Predictor (MAP). Results rBM-MSCs were positive for CD29 and CD90 and negative for CD45 surface markers. OA biomarkers were significantly elevated in the untreated OA group but decreased after treatment with intra-articular MSCs. The OA group treated with MSCs showed significant repair of the damaged cartilage compared to the control group. Conclusions Cartilage damage leads to an increase in inflammatory cytokine levels and is associated with an increase in serum biomarkers related to cartilage degradation. Intra-articular administration of MSCs showed beneficial effects, including regeneration of damaged cartilage and a reduction in inflammation-related serum biomarker levels.
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Affiliation(s)
- Abdulwahab Noorwali
- Regenerative Medicine Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
| | - Fadwa Aljoud
- Regenerative Medicine Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
- Scientific Research Center, Dar Al-Hekma University, Jeddah, 22246, Saudi Arabia
| | - Amani Alghamdi
- Regenerative Medicine Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
| | - Noora Sattami
- Regenerative Medicine Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
| | - Taghreed Bashah
- Regenerative Medicine Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
| | - Abdulsalam Noorwali
- Regenerative Medicine Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
| | - Peter Natesan Pushparaj
- Institute of Genomic Medicine Sciences (IGMS) and Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
- Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, 600077, India
| | - Kalamegam Gauthaman
- Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, 600077, India
- Pharmaceutical Division, Nibblen Life Sciences Private Limited, Chennai, 600061, India
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Peoples J, Tanner JJ, Bartley EJ, Domenico LH, Gonzalez CE, Cardoso JS, Lopez-Quintero C, Losin EAR, Staud R, Goodin BR, Fillingim RB, Terry EL. Association of neighborhood-level disadvantage beyond individual sociodemographic factors in patients with or at risk of knee osteoarthritis. BMC Musculoskelet Disord 2024; 25:887. [PMID: 39511529 PMCID: PMC11542459 DOI: 10.1186/s12891-024-08007-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Accepted: 10/29/2024] [Indexed: 11/15/2024] Open
Abstract
OBJECTIVE Lower socioeconomic status (SES) is a risk factor for poorer pain-related outcomes. Further, the neighborhood environments of disadvantaged communities can create a milieu of increased stress and deprivation that adversely affects pain-related and other health outcomes. Socioenvironmental variables such as the Area Deprivation Index, which ranks neighborhoods based on socioeconomic factors could be used to capture environmental aspects associated with poor pain outcomes. However, it is unclear whether the ADI could be used as a risk assessment tool in addition to individual-level SES. METHODS The current study investigated whether neighborhood-level disadvantage impacts knee pain-related outcomes above sociodemographic measures. Participants were 188 community-dwelling adults who self-identified as non-Hispanic Black or non-Hispanic White and reported knee pain. Area Deprivation Index (ADI; measure of neighborhood-level disadvantage) state deciles were derived for each participant. Participants reported educational attainment and annual household income as measures of SES, and completed several measures of pain and function: Short-form McGill Pain Questionnaire, Western Ontario and McMaster Universities Osteoarthritis Index, and Graded Chronic Pain Scale were completed, and movement-evoked pain was assessed following the Short Physical Performance Battery. Hierarchical linear regression analyses were used to assess whether environmental and sociodemographic measures (i.e., ADI 80/20 [80% least disadvantaged and 20% most disadvantaged]; education/income, race) were associated with pain-related clinical outcomes. RESULTS Living in the most deprived neighborhood was associated with poorer clinical knee pain-related outcomes compared to living in less deprived neighborhoods (ps < 0.05). Study site, age, BMI, education, and income explained 11.3-28.5% of the variance across all of the individual pain-related outcomes. However, the ADI accounted for 2.5-4.2% additional variance across multiple pain-related outcomes. CONCLUSION The ADI accounted for a significant amount of variance in pain-related outcomes beyond the control variables including education and income. Further, the effect of ADI was similar to or higher than the effect of age and BMI. While the effect of neighborhood environment was modest, a neighborhood-level socioenvironmental variable like ADI might be used by clinicians and researchers to improve the characterization of patients' risk profile for chronic pain outcomes.
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Affiliation(s)
- Jessica Peoples
- Biobehavioral Nursing Science, University of Florida, Gainesville, FL, USA
| | - Jared J Tanner
- Department of Clinical and Health Psychology, Gainesville, FL, USA
| | - Emily J Bartley
- Pain Research and Intervention Center of Excellence (PRICE), College of Nursing, University of Florida, 1225 Center Drive, PO Box 100197, Gainesville, FL, 32610-0197, USA
- Community Dentistry and Behavioral Science, University of Florida, Gainesville, FL, USA
| | - Lisa H Domenico
- Biobehavioral Nursing Science, University of Florida, Gainesville, FL, USA
| | - Cesar E Gonzalez
- Department of Psychology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Josue S Cardoso
- Department of Biobehavioral Health, Penn State University, University Park, PA, USA
| | | | | | - Roland Staud
- Department of Medicine, University of Florida, Gainesville, FL, USA
| | - Burel R Goodin
- Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO, USA
| | - Roger B Fillingim
- Pain Research and Intervention Center of Excellence (PRICE), College of Nursing, University of Florida, 1225 Center Drive, PO Box 100197, Gainesville, FL, 32610-0197, USA
| | - Ellen L Terry
- Biobehavioral Nursing Science, University of Florida, Gainesville, FL, USA.
- Pain Research and Intervention Center of Excellence (PRICE), College of Nursing, University of Florida, 1225 Center Drive, PO Box 100197, Gainesville, FL, 32610-0197, USA.
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Wang L, Yang H, Wang C, Wang M, Huang J, Nyunt T, Osorio C, Sun SY, Pacifici M, Lefebvre V, Moore DC, Wang S, Yang W. SHP2 ablation mitigates osteoarthritic cartilage degeneration by promoting chondrocyte anabolism through SOX9. FASEB J 2024; 38:e70013. [PMID: 39225365 PMCID: PMC11404350 DOI: 10.1096/fj.202400642r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2024] [Revised: 07/21/2024] [Accepted: 08/13/2024] [Indexed: 09/04/2024]
Abstract
Articular cartilage phenotypic homeostasis is crucial for life-long joint function, but the underlying cellular and molecular mechanisms governing chondrocyte stability remain poorly understood. Here, we show that the protein tyrosine phosphatase SHP2 is differentially expressed in articular cartilage (AC) and growth plate cartilage (GPC) and that it negatively regulates cell proliferation and cartilage phenotypic program. Postnatal SHP2 deletion in Prg4+ AC chondrocytes increased articular cellularity and thickness, whereas SHP2 deletion in Acan+ pan-chondrocytes caused excessive GPC chondrocyte proliferation and led to joint malformation post-puberty. These observations were verified in mice and in cultured chondrocytes following treatment with the SHP2 PROTAC inhibitor SHP2D26. Further mechanistic studies indicated that SHP2 negatively regulates SOX9 stability and transcriptional activity by influencing SOX9 phosphorylation and promoting its proteasome degradation. In contrast to published work, SHP2 ablation in chondrocytes did not impact IL-1-evoked inflammation responses, and SHP2's negative regulation of SOX9 could be curtailed by genetic or chemical SHP2 inhibition, suggesting that manipulating SHP2 signaling has translational potential for diseases of cartilage dyshomeostasis.
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Affiliation(s)
- Lijun Wang
- Department of Orthopaedic Surgery, Brown University Alpert Medical School, Rhode Island Hospital, Providence, Rhode Island, USA
| | - Huiliang Yang
- Department of Orthopaedic Surgery, Brown University Alpert Medical School, Rhode Island Hospital, Providence, Rhode Island, USA
| | - Changwei Wang
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
- Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA
- Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan, USA
| | - Mingliang Wang
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
- Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA
- Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan, USA
| | - Jiahui Huang
- Department of Orthopaedic Surgery, Brown University Alpert Medical School, Rhode Island Hospital, Providence, Rhode Island, USA
| | - Thedoe Nyunt
- Department of Orthopaedic Surgery, Brown University Alpert Medical School, Rhode Island Hospital, Providence, Rhode Island, USA
| | - Camilo Osorio
- Department of Orthopaedic Surgery, Brown University Alpert Medical School, Rhode Island Hospital, Providence, Rhode Island, USA
| | - Shi-Yong Sun
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Maurizio Pacifici
- Translational Research Program in Pediatric Orthopaedics, Division of Orthopaedic Surgery, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | - Véronique Lefebvre
- Translational Research Program in Pediatric Orthopaedics, Division of Orthopaedic Surgery, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | - Douglas C Moore
- Department of Orthopaedic Surgery, Brown University Alpert Medical School, Rhode Island Hospital, Providence, Rhode Island, USA
| | - Shaomeng Wang
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
- Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA
- Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan, USA
| | - Wentian Yang
- Department of Orthopaedic Surgery, Brown University Alpert Medical School, Rhode Island Hospital, Providence, Rhode Island, USA
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Eckstein KN, Hergert JE, Uzcategui AC, Schoonraad SA, Bryant SJ, McLeod RR, Ferguson VL. Controlled Mechanical Property Gradients Within a Digital Light Processing Printed Hydrogel-Composite Osteochondral Scaffold. Ann Biomed Eng 2024; 52:2162-2177. [PMID: 38684606 PMCID: PMC11989580 DOI: 10.1007/s10439-024-03516-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Accepted: 04/07/2024] [Indexed: 05/02/2024]
Abstract
Tissue engineered scaffolds are needed to support physiological loads and emulate the micrometer-scale strain gradients within tissues that guide cell mechanobiological responses. We designed and fabricated micro-truss structures to possess spatially varying geometry and controlled stiffness gradients. Using a custom projection microstereolithography (μSLA) system, using digital light projection (DLP), and photopolymerizable poly(ethylene glycol) diacrylate (PEGDA) hydrogel monomers, three designs with feature sizes < 200 μm were formed: (1) uniform structure with 1 MPa structural modulus ( E ) designed to match equilibrium modulus of healthy articular cartilage, (2) E = 1 MPa gradient structure designed to vary strain with depth, and (3) osteochondral bilayer with distinct cartilage ( E = 1 MPa) and bone ( E = 7 MPa) layers. Finite element models (FEM) guided design and predicted the local mechanical environment. Empty trusses and poly(ethylene glycol) norbornene hydrogel-infilled composite trusses were compressed during X-ray microscopy (XRM) imaging to evaluate regional stiffnesses. Our designs achieved target moduli for cartilage and bone while maintaining 68-81% porosity. Combined XRM imaging and compression of empty and hydrogel-infilled micro-truss structures revealed regional stiffnesses that were accurately predicted by FEM. In the infilling hydrogel, FEM demonstrated the stress-shielding effect of reinforcing structures while predicting strain distributions. Composite scaffolds made from stiff μSLA-printed polymers support physiological load levels and enable controlled mechanical property gradients which may improve in vivo outcomes for osteochondral defect tissue regeneration. Advanced 3D imaging and FE analysis provide insights into the local mechanical environment surrounding cells in composite scaffolds.
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Affiliation(s)
- Kevin N Eckstein
- Paul M. Rady Department of Mechanical Engineering, University of Colorado at Boulder, 427 UCB, Boulder, CO, 80309, USA
| | - John E Hergert
- Materials Science and Engineering Program, University of Colorado at Boulder, Boulder, CO, USA
| | - Asais Camila Uzcategui
- Materials Science and Engineering Program, University of Colorado at Boulder, Boulder, CO, USA
| | - Sarah A Schoonraad
- Department of Chemical and Biological Engineering, University of Colorado at Boulder, Boulder, CO, USA
| | - Stephanie J Bryant
- Materials Science and Engineering Program, University of Colorado at Boulder, Boulder, CO, USA
- BioFrontiers Institute, University of Colorado at Boulder, Boulder, CO, USA
- Department of Chemical and Biological Engineering, University of Colorado at Boulder, Boulder, CO, USA
| | - Robert R McLeod
- Materials Science and Engineering Program, University of Colorado at Boulder, Boulder, CO, USA
- Department of Electrical, Computer & Energy Engineering, University of Colorado at Boulder, Boulder, CO, USA
| | - Virginia L Ferguson
- Paul M. Rady Department of Mechanical Engineering, University of Colorado at Boulder, 427 UCB, Boulder, CO, 80309, USA.
- Materials Science and Engineering Program, University of Colorado at Boulder, Boulder, CO, USA.
- BioFrontiers Institute, University of Colorado at Boulder, Boulder, CO, USA.
