Pub Date : 2025-06-01Epub Date: 2024-06-09DOI: 10.1177/19476035241258170
Jonathan J Bjerre-Bastos, Casper Sejersen, Henning Bay Nielsen, Mikael Boesen, Niels H Secher, Gregorio Distajo, Vincent Flood, Yves Henrotin, Melanie Uebelhoer, Peter Krustrup, Carl-Christian Kitchen, Christian S Thudium, Jeppe R Andersen, Asger R Bihlet
ObjectiveTo investigate how running, cycling, and sedentary cardiovascular stress impact biomarkers of cartilage turnover acutely in subjects with knee osteoarthritis (OA).DesignThis was a sequential, cross-over, clinical study. Forty subjects with primary knee OA underwent moderate-to-high-intensity cycling, running, and adrenaline infusion on separate days. Blood was sampled before, during, and at 6-time points after intervention. On a control day, similar samples were taken. Biomarkers of type II collagen degradation (C2M, T2CM, Coll2-1, Coll2-1NO2), formation (PRO-C2), and aggrecan degradation (ARGS) were measured.ResultsMean age was 60.4 years, 40% were male, 45% had cumulated Kellgren-Lawrence (KL)-grade (Right + Left knee) of 2 to 3 and 55% had 4 to 6. Analyzing overall changes, area under the curve was significantly lower compared with resting values for ARGS and C2M after cycling and for ARGS after running. Considering individual time points, peak changes in biomarker levels showed reduction in C2M shortly following cycling (T20min = -12.3%, 95% confidence interval [CI]: -19.3% to -5.2%). PRO-C2 increased during cycling (T10min = 14.0%, 95% CI = 4.1% to 23.8%) and running (T20min = 16.5%, 95% CI = 4.3% to 28.6%). T2CM decreased after cycling (T50min = -19.9%, 95% CI = -29.2% to -10.6%), running (T50min = -22.8%, 95% CI = -32.1% to -13.5%), and infusion of adrenaline (peak, T50min = -9.8%, 95% CI = -20.0% to 0.4%). A latent increase was seen in Coll2-1 240 minutes after running (T260min = 21.7%, 95% CI = -1.6% to 45.1%).ConclusionExercise had an impact on cartilage markers, but it did not suggest any detrimental effect on cartilage. Changes following adrenaline infusion suggest a sympathomimetic influence on the serological composition of biomarkers.
{"title":"The Impact of Weight-bearing Exercise, Non-Weight-bearing Exercise, and Cardiovascular Stress on Biochemical Markers of Cartilage Turnover in Patients With Mild to Moderate Knee Osteoarthritis - A Sequential, Cross-Over, Clinical Study.","authors":"Jonathan J Bjerre-Bastos, Casper Sejersen, Henning Bay Nielsen, Mikael Boesen, Niels H Secher, Gregorio Distajo, Vincent Flood, Yves Henrotin, Melanie Uebelhoer, Peter Krustrup, Carl-Christian Kitchen, Christian S Thudium, Jeppe R Andersen, Asger R Bihlet","doi":"10.1177/19476035241258170","DOIUrl":"10.1177/19476035241258170","url":null,"abstract":"<p><p>ObjectiveTo investigate how running, cycling, and sedentary cardiovascular stress impact biomarkers of cartilage turnover acutely in subjects with knee osteoarthritis (OA).DesignThis was a sequential, cross-over, clinical study. Forty subjects with primary knee OA underwent moderate-to-high-intensity cycling, running, and adrenaline infusion on separate days. Blood was sampled before, during, and at 6-time points after intervention. On a control day, similar samples were taken. Biomarkers of type II collagen degradation (C2M, T2CM, Coll2-1, Coll2-1NO2), formation (PRO-C2), and aggrecan degradation (ARGS) were measured.ResultsMean age was 60.4 years, 40% were male, 45% had cumulated Kellgren-Lawrence (KL)-grade (Right + Left knee) of 2 to 3 and 55% had 4 to 6. Analyzing overall changes, area under the curve was significantly lower compared with resting values for ARGS and C2M after cycling and for ARGS after running. Considering individual time points, peak changes in biomarker levels showed reduction in C2M shortly following cycling (T<sub>20min</sub> = -12.3%, 95% confidence interval [CI]: -19.3% to -5.2%). PRO-C2 increased during cycling (T<sub>10min</sub> = 14.0%, 95% CI = 4.1% to 23.8%) and running (T<sub>20min</sub> = 16.5%, 95% CI = 4.3% to 28.6%). T2CM decreased after cycling (T<sub>50min</sub> = -19.9%, 95% CI = -29.2% to -10.6%), running (T<sub>50min</sub> = -22.8%, 95% CI = -32.1% to -13.5%), and infusion of adrenaline (peak, T<sub>50min</sub> = -9.8%, 95% CI = -20.0% to 0.4%). A latent increase was seen in Coll2-1 240 minutes after running (T<sub>260min</sub> = 21.7%, 95% CI = -1.6% to 45.1%).ConclusionExercise had an impact on cartilage markers, but it did not suggest any detrimental effect on cartilage. Changes following adrenaline infusion suggest a sympathomimetic influence on the serological composition of biomarkers.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"159-168"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11569697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ObjectiveAlthough knee osteoarthritis (KOA) is a common disease, there is a lack of specific prevention and early treatment methods. Hence, this study aimed to examine the molecular changes occurring at different stages of KOA to elucidate the dynamic nature of the disease.DesignUsing a low-force compression model and analyzing RNA sequencing data, we identified molecular changes in the transcriptome of knee joint cartilage, including gene expression and molecular pathways, between the cellular changes and structural damage stages of KOA progression. In addition, we validated hub genes using an external dataset.ResultsGene set enrichment analysis (GSEA) identified the following pathways to be associated with KOA: "B-cell receptor signaling pathway," "cytokine-cytokine receptor interaction," and "hematopoietic cell lineage." Expression analysis revealed 585 differentially expressed genes, with 579 downregulated and 6 upregulated genes. Enrichment and clustering analyses revealed that the main molecular clusters were involved in cell cycle regulation and immune responses. Furthermore, the hub genes Csf1r, Cxcr4, Cxcl12, and Ptprc were related to immune responses.ConclusionsOur study provides insights into the dynamic nature of early-stage KOA and offers valuable information to support the development of effective intervention strategies to prevent the irreversible damage associated with KOA, thereby addressing a major clinical challenge.
