Joint Swelling Research Articles

Application of superb microvascular imaging technology in clinical disease activity of rheumatoid arthritis.

Detection of synovitis is essential for assessing the activity and predicting the prognosis of rheumatoid arthritis (RA). The aim of this study was to investigate the diagnostic performance of superb microvascular imaging (SMI) in RA patients with high, moderate, and low activity. One hundred four patients with active RA were selected from the hospital between May 2022 and August 2023. The study observed the correlation between bone erosion of the carpal joint, joint cavity effusion, thickness of synovial hyperplasia of the carpal joint, positivity rate of synovial blood vessels, and their semiquantitative scores with the clinical disease activity of RA using SMI examination. The detection of synovial hyperplasia thickness and joint effusion in the high-activity group was higher than that in the low-activity group, and the difference was statistically significant (P < 0.05). The quantitative SMI test demonstrated that the synovial blood flow grading and semiquantitative grade increased gradually with activity level (P<0.05). During the high, moderate, and low-activity groups, the vascular index (VI) value of the hyperplastic synovial membrane decreased gradually, showing statistical significance both between and within the groups (P<0.05). SMI technology exhibited high sensitivity and accuracy in assessing disease activity in RA. It holds significant clinical application value as a reliable auxiliary tool for assessing disease activity in RA and treatment. Key Points • Super micro-vascular imaging (SMI) demonstrated higher detection rates of microvesselsin RA patients with high disease activity compared to those with low activity, showing statistical significance. • The quantitative SMI test revealed a clear correlation between synovial blood flow grading and disease activity levels in RA patients, highlighting the potential of SMI as a valuable tool for disease activity and treatment of rheumatoid arthritis.

Exploring the mechanism of tetramethylpyrazine in the treatment of osteoarthritis based on network pharmacology

BackgroundOsteoarthritis (OA) is the most common joint disease, which mainly damages articular cartilage and involves the whole joint tissue. It has the characteristics of long course, repeated symptoms and high disability rate, and the incidence trend is gradually increasing. Tetramethylpyrazine (TMP) is the main alkaloid active substance in Ligusticum wallichii, a traditional Chinese medicine, which has the effect of promoting blood circulation and dredging collaterals, and has a good effect on the treatment of early OA, but its molecular mechanism has not been fully clarified so far. Based on network pharmacology, molecular docking simulation and animal experiments, this study explored the target and molecular mechanism of TMP in the treatment of OA.MethodsWe used PubChem, SwissTargetPrediction, and PharmMapper databases to predict the molecular structure and potential targets of TMP. GeneCards and DisGeNET databases were used to predict the relevant targets of OA. Apply UniProt database to convert targets into unified gene names, and proofread and remove duplicate gene names. The intersection targets of TMP and OA obtained on venny2.1.0 website were submitted to the STRING database to construct a PPI network. CytoScape 3.8.2 software was used to analyze the PPI network and obtain the sub-network modules and 10 key targets. The intersection targets of TMP and OA were analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment using DAVID 6.8 database. The intersecting targets of TMP and OA, the biological process of GO enrichment, and KEGG signaling pathway were imported into Cytoscape 3.8.2 software to construct the TMP-target-pathway network diagram. Use molecular docking technology to simulate the interaction between TMP molecules and key targets, and predict the binding mode and binding ability. Animal models of rabbit knee osteoarthritis were prepared, and magnetic resonance imager (MRI) and fluorescence quantitative PCR (RT-qPCR) were used to observe the effect of TMP in treating OA as well as the expression of key target genes.Results585 potential targets of TMP, 3,857 potential targets of OA, and 49 intersecting targets of TMP and OA were obtained. The top 10 key target genes were obtained, in order of ranking: ALB, ESR1, IL10, CAT, F2, MPO, C3, CYP3A4, CYP2C9, ANXA1. GO and KEGG analysis implied that the key targets might act on OA by affecting endothelial cell permeability, peri-articular microcirculatory status, NETs production, activation of complement system and coagulation pathway, regulation of immune function of macrophages and T cells, and substance metabolism pathway in vivo, etc. The molecular mechanism might involve the formation of neutrophil extracellular trap, regulation of the actin cytoskeleton, complement and coagulation cascades, and T cell receptor signaling pathways, etc. Molecular docking simulations showed that the binding energy of IL10 and ANXA1 to TMP was greater than -5Kal/mol, but the other key target proteins showed better binding to TMP, and the binding energy was less than -5 kcal/mol. Animal experiments showed that TMP had a significant therapeutic effect on OA. The TMP group had significantly reduced knee joint effusion and bone marrow damage compared to the OA group (p &amp;lt; 0.05). The qRT-PCR results showed that compared with the OA group, the mRNA expression of ESR1, CAT, C3, CYP3A4, CYP2C9, and ANXA1 in the TMP group increased (p &amp;lt; 0.05), while there was no significant difference in mRNA expression of ALB, IL-10, F2, MPO, etc. (p &amp;gt; 0.05).ConclusionTMP is effective in the treatment of OA, with multi-target and multi-pathway interactions. ESR1, CAT, C3, CYP3A4, CYP2C9, and ANXA1 may be potential targets for TMP treatment of OA. The molecular mechanism mainly involves the formation of neutrophil extracellular trap, regulation of the actin cytoskeleton, complement and coagulation cascades, and T cell receptor signaling pathways, etc.

