Effects of Swimming Exercise on Serum Inflammatory Markers and HIF-2α mRNA Expression of Cartilage in Rheumatoid Arthritis Model Mice

Author(s):  
Yong-Seok Ji ◽  
Joung-Hee Jon ◽  
Jin-Hwan Yoon
2019 ◽  
Vol 13 (2) ◽  
pp. 140-148
Author(s):  
Mai Nasser ◽  
Noha M. Hazem ◽  
Amany Atwa ◽  
Amina Baiomy

Background: Rheumatoid Arthritis (RA) is an autoimmune, chronic, and systematic disease. It affects joints and bones. The exact etiology of RA is still unclear. Varied genetic and environmental factors have been associated with the increased risk for RA. Overactivation of Toll-Like Receptors (TLRs) could initiate the development of autoimmune diseases including RA. Objective: The aim of the study was to evaluate TLR2 gene expression in rheumatoid arthritis patients and investigate its correlation with the disease activity. Materials and Methods: This study included 60 patients and 20 healthy individuals. The patients were diagnosed with RA according to the 2010 American College of Rheumatology/ European League Against Rheumatism criteria (ACR/EULAR). All included subjects did not have any joint disorders and /or autoimmune diseases. RA disease activity was determined by the disease activity score of 28 joints. Whole blood was collected from all participants. Total RNA extraction was done. TLR2 mRNA expression was assessed by reverse transcription-PCR (RT-PCR). Results: TLR2 mRNA expression was found to be significantly higher in RA patients compared to healthy controls. Also, a strong positive correlation was found between TLR2 expression level and the disease activity score. A non significant positive correlation was found between TLR2 expression and serum Rheumatoid Factor (RF) level. Conclusion: TLR2 pathway may have an important role in RA pathogenesis and could be a new biomarker for diagnosis and monitoring disease activity.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1357.1-1357
Author(s):  
S. M. Lao ◽  
J. Patel

Background:Reactive arthritis is a form of spondyloarthritis with aseptic joint involvement occurring after a gastrointestinal or urogenital infection. Most commonly associated with Chlamydia trachomatis, Salmonella, Shigella, Campylobacter, and Yersinia. Syphilis is an infection caused by the spirochete Treponema pallidum and is not usually associated with reactive arthritis. Syphilis is a great imitator of other diseases due to its broad presentation including painless chancre, constitutional symptoms, adenopathy, rash, synovitis, neurological and ocular findings.Objectives:To discuss a patient who presented with symptoms of rheumatoid arthritis (RA) but was later diagnosed with syphilis.Methods:31 year old male, former tobacco smoker, referred to Rheumatology for sudden onset joint pains, elevated anti-cyclic citrullinated peptide (anti-CCP), and elevated inflammatory markers. He reported pain in bilateral wrists, fingers, and right elbow for 6 weeks. Associated with 45 minutes of morning stiffness and new onset lower back pain without stiffness. He denied trauma, fever, chills, skin rash, dysuria, or diarrhea. Initiated trial naproxen 500mg twice a day only to have minimal relief. Patient is sexually active with men and was recently diagnosed with oropharyngeal gonorrhea treated with azithromycin 4 months prior. All other STI screening including syphilis, gonorrhea, HIV were negative at that time. Patient is on emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis. He denied family history of immune mediated conditions. Exam was significant for mild synovitis of both wrists and bilateral 2nd metacarpophalangeal joints. Initial labs revealed weakly positive anti-CCP 21 (normal <20), sedimentation rate 64 (normal ESR 0-15 mm/hr), C-reactive protein 24 (normal CRP 0-10 mg/L), and negative RF, ANA, HLA B27. During a short trial of prednisone taper, there was temporary improvement in symptoms, however synovitis recurred upon completion. Hydroxychloroquine (HCQ) 200mg twice a day was started for possible RA and he was referred to Ophthalmology for baseline retinopathy screening. Incidentally, he developed right sided blurry vision 2 weeks after initiation of HCQ. He was diagnosed with panuveitis of the right eye with inflammation of the optic nerve head and prednisone 40mg daily was initiated for presumed ocular manifestation of RA. However, further workup of panuveitis revealed reactive Treponema pallidum antibody and RPR quantity 1:32. Prednisone was immediately discontinued and he was referred to the emergency department for possible neurosyphilis.Results:Lumbar puncture showed cerebral spinal fluid with 260 red blood cells, 1 white blood cell, 27mg/dL protein, 60mg/dL glucose, non reactive VDRL, reactive pallidum IgG antibody, and negative cultures. Meningitis and encephalitis panels were negative. Patient completed a 14 day course of IV penicillin G with complete remission of joint pain, visual symptoms, and normalization of anti-CCP, ESR, and CRP.Conclusion:This case highlights how syphilis may mimic signs and symptoms of RA including symmetrical small joint pain, morning stiffness, elevated inflammatory markers, and positive anti-CCP. Anti-CCP is >96% specific for RA but was a false positive in this patient. There have only been few reported cases noting positive anti-CCP with reactive arthritis. This is a rare case of reactive arthritis secondary to syphilis with resolution of symptoms upon treating the syphilis.References:[1]Carter JD. Treating reactive arthritis: insights for the clinician. Ther Adv Musculoskelet Dis. 2010 Feb;2(1):45-54.[2]Cohen SE, Klausner JD, Engelman J, Philip S. Syphilis in the modern era: an update for physicians. Infect Dis Clin North Am. 2013 Dec;27(4):705-22.[3]Singh Sangha M, Wright ML, Ciurtin C. Strongly positive anti-CCP antibodies in patients with sacroiliitis or reactive arthritis post-E. coli infection: A mini case-series based review. Int J Rheum Dis. 2018 Jan;21(1):315-321.Disclosure of Interests:None declared.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 475.2-476
Author(s):  
A. Osailan

