Hypophosphatemic Osteomalacia Associated with Tenofovir: a Multidisciplinary Approach is Required.

Tenofovir is widely used as first-line treatment of HIV infection, although its use is sometimes complicated by a reversible proximal renal tubulopathy

Identification of biomarkers in patients with rheumatoid arthritis responsive to DMARDs but with progressive bone erosion

IntroductionRheumatoid arthritis (RA) is an inflammatory autoimmune disease that may cause joint destruction and disability. The pharmacological treatment of RA aims at obtaining disease remission by effectively ceasing joint inflammation and arresting progressive bone erosions. Some patients present bone lesions accrual even after controlling joint inflammation with current therapies. Our study aimed to analyze lymphocyte subsets and levels of circulating cytokines in patients with RA with progressive bone erosions.MethodsWe enrolled 20 patients with a diagnosis of RA and 12 healthy donors (HD). Patients with RA were divided into patients with bone erosions (RA-BE+) and without bone erosions (RA-BE-). Lymphocyte subsets in peripheral blood were evaluated by flow cytometry. Circulating cytokines levels were evaluated by protein array.ResultsThe distribution of lymphocyte subsets was not able to separate HD from AR patients and RA-BE+ and RA-BE- in cluster analysis. We observed a significant expansion of CXCR5- PD1+ T peripheral helper cells (Tph cells) and a reduction in both total memory B cells and switched memory B cells in RA patients compared to HD. We observed an expansion in the frequency of total B cells in RA-BE+ patients compared to RA-BE- patients. Unsupervised hierarchical clustering analysis of 39 cytokines resulted in a fairly good separation of HD from RA patients but not of RA-BE+ patients from RA-BE- patients. RA-BE+ patients showed significantly higher levels of IL-11 and IL-17A than RA-BE- patients.ConclusionWe show that patients with progressive erosive disease are characterized by abnormalities in B cells and in cytokines with a proven role in bone reabsorption. Understanding the role played by B cells and the cytokine IL-11 and IL-17A in progressive erosive disease can help identify novel biomarkers of erosive disease and design treatment approaches aimed at halting joint damage in RA

Morphology of the toe flexor muscles in older people with toe deformities

Objective: Despite suggestions that atrophied, or weak toe flexor muscles are associated with the formation of toe deformities, there has been little evidence to support this theory. This study aimed to determine whether the size of the toe flexor muscles differed in older people with and without toe deformities. Methods: Forty-four older adults (>60 years) were recruited for the study. Each participant had their feet assessed for the presence of hallux valgus or lesser toe deformities. Intrinsic and extrinsic toe flexor muscles were imaged with an ultrasound system using a standardised protocol. Assessor blinded muscle thickness and cross-sectional area was measured using Image J software. Results: Participants with lesser toe deformities (n=20) were found to have significantly smaller quadratus plantae (p=0.003), flexor digitorum brevis (p=0.013), abductor halluces (p=0.004) and flexor halluces brevis (p=0.005) muscles than the participants without any toe deformities (n=19). Female participants with hallux valgus (n=10) were found to have significantly smaller abductor hallucis (p=0.048) and flexor halluces brevis (p=0.013) muscles than the female participants without any toe deformities (n=10; p<0.05). Conclusion: This is the first study to use ultrasound to investigate the size of the toe flexor muscles in older people with hallux valgus and lesser toe deformities compared to otherwise healthy older adults. The size of the abductor hallucis and flexor hallucis brevis muscles were decreased in participants with hallux valgus whereas the quadratus plantae, flexor digitorum brevis, abductor hallucis and flexor halluces brevis muscles were smaller in those participants with lesser toe deformities

