Extra-articular Tissues Research Articles

An Actual Insight into the Pathogenic Pathways of Ankylosing Spondylitis

Spondyloarthritis refers to a broad group of conditions that include ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and enteropathic arthritis associated with Crohn’s disease or ulcerative colitis. They have been classified by the ASAS group (ASsessment in Ankylosing Spondylitis) into axial spondyloarthritis and peripheral spondyloarthritis. Common features include the absence of autoantibodies, genetic predisposition, and clinical aspects such as axial joint involvement, peripheral manifestations, and extra-articular involvement. However, the pathogenic mechanisms remain complex and incompletely elucidated, despite the fact that the specialized literature has described several pathways that act in synergy: genetic predisposition, environmental factors (infections and mechanical stress), or innate and acquired immune mechanisms. Finally, an inflammatory response is triggered by the recruitment of a large number of inflammatory cells and the release of innate cytokines in the affected areas: joints or periarticular or extraarticular tissues. The current article aims to update and systematize the knowledge accumulated so far on this topic, focusing on the mechanisms that have been involved in the onset, progression, and severity of ankylosing spondylitis.

Effects of bariatric surgery on hyperuricemia and gout: a systematic review of the literature.

Gout is the most common form of inflammatory arthritis, and it is due to the deposition of monosodium urate crystals in the articular and extra-articular tissues. Body mass index is strongly correlated with elevated serum uric acid levels and gout is often associated with obesity and metabolic syndrome. Recommended nonpharmacological treatments for hyperuricemia and gout include dietary modifications and weight loss. Many studies have demonstrated that weight loss could reduce serum urate in patients with obesity and it is a commonly recommended treatment for gout. Bariatric surgery-induced weight loss exerts beneficial effects on hyperuricemia and gout, even if a possible raise of gout flares can be observed in patients with hyperuricemia early after surgery. The aim of this review is to systematically analyze all the studies published so far reporting a link between hyperuricemia and/or gout and bariatric surgery to obtain reliable figures on the incidence of this disease and describe the mechanisms underlying this association. Eleven studies accounting for 11,256 patients were included in the review. Mean preoperative prevalence of gout was 4.1%, while the preoperative prevalence of hyperuricemia ranged from 30.6% to 58%. After a mean follow-up of 8.5months, postoperative prevalence of gout significantly decreased to 2.9% (p < .007). The incidence of gout flares after bariatric surgery was higher in the early postoperative phase and progressively decreased over time. Similarly, serum uric acid concentrations showed an increase within the first postoperative month, which was followed by a progressive decrease below the preoperative value.

Flexible microneedles incorporating gold nanorods and tacrolimus for effective synergistic photothermal-chemotherapy of rheumatoid arthritis

Transdermal drug delivery systems for rheumatoid arthritis (RA) have garnered substantial attention due to their great potential to overcome limitations observed in conventional oral or injection strategies, including limited selectivity and adverse effects on extra-articular tissues. Microneedles (MNs) appear to be highly desirable carriers for transdermal drug delivery of RA. However, microneedles typically are unable to keep up with the flexibility of joints, which decreases the effectiveness of administration. In this study, we developed a flexible microneedles (FMNs) delivery system. And gelatin was employed for the fabrication of flexible backings for microneedles owing to its excellent ductility and biocompatibility. We achieved synergisticphotothermal-chemotherapy of RA by incorporating the chemical drug Tacrolimus (TAC) and the photothermal agent gold nanorods (AuNRs) into dissolving microneedles. Results showed a high mechanical strength of the proposed FMNs. In the animal model of adjuvant-induced arthritis (AA), it is indicated that the prepared FMNs inhibited the expression of related inflammatory cytokines such as IL-1ß and TNF-α while enhancing bone repair and other related factors. Thus, the combination therapy of FMNs-mediated hyperthermia and chemotherapy can serve as a novel and synergistic treatment option for RA.