Features of Magnetic Resonance Diagnostics of Tenosynovial Giant Cell Tumor (Pigmented Villonodular Synovitis)

Aim. Demonstrate the features of magnetic resonance diagnostics of tenosynovial giant cell tumor.Materials and Methods. Using magnetic resonance imaging, we identified patients with tenosynovial giant cell tumor of the knee joint, describing the diagnostic features and clinical course of diffuse and local forms of the tumor.Results. Specific MRI patterns of tenosynovial giant cell tumor are hemosiderin deposits, villous and nodular growths of the synovium of the knee joint, joint effusion and bone erosion.Conclusion. Тenosynovial giant cell tumor is a rare mesenchymal neoplasm arising from the synovium of joints and tendon sheaths, disabling young able-bodied people. Magnetic resonance imaging, being the “gold” standard for radiological diagnostics, helps to identify specific patterns.

IĸBζ as a Central Modulator of Inflammatory Arthritis Pathogenesis.

Current therapies targeting individual factors in inflammatory arthritis show variable efficacy, often requiring treatment with combinations of drugs, and are associated with undesirable side effects. NF-ĸB is critical for the production and function of most inflammatory cytokines. However, given its essential role in physiologic processes, targeting NF-ĸB is precarious. Hence, identifying pathways downstream of NF-ĸB that selectively govern the expression of inflammatory cytokines in inflammatory arthritis would be advantageous. We have previously identified IĸBζ as a unique inflammatory signature of NF-ĸB that controls the transcription of inflammatory cytokines only under pathologic conditions while sparing physiologic NF-ĸB signals. We generated mice harboring myeloid, lymphoid, and global deletion of Nfkbiz (the gene encoding IĸBζ). These models were subjected to serum transfer-induced arthritis. Additionally, pharmacologic inhibitors of IĸBζ were injected intraperitonially. Joint swelling, microcomputed tomography, immunohistochemistry, flow cytometry, and cytokine measurements were conducted using synovial tissue samples. Global deletion of Nfkbiz or depletion of neutrophils (vastly IĸBζ+ cells) reduced inflammatory synovial cells and increased anti-inflammatory and regenerative synovial cells, plummeted expression of inflammatory factors and ameliorated experimental mouse inflammatory arthritis. Further, expression of immune responsive gene-1, the enzyme responsible for itaconate production, was increased in synovial cells. Accordingly, the itaconate derivative dimethyl itaconate (DI) inhibited IĸBζ-mediated inflammatory factors. Further, in silico screen identified 8-hydroxyquinoline (HQ) as a putative inhibitor of IĸBζ not affecting physiologic NF-ĸB activity. Congruently, systemic administration of either DI or HQ inhibited joint swelling and damage. Our study positions IĸBζ as an inflammation-specific target for therapeutic consideration in rheumatoid arthritis because its inhibition spares the beneficial functions of NF-ĸB.

Feasibility of mNGS in joint replacement patients exhibiting elevated ESR and CRP levels without an underlying diagnosis

ObjectiveThe aim of this study is to investigate the viability of performing initial artificial joint replacement surgery in patients presenting with unexplained elevations in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels.MethodsA cohort of 22 patients, comprising 11 cases each for knee and hip joint replacements, who underwent initial artificial joint replacement surgery between November 2020 and January 2022, was recruited. All patients exhibited elevated levels of ESR and CRP prior to surgery, the etiology of which remained undetermined. Intraoperatively, joint effusion and periarticular tissues were preserved for subsequent bacterial culture and metagenomic next-generation sequencing (mNGS). Postoperatively, a combination of intravenous and local antibiotics was administered for anti-infective management. In cases where bacterial culture and/or mNGS yielded positive results, patients were diagnosed with periprosthetic joint infections (PJI) and underwent one-stage revision; conversely, negative findings led to the discontinuation of intravenous and local antibiotics therapy.ResultsAmong the cohort of 22 patients, bacterial cultures yielded negative results, while mNGS identified bacterial infection in 14 patients (63.63%), viral infection in 1 patient (4.55%), and yielded negative results in 7 patients (31.82%). All surgical incisions achieved per primam. Subsequent follow-up assessments conducted for more than 1 year postoperatively revealed absence of PJI among the patients, all of whom exhibited satisfactory progress in their rehabilitation exercises. Notably, the Knee Society Score (KSS) for knee joint patients significantly improved from a preoperative mean of 48.7 ± 3.3 points to 84.3 ± 2.2 points postoperatively, whereas the Harris Hip Score for hip joint patients increased significantly from preoperative mean of 50.6 ± 3.6 points to 87.1 ± 1.6 points (P < 0.01).ConclusionIn cases where patients present with unexplained elevations in ESR and CRP levels, primary artificial joint replacement can be undertaken following a one-stage revision approach for PJI.

Association of MRI findings with intra-articular tumour extension.