{"title":"Analysis of Molecular Changes and Features in Rat Knee Osteoarthritis Cartilage: Progress From Cellular Changes to Structural Damage.","authors":"Zixi Zhao, Akira Ito, Hiroshi Kuroki, Tomoki Aoyama","doi":"10.1177/19476035231213174","DOIUrl":"10.1177/19476035231213174","url":null,"abstract":"<p><p>ObjectiveAlthough knee osteoarthritis (KOA) is a common disease, there is a lack of specific prevention and early treatment methods. Hence, this study aimed to examine the molecular changes occurring at different stages of KOA to elucidate the dynamic nature of the disease.DesignUsing a low-force compression model and analyzing RNA sequencing data, we identified molecular changes in the transcriptome of knee joint cartilage, including gene expression and molecular pathways, between the cellular changes and structural damage stages of KOA progression. In addition, we validated hub genes using an external dataset.ResultsGene set enrichment analysis (GSEA) identified the following pathways to be associated with KOA: \"B-cell receptor signaling pathway,\" \"cytokine-cytokine receptor interaction,\" and \"hematopoietic cell lineage.\" Expression analysis revealed 585 differentially expressed genes, with 579 downregulated and 6 upregulated genes. Enrichment and clustering analyses revealed that the main molecular clusters were involved in cell cycle regulation and immune responses. Furthermore, the hub genes <i>Csf1r, Cxcr4, Cxcl12</i>, and <i>Ptprc</i> were related to immune responses.ConclusionsOur study provides insights into the dynamic nature of early-stage KOA and offers valuable information to support the development of effective intervention strategies to prevent the irreversible damage associated with KOA, thereby addressing a major clinical challenge.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"232-249"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136396559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-28DOI: 10.1177/19476035251339410
Yu Chen, Haotian Ren
ObjectiveTemporomandibular joint osteoarthritis (TMJOA) seriously influences the quality of life of patients. Chondrocyte mitochondrial dysfunction and pyroptosis play an important role in the development of osteoarthritis, but their role in TMJOA pathogenesis is elusive. We aimed to probe into the role and mechanism of mitochondrial dysfunction and pyroptosis in TMJOA.DesignTMJOA rat models were established by unilateral anterior crossbite operation. Pathological changes in cartilage tissues were observed by hematoxylin-eosin staining, and mitochondrial dysfunction and pyroptosis were evaluated by immunohistochemistry. The biological function and mechanism of ZC3H13 in mitochondrial dysfunction and pyroptosis were determined by cell experiments.ResultsWe discovered that mitochondrial dysfunction and pyroptosis occurred in cartilage tissues of TMJOA rats. The expression of ZC3H13 was observably upregulated in TMJOA rats. Further cell experiments showed that interference of ZC3H13 restrained mitochondrial dysfunction and pyroptosis of chondrocytes. RNA sequencing revealed that NSUN4 expression was significantly increased in chondrocytes after ZC3H13 knockdown. Silencing of ZC3H13 remarkably diminished the level of NSUN4 N6-methyladenosine (m6A) modification. Moreover, mitochondrial dysfunction and pyroptosis of chondrocytes were notably increased after NSUN4 knockdown.ConclusionOur study revealed that ZC3H13-mediated NSUN4 repressed TMJOA progression by modulating chondrocyte mitochondrial dysfunction and pyroptosis in an m6A-dependent manner, which may offer a potential strategy for TMJOA treatment.
