A machine learning approach for the design optimization of a multiple magnetic and inertial sensors wearable system for the spine mobility assessment.

BACKGROUND: Recently, magnetic and inertial measurement units (MIMU) based systems have been applied in the spine mobility assessment; this evaluation is essential in the clinical practice for diagnosis and treatment evaluation. The available systems are limited in the number of sensors, and neither develops a methodology for the correct placement of the sensors, seeking the relevant mobility information of the spine. METHODS: This work presents a methodology for analyzing a system consisting of sixteen MIMUs to reduce the amount of information and obtain an optimal configuration that allows distinguishing between different body postures in a movement. Four machine learning algorithms were trained and assessed using data from the range of motion in three movements (Mov.1-Anterior hip flexion; Mov.2-Lateral trunk flexion; Mov.3-Axial trunk rotation) obtained from 12 patients with Ankylosing Spondylitis. RESULTS: The methodology identified the optimal minimal configuration for different movements. The configuration showed good accuracy in discriminating between different body postures. Specifically, it had an accuracy of 0.963 ± 0.021 for detecting when the subject is upright or bending in Mov.1, 0.944 ± 0.038 for identifying when the subject is flexed to the left or right in Mov.2, and 0.852 ± 0.097 for recognizing when the subject is rotated to the right or left in Mov.3. CONCLUSIONS: Our results indicate that the methodology developed results in a feasible configuration for practical clinical studies and paves the way for designing specific IMU-based assessment instruments. TRIAL REGISTRATION: Study approved by the Local Ethics Committee of the General Hospital of Mexico "Dr. Eduardo Liceaga" (protocol code DI/03/17/471).

Polymorphic variation of the DEFB1 gene might contribute to the development of ankylosing spondylitis: a preliminary study.

BACKGROUND: Ankylosing spondylitis (AS) is an inflammatory disease that affects the spine and can cause peripheral arthritis, enthesitis, and dactylitis, as well as extra-articular manifestations such as uveitis and inflammatory bowel disease. ß-Defensins are antimicrobial peptides involved in the activation and regulation of several immune cell types that may influence the inflammatory response in AS. The aim was to analyze the association and interaction of two functional variants of the DEFB1 gene in AS patients, and their role with inflammatory markers. METHODS AND RESULTS: The rs11362 and rs1800972 variants were genotyped using TaqMan probes in Mexican AS patients and controls. C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) were quantified. SPSS software was used for statistical analysis and multifactor dimensionality reduction (MDR) for interactions. The AA and GG genotypes were associated with AS risk in the age- and sex-adjusted model (OR = 6.89, P = 0.008 and OR = 3.43, P = 0.046, respectively); furthermore, the A-G haplotype showed a significant association with AS risk (OR = 2.94, P = 0.012). ESR and CRP were elevated in carriers of the AA genotype compared to the GA and GG genotypes of the rs11362 variant (20.89 ± 9.78 vs. 5.63 ± 4.61 and 4.10 ± 2.65 mm/h, P < 0.0001; and 10.92 ± 14.09 vs. 2.14 ± 2.02 and 2.15 ± 2.13 mg/L, P < 0.001, respectively). Using the MDR method, strong interactions of the rs11362 variant with sex were identified in the adjusted and unadjusted models. CONCLUSIONS: These results suggest that the DEFB1 gene may play a key role in AS pathogenesis.

Prevalence of temporomandibular joint dysfunction in patients with ankylosing spondylitis and comparison of the findings with healthy controls.

OBJECTIVE: This study aimed to assess the prevalence of temporomandibular dysfunction in ankylosing spondylitis patients and healthy controls, examining the relationship between temporomandibular dysfunction and disease activity in ankylosing spondylitis patients, as well as associations with psychosocial factors. METHODS: The study included 113 ankylosing spondylitis patients and 110 healthy individuals aged 18-75. Temporomandibular dysfunction presence was evaluated using Diagnostic Criteria for Temporomandibular Disorders Axis I. Disease activity was assessed with the Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Metrology Index, and Bath Ankylosing Spondylitis Functional Index. RESULTS: Among healthy individuals, 60.9% did not receive a temporomandibular dysfunction diagnosis, while 39.1% received at least one diagnosis. In contrast, 69.9% of the 113 ankylosing spondylitis patients received at least one temporomandibular dysfunction diagnosis, and only 30.1% were not included in any diagnosis group (p<0.001). Joint (p=0.001) and pain disorders (p=0.008) were significantly more common in the ankylosing spondylitis group than in the healthy controls. Significant associations emerged between Bath Ankylosing Spondylitis Disease Activity Index (p<0.001) and Bath Ankylosing Spondylitis Functional Index (p=0.005) scores and pain disorders. CONCLUSION: Temporomandibular dysfunction is more prevalent in ankylosing spondylitis patients than in healthy individuals, linked to increased joint issues and pain associated with disease activity. CLINICALTRIALS.GOV ID: NCT05839925.

Tuberculin skin test repetition after TNF-α inhibitors in patients with chronic inflammatory arthritis: a long-term retrospective cohort in endemic area.