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Battaglia AG, D’Apolito R, Labionda F, Ramazzotti J, Zagra L. Ultrasound-Guided Hip Injections with High Density Hyaluronic Acid: Outcome at One Year Follow Up. J Clin Med 2024; 13:2515. [PMID: 38731044 PMCID: PMC11084914 DOI: 10.3390/jcm13092515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Revised: 04/14/2024] [Accepted: 04/22/2024] [Indexed: 05/13/2024] Open
Abstract
Background: The ultrasound-guided viscosupplementation of the hip joint with hyaluronic acid (HA) is considered a standard procedure among the conservative treatments for hip arthritis. The aim of this study was to evaluate the clinical benefit and the incidence of adverse events of the technique in an observational study at one year follow up. Methods: We evaluated a consecutive series of 85 patients with a diagnosis of symptomatic arthritis who underwent intra-articular ultrasound-guided hyaluronic acid injections. The scales used for evaluation were modified Harris Hip Score (mHHS), WOMAC (Western Ontario and McMaster University), and Hip Outcome Score (HOS) with subscale Sport (HOSs), for pain the Visual Analogic Scale (VAS). The patients were classified according to Tonnis' radiological classification of arthritis (range 0-3): 20 patients (grade 0), 32 (grade 1), 18 (grade 2), 15 (grade 3). Results: At last follow up, all the scales increased: mHHS from 59.35 to 82.1, HOS from 69.45 to 78.53, HOss from 47.4 to 58.11, VAS from 6.09 to 3.97, WOMAC from 33.2 to 31.5 (p < 0.05 for all the parameters); the results were elaborated with GraphPad Prism v5.0 (Prism Software La Jolla, CA, USA) using Wilcoxon's test. A total of 13 patients out of 85 needed arthroplasty, all classified as Tonnis grade 3. No serious adverse events were noted due to the procedure. Conclusions: Based on our findings, indication for the use of hyaluronic acid is limited to patients with mild to moderate arthritis. Patients in advanced arthritis refusing replacement surgery and asking for this treatment should be informed about the poor results of the technique even in the short term.
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Affiliation(s)
- Antonino Giulio Battaglia
- IRCCS Istituto Ortopedico Galeazzi, Hip Department, 20157 Milan, Italy; (R.D.); (F.L.); (J.R.); (L.Z.)
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10
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Campos-Villegas C, Pérez-Alenda S, Carrasco JJ, Igual-Camacho C, Tomás-Miguel JM, Cortés-Amador S. Effectiveness of proprioceptive neuromuscular facilitation therapy and strength training among post-menopausal women with thumb carpometacarpal osteoarthritis. A randomized trial. J Hand Ther 2024; 37:172-183. [PMID: 35948454 DOI: 10.1016/j.jht.2022.07.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 06/21/2022] [Accepted: 07/03/2022] [Indexed: 02/03/2023]
Abstract
BACKGROUND Thumb carpometacarpal osteoarthritis (CMC OA) greatly affects post-menopausal women. It is characterized by pain and functional deficits that limit the performance of activities of daily life and affect quality of life. PURPOSE Analyze the effects of 4/weeks strength training, with and without proprioceptive neuromuscular facilitation (PNF) on the disability among post-menopausal women with thumb CMC OA. Secondly, analyze the effects on pain, mobility, and strength. STUDY DESIGN Superiority randomized clinical trial. METHODS 42 women were randomly allocated to strength training program (SEG, n = 21) and to a strength training plus PNF therapy program (PNFG, n = 21). The Disability (disabilities of the arm, shoulder and hand questionnaire), pain (visual analogue scale), mobility (Kapandji Test), and hand strength were evaluated pre, post intervention (at 4 weeks) and follow-up (at 8 weeks). RESULTS Disability was significantly reduced in both groups after intervention, but reduction was statistically superior in PNFG (between-group mean difference [MD] = -16.69 points; CI = -21.56:-11.82; P<.001; d = 2.14). Similar results were observed for secondary outcomes: pain (MD = -2.03; CI = -2.83:-1.22; P<.001; d = 1.58), mobility (MD = 0.96; CI = 0.52:1.38; P<.001; d = 1.40) and strength (grip: MD = 3.47kg; CI = 1.25:5.69; P = .003; d = 0.97, palmar: MD = 0.97kg; CI = 0.14:1.80; P = .024; d = 0.72, tip: MD = 1.12kg; CI = 0.41:1.83; P = .003; d = 0.99 and key pinch: MD = 0.85kg; CI = 0.001:1.70; P = .049; d = 0.62). These improvements were maintained at follow-up. CONCLUSIONS The combination of PNF exercises and strength training is more effective for reducing disability pain and improve mobility and strength in post-menopausal women with CMC OA than a programme based solely on strength.
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Affiliation(s)
| | - Sofía Pérez-Alenda
- Physiotherapy in Motion Multispeciality Research Group (PTinMOTION), Department of Physiotherapy, University of Valencia, Valencia, Spain
| | - Juan J Carrasco
- Physiotherapy in Motion Multispeciality Research Group (PTinMOTION), Department of Physiotherapy, University of Valencia, Valencia, Spain.
| | - Celedonia Igual-Camacho
- Group of Physiotherapy in the Ageing Process, Department of Physiotherapy, University of Valencia, Valencia, Spain
| | | | - Sara Cortés-Amador
- UBIC research group, Department of Physiotherapy, University of Valencia, Valencia, Spain
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11
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Piccionello AP, Sassaroli S, Pennasilico L, Rossi G, Di Cerbo A, Riccio V, Di Bella C, Laghi L, Angelini M, Marini C, Magi GE. Comparative study of 1H-NMR metabolomic profile of canine synovial fluid in patients affected by four progressive stages of spontaneous osteoarthritis. Sci Rep 2024; 14:3627. [PMID: 38351089 PMCID: PMC10864333 DOI: 10.1038/s41598-024-54144-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Accepted: 02/08/2024] [Indexed: 02/16/2024] Open
Abstract
The study aimed to assess the metabolomic profile of the synovial fluid (SF) of dogs affected by spontaneous osteoarthritis (OA) and compare any differences based on disease progression. Sixty client-owned dogs affected by spontaneous OA underwent clinical, radiographic, and cytologic evaluations to confirm the diagnosis. The affected joints were divided into four study groups based on the Kallgreen-Lawrence classification: OA1 (mild), OA2 (moderate), OA3 (severe), and OA4 (extremely severe/deforming). The osteoarthritic joint's SF was subjected to cytologic examination and 1H-NMR analysis. The metabolomic profiles of the study groups' SF samples were statistically compared using one-way ANOVA. Sixty osteoarthritic joints (45 stifles, 10 shoulders and 5 elbows) were included in the study. Fourteen, 28, and 18 joints were included in the OA1, OA2, and OA3 groups, respectively (0 joints in the OA4 group). Metabolomic analysis identified 48 metabolites, five of which were significantly different between study groups: Mannose and betaine were elevated in the OA1 group compared with the OA2 group, and the 2-hydroxyisobutyrate concentration decreased with OA progression; in contrast, isoleucine was less concentrated in mild vs. moderate OA, and lactate increased in severe OA. This study identified different 1H-NMR metabolomic profiles of canine SF in patients with progressive degrees of spontaneous OA, suggesting 1H-NMR metabolomic analysis as a potential alternative method for monitoring OA progression. In addition, the results suggest the therapeutic potentials of the metabolomic pathways that involve mannose, betaine, 2-hydroxyisobutyrate, isoleucine, and lactate.
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Affiliation(s)
| | - Sara Sassaroli
- School of Biosciences and Veterinary Medicine, University of Camerino, 62024, Matelica, Italy
| | - Luca Pennasilico
- School of Biosciences and Veterinary Medicine, University of Camerino, 62024, Matelica, Italy.
| | - Giacomo Rossi
- School of Biosciences and Veterinary Medicine, University of Camerino, 62024, Matelica, Italy
| | - Alessandro Di Cerbo
- School of Biosciences and Veterinary Medicine, University of Camerino, 62024, Matelica, Italy
| | - Valentina Riccio
- School of Biosciences and Veterinary Medicine, University of Camerino, 62024, Matelica, Italy
| | - Caterina Di Bella
- School of Biosciences and Veterinary Medicine, University of Camerino, 62024, Matelica, Italy
| | - Luca Laghi
- Department of Agro-Food Science and Technology, University of Bologna, 47023, Cesena, Italy
| | - Maddalena Angelini
- School of Biosciences and Veterinary Medicine, University of Camerino, 62024, Matelica, Italy
| | - Carlotta Marini
- School of Biosciences and Veterinary Medicine, University of Camerino, 62024, Matelica, Italy
| | - Gian Enrico Magi
- School of Biosciences and Veterinary Medicine, University of Camerino, 62024, Matelica, Italy
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12
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Lu CT, Chang KY, Yii CY, Yong SB. Comment on "Efficacy and safety of Gutong Patch compared with NSAIDs for knee osteoarthritis: A real-world multicenter, prospective cohort study in China". Pharmacol Res 2024; 199:107027. [PMID: 38049042 DOI: 10.1016/j.phrs.2023.107027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 12/01/2023] [Indexed: 12/06/2023]
Affiliation(s)
- Chi-Tung Lu
- College of Medicine, China Medical University, Taichung, Taiwan
| | - Kai-Yen Chang
- College of Medicine, China Medical University, Taichung, Taiwan
| | - Chin-Yuan Yii
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Landseed International Hospital, Taoyuan, Taiwan; Department of Biomedical Sciences and Engineering, National Central University, Taoyuan, Taiwan.
| | - Su-Boon Yong
- Research Center for Allergy, Immunology, and Microbiome (A.I.M.), China Medical University Hospital, Taichung, Taiwan; Department of Allergy and Immunology, China Medical University Children's Hospital, Taichung, Taiwan; Department of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.
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13
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Zhao J, Liang G, Huang H, Yang W, Pan J, Luo M, Zeng L, Liu J. Potential Mechanisms Underlying the Therapeutic Roles of Gancao fuzi Decoction in Cold-dampness Obstruction Syndrome-type Knee Osteoarthritis. Curr Comput Aided Drug Des 2024; 20:384-395. [PMID: 37282569 PMCID: PMC10661966 DOI: 10.2174/1573409919666230605115940] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 03/23/2023] [Accepted: 04/19/2023] [Indexed: 06/08/2023]
Abstract
BACKGROUND The key active components and potential molecular mechanism of Gancao Fuzi decoction (GFD) in the treatment of cold-dampness obstruction-type knee osteoarthritis (KOA) remain unclear. OBJECTIVES To explore the mechanism of GFD in the treatment of cold-dampness obstruction syndrome-type KOA by network pharmacology. METHODS The potential active components and targets of the four herbs in GFD (Fuzi, Guizhi, Baizhu, and Gancao) were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. The targets of KOA were obtained with the Comparative Toxicogenomics Database (CTD), the GeneCards database, and the DisGeNET database, and the common targets of the drugs and disease were ultimately obtained. Cytoscape (v.3.7.1) was used to draw the active component-target network, and the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) (v.11.0) database was used to construct the protein interaction network. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for the Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the intersecting targets. RESULTS A total of 102 potential active components and 208 targets of GFD in the treatment of cold-dampness obstruction syndrome-type KOA were screened. GFD treatment was found to be closely related to many inflammatory signalling pathways in the treatment of KOA. CONCLUSION The effect of GFD on cold-dampness obstruction syndrome-type KOA is mediated by multicomponent, multitarget, and multichannel mechanisms, which provides the basis for further experimental study of its pharmacodynamic material basis and mechanism.
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Affiliation(s)
- Jinlong Zhao
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, China
- The Research Team on Bone and Joint Degeneration and Injury of Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, 510120, China
| | - Guihong Liang
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, China
- The Research Team on Bone and Joint Degeneration and Injury of Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, 510120, China
| | - Hetao Huang
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, China
| | - Weiyi Yang
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, China
| | - Jianke Pan
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, China
| | - Minghui Luo
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, China
| | - Lingfeng Zeng
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, China
- The Research Team on Bone and Joint Degeneration and Injury of Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, 510120, China
| | - Jun Liu
- The Research Team on Bone and Joint Degeneration and Injury of Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, 510120, China
- The Fifth Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China
- Guangdong Second Chinese Medicine Hospital Guangdong Province Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou, 510095, China
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14
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Yang HY, Seon JK. The landscape of surgical robotics in orthopedics surgery. Biomed Eng Lett 2023; 13:537-542. [PMID: 37873001 PMCID: PMC10590337 DOI: 10.1007/s13534-023-00321-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 08/17/2023] [Accepted: 09/07/2023] [Indexed: 10/25/2023] Open
Abstract
Orthopedic surgery is one of the first surgical specialties to apply surgical robotics in clinical practice, which has become an interesting field over the years with promising results. Surgical robotics can facilitate total joint arthroplasty by providing robotic support to accurately prepare the bone, improving the ability to reproduce alignment, and restoring normal kinematics. Various robotic systems are available on the market, each tailored to specific types of surgeries and characterized by a series of features with different requirements and/or modus operandi. Here, a narrative review of the current state of surgical robotic systems for total joint knee arthroplasty is presented, covering the different categories of robots, which are classified based on the operation, requirements, and level of interaction with the surgeon. The different robotic systems include closed/open platform, image-based/imageless, and passive/active/semi-active systems. The main goal of a robotic system is to increase the accuracy and precision of the operation regardless of the type of system. Despite the short history of surgical robots, they have shown clinical effectiveness compared to conventional techniques in orthopedic surgery. When considering which robotic system to use, surgeons should carefully evaluate the different benefits and drawbacks to select the surgical robot that fits their needs the best.
