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.

Sex differential impact of comorbidities in spondyloarthritis: data from COMOSPA study.

OBJECTIVES: To describe and compare the prevalence of comorbidities in female and male patients with spondyloarthritis (SpA) and to assess whether comorbidities had a different impact on disease outcomes in male and female patients. METHODS: This is a post hoc analysis of the COMOrbidities in SPondyloArthritis study. Differences in comorbidities regarding sex were assessed using logistic regression models. Comorbidities were evaluated for their impact on disease outcomes (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index, European health-related quality of life questionnaire) with linear models, which included sex and comorbidity as explanatory variables and their interaction. Age and treatment with biological synthetic disease-modifying antirheumatic drugs were included as confounders. RESULTS: We included 3982 patients with SpA (65% male, mean age 43.6 years). Male and female patients with SpA exhibited similar comorbidity profiles, except for a low prevalence of fibromyalgia in males and a higher prevalence of certain cardiovascular risk factors in males (hypertension, dyslipidaemia, renal impairment and ischaemic heart disease). Comorbidities, especially fibromyalgia, correlated with higher disease activity, decreased physical function and reduced health-related quality of life in both sexes. Some comorbidities exhibited sex-specific associations with disease outcomes. Peptic ulcers and high waist circumference had a greater impact on disease activity in females (with a higher impact in BASDAI than in ASDAS). In contrast, osteoporosis had a more pronounced effect on physical function in male patients. CONCLUSIONS: Comorbidities exert distinct influences on disease activity, physical function and health-related quality of life in male and female patients with SpA. Understanding these sex-specific effects is crucial for improving SpA management, emphasising the importance of assessing disease activity using ASDAS when comorbidities are present to mitigate sex-related disparities in disease assessment.

Contribution of major economies to global GDP and product reallocation around the world.

Economic globalization has led to production increasingly becoming concentrated in certain regions and countries of the world. This article develops an accounting framework to provide the trends for the contribution of countries to global gross domestic production (GDP). In particular, the method transforms the multiregional input-output model to quantify the relative importance of individual economies to world GDP. The proposal uses a world input-output database that distinguishes between three main economic areas: China, the United States of America and the European Union. The results suggest that identical changes in sectoral demand asymmetrically modify the relative contributions from individual economies, with China showing the highest positive (negative) impact after an increase (decrease) in world demand. These findings suggest that a generalized economic expansion (contraction) is linked to a boost (decline) in the asymmetries of production across the world.

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.

Insulin edema, a little known entity.

Insulin edema is an entity that should be considered in any patient who starts or intensifies an insulin regimen to improve metabolic control. Heart, liver, and kidney problems should always be ruled out beforehand. The exact mechanism is not clear. It is usually self-limiting within a few days and rarely requires specific therapy. It could be prevented with a more progressive improvement in glycemic control avoiding rapid increases in insulin dose. We present the case of two female adolescents with a new diagnosis of type 1 diabetes mellitus with ketoacidosis. A few days after starting treatment with a basal bolus regimen with subcutaneous insulin, edema started and limited to the lower extremities. In both cases, the symptoms resolved spontaneously.

Social Media Use Among Members of the Assessment of Spondyloarthritis International Society: Results of a Web-Based Survey.

BACKGROUND: The use of social media in health care may serve as a beneficial tool for education, information dissemination, telemedicine, research, networking, and communications. To better leverage the benefits of social media, it is imperative to understand the patterns of its use and potential barriers to its implementation in health care. A previous study in 2016 that investigated social media use among young clinical rheumatologists (≤45 years) and basic scientists showed that there was substantial social media use among them for social and professional reasons. However, there is a limited inquiry into social media use in different areas of rheumatology, such as spondyloarthritis. OBJECTIVE: We aimed to explore the motivations, barriers, and patterns of social media use among an international group of experts in spondyloarthritis. METHODS: We distributed a web-based survey via email from March 2021 to June 2021 to 198 members of the Assessment of Spondyloarthritis International Society. It contained 24 questions about demographic characteristics, patterns of current social media use, and perceptions of utility. Univariable and multivariable logistic regression analyses were performed to identify the characteristics associated with use trends. RESULTS: The response rate was 78.8% (156/198). Of these, 93.6% (146/156) of participants used at least one social media platform. Apart from internet-based shopping and entertainment, the use of social media for clinical updates (odds ratio [OR] 6.25, 95% CI 2.43-16.03) and research updates (OR 3.45, 95% CI 1.35-8.78) were associated with higher social media consumption. Among the respondents, 66% (103/156) used social media in a work-related manner. The use of social media for new web-based resources (OR 6.55, 95% CI 2.01-21.37), interaction with international colleagues (OR 4.66, 95% CI 1.21-17.90), and establishing a web-based presence (OR 4.05, 95% CI 1.25-13.13) were associated with higher levels of consumption for work-related purposes. Time investment, confidentiality concerns, and security concerns were the top 3 challenges to a wider adoption of social media. CONCLUSIONS: Most respondents (103/156, 66%) use social media in a work-related manner. Professional development, establishing a web-based presence, and international collaboration were associated with higher use. Challenges to social media adoption should be addressed to maximize its benefits.