OBJECTIVES: To evaluate the tuberculin skin test (TST) conversion in chronic inflammatory arthropathies (CIA) patients on TNFα inhibitors (TNFi) and without previous latent tuberculosis infection (LTBI) treatment. METHODS: Patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) with negative LTBI were retrospectively evaluated for TST conversion and active tuberculosis (TB) after six months of exposition to TNFi. Two groups were compared: patients who repeated TST (TST-repetition) during the follow-up and patients who did not (non-TST-repetition). RESULTS: A total of 355 CIA patients on TNFi were screened and 138 (38.9%) did not fulfill the inclusion criteria. Of the remaining 217 CIA patients, 81 (37.3%) repeated TST during TNFi treatment. TST conversion rate was observed in 18 (22.2%) patients without significant differences among CIA (p = 0.578). The number of TB cases was low (n = 10; 4.6%) and was similar in TST-repetition and non-TST-repetition groups [2 (2.5%) vs. 8 (5.9%), p = 0.328]. Of note, 30% of active TB occurred early (6-12 months of TNFi exposure) and the median (full range) time to incident TB was 1.3 (0.6-10.6) years, whereas the median (full range) time to TST repetition was later [3.3 (0.5-13.4) years]. The incidence of active TB was lower among RA patients than AS patients [342 (95% CI 41 - 1446) vs. 1.454 (95% CI 594-2993)/100,000 patient-years, p = 0.049]. CONCLUSION: These results indicate that TST repetition is associated with a high conversion rate, suggesting the need for recommended treatment. The delayed repetition of TST and low number of active TB cases hampered the evaluation of this strategy effectiveness to prevent active infection. Larger studies with systematic repetition patterns are necessary. In addition, the study highlights the need for a greater surveillance for TB in AS patients.

Comparative study of two laboratory techniques for the detection of HLA-B27 in patients with axial spondyloarthritis: a cross-sectional analysis.

BACKGROUND: The diagnostic and prognostic relevance of Human Leukocyte Antigen B-27 (HLA-B27) in Axial Spondyloarthritis (AxSpA) is undeniable, with 70% of Ankylosing Spondylitis (AS) patients carrying the B27 gene, contrasted with a mere 4.35% in the general population. Flow cytometry (FC) and Polymerase Chain Reaction (PCR) have emerged as the predominant techniques for routine HLA-B27 typing. While various studies have compared these methods, none have catered to the unique characteristics of the Brazilian demographic. Therefore, this research aims to compare FC and PCR in a Brazilian cohort diagnosed with AxSpA. METHODS: An analytical cross-sectional study was undertaken involving 62 AxSpA outpatients from a Brazilian University Hospital. Both FC and PCR-SSP assays were utilized to ascertain HLA-B27 typing. The outcomes (either confirming or refuting the allele's presence) underwent rigorous scrutiny. Agreement between the methodologies was assessed using the kappa statistic. A p-value of < 0.05 was deemed statistically significant. RESULTS: Of the participants, 90.3% (n = 56) were HLA-B27 positive according to FC, while 79% (n = 49) were identified as positive using the PCR method. FC exhibited a sensitivity rate of 98% paired with a specificity of 38.5%. The Positive Predictive Value for FC stood at 85.7%, and the Negative Predictive Value was 83.5%. Consequently, the overall accuracy of the FC method was gauged at 85.5%. A kappa coefficient of κ = 0.454 was derived. CONCLUSIONS: FC demonstrated noteworthy sensitivity and satisfactory accuracy in HLA-B27 detection, albeit with a reduced specificity when contrasted with PCR-SSP. Nevertheless, given its cost-effectiveness and streamlined operation relative to PCR, FC remains a pragmatic option for preliminary screening in clinical practice, especially in low-income regions. To optimize resource allocation, we advocate for a refined algorithm that initiates by assessing the relevance of HLA-B27 typing based on Choosing Wisely recommendations. It then leans on FC, and, if results are negative yet clinical suspicion persists, advances to PCR. This approach aims to balance diagnostic accuracy and financial prudence, particularly in regions contending with escalating medical costs.

[Faecal microbiota study reveals specific dysbiosis in spondyloarthritis according to subtype, disease activity and treatment]. / Estudio de microbiota fecal revela disbiosis específica en espondiloartritis, según subtipo, actividad de la enfermedad y tratamiento.

