Pub Date : 2025-11-27DOI: 10.1186/s13075-025-03698-2
Alex B Walinga, Stein J Janssen, Tobias Stornebrink, Rover Krips, Sander W Tas, Arthur J Kievit, Gino M M J Kerkhoffs
Background: Bacterial (i.e., septic) arthritis requires prompt source control, including drainage of the infected synovial fluid, often through arthrocentesis (needle aspiration) or surgical intervention, in combination with antibiotics to prevent joint damage; however, when surgical intervention is required, conventional arthroscopy can lead to treatment delays and anesthesia-related complications. To overcome these delays, needle arthroscopy was recently developed to offer the possibility of 2-mm diameter arthroscopy lavage under local anesthesia. The purpose of this study was to prospectively evaluate bedside needle arthroscopy under local anesthesia to demonstrate its potential as an effective, minimally invasive alternative for timely diagnosis and joint lavage in patients with (suspected) native bacterial arthritis in a real-world clinical practice setting.
Methods: Over a 30-month period, this prospective, double center cohort study included patients with either confirmed (positive synovial fluid culture) or highly suspected (≥ 2 local signs and ≥ 1 systemic sign) native joint bacterial arthritis. The primary outcome was the need for reoperation (conventional arthroscopy or arthrotomy) within 30 days. Bivariate analysis assessed differences in patient and treatment characteristics between successful and failed needle arthroscopic debridement.
Results: Forty-two patients (44 native joints) underwent needle arthroscopy. The mean age was 67 years (SD 16), the mean BMI was 26.8 kg/m2 (SD 3.9), and 69% were male. The knee (n = 34, 77%) was the most commonly involved joint. Within 30 days, 14% (6/44; 95% CI 5-27%) required a reoperation (conventional arthroscopy or arthrotomy). Two parameters were identified as risk factors for failure of a single debridement: the baseline level of ESR (112 mm/hr vs. 57 mm/hr, p = 0.027) and purulent synovial fluid (67% vs. 11%; p = 0.011). No serious procedure-related complications were observed.
Conclusions: A single bedside needle arthroscopy was effective in treating 86% of patients with confirmed or suspected native joint bacterial arthritis in a real-world practice, avoiding the need for general anesthesia or conventional surgery. This approach represents a safe and effective, minimally invasive alternative that can be rapidly implemented, enabling early joint lavage and potentially reducing the risk of secondary osteoarthritis.
Trial registration: We pre-registered this trial on the Dutch Trial Register, later called CCMO (NTR 21076, CCMO NL78387.018.21).
背景:细菌性(即脓毒性)关节炎需要及时控制源头,包括通过关节穿刺(针吸)或手术干预引流感染的滑液,并联合抗生素预防关节损伤;然而,当需要手术干预时,传统的关节镜检查可能导致治疗延迟和麻醉相关并发症。为了克服这些延迟,最近开发了针关节镜,在局部麻醉下提供2mm直径关节镜灌洗的可能性。本研究的目的是前瞻性评估局部麻醉下的床边针关节镜检查,以证明其在现实世界的临床实践中作为一种有效的、微创的替代方法,可以及时诊断(疑似)原生细菌性关节炎患者并进行关节灌洗。方法:在30个月的时间里,这项前瞻性双中心队列研究纳入了确诊(滑液培养阳性)或高度疑似(≥2个局部体征和≥1个全身体征)的原发性关节细菌性关节炎患者。主要结果是30天内是否需要再手术(常规关节镜检查或关节切开术)。双变量分析评估了成功和失败的关节镜针清创术患者和治疗特征的差异。结果:42例患者(44个原生关节)行关节针镜检查。平均年龄67岁(SD 16),平均BMI为26.8 kg/m2 (SD 3.9),男性占69%。膝关节(n = 34, 77%)是最常见的受累关节。在30天内,14% (6/44;95% CI 5-27%)需要再次手术(常规关节镜或关节切开术)。两个参数被确定为单次清创失败的危险因素:ESR基线水平(112 mm/hr vs 57 mm/hr, p = 0.027)和化脓性滑液(67% vs 11%, p = 0.011)。未见严重的手术相关并发症。结论:在现实世界的实践中,单床边针关节镜对86%确诊或疑似天然关节细菌性关节炎的患者有效,避免了全身麻醉或常规手术的需要。这种方法是一种安全、有效、微创的替代方法,可以快速实施,实现早期关节灌洗,并潜在地降低继发性骨关节炎的风险。试验注册:我们在荷兰试验注册中预先注册了该试验,后来称为CCMO (NTR 21076, CCMO NL78387.018.21)。
{"title":"Bedside needle arthroscopy for native joint bacterial arthritis in a real-world clinical practice setting: a prospective cohort study.","authors":"Alex B Walinga, Stein J Janssen, Tobias Stornebrink, Rover Krips, Sander W Tas, Arthur J Kievit, Gino M M J Kerkhoffs","doi":"10.1186/s13075-025-03698-2","DOIUrl":"10.1186/s13075-025-03698-2","url":null,"abstract":"<p><strong>Background: </strong>Bacterial (i.e., septic) arthritis requires prompt source control, including drainage of the infected synovial fluid, often through arthrocentesis (needle aspiration) or surgical intervention, in combination with antibiotics to prevent joint damage; however, when surgical intervention is required, conventional arthroscopy can lead to treatment delays and anesthesia-related complications. To overcome these delays, needle arthroscopy was recently developed to offer the possibility of 2-mm diameter arthroscopy lavage under local anesthesia. The purpose of this study was to prospectively evaluate bedside needle arthroscopy under local anesthesia to demonstrate its potential as an effective, minimally invasive alternative for timely diagnosis and joint lavage in patients with (suspected) native bacterial arthritis in a real-world clinical practice setting.</p><p><strong>Methods: </strong>Over a 30-month period, this prospective, double center cohort study included patients with either confirmed (positive synovial fluid culture) or highly suspected (≥ 2 local signs and ≥ 1 systemic sign) native joint bacterial arthritis. The primary outcome was the need for reoperation (conventional arthroscopy or arthrotomy) within 30 days. Bivariate analysis assessed differences in patient and treatment characteristics between successful and failed needle arthroscopic debridement.</p><p><strong>Results: </strong>Forty-two patients (44 native joints) underwent needle arthroscopy. The mean age was 67 years (SD 16), the mean BMI was 26.8 kg/m<sup>2</sup> (SD 3.9), and 69% were male. The knee (n = 34, 77%) was the most commonly involved joint. Within 30 days, 14% (6/44; 95% CI 5-27%) required a reoperation (conventional arthroscopy or arthrotomy). Two parameters were identified as risk factors for failure of a single debridement: the baseline level of ESR (112 mm/hr vs. 57 mm/hr, p = 0.027) and purulent synovial fluid (67% vs. 11%; p = 0.011). No serious procedure-related complications were observed.</p><p><strong>Conclusions: </strong>A single bedside needle arthroscopy was effective in treating 86% of patients with confirmed or suspected native joint bacterial arthritis in a real-world practice, avoiding the need for general anesthesia or conventional surgery. This approach represents a safe and effective, minimally invasive alternative that can be rapidly implemented, enabling early joint lavage and potentially reducing the risk of secondary osteoarthritis.</p><p><strong>Trial registration: </strong>We pre-registered this trial on the Dutch Trial Register, later called CCMO (NTR 21076, CCMO NL78387.018.21).</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":"1"},"PeriodicalIF":4.6,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12763899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145628326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-26DOI: 10.1186/s13075-025-03678-6
