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Performance of standardized patient reported outcomes developed for spondyloarthritis in primary and concomitant forms of fibromyalgia. 针对原发性脊柱关节炎和纤维肌痛并发症制定的标准化患者报告结果的性能。
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2024-07-26 DOI: 10.1186/s13075-024-03365-y
Styliani Tsiami, Piet Dukatz, Maria Gkelaki, Philipp Sewerin, Uta Kiltz, Xenofon Baraliakos

Background: In spondyloarthritides (SpA) and fibromyalgia (FM), patients suffer from generalized pain. The impact of FM on PRO validated in SpA has not been systematically studied.

Objective: Study the performance of PROs developed for SpA in patients with primary (p) FM without chronic inflammatory-rheumatic disease vs. SpA without and with concomitant (c) FM.

Methods: Patients with pFM, axSpA or PsA and indication for treatment adaptation were prospectively included. Standardized PROs were assessed: BASDAI, ASDAS-CRP, DAPSA, patient´s global assessment, BASFI, LEI, MASES, SPARCC Enthesitis Score and FIQ.

Results: 300 patients were included (100/diagnosis). More males were found in axSpA vs. PsA and pFM group (67, 33 and 2/100, respectively), while 12 axSpA (axSpA+) and 16 PsA (PsA+) patients had cFM. pFM patients showed significantly higher scores in all assessments vs. axSpA or PsA, with exception of ASDAS-CRP (3.3 ± 0.6 in FM vs. 3.1 ± 1.0 in axSpA) and duration of low lumbar morning stiffness. Similar results were also found in the subanalysis of female patients only. In addition, patients with axSpA + or PsA + showed no differences to patients with pFM, while significantly higher scores were found for FM, axSpA + and PsA + for almost all FIQ items compared to axSpA- or PsA-.

Conclusions: PROs originally developed for axSpA or PsA need to be interpreted differently in the presence or absence of cFM. ASDAS-CRP and duration of lumbar morning stiffness were not affected by cFM. FM-specific questionnaires also showed high scores in patients with SpA with cFM but not in those without.

背景:脊柱关节炎(SpA)和纤维肌痛(FM)患者会出现全身疼痛。目前尚未系统研究纤维肌痛对 SpA PRO 验证的影响:研究针对无慢性炎症性风湿病的原发性(p)纤维肌痛患者与无和伴有(c)纤维肌痛的 SpA 患者的 PROs 表现:方法:前瞻性地纳入患有原发性 FM、axSpA 或 PsA 且有适应治疗指征的患者。对标准化的PROs进行了评估:BASDAI、ASDAS-CRP、DAPSA、患者总体评估、BASFI、LEI、MASES、SPARCC 肌腱炎评分和 FIQ:共纳入 300 名患者(100/诊断)。除 ASDAS-CRP(FM 为 3.3 ± 0.6,axSpA 为 3.1 ± 1.0)和低腰椎晨僵持续时间外,pFM 患者在所有评估中的得分均明显高于 axSpA 或 PsA 患者。仅对女性患者进行的子分析也发现了类似的结果。此外,axSpA + 或 PsA + 患者与 pFM 患者没有差异,而 FM、axSpA + 和 PsA + 患者几乎所有 FIQ 项目的得分都明显高于 axSpA- 或 PsA- 患者:结论:最初为 axSpA 或 PsA 制定的 PROs 需要在有无 cFM 的情况下进行不同的解释。ASDAS-CRP和腰椎晨僵持续时间不受cFM的影响。FM特异性问卷也显示,有cFM的SpA患者得分较高,而没有cFM的患者得分则不高。
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引用次数: 0
Prevalence and location of inflammatory and structural lesions in patients with rheumatoid arthritis and radiographic axial spondyloarthritis with chronic neck pain evaluated by magnetic resonance imaging 通过磁共振成像评估类风湿关节炎和放射性轴性脊柱关节炎伴慢性颈部疼痛患者的炎症和结构性病变的发生率和位置
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2024-07-25 DOI: 10.1186/s13075-024-03377-8
David Kiefer, Mina Soltani, Parham Damirchi, Uta Kiltz, Bjoern Buehring, Ioana Andreica, Philipp Sewerin, Xenofon Baraliakos
Define the prevalence and location of inflammatory and structural lesions on magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA) and radiographic axial spondyloarthritis (r-axSpA) with neck pain as leading clinical symptom. Patients with diagnosis of RA and r-axSpA were consecutively included if they had chronic (> 3 months) neck pain. Clinical assessment, neck pain questionnaires and MRIs of the cervical spine (CS) were performed. 107 patients (59 RA and 48 r-axSpA) were included. While there was no difference in the Northwick-Park-Neck-Pain-questionnaire, patients with RA reported higher neck pain compared to r-axSpA on a numeric rating scale (5.0 ± 3.6 vs. 3.0 ± 3.1; p = 0.003). Inflammatory lesions occurred predominantly in the craniocervical area in RA and in the lower CS segments in r-axSpA. Bone marrow edema (BME) was more frequent in axSpA (BME-score axSpA/RA: 0.35vs0.17; p < 0.001) while synovitis was visible in both but was more prevalent in RA (synovitis-score axSpA/RA: 0.02vs0.1; p < 0.001). BME was found in 8 (13.6%) vertebral corner vs. 9 (18.8%), in 2 (3.4%) facet joints vs. 7 (14.6%) and in 1 (1.7%) spinous processes vs. 9 (18.8%) in patients with RA/r-axSpA. In contrast, more patients with RA (30.5% vs6.3%) showed erosive osteochondrosis with endplate BME (p = 0.002). While involvement of upper cervical inflammation was typically present in RA, r-axSpA patients showed more BME in lower CS segments, vertebral corners, facet joints and spinous processes. Neck pain is linked to upper and lower inflammatory and structural lesions of the CS in both diseases.