OBJECTIVE: To compare the diversity and composition of the gastrointestinal microbiome of patients with SpA. METHODS: MiSeq sequencing of the V3-V4 region of the 16S ribosomal RNA gene was performed on DNA isolated from stool. Patients with concurrent SpA and IBD were excluded. Differences were assessed for richness and diversity indices by QIIME 2™. Differences between means >0,2% with a p-value<0,05 were assumed significant. Institutional Ethics Committee endorsement. RESULTS: 69 individuals included, 49 with SpA (ankylosing spondylitis-AS 72,9%, psoriatic arthritis-PsA 18,8%, reactive arthritis-ReA 8,3%) 5 positive controls-dysbiosis and 15 controls-eubiosis. Conventional treatment in 42,9%, anti-IL-17 16,3% and anti-TNF 40,8%. By subtype, statistically significant differences in favour of AS were found for the diversity indices. AS vs PsA there was a difference in favour of AS for Clostridium clostridioforme (p=0,002), Gemmiger formicilis (p=0,009), Roseburia inulivorans (p=0,008) and Lachnospira pectinoschiza. AS vs ReA there was a difference in favour of AS for L. pectinoschiza (p=0,009), Ruminococcus callidus (p=0.006), Clostridium ruminantium (p=0.031); G. formicilis (p=0,034). Diversity and richness showed differences in patients with high activity for Simpson's and Pielou's indices. In high activity, lower enrichment of Bacteroides eggerthii (p= 0,0003), C. ruminantium (p= 0,026) and Alistipes putredinis (p=0,035) was found. The number of ASV was higher in the anti-IL-17 vs conventional group (p=0.025) and a trend between anti-IL-17 vs anti-TNF (p=0.09). In anti-TNF there was a lower proportion for C. clostridioforme (p=0.023), G. formicilis (p=0.030) and R. callidus (p= 0.003). In anti IL-17, Alistipes indistinctus (p= 0.012) was decreased. CONCLUSIONS: There are differences in microbial diversity for SpA subtypes. The level of disease activity is plausible to influence the composition of the faecal microbiota. Anti-TNFα treatment may influence the microbiome environment favouring restoration of the gut microbiota, while anti-IL-17 may maintain an inflammatory environment.

OBJETIVO: Comparar la diversidad y composición del microbioma gastrointestinal de pacientes con EspA. MÉTODOS: La secuenciación MiSeq de la región V3-V4 del gen ARN ribosomal 16, se realizó en ADN aislado de heces. Se excluyeron pacientes con EspA y EII simultánea. Se evaluaron diferencias para los índices de riqueza y diversidad por medio de QIIME 2™. Las diferencias entre medias> 0,2%, con un valor de p< 0,05, se asumieron significativas. Aval del Comité de Ética Institucional. RESULTADOS: 69 individuos incluidos, 49 con EspA (espondilitis anquilosante-EA 72,9%, artritis psoriásica-APs 18,8%, artritis reactiva-ARe 8,3%), cinco controles positivos-disbiosis y 15 controles-eubiosis. El tratamiento convencional en 42,9%, anti-IL-17 16,3%, y anti-TNF 40,8%. Por subtipo-EasP, se encontraron diferencias estadísticamente significativas a favor de EA para los índices de diversidad. Entre EA vs APs, hubo diferencia a favor de EA para Clostridium clostridioforme (p=0,002), Gemmiger formicilis (p=0,009), Roseburia inulivorans (p=0,008) y Lachnospira pectinoschiza. Entre EA vs ARe hubo diferencia a favor de EA para L. pectinoschiza (p=0,009), Ruminococcus callidus (p = 0,006), Clostridium ruminantium (p=0,031); G. formicilis (p=0,034). La diversidad y riqueza mostraron diferencias en pacientes con alta actividad para los índices de Simpson y Pielou. En alta actividad, se encontró menor enriquecimiento de Bacteroides eggerthii (p=0,0003), C. ruminantium (p= 0,026) y Alistipes putredinis (p= 0,035). El número de ASV fue superior en el grupo de anti IL-17 vs convencional (p=0.025), y una tendencia entre anti IL-17 vs anti-TNF (p=0,09). En anti TNF hubo menor proporción para C. clostridioforme (p=0,023), G. formicilis (p=0,030) y R. callidus (p= 0,003). Y en anti IL-17, Alistipes indistinctus (p= 0,012), estuvo disminuida. CONCLUSIONES: Existen diferencias en la diversidad microbiana para los subtipos de EspA. El nivel de actividad de la enfermedad es plausible para influir en la composición de microbiota fecal. El tratamiento con anti-TNFα, puede influenciar el ambiente del microbioma favoreciendo la restauración de la microbiota intestinal, mientras los anti IL-17 podrían mantener un ambiente inflamatorio.

Relationship between spinal structural damage and sagittal balance in axial spondyloarthritis: Is the thoracic spine the starting point?

OBJECTIVES: To assess the relationship between spinal structural damage, sagittal balance parameters and spine curvatures in patients with axial spondyloarthritis (axSpA). MATERIAL AND METHODS: In this cross-sectional study, the pelvic and sagittal balance parameters were obtained through EOS® (Biospace, Paris, France). Patients were divided into three groups according to the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) tertiles (G1 ≤6, n = 36; G2: 6.1-31, n = 36; G3 >31, n = 35) and pelvic and sagittal parameters were compared across them. Multivariable regression analysis was performed to analyze the impact of spinal structural damage and of other factors on sagittal vertical axis (SVA), an important sagittal balance parameter. RESULTS: A total of 107 patients was included. G2 and 3 exhibited higher mean values of thoracic kyphosis T1-T12 when compared to G1 (10.5°(12.3) vs. 22.3°(17.3) vs. 35.2°(14.6), p < 0.001), and G3 demonstrated lumbar L1-S1 straightening compared to the other groups (55.7°(9) and 50.7°(19.8), G1 and G2, respectively, vs. 35.7°(13.2), p < 0.001). Mean SVA values showed an increasing gradient from G1 to G3 (21.6(25.1) vs. 41(44.3) vs. 84.3(47.2)mm, p < 0.001). In the multivariable regression, a one-unit increase in total mSASSS was associated with an average 0.8 mm higher SVA. CONCLUSIONS: Our data showed that more spinal structural damage is associated with a higher SVA, reflecting poorer sagittal balance. Patients with increasing spinal damage have an important increase in thoracic kyphosis suggesting that postural modifications in patients with axSpA might have their origin in the thoracic spine.

