Polyautoimmunity in systemic lupus erythematosus: secondary Sjogren syndrome.

BACKGROUND: Sjogren's syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands. It can be associated with other connective tissue diseases, including systemic lupus erythematosus (SLE). OBJECTIVE: This study aimed to determine the incidence of secondary SS (sSS) in patients diagnosed with SLE (SLE-SS) and compare the clinical and serological features of SLE-SS to SLE only. METHODS: A retrospective observational study including patients diagnosed with SLE (SLICC criteria) seen at the Rheumatology Department between 1990 and 2020 was performed. A total of 453 SLE patients were assessed for fulfilment of the criteria for SS using the European questionnaire and Schirmer test, fluorescein staining/non-stimulated whole-salivary flow, anti-Ro/La antibodies, and lip biopsy. Anti-Ro/SSA and anti-La/SSB antibodies and rheumatoid factor (RF) were measured at entry and at SS assessment. SLE-SS was defined according to the American-European Consensus Criteria (AECC). SLE-SS was defined as a case that initially only fulfilled SLE classification criteria but which exhibited disease progression during follow-up and then met classification criteria for sSS. RESULTS: SLE-SS occurred in 11% of the SLE patients. In comparison to SLE-only patients, the SLE-SS group was older at inclusion and onset, and had a longer disease course. Sicca syndrome, oral ulcers, pulmonary involvement, and peripheral neuropathy were more frequent. Anti-SSA, anti-SSB, RF, and total IgG were higher in the SLE-SS group. CONCLUSION: SLE-SS appears to be a subgroup of patients with distinct clinical and serologic features. The frequency of SLE-SS increases with age. Patients with SLE-SS have a higher frequency of oral ulcers, anti-Ro and anti-La antibodies, and a lower frequency of renal disease, anti-dsDNA antibodies, anti-SM, and lower C3 and C4 hypocomplementemia.

Factors Associated With Adverse Outcomes in Uveitis Related to Spondyloarthritis: Development of an Outcome Score (SpA-U).

BACKGROUND: Evaluating the efficacy and refractoriness to treatment and determining factors associated with adverse outcomes in uveitis associated with spondylarthritis (SpA) are complicated by the lack of validated outcome measures. OBJECTIVES: The aims of this study were to develop an outcome score SpA-U in patients with uveitis associated with SpA and to determine factors associated with adverse outcomes in patients with uveitis under systemic treatment. METHODS: The outcome score SpA-U was defined by best-corrected visual acuity, anterior chamber inflammation, macular edema and inflammation of posterior chamber, global assessment, and refractoriness to treatment. Factors associated with adverse outcomes in uveitis were studied using linear regression. For categorical factors, marginal averages and their SEs are displayed together with linear regression coefficients with 95% confidence intervals. For continuous factors, averages and SDs are reported in addition to linear regression coefficients with 95% confidence interval. Two regression coefficients are reported for each variable: unadjusted and adjusted for age at diagnosis and sex. RESULTS: One hundred ninety-seven uveitis outbreaks were included. Sixty-two uveitis outbreaks (31%) were classified as severe, 42 as moderate (21%), and 93 as mild (47%) based on the definition and construction of outcome score. The results of the linear regression model revealed that the uveitis activity was more severe in patients with smoking history ( ß = 0.34), axial and peripheral involvement ( ß = 0.43), Ankylosing Spondylitis Disease Activity Score >2.1 ( ß = 0.45), positive HLA-B27 ( ß = 0.29), female sex ( ß = 0.19), patients with C-reactive protein elevation ( ß = 0.002), and bilateral ocular involvement ( ß = 0.32). At the same time, shorter disease evolution ( ß = -0.02) was associated with less severe uveitis activity. CONCLUSION: We have determined factors associated with adverse outcomes in patients with uveitis associated with SpA by developing an outcome score SpA-U that integrates ocular inflammatory activity, visual acuity, global assessment, and refractoriness to treatment.

Anti-TNF-α-induced lupus syndrome : Two case reports and review of current literature.

