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Multicenter Longitudinal Observational Study Pharmaceuticals Alflutop in Russia (message 2) 多中心纵向观察研究药物Alflutop在俄罗斯(消息2)
Pub Date : 2023-08-20 DOI: 10.14412/1996-7012-2023-4-75-85
A. Lila, E. Taskina, L. Alekseeva, N. Kashevarova
Osteoarthritis (OA) is one of the most important medical and social problems due to the steady increase in morbidity and disability. Prevention, management of risk factors, and early treatment of OA are critical.Objective of the ISKRA study was to evaluate the efficacy of Alflutop in patients with OA of different locations and/or low back pain (LBP) with or without concomitant diseases.Material and methods. We selected 11,136 patients with OA of specific localizations aged 50 to 72 years. The duration of the study ranged from 20 to 31 days, and the number of visits was 2 (B1 and B2). Alflutop was prescribed 1 ml intramuscularly (IM) daily No. 20 or 2 ml IM every other day No. 10.The efficacy of therapy was determined by the time of onset of clinical effect (pain reduction, as assessed by the patient), the dynamics of pain intensity in the studied joint during movement and/or LBP according to the visual analogue scale (VAS), the assessment of quality of life according to the EQ-5D questionnaire and the patient's general health status (PGH) according to VAS. We assessed treatment adherence, need for nonsteroidal anti-inflammatory drugs (NSAIDs), satisfaction with treatment (based on VAS). The presence of comorbidities was also considered.Results and discussion. In hand OA (n=2776), a positive effect of therapy was observed in 98.6% of cases, according to patients' assessment. During the course of therapy, there was a significant decrease in pain on movement in the hands (according to VAS), improvement in PGH and quality of life (according to EQ-5D). Rapid development of the analgesic effect was seen on average at day 9.In hip OA (n=6666), a decrease in pain was noted in 83.3% of cases (<40 mm), improvement in PGH and quality of life in most patients, and a decrease in the need for NSAIDs in 64.9%.In the generalized form of OA (n=1694), significant clinical improvement was achieved in 97.1% of patients. A pain reduction ≥50% from baseline was noted in nearly 65% of cases.Elderly age, more severe radiographic manifestations of OA, low quality of life and compliance, and concomitant diseases were associated with a lower effect of therapy in hand and hip OA. In hand OA, high pain scores and worse PGH VAS scores also played a role. In hip OA, lower success was observed more often in women, and in hand OA — in men.In the generalized form of OA, lower satisfaction with pain management was associated with age, female sex, high body mass index, long history of OA, advanced radiographic stages, poorer quality of life and compliance, and comorbidity.Conclusion. The results of the use of Alflutop in hand and hip OA and generalized form of OA suggest the usefulness of its wide application in real clinical practice. Consideration and correction of the factors associated with less pronounced analgesic effect of the drug will improve the effectiveness of OA therapy.
骨关节炎(Osteoarthritis, OA)由于其发病率和致残率的不断增加而成为最重要的医学和社会问题之一。预防、管理风险因素和早期治疗OA至关重要。ISKRA研究的目的是评估Alflutop对不同部位OA和/或腰痛(LBP)伴或不伴疾病患者的疗效。材料和方法。我们选择了11136例年龄在50 - 72岁的特定部位OA患者。研究持续时间为20 - 31天,就诊次数为2次(B1和B2)。Alflutop每日1 ml肌注(IM) No. 20或每隔一天2 ml IM No. 10。根据临床效果(由患者评估疼痛减轻)的开始时间,根据视觉模拟量表(VAS),根据EQ-5D问卷评估生活质量,根据VAS评估患者一般健康状况(PGH),确定研究关节在运动和/或LBP时的疼痛强度动态。我们评估了治疗依从性、非甾体抗炎药(NSAIDs)的需求、治疗满意度(基于VAS)。同时也考虑了合并症的存在。结果和讨论。在手部OA (n=2776)中,根据患者评估,98.6%的病例观察到治疗的积极效果。在治疗过程中,手部运动疼痛明显减轻(根据VAS), PGH和生活质量得到改善(根据EQ-5D)。平均在第9天镇痛效果发展迅速。在髋关节OA (n=6666)中,83.3%的病例(<40 mm)疼痛减轻,大多数患者的PGH和生活质量改善,64.9%的患者对非甾体抗炎药的需求减少。在广泛性骨性关节炎中(n=1694), 97.1%的患者获得了显著的临床改善。在近65%的病例中,疼痛比基线减轻≥50%。老年、骨性关节炎影像学表现较严重、生活质量和依从性较低以及伴随疾病与手部和髋部骨性关节炎治疗效果较低相关。在手OA中,较高的疼痛评分和较差的PGH VAS评分也起作用。女性髋部OA的成功率较低,男性手部OA的成功率较低。在广泛性骨关节炎中,较低的疼痛管理满意度与年龄、女性、高体重指数、骨关节炎病史长、影像学分期较晚、生活质量和依从性较差以及合并症有关。Alflutop在手部和髋部OA及广义OA中的应用结果表明其在实际临床实践中具有广泛的应用价值。考虑和纠正与药物镇痛作用不明显相关的因素,将提高OA治疗的有效性。
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引用次数: 0
Evaluation of the influence of polymorphisms of the transporter genes (RFC1, MDR1) and GGH on the efficacy of methotrexate in rheumatoid arthritis 转运体基因(RFC1、MDR1)和GGH多态性对甲氨蝶呤治疗类风湿性关节炎疗效的影响
Pub Date : 2023-08-20 DOI: 10.14412/1996-7012-2023-4-28-34
I. V. Devald, E. A. Hodus, D. Nokhrin, E. Khromova, G. Ignatova, D. Stashkevich, A. Lila, A. Burmistrova
