Objective: Rheumatoid arthritis (RA) affects multiple organ systems, including the esophagus. Moreover, one of the major side effects of methotrexate (MTX) is gastrointestinal disorders, which are said to affect medication adherence. We investigated the rate of MTX use, dosage, and the use of glucocorticoids (GCs) and oral non-steroidal anti-inflammatory drugs (NSAIDs) in relation to gastroesophageal (GE) symptoms, and whether they influence RA disease activity.
Methods: This study utilized the GerdQ questionnaire to analyze the influence of GE symptoms on RA disease activity and medication adherence. A total of 558 RA patients participated. On the day of the GerdQ questionnaire, data on age, gender, disease duration, RA disease activity, lab results, and lifestyle factors such as smoking history and alcohol consumption were recorded. Detailed drug information on conventional synthetic DMARDs (csDMARDs), biologic/targeted synthetic DMARDs (b/tsDMARDs), glucocorticoids, and NSAIDs were extracted from medical records. Propensity score matching adjusted patient background characteristics.
Results: Before matching, patients with moderate to high disease activity had higher GE symptoms (12.7% vs. 25.6%). After matching, higher GerdQ scores were correlated with increased tender joint counts 28 (TJC28) and worse visual analog scale (VAS) scores. Oral MTX usage was similar, but the dosage was significantly lower in the group with higher GerdQ scores (51.4% vs. 50.8% and 7.7 ± 2.4 mg/wks vs. 6.5 ± 2.6 mg/wks, p < 0.05*).
Conclusions: GE symptoms significantly impact MTX treatment and patient-reported outcomes such as TJC28 and VAS in RA disease activity, highlighting their importance in RA treatment strategies. For clinicians, the study's results will emphasize the importance of monitoring and managing GE symptoms in RA patients, particularly those on MTX therapy. Furthermore, the data could provide a basis for future studies that explore targeted interventions to mitigate GE symptoms and enhance medication adherence, potentially improving RA outcomes.
目的:类风湿关节炎(RA)影响包括食道在内的多个器官系统。此外,甲氨蝶呤(MTX)的主要副作用之一是胃肠道疾病,据说会影响药物依从性。我们调查了甲氨喋呤的使用率、剂量、糖皮质激素(GCs)和口服非甾体抗炎药(NSAIDs)的使用与胃食管(GE)症状的关系,以及它们是否影响RA疾病的活动性。方法:本研究采用GerdQ问卷分析GE症状对RA疾病活动性和药物依从性的影响。共有558名RA患者参与。在进行GerdQ问卷调查当天,记录年龄、性别、病程、类风湿性关节炎疾病活动度、实验室结果以及吸烟史和饮酒等生活方式因素的数据。从医疗记录中提取了常规合成DMARDs (csDMARDs)、生物/靶向合成DMARDs (b/tsDMARDs)、糖皮质激素和非甾体抗炎药的详细药物信息。倾向评分匹配调整患者背景特征。结果:配对前,疾病活动度中高的患者有较高的GE症状(12.7% vs. 25.6%)。匹配后,较高的GerdQ评分与压痛关节计数28 (TJC28)增加和视觉模拟量表(VAS)评分较差相关。口服MTX的使用相似,但在GerdQ评分较高的组中,剂量明显较低(51.4%对50.8%,7.7±2.4 mg/周对6.5±2.6 mg/周)。结论:GE症状显著影响MTX治疗和患者报告的结果,如TJC28和VAS在RA疾病活动性中,突出了它们在RA治疗策略中的重要性。对于临床医生来说,这项研究的结果将强调监测和管理RA患者GE症状的重要性,特别是那些接受MTX治疗的患者。此外,这些数据可以为未来的研究提供基础,探索有针对性的干预措施,以减轻GE症状,增强药物依从性,潜在地改善RA的预后。
{"title":"Utility of the GerdQ questionnaire in detecting gastroesophageal symptoms with RA patients.","authors":"Yuji Nozaki, Kazuya Kishimoto, Daisuke Tomita, Tetsu Itami, Chisato Ashida, Koji Kinoshita, Itaru Matsumura","doi":"10.1186/s41927-024-00442-2","DOIUrl":"10.1186/s41927-024-00442-2","url":null,"abstract":"<p><strong>Objective: </strong>Rheumatoid arthritis (RA) affects multiple organ systems, including the esophagus. Moreover, one of the major side effects of methotrexate (MTX) is gastrointestinal disorders, which are said to affect medication adherence. We investigated the rate of MTX use, dosage, and the use of glucocorticoids (GCs) and oral non-steroidal anti-inflammatory drugs (NSAIDs) in relation to gastroesophageal (GE) symptoms, and whether they influence RA disease activity.</p><p><strong>Methods: </strong>This study utilized the GerdQ questionnaire to analyze the influence of GE symptoms on RA disease activity and medication adherence. A total of 558 RA patients participated. On the day of the GerdQ questionnaire, data on age, gender, disease duration, RA disease activity, lab results, and lifestyle factors such as smoking history and alcohol consumption were recorded. Detailed drug information on conventional synthetic DMARDs (csDMARDs), biologic/targeted synthetic DMARDs (b/tsDMARDs), glucocorticoids, and NSAIDs were extracted from medical records. Propensity score matching adjusted patient background characteristics.</p><p><strong>Results: </strong>Before matching, patients with moderate to high disease activity had higher GE symptoms (12.7% vs. 25.6%). After matching, higher GerdQ scores were correlated with increased tender joint counts 28 (TJC28) and worse visual analog scale (VAS) scores. Oral MTX usage was similar, but the dosage was significantly lower in the group with higher GerdQ scores (51.4% vs. 50.8% and 7.7 ± 2.4 mg/wks vs. 6.5 ± 2.6 mg/wks, p < 0.05*).</p><p><strong>Conclusions: </strong>GE symptoms significantly impact MTX treatment and patient-reported outcomes such as TJC28 and VAS in RA disease activity, highlighting their importance in RA treatment strategies. For clinicians, the study's results will emphasize the importance of monitoring and managing GE symptoms in RA patients, particularly those on MTX therapy. Furthermore, the data could provide a basis for future studies that explore targeted interventions to mitigate GE symptoms and enhance medication adherence, potentially improving RA outcomes.</p>","PeriodicalId":9150,"journal":{"name":"BMC Rheumatology","volume":"8 1","pages":"73"},"PeriodicalIF":2.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-21DOI: 10.1186/s41927-024-00450-2
Huarun Li, Haobin Zhang, Xiangyue Zhao, Jinping Huang, Junguo Zhang, Zhaoyan Liu, Ju Wen, Si Qin
Background: Psoriasis is an immune-mediated chronic inflammatory disease associated with multiple factors. To evaluate the extent to which C-reactive protein (CRP) and genetic predisposition affect the incidence of psoriasis.