Prediction of leptospirosis outbreaks by hydroclimatic covariates: a comparative study of statistical models.

Leptospirosis, the infectious disease caused by a spirochete bacteria, is a major public health problem worldwide. In Argentina, some regions have climatic and geographical characteristics that favor the habitat of bacteria of the Leptospira genus, whose survival strongly depends on climatic factors, enhanced by climate change, which increase the problems associated with people's health. In order to have a method to predict leptospirosis cases, in this paper, five time series forecasting methods are compared: two parametric (autoregressive integrated moving average and an alternative one that allows covariates, ARIMA and ARIMAX, respectively), two nonparametric (Nadaraya-Watson Kernel estimator, one and two kernels versions, NW-1 K and NW-2 K), and one semiparametric (semi-functional partial linear regression, SFPLR) method. For this, the number of cases of leptospirosis registered from 2009 to 2020 in three important cities of northeastern Argentina is used, as well as hydroclimatic covariates related to the presence of cases. According to the obtained results, there is no method that improves considerably the rest and can be recommended as a unique tool for leptospirosis prediction. However, in general, the NW-2 K method gets a better performance. This work, in addition to using a long-term high-quality time series, enriches the area of applications of statistical models to epidemiological leptospirosis data by the incorporation of hydroclimatic variables, and it is recommended directing further efforts in this line of research, under the context of current climate change.

Uveitis in peripheral spondyloarthritis patients: an ancillary analysis of the ASAS-PerSpA study.

Background: Acute anterior uveitis (AAU) is the most frequent extra-musculoskeletal manifestation in spondyloarhtritis (SpA). Previous data on AAU focused on axial disease; therefore, it is not well known whether the clinical characteristics of patients with AAU and recurrent AAU differ between patients with axial and peripheral SpA. Objective: Primary objective was to compare the clinical characteristics of patients with AAU from patients without AAU in axial and peripheral spondyloarthritis (SpA) patients. Secondary objectives were to describe the clinical features of patients with AAU in the subset of patients with peripheral SpA (pSpA) and the clinical characteristics of patients with recurrent AAU in SpA patients. Design: This is an ancillary analysis of the ASAS-PerSpA study which included 3152 patients, 2719 patients with axSpA and 433 with pSpA according to rheumatologist judgement. Methods: Recurrent AAU was defined as the presence of two or more episodes of AAU ever. Univariable and multivariable binary logistic regression analyses were conducted to identify factors associated with the presence of AAU ever and the presence of recurrent AAU. Results: Overall, 663 patients (21%) presented AAU. Of them, 444 (66.9%) presented recurrent episodes. In patients with SpA, HLA-B27 positivity is the most important factor linked to the presence of AAU, odds ratio (OR) = 2.70 (95% CI = 2.04-3.6). In patients with pSpA, HLA-B27 positivity was also the most relevant factor linked to the presence of AAU, OR = 6.08 (95% CI = 2.72-15.68). Moreover, disease duration, younger age and higher body mass index (BMI) were the only factors slightly linked to the presence of recurrent episodes, OR = 1.03 (95% CI = 1.01-1.04), OR = 1.01 (95% CI = 1.00-1.03) and OR = 1.04 (95% CI = 1.01-1.08), respectively. Conclusion: HLA-B27 positivity is the most relevant factor linked to AAU risk in SpA patients, and this association is even stronger in those patients with pSpA. Moreover, our study did not find an association between HLA-B27 positivity and recurrent AAU in SpA patients.

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.

Sustained low disease activity measured by ASDAS slow radiographic spinal progression in axial spondyloarthritis patients treated with TNF-inhibitors: data from REGISPONSERBIO.

