Deposition Of Monosodium Urate Crystals Research Articles

Limb salvage and systemic management of gouty tophi: Case series.

Gout is a chronic disease characterized by deposition of monosodium urate crystals. Tophi develop in some individuals with untreated or uncontrolled gout, which leads to ulcerations, cosmetic problems, mechanical obstruction of joint movement, joint damage and musculoskeletal disability. Currently, the treatment of gouty tophi is controversial and challenging. Both surgical and internal medical treatments have limitations and require further exploration in clinical practice. In Case 1, we treated a patient with severe infection of diabetic foot ulcers with concomitant multiple gouty tophi in the same limb. A systematic management strategy was formulated to close the wound and save the limb. The ulcers healed successfully after half a year. In Case 2, a giant gouty tophi located in the first metatarsophalangeal joint of the left foot was removed by surgical treatment and vancomycin-loaded bone cement implantation. In Case 3, we present a case of gouty tophi that was resolved by standardized systemic medical management. Three patients were all diagnosed with gout accompanied by gouty deposition, although there were other different comorbidities. In case 1, we used debridement to gradually remove gouty tophi. In case 2, the giant gouty tophi was removed by surgical operation. In case 3, the gouty tophi disappeared after standardized treatment with medicine, diet and lifestyle management. Three patients underwent different treatment therapies to remove gouty tophi based on their specific conditions. We explored effective interventions for tophi in gout by surgical or other interventions in combination with pharmacotherapy.

Deficiency of histone deacetylases 3 in macrophage alleviates monosodium urate crystals-induced gouty inflammation in mice

BackgroundGout is caused by monosodium urate (MSU) crystals deposition to trigger immune response. A recent study suggested that inhibition of Class I Histone deacetylases (HDACs) can significantly reduce MSU crystals-induced inflammation. However, which one of HDACs members in response to MSU crystals was still unknown. Here, we investigated the roles of HDAC3 in MSU crystals-induced gouty inflammation.MethodsMacrophage specific HDAC3 knockout (KO) mice were used to investigate inflammatory profiles of gout in mouse models in vivo, including ankle arthritis, foot pad arthritis and subcutaneous air pouch model. In the in vitro experiments, bone marrow-derived macrophages (BMDMs) from mice were treated with MSU crystals to assess cytokines, potential target gene and protein.ResultsDeficiency of HDAC3 in macrophage not only reduced MSU-induced foot pad and ankle joint swelling but also decreased neutrophils trafficking and IL-1β release in air pouch models. In addition, the levels of inflammatory genes related to TLR2/4/NF-κB/IL-6/STAT3 signaling pathway were significantly decreased in BMDMs from HDAC3 KO mice after MSU treatment. Moreover, RGFP966, selective inhibitor of HDAC3, inhibited IL-6 and TNF-α production in BMDMs treated with MSU crystals. Besides, HDAC3 deficiency shifted gene expression from pro-inflammatory macrophage (M1) to anti-inflammatory macrophage (M2) in BMDMs after MSU challenge.ConclusionsDeficiency of HDAC3 in macrophage alleviates MSU crystals-induced gouty inflammation through inhibition of TLR2/4 driven IL-6/STAT3 signaling pathway, suggesting that HDAC3 could contribute to a potential therapeutic target of gout.

Gout, hyperuricemia and NLRP3 inflammasome: a literature review

Gout is a form of self-limiting inflammatory arthritis caused by hyperuricemia and the deposition of monosodium urate (MSU) crystals in joint tissues. This deposition causes the activation of the NLRP3 inflammasome, thus triggering an inflammatory cascade. Intense activation of the NLRP3 inflammasome is associated with the pathogenesis of several inflammatory diseases, including gout. For this reason, this inflammasome has become a potential target for controlling this type of inflammation. In this review, 33 publications were selected from the Google Scholar, Scielo and PubMed platforms, thus providing a comprehensive perspective on the condition of gout and its relationship with the NLRP3 inflammasome. This review provides a broad view of the inflammatory process associated with gout, focusing on the NLRP3 inflammasome. In this context, interventions targeting these inflammasome and IL-1 pathways appear promising for the treatment of this disease.