Ondansetron or beta-sitosterol antagonizes inflammatory responses in liver, kidney, lung and heart tissues of irradiated arthritic rats model.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder mainly affecting joints, yet the systemic inflammation can influence other organs and tissues. The objective of this study was to unravel the ameliorative capability of Ondansetron (O) or β-sitosterol (BS) against inflammatory reactions and oxidative stress that complicates Extra-articular manifestations (EAM) in liver, kidney, lung, and heart of arthritic and arthritic irradiated rats. This was accomplished by exposing adjuvant-induced arthritis (AIA) rats to successive weekly fractions of total body γ-irradiation (2Gray (Gy)/fraction once per week for four weeks, up to a total dose of 8Gy). Arthritic and/or arthritic irradiated rats were either treated with BS (40mg/kg b.wt. /day, orally) or O (2mg/kg) was given ip) or were kept untreated as model groups. Body weight changes, paw circumference, oxidative stress indices, inflammatory response biomarkers, expression of Janus kinase-2 (JAK-2), Signal transducer and activator of transcription 3 (STAT3), high mobility group box1 (HMGB1), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), as well as pro- and anti-inflammatory mediators in the target organs, besides histopathological examination of ankle joints and extra-articular tissues. Treatment of arthritic and/or arthritic irradiated rats with BS or O powerfully alleviated changes in body weight gain, paw swelling, oxidative stress, inflammatory reactions, and histopathological degenerative alterations in articular and non-articular tissues. The obtained data imply that BS or O improved the articular and EAM by regulating oxidative and inflammatory indices in arthritic and arthritic irradiated rats.

The role of CYP2C9 gene polymorphism in rheumatoid arthritis

Background/Aim: The inflammatory disorder rheumatoid arthritis (RA) affects quality of life and worsens with symptoms in the extra-articular tissues and systemic joints. The most significant member of the Cytochrome P450 enzyme family, Cytochrome P450 2C9 (CYP2C9), plays an essential role in the alkylation, demethylation, and hydroxylation of a variety of substances. Insufficient studies as to whether the susceptibility to rheumatoid arthritis is genetic exists. Therefore, our study presents new information on whether CYPC9 is a genetic risk factor. In this study, we sought to determine whether rheumatoid arthritis and the CYP2C9 gene polymorphism are related. Methods: This study was conducted as a prospective case-control study. Fifty patients with RA and 50 healthy individuals were included in our study group. Blood from the controls and patients was drawn into ethylenediaminetetraacetic acid (EDTA)-containing tubes, and using a DNA isolation kit, DNA was isolated from leukocytes. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to assess the genotypes of CYPC9*2 and CYP2C9*3 with the LightCycler-CYP2C9 mutation detection kit. Results: The heterozygous CYP2C9*2 genotype was found to carry a 2.85-fold risk when compared with the controls (odds ratio [OR]=2.85, 95% confidence interval [CI]: 0.52–15.50; P=0.22); however, this risk was not statistically significant. It was found that people with the CYP2C9*3 heterozygous genotype had a statistically significant 2.79-fold higher risk compared to the controls (OR=2.79, 95% CI: 1.13–7.00 P=0.04). Conclusion: The heterozygous genotype of CYP2C9*3 may contribute to the onset of RA.

NLRP3 expression in peripheral blood mononuclear cells of patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune disease mainly characterized by painful, swollen, and inflamed joints. Individual, genetic, and environmental factors influence the development of the disease, which causes involvement not only in the joints but also in other extra-articular tissues. However, its etiopathogenesis has not been fully elucidated yet. NLRP3, which is a key component of innate immune system, may contribute to recurrent and chronic inflammation, resulting in inflammation-related diseases. Therefore, we aimed to investigate the expression profile of NLRP3 in peripheral blood mononuclear cells isolated from patients with RA using immunocytochemical approaches in this study. Our findings demonstrated that NLRP3 expression was significantly increased in patients with RA in comparison with the healthy controls (p