Methods: The cohort study retrieved 420,040 participants without psoriasis at baseline from the UK Biobank. Serum CRP was categorized into two levels: < 2 mg/L (normal) and ≥ 2 mg/L (elevated). The polygenic risk score (PRS) was used to estimate genetic predisposition, and was characterized as low, moderate and high PRS. The possible interaction and joint associations between CRP and PRS were assessed using Cox proportional hazards models.
Results: Participants with high CRP levels had an increased risk of incident psoriasis compared to those with low CRP levels (HR: 1.26, 95% CI: 1.18-1.34). Participants with high CRP levels and high PRS had the highest risk of incident psoriasis [2.24 (95% CI: 2.01, 2.49)], compared with those had low CRP levels and low PRS. Significant additive and multiplicative interaction were found between CRP and PRS in relation to the incidence of psoriasis.
Conclusions: Our results suggest that higher CRP concentration may be associated with higher psoriasis incidence, with a more pronounced association observed in individuals with high PRS for psoriasis. So, clinicians should be aware that the risk of incident psoriasis may increase in general population with high CRP levels and high PRS, so that early investigation and intervention can be initiated.
{"title":"The role of C-reactive protein and genetic predisposition in the risk of psoriasis: results from a national prospective cohort.","authors":"Huarun Li, Haobin Zhang, Xiangyue Zhao, Jinping Huang, Junguo Zhang, Zhaoyan Liu, Ju Wen, Si Qin","doi":"10.1186/s41927-024-00450-2","DOIUrl":"10.1186/s41927-024-00450-2","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis is an immune-mediated chronic inflammatory disease associated with multiple factors. To evaluate the extent to which C-reactive protein (CRP) and genetic predisposition affect the incidence of psoriasis.</p><p><strong>Methods: </strong>The cohort study retrieved 420,040 participants without psoriasis at baseline from the UK Biobank. Serum CRP was categorized into two levels: < 2 mg/L (normal) and ≥ 2 mg/L (elevated). The polygenic risk score (PRS) was used to estimate genetic predisposition, and was characterized as low, moderate and high PRS. The possible interaction and joint associations between CRP and PRS were assessed using Cox proportional hazards models.</p><p><strong>Results: </strong>Participants with high CRP levels had an increased risk of incident psoriasis compared to those with low CRP levels (HR: 1.26, 95% CI: 1.18-1.34). Participants with high CRP levels and high PRS had the highest risk of incident psoriasis [2.24 (95% CI: 2.01, 2.49)], compared with those had low CRP levels and low PRS. Significant additive and multiplicative interaction were found between CRP and PRS in relation to the incidence of psoriasis.</p><p><strong>Conclusions: </strong>Our results suggest that higher CRP concentration may be associated with higher psoriasis incidence, with a more pronounced association observed in individuals with high PRS for psoriasis. So, clinicians should be aware that the risk of incident psoriasis may increase in general population with high CRP levels and high PRS, so that early investigation and intervention can be initiated.</p>","PeriodicalId":9150,"journal":{"name":"BMC Rheumatology","volume":"8 1","pages":"72"},"PeriodicalIF":2.1,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives: We investigated the longitudinal association between Serum Urate (SU) level and Acute Myocardial Infarction (AMI), Stroke, End Stage Renal Failure (ESRF) and all-cause mortality.
Design: We conducted a retrospective hospital-based cohort study of individuals with gout managed in specialist outpatient clinics. Cox proportional hazards regression was used to estimate HR and 95% CI, with adjustments for potential confounders. Where the proportional hazard assumption was violated, stratified Cox regression was applied instead.
Setting: An acute care tertiary hospital in Singapore.
Participants: Individuals with a first gout diagnosis between 2007-2017, identified through (i) primary discharge diagnosis, (ii) diagnosis from the Rheumatology SOC (iii) patient history of a clinical encounter at the Rheumatology SOC plus use of urate-lowering therapy/colchicine.
Main outcome measures: All-cause mortality, AMI, Stroke and ESRF ascertained through data linkage with the National Registry of Diseases Office.