{"title":"ZC3H13 Promotes NSUN4-Mediated Chondrocyte Mitochondrial Dysfunction and Pyroptosis in Temporomandibular Joint Osteoarthritis.","authors":"Yu Chen, Haotian Ren","doi":"10.1177/19476035251339410","DOIUrl":"10.1177/19476035251339410","url":null,"abstract":"<p><p>ObjectiveTemporomandibular joint osteoarthritis (TMJOA) seriously influences the quality of life of patients. Chondrocyte mitochondrial dysfunction and pyroptosis play an important role in the development of osteoarthritis, but their role in TMJOA pathogenesis is elusive. We aimed to probe into the role and mechanism of mitochondrial dysfunction and pyroptosis in TMJOA.DesignTMJOA rat models were established by unilateral anterior crossbite operation. Pathological changes in cartilage tissues were observed by hematoxylin-eosin staining, and mitochondrial dysfunction and pyroptosis were evaluated by immunohistochemistry. The biological function and mechanism of ZC3H13 in mitochondrial dysfunction and pyroptosis were determined by cell experiments.ResultsWe discovered that mitochondrial dysfunction and pyroptosis occurred in cartilage tissues of TMJOA rats. The expression of ZC3H13 was observably upregulated in TMJOA rats. Further cell experiments showed that interference of ZC3H13 restrained mitochondrial dysfunction and pyroptosis of chondrocytes. RNA sequencing revealed that NSUN4 expression was significantly increased in chondrocytes after ZC3H13 knockdown. Silencing of ZC3H13 remarkably diminished the level of NSUN4 N6-methyladenosine (m6A) modification. Moreover, mitochondrial dysfunction and pyroptosis of chondrocytes were notably increased after NSUN4 knockdown.ConclusionOur study revealed that ZC3H13-mediated NSUN4 repressed TMJOA progression by modulating chondrocyte mitochondrial dysfunction and pyroptosis in an m6A-dependent manner, which may offer a potential strategy for TMJOA treatment.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035251339410"},"PeriodicalIF":2.7,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-22DOI: 10.1177/19476035251325094
Daran Huang, Wenxian Png, Inderjeet Singh Rikhraj, Eric Wei Liang Cher
BackgroundHallux rigidus (HR) is a degenerative joint disorder of the first metatarsophalangeal joint (MTPJ), causing joint pain and stiffness. Surgical treatments, including cheilectomy, microfracture (MF) and dorsal oblique osteotomy (DOO), have been well described in current literature. However, the addition of matrix-induced chondrogenesis (MIC) via scaffold implantation with bone marrow aspirate concentrate (BMAC) is novel and hypothesized to significantly improve cartilage healing.ObjectivesThis study aimed to (1) describe the COMM procedure-a novel combination of cheilectomy, DOO, MF, and MIC, as well as to (2) evaluate its early clinical outcomes in a series of 12 HR cases.Study Design & MethodsThis is a retrospective study of 11 patients (12 feet) with HR treated with the COMM procedure in our hospital from May 2022 to June 2023 by 3 fellowship-trained foot and ankle surgeons. All the patients have completed their 1-year clinical review, where we evaluated their Numeric Pain Rating (NPR), European Foot and Ankle Society (EFAS), and Short Form-36 (SF-36) scores (Physical Function [SF-PF] and Mental Health [SF-MH]), as well as satisfaction. Preoperative and postoperative scores were compared to determine the effect of treatment.ResultsThere was statistically significant improvement in all scores (P < 0.05). EFAS Foot and/or Ankle and Sports scores improved from 9.3 to 20.0 and 3.8 to 9.4, respectively. SF-PF and SF-MH scores improved from 47.9% to 67.9% and 54.0% to 66.0%, respectively. Mean NPR at rest and during activity improved from 4.8 to 0.2 and 7.6 to 2.5, respectively. The mean postoperative satisfaction was 8.0, with 10 representing maximal satisfaction.ConclusionsDespite being a small series, our study has shown good clinical outcomes and promising satisfaction rates among all patients who have undergone our COMM procedure.
{"title":"Cheilectomy, Osteotomy, Microfracture, and Matrix-Induced Chondrogenesis (COMM): A Novel Combined Procedure for Treating Hallux Rigidus.","authors":"Daran Huang, Wenxian Png, Inderjeet Singh Rikhraj, Eric Wei Liang Cher","doi":"10.1177/19476035251325094","DOIUrl":"10.1177/19476035251325094","url":null,"abstract":"<p><p>BackgroundHallux rigidus (HR) is a degenerative joint disorder of the first metatarsophalangeal joint (MTPJ), causing joint pain and stiffness. Surgical treatments, including cheilectomy, microfracture (MF) and dorsal oblique osteotomy (DOO), have been well described in current literature. However, the addition of matrix-induced chondrogenesis (MIC) via scaffold implantation with bone marrow aspirate concentrate (BMAC) is novel and hypothesized to significantly improve cartilage healing.ObjectivesThis study aimed to (1) describe the COMM procedure-a novel combination of cheilectomy, DOO, MF, and MIC, as well as to (2) evaluate its early clinical outcomes in a series of 12 HR cases.Study Design & MethodsThis is a retrospective study of 11 patients (12 feet) with HR treated with the COMM procedure in our hospital from May 2022 to June 2023 by 3 fellowship-trained foot and ankle surgeons. All the patients have completed their 1-year clinical review, where we evaluated their Numeric Pain Rating (NPR), European Foot and Ankle Society (EFAS), and Short Form-36 (SF-36) scores (Physical Function [SF-PF] and Mental Health [SF-MH]), as well as satisfaction. Preoperative and postoperative scores were compared to determine the effect of treatment.ResultsThere was statistically significant improvement in all scores (<i>P</i> < 0.05). EFAS Foot and/or Ankle and Sports scores improved from 9.3 to 20.0 and 3.8 to 9.4, respectively. SF-PF and SF-MH scores improved from 47.9% to 67.9% and 54.0% to 66.0%, respectively. Mean NPR at rest and during activity improved from 4.8 to 0.2 and 7.6 to 2.5, respectively. The mean postoperative satisfaction was 8.0, with 10 representing maximal satisfaction.ConclusionsDespite being a small series, our study has shown good clinical outcomes and promising satisfaction rates among all patients who have undergone our COMM procedure.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035251325094"},"PeriodicalIF":2.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-28DOI: 10.1177/19476035251334737
