Specific-cytokine associations with outcomes in knee osteoarthritis subgroups: breaking down disease heterogeneity with phenotyping.

BACKGROUND: Despite existing extensive literature, a comprehensive and clinically relevant classification system for osteoarthritis (OA) has yet to be established. In this study, we aimed to further characterize four knee OA (KOA) inflammatory phenotypes (KOIP) recently proposed by our group, by identifying the inflammatory factors associated with KOA severity and progression in a phenotype-specific manner. METHODS: We performed an analysis within each of the previously defined four KOIP groups, to assess the association between KOA severity and progression and a panel of 13 cytokines evaluated in the plasma and synovial fluid of our cohort's patients. The cohort included 168 symptomatic female KOA patients with persistent joint effusion. RESULTS: Overall, our analyses showed that associations with KOA outcomes were of higher magnitude within the KOIP groups than for the overall patient series (all p-values < 1.30e-16) and that several of the cytokines showed a KOIP-specific behaviour regarding their associations with KOA outcomes. CONCLUSION: Our study adds further evidence supporting KOA as a multifaceted syndrome composed of multiple phenotypes with differing pathophysiological pathways, providing an explanation for inconsistencies between previous studies focussed on the role of cytokines in OA and the lack of translational results to date. Our findings also highlight the potential clinical benefits of accurately phenotyping KOA patients, including improved patient stratification, tailored therapies, and the discovery of novel treatments.

Biological and glucocorticoids treatment impair the medium-term immunogenicity to SARS-CoV-2 mRNA vaccines in autoimmune inflammatory rheumatic diseases.

BACKGROUND: This study aims to assess the sustained immunological response to the SARS-CoV-2 vaccine in patients with autoimmune inflammatory rheumatic diseases (AIRD) undergoing different treatment regimens. METHODS: We conducted a prospective observational study involving 157 AIRD patients without prior COVID-19 infection. Treatment regimens included non-treatment or glucocorticoid-only (not-treated/GCs), non-biological drugs, biological therapy, and JAK inhibitors. All participants completed the two-dose vaccine schedule, and 110 of them received an additional booster dose. Serum samples were collected approximately 3-6 months after the second and third vaccine doses to measure antibodies against the Spike protein (antiS-AB) and neutralizing antibodies (nAB) targeting six SARS-CoV-2 variants. RESULTS: Following the third dose, all patients exhibited a significant increase in antiS-AB (FC = 15, p < 0.0001). Patients under biological therapy had lower titres compared to the non-biological (66% decrease, p = 0.038) and the not-treated/GCs group (62% decrease, p = 0.0132), with the latter persisting after the booster dose (86% decrease, p = 0.0027). GC use was associated with lower antiS-AB levels in the biological group (87% decrease, p = 0.0124), although not statistically significant after confounders adjustment. nABs showed the highest positivity rates for the wild-type strain before (50%) and after the booster dose (93%), while the Omicron variant exhibited the lowest rates (11% and 55%, respectively). All variants demonstrated similar positivity patterns and good concordance with antiS-AB (AUCs from 0.896 to 0.997). CONCLUSIONS: The SARS-CoV-2 vaccine booster strategy effectively elicited a sustained antibody immune response in AIRD patients. However, patients under biological therapies exhibited a reduced response to the booster dose, particularly when combined with GCs.

Metabolic and inflammatory profiles define phenotypes with clinical relevance in female knee osteoarthritis patients with joint effusion.

OBJECTIVES: Osteoarthritis has been the subject of abundant research in the last years with limited translation to the clinical practice, probably due to the disease's high heterogeneity. In this study, we aimed to identify different phenotypes in knee osteoarthritis (KOA) patients with joint effusion based on their metabolic and inflammatory profiles. METHODS: A non-supervised strategy based on statistical and machine learning methods was applied to 45 parameters measured on 168 female KOA patients with persistent joint effusion, consecutively recruited at our hospital after a monographic OA outpatient visit. Data comprised anthropometric and metabolic factors and a panel of systemic and local inflammatory markers. The resulting clusters were compared regarding their clinical, radiographic and ultrasound severity at baseline and their radiographic progression at two years. RESULTS: Our analyses identified four KOA inflammatory phenotypes (KOIP): a group characterized by metabolic syndrome, probably driven by body fat and obesity, and by high local and systemic inflammation (KOIP-1); a metabolically healthy phenotype with mild overall inflammation (KOIP-2); a non-metabolic phenotype with high inflammation levels (KOIP-3); and a metabolic phenotype with low inflammation and cardiovascular risk factors not associated with obesity (KOIP-4). Of interest, these groups exhibited differences regarding pain, functional disability and radiographic progression, pointing to a clinical relevance of the uncovered phenotypes. CONCLUSION: Our results support the existence of different KOA phenotypes with clinical relevance and differing pathways regarding their pathophysiology and disease evolution, which entails implications in patients' stratification, treatment tailoring and the search of novel and personalized therapies.