E048 Spinal gout: an unusual cause of paraplegia

Abstract Background/Aims Gout is a common inflammatory arthritis caused by the deposition of monosodium urate crystals. Gout usually causes peripheral joint arthritis. Axial involvement is likely under-recognised, affecting an estimated 10-20% of gout patients. Spinal gout is an established phenomenon in patients with chronic tophaceous gout and sustained hyperuricaemia. Gout can affect any segment of the spine. Clinical presentation of spinal gout is variable including back pain, radiculopathy and cord compression. Due to its nonspecific presentation, it can be confused for other spinal pathologies such as epidural abscess, malignancy, spondylodiscitis and vertebral osteomyelitis. Methods We present a case report of a young male with tophaceous gout of the thoracic spine. Results A 37 year old man presented with 4 day history of acute thoracic back pain followed by flaccid lower limb paralysis. He was morbidly obese (BMI 60) and had a 13-year history of poorly controlled gout with most recent uric acid being 627. He had previously declined urate lowering therapy but commenced allopurinol treatment one month prior to admission. On examination power was 0/5 in both lower limbs with absent reflexes and a T12 sensory level. MRI showed multi-level facet joint arthropathy. An epidural collection was present at T8-10, causing complete occlusion of the vertebral artery. He underwent an urgent posterior thoracic decompression. ‘White cheese like epidural pus’ was removed and he was initially treated as facet joint infection. He had ongoing fevers [>38.5C], despite empirical antibiotics, and C-reactive-protein was persistently elevated [highest at 360mg/L]. Uric acid was 423. Enrichment culture of the epidural collection and serial blood cultures were negative. Repeat MRI of spine did not demonstrate any reoccurrence of collection. Subsequently the histology of the epidural collection was reported as characteristic of gout with ‘amorphous material and giant cells’. No urate crystals were identified as the sample was prepared with formalin, which would have dissolved any crystals present. He was referred to rheumatology who identified synovitis in his hands, wrist and elbows, consistent with active polyarticular gout. There were small tophi present on his heels and pinna. The patient was commenced on oral prednisolone and allopurinol was rapidly up-titrated. Unfortunately, the patient did not recover neurological function. Conclusion We present a unique case of acutely presenting tophaceous thoracic spinal gout causing irreversible paraplegia in a young patient, mimicking an epidural abscess. Our patient had hyperuricaemia for over 10 years without treatment, raising his risk of axial complications. A high index of suspicion for spinal gout is needed for patients presenting with acute back pain and neurological symptoms with a history of chronic gout. This case highlights diagnostic challenges in identifying spinal gout and the importance of treating tophaceous gout early to prevent devastating long-term complications. Disclosure C.A. Zollinger-Read: None. M. Cox: None. R. Kumari: None.

Identification of SOCS3 and PTGS2 as new biomarkers for the diagnosis of gout by cross-species comprehensive analysis

BackgroundGout is the most common inflammatory arthritis in adults. Gout is an arthritic disease caused by the deposition of monosodium urate crystal (MSU) in the joints, which can lead to acute inflammation and damage adjacent tissue. Hyperuricemia is the main risk factor for MSU crystal deposition and gout. With the increasing burden of gout disease, the identification of potential biomarkers and novel targets for diagnosis is urgently needed. MethodsFor the analysis of this subject paper, we downloaded the human gout data set GSE160170 and the gout mouse model data set GSE190138 from the GEO database. To obtain the differentially expressed genes (DEGs), we intersected the two data sets. Using the cytohubba algorithm, we identified the key genes and enriched them through GO and KEGG. The gene expression trends of three subgroups (normal control group, intermittent gout group and acute gout attack group) were analyzed by Series Test of Cluster (STC) analysis, and the key genes were screened out, and the diagnostic effect was verified by ROC curve. The expression of key genes in dorsal root nerve and spinal cord of gout mice was analyzed. Finally, the clinical samples of normal control group, hyperuricemia group, intermittent gout group and acute gout attack group were collected, and the expression of key genes at protein level was verified by ELISA. ResultWe obtained 59 co-upregulated and 28 co-downregulated genes by comparing the DEGs between gout mouse model data set and human gout data set. 7 hub DEGs(IL1B, IL10, NLRP3, SOCS3, PTGS2) were screened out via Cytohubba algorithm. The results of both GO and KEGG enrichment analyses indicate that 7 hub genes play a significant role in regulating the inflammatory response, cytokine production in immune response, and the TNF signaling pathway. The most representative hub genes SOCS3 and PTGS2 were screened out by Series Test of Cluster, and ROC analysis results showed the AUC values were both up to 1.000. In addition, we found that PTGS2 expression was significantly elevated in the dorsal root ganglia and spinal cord in monosodium urate(MSU)-induced gout mouse model. The ELISA results revealed that the expression of SOCS3 and PTGS2 was notably higher in the acute gout attack and intermittent gout groups compared to the normal control group. This difference was statistically significant, indicating a clear distinction between the groups. ConclusionThrough cross-species comprehensive analysis and experimental verification, SOCS3 and PTGS2 were proved to be new biomarkers for diagnosing gout and predicting disease progression.