确定以颈部疼痛为主要临床症状的类风湿性关节炎(RA)和放射性轴性脊柱关节炎(r-axSpA)患者的磁共振成像(MRI)中炎性和结构性病变的发生率和位置。被诊断出患有类风湿性关节炎(RA)和放射性轴状脊椎关节炎(r-axSpA)的患者,如果有慢性颈部疼痛(超过 3 个月),则被连续纳入研究。对患者进行临床评估、颈部疼痛问卷调查和颈椎(CS)核磁共振成像检查。共纳入 107 名患者(59 名 RA 和 48 名 r-axSpA)。虽然诺斯维克-帕克颈部疼痛问卷调查结果没有差异,但在数字评分量表上,RA 患者的颈部疼痛程度高于 r-axSpA 患者(5.0 ± 3.6 vs. 3.0 ± 3.1;p = 0.003)。RA患者的炎性病变主要发生在颅颈部,而r-axSpA患者的炎性病变主要发生在CS下段。骨髓水肿(BME)在axSpA中更为常见(BME-score axSpA/RA:0.35vs0.17;p < 0.001),而滑膜炎在两者中均可见,但在RA中更为普遍(滑膜炎-score axSpA/RA:0.02vs0.1;p < 0.001)。在RA/r-axSpA患者中,8个(13.6%)椎角(9个(18.8%))、2个(3.4%)面关节(7个(14.6%))和1个(1.7%)棘突(9个(18.8%))发现了BME。相比之下,更多的 RA 患者(30.5% 对 6.3%)出现了侵蚀性骨软骨病和终板 BME(p = 0.002)。RA患者的上颈部炎症通常会受累,而r-axSpA患者的下CS节段、椎角、面关节和棘突则显示出更多的BME。在这两种疾病中,颈痛都与CS的上下炎症和结构性病变有关。
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引用次数: 0
Elevated neutrophil extracellular traps in systemic sclerosis-associated vasculopathy and suppression by a synthetic prostacyclin analog 系统性硬化症相关血管病变中中性粒细胞胞外捕获物的升高以及合成前列环素类似物的抑制作用
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2024-07-25 DOI: 10.1186/s13075-024-03379-6
Neda Kortam, Wenying Liang, Claire Shiple, Suiyuan Huang, Rosemary Gedert, James St. Clair, Cyrus Sarosh, Caroline Foster, Pei-Suen Tsou, John Varga, Jason S. Knight, Dinesh Khanna, Ramadan A. Ali
Neutrophils and neutrophil extracellular traps (NETs) contribute to the vascular complications of multiple diseases, but their role in systemic sclerosis (SSc) is understudied. We sought to test the hypothesis that NETs are implicated in SSc vasculopathy and that treatment with prostacyclin analogs may ameliorate SSc vasculopathy not only through vasodilation but also by inhibiting NET release. Blood from 125 patients with SSc (87 diffuse cutaneous SSc and 38 limited cutaneous SSc) was collected at a single academic medical center. Vascular complications such as digital ulcers, pulmonary artery hypertension, and scleroderma renal crisis were recorded. The association between circulating NETs and vascular complications was determined using in vitro and ex vivo assays. The impact of the synthetic prostacyclin analog epoprostenol on NET release was determined. Neutrophil activation and NET release were elevated in patients with SSc-associated vascular complications compared to matched patients without vascular complications. Neutrophil activation and NETs positively correlated with soluble E-selectin and VCAM-1, circulating markers of vascular injury. Treatment of patients with digital ischemia with a synthetic prostacyclin analog boosted neutrophil cyclic AMP, which was associated with the blunting of NET release and reduced NETs in circulation. Our study demonstrates an association between NETs and vascular complications in SSc. We also identified the potential for an additional therapeutic benefit of synthetic prostacyclin analogs, namely to reduce neutrophil hyperactivity and NET release in SSc patients.