Results: The final cohort comprised 2,866 individuals. Post follow-up, there were 800 deaths and 362, 218 and 191 occurrences of AMI, ESRF and stroke respectively. Compared to the reference (second-lowest) SU quartile, being in the highest SU quartile was associated with a significantly increased hazard for mortality (HR:1.66, 95% CI:1.36-2.03), incident ESRF (HR:3.02, 95% CI:2.00-4.56), and increased hazard for incident AMI (HR:1.42, 95% CI:1.06-1.91). The p-trend for all 3 outcomes was significant. No significant association was found between SU quartile and hazard for incident stroke.
Conclusions: This study found that individuals with gout managed at SOC who had higher baseline SU levels had an increased hazard for all-cause mortality, ESRF, and AMI.
{"title":"Association between serum urate levels and all-cause mortality, cardiovascular and renal outcomes among gout patients in Singapore.","authors":"Moses Yidong Lim, Weixiang Lian, Hwee Pin Phua, Htet Lin Htun, Kok Ooi Kong, Ling Li Foo, Teo Min-Li Claire, Wei-Yen Lim","doi":"10.1186/s41927-024-00449-9","DOIUrl":"10.1186/s41927-024-00449-9","url":null,"abstract":"<p><strong>Objectives: </strong>We investigated the longitudinal association between Serum Urate (SU) level and Acute Myocardial Infarction (AMI), Stroke, End Stage Renal Failure (ESRF) and all-cause mortality.</p><p><strong>Design: </strong>We conducted a retrospective hospital-based cohort study of individuals with gout managed in specialist outpatient clinics. Cox proportional hazards regression was used to estimate HR and 95% CI, with adjustments for potential confounders. Where the proportional hazard assumption was violated, stratified Cox regression was applied instead.</p><p><strong>Setting: </strong>An acute care tertiary hospital in Singapore.</p><p><strong>Participants: </strong>Individuals with a first gout diagnosis between 2007-2017, identified through (i) primary discharge diagnosis, (ii) diagnosis from the Rheumatology SOC (iii) patient history of a clinical encounter at the Rheumatology SOC plus use of urate-lowering therapy/colchicine.</p><p><strong>Main outcome measures: </strong>All-cause mortality, AMI, Stroke and ESRF ascertained through data linkage with the National Registry of Diseases Office.</p><p><strong>Results: </strong>The final cohort comprised 2,866 individuals. Post follow-up, there were 800 deaths and 362, 218 and 191 occurrences of AMI, ESRF and stroke respectively. Compared to the reference (second-lowest) SU quartile, being in the highest SU quartile was associated with a significantly increased hazard for mortality (HR:1.66, 95% CI:1.36-2.03), incident ESRF (HR:3.02, 95% CI:2.00-4.56), and increased hazard for incident AMI (HR:1.42, 95% CI:1.06-1.91). The p-trend for all 3 outcomes was significant. No significant association was found between SU quartile and hazard for incident stroke.</p><p><strong>Conclusions: </strong>This study found that individuals with gout managed at SOC who had higher baseline SU levels had an increased hazard for all-cause mortality, ESRF, and AMI.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9150,"journal":{"name":"BMC Rheumatology","volume":"8 1","pages":"71"},"PeriodicalIF":2.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: This study aimed to determine the therapeutic efficacy of tacrolimus (TAC) with mycophenolate mofetil (MMF) or cyclophosphamide (CYC) on the renal response in systemic lupus erythematosus (SLE) patients.
Methods: A retrospective cohort study based on medical data was conducted among SLE patients who took at least one of the following medicines in 2010-2021: TAC, MMF and CYC. The odds ratio (OR) and 95% confidence interval (CI) were calculated, and the synergistic interaction was estimated using logistic regression models.
Results: Among 793 SLE patients, 27.9% patients (221 cases) achieved CR after at least 3 months. The TAC use was positively associated with CR with an adjusted OR (95% CI) of 2.82 (1.89, 4.22) overall and in subgroups of SLE patients with SLEDAI scores > 12, moderate or severe urinary protein and comorbidities. The dose-response effect on CR was also observed at TAC doses greater than 4 mg/d and more than 180 days, with adjusted ORs (95% CIs) of 5.65 (2.35, 13.55) and 3.60 (2.02, 6.41), respectively. Moreover, the combined effect of TAC with MMF or CYC was better than that of monotherapy, there was significant synergistic interactions with adjusted ORs (95% CIs) of 2.43 (1.20, 4.92) and 3.14 (1.49, 6.64), respectively, and similar results were observed for the combination of different doses of TAC with MMF or CYC.
Conclusion: TAC can effectively alleviate the condition of patients with SLE and may interact with MMF or CYC, which suggests that the combination therapy of TAC with MMF or CYC may produce greater benefits for patients with SLE.
Trial registration: This is a purely observational study that does not require registration.
