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Presented here is a case report of a 77-year-old woman affected by rheumatoid arthritis who underwent breast-conserving surgery followed by radiation therapy (RT) for left-breast cancer and developed bronchiolitis obliterans organizing pneumonia (BOOP) after RT and during a COVID-19 vaccination campaign. BOOP incidence is an uncommon morbidity after breast RT (1.2%-2.9%); however, specific predisposing factors can play a role. In this patient, both rheumatoid arthritis and the vaccine may have predisposed her to an increased risk of organizing pneumonia, probably by triggering a proinflammatory cascade. Our report highlights the importance of factors that influence the occurrence of uncommon radiation-induced morbidities, such as BOOP, in specific subsets of patients. Further studies are necessary to evaluate factors increasing radiation sensitivity., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Rheumatoid arthritis causes inflammation, pain, and joint degradation, necessitating treatment with anti-inflammatory drugs and corticosteroids, posing various challenges. We aimed to evaluate the effects of photobiomodulation (PBM) at two different doses associated to platelet-rich plasma (PRP) in an in vivo model of induced acute arthritis in Wistar rats' knee. Methods: Eighty-four Wistar rats were assigned into seven groups, including animals treated with PBM and/or PRP. On day 0, arthritis was induced in sham and treated groups through the intra-articular injection of zymosan (200 μg). Twenty-four hours after induction, the PBM groups were treated with an AsGaAl laser, whereas the PRP-treated groups received intra-articular injections with a concentration of 8 × 10 5 platelets obtained from another four animals. After 3 days, the animals were euthanized, and the interleukin (IL)-6 and complement C3 gene and protein expression levels were analyzed. Statistical analysis was performed using the mean ± SD with analysis of variance and Tukey's posttest, with a significance level set at 5% ( p < 0.05). Results: Synovial inflammation decreased in PBM-treated groups; however, PRP alone showed no significant difference. Gene expression analysis revealed a significant difference in IL-6 and C3 levels in the PBM and PBM+PRP-treated groups. Meanwhile, the PRP alone group exhibited significance for IL-6. Moreover, the PBM and PBM+PRP-treated groups showed a significant difference in C3 protein expression levels, whereas the PRP alone group showed no difference. Conclusion: The increase in cellular activity in the synovial membrane and the decrease protein expression levels are owing to the reduction in proinflammatory mediators following PBM therapy.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive joint inflammation, resulting in cartilage destruction and bone erosion. It was reported that low-dose radiation modulates immune disease. Here, we investigated whether low-dose whole-body irradiation has preventive and therapeutic effects in collagen-induced RA (CIA) mouse models. Fractionated low-dose irradiation (0.05 Gy/fraction, total doses of 0.1, 0.5 or 0.8 Gy) was administered either concurrently with CIA induction by Type II collagen immunization (preventive) or after CIA development (therapeutic). The severity of CIA was monitored using two clinical parameters, paw swelling and redness. We also measured total Immunoglobulin G (IgG) and inflammatory cytokines (interleukine (IL)-6, IL-1β and tumor necrosis factor-alpha (TNF-α)) in the serum by enzyme-linked immunosorbent assay, and we evaluated histological changes in the ankle joints by immunohistochemistry and hematoxylin and eosin staining. Low-dose irradiation reduced CIA clinical scores by up to 41% in the preventive model and by 28% in the therapeutic model, while irradiation in the preventive model reduced the typical CIA incidence rate from 82 to 56%. In addition, low-dose irradiation in the preventive model decreased total IgG by up to 23% and decreased IL-1β and TNF-α by 69 and 67%, and in the therapeutic model, decreased total IgG by up to 35% and decreased IL-1β and IL-6 by 59 and 42% with statistical significance (P < 0.01, 0.05 and 0.001). Our findings demonstrate that low-dose radiation has preventive and therapeutic anti-inflammatory effects against CIA by controlling the immune response, suggesting that low-dose radiation may represent an alternative therapy for RA, a chronic degenerative immune disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: Radiosynoviorthesis (RSO) is a nuclear medical local treatment modality for inflammatory joint diseases. It is indicated in patients with rheumatoid arthritis (RA) in joints with persistent synovitis despite adequate pharmacotherapy. Arthritis of the elbow joint occurs in up to 2/3 of patients with RA. Intra-articular radiotherapy using the beta emitter [ 186 Re] rhenium sulfide leads to sclerosis of the inflamed synovial membrane with subsequent pain alleviation. The clinical efficacy in cubital arthritis, however, has so far only been described in small monocentric studies., Objective: The degree of pain alleviation by RSO was analyzed in patients with rheumatoid cubital arthritis, treated in several nuclear medical practices specialized in RSO., Material and Methods: The subjective pain intensity before and after RSO was documented in a total of 107 patients with rheumatic cubital arthritis using a 10-step numeric rating scale (NRS). A difference of ≥ -2 is rated as a significant improvement. Follow-up examinations were done after a mean interval of 14 months after RSO (at least 3 months, maximum 50 months)., Results: The mean NRS value was 7.3 ± 2.1 before RSO and 2.8 ± 2.2 after RSO. A significant pain alleviation was seen in 78.5% of all patients treated. The subgroup analysis also showed a significant improvement in the pain symptoms in all groups depending on the time interval between the RSO and the control examination. A significant pain progression was not observed. The degree of pain relief was independent of the time of follow-up., Conclusion: Using RSO for local treatment of rheumatoid cubital arthritis leads to a significant and long-lasting pain relief in more than ¾ of the treated patients., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Rheumatoid arthritis (RA) and osteoarthritis (OA) have a significant impact on the quality of life of patients around the world, causing significant pain and disability. Furthermore, the drugs used to treat these conditions frequently have side effects that add to the patient's burden. Photobiomodulation (PBM) has emerged as a promising treatment approach in recent years. PBM effectively reduces inflammation by utilizing near-infrared light emitted by lasers or LEDs. In contrast to photothermal effects, PBM causes a photobiological response in cells, which regulates their functional response to light and reduces inflammation. PBM's anti-inflammatory properties and beneficial effects in arthritis treatment have been reported in numerous studies, including animal experiments and clinical trials. PBM's effectiveness in arthritis treatment has been extensively researched in arthritis-specific cells. Despite the positive results of PBM treatment, questions about specific parameters such as wavelength, dose, power density, irradiation time, and treatment site remain. The goal of this comprehensive review is to systematically summarize the mechanisms of PBM in arthritis treatment, the development of animal arthritis models, and the anti-inflammatory and joint function recovery effects seen in these models. The review also goes over the evaluation methods used in clinical trials. Overall, this review provides valuable insights for researchers investigating PBM treatment for arthritis, providing important references for parameters, model techniques, and evaluation methods in future studies.

