Higher mortality risk from gynaecological neoplasms and non-Hodgkin's lymphoma in patients with systemic lupus erythematosus: an observational study from the Spanish National Registry.

OBJECTIVE: To evaluate the impact of the different types of neoplasms and lineages on mortality of patients with SLE. METHODS: Retrospective and observational comparison of the neoplasm-related deaths in patients with SLE and the general Spanish population reported in the Spanish Hospital Discharge Database. To determine the impact of SLE on the risk of dying from each neoplasm lineage, a binary logistic regression considering age, female sex, tobacco and alcohol consumption, was performed. RESULTS: During 2016-2019, 139 531 in-hospital deaths from neoplasms were certified in Spain (91 in patients with SLE). Patients with SLE presented a lower mortality rate from solid organ neoplasms, (80.2% vs 91.1%, OR 0.393), linked to their lower risk of colorectal carcinoma (1.1% vs 10.8%, OR 0.110). By contrast, gynaecological neoplasms presented a higher risk (8.8% vs 3%, OR 3.039) in the deceased patients with SLE, associated with the higher frequency of vulvar neoplasms (2% vs 0.2%, OR 14.767) and cervical carcinomas (3.3% vs 0.5%, OR 3.809). Haematological neoplasm-related deaths were also more prevalent in patients with SLE (19.8% vs 8.9%, OR 2.546), mostly attributable to the higher proportion of deaths due to non-Hodgkin's lymphoma (11% vs 2.9%, OR 4.060) of B cell lineage (9.9% vs 2.5%, OR 4.133). CONCLUSIONS: Patients with SLE present a higher risk of death from vulvar neoplasms, cervical carcinomas and B-cell non-Hodgkin's lymphoma in comparison with the general Spanish population. In addition to developing strategies that might help to attenuate their occurrence and impact, such as decreasing the immunosuppressive burden, specific early detection programmes for these conditions should be investigated and considered carefully.

Sequential oral antibiotic in uncomplicated Staphylococcus aureus bacteraemia: a propensity-matched cohort analysis.

OBJECTIVES: We aimed to analyse the efficacy and safety of oral sequential therapy (OST) in uncomplicated Staphylococcus aureus bacteraemia (SAB). METHODS: Single-centre observational cohort at a tertiary hospital in Spain, including all patients with the first SAB episode from January 2015 to December 2020. We excluded patients with complicated SAB and those who died during the first week. Patients were classified into the OST group (patients who received oral therapy after initial intravenous antibiotic therapy [IVT]), and IVT group (patients who received exclusively IVT). We performed a propensity-score matching to balance baseline differences. The primary composite endpoint was 90-day mortality or microbiological failure. Secondary endpoints included 90-day SAB relapse. RESULTS: Out of 407 SAB first episodes, 230 (56.5%) were included. Of these, 112 (n = 48.7%) received OST and 118 (51.3%) IVT exclusively. Transition to oral therapy was performed after 7 days (interquartile range, 4-11). The primary endpoint occurred in 10.7% (11/112) in OST vs. 30.5% (36/118) in IVT (p < 0.001). SAB relapses occurred in 3.6% (4/112) vs. 1.7% (2/118) (p 0.436). None of the deaths in OST were related to SAB or its complications. After propensity-score matching, the primary endpoint was not more frequent in the OST group (relative risk, 0.42; 95% CI, 0.22-0.79). Ninety-day relapses occurred similarly in both groups (relative risk, 1.35; 95% CI, 0.75-2.39). DISCUSSION: After an initial intravenous antibiotic, patients with uncomplicated SAB can safely be switched to oral antibiotics without apparent adverse outcomes. This strategy could save costs and complications of prolonged hospital stays. Prospective randomized studies are needed.

Impact of severe infections in SLE: an observational study from the Spanish national registry.

OBJECTIVE: Infections are a common complication of SLE. Our objective was to evaluate their causes and impact on the survival of patients with SLE. METHODS: Analysis of the admissions and death causes in patients diagnosed with SLE from the Spanish Hospital Discharge Database and the infection-related deaths of the Spanish population from the National Statistical Institute, between 2016 and 2018.Only infections recorded as the main diagnosis were analysed (severe or clinically relevant infection). RESULTS: Among 18 430 admissions in patients with SLE, disease activity was the cause of admission in 19% of all patients and infection in 15%. However, infection was the main cause of death (25%) while SLE activity was responsible for only 6% of deaths (p<0.001). Severe infection exceeded SLE as a cause of death for patients dying at ages between 40-59 (23% vs 4%, p<0.001), 60-79 (26% vs 6%, p<0.001) and older than 80 years (25% vs 6%, p<0.001). Infection was the cause of death in 8% of the Spanish population, a significantly lower rate when compared with patients with SLE (p<0.001). Compared with the general population, infections were the highest relative cause of death in patients with SLE, particularly at younger ages: 40% vs 3% for those below 20 years old (p<0.01), 33% vs 4% between 20 and 39 (p<0.001), 23% vs 5% between 40 and 59 (p<0.001), 26% vs 5% between 60 and 79 (p<0.001) and 25% vs 9% for those older than 80 years (p<0.001). CONCLUSION: Our nationwide study confirms that infections are the leading cause of death in SLE in Spain, with the highest proportion occurring in young patients with lupus compared with the general population of the same age range.

Systemic Autoimmune Diseases in Patients Hospitalized with COVID-19 in Spain: A Nation-Wide Registry Study.

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.

Usefulness of the hemogram as a measure of clinical and serological activity in systemic lupus erythematosus.