BACKGROUND: To evaluate the influence of the disease activity on radiographic progression in axial spondyloarthritis (axSpA) patients treated with TNF inhibitors (TNFi). METHODS: The study included 101 axSpA patients from the Spanish Register of Biological Therapy in Spondyloarthritides (REGISPONSERBIO), which had clinical data and radiographic assessment available. Patients were classified into 2 groups based on the duration of TNFi treatment at baseline: (i) long-term treatment (≥4 years) and (ii) no long-term treatment (< 4 years). Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. Disease activity differences between patients' groups at each time point were assessed using a linear mixed-effect model. RESULTS: Radiographic progression was defined as an increase in ≥2 mSASSS units. At inclusion, approximately half of the patients (45.5%) were receiving long-term treatment with TNFi (≥4 years). In this group of subjects, a significant difference in averaged Ankylosing Spondylitis disease Activity Score (ASDAS) across follow-up was found between progressors and non-progressors (2.33 vs 1.76, p=0.027, respectively). In patients not under long-term TNFi treatment (54.5%) though, no significant ASDAS differences were observed between progressors and non-progressors until the third year of follow-up. Furthermore, no significant differences were found in progression status, when disease activity was measured by Bath Ankylosing spondylitis Disease Activity Index (BASDAI) and C reactive protein (CRP). CONCLUSIONS: Patients on long-term TNFi treatment with a mean sustained low disease activity measures by ASDAS presented lower radiographic progression than those with active disease.

Association between HLA-B27 and peripheral spondyloarthritis phenotype: results from the ASAS perSpA study.

OBJECTIVE: To analyse the influence of HLA-B27 in the phenotypical expression of peripheral spondyloarthritis (pSpA). METHOD: This is an observational cross-sectional study using data from the Assessment of SpondyloArthritis international Society perSpA registry, including all patients with an available HLA-B27 test result and with a diagnosis of pSpA or psoriatic arthritis (PsA) as per rheumatologist's judgement. Demographic and clinical data, presence of extra musculoskeletal manifestations (EMM) and fibromyalgia were the variables included in a simple and multiple logistic regression model to assess their association to HLA-B27 positivity. RESULTS: From the 4465 patients included in the registry, 790 were classified as having either pSpA or PsA and had the HLA-B27 typing available. HLA-B27-positive patients presented a male predominance, had an earlier disease onset and a shorter diagnostic delay compared with the negatives. HLA-B27-positive patients presented a higher frequency of axial involvement, radiographic sacroiliitis, enthesitis and uveitis. Also, root joint involvement, poliarticular joint patern and tarsitis were significantly higher within HLA-B27-positive patients. Furthermore, we did not observe any association between the presence of HLA-B27 and peripheral joint damage, dactylitis, other EMM (psoriasis, inflammatory bowel disease) or fibromyalgia.The multivariable analysis confirmed the independent association of HLA-B27 positivity with male sex, an earlier onset of the disease, the presence of axial involvement, tarsitis and uveitis. SUMMARY: In summary, the presence of HLA-B27 in pSpA patients was associated with earlier disease onset and higher axial involvement, tarsitis and uveitis, but not with other EMM, fibromyalgia or peripheral structural damage.

Enhanced removal of bisphenol A using pine-fruit shell-derived hydrochars: Adsorption mechanisms and reusability.

We synthesized NaOH-activated hydrochars via hydrothermal carbonization (HTC) of Brazilian pine fruit shells at HTC residence times of 24, 48, and 72 h. The hydrochars were used as adsorbents to remove bisphenol A (BPA) from aqueous solutions. The surface area of the samples can reach up to 2220 m2 g-1, and the maximum adsorption of BPA onto the surfaces was achieved at a pH of 7.0 (708 mg g-1). Adsorption occurred mainly via monolayer formation with a low retention time of the adsorbate (τ) on the surfaces, indicating that the BPA molecules reached the already occupied active sites and returned after undergoing heat exchange (τ > 0). Adsorption is an endothermic spontaneous process that results in a balance between entropic and enthalpic contributions. In such a reaction, ΔG°< 0, even with ΔH°> 0, the process occurs with an important increase in the entropy. The desorption was more efficient with ethanol and methanol than with HCl, NaOH, and NaCl owing to the dipole-dipole forces between the adsorbate and the alcohols. Additionally, the low desorption efficiency using acid, base, and salts can be attributed to competitive effects between the desorption agents and the active sites of the adsorbents.

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.

Assessment of radiographic sacroiliitis in anteroposterior lumbar vs conventional pelvic radiographs in axial spondyloarthritis.