Background:People with rheumatoid arthritis (RA) are at high risk for cardiovascular diseases (CVD) and CVD mortality. Reduced Chronotropic response (CR), which produces exercise intolerance, is known as a contributing factor to CVD and mortality. Studies have shown that people with RA have reduced CR. However, knowledge about the factors associated with CR in people with RA is limited.Objectives:To explore the factors associated with CR including CVD risk factors, inflammatory markers and cardiorespiratory fitness (VO2 peak).Methods:106 people with RA completed a treadmill exercise tolerance test while heart rate (HR) was monitored via 12 leads ECG. CR was defined as the percentage of [(achieved peak HR minus resting HR) divided by (age-predicted maximum HR minus resting HR)]. Serological CVD risk factors and inflammatory markers including lipids profile, markers of insulin resistance and sensitivity (HOMA, QUICKi), high sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), fibrinogen and white blood cells (WBC) were examined via a fasted blood sample. VO2 peak was assessed via breath-by-breath gas analysis.Results:34% had reduced CR based on the cut-off value (≤ 80%) and the average CR was 86.2 ± 21%. Body mass index (r=-0.33, p=.001), HOMA (r=-0.26, p=.009), hsCRP (r=-0.23, p=.02), ESR (r=-0.21, p=.04), fibrinogen (r=-0.2, p=.05), WBC (r=-0.21, p=.04) were inversely associated with CR, whereas, high density lipoprotein (HDL) (r=0.43, p<.001), QUICKi (r=0.31, p=.002), and VO2 peak (r=0.4, p<.001) were positively associated with CR. When all the variables were entered into a stepwise linear regression, HDL (p<.001) and VO2 peak (p=.009) were independently associated with CR.Conclusion:The current findings suggest that CR in RA was associated with many CVD risk factors, inflammatory markers, and cardiorespiratory fitness. Among all the varibales, HDL and cardiorespiratory fitness were moderately and independently associated with CR. Future studies should investigate the effect of improving these associated variables on CR in people with RA via exercise training programes.Acknowledgements:Thanks to physical activity in Rheumatoid arthritis research team and Research department in Dudley Hospital. Sincere appreciation and gratitude to Dr Jet Veldhuizen van Zanten, Prof. Joan Duda, and Prof. George Kitas from the University of Birmingham and Prof. George Metsios from the University of Wolverhampton.Disclosure of Interests:None declared