{"title":"Effect of tacrolimus with mycophenolate mofetil or cyclophosphamide on the renal response in systemic lupus erythematosus patients.","authors":"Siqin Sun, Xueyi Zhang, Qingqing Guo, Xiaojun Tang, Wei Shen, Jun Liang, Genhong Yao, Linyu Geng, Shuai Ding, Hongwei Chen, Hong Wang, Bingzhu Hua, Huayong Zhang, Xuebing Feng, Ziyi Jin, Lingyun Sun","doi":"10.1186/s41927-024-00439-x","DOIUrl":"10.1186/s41927-024-00439-x","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to determine the therapeutic efficacy of tacrolimus (TAC) with mycophenolate mofetil (MMF) or cyclophosphamide (CYC) on the renal response in systemic lupus erythematosus (SLE) patients.</p><p><strong>Methods: </strong>A retrospective cohort study based on medical data was conducted among SLE patients who took at least one of the following medicines in 2010-2021: TAC, MMF and CYC. The odds ratio (OR) and 95% confidence interval (CI) were calculated, and the synergistic interaction was estimated using logistic regression models.</p><p><strong>Results: </strong>Among 793 SLE patients, 27.9% patients (221 cases) achieved CR after at least 3 months. The TAC use was positively associated with CR with an adjusted OR (95% CI) of 2.82 (1.89, 4.22) overall and in subgroups of SLE patients with SLEDAI scores > 12, moderate or severe urinary protein and comorbidities. The dose-response effect on CR was also observed at TAC doses greater than 4 mg/d and more than 180 days, with adjusted ORs (95% CIs) of 5.65 (2.35, 13.55) and 3.60 (2.02, 6.41), respectively. Moreover, the combined effect of TAC with MMF or CYC was better than that of monotherapy, there was significant synergistic interactions with adjusted ORs (95% CIs) of 2.43 (1.20, 4.92) and 3.14 (1.49, 6.64), respectively, and similar results were observed for the combination of different doses of TAC with MMF or CYC.</p><p><strong>Conclusion: </strong>TAC can effectively alleviate the condition of patients with SLE and may interact with MMF or CYC, which suggests that the combination therapy of TAC with MMF or CYC may produce greater benefits for patients with SLE.</p><p><strong>Trial registration: </strong>This is a purely observational study that does not require registration.</p>","PeriodicalId":9150,"journal":{"name":"BMC Rheumatology","volume":"8 1","pages":"68"},"PeriodicalIF":2.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11654433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: This study aimed to compare the efficacy and safety of baricitinib in patients with rheumatoid arthritis (RA) receiving different doses based on renal function.
Methods: We conducted a retrospective study within the JAK Study Group, involving 23 facilities in Fukuoka Prefecture, examining patients treated with baricitinib for RA. Patients were categorized into two dose groups: 4 mg with normal/mild renal dysfunction and 2 mg with moderate renal dysfunction. Baricitinib's efficacy, retention rate, and safety were compared between the groups after propensity score matching.
Results: After propensity score matching, disease duration, methotrexate dosage, and anti-cyclic citrullinated peptide antibody positivity rate were balanced across 33 patients in both groups. No significant differences were observed between the groups in tender/swollen joint counts, changes in evaluator/patient global assessments, achievement rate of low disease activity, remission rate on clinical/simplified disease activity indices, or retention rate. Additionally, the incidence of adverse events aligned with previous reports, indicating similar drug safety profiles.
Conclusions: Baricitinib 2 mg in RA patients with moderate renal dysfunction showed comparable efficacy and retention rate to 4 mg in patients with normal/mild renal dysfunction. The incidence and types of adverse events were consistent with previous studies, indicating the safety of the drug at these dosages.
{"title":"Efficacy and safety of baricitinib in rheumatoid arthritis patients with moderate renal impairment: a multicenter propensity score matching study.","authors":"Akira Maeyama, Masakazu Kondo, Hiroshi Harada, Eisuke Shono, Ryuji Nagamine, Tomomi Tsuru, Yasushi Inoue, Munetoshi Nakashima, Yutaro Yamasaki, Hiroaki Niiro, Yasuharu Nakashima, Takuaki Yamamoto","doi":"10.1186/s41927-024-00446-y","DOIUrl":"10.1186/s41927-024-00446-y","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to compare the efficacy and safety of baricitinib in patients with rheumatoid arthritis (RA) receiving different doses based on renal function.</p><p><strong>Methods: </strong>We conducted a retrospective study within the JAK Study Group, involving 23 facilities in Fukuoka Prefecture, examining patients treated with baricitinib for RA. Patients were categorized into two dose groups: 4 mg with normal/mild renal dysfunction and 2 mg with moderate renal dysfunction. Baricitinib's efficacy, retention rate, and safety were compared between the groups after propensity score matching.</p><p><strong>Results: </strong>After propensity score matching, disease duration, methotrexate dosage, and anti-cyclic citrullinated peptide antibody positivity rate were balanced across 33 patients in both groups. No significant differences were observed between the groups in tender/swollen joint counts, changes in evaluator/patient global assessments, achievement rate of low disease activity, remission rate on clinical/simplified disease activity indices, or retention rate. Additionally, the incidence of adverse events aligned with previous reports, indicating similar drug safety profiles.</p><p><strong>Conclusions: </strong>Baricitinib 2 mg in RA patients with moderate renal dysfunction showed comparable efficacy and retention rate to 4 mg in patients with normal/mild renal dysfunction. The incidence and types of adverse events were consistent with previous studies, indicating the safety of the drug at these dosages.</p>","PeriodicalId":9150,"journal":{"name":"BMC Rheumatology","volume":"8 1","pages":"69"},"PeriodicalIF":2.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11653574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: In patients with Systemic lupus erythematosus (SLE), osteonecrosis of various joints is a debilitating complication associated with the disease and its treatment, in which a considerable proportion of osteonecrosis may be asymptomatic. Recognizing the crucial role of early and timely detection, as well as appropriate management of asymptomatic osteonecrosis, in preventing joint destruction, we conducted a study to evaluate the prevalence of asymptomatic osteonecrosis in SLE patients who have already been diagnosed with symptomatic osteonecrosis. Additionally, we aimed to examine the relationship between proposed risk factors of osteonecrosis and the development of asymptomatic osteonecrosis.