Treatment of high-grade limb bone sarcoma that invades a joint requires en bloc extra-articular excision. MRI can demonstrate joint invasion but is frequently inconclusive, and its predictive value is unknown. We evaluated the diagnostic accuracy of direct and indirect radiological signs of intra-articular tumour extension and the performance characteristics of MRI findings of intra-articular tumour extension. We performed a retrospective case-control study of patients who underwent extra-articular excision for sarcoma of the knee, hip, or shoulder from 1 June 2000 to 1 November 2020. Radiologists blinded to the pathology results evaluated preoperative MRI for three direct signs of joint invasion (capsular disruption, cortical breach, cartilage invasion) and indirect signs (e.g. joint effusion, synovial thickening). The discriminatory ability of MRI to detect intra-articular tumour extension was determined by receiver operating characteristic analysis. Overall, 49 patients underwent extra-articular excision. The area under the curve (AUC) ranged from 0.65 to 0.76 for direct signs of joint invasion, and was 0.83 for all three combined. In all, 26 patients had only one to two direct signs of invasion, representing an equivocal result. In these patients, the AUC was 0.63 for joint effusion and 0.85 for synovial thickening. When direct signs and synovial thickening were combined, the AUC was 0.89. MRI provides excellent discrimination for determining intra-articular tumour extension when multiple direct signs of invasion are present. When MRI results are equivocal, assessment of synovial thickening increases MRI's discriminatory ability to predict intra-articular joint extension. These results should be interpreted in the context of the study's limitations. The inclusion of only extra-articular excisions enriched the sample for true positive cases. Direct signs likely varied with tumour histology and location. A larger, prospective study of periarticular bone sarcomas with spatial correlation of histological and radiological findings is needed to validate these results before their adoption in clinical practice.

Evaluating the impact of structured POCUS training during internal medicine clerkship and residency training

Background: Point of Care Ultrasound (POCUS) is a vital tool in rheumatology for detecting pathologies like osteophytes and joint effusion. Its integration into rheumatology electives during internal medicine clerkship and residency is limited, despite its emphasis in pre-clinical years. Methods: In this QIRB-approved, single-center, prospective study (2022–2023), third- and fourth-year medical students and internal medicine residents in a two-week rheumatology elective voluntarily completed online surveys. These surveys assessed their confidence using POCUS in rheumatology, using a 5-point Likert scale. Results: A survey of 25 residents and 10 medical students found that 84% of residents and 90% of students rated POCUS training as valuable or very valuable. Both groups felt more confident identifying knee joint effusion (average scores: 3.5 for students, 2.6 for residents) compared to other ultrasound techniques and pathologies. Confidence was lower in hip ultrasounds (2.20 for students, 1.68 for residents) and chondrocalcinosis identification (2.20 for students, 1.76 for residents). Among participants, 28% of residents and 70% of students had prior informal POCUS training. Previous training significantly increased comfort levels, with average scores of 2.86 for students and 2.30 for residents, compared to 2.69 and 1.91 for those without prior training (P-values: &lt;0.001). Conclusion: Prior experience significantly enhances confidence and comfort, reinforcing the need for early, comprehensive, and targeted POCUS training in medical curricula to address proficiency gaps. Keywords: Education, medical, undergraduate, rheumatology, point-of-care systems, ultrasonography

Early clinical efficacy study on the efficacy of a three-stage conservative Chinese medicine external treatment for acute lateral ankle ligament injuries

To evaluate the clinical effect of a new three-phase Chinese medicine (CM) external treatment for acute lateral ankle ligament injuries. From July to December 2023, 64 patients with acute lateral ankle ligament injuries were randomly assigned to receive either the new three-phase CM external treatment combined with the POLICE(protect, optimal loading, ice, compression, elevation) treatment (observation group) or the POLICE treatment (control group), with 32 cases in each group. The observation group consisted of 17 males and 15 females, with an average age of(30.59±3.10) years old ranging from 25 to 36 years old, while the control group included 14 males and 18 females, with an average age of(30.03±3.19) years old ranging from 24 to 37 years old. Visual analogue scale (VAS) evaluation and Figure of 8 measurement were used to evaluate the degree of ankle joint pain and swelling of the subjects at the initial enrollment and after 1 week and sixth weeks of treatment. At the same time, the American Orthopaedic Foot and Ankle Society (AOFAS) and Karlsson Ankle Function Score System were used to evaluate the improvement of ankle joint function in patients at all stages. MRI imaging was employed to observe the degree of biological healing of the anterior talofibular ligament, with the signal to noise ratio(SNR) indicating the level of healing. A lower SNR suggests better ligament healing, as it represents lower water content in the ligament. All patients completed a 6-week follow-up. There was no significant difference in VAS, AOFAS score and Karlsson score between the two groups before treatment (P>0.05). After 1 week and 6 weeks of treatment, the VAS, AOFAS score and Karlsson score of the two groups were significantly improved (P<0.05). After 1 week of treatment, the VAS score of the observation group (3.21±0.87) was lower than that of the control group (4.21±1.50), and the difference was statistically significant (P<0.05). After 1 weeks of treatment, the AOFAS and Karlsson scores [(50.84±4.70) points, (49.97±4.00) points] of the observation group were higher than those [(46.91±5.56) points, (46.66±5.36) points]of the control group (P<0.05). MRI images showed that after 6 weeks of treatment, the SNR value of the observation group was significantly lower than that of the control group, and the difference was statistically significant(SNR of the observation group was 75.25±16.59, the contral gruop was 85.81±15.55), (P<0.05). Compared with the control group, the new three-phase CM external treatment is significantly effective in reducing pain and swelling, enhancing ligament repair quality, and promoting functional recovery of the ankle joint in patients with acute lateral malleolar ligament injuries.

