OA Patients Research Articles

Ultrasound-Guided Injections of HYADD4 for Knee Osteoarthritis Improves Pain and Functional Outcomes at 3, 6, and 12 Months without Changes in Measured Synovial Fluid, Serum Collagen Biomarkers, or Most Synovial Fluid Biomarker Proteins at 3 Months.

Prior studies have demonstrated improved efficacy when intra-articular (IA) therapeutics are injected using ultrasound (US) guidance. The aim of this study was to determine if clinical improvement in pain and function after IA hyaluronic acid injections using US is associated with changes in SF volumes and biomarker proteins at 3 months. 49 subjects with symptomatic knee OA, BMI < 40, and KL radiographic grade II or III participated. Subjects with adequate aspirated synovial fluid (SF) volumes received two US-guided IA-HA injections of HYADD4 (24 mg/3 mL) 7 days apart. Clinical evaluations at 3, 6, and 12 months included WOMAC, VAS, PCS scores, 6 MWD, and US-measured SF depth. SF and blood were collected at 3 months and analyzed for four serum OA biomarkers and fifteen SF proteins. Statistical differences were observed at 3, 6, and 12 months compared to baseline values, with improvements at 12 months for WOMAC scores (50%), VAS (54%), and PCS scores (24%). MMP10 levels were lower at 3 months without changes in SF volumes, serum levels of C2C, COMP, HA, CPII, or SF levels of IL-1 ra, IL-4, 6, 7, 8, 15, 18, ILGFBP-1, 3, and MMP 1, 2, 3, 8, 9. Baseline clinical features or SF biomarker protein levels did not predict responsiveness at 3 months. Clinical improvements were observed at 12 months using US needle guidance for IA HA, whereas only one SF protein biomarker protein was different at 3 months. Larger studies are needed to identify which SF biomarkers will predict which individual OA patients will receive the greatest benefit from IA therapeutics.

Identification of basement membrane-related biomarkers associated with the diagnosis of osteoarthritis based on machine learning

BackgroundOsteoarthritis is a very common clinical disease in middle-aged and elderly individuals, and with the advent of ageing, the incidence of this disease is gradually increasing. There are few studies on the role of basement membrane (BM)-related genes in OA.MethodWe used bioinformatics and machine learning methods to identify important genes related to BMs in OA patients and performed immune infiltration analysis, lncRNA‒miRNA-mRNA network prediction, ROC analysis, and qRT‒PCR.ResultBased on the results of machine learning, we determined that LAMA2 and NID2 were the key diagnostic genes of OA, which were confirmed by ROC and qRT‒PCR analyses. Immune analysis showed that LAMA2 and NID2 were closely related to resting memory CD4 T cells, mast cells and plasma cells. Two lncRNAs, XIST and TTTY15, were simultaneously identified, and lncRNA‒miRNA‒mRNA network prediction was performed.ConclusionLAMA2 and NID2 are important potential targets for the diagnosis and treatment of OA.

Clinicopathological characteristics and prognosis of adolescents and young adults with gastric cancer after gastrectomy: a propensity score matching analysis.

Gastric cancer (GC) among adolescents and young adults (AYAs, aged 15-39 years) has limited data on clinicopathological characteristics and prognosis. This study aimed to compare the clinicopathological characteristics, perioperative outcomes, and long-term outcomes of AYAs and older adults (OAs, aged > 39 years) with GC who underwent curative gastrectomy. From January 1994 to June 2019, patients with GC undergoing curative gastrectomy were enrolled and divided into AYA group and OA group. The clinicopathological characteristics, treatment variables, perioperative outcomes and long-term outcomes were compared between the two groups, both before and after propensity score matching (PSM). AYAs had fewer comorbid conditions and were more likely to be females, have normal carcinoembryonic antigen (CEA) levels, poorly differentiated tumors with perineural invasion, and receive adjuvant chemotherapy. AYA patients had lower incidence of postoperative complications and shorter length of postoperative hospital stay than OA patients. No significant differences in postoperative 30-day or 90-day mortality were observed between AYAs and OAs, both before and after PSM. In the entire cohort, AYAs had similar median overall survival (OS) to OAs. However, in the PSM cohort, AYAs had significantly shorter median OS. Young age (15-39 years) was an independent risk factor for OS in GC patients following gastrectomy. The clinicopathological characteristics were significantly different between AYA and OA patients with GC. AYA patients with GC had worse long-term prognosis than OA patients, and young age was an independent risk factor for OS in GC patients following gastrectomy.