The efficacy of methotrexate (MT) in patients with rheumatoid arthritis (RA) may be determined by genetic factors.Objective: to evaluate the isolated and combined effects of single nucleotide polymorphisms (SNPs) of membrane transporter proteins (RFC1 80G>A and MDR1 3435C>T) and the GGH -401C>T gamma-glutamyl hydrolase enzyme genes on the efficacy of MT in patients with RA.Material and methods. The study group consisted of 85 patients with a confirmed diagnosis of RA, who received therapy with MT starting at 10 mg/week and increasing in dose to a maximum of 25 mg/week. Efficacy was assessed after six months of treatment using the dynamics of the DAS28 index, identifying patients who responded and those who did not respond to MT therapy.Genotyping of RFC1, MDR1 and GGH gene polymorphisms was performed by real-time polymerase chain reaction. Three different approaches were used to analyze the results: 1) analysis for each of the genes; 2) logistic regression; and 3) multifactor dimensionality reduction (MDR).Results and discussion. Single gene analysis was used to determine the most likely predictors of non-response to therapy: 1) for GGH-401C>T, TT genotype (odds ratio, OR 5.09; 95% confidence interval, C11.11—23.3); 2) forMDR13435C>T, the TT genotype (OR 2.38; 95% CI0.89-6.37); 3) for RFC180G>A, not - AA genotype (OR 1.87; 95% CI 0.93-3.76).The logistic regression model showed a significant effect of homozygous genotype GGH -401TT on the efficacy of MT with low sensitivity of the method. The multifactorial dimensionality reduction results show a significant synergistic effect of the MT transport genes (MDR1, RFC1) and the GGH enzyme encoding the conversion of MT to the elimination form.Conclusion. Using various statistical methods, the following results were obtained: Single gene analysis revealed the most likely predictors of nonresponse to MT therapy: GGH -401C>T - TT genotype, MDR1 3435C>T - TT genotype, RFC1 80G>A - not-AA genotype; the method of multiple logistic regression allowed to determine the significant effect of GGH -401ТТ genotype on the effect of the drug with a low sensitivity of the method; the isolated effect of polymorphisms is probably less pronounced than their combined effect on the effectiveness of MT. SNP synergism is a major contributor to the development of treatment resistance. MDR is a promising method that can be used in the future to assess the impact of SNPs.
甲氨蝶呤(MT)治疗类风湿性关节炎(RA)的疗效可能由遗传因素决定。目的:评价膜转运蛋白(RFC1 80G>A和MDR1 3435C>T)单核苷酸多态性(snp)和γ -谷氨酰水解酶基因GGH -401C>T对类风湿关节炎患者MT疗效的分离和联合影响。材料和方法。研究组由85名确诊为RA的患者组成,他们接受MT治疗,从10mg /周开始,剂量增加到最大25mg /周。治疗6个月后,使用DAS28指数动态评估疗效,确定对MT治疗有反应和无反应的患者。实时聚合酶链反应对RFC1、MDR1和GGH基因多态性进行基因分型。分析结果采用了三种不同的方法:1)对每个基因进行分析;2)逻辑回归;3)多因素降维(MDR)。结果和讨论。单基因分析用于确定对治疗无反应的最可能的预测因素:1)ghg - 401c >T, TT基因型(优势比,OR 5.09;95%置信区间(C11.11-23.3);2) TT基因型forMDR13435C>T (OR 2.38;95% ci0.89 - 6.37);3) RFC180G>A,非- AA基因型(OR 1.87;95% ci 0.93-3.76)。logistic回归模型显示,纯合子基因型GGH -401TT对MT疗效影响显著,但该方法敏感性较低。多因子降维结果表明,MT转运基因(MDR1、RFC1)和编码MT转化为消除形式的GGH酶具有显著的协同作用。采用多种统计方法,得到以下结果:单基因分析揭示了MT治疗无反应最可能的预测因子:GGH - 401c >T - TT基因型,MDR1 3435C>T - TT基因型,RFC1 80G>A -非aa基因型;采用多元logistic回归的方法可以确定GGH -401ТТ基因型对药物疗效的显著影响,但该方法的敏感性较低;多态性的单独影响可能不如它们对MT有效性的综合影响那么明显。SNP协同作用是产生治疗耐药性的主要因素。MDR是一种很有前途的方法,可以在未来用于评估snp的影响。
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引用次数: 0
Autoimmunity and autoinflammation — the key to understanding the pathogenesis of osteoarthritis and developing new ways for its prevention and therapy 自身免疫和自身炎症是了解骨关节炎发病机制和开发防治新途径的关键
Pub Date : 2023-08-20 DOI: 10.14412/1996-7012-2023-4-103-114
I. Sarvilina, A. Lila, L. Alekseeva, O. Gromova, E. Taskina
The review considers the full spectrum of currently known autoantigens in osteoarthritis (OA) and discusses their role in the development and/or persistence of synovitis and the initiation of subsequent destruction of articular cartilage with the development of an autoimmune response and auto-inflammation. Of great interest are methods of drug prevention of OA considering autoimmunity responses and associated auto-inflammation, including the use of pharmaconutraceuticals.Preclinical and clinical studies of the safety and efficacy of pharmaconutraceuticals containing native type II collagen are presented. A clear relationship between the composition/chemical structure of the collagen components and its mechanism of action and efficacy is discussed. Taking into account the autoimmune pathogenesis of OA, new combined pharmaconutraceuticals aimed at reducing the manifestations of autoinflammation (chondroitin sulfate, glucosamine sulfate) are developed. They have an optimal ratio of active ingredients with a sufficient level of evidence, which allows enhancing their beneficial pharmacological effects.