Anti-tumor necrosis factor­α (TNF-α)-induced lupus (ATIL) represents a diagnostic and treatment challenge. Most cases are caused by infliximab and in some cases by etanercept and adalimumab. Symptoms can range from cutaneous manifestations to more rare and serious conditions. Diagnosis requires a temporal relationship between symptoms and positive autoantibody determination. Arthritis and cutaneous symptoms are the most common manifestations accompanied by positive antinuclear antibody (ANA) and anti-double strand DNA (dsDNA) determinations. The etiology of ATILS remains to be definitively established. Several mechanisms have been proposed for anti-TNF-α-induced lupus, including apoptosis, immunosuppression and humoral autoimmunity. Treatment includes discontinuation of anti-TNF­α agents and in some cases corticosteroids and immunosuppressors. Questions to be answered: (1) Are soluble TNF receptor fusion proteins such as etanercept and anti-TNF chimeric antibodies equally likely to cause ATIL? (2) Can patients with ATIL switch from one anti-TNF­α antagonist to another? (3) Can the concurrent use of a conventional synthetic disease-modifying antirheumatic drug (csDMARD) like methotrexate or hydroxychloroquine reduce the probability of ATIL?

Haplosporidium pinnae sp. nov., a haplosporidan parasite associated with mass mortalities of the fan mussel, Pinna nobilis, in the Western Mediterranean Sea.

This study provides morphological and molecular characterization of a new species, Haplosporidium pinnae), very likely responsible for mass mortality of fan mussels, Pinna nobilis, in the Western Mediterranean Sea. The parasite was found in dead or moribund P. nobilis but did not occur in healthy fan mussels from locations that were not affected by abnormal mortality. Histological examination of infected fan mussels showed uninucleate cells of a haplosporidan parasite throughout the connective tissue and hemolymph sinuses of the visceral mass and binucleate cells and, rarely, multinucleate plasmodia were also detected in the connective tissue. Additionally, stages of sporulation occurred in the epithelium of the host digestive gland tubules. Spores were slightly ellipsoidal with a hinged operculum in one pole. Typical haplosporosomes were not found with TEM but vesicles with two concentric membranes resembling haplosporosomes were abundant in the cytoplasm of the multinucleate plasmodia occurring in host digestive gland tubules. SEM analysis showed multiple structures on the spore surface; some spores had two or four long tape-like filaments attached to the spore wall. Phylogenetic analysis based on the SSU rDNA sequence placed this parasite within a large clade including species of the order Haplosporida, not in the Bonamia/Minchinia subclade or the subclade containing most Haplosporidium species, but within a subclade of Haplosporidium sp. from Penaeus vannamei. Our results suggested that H. pinnae and the parasite of P. vannamei may represent a distinct new genus within the order Haplosporida.

Juvenile- and adult-onset systemic lupus erythematosus: a comparative study in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER).

OBJECTIVES: We aimed to describe juvenile-onset systemic lupus erythematosus (jSLE) features and to establish its differences compared to adult-onset SLE (aSLE) from a large national database. METHODS: Data from patients (≥4 ACR criteria) included in Spanish Society of Rheumatology Lupus Registry (RELESSER) were analysed. Sociodemographic, clinical, serological, activity, treatment, cumulative damage, comorbidities and severity data were collected. Patients with disease onset <18 years were described and compared to those with disease onset ≥18 years. RESULTS: We reviewed 3,428 aSLE patients (89.6% women) and 484 jSLE patients (89.8% girls), 93% Caucasian (both groups). Mean age at diagnosis was 38.1±14 and 16.6±6.3 years (p<0.001) and mean age at the end of follow-up was 48.8±14.3 and 31.5±30 years (p<0.001), respectively. jSLE showed significantly more clinical (including lymphadenopathy, fever, malar rash, mucosal ulcers, pericarditis, pleuritis, Raynaud's phenomenon, lupus nephritis, recurrent nephritis, histologic nephritis changes, thrombocytopenia, haemolytic anaemia, thrombotic thrombocytopenic purpura, seizures, lupus headache and organic brain syndrome) and immunological (a-dsDNA and a-Sm antibodies, hypocomplementaemia) involvement than did aSLE, except for secondary Sjögren's syndrome, a-Ro antibodies, fibromyalgia and osteoporosis. jSLE also showed more SLE family history, longer diagnosis delay, higher SLEDAI and Katz scores, but lower Charlson scores than aSLE. Several specific domains were more frequently involved in SLICC/ACR DI in jSLE. jSLE patients more frequently underwent all SLE-related treatment and procedures, as well as dialysis and kidney transplantations. CONCLUSIONS: jSLE shares many clinical and serological features with aSLE. However, jSLE patients typically manifested more activity, severity, cumulative damage in certain areas, than their aSLE counterparts.