Glucocorticoids' treatment impairs the medium-term immunogenic response to SARS-CoV-2 mRNA vaccines in Systemic Lupus Erythematosus patients.

Limited data exists on SARS-CoV-2 sustained-response to vaccine in patients with rheumatic diseases. This study aims to evaluate neutralizing antibodies (nAB) induced by SARS-CoV-2 vaccine after 3 to 6 months from administration in Systemic Lupus Erythematosus (SLE) patients, as a surrogate of sustained-immunological response. This cross-sectional study compared nAB titre of 39 SLE patients and 37 Healthy individuals with no previous SARS-CoV-2 infection, who had all received a complete regimen of a mRNA SARS-CoV-2 vaccine within the last 3 to 6 months. We included four lines of SLE treatment including Not-treated, Hydroxychloroquine, immunosuppressive drugs and biological therapy. Glucocorticoids were allowed in all groups. Healthy and Not-treated individuals showed the highest levels of nAB. Treated patients presented lower nAB titres compared to Healthy: a 73% decrease for First-Line patients, 56% for Second-Line treatment and 72% for Third-Line. A multivariate analysis pointed to Glucocorticoids as the most associated factor with declining nAB levels (75% decrease) in treated SLE. Furthermore, a significant reduction in nAB titres was observed for Rituximab-users compared to Healthy subjects (89% decrease). Medium-term response of SLE patients to SARS-CoV-2 mRNA vaccines is negatively impacted in Glucocorticoids and Rituximab users. These findings might help to inform recommendations in vaccination protocols for SLE patients.

Biomarker candidates for progression and clinical management of COVID-19 associated pneumonia at time of admission.

COVID-19 pathophysiology is currently not fully understood, reliable prognostic factors remain elusive, and few specific therapeutic strategies have been proposed. In this scenario, availability of biomarkers is a priority. MS-based Proteomics techniques were used to profile the proteome of 81 plasma samples extracted in four consecutive days from 23 hospitalized COVID-19 associated pneumonia patients. Samples from 10 subjects that reached a critical condition during their hospital stay and 10 matched non-severe controls were drawn before the administration of any COVID-19 specific treatment and used to identify potential biomarkers of COVID-19 prognosis. Additionally, we compared the proteome of five patients before and after glucocorticoids and tocilizumab treatment, to assess the changes induced by the therapy on our selected candidates. Forty-two proteins were differentially expressed between patients' evolution groups at 10% FDR. Twelve proteins showed lower levels in critical patients (fold-changes 1.20-3.58), of which OAS3 and COG5 found their expression increased after COVID-19 specific therapy. Most of the 30 proteins over-expressed in critical patients (fold-changes 1.17-4.43) were linked to inflammation, coagulation, lipids metabolism, complement or immunoglobulins, and a third of them decreased their expression after treatment. We propose a set of candidate proteins for biomarkers of COVID-19 prognosis at the time of hospital admission. The study design employed is distinctive from previous works and aimed to optimize the chances of the candidates to be validated in confirmatory studies and, eventually, to play a useful role in the clinical practice.

Synovial fluid but not plasma interleukin-8 is associated with clinical severity and inflammatory markers in knee osteoarthritis women with joint effusion.