这篇综述考虑了目前已知的骨关节炎(OA)中所有的自身抗原,并讨论了它们在滑膜炎的发展和/或持续以及随着自身免疫反应和自身炎症的发展而开始的关节软骨破坏中的作用。考虑到自身免疫反应和相关的自身炎症,包括药物的使用,药物预防OA的方法引起了极大的兴趣。介绍了含有天然II型胶原蛋白的药物的安全性和有效性的临床前和临床研究。讨论了胶原成分的组成/化学结构与其作用机制和功效之间的明确关系。考虑到OA的自身免疫性发病机制,新的联合药物旨在减少自身炎症的表现(硫酸软骨素,硫酸氨基葡萄糖)被开发出来。他们有一个最佳比例的活性成分与充分的证据水平,这允许增强其有益的药理作用。
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引用次数: 0
Clinical and immunologic features of the phenotype of systemic lupus erythematosus combined with Sjögren's syndrome 系统性红斑狼疮合并Sjögren综合征的临床和免疫学特征
Pub Date : 2023-08-20 DOI: 10.14412/1996-7012-2023-4-50-56
S. Solovyev, E. Aseeva, A. Baranov, A. Lila, N. Nikishina, S. Glukhova
The problem of clinical and immunological heterogeneity of systemic lupus erythematosus (SLE) is of great interest, especially the combination of SLE and Sjögren's syndrome (SjS) determines a more favorable prognosis and specifics of therapy.Objective: to characterize the clinical and immunological features of SLE combined with SjS.Material and methods. The retrospective study included 44 patients with SLE combined with SjS and 356 patients with SLE without SjS, hospitalized at the V.A. Nasonova Research Institute of Rheumatology between 2013 and 2021. The two groups of patients were compared in terms of life expectancy, clinical manifestations, laboratory parameters and therapy.Results and discussion. The following phenotypic features of the clinical and immunological variant of SLE combined with SjS were found: significantly longer duration of SLE (p<0.01); higher incidence of polyarthritis (p=0.01) and Raynaud's syndrome (p<0.003) at disease onset. Subacute cutaneous lupus erythematosus, Raynaud's syndrome, peripheral nervous system involvement (sensory polyneuropathy and distal sensory-motor polyneuropathy) were found more frequently in SLE combined with SjS than in SLE without SjS, p<0.0001. Among laboratory abnormalities in SLE patients with SjS, leukopenia (p<0.0001), antibodies to SSA/Ro, SSB/La, and rheumatoid factor (p<0.0001) were observed in a greater number of cases. In the group of SLE combined with SjS, the chronic variant of SLE course according to the classification of V.A. Nasonova, and lower activity were observed, which didn't not require therapy with high doses of glucocorticoids; in this group, rituximab (p<0.01), cyclophosphamide and methotrexate were used significantly more often.Conclusion. Thus, significant clinical and laboratory differences were found between SLE with SjS and without SjS. They determine prognosis, approaches to pathogenetic therapy and monitoring.
系统性红斑狼疮(SLE)的临床和免疫学异质性问题引起了人们的极大兴趣,特别是SLE合并Sjögren综合征(SjS)决定了更有利的预后和治疗的特异性。目的:探讨SLE合并SjS的临床及免疫学特点。材料和方法。该回顾性研究纳入了2013年至2021年期间在va Nasonova风湿病研究所住院的44例SLE合并SjS患者和356例无SjS的SLE患者。比较两组患者的预期寿命、临床表现、实验室指标及治疗方法。结果和讨论。SLE合并SjS的临床和免疫学变异有以下表型特征:SLE病程明显延长(p<0.01);发病时多发关节炎(p=0.01)和雷诺综合征(p<0.003)的发生率较高。亚急性皮肤红斑狼疮、雷诺综合征、周围神经系统受累(感觉多神经病变和远端感觉-运动多神经病变)在SLE合并SjS中比在不合并SjS的SLE中更常见,p<0.0001。SLE合并SjS患者的实验室异常中,白细胞减少(p<0.0001)、SSA/Ro抗体、SSB/La抗体和类风湿因子抗体(p<0.0001)较多。SLE合并SjS组SLE病程按va . Nasonova分类为慢性变型,且活性较低,不需要大剂量糖皮质激素治疗;该组利妥昔单抗(p<0.01)、环磷酰胺和甲氨蝶呤的使用频率明显高于对照组。因此,SLE合并SjS和不合并SjS之间存在显著的临床和实验室差异。它们决定预后、病理治疗方法和监测。
{"title":"Clinical and immunologic features of the phenotype of systemic lupus erythematosus combined with Sjögren's syndrome","authors":"S. Solovyev, E. Aseeva, A. Baranov, A. Lila, N. Nikishina, S. Glukhova","doi":"10.14412/1996-7012-2023-4-50-56","DOIUrl":"https://doi.org/10.14412/1996-7012-2023-4-50-56","url":null,"abstract":"The problem of clinical and immunological heterogeneity of systemic lupus erythematosus (SLE) is of great interest, especially the combination of SLE and Sjögren's syndrome (SjS) determines a more favorable prognosis and specifics of therapy.Objective: to characterize the clinical and immunological features of SLE combined with SjS.Material and methods. The retrospective study included 44 patients with SLE combined with SjS and 356 patients with SLE without SjS, hospitalized at the V.A. Nasonova Research Institute of Rheumatology between 2013 and 2021. The two groups of patients were compared in terms of life expectancy, clinical manifestations, laboratory parameters and therapy.Results and discussion. The following phenotypic features of the clinical and immunological variant of SLE combined with SjS were found: significantly longer duration of SLE (p<0.01); higher incidence of polyarthritis (p=0.01) and Raynaud's syndrome (p<0.003) at disease onset. Subacute cutaneous lupus erythematosus, Raynaud's syndrome, peripheral nervous system involvement (sensory polyneuropathy and distal sensory-motor