中性粒细胞和中性粒细胞胞外捕获物(NETs)会导致多种疾病的血管并发症,但它们在系统性硬化症(SSc)中的作用却未得到充分研究。我们试图验证这样一个假设:NET 与 SSc 血管病变有关,使用前列环素类似物治疗不仅可以通过扩张血管,还可以通过抑制 NET 释放来改善 SSc 血管病变。研究人员在一家学术医疗中心采集了 125 名 SSc 患者(87 名弥漫性皮肤 SSc 患者和 38 名局限性皮肤 SSc 患者)的血液。记录了血管并发症,如数字溃疡、肺动脉高压和硬皮病肾危象。通过体外和体内试验确定了循环NET与血管并发症之间的关系。研究还确定了合成前列环素类似物表前列醇对 NET 释放的影响。与无血管并发症的匹配患者相比,SSc相关血管并发症患者的中性粒细胞活化和NET释放均升高。中性粒细胞活化和NET与血管损伤的循环标志物可溶性E-选择素和VCAM-1呈正相关。用合成前列环素类似物治疗数字缺血患者可提高中性粒细胞环磷酸腺苷的活性,这与抑制NET释放和减少循环中的NET有关。我们的研究表明,NET 与 SSc 的血管并发症之间存在关联。我们还发现了合成前列环素类似物的另一种潜在治疗功效,即减少 SSc 患者中性粒细胞的过度活跃和 NET 的释放。
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引用次数: 0
Risk factors of mortality in patients with rheumatoid arthritis-associated interstitial lung disease: a single-centre prospective cohort study 类风湿性关节炎相关间质性肺病患者的死亡风险因素:一项单中心前瞻性队列研究
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2024-07-19 DOI: 10.1186/s13075-024-03362-1
Yeo-Jin Song, Hyoungyoung Kim, Soo-Kyung Cho, Hye Won Kim, Chaewhi Lim, Eunwoo Nam, Chan-Bum Choi, Tae-Hwan Kim, Jae-Bum Jun, Sang-Cheol Bae, Dae Hyun Yoo, Su Jin Hong, Seung-Jin Yoo, Youkyung Lee, Yoon-Kyoung Sung
To determine the risk factors for mortality in Korean patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) in comparison to patients with RA but without ILD (RA-nonILD). Data were extracted from a single-centre prospective cohort of RA patients with a chest computed tomography scan at an academic referral hospital in Korea. Patients with RA-ILD enroled between May 2017 and August 2022 were selected, and those without ILD were selected as comparators. The mortality rate was calculated, and the causes of each death were investigated. We used Cox proportional hazard regression with Firth’s penalised likelihood method to identify the risk factors for mortality in patients with RA-ILD. A total of 615 RA patients were included: 200 with ILD and 415 without ILD. In the RA-ILD group, there were 15 deaths over 540.1 person-years (PYs), resulting in mortality rate of 2.78/100 PYs. No deaths were reported in the RA-nonILD group during the 1669.9 PYs. The primary causes of death were infection (nine cases) and lung cancer (five cases), with only one death attributed to ILD aggravation. High RA activity (adjusted HR 1.87, CI 1.16–3.10), baseline diffusing capacity for carbon monoxide (DLCO) < 60% (adjusted HR 4.88, 95% CI 1.11–45.94), and usual interstitial pneumonia (UIP) pattern (adjusted HR 5.13, 95% CI 1.00–57.36) were identified as risk factors for mortality in RA-ILD patients. Patients with RA-ILD have an elevated risk of mortality compared with those without ILD. Infection-related deaths are the main causes of mortality in this population. High RA activity, low DLCO, and the UIP pattern are significantly associated with the mortality in patients with RA-ILD.