Fibromyalgia prevalence and related factors in a large registry of patients with systemic lupus erythematosus.

OBJECTIVES: The objective of this study is to determine the prevalence of fibromyalgia (FM) in systemic lupus erythematosus (SLE) patients and to study its relationship to depression and other SLE-related factors. METHODS: A cross-sectional data analysis from the RELESSER-Transversal Spanish Registry, which includes SLE patients in a national multicentre retrospective charts review, was performed. INCLUSION CRITERIA: patients who fulfilled ≥4 ACR 1997 SLE criteria. Main variables were disease duration, depression, sociodemographics, comorbidities, SLE activity symptoms, serological findings, therapies and different disease status indices. Statistical analyses included a descriptive, associative and logistic regression analyses. A literature review was performed. RESULTS: 3,591 SLE patients were included, 90.1% women, 34.6 years of age at diagnosis (SD 14.6 years) and 93.1% Caucasians. FM prevalence was 6.2%. SLE patients with disease duration >5 years showed more FM than those with duration <5 years: 6.9% vs. 4.0%, respectively (p<0.05). SLE-FM patients showed higher prevalence of depression compared to non-FM-SLE patients: 53.1% vs. 14.6%, respectively (p<0.001). After adjusting by risk factors, the OR (CI) of suffering depression in FM-SLE patients was 6.779 (4.770-9.636), p<0.001. The OR of having secondary Sjögren's 2.447 (1.662-3.604), p<0.001, photosensitivity 2.184 (1.431-3.334), p<0.001, and oral ulcers 1.436 (1.005-2.051), p=0.047. CONCLUSIONS: Prevalence of FM in Caucasian SLE patients was high compared to the general population, and was significantly higher in those in later stages of disease. SLE patients with depression showed a strong risk of developing FM. Photosensitivity, oral ulcers and secondary Sjögren's were the only SLE-related factors associated with FM.

The Pen Shell, Pinna nobilis: A Review of Population Status and Recommended Research Priorities in the Mediterranean Sea.

The pen shell Pinna nobilis (also known as the fan mussel) is an endemic bivalve of the Mediterranean Sea. Threatened by human activities, it has been listed as an endangered and protected species under the European Council Directive 92/43/EEC since 1992. The ecological role of this species is of importance because it filters and retains large amounts of organic matter from suspended detritus contributing to water clarity. In addition, as a hard substrate in the soft-bottom seafloor, it provides a surface that can be colonized by other (floral and faunal) benthic species. Here, we provide an overview of all available published studies on the pen shell, compiling available data and summarizing current knowledge on the conservation status and viability of populations over the full range of the Mediterranean Basin. Additionally, we discuss the different practices in applied methodology and identify gaps and new research areas in order to render conservation programmes of the species more effective.

The validity of recommendations from clinical guidelines: a survival analysis.

BACKGROUND: Clinical guidelines should be updated to maintain their validity. Our aim was to estimate the length of time before recommendations become outdated. METHODS: We used a retrospective cohort design and included recommendations from clinical guidelines developed in the Spanish National Health System clinical guideline program since 2008. We performed a descriptive analysis of references, recommendations and resources used, and a survival analysis of recommendations using the Kaplan-Meier method. RESULTS: We included 113 recommendations from 4 clinical guidelines with a median of 4 years since the most recent search (range 3.9-4.4 yr). We retrieved 39 136 references (range 3343-14 787) using an exhaustive literature search, 668 of which were related to the recommendations in our sample. We identified 69 (10.3%) key references, corresponding to 25 (22.1%) recommendations that required updating. Ninety-two percent (95% confidence interval 86.9-97.0) of the recommendations were valid 1 year after their development. This probability decreased at 2 (85.7%), 3 (81.3%) and 4 years (77.8%). INTERPRETATION: Recommendations quickly become outdated, with 1 out of 5 recommendations being out of date after 3 years. Waiting more than 3 years to review a guideline is potentially too long.

Cardiovascular disease in patients with systemic autoimmune diseases: The relationship between self-perceived risk and actual risk.

