Construction of a highly specific fluorescence "turn-on" probe for H2S detection and imaging in drug-induced live cells, zebrafish and mice arthritis models.

Quantitatively and selectively detecting the biomarker of hydrogen sulfide (H2S) in arthritis diseases is of great significance for the early diagnosis and treatment of arthritis. Modern medical studies show that H2S as a biomarker is involved in the development of inflammation. In this work, a new highly specific fluorescence "turn-on" probe JMD-H2S was tailored for H2S detection and imaging in drug-induced live cells, zebrafish and mice arthritis models, which utilized pyrazoline molecule as the fluorescence signal reporter group and 2,4-dinitrophenyl ether group (DNB) with strong intramolecular charge transfer (ICT) effect as the H2S recognition moiety and fluorescence quenching group. JMD-H2S showed a fast response time (<60 s), a large fluorescence response ratio (enhanced ∼20 folds) at I453/I0, excellent sensitivity toward H2S over other analytes, and an outstanding limit of detection (LOD) as low as 25.3 nM. In addition, JMD-H2S has been successfully applied for detecting and imaging H2S in drug-induced live cells, zebrafish, and mice arthritis models with satisfactory results, suggesting it can be used as a robust molecular tool for investigating the occurrence and development of H2S and arthritis.

Blau syndrome-the skin as a warning sign.

Blau syndrome is an autosomal dominant chronic inflammatory disease, which may begin with skin manifestations in the first months of life, alerting physicians to the diagnosis. This case reports a patient diagnosed jointly by pediatric dermatology and rheumatology consultants at two years of age.

Association between different triglyceride-glucose index combinations with obesity indicators and arthritis: results from two nationally representative population-based study.

BACKGROUND: Insulin resistance (IR) and arthritis are strongly associated, and the triglyceride-glucose (TyG) index combinations with obesity indicators [including TyG-BMI (glucose triglyceride-body mass index), TyG-WC (glucose triglyceride-waist circumference), and TyG-WHtR (glucose triglyceride-waist height ratio)] has recently been recognized as a more effective indicator for assessing IR. However, there is a lack of research on its association with arthritis, and it is also important to assess in different populations. METHODS: The analysis utilized data from the China Health and Retirement Longitudinal Study (CHARLS) and the National Health and Nutrition Examination Survey (NHANES). Arthritis diagnosis relied on self-reporting confirmed by physicians. The association of TyG-BMI, TyG-WC, and TyG-WHtR with arthritis was analyzed through weighted logistic regression models, and exploring nonlinear effects with restricted cubic spline (RCS) models. Secondary and sensitivity analyses included receiver operating characteristic curve (ROC) analysis, comparisons of z score-related odds ratios, subgroup analyses, and multiple imputation. RESULTS: The study involved 6141 CHARLS participants and 17,091 NHANES participants. Adjusting for confounding variables, TyG-BMI and TyG-WHtR demonstrate a positive correlation with arthritis prevalence in both CHARLS (TyG-BMI: OR = 1.02, 95% CI 1.00-1.04; TyG-WHtR: OR = 1.13, 95% CI 1.03-1.24) and NHANES (TyG-BMI: OR = 1.07, 95% CI 1.06-1.08; TyG-WHtR: OR = 1.50, 95% CI 1.40-1.60). RCS regression analysis demonstrated a significant nonlinear association. ROC analysis indicated that TyG-BMI and TyG-WHtR were superior to TyG for the diagnosis of arthritis in both CHARLS and NHANES. CONCLUSIONS: TyG-BMI and TyG-WHtR demonstrate a positive correlation with arthritis prevalence in both Chinese and the U.S. populations, displaying superior diagnostic relevance compared to TyG.

Cost of lost productivity in inflammatory arthritis and osteoarthritis in the year before and after diagnosis: An inception cohort study.