Safety of Upadacitinib in Immune-Mediated Inflammatory Diseases: Systematic Literature Review of Indirect and Direct Treatment Comparisons of Randomized Controlled Trials.

INTRODUCTION: Immune-mediated inflammatory diseases including rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), non-radiographic axial spondylarthritis (nr-axSpA), atopic dermatitis (AD), ulcerative colitis (UC), and Crohn's disease (CD) pose a substantial burden on patients and their quality of life. Upadacitinib is an orally administered, selective, and reversible Janus kinase inhibitor indicated for seven conditions, but data on its safety versus other active treatments are limited. A systematic literature review of indirect and direct treatment comparisons of randomized controlled trials (RCTs) was conducted to assess the safety profile of upadacitinib. METHODS: MEDLINE, Embase, and Cochrane Library databases were searched for indirect and direct treatment comparisons of RCTs that (1) included licensed upadacitinib dosages; (2) studied any of the seven conditions; (3) reported any adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation, major adverse cardiovascular event, venous thromboembolism, malignancies, infections or serious infections, and death; and (4) were published between January 2018 and August 2022. RESULTS: A total of 25 studies were eligible for inclusion. SAEs, AEs leading to discontinuation, and any AEs were commonly studied. RA was the most studied condition, followed by AD and UC. Most studies (16/25, 64%) reported no statistically significant difference in the studied safety outcomes between upadacitinib and other active treatments (e.g., tumor necrosis factor blockers, interleukin receptor antagonists, integrin receptor antagonists, T cell co-stimulation modulator), or placebo (placebo ± methotrexate or topical corticosteroids). Other studies (9/25, 36%) reported mixed results of no statistically significant difference and either statistically higher (8/25, 32%) or lower rates (1/25, 4%) on upadacitinib. CONCLUSION: Most studies suggested that upadacitinib has no statistically significant difference in the studied safety outcomes compared to active treatments or placebo in patients with RA, PsA, AS, AD, UC, and CD. A few studies reported higher rates, but findings were inconsistent with limited interpretation.

MICA and NLRP3 gene polymorphisms interact synergistically affecting the risk of ankylosing spondylitis.

Ankylosing spondylitis (AS) is an autoinflammatory disease that affects the sacroiliac joints, causing stiffness and pain in the back. MICA is a ligand of the NKG2D receptor, and an increase in its expression affects the immune response in various diseases. NLRP3 is a multiprotein complex that promotes the release of IL-1ß, but its role in AS has been minimally explored. The objective of this study was to analyze the association and interaction of polymorphic variants of the MICA and NLRP3 genes in patients with AS. In this case-control study, patients with AS were included and compared with healthy controls of Mexican origin. The polymorphisms rs4349859 and rs116488202 of MICA and rs3806268 and rs10754558 of NLRP3 were genotyped using TaqMan probes. Associations were determined using logistic regression models, while interactions were analyzed by the multifactorial dimensionality reduction (MDR) method. A P value < 0.05 was considered statistically significant. The minor allele of rs4349859 (A) and rs116488202 (T) of MICA polymorphisms showed risk associations with AS (OR = 9.22, 95% CI = 4.26-20.0, P < 0.001; OR = 9.36, 95% CI = 4.17-21.0, P < 0.001), while the minor allele of the rs3806268 (A) polymorphism of NLRP3 was associated with protection (OR = 0.55, 95% CI = 0.33-0.91, P = 0.019). MDR analysis revealed synergistic interactions between the MICA and NLRP3 polymorphisms (P = 0.012). In addition, high- and low-risk genotypes were identified among these variants. The study findings suggest that the MICA rs4349859 A allele and rs116488202 T allele are associated with AS risk. An interaction between MICA and NLRP3 was observed which could increase the genetic risk in AS.

Prevalence of axial spondyloarthritis in Colombia: data from the National Health Registry 2017-2021.