High-throughput quantitation of serological dimethylarginines by LC/MS/MS: Potential cardiovascular biomarkers for rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by systemic inflammation of the joints and extra-articular tissues. The incidence of cardiovascular disease (CVD) remains the main cause of morbidity and mortality in patients with RA. Despite the development of new therapeutics targeting the articular manifestations, the relief of the cardiovascular burden is still an unmet medical need during the management of RA. So, the early prognosis of RA-associated CVD plays a crucial role in improving the clinical outcomes of RA patients. Recently, circulating dimethylarginines have gained attention as potential biomarkers for CVDs. Here, we present the development and validation of a high-throughput liquid chromatography-tandem mass spectrometric (LC/MS/MS) method for simultaneous quantification of creatinine, arginine, and dimethylarginines in human serum within 2 mins by isotope dilution mass spectrometry. This method employed a protein precipitation method for rapid sample preparation, trichloroacetic acid (TCA)-based ion pairing chromatography for fast analyte separation, and multiple reaction monitoring (MRM) with stable isotope-labeled internal standards (ISs) for simultaneous quantitation. To assure the quality, our method was validated against the FDA guidelines for lower limit of quantitation (0.2 µM), linearity (square of coefficient correlation>0.99), precision (intra-&inter-assay imprecision < 10 %), accuracy (intra-&inter-assay inaccuracy < 10 %), sample preparation recovery (recovery ≥ 90 %), stability (instability < 10 %), matrix effect (signal suppression < 55 %), and carryover ( < 0.01 %). Afterward, we applied the validated method to a retrospective cross-sectional study. We aimed to evaluate the utility of serological dimethylarginines as potential cardiovascular biomarkers in the development of RA-associated CVD. Our results revealed that the serological ratio of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), an indicator of physiological arginine methylation status, was significantly elevated in patients with RA. This finding might provide value in detecting CVD to improve clinical outcomes in RA management.

Polymorphisms in DNA Repair Genes and Association with Rheumatoid Arthritis in a Pilot Study on a Central European Population.

Rheumatoid arthritis (RA) is a chronic, multifactorial autoimmune disease characterized by chronic arthritis, a tendency to develop joint deformities, and involvement of extra-articular tissues. The risk of malignant neoplasms among patients with RA is the subject of ongoing research due to the autoimmune pathogenesis that underlies RA, the common etiology of rheumatic disease and malignancies, and the use of immunomodulatory therapy, which can alter immune system function and thus increase the risk of malignant neoplasms. This risk can also be increased by impaired DNA repair efficiency in individuals with RA, as reported in our recent study. Impaired DNA repair may reflect the variability in the genes that encode DNA repair proteins. The aim of our study was to evaluate the genetic variation in RA within the genes of the DNA damage repair system through base excision repair (BER), nucleotide excision repair (NER), and the double strand break repair system by homologous recombination (HR) and non-homologous end joining (NHEJ). We genotyped a total of 28 polymorphisms in 19 genes encoding DNA repair-related proteins in 100 age- and sex-matched RA patients and healthy subjects from Central Europe (Poland). Polymorphism genotypes were determined using the Taq-man SNP Genotyping Assay. We found an association between the RA occurrence and rs25487/XRCC1, rs7180135/RAD51, rs1801321/RAD51, rs963917/RAD51B, rs963918/RAD51B, rs2735383/NBS1, rs132774/XRCC6, rs207906/XRCC5, and rs861539/XRCC3 polymorphisms. Our results suggest that polymorphisms of DNA damage repair genes may play a role in RA pathogenesis and may be considered as potential markers of RA.

The novel delivery-exosome application for diagnosis and treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic degenerative disease characterized by persistent systemic synovitis, with a high risk of stiffness, pain, and swelling. It may affect the other extra-articular tissues. There is no ideal treatment for this disease at present, and it can only be controlled by medication to alleviate the prognosis. Exosomes are small vesicles secreted by various cells in the organism under normal or pathological conditions, and play a role in immune response, antigen presentation, cell migration, cell differentiation, tumor invasion and so on. Due to the adverse effects of conventional drugs and treatments in the treatment of RA, exosomes, as a nanocarrier with many advantages, can have a great impact on the loading of drugs for the treatment of RA. This article reviews the role of exosomes in the pathogenesis of RA and the progress of exosome-based therapy for RA.

Association between polymorphisms within the gene coding for tumor necrosis factor (TNF)-alpha with outcomes of treatment in a sample of Iraqi patients with ankylosing spondylitis taking etanercept: an observational study