INTRODUCTION: Autoimmune diseases are known to be associated with an elevated risk of cardiovascular diseases; however, there exists a lack of awareness regarding this increased risk among patients. OBJECTIVE: This study aimed to assess the prevalence of cardiovascular risk factors and events in various systemic autoimmune diseases, including Systemic Sclerosis (SSc), Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), and Sjögren's syndrome (SS), matched by age, sex, and disease duration. Additionally, the study aimed to evaluate the perceived and actual risks of cardiovascular disease among patients. METHODS: A cross-sectional self-reported survey on the patient's perspective of cardiovascular risk was conducted between January and June 2023. Sociodemographic and clinical data, including disease activity, were collected through medical records and questionnaires. Traditional cardiovascular risk factors and events were assessed, alongside the perceived cardiovascular risk. The SCORE calculation and Charlson Comorbidity Index (CCI) were employed for cardiovascular risk assessment. RESULTS: Survey responses from 180 patients (45 patients each with SSc, SLE, RA, and SS) with systemic autoimmune diseases revealed that 20% perceived a low risk, 23% perceived neither lower nor higher, and 56% perceived a higher risk of developing cardiovascular diseases in the next ten years. Only 45% agreed that their autoimmune disease could increase the risk of a heart attack, even in the absence of other risk factors, and 46.7% were unaware that NSAIDs pose a cardiovascular risk. An association between cardiovascular risk measured by SCORE, comorbidities, and risk perception was observed in RA, SSc, and SS patients, with no association found in SLE patients (p=0.27). Except for SS patients (p=0.02), no association between CCI and disease activity level was found. Regarding the influence of age, working status, and education in CVD risk perception, an association between CVD risk perception and age was observed (p=0.01), with patients over 40 years exhibiting a higher perception of CVD risk. No differences were found regarding working status (p=0.19) nor education level (p=0.06). CONCLUSIONS: Patients with SS, RA, and SSc displayed a heightened perception of cardiovascular risk, correlating with their actual risk and preexisting comorbidities. However, patients exhibited unawareness of certain cardiovascular risk behaviors. This underscores the need for tailored education programs on cardiovascular risk for autoimmune disease patients, to be implemented at the time of diagnosis and during follow-up in outpatient clinics.

Screening of organic chemicals associated to virgin low-density polyethylene microplastic pellets exposed to the Mediterranean Sea environment by combining gas chromatography and liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry.

In this work, organic chemicals associated with microplastics (MPs) exposed to a coastal anthropogenized environment for up to eight weeks have been screened for, in order to discern the (de)sorption dynamics of chemicals in the marine ecosystem. Low-density polyethylene (LDPE) pellets were studied since they represent primary MPs used by the plastic industry and a relevant input of MPs into the oceans. To maximize the coverage of chemicals that could be detected, both liquid and gas chromatography coupled to quadrupole-time-of-flight (GC-QTOF and LC-QTOF, respectively) were used. In the case of LC-QTOF, an electrospray ionization source was employed, and the compounds were investigated by combining suspect and non-target screening workflows. The GC-QTOF was equipped with an electron ionization source and compounds were screened in raw and derivatized (silylated) extracts by deconvolution and contrast to high- and low-resolution libraries. A total of 50 compounds of multifarious classes were tentatively identified. Among them, melamine and 2-ethylhexyl salicylate (EHS) were detected in the original MPs but were rapidly desorbed. Melamine was completely released into the marine environment, while EHS was partly released but a portion remained bound to the MPs. On the other hand, many other chemicals of both anthropogenic (e.g. phenanthrene or benzophenone) and natural origin (e.g. betaine and several fatty acids) accumulated onto MPs over time. Quantification of 12 unequivocally identified chemicals resulted into a total concentration of 810 µg/kg after MPs exposure for 8 weeks.

Multidisciplinary consensus on the use of hydroxychloroquine in patients with systemic lupus erythematosus.

BACKGROUND: Hydroxychloroquine (HCQ) is the first-line treatment for systemic lupus erythematosus (SLE); however, there is heterogeneity in its clinical use. This consensus aims to bridge the gap in SLE treatment by providing practical and valuable recommendations for health professionals. METHODS: The methodology used is based on a systematic literature review and a nominal group technique (NGT). A ten-member scientific committee formulated eight clinically relevant questions. First, a systematic review was conducted to identify the available evidence, which the scientific committee evaluated to developed recommendations based on their expertise, achieving consensus through NGT. RESULTS: 1673 titles and abstracts were screened, and 43 studies were included for meeting the inclusion criteria. The scientific committee established 11 recommendations for HCQ use in initiation, maintenance, and monitoring, considering benefits and potential adverse effects of HCQ. Unanimous agreement was achieved on all recommendations. CONCLUSIONS: The available evidence supports HCQ's effectiveness and safety for SLE. Individualized assessment of the initial HCQ dose is important, especially in situations requiring dose reduction or discontinuation. This risk-benefit assessment, specifically focusing on the balance between retinal toxicity and the risk of SLE relapse, should guide decisions regarding medication withdrawal, considering disease activity, risk factors, and HCQ potential benefits. Close monitoring is essential for optimal disease management and minimize potential risks, such as QT prolongation or retinal toxicity.