Effectiveness of the re-engineered discharge (RED) care model in patients with rheumatoid arthritis.

This study aims to investigate whether the re-engineered discharge (RED) model can significantly improve the quality of life, enhance the health status, and reduce the levels of depression and anxiety in patients with rheumatoid arthritis during hospitalization. This study selected 108 rheumatoid arthritis patients treated at our facility between February 2023 and February 2024. Based on the different treatment methods, these patients were divided into a control group and an observation group, with 54 patients in each group. During hospitalization, both groups received standardized routine care provided by the hospital. After discharge, the control group continued with regular follow-up visits, while the observation group received a more comprehensive and multidimensional extended care based on the RED model. The intervention period for both groups was set to 3 months. The core observation indicators of this study focused on the emotional fluctuations, symptom improvement, and changes in self-care ability of the patients before and after the intervention. After the intervention, the scores of the Self-Rating Anxiety Scale and Self-Rating Depression Scale in both groups showed significant decreases, with the scores in the observation group being significantly lower than those in the control group, showing a highly significant statistical difference (P < .01). Additionally, the joint pain scores in both groups were alleviated, reflected by shorter morning stiffness times, reduced joint swelling, and increased grip strength. The observation group had lower joint pain scores, shorter morning stiffness times, fewer swollen joints, and stronger grip strength, all of which were statistically significant (P < .01). Furthermore, the distribution of self-care abilities in the observation group showed a significant difference compared to the control group (P < .05), with the observation group having a higher proportion of self-care abilities, which was also statistically significant (P < .05). For patients with rheumatoid arthritis, the implementation of the RED model nursing strategy can significantly alleviate negative emotions, reduce the distress caused by symptoms, and markedly improve their quality of life, providing a more comfortable and reassuring treatment experience.

Hyaluronic acid dissolving microneedle patch-assisted acupoint transdermal delivery of triptolide for effective rheumatoid arthritis treatment

Triptolide (TP), a major active component of the herb Tripterygium wilfordii Hook F, has been shown excellent pharmacological effects on rheumatoid arthritis. However, TP is prone to causing severe organ toxicity, which limits its clinical application. In recent years, microneedle technology has provided a new option for the treatment of arthritis due to its advantages of efficient local transdermal drug delivery. In this study, we constructed a microneedle platform to deliver TP locally to the joints, thereby enhancing TP penetration and reducing systemic toxicity. Additionally, we investigated whether acupoint drug delivery can produce a synergistic effect of needles and drugs. First, TP was loaded into microneedles using polyvinylpyrrolidone and hyaluronic acid as matrix materials. Next, we established a rat adjuvant-induced arthritis (AIA) model to evaluate the therapeutic effect of TP-loaded microneedles. The experiments showed that TP-loaded microneedles alleviated the AIA rats’ inflammatory response, joint swelling, and bone erosion. However, there was no significant difference in the therapeutic effect observed in the acupoint and non-acupoint administration groups. In conclusion, TP-loaded microneedles have the advantages of safety, convenience, and high efficacy over conventional administration routes, laying a foundation for the transdermal drug delivery system-based treatment of rheumatoid arthritis.

Effective Assessment of Rheumatoid Arthritis Disease Activity and Outcomes Using Monocyte Chemotactic Protein-1 (MCP-1) and Disease Activity Score 28-MCP-1

The effectiveness of monocyte chemotactic protein-1 (MCP-1) and Disease Activity Score 28 (DAS28)-MCP-1 (DAS28-MCP-1) in assessing rheumatoid arthritis (RA) disease activity is unclear, although some studies have demonstrated their potential usefulness. The present study investigated relationships between MCP-1 and different DAS28 measures, the occurrence of residual swollen joints in different DAS28 remission statuses, changes in medication dosage in relation to the 2005 modified American Rheumatism Association and 2011 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) remission definitions, and the correlations between different DAS28-related scores and Health Assessment Questionnaire Disability Index (HAQ-DI) scores in two RA patient cohorts. The results revealed that the MCP-1 level was correlated with five disease activity measures (DAS28-erythrocyte sedimentation rate [DAS28-ESR], DAS28-C-reactive protein [CRP], Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), and DAS28-MCP-1) in multivariable regression analysis (all p &lt; 0.05; ESR, CRP, and MCP-1 as independent variables). However, ESR was not significantly associated with SDAI and CDAI scores (p = 0.343 and 0.323, respectively). Residual swollen joints were more frequently observed in patients who met the DAS28-ESR remission criteria (&lt;2.6) compared with those meeting the other four remission criteria, with a difference ranging from 71% to 94%. Among patients meeting the DAS28-ESR remission criteria (&lt;2.6), medication changes (dose increase by ≥30% or new medications prescribed) were less frequent in those who also met the 2011 ACR/EULAR remission criteria than in those who did not meet them (p = 0.006). Moreover, the correlation coefficients for the relationship between DAS28-ESR and HAQ-DI scores were the lowest among the five disease activity measures. In conclusion, MCP-1 and DAS28-MCP-1 are effective in assessing RA disease activity, with less residual joint swelling and less frequent medication increases observed in the DAS28-MCP-1 remission &lt; 2.2 subgroup.