Background: Ankylosing spondylitis (AS) is a progressive, chronic inflammatory illness with an unclear etiology that explicitly targets the vertebral column, peripheral joints, and extraarticular tissues. The purpose of this research was to investigate if the existence of single nucleotide polymorphisms (SNPs) in the promoter region of the tumor necrosis factor-alpha (TNF-α) gene at positions -1031T/C (rs199964), -857C/T (rs1799724) and -806C/T (rs4248158) in a sample of Iraqi AS patients could influence the patients' outcomes with etanercept. Methods: Sixty patients with established AS receiving only etanercept were selected to enroll in this study, with a mean age of 40.75±8.67 years; 51 patients were male. Patients were classed as "responders" if they obtained a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 clinical response and as "non-responders" if they did not achieve a BASDAI 50 clinical improvement after at least six months of treatment. After polymerase chain reaction (PCR) product amplification of the purified blood DNA, the promoter region of TNF-α gene SNPs was established by Sanger sequencing. Results: This research found a significant difference in the TT genotype of rs1799964, P = 0.02, in the responder group, in contrast to the TC genotype of rs1799964, which was significantly more frequent in the non-responder group, P = 0.01. The wild TT genotype of rs1799964 seemed to enhance the probability of being a responder. Nevertheless, the heterozygote TC genotype of rs1799964 showed a negative and significant correlation for responsiveness to etanercept. Conclusion: The TT genotype of rs1799964 is associated with a higher likelihood of responding to ETN, suggesting that it is a valuable diagnostic for predicting response in Iraqi AS patients.

Tophaceous Gout in Adults: Case Report and Review of the Literature

Gout is a microcrystalline arthropathy resulting from the deposition of sodium urate microcrystals in the articular and periarticular tissues, and even in the extra-articular tissues. It affects mainly men and its mechanism is at the origin of a delay in diagnosis, and consequently its severe forms can occur. We report a case of tophaceous gout in a 59 year old adult, with no family history of gout. Gout, whose first attack was at the age of 40, was polyarticular and affected the left wrist, elbows, knees, ankles and the left big toe. The diagnosis was based on clinical signs (tophi at the elbows, ankles, hands, and auricles) and paraclinical signs ( hyperuricemia at 620 ʯmol/l With normal at150-360 ʯmol/l in women and 310-420 ʯmol/l in men, presence of sodium urate cristals in the puncture fluid of the right knee, double- contour image on ultrasonography) by the ACR/Eular classification criteria. The background treatment was based on 120mg of Febuxostat per day with a favorable follow-up marked by the regression of signs.

PERIPHERAL BLOOD CELL SUBSET EPIGENOTYPING OF KNEE OSTEOARTHRITIS PAIN, RADIOGRAPHIC, AND DUAL PROGRESSORS VIA DECONVOLUTION USING TENSOR COMPOSITION ANALYSIS: DATA AND BIOSPECIMENS FROM THE OSTEOARTHRITIS INITIATIVE

Purpose: Knee osteoarthritis (OA) is a heterogeneous disease characterized by a variety of clinical and molecular phenotypes, and has been described as a chronic systemic inflammatory disease. Substantial epigenetic changes have been identified in OA joints, but less is known about extraarticular tissues. In this study, we apply tensor composition analysis to extract cell-type-specific DNA methylation data from baseline buffy coat DNA samples in a subgroup of osteoarthritis initiative (OAI) patients who exhibited future pain, radiographic, or pain+radiographic progression compared to nonprogressor controls.

Raised Inflammatory Markers as Predictors of Response to Anti-Tumor Necrosis Factor Drugs (Etanercept and Infliximab) in a Sample of Iraqi Patients with Ankylosing Spondylitis

Background: Ankylosing spondylitis (AS) is a chronic systemic inflammatory disorder mainly affecting the axial skeleton, although peripheral joints, entheses, and extra-articular tissues such as eyes, heart, and lungs may also be involved. Raised inflammatory markers in patients with AS at the start of anti-tumor necrosis factor (anti-TNF) therapy are associated with more clinical response. Objectives: The aim of this article is to assess the role of raised inflammatory markers in predicting response to anti-TNF drugs in patients with AS. Materials and Methods: The prospective cohort study enrolled a total of 71 patients with AS. Nineteen patients were excluded from the study due to discontinuation of anti-TNF therapy and 52 patients continued in the study and were followed for 3 months. Results: The mean age of the patients was 35.2±9.6 years, males constitute 84.6% of them and the median disease duration was 5 (3–10) years. Univariate analysis showed that the predictors of response to anti-TNF drugs were raised baseline C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), Bath Ankylosing Spondylitis Disease Activity Index, and Bath Ankylosing Spondylitis Functional Index. Multivariate analysis showed that the only independent predictor for response to anti-TNF drugs was raised baseline CRP. The optimal cut point for CRP to predict response was &gt;7.5 mg/L, whereas that for ESR was &gt;32 mm/h. Conclusion: Raised inflammatory markers at baseline predict better response to anti-TNF drugs in AS patients. CRP had better prediction of response to anti-TNF drugs than ESR.