KL6 and IL-18 levels are negatively correlated with respiratory function tests and ILD extent assessed on HRCT in patients with systemic sclerosis-related interstitial lung disease (SSc-ILD).

BACKGROUND: Interstitial lung disease (ILD) is one of the leading causes of mortality in patients with systemic sclerosis (SSc). Serum biomarkers have been suggested as indicators for pulmonary damage with clinical value in the diagnosis and prognosis of SSc-ILD. OBJECTIVES: To investigate the role of serum biomarkers (Krebs von den Lungen-6 KL-6, IL-18 and IL-18BP) as a potential biomarker reflecting the severity of SSc-ILD as assessed through high-resolution computed tomography (HRCT) and pulmonary function tests (PFT), including forced vital capacity (%FVC) and diffusing capacity of the lung for carbon monoxide (%DLCO). METHODS: A cross-sectional study including patients with SSc fulfilling the 2013 ACR/EULAR criteria was performed. Patients were classified according to disease duration and pulmonary involvement (presence of ILD). All SSc patients underwent chest HRCT scans and pulmonary function test at baseline. Serum concentration of KL-6, IL8 and IL18BP were determined using the quantitative ELISA technique, sandwich type (solid phase sandwich Enzyme Linked-Immuno-Sorbent Assay), with kits from MyBiosource for KL-6 and from Invitrogen for IL18 and IL18BP. A semiquantitative grade of ILD extent was evaluated through HRCT scan (grade 1, 0-20%; grade 2, >20%). Extensive disease was defined as >20% lung involvement on HRCT, and FVC <70% predicted and limited lung involvement as ≤20% ILD involvement on HRCT, and an FVC ≥70% predicted. RESULTS: 74 patients were included, 27% were male. The mean age at diagnosis was 57.5±15 years and the mean time since diagnosis was 7.67±8 years. 28 patients had ILD (38%). 64% of patients had <20% ILD extent classified through HRCT scan. SSc-ILD patients had elevated serum KL-6 and IL-18 levels compared to patients without ILD (p=0.003 and p=0.04), and those findings were preserved after adjusting for age and sex. Negative correlation between KL-6 levels and%FVC (ß=-0.25, p 0.037) and% DLCO (ß=-0.28, p 0.02) and between IL-18 levels and%FVC (ß=-0.38, p 0.001) and%DLCO (ß=-0.27, p 0.03) were found. Serum KL-6 and IL-18 levels successfully differentiated grades 1 and 2 of the semiquantitative grades of ILD extent (p = 0.028 and p = 0.022). Semiquantitative grades of ILD on the HRCT scan were significantly proportional to the KL-6 (p = 0.01) and IL-18 (p = 0.03). A positive correlation between extensive lung disease and KL-6 (ß=0.42, p = 0.007) but not with IL-18 was found. CONCLUSIONS: Serum KL-6 levels and IL-18 were increased in patients with SSc-ILD and showed a positive correlation with ILD severity as measured using a semiquantitative CT grading scale and negative correlation with PFT parameters. Serum KL-6 and IL-18 could be a clinically useful biomarker in screening and evaluating SSc-ILD.

Atypical Debut of Granulomatosis with Polyangiitis as Acute Tonsilitis and Strawberry Gum: A Case Report.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis characterized by necrosis, granulomatous inflammation, and vasculitis. It is characterized by the triad of the upper and lower respiratory system, lung, and kidney disease. Although it is usually a multisystemic disease, limited forms have also been described, and otolaryngological involvement is the first manifestation in up to 80-95% of the cases. CASE PRESENTATION: In this report, we describe the case of an ANCA negative patient with a limited form of GPA that presented a necrotic lesion confined to the right tonsil compatible with granulomatosis with polyangiitis, which later presented positive ANCA antibodies. Oral lesions may be the initial manifestation of GPA, and systemic involvement can be presented within weeks or months. Although the oral manifestations have been well described, the initial presentation with oral lesions is very rare, and presentation with oropharyngeal manifestation is even rarer. This disease is generally characterized by anti-neutrophil cytoplasmic antibodies (ANCA); however, there are rare cases with negative ANCA. CONCLUSION: The diagnosis was established based on the clinical presentation and the histopathological findings of the characteristic inflammatory pattern.