INTRODUCTION: Registries allow ascertaining the epidemiology of chronic diseases such as axial spondyloarthritis (axSpA). The Colombian Ministry of Health has implemented a National Health Registry (SISPRO) that collects data from each medical contact in the system, which provides close to universal coverage (around 98%). OBJECTIVE: To establish the 5-year prevalence of axSpA in Colombia, and to describe its demographics, using data from January 1st, 2017, to December 31st, 2021. METHODS: We performed an observational, cross-sectional study using the International Statistical Classification of Diseases and Related Health Problems as search terms related to ax-SpA, based on SISPRO data. We estimated the prevalence using three approaches: (1) ankylosing spondylitis (AS) diagnoses; (2) diagnoses compatible with axSpA; and (3) diagnoses compatible with axSpA, including sacroiliitis. We calculated prevalence per 100,000 inhabitants. RESULTS: Based on our three approaches, patients with a primary diagnosis compatible with ax-SpA ranged between 12,684 and 117,648, with an estimated 5-year adjusted prevalence between 26.3 and 244 cases per 100,000 inhabitants (0.03-0.2%). The male-to-female ratio ranged between 1.2:1 and 0.4:1, which was markedly skewed towards a higher prevalence in women when we included the code for sacroiliitis. We found the highest frequency of cases in the 50-54 years group. A differential prevalence was observed between different regions in our country, particularly in regions known to have European ancestors. CONCLUSION: This is the first study that describes demographic characteristics of ax-SpA in Colombia and offers valuable information for stakeholders. Key Points • Using the official country-level health database, the prevalence of axSpA in Colombia ranges between 26.3 and 244 cases per 100,000 inhabitants (0.03% - 0.2%) • The prevalence of axSpA peaked among the 50-54 years patient group, suggesting an increased survival • Nations with a substantial admixture, such as Colombia, may present a differential prevalence of axSpA among regions within the country • Including the ICD-10 code for sacroiliitis (M46.1) in epidemiological studies probably overestimates the frequency of axSpA.

Effectiveness of functional training versus resistance exercise in patients with psoriatic arthritis: randomized controlled trial.

OBJECTIVE: This study aims to evaluate the effect of functional versus resistance exercise training on the functional capacity and quality of life of psoriatic arthritis patients. METHODS: Forty-one psoriatic arthritis patients (18 to 65 years old) were randomized into two groups: functional training group and resistance exercise group. The functional training group underwent functional exercises with elastic band and the functional training group underwent machine resistance exercise twice a week for 12 weeks. Outcome measures were: The Bath Ankylosing Spondylitis Functional Index (BASFI) and Health Assessment Questionnaire for the Spondyloarthropathies (HAQ-S) for functional capacity and functional status, one-repetition maximum test for muscle strength, the Short Form 36 health survey questionnaire (SF-36) for quality of life, and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Disease Activity Score 28 (DAS-28) for disease activity. Analyzes were performed by a blinded evaluator at baseline (T0), six (T6) and twelve (T12) weeks after the beginning of the exercise. RESULTS: At baseline, the groups were homogeneous in the clinical and demographic characteristics. There was a statistical intra-group improvement for both groups in the BASFI, BASDAI, HAQ-s, and DAS-28. In the quality-of-life assessment, both groups showed statistical intra-group improvements for all domains except the "emotional aspect" domain in the resistance exercise group. In the muscle strength, there was a statistical improvement for all exercises in both groups, except for the "alternate biceps (bilateral)" exercise. CONCLUSION: Functional training and resistance exercise are similarly effective in improving functional capacity, functional status, disease activity, general quality of life, and muscle strength in patients with psoriatic arthritis. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04304326. Registered 11 March 2020, https://clinicaltrials.gov/ct2/show/NCT04304326?term=NCT04304326&draw=2&rank=1 .

Use of the Oswestry Disability Index in ankylosing spondylitis.

OBJECTIVE: The Oswestry Disability Index is considered the gold standard in the evaluation of disability in patients with chronic mechanical back pain. The aim of this study was to assess the applicability of Oswestry Disability Index in patients with ankylosing spondylitis and its relationship with disease assessment parameters for ankylosing spondylitis. METHODS: A total of 100 patients diagnosed with ankylosing spondylitis were included in the study group. The control group consisted of 50 individuals with nonspecific low back pain. The Oswestry Disability Index and Bath Ankylosing Spondylitis Disease Activity Index were applied to both groups. In addition, the Visual Analog Scale, the Ankylosing Spondylitis Disease Activity Score C-Reactive Protein, the Ankylosing Spondylitis Disease Activity Score-the Erythrocyte Sedimentation Rate, the Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index, and the Ankylosing Spondylitis Quality of Life scales were applied in the study group. the Erythrocyte Sedimentation Rate, C-Reactive Protein levels, and HLA-B27 analysis were noted as laboratory markers in ankylosing spondylitis patients. RESULTS: The scores of Oswestry Disability Index had a significant correlation with scores of Bath Ankylosing Spondylitis Disease Activity Index in ankylosing spondylitis patients (r=0.543) and in the control group (r=0.401). There was a significant correlation between the scores of Oswestry Disability Index and the Bath Ankylosing Spondylitis Functional Index (r=0.544), Bath Ankylosing Spondylitis Metrology Index (r=0.317), the Ankylosing Spondylitis Quality of Life (r=0.723), the Ankylosing Spondylitis Disease Activity Score-the Erythrocyte Sedimentation Rate (r=0.501), the Ankylosing Spondylitis Disease Activity Score C-Reactive Protein (r=0.530), Visual Analog Scale-Rest (r=0.476), and Visual Analog Scale-Activity (r=0.441) values in patients with ankylosing spondylitis. CONCLUSION: Evaluation of Oswestry Disability Index in conjunction with Bath Ankylosing Spondylitis Disease Activity Index may warn the physician to interpret high Bath Ankylosing Spondylitis Disease Activity Index scores in the context of mechanical pain. Therefore, the use of Oswestry Disability Index in patients with ankylosing spondylitis will be beneficial.