Rheumatoid arthritis (RA) is an inflammatory, systemic and chronic disease that mainly affects the joints. It is characterized mainly by pain, edema and joint stiffness, which can lead to significant loss of functional capacity and quality of life. Several physical therapy resources are used in the treatment of AR, such as low-level laser therapy (LLLT) and its analgesic and anti-inflammatory effects. However, the efficacy of LLLT in AR is still controversial. The objective of this study is to evaluate the efficacy of low-level laser therapy in adults with RA. Methods and findings: We searched MEDLINE, EMBASE, CENTRAL, PEDro, LILACS, IBECS, CUMED, SCIELO and ClinicalTrials.gov. Two researchers independently selected studies, extracted data, evaluated the risk of bias and assessed the certainty of evidence using GRADE approach. Disagreements were resolved by a third author. Meta-analyses were performed. Currently available evidence was from 18 RCTs, with a total of 793 participants. We found low-quality evidence suggesting there may be no difference between using infrared laser and sham in terms of pain, morning stiffness, grip strength, functional capacity, inflammation, ROM, disease activity and adverse events. The evidence is very uncertain about the effects of red laser compared to sham in pain, morning stiffness. The evidence is also very uncertain about the effects of laser acupuncture compared to placebo in functional capacity, quality of life, range of motion and inflammation. Conclusions: Thus, infrared laser may not be superior to sham in RA patients. There is insufficient information to support or refute the effectiveness of red laser, laser acupuncture and reflexology for treating patients with RA., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lourinho et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The risk of developing late radiotoxicity after radiotherapy in patients with high chromosomal radiosensitivity after radiotherapy could potentially be higher compared to the risk in patients with average radiosensitivity. In case of extremely high radiosensitivity, dose reduction may be appropriate. Some rheumatic diseases (RhD), including connective tissue diseases (CTDs) appear to be associated with higher radiosensitivity. The question arises as to whether patients with rheumatoid arthritis (RA) also generally have a higher radiosensitivity and whether certain parameters could indicate clues to high radiosensitivity in RA patients which would then need to be further assessed before radiotherapy., Methods: Radiosensitivity was determined in 136 oncological patients with RhD, 44 of whom were RA patients, and additionally in 34 non-oncological RA patients by three-colour fluorescence in situ hybridization (FiSH), in which lymphocyte chromosomes isolated from peripheral blood are analysed for their chromosomal aberrations of an unirradiated and an with 2 Gy irradiated blood sample. The chromosomal radiosensitivity was determined by the average number of breaks per metaphase. In addition, correlations between certain RA- or RhD-relevant disease parameters or clinical features such as the disease activity score 28 and radiosensitivity were assessed., Results: Some oncological patients with RhD, especially those with connective tissue diseases have significantly higher radiosensitivity compared with oncology patients without RhD. In contrast, the mean radiosensitivity of the oncological patients with RA and other RhD and the non-oncological RA did not differ. 14 of the 44 examined oncological RA-patients (31.8%) had a high radiosensitivity which is defined as ≥ 0.5 breaks per metaphase. No correlation of laboratory parameters with radiosensitivity could be established., Conclusions: It would be recommended to perform radiosensitivity testing in patients with connective tissue diseases in general. We did not find a higher radiosensitivity in RA patients. In the group of RA patients with an oncological disease, a higher percentage of patients showed higher radiosensitivity, although the average radiosensitivity was not high., (© 2023. The Author(s).)

Introduction: Rheumatoid arthritis (RA) is a chronic destructive inflammatory disease that afflicts over one percent of the world's population. Current pharmacological treatments remain relatively ineffective. In this context, photobiomodulation (PBM) is a potential resource for the treatment of RA. This study investigates investigate the anti-arthritic effects and related mechanisms of PBM on fibroblast-like synoviocytes (FLSs) from RA patients and a mouse model of collagen-induced arthritis (CIA)., Methods: The RA-FLSs were irradiated with a light emitting diode (LED) at a wavelength of 610 nm for 20 min, and the corresponding power intensities were 5 and 10 mW/cm 2 . After the LED irradiation, cell viability, proliferation, migration, and invasion assays were performed. Male DBA/1J mice were used to establish an animal model of CIA. Light stimulation with 10 mW/cm 2 was applied to the ankle joints via direct contact with the skin for 40 min, daily for 2 weeks., Results and Discussion: PBM significantly reduced tumor necrosis factor (TNF)-α-induced increase in proliferation, migration, and invasion in RA-FLSs, and downregulated the activation of nuclear factor-κappa B (NF-κB) and NLRP3 inflammasome by TNF-α. Moreover, PBM greatly inhibited the induction and development of CIA, resulting in the inhibition of synovial inflammation and cartilage degradation. PBM therapy decreased the serum levels of pro-inflammatory cytokines, while increasing the anti-inflammatory cytokines. PBM suppressed the translocation of NF-κB and activation of NLRP3 inflammasome in the ankle joint. Furthermore, PBM showed a more pronounced anti-arthritic effect when combined with methotrexate (MTX), a disease-modifying anti-rheumatic drug (DMARD). The results showed that the effectiveness of MTX + PBM in CIA is superior to that of either MTX or PBM and that both work synergistically. Therefore, PBM with LED may be a potential therapeutic intervention for against RA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ryu, Park, Kim, Kim, Kim and Shin.)

Background: The aim of this study was to assess the long-term anti-inflammatory effect and safety of 90-Yttrium and 166-Holmium radiosynoviorthesis (RSO) for treating chronic knee synovitis of various origins., Methods: A total of 820 patients were included in this study and were followed up to 10 years after the procedure for objective and subjective changes in signs and symptoms of inflammation., Results: Five years after RSO, excellent and good results were seen in 71% (95% CI 67-74%) of patients. Six, seven, eight and nine years following RSO, efficacy did not decrease significantly. Ten years after RSO, the effectiveness of the therapy fell to 65% (95% CI 59-71%). Overall, 64% of patients did not need another joint puncture ten years after RSO. We achieved excellent to good results at 5 years in 79% of patients with rheumatoid arthritis, 59% with ankylosing spondylitis, and 62% with osteoarthritis. Efficacy was mainly affected by the local X-ray stage of the knee joint. A significant association was also found between the diagnosis of the underlying disease and the success of radiosynoviorthesis. Efficacy, however, was not substantially affected by any of the following factors: the duration of synovitis, the number of punctures before radiosynoviorthesis, the number of intraarticular steroid injections before the procedure, or the number of interventions before radiosynoviorthesis (radiotherapy, surgery)., Conclusions: Radiosynoviorthesis is an effective long-term method of treating chronic synovitis. The treatment showed the most favorable effects in patients with rheumatoid arthritis and those with mild to moderate degenerative osseous changes.

Background: Inflammatory cytokine secretion from fibroblast-like synoviocytes (FLS) plays a vital role in the pathological process of rheumatoid arthritis (RA). Photobiomodulation (PBM) has been widely used in the treatment of RA. However, the mechanism of PBM in RA has not been clarified. Objective: In this study, we investigated the underlying mechanism of 630 nm light-emitting diode (LED) irradiation on anti-inflammation using mRNA sequencing analysis. Methods and results: Reverse transcription (RT)-quantitative polymerase chain reaction (RT-qPCR) results showed that 630 nm LED irradiation significantly inhibited interleukin (IL)-1β, IL-6, and IL-8 mRNA expression in rheumatoid arthritis fibroblast synovial cells (RA-FLS) and MH7A cells. A total of 1730 differentially expressed genes (DEGs) were identified between tumor necrosis factor α (TNF-α)+LED and TNF-α-treated RA-FLS and 1219 DEGs in MH7A cells by mRNA sequencing analysis. A total of 646 intersecting DEGs from the 2 cell models were used for gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Protein-protein interaction (PPI) network of DEGs was used, and 502 nodes and 1452 edges were found. A total of 14 clusters were generated in MCODE, and the top 3 clusters were selected as hub modules. PPI network showed that most of the nodes were DEGs of the heat shock protein (HSP) family. RT-qPCR verified that 630 nm LED irradiation significantly increased HSP70 mRNA expression in FLS. Conclusions: Taken together, our results revealed the correlation between HSP70 and the inhibition of inflammation caused by 630 nm LED irradiation. These findings suggested that HSP may be a novel target of 630 nm LED irradiation to alleviate inflammation in the treatment of RA.

Objective: Radiosynovectomy (RSO) describes the internal low-dose radiotherapy of the synovia via intra-articular administration of small radioactive particles. Since the introduction of biologics, the main aetiology of arthritic joints for RSO changed to mostly osteoarthritis with concordant change in typically affected joints. Thus, the effect of RSO in thumb basal joint arthritis (BJTh) with focus on osteoarthritis needs to be explored., Design: From 2017 to 2020, 219 BJTh were treated in 125 patients, 17 patients with rheumatoid arthritis (RA) and 108 patients with osteoarthritis (OA). The therapeutic effect was assessed using a four-step subjective scoring., Results: 20% of the treated joints were symptom free, 48% had a very good response, 16% slight and 16% no response. RSO was performed in 71 patients singularly and in 54 patients repetitively. The mean response duration was 6.8 months with a maximum of 48 months. 35% of patients had post-therapeutic pain relief followed by relapse after 3 months. Response duration showed no significant difference the between first and repetitive therapy, primary responder and primary non-responder and RA and OA., Conclusion: In thumb basal joint arthritis, RSO leads to response rates from 66 to 79%, mean response duration from 6 to 12 months and individual response duration 48 months. The present results are in line with previously published response rates in smaller joints. In respect to 35% of patients with relapse within 3 months post-therapy, we recommend a primary follow-up after 3-4 months., (© 2021. The Japanese Society of Nuclear Medicine.)