AIM: Existing studies on the cost of inflammatory arthritis (IA) and osteoarthritis (OA) are often cross-sectional and/or involve patients with various disease durations, thus not providing a comprehensive perspective on the cost of illness from the time of diagnosis. In this study, we therefore assessed the cost of lost productivity in an inception cohort of patients with IA and OA in the year before and after diagnosis. METHODS: Employment status, monthly income, days absent from work, and presenteeism were collected at diagnosis and 1 year later to estimate the annual costs of unemployment, absenteeism, and presenteeism using human capital approach. Non-parametric bootstrapping was performed to account for the uncertainty of the estimated costs. RESULTS: Compared to patients with OA (n = 64), patients with IA (n = 102, including 48 rheumatoid arthritis, 19 spondyloarthritis, 23 psoriatic arthritis, and 12 seronegative IA patients) were younger (mean age: 52.3 vs. 59.5 years) with a greater proportion receiving treatment (99.0% vs. 67.2%) and a greater decrease in presenteeism score (median: 15% vs 10%) 1 year after diagnosis. Annual costs of absenteeism and presenteeism were lower in patients with IA than those with OA both in the year before (USD566 vs. USD733 and USD8,472 vs. USD10,684, respectively) and after diagnosis (USD636 vs. USD1,035 and USD6,866 vs. USD9,362, respectively). CONCLUSION: Both IA and OA impose substantial cost of lost productivity in the year before and after diagnosis. The greater improvement in productivity seen in patients with IA suggests that treatment for IA improves work productivity.

Sarcoidosis Presenting as Granulomatous Mastitis, Erythema Nodosum, and Arthritis Syndrome: A Case Report and Comprehensive Review of the Literature.

Granulomatous mastitis (GM) is a long-term inflammatory disease of the breast that usually occurs in women of reproductive age. Autoimmune mastitis is one of the most common pathological breast conditions necessitating tailored treatment. However, GM as a first clinical manifestation of sarcoidosis is uncommon. Simultaneous occurrence of GM, erythema nodosum (EN), and arthritis, termed "GMENA" syndrome, is a rare clinical entity associated with autoimmune rheumatic diseases. Herein, we report the case of a 31-year-old female patient with GMENA syndrome, who presented with a painful nodule of the left breast. Initial treatment entailed antibiotics under the presumption of a breast abscess, yielding negligible improvement. During this period, the patient developed polyarthritis and bilateral EN on the lower extremities. Histopathologic examination of the breast tissue exhibited noncaseating granulomas. The patient responded positively to prednisolone and methotrexate treatment. Literature review revealed a coherent pattern across GMENA cases. Our findings suggest that the "GMENA" syndrome represents a unique acute manifestation of sarcoidosis and highlight the necessity for heightened awareness, accurate diagnosis, and tailored therapeutic approaches for GMENA syndrome. Further research is warranted to elucidate its cause and optimize patient management. This case highlights the importance of identifying and effectively managing such interrelated clinical presentations.

Blau Syndrome: Challenging Molecular Genetic Diagnostics of Autoinflammatory Disease.

The aim of this study was to describe the clinical and molecular genetic findings in seven individuals from three unrelated families with Blau syndrome. A complex ophthalmic and general health examination including diagnostic imaging was performed. The NOD2 mutational hot spot located in exon 4 was Sanger sequenced in all three probands. Two individuals also underwent autoinflammatory disorder gene panel screening, and in one subject, exome sequencing was performed. Blau syndrome presenting as uveitis, skin rush or arthritis was diagnosed in four cases from three families. In two individuals from one family, only camptodactyly was noted, while another member had camptodactyly in combination with non-active uveitis and angioid streaks. One proband developed two attacks of meningoencephalitis attributed to presumed neurosarcoidosis, which is a rare finding in Blau syndrome. The probands from families 1 and 2 carried pathogenic variants in NOD2 (NM_022162.3): c.1001G>A p.(Arg334Gln) and c.1000C>T p.(Arg334Trp), respectively. In family 3, two variants of unknown significance in a heterozygous state were found: c.1412G>T p.(Arg471Leu) in NOD2 and c.928C>T p.(Arg310*) in NLRC4 (NM_001199139.1). In conclusion, Blau syndrome is a phenotypically highly variable, and there is a need to raise awareness about all clinical manifestations, including neurosarcoidosis. Variants of unknown significance pose a significant challenge regarding their contribution to etiopathogenesis of autoinflammatory diseases.