Priscilla M Tjandra, Bethany A Andoko, Jooyoung A Kim, Jacob G Brockert, Andreana G Gomez, Sonya Sar, Megha R Aepala, Tiffany T K Pham, Darren Dumlao, Hope D Welhaven, Kelsey H Collins
Background: Osteoarthritis (OA) is the leading cause of pain worldwide. However, clinical discordance between pain and cartilage damage presents challenges in determining the mechanisms of OA pain, thus creating a need for well-controlled models that probe the separable mechanisms of structural damage and knee pain. We previously identified that deletion of complement factor D (FD) results in increased pressure-pain hyperalgesia despite cartilage protection after destabilization of the medial meniscus (DMM) surgery. However, how these discordant OA phenotypes manifest is not understood. We employed a novel targeted lipidomics approach to elucidate the role of eicosanoids in FD-mediated pain. We hypothesize that the absence of Cfd (FD-/-) will protect cartilage but cause increased pressure-pain hyperalgesia and eicosanoid dysregulation persisting throughout OA development.
Methods: Male and female FD-/- and wild-type (WT) mice were challenged with DMM or remained naïve at 16 weeks old. Pressure-pain hyperalgesia was measured every two weeks for 8 weeks post-DMM. A second cohort was evaluated at 2 weeks post-DMM to investigate DMM injury response. Structural damage was scored using the Modified Mankin system. Eicosanoid profiles were characterized via liquid chromatography-mass spectrometry (LC-MS) on serum and synovial fluid samples. Statistical analysis was performed with unpaired t-test or two-way ANOVA with Sidak's posthoc test, p < 0.05.
Results: Unlike WT mice, FD-/- mice exhibited no differences in Modified Mankin scores 8 weeks post-DMM in both sexes. As expected, FD-/- and WT hyperalgesia was present at 2 weeks, persisted through 8 weeks, and was not associated with knee structural changes. Despite both sexes exhibiting similar levels of hyperalgesia, eicosanoid profiles differed. Male FD-/- demonstrated greater pain-driving (12-HETE, 13-HODE) and lower pain-driving (15-HETE) and pain-suppressing (14-HDHA) abundances of eicosanoids compared to WT. Paradoxically, female FD-/- exhibited bi-directional differences in pain-suppressive factors (palmitoyl ethanolamide, EPA, 14-HDHA) and lower abundances of pro-inflammatory arachidonic acid compared to WT.
Conclusion: The absence of Cfd protects cartilage but does not prevent hyperalgesia after DMM. Changes in eicosanoid profiles suggests that loss in FD drives pain acutely and creates a hyperalgesia phenotype early in response to DMM. Eicosanoid profiling is a novel tool to mechanistically determine pain drivers in osteoarthritis.
{"title":"Complement factor D (adipsin) mediates pressure-pain hypersensitivity post destabilization of medial meniscus injury.","authors":"Priscilla M Tjandra, Bethany A Andoko, Jooyoung A Kim, Jacob G Brockert, Andreana G Gomez, Sonya Sar, Megha R Aepala, Tiffany T K Pham, Darren Dumlao, Hope D Welhaven, Kelsey H Collins","doi":"10.1186/s13075-025-03678-6","DOIUrl":"10.1186/s13075-025-03678-6","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA) is the leading cause of pain worldwide. However, clinical discordance between pain and cartilage damage presents challenges in determining the mechanisms of OA pain, thus creating a need for well-controlled models that probe the separable mechanisms of structural damage and knee pain. We previously identified that deletion of complement factor D (FD) results in increased pressure-pain hyperalgesia despite cartilage protection after destabilization of the medial meniscus (DMM) surgery. However, how these discordant OA phenotypes manifest is not understood. We employed a novel targeted lipidomics approach to elucidate the role of eicosanoids in FD-mediated pain. We hypothesize that the absence of Cfd (FD<sup>-/-</sup>) will protect cartilage but cause increased pressure-pain hyperalgesia and eicosanoid dysregulation persisting throughout OA development.</p><p><strong>Methods: </strong>Male and female FD<sup>-/-</sup> and wild-type (WT) mice were challenged with DMM or remained naïve at 16 weeks old. Pressure-pain hyperalgesia was measured every two weeks for 8 weeks post-DMM. A second cohort was evaluated at 2 weeks post-DMM to investigate DMM injury response. Structural damage was scored using the Modified Mankin system. Eicosanoid profiles were characterized via liquid chromatography-mass spectrometry (LC-MS) on serum and synovial fluid samples. Statistical analysis was performed with unpaired t-test or two-way ANOVA with Sidak's posthoc test, p < 0.05.</p><p><strong>Results: </strong>Unlike WT mice, FD<sup>-/-</sup> mice exhibited no differences in Modified Mankin scores 8 weeks post-DMM in both sexes. As expected, FD<sup>-/-</sup> and WT hyperalgesia was present at 2 weeks, persisted through 8 weeks, and was not associated with knee structural changes. Despite both sexes exhibiting similar levels of hyperalgesia, eicosanoid profiles differed. Male FD<sup>-/-</sup> demonstrated greater pain-driving (12-HETE, 13-HODE) and lower pain-driving (15-HETE) and pain-suppressing (14-HDHA) abundances of eicosanoids compared to WT. Paradoxically, female FD<sup>-/-</sup> exhibited bi-directional differences in pain-suppressive factors (palmitoyl ethanolamide, EPA, 14-HDHA) and lower abundances of pro-inflammatory arachidonic acid compared to WT.</p><p><strong>Conclusion: </strong>The absence of Cfd protects cartilage but does not prevent hyperalgesia after DMM. Changes in eicosanoid profiles suggests that loss in FD drives pain acutely and creates a hyperalgesia phenotype early in response to DMM. Eicosanoid profiling is a novel tool to mechanistically determine pain drivers in osteoarthritis.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"27 1","pages":"221"},"PeriodicalIF":4.6,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12659361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145628323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-25DOI: 10.1186/s13075-025-03696-4
Soonsu Shin, Min-Ho Kim, Chang-Mo Oh, Dosang Cho, Jae-Hong Ryoo
Background: The risk of non-Hodgkin's lymphoma in patients with primary Sjögren's syndrome (pSS) is well established. However, the association between pSS and the risk of gastrointestinal cancers remains underexplored. This study aims to assess the risk of gastrointestinal cancers in pSS patients in Korea compared with the general population.