目的:与患有类风湿性关节炎(RA)但无间质性肺病(RA-nonILD)的患者相比,确定韩国类风湿性关节炎(RA)相关间质性肺病(ILD)患者的死亡风险因素。数据摘自韩国一家学术转诊医院对接受过胸部计算机断层扫描的 RA 患者进行的单中心前瞻性队列研究。研究选取了2017年5月至2022年8月期间登记的RA-ILD患者,并选取了无ILD的患者作为比较对象。我们计算了死亡率,并调查了每例死亡的原因。我们使用Cox比例危险回归法和Firth惩罚似然法确定RA-ILD患者的死亡风险因素。共纳入了 615 名 RA 患者:其中200例患有ILD,415例未患有ILD。在RA-ILD组中,540.1人年中有15人死亡,死亡率为2.78/100人年。RA-非ILD组在1669.9人年中没有死亡报告。死亡的主要原因是感染(9 例)和肺癌(5 例),只有 1 例死亡归因于 ILD 恶化。高RA活性(调整后HR为1.87,CI为1.16-3.10)、基线一氧化碳弥散能力(DLCO)<60%(调整后HR为4.88,95% CI为1.11-45.94)和常见间质性肺炎(UIP)模式(调整后HR为5.13,95% CI为1.00-57.36)被认为是RA-ILD患者死亡的风险因素。与无 ILD 的患者相比,RA-ILD 患者的死亡风险较高。与感染相关的死亡是该人群死亡的主要原因。高RA活性、低DLCO和UIP模式与RA-ILD患者的死亡率显著相关。
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引用次数: 0
Stabilizing the integrity of intestinal barrier to control arthritis. 稳定肠道屏障的完整性,控制关节炎。
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2024-07-18 DOI: 10.1186/s13075-024-03378-7
George D Kalliolias, Athanasios G Papavassiliou

With great interest, we have read the recent article "Expression of HIF1α in intestinal epithelium restricts arthritis inflammation by inhibiting RIPK3-induced cell death machinery" published by Lyu et al. in Annals of the Rheumatic Diseases. The authors pose that the expression of hypoxia-inducible factor 1 alpha in intestinal epithelial cells represents a crucial check point for the development of arthritis by impeding necroptosis of intestinal epithelial cells and safeguarding the intestinal barrier integrity. Previous studies suggest a potential mechanistic link between faulty intestinal barrier function and potentiation of arthritogenic immune cells. From this perspective, bolstering the intestinal barrier integrity arose as an attractive therapeutic strategy for rheumatoid arthritis.

我们饶有兴趣地阅读了 Lyu 等人最近发表在《风湿病年鉴》上的文章《肠上皮细胞中 HIF1α 的表达通过抑制 RIPK3 诱导的细胞死亡机制限制了关节炎炎症》。作者认为,低氧诱导因子1α在肠上皮细胞中的表达阻碍了肠上皮细胞的坏死,保护了肠屏障的完整性,是关节炎发展的一个关键检查点。以往的研究表明,肠屏障功能缺陷与致关节炎免疫细胞的增效之间存在潜在的机制联系。从这个角度来看,加强肠道屏障的完整性是治疗类风湿性关节炎的一种有吸引力的策略。
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引用次数: 0
Effect of ambrisentan in patients with systemic sclerosis and mild pulmonary arterial hypertension: long-term follow-up data from EDITA study. 安利生坦对系统硬化症和轻度肺动脉高压患者的疗效:EDITA 研究的长期随访数据。
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2024-07-18 DOI: 10.1186/s13075-024-03363-0
Panagiota Xanthouli, Paul Uesbeck, Hanns-Martin Lorenz, Norbert Blank, Christina A Eichstaedt, Satenik Harutyunova, Benjamin Egenlauf, Jerry G Coghlan, Christopher P Denton, Ekkehard Grünig, Nicola Benjamin

Background: In the EDITA trial, patients with systemic sclerosis (SSc) and mild pulmonary vascular disease (PVD) treated with ambrisentan had a significant decline of pulmonary vascular resistance (PVR) but not of mean pulmonary arterial pressure (mPAP) vs. placebo after six months. The EDITA-ON study aimed to assess long-term effects of open label therapy with ambrisentan vs. no pulmonary arterial hypertension (PAH) therapy.

Methods: Patients who participated in the EDITA study and received regular follow-up were included in EDITA-ON. Clinical, echocardiographic, laboratory, exercise and hemodynamic parameters during follow-up were analysed. The primary endpoint was to assess whether continued treatment with ambrisentan vs. no treatment prevented the development of PAH according to the new definition.

Results: Of 38 SSc patients included in the EDITA study four were lost to follow-up. Of the 34 remaining patients (age 55 ± 11 years, 82.1% female subjects), 19 received ambrisentan after termination of the blinded phase, 15 received no PAH medication. The mean follow-up time was 2.59 ± 1.47 years, during which 29 patients underwent right heart catheterization. There was a significant improvement of mPAP in catheterised patients receiving ambrisentan vs. no PAH treatment (-1.53 ± 2.53 vs. 1.91 ± 2.98 mmHg, p = 0.003). In patients without PAH treatment 6/12 patients had PAH vs. 1/17 of patients receiving ambrisentan (p < 0.0001).

