Laura Tío

Introduction: Total knee replacement (TKR) is the primary treatment for knee osteoarthritis (KOA) with severe symptoms, yet decision-making is influenced by subjective judgment. Long-term outcomes for 10-34% of patients are unclear, prompting the need for objective patient stratification. Objective: This study aimed to identify biomechanical descriptors differentiating TKR-scheduled from conservatively managed KOA patients and to examine their association with patient-reported outcomes. Methods: Sixty-six women (27 TKR, 39 conservative) with moderate KOA (Kellgren-Lawrence grades 2-3) underwent gait analysis. Participants were classified by age, body mass index and treatment at baseline. The effect of these factors on joint kinematics was assessed across three stance sub-phases (loading response (t 1 ), mid-stance (t 2 ), and terminal stance (t 3 )) using repeatedmeasures multifactorial MANOVA. Stance-phase kinematic changes (D = t 3 -t 1 ) were analyzed using Random Forest models with nested cross-validation and exhaustive feature selection, and their associations with clinical variables were examined through logistic regression. Clinical construct consistency was assessed against the Osteoarthritis Initiative dataset. Results: MANOVA revealed significant Time × Treatment interactions (p-value = 0.001). The univariate test showed knee flexionextension (KFE) and pelvis tilt (PTILT) associated with treatment. Machine learning achieved mean ROC-AUC of 0.79 (F1-score 0.72), with DKFE, DPTILT, and DAFE as the most stable predictors. DPTILT predicted functional limitation (AUC 0.71), pain (0.80), and depression (0.73). Clinical construct structure was preserved between datasets, though WOMAC subscales alone yielded poor classification accuracy (<0.70). Conclusions: Stance-phase kinematics differentiate treatment pathways and show promise for supporting objective treatment stratification, though validation and multi-modal integration are essential.

Knee osteoarthritis (KOA) has a complex, multifactorial nature with well-established risk factors which may influence treatment decisions. Here we want to identify distinctive characteristics between patients receiving conservative treatment versus total knee replacement (TKR), analyzing both patient-specific and knee-specific features. This case–control study compared patients assigned to TKR versus conservative management, examining subjects aged 60–75 years with radiographically confirmed KOA (Kellgren–Lawrence grades 2–3), with all participants evaluated by blinded clinicians using validated assessment tools including Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Hospital Anxiety and Depression Scale (HADs), Pain Catastrophizing Scale (PCS) and Daily physical activity (DPA) questionnaires. The study employed multivariate analysis of variance for continuous variables at both patient and knee levels, followed by univariate analysis of variance for significant factors, while logistic and linear regression analyses were used to calculate odds ratios, with Bonferroni corrections applied to adjust p-values for multiple comparisons. Between 2016 and 2020, the study included 87 patients (51 women and 36 men) with a mean age of 67.7 years in both treatment groups, with a slightly higher body mass index (BMI) of 31.9 kg/m2 in the TKR group vs 30.5 kg/m2 in the conservative management group. TKR patients demonstrated significantly worse scores in WOMAC, HADS, and PCS compared to the conservative management group, though DPA levels remained similar between both groups. At the knee level, women demonstrated significantly higher pain sensitivity and central sensitization compared to men, with no differences between conservative and TKR groups. Patients undergoing TKR exhibited significantly worse baseline clinical outcomes, particularly in WOMAC scores, despite having similar radiographic severity to those receiving conservative treatment, suggesting that functional and symptomatic measures may be more valuable than radiographic findings in determining surgical intervention.

Background/Objectives: Radiculopathy leads to pain, consequently reducing patient’s quality of life (QoL). Research indicates that certain nucleotides, such as cytidine and uridine, along with vitamins B1 and B12, may help alleviate pain and enhance QoL. This study assessed the impact of adding a supplement containing cytidine and uridine nucleotides and vitamins B1 and B12, alongside standard treatment, on radiculopathy-associated pain. Methods: A multicenter, prospective, two-cohort, randomized, open-label study was conducted. The control group received standard treatment, while the experimental group received standard treatment plus the supplement. The primary endpoint was pain reduction measured by a Visual Analog Scale (VAS). Secondary endpoints included functional improvement (Roland Morris questionnaire), clinical improvement (Clinical Global Impression [CGI] scale), and QoL improvement (EQ-5D-5L questionnaire). Results: A total of 122 patients were included from 17 centers across Spain. Both groups showed pain improvement, but the VAS reduction (control: 24.58 vs. experimental: 31.35) was not statistically significant. The Roland Morris score decreased significantly in the experimental group (estimate: −1.70, 95% CI −3.29 to −0.10; p = 0.038), and these patients were 5 times more likely to progress to a better CGI category (OR = 0.20, 95% CI 0.07 to 0.57; p = 0.003). No significant differences were observed in EQ-5D-5L scores or analgesic consumption. Conclusions: The addition of supplemental pyrimidine nucleotides and vitamins B1 and B12 to standard of care treatment improved radiculopathy functional and clinical outcomes. Regarding pain, however, although there was a numerical improvement, it did not reach statistical significance.