Introduction: Far-infrared radiation (FIR) is widely used in the treatment of various diseases such as insomnia and cardiovascular risk. Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease in which the therapeutic potential of FIR in RA is unclear., Objectives: To determine the therapeutic potential and mechanistic actions of FIR in treatment of RA., Methods: Adjuvant-induced arthritis (AIA) rat models were established to assess the therapeutic potency of FIR in RA treatment. The scoring parameters such as arthritis score, swelling of the hind paw, spleen and thymus indices, micro-CT analysis indices were adopted to estimate the beneficial effects of FIR during RA treatment in AIA model. PCR gene expression arrays were used to analyze inflammatory and autoimmune genes expression profiles in rat synovium. The inflammatory and immunity genes profiling was further analyzed through transcription factor prediction using PROMO. A signaling network map of possible molecular circuits connecting the identified differential genes to the RA's pathogenesis was constructed based on extensive literature reviews, and the major signaling pathways were validated by Western blotting., Results: Thirty minutes of FIR treatment significantly improved the symptoms of AIA in rats. Gene expression profiling indicated that 27 out of 370 genes were down-regulated by FIR. AP-1, CEBPα, CEBPβ, c-Fos, GR, HNF-3β, USF-1, and USF-2 were predicted as key transcription factors that regulated the identified differential genes. In addition, MAPK, PI3K-Akt, and NF-κB signaling are the major molecular pathways down-regulated by FIR treatment., Conclusion: FIR may provide beneficial effects on the AIA rat model of arthritis by suppression of the MAPK, PI3K-Akt and NF-κB signaling pathways. Therefore, we believe that FIR may provide an alternative non-pharmacological and non-surgical therapeutic approach for the treatment of RA., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier B.V. on behalf of Cairo University.)

The development of collagen type II (CII)-induced arthritis (CIA), a model of rheumatoid arthritis, in rats housed in cages with bedding composed of Celliant fibres containing ceramic particles, which absorb body heat and re-emit the energy back to the body in the form of infrared radiation (+IRF rats), and those housed in cages with standard wooden shaving bedding (-IRF control rats) was examined. The appearance of the first signs of CIA was postponed, while the disease was milder (judging by the arthritic score, paw volume, and burrowing behaviour) in +IRF compared with -IRF rats. This correlated with a lower magnitude of serum anti-CII IgG antibody levels in +IRF rats, and lower production level of IL-17, the Th17 signature cytokine, in cultures of their paws. This could be partly ascribed to impaired migration of antigen-loaded CD11b + dendritic cells and their positioning within lymph nodes in +IRF rats reflecting diminished lymph node expression of CCL19 /CCL21. Additionally, as confirmed in rats with carrageenan-induced paw inflammation (CIPI), the infrared radiation from Celliant fibres, independently from immunomodulatory effects, exerted anti-inflammatory effects (judging by a shift in pro-inflammatory mediator to anti-inflammatory/immunoregulatory mediator ratio towards the latter in paw cultures) and ameliorated burrowing behaviour in CIA rats.

Background: Rheumatoid arthritis (RA) is an inflammatory chronic disease characterized by inflammation, pain, swelling and disability, and radiosynovectomy is one of the disease treatment lines. In this study, the possibility of providing rhenium-186/rhenium-188 chitosan radiopharmaceuticals, optimization of conditions for their production and bio-distribution are reported., Objective: In order to build perrhenic acid for labeling, natural rhenium was exposed to radiation. Radionuclidic and radiochemical purities of (186/188Re)-NaReO4 were examined by gamma spectroscopy and paper chromatography methods, respectively., Methods: Labeling of chitosan with rhenium was done in different acidic situations. The radiochemical purity 186/188Re-chitosan was applied by radio thin layer chromatography (RTLC). Lastly, the bio-distribution of the radiolabeled chitosan was studied in various organs after intra articular injection of the complex to lab rats. Gamma spectrometry confirmed the high rhenium radionuclidic purity. Chromatography results showed that perrhenic acid was produced with purity greater than 97% and rhenium chitosan labeling was done over 98% in pH = 3. Dissection results showed a high bio-distribution of 186/188Re-chitosan after injection into the joint with no leakage to surrounding organs., Conclusion: According to the results, there is a possibility of labeling rhenium with chitosan in very high radiochemical purity. Regarding the high retention of these radiopharmaceuticals in joints with no leakage to surrounding organs, 186/188Re-chitosan can be applied as new radiosynovectomy drugs for rheumatoid arthritis treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Rheumatoid arthritis denotes hyperplasia and intense inflammatory process. Treatment involves exercise protocols and use of resources such as low-level laser therapy (LLLT) to modulate the inflammatory process and maintain physical capacity. The objective was to investigate whether treatment with LLLT and exercise modulates the inflammatory process and peripheral functionality. Sample is composed of 128 male rats, separated into three groups, control, treated and untreated, in the acute and chronic period of the disease with 64 animals in each group, divided into 8 subgroups with n = 8. The animals were immunized with injection at the base of the tail and 7 days after intra-articular injection with complete Freund adjuvant (CFA) for lesion groups, and saline solution for the controls. Joint disability was evaluated by PET (paw elevation time) and joint edema and treated with LLLT and/or resisted stair climbing exercise. Normality Shapiro-Wilk test, ANOVA mixed for the functional analyses, and ANOVA one-way for the variables of cellular differentiation, with Bonferroni post hoc, p = 5% were used. For the evaluations of joint disability and nociception, there was a significant difference between the evaluations, the groups, and the interaction groups-evaluations. The treated groups showed recovery of functionality; it is still verified that laser therapy increased the nociceptive threshold of the chronic inflammatory period, and the exercise reflected in significant functional improvement and modulation of the inflammatory process both in the acute and chronic periods. LLLT, resistance exercise, or a combination of treatments had a positive effect on the modulation of the inflammatory process, reducing the migration of leukocytes, in addition to helping the return of peripheral functionality by reducing joint disability in a model of rheumatoid arthritis induced by CFA in rats.

Objective:  The study objective was to evaluate the long-term effect of radiosynoviorthesis (RSO) on the progression of radiological and nuclear-medical osteoarthritic features of hip and ankle joint in patients with osteoarthritis and rheumatoid arthritis., Patients and Methods:  The study included 89 hip joints of 81 patients, of which 48 had osteoarthritis (OA) and 33 had rheumatoid arthritis (RA). In terms of ankle joints, 64 patients were included of which 43 suffered from OA and 21 from RA. The mean follow-up time was 9.2 years for OA and 8.9 years for RA patients. Patients with RA were the active control group. Structural alterations of the hip joints were evaluated following Kellgren-Lawrence score and of ankle joint following Takakura score for both disease entities. For the evaluation of synovitis 2-phase bone scintigraphy was performed., Results:  RSO could prevent radiologic status deterioration among 70.6 % of hip osteoarthritic patients and 73.7 % among the hip RA patients. No structural progression was observed in 79.1 % of the treated ankle joints in patients with OA and in 85.7 % of the ankle joints in patients with RA.The scintigraphic response rate for the hip joints of OA patients was 68.6 %, 76.3 % for hip joints of RA patients, 83.1 %, ankle joints of OA patients, and 90.4 % ankle joints of RA patients.The radiographic and scintigraphic RSO response rates were not significantly higher for both joints in RA than OA patients., Conclusion:  RSO can be a good alternative in the treatment of synovitis and prevention of deterioration of inflammatory and radiographic features even in patients suffering from osteoarthritis and rheumatoid arthritis. RSO may have also a long-term effect to stop or delay progression of both diseases., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: The aim of this study was to assess the treatment results of 90 Y radiation synovectomy for chronic exudative synovitis of knee joints., Methods: The retrospective data consist of 394 consecutive knee radiation synovectomies performed using 6 mCi (222 MBq) of 90 Y. The assessment included 3-point custom pain and joint mobility scale, evaluation of joint's circumference, binary joint's temperature evaluation, patellar ballottement test, indications for puncture and its volume in applicable cases. 21 cases had to be forfeited due to missing data regarding follow-up., Results: The final analysis of 373 treatment procedures performed in 253 patients yielded following results-at 6 months after treatment, 80.9% of the patients reported at least partial pain relief (including 33.3% with complete pain relief), which increased to 86.7% at one year. The pain intensity decreased over time, however, the outcomes were worse in older patients. The probability of pain recurrence was 15% at 6 months, and 28% at one year. It was highest in post-traumatic synovitis, and lowest in pigmented villonodular synovitis. The circumference of the treated knee joints decreased over the course of follow-up, however, the decrease was significantly lower in older patients. The fraction of patients with full knee joint mobility increased from 34.6 to 40.6% at 6 months and 49.2% at one year. The percentage of patients that required articular puncture decreased from 62.8% at baseline to about 35.6% at 6 months, and 32.8% at one year. Positive patellar ballottement was found in 68.5% before treatment and remained at about 40-50% during the course of follow-up. The increased temperature of the joint was reported in 51.2% at baseline and decreased to 33% at 6 months and 28.3% at one year., Conclusions: (1) Radiation synovectomy is a safe and effective method of treatment in patients with exudative synovitis, however, the pain recurrence rate is significantly higher in post-traumatic exudative synovitis compared to pigmented villonodular, undifferentiated, and rheumatoid arthritis. (2) Our results suggest that older patients have worse treatment results with radiation synovectomy compared to younger patients.