Conclusion: In SSc patients with early PVD, the development of PAH and/or deterioration was less frequent among patients receiving ambrisentan, indicating that early treatment and close follow-up could be beneficial in this high-risk group. Future trials in this field are needed to confirm these results.

研究背景在EDITA试验中,与安慰剂相比,接受安利生坦治疗的系统性硬化症(SSc)和轻度肺血管疾病(PVD)患者在6个月后肺血管阻力(PVR)显著下降,但平均肺动脉压(mPAP)并没有下降。EDITA-ON研究旨在评估使用安利生坦进行开放标签治疗与不使用肺动脉高压(PAH)治疗的长期效果:EDITA-ON研究纳入了参与EDITA研究并接受定期随访的患者。分析随访期间的临床、超声心动图、实验室、运动和血液动力学参数。主要终点是评估继续使用安利生坦治疗与不使用安利生坦治疗是否能根据新定义预防PAH的发生:在EDITA研究中纳入的38名SSc患者中,有4人失去了随访机会。在剩下的34名患者中(年龄55±11岁,82.1%为女性),19人在盲法阶段结束后接受了安利生坦治疗,15人未接受任何PAH药物治疗。平均随访时间为(2.59 ± 1.47)年,其间29名患者接受了右心导管检查。与未接受 PAH 治疗相比,接受安利生坦治疗的导管患者的 mPAP 有明显改善(-1.53 ± 2.53 vs. 1.91 ± 2.98 mmHg,p = 0.003)。在未接受 PAH 治疗的患者中,6/12 的患者患有 PAH,而在接受安利生坦治疗的患者中,1/17 的患者患有 PAH(P = 0.003):在患有早期心血管疾病的 SSc 患者中,接受安利生坦治疗的患者发生 PAH 和/或病情恶化的频率较低,这表明早期治疗和密切随访对这一高风险群体有益。未来需要在该领域进行试验,以证实这些结果。
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引用次数: 0
JAK inhibitors attenuate hyperactivation of nonswitched memory B cells in rheumatoid arthritis patients in remission JAK 抑制剂可减轻缓解期类风湿性关节炎患者非开关记忆 B 细胞的过度激活
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2024-07-17 DOI: 10.1186/s13075-024-03374-x
Jing Luo, Jing Zhang, Bomiao Ju, Yanhua Wang, Nan Hu, Qian Li, Qianyun Xu, Dan Pu, Zhiming Hao, Yongwei Huo, Xiaohong Lv, Lan He
To investigate the distribution and activation of B-cell subpopulations in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKis) and to analyze their correlation with disease remission. Peripheral blood samples were collected from 23 adult healthy controls and 58 RA patients, 31 of whom were treated with JAKis and assessed during a 24-month follow-up. The number of peripheral B-cell subpopulations (including naive B cells, nonswitched memory B (NSMB) cells, switched memory B cells, and double-negative B cells), their activation, and phosphorylation of SYK and AKT upon B-cell receptor (BCR) stimulation in each population were analyzed by flow cytometry. Compared with that in healthy controls, the frequency of NSMB cells was significantly lower in new-onset untreated RA patients. However, expression of CD40, CD80, CD95, CD21low and pAKT significantly increased in these NSMB cells. Additionally, the number of NSMB cells correlated negatively with DAS28-ESR and IgG and IgA levels in these patients; expression of CD80, CD95 and CD21low on NSMB cells correlated positively with DAS28-ESR and IgG and IgA levels. After treatment with JAKis, the serum IgG concentration significantly decreased in RA patients in remission, but CD40, CD95 and pAKT levels in NSMB cells significantly decreased. RA patients present different B-cell subpopulations, in which the frequency of NSMB cells is negatively associated with disease activity. However, treatment with JAKis can inhibit activation of NSMB cells, restore the balance of kinase phosphorylation, and facilitate disease remission in RA patients.