Clinical phenotype in scleroderma patients based on autoantibodies.

Objective: We aimed to characterize the clinical phenotype of patients with SSc based on autoantibodies (topoisomerase antibody (Scl-70), ACA and ANA). Methods: We included patients with SSc who fulfilled the 2013 ACR/EULAR criteria, with disease duration ≤15 years. Six groups of patients were defined: ACA-lcSSC, Scl-70-lcSSc, ANA-lcSSc, Scl-70-dcSSc, ANA-dcSSc and ACA-dcSSc patients. We compared the different groups of patients. In the ANA subgroup, we included patients negative for SSc-specific antibodies (Scl-70 and ACA). We assessed the following: risk of interstitial lung disease (ILD), myositis, scleroderma renal crisis, cardiac involvement, gastrointestinal involvement, pulmonary hypertension, treatment, cancer and all-cause mortality. Results: One hundred and thirteen SSc patients were included: 72 (64%) females, 82 (73%) lcSSc and 31 (27%) dcSSc. Among patients with lcSSc, 43 (52%) were ACA+, 16 (19%) Scl-70+ and 23 (28%) ANA+, and among patients with dcSSc, 13 (42%) patients were Scl-70+, 11 (35%) ANA+ and 7 (23%) ACA+. Scl-70-lcSSc patients had a significantly shorter time from RP to SSc diagnosis (P = 0.04), higher CRP (P = 0.04), renal scleroderma crisis (P = 0.02), ILD (P = 0.03) and diastolic dysfunction (P = 0.04) than ANA-lcSSc patients. Scl-70-dcSSc patients had a higher rate of myositis (P = 0.04), renal crisis (P = 0.03), CRP elevation (P = 0.002), ILD (P = 0.04), pericardial effusion (P = 0.03) and cancer (P = 0.04) than ANA-dcSSc patients. The risk of ILD was higher in Scl-70 patients during the first 10 years than in ACA+ and ANA+ patients (P = 0.03 and P = 0.02, respectively). The risk of major organ involvement was higher in Scl-70+ patients, followed by ANA+ and ACA+ patients, throughout 15 years of follow-up. All-cause mortality was higher in dcSSc patients than in lcSSc patients, but no differences were found regarding antibody positivity. Conclusion: We have characterized the clinical phenotype of patients based on autoantibodies: Scl-70 patients show the greatest risk of major organ involvement, followed by ANA+ patients and ACA+ patients. The risk of ILD in Scl-70+ patients suggests that these patients should be monitored closely, irrespective of skin involvement. These results might provide new ways to help with the early diagnosis and management and in assessment of the prognosis of the disease.

Risk factors for cardiovascular disease in primary Sjögren's syndrome (pSS): a 20-year follow-up study.