Jianpi qingre tongluo prescription alleviates the senescence-associated secretory phenotype with osteoarthritis by regulating STAG1/TP53/P21 signaling pathway

Ethnopharmacological relevanceJianpi Qingre Chubi prescription primarily consists of a compound formula, also known as Huangqin Qingre Chubi Capsules (HQC), which strengthens the spleen and resolves dampness, clear heat, and collaterals. Long-term clinical use has shown that HQC improves joint swelling and pain in patients with osteoarthritis. Mechanistically, we demonstrated that HQC inhibits inflammatory responses, extracellular matrix degradation, and delays chondrocyte senescence. AimTo determine the bioactivity and mechanism of action of Jianpi Qingre Tongluo prescription (HQC) on osteoarthritis (OA). Materials and methodsFirst, the chondroprotective effects of HQC were assessed using histopathology, immunohistochemical staining and protein blotting in an OA rat model. Additionally, we identified key targets for crucial targets of HQC in OA using the Network Pharmacology and Gene Expression Omnibus (GEO) dataset (GSE98918 and GSE152805). In vitro conditions, IL-1β-treated chondrocytes served to study the impact of HQC on OA development and the senescence-associated secretory phenotype (SASP). This was evaluated using a series of approaches, such as flow cytometry assays, and immunofluorescence staining, and then verified by rescue experiments. ResultsTherapy with HQC attenuated the severity of osteoarthritis (demonstrated by histopathology, OARSI grading scores, and Mankin scores) and SASP factors (as indicated by IL-1β, IL-6, IL-4, IL-37, MMP13, ADAMTS5, COL2A1, and ACAN levels, and apoptotic cell death). HQC might treat osteoarthritis via four important targets (STAG1, TP53, P21, and P16), with the p53 signalling pathway representing one of the main pathways. The HQC acts primarily on chondrocyte clusters. In vitro experiments indicated that STAG1 overexpression accelerates chondrocyte apoptosis, promotes SASP factor expression and extracellular matrix (ECM) degradation, and facilitates OA progression. HQC-containing serum suppressed the expression of the STAG1/TP53/P21 pathway, regulated SASP factors, and restored ECM balance. ConclusionJianpi Qingre Tongluo prescription modulated SASP factors by regulating the STAG1/TP53/P21 signal transduction axis and decelerating cartilage senescence and degradation in patients with OA. Jianpi Qingre Tongluo may be an effective drug candidate.

Prolonged Neurological and Musculoskeletal Symptoms Following Shingrix Vaccination

Background: The recombinant zoster vaccine (Shingrix) helps prevent shingles and its complications in adults 50 and older. While minor side effects are common, severe adverse reactions are thought to be rare, and long-term side effects are not well documented. Case Presentation: A 50-year-old woman with Crohn’s disease developed joint pain, effusion, and neurological symptoms such as numbness and tingling shortly after receiving the first dose of the recombinant zoster vaccine. Symptoms waxed and waned but persisted for over a year despite anti-inflammatories and specialist referrals. Diagnostic imaging and labs were unrevealing. Conclusions: This case of prolonged somatic and neurological symptoms associated temporally with Recombinant zoster vaccine administration reinforces the critical need for thorough pharmacovigilance and investigation of possible long-term adverse vaccine reactions. Provider documentation and reporting of individual experiences can help improve the detection of rare vaccine-related risks, elucidate potential risk factors, and refine safety screening. Diligent monitoring and research into longitudinal vaccine outcomes remain paramount, especially following recent emergency authorizations.

Diagnostic imaging findings in lame Warmblood horses with bone injuries of the medial proximal phalanx glenoid cavity.

This retrospective study aims to describe baseline and follow-up imaging findings in subchondral and trabecular bone damage occurring outside of the sagittal groove in the proximal phalanx (P1) glenoid in a case series of lame Warmblood horses. Thirteen lame horses (16 forelimbs) with standing magnetic resonance imaging (sMRI) evidence of nonsagittal groove glenoid subchondral and trabecular bone injury of P1 as the main lesion were included. All injuries were located at the medial aspect of the P1 glenoid. At sMRI, changes included subchondral bone plate thickening and trabecular sclerosis, bone marrow edema-like signal, subchondral bone resorption (11/16), and new bone production (8/16). Subchondral bone resorption in the transverse plane was linear (8/11), round (2/11), or ill-defined (1/11). Sclerosis, bone resorption, and new bone production were seen radiographically in 10, 4, and 5 limbs, respectively. All limbs had concurrent metacarpal condyle sMRI imaging abnormalities, osteophytosis, and joint effusion. Follow-up sMRIs were obtained in 8 of 16 limbs, five of which showing progression of the resorptive lesion. One horse encountered a comminuted fracture of the affected P1 18 months after the follow-up sMRI examination. The imaging appearance of the medial glenoid bone injuries of P1 in this case series is consistent with chronic bone overload. The linear configuration of bone resorption seen in eight lesions suggests short, incomplete stress fractures, which is supported by the ultimate catastrophic fracture occurring in one case.