Several cytokines and adipokines are related to clinical severity and progression in knee osteoarthritis. The aim of this study was to evaluate the associations of IL-8 with clinical severity and with local and systemic adipokines and cytokines. This is a Cross-sectional study including 115 women with symptomatic primary knee osteoarthritis with ultrasound-confirmed joint effusion. Age, symptoms duration and body mass index were collected. Radiographic severity was evaluated according to Kellgren-Lawrence. Pain and disability were assessed by Lequesne and Knee injury and Osteoarthritis Outcome Score pain, symptoms and function scales. Three inflammatory markers and five adipokines were measured by ELISA in serum and synovial fluid. Partial correlation coefficient (PCC) and corresponding 95% confidence interval were used to evaluate association. Synovial fluid IL-8 was significantly associated with clinical severity scales. After controlling for potential confounders, associations measured by a Partial Correlation Coefficient (PCC) remained essentially unaltered for Lequesne (PCC = 0.237), KOOS pain (PCC = - 0.201) and KOOS symptoms (PCC = - 0.209), KOOS function (PCC = - 0.185), although the later did not reach statistical significance. Also in synovial fluid samples, associations were found between IL-8 and TNF (PCC = 0.334), IL6 (PCC = 0.461), osteopontin (PCC = 0.575), visfatin (PCC = 0.194) and resistin (PCC = 0.182), although significance was not achieved for the later after statistical control for confounders. None of these associations were detected in serum. In conclusion, IL-8 was associated with clinical severity, inflammatory markers and adipokines in synovial fluid, but not in blood. Although the reported associations are weak to moderate in magnitude, these findings reinforce the notion that local and not systemic inflammation is more relevant to clinical severity in knee OA women with joint effusion.

Synovial Adiponectin Was More Associated with Clinical Severity than Synovial Leptin in Women with Knee Osteoarthritis.

OBJECTIVE: Different adipokines have been reported to play a role in the development, progression, and severity of knee osteoarthritis, but this association may be mediated by obesity. The aim of this study was to evaluate separately the associations of leptin and adiponectin with clinical severity and inflammatory markers in nonobese and obese women with knee osteoarthritis. DESIGN: Cross-sectional study with systematic inclusion of 115 women with symptomatic primary knee osteoarthritis. Age, physical exercise, symptoms duration, and body mass index were collected. Radiographic severity was evaluated according to Kellgren-Lawrence scale. Pain and disability were assessed by WOMAC-total, -pain, -function subscales. Two adipokines (leptin and adiponectin) and 3 inflammatory markers (TNF-α, hsCRP, and IL-6) were measured by ELISA in synovial fluid and serum. RESULTS: Synovial fluid adiponectin was associated with WOMAC pain, function, and total and with synovial fluid IL-6 in nonobese female knee osteoarthritis after controlling by confounders (partial correlation coefficient [PCC] = 0.395, 0.387, 0.427, and 0.649, respectively). Synovial fluid and serum leptin were significantly associated with IL-6 (PCC = 0.354) after controlling by confounders but associations with clinical severity and the rest of inflammatory markers were mitigated after control. CONCLUSIONS: Adiponectin in synovial fluid was associated with clinical severity and local inflammatory markers in knee osteoarthritis women, while leptin relation was attenuated when controlled by confounders.

CD4 and CD8 Lymphocyte Counts as Surrogate Early Markers for Progression in SARS-CoV-2 Pneumonia: A Prospective Study.

BACKGROUND: COVID-19 pathophysiology and the predictive factors involved are not fully understood, but lymphocytes dysregulation appears to play a role. This paper aims to evaluate lymphocyte subsets in the pathophysiology of COVID-19 and as predictive factors for severe disease. PATIENT AND METHODS: A prospective cohort study of patients with SARS-CoV-2 bilateral pneumonia recruited at hospital admission. Demographics, medical history, and data regarding SARS-CoV-2 infection were recorded. Patients systematically underwent complete laboratory tests, including parameters related to COVID-19 as well as lymphocyte subsets study at the time of admission. Severe disease criteria were established at admission, and patients were classified on remote follow-up according to disease evolution. Linear regression models were used to assess associations with disease evolution, and Receiver Operating Characteristic (ROC) and the corresponding Area Under the Curve (AUC) were used to evaluate predictive values. RESULTS: Patients with critical COVID-19 showed a decrease in CD3+CD4+ T cells count compared to non-critical (278 (485 IQR) vs. 545 (322 IQR)), a decrease in median CD4+/CD8+ ratio (1.7, (1.7 IQR) vs. 3.1 (2.4 IQR)), and a decrease in median CD4+MFI (21,820 (4491 IQR) vs. 26,259 (3256 IQR)), which persisted after adjustment. CD3+CD8+ T cells count had a high correlation with time to hospital discharge (PC = -0.700 (-0.931, -0.066)). ROC curves for predictive value showed lymphocyte subsets achieving the best performances, specifically CD3+CD4+ T cells (AUC = 0.756), CD4+/CD8+ ratio (AUC = 0.767), and CD4+MFI (AUC = 0.848). CONCLUSIONS: A predictive value and treatment considerations for lymphocyte subsets are suggested, especially for CD3CD4+ T cells. Lymphocyte subsets determination at hospital admission is recommended.