P Niemeyer, M Hanus, J Belickas, T László, R Gudas, M Fiodorovas, A Cebatorius, M Pastucha, K Izadpanah, J Prokeš, K Sisák, M Mohyla, C Farkas, O Kessler, S Kybal, R Spiro, S Trattnig, A Köhler, A Kirner, C Gaissmaier
ObjectiveTo evaluate efficacy and safety at 5 years after treatment with hydrogel-based autologous chondrocyte implantation (ACI) for large cartilage defects in the knee.DesignProspective, multicenter, single-arm, Phase III clinical trial. ACI was performed in 100 patients with focal full-thickness cartilage defects ranging from 4 to 12 cm2 in size. The primary outcome measure was the responder rate (defined as improvement by ≥10 points) at 2 years using the Knee Injury and Osteoarthritis Outcome Score (KOOS).ResultsThe preoperative overall KOOS was 39.8 points and continuously increased to 84.7 points at 5 years (mean increase 44.1 points, 95% CI = 40.4-47.9, P < 0.0001). The primary study endpoint (i.e., a KOOS responder rate of >40%) was descriptively met at each assessment timepoint from 3 months to 5 years (Month 3: 75.5%, 95% CI = 65.6-83.8; Year 2: 93.0%, 95% CI = 86.1-97.1, Year 5: 92.8%, 95% CI = 85.7-97.0). International Knee Documentation Committee (IKDC) subjective and objective scores and quality of life assessments (EQ-5D-5L) supported the results seen for the KOOS. The overall treatment failure rate at 5 years was 1%. All treatment-related adverse events were of mild or moderate intensity and mostly occurred within the first year after treatment.ConclusionsHydrogel-based ACI has been shown to be a safe and effective treatment option for patients with large knee cartilage defects with sustained efficacy up to 5 years as demonstrated by consistent and clinically relevant improvements in all investigated efficacy variables. No remarkable adverse events or safety issues were noted.
目的评价水凝胶自体软骨细胞植入术(ACI)治疗膝关节大软骨缺损5年的疗效和安全性。前瞻性、多中心、单组、III期临床试验。我们对100例局灶性全层软骨缺损患者进行了ACI,软骨缺损的大小从4到12 cm2不等。主要结局指标是2年的应答率(定义为改善≥10分),采用膝关节损伤和骨关节炎结局评分(oos)。结果术前总KOOS为39.8分,5年持续增加至84.7分,平均增加44.1分,95% CI = 40.4 ~ 47.9, P < 0.0001)。在3个月至5年的每个评估时间点(第3个月:75.5%,95% CI = 65.6-83.8;2年级:93.0%,95% CI = 86.1-97.1, 5年级:92.8%,95% CI = 85.7-97.0)。国际膝关节文献委员会(IKDC)主客观评分和生活质量评估(EQ-5D-5L)支持oos的结果。5年的总体治疗失败率为1%。所有与治疗相关的不良事件均为轻度或中度强度,且大多发生在治疗后的第一年。结论基于水凝胶的ACI已被证明是一种安全有效的治疗选择,对于大膝关节软骨缺损患者,其持续疗效可达5年,所有研究的疗效变量均有一致和临床相关的改善。没有发现明显的不良事件或安全问题。
{"title":"Treatment of Large Cartilage Defects in the Knee by Hydrogel-Based Autologous Chondrocyte Implantation: A 5-Year Follow-Up of a Prospective, Multicenter, Single-Arm Phase III Trial.","authors":"P Niemeyer, M Hanus, J Belickas, T László, R Gudas, M Fiodorovas, A Cebatorius, M Pastucha, K Izadpanah, J Prokeš, K Sisák, M Mohyla, C Farkas, O Kessler, S Kybal, R Spiro, S Trattnig, A Köhler, A Kirner, C Gaissmaier","doi":"10.1177/19476035251334737","DOIUrl":"https://doi.org/10.1177/19476035251334737","url":null,"abstract":"<p><p>ObjectiveTo evaluate efficacy and safety at 5 years after treatment with hydrogel-based autologous chondrocyte implantation (ACI) for large cartilage defects in the knee.DesignProspective, multicenter, single-arm, Phase III clinical trial. ACI was performed in 100 patients with focal full-thickness cartilage defects ranging from 4 to 12 cm<sup>2</sup> in size. The primary outcome measure was the responder rate (defined as improvement by ≥10 points) at 2 years using the Knee Injury and Osteoarthritis Outcome Score (KOOS).ResultsThe preoperative overall KOOS was 39.8 points and continuously increased to 84.7 points at 5 years (mean increase 44.1 points, 95% CI = 40.4-47.9, <i>P</i> < 0.0001). The primary study endpoint (i.e., a KOOS responder rate of >40%) was descriptively met at each assessment timepoint from 3 months to 5 years (Month 3: 75.5%, 95% CI = 65.6-83.8; Year 2: 93.0%, 95% CI = 86.1-97.1, Year 5: 92.8%, 95% CI = 85.7-97.0). International Knee Documentation Committee (IKDC) subjective and objective scores and quality of life assessments (EQ-5D-5L) supported the results seen for the KOOS. The overall treatment failure rate at 5 years was 1%. All treatment-related adverse events were of mild or moderate intensity and mostly occurred within the first year after treatment.ConclusionsHydrogel-based ACI has been shown to be a safe and effective treatment option for patients with large knee cartilage defects with sustained efficacy up to 5 years as demonstrated by consistent and clinically relevant improvements in all investigated efficacy variables. No remarkable adverse events or safety issues were noted.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035251334737"},"PeriodicalIF":2.7,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12037527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-28DOI: 10.1177/19476035251335008
Felix Ragnar Merlin Koenig, Marcus Raudner, Gregor Wollner, Vladimir Juras, Pavol Szomolanyi, Veronica Vetchy, Johannes Leitner, Victor Schmidbauer, Siegfried Trattnig