Gout and its management.

Gout is a common and treatable chronic disease of monosodium urate crystal deposition. It is experienced as extremely painful episodes of joint inflammation that impact all aspects of the person's life. This Clinical Perspectives article provides an update on gout diagnosis, medications and strategies to improve the quality of gout care.

The Clinical Significance of Serum Interleukin-36α Levels in Patients with Gout

ABSTRACT Background Gout is a chronic inflammatory diseases caused by monosodium urate crystal deposition. However, the role of interleukin (IL)-36 in gout has not dbeen elucidated. Methods We enrolled 75 subjects, including 20 healthy controls (HC), 30 patients with acute gout attack and 25 patients in remission. Baseline data were obtained through clinical interrogation and laboratory data were obtained through tests of blood samples. Serum levels of IL-36α were detected using enzyme-linked immunosorbent assay. Spearman correlation analysis was used to investigate the correlation of IL-36α with other parameters. The diagnostic value of IL-36α was demonstrated using a receiver operating characteristic curve. Results The serum IL-36α level of gout patients in acute attack and remission stage was significantly higher than that of HC. Serum IL-36α was positively correlated with alanine transaminase (ALT) and aspartate transaminase (AST). Serum amyloid A (SAA) levels positively correlated with C-reactive protein levels and erythrocyte sedimentation rates. Glutamyl transpeptidase levels positively correlated with AST and ALT levels. Conclusion In conclusion, serum IL-36α levels were elevated in patients with gout and correlated with the clinical markers of inflammation. Our findings suggest that IL-36α may be a novel inflammatory indicator for gout.

Gout: physical activity in therapy and prevention of the disease

Gout is a systemic chronic inflammatory disease associated with purine metabolism disorders. Risk factors for gout are a combination of genetic and environmental factors. Taking into account such features of the pathogenesis of gout as hyperuricemia and the deposition of monosodium urate crystals in tissues and joints, the development of the inflammatory, researchers studied the effect of physical activity on its main links. The intensity of the load and the type of physical exercise were taken into account due to their possible effect on metabolic processes. There is currently no reliable evidence on the importance of physical activity in reducing serum uric acid levels. Research has shown that physical activity has a positive effect on inflammation between gout attacks. The use of physical exercise can indirectly affect uric acid levels by reducing body weight in comorbid pathologies. EULAR emphasizes physical activity to prevent cardiovascular risks, which is also important for gout. Conclusions. Physical activity as one of the components of lifestyle is important for gout due to its effect on the inflammatory process and the prevention of relapses, a general strengthening effect on the body, an effect on hyperuricemia due to the positive effect associated with comorbid pathology, and a decrease in cardiovascular risk and associated him premature death. Physical activity of low and moderate intensity is effective for gout. Preference is given to aerobic exercise, taking into account the nature of metabolism and the possible impact on the occurrence of gout attacks. Further study and development of the characteristics of physical activity in gout are necessary to improve the prevention and treatment of the disease, and the development of individual recommendations for patients (for the management of gout).

Targeting Neutrophil Extracellular Traps in Gouty Arthritis: Insights into Pathogenesis and Therapeutic Potential.

