Susana Mellor-Pita

Background/Objectives: Chronic inflammation accompanies obesity, but correlations of longitudinal changes during dietary follow-up remain unclear. We described inflammatory profiles and examined associations of baseline ferritin and body composition with changes during a 32-week energy-restricted Mediterranean-style intervention. Methods: This prospective cohort included 190 adults classified as healthy overweight (n = 49), long COVID with overweight (n = 108), or metabolic syndrome (MS) with overweight (n = 33); 61 healthy normal-weight participants without long COVID or metabolic syndrome contributed to baseline comparisons only. The program prescribed a 30% energy deficit using a Mediterranean-style food-exchange system. Anthropometric, biochemical, inflammatory, lifestyle, and hepatic markers were assessed. MANOVA and multivariable regression examined inflammatory profiles and ferritin-change correlates. Results: Participants with overweight/obesity had a less favorable metabolic and inflammatory profile than normal-weight participants. Baseline ferritin was 100.5 (53.5–178.5), 76.0 (34.0–137.0), and 149.5 (102.0–245.0) ng/mL in the healthy overweight, long-COVID, and MS groups, respectively (omnibus p < 0.001). Mean changes were 8.0 ± 36.4, 3.3 ± 32.6, and −22.0 ± 58.8 ng/mL, respectively (omnibus p = 0.039), with the MS group showing greater decreases. Sex and muscle mass were associated with the multivariate inflammatory profile (both p < 0.001). Clinical group, baseline ferritin, muscle-mass change, MEDAS change, and Fatty Liver Index change were associated with ferritin change, although explanatory performance was limited (adjusted R² = 0.16). Conclusions: Baseline ferritin and body composition were correlates of heterogeneous inflammatory-metabolic profiles and ferritin changes. These hypothesis-generating associations do not establish causal or mechanistic effects and require controlled confirmation with comprehensive iron-status assessment.

Objective: Evaluate the association of APS and SLE, focusing on LN, with risk of pre-eclampsia (PE) and PE with severity criteria (PESC). Methods: Analysis of pregnant women admitted between 2016–2022, using data from the Spanish Hospital Discharge Database. Factors associated with PE and PESC, including early-onset PE, severe PE, eclampsia and HELLP syndrome were evaluated. Results: Among 1 973 249 admissions, 1787 patients had SLE (9.1‰), with prior LN in 13.2%. SLE patients experienced higher PE (5.5% vs 2.1%) and PESC (2.1% vs 0.6%) rates; these rose further in SLE women with LN alone (PE: 10.3%, PESC: 4.2%) or with both LN and APS (PE: 22.7%, PESC: 9.1%) . Adjusted analyses showed PE and PESC were each associated with SLE (OR = 1.78, 95% CI 1.39–2.28; OR = 2.17, 95% CI 1.47–3.22), LN (OR = 1.94, 95% CI 1.18–3.19; OR = 2.45, 95% CI 1.18–5.09) and APS (OR = 1.53, 95% CI 1.28–1.84; OR = 1.91, 95% CI 1.44–2.54). Within SLE patients, baseline hypertension (OR = 4.27, 95% CI 2.45–7.44), LN (OR = 2.06, 95% CI 1.26–3.37) and APS (OR = 1.85, 95% CI 1.03–3.32) were linked to PE, while LN alone predicted PESC (OR = 2.88, 95% CI 1.41–5.91). Conclusion: The risk of PE and PESC that patients with SLE exhibit is further amplified in those with a history of LN or APS. Recognizing SLE, APS and especially LN is crucial for precise risk stratification and tailored management to improve maternal and fetal outcomes.