Objectives: To determine the efficacy of Phosphorus-32 radiation synovectomy in the treatment of patients with severe rheumatoid arthritis (RA) unresponsive to systematic or local medical therapy., Methods: Twenty-three knees in 16 patients with severe chronic RA were prospectively treated by intra-articular installation of Phosphorus-32 and evaluated at 1, 3, 6, and 12 months. The Western Ontario and McMaster Universities Arthritis index (WOMAC), visual analog scale (VAS), Health Assessment Questionnaire (HAQ), pain scale, and grade of joint effusion and tenderness were assessed. At the 12-month time interval, the treated knees were classified into four categories: excellent response (no symptoms), good response (significant reduction of symptoms), moderate response (slight decrease), and poor response (no change or worsening)., Results: Excellent response or good response was observed in 13/23 (56.5%) of the treated knees, moderate response in 2/23 (8.7%) of the treated knees, and poor response in 8/23 (34.8%) of the treated knees. The grades of effusion and tenderness were significantly decreased one-month posttreatment (P< 0.05); however, these changes did not persist at other time intervals (P > 0.05). There was a significant improvement in the HAQ, WOMAC, VAS, and pain scores at all time points compared with baseline, including at the 12-month time interval (P < 0.05)., Conclusion: Phosphorus-32 radiosynovectomy is an effective therapeutic treatment for patients with RA of the knee unresponsive to conventional pharmacotherapy.

Currently, there is no imaging procedure for radionuclide therapy utilizing Erbium-169 (Er-169). We have recently published the first post-radiosynovectomy imaging of Er-169 citrate in a case report (Farahati et al., 2017). In this study, we performed in-vitro and in-vivo studies to evaluate the feasibility to assess the distribution of Er-169 citrate after radiosynovectomy in fourteen patients with seventeen affected joints treated for refractory chronic synovitis. Post-radiosynovectomy imaging revealed the feasibility of post-radiosynovectomy detection and distribution utilizing Er-169 citrate in all cases. However, additional in-vitro studies including in-vitro imaging, gamma spectrometry and analysis of half-life indicated that emitted gamma-rays of the Ytterbium-169 in the radiopharmaceutical together with bremsstrahlung induced by Er-169 are the imaging source of emitted counts. Post-radiosynovectomy imaging utilizing Er-169 citrate is feasible and should be implemented in the guidelines for theranostics for quality control, patient safety and therapy monitoring., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Despite major advances in rheumatoid arthritis outcome, not all patients achieve remission, and there is still an unmet need for new therapeutic approaches. This study aimed at evaluating in a pre-clinical murine model the efficacy of extracorporeal photopheresis (ECP) in the treatment of rheumatoid arthritis, and to provide a relevant study model for dissecting ECP mechanism of action in autoimmune diseases., Methods: DBA/1 mice were immunized by subcutaneous injection of bovine collagen type II, in order to initiate the development of collagen-induced arthritis (CIA). Arthritic mice received 3 ECP treatments every other day, with psoralen + UVA-treated (PUVA) spleen cells obtained from arthritic mice. Arthritis score was measured, and immune cell subsets were monitored., Results: ECP-treated mice recovered from arthritis as evidenced by a decreasing arthritic score over time. Significant decrease in the frequency of Th17 cells in the spleen of treated mice was observed. Interestingly, while PUVA-treated spleen cells from healthy mouse had no effect, PUVA-treated arthritic mouse derived-spleen cells were able to induce control of arthritis development., Conclusions: Our results demonstrate that ECP can control arthritis in CIA-mice, and clarifies ECP mechanisms of action, showing ECP efficacy and Th17 decrease only when arthritogenic T cells are contained within the treated sample. These data represent a pre-clinical proof of concept supporting the use of ECP in the treatment of RA in Human.

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease whose main hallmark is inflammation and destruction of the joints. Two cell types within the synovium that play an important role in RA are fibroblast-like synoviocytes (FLS) and macrophages. The latter innate immune cells show a high plasticity in their phenotype and are central in inflammatory processes. Low-dose radiotherapy (LD-RT) with particularly a single dose of 0.5 Gy has been demonstrated to have a positive impact on pain, inflammation, and bone in inflamed joints. We now examined for the first time how LD-RT influences FLS and bone marrow-derived macrophages in co-culture systems of an experimental model of RA to reveal further mechanisms of immune modulatory effects of low and intermediate dose of ionizing radiation. For this, the bone marrow of h TNF-α tg mice was differentiated either with cytokines to obtain key macrophage phenotypes (M0, M1, and M2) or with supernatants (SN) of untreated or irradiated FLS. Flow cytometry analyses were used to analyse the impact of radiation (0.1, 0.5, 1.0, and 2.0 Gy) on the phenotype of macrophages in the presence or absence of SN of FLS. LD-RT had no impact on cytokine-mediated macrophage polarization in M0, M1, or M2 macrophages. However, SN of irradiated FLS particularly reduced CD206 expression on macrophages. Macrophage phenotype was stable when being in contact with SN of nonirradiated FLS, but significantly increased surface expression of CD206 and slightly decreased CD80 and CD86 expression were observed when macrophage themselves were irradiated with 0.5 Gy under these microenvironmental conditions, again highlighting discontinuous dose dependencies in the low and intermediate dose range. One can conclude that FLS-dependent microenvironmental conditions have a slight influence on the modulation of macrophage phenotype under radiation exposure conditions. Future studies are needed to reveal the impact of radiation exposure on the functions of treated macrophages under such microenvironmental conditions., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper.