Correction to: Influence of HLA-B27 on the Ankylosing Spondylitis phenotype: results from the REGISPONSER database.

An amendment to this paper has been published and can be accessed via the original article.

Ultrasound Findings in Patients With Femoracetabular Impingement Without Radiographic Osteoarthritis: A Pilot Study.

OBJECTIVES: To assess ultrasound (US) abnormalities in patients with clinical and radiographic features of femoracetabular impingement (FAI) without radiologic osteoarthritis. METHODS: This study included patients aged 50 years or younger with hip pain and clinical and radiographic signs suggestive of FAI but without radiographic hip osteoarthritis. Demographic characteristics, the symptom duration, and the radiologic type of FAI were recorded. Ultrasound examinations assessed for anterior labral abnormalities, osteophytes, bone cortex irregularities, capsular distension, and acetabulofemoral and femoral head-to-neck distances. A balanced group of healthy volunteers was used as control participants. RESULTS: Forty-four patients with FAI were evaluated. Ultrasound changes were found in 93.2% of patients, with 63.6% showing some kind of labral abnormality, 40.9% showing articular cartilage abnormalities, 38.6% showing bone contour irregularities, and 29.5% showing osteophytes. The cartilage width and symptom duration were inferior in patients with a damaged articular surface compared with those without (P = .005 and .012, respectively). Patients showing osteophytes on US examinations were slightly older (P = .048). Patients with cam-type FAI were more frequently male (P = .0001) and younger (P = .022) compared with those who had pincer-type FAI and also had a shorter symptom duration (P < .05). Patients with symptoms for 2 years or less had a shorter femoral cartilage width (P = .027). Femoral head-to-neck distances were shorter in patients compared with controls (P = .0005). Only 1 patient in the control group showed some US abnormality. CONCLUSIONS: Ultrasound showed detected abnormalities in a significant proportion of patients with symptomatic FAI in early phases of the disease. Additional longitudinal studies are warranted to establish the prognostic importance of these US changes.© 2018 by the American Institute of Ultrasound in Medicine.

Influence of HLA-B27 on the Ankylosing Spondylitis phenotype: results from the REGISPONSER database.

OBJECTIVE: To assess HLA-B27 influence on the clinical phenotype of Ankylosing Spondylitis (AS) patients. METHOD: An observational, cross-sectional and descriptive study of AS patients from the Spanish REGISPONSER database was performed. Demographic, clinical, disease activity (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)), and radiographic data (Bath Ankylosing Spondylitis Radiology Index (BASRI) score) were compared regarding HLA-B27 status. A univariate and multivariate analysis was performed to identify variables independently related to the presence of HLA-B27. RESULTS: Data from 1235 patients (74.8% male) were analyzed; 1029 were HLA-B27 positive (83%). HLA-B27-positive patients showed higher family aggregation and an earlier onset of disease compared with those who were HLA-B27 negative. HLA-B27-negative patients presented statistically higher BASDAI and BASFI scores and higher prevalence of arthritis, dactylitis, and extra-articular manifestations (psoriasis and inflammatory bowel disease (IBD)) but not anytime uveitis compared with those who were HLA-B27 positive. In the multivariate analysis, family history (odds ratio (OR) 2.10, 95% confidence interval (CI) 1.27-3.49), younger age at diagnosis (OR 0.97, 95% CI 0.96-0.98), presence of peripheral arthritis (OR 0.53, 95% CI 0.32-0.89), dactylitis (OR 0.16, 95% CI 0.05-0.56), psoriasis (OR 0.45, 95% CI 0.26-0.78), and IBD (OR 0.22, 95% CI 0.12-0.40) were the main variables independently related to the presence or not of HLA-B27. CONCLUSION: In Caucasian AS patients, the presence of HLA-B27 is related to an earlier disease onset and higher family aggregation. Absence of HLA-B27 is related to a higher frequency of peripheral arthritis, dactylitis, and extra-articular manifestations. Being HLAB27 positive is not related to a higher burden of disease or anytime uveitis.