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Affiliation(s)
- Hong Yeol Yang
- Department of Orthopedic Surgery, Chonnam National University Medical School and Hwasun Hospital, Seoyang-ro 322, Hwasun-gun, Chonnam, Republic of Korea
| | - Jong Keun Seon
- Department of Orthopedic Surgery, Chonnam National University Medical School and Hwasun Hospital, Seoyang-ro 322, Hwasun-gun, Chonnam, Republic of Korea
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Vo NX, Che UTT, Ngo TTT, Bui TT. Economic Evaluation of Glucosamine in Knee Osteoarthritis Treatments in Vietnam. Healthcare (Basel) 2023; 11:2502. [PMID: 37761699 PMCID: PMC10531128 DOI: 10.3390/healthcare11182502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 09/08/2023] [Accepted: 09/08/2023] [Indexed: 09/29/2023] Open
Abstract
Osteoarthritis (OA) is the degeneration of cartilage in joints that results in bones rubbing against each other; it causes uncomfortable symptoms such as pain, swelling, and stiffness and can lead to disability. It usually occurs in the elderly and causes a large medical burden. The aim of this study is to evaluate the cost-effectiveness between the standard treatment for osteoarthritis and standard treatment with added crystalline glucosamine sulfate at various stages. Markov analysis modeling was applied to evaluate the effect of both adding glucosamine compared to standard treatment from a societal perspective during whole patients' lifetimes. Data input was collected from reviews in previous studies. The outcome was measured in quality-adjusted life years (QALYs), and the Incremental Cost-Effectiveness Ratio (ICER) from a societal perspective was applied with 3% and discounted for all costs and outcomes. One-way analysis via the Tornado diagram was performed to investigate the change in factors in the model. In general, adding glucosamine into the standard treatment proved to be more cost-effective compared to the standard treatment. Particularly, the early-stage addition of glucosamine in the treatment was cost-effective compared to the post-stage addition of glucosamine. The addition of supplementing crystalline glucosamine sulfate to the whole regimen at any stage was cost-effective at the willingness-to-pay (WTP) threshold.
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Affiliation(s)
- Nam Xuan Vo
- Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City 700000, Vietnam; (U.T.T.C.); (T.T.T.N.)
| | - Uyen Thi Thuc Che
- Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City 700000, Vietnam; (U.T.T.C.); (T.T.T.N.)
| | - Thanh Thi Thanh Ngo
- Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City 700000, Vietnam; (U.T.T.C.); (T.T.T.N.)
| | - Tien Thuy Bui
- Faculty of Pharmacy, Le Van Thinh Hospital, Ho Chi Minh City 700000, Vietnam;
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16
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Yu H, Gong Z, Wang G, Cao R, Yin H, Ma L, Guo A. DHA attenuates cartilage degeneration by mediating apoptosis and autophagy in human chondrocytes and rat models of osteoarthritis. In Vitro Cell Dev Biol Anim 2023; 59:455-466. [PMID: 37450265 DOI: 10.1007/s11626-023-00781-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Accepted: 07/03/2023] [Indexed: 07/18/2023]
Abstract
Osteoarthritis (OA) is a degenerative joint disease that usually occurs in the elderly, and docosahexaenoic acid (DHA) plays a therapeutic role in cardiovascular disease, diabetes, and rheumatoid arthritis (RA) with its anti-inflammatory and antioxidant effects. The objective of this study is to investigate the effect and mechanism of DHA on hypertrophic differentiation and senescence of OA chondrocytes to provide a theoretical basis for the effect of OA clinical treatment. A human OA chondrocyte model was established by IL-1β, and a rat model of OA was established by anterior cruciate ligament (ACL) transection and medial meniscectomy. The result showed DHA promoted chondrocyte proliferation and reduced apoptosis. Transmission electron microscopy (TEM) analysis showed that there were more autophagosomes in the cytoplasm under the treatment of DHA. Compared to the OA group, samples from the OA + DHA group showed thickened cartilage, reduced degeneration, and an increased rate of collagen II-positive cells, while the Mankin score was significantly lower. In addition, DHA decreased the expression of phosphorylated mammalian target of rapamycin (p-mTOR) and the ratio of light chain 3-I/II (LC3-I/II) and increased the expression of Beclin-1 and Bcl-2 measured by western blot analysis. Therefore, DHA promotes chondrocyte proliferation, reduces apoptosis, and increases autophagy in OA chondrocytes, a process that is accomplished by inhibiting the expression of mTOR, c-Jun N-terminal kinase (JNK), and p38 signaling pathways, providing new perspectives and bootstrap points for the prevention and treatment of OA.
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Affiliation(s)
- Haomiao Yu
- Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Yongan Road 95, Xicheng Distinct, Beijing, 100050, People's Republic of China
| | - Zishun Gong
- Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Yongan Road 95, Xicheng Distinct, Beijing, 100050, People's Republic of China
| | - Guodong Wang
- Department of Orthopaedics, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Ruiqi Cao
- Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Yongan Road 95, Xicheng Distinct, Beijing, 100050, People's Republic of China
| | - Heyong Yin
- Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Yongan Road 95, Xicheng Distinct, Beijing, 100050, People's Republic of China
| | - Lifeng Ma
- Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Yongan Road 95, Xicheng Distinct, Beijing, 100050, People's Republic of China.
| | - Ai Guo
- Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Yongan Road 95, Xicheng Distinct, Beijing, 100050, People's Republic of China.
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Morejon A, Schwartz G, Best TM, Travascio F, Jackson AR. Effect of molecular weight and tissue layer on solute partitioning in the knee meniscus. OSTEOARTHRITIS AND CARTILAGE OPEN 2023; 5:100360. [PMID: 37122844 PMCID: PMC10133802 DOI: 10.1016/j.ocarto.2023.100360] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 04/04/2023] [Indexed: 05/02/2023] Open
Abstract
Objective Knee meniscus tissue is partly vascularized, meaning that nutrients must be transported through the extracellular matrix of the avascular portion to reach resident cells. Similarly, drugs used as therapeutic agents to treat meniscal pathologies rely on transport through the tissue. The driving force of diffusive transport is the gradient of concentration, which depends on molecular solubility. The meniscus is organized into a core region sandwiched between the tibial and femoral superficial layers. Structural differences exist across meniscal regions; therefore, regional differences in solubility are also hypothesized. Methods Samples from the core, tibial and femoral layers were obtained from 5 medial and 5 lateral porcine menisci. The partition coefficient (K) of fluorescein, 3 kDa and 40 kDa dextrans in the layers of the meniscus was measured using an equilibration experiment. The effect of meniscal compartment, layer, and solute molecular weight on K was analyzed using a three-way ANOVA. Results K ranged from a high of ∼2.9 in fluorescein to a low of ∼0.1 in 40 kDa dextran and was inversely related to the solute molecular weight across all tissue regions. Tissue layer only had a significant effect on partitioning of 40k Dex solute, which was lower in the tibial surface layer relative to the core (p = 0.032). Conclusion This study provides insight into depth-dependent partitioning in the meniscus, indicating the limiting effect of the meniscus superficial layer on solubility increases with solute molecular size. This illustrates how the surface layers could potentially reduce the effectiveness of drug delivery therapies incorporating large molecules (>40 kDa).
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Affiliation(s)
- Andy Morejon
- Department of Mechanical and Aerospace Engineering, University of Miami, Coral Gables, FL, USA
| | - Gabi Schwartz
- Department of Biomedical Engineering, University of Miami, Coral Gables, FL, USA
| | - Thomas M. Best
- Department of Biomedical Engineering, University of Miami, Coral Gables, FL, USA
- Department of Orthopedic Surgery, University of Miami, Coral Gables, FL, USA
- UHealth Sports Medicine Institute, Coral Gables, FL, USA
| | - Francesco Travascio
- Department of Mechanical and Aerospace Engineering, University of Miami, Coral Gables, FL, USA
- Department of Orthopedic Surgery, University of Miami, Coral Gables, FL, USA
- Max Biedermann Institute for Biomechanics at Mount Sinai Medical Center, Miami Beach, FL, USA
- Corresponding author. College of Engineering, University of Miami, 1251 Memorial Drive, MEB 276, Coral Gables, FL 33146, USA.
| | - Alicia R. Jackson
- Department of Biomedical Engineering, University of Miami, Coral Gables, FL, USA
- Corresponding author. College of Engineering, University of Miami, 1251 Memorial Drive, MEA 219, Coral Gables, FL 33146 USA.
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Higa S, Nakata K, Karasawa Y, Ohwaki K. Comparative effectiveness of early initiation of oral nonsteroidal anti-inflammatory drug and oral acetaminophen therapies on the time to knee replacement in patients with knee osteoarthritis in Japan. BMC Musculoskelet Disord 2023; 24:297. [PMID: 37060072 PMCID: PMC10103473 DOI: 10.1186/s12891-023-06415-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 04/10/2023] [Indexed: 04/16/2023] Open
Abstract
BACKGROUND Although disease-modifying properties of nonsteroidal anti-inflammatory drugs (NSAIDs) for osteoarthritis (OA) have been reported, the effects of NSAIDs on OA progression remain controversial. The purpose of this study was to investigate the effect of early initiation of oral NSAID therapy on the progression of knee OA. METHODS In this retrospective cohort study, we extracted data of patients newly diagnosed with knee OA between November 2007 and October 2018 from a Japanese claims database. The primary outcome was the time to knee replacement (KR), and the secondary outcome was the time to composite event including joint lavage and debridement, osteotomy, or arthrodesis in addition to KR. Weighted Cox regression analysis with standardized mortality/morbidity ratio (SMR) weight was performed to compare the outcomes between patients prescribed oral NSAID (NSAID group) and those prescribed oral acetaminophen (APAP) (APAP group) early after a diagnosis of knee OA. Propensity scores were calculated using logistic regression conditioned on potential confounding factors, and SMR weights were calculated using the propensity scores. RESULTS The study population comprised 14,261 patients, who were divided into two groups as follows: 13,994 in the NSAID group and 267 in the APAP group. The mean ages of patients in the NSAID and APAP groups were 56.9 and 56.1 years, respectively. Furthermore, 62.01% and 68.16% patients in the NSAID and APAP groups, respectively, were female. The NSAID group had a reduced risk of KR compared with the APAP group in the analysis using SMR weighting (SMR-weighted hazard ratio, 0.19; 95% confidence interval, 0.05-0.78). While no statistically significant difference was found for the risk of composite event between the two groups (SMR-weighted hazard ratio, 0.56; 95% confidence interval, 0.16-1.91). CONCLUSIONS The risk of KR in the NSAID group was significantly lower than that in the APAP group after accounting for residual confounding using SMR weighting. This finding suggests that oral NSAID therapy early after the initial diagnosis is associated with a reduced risk of KR in patients with symptomatic knee OA.
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Affiliation(s)
- Shingo Higa
- Teikyo University Graduate School of Public Health, Tokyo, Japan.
- Medical Affairs, Viatris Pharmaceuticals Japan Inc., Tokyo, Japan.
| | - Ken Nakata
- Department of Health and Sport Sciences, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Yusuke Karasawa
- Medical Affairs, Viatris Pharmaceuticals Japan Inc., Tokyo, Japan
| | - Kazuhiro Ohwaki
- Teikyo University Graduate School of Public Health, Tokyo, Japan
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Yau MS, Jonsson H, Lynch JA, Lewis CE, Torner JC, Nevitt MC, Felson DT. Do associations with hand OA vary by knee osteoarthritis phenotype? Cross-sectional data from the Multicenter Osteoarthritis Study. OSTEOARTHRITIS AND CARTILAGE OPEN 2023; 5:100331. [PMID: 36605850 PMCID: PMC9807822 DOI: 10.1016/j.ocarto.2022.100331] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Revised: 12/07/2022] [Accepted: 12/19/2022] [Indexed: 12/24/2022] Open
Abstract
Objective Osteoarthritis (OA) is highly heterogeneous and has both biomechanical and systemic components that may not have the same etiology. We therefore aimed to identify specific knee OA phenotypes that may be more strongly associated with hand OA to refine the criteria used to define multi-joint OA. Design We assessed data from the Multicenter Osteoarthritis Study (MOST). We ascertained hand OA from bilateral hand photographs; scores for each joint row were summed to yield an aggregate hand OA score. Knee OA was ascertained from bilateral posteroanterior knee radiographs read for Kellgren-Lawrence grade and individual radiographic features. We tested associations between hand and knee OA with phenotypes including symptomatic OA, hyper- and atrophic knee OA, and one excluding post-traumatic OA. Associations between hand and knee OA were assessed with logistic regression, adjusted for age. Results We studied 2493 participants with hand and knee OA measures. Median age was 63 years with 57% women. 55% had an aggregate hand OA score ≥2; frequency of knee OA phenotypes ranged from 8% to 34%. The age-adjusted odds ratio (OR) was 1.14 (95% confidence interval (CI) = 1.04-1.26) for knee OA per standard deviation of the hand OA aggregate score. Hand OA associations with symptomatic knee OA and knee OA excluding post-traumatic knee OA were OR = 1.16 (95% CI = 1.03-1.31) and OR = 1.21 (95% CI = 1.08-1.35), respectively. No other knee OA phenotype reached statistical significance. Conclusions Age-adjusted associations between hand and knee OA were modest and were largely similar across knee OA phenotypes.
