Survival, Mortality, Causes of Death and Risk Factors of Poor Outcome

Systemic sclerosis is a rare autoimmune disorder with a historically bad prognosis. Survival has been improving over time and we can currently estimate a 1-year survival, 94.9; a 5-year survival, 84.4; a 10-year survival, 70.9 and a 20-year survival, 44.9%, from the time of diagnosis. Accordingly, mortality has been decreasing over time, being the overall standardized mortality ratio (SMR) 2.72 (1.90–3.83), SMR 2.4 after 1990. Among the SSc-related causes of death, the lung death is the most important cause and its relative percentage is increasing over time since the introduction of ACE inhibitors for the treatment of scleroderma renal crisis (SRC) in early 1990s. Among the SSc-non-related causes of death, cancer, infection and cardiovascular disorders are the leading causes of death. Risk factor predictors of poor outcomes are an elder age at diagnosis, the male gender, diffuse subset, visceral involvement and non-Raynaud’s phenomenon onset

Calibración libre aplicada a la determinación de metales en muestras de la XXXIII campaña antártica mediante técnica láser

La espectrometría de descomposición inducida por láser (LIBS) es una técnica capaz de realizar un análisis multielemental de una manera rápida, sencilla y sin necesidad de tratamiento de muestra. Esta técnica cuenta con un amplio campo de aplicaciones, destacando el análisis medioambiental. En el presente trabajo se ha realizado una búsqueda bibliográfica de la técnica, se ha estudiado su fundamento y manejado la instrumentación analítica para tal fin. Además, se ha utilizado en la determinación de metales en filtros de material particulado antárticos. Como novedad se ha desarrollado una metodología que la convierte en un método analítico de respuesta rápida ya que no es necesario utilizar patrones de calibración, la calibración libre (CL). LIBS-CL es una técnica muy prometedora, a juzgar por los resultados del presente TFG, abriendo las puertas para innovar y utilizar otras estrategias que aumenten la sensibilidad de la técnica.Las muestras de filtros antárticos fueron observadas en el microscopio de barrido electrónico obteniendo unas fotografías en las que se detecta la presencia de metales y, en algún filtro, posible material biológico<br /

Hydroxychloroquine Myocardial Toxicity in a Patient with Systemic Lupus Erythematosus

Hydroxychloroquine is an antimalarial drug used in many rheumatologic and systemic diseases. Although considered by clinicians to be relatively safe, serious side effects have been documented (retinotoxicity, neuromyotoxicity and cardiotoxicity). We present the case of a 41-year-old woman with systemic lupus erythematosus (SLE) who presented at our institution with acute heart failure after taking hydroxychloroquine for a period of 3 months. An endomyocardial biopsy ruled out myocarditis related to systemic lupus erythematosus but demonstrated pathological changes related to hydroxychloroquine toxicity. It is exceptional to observe such cardiac toxicity after such a low cumulative dose (16 grams). The potential severity and reversibility of this complication underscores the importance of a high level of suspicion and timely diagnosis

Standardized incidence ratios and risk factors for cancer in patients with systemic sclerosis: Data from the Spanish Scleroderma Registry (RESCLE)

Anticentromere antibody; Cancer; Systemic sclerosisAnticuerpo anticentrómero; Cáncer; Esclerosis sistémicaAnticòs anticentròmer; Càncer; Esclerosi sistèmicaAim Patients with systemic sclerosis (SSc) are at increased risk of cancer, a growing cause of non–SSc-related death among these patients. We analyzed the increased cancer risk among Spanish patients with SSc using standardized incidence ratios (SIRs) and identified independent cancer risk factors in this population. Material and methods Spanish Scleroderma Registry data were analyzed to determine the demographic characteristics of patients with SSc, and logistic regression was used to identify cancer risk factors. SIRs with 95% confidence intervals (CIs) relative to the general Spanish population were calculated. Results Of 1930 patients with SSc, 206 had cancer, most commonly breast, lung, hematological, and colorectal cancers. Patients with SSc had increased risks of overall cancer (SIR 1.48, 95% CI 1.36–1.60; P < 0.001), and of lung (SIR 2.22, 95% CI 1.77–2.73; P < 0.001), breast (SIR 1.31, 95% CI 1.10–1.54; P = 0.003), and hematological (SIR 2.03, 95% CI 1.52–2.62; P < 0.001) cancers. Cancer was associated with older age at SSc onset (odds ratio [OR] 1.22, 95% CI 1.01–1.03; P < 0.001), the presence of primary biliary cholangitis (OR 2.35, 95% CI 1.18–4.68; P = 0.015) and forced vital capacity <70% (OR 1.8, 95% CI 1.24–2.70; P = 0.002). The presence of anticentromere antibodies lowered the risk of cancer (OR 0.66, 95% CI 0.45–0.97; P = 0.036). Conclusions Spanish patients with SSc had an increased cancer risk compared with the general population. Some characteristics, including specific autoantibodies, may be related to this increased risk.This work was financed in part by the Autoimmune Diseases Study Group of the Spanish Society of Internal Medicine