polyneuropathy) were found more frequently in SLE combined with SjS than in SLE without SjS, p<0.0001. Among laboratory abnormalities in SLE patients with SjS, leukopenia (p<0.0001), antibodies to SSA/Ro, SSB/La, and rheumatoid factor (p<0.0001) were observed in a greater number of cases. In the group of SLE combined with SjS, the chronic variant of SLE course according to the classification of V.A. Nasonova, and lower activity were observed, which didn't not require therapy with high doses of glucocorticoids; in this group, rituximab (p<0.01), cyclophosphamide and methotrexate were used significantly more often.Conclusion. Thus, significant clinical and laboratory differences were found between SLE with SjS and without SjS. They determine prognosis, approaches to pathogenetic therapy and monitoring.","PeriodicalId":18651,"journal":{"name":"Modern Rheumatology Journal","volume":"122 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83201416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Musculoskeletal symptoms in juvenile onset systemic lupus erythematosus 青少年发病系统性红斑狼疮的肌肉骨骼症状
Pub Date : 2023-08-20 DOI: 10.14412/1996-7012-2023-4-90-96
M. Kaleda, A. Arefieva, I. Nikishina
In juvenile onset systemic lupus erythematosus (SLE), musculoskeletal involvement is one of the most common manifestations. Musculoskeletal symptoms may be due to disease activity itself, organ damage due to SLE activity, drug exposure, or comorbidities. Although they are not life-threatening, they still have a significant impact on disability severity and social exclusion. This article discusses the clinical features of various causes of musculoskeletal manifestations in SLE with onset in childhood and adolescence, the adequate interpretation of which is important for diagnosing and evaluating SLE activity and for correcting the treatment of the disease, thereby improving the long-term prognosis and quality of life of patients.
在青少年发病的系统性红斑狼疮(SLE)中,肌肉骨骼受累是最常见的表现之一。肌肉骨骼症状可能是由疾病活动本身、SLE活动引起的器官损害、药物暴露或合并症引起的。虽然它们不会危及生命,但它们仍然对残疾严重程度和社会排斥产生重大影响。本文讨论了儿童期和青春期起病的SLE中引起肌肉骨骼表现的各种原因的临床特征,充分解释这些特征对于SLE活动性的诊断和评估以及纠正疾病的治疗,从而改善患者的长期预后和生活质量具有重要意义。
{"title":"Musculoskeletal symptoms in juvenile onset systemic lupus erythematosus","authors":"M. Kaleda, A. Arefieva, I. Nikishina","doi":"10.14412/1996-7012-2023-4-90-96","DOIUrl":"https://doi.org/10.14412/1996-7012-2023-4-90-96","url":null,"abstract":"In juvenile onset systemic lupus erythematosus (SLE), musculoskeletal involvement is one of the most common manifestations. Musculoskeletal symptoms may be due to disease activity itself, organ damage due to SLE activity, drug exposure, or comorbidities. Although they are not life-threatening, they still have a significant impact on disability severity and social exclusion. This article discusses the clinical features of various causes of musculoskeletal manifestations in SLE with onset in childhood and adolescence, the adequate interpretation of which is important for diagnosing and evaluating SLE activity and for correcting the treatment of the disease, thereby improving the long-term prognosis and quality of life of patients.","PeriodicalId":18651,"journal":{"name":"Modern Rheumatology Journal","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83021224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ways to predict interstitial lung disease in patients with systemic sclerosis: results of an observational study 预测系统性硬化症患者间质性肺疾病的方法:一项观察性研究的结果
Pub Date : 2023-08-20 DOI: 10.14412/1996-7012-2023-4-57-63
D. V. Khorolsky, A. Klimenko, E. Pershina, N. M. Babadeva, A. Kondrashov, N. Shostak, E. Mikheeva, E. Zhilyaev
In patients with systemic sclerosis (SSc), interstitial lung disease (ILD) is a factor in the decline of functional capacity up to disability and is also the leading cause of death. Therefore, one of the most important tasks in the treatment of this group of patients is not only to detect involvement of respiratory system, but also to predict the likelihood of its development.Objective: to study the possibility of predicting the development of ILD and advanced ILD in patients with SSc.Material and methods. The study included 79 patients with SSc (mean age 64.4±11.5 years; 94.9% women) from the Registry of myositis, SSc and Mixed Connective Tissue Diseases (РЕМИССиС) who underwent high-resolution computed tomography (HRCT) of the lungs. Classification trees (CTr) were constructed to predict the development of widespread ILD using the CHAID algorithm (exhaustive). All patients were tested for antibodies against Scl-70 (anti-Scl-70), CENP-B (anti-CENP-B), and PmScl (anti-PmScl).Results and discussion. ILD signs according to HRCT were detected in 53 patients. Fibrotic (34.2%) and cellular (15.2%) types of nonspecific interstitial pneumonia were the most common, and common interstitial pneumonia was less frequent (11.4%).The presence of ILD and advanced ILD (involvement of more than 20% of the lung parenchyma) were significantly associated with the detection of any autoantibodies, except anti-centromere antibodies, an increase in pulmonary artery systolic pressure, a decrease in forced vital capacity, diffusing capacity of the lungs, blood oxygen saturation at rest, and all parameters of six-minute walk test (6MWT), and complaints of shortness of breath. In addition, the presence of extensive ILD was also significantly associated with diffuse SSc and with SSc without skin manifestations.In establishing the CTr, it was found that the development of widespread ILD was unlikely in individuals who were able to walk more than 440 m in 6MWT and had neither anti-Scl-70 nor anti-PmScl.Significant associations were also found between the radiological pattern of ILD and the types of disease-specific antibodies.Conclusion. The 6MWT data in conjunction with the results of testing for SSc-specific autoantibodies provide a very accurate prediction of the presence and extent of ILD. It is advisable to include these indicators in the algorithm for screening and monitoring patients with SSc.
在系统性硬化症(SSc)患者中,间质性肺疾病(ILD)是导致功能下降直至残疾的一个因素,也是导致死亡的主要原因。因此,在这组患者的治疗中,最重要的任务之一不仅是检测呼吸系统的受累,而且要预测其发展的可能性。目的:探讨预测SSc患者ILD及晚期ILD发展的可能性。材料和方法。本研究纳入79例SSc患者(平均年龄64.4±11.5岁;94.9%的女性)来自肌炎、SSc和混合性结缔组织疾病登记处(РЕМИССиС),他们接受了肺部高分辨率计算机断层扫描(HRCT)。构建分类树(CTr),使用CHAID算法(穷举)预测广泛ILD的发展。所有患者均检测Scl-70(抗Scl-70)、CENP-B(抗CENP-B)和PmScl(抗PmScl)抗体。结果和讨论。53例患者HRCT检出ILD征象。非特异性间质性肺炎以纤维化型(34.2%)和细胞型(15.2%)最为常见,普通间质性肺炎发生率较低(11.4%)。ILD和晚期ILD(累及超过20%的肺实质)的存在与除抗着丝粒抗体外的任何自身抗体检测、肺动脉收缩压升高、强迫肺活量降低、肺弥散能力、静息时血氧饱和度和6分钟步行试验(6MWT)的所有参数以及呼吸短促的主叫显著相关。此外,广泛ILD的存在也与弥漫性SSc和无皮肤表现的SSc显著相关。在建立CTr的过程中,研究人员发现,在6MWT中能够行走超过440米且既没有抗scl -70也没有抗pmscl的个体中,不太可能发生广泛的ILD。在ILD的影像学表现和疾病特异性抗体类型之间也发现了显著的相关性。6MWT数据与ssc特异性自身抗体检测结果相结合,可以非常准确地预测ILD的存在和程度。建议将这些指标纳入SSc患者的筛查和监测算法中。
{"title":"Ways to predict interstitial lung disease in patients with systemic sclerosis: results of an observational study","authors":"D. V. Khorolsky, A. Klimenko, E. Pershina, N. M. Babadeva, A. Kondrashov, N. Shostak, E. Mikheeva, E. Zhilyaev","doi":"10.14412/1996-7012-2023-4-57-63","DOIUrl":"https://doi.org/10.14412/1996-7012-2023-4-57-63","url":null,"abstract":"In patients with systemic sclerosis (SSc), interstitial lung disease (ILD) is a factor in the decline of functional capacity up to disability and is also the leading cause of death. Therefore, one of the most important tasks in the treatment of this group of patients is not only to detect involvement of respiratory system, but also to predict the likelihood of its development.Objective: to study the possibility of predicting the development of ILD and advanced ILD in patients with SSc.Material and methods. The study included 79 patients with SSc (mean age 64.4±11.5 years; 94.9% women) from the Registry of myositis, SSc and Mixed Connective Tissue Diseases (РЕМИССиС) who underwent high-resolution computed tomography (HRCT) of the lungs. Classification trees (CTr) were constructed to predict the development of widespread ILD using the CHAID algorithm (exhaustive). All patients were tested for antibodies against Scl-70 (anti-Scl-70), CENP-B (anti-CENP-B), and PmScl (anti-PmScl).Results and discussion. ILD signs according to HRCT were detected in 53 patients. Fibrotic (34.2%) and cellular (15.2%) types of nonspecific interstitial pneumonia were the most common, and common interstitial pneumonia was less frequent (11.4%).The presence of ILD and advanced ILD (involvement of more than 20% of the lung parenchyma) were significantly associated with the detection of any autoantibodies, except anti-centromere antibodies, an increase in pulmonary artery systolic pressure, a decrease in forced vital capacity, diffusing capacity of the lungs, blood oxygen saturation at rest, and all parameters of six-minute walk test (6MWT), and complaints of shortness of breath. In addition, the presence of extensive ILD was also significantly associated with diffuse SSc and with SSc without skin manifestations.In establishing the CTr, it was found that the development of widespread ILD was unlikely in individuals who were able to walk more than 440 m in 6MWT and had neither anti-Scl-70 nor anti-PmScl.Significant associations were also found between the radiological pattern of ILD and the types of disease-specific antibodies.Conclusion. The 6MWT data in conjunction with the results of testing for SSc-specific autoantibodies provide a very accurate prediction of the presence and extent of ILD. It is advisable to include these indicators in the algorithm for screening and monitoring patients with SSc.","PeriodicalId":18651,"journal":{"name":"Modern Rheumatology Journal","volume":"88 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79978518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Early diagnosis of coxitis in ankylosing spondylitis 强直性脊柱炎中结缔炎的早期诊断