Thymic carcinoma presenting with overlap polyarthritis and myositis: A rare paraneoplastic syndrome in childhood.

Thymic tumors are very rare neoplasms in children and account for less than 1% of mediastinal tumors in pediatric patients. One-third of the pediatric patients present with symptoms related to the compression of the tumor mass on the surrounding anatomic structures, and paraneoplastic syndromes such as myasthenia gravis, pure red cell aplasia, acquired hypogammaglobulinemia, and connective tissue disorders, which rarely occur in children with thymic tumors. Herein, we report a case of thymic carcinoma mimicking the symptoms of a connective tissue disease with symmetrical polyarthritis accompanying myositis, fever, weight loss, and malaise in a 15-year-old male patient. To our knowledge, this is the first case pediatric thymic carcinoma accompany with severe polyarthritis and myopathy, thus we have reviewed the current literature regarding the cases of thymic malignancies coexisting with paraneoplastic syndromes in children.

A Novel COL2A1 Gene Pathogenic Variant in a Turkish Family With Ocular Stickler Syndrome.

A 6-month-old female infant with megalophthalmos was referred with the suspicion of congenital glaucoma. Refractive measurements obtained with handheld autorefractometry were -7.00 -2.00 × 90° in the right eye and -6.00 -2.00 × 100° in the left eye and ultrasonic axial lengths were 22.50 mm in both eyes. Intraocular pressures and vertical and horizontal corneal diameters of the proband were 11 mm Hg, 11 mm, and 11.50 mm in both eyes, respectively. She was diagnosed as having early-onset high myopia. Her father also had degenerative high myopia (-12.00 diopters) in the right eye, bilateral congenital lens opacities, and retinal detachment in the left eye. Her mother was emmetropic with normal eye examination results. Clinical exome sequencing analysis revealed a novel ENST00000380518.3 c.3528_3530 delins GACCATTAGCA (Chr12:48369813: GCA > TGCTAATGGTC) variant in the collagen type II alpha 1 chain (COL2A1) on chromosome 12q13 (OMIM 108300), consistent with the Stickler syndrome type 1. Subsequent segregation analysis revealed paternal inheritance. Although many pathogenic null variants have been described within the COL2A1 gene, there is currently no documented literature pertaining to this specific variant, making this the inaugural report of its manifestation in scientific discourse. [J Pediatr Ophthalmol Strabismus. 2024;61(3):e23-e27.].

International Classification of Diseases Coding for Inflammatory Arthritides.

This quality improvement study investigates usage patterns of codes for inflammatory arthritides under International Statistical Classification of Diseases and Related Health Problems, Tenth Revision vs International Classification of Diseases, Ninth Revision.

Synovial Lipomatosis With Extra-articular Extension in the Arthritic Wrist: An Unexpected Diagnosis.

ABSTRACT: Synovial lipomatosis is a rare condition characterized by adipocyte proliferation within joint synovial tissue. It most commonly affects the knee and is typically intra-articular. Only 5 published case reports describe extra-articular synovial lipomatosis of the wrist. We present a case of a sexagenarian patient seen for his wrist arthropathy. His x-ray revealed pan-wrist arthritis and inflammatory soft tissue swelling. The patient was slated for a wrist fusion and Darrach procedure. Following the dorsal skin incision in the operating room, an unusual adipose mass was identified infiltrating all extensor compartments: midcarpal, radiocarpal, and distal radioulnar joints. The mass was excised and sent to pathology prior to proceeding with the slated surgery. Synovial lipomatosis was diagnosed postoperatively based on histopathology. Six weeks postoperatively, the wrist fusion had healed clinically and radiographically, and his pain had improved. There was no evidence of recurrence. Synovial lipomatosis is a rare entity that may imitate multiple other pathologies. It is possible that synovial lipomatosis may represent a secondary occurrence following degenerative articular disease or trauma in older patients. This is the first case report to date describing synovial lipomatosis of the wrist with extra-articular extension in the setting of pan-carpal wrist arthritis.