ObjectivesThis study aimed to assess the impact of intralesional bony overgrowth (ILBO) after cartilage repair on the integrity of opposing articulating cartilage (OpAC) using T2 mapping and to correlate these findings with clinical outcomes.MethodsIn this multicenter study, magnetic resonance imaging (MRI) examinations were performed in the follow-up after cartilage repair (Microfracturing (MFX) and Matrix-Induced Autologous Chondrocyte Implantation (MACI)) in 45 patients up to 5 years after surgery. T2 values of the OpAC after 3, 12, and 60 months in patients with and without ILBO after 60 months were conducted along with clinical assessments (International Knee Documentation Committee (IKDC) and Knee injury and Osteoarthritis Outcome Score (KOOS)).ResultsAt 60 months post-surgery, 44.4% of patients presented with ILBO, which was associated with significantly higher T2 values in OpAC (P = 0.004). A tendency toward increased T2 values was observed after 12 months, although this did not reach statistical significance (P = 0.06). However, no significant differences were found in clinical outcomes between patients with or without ILBO, nor between those with or without T2 values comparable to reference cartilage.ConclusionILBO significantly affects the biophysical MRI properties of OpAC as indicated by higher T2 values after 60 months. These alterations, though not reflected in any clinical score, can suggest potential long-term implications for cartilage degeneration and may inform future monitoring strategies for cartilage repair. Further research is required to evaluate the long-term effects of these altered mechanical impacts on articulating cartilage and their clinical implications.
{"title":"Long-Term Impact of Intralesional Bony Overgrowth on Opposing Cartilage Integrity: Five-Year Results Following Cartilage Repair.","authors":"Felix Ragnar Merlin Koenig, Marcus Raudner, Gregor Wollner, Vladimir Juras, Pavol Szomolanyi, Veronica Vetchy, Johannes Leitner, Victor Schmidbauer, Siegfried Trattnig","doi":"10.1177/19476035251335008","DOIUrl":"https://doi.org/10.1177/19476035251335008","url":null,"abstract":"<p><p>ObjectivesThis study aimed to assess the impact of intralesional bony overgrowth (ILBO) after cartilage repair on the integrity of opposing articulating cartilage (OpAC) using T2 mapping and to correlate these findings with clinical outcomes.MethodsIn this multicenter study, magnetic resonance imaging (MRI) examinations were performed in the follow-up after cartilage repair (Microfracturing (MFX) and Matrix-Induced Autologous Chondrocyte Implantation (MACI)) in 45 patients up to 5 years after surgery. T2 values of the OpAC after 3, 12, and 60 months in patients with and without ILBO after 60 months were conducted along with clinical assessments (International Knee Documentation Committee (IKDC) and Knee injury and Osteoarthritis Outcome Score (KOOS)).ResultsAt 60 months post-surgery, 44.4% of patients presented with ILBO, which was associated with significantly higher T2 values in OpAC (<i>P</i> = 0.004). A tendency toward increased T2 values was observed after 12 months, although this did not reach statistical significance (<i>P</i> = 0.06). However, no significant differences were found in clinical outcomes between patients with or without ILBO, nor between those with or without T2 values comparable to reference cartilage.ConclusionILBO significantly affects the biophysical MRI properties of OpAC as indicated by higher T2 values after 60 months. These alterations, though not reflected in any clinical score, can suggest potential long-term implications for cartilage degeneration and may inform future monitoring strategies for cartilage repair. Further research is required to evaluate the long-term effects of these altered mechanical impacts on articulating cartilage and their clinical implications.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035251335008"},"PeriodicalIF":2.7,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12037522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-15DOI: 10.1177/19476035251333374
Jari Dahmen, Julian J Hollander, James J Butler, Kaj S Emanuel, Quinten G H Rikken, Sjoerd A S Stufkens, John G Kennedy, Gino M M J Kerkhoffs
BackgroundThe exact incidence of cyst formation after graft transplantation for osteochondral lesions is unknown. The primary purpose was to assess and compare cystic occurrence after autografting, allografting, and osteoperiosteal grafting for osteochondral lesions of the talus. Our secondary aim was to assess the correlation of clinical outcomes with the presence of postoperative cysts.MethodsA literature search was performed up to October 2023 through PubMed, Embase (Ovid), and Cochrane Library. The primary outcome was the postoperative cystic occurrence rate. A random-effects model with moderator analysis was used to calculate differences in occurrence rates between treatment groups. The relationship between the presence of cysts and clinical outcomes was described.ResultsThirteen studies were included with 382 ankles. The average radiological follow-up at which the presence of cystic occurrence was assessed ranged from 12 to 84 months. The rates of cystic occurrence for the osteochondral autograft transplantation group, the allograft transplantation group, and the osteoperiosteal transplantation group were 42% (95% confidence interval [CI] = 24-61), 58% (95% CI = 40-74), and 34% (95% CI = 12-67), respectively, without any significant differences noted. No relationship between the presence of cysts and clinical outcomes was found.ConclusionPostoperative cystic occurrence is common after osteochondral autograft transplantation (42%), allograft transplantation (58%), and osteoperiosteal transplantation (34%) in osteochondral lesions of the talus-without significant intertreatment differences. The postoperative presence of cysts was not correlated with clinical outcomes. Future research should assess whether the postoperative presence of cysts correlates with (clinical) outcomes at longer follow-up.Level of Evidence:Level IV, systematic review and meta-analysis.