Background and objectives: Systemic Lupus Erythematosus (SLE) follow-up is based on clinical, and analytical parameters. We aimed to determine the differences between the Neutrophil-to-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR) and Red blood cell distribution width (RDW) between SLE patients and healthy controls and to assess their association with anemia status, classical inflammatory biomarkers and cytokines, disease activity, SLE related factors and treatment received for SLE. Methods: Seventy-seven patients with SLE according to 2012 SLICC criteria and 80 healthy controls were included. Patients with SLE were classified in SLE with anemia (SLE-a) and SLE without anemia (SLE-na). Statistical analysis between SLE patients and controls and the association of serological and clinical activity markers with proposed hematological indices among SLE patients were performed. Results: RDW, NLR and PLR, were significantly higher in SLE patients than in healthy control group (p < 0.001), in SLE-a patients as compared to SLE-na (p < 0.0001) and were significantly associated with hypocomplementemia (p < 0.05). PLR was higher in active patients measured by SLEDAI-2K score and with longer disease duration (p < 0.05). RDW was associated with serological activity of the patients (p < 0.05) and was correlated with SLEDAI-2K and SLICC/ACR scores, hsCRP, D-dimer, fibrinogen, IL-6 and TNF as well as with corticosteroids intake (p = 0.05). A logistic regression analysis confirmed that after adjustment by age and hemoglobin values, RDW presented linear correlation with IL-6 levels (Beta-coefficient = 0.369, p = 0.003). Conclusion: NLR, PLR and RDW values suggest SLE serological and clinical activity. Given their availability, these markers not only could be useful tools to identify and monitor active SLE patients but whose application should be considered in inflammatory pathologies orchestrated by IL-6 and TNF.

Serum cytokines to predict systemic lupus erythematosus clinical and serological activity.

We aimed to explore the role of interleukin (IL)-6, interferon-gamma (IFNγ), IL-10, and tumor necrosis factor (TNF) as predictors of systemic lupus erythematosus (SLE) clinical and serological activity, and their correlation with the treatment received. We performed a retrospective analysis of 77 patients with SLE according to the 2012 Systemic Lupus International Collaborative Clinics (SLICC) criteria. The outcomes were serological activity (SA), active disease (AD), complete remission (CR), the low-disease activity state (LDAS), and immunosuppressive treatment. SA was present in 17.1%, AD in 17.3%, CR in 13%, and LDAS in 64.9% of patients. IL-6 values were higher in patients in SA, in AD, in those receiving steroids alone, and in patients without CR or LDAS (p < 0.05). IFNγ was associated with anti-double stranded DNA (dsDNA) antibodies positivity and immunosuppression, whereas IL-10 values were higher in patients with CR (p < 0.05). The IL6-IFN product was able to predict anti-double stranded DNA (anti-dsDNA) antibodies positivity (area under the receiver operating characteristic curve [AUC-ROC] = 0.705, 95% confidence interval [CI] 0.563-0.847), SA (AUC-ROC = 0.720, 95% CI 0.542-0.899), AD (AUC-ROC = 0.701, 95% CI 0.520-0.882), steroid treatment (AUC-ROC = 0.751, 95% CI 0.622-0.879), and the absence of LDAS (AUC-ROC = 0.700, 95% CI 0.558-0.834). The IL6-IFN/IL10 ratio predicted AD (AUC-ROC = 0.742, 955 CI 0.540-0.944), steroid treatment (AUC-ROC = 0.721, 95% CI 0.572-0.870), and the absence of LDAS (AUC-ROC = 0.694, 95% CI 0.536-0.853). In conclusion, IL-6, IL-10, and IFNγ might help to assess SLE serological and clinical activity. Their combination in the IL-6-IFN product and the IL-6xIFN to IL-10 ratio results in novel tools to determine and predict SA, AD, and LDAS. Prompt detection of SLE activity might allow a rapid intervention to avoid established or chronic damage.

Unreliability of Clinical Prediction Rules to Exclude without Echocardiography Infective Endocarditis in Staphylococcus aureus Bacteremia.

BACKGROUND: It is unclear whether the use of clinical prediction rules is sufficient to rule out infective endocarditis (IE) in patients with Staphylococcus aureus bacteremia (SAB) without an echocardiogram evaluation, either transthoracic (TTE) and/or transesophageal (TEE). Our primary purpose was to test the usefulness of PREDICT, POSITIVE, and VIRSTA scores to rule out IE without echocardiography. Our secondary purpose was to evaluate whether not performing an echocardiogram evaluation is associated with higher mortality. METHODS: We conducted a unicentric retrospective cohort including all patients with a first SAB episode from January 2015 to December 2020. IE was defined according to modified Duke criteria. We predefined threshold cutoff points to consider that IE was ruled out by means of the mentioned scores. To assess 30-day mortality, we used a multivariable regression model considering performing an echocardiogram as covariate. RESULTS: Out of 404 patients, IE was diagnosed in 50 (12.4%). Prevalence of IE within patients with negative PREDICT, POSITIVE, and VIRSTA scores was: 3.6% (95% CI 0.1-6.9%), 4.9% (95% CI 2.2-7.7%), and 2.2% (95% CI 0.2-4.3%), respectively. Patients with negative VIRSTA and negative TTE had an IE prevalence of 0.9% (95% CI 0-2.8%). Performing an echocardiogram was independently associated with lower 30-day mortality (OR 0.24 95% CI 0.10-0.54, p = 0.001). CONCLUSION: PREDICT and POSITIVE scores were not sufficient to rule out IE without TEE. In patients with negative VIRSTA score, it was doubtful if IE could be discarded with a negative TTE. Not performing an echocardiogram was associated with worse outcomes, which might be related to presence of occult IE. Further studies are needed to assess the usefulness of clinical prediction rules in avoiding echocardiographic evaluation in SAB patients.