Objective: To evaluate the impact of the different types of neoplasms and lineages on Sjögren syndrome (SjS) patient mortality. Methods: Medical records review study based on the Spanish Hospital Discharge Database and the International Classification of Diseases, Tenth Revision, Clinical Modification coding list. The neoplasm-related deaths in SjS patients with the general population during the period 2016–2019 were compared. A binary logistic regression analysis considering age, sex, tobacco use, and alcohol use was performed to determine the impact of SjS on the risk of dying from each neoplasm group and lineage. Results: In the period studied, 705,557 in-hospital deaths were certified in Spain, 139,531 (19.8%) from neoplasms. Neoplasms surpassed SjS activity as a cause of mortality in primary SjS patients (11.3% vs. 1.6%, p < 0.001). SjS patients presented higher mortality rates from small bowel carcinoma (0.3% vs. 1.8%; odds ratio [OR], 5.41; 95% confidence interval [CI], 1.33–22) and gynecological neoplasms (6.4% vs. 3%; OR, 2.13; 95% CI, 1.01–4.58), related to ovarian carcinomas (4.6% vs. 1.3%; OR, 3.65; 95% CI, 1.48–8.97), than the general population. Hematological neoplasm–related deaths were more prevalent in SjS patients than in the non-SjS population (18.3% vs. 8.9%; OR, 2.04; 95% CI, 1.25–3.31), mostly attributable to the higher proportion of deaths from B-cell non-Hodgkin lymphoma (8.3% vs. 2.5%; OR, 3.04; 95% CI, 1.54–6.03) and mucosa-associated lymphoid tissue lymphoma (1.8% vs. 0.1%; OR, 70.17; 95% CI, 16.61–296.36). Conclusion: SjS patients face an elevated risk of mortality from small bowel neoplasms, ovarian carcinomas, and B-cell and mucosa-associated lymphoid tissue lymphoma compared with the general Spanish population. Apart from developing approaches to mitigate their occurrence, it is crucial to explore thoroughly and consider the implementation of targeted early-detection programs for these specific conditions.

Patients with COVID-19 may develop a hypercoagulable state due to tissue and endothelial injury, produced by an unbalanced immune response. Therefore, an increased number of thromboembolic events has been reported in these patients. The aim of this study is to investigate the presence of antiphospholipid antibodies (aPL) in COVID-19 patients, their role in the development of thrombosis and their relationship with the severity of the disease. In this retrospective study, serum samples from 159 COVID-19 patients and 80 healthy donors were analysed for the presence of aPL. A total of 29 patients (18.2%) and 14 healthy donors (17.5%) were positive for aPL. Nineteen COVID-19 patients (12%) but no healthy donor presented a positive percentage of the IgA isotype aPL. IgA anti-β2-glycoprotein I antibodies (anti-β2GPI) were the most frequent type (6.3%) in patients but was not detected in any healthy donor. The positivity of this antibody was found to be significantly elevated in patients with thromboembolic events (25% vs. 5%, p = 0.029); in fact, patients with positive IgA anti-β2GPI had an incidence of thrombosis over six times higher than those who had normal antibody concentrations [OR (CI 95%) of 6.67 (1.5–30.2), p = 0.014]. Additionally, patients with moderate-severe disease presented a higher aPL positivity than patients with mild disease according to the Brescia (p = 0.029) and CURB-65 (p = 0.011) severity scales. A multivariate analysis showed that positivity for IgA anti-β2GPI is significantly associated with disease severity measured by CURB-65 [OR (CI 95%) 17.8 (1.7–187), p = 0.0016]. In conclusion, COVID-19 patients have a significantly higher positive percentage of the IgA isotype aPL than healthy donors. IgA anti-β2GPI antibodies were the most frequently detected aPL in COVID-19 patients and were associated with thrombosis and severe COVID-19 and are thus proposed as a possible marker to identify high-risk patients.

We aimed to evaluate the clinical outcome of Systemic Autoimmune Diseases (SADs) patients hospitalized with COVID-19 in Spain, before the introduction of SARS-CoV-2 vaccines. A nationwide, retrospective and observational analysis of the patients admitted during 2020, based on the ICD10 codes in the National Registry of Hospital Discharges, was performed. Among 117,694 patients, only 892 (0.8%) presented any type of SAD before COVID-19-related admission: Sjogren’s Syndrome constituted 25%, Systemic Vasculitides 21%, Systemic Lupus Erythematosus 19%, Sarcoidosis 17%, Systemic Sclerosis 11%, Mixed and Undifferentiated Connective Tissue Disease 4%, Behçet’s Disease 4% and Inflammatory Myopathies 2%. The in-hospital mortality rate was higher in SAD individuals (20% vs. 16%, p < 0.001). After adjustment by baseline conditions, SADs were not associated with a higher mortality risk (OR = 0.93, 95% CI 0.78–1.11). Mortality in the SADs patients was determined by age (OR = 1.05, 95% CI 1.04–1.07), heart failure (OR = 1.67, 95% CI 1.10–2.49), chronic kidney disease (OR = 1.29, 95% CI 1.05–1.59) and liver disease (OR = 1.97, 95% CI 1.13–3.44). In conclusion, the higher COVID-19 mortality rate seen in SADs patients hospitalized in Spain in 2020 was related to the higher burden of comorbidities, secondary to direct organ damage and sequelae of their condition. Whilst further studies should evaluate the impact of baseline immunosuppression on COVID-19 outcomes in this population, efforts should be focused on the optimal management of SAD to minimize the impact of the organ damage that has been shown to determine COVID-19 prognosis.