Methods: In this cross-sectional study, Patients with recently diagnosed symptomatic osteonecrosis of at least one joint were selected by reviewing data from the digital medical record system of the Rheumatology Research Center. The patients underwent three-phase Single Photon Emission Computed Tomography (SPECT) bone scintigraphy to screen for other asymptomatic osteonecrotic joints. MRI was subsequently performed on the asymptomatic osteonecrotic sites for further diagnostic confirmation. The study evaluated the prevalence of asymptomatic osteonecrosis, the extent of joint involvement, the specific locations of osteonecrosis, the most commonly affected joints, and the risk factors for asymptomatic osteonecrosis.
Results: Eight out of the 17 patients (47%) who participated in our research were found to have asymptomatic osteonecrosis. The most commonly affected joint without symptoms was the left knee (25%), while the most frequently affected joint with symptoms was the left hip (23.07%). The only statistically significant difference observed between patients with and without asymptomatic osteonecrosis in this study was the age at which the disease first appeared (p = 0.046) and this age was higher among patients with asymptomatic osteonecrosis.
Conclusions: Our research provides further evidence of the high incidence of asymptomatic osteonecrosis in individuals with SLE due to the nature of the disease and the frequent use of high-dose corticosteroids. It underscores the importance of early detection through whole-body SPECT bone scintigraphy and MRI, as well as prompt intervention in order to avert the incapacitating effects of osteonecrosis.
{"title":"Asymptomatic multifocal avascular necrosis, a commonly overlooked finding in patients with systemic lupus erythematosus.","authors":"Forough Nadi, Esmat Abdollahpour, Babak Fallahi, Leila Aghaghazvini, Majid Alikhani, Mohammad Nejadhosseinian, Seyedeh Tahereh Faezi","doi":"10.1186/s41927-024-00440-4","DOIUrl":"10.1186/s41927-024-00440-4","url":null,"abstract":"<p><strong>Background: </strong>In patients with Systemic lupus erythematosus (SLE), osteonecrosis of various joints is a debilitating complication associated with the disease and its treatment, in which a considerable proportion of osteonecrosis may be asymptomatic. Recognizing the crucial role of early and timely detection, as well as appropriate management of asymptomatic osteonecrosis, in preventing joint destruction, we conducted a study to evaluate the prevalence of asymptomatic osteonecrosis in SLE patients who have already been diagnosed with symptomatic osteonecrosis. Additionally, we aimed to examine the relationship between proposed risk factors of osteonecrosis and the development of asymptomatic osteonecrosis.</p><p><strong>Methods: </strong>In this cross-sectional study, Patients with recently diagnosed symptomatic osteonecrosis of at least one joint were selected by reviewing data from the digital medical record system of the Rheumatology Research Center. The patients underwent three-phase Single Photon Emission Computed Tomography (SPECT) bone scintigraphy to screen for other asymptomatic osteonecrotic joints. MRI was subsequently performed on the asymptomatic osteonecrotic sites for further diagnostic confirmation. The study evaluated the prevalence of asymptomatic osteonecrosis, the extent of joint involvement, the specific locations of osteonecrosis, the most commonly affected joints, and the risk factors for asymptomatic osteonecrosis.</p><p><strong>Results: </strong>Eight out of the 17 patients (47%) who participated in our research were found to have asymptomatic osteonecrosis. The most commonly affected joint without symptoms was the left knee (25%), while the most frequently affected joint with symptoms was the left hip (23.07%). The only statistically significant difference observed between patients with and without asymptomatic osteonecrosis in this study was the age at which the disease first appeared (p = 0.046) and this age was higher among patients with asymptomatic osteonecrosis.</p><p><strong>Conclusions: </strong>Our research provides further evidence of the high incidence of asymptomatic osteonecrosis in individuals with SLE due to the nature of the disease and the frequent use of high-dose corticosteroids. It underscores the importance of early detection through whole-body SPECT bone scintigraphy and MRI, as well as prompt intervention in order to avert the incapacitating effects of osteonecrosis.</p>","PeriodicalId":9150,"journal":{"name":"BMC Rheumatology","volume":"8 1","pages":"70"},"PeriodicalIF":2.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11653805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-05DOI: 10.1186/s41927-024-00441-3
L F Perez-Garcia, E Röder, H Pastoor, A C Lozada-Navarro, I Colunga-Pedraza, T Vargas-Aguirre, J van Exel, A Vargas-Guerrero, R J E M Dolhain
Objectives: Inflammatory arthritis (IA) has been associated with various problems related to male sexual and reproductive health (SRH). However, addressing these issues in the clinic remains a challenge. In this study, we aimed to describe the viewpoints of rheumatologists and male patients with IA regarding the aspects that influence their communication about SRH.
Methods: Rheumatologists and adult men with IA were invited to participate. This study uses Q-methodology, a mixed methods approach to systematically study subjectivity. Participants ranked 32 aspects according to their degree of influence (least-most influence) in addressing SRH and were then interviewed. Factor analysis was used to identify common patterns in the rankings. These patterns were interpreted as the different viewpoints of rheumatologists and male patients, supported by the qualitative data from the interviews. To obtain more generalizable results, the study was conducted in two countries with different socio-cultural backgrounds and healthcare systems, The Netherlands and Mexico.
Results: 30 rheumatologists and 30 men with IA were included in each country. The analysis revealed three viewpoints in each group. Rheumatologists are more likely to be influenced by aspects such as the patient's desire to become a father or the patients' (young) age, but patients by a much more diverse pool of aspects, such as potential side effects of medication on their sexual function.
Conclusions: This study identified different viewpoints on the aspects that influence discussing SRH between rheumatologists and male patients, and important differences in viewpoints between both groups. Further research is needed to reach consensus on how and when rheumatologists and male patients should discuss SRH.