Pan American League of Associations for Rheumatology recommendations for the management of axial spondyloarthritis.

Axial spondyloarthritis (axSpA) comprises a spectrum of chronic inflammatory manifestations affecting the axial skeleton and represents a challenge for diagnosis and treatment. Our objective was to generate a set of evidence-based recommendations for the management of axSpA for physicians, health professionals, rheumatologists and policy decision makers in Pan American League of Associations for Rheumatology (PANLAR) countries. Grading of Recommendations, Assessment, Development and Evaluation-ADOLOPMENT methodology was used to adapt existing recommendations after performing an independent systematic search and synthesis of the literature to update the evidence. A working group consisting of rheumatologists, epidemiologists and patient representatives from countries within the Americas prioritized 13 topics relevant to the context of these countries for the management of axSpA. This Evidence-Based Guideline article reports 13 recommendations addressing therapeutic targets, the use of NSAIDs and glucocorticoids, treatment with DMARDs (including conventional synthetic, biologic and targeted synthetic DMARDs), therapeutic failure, optimization of the use of biologic DMARDs, the use of drugs for extra-musculoskeletal manifestations of axSpA, non-pharmacological interventions and the follow-up of patients with axSpA.

Evaluation of the relationship between blood cell markers and inflammation, disease activity, and general health status in ankylosing spondylitis.

OBJECTIVE: The aim of this study was to assess the relation of systemic immune inflammation index, systemic inflammation response index, and systemic inflammation aggregate index with disease activity, functional status, and general health status in ankylosing spondylitis. METHODS: Patients with ankylosing spondylitis and healthy volunteers were included in this cross-sectional study. Demographic data; disease activity measurements such as the Bath Ankylosing Spondylitis Disease Activity Index, the Ankylosing Spondylitis Disease Activity Score with C-reactive protein, and the Ankylosing Spondylitis Disease Activity Score with erythrocyte sedimentation rate; functional status such as the Bath Ankylosing Spondylitis Functional Index; and general health status such as the Assessment of Spondyloarthritis International Society Health Index of the patients were recorded. C-reactive protein, erythrocyte sedimentation rate, platelet to lymphocyte ratio, neutrophil to lymphocyte ratio, monocyte to lymphocyte ratio, systemic immune inflammation index, systemic inflammation response index, and systemic inflammation aggregate index values were recorded. Patients were grouped as active and remission according to the Bath Ankylosing Spondylitis Disease Activity Index score and as inactive-low and high-very high disease activity according to the Ankylosing Spondylitis Disease Activity Score. The correlation of laboratory parameters with disease-related parameters was tested. RESULTS: The indexes were significantly higher in patients compared to controls (p<0.001, for platelet to lymphocyte ratio p=0.03). No significant differences existed in any blood cell-derived indexes among patient groups categorized by disease activity (p<0.05 for all). Systemic immune inflammation index was weakly correlated with Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ρ=0.197 and p=0.049) and Ankylosing Spondylitis Disease Activity Score-erythrocyte sedimentation rate (ρ=0.201 and p=0.045). Systemic immune inflammation index was not correlated with Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, and Assessment of Spondyloarthritis International Society Health Index. No correlation was found between other indexes and disease-related variables. Platelet to lymphocyte ratio, systemic immune inflammation index, systemic inflammation response index, and systemic inflammation aggregate index showed a weak positive correlation with C-reactive protein and erythrocyte sedimentation rate (ρ=0.200-0.381). CONCLUSION: Systemic immune inflammation index, systemic inflammation response index, and systemic inflammation aggregate index can be used to indicate systemic inflammatory burden in ankylosing spondylitis patients. However, these indexes are not effective in indicating patients' disease activity, general health status, and functional status.

Implementation of screening criteria for inflammatory bowel disease in patients with spondyloarthritis and its association with disease and endoscopic activity.

There is little literature on the implementation of screening criteria for inflammatory bowel disease (IBD) in patients with spondyloarthritis (SpA). This study aimed to apply IBD screening criteria in a group of patients with SpA without IBD diagnosis and correlate them to endoscopic findings and disease activity. A total of 82 patients with SpA were included. The IBD screening test and ileocolonoscopy with digital chromoendoscopy with magnification and histological analysis were performed. The data were analysed with Chi-square test/Fisher's exact test and multiple correspondence analysis. The major screening criteria found in 48.7% of the patients were associated with a history of infection (p = 0.037). Rectal bleeding was associated with the diagnosis of ankylosing spondylitis, acute inflammation, enthesitis and tissue architecture alteration in the ileum (p < 0.050). Diarrhoea was associated with a higher disease activity score (p = 0.02). Minor screening criteria were associated with painful inflammatory joint (p = 0.05), high disease activity score (p = 0.001) and high calprotectin levels (p = 0.050). Abdominal pain (36.9%) was associated with axial/peripheral compromise (p = 0.017), inflammatory back pain (p = 0.01), enthesitis (p = 0.021), higher disease activity score (p = 0.023) and acute ileum inflammation (p = 0.046). Diarrhoea of 4 weeks and abdominal pain were the most prevalent major and minor screening criteria, respectively, being related to early manifestations of inflammatory bowel compromise and higher disease activity score. This screening test grants a chance of opportune referral of SpA patients from rheumatology to gastroenterology.

