Laura Triginer

Objectives: Gastroesophageal reflux disease (GERD) is highly prevalent in SSc and frequently persists despite proton pump inhibitor (PPI) therapy. We aimed to characterize the contribution of oesophageal and gastric dysmotility to PPI-refractory GERD in SSc. Methods: We conducted a single‑centre, retrospective study of adults with SSc who underwent ambulatory pH–multichannel intraluminal impedance (pH/MII) monitoring while receiving twice‑daily PPI therapy (2021–25). Oesophageal motility (high‑resolution manometry, HREM) and gastric emptying scintigraphy were integrated to examine associations between gastro-oesophageal dysmotility and reflux phenotypes. Results: Thirty patients were included, of whom 67% had PPI-refractory reflux symptoms and 33% were undergoing pre–lung transplantation evaluation. Refractory GERD was present in 29/30 patients (97%) based on Lyon 2.0 classification, with conclusive evidence in 53% and borderline evidence in 43%. Oesophageal dysmotility was identified in 80%, most commonly absent contractility (67%), and was associated with impaired reflux clearance, reflected by longer acid clearance times [2.20 (1.15–3.75) vs 1.15 (0.43–1.90) min] and more prolonged reflux episode duration [16.60 (4.38–40.63) vs 1.95 (0.53–20.43) min]. Gastric dysmotility was identified in 60.7% and was associated with an increased reflux episode burden [51.00 (30.00–81.50) vs 25.00 (21.00–54.00) episodes/24 h]. Conclusion: PPI‑refractory GERD is nearly universal in this SSc cohort and reflects heterogeneous, quantifiable abnormalities across the foregut, including impaired oesophageal clearance and increased reflux burden related to gastric retention. These findings support integrated physiologic evaluation to define reflux mechanisms, inform risk stratification (including lung transplantation) and guide targeted, mechanism-based therapies beyond acid suppression.

Background/Objectives: Gastric antral vascular ectasia (GAVE) is a gastrointestinal manifestation associated with systemic sclerosis (SSc) that can lead to significant morbidity. This study aimed to characterise and compare the clinical profiles, laboratory findings, therapeutic approaches and survival outcomes of SSc patients with and without GAVE, based on data obtained during their first oesophagogastroduodenoscopy (EGD). Methods: A total of 269 patients who had undergone at least one EGD were selected. Twenty-seven were diagnosed with GAVE and compared with the remaining 242. Results: The overall prevalence of GAVE in SSc patients was 10%. Patients with GAVE had specific features such as a higher median age SSc onset (56.6 vs 48.0 years, p = 0.001), a higher prevalence of Barrett’s oesophagus (14.8% vs. 3.7%, p = 0.011), intestinal involvement (37% vs. 18.6%, p = 0.024) and a trend towards a lower prevalence of interstitial lung disease (25.9% vs. 45.0%, p = 0.057). A higher frequency of early or active Cutolo capillaroscopy pattern (84.6% vs. 62.4%, p = 0.025), greater frequency of anti-centromere antibodies (63.0% vs. 42.1%, p = 0.039) and a trend towards a lower proportion of anti-topoisomerase I (3.7% vs. 18.6%, p = 0.052) was also observed. No difference was found in the prevalence of anti-RNA polymerase III antibodies, survival or mortality. Conclusions: SSc patients with GAVE exhibit a distinct phenotype characterised by older age at disease onset, gastrointestinal involvement, anti-centromere antibodies and early or active capillaroscopic pattern, without differences in survival.

Background. Gastroesophageal reflux disease (GERD) is highly prevalent in systemic sclerosis (SSc) and frequently persists despite proton pump inhibitor (PPI) therapy. However, the mechanisms underlying PPI refractory GERD in SSc remain incompletely understood. Methods. We conducted a single centre, retrospective study of adults with SSc who underwent ambulatory pH multichannel intraluminal impedance (pH/MII) monitoring while receiving twice daily PPI therapy (2021 to 2025). Esophageal motility (high resolution manometry, HREM) and gastric emptying scintigraphy were integrated to examine associations between gastroesophageal dysmotility and reflux phenotypes. Results. Thirty patients were included, of whom 67% had PPI refractory reflux symptoms and 33% were undergoing prelung transplantation evaluation. Refractory GERD was present in 29/30 patients (97%) based on Lyon 2.0 classification, with conclusive evidence in 53% and borderline evidence in 43%. Esophageal dysmotility was identified in 80%, most commonly absent contractility (67%), and was associated with impaired reflux clearance, reflected by longer acid clearance times (2.20 [1.15, 3.75] vs 1.15 [0.43, 1.90] min) and prolonged reflux episode duration (16.60 [4.38, 40.63] vs 1.95 [0.53, 20.43] min). Gastric dysmotility was identified in 60.7% and was associated with an increased reflux episode burden (51.00 [30.00, 81.50] vs 25.00 [21.00, 54.00] episodes/24h). Conclusions. PPI refractory GERD is nearly universal in this SSc cohort and reflects heterogeneous, quantifiable abnormalities across the foregut, including impaired esophageal clearance and increased reflux burden related to gastric retention. These findings support integrated physiologic evaluation to define reflux mechanisms, inform risk stratification (including lung transplantation), and guide targeted, mechanism based therapies beyond acid suppression.