Methods: We included 320,082 participants from National Health Insurance Service-National Sample Cohort (NHIS-NSC) database. Of these, there were 850 patients with pSS and 319,232 in the non-pSS group. All participants were followed-up until 2019 or the development of gastrointestinal cancers, whichever occurred first. Hazard ratio (HR) and 95% confidence intervals (95% CI) for gastrointestinal cancers were calculated by multivariable Cox proportional hazards models.
Results: Compared with the non-pSS group, patients with pSS had a higher risk of developing all gastrointestinal cancers, but the association did not reach statistical significance (adjusted HR: 1.240, 95% CI: 0.990-1.543). Site-specific analyses showed that pSS patients had a higher risk of colorectal cancer (adjusted HR: 1.597, 95% CI: 1.122-2.273) and pancreatic cancer (adjusted HR: 2.294, 95% CI: 1.267-4.151). The association was found to be more prominent in females and elderly (aged ≥ 60) individuals according to subgroup analyses.
Conclusions: pSS was associated with increased risks of colorectal and pancreatic cancers, particularly among females and older adults. Further research should explore the underlying mechanisms and the impact of pSS duration and severity on cancer risk.
{"title":"Risk of gastrointestinal cancers in patients with primary Sjögren's syndrome in Korea: a nationwide retrospective cohort study.","authors":"Soonsu Shin, Min-Ho Kim, Chang-Mo Oh, Dosang Cho, Jae-Hong Ryoo","doi":"10.1186/s13075-025-03696-4","DOIUrl":"10.1186/s13075-025-03696-4","url":null,"abstract":"<p><strong>Background: </strong>The risk of non-Hodgkin's lymphoma in patients with primary Sjögren's syndrome (pSS) is well established. However, the association between pSS and the risk of gastrointestinal cancers remains underexplored. This study aims to assess the risk of gastrointestinal cancers in pSS patients in Korea compared with the general population.</p><p><strong>Methods: </strong>We included 320,082 participants from National Health Insurance Service-National Sample Cohort (NHIS-NSC) database. Of these, there were 850 patients with pSS and 319,232 in the non-pSS group. All participants were followed-up until 2019 or the development of gastrointestinal cancers, whichever occurred first. Hazard ratio (HR) and 95% confidence intervals (95% CI) for gastrointestinal cancers were calculated by multivariable Cox proportional hazards models.</p><p><strong>Results: </strong>Compared with the non-pSS group, patients with pSS had a higher risk of developing all gastrointestinal cancers, but the association did not reach statistical significance (adjusted HR: 1.240, 95% CI: 0.990-1.543). Site-specific analyses showed that pSS patients had a higher risk of colorectal cancer (adjusted HR: 1.597, 95% CI: 1.122-2.273) and pancreatic cancer (adjusted HR: 2.294, 95% CI: 1.267-4.151). The association was found to be more prominent in females and elderly (aged ≥ 60) individuals according to subgroup analyses.</p><p><strong>Conclusions: </strong>pSS was associated with increased risks of colorectal and pancreatic cancers, particularly among females and older adults. Further research should explore the underlying mechanisms and the impact of pSS duration and severity on cancer risk.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":"12"},"PeriodicalIF":4.6,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12817787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145601746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-25DOI: 10.1186/s13075-025-03684-8
Yeo-Jin Lee, Eun-Ju Lee, Kyunggon Kim, Minji Kim, Ji Young Yu, Minjoong Kim, Soo Min Ahn, Seokchan Hong, Chang-Keun Lee, Bin Yoo, Yong-Gil Kim
{"title":"Urinary acetylated protein as a biomarker of lupus nephritis: a prospective cohort study.","authors":"Yeo-Jin Lee, Eun-Ju Lee, Kyunggon Kim, Minji Kim, Ji Young Yu, Minjoong Kim, Soo Min Ahn, Seokchan Hong, Chang-Keun Lee, Bin Yoo, Yong-Gil Kim","doi":"10.1186/s13075-025-03684-8","DOIUrl":"10.1186/s13075-025-03684-8","url":null,"abstract":"","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"27 1","pages":"220"},"PeriodicalIF":4.6,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12645779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145601731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study aimed to investigate whether discontinuation of biological or targeted synthetic antirheumatic disease-modifying drugs (bDMARDs or tsDMARDs) influences the incidence of postoperative complications in patients with rheumatoid arthritis (RA) undergoing orthopedic surgery. A retrospective multicenter cohort study including patients receiving bDMARDs or tsDMARDs who underwent orthopedic surgery was conducted. Data collected encompassed the duration of drug discontinuation and postoperative adverse events, such as delayed wound healing, surgical site infection (SSI), disease flare-ups, and mortality. The association between drug discontinuation and these outcomes was analyzed. Multivariate analyses were conducted to identify potential risk factors for these events. A total of 2,060 cases were initially enrolled. After applying inclusion and exclusion criteria, data from 1,953 patients were analyzed. No significant differences were observed between the groups regarding delayed wound healing, SSI, or mortality. However, the incidence of disease flare-ups was substantially higher in the drug discontinuation group and in the interleukin (IL)-6 inhibitor group. Multivariate analysis identified that tumor necrosis factor α and IL-6 inhibitor use was associated with a higher risk of delayed wound healing relative to T-cell function modifiers. In orthopedic surgery for patients with RA, maintaining the standard or the half of administration interval of bDMARD appears safe in the preoperative period. However, the drug discontinuation may increase the risk of postoperative flare-ups, particularly with IL-6 inhibitors. In addition, T-cell function modifiers may be associated with a lower risk of delayed wound healing, suggesting their safety profile in this context.