The impact of moderate to severe osteoarthritis on the physical performance and quality of life: a cross-sectional study in Greek patients (PONOS study)

BackgroundOsteoarthritis (OA) represents a leading cause of disability with limited data available for the Greek patients.ObjectivesTo evaluate the impact of moderate to severe symptomatic hip/knee OA under treatment on physical performance and quality of life.MethodsA non-interventional, cross-sectional, epidemiological study of patients with moderate/severe OA, recruited in a single visit from 9 expert sites in Athens, Greece. Assessments were based on commonly used outcome scales: the Hip disability and Osteoarthritis Outcome Score (HOOS), the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the EuroQol-5-Dimensions 3-levels questionnaire (EQ-5D-3L).ResultsOne hundred sixty-four patients were included in the analysis. Most of the patients were females (78.7%), with a mean age of 70.5 ± 10.2 years. Comorbidities were reported by 87.2% of patients with hypertension being the most frequently reported (53.7%), followed by dyslipidemia (31.1%), obesity (24.4%) and diabetes mellitus (23.2%). Paracetamol was the most common treatment (96%), followed by NSAIDs (75%), opioids (50%) and locally applied medications (42.7%). Both hip and knee OA patients showed substantial deterioration in health-related quality of life (QoL) and health status as reflected by the HOOS/KOOS (Function in sport and recreation was the most impaired subscale, followed by Hip- or Knee-related QoL). The mean EQ-5D-3L index score was 0.396 ± 0.319 and the mean EQ-VAS score was 52.1 ± 1.9. When compared indirectly to the local population norms our OA population had worse QoL indices.ConclusionOur findings suggest the functional disability and impaired QoL of Greek patients with moderate/severe hip/knee OA under treatment emphasizing the need for novel treatments that will reduce the burden of the disease.

Efficacy of tumor necrosis factor inhibitors in hand osteoarthritis: A systematic review and meta-analysis of randomized controlled trials

ObjectivesThis study aimed at systematically review the evidence for the efficacy of Tumor Necrosis Factor (TNF) inhibitors on symptoms and structural outcomes in hand osteoarthritis. MethodsThree databases were searched for randomized controlled trials examining the efficacy of TNF inhibitors in hand osteoarthritis. Two authors extracted data and assessed the risk of bias. The mean difference (MD) was calculated, and a random-effects meta-analysis was performed. ResultsFour studies were identified involving 276 participants. Meta-analysis showed that TNF inhibitors had no effect on pain at 4–6 weeks (MD -0.93, 95%CI -7.41 to 5.55; 2 studies) and 24–26 weeks (MD -3.82, 95%CI -11.46 to 3.83; 2 studies) and no effect on grip strength at 12 months (MD -0.35, 95%CI -1.08 to 0.37; 2 studies). There was limited evidence for the effect of TNF inhibitors on structural outcomes at 12 months. Subgroup analysis from 2 studies showed beneficial effect of TNF inhibitors on reducing the progression of structural outcomes in hand OA patients with signs of inflammation but not in those without inflammation. The certainty of the evidence was low for the effect of TNF inhibitor on pain and moderate for the effect on grip strength. ConclusionThis study found no effect of TNF inhibitors on clinical outcomes in hand osteoarthritis over the short term (<6 weeks) and within one year, with some evidence for beneficial effect on structural outcomes.

Adaptation and validation of the chronic illness-related shame scale among patients with knee osteoarthritis in Singapore

BackgroundOsteoarthritis (OA) of the knee is one of the most common and disabling conditions worldwide. A neglected aspect of knee OA is its psychosocial impact, such as shame. However, assessment tools to measure shame among patients diagnosed with knee OA are lacking. In this study, the psychometric properties of the Chronic Illness-related Shame Scale (CISS) were evaluated among knee OA patients in Singapore.MethodsAdaptations were made to CISS for use among the knee OA population. An exploratory factor analysis (EFA) was performed to analyze the factor structure. Cronbach’s Alpha and corrected item-total correlations were used to evaluate the internal consistency. Spearman correlation coefficient was used to test the correlation between CISS and Patient Health Questionnaire-4 (PHQ-4) to determine the validity of the instrument.ResultsThe EFA yielded a one-factor structure, with an eigenvalue of 4.78 explaining 68.25% of variance. Cronbach Alpha was 0.92, which indicated good internal consistency. The Spearman correlation revealed a significant correlation between CISS and PHQ-4.ConclusionsThe adapted CISS is a valid and reliable instrument to measure shame for knee OA patients. Both research and clinical settings can benefit from the use of the adapted CISS for assessing shame among knee OA patients.