INTRODUCTION: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterized by a chronic grade of inflammation. Cardiovascular events represent the major causes of morbidity and mortality in patients with inflammatory rheumatic diseases; however, the significance and prevalence of cardiovascular disease in patients with pSS remain unclear. OBJECTIVE: To determine the clinical significance of cardiovascular disease in pSS and analyze the risk of cardiovascular disease according to glandular/extraglandular involvement and positivity to anti-Ro/SSA and/or anti-La/SSB autoantibodies. METHODS: A retrospective study including patients diagnosed with pSS fulfilling the 2016 ACR/EULAR classification criteria was followed and evaluated in our outpatient clinic between 2000 and 2022. The prevalence of cardiovascular risk factors with pSS was evaluated, and a possible association with clinical and immunological characteristics, the treatments received, and the impact on cardiovascular disease were determined. Univariate and multivariate regression analyses were performed in an attempt to determine potential risk factors associated with cardiovascular involvement. RESULTS: A total of 102 pSS patients were included. Eighty-two percent were female, with a mean age of 65±24 years and a disease duration of 12.5 ±6 years. Thirty-six patients (36%) had at least one cardiovascular risk factor. Arterial hypertension was diagnosed in 60 (59%) patients, dyslipidemia in 28 (27%), diabetes in 15 (15%), obesity in 22 (22%), and hyperuricemia in 19 (18%). History of arrhythmia was found in 25 (25%), conduction defects in 10 (10%), arterial peripheral vascular disease in 7 (7%), venous thrombosis in 10 (10%), coronary artery disease in 24 (24%), and cerebrovascular disease in 22 (22%) of patients. Patients with extraglandular involvement had a higher prevalence of arterial hypertension (p=0.04), dyslipidemia (p=0.003), LDL mean values (p=0.038), hyperuricemia (p=0.03), and coronary artery disease (p=0.01) after adjusting for age, sex, disease duration, and the significant variables in the univariate analysis. Patients with Ro/SSA and La/SSB autoantibodies had a substantially higher risk of hyperuricemia (p=0.01), arrhythmia (p=0.01), coronary artery disease (p=0.02), cerebrovascular disease (p=0.02), and venous thrombosis (p =0.03). In the multivariate logistic regression analysis, higher odds of cardiovascular risk factors were associated with extraglandular involvement (p=0.02), treatment with corticosteroids (p=0.02), ESSDAI>13 (p=0.02), inflammatory markers including ESR levels (p 0.007), and serologic markers such as low C3 levels (p=0.03) and hypergammaglobulinemia (p=0.02). CONCLUSIONS: Extraglandular involvement was associated with a higher prevalence of arterial hypertension, dyslipidemia, hyperuricemia, and coronary artery disease. Anti-Ro/SSA and anti-La/SSB seropositivity was associated with a higher prevalence of cardiac rhythm abnormalities, hyperuricemia, venous thrombosis, coronary artery disease, and cerebrovascular disease. Raised inflammatory markers, disease activity measured by ESSDAI, extraglandular involvement, serologic markers including hypergammaglobulinemia and low C3, and treatment with corticosteroids were associated with a higher risk for cardiovascular comorbidities. Key Points • Patients with pSS are vulnerable to cardiovascular risk factors. There is an interconnection between extraglandular involvement, disease activity, inflammatory markers, and cardiovascular risk comorbidities. • Anti-Ro/SSA and anti-La/SSB seropositivity was associated with a higher frequency of cardiac conduction abnormalities, coronary artery disease, venous thrombosis, and stroke. • Hypergammaglobulinemia, elevated ESR, and low C3 are associated with a higher prevalence of cardiovascular comorbidities. • Valid risk stratification tools to help with prevention and consensus on the management of CVDs in pSS patients are warranted.

Reduction of disease activity, corticosteroids use, and healthcare resource utilisation in patients with systemic lupus erythematosus treated with belimumab in clinical practice settings: OBSErve Spain multicentre study.

INTRODUCTION AND OBJECTIVES: This OBSErve Spain study, a part of the international OBSErve programme, evaluated belimumab real-world use and effectiveness following 6 months of treatment in patients with active systemic lupus erythematosus (SLE) in clinical practice in Spain. MATERIALS AND METHODS: In this retrospective, observational study (GSK Study 200883), eligible patients with SLE receiving intravenous belimumab (10mg/kg) had their disease activity (physician assessed), SELENA-SLEDAI scores, corticosteroid use, and healthcare resource utilisation (HCRU), assessed after 6 months of treatment versus index (belimumab initiation) or 6 months pre-index. RESULTS: Overall, 64 patients initiated belimumab, mainly due to ineffectiveness of previous treatments (78.1%) and to reduce corticosteroid use (57.8%). Following 6 months of treatment, 73.4% of patients achieved ≥20% overall clinical improvement, while only 3.1% of patients worsened. Mean (standard deviation, SD) SELENA-SLEDAI score decreased from 10.1 (6.2) at index to 4.5 (3.7) 6 months post-index. HCRU decreased from 6 months pre-index to 6 months post-index, with fewer hospitalisations (10.9% vs 4.7% patients) and ER visits (23.4% vs 9.4% patients). Mean (SD) corticosteroid dose decreased from 14.5 (12.5)mg/day at index to 6.4 (5.1)mg/day 6 months post-index. CONCLUSIONS: Patients with SLE receiving belimumab for 6 months in real-world clinical practice in Spain experienced clinical improvements and a reduction in HCRU and corticosteroid dose.

Are the seafloors of marine protected areas sinks for marine litter? Composition and spatial distribution in Cabrera National Park.