研究类风湿性关节炎(RA)患者接受 Janus 激酶抑制剂(JAKis)治疗后 B 细胞亚群的分布和活化情况,并分析其与疾病缓解的相关性。研究人员采集了23名成年健康对照者和58名类风湿关节炎患者的外周血样本,其中31人接受了JAKis治疗,并在24个月的随访期间进行了评估。流式细胞术分析了外周 B 细胞亚群(包括幼稚 B 细胞、非开关记忆 B 细胞(NSMB)、开关记忆 B 细胞和双阴性 B 细胞)的数量、其活化情况以及每个亚群在 B 细胞受体(BCR)刺激下的 SYK 和 AKT 磷酸化情况。与健康对照组相比,新发未经治疗的RA患者中NSMB细胞的频率明显降低。但是,CD40、CD80、CD95、CD21low 和 pAKT 在这些 NSMB 细胞中的表达明显增加。此外,在这些患者中,NSMB细胞的数量与DAS28-ESR以及IgG和IgA水平呈负相关;NSMB细胞上CD80、CD95和CD21low的表达与DAS28-ESR以及IgG和IgA水平呈正相关。使用 JAKis 治疗后,缓解期 RA 患者的血清 IgG 浓度明显降低,但 NSMB 细胞中的 CD40、CD95 和 pAKT 水平明显下降。RA 患者有不同的 B 细胞亚群,其中 NSMB 细胞的频率与疾病活动性呈负相关。然而,使用 JAKis 治疗可以抑制 NSMB 细胞的活化,恢复激酶磷酸化的平衡,促进 RA 患者的疾病缓解。
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引用次数: 0
A novel method to monitor rheumatoid arthritis prevalence using hospital and medication databases 利用医院和药物数据库监测类风湿关节炎患病率的新方法
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2024-07-16 DOI: 10.1186/s13075-024-03366-x
Louise Koller-Smith, Ahmed Mehdi, Lyn March, Leigh Tooth, Gita D. Mishra, Ranjeny Thomas
Most estimates of rheumatoid arthritis (RA) prevalence, including all official figures in Australia and many other countries, are based on self-report. Self-report has been shown to overestimate RA, but the ‘gold standard’ of reviewing individual medical records is costly, time-consuming and impractical for large-scale research and population monitoring. This study provides an algorithm to estimate RA cases using administrative data that can be adjusted for use in multiple contexts to provide the first approximate RA cohort in Australia that does not rely on self-report. Survey data on self-reported RA and medications from 25 467 respondents of the Australian Longitudinal Study on Women’s Health (ALSWH) were linked with data from the national medication reimbursement database, hospital and emergency department (ED) episodes, and Medicare Benefits codes. RA prevalence was calculated for self-reported RA, self-reported RA medications, dispensed RA medications, and hospital/ED RA presentations. Linked data were used to exclude individuals with confounding autoimmune conditions. Of 25 467 survey respondents, 1367 (5·4%) women self-reported disease. Of the 26 840 women with hospital or ED presentations, 292 (1·1%) received ICD-10 codes for RA. There were 1038 (2·8%) cases by the medication database definition, and 294 cases (1·5%) by the self-reported medication definition. After excluding individuals with other rheumatic conditions, prevalence was 3·9% for self-reported RA, 1·9% based on the medication database definition and 0·5% by self-reported medication definition. This confirms the overestimation of RA based on self-reporting. We provide an algorithm for identifying individuals with RA, which could be used for population studies and monitoring RA in Australia and, with adjustments, internationally. Its balance of accuracy and practicality will be useful for health service planning using relatively easily accessible input data.
对类风湿性关节炎(RA)患病率的大多数估计,包括澳大利亚和许多其他国家的所有官方数字,都是基于自我报告。自我报告已被证明会高估类风湿关节炎的患病率,但审查个人医疗记录这一 "黄金标准 "成本高昂、耗时长,对于大规模研究和人口监测来说并不实用。本研究提供了一种利用行政数据估算RA病例的算法,该算法可根据多种情况进行调整,从而提供澳大利亚首个不依赖自我报告的RA近似队列。澳大利亚妇女健康纵向研究(ALSWH)的25 467名受访者自我报告的RA和药物调查数据与来自国家药物报销数据库、医院和急诊科(ED)病例以及医疗保险福利代码的数据进行了关联。根据自我报告的RA、自我报告的RA药物、配发的RA药物以及医院/急诊科的RA病例计算RA患病率。使用关联数据排除了患有自身免疫性疾病的混杂个体。在 25 467 名调查对象中,1367 名(5-4%)女性自我报告患有疾病。在 26 840 名曾在医院或急诊室就诊的女性中,有 292 人(1-1%)获得了 ICD-10 的 RA 代码。根据药物数据库定义的病例有 1038 例(2-8%),根据自我报告的药物定义的病例有 294 例(1-5%)。排除患有其他风湿病的患者后,自我报告的 RA 患病率为 3-9%,根据药物数据库的定义为 1-9%,根据自我报告的药物定义为 0-5%。这证实了基于自我报告的 RA 患病率被高估。我们提供了一种识别RA患者的算法,可用于澳大利亚的人口研究和RA监测,经调整后也可用于国际研究。该算法兼顾了准确性和实用性,将有助于利用相对容易获取的输入数据进行医疗服务规划。