{"title":"Does perioperative discontinuation of anti-rheumatic drugs increase postoperative complications in orthopedic surgery for rheumatoid arthritis?","authors":"Hiromu Ito, Hajime Ishikawa, Shigeyoshi Tsuji, Masanori Nakayama, Keiichiro Nishida, Takeshi Mochizuki, Kosuke Ebina, Toshihisa Kojima, Takumi Matsumoto, Ayako Kubota, Arata Nakajima, Atsushi Kaneko, Isao Matsushita, Ryota Hara, Koji Sakuraba, Yukio Akasaki, Tsukasa Matsubara, Yuichi Mochida, Katsuaki Kanbe, Natsuko Nakagawa, Koichi Murata, Shigeki Momohara","doi":"10.1186/s13075-025-03683-9","DOIUrl":"https://doi.org/10.1186/s13075-025-03683-9","url":null,"abstract":"This study aimed to investigate whether discontinuation of biological or targeted synthetic antirheumatic disease-modifying drugs (bDMARDs or tsDMARDs) influences the incidence of postoperative complications in patients with rheumatoid arthritis (RA) undergoing orthopedic surgery. A retrospective multicenter cohort study including patients receiving bDMARDs or tsDMARDs who underwent orthopedic surgery was conducted. Data collected encompassed the duration of drug discontinuation and postoperative adverse events, such as delayed wound healing, surgical site infection (SSI), disease flare-ups, and mortality. The association between drug discontinuation and these outcomes was analyzed. Multivariate analyses were conducted to identify potential risk factors for these events. A total of 2,060 cases were initially enrolled. After applying inclusion and exclusion criteria, data from 1,953 patients were analyzed. No significant differences were observed between the groups regarding delayed wound healing, SSI, or mortality. However, the incidence of disease flare-ups was substantially higher in the drug discontinuation group and in the interleukin (IL)-6 inhibitor group. Multivariate analysis identified that tumor necrosis factor α and IL-6 inhibitor use was associated with a higher risk of delayed wound healing relative to T-cell function modifiers. In orthopedic surgery for patients with RA, maintaining the standard or the half of administration interval of bDMARD appears safe in the preoperative period. However, the drug discontinuation may increase the risk of postoperative flare-ups, particularly with IL-6 inhibitors. In addition, T-cell function modifiers may be associated with a lower risk of delayed wound healing, suggesting their safety profile in this context.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"32 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-21DOI: 10.1186/s13075-025-03677-7
Abu Moro, Hongyu Qin, ShuangShuang Yuan, Hao Li, ShiAn Liao, JinSong Yang
Studies have documented that exercise programs have symptomatic relief benefits for ankylosing spondylitis patients. It has also been reported that MGF (Mechanical/Mechano Growth Factor) and related gene expressions can be stimulated by certain exercises. In this study, we explored the possible role(s) MGF could play in controlling arthritis and ankylosing spondylitis-like symptoms in HLA-B27/Hu-β2m transgenic rats. HLA-B27/ Hu-β2m transgenic rats were inoculated with inactivated Mycobacterium tuberculosis to induce arthritis and ankylosing spondylitis, followed by MGF treatment for seven weeks. The animal models were monitored for the onset, severity, and progression of clinical symptoms. Our results indicated a dose-dependent increase in the time of onset of arthritis symptoms from 14 days in the control group to 23 days in the high-dose MGF group. Our results also indicated a dose-dependent increase in the anti-inflammatory cytokines IL-2 and IL-10 and decrease in the pro-inflammatory cytokine TNF-α in the peripheral circulation and in bony infiltrations. Likewise, there was a dose-dependent inhibition of STAT3 (signal transducer and activator of transcription 3) and RORγt (retinoic acid-related orphan receptor gamma-t) expression, which was further confirmed by the inhibition of IL-17 expression. From the results of our study, it can be concluded that MGF controlled inflammation and inhibited bone erosion and syndesmophyte formation in HLA-B27/Hu-β2m transgenic rats by stimulating IL-2 and IL10 production while downregulating TNF-α, STAT3, RORγt, and IL-17 expression in a dose-dependent manner, leading to a significant reduction in arthritis and AS-like clinical symptoms.
{"title":"Mechanical growth factor inhibited syndesmophyte formation and the progression of osteoarthritis and ankylosing spondylitis-like symptoms in HLA-B27/Hu-β2m transgenic rats","authors":"Abu Moro, Hongyu Qin, ShuangShuang Yuan, Hao Li, ShiAn Liao, JinSong Yang","doi":"10.1186/s13075-025-03677-7","DOIUrl":"https://doi.org/10.1186/s13075-025-03677-7","url":null,"abstract":"Studies have documented that exercise programs have symptomatic relief benefits for ankylosing spondylitis patients. It has also been reported that MGF (Mechanical/Mechano Growth Factor) and related gene expressions can be stimulated by certain exercises. In this study, we explored the possible role(s) MGF could play in controlling arthritis and ankylosing spondylitis-like symptoms in HLA-B27/Hu-β2m transgenic rats. HLA-B27/ Hu-β2m transgenic rats were inoculated with inactivated Mycobacterium tuberculosis to induce arthritis and ankylosing spondylitis, followed by MGF treatment for seven weeks. The animal models were