背景骨软骨病变移植后囊肿形成的确切发生率尚不清楚。主要目的是评估和比较自体骨移植、同种异体骨移植和骨骨膜移植治疗距骨软骨病变后的囊性发生率。我们的第二个目的是评估临床结果与术后囊肿存在的相关性。方法通过PubMed、Embase (Ovid)和Cochrane Library检索至2023年10月的文献。主要观察指标为术后囊性发生率。采用随机效应模型和慢化剂分析来计算治疗组间发生率的差异。描述了囊肿的存在与临床结果之间的关系。结果纳入13项研究,涉及382例踝关节。评估囊性发生的平均放射随访时间为12至84个月。自体骨软骨移植组、同种异体骨软骨移植组和骨骨膜移植组的囊性发生率分别为42%(95%可信区间[CI] = 24-61)、58% (95% CI = 40-74)和34% (95% CI = 12-67),差异无统计学意义。没有发现囊肿的存在与临床结果之间的关系。结论距骨软骨病变自体骨软骨移植(42%)、同种异体骨软骨移植(58%)和骨骨膜移植(34%)术后均有囊性发生,治疗间无显著差异。术后出现的囊肿与临床结果无关。未来的研究应该评估术后出现的囊肿是否与长期随访的(临床)结果相关。证据等级:四级,系统评价和荟萃分析。
{"title":"What are These Cysts Doing in My Graft? A Meta-Analysis on Cystic Occurrence After Autografting and Allografting for Osteochondral Lesions of the Talus.","authors":"Jari Dahmen, Julian J Hollander, James J Butler, Kaj S Emanuel, Quinten G H Rikken, Sjoerd A S Stufkens, John G Kennedy, Gino M M J Kerkhoffs","doi":"10.1177/19476035251333374","DOIUrl":"https://doi.org/10.1177/19476035251333374","url":null,"abstract":"<p><p>BackgroundThe exact incidence of cyst formation after graft transplantation for osteochondral lesions is unknown. The primary purpose was to assess and compare cystic occurrence after autografting, allografting, and osteoperiosteal grafting for osteochondral lesions of the talus. Our secondary aim was to assess the correlation of clinical outcomes with the presence of postoperative cysts.MethodsA literature search was performed up to October 2023 through PubMed, Embase (Ovid), and Cochrane Library. The primary outcome was the postoperative cystic occurrence rate. A random-effects model with moderator analysis was used to calculate differences in occurrence rates between treatment groups. The relationship between the presence of cysts and clinical outcomes was described.ResultsThirteen studies were included with 382 ankles. The average radiological follow-up at which the presence of cystic occurrence was assessed ranged from 12 to 84 months. The rates of cystic occurrence for the osteochondral autograft transplantation group, the allograft transplantation group, and the osteoperiosteal transplantation group were 42% (95% confidence interval [CI] = 24-61), 58% (95% CI = 40-74), and 34% (95% CI = 12-67), respectively, without any significant differences noted. No relationship between the presence of cysts and clinical outcomes was found.ConclusionPostoperative cystic occurrence is common after osteochondral autograft transplantation (42%), allograft transplantation (58%), and osteoperiosteal transplantation (34%) in osteochondral lesions of the talus-without significant intertreatment differences. The postoperative presence of cysts was not correlated with clinical outcomes. Future research should assess whether the postoperative presence of cysts correlates with (clinical) outcomes at longer follow-up.Level of Evidence:Level IV, systematic review and meta-analysis.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035251333374"},"PeriodicalIF":2.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11999998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-15DOI: 10.1177/19476035251322730
Luca De Marziani, Angelo Boffa, Marco Franceschini, Luca Andriolo, Alessandro Di Martino, Stefano Zaffagnini, Giuseppe Filardo
ObjectiveThe aim of this study was to establish the minimal clinically important difference (MCID) thresholds for the International Knee Documentation Committee (IKDC) subjective and Visual Analogue Scale (VAS) pain scores in patients affected by knee chondral and osteochondral lesions treated with cell-free scaffold implantation.DesignFor the MCID definition, 186 patients who underwent an osteochondral scaffold implantation were included. Patients were evaluated through the IKDC subjective and VAS pain scores at baseline, 12 and 24 months. The MCID was calculated using a distribution-based method for both IKDC subjective and VAS pain scores at 12 and 24 months, as well as with an anchor-based method.ResultsThe MCID values were 10.1 and 1.5 for the IKDC subjective and VAS pain scores, respectively, both at 12 and 24 months of follow-up. The rate of patients who achieved the MCID was 83% at 12 months and 88% at 24 months. The anchor-based method led to higher MCID values. Factors identified to increase the probability to reach the MCID were younger age (P = 0.042), male sex (P = 0.042), and lateral femoral condyle lesions (P = 0.002), while patellar lesions were less likely to reach the MCID (P = 0.009).ConclusionsThis study defined the MCID values for the IKDC subjective and VAS pain scores after treatment with a cell-free biomimetic scaffold, with 88% of the patients achieving clinically relevant results at 2 years. Younger patients, males and lateral femoral condyle lesions were more likely to reach the MCID. However, the identified thresholds can be influenced by the method chosen, which warrants caution when interpreting study results.