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Affiliation(s)
- Michelle S. Yau
- Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
| | - Helgi Jonsson
- Department of Rheumatology, Landspitalinn University Hospital, University of Iceland, Reykjavik, Iceland
| | - John A. Lynch
- MRI Quality Assurance, Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA
| | - Cora E. Lewis
- Division of Preventive Medicine, Department of Epidemiology, University of Alabama, Birmingham, AL, USA
| | - James C. Torner
- Department of Epidemiology, University of Iowa, Iowa City, IA, USA
| | - Michael C. Nevitt
- Department of Epidemiology & Biostatistics, University of California, San Francisco, USA
| | - David T. Felson
- Section of Rheumatology, Department of Medicine, Boston University School of Medicine, USA
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20
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Singh JA. Making the current non-surgical treatments for knee osteoarthritis more effective: Solutions from a diverse patient group. Joint Bone Spine 2023; 90:105535. [PMID: 36706945 DOI: 10.1016/j.jbspin.2023.105535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 12/21/2022] [Accepted: 12/28/2022] [Indexed: 01/26/2023]
Abstract
OBJECTIVE To examine patient perceived solutions to barriers to effective non-surgical knee osteoarthritis (OA) treatments in a diverse racial/ethnic group. METHODS Nominal groups were conducted with consecutive patients with knee OA at a medical center clinic, oversampling for African Americans with knee OA. Participants discussed potential solutions and rank-ordered their concerns. RESULTS Thirteen nominal groups with 46 knee OA patients were conducted with mean age, 60.8 years (standard deviation [sd], 10.0) and knee OA duration, 8.1 years (sd, 5.4); 22% were men, and 56% were African American. The following solutions were in the top three ranked solutions in 13 NGTs: (A) more research, effective and/or safer new medications/treatments, and joint cartilage restoration (8 groups; 15% votes [43/276]); (B) early diagnosis (2 groups; 7% votes [20/276]); (C) better and more effective communication (5 groups; 10% votes [29/276]); (D) public and patient education (4 groups; 8% votes [22/276]); (E) motivation and behavioral modification (4 groups; 9% votes [26/276]); (F) team approach (1 group; 1% votes [2/276]); (G) personalized medicine (6 groups; 8% votes [24/276]); (H) cheaper and more affordable medications and treatments (3 groups; 5% votes [15/276]). CONCLUSIONS A diverse group of participants with knee OA identified several solutions to barriers to the effectiveness of current knee OA treatments. This new knowledge can inform the development and implementation of future interventions to improve the outcomes of people with knee OA.
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Affiliation(s)
- Jasvinder A Singh
- Medicine Service, VA Medical Center, 510, 20th street South, FOT 805B, Birmingham, AL 35233, USA; Department of Medicine at School of Medicine, University of Alabama at Birmingham, 1720 Second Ave. South, Birmingham, AL 35294-0022, USA; Division of Epidemiology at School of Public Health, University of Alabama at Birmingham, 1720 Second Ave. South, Birmingham, AL 35294-0022, USA.
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21
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Khokhar NS, DePalma MJ. Joints. Regen Med 2023. [DOI: 10.1007/978-3-030-75517-1_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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22
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Chan DD, Mashiatulla M, Li J, Ross RD, Pendyala M, Patwa A, Grinstaff MW, Plaas A, Sumner DR. Contrast-enhanced micro-computed tomography of compartment and time-dependent changes in femoral cartilage and subchondral plate in a murine model of osteoarthritis. Anat Rec (Hoboken) 2023; 306:92-109. [PMID: 35751529 PMCID: PMC10084428 DOI: 10.1002/ar.25027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 06/13/2022] [Accepted: 06/15/2022] [Indexed: 01/29/2023]
Abstract
A lack of understanding of the mechanisms underlying osteoarthritis (OA) progression limits the development of effective long-term treatments. Quantitatively tracking spatiotemporal patterns of cartilage and bone degeneration is critical for assessment of more appropriately targeted OA therapies. In this study, we use contrast-enhanced micro-computed tomography (μCT) to establish a timeline of subchondral plate (SCP) and cartilage changes in the murine femur after destabilization of the medial meniscus (DMM). We performed DMM or sham surgery in 10-12-week-old male C57Bl/6J mice. Femora were imaged using μCT after 0, 2, 4, or 8 weeks. Cartilage-optimized scans were performed after immersion in contrast agent CA4+. Bone mineral density distribution (BMDD), cartilage attenuation, SCP, and cartilage thickness and volume were measured, including lateral and medial femoral condyle and patellar groove compartments. As early as 2 weeks post-DMM, cartilage thickness significantly increased and cartilage attenuation, SCP volume, and BMDD mean significantly decreased. Trends in cartilage and SCP metrics within each joint compartment reflected those seen in global measurements, and both BMDD and SCP thickness were consistently greater in the lateral and medial condyles than the patellar groove. Sham surgery also resulted in significant changes to SCP and cartilage metrics, highlighting a potential limitation of using surgical models to study tissue morphology or composition changes during OA progression. Contrast-enhanced μCT analysis is an effective tool to monitor changes in morphology and composition of cartilage, and when combined with bone-optimized μCT, can be used to assess the progression of degenerative changes after joint injury.
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Affiliation(s)
- Deva D Chan
- Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA.,Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA.,Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, USA
| | - Maleeha Mashiatulla
- Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, Illinois, USA
| | - Jun Li
- Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA
| | - Ryan D Ross
- Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, Illinois, USA
| | - Meghana Pendyala
- Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, USA
| | - Amit Patwa
- Department of Biomedical Engineering Department of Chemistry, Boston University, Boston, Massachusetts, USA.,Department of Chemistry, Boston University, Boston, Massachusetts, USA.,Division of Chemistry, Navrachana University, Vadodara, Gujarat, India
| | - Mark W Grinstaff
- Department of Biomedical Engineering Department of Chemistry, Boston University, Boston, Massachusetts, USA.,Department of Chemistry, Boston University, Boston, Massachusetts, USA
| | - Anna Plaas
- Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA
| | - D Rick Sumner
- Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, Illinois, USA
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23
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Talebi Jouybari M, Fani N, Jahangir S, Bagheri F, Golru R, Taghiyar L. Validation of Tissue-Engineered Constructs: Preclinical and Clinical Studies. CARTILAGE: FROM BIOLOGY TO BIOFABRICATION 2023:491-527. [DOI: 10.1007/978-981-99-2452-3_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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24
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Vargel İ, Tuncel A, Baysal N, Hartuç-Çevik İ, Korkusuz F. Autologous Adipose-Derived Tissue Stromal Vascular Fraction (AD-tSVF) for Knee Osteoarthritis. Int J Mol Sci 2022; 23:13517. [PMID: 36362308 PMCID: PMC9658499 DOI: 10.3390/ijms232113517] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 10/28/2022] [Accepted: 10/30/2022] [Indexed: 07/30/2023] Open
Abstract
Adipose tissue contains adult mesenchymal stem cells that may modulate the metabolism when applied to other tissues. Stromal vascular fraction (SVF) can be isolated from adipose tissue mechanically and/or enzymatically. SVF was recently used to decrease the pain and improve the function of knee osteoarthritis (OA) patients. Primary and/or secondary OA causes inflammation and degeneration in joints, and regenerative approaches that may modify the natural course of the disease are limited. SVF may modulate inflammation and initiate regeneration in joint tissues by initiating a paracrine effect. Chemokines released from SVF may slow down degeneration and stimulate regeneration in joints. In this review, we overviewed articular joint cartilage structures and functions, OA, and macro-, micro-, and nano-fat isolation techniques. Mechanic and enzymatic SVF processing techniques were summarized. Clinical outcomes of adipose tissue derived tissue SVF (AD-tSVF) were evaluated. Medical devices that can mechanically isolate AD-tSVF were listed, and publications referring to such devices were summarized. Recent review manuscripts were also systematically evaluated and included. Transferring adipose tissues and cells has its roots in plastic, reconstructive, and aesthetic surgery. Micro- and nano-fat is also transferred to other organs and tissues to stimulate regeneration as it contains regenerative cells. Minimal manipulation of the adipose tissue is recently preferred to isolate the regenerative cells without disrupting them from their natural environment. The number of patients in the follow-up studies are recently increasing. The duration of follow up is also increasing with favorable outcomes from the short- to mid-term. There are however variations for mean age and the severity of knee OA patients between studies. Positive outcomes are related to the higher number of cells in the AD-tSVF. Repetition of injections and concomitant treatments such as combining the AD-tSVF with platelet rich plasma or hyaluronan are not solidified. Good results were obtained when combined with arthroscopic debridement and micro- or nano-fracture techniques for small-sized cartilage defects. The optimum pressure applied to the tissues and cells during filtration and purification of the AD-tSVF is not specified yet. Quantitative monitoring of articular joint cartilage regeneration by ultrasound, MR, and synovial fluid analysis as well as with second-look arthroscopy could improve our current knowledge on AD-tSVF treatment in knee OA. AD-tSVF isolation techniques and technologies have the potential to improve knee OA treatment. The duration of centrifugation, filtration, washing, and purification should however be standardized. Using gravity-only for isolation and filtration could be a reasonable approach to avoid possible complications of other methodologies.
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Affiliation(s)
- İbrahim Vargel
- Department of Plastic Reconstructive and Aesthetic Surgery, Medical Faculty, Hacettepe University, Altındag, Ankara 06230, Turkey
| | - Ali Tuncel
- Department of Chemical Engineering, Engineering Faculty, Hacettepe University, Universiteler Mahallesi, Hacettepe Beytepe Campus #31, Çankaya, Ankara 06800, Turkey
| | - Nilsu Baysal
- Medical Faculty, Hacettepe University, Altındag, Ankara 06230, Turkey
| | - İrem Hartuç-Çevik
- Department of Sports Medicine, Medical Faculty, Hacettepe University, Altındag, Ankara 06230, Turkey
| | - Feza Korkusuz
- Department of Sports Medicine, Medical Faculty, Hacettepe University, Altındag, Ankara 06230, Turkey
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25
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Public Interest in Hyaluronic Acid Injections for Knee Osteoarthritis in the United States and Europe: An International Google Trends Analysis. Arthroplast Today 2022; 18:157-162. [PMID: 36353188 PMCID: PMC9638715 DOI: 10.1016/j.artd.2022.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Accepted: 09/07/2022] [Indexed: 11/11/2022] Open
Abstract
Background Hyaluronic acid injections remain a common nonsurgical alternative for the treatment of knee osteoarthritis despite limited clinical evidence and varying global recommendations regarding its use. We used the Google Trends tool to provide a quantitative analysis of public interest in hyaluronic acid injections for knee osteoarthritis in the United States and Europe. Methods We customized Google Trends parameters to obtain search data from January 2009 to December 2019 in both the United States and Europe. Combinations of "arthritis", "osteoarthritis", "hyaluronic acid", "knee arthritis", "knee osteoarthritis", and "knee injection" were entered into the Google Trends tool, and trend analyses were performed. Results The models generated to describe public interest in hyaluronic acid for knee injections in both the United States and Europe showed increased Google queries as time progressed (P < .001). The United States growth model displayed linear growth (r2 = 0.90) while the European growth model displayed exponential growth (r2 = 0.90). Conclusions Our results indicate a significant increase in Google queries related to hyaluronic acid injections for knee osteoarthritis since 2009 in both the United States and Europe. Our models suggest that despite mixed evidence supporting its use, orthopedic surgeons should expect continued public interest in hyaluronic acid for knee osteoarthritis. The results of our study may help to prepare surgeons for patient inquiries, inform the creation of evidence-based shared decision-making tools, and direct future research.
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26
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Xu H, Chai Q, Xu X, Li Z, Bao W, Man Z, Li W. Exosome-Functionalized Ti6Al4V Scaffolds Promoting Osseointegration by Modulating Endogenous Osteogenesis and Osteoimmunity. ACS APPLIED MATERIALS & INTERFACES 2022; 14:46161-46175. [PMID: 36203406 DOI: 10.1021/acsami.2c11102] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Periprosthetic bone defects are the most serious problem of revision total hip arthroplasty, which can easily lead to insufficient osteointegration between the prosthesis and host bone. Bone marrow mesenchymal stem cells (BMSCs) and a moderate inflammatory response at the prosthesis-bone interface play an important role in osteointegration. Here, we developed microarc oxide titanium implant loaded engineered exosomes (S-Exos) to promote osseointegration at the prosthesis-bone interface. First, Smurf1-shRNA was transferred into the BMSCs using a viral vector to prepare S-Exos, which were subsequently immobilized to the microarc oxide titanium implant surface with positively charged polyethyleneimine. The immobilized S-Exos could be slowly and uniformly released and subsequently phagocytosed by BMSCs and macrophages. Once the S-Exos were phagocytosed, they could simultaneously activate the BMP/Smad signaling pathway in the BMSCs and promote macrophage M2 polarization, both of which enhance osseointegration. Specifically, this S-Exos coating exhibits a dual effect of promoting osseointegration, including the osseointegration of BMSCs by activating the BMP/Smad signaling pathway and the macrophage M2 polarization promoting osseointegration. In summary, the construction of S-Exos modified microarc oxide titanium implants could provide a new method for promoting osteointegration between the prosthesis and host bone in revision total hip arthroplasty.