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Melissa Ong ◽  
Mark Gibson ◽  
Gerald Coakley

Abstract Case report - Introduction Severe acute respiratory coronavirus 2 (SARS-CoV-2) is a novel virus that can lead to an excessive immune activation and cytokine response known as Coronavirus disease 2019 (COVID-19) which predominantly affects the lungs. Patients with chronic inflammatory disease on biological immunosuppressive treatments may be at a higher risk of contracting SARS-CoV-2. However, it is yet to be determined whether immunomodulatory medications used in inflammatory diseases have protective capabilities against severe outcomes. Case report - Case description A 51-year old female with a 13-year history of rheumatoid arthritis (RA) presented to hospital with fever, exertional breathlessness, and a non-productive cough. She was diagnosed with seropositive erosive RA at the age of 38 and was on 6-monthly Rituximab infusions and Leflunomide on admission. She had relatively stable pulmonary fibrosis (diagnosed in 2010). Her chest CTs in 2010 and 2018 noted bilateral basal subpleural ground glass change with limited honeycombing and spirometry study revealed FEV1 of 2.2 (82% predicted), VC of 2.7 (87% predicted), DLCO of 7.0 (78% predicted) and kCO of 1.6 (78% predicted). On admission in March 2020, she was hypoxic (oxygen saturation of 88% in room air) and had raised inflammatory markers (CRP 341mg/dL, d-Dimer 914ng/ml, Ferritin 3141ng/ml, LDH 672U/L). Her last Rituximab infusion was 3 months prior and leflunomide was withheld on admission. SARS-CoV-2 PCR nasopharyngeal swab was positive, and she was recruited to the RECOVERY trial, being randomized to Lopinavir-Ritonavir for 10 days. Her oxygen requirements increased, and a CT pulmonary angiogram excluded pulmonary embolism but revealed ground glass changes and extensive multilobar consolidation. She was eligible for recruitment into RECOVERY-2 (tocilizumab) given the ongoing oxygen requirement and elevated CRP, but she was randomised to usual care. She was commenced on 80mg of IV methylprednisolone, a dose chosen because of its proven effectiveness in Acute Respiratory Distress Syndrome. She clinically improved and was discharged from hospital 20 days after starting Methylprednisolone with a CRP of 17mg/dL. Two months after discharge, the patient had repeat spirometry study which noted FEV1 of 1.4 (57% predicted), VC of 1.5 (52% predicted), DLCO of 2.4 (28% predicted) and kCO of 1.0 (47% predicted). A repeat high-resolution chest CT reported significant improvement of peripheral ground glass changes and consolidation, but she is still fatigued and more breathless than previously. Case report - Discussion The RECOVERY trial concluded that Dexamethasone reduced mortality in intubated patients and in hospitalised patients with COVID-19 with a high oxygen requirement. The results were published after this patient was discharged. A hyperinflammatory response to COVID-19 is seen in a subset of patients, and our own hospital data suggest that this condition affects around 5% of admitted COVID-19 patients, but that extreme hyperferritinaemia above 10,000 is extremely rare. Similar responses (known as Haemophagocytic Lymphohistiocytosis [HLH]) are seen with a variety of viral and bacterial infections, in malignancy and in inflammatory rheumatic diseases (Macrophage Activation Syndrome [MAS]), but typically HLH and MAS patients have ferritin &gt; 10,000. It appears unlikely that true HLH is a significant manifestation of COVID-19 infection, but moderate hyperferritinaemia is not uncommon and the results of this study, taken together with case reports and series from China and Italy suggest that similar treatments to those used in HLH may transform the prognosis for COVID-19 patients in this subset. It is unknown whether the recent Rituximab infusion had a role in reducing the “cytokine storm” and delaying progression to severe COVID-19. However, it may be argued that the remaining T cells in B cell depleted patients are sufficient for viral clearance. The long-term impact of SARS-CoV-2 on pulmonary function is still unclear. Our patient had a major deterioration in her lung function when compared to her baseline. There was severe reduction in gas transfer post COVID-19. However, her repeat high resolution CT chest reported substantial improvement in ground glass changes and consolidation. The long-term prognosis is still uncertain. Initial fears that patients on DMARDs and biological therapies for inflammatory rheumatic disease would be extremely vulnerable to COVID-19 have not been confirmed, but patients with extra-articular manifestations on combinations of DMARDs and biological therapies may be a subset at higher risk. Case report - Key learning points Our Intensivist colleagues, early in the COVID-19 outbreak, were understandably cautious about using heavily immunosuppressive treatments for a life-threatening viral infection. Using a multi-disciplinary approach at a time when knowledge of how to treat this condition was rudimentary, along with informed consent from an intelligent and thoughtful patient, we were able to plot a middle path to suppress hyperinflammation without using massively immunosuppressive doses of steroid, with a successful outcome. This patient illustrates one aspect of the hyper-inflammatory response seen in a subset of the most critically ill patients with COVID-19. At the time of writing, the RECOVERY 2 trial is yet to be published, but the rapid improvement in inflammatory markers including CRP and Ferritin, along with a dramatic improvement in clinical state, suggest that relatively modest doses of parenteral steroid have life-saving potential at far lower cost and greater worldwide availability than biological therapies such as Tocilizumab or Anakinra. Trials of Tocilizumab in RECOVERY2 and of Anakinra coordinated by the Hyperinflammation Histio UK Haemophagocytosis Across Specialty Collaboration (HASC), as well as international randomised controlled trials will be critical in determining the optimal treatment strategy for this subset of critically ill COVID-19 patients. The experience of our patient suggests that one arm of such studies should include a relatively modest dose of parenteral steroid, be that Dexamethasone or Methylprednisolone, particularly given that COVID-19 is affecting countries across the developing, as well as the developed, world.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jae-Hoon Lee ◽  
Hye Sun Lee ◽  
Soyoung Kim ◽  
Eun Jung Park ◽  
Seung Hyuk Baik ◽  
...  