Kidney Disease in Ankylosing Spondylitis: a case series and review of the literature.

BACKGROUND: Kidney disease is a rare manifestation of ankylosing spondylitis (AS) and its pathological alterations remain poorly described. The aim of this study was to investigate the clinical presentation and pathological alterations on kidney biopsy of AS patients and review and discuss the current literature on the issue. METHODS: We retrospectively studied the clinical presentation and kidney pathological alterations of 15 Caucasian AS patients submitted to kidney biopsy between October 1985 and March 2021. RESULTS: Patients were predominantly male (66.7%) with median age at the time of kideney biopsy of 47 years [IQR 34 - 62]. Median serum creatinine at presentation was 1.3 mg/dL [IQR 0.9 - 3] and most patients also had either proteinuria (85.7%) and/or hematuria (42.8%). The most common indication for kidney biopsy was nephrotic syndrome (33.3%), followed by acute or rapidly progressive kidney injury (20%) and chronic kidney disease of unknown etiology (20%). Chronic interstitial nephritis (CIN) (n=3) and AA amyloidosis (n=3) were the most common diagnosis. Others included IgA nephropathy (IgAN) (n=2), focal segmental glomerulosclerosis (n=2), membranous nephropathy (n=1), and immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN)(n=1). CONCLUSIONS: We present one of the largest series of biopsy-proven kidney disease in Caucasian AS patients. We found a lower prevalence of IgAN than previously reported in Asian cohorts. We found a higher prevalence of CIN and a lower prevalence of AA amyloidosis than that described in previous series of Caucasian patients. We also present the first case of AS-associated IC-MPGN.

Upadacitinib en el tratamiento de la espondilitis anquilosante activa / Upadacitinib in the treatment of active ankylosing spondylitis

INTRODUCCIÓN: Las espondiloartritis constituyen un conjunto de enfermedades reumáticas, que comparten características clínicas, patogénicas, genéticas, radiográficas, epidemiológicas y terapéuticas, y que engloba entre otras patologías a la espondilitis anquilosante. Estas entidades afectan a personas jóvenes, frecuentemente antes de los 45 años. La prevalencia de la espondilitis anquilosante es de aproximadamente 0,5% a 1,5% de la población mundial, y en América Latina afecta a alrededor de 10,2 personas por 10.000 habitantes. En Uruguay no se dispone de datos epidemiológicos oficiales sobre esta patología. Es una enfermedad inflamatoria crónica y progresiva que altera sobre todo las articulaciones de la columna vertebral y las articulaciones sacroilíacas, provocando dolor, rigidez y limitación de movimiento a nivel de la espalda. Es esencial realizar un diagnóstico temprano e implementar un tratamiento adecuado para mejorar la calidad de vida de los pacientes. Los objetivos del tratamiento de la espondilitis anquilosante son aliviar los síntomas, mejorar la flexibilidad de la columna y la postura normal, reducir las limitaciones funcionales y las complicaciones. Los pilares del tratamiento farmacológico implican medicamentos antiinflamatorios no esteroideos (AINE) e inhibidores del TNF-α (TNFi). Los tratamientos adicionales incluyen productos biológicos no TNFi (secukinumab, upadacitinib), metotrexato y sulfasalazina. Upadacitinib es un inhibidor de la Janus quinasa, incluido en el Formulario Terapéutico de Medicamentos y financiado por el Fondo Nacional de Recursos para el tratamiento de la artritis reumatoidea activa de moderada a grave en pacientes adultos con respuesta inadecuada o intolerancia a uno o más FAME, pero no para la espondilitis anquilosante. OBJETIVO: Evaluar la evidencia disponible acerca de la eficacia, calidad de vida, seguridad y aspectos relacionados a la cobertura en Uruguay del uso de upadacitinib en el tratamiento de la espondilitis anquilosante activa. METODOLOGÍA: Se efectuó la revisión y el análisis de evidencias del Informe Rápido de Síntesis de Evidencia (IR 2023-104 B) realizado por el departamento de Documentación y Análisis de AETSU, y posterior extracción de los datos para su procesamiento. Considerando que la indicación para esta patología sería reciente y que la evidencia directa puede resultar incompleta para apoyar de manera informada a la toma de decisión, se realizaron búsquedas complementarias de información proveniente de fuentes indirectas (ej. metaanálisis en red) y/o decisiones de cobertura publicadas en informes de otras agencias referentes en evaluaciones de tecnologías sanitarias (ETS). RESULTADOS: Un total de dos estudios clínicos aleatorizados (Select-AXIS 1 y Select-AXIS 2) incluidos en tres publicaciones fueron seleccionados. Los resultados de los dos ECAs mostraron que, el tratamiento con upadacitinib a 15 mg/día comparado con placebo fue superior en cuanto a la eficacia a las 14 semanas en pacientes adultos con espondilitis anquilosante que cumplieran con los criterios modificados de Nueva York, tuvieran la enfermedad activa (definida por una puntuación del Índice de actividad de la enfermedad de la espondilitis anquilosante de Bath) y una puntuación del dolor de espalda >4 con una respuesta inadecuada a mayor igual 4 con una respuesta inadecuada a menos igual 2 AINES o intolerancia o contraindicación para estos fármacos. Además, en Selecta AXIS-1 se demostró que el efecto positivo de upadacitinib comparado con placebo se mantiene a largo plazo (104 semanas). El Selecta-AXIS 2 evidenció una eficacia superior de upadacitinib vs. placebo en pacientes con las mismas características que los pacientes incluidos en Selecta-AXIS 1 pero que además presentaban una respuesta inadecuada a los FAME biológicos. Upadacitinib también fue superior en eficacia frente a placebo en los subgrupos de pacientes con una respuesta inadecuada a uno y dos FAME biológicos a la semana 14. El perfil de seguridad fue similar entre ambos tratamientos. No se reportaron infecciones graves, neoplasias malignas, herpes zóster, insuficiencia renal, eventos cardiovasculares adversos severos, eventos tromboembólicos venosos o muertes tanto hasta las 14 como a hasta las 104 semanas. En cuanto a la calidad de vida los resultados no fueron concluyentes. CONCLUSIONES: Upadacitinib es superior en cuanto a la eficacia comparado con placebo en pacientes con espondilitis anquilosante activa que cumplan con los criterios modificados de Nueva York, con una respuesta inadecuada a AINES o intolerancia o contraindicación para estos fármacos y respuesta inadecuada a FAME biológicos a corto plazo, con un perfil de seguridad aceptable y resultados en cuanto a la calidad de vida no concluyentes aún.