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Affiliation(s)
- Hailun Xu
- Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P. R. China
| | - Qihao Chai
- Department of Joint Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P. R. China
| | - Xianxing Xu
- Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P. R. China
| | - Ziyang Li
- Department of Joint Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P. R. China
| | - Wenfei Bao
- Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P. R. China
| | - Zhentao Man
- Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P. R. China
- Department of Joint Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P. R. China
| | - Wei Li
- Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P. R. China
- Department of Joint Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P. R. China
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27
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Luksameesate P, Tanavalee A, Taychakhoonavudh S. An economic evaluation of knee osteoarthritis treatments in Thailand. Front Pharmacol 2022; 13:926431. [PMID: 36225578 PMCID: PMC9549147 DOI: 10.3389/fphar.2022.926431] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 08/30/2022] [Indexed: 11/13/2022] Open
Abstract
Objective: The objective of this study is to evaluate the cost-effectiveness of different knee OA care sequences compared to standard treatment reimbursed by the major health insurance payer in Thailand.Method: We used decision analytical modeling to evaluate the effect of either adding etoricoxib or crystalline glucosamine sulfate compared to standard treatment from a societal perspective over patients’ lifetimes. Data were analyzed based on efficacy, whereas adverse events were considered as a substate. Model input data were retrieved from relevant published literature and the Standard Cost Lists for Health Technology Assessment, Thailand. All health outcomes were measured in a unit of quality-adjusted life-year (QALY). An incremental cost-effectiveness ratio (ICER) was applied to examine the costs and QALYs. Sensitivity analysis was performed to investigate the robustness of the model.Result: The results demonstrated that adding crystalline glucosamine sulfate (before diclofenac plus proton pump inhibitors, PPI) into the standard care sequence was a dominant strategy compared to the standard care sequence. Adding etoricoxib alone or including crystalline glucosamine sulfate (after diclofenac plus PPI) was dominated by adding crystalline glucosamine sulfate (before diclofenac plus PPI), whereas in a willingness-to-pay (WTP) threshold in Thailand, adding of both crystalline glucosamine sulfate (before diclofenac plus PPI) and etoricoxib were cost-effective when compared to adding crystalline glucosamine sulfate alone with ICER of 125,547 Thai baht/QALY (3,472 US dollars/QALY).Conclusion: The addition of crystalline glucosamine sulfate and etoricoxib into standard knee OA treatment were cost-effective at the WTP threshold in Thailand. In addition, early initiation of crystalline glucosamine sulfate would be less costly and more effective than delayed treatment or the use of standard treatment alone.
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Affiliation(s)
- Parnnaphat Luksameesate
- Department of Social and Administrative Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
| | - Aree Tanavalee
- Department of Social and Administrative Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
| | - Suthira Taychakhoonavudh
- Department of Orthopaedics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- *Correspondence: Suthira Taychakhoonavudh,
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Yunus U, Amin J, Sharif M, Yasmin M, Kadry S, Krishnamoorthy S. Recognition of Knee Osteoarthritis (KOA) Using YOLOv2 and Classification Based on Convolutional Neural Network. Life (Basel) 2022; 12:1126. [PMID: 36013305 PMCID: PMC9410095 DOI: 10.3390/life12081126] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 07/02/2022] [Accepted: 07/05/2022] [Indexed: 12/23/2022] Open
Abstract
Knee osteoarthritis (KOA) is one of the deadliest forms of arthritis. If not treated at an early stage, it may lead to knee replacement. That is why early diagnosis of KOA is necessary for better treatment. Manually KOA detection is a time-consuming and error-prone task. Computerized methods play a vital role in accurate and speedy detection. Therefore, the classification and localization of the KOA method are proposed in this work using radiographic images. The two-dimensional radiograph images are converted into three-dimensional and LBP features are extracted having the dimension of N × 59 out of which the best features of N × 55 are selected using PCA. The deep features are also extracted using Alex-Net and Dark-net-53 with the dimensions of N × 1024 and N × 4096, respectively, where N represents the number of images. Then, N × 1000 features are selected individually from both models using PCA. Finally, the extracted features are fused serially with the dimension of N × 2055 and passed to the classifiers on a 10-fold cross-validation that provides an accuracy of 90.6% for the classification of KOA grades. The localization model is proposed with the combination of an open exchange neural network (ONNX) and YOLOv2 that is trained on the selected hyper-parameters. The proposed model provides 0.98 mAP for the localization of classified images. The experimental analysis proves that the presented framework provides better results as compared to existing works.
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Affiliation(s)
- Usman Yunus
- Department of Computer Science, COMSATS University Islamabad, Wah Campus, Wah Cantt 47010, Pakistan; (U.Y.); (M.S.); (M.Y.)
| | - Javeria Amin
- Department of Computer Science, University of Wah, Wah Cantt 47010, Pakistan;
| | - Muhammad Sharif
- Department of Computer Science, COMSATS University Islamabad, Wah Campus, Wah Cantt 47010, Pakistan; (U.Y.); (M.S.); (M.Y.)
| | - Mussarat Yasmin
- Department of Computer Science, COMSATS University Islamabad, Wah Campus, Wah Cantt 47010, Pakistan; (U.Y.); (M.S.); (M.Y.)
| | - Seifedine Kadry
- Department of Applied Data Science, Noroff University College, 4612 Kristiansand, Norway;
| | - Sujatha Krishnamoorthy
- Zhejiang Bioinformatics International Science and Technology Cooperation Center, Wenzhou-Kean University, Wenzhou 325060, China
- Wenzhou Municipal Key Lab of Applied Biomedical and Biopharmaceutical Informatics, Wenzhou-Kean University, Wenzhou 325060, China
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Effects of Intra-Articular Autologous Adipose Micrograft for the Treatment of Osteoarthritis in Dogs: A Prospective, Randomized, Controlled Study. Animals (Basel) 2022; 12:ani12141844. [PMID: 35883392 PMCID: PMC9311928 DOI: 10.3390/ani12141844] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 07/14/2022] [Indexed: 12/12/2022] Open
Abstract
The purpose of this study was to estimate the safety, feasibility, and efficacy of the intra-articular treatment of autologous microfragmented adipose tissue in dogs with spontaneous osteoarthritis (OA) in comparison with hyaluronic acid (HA), the standard intra-articular treatment. Specifically, it clinically evaluated pain and lameness, the radiographic progression of osteoarthritis, and synovial fluid inflammation. This was a prospective, single-center, parallel-group, randomized, controlled, in vivo clinical study. Participants (n = 40) received either a single intra-articular injection of microfragmented adipose tissue or a single intra-articular injection of HA (1:1). Clinical outcomes were determined using a specialistic clinician assessment obtained by the completion of a specific clinical form based on the Vesseur modified lameness classification system, a pain evaluation using the Visual Analogue Scale (VAS), the measurement of the range of motion (ROM) of the affected joint, limb circumference, and the owners' score evaluation using the Canine Brief Pain Inventory (CBPI) for up to 6 months after the time of injection. Patients underwent a radiographic examination to establish the degree of OA in the affected joint, and synovial fluid samples were collected to assess the biochemical environment of the joint and evaluate and quantify the cellular population and the presence of three specific inflammation biomarkers for up to 60 days. The results of this study suggest that microfragmented autologous adipose tissue is safe and can effectively relieve pain and improve function in dogs with spontaneous articular OA. This one-step procedure is simple, timesaving, cost-effective, minimally invasive, and eliminates the need for complex and time-intensive cell culture processing. Furthermore, the clinical evidence and cytological results suggest better long-term pain control, resulting in an improvement in joint function, compared to HA treatment. The canine spontaneous OA model could play a key role in developing successful treatments for human medicine.
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Kim JG, Rim YA, Ju JH. The Role of Transforming Growth Factor Beta in Joint Homeostasis and Cartilage Regeneration. Tissue Eng Part C Methods 2022; 28:570-587. [PMID: 35331016 DOI: 10.1089/ten.tec.2022.0016] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Transforming growth factor-beta (TGF-β) is an important regulator of joint homeostasis, of which dysregulation is closely associated with the development of osteoarthritis (OA). In normal conditions, its biological functions in a joint environment are joint protective, but it can be dramatically altered in different contexts, making its therapeutic application a challenge. However, with the deeper insights into the TGF-β functions, it has been proven that TGF-β augments cartilage regeneration by chondrocytes, and differentiates both the precursor cells of chondrocytes and stem cells into cartilage-generating chondrocytes. Following documentation of the therapeutic efficacy of chondrocytes augmented by TGF-β in the last decade, there is an ongoing phase III clinical trial examining the therapeutic efficacy of a mixture of allogeneic chondrocytes and TGF-β-overexpressing cells. To prepare cartilage-restoring chondrocytes from induced pluripotent stem cells (iPSCs), the stem cells are differentiated mainly using TGF-β with some other growth factors. Of note, clinical trials evaluating the therapeutic efficacy of iPSCs for OA are scheduled this year. Mesenchymal stromal stem cells (MSCs) have inherent limitations in that they differentiate into the osteochondral pathway, resulting in the production of poor-quality cartilage. Despite the established essential role of TGF-β in chondrogenic differentiation of MSCs, whether the coordinated use of TGF-β in MSC-based therapy for degenerated cartilage is effective is unknown. We herein reviewed the general characteristics and mechanism of action of TGF-β in a joint environment. Furthermore, we discussed the core interaction of TGF-β with principal cells of OA cell-based therapies, the chondrocytes, MSCs, and iPSCs. Impact Statement Transforming growth factor-beta (TGF-β) has been widely used as a core regulator to improve or formulate therapeutic regenerative cells for degenerative joints. It differentiates stem cells into chondrocytes and improves the chondrogenic potential of differentiated chondrocytes. Herein, we discussed the overall characteristics of TGF-β and reviewed the comprehension and utilization of TGF-β in cell-based therapy for degenerative joint disease.
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Affiliation(s)
- Jung Gon Kim
- Division of Rheumatology, Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea
| | - Yeri Alice Rim
- Catholic iPSC Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Ji Hyeon Ju
- Catholic iPSC Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.,Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Knee Pain from Osteoarthritis: Pathogenesis, Risk Factors, and Recent Evidence on Physical Therapy Interventions. J Clin Med 2022; 11:jcm11123252. [PMID: 35743322 PMCID: PMC9224572 DOI: 10.3390/jcm11123252] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Revised: 06/02/2022] [Accepted: 06/06/2022] [Indexed: 01/04/2023] Open
Abstract
For patients presenting knee pain coming from osteoarthritis (OA), non-pharmacological conservative treatments (e.g., physical therapy interventions) are among the first methods in orthopedics and rehabilitation to prevent OA progression and avoid knee surgery. However, the best strategy for each patient is difficult to establish, because knee OA's exact causes of progression are not entirely understood. This narrative review presents (i) the most recent update on the pathogenesis of knee OA with the risk factors for developing OA and (ii) the most recent evidence for reducing knee pain with physical therapy intervention such as Diathermy, Exercise therapy, Ultrasounds, Knee Brace, and Electrical stimulation. In addition, we calculated the relative risk reduction in pain perception for each intervention. Our results show that only Brace interventions always reached the minimum for clinical efficiency, making the intervention significant and valuable for the patients regarding their Quality of Life. In addition, more than half of the Exercise and Diathermy interventions reached the minimum for clinical efficiency regarding pain level. This literature review helps clinicians to make evidence-based decisions for reducing knee pain and treating people living with knee OA to prevent knee replacement.
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Novack TA, Mazzei CJ, Patel JN, Poletick EB, D'Achille R, Wittig JC. Providing Inpatient Mobilization with a Mobility Technician Constrains Cost in Primary Total Knee Arthroplasty. J Knee Surg 2022; 35:750-756. [PMID: 33111274 DOI: 10.1055/s-0040-1718597] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Since the 2016 implementation of the comprehensive care for joint replacement (CJR) bundled payment model, our institutions have sought to decrease inpatient physical therapy (PT) costs by piloting a mobility technician program (MTP), where mobility technicians (MTs) ambulate postoperative total knee arthroplasty (TKA) patients under the supervision of nursing staff members. MTs are certified medical assistants given specialized gate and ambulation training by the PT department. The aim of this study was to examine the economic and clinical impact of MTs on the primary TKA postoperative pathway. We performed a retrospective review of TKA patients who underwent surgery at our institution between April 2018 and March 2019 and who were postoperatively ambulated by MTs. The control group included patients who had surgery during the same months of the prior year, preceding introduction of MTs to the floor. Inclusion criteria included: unilateral primary TKA for arthritic conditions and conversion to unilateral primary TKA from a previous knee surgery. Minitab Software (State College, PA) was used to perform the statistical analysis. There were 658 patients enrolled in the study group and 1,400 in the control group. The two groups shared similar demographics and an average age of 68 (p = 0.177). The median length of stay (LOS) was 2 days in both groups (p = 0.133) with 90.5% of patients in the study group discharged to home versus 81.5% of patients in the control group (p < 0.001). The ability of MTs to increase patient discharge to home without negatively impacting LOS suggest MTs are valuable both clinically to patients, and economically to the institution. Cost analysis highlighted the substantial cost savings that MTs may create in a bundled payment system. With the well-documented benefits of early ambulation following TKA, we demonstrate how MTs can be an asset to optimizing the care pathway of TKA patients.