Gouty arthritis (GA) is an immune-mediated disorder characterized by severe inflammation due to the deposition of monosodium urate (MSU) crystals in the joints. The pathophysiological mechanisms of GA are not yet fully understood, and therefore, the identification of effective therapeutic targets is of paramount importance. Neutrophil extracellular traps (NETs), an intricate structure of DNA scaffold, encompassing myeloperoxidase, histones, and elastases - have gained significant attention as a prospective therapeutic target for gouty arthritis, due to their innate antimicrobial and immunomodulatory properties. Hence, exploring the therapeutic potential of NETs in gouty arthritis remains an enticing avenue for further investigation. During the process of gouty arthritis, the formation of NETs triggers the release of inflammatory cytokines, thereby contributing to the inflammatory response, while MSU crystals and cytokines are sequestered and degraded by the aggregation of NETs. Here, we provide a concise summary of the inflammatory processes underlying the initiation and resolution of gouty arthritis mediated by NETs. Furthermore, this review presents an overview of the current pharmacological approaches for treating gouty arthritis and summarizes the potential of natural and synthetic product-based inhibitors that target NET formation as novel therapeutic options, alongside elucidating the intrinsic challenges of these inhibitors in NETs research. Lastly, the limitations of HL-60 cell as a suitable substitute of neutrophils in NETs research are summarized and discussed. Series of recommendations are provided, strategically oriented towards guiding future investigations to effectively address these concerns. These findings will contribute to an enhanced comprehension of the interplay between NETs and GA, facilitating the proposition of innovative therapeutic strategies and novel approaches for the management of GA.

Tetrandrine alleviates inflammation and promotes macrophage M2 polarization in gouty arthritis by NF-κB-mediated Lcp1.

Gouty arthritis (GA) is an inflammatory disease caused by the deposition of monosodium urate (MSU) crystals into joints. Tetrandrine (TET) is a bisbenzylisoquinoline alkaloid extracted from the root of Stephania tetrandra and can exert an anti-inflammatory function in different diseases. Nevertheless, the specific function of TET in GA remains unclear. We established the GA mouse model by MSU injection into joints of mice. Paw volume and gait score were detected for measuring the degree of joint swelling and the situation of joint dysfunction. Western blot were utilized to test the alterations of M1-related factors (IL-6, IL-1β, TNF-α, IL-12, and iNOS) and M2-related factors (Mgl1, Mgl2, Pgc1-β, Arg-1, and IL-10). The activity of NF-κB p65 in tissues was determined. The interaction of NF-κB p65 and Lcp1 was measured by ChIP and luciferase reporter assay. Lcp1 KO mice were utilized to detect the effect of Lcp1 depletion on GA process. TET treatment markedly suppressed MSU-induced joint swelling, joint dysfunction, and joint injury in GA mice. TET can also reduce inflammatory reactions in MUS-induced mice. Furthermore, we proved that TET facilitated M2 macrophage polarization and inhibited M1 macrophage polarization in GA mice. In addition, TET was found to inhibit NF-κB activity and NF-κB-mediated Lcp1 expression. Lcp1 knockdown can improve joint injury and promote M2 macrophage polarization in GA mice, while this effect was further enhanced by TET. TET alleviates inflammation and facilitates macrophage M2 polarization in GA by NF-κB-mediated Lcp1.

Osteostatin Mitigates Gouty Arthritis through the Inhibition of Caspase-1 Activation and Upregulation of Nrf2 Expression.

Gouty arthritis results from monosodium urate (MSU) crystal deposition in joints, initiating (pro)-interleukin (IL)-1β maturation, inflammatory mediator release, and neutrophil infiltration, leading to joint swelling and pain. Parathyroid hormone-related protein (107-111) C-terminal peptide (osteostatin) has shown anti-inflammatory properties in osteoblasts and collagen-induced arthritis in mice, but its impact in gouty arthritis models remains unexplored. We investigated the effect of osteostatin on pyroptosis, inflammation, and oxidation in macrophages, as well as its role in the formation of calcium pyrophosphate dihydrate crystals and MSU-induced gouty arthritis in mice models. Osteostatin ameliorated pyroptosis induced by lipopolysaccharide and adenosine 5'-triphosphate (LPS + ATP) in mice peritoneal macrophages by reducing the expression of caspase-1, lactate dehydrogenase release, and IL-1β and IL-18 secretion. Additionally, IL-6 and tumor necrosis factor-α (TNF-α) were also decreased due to the reduced activation of the NF-κB pathway. Furthermore, osteostatin displayed antioxidant properties in LPS + ATP-stimulated macrophages, resulting in reduced production of mitochondrial and extracellular reactive oxygen species and enhanced Nrf2 translocation to the nuclei. In both models of gouty arthritis, osteostatin administration resulted in reduced pro-inflammatory cytokine production, decreased leukocyte migration, and reduced caspase-1 and NF-κB activation. These results highlight the potential of osteostatin as a therapeutic option for gouty arthritis.