OBJECTIVE: The aim was to investigate the reliability and validity of radiographic sacroiliitis assessment in anteroposterior (AP) lumbar radiographs compared with conventional pelvic radiographs in patients with axial spondyloarthritis (axSpA). METHODS: Patients from the German Spondyloarthritis Inception Cohort were selected based on the availability of pelvic and AP lumbar radiographs with visible SI joints at baseline and year 2. Two readers scored the images independently in a random order according to the modified New York criteria. The sacroiliitis sum score was calculated as the mean of both readers. Patients were classified as radiographic (r-)axSpA if radiographic sacroiliitis of grade ≥2 bilaterally or grade ≥3 unilaterally was present in the opinion of both readers and as non-radiographic (nr-)axSpA otherwise. The reliability and validity of sacroiliitis assessment in AP lumbar radiographs was assessed using intraclass correlation coefficients (ICCs), absolute agreement and κ statistics. RESULTS: A total of 226 sets of radiographs were scored from 113 patients included in the study. The ICC for the sacroiliitis sum score was 0.91 at both baseline and year 2. A total of 62 (54.9%) and 55 (48.7%) patients were classified as r-axSpA at baseline and 65 (57.5%) and 60 (53.1%) patients at year 2 based on evaluation of pelvic and AP lumbar radiographs, respectively. The absolute agreement between the methods on the classification was 84.9 and 85.0% at baseline and year 2, respectively, with the κ of 0.70 at both time points. CONCLUSION: Radiographic sacroiliitis can be assessed in AP lumbar radiographs with a similar reliability to conventional pelvic radiographs.

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.

Evaluation of the fracture risk assessment tool for determining bone disease and the impact of secondary causes of osteoporosis in people living with HIV.

BACKGROUND: Among HIV-infected individuals, screening for bone disease is encouraged to assess reversible risk factors and plan therapeutic interventions. OBJECTIVE: We assessed the usefulness of Fracture Risk Assessment (FRAX) tool to identify candidates for dual X-ray absorptiometry (DXA) scan, or individuals with bone loss progression. We further explored how secondary causes of osteoporosis are reflected on FRAX. METHODS: Longitudinal study of 217 consecutive individuals (mean, 45.8 years, 24% females) included after DXA scan. FRAX was calculated without/with femoral neck bone mineral density (BMD), checking the box of "secondary osteoporosis" for all the individuals. RESULTS: Low BMD was observed in 133/217 (61%) individuals, of whom 98.5% had not been selected as candidates for DXA by current FRAX thresholds. Specifically, 23% of individuals aged <50 had low BMD but none was candidate for DXA. Adding BMD data, FRAX results increased by 50-100%, with 2/217 individuals (1%) above the thresholds. Classical and HIV-related secondary causes of osteoporosis (observed in 98% overall) correlated with low BMD, modifying significantly FRAX results (HCV coinfection, +124%; longer time of HIV infection, +93%; longer time on antiretroviral therapy, +147%; tenofovir exposure +36%). Individuals with lower BMD and higher FRAX results at inclusion had less bone decline in a follow-up DXA after a median of 3.5 years. CONCLUSIONS: Currently recommended FRAX thresholds are not useful to select candidates for DXA scan, which could delay its performance in a population with a high prevalence of secondary factors for low BMD. Classical and HIV-related factors alter BMD and fracture risk estimation.

Clinical and imaging characteristics of osteitis condensans ilii as compared with axial spondyloarthritis.

OBJECTIVES: Osteitis condensans ilii (OCI) has become an important differential diagnosis for axial spondyloarthritis (axSpA). The objective of this matched case-control study was to investigate demographic, clinical, laboratory and MRI characteristics of OCI as compared with axial spondyloarthritis (axSpA). METHODS: A total of 60 patients diagnosed with OCI were included in the final analysis. From 27 of these patients, MRIs of the sacroiliac joints were available. OCI patients were matched with a 1:1 ratio by back pain duration to patients with definite axSpA in order to compare clinical, laboratory and MRI characteristics. RESULTS: The OCI patients were nearly all females (96.7 vs 46.7%), had a significantly lower prevalence of inflammatory back pain (39.5 vs 88.9%), a significantly lower percentage of HLA-B27 positives (35.2 vs 80.0%) and a lower prevalence of the majority of other SpA features as compared with axSpA patients. Interestingly, there was no difference in the prevalence of osteitis in the sacroiliac joints (92.6 vs 85.2% in OCI and axSpA, respectively, P = 0.44), but there was a difference in the prevalence of erosions (7.4 vs 66.7%, respectively, P = 0.0001). In addition, in OCI nearly all lesions were localized in the anterior part of the sacroiliac joints while in axSpA lesions were localized predominantly in the middle part of the joint (for osteitis: 96 vs 4% in OCI and 28.6 vs 71.4% in axSpA; P = 0.0002 for the inter-group difference). CONCLUSION: Clinical and imaging features of OCI compared with axSpA are described that should help in differential diagnosis.