Dynamic interaction of obesity, age, MCP-1 Level, and ACE-1 gene with the severity of knee osteoarthritis: a cross-sectional study.

A total of 80 knee OA patients were included in this cross-sectional study. The severity of knee OA was determined based on the Kellgren-Lawrence system. All patients underwent physical and radiological examination; monocyte chemoattractant protein 1 (MCP-1) markers were measured. The parameters of the ACE-1 gene were examined with sequencing DNA. There was a significant relationship between age and severity of knee OA (P=0.007), with subjects aged greater than or equal to 65 having a 3.56-fold higher risk of developing moderate to severe OA than subjects aged less than 65. There was a significant difference between body weight and knee OA severity (P=0.026), in which subjects weighing greater than or equal to 60kg had 3.14 times the risk of experiencing severe knee OA. Multivariate regression analysis indicated that age was the strongest independent variable for knee OA severity compared with body weight. MCP-1 levels were significantly higher in mild knee OA than in moderate to severe knee OA. The DD genotype of the ACE-1 gene increases the risk of severe knee OA by four times in subjects aged greater than or equal to 65 compared to subjects aged less than 65. However, the DD genotype of the ACE-1 gene does not increase the risk of severe knee OA in subjects weighing greater than or equal to 60kg. While obesity and age were found to be associated with the severity of knee OA, age emerged as the independent risk factor for knee OA severity. Furthermore, MCP-1 levels were significantly higher in cases of mild knee OA compared to severe knee OA. It was observed that the DD genotype of the ACE-1 gene increases the risk of severe knee OA in individuals aged 65 years or older.

Investigating the Efficacy and Safety of Diacerein in the Management of Knee Osteoarthritis with reference to its conventional management.

Designated as a "priority disease" by World Health Organization, Osteoarthritis is the most common chronic rheumatic disease. Providing a proper treatment for Osteoarthritis is still a major public health challenge. Diacerein has been proposed as a slow acting, symptom modifying or even disease modifying drug used in Osteoarthritis having a risk-benefit ratio far better than conventionally used drugs. However, the evidence of efficacy and safety of use of Diacerein in Osteoarthritis is yet to be explored. Hence, this study attempted to investigate the efficacy and safety of Diacerein in the management of knee osteoarthritis. This is an analytical cohort study comparing Diacerein with Non-steroidal anti-inflammatory drugs for two months in the management of knee OA. Efficacy was assessed by scores of Lysholm Knee Scoring Scale, Knee injury and Osteoarthritis Outcome Score - Physical Function Short form and Western Ontario and McMaster Universities Osteoarthritis Index. After two months of treatment, the post- treatment scores were significantly superior to the baseline scores in both the treatment groups (p<0.001). There were no significant differences among the post-treatment scores in two different treatment groups (p>0.05). Discoloration of urine and gastritis were the frequently reported adverse effects in Diacerein treatment group and Non-steroidal anti-inflammatory drugs treatment group respectively. Our findings have shown Diacerein is as effective as Non-steroidal anti-inflammatory drugs in treating knee OA patients. Diacerein was generally well tolerated, with a good safety profile. These findings indicate the need for further studies with experimental study design in larger scale.

Increase in TPSB2 and TPSD1 Expression in Synovium of Hip Osteoarthritis Patients Who Are Overweight.

While research suggests that increasing body mass index (BMI) is a risk factor for hip osteoarthritis (HOA), the mechanisms of this effect are not fully understood. Tryptases are among the main proteases found in mast cells (MCs) and contribute to OA pathology. TPSB2, which encodes β-tryptase, is increased in the synovium of overweight and obese knee OA patients. However, it remains unclear whether tryptase in the synovium of HOA is increased with increasing BMI. Here, we investigated tryptase genes (TPSB2 and TPSD1) in the synovium of overweight HOA patients. Forty-six patients radiographically diagnosed with HOA were allocated to two groups based on BMI, namely normal (<25 kg/m2) and overweight (25-29.99 kg/m2). TPSB2 and TPSD1 expression in the synovium of the two groups was compared using real-time polymerase chain reaction. To compare TPSB2 and TPSD1 expression in MCs between the groups, we isolated the MC-rich fraction (MC-RF) and MC-poor fraction (MC-PF), extracted using magnetic isolation. TPSB2 and TPSD1 expression was increased in the overweight group compared with the normal group. Expression of both genes in the MC-RF was significantly higher than that in MC-PF in both groups. However, TPSB2 and TPSD1 expression levels in the MC-RF did not differ between the groups. Tryptase genes were highly expressed in the synovium of overweight HOA patients. Further investigation to reveal the role of tryptase in the relationship between increasing BMI and HOA pathology is required.