MRI features distinguishing pediatric Lyme arthritis from septic arthritis.

This study aims to identify distinguishing MRI features of Lyme arthritis (LA), an increasingly prevalent cause of pediatric infectious arthritis in the USA, to enable rapid discrimination from septic arthritis (SA) and facilitate appropriate management. A single-center, retrospective analysis was conducted on a convenience sample of pediatric patients with LA in an endemic area using EPIC electronic health record data between January 2010 and December 2020. Patients with positive serologic testing and concurrent MRI were selected. MRI scans were reviewed by a subspecialty-trained pediatric radiologist. Key MRI features analyzed include joint effusion, synovitis, myositis, soft tissue edema, and osseous edema and erosions. MRI features, demographics, and clinical data were compared using univariable and multivariable analyses. Fifty cases of knee LA and 13 cases of knee SA were included. Larger joint effusion (p = 0.0055, z = - 2.779) and abnormally thickened synovium (p = 0.0011, χ2 = 10.622) were more associated with LA. In contrast, increased myositis, subcutaneous edema, and osseous changes were more prevalent in SA. Abnormal bone marrow signal (p < 0.0001, χ2 = 36.893) and bone erosion (p < 0.0001, χ2 = 25.506) were observed in 84.6% (11/13) and 46.2% (6/13) of SA cases, respectively, while no bone erosion was found in LA. MRI can be a valuable tool in differentiating LA from SA. Abnormal synovium and increasing joint effusion favor LA, while increasing soft tissue edema and osseous changes favor SA. Notably, the presence of bone erosion effectively excluded LA from consideration.

A comparative randomised clinical trial of Amrutadi kwath and Vasadi kath in the management of Vatarakta (Gout)

Vatarakta specially occurs in Madhyavastha which is Parihanikala in which Dhatukshaya takes place. Khavaigunya (Rikta srotas) occurs in Asthi which is responsible for the production of Vatarakta. Vatarakta is a disease related with khavaigunya found in raktavaha strotas which include vitiated vata and rakta, so termed as vatarakta. Due to properties of sukshmatva and saratva of vayu, dravatva and saratva of rakta they spread all over the body. Symptoms of Vatarakta are shool, toda, daha, vaivarnya described by various acharya. Symptoms of Gouty arthritis are similar as of vatarakta Joint pain, Swelling, stiffness, disability and crepitations over small joint. Gouty arthritis is the most common form of arthritis, which occurs in middle age. Amrutadi Kwath and Vasadi Kwath have most of contents are snigdha, guru and mrudu. By virtue of these properties, this alleviates vata and pitta. Hence these are used in diseases which arise due to vitiation of vata and pitta. in vatarakta by its vatapittashamaka prabhav and snigddha, mrudu gunas by vatanulomana kriya. Amrutadi kwath is very effective in relieving the symptoms of vatarakta. Materials and Method: Total 80 patients of the age group 25-60 years presenting with signs and symptoms of vatarakta were selected randomly from OPD of the department of kayachiktsa. The 40 patients of trial group were treated with Amrutadi kwath and 40 patients of control group were subjected to vasadi kwath. Conclusion: Amrutadi Kwath showing significant results than Vasadi Kwath in symptoms of Vatarakta (Gout).

Chromone components of Saposhnikovia divaricate attenuate rheumatoid arthritis development by inhibiting the inflammatory response

Ethnopharmacological relevanceSaposhnikovia divaricata (Turcz.) Schisck., a traditional Chinese medicine (TCM), has historically been utilized in the clinical treatment of RA. It was initially documented in the 'Shennong Ben Cao Jing' as a superior quality, with the text stating: 'The herb is widely renowned for its efficacy in alleviating whole-body discomfort, bone pain, malaise, and promoting long-lasting vitality. Chromones (CHR) were identified as the primary active components in Saposhnikovia divaricata. However, the specific molecular mechanisms by which CHR impacts RA remain incompletely understood. Aim of the studyTo explore the therapeutic efficacy of CHR, a class of compound derived from Saposhnikovia divaricata, in alleviating arthropathy and immune hyperactivity in a collagen-induced arthritis (CIA) mouse model. Material and methodsSurface plasmon resonance (SPR) molecular fishing and UHPLC-QTOF/MS technology were used to identify CHR in Saposhnikovia divaricata as an active ingredient for treating RA. A CIA mouse model was used to verify the anti-RA effect of CHR in vivo. The anti-RA efficacy of CHR in vivo was evaluated by body weight change, joint swelling, arthritis index, immune organ index, ankle joint disease, and immunoglobulin G (IgG) content. The mechanism of improving RA was further analyzed by a protein chip assay and verified by Western blotting. ResultsCHR treatment reduced swelling, arthritis index, and IgG, IgG1, IgG2a, and IgG2b levels in CIA mice. Protein microarray indicated that CHR mitigated CIA-induced joint inflammation by inhibiting immune cell activation, reducing the expression of inflammatory factors and chemokines, potentially by modulating the rheumatoid arthritis pathway involving tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), and chemokines. This hypothesis was supported by the upregulation of bone morphogenetic proteins 3 (BMP3) and phospho-Smad2 (p-Smad2) proteins, coupled with the downregulation of interleukin-6 (IL-6), interleukin-1β (IL-1β), TNF-α, and IL-17A proteins in the joints of CHR-treated mice. ConclusionCHR shows promise as a potential therapeutic agent for RA, exerting its effects through anti-inflammatory mechanisms.