Vitamin D in skin psoriasis and psoriatic arthritis: where does it stand?

Background Psoriasis can affect skin, as well as articular and extra-articular tissues. It has a multifactorial pathogenesis in which vitamin D has been implicated.Objective To assess vitamin D status in patients with skin psoriasis (PsO) and/or psoriatic arthritis (PsA) and its correlation with disease activity and quality of life (QOL) in a cohort of Egyptian patients.Patients and methods This cross-sectional study included 45 patients, divided into group A (21 patients) with PsO and group B (24 patients) with PsA, as well as 38 healthy controls as group C. Disease activity and QOL were assessed in all patients. The serum total 25-hydroxy vitamin D (25(OH)D) level was measured for all participants.Results The median psoriasis area severity index was 8.4 (0.8–45.8) in group A and 10.9 (0.9–44.4) in group B. The median dermatology life quality index in group A was 7 (2–18) and in group B was 12 (3–30). In group B, the mean disease activity in PsA was 40.2±21.2 and PsAQOL was 14.5±4.18. Serum 25(OH)D levels were not statistically different among the three studies groups (H=4.213 at P=0.122). However, the receiver operating characteristic curve cutoff value (26.8 ng/ml) showed that group C had a statistically higher number of participants with normal vitamin D status compared with groups A and B.Conclusion Although a higher percentage of vitamin D deficiency may be found among patients with PsO and PsA, 25(OH)D levels did not correlate with different parameters in both patient groups.

Immunotherapy for the rheumatoid arthritis-associated coronary artery disease: promise and future.

Objective:To review the latest progress on the pathogenic mechanism and management of rheumatoid arthritis (RA)-associated coronary artery disease (CAD), and propose advice on future management optimization as well as prospects for research and development of new therapeutic regimen.Data sources:This study was based on data obtained from PubMed up to May 2019 using various search terms and their combinations, including coronary artery disease, myocardial ischemia, cardiovascular diseases, RA, rheumatic diseases, treatment, therapy, strategies, immunotherapy, inflammation, and anti-inflammation.Study selection:All retrieved literature was scrutinized, most relevant articles about the pathogenic mechanism and clinical management, especially anti-inflammatory therapy of RA-associated CAD were reviewed.Results:RA is an immune-mediated chronic inflammatory disease which has a great social disease burden. In addition to typical arthritic manifestations, RA also affects extra-articular tissues and organs, within which the involvement of the cardiovascular system, especially incorporating CAD, is the leading cause of death for patients with RA. Recently, numerous basic and clinical studies have been carried out on the mechanism of CAD development and progression under the inflammatory cascade of RA. The effect of traditional RA drugs on CAD risk management has been gradually clarified, and more emerging biologic agents are being explored and studied, which have also achieved satisfactory outcomes. Furthermore, with the success of the CANTOS clinical trial, novel anti-inflammatory therapy for the prevention of cardiovascular disease is believed to have a broad prospect.Conclusions:RA is an independent risk factor for CAD, which mainly results from the underlying inflammatory cascade; therefore, anti-inflammatory therapy, especially the emerging novel biologic drugs, is important for CAD management in patients with RA and may also be a promising approach among the general population.

Pigmented Villonodular Synovitis of the Hip Managed with Arthroscopic Synovectomy: An Analysis of 19 Cases with up to 10-year Follow-up