Multidisciplinary approach and long-term follow-up in a series of 640 consecutive patients with sarcoidosis: cohort study of a 40-year clinical experience at a tertiary referral center in Barcelona

Cohort studies of large series of patients with sarcoidosis over a long period of time are scarce. The aim of this study is to report a 40-year clinical experience of a large series of patients at Bellvitge University Hospital, a tertiary university hospital in Barcelona, Spain. Diagnosis of sarcoidosis required histological confirmation except in certain specific situations. All patients underwent a prospective study protocol. Clinical assessment and follow-up of patients were performed by a multidisciplinary team.From 1976 to 2015, 640 patients were diagnosed with sarcoidosis, 438 of them (68.4%) were female (sex ratio F/M 2:1). The mean age at diagnosis was 43.3 ± 13.8 years (range, 14-86 years), and 613 patients (95.8%) were Caucasian. At diagnosis, 584 patients (91.2%) showed intrathoracic involvement at chest radiograph, and most of the patients had normal pulmonary function. Erythema nodosum (39.8%) and specific cutaneous lesions (20.8%) were the most frequent extrapulmonary manifestations, but there was a wide range of organ involvement. A total of 492 patients (76.8%) had positive histology. Follow-up was carried out in 587 patients (91.7%), over a mean of 112.4 ± 98.3 months (range, 6.4-475 months). Corticosteroid treatment was administered in 255 patients (43.4%), and steroid-sparing agents in 49 patients (7.7%). Outcomes were as follows: 111 patients (18.9%) showed active disease at the time of closing this study, 250 (42.6%) presented spontaneous remission, 61 (10.4%) had remission under treatment, and 165 (28.1%) evolved to chronic sarcoidosis; among them, 115 (19.6%) with mild disease and 50 (8.5%) with moderate to severe organ damage. A multivariate analysis showed that at diagnosis, age more than 40 years, the presence of pulmonary involvement on chest radiograph, splenic involvement, and the need of treatment, was associated with chronic sarcoidosis, whereas Löfgren syndrome and mediastinal lymphadenopathy on chest radiograph were indicators of good outcome.Sarcoidosis is a multisystem disease with protean clinical-radiographic manifestations. Although almost half of patients follow a spontaneous resolution or under treatment, a significant number of them may have several degrees of organ damage. This study emphasizes the value of a multidisciplinary approach and long-term follow-up by specialized teams in sarcoidosis

Key Genes of the Immune System and Predisposition to Acquired Hemophilia A: Evidence from a Spanish Cohort of 49 Patients Using Next-Generation Sequencing