The seafloors of oceans and seas are becoming major sinks for marine litter (ML) at a global scale and especially within the Mediterranean Sea. Within global oceans and seas, Marine Protected Areas (MPAs) have been established to protect and conserve marine habitats and increase marine biodiversity. In this study, extensive coastal shallow scuba diving surveys were conducted in 2019 and 2020 to identify the distribution of ML in the MPA of Cabrera Marine-Terrestrial National Park (Cabrera MPA) in the Balearic Islands. Approximately 900 items weighing 70.1 kg were collected throughout the MPA during the underwater surveys. Glass bottles, including pieces (25-30%) and glass or ceramic fragments >2.5 cm (8-19%) were the most common identified items followed by plastic food containers and plastic bags (~8%). Overall, 75% of the abundance of collected ML was observed during the first year. In terms of the protection status of the different locations, similar abundances of ML were found in public access areas and no-take areas. Additionally, no significant differences were identified according to location indicating that ML on the seafloor was homogeneous within the studied shallow coastal areas. Overall, the results indicate that Cabrera MPA is a hotspot for ML and mitigation actions and measures, such as annual cleaning efforts, can help to prevent and minimize ML accumulation on the seafloor.

Spatial distribution of macro- and micro-litter items along rocky and sandy beaches of a Marine Protected Area in the western Mediterranean Sea.

In this study, the spatial distribution and physical characteristics of beach macro- and micro-litter within the Cabrera Archipelago Maritime-Terrestrial National Park (Cabrera MPA), in the Balearic Islands have been analysed. For macro-litter items, a mean concentration of 1.9 ± 2.4 items/m2 weighing a total of 13 kg was quantified. In terms of beach composition, cobble beaches with deposited seagrass had almost twice as much marine litter as other beaches. For beach micro-litter items, white and transparent microplastics within the size class of 1-2 mm were the most abundant on all the beaches, and the most common polymer types were polyethylene (64%) and polypropylene (17.2%). Overall, for both macro- and micro-litter items, plastic was the most dominant material (90%) identified on all beaches surveyed within Cabrera MPA, indicating areas of low anthropogenic pressures are increasingly becoming sinks for marine litter.

Factors associated with adverse pregnancy outcomes in patients with systemic lupus erythematosus.

BACKGROUND: Pregnancies in Systemic lupus erythematosus (SLE) are considered high risk and associated with maternal and obstetric complications. OBJECTIVES: To determine the most important predictors for each of the main adverse pregnancy outcomes in SLE patients. METHODS: Patients with SLE were retrospectively analysed from 1990 to 2020. Maternal and fetal complications in pregnant women with SLE were retrieved. We compared clinical and analytical characteristics of SLE patients with adverse pregnancy outcomes to controls with SLE diagnosis without adverse pregnancy outcomes. Qualitative data were analysed by Chi-square test and Fisher's exact test. Continuous variables were analysed by using Student's t test. Multiple logistic regression was performed to determine the predictive factors for adverse pregnancy outcomes with adjustment of confounding factors. RESULTS: 135 multiparous women were included (42% with adverse pregnancy outcomes). A total of 57 pregnancies (42%) were linked to adverse outcomes. The occurrence of abortion was correlated with anti-DNAds (ß = 0.71, p = 0.04), renal involvement (ß = 0.28, p 0.03), antiphospholipid antibodies (APA) (ß = 0.29, p 0.03), erythrocyte sedimentation rate (ESR) elevation (ß = 0.81, p = 0.02) and C-reactive protein (CPR) elevation (ß = 0.91, p = 0.01). Stillbirth was also correlated with renal involvement (ß = 0.26, p = 0.04), APA (ß = 0.22, p = 0.03) and ESR elevation (ß = 0.53, p = 0.02). Preeclampsia was correlated with direct Coombs positivity (ß = 0.42, p = 0.01), serositis (ß = 0.31, p = 0.02), ESR elevation (ß = 0.52, p = 0.03) and CPR elevation (ß = 0.32, p = 0.04). Neonatal Lupus was correlated with anti-RNP (ß = 0.16, p = 0.03) and anti-Ro/SSA (ß = 0.16, p 0.02). CONCLUSIONS: The most unfavourable pregnancy outcome in women with SLE was spontaneous abortion. Renal involvement, anti-DNAds positivity, antiphospholipid antibody positivity, anti-Ro/SSA, elevated ESR and a younger age at disease onset increased the risk of pregnancy complications.