Clinical and ultrasonographic features associated to response to intraarticular corticosteroid injection. A one year follow up prospective cohort study in knee osteoarthritis patient with joint effusion.

OBJECTIVES: Intraarticular injection is used for pain relief in knee osteoarthritis (OA), but there is not a well defined profile of patient who could get more benefit from it. The purpose of this study was to evaluate the frequency of pain relief at one year after corticosteroids intraarticular injection and to identify clinical factors associated to response in patients with knee osteoarthritis with joint effusion. METHODS: One-year prospective cohort study of patients with knee OA with joint effusion confirmed by ultrasound. An intraarticular injection was performed following a clinical protocol. Anthropometric measurements, laboratory parameters, clinical severity, ultrasound parameters and radiological severity were collected. Response regarding pain and presence of synovial fluid on ultrasound at one month and at one year were evaluated. Clinical responder were consider in subjects with enough improvement to carry out normal daily activities with pain VAS<40mm. RESULTS: One hundred and thirty-two patients were included.A significant number of patients (61.4%) improved pain at one year following the protocol established in this study. Pain and ultrasound synovial fluid at one month appeared to predict the response at one year. The Lequesne index and the percentage of body fat were independently associated to pain at one year while the Lequesne index and ultrasound synovial hypertrophy were independently related to the presence of synovial fluid at one year. CONCLUSIONS: The status regarding pain or ultrasound synovial fluid at one month after an intraarticular joint injection appeared to predict the status at one year in patients with knee osteoarthritis and synovial effusion.

Efecto del condroitín sulfato en la sinovitis de pacientes con artrosis de rodilla / Effect of chondroitin sulphate on synovitis of knee osteoarthritic patients

Objetivo: Evaluar mediante ecografía el efecto del condroitín sulfato (CS) en la sinovitis de pacientes con artrosis (OA) de rodilla, y colaborar en el conocimiento de los mecanismos bioquímicos involucrados en la inflamación sinovial. Métodos: Estudio controlado, aleatorizado, ciego simple de 70 pacientes con OA de rodilla tratados durante 6 meses con CS o paracetamol (PCT). Los pacientes fueron visitados a tiempo basal, a las 6 semanas, y a los 3 y 6 meses para valorar el estado de su OA según los siguientes parámetros: sinovitis evaluada mediante ecografía (según definición de expertos OMERACT); dolor y función, mediante la escala visual analógica y el índice de Lequesne; y concentración de mediadores inflamatorios en suero y líquido sinovial, mediante ELISA. Resultados: El tratamiento con CS redujo en un 50% el número de individuos que presentaban sinovitis; sin embargo, se observó un incremento de un 123% en el grupo tratado con PCT. En los pacientes sin sinovitis inicial, se observó el establecimiento de esta en un 85,71 y 25% de los casos tratados con PCT y CS, respectivamente. Ambas terapias mejoraron la función articular, pero únicamente el tratamiento con CS produjo una mejora significativa del dolor al final del tratamiento. Se observó una asociación entre el tratamiento con CS y los cambios en la concentración de RANTES y UCN en el líquido sinovial. Conclusiones: El tratamiento con CS tiene un efecto mantenido beneficioso, previniendo la aparición de sinovitis o disminuyendo su presencia, así como reduciendo los síntomas de la artrosis. El PCT también mejora los síntomas clínicos, pero no tiene ningún efecto sobre la inflamación. Las variaciones observadas en la concentración de RANTES y UCN podrían estar relacionadas con el efecto antiinflamatorio asociado al tratamiento con CS (AU)