Proteomic Analysis of Testicular Interstitial Fluid in Men with Azoospermia

BackgroundThe primary microenvironment of the testis comprises testicular interstitial fluid (TIF) surrounding the seminiferous tubules and testicular interstitial tissue. The pathological alterations of germ and Sertoli cells could affect the TIF composition and might contain putative biomarkers for monitoring active spermatogenesis. ObjectiveWe identified differentially expressed proteins in the TIF of patients with obstructive (OA) or nonobstructive (NOA) azoospermia to elucidate the underlying etiology of defective spermatogenesis. Design, setting, and participantsWe prospectively enrolled nine patients, including three men with OA and six with NOA with (n = 3) and without (n = 3) successful sperm retrieval. Their TIF was collected during the testicular sperm extraction procedure. Outcome measurements and statistical analysisTIF was analyzed using liquid chromatography-tandem mass spectrometry to identify differentially expressed proteins specific to OA and NOA with or without successful sperm retrieval. The dysregulated protein was further validated using Western blotting. Results and limitationsAmong the 555 TIF proteins identified in NOA patients, 14 were downregulated relative to OA patients. These proteins participate in biological processes such as proteolysis, complement activation, and immune responses; complement and coagulation cascade pathways were also enriched. Furthermore, 68 proteins with significantly higher levels were identified in the TIF of NOA patients with successful sperm retrieval than in those with failed sperm retrieval; these are mainly implicated in oxidation-reduction processes. The expression of calreticulin, which can distinguish successful and failed testicular sperm retrieval in the NOA group, was validated by Western blotting. ConclusionsWe provide the first scientific evaluation of TIF protein composition in men with azoospermia. These findings will help identify the physiological and pathological roles of each protein in regulating sperm production. Thus, our study underscores the potential of TIF in sperm retrieval biomarker discovery and would serve as a foundation for further studies to improve treatment strategies against azoospermia. Patient summaryUsing a proteomic approach, we identified and analyzed the total protein content of testicular interstitial fluid in humans with defective spermatogenesis for the first time and discovered altered protein expression patterns in patients with nonobstructive azoospermia (NOA). Proteins related to oxidation-reduction processes were upregulated in NOA patients with successful sperm retrieval compared with those with failed sperm retrieval. This can aid the development of novel diagnostic tools for successful testicular sperm retrieval.

Effect of osteoarthritis and its surgical treatment on patients’ quality of life: a longitudinal study

BackgroundOsteoarthritis (OA) is one of the primary causes of pain and disability worldwide leading to patients having some of the worst health-related quality of life (QOL). The purpose of our study was to investigate the progression of the generic and disease-specific QOL of osteoarthritic patients going through total hip or knee replacement surgery and the factors that might alter the effect of surgery on QOL.MethodsA longitudinal study was performed based on data collected from 120 OA patients who filled in the short version of the WHO’s generic measure of quality of life (WHOQOL-BREF) and the disease-specific Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) before and after surgery.ResultsDomains related to physical health status showed relatively lower scores in patients before surgery. Patients reported a significant increase of QOL after surgery in the WHOQOL-BREF physical domain, especially if they were from the younger group (< 65 years, p = 0.022) or had a manual job (p = 0.008). Disease-specific QOL outcome results indicate that overall patients gained significantly better QOL in all domains of the WOMAC score. Patients with hip OA seemed to have the most benefit of their operation as they reported better outcome in WOMAC pain (p = 0.019), stiffness (p = 0.010), physical function domains (p = 0.011) and total score (p = 0.007) compared to knee OA patients.ConclusionThere was a statistically significant improvement in all domains concerning physical functions in the study population. Patients also reported significant improvement in the social relationship domain, which indicates that OA itself as well as its management might have a profound effect on patients’ life beyond the reduction of their pain.