monitored for the onset, severity, and progression of clinical symptoms. Our results indicated a dose-dependent increase in the time of onset of arthritis symptoms from 14 days in the control group to 23 days in the high-dose MGF group. Our results also indicated a dose-dependent increase in the anti-inflammatory cytokines IL-2 and IL-10 and decrease in the pro-inflammatory cytokine TNF-α in the peripheral circulation and in bony infiltrations. Likewise, there was a dose-dependent inhibition of STAT3 (signal transducer and activator of transcription 3) and RORγt (retinoic acid-related orphan receptor gamma-t) expression, which was further confirmed by the inhibition of IL-17 expression. From the results of our study, it can be concluded that MGF controlled inflammation and inhibited bone erosion and syndesmophyte formation in HLA-B27/Hu-β2m transgenic rats by stimulating IL-2 and IL10 production while downregulating TNF-α, STAT3, RORγt, and IL-17 expression in a dose-dependent manner, leading to a significant reduction in arthritis and AS-like clinical symptoms.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"14 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-19DOI: 10.1186/s13075-025-03689-3
Vassilis L. Souliotis, Konstantinos Vougas, Vassilis G. Gorgoulis, Petros P. Sfikakis
<p><b>Retraction Note: Arthritis Research & Therapy 18, 182 (2016) </b></p><p><b>https://doi.org/10.1186/s13075-016-1081-3</b></p><p>The Editors in Chief have retracted this article. In Fig. 2 d, the Rad51 and DAPI panels at 8 h appear to overlap with the “pATM-treated” panels in Fig. 1D in a previously-published article by some of the same authors [1]. Additionally, the HC panels at 24 h in Fig. 2 d appear to overlap with the QSLE panels at 48 h in the same figure, and lanes 5 and 6 in Fig. 4c appear to overlap adjusted for exposure, with lane 6 apparently overlapping with lane RL5 in Fig. 1k in another paper by the same corresponding author that was under submission at the same time [2]. The authors were unable to provide the original images for Fig. 4k; although they did provide images for Fig. 2 d, the editors were unable to verify that these images came from the same experiment. Vassilis L. Souliotis and Petros P. Sfikakis agree to this retraction. Konstantinos Vougas and Vassilis G. Gorgoulis have not replied to correspondence about this retraction.</p><ol data-track-component="outbound reference" data-track-context="references section"><li data-counter="1."><p>Stefanou DT, Bamias A, Episkopou H, Kyrtopoulos SA, Likka M, Kalampokas T, et al. Aberrant DNA damage response pathways may predict the outcome of platinum chemotherapy in ovarian cancer. PLoS One. 2015;10(2):e0117654. https://doi.org/10.1371/journal.pone.0117654.</p><p>Article CAS PubMed PubMed Central Google Scholar </p></li><li data-counter="2."><p>Maria Gkotzamanidou E, Terpos C, Bamia NC, Munshi, Meletios A, Dimopoulos, Vassilis L, Souliotis. DNA repair of myeloma plasma cells correlates with clinical outcome: the effect of the nonhomologous end-joining inhibitor SCR7. Blood. 2016;128(9):1214–25. https://doi.org/10.1182/blood-2016-01-691618.</p><p>Article CAS PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden="true" focusable="false" height="16" role="img" width="16"><use xlink:href="#icon-eds-i-download-medium" xmlns:xlink="http://www.w3.org/1999/xlink"></use></svg></p><h3>Authors and Affiliations</h3><ol><li><p>Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, Athens, Greece</p><p>Vassilis L. Souliotis</p></li><li><p>Joint Rheumatology Program and First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece</p><p>Vassilis L. Souliotis & Petros P. Sfikakis</p></li><li><p>Biomedical Research Foundation, Academy of Athens, Athens, Greece</p><p>Konstantinos Vougas & Vassilis G. Gorgoulis</p></li><li><p>Molecular Carcinogenesis Group, Department of Histology and Embryology, National and Kapodistrian University of Athens Medical School, Athens, Greece</p><p>Vassilis G. Gorgoulis</p></li></ol><span>Authors</span><ol><li><span>Vassilis L. Souliotis</span>View author publications<p><span>Search author on:</span><span>P
撤稿说明:Arthritis Research & Therapy 18, 182 (2016) https://doi.org/10.1186/s13075-016-1081-3The主编已撤回本文。在图2 d中,8 h时的Rad51和DAPI面板似乎与图1 d中“经patm处理”的面板重叠,这是一些作者之前发表的文章。此外,图2d中24 h的HC面板似乎与同图中48 h的QSLE面板重叠,图4c中的5道和6道似乎因曝光调整而重叠,其中6道明显与同一通讯作者在[2]同时提交的另一篇论文中的RL5道重叠。作者无法提供图4k的原始图像;尽管他们确实为图2提供了图像,但编辑无法验证这些图像是否来自同一实验。Vassilis L. Souliotis和Petros P. Sfikakis同意撤稿。康斯坦丁诺斯·沃加斯和瓦西里斯·g·戈尔古利斯没有回复有关撤回声明的信件。Stefanou DT, Bamias A, Episkopou H, Kyrtopoulos SA, Likka M, Kalampokas T等。异常DNA损伤反应途径可能预测卵巢癌铂化疗的结果。科学通报,2015;10(2):e0117654。https://doi.org/10.1371/journal.pone.0117654.Article CAS PubMed PubMed Central谷歌学者Maria Gkotzamanidou E, Terpos C, Bamia NC, Munshi, Meletios A, Dimopoulos, Vassilis L, Souliotis。骨髓瘤浆细胞DNA修复与临床预后的关系:非同源末端连接抑制剂SCR7的作用血。2016;128(9):1214 - 25所示。https://doi.org/10.1182/blood-2016-01-691618.Article CAS PubMed PubMed Central b谷歌学者下载参考文献作者和联系希腊雅典国家希腊研究基金会生物、药物化学和生物技术研究所雅典国立和卡波迪兰雅典大学医学院风湿病联合项目和儿科内科第一系希腊雅典科学院生物医学研究基金会,雅典,雅典;康斯坦丁诺斯·沃加斯;Vassilis G. gorgoulis分子癌变小组,雅典国立和卡波迪特里亚大学医学院组织学和胚胎学系,雅典;GreeceVassilis G. gorgoulisauthorsassilis L. souliotis查看作者出版物搜索作者on:PubMed谷歌ScholarKonstantinos VougasView作者出版物搜索作者on:PubMed谷歌ScholarVassilis G. GorgoulisView作者出版物搜索作者on:PubMed谷歌ScholarPetros P. SfikakisView作者出版物搜索作者on:PubMed谷歌scholar通讯作者Vassilis L. Souliotis通讯作者。开放获取本文遵循知识共享署名-非商业-非衍生品4.0国际许可协议,该协议允许以任何媒介或格式进行非商业用途、共享、分发和复制,只要您适当注明原作者和来源,提供知识共享许可协议的链接,并注明您是否修改了许可材料。根据本许可协议,您无权分享源自本文或其部分内容的改编材料。本文中的图像或其他第三方材料包含在文章的知识共享许可协议中,除非在材料的署名中另有说明。如果材料未包含在文章的知识共享许可中,并且您的预期用途不被法律法规允许或超过允许的用途,您将需要直接获得版权所有者的许可。要查看本许可证的副本,请访问http://creativecommons.org/licenses/by-nc-nd/4.0/.Cite这篇文章:ouloulis, V., Vougas, K., Gorgoulis, V.G.等。注:静止系统性红斑狼疮患者的DNA修复和染色质组织缺陷。中国生物医学工程学报,2016,33(2):444 - 444。https://doi.org/10.1186/s13075-025-03689-3Download citation发布日期:2025年11月19日记录版本:2025年11月19日doi: https://doi.org/10.1186/s13075-025-03689-3Share这篇文章任何你分享以下链接的人都可以阅读到这篇文章:获取可共享链接对不起,这篇文章目前没有可共享的链接。复制可共享的链接到剪贴板提供的施普林格自然共享内容的倡议