It has been postulated that advanced glycation end products (AGEs) and their soluble receptor (sRAGE) may play a relevant role as inducers in the chronic inflammatory pathway in various conditions, among them, in immune-mediated diseases such as systemic lupus erythematosus (SLE). However, previous studies show conflicting results about their association with SLE characteristics and their usefulness as disease biomarkers. We aimed to study the association of specific serum AGEs (pentosidine, Nξ-(carboxymethyl)lysine (CML), Nξ-(carboxyethyl)lysine (CEL)), sRAGE levels and AGEs (specific serum AGEs and skin AGEs) to sRAGE ratios with various disease parameters, in order to clarify their potential as new biomarkers in SLE and to study their relationship with cardiovascular disease (CVD). To this aim, serum pentosidine, CML, CEL and sRAGE were measured via ELISA, and skin AGEs levels were measured by skin autofluorescence. Correlations of pentosidine levels with demographic and clinical data, indexes of activity, accrual damage and patient-reported outcomes were analyzed through multiple linear regression models, while correlations of the rest of the AGEs, sRAGE and AGE to sRAGE ratios (non-normal) were analyzed using both an OLS regression model and a GML. All of the analyses were adjusted for confounders. A total of 119 SLE patients were recruited. Serum AGEs and sRAGEs were significantly associated with SLE activity indexes and/or demographic or disease characteristics: pentosidine with pulmonary manifestations; CML with anti-dsDNA antibodies, IL-6, disease duration and non-Caucasian ethnicities; CEL with anti-dsDNA antibodies, IL-6 and accumulated number of manifestations; and sRAGE with male gender, photosensitivity and being on specific immunosuppressants. These results suggest that the AGE–sRAGE axis may serve as a novel biomarker for managing and prognosticating this disease. Its correlation with certain antibodies, demographics and disease presentations may indicate a distinct clinical phenotype associated with varying levels of AGEs and/or sRAGE. The significance of specific AGE/sRAGE ratios, introduced in this study for the first time, warrants additional investigation in forthcoming research. Our study did not confirm the link between serum AGEs and CVD, which merits further exploration through studies designed for this specific purpose.

Advanced glycation end-products (AGEs) may play a relevant role as inducers in the chronic inflammatory pathway present in immune-mediated diseases, such as systemic lupus erythematosus (SLE). AGEs concentrations have been associated, with discrepant results to date, with some parameters such as disease activity or accrual damage, suggesting their potential usefulness as biomarkers of the disease. Our objectives are to confirm differences in AGEs levels measured by cutaneous autofluorescence between SLE patients and healthy controls (HC) and to study their correlation with various disease parameters. Cross-sectional study, where AGEs levels were measured by skin autofluorescence, and SLE patients’ data were compared with those of sex- and age-matched HC in a 1:3 proportion through a multiple linear regression model. Associations of AGEs levels with demographic and clinical data were analyzed through ANOVA tests. Both analyses were adjusted for confounders. AGEs levels in SLE patients were significantly higher than in HC (p < 0.001). We found statistically significant positive associations with SLE disease activity index (SLEDAI) and damage index (SDI), physician and patient global assessment, C-reactive protein, leukocyturia, complement C4, IL-6 and oral ulcers. We also found a negative statistically significant association with current positivity of anti-nuclear and anti-Ro60 antibodies. AGEs seem to have a contribution in LES pathophysiology, being associated with activity and damage and having a role as a new management and prognosis biomarker in this disease. The association with specific antibodies and disease manifestations may indicate a specific clinical phenotype related to higher or lower AGEs levels.