Mimickers of Immune Checkpoint Inhibitor-induced Inflammatory Arthritis.

The differential diagnosis of inflammatory arthritis as an immune-related adverse event can be challenging as patients with cancer can present with musculoskeletal symptoms that can mimic arthritis because of localized or generalized joint pain. In addition, immune checkpoint inhibitors can exacerbate joint conditions such as crystal-induced arthritis or osteoarthritis, or induce systemic disease that can affect the joints such as sarcoidosis. This distinction is important as the treatment of these conditions can be different from that of immune-related inflammatory arthritis.

Blau Syndrome With Delayed Cutaneous Manifestations: A Case Report.

ABSTRACT: Blau syndrome is a rare familial autoinflammatory disorder characterized by the triad of granulomatous dermatitis, polyarthritis, and uveitis. Blau syndrome exhibits an autosomal dominant inheritance pattern and can be caused by a gain-of-function mutation in nucleotide-binding oligomerization domain 2 (NOD2), a member of the NOD-like receptor family of pattern recognition receptors. Mutations in NOD2 cause upregulation of inflammatory cytokines and resultant autoinflammation. Because of the rarity of this condition and early onset of symptoms, Blau syndrome may be misdiagnosed as juvenile idiopathic arthritis. We present a case of a 37-year-old male patient with a long-documented history of juvenile idiopathic arthritis and uveitis, who developed an asymptomatic eruption of pink papules on the trunk and upper extremities. A biopsy demonstrated noncaseating, well-formed dermal granulomas with relatively sparse lymphocytic inflammation and Langerhans-type giant cells. Genetic testing confirmed a mutation in NOD2. Based on the patient's clinical history, histologic findings, genetic testing, the diagnosis of Blau syndrome was made.

Performance of adenosine deaminase in synovial fluid for the diagnosis of tuberculous arthritis: A systematic review and meta-analysis / Rendimiento de la adenosina desaminasa en el líquido sinovial para el diagnóstico de la artritis tuberculosa: una revisión sistemática y metaanálisis

Objectives: Adenosine deaminase (ADA) activity has shown good performance in diagnosing pleural, peritoneal, and meningeal tuberculosis. This meta-analysis aimed to evaluate the performance of measuring ADA activity in synovial fluid for the early diagnosis of joint tuberculosis. Methods: We searched published information in MEDLINE, Embase, Cochrane Library, Web of Science, and MedRxiv databases, as well as unpublished information in the American College of Rheumatology and European League Against Rheumatism for conference abstracts (2012–2021). We also scanned the reference lists of articles. Two reviewers independently applied the criteria for selection, assessed quality, and extracted data (PROSPERO number CRD42021284472). Results: Seven independent studies (N=305 subjects) that compared ADA activity in synovial fluid with a composite reference diagnostic method for tuberculosis were included. Overall, the risk of bias was judged low. Studies were classified as high quality (n=3; 148 subjects) and low quality (n=4; 157 subjects). Pooled sensitivity and specificity of ADA activity was 94% (95% confidence interval [CI], 0.89–98; I2=23%) and 88% (95% CI, 83–92; I2=83%), respectively. The random-effects model for pooled diagnostic Odds ratio was 67.1 (95%CI, 20.3–222.2; I2=30%). The receiver operating characteristic curve area was 0.96 (95% CI, 0.92–0.99). Meta-regression did not identify the quality of the study, country of publication, or the type of assay as a source of heterogeneity. Conclusions: Measuring ADA activity in synovial fluid demonstrates good performance for the early diagnosis of joint tuberculosis.(AU)