Stair Climbing Ability and Identification of the Nine Stairs Ascent and Descent Test Cut-Off Points in Hip Osteoarthritis Patients: A Retrospective Study.

Objectives As the prevalence and incidence of hip osteoarthritis (hip OA) continue to rise, measuring the impact of hip OA severity on a patient's functionality is essential. Stair walking is a particularly relevant task to assess hip OA patients, as difficulty with stair ascent is one of the driving factors in deciding to undergo a total hip arthroplasty. Although stairs tests often arise in post-arthroplasty measures, there is a lack of reported stairs performance time in hip OA patients. Therefore, this retrospective study aimed to report the stair performance time of hip OA patients categorized by disease severity and determine cut-off points that differentiate between severity grades. Materials and methods The patient selection was based on the review of de-identified data from our research laboratory database. 254 hip OA patients (aged ≥ 50 years)were divided according to the Kellgren-Lawrence classification system into three groups: Grade 2 (n=68), Grade 3 (n=109), and Grade 4 (n= 68). The stair-walking ability was evaluated using the 9S-A/D test. The time taken to ascendand descendthe stairs was measured separately, and the total time (9S-A/D) was also recorded. The one-way ANOVA model, Welch test, Games-Howell posthoc test, Chi-Square tests, and Two-Way ANOVA model were used for the statistical analysis of the data. The cut-off points were obtained by receiver operating curve (ROC) analysis. The statistical significance was set at p<0.05. Results Homogeneity was found between the three groups regarding demographic and clinical characteristics, except age and gender (p<0.001). The comparison of the variables (9S-ascent, 9S-descent, and 9S-A/D) between groups, adjusted for gender and age,showed significant differences: Grade 2 individuals had shorter performance times compared to those in Grade 3 and Grade 4 (p<0.005). Simultaneously, patients with Grade 3 hip OA have a shorter performance time than those with Grade 4 hip OA (p<0.005). Regarding ROC analysis of Grade 2 versus Grade 3: The AUCs of 9S-ascend, 9S-descent, and 9S-A/D were 0.742 (95%CI 0.67-0.81), 0.734 (95%CI 0.66-0.81), and 0.745 (95%CI 0.54-0.90), respectively (all p values <0.005). The cut-off points of 9S-ascend, 9S-descent, and 9S-A/D were 8.7 s (sensitivity 56%, specificity 88%), 7.1 s (sensitivity 58%, specificity 80%), and 16.25 s (sensitivity 54%, specificity 90%), respectively. Concerning ROC analysis of Grade 3 versus Grade 4: The AUCs of 9S-ascend, 9S-descent, and 9S-A/D were 0.702 (95%CI 0.62-0.78), 0.711 (95%CI 0.63-0.79), and 0.715 (95%CI 0.64-0.80), respectively (all p values <0.005). The cut-off points of 9S-ascend, 9S-descent, and 9S-A/D were 11.5 s (sensitivity 66%, specificity 65%), 8.3 s (sensitivity 71%, specificity 62%), and 19.05 s (sensitivity 71%, specificity 61%), respectively. Conclusions The study provides evidence that the progression of hip OA affected stair walking; the performance time of 9S-ascent, 9S-ascent, and 9S-A/D tests was significantly longer as the severity of hip OA worsened. ROC analysis results show tests' ability to distinguish the cut-off point between different hip OA grades. However, further research is required for the reporting and classification of stair performance time values in hip OA patients and to further investigate the ability of 9S-ascent, 9S-descent, and 9S-A/D tests to predict the grade of hip OA.

Enabling early detection of knee osteoarthritis using diffusion–relaxation correlation spectrum imaging