Background and Objective: The biomedical fluid which fills the Synovial joint cavity is called Synovial fluid which behaves as in the fluid classifications to Non-Newtonian fluids. Also it's described as a several micrometers thick layer among the interstitial cartilages with very low friction coefficient. Consequently, the present paper opts to investigate the influence of the concentration-dependent viscosity on Magnetohydrodynamic peristaltic flow of Synovial Nanofluid in an asymmetric channel in presence of thermal radiation effect., Method: Our problem is solved for two models, in the first model which referred as Model-(I), viscosity is considered exponentially dependent on the concentration. Model-(2), Shear thinning index is considered as a function of concentration. Those models are introduced for the first time in peristaltic or Nanofluid flows literature. The governing problem is reformulated under the assumption of low Reynolds number and long wavelength. The resulting system of equations is solved numerically with the aid of Parametric ND Solve., Results: Detailed comparisons have been made between Model-(I) and Model-(2) and found unrealistic results between them. Results for velocity, temperature and nanoparticle concentration distributions as well as pressure gradient and pressure rise are offered graphically for different values of various physical parameters., Conclusions: Such models are applicable to rheumatoid arthritis (RA) treatment. Rheumatoid arthritis patients can be treated by applying the magnetic field on an electrically conducting fluid, due to the movement of the ions within the cell which accelerates the metabolism of fluids., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: There is a clinical need for therapeutic alternative in patients with persisting painful arthritis of AC-joint and failure of previous treatments. However, no radiopharmaceutical is currently explicitly approved for radiosynoviorthesis of acromioclavicular joint. The aim of our study was to prospectively assess the efficacy and safety of radiosynoviorthesis of acromioclavicular joint using erbium-169 citrate., Material and Methods: Radiosynoviorthesis of acromioclavicular joint was performed in 51 consecutive patients (18 males, 33 females) mean age 64.3 (range 43.8-82.6, median 63.6) years with clinically confirmed arthritis of 85 acromioclavicular joints. The efficacy of RSO was reported by patients according to 10-step visual analogue scale of pain (VAS) (0 = no pain, 10 = most severe pain) at 6 months after radiosynoviorthesis and by ranking the global therapeutic effect of RSO in 4 categories (1 = the best effect, 4 = no change). To assess the variation of blood perfusion in treated joints, the efficacy of RSO was also evaluated by variation of target (acromioclavicular joint)/non-target (soft tissue) uptake ratio (T/NTR) of metylendiphosphonate (99mTc) measured as number of counts over region of interest on blood pool phase of two-phase bone scintigraphy performed before and 6 months after RSO., Results: Radiosynoviorthesis was followed by significant decrease in VAS, mean - 3.1 (-47%). Excellent, good, moderate and bad response was observed in 57 (67%), 25 (29%), 1 (1%) and in 2 (2%) of acromioclavicular joints respectively. A significant correlation between decrease of T/NTR and variation of VAS in % (ρ = 0.532, p < 0.0001) and between T/NTR and subjective evaluation of therapeutic effect in scale 1-4 (ρ = 0.388, p = 0.0002) was observed. However, it was not possible to identify the cut-off value of relative decrease in T/NTR showing sufficient sensitivity and specificity to detect the therapeutic response., Conclusion: Results of this prospective study permit to conclude a good efficacy and safety of radiosynoviorthesis using erbium-169 citrate in a series of patients with arthritis of acromioclavicular joint in whom previous line(s) of treatment did not lead to satisfactory pain relief.

Aim: To investigate the efficacy and safety of technetium-99 conjugated with methylene diphosphonate ( 99 Tc-MDP, Yunke Pharmaceutical industry) in the treatment of rheumatoid arthritis (RA)., Methods: A total of 120 patients with active RA were randomly divided into three groups: Group A (receiving oral meloxicam tablets); Group B (receiving intravenous drip of 99 TC-MDP); Group C (receiving combination treatment of intravenous drip of 99 Tc-MDP and oral meloxicam tablets). The main clinical and laboratory parameters were evaluated at baseline and after 14 days of therapy., Results: After 14 days of treatment, American College of Rheumatology 20 response was 15.62%, 34.04% and 48.78% in the three groups, respectively. The incidence of adverse events in three groups were 3.13%, 8.51% and 9.76% respectly, and has no significant difference. In addition, biochemical markers of bone metabolism including bone alkaline phosphatase (BAP), tartrate resistant acid phosphatase (TRAP) and dickkopf-1 (DKK-1), all improved in the three groups, although more significant in Group B than Group A, and more significant in the combination group than monotherapy groups., Conclusion: 99 Tc-MDP has good efficacy and safety in the treatment of active RA patients; the benefit was more remarkable when 99 Tc-MDP was combined with NSAIDs. 99 Tc-MDP may also have potential to improve bone metabolism., (© 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Purpose: To evaluate the impact of rheumatoid arthritis (RA) on toxicity and cosmesis in women undergoing radiotherapy for breast cancer., Methods: We queried an institutional database for women with RA treated with external beam radiotherapy for breast cancer between 1981 and 2016. Matching each patient to three controls without RA was attempted. Radiation toxicity was graded using CTCAE 4.0. Cosmesis was graded using the Global Harris Scoring System of Excellent, Good, Fair, or Poor. Grade 2+ (G2+) acute and late toxicities were compared between women with RA and their matched pairs using a generalized estimating equation (GEE). Wilcoxon test and mixed effects model were used to compare the cosmesis between two groups., Results: Forty women with RA at time of radiation were matched to 117 controls. The median radiation dose was 60 Gy (50-66 Gy) and the median follow-up was 94 months (1-354 months). When comparing the women with RA to their matched pairs, there was no significant difference in the rates of G2+ acute toxicity (25.0 vs. 13.7%, O 2.1, CI 0.91-4.9) or G2+ late toxicity (7.5 vs. 4.3%, OR 1.8, CI 0.48-6.8). Mean cosmesis was between Good and Excellent for both groups of patients, although women with RA were less likely to get Excellent cosmesis compared to their matched pairs (OR 0.35, CI 0.15-0.84)., Conclusions: Among women with RA, radiation for breast cancer was well tolerated without significantly increased toxicity. Their cosmesis was generally Good to Excellent, although they might be less likely to get Excellent cosmesis compared to their matched pairs.

Background: In low level laser therapy (LLLT) low wattage lasers are used to irradiate the affected skin areas, joints, nerves, muscles and tendons without any sensation or thermal damage. Although the exact mechanism of its effect is still unknown, it seems beyond dispute that LLLT induces a variety of stimulating processes at the cellular level affecting cell repair mechanisms, the vascular system and lymphatic system. LLLT has been popular among orthopaedic practitioners for many years, whereas university medicine has remained rather sceptical about it., Objectives: Overview of studies on the efficacy of LLLT in the treatment of rheumatic orthopaedic conditions, i. e. muscle, tendon lesions and arthropathies., Materials and Methods: Narrative literature review (PubMed, Web of Science)., Results: While earlier studies often failed to demonstrate the efficacy of LLLT, several recent studies of increasing quality proved the efficacy of LLLT in the treatment of multiple musculoskeletal pain syndromes like neck or lower back pain, tendinopathies (especially of the Achilles tendon) and epicondylolpathies, chronic inflammatory joint disorders like rheumatoid arthritis or chronic degenerative osteoarthritis of the large and small joints. In addition, there is recent evidence that LLLT can have a preventive capacity and can enhance muscle strength and accelerate muscle regeneration., Conclusion: LLLT shows potential as an effective, noninvasive, safe and cost-efficient means to treat and prevent a variety of acute and chronic musculoskeletal conditions. Further randomized controlled studies, however, are required to confirm this positive assessment.

Radiosynoviorthesis is used for local treatment of recurrent joint effusions, leads to necrosis of inflamed synovium due to beta radiation energy served after intraarticular radionuclide administration. The aim of the therapy is destruction and fibrosis of abnormal, hypertrophic synovial membrane and then full recovery of its normal function after local corticosteroids and systemic modifying drugs failure. Radiosynoviorthesis is effective in different type of peripheral arthritis like rheumatoid arthritis, inflammatory spondyloarthtropaties, gout, chondrocalcinosis, pigmented villo-nodular synovitis, recurrent knee effusion after total joint replacement, idiopathic knee joint effusion, osteoarthritis and secondary prevention of intraarticular bleeding in haemophilia. The absolute contraindications are: pregnancy and breastfeeding, uncontrolled coagulation disorders in haemophilic patients, septic skin changes around area of joint puncture, septic arthritis, raptured Baker's cyst. The commonly used radioisotypes in Europe are: 90Yttrium, 186Rhenium, 169Erbium. The favourable results could be reached on average in 60-80% of treated joints regardless of radionuclide used. The efficacy of radiosynoviorthesis is comparable with surgical synovectomy and in some selected situations both methods could be combined. If the primary failure of radiosynoviorthesis appeared procedure could be repeated, good results are obtained very frequently regardless of poor primary effect. Radiosynoviorthesis is safe, effective, simple and patient-friendly procedure, working fast in different type of arthtritis. The team consisted of rheumatologist, orthopedic surgeon and nuclear medicine specialist is essential for proper indications for local radiation therapy.

Intra-articular radiation synovectomy is an established and well documented therapy in rheumatology. A rare side effect is necrosis of surrounding tissue caused by leakage of the radionuclide.We describe the case of a 34-year old patient with rheumatoid arthritis who developed skin necrosis 4 weeks after an intra-articular radiation synovectomy of the left wrist. When these lesions are recognized early surgical therapy or hyperbaric oxygen therapy can be initiated.