Acquired hemophilia A (AHA) is a rare bleeding disorder caused by the presence of autoantibodies against factor VIII (FVIII). As with other autoimmune diseases, its etiology is complex and its genetic basis is unknown. The aim of this study was to identify the immunogenetic background that predisposes individuals to AHA. HLA and KIR gene clusters, as well as KLRK1, were sequenced using next-generation sequencing in 49 AHA patients. Associations between candidate genes involved in innate and adaptive immune responses and AHA were addressed by comparing the alleles, genotypes, haplotypes, and gene frequencies in the AHA cohort with those in the donors' samples or Spanish population cohort. Two genes of the HLA cluster, as well as rs1049174 in KLRK1, which tags the natural killer (NK) cytotoxic activity haplotype, were found to be linked to AHA. Specifically, A*03:01 (p = 0.024; odds ratio (OR) = 0.26[0.06-0.85]) and DRB1*13:03 (p = 6.8 x 103, OR = 7.56[1.64-51.40]), as well as rs1049174 (p = 0.012), were significantly associated with AHA. In addition, two AHA patients were found to carry one copy each of the low-frequency allele DQB1*03:09 (nallele = 2, 2.04%), which was completely absent in the donors. To the best of our knowledge, this is the first time that the involvement of these specific alleles in the predisposition to AHA has been proposed. Further molecular and functional studies will be needed to unravel their specific contributions. We believe our findings expand the current knowledge on the genetic factors involved in susceptibility to AHA, which will contribute to improving the diagnosis and prognosis of AHA patients

The Use of Corticosteroids or Tocilizumab in COVID-19 Based on Inflammatory Markers

SEMI-COVID-19 Network.[Background] The inflammatory cascade is the main cause of death in COVID-19 patients. Corticosteroids (CS) and tocilizumab (TCZ) are available to treat this escalation but which patients to administer it remains undefined.[Objective] We aimed to evaluate the efficacy of immunosuppressive/anti-inflammatory therapy in COVID-19, based on the degree of inflammation. .[Design] A retrospective cohort study with data on patients collected and followed up from March 1st, 2020, to May 1st, 2021, from the nationwide Spanish SEMI-COVID-19 Registry. Patients under treatment with CS vs. those under CS plus TCZ were compared. Effectiveness was explored in 3 risk categories (low, intermediate, high) based on lymphocyte count, C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, and d-dimer values.[Patients] A total of 21,962 patients were included in the Registry by May 2021. Of these, 5940 met the inclusion criteria for the present study (5332 were treated with CS and 608 with CS plus TCZ).[Main Measures] The primary outcome of the study was in-hospital mortality. Secondary outcomes were the composite variable of in-hospital mortality, requirement for high-flow nasal cannula (HFNC), non-invasive mechanical ventilation (NIMV), invasive mechanical ventilation (IMV), or intensive care unit (ICU) admission.[Key Results] A total of 5940 met the inclusion criteria for the present study (5332 were treated with CS and 608 with CS plus TCZ). No significant differences were observed in either the low/intermediate-risk category (1.5% vs. 7.4%, p=0.175) or the high-risk category (23.1% vs. 20%, p=0.223) after propensity score matching. A statistically significant lower mortality was observed in the very high–risk category (31.9% vs. 23.9%, p=0.049).[Conclusions] The prescription of CS alone or in combination with TCZ should be based on the degrees of inflammation and reserve the CS plus TCZ combination for patients at high and especially very high risk.Peer reviewe

Ethnicity and Clinical Outcomes in Patients Hospitalized for COVID-19 in Spain: Results from the Multicenter SEMI-COVID-19 Registry

Background: This work aims to analyze clinical outcomes according to ethnic groups in patients hospitalized for COVID-19 in Spain. (2) Methods: This nationwide, retrospective, multicenter, observational study analyzed hospitalized patients with confirmed COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry) from 1 March 2020 to 31 December 2021. Clinical outcomes were assessed according to ethnicity (Latin Americans, Sub-Saharan Africans, Asians, North Africans, Europeans). The outcomes were in-hospital mortality (IHM), intensive care unit (ICU) admission, and the use of invasive mechanical ventilation (IMV). Associations between ethnic groups and clinical outcomes adjusted for patient characteristics and baseline Charlson Comorbidity Index values and wave were evaluated using logistic regression. (3) Results: Of 23,953 patients (median age 69.5 years, 42.9% women), 7.0% were Latin American, 1.2% were North African, 0.5% were Asian, 0.5% were Sub-Saharan African, and 89.7% were European. Ethnic minority patients were significantly younger than European patients (median (IQR) age 49.1 (40.5-58.9) to 57.1 (44.1-67.1) vs. 71.5 (59.5-81.4) years, p < 0.001). The unadjusted IHM was higher in European (21.6%) versus North African (11.4%), Asian (10.9%), Latin American (7.1%), and Sub-Saharan African (3.2%) patients. After further adjustment, the IHM was lower in Sub-Saharan African (OR 0.28 (0.10-0.79), p = 0.017) versus European patients, while ICU admission rates were higher in Latin American and North African versus European patients (OR (95%CI) 1.37 (1.17-1.60), p < 0.001) and (OR (95%CI) 1.74 (1.26-2.41), p < 0.001). Moreover, Latin American patients were 39% more likely than European patients to use IMV (OR (95%CI) 1.43 (1.21-1.71), p < 0.001). (4) Conclusion: The adjusted IHM was similar in all groups except for Sub-Saharan Africans, who had lower IHM. Latin American patients were admitted to the ICU and required IMV more often