To present a technique that enables detection of early stage OA of the knee using diffusion-relaxation correlation spectrum imaging (DR-CSI).Fifty-five early osteoarthritis patients (OA, Kellgren-Lawrence [KL] score 1 to 2; mean age, 56.4 years) and 49 healthy volunteers (mean age, 56.7 years) were underwent magnetic resonance imaging (MRI) with T2-mapping and DR-CSI techniques. Maps of mean apparent diffusion coefficient (ADC), T2 relaxation time and volume fraction Vi for DR-CSI compartment i (A, B, C, D) sensitivity, specificity, and positive and negative likelihood ratio (PLR, NLR) were assessed to determine the diagnostic accuracy for detection of early-stage degeneration of knee articular cartilage. The structural abnormalities of articular cartilage were evaluated using modified Whole-Organ MR Imaging Scores (WORMS).All intra- and interobserver agreements for DR-CSI compartment volume fractions and modified WORMS of cartilage were excellent. Early OA versus the controls had higher VC, lower VA and VB (p<0.001), but comparable VD (p>0.05). VA, VB and VC had a moderate association with WORMS. No significant correlation was identified between VD and WORMS. VC had better ability than VA,VB, VD, T2 and ADC to discriminate early OA patients from healthy controls (area under the curve, 0.898). Sensitivity, specificity, PLR, and NLR of VC with a cut-off value of 29.9% were 81.8% (95% confidence interval [CI], 69.1-90.9%), 95.9% (86-99.5%), 20.05% (5.13-78.34%), and 0.19% (0.11-0.33%).DR-CSI compartment volume fractions may be sensitive indicators for detecting early-stage degeneration in knee articular cartilage.

Characteristics of NSAIDs Prescription in Elderly Knee Osteoarthritis Patients

&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The prescribing of non-steroidal anti-inflammatory drugs (NSAIDs) as pharmacological therapy for OA was found to be imprecise. In 2018, the rationality of NSAIDs prescribed at Wolter Monginsidi Hospital, Manado showed as much as 100% proper indication, 77% proper dose, and 89% proper medication. This shows that the rationality of NSAIDs prescription is still irrational. Irrational prescribing has the potential to result in side effects or the incidence of drug-related problems&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;To determine the characteristics and the rationality of NSAIDs prescriptions in elderly knee OA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This is a descriptive study of 108 medical records for the period January 2020-April 2021 at BS Clinic, Semarang, using purposive sampling method.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Result: &lt;/strong&gt;Results showed the characteristics of elderly knee OA patients at BS Clinic were 74.1% women, 47.2% belonging to obese group, and 41.7% experiencing severe pain. Patient’s age had a median value of 66 years. In the number of comorbidity, the median value was 1. The rationality of NSAIDs prescription was 95,4% proper diagnosis, 100% proper drug, 97.2% proper dose, and 99.1% proper indication with the incidence of side effects of NSAIDs prescribing was 1.9%.&lt;/p&gt;

CCL20 inhibition for treating inflammation in ankylosing spondylitis.

Th17 cells are known to play a significant role in AS. C-C motif chemokine ligand 20 (CCL20) binds to C-C chemokine receptor 6 (CCR6) on Th17 cells, promoting their migration to inflammation sites. The aim of this research is to examine the effectiveness of CCL20 inhibition in treating inflammation in AS. Mononuclear cells from peripheral blood (PBMC) and SF (SFMC) were collected from healthy individuals and AS. Flow cytometry was used to analyse cells producing inflammatory cytokines. CCL20 levels were determined using ELISA. The impact of CCL20 on Th17 cell migration was verified using a Trans-well migration assay. The in vivo efficacy of CCL20 inhibition was evaluated using an SKG mouse model. The presence of Th17 cells and CCL20 expressing cells was higher in SFMCs from AS patients compared with their PBMCs. The CCL20 level in AS SF was significantly higher than in OA patients. The percentage of Th17 cells in PBMCs from AS patients increased when exposed to CCL20, whereas the percentage of Th17 cells in SFMCs from AS patients decreased when treated with CCL20 inhibitor. The migration of Th17 cells was found to be influenced by CCL20, and this effect was counteracted by the CCL20 inhibitor. In the SKG mouse model, the use of CCL20 inhibitor significantly reduced joint inflammation. This research validates the critical role of CCL20 in AS and suggests that targeting CCL20 inhibition could serve as a novel therapeutic approach for AS treatment.

Factors Influencing Surgical Decision Making in Trapeziometacarpal Osteoarthritis