{"title":"Retraction Note: Defective DNA repair and chromatin organization in patients with quiescent systemic lupus erythematosus","authors":"Vassilis L. Souliotis, Konstantinos Vougas, Vassilis G. Gorgoulis, Petros P. Sfikakis","doi":"10.1186/s13075-025-03689-3","DOIUrl":"https://doi.org/10.1186/s13075-025-03689-3","url":null,"abstract":"<p><b>Retraction Note: Arthritis Research & Therapy 18, 182 (2016) </b></p><p><b>https://doi.org/10.1186/s13075-016-1081-3</b></p><p>The Editors in Chief have retracted this article. In Fig. 2 d, the Rad51 and DAPI panels at 8 h appear to overlap with the “pATM-treated” panels in Fig. 1D in a previously-published article by some of the same authors [1]. Additionally, the HC panels at 24 h in Fig. 2 d appear to overlap with the QSLE panels at 48 h in the same figure, and lanes 5 and 6 in Fig. 4c appear to overlap adjusted for exposure, with lane 6 apparently overlapping with lane RL5 in Fig. 1k in another paper by the same corresponding author that was under submission at the same time [2]. The authors were unable to provide the original images for Fig. 4k; although they did provide images for Fig. 2 d, the editors were unable to verify that these images came from the same experiment. Vassilis L. Souliotis and Petros P. Sfikakis agree to this retraction. Konstantinos Vougas and Vassilis G. Gorgoulis have not replied to correspondence about this retraction.</p><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Stefanou DT, Bamias A, Episkopou H, Kyrtopoulos SA, Likka M, Kalampokas T, et al. Aberrant DNA damage response pathways may predict the outcome of platinum chemotherapy in ovarian cancer. PLoS One. 2015;10(2):e0117654. https://doi.org/10.1371/journal.pone.0117654.</p><p>Article CAS PubMed PubMed Central Google Scholar </p></li><li data-counter=\"2.\"><p>Maria Gkotzamanidou E, Terpos C, Bamia NC, Munshi, Meletios A, Dimopoulos, Vassilis L, Souliotis. DNA repair of myeloma plasma cells correlates with clinical outcome: the effect of the nonhomologous end-joining inhibitor SCR7. Blood. 2016;128(9):1214–25. https://doi.org/10.1182/blood-2016-01-691618.</p><p>Article CAS PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><h3>Authors and Affiliations</h3><ol><li><p>Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, Athens, Greece</p><p>Vassilis L. Souliotis</p></li><li><p>Joint Rheumatology Program and First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece</p><p>Vassilis L. Souliotis & Petros P. Sfikakis</p></li><li><p>Biomedical Research Foundation, Academy of Athens, Athens, Greece</p><p>Konstantinos Vougas & Vassilis G. Gorgoulis</p></li><li><p>Molecular Carcinogenesis Group, Department of Histology and Embryology, National and Kapodistrian University of Athens Medical School, Athens, Greece</p><p>Vassilis G. Gorgoulis</p></li></ol><span>Authors</span><ol><li><span>Vassilis L. Souliotis</span>View author publications<p><span>Search author on:</span><span>P","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"220 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145545722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-18DOI: 10.1186/s13075-025-03680-y
Hao Wu, Weixue Sun, Qian Zhang, Gong Cheng, Zhilin Cao
This study aimed to evaluate the therapeutic effects of Omentin-1 on osteoarthritis and explore its protective mechanisms. Two osteoarthritis mouse models were created: wild-type and SIRT6−/−. After five weeks of Omentin-1 injection, we evaluated M1 and M2 macrophage distribution in the mouse synovium and measured inflammatory factor levels. Matrix proteins related to cartilage repair were detected, and safranin O-green and toluidine blue staining were used to evaluate the repair. Furthermore, we evaluated how Omentin-1 regulated macrophage polarization and explored potential mechanisms. Omentin-1 was low in osteoarthritis mice and linked to M1 macrophage polarization. It protected these mice by reducing synovial inflammation, decreasing M1 macrophages, increasing M2 macrophages, and lowering pro-inflammatory factors while raising anti-inflammatory factors and minimizing inflammatory cell infiltration in the synovium. Omentin-1 enhanced Collagen II and α-SMA expression in cartilage, aiding repair. Further mechanistic studies indicated that Omentin-1 can enhance the expression of SIRT6 in the joint tissues of mice with osteoarthritis. Omentin-1’s inhibition of inflammation in osteoarthritis mice was linked to SIRT6. Elevated Omentin-1 levels can mitigate the inflammatory response in osteoarthritis by enhancing SIRT6 expression, inhibiting inflammatory factors, suppressing M1 macrophages, and increasing M2 macrophages.