7425 Biochemical Response, Symptom Control, and Safety of Oral Octreotide Capsules Treatment in Acromegaly: A Post Hoc Analysis of a Large Pooled Database from Three Phase 3 Clinical Trials

Abstract Disclosure: M. Fleseriu: Consulting Fee; Self; Novo Nordisk, Amryt Pharma Holdings Ltd, Ascend Therapeutics (A Besins Healthcare company). Speaker; Self; Xeris Pharmaceuticals, Inc., RECORDATI_RARE_DISEASES_INC., Ipsen Pharma SAS. S.L. Samson: Advisory Board Member; Self; Amryt. Research Investigator; Self; Amryt. N. Biermasz: Advisory Board Member; Self; Recordati, Pfizer Global R&amp;D. Grant Recipient; Self; Macro Registry Grant, Amryt. C.J. Strasburger: Advisory Board Member; Self; Sandoz, Ipsen, Recordati. Consulting Fee; Self; Ascendis, Amryt, Novo Nordisk, Merck, Sandoz, Recordati. Speaker; Self; Ipsen, Novo Nordisk, HRA-Pharma. S. Fuchs Orenbach: Employee; Self; Chiesi Global Rare Diseases. J.A. Crompton: Employee; Self; Chiesi Global Rare Diseases. S. Melmed: Advisory Board Member; Self; Ionis, Crinetics. Consulting Fee; Self; Ipsen. Grant Recipient; Self; Pfizer. Background: Treatment with oral octreotide capsules (OOC) was evaluated in three phase 3 trials (CH-ACM-01, OPTIMAL, MPOWERED) in patients with acromegaly who previously tolerated and responded to the injectable somatostatin receptor ligands (iSRLs) octreotide and lanreotide. Results demonstrated efficacy and safety despite differences in trial design. Pooling data from all three trials can provide further insight into the biochemical response, symptom improvement, and safety profile of OOC. Objective: Analyze the biochemical changes, symptom control, and safety of OOC through a pooled analysis of phase 3 clinical trial datasets. Methods: Patients included were aged ≥18 years with acromegaly and responded biochemically to iSRL therapy before the initiation of OOC (defined as IGF-I &amp;lt;1.3 × ULN and mean integrated GH &amp;lt;2.5 ng/mL for CH-ACM-01 and MPOWERED, and IGF-I ≤1.0 × ULN for OPTIMAL). Data analyzed were from the following periods: baseline until the end of the double-blind placebo-controlled phase of OPTIMAL (36 weeks); the run-in phase of MPOWERED (26 weeks); end of dose escalation (2-5 months; efficacy data) and end of fixed dose phase (up to 7 months, safety data) for CH-ACM-01. Effect of prior iSRL dose was analyzed using a random effects meta-analysis. Symptom severity was scored using the Acromegaly Index of Severity (AIS) tool. Results: Efficacy, symptom, and safety data were available for 318, 194, and 329 patients, respectively. The overall response rate was 65% with no effect of prior iSRL dose (p&amp;gt;0.05). Mean (SD) IGF-I change from baseline was +0.17 (0.32; n=214), +0.19 (0.39; n=81), and +0.22 (0.57; n=23) for patients with baseline IGF-I levels ≤1 × ULN, 1 to &amp;lt;1.3 × ULN, and ≥1.3 × ULN. Twenty percent (16/81) and 35% (8/23) of patients with baseline IGF-I of 1 to &amp;lt;1.3 x ULN and ≥1.3 x ULN shifted to an improved category of response. There was a median decrease of one symptom per patient (p&amp;lt;0.05) and a mean decrease of 0.8 in AIS (p&amp;lt;0.05). The proportion of OOC responders reporting ≤1, 2, or 3 moderate/severe acromegaly symptoms at baseline and month 6 decreased from 56% to 39%, 32% to 20%, and 20% to 12%. At month 6, improvement was seen for all individual symptoms (joint pain, swelling, sweating, fatigue, headache) of moderate/severe grade and was significant for joint pain (36% to 22%) and swelling (15% to 10%) (p&amp;lt;0.02). Most adverse events (AEs) were gastrointestinal (GI) in nature (54%, n=179/329) with a median onset and duration of 15 and 12 days for first reported GI events. Conclusion: Pooled analysis confirms overall maintenance of biochemical control in patients previously responding to iSRL therapy, with decreased symptom burden in OOC responders. OOC was generally well tolerated with no new safety signals. GI-related AEs were largely transient. These results support OOC as a therapeutic option for treating acromegaly. Presentation: 6/3/2024