Objectives:A tenosynoival giant cell tumor known as pigmented villonodular synovitis (PVNS) is a rare, benign, yet locally aggressive neoplasm arising from the synovium. Although most frequently encountered in the knee joint, PVNS is secondly most commonly seen in the hip joint. Occurrence of PVNS in the hip may destroy intra-articular soft tissue and bone, and at times invade extra-articular tissues. There are two categorizations of PVNS: localized and diffuse. The localized manifestation, often referred to as nodular, involves a focal or limited area of the synovium, while the diffuse manifestation involves more widespread areas throughout the synovium. Surgical management by resection of the PVNS within the hip joint has been described with open procedures and arthroscopic procedures. Although surgical management has been shown to be promising, PVNS has a high recurrence rate, of 15-50%. To date, we present the largest cohort of hip joint PVNS managed by arthroscopic synovectomy with mid-term follow-up.Methods:A cohort of 19 patients were diagnosed with hip PVNS and underwent arthroscopic synovectomy between 2008 and 2016. Patients were identified preoperatively based on suspected MRI findings of PVNS or intraoperatively after unexpected PVNS was identified during arthroscopy for another pathology. We assessed patients’ functional ability at a minimum of 2-years follow-up using five patient reported outcome measures (PROMs): mHHS (modified Harris Hip Score), HOS (Hip Outcome Score), iHOT-33 (international Hip Outcome Tool), NAHS (Non-Arthritic Hip Score), and LEFS (Lower Extremity Functional Score).Results:Nineteen patients with hip PVNS were treated with an arthroscopic hip synovectomy. Sixteen of the patients completed patient reported outcome measures. This cohort consisted of 7 (44%) females and 9 (56%) males. The mean patient age was 37 years (range, 25-54). Mean follow-up was 83 months (6.9 years), ranging from 24 months (2 years) to 123 months (10.3 years). Eight (50%) patients had diffuse PVNS and 8 (50%) of patients had nodular PVNS. Laterality of the arthroscopic procedure was 8 (50%) right hip and 8 (50%) left hip. Five (31%) of the patients had a smoking history, while 11 (69%) were non-smokers. Four (25%) had a cam lesion, 4 (25%) had a pincer lesion, 8 (50%) had neither cam nor pincer lesion, and 0 (0%) had combined cam and pincer lesion. Fourteen (88%) patients had histologically confirmed PVNS. Eleven (69%) patients had MRI suspected PVNS prior to arthroscopy, while 5 (31%) patients had unexpected PVNS discovered intraoperatively. Concomitant pathology addressed at the time of arthroscopy, includes 11 (79%) labral tear repair. For the sixteen patients that completed patient reported outcome measures, the mean mHHS was 78.2 (SD, 10.6). Mean HOS-ADL was 10 (SD, 10). Mean HOS-SSS was 21 (SD, 20). Mean iHOT-33 was 69.4 (SD, 16.3). Mean NAHS was 86.5 (SD, 10.2). Mean LEFS was 70.8 (SD, 7.7). A mean percentage of maximal function was 88.6% (SD, 9.8%). To date, 0 (0%) patients have shown evidence of recurrence upon physical exam, follow-up MRI, or repeat arthroscopy.Conclusion:Based on the largest arthroscopically managed cohort of PVNS in the hip to date, we conclude that arthroscopic synovectomy is a reliable and effective treatment of hip PVNS. Patients reported good functional outcomes without evidence of recurrence in a 19 patient cohort with an average follow-up of almost 7 years.

Electrocautery in arthroscopic surgery: intra-articular fluid temperatures above 43°C cause potential tissue damage.

The use of electrocautery during arthroscopy may heat intra-articular saline and subsequently damage intra- and extra-articular tissue. Newer electrocautery devices have the ability to measure the outflow fluid temperature and switch off before reaching a certain threshold; however, the scientific evidence establishing these temperature thresholds' potential for inadvertent damage is lacking. The aim of this study was to analyse current available literature on temperature thresholds for tissue damage after exposure to heated fluid and provide a recommendation for the maximum temperature of intra-articular fluid to prevent tissue damage. In February 2018, a systematic literature review was performed using the MEDLINE/PubMed and Embase databases. Inclusion was limited to studies investigating temperature thresholds for thermal damage to at least one of the tissues of interest: skin, bone, cartilage, soft tissues, and nerves. Studies not reporting specific temperature thresholds for thermal damage were excluded. Twenty articles were selected for the final evaluation and data extraction. Varying temperature thresholds, based on the lowest reported temperature causing tissue damage, were found for the different tissues of interest: 44°C for dermal tissues, between 47 and 50°C for bony tissues, 50°C for cartilage, between 43 and 55°C for soft tissues, and 43°C for nerves. Based on the current literature, a temperature threshold for intra-articular fluid of 43°C during an arthroscopic procedure is recommended to prevent tissue damage. Higher temperatures may cause damage to surrounding intra- and extra-articular tissues. The threshold for irreversible damage is likely to be higher. In clinical practise, one should be aware of possible heating of intra-articular fluid when using electrocautery and related risk of tissue damage. III.