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Affiliation(s)
- Thomas A Novack
- Department of Orthopaedic Surgery, St. Joseph's University Medical Center/Hackensack Meridian School of Medicine at Seton Hall University, Paterson, New Jersey
| | | | - Jay N Patel
- Department of Orthopaedic Surgery, Morristown Medical Center, Morristown, New Jersey
| | - Eileen B Poletick
- Department of Orthopaedic Surgery, Morristown Medical Center, Morristown, New Jersey
| | - Roberta D'Achille
- Department of Physical Therapy, Morristown Medical Center, Morristown, New Jersey
| | - James C Wittig
- Department of Orthopaedics, Morristown Medical Center, Morristown, New Jersey
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Ferucci ED, Holck P. Hospitalizations Associated With Rheumatic Disease in Alaska, 2015-2018. ACR Open Rheumatol 2022; 4:520-527. [PMID: 35305078 PMCID: PMC9190222 DOI: 10.1002/acr2.11429] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 02/17/2022] [Indexed: 11/20/2022] Open
Abstract
Objective Few studies have evaluated hospitalizations associated with rheumatic disease in Indigenous North American populations. The objective of this study was to determine the characteristics of people hospitalized with rheumatic disease in Alaska, including a comparison of hospitalizations for Alaska Native/American Indian (AN/AI) people in Alaska compared with those of other races. Methods We used statewide hospital discharge data from the Alaska Health Facilities Data Reporting Program from 2015 to 2018 for this study. Cases were ascertained based on discharge diagnosis (any listed) of a defined set of rheumatic diseases. We determined characteristics associated with rheumatic disease hospitalizations, including age, gender, and race. Using multivariate modeling, we determined risk factors for hospitalization overall, as well as for specific rheumatic diseases. We compared characteristics of hospital encounters for people with or without rheumatic diseases and by race. Results We identified 15975 people ever hospitalized with rheumatic disease in the study period and 87138 controls hospitalized but without any rheumatic disease diagnosis. Cases were older than controls and more likely to be female. The three most common types of rheumatic disease associated with hospitalization were osteoarthritis, gout, and rheumatoid arthritis. Compared with other races, AN/AI people were more likely to be hospitalized with rheumatic disease, and this association was true for all specific diseases other than gout. Conclusion Hospitalizations associated with rheumatic disease are common in Alaska, with an increased likelihood of hospitalization for AN/AI people. This adds to the literature on health disparities in Indigenous North American populations.
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Degen RM, Hiemstra LA, Lobo J, Woodmass JM, Sommerfeldt M, Khan M, Carsen S, Pauyo T, Chahal J, Urquhart N, Grant J, Rousseau-Saine A, Lebel ME, Sheehan B, Sandman E, Tucker A, Kopka M, Wong I. Arthroscopy Association of Canada Position Statement on Intra-articular Injections for Hip Osteoarthritis. Orthop J Sports Med 2022; 10:23259671211066966. [PMID: 35155702 PMCID: PMC8832617 DOI: 10.1177/23259671211066966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Affiliation(s)
- Ryan M. Degen
- Arthroscopy Association of Canada
- Fowler Kennedy Sport Medicine Clinic, Western University, London, Ontario, Canada
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Singh JA. "I wish it had a place to go": a nominal group study of barriers to the effectiveness of non-surgical treatments for knee osteoarthritis inclusive of minority populations. Arthritis Res Ther 2021; 23:291. [PMID: 34852836 PMCID: PMC8633910 DOI: 10.1186/s13075-021-02676-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 11/09/2021] [Indexed: 11/30/2022] Open
Abstract
Objective To examine patient experience, views, and opinions regarding the ineffectiveness of the current knee osteoarthritis (OA) treatments. Methods Nominal groups were conducted with consecutive clinic patients with knee OA, oversampling African Americans. Patients discussed and rank-ordered their concerns. Results Fourteen nominal groups with 48 knee OA patients were conducted with a mean age of 60.6 years (standard deviation, 9.8) and a knee OA duration of 7.8 years (sd, 5.4); 25% were men, and 54% were African American. The most frequently cited highly ranked concerns for the ineffectiveness of current knee OA treatments were as follows: (1) medication-related—(A) side effects (3 groups; 4% vote), (B) limited efficacy (5 groups; 11% vote), (C) medication not targeting underlying disease (7 groups; 16% vote), (D) lack of personalized medication use (3 groups; 4% vote), (E) temporary benefit (3 groups; 6% vote), and (F) fear of addiction/natural treatment preference (2 groups; 3% vote); (2) exercise/physical therapy-related—(G) exacerbation of joint pain (1 group; 3% vote), (H) difficulty in doing exercises (2 groups; 2% vote), (I) lack of motivation (8 groups; 12% vote), (J) technical challenges/lack of personalized exercise regimens (1 group; 1% vote), and (K) cost (2 groups; 3% vote); and (3) weight loss-related—(L) difficulty in achieving weight loss (4 groups; 6% vote) and (M) motivation (1 group; 1% vote). Conclusions A representative sample of participants with knee OA identified several barriers to the effectiveness of current knee OA treatments. This new knowledge provides insights for making the current treatment options potentially more usable and/or more effective. Supplementary Information The online version contains supplementary material available at 10.1186/s13075-021-02676-8.
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Affiliation(s)
- Jasvinder A Singh
- Medicine Service, Birmingham VA Medical Center, Birmingham, AL, USA. .,Department of Medicine at School of Medicine, Division of Epidemiology at School of Public Health, University of Alabama, Faculty Office Tower 805B, 510 20th Street S, Birmingham, AL, 35294, USA.
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Hemp Seeds in Post-Arthroplasty Rehabilitation: A Pilot Clinical Study and an In Vitro Investigation. Nutrients 2021; 13:nu13124330. [PMID: 34959882 PMCID: PMC8709006 DOI: 10.3390/nu13124330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 11/26/2021] [Accepted: 11/27/2021] [Indexed: 11/20/2022] Open
Abstract
Osteoarthritis is a type of degenerative joint disease that results from the breakdown of joint cartilage and underlying bone. Due to their antioxidants and anti-inflammatory action, the phytochemical constituents of many vegetable varieties could represent a new frontier for the treatment of patients with Osteoarthritis and are still being explored. The aim of this pilot human study was to investigate the effects of pasta enriched with hemp seed flour on osteoarticular pain and bone formation markers in patients in post-arthroplasty rehabilitation. Another purpose was to evaluate the effect of hemp seed extract on bone metabolism, in vitro. A pilot, controlled, clinical study was conducted to verify the feasibility of pain symptom reduction in patients with Osteoarthritis undergoing arthroplasty surgery. We also investigated the effect of hemp seed extract on the Wnt/β-catenin and ERK1/2 pathways, alkaline phosphatase, RANKL, RUNX-2, osteocalcin, and COL1A on Saos-2. After 6 weeks, the consumption of hemp seed pasta led to greater pain relief compared to the regular pasta control group (−2.9 ± 1.3 cm vs. −1.3 ± 1.3 cm; p = 0.02). A significant reduction in serum BALP was observed in the participants consuming the hemp seed pasta compared to control group (−2.8 ± 3.2 µg/L vs. 1.1 ± 4.3 µg/L; p = 0.04). In the Saos-2 cell line, hemp seed extract also upregulated Wnt/β-catenin and Erk1/2 pathways (p = 0.02 and p = 0.03) and osteoblast differentiation markers (e.g., ALP, OC, RUNX2, and COL1A) and downregulated RANKL (p = 0.02), compared to the control. Our study demonstrated that hemp seed can improve pain symptoms in patients with osteoarthritis undergoing arthroplasty surgery and also improves bone metabolism both in humans and in vitro. However, more clinical studies are needed to confirm our preliminary findings.
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Ferrara PE, Codazza S, Coraci D, Malerba G, Ferriero G, Ronconi G. State of art in intra-articular hip injections of different medications for osteoarthritis: a systematic review. BMC Musculoskelet Disord 2021; 22:997. [PMID: 34844603 PMCID: PMC8630838 DOI: 10.1186/s12891-021-04866-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 11/12/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Intra-articular hip injections for osteoarthritis represent a useful instrument to reduce pain and disability in the common clinical practice. Several medications can be injected locally with different level of evidence-based efficacy. OBJECTIVE The objective of this systematic review is to investigate the effectiveness of intra-articular injections of different medications or substances for the pain treatment and the management of disability in subjects affected by hip osteoarthritis. METHODS Two reviewers selected independently randomised controlled trials published in the last 10 years, using PubMed and Scopus databases. The risk of bias was evaluated with Cochrane library assessment tool. RESULTS 12 randomised controlled trials have been selected. We found 8 papers comparing hyaluronic acid with platelet rich plasma, with corticosteroids and with saline solution; 1 paper compares two types of hyaluronic acid with different molecular weights; 3 papers study the effects of corticosteroids alone or compared to ketorolac or saline solution. CONCLUSIONS The studies reviewed were heterogeneous regarding sample size, level of osteoarthritis, evaluated with Kellegren-Lawrence score, medications used and follow up timings. However, we have observed that intra-articular injections of platelet-rich plasma seem to decrease pain at short term and disability at long term, in patients affected by hip osteoarthritis better than hyaluronic acid. The association of hyaluronic acid and corticosteroids could give better results compared to hyaluronic acid alone, while the use of intra-articular ketorolac and saline solution requires more studies.
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Affiliation(s)
| | - Sefora Codazza
- University Polyclinic Foundation Agostino Gemelli IRCCS, Rome, Italy.
| | - Daniele Coraci
- High Intensity Neurorehabilitation, University Polyclinic Foundation Agostino Gemelli IRCSS, Rome, Italy
| | - Giuseppe Malerba
- University Polyclinic Foundation Agostino Gemelli IRCSS, Catholic University of Sacred Heart, Rome, Italy
| | - Giorgio Ferriero
- Istituti Clinici Scientifici Maugeri IRCCS, PRM Unit of Tradate Institute, Tradate, VA, Italy
| | - Gianpaolo Ronconi
- University Polyclinic Foundation Agostino Gemelli IRCSS, Catholic University of Sacred Heart, Rome, Italy
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Taylor E, Weaver S, Zars E, Turner C, Buhrow S, Reid J, Bradley E, Westendorf J. Chondrocytic and pharmacokinetic properties of Phlpp inhibitors. OSTEOARTHRITIS AND CARTILAGE OPEN 2021; 3:100190. [DOI: 10.1016/j.ocarto.2021.100190] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 06/04/2021] [Indexed: 01/10/2023] Open
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Natarajan ABMT, Sivadas VPD, Nair PDPD. 3D-printed biphasic scaffolds for the simultaneous regeneration of osteochondral tissues. Biomed Mater 2021; 16. [PMID: 34265754 DOI: 10.1088/1748-605x/ac14cb] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Accepted: 07/15/2021] [Indexed: 12/19/2022]
Abstract
Osteochondral tissue engineering (OCTE) involves the simulation of highly complex tissues with disparate biomechanical properties. OCTE is regarded as the best option for treating osteochondral defects, most of the drawbacks of current treatment methodologies can be addressed by this method. In recent years, the conventional scaffolds used in cartilage and bone regeneration are gradually being replaced by 3D printed scaffolds (3DP). In the present study, we devised the strategy of 3D printing for fabricating biphasic and integrated scaffolds that are loaded with bioactive factors for enhancing the osteochondral tissue regeneration. Polycaprolactone (PCL) and poly(lactic-co-glycolic acid) (PLGA), is used along with bioactive factors (chondroitin sulphate and beta-tricalcium phosphate (βTCP)) for the upper cartilage and lower bone layer respectively. The 3D printed bi-layered scaffolds with varying infill density, to mimic the native tissue, are not previously explored for OCTE. Hence, we tested the simultaneous osteochondrogenic differentiation inducing potential of the aforesaid 3D printed biphasic scaffoldsin vitro, using rabbit adipose derived mesenchymal stem cells (ADMSCs). Further, the biphasic scaffolds were highly cytocompatible, with excellent cell adhesion properties and cellular morphology. Most importantly, these biphasic scaffolds directed the simultaneous differentiation of a single stem cell population in to two cell lineages (simultaneous differentiation of rabbit ADMSCs into chondrocytes and osteoblasts). Further, these scaffolds enhanced the production of ECM and induced robust expression of marker genes that is specific for respective cartilage and bone layers. The 3D printed OCTE scaffold of our study hence can simulate the native osteochondral unit and could be potential futuristic biomimetic scaffold for osteochondral defects. Furtherin vivostudies are warranted.