Objective: To evaluate by ultrasonography the effect of chondroitin sulfate (CS) on synovitis in patients with knee osteoarthritis (KOA). To collaborate in the understanding of the biochemical mechanisms involved in the synovial inflammation process. Methods: Randomized, single-blind, controlled trial involving 70 patients with primary KOA treated for 6 months with CS or acetaminophen (ACT). Evaluation of KOA status at baseline, 6 weeks, 3 and 6 months included: ultrasonography to assess synovitis (following the OMERACT expertise group definition), visual analogue scale and Lequesne index to measure pain and function, and ELISA to quantify inflammatory mediators in serum and synovial fluid. Results: Synovitis presence was reduced by 50% in the CS group while a 123% increase was observed in ACT group. Conversely, patients without initial synovitis and treated with ACT reached 85.71% synovitis onset, but only 25% in CS group. Both therapies improved articular function, but only CS resulted in significant pain improvement at the end of the treatment. Changes in RANTES and UCN synovial fluid concentration were associated with CS treatment. Conclusions: Treatment with CS had a sustained beneficial effect, preventing synovitis onset or reducing its presence as well as reducing KOA symptoms. ACT ameliorated clinical symptoms but had no effect on inflammation. The CS anti-inflammatory effect could be related to the observed changes in RANTES and UCN concentration (AU)

Effect of chondroitin sulphate on synovitis of knee osteoarthritic patients. / Efecto del condroitín sulfato en la sinovitis de pacientes con artrosis de rodilla.

OBJECTIVE: To evaluate by ultrasonography the effect of chondroitin sulfate (CS) on synovitis in patients with knee osteoarthritis (KOA). To collaborate in the understanding of the biochemical mechanisms involved in the synovial inflammation process. METHODS: Randomized, single-blind, controlled trial involving 70 patients with primary KOA treated for 6 months with CS or acetaminophen (ACT). Evaluation of KOA status at baseline, 6 weeks, 3 and 6 months included: ultrasonography to assess synovitis (following the OMERACT expertise group definition), visual analogue scale and Lequesne index to measure pain and function, and ELISA to quantify inflammatory mediators in serum and synovial fluid. RESULTS: Synovitis presence was reduced by 50% in the CS group while a 123% increase was observed in ACT group. Conversely, patients without initial synovitis and treated with ACT reached 85.71% synovitis onset, but only 25% in CS group. Both therapies improved articular function, but only CS resulted in significant pain improvement at the end of the treatment. Changes in RANTES and UCN synovial fluid concentration were associated with CS treatment. CONCLUSIONS: Treatment with CS had a sustained beneficial effect, preventing synovitis onset or reducing its presence as well as reducing KOA symptoms. ACT ameliorated clinical symptoms but had no effect on inflammation. The CS anti-inflammatory effect could be related to the observed changes in RANTES and UCN concentration.

Synovial fluid adipokines are associated with clinical severity in knee osteoarthritis: a cross-sectional study in female patients with joint effusion.

BACKGROUND: Adipokines are related to knee osteoarthritis, but their exact role is not well known. The aim of this study was to evaluate the association between adipokines in synovial fluid and clinical severity in patients with knee osteoarthritis with joint effusion. METHODS: Cross-sectional study with systematic inclusion of female patients with symptomatic primary knee osteoarthritis with ultrasound-confirmed joint effusion. Age, physical exercise, knee osteoarthritis symptoms duration, classical cardiovascular risk factors and different anthropometric measurements were collected. Metabolic syndrome was defined in accordance to National Cholesterol Education Program-Adult Treatment Panel III. Radiographic severity was evaluated according to Kellgren-Lawrence scale and Lequesne index was used to assess clinical severity. Seven adipokines (leptin, adiponectin, resistin, visfatin, osteopontin, omentin and chemerin) and three inflammatory markers (tumor necrosis factor α, interleukin 6 and high sensitivity C-reactive protein) were measured by enzyme-linked immunosorbent assay in synovial fluid. RESULTS: Kellgren-Lawrence grade, physical exercise, all anthropometric measurements (especially waist circumference), tumor necrosis factor α, and high levels of leptin, resistin, and ostepontin were related to knee osteoarthritis severity. After adjustment for clinical confounders (age, symptom duration, and radiology), anthropometric measurements, inflammatory markers, and all evaluated adipokines, there were independent associations with clinical severity for resistin (directly associated) and visfatin (inversely associated). No other adipokines or inflammatory markers were independently associated with Lequesne index. The association of radiological parameters, physical exercise, and waist circumference with Lequesne index remained after adjustment. CONCLUSIONS: Resistin was directly associated, and visfatin was inversely associated, with clinical severity in female patients with knee osteoarthritis with joint effusion. These associations were more important after adjustment for confounders, especially when all adipokines were evaluated.