AbstractSerum inflammatory markers are used in the prognostication of colorectal cancer (CRC); however, the corresponding role of positron emission tomography (PET)-derived inflammatory markers remains unclear. This study aimed to investigate the prognostic value of 18F-fluorodeoxyglucose (FDG) uptake in the bone marrow and spleen of patients with CRC and evaluate the relationship between FDG uptake estimates in these organs and serum inflammatory markers. In total, 411 patients who underwent preoperative FDG PET/computed tomography (CT) within 1 month of surgery were enrolled. The mean standardized uptake values of the bone marrow and spleen were normalized to the value of the liver, thereby generating bone marrow-to-liver uptake ratio (BLR) and spleen-to-liver uptake ratio (SLR) estimates. The value of BLR and SLR in predicting overall survival (OS) was assessed using the Cox proportional hazards model. The correlation between BLR or SLR and neutrophil-to-lymphocyte ratio (NLR) was evaluated. The predictive accuracy of BLR alone and in combination with SLR was compared using the integrated area under the receiver operating characteristic curves (iAUC). In the univariate analysis, BLR (> 1.06) and SLR (> 0.93) were significant predictors of OS. In the multivariate analysis, BLR was an independent predictor of OS (hazard ratio = 5.279; p < 0.001). Both BLR and SLR were correlated with NLR (p < 0.001). A combination of BLR and SLR was better than BLR alone at CRC prognostication (iAUC, 0.561 vs. 0.542). FDG uptake estimates in the bone marrow and spleen may be useful imaging-derived biomarkers of systemic inflammation, supporting CRC prognostication.


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