The value of musculoskeletal ultrasound in predicting gout flares in index joints: A prospective cohort study of people with gout starting urate-lowering therapy

ObjectivesTo evaluate whether ultrasound findings of monosodium urate (MSU) crystal deposition predict frequent gout flares in index joints over 12 months. MethodsThis single-center study enrolled people with at least one gout flare involving the MTP1, ankle or knee joint. The most painful or most frequently joint was identified as index joint for analysis. All participants were started on urate-lowering therapy and had an ultrasound scan of the index joints at the baseline visit. OMERACT scores (for tophus, double contour sign and aggregates) were used to analyze whether ultrasound scores predicted frequent (≥2) gout flares in the index joint over 12 months. ResultsFrequent flares were significantly higher in those with ultrasound findings in all index joints (MTP1: tophus: 85.0% vs 46.0%, P < 0.001, aggregates: 78.8% vs 59.0%, P < 0.01; ankle: tophus: 54.6% vs 20.8%, P < 0.001; aggregates: 60.0% vs 35.9%, P < 0.05; knee: tophus: 68.4% vs 28.6%, P < 0.05). For the MTP1, for each 1-point increase in tophus score, the odds of frequent gout flares increased by 5.19 [(95%CI: 1.26–21.41), 7.91 [(95%CI: 2.23–28.14), and 13.79 [(95%CI: 3.79–50.20)] fold respectively. For the ankle, a tophus score of 3 markedly improved the prediction of the frequent flares [OR= 9.24 (95%CI=2.85–29.91)]. Semi-quantitative sum scores were associated with frequent flares with an OR (95%CI) of 13.66 (3.44–54.18), P < 0.001 at the MTP1, 7.05 (1.98–25.12), P < 0.001 at the ankle. ConclusionUltrasound features of MSU crystal deposition at the MTP1 and knee predict subsequent risk of frequent gout flares in the same joints following initiation of urate-lowering therapy, with the highest risk in those with high tophus scores.

Vegetarian diet induced new onset acute gouty arthritis in a middle-aged genetically predisposed male: A rare presentation

Gout is a metabolic disease characterised by acute or chronic arthritis which is due to deposition of Monosodium urate (MSU) crystals in joints and soft tissues. Classically described as a disease associated with hyperuricemia which may be due to metabolic defect in uric acid production or due to impaired renal excretion.We present a case of 45 year old nondiabetic, non-alcoholic, non-smoker male presented to orthopaedic OPD with complain of pain in right hand and left leg with restriction of joint mobility for past 14 hours.On carefully eliciting the dietary history patient revealed that he was a vegetarian and was on high purine rich diet for past 2 weeks due to family functions and various gatherings. Patient gave the history of consumption of cauliflower, mushrooms, beans along with sweetened carbonated drinks on two consecutive days before the onset of these symptoms.Serum uric acid 4.5 mg/dl, C-reactive protein was 9 mg/dl. To best of our knowledge this is the first case being reported in literatures where purine rich vegetarian diet has induced new case of gout.This kind of gout precipitation after consuming vegetarian diet is rarely reported in literature. This case report emphasizes upon the need of special caution to be taken by persons who are genetically predisposed to gout, while consuming purine rich diet like red meat, seafood, cauliflowers, spinach, rajma, Bengal gram, mushrooms, soft drinks sweetened with fructose.