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引用次数: 0
Clinical relevance of positively determined myositis antibodies in rheumatology: a retrospective monocentric analysis 风湿病学中阳性肌炎抗体的临床意义:回顾性单中心分析
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2024-07-16 DOI: 10.1186/s13075-024-03368-9
Falk Schumacher, Maximilian Zimmermann, Malte Kanbach, Wigbert Schulze, Maximilian Wollsching-Strobel, Doreen Kroppen, Sarah Bettina Stanzel, Daniel Majorski, Wolfram Windisch, Johannes Strunk, Melanie Berger
The increased availability of myositis autoantibodies represents new possibilities and challenges in clinical practice (Lundberg IE, Tjärnlund A, Bottai M, Werth VP, Pilkington C, de Visser M, et al. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis. 2017;76:1955–64. https://doi.org/10.1136/annrheumdis-2017-211468 .). The aim of this study was to perform a retrospective data analysis of patient cases with positive myositis autoantibodies to analyse their significance in routine rheumatology practice. A monocentric analysis of all the orders used to determine myositis autoantibodies from July 2019 to May 2022 in the Department of Rheumatology, Krankenhaus Porz am Rhein, Cologne, Germany, was carried out. In the defined time interval, a total of 71,597 laboratory values for the antibodies mentioned above were obtained. A total of 238 different positive autoantibodies ​​were detected in 209 patients. Idiopathic inflammatory myopathy was diagnosed in 37 patients (18%), and inflammatory rheumatic diseases other than idiopathic inflammatory myopathy were diagnosed in 90 patients (43%). No inflammatory rheumatic disease was diagnosed in 82 patients (39%). General clusters of clinical manifestations were observed. In our cohort, we were able to show that a relevant proportion of patients with positive myositis antibodies did not have idiopathic inflammatory myopathies or inflammatory rheumatic diseases. This finding indicates the importance of myositis autoantibodies in this group of patients. However, further studies on the course of symptoms and examination results in patients without inflammatory rheumatic diseases and with positive myositis antibodies are necessary.
肌炎自身抗体的增加为临床实践带来了新的可能性和挑战(Lundberg IE、Tjärnlund A、Bottai M、Werth VP、Pilkington C、de Visser M 等:《2017 年欧洲抗风湿联盟/美国风湿病学会成人和青少年特发性炎症性肌病及其主要亚组分类标准》。Ann Rheum Dis.2017;76:1955–64. https://doi.org/10.1136/annrheumdis-2017-211468 .).本研究旨在对肌炎自身抗体阳性的患者病例进行回顾性数据分析,分析其在常规风湿病学实践中的意义。本研究对德国科隆波茨莱茵医院(Krankenhaus Porz am Rhein)风湿病学部 2019 年 7 月至 2022 年 5 月期间用于确定肌炎自身抗体的所有医嘱进行了单中心分析。在规定的时间间隔内,共获得了 71597 个上述抗体的实验室值。在 209 名患者身上共检测出 238 种不同的阳性自身抗体。37名患者(18%)被确诊为特发性炎症性肌病,90名患者(43%)被确诊为特发性炎症性肌病以外的炎症性风湿病。82名患者(39%)未确诊任何炎症性风湿病。临床表现普遍呈群集性。在我们的队列中,我们能够证明肌炎抗体阳性的患者中有相当一部分没有特发性炎症性肌病或炎症性风湿病。这一发现表明了肌炎自身抗体在这类患者中的重要性。不过,有必要对无炎症性风湿病但肌炎抗体阳性患者的症状过程和检查结果进行进一步研究。
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引用次数: 0
TGFβ signaling pathway is altered by HLA-B27 expression, resulting in pathogenic consequences relevant for spondyloarthritis TGFβ 信号通路因 HLA-B27 表达而改变,导致脊柱关节炎的致病后果
IF 4.9 2区 医学 Q1 Medicine Pub Date : 2024-07-15 DOI: 10.1186/s13075-024-03370-1
Marc Lauraine, Maxence de Taffin de Tilques, Dganit Melamed-Kadosh, Bilade Cherqaoui, Vincent Rincheval, Erwan Prevost, Aurore Rincheval-Arnold, Eneida Cela, Arie Admon, Isabelle Guénal, Luiza M. Araujo, Maxime Breban