{"title":"Discussing male sexual and reproductive health in the rheumatology outpatient clinic: a Q-methodology study.","authors":"L F Perez-Garcia, E Röder, H Pastoor, A C Lozada-Navarro, I Colunga-Pedraza, T Vargas-Aguirre, J van Exel, A Vargas-Guerrero, R J E M Dolhain","doi":"10.1186/s41927-024-00441-3","DOIUrl":"10.1186/s41927-024-00441-3","url":null,"abstract":"<p><strong>Objectives: </strong>Inflammatory arthritis (IA) has been associated with various problems related to male sexual and reproductive health (SRH). However, addressing these issues in the clinic remains a challenge. In this study, we aimed to describe the viewpoints of rheumatologists and male patients with IA regarding the aspects that influence their communication about SRH.</p><p><strong>Methods: </strong>Rheumatologists and adult men with IA were invited to participate. This study uses Q-methodology, a mixed methods approach to systematically study subjectivity. Participants ranked 32 aspects according to their degree of influence (least-most influence) in addressing SRH and were then interviewed. Factor analysis was used to identify common patterns in the rankings. These patterns were interpreted as the different viewpoints of rheumatologists and male patients, supported by the qualitative data from the interviews. To obtain more generalizable results, the study was conducted in two countries with different socio-cultural backgrounds and healthcare systems, The Netherlands and Mexico.</p><p><strong>Results: </strong>30 rheumatologists and 30 men with IA were included in each country. The analysis revealed three viewpoints in each group. Rheumatologists are more likely to be influenced by aspects such as the patient's desire to become a father or the patients' (young) age, but patients by a much more diverse pool of aspects, such as potential side effects of medication on their sexual function.</p><p><strong>Conclusions: </strong>This study identified different viewpoints on the aspects that influence discussing SRH between rheumatologists and male patients, and important differences in viewpoints between both groups. Further research is needed to reach consensus on how and when rheumatologists and male patients should discuss SRH.</p>","PeriodicalId":9150,"journal":{"name":"BMC Rheumatology","volume":"8 1","pages":"67"},"PeriodicalIF":2.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11622486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Cholesterol embolism causes various organ dysfunctions, including skin, kidney, and gastrointestinal tract dysfunction, as well as immunological abnormalities, such as hypocomplementemia and eosinophilia. However, only a few cases of vasculitis accompanied by cholesterol embolism have been reported.
Case presentation: We present the case of an 82-year-old man with cholesterol embolism who also developed small-vessel vasculitis of the skin and muscles. The patient had a persistent fever, and blood tests showed eosinophilia and hypocomplementemia. Two months later, the patient developed a skin rash and myalgia in the thighs. Magnetic resonance imaging of the thighs revealed diffuse intramuscular hyperintensities on T2-weighted images and short tau inversion recovery sequences in the hamstrings and quadriceps femoris. Histological findings of the skin and muscle revealed small-vessel vasculitis, and random skin biopsy revealed cholesterol embolism. We diagnosed the patient with cholesterol embolism accompanied by small-vessel vasculitis of the skin and femoral muscles. Methylprednisolone was administered intravenously, and oral prednisolone was initiated. Muscle tenderness improved rapidly after the initiation of glucocorticoid therapy. However, he developed superior mesenteric artery embolization and died.
Conclusions: Our case demonstrates that cholesterol embolism can be accompanied by small-vessel vasculitis of the skin and muscles.
{"title":"Small-vessel vasculitis associated with cholesterol embolism: a case report.","authors":"Daichi Umemoto, Ichizo Nishino, Daisuke Yamashita, Naoto Ishimaru, Hiroaki Nishioka","doi":"10.1186/s41927-024-00437-z","DOIUrl":"10.1186/s41927-024-00437-z","url":null,"abstract":"<p><strong>Background: </strong>Cholesterol embolism causes various organ dysfunctions, including skin, kidney, and gastrointestinal tract dysfunction, as well as immunological abnormalities, such as hypocomplementemia and eosinophilia. However, only a few cases of vasculitis accompanied by cholesterol embolism have been reported.</p><p><strong>Case presentation: </strong>We present the case of an 82-year-old man with cholesterol embolism who also developed small-vessel vasculitis of the skin and muscles. The patient had a persistent fever, and blood tests showed eosinophilia and hypocomplementemia. Two months later, the patient developed a skin rash and myalgia in the thighs. Magnetic resonance imaging of the thighs revealed diffuse intramuscular hyperintensities on T2-weighted images and short tau inversion recovery sequences in the hamstrings and quadriceps femoris. Histological findings of the skin and muscle revealed small-vessel vasculitis, and random skin biopsy revealed cholesterol embolism. We diagnosed the patient with cholesterol embolism accompanied by small-vessel vasculitis of the skin and femoral muscles. Methylprednisolone was administered intravenously, and oral prednisolone was initiated. Muscle tenderness improved rapidly after the initiation of glucocorticoid therapy. However, he developed superior mesenteric artery embolization and died.</p><p><strong>Conclusions: </strong>Our case demonstrates that cholesterol embolism can be accompanied by small-vessel vasculitis of the skin and muscles.</p>","PeriodicalId":9150,"journal":{"name":"BMC Rheumatology","volume":"8 1","pages":"66"},"PeriodicalIF":2.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-29DOI: 10.1186/s41927-024-00433-3
Klara Drake Af Hagelsrum, Ingrid Larsson, Ann Bremander, Jon T Einarsson, Elisabet Lindqvist, Elisabeth Mogard
Background: Healthy lifestyle habits (regular physical activity, a healthy diet, no smoking and non-hazardous alcohol consumption) alongside pharmacological treatment can lower the risk of cardiovascular diseases and improve symptoms and quality of life in patients with rheumatoid arthritis (RA). Therefore, healthcare professionals in rheumatology care are urged to discuss lifestyle habits with all patients. The aim of this study was to explore patients' perceptions of lifestyle discussions in early rheumatology care.