GWAS-identified hyperuricemia-associated IGF1R variant rs6598541 has a limited role in urate mediated inflammation in human mononuclear cells

Gout is a common autoinflammatory joint diseases characterized by deposition of monosodium urate (MSU) crystals which trigger an innate immune response mediated by inflammatory cytokines. IGF1R is one of the loci associated with both urate levels and gout susceptibility in GWAS to date, and IGF-1-IGF-1R signaling is implicated in urate control. We investigate the role of IGF-1/IGF1R signaling in the context of gouty inflammation. Also, we test the gout and urate-associated IGF1R rs6598541 polymorphism for association with the inflammatory capacity of mononuclear cells. For this, freshly isolated human peripheral blood mononuclear cells (PBMCs) were exposed to recombinant IGF-1 or anti-IGF1R neutralizing antibody in the presence or absence of solubilized urate, stimulated with LPS/MSU crystals. Also, the association of rs6598541 with IGF1R and protein expression and with ex vivo cytokine production levels after stimulation with gout specific stimuli was tested. Urate exposure was not associated with IGF1R expression in vitro or in vivo. Modulation of IGF1R did not alter urate-induced inflammation. Developing urate-induced trained immunity in vitro was not influenced in cells challenged with IGF-1 recombinant protein. Moreover, the IGF1R rs6598541 SNP was not associated with cytokine production. Our results indicate that urate-induced inflammatory priming is not regulated by IGF-1/IGF1R signaling in vitro. IGF1R rs6598541 status was not asociated with IGF1R expression or cytokine production in primary human PBMCs. This study suggests that the role of IGF1R in gout is tissue-specific and may be more relevant in the control of urate levels rather than in inflammatory signaling in gout.

Are gout patients with negative dual-energy computed tomography for monosodium urate crystal deposition easy to treat?

Abstract Objectives To determine the clinical associations and predictive value of two thresholds of negative dual-energy CT (DECT) for MSU crystal deposition in gout patients initiating urate-lowering therapy (ULT) and identify which threshold is more clinically relevant. Methods Patients from the CRYSTALILLE cohort with a diagnosis of gout naïve to ULT with baseline DECT scans of the knees and feet were selected. Two thresholds of positivity for DECT detection of MSU crystal deposition were considered (&amp;lt;0.01 cm3 and &amp;lt;0.1 cm3). Baseline characteristics and the prediction of key outcomes after ULT initiation, including reaching serum urate (SU) levels &amp;lt;6.0 and 5.0 mg/dl and occurrence of flares at 6, 12 and 24 months, associated with both thresholds of negative DECTs were compared with those of patients having positive DECT scans. Results A total of 211 patients, median age 66.2 years [interquartile range (IQR) 57–75.8], with a median symptom duration of 3 years (IQR 0–7.8) were included. A total of 38/211 (18%) and 90/211 (43%) had negative DECT scans for the 0.01 and 0.1 cm3 thresholds, respectively. Factors associated with negative DECT scans were younger age, shorter symptom duration and an absence of cardiovascular disease for both volume thresholds. A total of 9/39 (23.1%), 3/26 (11.5%) and 1/18 (5.6%) patients with &amp;lt;0.1 cm3 MSU crystals had flares at 6, 12 and 24 months, respectively, compared with 18/45 (40.0%), 9/36 (25.0%) and 2/18 (11.1%) patients with ≥0.1 cm3 (P &amp;gt; 0.05). Overall, 95 patients (68.3%) reached SU levels &amp;lt;6.0 mg/dl and 68 (48.9%) reached levels &amp;lt;5.0 mg/dl, without any difference between positive and negative DECTs, with ULT dosages that tended to be lower in patients with negative DECTs. Conclusion The 0.1 cm3 threshold was better correlated with clinical presentation and evolution than the 0.01 cm3 threshold. Gout patients with negative DECTs exhibit milder disease and a lower comorbidity burden. They do not exhibit particularly easy-to-treat hyperuricaemia but they may have a lower risk of flares.

Novel Leflunomide Analog, UTLOH-4e, Ameliorates Gouty Arthritis Induced by Monosodium Urate Via NF-κB/NLRP3 Signaling Pathway.

