Role of IP-10 to Predict Clinical Progression and Response to IL-6 Blockade With Sarilumab in Early COVID-19 Pneumonia. A Subanalysis of the SARICOR Clinical Trial.

Background: The Clinical Trial of Sarilumab in Adults With COVID-19 (SARICOR) showed that patients with coronavirus disease 2019 (COVID-19) pneumonia and increased levels of interleukin (IL)-6 might benefit from blockade of the IL-6 pathway. However, the benefit from this intervention might not be uniform. In this subanalysis, we sought to determine if other immunoactivation markers, besides IL-6, could identify which subgroup of patients benefit most from this intervention. Methods: The SARICOR trial was a phase II, open-label, multicenter, controlled trial (July 2020-March 2021) in which patients were randomized to receive usual care (UC; control group), UC plus a single dose of sarilumab 200 mg (sarilumab-200 group), or UC plus a single dose of sarilumab 400 mg (sarilumab-400 group). Patients who had baseline serum samples for cytokine determination (IL-8, IL-10, monocyte chemoattractant protein-1, interferon-inducible protein [IP]-10) were included in this secondary analysis. Progression to acute respiratory distress syndrome (ARDS) according to cytokine levels and treatment received was evaluated. Results: One hundred one (88%) of 115 patients enrolled in the SARICOR trial had serum samples (control group: n = 33; sarilumab-200: n = 33; sarilumab-400: n = 35). Among all evaluated biomarkers, IP-10 showed the strongest association with treatment outcome. Patients with IP-10 ≥2500 pg/mL treated with sarilumab-400 had a lower probability of progression (13%) compared with the control group (58%; hazard ratio, 0.19; 95% CI, 0.04-0.90; P = .04). Conversely, patients with IP-10 <2500 pg/mL did not show these differences. Conclusions: IP-10 may predict progression to ARDS in patients with COVID-19 pneumonia and IL-6 levels >40 pg/mL. Importantly, IP-10 value <2500 pg/mL might discriminate those individuals who might not benefit from sarilumab therapy among those with high IL-6 levels.

Early Use of Sarilumab in Patients Hospitalized with COVID-19 Pneumonia and Features of Systemic Inflammation: the SARICOR Randomized Clinical Trial.

The objective of this study was to investigate the efficacy and safety of early treatment with sarilumab, added to standard of care (SOC), in hospitalized adults with COVID-19. Methods included phase II, open-label, randomized, controlled clinical trial of hospitalized patients with COVID-19 pneumonia and interleukin (IL)-6 levels ≥ 40 pg/mL and/or d-dimer > 1,500 ng/mL. Participants were randomized (1:1:1) to receive SOC (control group), SOC plus a single subcutaneous dose of sarilumab 200 mg (sarilumab-200 group), or SOC plus a single subcutaneous dose of sarilumab 400 mg (sarilumab-400 group). The primary outcome variable was the development of acute respiratory distress syndrome (ARDS) requiring high-flow nasal oxygenation (HFNO), non-invasive mechanical ventilation (NIMV) or invasive mechanical ventilation (IMV) at day 28. One-hundred and 15 participants (control group, n = 39; sarilumab-200, n = 37; sarilumab-400, n = 39) were included. At randomization, 104 (90%) patients had supplemental oxygen and 103 (90%) received corticosteroids. Eleven (28%) patients in the control group, 10 (27%) in sarilumab-200, and five (13%) in sarilumab-400 developed the primary outcome (hazard ratio [95% CI] of sarilumab-400 vs control group: 0.41 [0.14, 1.18]; P = 0.09). Seven (6%) patients died: three in the control group and four in sarilumab-200. There were no deaths in sarilumab-400 (P = 0.079, log-rank test for comparisons with the control group). In patients recently hospitalized with COVID-19 pneumonia and features of systemic inflammation, early IL-6 blockade with a single dose of sarilumab 400 mg was safe and associated with a trend for better outcomes. (This study has been registered at ClinicalTrials.gov under identifier NCT04357860.).