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Affiliation(s)
- Amrita Bds MTech Natarajan
- Division of Tissue Engineering and Regeneration Technologies, Department of Applied Biology, Biomedical Technology Wing, Sree Chitra Tirunal Institute of Medical Sciences and Technology, Thiruvananthapuram, Kerala 695012, India
| | - Vp Ph D Sivadas
- Division of Tissue Engineering and Regeneration Technologies, Department of Applied Biology, Biomedical Technology Wing, Sree Chitra Tirunal Institute of Medical Sciences and Technology, Thiruvananthapuram, Kerala 695012, India
| | - Prabha D Ph D Nair
- Division of Tissue Engineering and Regeneration Technologies, Department of Applied Biology, Biomedical Technology Wing, Sree Chitra Tirunal Institute of Medical Sciences and Technology, Thiruvananthapuram, Kerala 695012, India
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Charon N, Islam A, Zbijewski W. Landmark-free morphometric analysis of knee osteoarthritis using joint statistical models of bone shape and articular space variability. J Med Imaging (Bellingham) 2021; 8:044001. [PMID: 34250198 DOI: 10.1117/1.jmi.8.4.044001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Accepted: 06/21/2021] [Indexed: 11/14/2022] Open
Abstract
Purpose: Osteoarthritis (OA) is a common degenerative disease involving a variety of structural changes in the affected joint. In addition to narrowing of the articular space, recent studies involving statistical shape analysis methods have suggested that specific bone shapes might be associated with the disease. We aim to investigate the feasibility of using the recently introduced framework of functional shapes (Fshape) to extract morphological features of OA that combine shape variability of articular surfaces of the tibia (or femur) together with the changes of the joint space. Approach: Our study uses a dataset of three-dimensional cone-beam CT volumes of 17 knees without OA and 17 knees with OA. Each knee is then represented as an object (Fshape) consisting of a triangulated tibial (or femoral) articular surface and a map of joint space widths (JSWs) measured at the points of this surface (joint space map, JSM). We introduce a generative atlas model to estimate a template (mean) Fshape of the sample population together with template-centered variables that model the transformations from the template to each subject. This approach has two potential advantages compared with other statistical shape modeling methods that have been investigated in knee OA: (i) Fshapes simultaneously consider the variability in bone shape and JSW, and (ii) Fshape atlas estimation is based on a diffeomorphic transformation model of surfaces that does not require a priori landmark correspondences between the subjects. The estimated atlas-to-subject Fshape transformations were used as input to principal component analysis dimensionality reduction combined with a linear support vector machine (SVM) classifier to identify the morphological features of OA. Results: Using tibial articular surface as the shape component of the Fshape, we found leave-one-out cross validation scores of ≈ 91.18 % for the classification based on the bone surface transformations alone, ≈ 91.18 % for the classification based on the residual JSM, and ≈ 85.29 % for the classification using both Fshape components. Similar results were obtained using femoral articular surfaces. The discriminant directions identified in the statistical analysis were associated with medial narrowing of the joint space, steeper intercondylar eminence, and relative deepening of the medial tibial plateau. Conclusions: The proposed approach provides an integrated framework for combined statistical analysis of shape and JSPs. It can successfully extract features correlated to OA that appear consistent with previous studies in the field. Although future large-scale study is necessary to confirm the significance of these findings, our results suggest that the functional shape methodology is a promising new tool for morphological analysis of OA and orthopedics data in general.
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Affiliation(s)
- Nicolas Charon
- Johns Hopkins University, Center of Imaging Sciences, Baltimore, Maryland, United States
| | - Asef Islam
- Johns Hopkins University, Department of Biomedical Engineering, Baltimore, Maryland, United States
| | - Wojciech Zbijewski
- Johns Hopkins University, Department of Biomedical Engineering, Baltimore, Maryland, United States
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Evaluation of the Efficacy and Safety of an Exercise Program for Persons with Total Hip or Total Knee Replacement: Study Protocol for a Randomized Controlled Trial. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18136732. [PMID: 34201439 PMCID: PMC8268118 DOI: 10.3390/ijerph18136732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 06/10/2021] [Accepted: 06/17/2021] [Indexed: 11/17/2022]
Abstract
Total hip replacement (THR) and total knee replacement (TKR) are among the most common elective surgical procedures. There is a large consensus on the importance of physical activity promotion for an active lifestyle in persons who underwent THR or TKR to prevent or mitigate disability and improve the quality of life (QoL) in the long term. However, there is no best practice in exercise and physical activity specifically designed for these persons. The present protocol aims to evaluate the efficacy and safety of an exercise program (6 month duration) designed for improving quality of life in people who had undergone THR or TKR. This paper describes a randomized controlled trial protocol that involves persons with THR or TKR. The participant will be randomly assigned to an intervention group or a control group. The intervention group will perform post-rehabilitation supervised training; the control group will be requested to follow the usual care. The primary outcome is QoL, measured with the Short-Form Health Survey (SF-36); Secondary outcomes are clinical, functional and lifestyle measures that may influence QoL. The results of this study could provide evidence for clinicians, exercise trainers, and policymakers toward a strategy that ensures safe and effective exercise physical activity after surgery.
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Li D, Gupta P, Sgaglione NA, Grande DA. Exosomes Derived from Non-Classic Sources for Treatment of Post-Traumatic Osteoarthritis and Cartilage Injury of the Knee: In Vivo Review. J Clin Med 2021; 10:jcm10092001. [PMID: 34066986 PMCID: PMC8124969 DOI: 10.3390/jcm10092001] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 04/26/2021] [Accepted: 04/29/2021] [Indexed: 12/11/2022] Open
Abstract
Osteoarthritis of the knee is one of the most common chronic, debilitating musculoskeletal conditions. Current conservative treatment modalities such as weight loss, non-steroidal anti-inflammatory drugs, and intra-articular steroid injections often only provide temporary pain relief and are unsatisfactory for long-term management. Though end stage osteoarthritis of the knee can be managed with total knee arthroplasty (TKA), finding alternative non-surgical options to delay or prevent the need for TKA are needed due to the increased healthcare costs and expenditures associated with TKA. Exosomes have been of particular interest given recent findings highlighting that stem cells may at least partially mediate some of their effects through the release of extracellular vesicles, such as exosomes. As such, better understanding the biological mechanisms and potential therapeutic effects of these exosomes is necessary. Here, we review in vivo studies that highlight the potential clinical use of exosomes derived from non-classical sources (not bone marrow or adipose derived MSCs derived MSCs) for osteoarthritis of the knee.
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Affiliation(s)
- Dan Li
- Orthopedic Research Laboratory, The Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY 11030, USA;
| | - Puneet Gupta
- Department of Orthopaedic Surgery, George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA;
| | - Nicholas A. Sgaglione
- Department of Orthopaedic Surgery, Long Island Jewish Medical Center, Northwell Health, New Hyde Park, NY 11040, USA;
| | - Daniel A. Grande
- Orthopedic Research Laboratory, The Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY 11030, USA;
- Department of Orthopaedic Surgery, Long Island Jewish Medical Center, Northwell Health, New Hyde Park, NY 11040, USA;
- Correspondence: ; Tel.: +1-(516)-562-1138
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Galluccio F, D’Angela D, Polistena B, Porta F, Barskova T, Tofani L, Spandonaro F, Matucci-Cerinic M. Comparison of three treatment protocols with intra-articular low or intermediate molecular weight hyaluronic acid in early symptomatic knee osteoarthritis. Ther Adv Musculoskelet Dis 2021; 13:1759720X21994024. [PMID: 33959197 PMCID: PMC8064515 DOI: 10.1177/1759720x21994024] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2019] [Accepted: 01/05/2021] [Indexed: 12/26/2022] Open
Abstract
INTRODUCTION Viscosupplementation with hyaluronic acid (HA) is indicated for non-responders to non-pharmacological therapy, to analgesics or when non-steroidal anti-inflammatory drugs (NSAIDs) are contraindicated. The aim of this study is to compare the efficacy, safety and costs of three different HA treatments (Sinovial® Forte, sinovial one and hyalgan). PATIENTS AND METHODS Ninety patients with grade I/II Kellgren-Lawrence knee osteoarthritis were included in three groups, the first was treated with hyalgan (weekly for 5 weeks), the second with Sinovial® Forte (weekly for 3 weeks) and the third group with a single injection of sinovial one. RESULTS All three treatments were effective, with an average reduction in the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) score of 18.9 points for hyalgan, 18.04 points for Sinovial® Forte and 17.92 points for sinovial one. The comparison of the three groups did not show any statistical difference in terms of efficacy. National health system (NHS) and social costs are, respectively, €419.12 and €853.43 for hyalgan, €338.64 and €599.22 for Sinovial® Forte, €221.56 and €308.42 for sinovial one. CONCLUSION All three treatments were equally effective with no statistically significant differences; thus, the treatment with sinovial one may be considered as clinically effective as the other two regimens, but with a very efficient cost profile in early symptomatic knee osteoarthritis.
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Affiliation(s)
- Felice Galluccio
- Department of Clinical and Experimental Medicine, University of Florence and Department of Geriatric Medicine, Div. of Rheumatology AOUC, Florence, Italy
| | - Daniela D’Angela
- C.R.E.A. Sanità (Consortium for Applied Economic Research in Healthcare), Department of Economic and Finance, University Tor Vergata, Rome, Italy
| | - Barbara Polistena
- C.R.E.A. Sanità (Consortium for Applied Economic Research in Healthcare), Department of Economic and Finance, University Tor Vergata, Rome, Italy
| | - Francesco Porta
- Department of Clinical and Experimental Medicine, University of Florence and Department of Geriatric Medicine, Div. of Rheumatology AOUC, Florence, Italy
| | - Tatiana Barskova
- Department of Clinical and Experimental Medicine, University of Florence and Department of Geriatric Medicine, Div. of Rheumatology AOUC, Florence, Italy
| | - Lorenzo Tofani
- Department of Clinical and Experimental Medicine, University of Florence and Department of Geriatric Medicine, Div. of Rheumatology AOUC, Florence, Italy
| | - Federico Spandonaro
- C.R.E.A. Sanità (Consortium for Applied Economic Research in Healthcare), Department of Economic and Finance, University Tor Vergata, Rome, Italy
| | - Marco Matucci-Cerinic
- Department of Clinical and Experimental Medicine, University of Florence and Department of Geriatric Medicine, Div. of Rheumatology AOUC, SOD Reumatologia, via delle Oblate 4, Firenze (FI), 50139, Italy
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Novack TA, Patel JN, Koss J, Mazzei C, Harrington CJ, Wittig JC, Dundon J. Is There a Need for Recovery Room Radiographs Following Uncomplicated Primary Total Knee Arthroplasty? Cureus 2021; 13:e14544. [PMID: 34017659 PMCID: PMC8130648 DOI: 10.7759/cureus.14544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Abstract
Introduction Total knee arthroplasty (TKA) is one of the most common orthopedic procedures performed in the United States. Obtaining radiographs in the post-anesthesia care unit (PACU) has been the standard of care at most hospitals. The purpose of this study was to examine the utility and cost-effectiveness of immediate, postoperative radiographs in regards to operative decision-making to prevent complications within 90 days after primary TKA. Methods A retrospective review of 4,830 consecutive patients who underwent cemented or uncemented TKA between January 2016 and June 2019 at a large, regional medical center was performed. International Classification of Diseases, Tenth Revision (ICD-10) codes were used to track any readmissions within 90 days of TKA. If readmission was for a mechanical complication, including fracture, dislocation, or component loosening, PACU radiographs were reviewed for any abnormalities that may have prevented readmission. Results There were 195 readmissions (195 patients), of which 17 were due to mechanical complications. There was no evidence of fracture or abnormality appreciated on any of the reviewed PACU radiographs by either the reading radiologist or the senior authors. Assuming all fractures were noted on immediate, postoperative radiographs, the cost associated with identifying a single fracture in 2,415 patients was $1,072,260. Conclusion Routine radiographs in the recovery room after an uncomplicated primary TKA are not a reliable mechanism for preventing mechanical complications and do not alter patient care.