C-Reactive Protein and Serum Albumin Ratio: A Feasible Prognostic Marker in Hospitalized Patients with COVID-19

Background: C-reactive protein (CRP) and albumin are inflammatory markers. We analyzed the prognostic capacity of serum albumin (SA) and CRP for an outcome comprising mortality, length of stay, ICU admission, and non-invasive mechanical ventilation in hospitalized COVID-19 patients. (2) Methods: We conducted a retrospective cohort study based on the Spanish national SEMI-COVID-19 Registry. Two multivariate logistic models were adjusted for SA, CRP, and their combination. Training and testing samples were used to validate the models. (3) Results: The outcome was present in 41.1% of the 3471 participants, who had lower SA (mean [SD], 3.5 [0.6] g/dL vs. 3.8 [0.5] g/dL; p < 0.001) and higher CRP (108.9 [96.5] mg/L vs. 70.6 [70.3] mg/L; p < 0.001). In the adjusted multivariate model, both were associated with poorer evolution: SA, OR 0.674 (95% CI, 0.551-0.826; p < 0.001); CRP, OR 1.002 (95% CI, 1.001-1.004; p = 0.003). The CRP/SA model had a similar predictive capacity (honest AUC, 0.8135 [0.7865-0.8405]), with a continuously increasing risk and cutoff value of 25 showing the highest predictive capacity (OR, 1.470; 95% CI, 1.188-1.819; p < 0.001). (4) Conclusions: SA and CRP are good independent predictors of patients hospitalized with COVID-19. For the CRP/SA ratio value, 25 is the cutoff for poor clinical course

Impact of Arterial Stiffness on All-Cause Mortality in Patients Hospitalized With COVID-19 in Spain

Older age and cardiovascular comorbidities are well-known risk factors for all-cause mortality in patients with coronavirus disease 2019 (COVID-19). Hypertension and age are the 2 principal determinants of arterial stiffness (AS). This study aimed to estimate AS in patients with COVID-19 requiring hospitalization and analyze its association with all-cause in-hospital mortality. This observational, retrospective, multicenter cohort study analyzed 12 170 patients admitted to 150 Spanish centers included in the SEMI-COVID-19 Network. We compared AS, defined as pulse pressure ≥60 mm Hg, and clinical characteristics between survivors and nonsurvivors. Mean age was 67.5 (±16.1) years and 42.5% were women. Overall, 2606 (21.4%) subjects died. Admission systolic blood pressure (BP) <120 and ≥140 mm Hg was a predictor of higher all-cause mortality (23.5% and 22.8%, respectively, P<0.001), compared with systolic BP between 120 and 140 mm Hg (18.6%). The 4379 patients with AS (36.0%) were older and had higher systolic and lower diastolic BP. Multivariate analysis showed that AS and systolic BP <120 mm Hg significantly and independently predicted all-cause in-hospital mortality (adjusted odds ratio [ORadj]: 1.27, P=0.0001; ORadj: 1.48, P=0.0001, respectively) after adjusting for sex (males, ORadj: 1.6, P=0.0001), age tertiles (second and third tertiles, ORadj: 2.0 and 4.7, P=0.0001), Charlson Comorbidity Index (second and third tertiles, ORadj: 4.8 and 8.6, P=0.0001), heart failure, and previous and in-hospital antihypertensive treatment. Our data show that AS and admission systolic BP <120 mm Hg had independent prognostic value for all-cause mortality in patients with COVID-19 requiring hospitalization