Improved prediction of knee osteoarthritis progression by genetic polymorphisms: the Arthrotest Study.

OBJECTIVE: The aim of this study was to develop a genetic prognostic tool to predict radiographic progression towards severe disease in primary knee OA (KOA) patients. METHODS: This investigation was a cross-sectional, retrospective, multicentric association study in 595 Spanish KOA patients. Caucasian patients aged ≥40 years at the time of diagnosis of primary KOA of Kellgren-Lawrence grade 2 or 3 were included. Patients who progressed to Kellgren-Lawrence score 4 or who were referred for total knee replacement within 8 years after diagnosis were classified as progressors to severe disease. Clinical variables of the initial stages of the disease (gender, BMI, age at diagnosis, OA in the contralateral knee, and OA in other joints) were registered as potential predictors. Single nucleotide polymorphisms and clinical variables with an association of P < 0.05 were included in the multivariate analysis using forward logistic regression. RESULTS: A total of 23 single nucleotide polymorphisms and the time of primary KOA diagnosis were significantly associated with KOA severe progression in the exploratory cohort (n = 220; P < 0.05). The predictive accuracy of the clinical variables was limited: area under the curve (AUC) = 0.66. When genetic variables were added to the clinical model (full model), the prediction of KOA progression was significantly improved (AUC = 0.82). Combining only genetic variables (rs2073508, rs10845493, rs2206593, rs10519263, rs874692, rs7342880, rs780094 and rs12009), a predictive model with good accuracy was also obtained (AUC = 0.78). The predictive ability for KOA progression of the full model was confirmed on the replication cohort (two-sample Z-test; n = 62; P = 0.190). CONCLUSION: An accurate prognostic tool to predict primary KOA progression has been developed based on genetic and clinical information from OA patients.

Comparative efficacy of intra-articular hyaluronic acid and corticoid injections in osteoarthritis of the first carpometacarpal joint: results of a 6-month single-masked randomized study.

OBJECTIVE: The study aim was to compare the efficacy and safety of ultrasound-guided intra-articular injections of hyaluronic acid and betamethasone in the management of patients with osteoarthritis of the thumb. METHODS: Eighty-eight evaluable patients diagnosed with osteoarthritis of the thumb (Kellgren-Lawrence grade II-III) received ultrasound-guided intra-articular treatment with hyaluronic acid (48) or betamethasone (40). In total, 3 local injections were scheduled at 7-day intervals. Assessments were performed at baseline and at 7, 14, 30, 90, and 180 days. RESULTS: In both study groups, the pain Visual Analogue Scale and Functional Index for Hand Osteoarthritis scores decreased significantly during follow-up compared to baseline. There were no significant differences between the groups. However, at 90 days, the functional score showed a trend towards greater clinical improvement in the hyaluronic acid group (P 0.071). A subanalysis of patients with Functional Index score≥5 and Visual Analogue Scale score≥3 at baseline showed a significantly higher median functionality score in the hyaluronic acid group (P 0.005 at 90 days and P 0.020 at 180 days). Further limiting analysis to a baseline pain score≥5 showed significantly greater improvement in functionality score (P 0.004 at 180 days), which was already apparent after the second intra-articular injection at 14 days (P 0.028). In this patient subset, the mean pain score also improved significantly at 180 days (P 0.02). CONCLUSIONS: Both hyaluronic acid and betamethasone were effective and well-tolerated for the management of rhizarthrosis. Hyaluronic acid was more effective over time and more efficiently improved functionality and pain in patients with more severe symptoms.

Sexual dysfunction in patients with fibromyalgia.

Several studies have investigated sexual function in patients with fibromyalgia (FM). All reports agree that sexual function seems frequently impaired in this condition. This dysfunction is usually severe and may affect all domains of sexuality. Given the complexity of factors involved in human sexual function and the intricacy of the physiopathology of FM, many factors and mechanisms have been implicated. Per our literature review, depression may be the main contributing factor to FM-related sexual dysfunction. However, prospective studies are needed, as reports have lacked sufficient quality to draw definitive conclusions. Recognition of sexual dysfunction and its inclusion in multidisciplinary management are needed to improve quality of life for patients with FM.

Sinus reactions to immediately loaded zygoma implants: a clinical and radiological study.