Rapid immunoglobulin test confirms a suspected case of COVID-19 / El test rápido de inmunoglobulinas confirma un caso sospechoso de COVID-19

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DALBACEN cohort: dalbavancin as consolidation therapy in patients with endocarditis and/or bloodstream infection produced by gram-positive cocci.

OBJECTIVES: To analyse the effectiveness of dalbavancin (DBV) in clinical practice as consolidation therapy in patients with bloodstream infection (BSI) and/or infective endocarditis (IE) produced by gram-positive cocci (GPC), as well as its safety and pharmacoeconomic impact. METHODS: A multicentre, observational and retrospective study was conducted of hospitalised patients with IE and/or BSI produced by GPC who received at least one dose of DBV. Clinical response was assessed during hospitalization, at 3 months and at 1 year. RESULTS: Eighty-three patients with median age of 73 years were enrolled; 73.5% were male; 59.04% had BSI and 49.04% IE (44.04% prosthetic valve IE, 32.4% native IE, 23.5% pacemaker lead). The most frequently isolated microorganism was Staphylococcus aureus in BSI (49%) and coagulase-negative staphylococci in IE (44.1%). All patients with IE were clinically cured in hospital; at 12 months, there was 2.9% loss to follow-up, 8.8% mortality unrelated to IE, and 2.9% therapeutic failure rate. The percentage effectiveness of DBV to treat IE was 96.7%. The clinical cure rate for BSI was 100% during hospital stay and at 3 months; there were no recurrences or deaths during the follow-up. No patient discontinued treatment for adverse events. The saving in hospital stay was 636 days for BSI (315,424.20€) and 557 days for IE (283,187.45€). CONCLUSIONS: DBV is an effective consolidation antibiotic therapy in clinically stabilized patients with IE and/or BSI. It proved to be a cost-effective treatment, reducing the hospital stay, thanks to the pharmacokinetic/pharmacodynamic profile of this drug.

Comportamiento de la prueba KAtex en el cribado y diagnóstico de la leishmaniasis visceral en un hospital de referencia / Performance of the KAtex test in screening and diagnosis for visceral leishmaniasis in a reference hospital

Introducción. La utilización de pruebas diagnósticas simples empleando muestras no invasivas en el diagnóstico de la leishmaniasis visceral (LV) en nuestro entorno puede resultar muy útil, siendo necesario compararlas con los métodos tradicionales. El objetivo de este trabajo fue conocer la utilidad diagnóstica de la prueba KAtex en la orina de pacientes con sospecha de LV en nuestro medio. Material y métodos. De forma retrospectiva se revisaron las historias clínicas de los pacientes con sospecha de LV a los que se les realizó la prueba KAtex entre 2009 y 2015. Para la evaluación de su capacidad diagnóstica se seleccionaron los pacientes a los que se les había investigado la presencia del parásito en médula ósea. Resultados. De los 110 pacientes estudiados, en 44 (40%) se realizó biopsia de médula ósea para la investigación de Leishmania. En estos pacientes la sensibilidad de la prueba KAtex fue del 50%, la especificidad del 96,7%, el valor predictivo positivo del 87,5% y el valor predictivo negativo del 80,5%. Conclusiones. La sensibilidad de la antigenuria KAtex es demasiado baja para recomendarla como único método en la detección de LV en nuestro medio (AU)

Introduction. Performing of diagnostic test simple using samples not invasive in the diagnosis of visceral leishmaniasis (VL) may be very beneficial, being necessary comparing to traditional methods. The objective of this study was to know the reliability of test KAtex in the urine of patients with suspicion of VL. Material and methods. Retrospectively were reviewed the medical histories of patients with suspected of VL to which are performed the test between 2009 and 2015. For its analysis were selected the patients to which is them had made study of the parasite in bone marrow. Results. A total of 110 patients were studied, and bone marrow biopsy for research of Leishmania was performed in 44 (40%). In these patients the sensitivity of the test was 50%, the specificity of 96.7%, positive predictive value of 87.5% and negative predictive value of 80.5%. Conclusions. KAtex antigenuria sensitivity is too low recommending it as a unique method in the detection of VL in our medium (AU)

Sclerostin serum levels in patients with systemic autoimmune diseases.