Rheumatoid arthritis is a chronic autoimmune pathology characterized by the proliferation and inflammation of the synovium. Boron neutron capture synovectomy (BNCS), a binary treatment modality that combines the preferential incorporation of boron carriers to target tissue and neutron irradiation, was proposed to treat the pathological synovium in arthritis. In a previous biodistribution study, we showed the incorporation of therapeutically useful boron concentrations to the pathological synovium in a model of antigen-induced arthritis (AIA) in rabbits, employing two boron compounds approved for their use in humans, i.e., decahydrodecaborate (GB-10) and boronophenylalanine (BPA). The aim of the present study was to perform low-dose BNCS studies at the RA-1 Nuclear Reactor in the same model. Neutron irradiation was performed post intra-articular administration of BPA or GB-10 to deliver 2.4 or 3.9 Gy, respectively, to synovium (BNCS-AIA). AIA and healthy animals (no AIA) were used as controls. The animals were followed clinically for 2 months. At that time, biochemical, magnetic resonance imaging (MRI) and histological studies were performed. BNCS-AIA animals did not show any toxic effects, swelling or pain on palpation. In BNCS-AIA, the post-treatment levels of TNF-α decreased in four of six rabbits and IFN-γ levels decreased in five of six rabbits. In all cases, MRI images of the knee joint in BNCS-AIA resembled those of no AIA, with no necrosis or periarticular effusion. Synovial membranes of BNCS-AIA were histologically similar to no AIA. BPA-BNCS and GB-10-BNCS, even at low doses, would be therapeutically useful for the local treatment of rheumatoid arthritis.

Aim: γδ T cells exhibit important functions in the pathogenesis of rheumatoid arthritis (RA). In recent years, numerous studies harnessed the γδ T cell-activating capacity of aminobiphosphonates for the treatment of malignant tumors. As (99) Tc-methylene diphosphonate ((99) Tc-MDP) has long been widely used for the treatment of RA in China with good efficacy, we are interested in whether this drug exerts its therapeutic effect on RA by modulating peripheral γδ T cells of RA patients., Objectives: To investigate the effect of (99) Tc-MDP on the frequency of γδ T cells and CD4(+) CD25(+) Foxp3(+) Tregs in the peripheral blood of patients with active RA., Methods: Nineteen patients with active RA were treated with (99) Tc-MDP intravenously at a dose of 20 μg/day consecutively for 10-14 days. Before and after treatment, the main clinical and laboratory parameters for each patient were evaluated. The frequency of CD3(+) γδ(+) T cells and CD4(+) CD25(+) Foxp3(+) Tregs was detected by flow cytometry. Serum levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and transforming growth factor (TGF)-β were measured with enzyme-linked immunosorbent assay., Results: After intravenous (99) Tc-MDP therapy, the frequency of peripheral CD3(+) γδ(+) T cells and CD4(+) CD25(+) Foxp3(+) Tregs were significantly elevated, paralleled with decreased serum levels of TNF-α and IL-6 and increased level of serum TGF-β. The elevation of peripheral CD3(+) γδ(+) T cells was positively correlated with increased serum TGF-β and decreased disease activity., Conclusion: (99) Tc-MDP may improve the activity of RA through upregulating the frequency of peripheral γδ T cells and CD4(+) CD25(+) Foxp3(+) Tregs as well as affecting the serum cytokine environment by increasing TGF-β and decreasing TNF-α and IL-6., (© 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

Aim: The objective of the present study was to estimate the influence of intravenous laser irradiation of the blood on the dynamics of leptin levels and the quality of life of the patients presenting with rheumatoid arthritis., Material and Methods: A total of 132 patients at the age varying from 18 to 65 (mean 52.9 ± 11.3) years presenting with rheumatoid arthritis (RA) were available for the examination. The diagnosis of RA was based on the results of clinical, laboratory, and instrumental studies in accordance with the criteria of the American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) dated 2010. The patients were divided into two groups. The control group was comprised of the patients who received the traditional medicamental treatment alone (n = 30) while the study group consisted of the patients given a course of intravenous laser irradiation of the blood in addition to the traditional medicamental treatment (n = 102).The course of intravenous laser therapy was performed with the use of a Matrix-VLOK apparatus ("Matrix", Russia) by means of the VLOK + UBI procedure. Each course consisted of 10 sessions per patient without a break for the weekend., Results: The data obtained indicate that the patients with rheumatoid arthritis had the increased plasma leptin level suggesting the development of the inflammatory process. Moreover, the quality of the patients' life was deteriorated., Conclusion: The results of this study demonstrate that the combined treatment by means of low-intensity laser irradiation is accompanied by the normalization of the plasma leptin level, suppression of the inflammatory process, and a significant improvement of the quality of life of the patients suffering from rheumatoid arthritis.

Objective: To evaluate the indicators of oxidative modification of proteins (OMP) in the patients presenting with secondary osteoarthrosis associated with rheumatoid arthritis (RA) and to determine their dynamics under the influence of the combined treatment with the use of low-intensity laser irradiation (LILI)., Material and Methods: A total of 50 patients with RA associated with secondary osteoarthritis and 25 healthy subjects were enrolled in this study. The patients of one study sub-group (n = 25) were given combined therapy with the use of LLLI, those in the second sub-group (n = 25) received only drug therapy. We made use of the VAS and DAS 28 scales to estimate dynamics of pain and compared serum OMP in the patients and healthy subjects., Results: The analyses of the data obtained demonstrated the increased OMP in the patients with RA in comparison with the healthy subjects. The patients of sub-group 1 experienced a significant decrease in the clinical parameters of pain based on the VAS and DAS 28 scales accompanied by the marked reduction of OMP. In sub-group 2, the patients also exhibited the statistically significant dynamics of these indicators, but it was less pronounced than in sub-group 2., Conclusion: The patients presenting with rheumatoid arthritis are characterized by the elevated level of protein oxidative modification, a marker of oxidative stress. LlLI introduced in the combined treatment of the patients with RA not only increases the anti-inflammatory and analgesic effects but also has the antioxidant properties.

The article concerns the efficacy of the use of new therapeutic approach in the therapy of secondary osteoarthritis in patients with rheumatoid arthritis. The dynamic of Cartilage Oligomeric Matrix Protein, activity of the disease on DAS28, cytokine profile was estimated. The analysis of the results showed the advantages of the use of inhibitor of IL-1 combined with laser therapy in the treatment of secondary osteoarthritis in patients with rheumatoid arthritis.

Aim: To evaluate clinical response rates, duration of response and complication rates of yttrium radiosynovectomy (RSV) in an era of improved disease modifying antirheumatic drugs (DMARDS) and increased access to replacement therapy for clotting factor deficiencies introduced in the mid 2000s., Methods: A retrospective review of 167 consecutive joints treated with RSV between 2000 and 2010 was conducted. Clinical response and complication rates in 167 joints (119 patients: 45 female,74 male, mean age 52 years) with rheumatoid, psoriatic, hemophilic, large joint mono-arthropathy and miscellaneous arthropathies refractory to conventional therapy were reviewed. Clinical response was determined at 3 months with responding patients reviewed again at 36 months to assess whether response was sustained. Comparison of response rates pre- and post-introduction of improved DMARDS in the mid 2000s was also performed., Results: Satisfactory clinical response was highest for large joint mono-arthropathy (85%) and lower for other arthropathies (47-64%). A strong relationship was demonstrated between degree and duration of response with 90% of complete responders compared to 41% of incomplete responders having a sustained response at 36 months (P ≤ 0.0001). Major complication rates were low (1%). No difference was demonstrated in response rates pre- and post-introduction of improved DMARDS in the mid 2000s., Conclusion: In an era of improved DMARDS, yttrium synovectomy remains a safe and effective procedure across a broad spectrum of arthropathies and should continue to be considered in cases refractory to conventional therapies. Complete responders can be expected to have symptom relief for at least 36 months and complication rates are low., (© 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease of unknown etiology. Treatment of RA is very complex, and in the past years, some studies have investigated the use of low-level laser therapy (LLLT) in treatment of RA. However, it remains unknown if LLLT can modulate early and late stages of RA. With this perspective in mind, we evaluated histological aspects of LLLT effects in different RA progression stages in the knee. It was performed a collagen-induced RA model, and 20 male Wistar rats were divided into 4 experimental groups: a non-injured and non-treated control group, a RA non-treated group, a group treated with LLLT (780 nm, 22 mW, 0.10 W/cm(2), spot area of 0.214 cm(2), 7.7 J/cm(2), 75 s, 1.65 J per point, continuous mode) from 12th hour after collagen-induced RA, and a group treated with LLLT from 7th day after RA induction with same LLLT parameters. LLLT treatments were performed once per day. All animals were sacrificed at the 14th day from RA induction and articular tissue was collected in order to perform histological analyses related to inflammatory process. We observed that LLLT both at early and late RA progression stages significantly improved mononuclear inflammatory cells, exudate protein, medullary hemorrhage, hyperemia, necrosis, distribution of fibrocartilage, and chondroblasts and osteoblasts compared to RA group (p < 0.05). We can conclude that LLLT is able to modulate inflammatory response both in early as well as in late progression stages of RA.