Methods: Individual interviews were conducted with 20 patients with RA, 14 women and six men, aged 23 to 77 years, and with a mean disease duration of 2.4 years. All lifestyle discussions were performed during the first year with RA. A qualitative content analysis was performed.
Results: An overarching theme emerged, exploring how patients with RA perceived lifestyle discussions as facilitating self-management. Three categories illustrated this: (1) the usefulness of lifestyle discussions depended on the individual patient's preferences and prioritization for lifestyle support; (2) the design of lifestyle discussions should be based on a person-centred approach, incorporating personalized lifestyle information and providing structured and recurrent support; (3) the outcomes of lifestyle discussions should contribute to enhanced knowledge and motivation for making healthy lifestyle changes.
Conclusion: Lifestyle discussions in early rheumatology care should, according to patients with RA, be based on a person-centred approach, be tailored to each patient's preferences and needs, and have outcomes focusing on patient support for healthy lifestyle changes, all essential elements to facilitate self-management. The present findings can be used to guide the development and implementation of more person-centred lifestyle approaches targeted to facilitate lifestyle changes and benefit cardiovascular disease risk management in early rheumatology care.
{"title":"Lifestyle discussions facilitate self-management in RA: a qualitative study of patients' perceptions.","authors":"Klara Drake Af Hagelsrum, Ingrid Larsson, Ann Bremander, Jon T Einarsson, Elisabet Lindqvist, Elisabeth Mogard","doi":"10.1186/s41927-024-00433-3","DOIUrl":"10.1186/s41927-024-00433-3","url":null,"abstract":"<p><strong>Background: </strong>Healthy lifestyle habits (regular physical activity, a healthy diet, no smoking and non-hazardous alcohol consumption) alongside pharmacological treatment can lower the risk of cardiovascular diseases and improve symptoms and quality of life in patients with rheumatoid arthritis (RA). Therefore, healthcare professionals in rheumatology care are urged to discuss lifestyle habits with all patients. The aim of this study was to explore patients' perceptions of lifestyle discussions in early rheumatology care.</p><p><strong>Methods: </strong>Individual interviews were conducted with 20 patients with RA, 14 women and six men, aged 23 to 77 years, and with a mean disease duration of 2.4 years. All lifestyle discussions were performed during the first year with RA. A qualitative content analysis was performed.</p><p><strong>Results: </strong>An overarching theme emerged, exploring how patients with RA perceived lifestyle discussions as facilitating self-management. Three categories illustrated this: (1) the usefulness of lifestyle discussions depended on the individual patient's preferences and prioritization for lifestyle support; (2) the design of lifestyle discussions should be based on a person-centred approach, incorporating personalized lifestyle information and providing structured and recurrent support; (3) the outcomes of lifestyle discussions should contribute to enhanced knowledge and motivation for making healthy lifestyle changes.</p><p><strong>Conclusion: </strong>Lifestyle discussions in early rheumatology care should, according to patients with RA, be based on a person-centred approach, be tailored to each patient's preferences and needs, and have outcomes focusing on patient support for healthy lifestyle changes, all essential elements to facilitate self-management. The present findings can be used to guide the development and implementation of more person-centred lifestyle approaches targeted to facilitate lifestyle changes and benefit cardiovascular disease risk management in early rheumatology care.</p>","PeriodicalId":9150,"journal":{"name":"BMC Rheumatology","volume":"8 1","pages":"65"},"PeriodicalIF":2.1,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-25DOI: 10.1186/s41927-024-00436-0
Rubén Cuevas-Martínez, Susana Aideé González-Chávez, Mercedes Bermúdez, Joan Sebastian Salas-Leiva, Gregorio Vázquez-Olvera, Luis Carlos Hinojos-Gallardo, Eduardo Chaparro-Barrera, César Pacheco-Silva, Consuelo Romero-Sánchez, Carlos Esteban Villegas-Mercado, César Pacheco-Tena
Background: Intermittent fasting (IF) has shown benefits in various pathological conditions. Although its anti-inflammatory potential has been recognized, its effects on the mechanism underlying rheumatoid arthritis (RA) remain insufficiently characterized. This study aimed to investigate the effects of IF in a murine model of RA.
Methods: Collagen-induced arthritis (CIA) was developed in sixteen male DBA/1 mice, randomly assigned to two groups, with one undergoing IF every other day for four weeks. The effects of IF on joint inflammation and remodeling were evaluated clinically, histologically, and through tomography. Transcriptomic changes were characterized using expression microarrays, validated by RT-qPCR, and confirmed by immunohistochemistry. Additionally, modifications in gut microbiota were assessed through 16 S sequencing.
