To assess HLA-B27 influence on the clinical phenotype of Ankylosing Spondylitis (AS) patients.
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.
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.
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.
BACKGROUND: The main objective of this study was to determine the efficacy of intravenous (IV) iron sucrose therapy reducing transfusion requirements in elderly patients undergoing hip fracture ...surgery.
STUDY DESIGN AND METHODS: This study was a prospective randomized controlled trial involving 200 patients undergoing hip fracture surgery. Group A (100 patients) received standard treatment, while Group B (100 patients) received iron sucrose (600 mg IV). The primary endpoint was the number of patients that were transfused postoperatively. The secondary endpoints were the rate of red blood cell units used, hematimetric variables of blood tests, mortality, infection rates, length of hospital stay, and appearance of side effects.
RESULTS: Differences in the percentage of patients requiring transfusion (Group A 41.3% vs. Group B 33.3%) and in the number of concentrates transfused (0.87 ± 1.21 for Group A vs. 0.76 ± 1.16 for Group B) were not significant for the patient group as a whole, but were significant for patients with intracapsular fractures (45.7% required transfusion in Group A vs. 14.3% in Group B; p < 0.005) and in patients with a baseline hemoglobin (Hb) level of 12 g/dL or more (35.2% required transfusions in Group A vs. 19% in Group B; p < 0.05).
CONCLUSIONS: Transfusion requirements in patients with intracapsular fracture or baseline Hb level of 12 g/dL or more appear to be reduced by IV iron sucrose therapy, but there was no difference in morbidity, mortality, or length of hospital stay. The treatment is safe and hastens recovery from blood loss.
Introduction
Brodalumab is a recombinant monoclonal antibody (IgG2) that binds with high affinity to the human interleukin‐17 (IL‐17) receptor A and blocks the biological activity of the ...proinflammatory cytokines IL‐17A, IL‐17F, IL‐17A/F heterodimer, and IL‐ 25, resulting in inhibition of inflammation and clinical symptoms associated with psoriasis. Its introduction has managed to increase the levels of efficacy, safety (improving that previously presented by the anti‐IL‐17 class), and survival.
Material and methods
Retrospective analysis of a multicenter, observational study of real clinical practice including patients with moderate to severe plaque psoriasis in treatment with brodalumab. This cross‐sectional analysis includes information of patients between February 2019 and February 2022. A total of five tertiary hospitals in Andalusia (Spain) participated in this study. Analyses were performed “as observed” using GraphPad Prism version 8.3.0 for Windows.
Results
Our study included 85 patients, 54 men (63.5%) and 31 women (36.5%), with moderate–severe psoriasis treated with brodalumab. In order to evaluate the efficacy of brodalumab, our patients started with mean Psoriasis Area and Severity Index (PASI) values of 12.8 and body surface area (BSA) of 16.9, as well as a Dermatology Life Quality Index (DLQI) of 15.6, highlighting that they reported that the mean baseline visual analog scale (VAS) pruritus was 6.15. On week 52, mean PASI reached 1.26 and mean BSA 2.3, showing a clear stabilization and even sustained improvement regarding results on week 12. Concerning the brodalumab survival, we obtained 85.8% persistence at week 52.
Discussion
Brodalumab showed excellent results in the control of psoriasis in the mid‐term with an elevated number of patients maintaining treatment after 52 weeks. There were no statistically significant differences in the efficiency, safety, or survival results of brodalumab between patients coming from previous therapies.
Tocilizumab (TCZ) is an effective treatment for rheumatoid arthritis (RA). However, the changes that occurred after TCZ therapy on endothelial dysfunction, monocyte activity, NETosis, and oxidative ...stress, the principal effectors of atherosclerosis and cardiovascular disease, have not been analyzed yet. A total of 20 RA patients received 162 mg per week subcutaneous TCZ for 6 months. Endothelial function was measured through postocclusive hyperemia using Laser Doppler. Oxidative stress markers in monocytes and neutrophils were analyzed by flow cytometry. NETosis was measured through SYTOX staining of DNA fibers and the expression of myeloperoxidase and neutrophil elastase. Percentage of low-density granulocytes was analyzed through flow cytometry. Gene expression and phosphorylation of intracellular pathways was analyzed in monocytes. TCZ improved endothelial function and decreased oxidative stress in RA leukocytes. Percentage of low-density granulocytes and NETosis generation were reduced. The proinflammatory and prothrombotic status of RA monocytes was also reversed through a modulation of specific intracellular pathways. All these results were recapitulated after in vitro treatment with TCZ of monocytes and neutrophils purified from RA patients and cocultured with endothelial cells. TCZ might reduce the proatherothrombotic profile in RA patients through the restoration of the endothelial function, oxidative stress reduction, inhibition of monocytes' prothrombotic and inflammatory profile, and abridged NETosis generation.
This study aimed to: 1) analyze the inflammatory profile of Rheumatoid Arthritis (RA) patients, identifying clinical phenotypes associated with cardiovascular (CV) risk; 2) evaluate biologic and ...targeted-synthetic disease-modifying antirheumatic drugs (b-DMARDs and ts-DMARDs’: TNFi, IL6Ri, JAKinibs) effects; and 3) characterize molecular mechanisms in immune-cell activation and endothelial dysfunction.
A total of 387 RA patients and 45 healthy donors were recruited, forming three cohorts: i) 208 RA patients with established disease but without previous CV events; ii) RA-CVD: 96 RA patients with CV events, and iii) 83 RA patients treated with b-DMARDs/ts-DMARDs for 6 months. Serum inflammatory profiles (cytokines/chemokines/growth factors) and NETosis/oxidative stress-linked biomolecules were evaluated. Mechanistic in vitro studies were performed on monocytes, neutrophils and endothelial cells (EC).