Background: the admission and death causes of SLE patients might have changed over the last years. Methods: Analysis of the Spanish National Hospital Discharge database. All individuals admitted with SLE, according to ICD-9, were selected. The following five admission categories were considered: SLE, cardiovascular disease (CVD), neoplasm, infection, and venous-thromboembolic disease (VTED), along four periods of time (1997–2000, 2001–2005, 2006–2010, and 2011–2015). Results: The admissions (99,859) from 43.432 patients with SLE were included. The absolute number of admissions increased from 15,807 in 1997–2000 to 31,977 in 2011–2015. SLE decreased as a cause of admission (from 47.1% to 20.8%, p < 0.001), while other categories increased over the time, as follows: 5% to 8.6% for CVD, 8.2% to 13% for infection, and 1.4% to 5.5% for neoplasm (p < 0.001 for all). The admission mortality rate rose from 2.22% to 3.06% (p < 0.001) and the causes of death evolved in parallel with the admission categories. A significant trend to older age was observed over time in the overall population and deceased patients (p < 0.001). Conclusions: Better control of SLE over the past two decades has led to a decrease in early admissions, and disease chronification. As a counterpart, CVD, infections, and neoplasm have become the main causes of admissions and mortality.

Objective To investigate the contribution of T lymphocytes and monocytes to cytokine production in systemic lupus erythematosus (SLE). Methods Forty‐five SLE patients and 19 healthy volunteers were included. Serum levels of tumor necrosis factor alpha (TNFα), interferon gamma (IFNγ), interleukin (IL)‐6, and IL10 were quantified by ELISA. The cytokine production capacities of peripheral blood mononuclear cells were assessed by culturing in vitro with PMA+Ionomycin or LPS. The intracellular cytokine expression was measured by flow cytometry in T lymphocytes and monocytes, respectively. The influence of the disease activity (measured as the SLE‐disease activity index; SLEDAI) and the treatment the patients were receiving was evaluated. Results Serum IL10, IL6, and TNFα levels were increased in patients (P ≤ 0.01), and a higher spontaneous (without stimuli) intracellular expression of IL10 in CD4+ and CD8+ T lymphocytes (P < 0.05) and of IL6 in monocytes (P = 0.01) were found. After stimulation, patients presented a higher percentage of CD4+ and CD8+ T lymphocytes producing IL4 and IL10 (P ≤ 0.01), and of monocytes producing IL6 (P = 0.04) and IL10 (P = 0.008). The SLEDAI score was positively correlated with the percentage of CD4+IL10+ and CD8+IL10+ T lymphocytes (P < 0.01), and inversely correlated with CD8+TNFα+ (P= 0.02), CD4+IFNγ+ (P = 0.04) and CD8+ IFNγ+ (P = 0.002) T lymphocytes. Patients receiving high dose prednisone produced higher IL10, but they also were the patients with a more active disease. Conclusion Monocytes and T lymphocytes (CD4+ and CD8+) contribute to an overproduction of IL6 and IL10 in SLE; this correlates with the disease activity but is independent of the treatment the patients are receiving. © 2009 Clinical Cytometry Society

Thirty three patients with SLE (26 women, 7 men) and 14 healthy volunteers matched for age and sex (11 women, 3 men) with a mean age of 39.9 and 36 years, respectively, were studied. All patients fulfilled at least four of the American College of Rheumatology 1982 revised criteria for the classification of SLE.⁶ Disease activity at the time of blood sampling was assessed using the SLE Disease Activity Index (SLEDAI).⁷ …