{"title":"Omentin-1 reduced synovial M1 macrophages through SIRT6 signaling pathway and alleviated knee osteoarthritis response in mice","authors":"Hao Wu, Weixue Sun, Qian Zhang, Gong Cheng, Zhilin Cao","doi":"10.1186/s13075-025-03680-y","DOIUrl":"https://doi.org/10.1186/s13075-025-03680-y","url":null,"abstract":"This study aimed to evaluate the therapeutic effects of Omentin-1 on osteoarthritis and explore its protective mechanisms. Two osteoarthritis mouse models were created: wild-type and SIRT6−/−. After five weeks of Omentin-1 injection, we evaluated M1 and M2 macrophage distribution in the mouse synovium and measured inflammatory factor levels. Matrix proteins related to cartilage repair were detected, and safranin O-green and toluidine blue staining were used to evaluate the repair. Furthermore, we evaluated how Omentin-1 regulated macrophage polarization and explored potential mechanisms. Omentin-1 was low in osteoarthritis mice and linked to M1 macrophage polarization. It protected these mice by reducing synovial inflammation, decreasing M1 macrophages, increasing M2 macrophages, and lowering pro-inflammatory factors while raising anti-inflammatory factors and minimizing inflammatory cell infiltration in the synovium. Omentin-1 enhanced Collagen II and α-SMA expression in cartilage, aiding repair. Further mechanistic studies indicated that Omentin-1 can enhance the expression of SIRT6 in the joint tissues of mice with osteoarthritis. Omentin-1’s inhibition of inflammation in osteoarthritis mice was linked to SIRT6. Elevated Omentin-1 levels can mitigate the inflammatory response in osteoarthritis by enhancing SIRT6 expression, inhibiting inflammatory factors, suppressing M1 macrophages, and increasing M2 macrophages.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145535327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anti-melanoma differentiation-associated gene 5-positive dermatomyositis (anti-MDA5 + DM) is a unique subtype of idiopathic inflammatory myopathy (IIM) with a poorer prognosis. The immune-metabolic landscape underlying anti-MDA5 + DM pathogenesis remains poorly defined. In our study, we integrated metabolomic profiling of plasma and peripheral blood mononuclear cells (PBMCs) in anti-MDA5 + DM. This study enrolled 183 patients with IIM and 104 healthy controls (HCs), comprising a discovery cohort of 150 patients (67 anti-MDA5 + DM patients and 83 anti-MDA5- IIM patients serving as disease controls) and 71 HCs, as well as a validation cohort of 33 patients and 33 HCs. To establish a robust diagnostic model, we implemented a dual analytical approach: seven machine learning algorithms were initially employed to identify key differentially expressed metabolites (DEMs), followed by LASSO regression analysis for optimal feature selection and model construction. Decision curve analysis (DCA) was subsequently conducted to assess their clinical applicability in decision-making scenarios. DHEAS and citrate in plasma were validated using enzyme-linked immunosorbent assay (ELISA) and biochemical assay, respectively. Non-targeted metabolomic profiling of plasma identified 90DEMs distinguishing anti-MDA5 + DM patients from HCs, including 65 upregulated and 25 downregulated metabolites. Pathway enrichment analysis revealed the predominant involvement of these plasma DEMs in beta-alanine metabolism. PBMC-derived targeted metabolomics identified 41 DEMs in anti-MDA5 + DM compared with HCs, comprising 21 upregulated and 20 downregulated metabolites. The DEMs in PBMCs also mainly participated in the beta-alanine metabolism pathway. From these DEMs, DHEAS, citrate, dimethylglycine, histidine, PAGN and Melilotate were identified as candidate biomarkers in anti-MDA5 + DM. Clinically, DHEAS levels showed a negative correlation with the prevalence of rapidly progressive interstitial lung disease (RP-ILD), citrate exhibited a negative association with rash, while dimethylglycine displayed a positive association with mortality and RP-ILD. Further combined analysis showed that the expression of plasma and PBMC dehydroepiandrosterone sulfate (DHEAS) and citrate may serve as reliable diagnostic biomarkers. Finally, DHEAS and citrate exhibited concordant variation patterns in the validation cohort. Our study underscores the pivotal role of DHEAS and citrate as promising diagnostic biomarkers of IIM and anti-MDA5 + DM, respectively, providing novel insights into the pathogenic mechanism and potential therapeutic targets.
{"title":"Integrated metabolomic profiling identifies citrate as novel diagnostic biomarker for Anti-MDA5-Positive dermatomyositis","authors":"Tianqi Li, Jinlei Sun, Ting Li, Junyao Liu, Yi Cao, Peiling Liu, Cong Wang, Fang Dong, Liangzhi Liu, Wenhui Lou, Shengyun Liu, Yusheng Zhang, Panpan Zhang","doi":"10.1186/s13075-025-03676-8","DOIUrl":"https://doi.org/10.1186/s13075-025-03676-8","url":null,"abstract":"Anti-melanoma differentiation-associated gene 5-positive dermatomyositis (anti-MDA5 + DM) is a unique subtype of idiopathic inflammatory myopathy (IIM) with a poorer prognosis. The immune-metabolic landscape underlying anti-MDA5 + DM pathogenesis remains poorly defined. In our study, we integrated metabolomic profiling of plasma and peripheral blood mononuclear cells (PBMCs) in anti-MDA5 + DM. This study enrolled 183 patients with IIM and 104 healthy controls (HCs), comprising a discovery cohort of 150 patients (67 anti-MDA5 + DM patients and 83 anti-MDA5- IIM patients serving as disease controls) and 71 HCs, as well as a validation cohort of 33 patients and 33 HCs. To establish a robust diagnostic model, we implemented a dual analytical approach: seven machine learning algorithms were initially employed to identify key differentially expressed metabolites (DEMs), followed by LASSO regression analysis for optimal feature selection and model construction. Decision curve analysis (DCA) was subsequently conducted to assess their clinical applicability in decision-making scenarios. DHEAS and citrate in plasma were validated using enzyme-linked immunosorbent assay (ELISA) and biochemical assay, respectively. Non-targeted metabolomic profiling of plasma identified 90DEMs distinguishing anti-MDA5 + DM patients from HCs, including 65 upregulated and 25 downregulated metabolites. Pathway enrichment analysis revealed the predominant involvement of these plasma DEMs in beta-alanine metabolism. PBMC-derived targeted metabolomics identified 41 DEMs in anti-MDA5 + DM compared with HCs, comprising 21 upregulated and 20 downregulated metabolites. The DEMs in PBMCs also mainly participated in the beta-alanine metabolism pathway. From these DEMs, DHEAS, citrate, dimethylglycine, histidine, PAGN and Melilotate were identified as candidate biomarkers in anti-MDA5 + DM. Clinically, DHEAS levels showed a negative correlation with the prevalence of rapidly progressive interstitial lung disease (RP-ILD), citrate exhibited a negative association with rash, while dimethylglycine displayed a positive association with mortality and RP-ILD. Further combined analysis showed that the expression of plasma and PBMC dehydroepiandrosterone sulfate (DHEAS) and citrate may serve as reliable diagnostic biomarkers. Finally, DHEAS and citrate exhibited concordant variation patterns in the validation cohort. Our study underscores the pivotal role of DHEAS and citrate as promising diagnostic biomarkers of IIM and anti-MDA5 + DM, respectively, providing novel insights into the pathogenic mechanism and potential therapeutic targets.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"29 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145535330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-14DOI: 10.1186/s13075-025-03675-9
Shuai Zhu, Shanshan Li, Lipu Shi, Tianshu Chu, Zhenguo Huang, Xin Lu, Guochun Wang, Yongpeng Ge
Currently, there are only a few effective treatments for anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5) positive dermatomyositis (DM)-associated interstitial lung disease (ILD). The aim of this study was to evaluate the efficacy and safety of baricitinib in patients with MDA5 + DM-ILD. The study was a retrospective cohort design that evaluated patients with MDA5 + DM-ILD who had received or not received baricitinib. Clinical symptoms, laboratory data, and survival were compared in the two groups. Thirty-nine patients with MDA5 + DM-ILD who received baricitinib were included in the study. After baricitinib therapy, 31 patients (79.5%) had a clinical improvement that included Gottron’s sign (p < 0.001), heliotrope rash (p < 0.001), and dyspnea (p = 0.003). The median HRCT score decreased from 115 to 97.5 (p < 0.001), while the FVC improved significantly (76.44% vs. 90.73%, p < 0.001). In addition, serum ferritin levels (739.9 ng/ml vs. 56.3 ng/ml, p < 0.001) and lactate dehydrogenase (LDH) levels (313 U/L vs. 233 U/L, p = 0.003) decreased significantly. Notably, lymphocyte counts increased significantly, CD4 + T cells (354 cells/µl vs. 663 cells/µl, p < 0.001), and CD8 + T cells (180 cells/µl vs. 449 cells/µl, p < 0.001). Furthermore, the glucocorticoid dose reduced significantly from 40 mg daily to 10 mg daily (p < 0.001). Compared with the control group, the baricitinib group had a greater six-month survival (87.2% vs. 70%, p = 0.047). While first-line baricitinib showed a superior survival rate compared to conventional therapy (84.6% vs. 52.9%, p = 0.046). This study indicates that Baricitinib is a potential therapeutic for MDA5 + DM-ILD, reducing LDH and ferritin, ameliorating ILD progression, and improving survival, with first-line use may provide a significant survival advantage. However, larger prospective controlled studies are required to evaluate its efficacy. 1. This is the retrospective cohort study of baricitinib in the treatment of MDA5 + DM-ILD. 2. Baricitinib improve clinical symptoms, reduce LDH and serum ferritin levels, and reduce ILD progression in MDA5 + DM. 3. Baricitinib could improve MDA5 + DM patients’ survival, with first-line use may provide a significant survival advantage.