{"title":"Minimal Clinically Important Difference in Patients with Knee Cartilage Lesions Treated with a Cell-Free Scaffold Implantation.","authors":"Luca De Marziani, Angelo Boffa, Marco Franceschini, Luca Andriolo, Alessandro Di Martino, Stefano Zaffagnini, Giuseppe Filardo","doi":"10.1177/19476035251322730","DOIUrl":"https://doi.org/10.1177/19476035251322730","url":null,"abstract":"<p><p>ObjectiveThe aim of this study was to establish the minimal clinically important difference (MCID) thresholds for the International Knee Documentation Committee (IKDC) subjective and Visual Analogue Scale (VAS) pain scores in patients affected by knee chondral and osteochondral lesions treated with cell-free scaffold implantation.DesignFor the MCID definition, 186 patients who underwent an osteochondral scaffold implantation were included. Patients were evaluated through the IKDC subjective and VAS pain scores at baseline, 12 and 24 months. The MCID was calculated using a distribution-based method for both IKDC subjective and VAS pain scores at 12 and 24 months, as well as with an anchor-based method.ResultsThe MCID values were 10.1 and 1.5 for the IKDC subjective and VAS pain scores, respectively, both at 12 and 24 months of follow-up. The rate of patients who achieved the MCID was 83% at 12 months and 88% at 24 months. The anchor-based method led to higher MCID values. Factors identified to increase the probability to reach the MCID were younger age (<i>P</i> = 0.042), male sex (<i>P</i> = 0.042), and lateral femoral condyle lesions (<i>P</i> = 0.002), while patellar lesions were less likely to reach the MCID (<i>P</i> = 0.009).ConclusionsThis study defined the MCID values for the IKDC subjective and VAS pain scores after treatment with a cell-free biomimetic scaffold, with 88% of the patients achieving clinically relevant results at 2 years. Younger patients, males and lateral femoral condyle lesions were more likely to reach the MCID. However, the identified thresholds can be influenced by the method chosen, which warrants caution when interpreting study results.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035251322730"},"PeriodicalIF":2.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11999993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-09DOI: 10.1177/19476035251319404
Eric M Milliron, Parker A Cavendish, James Carey, Tyler Barker, David C Flanigan
ObjectiveTo determine whether there are differences in MACI (matrix-induced autologous chondrocyte implantation) treatment in the United States, by comparing cartilage defects and patient characteristics between the initial 1,000 patients treated with the next 5,000MethodsFollowing initial analysis of the first 1,000 consecutive patients treated with MACI, data were collected and analyzed for the subsequent 5,000. Patients were identified by MACI lot number and surgery date. Adverse events were summarized with descriptive statistics. Group differences were assessed with t-tests and chi-square, with significance set at P < 0.05.ResultsFive thousand adults (5,198 knees) were implanted with MACI by 1,130 surgeons. Patient sex (male 49.2%) was evenly split, and the mean age was 33.6 years. Most patients had a single cartilage defect treated, and the mean defect size was 4.4 cm2. The patella was the most treated surface (38.4%), followed by the medial femoral condyle (25.7%). Most patients (85.5%) had concomitant surgical procedures at the time of cartilage biopsy procurement. There were statistically significant differences in the number of patella (P < 0.001), medial femoral condyle (P < 0.001), and "not specified" (P = 0.008) between groups. Mean defect size and mean total defect size were both larger (P < 0.001 and P = 0.009, respectively) in the subsequent 5,000 patients.ConclusionThe utilization of MACI has remained consistent. Patient demographics and concomitant surgical procedures between the first 1,000 MACI patients and subsequent 5,000 MACI patients were comparable. Patellofemoral defects were the most treated in both subsets, and an overall low rate of adverse events was observed.
{"title":"Use of MACI (Autologous Cultured Chondrocytes on Porcine Collagen Membrane) in the United States: Expanded Experience over 5,000 Cases.","authors":"Eric M Milliron, Parker A Cavendish, James Carey, Tyler Barker, David C Flanigan","doi":"10.1177/19476035251319404","DOIUrl":"10.1177/19476035251319404","url":null,"abstract":"<p><p>ObjectiveTo determine whether there are differences in MACI (matrix-induced autologous chondrocyte implantation) treatment in the United States, by comparing cartilage defects and patient characteristics between the initial 1,000 patients treated with the next 5,000MethodsFollowing initial analysis of the first 1,000 consecutive patients treated with MACI, data were collected and analyzed for the subsequent 5,000. Patients were identified by MACI lot number and surgery date. Adverse events were summarized with descriptive statistics. Group differences were assessed with <i>t</i>-tests and chi-square, with significance set at <i>P</i> < 0.05.ResultsFive thousand adults (5,198 knees) were implanted with MACI by 1,130 surgeons. Patient sex (male 49.2%) was evenly split, and the mean age was 33.6 years. Most patients had a single cartilage defect treated, and the mean defect size was 4.4 cm<sup>2</sup>. The patella was the most