With trapeziometacarpal osteoarthritis (TMC OA), the relationship between disease severity and pretreatment dysfunction, patient expectations, and preferred patient treatment and management remains unclear. This study aimed to assess the association between functional status, pretreatment expectations, and demographic and clinical characteristics of TMC OA patients who decide to undergo operative management. Patients diagnosed with TMC OA (n= 96) were administered the Thumb Arthritis Expectations Survey and the Brief Michigan Hand Questionnaire (bMHQ) during their initial office visit. Demographic data (sex, age, race, education level, marital status, comorbidities, and hand dominance) and clinical characteristics (prior injury, and therapeutic interventions including splinting, steroid injections, therapy, and anti-inflammatory medication) were collected. Multiple logistic regression was used to assess the association between surgical treatment and expectation scores. Our logistic regression model found that lower bMHQ scores, high thumb arthritis expectation survey scores, and prior treatments for TMC OA were associated significantly with the surgical treatment of TMC OA. After controlling for all possible covariates, the odds of having surgery was 3.9 times higher among patients with high expectations (above median) compared to patients with low expectations (adjusted odds ratio [AOR], 3.9; 95% confidence interval [CI], 1.3-11.2). Patients with average function, as measured by bMHQ scores, were 74.5% less likely to elect for surgery than those with the lowest bMHQ (AOR, 0.3; 95% CI, 0.1-0.9). Patients treated previously with steroids were 13 times more likely to elect for surgery than those who were never treated for TMC arthritis (AOR,13.1; 95% CI, 2.2-77.0). Patients with TMC OA who elect to proceed with surgical management have lower bMHQ (greater perceived dysfunction) and higher expectations, and have had prior treatment. Age was not a significant predictor of surgical management of TMC OA. Prognostic IV.

The relationship between clinical phenotype and kallikrein-kinin bioregulation in different forms of arthritis

ObjectivePatients with rheumatoid arthritis (RA) have shown increased levels of neutrophils generating kallikrein-kinin peptides in blood which are potent mediators of inflammation. This study investigated the association between the bioregulation of kinin-mediated inflammation with the clinical, quality of life, and imaging characteristics (e.g. ultrasonography) of different arthritides.MethodsPatients with osteoarthritis (OA, n = 29), gout (n = 10) and RA (n = 8) were recruited and screened for clinical symptoms, quality of life, and ultrasonographical assessment of arthritis. Blood neutrophils were assessed for the expression of bradykinin receptors (B1R and B2R), kininogens and kallikreins by immunocytochemistry with visualization by bright field microscopy. Levels of plasma biomarkers were measured by ELISA and cytometric bead array.ResultsQuality of life (SF-36 domains and summary scores; including pain; and, HAQ) was similar across OA, gout and RA patients; with the exception of worse physical functioning scores between OA and gout patients. Synovial hypertrophy (on ultrasound) differed between groups (p = 0.001), and the dichotomised Power Doppler (PD) score of greater than or equal to 2 (PD-GE2) was marginally significant (p = 0.09). Plasma IL-8 were highest in patients with gout followed by RA and OA (both, P < 0.05). Patients with RA had higher plasma levels of sTNFR1, IL-1β, IL-12p70, TNF and IL-6, compared to OA and gout patients (all, P < 0.05). Patients with OA had higher expression of K1B and KLK1 on blood neutrophils followed by RA and gout patients (both, P < 0.05). Bodily pain correlated with B1R expression on blood neutrophils (r = 0.334, p = 0.05), and inversely with plasma levels of CRP (r = −0.55), sTNFR1 (r = −0.352) and IL-6 (r = −0.422), all P < 0.05. Expression of B1R on blood neutrophils also correlated with Knee PD (r = 0.403) and PD-GE2 (r = 0.480), both P < 0.05.ConclusionsPain levels and quality of life were similar between patients with OA, RA and gout with knee arthritis. Plasma inflammatory biomarkers and B1R expression on blood neutrophils correlated with pain. Targeting B1R to modulate the kinin-kallikrein system may pose as a new therapeutic target in the treatment of arthritis.

Potential of secretome of human fetal cartilage progenitor cells as disease modifying agent for osteoarthritis

AimsOsteoarthritis (OA) is caused by an imbalance in the synthesis and degradation of cartilage tissue by chondrocytes. Therefore, a therapeutic agent for OA patients that can positively affect both synthesis and degradation is needed. However, current nonsurgical treatments for OA can barely achieve satisfactory long-term outcomes in cartilage repair. Human fetal cartilage progenitor cells-secretome (ShFCPC) has shown potent anti-inflammatory and tissue-repair effects; however, its underlying mechanisms and effects on OA have rarely been systematically elucidated. This study aims to analyze and evaluate the potency of ShFCPC in modifying OA process. Main methodsHerein, secreted proteins enriched in ShFCPC have been characterized, and their biological functions both in vitro and in vivo in an OA model are compared with those of human bone marrow-derived mesenchymal stem cells-secretome (ShBMSC) and hyaluronan (HA). Key findingsSecretome analysis has shown that ShFCPC is significantly enriched with extracellular matrix molecules involved in many effects of cellular processes required for homeostasis during OA progression. Biological validation in vitro has shown that ShFCPC protects chondrocyte apoptosis by suppressing the expression of inflammatory mediators and matrix-degrading proteases and promotes the secretion of pro-chondrogenic cytokines in lipopolysaccharide-induced coculture of human chondrocytes and SW982 synovial cells compared with ShBMSC. Moreover, in a rat OA model, ShFCPC protects articular cartilage by reducing inflammatory cell infiltration and M1/M2 macrophage ratio in the synovium, which directly contributes to an increase in immunomodulatory atmosphere and enhances cartilage repair compared to ShBMSC and HA. SignificanceOur findings support clinical translations of ShFCPC as a novel agent for modifying OA process.