Association of HLA-B27 with spondyloarthritis (SpA) has been known for 50 years, but still remains unexplained. We recently showed that HLA-B27 expressed in wing imaginal disc from HLA-B27/human-β2 microglobulin (hβ2m) transgenic Drosophila deregulated bone morphogenetic protein (BMP) pathway by interacting physically with type I BMP receptor (BMPR1) Saxophone (Sax), leading to crossveinless phenotype. Genetic interaction was studied between activin/transforming growth factor β (TGFβ) pathway and HLA-B27/hβ2m in transgenic Drosophila wings. The HLA-B27-bound peptidome was characterized in wing imaginal discs. In mesenteric lymph node (mLN) T cells from HLA-B27/hβ2m rat (B27 rat), physical interaction between HLA-B27 and activin receptor-like kinase-2 (ALK2), ALK3 and ALK5 BMPR1s, phosphorylation of small mothers against decapentaplegic (SMADs) and proteins of the non-canonical BMP/TGFβ pathways induced by its ligands, and the transcript level of target genes of the TGFβ pathway, were evaluated. In HLA-B27/hβ2m transgenic Drosophila, inappropriate signalling through the activin/TGFβ pathway, involving Baboon (Babo), the type I activin/TGFβ receptor, contributed to the crossveinless phenotype, in addition to deregulated BMP pathway. We identified peptides bound to HLA-B27 with the canonical binding motif in HLA-B27/hβ2m transgenic Drosophila wing imaginal disc. We demonstrated specific physical interaction, between HLA-B27/hβ2m and mammalian orthologs of Sax and Babo, i.e. ALK2 and ALK5 (i.e. TGFβ receptor I), in the mLN cells from B27 rat. The magnitude of phosphorylation of SMAD2/3 in response to TGFβ1 was increased in T cells from B27 rats, showing evidence for deregulated TGFβ pathway. Accordingly, expression of several target genes of the pathway was increased in T cells from B27 rats, in basal conditions and/or after TGFβ exposure, including Foxp3, Rorc, Runx1 and Maf. Interestingly, Tgfb1 expression was reduced in naive T cells from B27 rats, even premorbid, an observation consistent with a pro-inflammatory pattern. This study shows that HLA-B27 alters the TGFβ pathways in Drosophila and B27 rat. Given the importance of this pathway in CD4 + T cells differentiation and regulation, its disturbance could contribute to the abnormal expansion of pro-inflammatory T helper 17 cells and altered regulatory T cell phenotype observed in B27 rats.
HLA-B27与脊柱关节炎(Spondyloarthritis,SpA)的关系已经存在了50年,但至今仍未解释清楚。我们最近发现,在HLA-B27/人β2微球蛋白(hβ2m)转基因果蝇的翅胚盘中表达的HLA-B27通过与I型BMP受体(BMPR1)Saxophone(Sax)发生物理相互作用,从而干扰了骨形态发生蛋白(BMP)通路,导致无交叉脉表型。研究了转基因果蝇翅膀中活化素/转化生长因子β(TGFβ)通路与HLA-B27/hβ2m之间的遗传相互作用。研究人员对翅膀显像盘中与HLA-B27结合的肽组进行了表征。在HLA-B27/hβ2m大鼠(B27大鼠)的肠系膜淋巴结(mLN)T细胞中,评估了HLA-B27与活化素受体样激酶-2(ALK2)、ALK3和ALK5 BMPR1s之间的物理相互作用、其配体诱导的抗断头小母(SMADs)和非经典BMP/TGFβ通路蛋白的磷酸化以及TGFβ通路靶基因的转录水平。在HLA-B27/hβ2m转基因果蝇中,除了BMP通路失调外,通过I型激活素/TGFβ受体巴布(Babo)参与的激活素/TGFβ通路的不恰当信号传导也导致了无横纹表型。我们在HLA-B27/hβ2m转基因果蝇翼像盘中发现了与HLA-B27结合的具有典型结合基序的肽。我们在 B27 大鼠的 mLN 细胞中证实了 HLA-B27/hβ2m 与哺乳动物 Sax 和 Babo 的直向同源物,即 ALK2 和 ALK5(即 TGFβ 受体 I)之间的特异性物理相互作用。在 B27 大鼠的 T 细胞中,SMAD2/3 对 TGFβ1 的磷酸化程度增加,表明 TGFβ 通路失调。相应地,在基础条件下和/或暴露于 TGFβ 后,B27 大鼠 T 细胞中该通路的几个靶基因(包括 Foxp3、Rorc、Runx1 和 Maf)的表达增加。有趣的是,B27 大鼠的幼稚 T 细胞中 Tgfb1 的表达减少,甚至在发病前也是如此,这一观察结果与促炎模式一致。这项研究表明,HLA-B27 改变了果蝇和 B27 大鼠的 TGFβ 通路。鉴于该通路在 CD4 + T 细胞分化和调节中的重要性,它的干扰可能会导致 B27 大鼠中观察到的促炎性 T 辅助细胞 17 的异常扩增和调节性 T 细胞表型的改变。
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Arthritis Research & Therapy
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