Pub Date : 2023-08-20 DOI: 10.14412/1996-7012-2023-4-7-12
S. Erdes, E. Agafonova, T. Dubinina, A. Demina, A. Smirnov
Coxitis is one of the characteristic clinical manifestations of ankylosing spondylitis (AS). Hip joint (HJ) involvement in AS is considered an un-favorable prognostic factor. Early detection of coxitis is of great importance, since with the timely initiation of adequate treatment, the risk of developing irreversible changes in HJ can be reduced.The lecture discusses the issues of clinical and instrumental diagnosis of coxitis in AS and presents an algorithm for its early detection developed by the authors.
脊柱炎是强直性脊柱炎(AS)的特征性临床表现之一。髋关节(HJ)受累被认为是不利的预后因素。早期发现结肠炎是非常重要的,因为及时开始适当的治疗,可以降低HJ发生不可逆变化的风险。讲座讨论的问题,临床和仪器诊断的结肠炎,并提出了一个算法,其早期检测开发的作者。
{"title":"Early diagnosis of coxitis in ankylosing spondylitis","authors":"S. Erdes, E. Agafonova, T. Dubinina, A. Demina, A. Smirnov","doi":"10.14412/1996-7012-2023-4-7-12","DOIUrl":"https://doi.org/10.14412/1996-7012-2023-4-7-12","url":null,"abstract":"Coxitis is one of the characteristic clinical manifestations of ankylosing spondylitis (AS). Hip joint (HJ) involvement in AS is considered an un-favorable prognostic factor. Early detection of coxitis is of great importance, since with the timely initiation of adequate treatment, the risk of developing irreversible changes in HJ can be reduced.The lecture discusses the issues of clinical and instrumental diagnosis of coxitis in AS and presents an algorithm for its early detection developed by the authors.","PeriodicalId":18651,"journal":{"name":"Modern Rheumatology Journal","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77476855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
DNA double-strand breaks in immunoinflammatory rheumatic diseases 免疫炎性风湿病的DNA双链断裂
Pub Date : 2023-08-20 DOI: 10.14412/1996-7012-2023-4-13-18
A. Avdeeva, A. Aleksankin, Z. Verizhnikova, V. Rybakova, M. Diatroptov, Y. Gorbunova, A. Mesnyankina, D. A. Paranich, A. Lila, E. Nasonov
Objective: To study the frequency of spontaneous foci of DNA double-strand breaks (DSBs) in patients with immune-inflammatory rheumatic diseases (IIRD), their relationship to disease activity, levels of inflammatory markers, and levels of autoantibodies.Material and methods. The analysis included 40 patients with IIRD, including 19 patients with rheumatoid arthritis (RA, including 16 women, median disease duration 60 [20; 103] months, DAS28 was 5.05 [4.06; 5.9]) and 21 patients with systemic lupus erythematosus (SLE, 19 women, median disease duration 96.0 [40.0; 158.0] months, SLEDAI-2K 8.0 [4.0; 12.0]). The control group consisted of 17 healthy donors matched for sex and age.DNA DSBs were identified as discrete foci by immunofluorescence staining of lymphocyte cultures with antibodies against γH2AX and 53BP1 and subsequently analysed using the automated AKLIDES automated platform (Medipan).Results and discussion. There were no significant differences in the number of spontaneous DNA DSBs in patients with RA and healthy donors (p>0.05), a lower number of cells with the 53BP1 focus and a lower percentage of cells damaged in this focus were found in patients with SLE than in controls. There was a positive correlation between the number of γH2AXdamaged cells and CDAI(r=0.45, p=0.035), the number of cells with 53BP1 ruptures and the level of rheumatoid factor IgM (r=0.63, p=0.005) and ESR (r=0.53, p=0.02). In the group of SLE patients, a positive correlation was observed between the number of cells with breaks in the γH2AX focus and the level of antibodies against double-stranded DNA (anti-dsDNA; r=0.56, p=0.007), the average number of breaks in the cell in the γH2AX focus with the level of anti-dsDNA (r=0.57, p=0.004).Conclusion. The number of DNA DSBs may be an additional indicator of IIRD activity. In patients with SLE, DNA repair processes appear to be impaired, which is associated with the high activity of the disease.