12526 Acromegaly Secondary to Sparsely Granulated Adenoma

Abstract Disclosure: D. John: None. M. Kinaan: None. J. Titus: None. K. Lamar: None. The most common pathological finding in acromegaly is a densely granulated adenoma which is composed of large round eosinophilic cells with prominent nucleoli and spherical nuclei that closely resemble a somatotroph cell. Less common finding is a sparsely granulated adenoma that is composed of sheets of poorly cohesive, pleiomorphic nuclei, chromophobic cells. We present a case of a 58-year-old gentleman presenting to our endocrine clinic for evaluation of a pituitary macroadenoma. The patient was hospitalized for nausea, vertigo, headaches, and blurring of vision. CT brain at that time showed a pituitary mass measuring 2.4 x 1.6 x 1.7 cm centered in the right cavernous sinus and inseparable from the pituitary gland. Hormonal work-up in the hospital was remarkable for high GH level. IGF-1 level was not done. Patient was advised to follow-up with neurosurgery as outpatient and no emergent surgery was planned. In the clinic, patient denied symptoms of DI, adrenal insufficiency or hypothyroidism. He has history of hypogonadotropic hypogonadism and was on testosterone therapy, but he stopped it since his hospitalization. On physical examination, he was noted to have macroglossia, deep voice, prominent jawbone, and soft tissue swelling in the hands and feet. Patient did not have any visible joint swelling. He stated he did not notice these changes personally and that he’s always been a “big guy” and always had a deep voice since he was a teenager. Repeat hormonal workup (done at 8 AM) showed: normal CMP, ACTH, cortisol, prolactin, TSH, T4, and T3. Testosterone was low with LH and FSH inappropriately within the normal reference range consistent withhypogonadotropic hypogonadism. IGF-I was elevated at 628ng/mL with a Z score of 3.9. These findings were consistent with acromegaly. He underwent surgery for tumor resection and pathology report showed that about 40% of the cells demonstrated weak immunoreactivity for GH, and rare (less than 1%) prolactin-positive cells were present within the tumor. The specimen was negative for TSH, ACTH, FH, and LH immunostains. Immunostain for CAM5.2 showed predominantly perinuclear dot-like immunoreactivity. The *MIB1 proliferation index is about 1%. The findings were consistent with a sparsely granulated gonadotrophic adenoma, which may demonstrate aggressive behavior. Postoperative MRI showed postoperative changes with residual pituitary tissue (normal gland vs. residual tumor). Postoperative cortisol &amp;gt;16. Postoperative GH dropped from 4.39 to 2.69 after 1 month. After 3 months, patient was doing well with no symptoms. However, IGF1 level (&amp;gt;400) showing that surgery was not curative. Currently he is awaiting gamma knife radiation therapy with possible medical therapy afterwards. Our case will provide an overview of the specific management considerations for these tumor and how they differ from densely-granulated tumors. Presentation: 6/3/2024

Etiology of septic arthritis in children of Qatar.

Septic arthritis is an orthopedic emergency and if not evaluated and treated appropriately, it can lead to poor clinical outcomes. Previously several studies have been performed to identify the etiology of septic arthritis in the pediatric population in developed countries. The main objective of our study was to identify the etiology of septic arthritis in children in Qatar in previously healthy and fully vaccinated children. We performed retrospective chart analysis of children presenting to our emergency department between July 2018 and June 2024, who were diagnosed and treated with septic arthritis. The study was conducted at a level 1 pediatric trauma center and the only children's hospital in the country. We used ICD 9 and ICD 10 codes to identify such cases. After using predefined exclusion criteria, children with positive blood cultures, blood titers for Brucella and/or synovial cultures were included in the analysis. Clinical symptoms and signs, ultrasound findings, and culture results were tabulated using descriptive statistics. A total of 45 patients were included. The median age of children was 5 years (interquartile range [IQR] 2-10 years). Majority (60%) were male. The most common clinical findings were limping/limitation of joint movement (100%), fever (80%), and swelling of joints (58%). The median C-reactive protein and erythrocyte sedimentation rate were 94mg/L and 47mm/h. The knee and hip were the most common joints affected. The most common causative organisms were Staphylococcus aureus (56%), Streptococcus pyogenes (13%), and Brucella (11%). Pre-intervention imaging, such as ultrasound and/or magnetic resonance imaging, was performed in 95% of patients. All patients recovered without any complications. One of the limitations of our study is that cases of Kingella kingae septic arthritis may be underreported as polymerase chain reaction (PCR) analysis of synovial fluid was not performed on all patients. Gram-positive cocci, especially S. aureus, remains the most common cause of septic arthritis in vaccinated children. We also identified Gram-negative bacilli as causative organisms in our study. We suggest including empiric coverage for both Gram- and Gram-negative bacilli when treating children with suspected septic arthritis till culture results are available.