AIM: There are no published studies regarding sinus reactions to immediately loaded zygomatic implants. The aim of this study was to evaluate the maxillary sinus in a cohort of patients by means of clinical criteria and computerised tomography performed before surgery and after zygomatic implant placement (immediate function protocol). MATERIALS AND METHODS: A total of 36 patients with 71 immediately loaded zygomatic implants were evaluated to find clinical criteria of maxillary sinus disturbance 13 to 42 months (average 21.9 months) after zygoma implant placement. A total of 44 implants had a machined surface and 27 had a porous titanium oxide surface. Twenty-six patients with 52 immediately loaded zygomatic implants were evaluated by means of a CT scan of the paranasal sinuses, 3 to 20 months (average 10.5 months) after zygomatic implant placement. All patients had no sinus symptoms before surgery and had a preoperative CT scan. RESULTS: No clinical signs or symptoms of sinusitis were found. Radiological opacity of the antrum was found in two sinuses (out of 52), and minimal thickening of the Schneiderian membrane was found in 12 patients (out of 26). In eight of them, this was present in the preoperative CT scan. CONCLUSIONS: Sinuses penetrated by zygomatic implants seem to maintain a normal physiology. However, in approximately 15 to 20% of patients, early radiological findings without clinical symptoms were observed.

Utilidad del pamidronato en el tratamiento de la artropatía de Charcot / Usefulness of pamidronate in the treatment of Charcot’s arthropathy

Objetivo: Investigar la utilidad del pamidronato en el tratamiento de la neuroartropatía en fase activa. Material y métodos: Estudio prospectivo, abierto, con un seguimiento de 12 meses. En un período de 3 años todos los pacientes con neuroartropatía activa visitados en la unidad de reumatología recibieron tres infusiones de pamidronato a los 0, 2 y 4 meses. Se realizó valoración clínica, de marcadores de remodelado óseo en sangre y orina, radiografía simple y gammagrafía ósea cuantitativa antes y después del tratamiento. Resultados: Se incluyó a 7 pacientes (4 varones y 3 mujeres), con una media de edad de 51,3 (30-64) años. La enfermedad de base fue diabetes mellitus en 4 casos, siringomielia en 2 y neuropatía sensitiva autonómica en 1. Las articulaciones afectadas fueron hombro, tobillo, tarsianas, metatarsofalángicas y metacarpofalángicas. Todos los pacientes mostraron una rápida resolución de los síntomas, con una clara reducción de todos los marcadores de remodelado óseo siendo estadísticamente significativa en el caso del NTX y piridolina en orina (p = 0,04 y p = 0,03, respectivamente). Seis de los 7 pacientes mostraron una mejoría radiológica. La gammagrafía cuantitativa mostró una reducción evidente de la captación. No se observaron efectos adversos importantes. Conclusiones: El pamidronato parece un tratamiento útil para la artropatía de Charcot independientemente de la enfermedad de base. El diagnóstico precoz y la administración rápida del tratamiento puede evitar complicaciones articulares graves (AU)

Objective: To investigate the usefulness of pamidronate in the management of active Charcot’s arthropathy. Material and methods: Open prospective study with a follow-up of 12 months, including patients with active neuroarthropathy seen over a period of 3 years in our rheumatology unit. Patients received three pamidronate infusions at 0, 2, and 4 months. Clinical assessment, serum and urine bone turnover markers, radiological exam, and scintigraphy were performed before and after treatment. Results: Seven patients were included (4F/3M), mean age, 51.3 years (30-64). The underlying disease was diabetes mellitus in 4 cases, syringomyelia in 2, and sensory and autonomic neuropathy in 1. The joints affected were shoulder, ankle, tarsians, metacarpophalaneal, and metatarsophalangeal. All patients showed a rapid resolution of clinical symptoms, with a clear reduction of all bone remodeling markers that achieved statistical significance for urine NTX and urinary pyridoline (P=.04 and P=.03, respectively). Six of 7 patients disclosed at the end of follow-up a radiological healing. Quantitative scyntigraphy showed a clear reduction of the bone 99Tm uptake. No important side affects were reported. Conclusions: Pamidronate appears as a useful treatment for neuroarthropathy independently of the underlying disease. A rapid diagnosis and early pamidronate treatment could avoid severe articular consequences (AU)