In the first RA-cohort, unsupervised clustering unveiled three distinct groups: cluster 3 (C3) displayed the highest inflammatory profile, significant CV-risk score, and greater atheroma plaques prevalence. In contrast, cluster 1 (C1) exhibited the lowest inflammatory profile and CV risk score, while cluster 2 (C2) displayed an intermediate phenotype. Notably, 2nd cohort RA-CVD patients mirrored C3's inflammation.
Treatment with b-DMARDs or ts-DMARDs effectively reduced disease-activity scores (DAS28) and restored normal biomolecules levels, controlling CV risk. In vitro, serum from C3-RA or RA-CVD patients increased neutrophils activity and CV-related protein levels in cultured monocytes and EC, which were partially prevented by pre-incubation with TNFi, IL6Ri, and JAKinibs.
Overall, analyzing circulating molecular profiles in RA patients holds potential for personalized clinical management, addressing CV risk and assisting healthcare professionals in tailoring treatment, ultimately improving outcomes.
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•Unsupervised clustering of RA profiles revealed 3 groups with diverse inflammatory, oxidative, and netotic profiles.•RA patients without CV events but highest CV-risk showed inflammatory profiles akin to those with prior CV events.•TNFi, IL6Ri, and JAKi treatment for six months restores normal inflammatory biomolecule levels, cutting-RA-related CV-risk.•High CV risk RA serum activates neutrophils, modulates monocytes, and disrupts endothelial cells, reversed by b/ts-DMARDS.•Analyzing RA patients' molecular profiles enhances personalized management, addressing their cardiovascular risk.
This prospective multicenter study developed an integrative clinical and molecular longitudinal study in Rheumatoid Arthritis (RA) patients to explore changes in serologic parameters following ...anti-TNF therapy (TNF inhibitors, TNFi) and built on machine-learning algorithms aimed at the prediction of TNFi response, based on clinical and molecular profiles of RA patients.
A total of 104 RA patients from two independent cohorts undergoing TNFi and 29 healthy donors (HD) were enrolled for the discovery and validation of prediction biomarkers. Serum samples were obtained at baseline and 6 months after treatment, and therapeutic efficacy was evaluated. Serum inflammatory profile, oxidative stress markers and NETosis-derived bioproducts were quantified and miRNomes were recognized by next-generation sequencing. Then, clinical and molecular changes induced by TNFi were delineated. Clinical and molecular signatures predictors of clinical response were assessed with supervised machine learning methods, using regularized logistic regressions.
Altered inflammatory, oxidative and NETosis-derived biomolecules were found in RA patients vs. HD, closely interconnected and associated with specific miRNA profiles. This altered molecular profile allowed the unsupervised division of three clusters of RA patients, showing distinctive clinical phenotypes, further linked to the TNFi effectiveness. Moreover, TNFi treatment reversed the molecular alterations in parallel to the clinical outcome. Machine-learning algorithms in the discovery cohort identified both, clinical and molecular signatures as potential predictors of response to TNFi treatment with high accuracy, which was further increased when both features were integrated in a mixed model (AUC: 0.91). These results were confirmed in the validation cohort.
Our overall data suggest that: 1. RA patients undergoing anti-TNF-therapy conform distinctive clusters based on altered molecular profiles, which are directly linked to their clinical status at baseline. 2. Clinical effectiveness of anti-TNF therapy was divergent among these molecular clusters and associated with a specific modulation of the inflammatory response, the reestablishment of the altered oxidative status, the reduction of NETosis, and the reversion of related altered miRNAs. 3. The integrative analysis of the clinical and molecular profiles using machine learning allows the identification of novel signatures as potential predictors of therapeutic response to TNFi therapy.
To evaluate long-term visual and anatomical outcomes in neovascular age-related macular degeneration (nAMD) patients treated with anti-vascular endothelial growth factor (VEGF) agents depending on ...the time delay from confirmed diagnosis to treatment initiation.
Seventy-three nAMD patients (73 eyes) treated with anti-VEGF agents for 12 months using the pro re nata regimen were included in this retrospective longitudinal study. Patients were split into 3 groups according to the time from diagnosis to first anti-VEGF injection: < 48 h (group 1); 48 h-7 days (group 2); > 7 days (group 3). Decimal best-corrected visual acuity (VA) and macular thickness (MT) were recorded at baseline and 1–2-, 3–4-, 6- and 12-month later. Furthermore, age, gender as well as the applied treatment and number of injections after 12 months of treatment were also registered and compared.
Long-term effect of the treatment demonstrated enhanced VA in group 1 patients compared with the rest of groups after 1–2-, 6-, and 12-month follow-up (P < 0.05). Positive effects of early treatment were additionally corroborated by the augmented percentage of patients with normal VA in the group 1 respect to the rest of groups over studied time points (P < 0.05). Moreover, the VA gain in nAMD at group 1 was obtained with a mean of 3.7 intravitreal injections over 1-year follow-up period. Regarding MT, non-significant difference was observed among groups.
An early initial treatment with VEGF inhibitors is critical to achieve the best functional benefits of this therapy in new-onset nAMD patients.
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•Anti-VEGF therapy within 48 h from diagnosis leads to long-term visual gain in nAMD.•Visual gain is achieved with low IV injection number if early treatment is applied.•A prompt first anti-VEGF injection promotes long-term anatomical benefits in nAMD.
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