目的:探讨免疫-炎症性风湿病(IIRD)患者DNA双链断裂(DSBs)自发灶发生频率及其与疾病活动度、炎症标志物水平和自身抗体水平的关系。材料和方法。分析纳入40例IIRD患者,其中类风湿关节炎(RA)患者19例,女性16例,中位病程60 [20;103]月,DAS28为5.05 [4.06;5.9])和21例系统性红斑狼疮(SLE,女性19例,中位病程96.0 [40.0;158.0]月,SLEDAI-2K 8.0 [4.0;12.0])。对照组由17名符合性别和年龄的健康捐赠者组成。用抗γH2AX和53BP1抗体对淋巴细胞培养物进行免疫荧光染色,鉴定DNA dsb为离散灶,随后使用自动化AKLIDES自动化平台(Medipan)进行分析。结果和讨论。RA患者和健康供者自发性DNA dsb的数量没有显著差异(p>0.05), SLE患者中53BP1病灶的细胞数量和该病灶的细胞受损百分比低于对照组。γ - h2ax损伤细胞数与CDAI(r=0.45, p=0.035)、53BP1破裂细胞数与类风湿因子IgM (r=0.63, p=0.005)、ESR (r=0.53, p=0.02)呈正相关。在SLE患者组中,观察到γ - h2ax病灶断裂的细胞数量与抗双链DNA (anti-dsDNA;r=0.56, p=0.007),抗dsdna水平与γ - h2ax灶细胞的平均断裂数呈正相关(r=0.57, p=0.004)。DNA dsb的数量可能是IIRD活性的另一个指标。在SLE患者中,DNA修复过程似乎受损,这与疾病的高活性有关。
{"title":"DNA double-strand breaks in immunoinflammatory rheumatic diseases","authors":"A. Avdeeva, A. Aleksankin, Z. Verizhnikova, V. Rybakova, M. Diatroptov, Y. Gorbunova, A. Mesnyankina, D. A. Paranich, A. Lila, E. Nasonov","doi":"10.14412/1996-7012-2023-4-13-18","DOIUrl":"https://doi.org/10.14412/1996-7012-2023-4-13-18","url":null,"abstract":"Objective: To study the frequency of spontaneous foci of DNA double-strand breaks (DSBs) in patients with immune-inflammatory rheumatic diseases (IIRD), their relationship to disease activity, levels of inflammatory markers, and levels of autoantibodies.Material and methods. The analysis included 40 patients with IIRD, including 19 patients with rheumatoid arthritis (RA, including 16 women, median disease duration 60 [20; 103] months, DAS28 was 5.05 [4.06; 5.9]) and 21 patients with systemic lupus erythematosus (SLE, 19 women, median disease duration 96.0 [40.0; 158.0] months, SLEDAI-2K 8.0 [4.0; 12.0]). The control group consisted of 17 healthy donors matched for sex and age.DNA DSBs were identified as discrete foci by immunofluorescence staining of lymphocyte cultures with antibodies against γH2AX and 53BP1 and subsequently analysed using the automated AKLIDES automated platform (Medipan).Results and discussion. There were no significant differences in the number of spontaneous DNA DSBs in patients with RA and healthy donors (p>0.05), a lower number of cells with the 53BP1 focus and a lower percentage of cells damaged in this focus were found in patients with SLE than in controls. There was a positive correlation between the number of γH2AXdamaged cells and CDAI(r=0.45, p=0.035), the number of cells with 53BP1 ruptures and the level of rheumatoid factor IgM (r=0.63, p=0.005) and ESR (r=0.53, p=0.02). In the group of SLE patients, a positive correlation was observed between the number of cells with breaks in the γH2AX focus and the level of antibodies against double-stranded DNA (anti-dsDNA; r=0.56, p=0.007), the average number of breaks in the cell in the γH2AX focus with the level of anti-dsDNA (r=0.57, p=0.004).Conclusion. The number of DNA DSBs may be an additional indicator of IIRD activity. In patients with SLE, DNA repair processes appear to be impaired, which is associated with the high activity of the disease.","PeriodicalId":18651,"journal":{"name":"Modern Rheumatology Journal","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81998419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cardiovascular safety of xanthine oxidase inhibitors: an optimistic and unfinished story 黄嘌呤氧化酶抑制剂的心血管安全性:一个乐观和未完成的故事
Pub Date : 2023-08-20 DOI: 10.14412/1996-7012-2023-4-97-102
Максим Сергеевич Елисеев, Eliseev M. Zhelyabina O.V V.A. Nasonova, Maxim Sergeevich Eliseev
Gout is associated with a high risk of cardiovascular diseases and associated mortality. Possible causes of the disease include persistent uncontrolled hyperuricemia, a chronic microcrystalline inflammation that develops in the vascular wall and even in atherosclerotic plaques. These processes, which contribute to oxidative stress and the formation of peroxidation products, may be a target for xanthine oxidase inhibitors — allopurinol and febuxostat. Their rational use, aimed at complete dissolution of urate crystal deposits in gout patients, results in improvement of endothelial function, lowering of blood pressure, and possibly reduction of all-cause and cardiovascular mortality. The effects on cardiovascular risk and safety of these drugs are believed to be comparable, greatly expanding the options for gout therapy.