Development and First Validation of a Disease Activity Score for Gout

none51OBJECTIVE: To develop a new composite disease activity score for gout and provide its first validation. METHODS: Disease activity has been defined as the ongoing presence of urate deposits that lead to acute arthritis and joint damage. Every measure for each Outcome Measures in Rheumatology core domain was considered. A 3-step approach (factor analysis, linear discriminant analysis, and linear regression) was applied to derive the Gout Activity Score (GAS). Decision to change treatment or 6-month flare count were used as the surrogate criteria of high disease activity. Baseline and 12-month followup data of 446 patients included in the Kick-Off of the Italian Network for Gout cohort were used. Construct- and criterion-related validity were tested. External validation on an independent sample is reported. RESULTS: Factor analysis identified 5 factors: patient-reported outcomes, joint examination, flares, tophi, and serum uric acid (sUA). Discriminant function analysis resulted in a correct classification of 79%. Linear regression analysis identified a first candidate GAS including 12-month flare count, sUA, visual analog scale (VAS) of pain, VAS global activity assessment, swollen and tender joint counts, and a cumulative measure of tophi. Alternative scores were also developed. The developed GAS demonstrated a good correlation with functional disability (criterion validity) and discrimination between patient- and physician-reported measures of active disease (construct validity). The results were reproduced in the external sample. CONCLUSION: This study developed and validated a composite measure of disease activity in gout. Further testing is required to confirm its generalizability, responsiveness, and usefulness in assisting with clinical decisions.noneScirè, Carlo A; Carrara, Greta; Viroli, Cinzia; Cimmino, Marco A.; Taylor, William J.; Manara, Maria; Govoni, Marcello; Salaffi, Fausto; Punzi, Leonardo; Montecucco, Carlomaurizio; Matucci-Cerinic, Marco; Minisola, Giovanni; Ariani, Alarico; Galossi, Alessandra; Lauriti, Ciro; Fracassi, Elena; Idolazzi, Luca; Bardelli, Marco; Selvi, Enrico; Tirri, Enrico; Furini, Federica; Inverardi, Flora; Calabrò, Andrea; Porta, Francesco; Bittelli, Raffaele; Venturino, Francesco; Capsoni, Franco; Prevete, Immacolata; Sebastiani, Giandomenico; Selmi, Carlo; Fabbriciani, Gianluigi; D'Avola, Giovanni; Botticella, Giulia; Serale, Francesca; Seminara, Giulia; D'Alessandro, Giuseppe; Santo, Leonardo; Longato, Lorena; Zaccara, Eleonora; Sinigaglia, Luigi; Atteritano, Marco; Broggini, Marco; Caprioli, Marta; Favero, Marta; Sallì, Salvatore; Scarati, Marco; Parisi, Simone; Malavolta, Nazzarena; Corvaglia, Stefania; Scarpato, Salvatore; Veneto, VittorioScirè, Carlo A; Carrara, Greta; Viroli, Cinzia; Cimmino, Marco A.; Taylor, William J.; Manara, Maria; Govoni, Marcello; Salaffi, Fausto; Punzi, Leonardo; Montecucco, Carlomaurizio; Matucci Cerinic, Marco; Minisola, Giovanni; Ariani, Alarico; Galossi, Alessandra; Lauriti, Ciro; Fracassi, Elena; Idolazzi, Luca; Bardelli, Marco; Selvi, Enrico; Tirri, Enrico; Furini, Federica; Inverardi, Flora; Calabrò, Andrea; Porta, Francesco; Bittelli, Raffaele; Venturino, Francesco; Capsoni, Franco; Prevete, Immacolata; Sebastiani, Giandomenico; Selmi, Carlo; Fabbriciani, Gianluigi; D'Avola, Giovanni; Botticella, Giulia; Serale, Francesca; Seminara, Giulia; D'Alessandro, Giuseppe; Santo, Leonardo; Longato, Lorena; Zaccara, Eleonora; Sinigaglia, Luigi; Atteritano, Marco; Broggini, Marco; Caprioli, Marta; Favero, Marta; Sallì, Salvatore; Scarati, Marco; Parisi, Simone; Malavolta, Nazzarena; Corvaglia, Stefania; Scarpato, Salvatore; Veneto, Vittori