Results: Mice subjected to IF significantly reduced the incidence and severity of clinical arthritis. Histological and radiographic assessments confirmed a decrease in inflammation and joint damage. Transcriptomic analysis revealed that IF led to the upregulation of 364 genes and the downregulation of 543 genes, with notable reductions in inflammatory signaling pathways associated with RA-related genes, including Cd72, Cd79a, Ifna, Il33, and Bglap 2. Notably, IL33 emerged as a pivotal mediator in the inflammatory processes mitigated by fasting. Key regulators associated with IF effects, such as CEBPA, FOXO1, HIF1A, PPARG, and PPARA, were identified, indicating a complex interplay between metabolic and inflammatory pathways. Furthermore, differential expression of microRNAs and lncRNAs, including miR-15b, miR-103-2, miR-302a, miR-6985, and miR- 5624, was observed. Metagenomic analysis indicated that IF enhanced the abundance and diversity of the gut microbiome, explicitly promoting anti-inflammatory bacterial populations, notably within the genus Ruminococcaceae.
Conclusion: Our findings suggest that IF exerts significant anti-inflammatory and immunoregulatory effects in the context of CIA. Given its non-risky nature, further investigation into the potential benefits of IF in patients with RA is warranted.
Clinical trial number: Not applicable.
背景:间歇性禁食(IF)对各种病理情况都有好处。尽管其抗炎潜力已得到认可,但其对类风湿性关节炎(RA)潜在机制的影响仍未得到充分表征。本研究旨在探讨 IF 在小鼠 RA 模型中的作用:方法:16只雄性DBA/1小鼠被随机分为两组,一组接受IF治疗,每隔一天一次,持续四周;另一组接受IF治疗,持续两周。通过临床、组织学和断层扫描评估了 IF 对关节炎症和重塑的影响。使用表达微阵列描述转录组变化,通过 RT-qPCR 验证,并通过免疫组化证实。此外,还通过 16 S 测序评估了肠道微生物群的变化:结果:接受 IF 治疗的小鼠明显降低了临床关节炎的发病率和严重程度。组织学和放射学评估证实炎症和关节损伤有所减轻。转录组分析显示,IF导致364个基因上调,543个基因下调,与RA相关的炎症信号通路基因明显减少,包括Cd72、Cd79a、Ifna、Il33和Bglap 2。值得注意的是,IL33 是禁食缓解炎症过程的关键介质。与 IF 影响相关的关键调节因子,如 CEBPA、FOXO1、HIF1A、PPARG 和 PPARA,也被确定了出来,这表明代谢和炎症途径之间存在着复杂的相互作用。此外,还观察到了微RNA和lncRNA的差异表达,包括miR-15b、miR-103-2、miR-302a、miR-6985和miR-5624。元基因组分析表明,IF 提高了肠道微生物组的丰度和多样性,明确促进了抗炎细菌种群,尤其是反刍球菌属中的细菌种群:我们的研究结果表明,IF 对 CIA 有显著的抗炎和免疫调节作用。鉴于其无风险的特性,有必要进一步研究 IF 对 RA 患者的潜在益处:临床试验编号:不适用。
{"title":"Intermittent fasting reduces inflammation and joint damage in a murine model of rheumatoid arthritis: insights from transcriptomic and metagenomic analyses.","authors":"Rubén Cuevas-Martínez, Susana Aideé González-Chávez, Mercedes Bermúdez, Joan Sebastian Salas-Leiva, Gregorio Vázquez-Olvera, Luis Carlos Hinojos-Gallardo, Eduardo Chaparro-Barrera, César Pacheco-Silva, Consuelo Romero-Sánchez, Carlos Esteban Villegas-Mercado, César Pacheco-Tena","doi":"10.1186/s41927-024-00436-0","DOIUrl":"10.1186/s41927-024-00436-0","url":null,"abstract":"<p><strong>Background: </strong>Intermittent fasting (IF) has shown benefits in various pathological conditions. Although its anti-inflammatory potential has been recognized, its effects on the mechanism underlying rheumatoid arthritis (RA) remain insufficiently characterized. This study aimed to investigate the effects of IF in a murine model of RA.</p><p><strong>Methods: </strong>Collagen-induced arthritis (CIA) was developed in sixteen male DBA/1 mice, randomly assigned to two groups, with one undergoing IF every other day for four weeks. The effects of IF on joint inflammation and remodeling were evaluated clinically, histologically, and through tomography. Transcriptomic changes were characterized using expression microarrays, validated by RT-qPCR, and confirmed by immunohistochemistry. Additionally, modifications in gut microbiota were assessed through 16 S sequencing.</p><p><strong>Results: </strong>Mice subjected to IF significantly reduced the incidence and severity of clinical arthritis. Histological and radiographic assessments confirmed a decrease in inflammation and joint damage. Transcriptomic analysis revealed that IF led to the upregulation of 364 genes and the downregulation of 543 genes, with notable reductions in inflammatory signaling pathways associated with RA-related genes, including Cd72, Cd79a, Ifna, Il33, and Bglap 2. Notably, IL33 emerged as a pivotal mediator in the inflammatory processes mitigated by fasting. Key regulators associated with IF effects, such as CEBPA, FOXO1, HIF1A, PPARG, and PPARA, were identified, indicating a complex interplay between metabolic and inflammatory pathways. Furthermore, differential expression of microRNAs and lncRNAs, including miR-15b, miR-103-2, miR-302a, miR-6985, and miR- 5624, was observed. Metagenomic analysis indicated that IF enhanced the abundance and diversity of the gut microbiome, explicitly promoting anti-inflammatory bacterial populations, notably within the genus Ruminococcaceae.</p><p><strong>Conclusion: </strong>Our findings suggest that IF exerts significant anti-inflammatory and immunoregulatory effects in the context of CIA. Given its non-risky nature, further investigation into the potential benefits of IF in patients with RA is warranted.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9150,"journal":{"name":"BMC Rheumatology","volume":"8 1","pages":"64"},"PeriodicalIF":2.1,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}