Gouty arthritis (GA) is a common form of inflammatory arthritis caused by intra-articular deposition of monosodium urate (MSU) crystals; however, there is a tremendous lack of safe and effective therapy in the clinic. The goal of this work was to investigate a novel leflunomide analogue, N-(2,4- dihydroxyphenyl)-5-methyl-1,2-oxazole-3-carboxamide (UTLOH-4e), for its potential to prevent/ treat gouty arthritis. In this study, the anti-inflammatory activity of UTLOH-4e was evaluated by MSUinduced GA model in vivo and in vitro, and the molecular docking test was applied to estimate the affinity of UTLOH-4e/UTL-5g/b for MAPKs, NF-κB, and NLRP3. In vitro, UTLOH-4e (1~100 μM) treatment inhibited the inflammatory reaction with no obvious cytotoxicity in PMA-induced THP-1 macrophages exposed to MSU crystals for 24 h, involving the prominent decreased production and gene expression of IL-1β, TNF-α, and IL-6. Western blot analyses demonstrated that UTLOH-4e (1~100 μM) significantly suppressed the activation of NLRP3 inflammasomes, NF-κB, and MAPK pathways. Furthermore, the data from the experiment on gouty rats induced by intra-articular injection of MSU crystal confirmed that UTLOH-4e markedly ameliorated rat paw swelling, articular synovium inflammation and reduced the concentration of IL-1β and TNF-α in serum through down-regulating NLRP3 protein expression. These results manifested that UTLOH-4e ameliorates GA induced by MSU crystals, which contributes to the modulation of NF-κB/ NLRP3 signaling pathway, suggesting that UTLOH- 4e is a promising and potent drug candidate for the prevention and treatment of gouty arthritis.

Imaging Follow-Up of MSU Crystal Depletion

Imaging modalities such as ultrasonography (US) and dual-energy computed tomography (DECT) have been recognized for their abilities to detect monosodium urate (MSU) crystals. The main described features of gout detected by DECT (tophus) or US (tophus, double contour [DC] sign and aggregates) are very specific for the diagnosis of gout, but the impact of imaging on the follow-up of MSU deposits is not well known. US and DECT allow for visualization of the disappearance of MSU crystals under adequate urate-lowering therapy (ULT). An OMERACT US score and a DECT urate score have been described. The dissolution of the DC sign is detectable on US after 3 months, whereas a decreased size or volume in tophus can be observed on US or DECT after 6 months of ULT. Serum urate level decrease is associated with a reduction in MSU crystal deposition. Finally, the risk of gout flare is associated with the baseline MSU burden and with the degree of dissolution of crystal deposition. All these data confirm that imaging could be useful in managing gout, even if its exact place in routine practice remains unclear.

Comparison between dual-energy computed tomography and ultrasound in the diagnosis of gout

Objectives: Gout is one of the most common inflammatory arthritic conditions that arise due to the super saturation of urate levels in body tissues, resulting in the formation of monosodium urate (MSU) crystals that get deposited in and around the joints. Clinical diagnosis of gout is generally made based on signs and symptoms. The biochemical diagnosis is based on the levels of serum uric acid. However, hyperuricemia is a weak marker for gout diagnosis. The gold standard for diagnosing gout is the identification of MSU crystals in the synovial fluid by Polaroid microscopy. However, it is an invasive procedure that could lead to complications such as joint effusion and intra-articular hemorrhage. Imaging offers a non-invasive method for the diagnosis of gout. Ultrasound (USG) has emerged as a useful measure for detecting joint effusion and synovitis, studying cartilage, describing early bone erosions, and evaluating tendons and crystal deposition. Dual-energy computed tomography (DECT) is a useful non-invasive technique that helps visualize MSU crystals, along with other soft tissue changes and erosive pathologies, at high resolution, much earlier than conventional radiography could do. Material and Methods: Clinically suspected or diagnosed gout patients in the age group of 20–75 years of both genders attending outpatient services were selected for the study. All the patients fulfilling the inclusion criteria of clinical suspicion of gout or already proven cases of gout were clinically examined, and body mass index, presenting complaints, symptomatic joints, past medical history, family history, and personal habits were noted. The diagnosis of gout was confirmed using the 2015 American college of rheumatology/European league against rheumatism (ACR/EULAR) classification criteria: A cut-off score &gt;8 was considered diagnostic. Thereafter, all the patients underwent ultrasonographic and computed tomography evaluations. All the patient’s assessments were made at nine locations bilaterally – shoulder, neck, wrist, metacarpal, metatarsophalangeal, ankle, hip, knee, and elbow to check for multiple joint involvements. All the DECT images were post-processed, allowing analysis of images using the three material decomposition methods. On reconstructed DECT images, green color-coded MSU crystals were considered suggestive of gout. Results: The present study reported a higher detection of gout on DECT (97.1%) as compared to the USG (88.2%). Similarly, several studies reported a higher detection rate of MSU crystal deposition by DECT as compared to the detection of the double-contour sign by USG. This study reported sensitivity, specificity, positive predictive, and negative predictive value (PPV and NPV) of USG as 91%, 92%, 95%, and 85%, respectively. In contrast, DECT’s sensitivity, specificity, PPV, and NPVs were 96%, 100%, 100%, and 92%, respectively. DECT showed to have a high sensitivity as well as specificity. Conclusion: The study showed that DECT is more sensitive and had a better PPV and accuracy than USG in the diagnosis of gout. Keeping in view the high efficacy of DECT in diagnosing gouty joints, it is a strong candidate to emerge as a non-invasive imaging modality of choice for diagnosing gout.