Counseling on the Potential of Platelet Growth Factor as a Biological Agent to Overcome Osteoarthritis Disorders at Ar-Rasyid Hospital Palembang Indonesia

Growth factor is a cytokine that plays a role in triggering a series of inhibition of inflammatory processes and triggers repair of joint cartilage which acts as a shock absorber. However, the current phenomenon shows that patients are still very hesitant to take advantage of the potential of platelet growth factor as a modality for the treatment of OA. The aspect of patient ignorance related to the potential of this modality is believed to be the reason for the lack of interest in OA patients utilizing this therapeutic modality. This community service aims to increase aspects of knowledge of OA patients about the potential, benefits and possible risks of using platelet growth factor through the process of counseling and education for OA patients at Ar-Rasyid Hospital Palembang Indonesia. This counseling activity was carried out on outpatients at the polyclinic of Ar-Rasyid Hospital Palembang Indonesia. There was an increase in the response knowledge score after counseling on the potential growth factor of platelets to overcome OA, with p&lt;0.05. The results of the study also showed that there was an increase in aspects of attitude and behavior to choose the modality of platelet growth factor therapy after thecounseling process, with p &lt; 0.05. Counseling activities are effective in improving aspects of knowledge and patient behavior at RS Ar Rasyid Palembang Indonesia in choosing growth factor therapy modalities from platelets for OA.

EPISOMAL VECTOR-BASED GENERATION OF IPSC LINES FROM HEALTHY AND OSTEOARTHRITIS (OA) PATIENT SYNOVIOCYTES FOR OA MODELLING IN VITRO

The development of a representative human, in vitro OA model could deepen understanding of disease mechanisms. Our research aimed to reprogram healthy and OA-derived synoviocytes to induced pluripotent stem cells (iPSCs), thereby generating a novel OA in vitro model. Comparison between the two models shall enable research into underlying processes with potential for clinical translation.A meta-analysis of OA synovial biomarkers was conducted, identifying up to thirteen relevant pathophysiology-related factors, including, amongst others, IL-13, IL-10, IL-6, PIICP, and HA, with PIICP demonstrating the largest effect (SMD 6.11 [3.50, 8.72], p &lt;0.00001). With these findings in mind, human fibroblast-like synoviocytes (HFLS) from healthy and OA patients were transduced using Sendai viral reprogramming. Two clones for each of the resulting iPSC lines were expanded and preliminarily analysed in triplicate by ICC and RT-qPCR for pluripotency characteristics.Healthy HFLS-derived and OA-HFLS-derived iPSC (UoS-B and UoS-C lines, respectively) were generated, indicating successful reprogramming. Morphological observations demonstrated typical iPSC appearance, and ICC confirmed presence of pluripotency markers Tra-1-60, Oct3/4 and Nanog. Expression of Oct3/4, Nanog and Sox2 were confirmed by RT-qPCR with OA-iPSC lines expressing higher levels of all markers compared to non-OA iPSC. In particular, expression of Oct3/4 and Sox2 was 3.5 fold and 4.6 fold higher (p &lt;0.001) in OA-iPSCs (UoS-C) vs. non-OA iPSCs (UoS-B), respectively. Sendai virus clearance was confirmed by passage 4.The successfully obtained OA and non-OA iPSCs can be differentiated towards mesenchymal lineages, including chondrocyte and bone progenitor cells, enabling phenotypic comparison and biomarker analysis as identified in meta-analysis. Cell bank dissemination of these cell lines could deepen further in vitro OA research, with potential impact for clinical translation via the identification of novel cellular and molecular targets.