treated surface (38.4%), followed by the medial femoral condyle (25.7%). Most patients (85.5%) had concomitant surgical procedures at the time of cartilage biopsy procurement. There were statistically significant differences in the number of patella (<i>P</i> < 0.001), medial femoral condyle (<i>P</i> < 0.001), and \"not specified\" (<i>P</i> = 0.008) between groups. Mean defect size and mean total defect size were both larger (<i>P</i> < 0.001 and <i>P</i> = 0.009, respectively) in the subsequent 5,000 patients.ConclusionThe utilization of MACI has remained consistent. Patient demographics and concomitant surgical procedures between the first 1,000 MACI patients and subsequent 5,000 MACI patients were comparable. Patellofemoral defects were the most treated in both subsets, and an overall low rate of adverse events was observed.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035251319404"},"PeriodicalIF":2.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-05DOI: 10.1177/19476035251329571
Goetz Hannes Welsch, Marc Regier, Karl-Heinz Frosch, Milena L Pachowsky, Frank Oliver Henes, Gerhard Adam, Kai-Jonathan Maas, Malte Lennart Warncke
ObjectiveThe goal of our study was to assess the prevalence of osteoarthritis in the knee joint of active male professional soccer players by means of the semi-quantitative Whole-Organ Magnetic Resonance Imaging Score (WORMS).DesignMagnetic resonance imagings (MRIs) of both knees were performed on 85 male professional soccer players during their "medicals" (age = 24 ± 4 years). All baseline data (age, playing position) were obtained. Based on the WORMS, the status of the cartilage and bone in the medial and lateral femoro-tibial joint (MFTJ and LFTJ), as well as the patellofemoral joint was assessed. Menisci and ligaments were evaluated separately. The final score was the sum of all regional scores.ResultsThe mean WORMS of the 170 knee joints was 13.3 ± 13.5 points (range = 0-111, achievable scores: 0-290). Cartilage changes were the most common pathologies, observed in 141 of the 170 knee joints. Structural cartilage lesions (WORMS ≥ 2) were observed in 54% of the studied knees. Pathologies of the medial meniscus were associated with cartilage damage of the corresponding MFTJ (r = 0.424, P < 0.0001). The same effect was observed for the lateral meniscus and the corresponding LFTJ (r = 0.553, P < 0.0001). However, lateral meniscal lesions could be correlated with more other joint pathologies compared to medial meniscal lesions. Total WORMS correlated significantly with increasing age (r = 0.386, P = 0.001).ConclusionThe provided data show the high incidence of knee joint damage in professional football players. In particular, the lateral meniscus appears to play a critical role.
目的采用半定量全器官磁共振成像评分(WORMS)评估现役男性职业足球运动员膝关节骨关节炎的患病率。设计对85名男性职业足球运动员(年龄= 24±4岁)在体检期间进行双膝磁共振成像(mri)。获得所有基线数据(年龄、比赛位置)。基于WORMS,评估股骨内侧和外侧股胫关节(MFTJ和LFTJ)以及髌股关节的软骨和骨的状态。半月板和韧带分别评估。最后的分数是所有地区分数的总和。结果170个膝关节的WORMS平均为13.3±13.5分(范围0 ~ 111分,可达分0 ~ 290分)。软骨改变是最常见的病变,在170个膝关节中有141个观察到。54%的膝关节存在结构性软骨病变(WORMS≥2)。内侧半月板病变与相应MFTJ软骨损伤相关(r = 0.424, P < 0.0001)。外侧半月板和相应的LFTJ也有相同的效果(r = 0.553, P < 0.0001)。然而,与内侧半月板病变相比,外侧半月板病变可能与更多其他关节病变相关。蠕虫总数与年龄的增长呈显著相关(r = 0.386, P = 0.001)。结论职业足球运动员膝关节损伤的发生率较高。特别是外侧半月板似乎起着关键作用。
{"title":"Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the Knee in Professional Soccer Players.","authors":"Goetz Hannes Welsch, Marc Regier, Karl-Heinz Frosch, Milena L Pachowsky, Frank Oliver Henes, Gerhard Adam, Kai-Jonathan Maas, Malte Lennart Warncke","doi":"10.1177/19476035251329571","DOIUrl":"10.1177/19476035251329571","url":null,"abstract":"<p><p>ObjectiveThe goal of our study was to assess the prevalence of osteoarthritis in the knee joint of active male professional soccer players by means of the semi-quantitative Whole-Organ Magnetic Resonance Imaging Score (WORMS).DesignMagnetic resonance imagings (MRIs) of both knees were performed on 85 male professional soccer players during their \"medicals\" (age = 24 ± 4 years). All baseline data (age, playing position) were obtained. Based on the WORMS, the status of the cartilage and bone in the medial and lateral femoro-tibial joint (MFTJ and LFTJ), as well as the patellofemoral joint was assessed. Menisci and ligaments were evaluated separately. The final score was the sum of all regional scores.ResultsThe mean WORMS of the 170 knee joints was 13.3 ± 13.5 points (range = 0-111, achievable scores: 0-290). Cartilage changes were the most common pathologies, observed in 141 of the 170 knee joints. Structural cartilage lesions (WORMS ≥ 2) were observed in 54% of the studied knees. Pathologies of the medial meniscus were associated with cartilage damage of the corresponding MFTJ (r = 0.424, <i>P</i> < 0.0001). The same effect was observed for the lateral meniscus and the corresponding LFTJ (r = 0.553, <i>P</i> < 0.0001). However, lateral meniscal lesions could be correlated with more other joint pathologies compared to medial meniscal lesions. Total WORMS correlated significantly with increasing age (r = 0.386, <i>P</i> = 0.001).ConclusionThe provided data show the high incidence of knee joint damage in professional football players. In particular, the lateral meniscus appears to play a critical role.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035251329571"},"PeriodicalIF":2.7,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}