Introduction: Advanced glycation end-products (AGEs) may play a relevant role as inducers in the chronic inflammatory pathway present in immune-mediated diseases, such as systemic lupus erythematosus (SLE). AGEs concentrations have been associated, with discrepant results to date, with some parameters such as disease activity or accrual damage, suggesting their potential usefulness as biomarkers of the disease. Objectives: To confirm differences in AGEs levels measured by cutaneous autofluorescence between SLE patients and healthy controls (HC) and study their correlation with various disease parameters. Methods: Cross-sectional study, where AGEs levels were measured by skin autofluorescence, and SLE patients’ data were compared with those of sex- and age-matched HC in a 1:3 proportion through a multiple linear regression model. Correlations of AGEs levels with demographic and clinical data were analyzed through ANOVA tests. Both analyses were adjusted for confounders. Results: AGEs levels in SLE patients were significantly higher than in HC (p<0.001). We found statistically significant positive correlation with SLE disease activity index (SLEDAI) and damage index (SDI), physician and patient global assessment, C-reactive protein, leukocyturia, complement C4, IL6 and oral ulcers. We also found a negative statistically significant correlation with current positivity of anti-nuclear and anti-Ro60 antibodies. Conclusions: AGEs seem to have a role in LES pathophysiology, becoming a new management and prognosis biomarker in this disease. The association with specific antibodies and disease manifestations may indicate a specific clinical phenotype related to higher AGEs levels.

Purpose: The role of mesenchymal stem cells (MSC) in supporting the formation of new meniscal tissue in a meniscal scaffold is not well understood. The objective of this study was to assess the quality of the meniscal tissue produced in a fibronectin (FN)‐coated polyurethane (PU) meniscal scaffold after a meniscal injury was made in an experimental rabbit model.Methods: Twelve New Zealand white rabbits were divided in two groups after performing a medial meniscectomy of the anterior horn. In group 1, the meniscal defect was reconstructed with a non‐MSC supplemented FN‐coated PU scaffold. On the other hand, the same scaffold supplemented with MSCs was used in group 2. The animals were sacrificed at 12 week after index surgery. A modified scoring system was used for histological assessment. This new scoring (ranging from 0 to 15) includes a structural evaluation (meniscal scaffold interface and extracellular matrix production) and tissue quality evaluation (proteoglycan and type I‐collagen content).Results: The meniscal scaffold was found loose in the joint in three cases, corresponding to two cases in group 1 and 1 case in group 2. No differences were observed between the groups in terms of the total score (7.0 ± 0.9 vs. 9.4 ± 2.6, p = 0.09). However, differences were observed in group 2 in which 2 out of the 5 scored items, scaffold integration (1 ± 0.0 vs. 1.9 ± 0.6, p = 0.03) and proteoglycan production (1.2 ± 0.3 vs. 2.4 ± 0.2, p = 0.001). A trend to a higher production of Type I‐Collagen production was also observed in group 2 (1.1 ± 0.4 vs. 1.4 ± 0.7, p = 0.05).Conclusion: In a rabbit model at 12 weeks, the adhesion of MSCs to a FN‐coated PU scaffold improves scaffold integration, proteoglycan production and the characteristics of the new meniscal‐like tissue obtained when compared to a non‐supplemented scaffold. This fact could be a major step toward improving the adhesion of the MSCs to meniscal scaffolds and, consequently, the obtention of better quality meniscal tissue.

The SLRP opticin (OPTC) has been demonstrated to be produced and degraded in osteoarthritic (OA) human cartilage. Here, we investigated the in vivo effect of OPTC deficiency in OA cartilage. OA was induced in 10-week-old Optc^−/− and Optc^+/+ mice. Ten weeks post-surgery, cartilage was processed for histology and immunohistochemistry. SLRP expression was determined in non-operated mouse cartilage. OA Optc^−/− demonstrated significant protection against cartilage degradation. Data revealed that in non-operated Optc^−/− cartilage, expression of SLRPs lumican and epiphycan was up-regulated at day 3 and in 10-week-olds (p ≤ 0.039), and fibromodulin down-regulated in 10-week-olds (p = 0.001). Immunohistochemistry of OA mice showed a similar pattern. In OA Optc^−/− cartilage, markers of degradation and complement factors were all down-regulated (p ≤ 0.038). In OA Optc^−/− cartilage, collagen fibers were thinner and better organized (p = 0.038) than in OA Optc^+/+ cartilage. The protective effect of OPTC deficiency during OA results from an overexpression of lumican and epiphycan, known to bind and protect collagen fibers, and a decrease in fibromodulin, contributing to a reduction in the complement activation/inflammatory process. This work suggests that the evaluation of the composition of the different SLRPs in OA cartilage could be applied as a new tool for OA prognosis classification.