Clinical Relevance of Galectin-1 and Galectin-3 in Rheumatoid Arthritis Patients: Differential Regulation and Correlation With Disease Activity.

Galectins, a family of animal lectins, play central roles in immune system regulation, shaping both innate and adaptive responses in physiological and pathological processes. These include rheumatoid arthritis (RA), a chronic multifactorial autoimmune disease characterized by inflammatory responses that affects both articular and extra-articular tissues. Galectins have been reported to play central roles in RA and its experimental animal models. In this perspective article we present new data highlighting the regulated expression of galectin-1 (Gal-1) and galectin-3 (Gal-3) in sera from RA patients under disease-modifying anti-rheumatic drugs (DMARDs) and/or corticoid treatment in the context of a more comprehensive discussion that summarizes the roles of galectins in joint inflammation. We found that Gal-1 levels markedly increase in sera from RA patients and positively correlate with erythrocyte sedimentation rate (ERS) and disease activity score 28 (DAS-28) parameters. On the other hand, Gal-3 is downregulated in RA patients, but positively correlates with health assessment questionnaire parameter (HAQ). Finally, by generating receiver-operator characteristic (ROC) curves, we found that Gal-1 and Gal-3 serum levels constitute good parameters to discriminate patients with RA from healthy individuals. Our findings uncover a differential regulation of Gal-1 and Gal-3 which might contribute to the anti-inflammatory effects elicited by DMARDs and corticoid treatment in RA patients.

Thermoacoustic Tomography of In Vivo Human Finger Joints.

the purpose of this study was to demonstrate the potential of thermoacoustic tomography (TAT) to reveal anatomic structures of in vivo human finger joints. all the participating volunteers provided written informed consent. Eight healthy middle and index fingers from five volunteers were imaged in vivo by our TAT imaging system. AxialT1-weighted MR imaging (3.0T) was used to validate the TAT findings. Comparative analyses between TAT and MRI images were performed in two dimension for all the fingers imaged. Three-dimensional (3-D) images and animations were also obtained for some of the fingers thermoacoustically scanned. various intra- and extra-articular tissues were identified in TAT images in high fidelity. These TAT images matched well with the MRI images. Both the 3-D images and animations effectively displayed the extension and transformation of the entire finger along the axis. TAT can noninvasively visualize anatomic structures of the finger joints based on the electrical properties of the joint tissues. The results obtained indicate that TAT may have the potential to contribute to the detection of joint and bone diseases. this study represents the first for TAT of in vivo human joints and fingers. This study reveals that TAT can effectively recover both soft and hard tissues of the healthy interphalangeal joints, which provides a foundation for its clinical application to detection and diagnosis of joint and bone diseases.

Imaging and Methotrexate Response Monitoring of Systemic Inflammation in Arthritic Rats Employing the Macrophage PET Tracer [18F]Fluoro-PEG-Folate.

Background In rheumatoid arthritis, articular inflammation is a hallmark of disease, while the involvement of extra-articular tissues is less well defined. Here, we examined the feasibility of PET imaging with the macrophage tracer [18F]fluoro-PEG-folate, targeting folate receptor β (FRβ), to monitor systemic inflammatory disease in liver and spleen of arthritic rats before and after methotrexate (MTX) treatment. Methods [18F]Fluoro-PEG-folate PET scans (60 min) were acquired in saline- and MTX-treated (1 mg/kg, 4x) arthritic rats, followed by tissue resection and radiotracer distribution analysis. Liver and spleen tissues were stained for ED1/ED2-macrophage markers and FRβ expression. Results [18F]Fluoro-PEG-folate PET and ex vivo tissue distribution studies revealed a significant (p < 0.01) 2-fold lower tracer uptake in both liver and spleen of MTX-treated arthritic rats. Consistently, ED1- and ED2-positive macrophages were significantly (p < 0.01) decreased in liver (4-fold) and spleen (3-fold) of MTX-treated compared with saline-treated rats. Additionally, FRβ-positive macrophages were also significantly reduced in liver (5-fold, p < 0.005) and spleen (3-fold, p < 0.01) of MTX- versus saline-treated rats. Conclusions MTX treatment reduced activated macrophages in liver and spleen, as markers for systemic inflammation in these organs. Macrophage PET imaging with [18F]fluoro-PEG-folate holds promise for detection of systemic inflammation in RA as well as therapy (MTX) response monitoring.