Objetivos: La actividad de la adenosina desaminasa (ADA) ha mostrado un buen desempeño en el diagnóstico de la tuberculosis pleural, peritoneal y meníngea. Este metaanálisis tuvo como objetivo evaluar el rendimiento de la medición de la actividad de la ADA en el líquido sinovial para el diagnóstico precoz de la tuberculosis articular. Métodos: Se realizaron búsquedas de resúmenes de congresos en la información publicada en las bases de datos MEDLINE, Embase, Cochrane Library, Web of Science y MedRxiv, así como en información no publicada en el American College of Rheumatology y la European League Against Rheumatism (2012-2021). También se escanearon las listas de referencias de los artículos. Dos revisores aplicaron de forma independiente los criterios de selección, evaluaron la calidad y extrajeron los datos (número PROSPERO CRD42021284472). Resultados: Se incluyeron siete estudios independientes (n=305 sujetos) que compararon la actividad de la ADA en el líquido sinovial con un método diagnóstico compuesto de referencia para la tuberculosis. En general, el riesgo de sesgo se consideró bajo. Los estudios se clasificaron como de alta calidad (n=3; 148 sujetos) y de baja calidad (n=4; 157 sujetos). La sensibilidad y la especificidad agrupadas de la actividad de la ADA fueron del 94% (intervalo de confianza [IC] del 95%: 0,89-98; I2=23%) y del 88% (IC95%: 83-92; I2=83%), respectivamente. El modelo de efectos aleatorios para el odds ratio diagnóstico agrupado fue de 67,1 (IC95%: 20,3-222,2; I2=30%). El área de la curva característica de operación del receptor fue de 0,96 (IC95%: 0,92-0,99). La metarregresión no identificó la calidad del estudio, el país de publicación o el tipo de ensayo como fuente de heterogeneidad.Conclusiones: La medición de la actividad de ADA en el líquido sinovial demuestra un buen rendimiento para el diagnóstico precoz de la tuberculosis articular.(AU)

Triglyceride-glucose index in the prediction of new-onset arthritis in the general population aged over 45: the first longitudinal evidence from CHARLS.

OBJECTIVE: Insulin resistance (IR) imposes a significant burden on inflammatory diseases, and the triglyceride-glucose (TyG) index, which is an easily accessible indicator for detecting IR, holds great application potential in predicting the risk of arthritis. The aim of this study is to analyze the association between the TyG index and the risk of new-onset arthritis in the common population aged over 45 using a prospective cohort study design. METHOD: This population-based cohort study involved 4418 participants from the China Health and Retirement Longitudinal Study (from Wave 1 to Wave 4). Multivariate logistic regression models were employed to investigate the association between the TyG index and new-onset arthritis, and RCS analyses were used to investigate potential non-linear relationships. Moreover, decision trees were utilized to identify high-risk populations for incident arthritis. RESULT: Throughout a 7-year follow-up interval, it was found that 396 participants (8.96%) developed arthritis. The last TyG index quartile group (Q4) presented the highest risk of arthritis (OR, 1.39; 95% CI, 1.01, 1.91). No dose-response relationship between the TyG index and new-onset arthritis was identified (Poverall=0.068, Pnon-linear=0.203). In the stratified analysis, we observed BMI ranging from 18.5 to 24 exhibited a heightened susceptibility to the adverse effects of the TyG index on the risk of developing arthritis (P for interaction = 0.035). CONCLUSION: The TyG index can be used as an independent risk indicator for predicting the start of new-onset arthritis within individuals aged 45 and above within the general population. Improving glucose and lipid metabolism, along with insulin resistance, may play a big part in improving the primary prevention of arthritis.