痛风与心血管疾病和相关死亡率的高风险相关。可能的病因包括持续不受控制的高尿酸血症,一种发生在血管壁甚至动脉粥样硬化斑块中的慢性微晶炎症。这些过程有助于氧化应激和过氧化产物的形成,可能是黄嘌呤氧化酶抑制剂-别嘌呤醇和非布司他的靶标。合理使用它们,旨在完全溶解痛风患者的尿酸盐晶体沉积,从而改善内皮功能,降低血压,并可能降低全因死亡率和心血管死亡率。这些药物对心血管风险和安全性的影响被认为是相当的,极大地扩大了痛风治疗的选择。
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引用次数: 0
Dystrophic calciphylaxis in panniculitis: features of the clinical picture and diagnosis 泛膜炎的营养不良性钙化反应:临床表现和诊断的特点
Pub Date : 2023-08-20 DOI: 10.14412/1996-7012-2023-4-42-49
O. Egorova, A. Datsina, M. Severinova
The clinical presentation of lobular panniculitis (PN) associated with calciphylaxis (CP, calcification) can vary widely and may be associated with joint and internal organs involvement, making the diagnosis of the disease difficult.Objective: to evaluate the frequency and significance of CP in patients with PN using long-term prospective follow-up.Material and methods. From 2018 to 2023, at the V.A. Nasonova Research Institute of Rheumatology 217 patients with referral diagnosis "erythema nodosum" or "panniculitis" were examined. In 19.3% of cases (9 men and 33 women aged 37 to 72 years) CP was confirmed with an average disease duration of 56.3±11.2 months. Clinical examination of patients was performed according to the standards recommended by the Russian Association of Rheumatologists. International criteria were used to confirm the diagnosis of systemic lupus erythematosus (SLE), idiopathic inflammatory myopathies (IIM), systemic sclerosis (SS), and lipodermatosclerosis (LDS). In 12 patients with indurations, pathological examination of biopsy specimens of skin and subcutaneous fatty tissue from the area of induration was performed, which allowed confirming the diagnosis of idiopathic lobular PN (ILPN) in 3 cases. Four grades of calcification were distinguished according to the size and depth of the calcifications. In addition, considering the type of radiological changes and clinical manifestations, four subtypes of CP were identified: mousse-like, stone-like, mesh-like and lamellar-like.Results and discussion. In the study group, the ratio of women to men was 3.6:1, and the mean age was 43.8±7.6 years. On clinical examination we determined, in 60% of cases CP predominantly stone-like subtype (71.4%) of first grade (47.6%), which was significantly more frequently located on the upper and/or lower extremities and/or trunk (57.1%; p=0.05). Using clinical, laboratory and instrumental data, we confirmed the development of CP in ILPN (n=3), SLE (n=3), LDS (n=21), IIM (n=5), SS (n=1), and idiopathic CP (n=9) with a mean disease duration of 8.7±2.4 years.An increase in ESR and CRP levels occurred in different diseases, while urinary syndrome was associated with SLE (66.6%) and an increase in creatinine phosphokinase with IIM. Decreased calcium and 25-hydroxyvitamin D levels and increased phosphorus and parathyroid hormone levels were found in many patients studied.Conclusion. In the absence of clear diagnostic criteria for CP in patients with PN, early diagnosis is critical for the development of an effective multidisciplinary treatment plan.
与钙化反应(CP,钙化)相关的小叶性泛膜炎(PN)的临床表现差异很大,可能与关节和内脏受累有关,使疾病的诊断变得困难。目的:通过长期前瞻性随访,评价PN患者发生CP的频率及意义。材料和方法。从2018年到2023年,在va Nasonova风湿病研究所,研究了217例转诊诊断为“结节性红斑”或“泛膜炎”的患者。19.3%的病例(男9例,女33例,年龄37 ~ 72岁)确诊为CP,平均病程56.3±11.2个月。根据俄罗斯风湿病学家协会推荐的标准对患者进行临床检查。采用国际标准确定系统性红斑狼疮(SLE)、特发性炎性肌病(IIM)、系统性硬化症(SS)和脂质皮肤硬化(LDS)的诊断。在12例硬结患者中,对硬结区皮肤及皮下脂肪组织活检标本进行病理检查,确认3例为特发性小叶PN (idiopathic lobular PN, ILPN)。根据钙化的大小和深度,将钙化分为四个等级。结合影像学改变类型和临床表现,将CP分为摩丝样、石样、网状和板层样4种亚型。结果和讨论。研究组男女比例为3.6:1,平均年龄43.8±7.6岁。在临床检查中,我们确定,在60%的病例中,CP主要是石样亚型(71.4%),一级(47.6%),明显更多地位于上肢和/或下肢和/或躯干(57.1%);p = 0.05)。通过临床、实验室和仪器数据,我们确认了ILPN (n=3)、SLE (n=3)、LDS (n=21)、IIM (n=5)、SS (n=1)和特发性CP (n=9)的CP发展,平均病程为8.7±2.4年。ESR和CRP水平升高发生在不同的疾病中,而泌尿综合征与SLE(66.6%)相关,肌酸酐磷酸激酶升高与IIM相关。在许多患者中发现钙和25-羟基维生素D水平降低,磷和甲状旁腺激素水平升高。在缺乏明确的PN患者CP诊断标准的情况下,早期诊断对于制定有效的多学科治疗计划至关重要。
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引用次数: 0
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Modern Rheumatology Journal
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