目前,对于抗黑色素瘤分化相关基因5抗体(anti-MDA5)阳性的皮肌炎(DM)相关间质性肺疾病(ILD),仅有少数有效的治疗方法。本研究的目的是评估巴西替尼对MDA5 + DM-ILD患者的疗效和安全性。该研究采用回顾性队列设计,评估了接受或未接受巴西替尼治疗的MDA5 + DM-ILD患者。比较两组患者的临床症状、实验室数据和生存率。39例接受巴西替尼治疗的MDA5 + DM-ILD患者纳入研究。baricitinib治疗后,31例(79.5%)患者的临床改善包括Gottron体征(p < 0.001)、heliotrope皮疹(p < 0.001)和呼吸困难(p = 0.003)。HRCT中位评分从115降至97.5 (p < 0.001), FVC显著改善(76.44% vs. 90.73%, p < 0.001)。血清铁蛋白水平(739.9 ng/ml vs. 56.3 ng/ml, p < 0.001)和乳酸脱氢酶(LDH)水平(313 U/L vs. 233 U/L, p = 0.003)显著降低。值得注意的是,淋巴细胞计数明显增加,CD4 + T细胞(354个细胞/µl比663个细胞/µl, p < 0.001)和CD8 + T细胞(180个细胞/µl比449个细胞/µl, p < 0.001)。此外,糖皮质激素剂量从每天40毫克显著减少到每天10毫克(p < 0.001)。与对照组相比,baricitinib组6个月生存率更高(87.2% vs 70%, p = 0.047)。与常规治疗相比,一线巴西替尼的生存率更高(84.6% vs. 52.9%, p = 0.046)。该研究表明Baricitinib是MDA5 + DM-ILD的潜在治疗药物,降低LDH和铁蛋白,改善ILD进展,提高生存率,一线使用可能提供显着的生存优势。然而,需要更大规模的前瞻性对照研究来评估其疗效。1. 这是baricitinib治疗MDA5 + DM-ILD的回顾性队列研究。2. Baricitinib改善临床症状,降低LDH和血清铁蛋白水平,并减少MDA5 + DM的ILD进展。3. Baricitinib可以改善MDA5 + DM患者的生存,一线使用可能提供显著的生存优势。
{"title":"Baricitinib could improve the prognosis of anti-MDA5 antibody positive dermatomyositis associated interstitial lung disease","authors":"Shuai Zhu, Shanshan Li, Lipu Shi, Tianshu Chu, Zhenguo Huang, Xin Lu, Guochun Wang, Yongpeng Ge","doi":"10.1186/s13075-025-03675-9","DOIUrl":"https://doi.org/10.1186/s13075-025-03675-9","url":null,"abstract":"Currently, there are only a few effective treatments for anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5) positive dermatomyositis (DM)-associated interstitial lung disease (ILD). The aim of this study was to evaluate the efficacy and safety of baricitinib in patients with MDA5 + DM-ILD. The study was a retrospective cohort design that evaluated patients with MDA5 + DM-ILD who had received or not received baricitinib. Clinical symptoms, laboratory data, and survival were compared in the two groups. Thirty-nine patients with MDA5 + DM-ILD who received baricitinib were included in the study. After baricitinib therapy, 31 patients (79.5%) had a clinical improvement that included Gottron’s sign (p < 0.001), heliotrope rash (p < 0.001), and dyspnea (p = 0.003). The median HRCT score decreased from 115 to 97.5 (p < 0.001), while the FVC improved significantly (76.44% vs. 90.73%, p < 0.001). In addition, serum ferritin levels (739.9 ng/ml vs. 56.3 ng/ml, p < 0.001) and lactate dehydrogenase (LDH) levels (313 U/L vs. 233 U/L, p = 0.003) decreased significantly. Notably, lymphocyte counts increased significantly, CD4 + T cells (354 cells/µl vs. 663 cells/µl, p < 0.001), and CD8 + T cells (180 cells/µl vs. 449 cells/µl, p < 0.001). Furthermore, the glucocorticoid dose reduced significantly from 40 mg daily to 10 mg daily (p < 0.001). Compared with the control group, the baricitinib group had a greater six-month survival (87.2% vs. 70%, p = 0.047). While first-line baricitinib showed a superior survival rate compared to conventional therapy (84.6% vs. 52.9%, p = 0.046). This study indicates that Baricitinib is a potential therapeutic for MDA5 + DM-ILD, reducing LDH and ferritin, ameliorating ILD progression, and improving survival, with first-line use may provide a significant survival advantage. However, larger prospective controlled studies are required to evaluate its efficacy. 1. This is the retrospective cohort study of baricitinib in the treatment of MDA5 + DM-ILD. 2. Baricitinib improve clinical symptoms, reduce LDH and serum ferritin levels, and reduce ILD progression in MDA5 + DM. 3. Baricitinib could improve MDA5 + DM patients’ survival, with first-line use may provide a significant survival advantage.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"92 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145515645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}