Objectives: To determine the prevalence of objectively defined gastric dysmotility in SSc and to evaluate its associations with SSc clinical and immunological features and adverse outcomes (SSc-related death and/or lung transplantation). Methods: We conducted a retrospective cohort study. All participants underwent a standardized 4-h solid gastric emptying scintigraphy. Gastric dysmotility was defined as ≥20% gastric retention at 4-h. We examined associations between gastric dysmotility and demographic, clinical and immunologic characteristics of SSc, as well as relevant clinical outcomes. Results: Ninety-four patients were included (mean age 48 ± 12 years; 81% female). Gastric dysmotility was identified in 33 patients (35%). Patients with gastric dysmotility had a higher prevalence of interstitial lung disease (63.6% vs 30.3%, P = 0.033) and absent oesophageal contractility (75.8% vs 45.9%, P < 0.001) compared with those without. Gastric dysmotility was less frequent in patients with ACAs (27.3% vs 55.0%, P = 0.009) but more common in those with anti-U1RNP antibodies (15.6% vs 1.7%, P = 0.011). During follow-up (mean duration 2.8 ± 1.7 years; 260 person-years), 16 patients (17.0%) experienced the composite end point of SSc-related death and/or lung transplantation. In unadjusted Cox regression, gastric dysmotility was strongly associated with adverse outcomes (HR = 6.47, 95% CI: 2.09–20.10, P = 0.001), which remained significant after adjustment for confounders (HR = 4.23, 95% CI: 1.25–14.33, P = 0.020). Conclusions: In SSc, we have confirmed that gastric dysmotility is associated with a distinct clinical and serological phenotype and that it independently predicts serious adverse outcomes. These findings underscore the importance of objective assessment of gastric function and its potential role in risk stratification.

Objectives: Lung transplantation (LT) is a rescue therapy for end-stage pulmonary diseases, including systemic autoimmune diseases. The aim of this study was to analyse the evolution of patients with systemic sclerosis (SSc) who, after undergoing LT, become negative for antinuclear antibodies (ANA) and to assess whether they have different clinical and prognostic characteristics than patients who do not become negative. Material and Methods: A retrospective, descriptive analysis was performed over a cohort of patients with a diagnosis of SSc, who underwent unilateral or bilateral LT between 2006 and 2021 at the Vall d’Hebron University Hospital. Clinical and analytical data were obtained from these patients by reviewing their electronic medical records. Two groups of patients were compared: those who tested negative for ANA after LT and those who did not. Statistical analysis was performed with SPSS Statistics 20.0. Results: Eighteen patients were included. The most frequent indication for LT was interstitial lung disease (ILD) combined with pulmonary hypertension (PH), in 13 (72%) patients. All had ANA before the LT (n = 18), and regarding specific SSc autoantibodies, anti-topoisomerase I was presented in 44% (n = 8), anti-U11/U12RNP in 17% (n = 3), anti-RNA Polymerase III in 11.1% (n = 2), anti-Ro52 in 11% (n = 2) and anti-centromere in 6% of individuals (n = 1). 39% (n = 7) of the patients had negative post-LT ANA, 44% (n = 8) had declining titres, and 17% (n = 3) had stable ANA titres. Titres did not increase in any case after LT. Those patients who became ANA-negative after LT were those who had significantly lower titres before LT. No statistically significant differences between groups were found related to pre-LT clinical characteristics, immunosuppressive regimen applied after LT, or in post-LT outcomes. A non-significant trend towards better survival was observed in patients who became ANA negative, with a cumulative survival at 5 years of 85.7% compared to 72.7% among those who remained ANA-positive. Conclusions: Most patients with SSc clear ANA or reduce their levels after LT. A trend towards better survival was observed in this group, compared to the group of transplanted patients who remained positive.

Objectives: Oesophageal dysmotility is a common manifestation of SSc, contributing to substantial morbidity. We sought to determine whether oesophageal dysmotility patterns by high-resolution oesophageal manometry were associated with distinct SSc clinical phenotypes and different outcomes. Methods: We analysed a cohort of SSc patients with detailed clinical and immunological data. Oesophageal motility was classified using Chicago 4.0 criteria, and baseline characteristics were compared across motility patterns [absent contractility (AC), ineffective oesophageal motility (IEM) and normal motility]. Associations with adverse outcomes (death or lung transplantation) were evaluated using Kaplan–Meier and Cox regression analyses. Results: Our cohort included 201 patients with SSc (84% female, mean age 45 ± 17 years, follow-up 442 person-years). Oesophageal dysmotility patterns were classified as AC in 86 (43%), IEM in 57 (28%) and normal motility in 58 (29%). AC was associated with dcSSc, more severe digital ulcers, gastric vascular ectasia, anti-Ro60 antibodies and a late pattern on nailfold capillaroscopy (P < 0.05), while IEM was linked to limited SSc, anti-centromere antibodies and an early/active nailfold pattern. Multivariate time-to-event analysis identified AC as an independent risk factor for lung transplantation (HR = 7.004, 95%CI: 1.481–33.135, P = 0.014) after adjusting for both interstitial lung disease and male sex, and for SSc-related death (HR = 3.472, 95%CI: 1.071–10.969, P = 0.038) after adjusting for DcSSc and interstitial lung disease. Conclusions: We found that patients with AC and IEM have distinct clinical phenotypes, suggesting they are distinct entities. In patients with SSc, AC is independently associated with worse outcomes. These data suggest that HREM may be useful in risk stratification and outcome predictions in patients with SSc.

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.