Assessment of Primary Healthcare Providers' Knowledge and Practices in Addressing Asymptomatic Hyperuricemia and Gout in the Asir Region of Saudi Arabia.

Introduction and aim Gout, the most common form of inflammatory arthritis, arises from hyperuricemia, a condition where elevated levels of uric acid lead to the deposition of monosodium urate (MSU) crystals in the joints. Nevertheless, it's important to note that not all cases of hyperuricemia result in gout. Methodology This cross-sectional study was conducted in the Asir region of Saudi Arabia, targeting primary healthcare physicians (PHPs) specializing in family medicine and general practice. The study utilized a modified electronic questionnaire, inspired by similar studies and aligned with recent guidelines, to assess PHPs' knowledge and practices concerning asymptomatic hyperuricemia (AH) and gout. The questionnaire encompassed the PHPs' demographic data and their knowledge and practices for AH and gout management. Results Out of 201 participating PHPs, the majority were male (68.2%), predominantly aged 25-34 years (73.1%), and practicing as general practitioners (61.2%). A significant proportion of PHPs had less than five years of experience (63.7%). In terms of education, 36.8% attended continuing medical education (CME) on AH or gout, and 66.7% were aware of the related management guidelines. The study revealed that the total knowledge score among PHPs averaged 5.18 out of seven, indicating a moderate level of knowledge. However, their practice level was moderate, with a mean practice score of 6.75 out of 12. The study also found no significant differences in knowledge scores based on gender, age, or years of experience, but significant variations were noted based on medical specialty. Conclusion There is a moderate level of knowledge and practice among PHPs in managing AH and gout in the Asir region. Despite adequate knowledge levels, there appears to be a gap in implementing this knowledge into practice, particularly in long-term management strategies. The findings emphasize the need for ongoing medical education and specialized training programs to bridge these gaps. The study provides a valuable framework for identifying and addressing similar challenges in other regions and medical practices.

Single-nucleotide polymorphisms link gout with health-related lifestyle factors in Korean cohorts

Gout—a very painful inflammatory arthritis caused by the deposition of monosodium urate crystals in the joints—is influenced by several factors. We identified the association of single- nucleotide polymorphisms (SNPs) that link gout with health-related lifestyle factors using genomic data from the Korean Genome and Epidemiology Study. We conducted a genome-wide association study (GWAS) on 18,927 samples of 438 Korean patients with gout and 18,489 controls for the discovery stage. For the replication stage, another batch containing samples of 326 patients with gout and 2,737 controls were analyzed. Lastly, a meta-analysis was performed using these two cohorts. We analyzed the effects of health-related lifestyle factors, including eating habits, physical activity, drinking behavior, and smoking behavior, on gout. After identifying the association between GWAS-derived SNPs and health-related lifestyle factors, we confirmed the interaction between the polygenic risk score (PRS) and health-related lifestyle factors. We identified 15 SNPs related to gout, among which rs1481012 of ABCG2 located on chromosome 4 has been newly discovered (P = 2.46e-11). On examining the interaction between SNPs and health-related lifestyles, rs3109823—located in ABCG2—was found to be associated with smoking status. In addition, rs11936395—located in SLC2A9—was significantly associated with the average momentum of exercise per session, whereas rs11066325 located in PTPN11, showed a significant association with the number of exercise sessions per week, smoking status, drinking status, and amount of soju drink per session. rs9421589—located in FAM35A—was significantly associated with the duration of smoking. In addition, we verified that the association between PRS and duration of smoking affects gout. Thus, in this study, we identified novel SNPs that link gout with health-related lifestyle factors in the Korean population.