Radiosynoviorthesis (RS) is an intra-articular injection of a radioactive colloid for the treatment of synovitis administered most often to patients with rheumatoid arthritis or haemophilia. Although highly cost-effective in comparison with surgical or arthroscopic synovectomy, the risk of cancer associated with this treatment is not well known. We evaluated the incidence of cancer in a group of patients treated with RS. A cohort of 2412 adult patients with a variety of underlying conditions (mainly rheumatoid arthritis) and treated with at least one RS between January 1976 and December 2001, was recruited from two centres in Montréal. Cancer incidence and mortality data for cohort members over that time period were obtained from regulatory agencies using linkage. Background rates for all and specific types of cancer were obtained for the provincial (Québec) and national (Canada) population according to age, gender and calendar period categories. Category-specific rates in the cohort were compared with rates in similar categories from the general population generating standardized incidence ratios (SIR). The effects of specific isotope doses and of number of RS treatments were analysed using a Cox-regression model. No increase in the risk of cancer was observed (SIR 0.96; 95% confidence interval 0.82-1.12). There was no dose-response relationship with the amount of radioisotope administered or number of RS treatments. The study provides some indication for the safety of the procedure but homogenous diagnostic groups of younger patients (such as haemophilic patients) receiving RS will need more evaluation., (© 2012 Blackwell Publishing Ltd.)

Radiosynoviorthesis is used for the local treatment of recurrent joint effusions and leads to synovium necrosis after radionuclide administration. This procedure provides opportunity to full recovery of normal synovium function after local corticosteroids and systemic modifying drugs failure.

Rhenium-188 is one of the most readily available generator derived and useful radionuclides for therapy emitting β(-) particles (2.12 MeV, 71.1% and 1.965 MeV, 25.6%) and imageable gammas (155 keV, 15.1%). The (188)W/(188)Re generator is an ideal source for the long term (4-6 months) continuous availability of no carrier added (nca) (188)Re suitable for the preparation of radiopharmaceuticals for radionuclide therapy. The challenges associated with the double neutron capture route of production of the parent (188)W radionuclide have been a major impediment in the progress of application of (188)Re. Tungsten-188 of adequate specific activity can be prepared only in 2-3 of the high flux reactors operating in the World. Several useful technologies have been developed for the preparation of clinical grade (188)W/(188)Re generators. Since the specific activity of (188)W used in the generator is relatively low 185 GBq( < 5 Ci)/g], the eluted (188)ReO(4)(-) can have low radioactive concentration often insufficient for radiopharmaceutical preparation. However, several efficient post elution concentration techniques have been developed that yield clinically useful (188)ReO(4)(-) solutions. Rhenium-188 has been used for the preparation of therapeutic radiopharmaceuticals for the management of diseases such as bone metastasis, rheumatoid arthritis and primary cancers. Several early phase clinical studies using radiopharmaceuticals based on (188)Re-labeled phosphonates, antibodies, peptides, lipiodol and particulates have been reported. This article reviews the availability and use of (188)Re including a discussion of why broader use of (188)Re has not progressed as expected as a popular radionuclide for therapy.

We conducted a thermovisual comparison of mean hand surface temperature changes upon local heating with two different IR sources. Sixty-six patients with rheumatoid arthritis (47 women and 19 men; average age, 56.1 ± 8.6 years) were subjected to topical heat therapy for one hand with either the standard IR radiator (SIR) or the water filter IRA (wIRA). The surface temperature of the dorsal side of both hands was measured, and thermal images were taken before and up to 2 h after treatment. At 1 min after treatment, SIR application increased the surface skin temperature of the heated hand from 31.5 ± 1.9 to 35.0 ± 1.9 °C (P<0.05), while wIRA increased it from 32.1 ± 1.6 to 34.2 ± 1.1 °C (P<0.05). Constant decline in temperature was observed immediately after treatment, with the temperatures reaching baseline in about 30 and 120 min after wIRA and SIR treatment, respectively. Similar temperature changes were observed in the heated hands for wIRA and SIR, except at 1 min after treatment. Changes in the untreated hands indicated contralateral reaction. The temperature of the warmed hand showed a correlation to the body mass index., (© 2011 The Authors. Photochemistry and Photobiology © 2011 The American Society of Photobiology.)

Rheumatoid arthritis (RA) is an inflammatory joint disorder whose progression leads to the destruction of cartilage and bone. Although low-level laser irradiation (LLLI) is currently being evaluated for the treatment of RA, the molecular mechanisms underlying its effectiveness remain unclear. To investigate possible LLLI-mediated antiinflammatory effects, we utilized a collagen-induced arthritis (CIA) rat model and analyzed gene expression profiles in the synovial membranes of the knee joint. Total RNA was isolated from the synovial membrane tissue of the joints of untreated CIA rats or CIA rats treated with LLLI (830 nm Ga-Al-As diode), and gene expression profiles were analyzed by DNA microarray (41,000 rat genes), coupled with Ingenuity pathways analysis (IPA). DNA microarray analysis showed that CCL2 gene expression was increased in CIA tissue, and that LLLI treatment significantly decreased CIA-induced CCL2 mRNA levels. IPA revealed that chemokine signal pathways were involved in the activation of CCL2 production. These microarray data were further validated using real-time PCR and reverse transcription PCR. Immunohistochemistry confirmed that CCL2 production was decreased in CIA rats treated with LLLI. These findings suggest that decreased CCL2 expression may be one of the mechanisms involved in LLLI-mediated RA inflammation reduction.

Radiosynovectomy or radiosynoviorthesis (RSO), the intra-articular injection of beta-emitting radionuclides (e.g. colloidal preparations of 90-Yttrium, 186-Rhenium or 169-Erbium), is an approved, reliable and easily performed therapy for the treatment of chronic synovitis without harmful side effects. The best clinical results have been obtained in patients with predominantly inflammatory joint disease such as rheumatoid arthritis or reactive arthritis. But RSO is also established to treat pain and persistent effusions after total knee replacement. It also represents an adjuvant therapy in patients with pigmented villonodular synovitis to protect against recurrence following synovectomy. In patients with hemophilia and arthropathy a reduction in joint bleeding is seen and the use of coagulation factor is reduced. The indication for RSO should be made in close cooperation between the referring physician, the rheumatologist and the nuclear medicine expert in the context of a multimodal therapy concept. In this way, success rates of over 80%, with only few side effects, can be achieved, particularly in rheumatoid arthritis, reactive arthritis and hemophilic arthropathy.