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Affiliation(s)
- Thomas A Novack
- Orthopedics, St. Joseph's Regional Medical Center, Paterson, USA
| | - Jay N Patel
- Orthopedics, Morristown Medical Center, Morristown, USA
| | - Justin Koss
- Orthopedics, Morristown Medical Center, Morristown, USA
| | | | - Colin J Harrington
- Orthopedics, Walter Reed National Military Medical Center, Bethesda, USA
| | | | - John Dundon
- Orthopedic Surgery, Orthopedic Institute of New Jersey, Morristown, USA
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45
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Wang YC, Huang HT, Huang PJ, Liu ZM, Shih CL. Efficacy and Safety of Extracorporeal Shockwave Therapy for Treatment of Knee Osteoarthritis: A Systematic Review and Meta-analysis. PAIN MEDICINE 2021; 21:822-835. [PMID: 31626282 DOI: 10.1093/pm/pnz262] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
OBJECTIVE The objective of this study was to assess the efficacy and safety of extracorporeal shockwave therapy (ESWT) for treatment of knee osteoarthritis (OA) using a systemic review and meta-analysis. METHODS An extensive search of relevant articles from electronic databases Pubmed, Embase, and Cochrane Library from inception to March 2019 was conducted. The treatment outcomes (visual analog scale [VAS] and the Western Ontario and McMaster Universities Arthritis Index [WOMAC]) of the included articles were pooled to calculate effect sizes. The assessment of heterogeneity among articles was evaluated using I2. Statistical analyses were conducted using RevMan software. RESULTS The results showed that the ESWT group had significant improvement in pain relief compared with the control group through 12 months based on WOMAC and VAS scores. Compared with the baseline level, the patients had significant improvement in pain relief at most follow-up points (one week to 12 months) based on WOMAC and VAS scores. The patients showed significant improvement in physical function at six- and 12-month follow-up when compared with the control group and for all follow-up (one to 12 months) when compared with the baseline level. Additionally, only minor complications were observed after ESWT treatment. CONCLUSIONS The use of ESWT for treatment of knee OA had a beneficial effect on pain relief and physical function improvement for up to 12 months, and only minor complications occurred after ESWT treatment. However, there remains a lack of clarity regarding the frequency and dosage levels of ESWT required to achieve the maximum improvement.
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Affiliation(s)
- Ying-Chun Wang
- Department of Orthopedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsuan-Ti Huang
- Department of Orthopedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Orthopedics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Peng-Ju Huang
- Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Orthopedics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Zi-Miao Liu
- Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Lung Shih
- Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
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Zhen G, Guo Q, Li Y, Wu C, Zhu S, Wang R, Guo XE, Kim BC, Huang J, Hu Y, Dan Y, Wan M, Ha T, An S, Cao X. Mechanical stress determines the configuration of TGFβ activation in articular cartilage. Nat Commun 2021; 12:1706. [PMID: 33731712 PMCID: PMC7969741 DOI: 10.1038/s41467-021-21948-0] [Citation(s) in RCA: 100] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Accepted: 02/19/2021] [Indexed: 01/18/2023] Open
Abstract
Our incomplete understanding of osteoarthritis (OA) pathogenesis has significantly hindered the development of disease-modifying therapy. The functional relationship between subchondral bone (SB) and articular cartilage (AC) is unclear. Here, we found that the changes of SB architecture altered the distribution of mechanical stress on AC. Importantly, the latter is well aligned with the pattern of transforming growth factor beta (TGFβ) activity in AC, which is essential in the regulation of AC homeostasis. Specifically, TGFβ activity is concentrated in the areas of AC with high mechanical stress. A high level of TGFβ disrupts the cartilage homeostasis and impairs the metabolic activity of chondrocytes. Mechanical stress stimulates talin-centered cytoskeletal reorganization and the consequent increase of cell contractile forces and cell stiffness of chondrocytes, which triggers αV integrin-mediated TGFβ activation. Knockout of αV integrin in chondrocytes reversed the alteration of TGFβ activation and subsequent metabolic abnormalities in AC and attenuated cartilage degeneration in an OA mouse model. Thus, SB structure determines the patterns of mechanical stress and the configuration of TGFβ activation in AC, which subsequently regulates chondrocyte metabolism and AC homeostasis.
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Affiliation(s)
- Gehua Zhen
- Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, USA
| | - Qiaoyue Guo
- Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, USA
| | - Yusheng Li
- Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, USA
| | - Chuanlong Wu
- Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, USA
| | - Shouan Zhu
- Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, USA
| | - Ruomei Wang
- Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, USA
| | - X Edward Guo
- Department of Biomedical Engineering, Columbia University, New York, NY, USA
| | - Byoung Choul Kim
- Department of Biophysics and Biophysical Chemistry, The Johns Hopkins University, Baltimore, MD, USA
| | - Jessie Huang
- Department of Pharmacology, Rutgers-Robert Wood Johnson Medical School, The State University of New Jersey, Piscataway, NJ, USA
| | - Yizhong Hu
- Department of Biomedical Engineering, Columbia University, New York, NY, USA
| | - Yang Dan
- Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, USA
| | - Mei Wan
- Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, USA
| | - Taekjip Ha
- Department of Biophysics and Biophysical Chemistry, The Johns Hopkins University, Baltimore, MD, USA
| | - Steven An
- Department of Pharmacology, Rutgers-Robert Wood Johnson Medical School, The State University of New Jersey, Piscataway, NJ, USA
- Rutgers Institute for Translational Medicine and Science, New Brunswick, NJ, USA
| | - Xu Cao
- Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, USA.
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Zlotnick HM, Stoeckl BD, Henning EA, Steinberg DR, Mauck RL. Optimized Media Volumes Enable Homogeneous Growth of Mesenchymal Stem Cell-Based Engineered Cartilage Constructs. Tissue Eng Part A 2020; 27:214-222. [PMID: 32552444 DOI: 10.1089/ten.tea.2020.0123] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Despite marked advances in the field of cartilage tissue engineering, it remains a challenge to engineer cartilage constructs with homogeneous properties. Moreover, for engineered cartilage to make it to the clinic, this homogeneous growth must occur in a time-efficient manner. In this study we investigated the potential of increased media volume to expedite the homogeneous maturation of mesenchymal stem cell (MSC) laden engineered constructs over time in vitro. We assessed the MSC-laden constructs after 4 and 8 weeks of chondrogenic culture using bulk mechanical, histological, and biochemical measures. These assays were performed on both the intact total constructs and the construct cores to elucidate region-dependent differences. In addition, local strain transfer was assessed to quantify depth-dependent mechanical properties throughout the constructs. Our findings suggest that increased media volume enhances matrix deposition early in culture and ameliorates unwanted regional heterogeneities at later time points. Taken together, these data support the use of higher media volumes during in vitro culture to hasten tissue maturation and increase the core strength of tissue constructs. These findings will forward the field of cartilage tissue engineering and the translation of tissue engineered constructs.
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Affiliation(s)
- Hannah M Zlotnick
- McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania, USA.,Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.,Translational Musculoskeletal Research Center, Philadelphia Veterans Administration Medical Center, Philadelphia, Pennsylvania, USA
| | - Brendan D Stoeckl
- McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania, USA.,Translational Musculoskeletal Research Center, Philadelphia Veterans Administration Medical Center, Philadelphia, Pennsylvania, USA
| | - Elizabeth A Henning
- McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania, USA.,Translational Musculoskeletal Research Center, Philadelphia Veterans Administration Medical Center, Philadelphia, Pennsylvania, USA
| | - David R Steinberg
- McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania, USA.,Translational Musculoskeletal Research Center, Philadelphia Veterans Administration Medical Center, Philadelphia, Pennsylvania, USA
| | - Robert L Mauck
- McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania, USA.,Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.,Translational Musculoskeletal Research Center, Philadelphia Veterans Administration Medical Center, Philadelphia, Pennsylvania, USA
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48
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Uddin MJ, Vemulapalli A, Niitsu H, Crews BC, Oltman CG, Kingsley PJ, Kavanaugh TE, Bedingfield SK, Mcintyre JO, Milad M, Aleem AM, Coffey RJ, Duvall CL, Marnett LJ. Molecular Imaging of Inflammation in Osteoarthritis Using a Water-Soluble Fluorocoxib. ACS Med Chem Lett 2020; 11:1875-1880. [PMID: 33062167 DOI: 10.1021/acsmedchemlett.9b00512] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 02/24/2020] [Indexed: 12/18/2022] Open
Abstract
Clinical imaging approaches to detect inflammatory biomarkers, such as cyclooxygenase-2 (COX-2), may facilitate the diagnosis and therapy of inflammatory diseases. To this end, we report the discovery of N-[(rhodamin-X-yl)but-4-yl]-2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetamide chloride salt (fluorocoxib D), a hydrophilic analog of fluorocoxib A. Fluorocoxib D inhibits COX-2 selectively in purified enzyme preparations and cells. It exhibits adequate photophysical properties to enable detection of COX-2 in intact cells, in a mouse model of carrageenan-induced acute footpad inflammation and inflammation in a mouse model of osteoarthritis. COX-2-selectivity was verified either by blocking the enzyme's active site with celecoxib or by molecular imaging with nontargeted 5-carboxy-X-rhodamine dye. These data indicate that fluorocoxib D is an ideal candidate for early detection of inflammatory or neoplastic lesions expressing elevated levels of COX-2.
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Affiliation(s)
- Md. Jashim Uddin
- A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States
| | - Anoop Vemulapalli
- A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States
| | - Hiroaki Niitsu
- Department of Medicine, and Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States
| | - Brenda C. Crews
- A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States
| | - Connor G. Oltman
- A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States
| | - Philip J. Kingsley
- A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States
| | - Taylor E. Kavanaugh
- Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37232, United States
| | - Sean K. Bedingfield
- Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37232, United States
| | - J. Oliver Mcintyre
- Department of Cancer Biology, Vanderbilt Institute of Imaging Science, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States
| | - Matthew Milad
- A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States
| | - Ansari M. Aleem
- A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States
| | - Robert J. Coffey
- Department of Medicine, and Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States
| | - Craig L. Duvall
- Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37232, United States
| | - Lawrence J. Marnett
- A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States
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Singh JA, Cleveland JD. Hospitalized Infections in People With Osteoarthritis: A National US Study. J Rheumatol 2020; 48:933-939. [PMID: 32739891 DOI: 10.3899/jrheum.191383] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/10/2020] [Indexed: 11/22/2022]
Abstract
OBJECTIVE To study the incidence, time trends, and outcomes of serious infections in people with osteoarthritis (OA). METHODS We used 1998-2016 US National Inpatient Sample (NIS) data. Using recommended weights, we examined the epidemiology of 5 types of serious infections requiring hospitalization in people with OA (opportunistic infections [OIs], skin and soft tissue infections [SSTIs], urinary tract infections [UTIs], pneumonia, and sepsis/bacteremia). We performed multivariable-adjusted logistic regression analyses to analyze factors associated with healthcare utilization (hospital charges, length of hospital stay, discharge to nonhome setting), and in-hospital mortality. RESULTS Of all serious infection hospitalizations, 46,708,154 were without OA and 3,258,416 had OA. People with OA were 16.4 years older, more likely to be female (52% vs 65%), White (59% vs 70%), have a Deyo-Charlson Comorbidity Index (DCCI) ≥ 2 (42% vs 51%), receive Medicare (54% vs 80%), and less likely to receive care at an urban teaching hospital (45% vs 39%). Serious infection rates per 100,000 NIS hospitalizations increased from the study period of 1998-2000 to 2015-2016: OI (from 4.5 to 7.2); SSTI (from 48.4 to 145.9); UTI (from 8.4 to 104.6); pneumonia (from 164.0 to 224.3); and sepsis (from 39.4 to 436.3). In multivariable-adjusted analyses, older age, higher DCCI, sepsis, northeast region, urban hospital, and medium or large hospital bed size were significantly associated with higher healthcare utilization outcomes and in-hospital mortality; Medicaid insurance, non-White race, and female sex were significantly associated with higher healthcare utilization. CONCLUSION Serious infection rates have increased in people with OA. Association of demographic, clinic, and hospital variables with serious infection outcomes identifies potential targets for future interventions.
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Affiliation(s)
- Jasvinder A Singh
- J.A. Singh, MBBS, MPH, Medicine Service, VA Medical Center, and Department of Medicine at School of Medicine, University of Alabama at Birmingham, and Division of Epidemiology at School of Public Health, University of Alabama at Birmingham;
| | - John D Cleveland
- J.D. Cleveland, MS, Department of Medicine at School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
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50
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Booker SQ, Tripp-Reimer T, Herr KA. "Bearing the Pain": The Experience of Aging African Americans With Osteoarthritis Pain. Glob Qual Nurs Res 2020; 7:2333393620925793. [PMID: 32548212 PMCID: PMC7271276 DOI: 10.1177/2333393620925793] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 04/08/2020] [Accepted: 04/16/2020] [Indexed: 12/18/2022] Open
Abstract
Studies document that osteoarthritis-related joint pain is more severe in
African American older adults, but research on the personal experience
of osteoarthritis pain self-management in this population is limited.
Using a qualitative descriptive design, our objective was to extend
our understanding of the experience of life with osteoarthritis pain.
Eighteen African Americans (50 years and older) were recruited from
Louisiana to participate in a single semi-structured, in-depth
interview. A conventional content analysis revealed that “Bearing the
pain” characterized how older African Americans dealt with
osteoarthritis. Bearing the pain comprised three actions: adjusting to
pain, sharing pain with others, and trusting God as healer. We
discovered that a metapersonal experience subsumes the complex
biopsychosocial-cultural patterns and the intricate interaction of
self, others, and God in living with and managing osteoarthritis pain.
Study findings have implications for application of more inclusive
self-management frameworks and interventions.
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