TNF-alpha and IL-17 cytokine levels in Brazilian patients with ankylosing spondylitis after anti-TNF therapy

Abstract The aim of this study was to evaluate tumor necrosis factor alpha (TNF-α), interleukin (IL)- 17A/F levels in the serum of ankylosing spondylitis (AS) patients after anti-TNF therapy, in order to understand how these cytokines are involved in this therapeutic response. Forty-four AS patients were included in the study: thirty using anti-TNF therapy were classified according to their therapy response as responders (15) and non-responders (15) and 14 without anti-TNF therapy were classified as AS control. Fifteen healthy individuals formed the control group. Serum levels of TNF-α were determined using Luminex technology and for IL-17A and IL-17F using ELISA. The non-responder patients presented higher serum levels of TNF-α than the responders and AS control; the same results were found when HLA-B*27 positive or negative patients were separately analyzed. IL-17A and IL17F serum levels were similar for all groups. According to the clinical disease activity, AS patients with BASDAI ≥4 had higher serum levels of TNF-α than AS patients with BASDAI <4. Positive correlation was found between TNF-α levels and BASDAI. In AS patients, TNF-α serum levels were associated with anti-TNF therapy and disease activity independently of HLA-B*27, and IL-17A and IL-17F were not related to anti-TNF treatment

Optical coherence tomography changes in ankylosing spondylitis patients on long-term adalimumab treatment.

OBJECTIVE: Long-term ocular effects of tumor necrosis factor-alpha inhibitors remain to be elucidated. This study aimed to examine the long-term effects of adalimumab use on neural tissue of the anterior visual pathways using optical coherence tomography in patients with ankylosing spondylitis. METHODS: This was a single-center, open-label, cross-sectional study conducted at the Giresun University Faculty of Medicine, Physical Medicine and Rehabilitation Department, between November 2019 and August 2020. This study included 26 ankylosing spondylitis patients receiving adalimumab for at least 1 year and 21 healthy controls. All subjects underwent a full ophthalmological examination and optical coherence tomography examination with the following measurements: peripapillary retinal nerve fiber layer thickness, peripapillary retinal thickness, peripapillary choroidal thickness, ganglion cell complex thickness, and the optic head properties. RESULTS: Peripapillary retinal nerve fiber layer thickness and retinal thickness measurements were lower in the adalimumab group. In addition, ganglion cell complex thickness was significantly lower and the cup-to-disc ratio was significantly higher in the adalimumab group (p<0.05). However, the two groups did not differ in terms of peripapillary choroidal thickness and disc area (p>0.05). CONCLUSION: Although tumor necrosis factor-alpha inhibitors have some favorable effects on the ocular involvement of patients with ankylosing spondylitis, they may also have paradoxical detrimental effects as evidenced by structural changes observed by optical coherence tomography. Future studies with better design, probably including a large number of patients with a range of rheumatological diseases and tumor necrosis factor-alpha inhibitors, are warranted.