The closing of the last century opened a wide variety of approaches for inflammation imaging and treatment of patients with rheumatoid arthritis (RA). The introduction of biological therapies for the management of RA started a revolution in the therapeutic armamentarium with the development of several novel monoclonal antibodies (mAbs), which can be murine, chimeric, humanised and fully human antibodies. Monoclonal antibodies specifically bind to their target, which could be adhesion molecules, activation markers, antigens or receptors, to interfere with specific inflammation pathways at the molecular level, leading to immune-modulation of the underlying pathogenic process. These new generation of mAbs can also be radiolabelled by using direct or indirect method, with a variety of nuclides, depending upon the specific diagnostic application. For studying rheumatoid arthritis patients, several monoclonal antibodies and their fragments, including anti-TNF-alpha, anti-CD20, anti-CD3, anti-CD4 and anti-E-selectin antibody, have been radiolabelled mainly with (99m)Tc or (111)In. Scintigraphy with these radiolabelled antibodies may offer an exciting possibility for the study of RA patients and holds two types of information: (1) it allows better staging of the disease and diagnosis of the state of activity by early detection of inflamed joints that might be difficult to assess; (2) it might provide a possibility to perform 'evidence-based biological therapy' of arthritis with a view to assessing whether an antibody will localise in an inflamed joint before using the same unlabelled antibody therapeutically. This might prove particularly important for the selection of patients to be treated since biological therapies can be associated with severe side-effects and are considerably expensive. This article reviews the use of radiolabelled mAbs in the study of RA with particular emphasis on the use of different radiolabelled monoclonal antibodies for therapy decision-making and follow-up.

Infrared (IR)-A irradiation can be useful in back and musculoskeletal pain therapy. In this study joint and vertebral column pain and mobility were measured during two weeks of IR-A irradiation treatment of patients suffering from degenerative osteoarthritis of hip and knee, low back pain, or rheumatoid arthritis. Additionally, before and after IR-A treatment MDA serum levels were measured to check if MDA variations accompany changes in pain intensity and mobility. Two-hundred and seven patients were divided into verum groups getting IR-irradiation, placebo groups getting visible, but not IR irradiation, and groups getting no irradiation. In osteoarthritis significant pain reduction according to Visual Analogue Scale and mobility improvements occurred in the verum group. Even though beneficial mean value changes occurred in the placebo group, the improvements in the placebo and No Irradiation groups were without statistical significance. In low back pain, pain and mobility improvements (by 35-40%) in the verum group were found, too. A delayed (2nd week) mobility improvement in rheumatoid arthritis was seen. However, pain relief was seen immediately. In patients suffering from low back pain or rheumatoid arthritis, the pain and mobility improvements were accompanied by significant changes of MDA serum levels. However, MDA appears not a sensitive biofactor for changes of the pain intensity in degenerative osteoarthritis. Nevertheless, unaffected or lowered MDA levels during intensive IR-A therapy argue against previous reports on free radical formation upon infrared. In conclusion, rapid beneficial effects of IR-A towards musculoskeletal pain and joint mobility loss were demonstrated.

The main objective of this paper was to obtain the absorbed dose profiles for radionuclides of frequent or potential use in radiosynoviortheses. These profiles reveal the absorbed dose per activity of injected radionuclide (Gy/h*MBq) in the synovial membrane and the articular cartilage. The researched radionuclides were (32)P, (90)Y, (188)Re, (177)Lu, (153)Sm and (169)Er. The therapeutic range of each radionuclides in synovial tissue were also calculated. This range determines the synovial thickness that can be sufficiently irradiated and thus successfully treated. The S values for the synovial membrane and articular cartilage were calculated using as a model a cylinder with the source uniformly distributed in its volume. The synovial membrane was simulated varying the radius of the cylinder (from 0.5cm to 9cm) and its height (from 0.01cm to 0.04cm). The area in the base of the cylinder represents different sizes of the synovial surface (small, medium and large joints). The height of the cylinder represents different stages of the progression of the rheumatoid arthritis. The same model was used to simulate the articular cartilage but, the source was uniformly distributed into a cylindrical slab (0.01cm height and 1cm of radius. The results obtained allow the estimation of the dose that will be delivered to the synovial membrane and the articular cartilage for different joint sizes and different stages of progression of the rheumatoid arthritis (RA).

Objectives: To compare work disability (WD) and health status between males and females with rheumatoid arthritis (RA) in the age group 18-45 years, and to compare health status between patients with and without WD within each gender, and finally to identify factors independently associated with WD in this age group., Methods: A cross-sectional study of RA patients at the time starting with disease-modifying antirheumatic drug (DMARD) therapy and/or biological treatment. Patients receiving a permanent, national WD pension corresponding to >or= 50% were defined as work disabled. We examined gender differences with regard to disease characteristics, health status and WD. The Mann-Whitney U-test and Pearson's chi(2)-test were applied for group comparisons. Multiple logistic regression analyses with adjustments for duration of education, disease duration, age, erosive disease, disability score [using the Modified Health Assessment Questionnaire (MHAQ)], Disease Activity Score-28 (DAS-28), the Short Form Health Survey (SF-36) mental health score and gender were used to identify variables associated with WD., Results: Out of 474 (372 females) patients, the number (%) of work-disabled females/males was 91 (24.7)/8 (8.1) (p<0.001). WD was associated with worse health status in both genders. The odds ratio (95% confidence interval) [OR (95% CI)] for WD in females vs. males was 4.84 (1.85-12.65) in the multivariate analyses. Other factors independently associated with WD were worse mental health, disease duration and low level of education., Conclusion: Females with RA had a fourfold increased risk of WD compared to men. Low level of education, disease duration and worse mental health were also independently associated with WD.

Background and Objective: Low level light therapy (LLLT) is being evaluated for treating chronic and acute pain associated with rheumatoid arthritis (RA) and other inflammatory diseases. The mechanisms underlying the effectiveness of LLLT for pain relief in RA are not clear. The objectives of this study were to determine whether LLLT decreased production of pro-inflammatory cytokines by cells from RA joints, and, if so, to identify cellular mechanisms., Study Design/materials and Methods: Synoviocytes from RA patients were treated with 810 nm radiation before or after addition of tumor necrosis factor-alpha (TNF-alpha). mRNA for TNF-alpha, interleukin (IL)-1beta, IL-6, and IL-8 was measured after 30, 60, and 180 minutes using RT-PCR. Intracellular and extracellular protein levels for 12 cytokines/chemokines were measured at 4, 8, and 24 hours using multiplexed ELISA. NF-kappaB activation was detected using Western blotting to follow degradation of IkappaBalpha and nuclear localization of the p65 subunit of NF-kappaB., Results: Radiation at 810 nm (5 J/cm(2)) given before or after TNF-alpha decreases the mRNA level of TNF-alpha and IL-1beta in RA synoviocytes. This treatment using 25 J/cm(2) also decreases the intracellular levels of TNF-alpha, IL-1beta, and IL-8 protein but did not affect the levels of seven other cytokines/chemokines. TNF-alpha-induced activation of NF-kappaB is not altered by 810 nm radiation using 25 J/cm(2)., Conclusions: The mechanism for relieving joint pain in RA by LLLT may involve reducing the level of pro-inflammatory cytokines/chemokines produced by synoviocytes. This mechanism may be more general and underlie the beneficial effects of LLLT on other inflammatory conditions.

Objective: To perform a systemic review and meta-analysis on the effectiveness of radiosynoviorthesis (RSO)., Methods: A search of medical databases was conducted. Criteria for inclusion: articles in English, minimum follow-up of 6 months, specification of joint disease, reported outcome of at least 5 RSOs. The studies were scored for quality by the Oxford Centre of Evidenced-based Medicine Levels of Evidence, from 1 to 4., Results: Twenty-one (21) studies were included (3 quality 1b, 5 2b and 13 4), analysing 169Erbium/186Rhenium-RSO used predominantly in small joints and 49 (1 quality 1b, 10 2b and 38 4) on 90Yttrium-RSO used predominantly in knee joints. The reported success rates of 169Erbium/186Rhenium-RSO ranged from 69-100% at 6 months, and from 54-100% at > or =12 months; for 90Yttrium they were 24-100% and 29-94%, res-pectively. Studies comparing the effect of RSO with that of glucocorticoid (GC) or saline injection alone were pooled. At 6 months, the pooled odds ratio favouring RSO of the knee with Yttrium over control is 4 (confidence interval (CI) 95% 1.2-14), p=0.02, but at 12 months the ratio was 1.7 (CI95% 0.69-4), p=0.26. For RSO of small joints with Erbium/Rhenium compared to controls, the pooled odds ratio at 6 months is 2 (CI95% 0.66-6), p=0.22 and at 12 months 2 (CI95% 1.09-3.5), p=0.03., Conclusion: Reported success rates of RSO are high, but differences in effect with GC injection are less evident, although there is marked heterogeneity in study design of the (small number of) comparative studies.