Systemic autoimmune diseases (SADs) are associated with lower bone mass and an increased risk of fractures. Sclerostin has a pivotal role in bone metabolism. Available data on circulating sclerostin levels in healthy subjects are limited, whereas those in SAD patients are absent. Our objective was to determine circulating sclerostin concentrations in systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and Crohn's disease (CD) patients, and to analyze the factors associated with sclerostin concentrations. In this cross-sectional case-control study, serum sclerostin levels were measured in 38 SLE patients, 20 CD patients, 8 SSc patients and 20 healthy controls using a sclerostin ELISA. The mean values of the sclerostin (95% confidence interval) were 35.36 pmol l(-1) (12-101) in patients and 33.92 pmol l(-1) (2.31-100) in control subjects. The mean sclerostin value was 36.4 pmol l(-1) (22.1-48.5) in SLE patients, 26.7 pmol l(-1) (17.3-36.3) in CD patients and 51.8 pmol l(-1) (26.5-77.1) in SSc patients (P=0.001). Serum sclerostin levels were positively correlated with age (P<0.001), body mass index (BMI) (P=0.01) and lumbar spine Z-score (P=0.001) and negatively with creatinine clearance (P=0.001). Glucocorticoid treatment did not affect sclerostin levels. Sclerostin levels seem to have a heterogeneous pattern in different autoimmune diseases. SLE and SSc patients did not differ from healthy controls regarding sclerostin levels. The CD group had significantly lower values compared with SSc patients. Factors associated with sclerostin levels in autoimmune diseases seem to be the same than in the general population.

IFI44L promoter methylation as a blood biomarker for systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease with limited reliable diagnostic biomarkers. We investigated whether gene methylation could meet sensitivity and specificity criteria for a robust biomarker. METHODS: IFI44L promoter methylation was examined using DNA samples from a discovery set including 377 patients with SLE, 358 healthy controls (HCs) and 353 patients with rheumatoid arthritis (RA). Two independent sets including 1144 patients with SLE, 1350 HCs, 429 patients with RA and 199 patients with primary Sjögren's syndrome (pSS) were used for validation. RESULTS: Significant hypomethylation of two CpG sites within IFI44L promoter, Site1 (Chr1: 79 085 222) and Site2 (Chr1: 79 085 250; cg06872964), was identified in patients with SLE compared with HCs, patients with RA and patients with pSS. In a comparison between patients with SLE and HCs included in the first validation cohort, Site1 methylation had a sensitivity of 93.6% and a specificity of 96.8% at a cut-off methylation level of 75.5% and Site2 methylation had a sensitivity of 94.1% and a specificity of 98.2% at a cut-off methylation level of 25.5%. The IFI44L promoter methylation marker was also validated in an European-derived cohort. In addition, the methylation levels of Site1 and Site2 within IFI44L promoter were significantly lower in patients with SLE with renal damage than those without renal damage. Patients with SLE showed significantly increased methylation levels of Site1 and Site2 during remission compared with active stage. CONCLUSIONS: The methylation level of IFI44L promoter can distinguish patients with SLE from healthy persons and other autoimmune diseases, and is a highly sensitive and specific diagnostic marker for SLE.

Bone mass and vitamin D in patients with systemic sclerosis from two Spanish regions.

OBJECTIVES: To study the bone mass in patients with scleroderma (SSc) from two different Spanish regions and to evaluate the prevalence of vitamin D deficiency and insufficiency in this population and its possible relation to bone mineral density (BMD). METHODS: Disease, bone mineral density related variables and vitamin D were collected from all patients. Statistical analysis was carried out using the SPSS 17 statistics software for Windows. A p<0.05 was considered significant. RESULTS: A Z-score <-1 was found in 21.9% of the control population and 43% of SSc patients. The prevalence of osteopenia/osteoporosis was 50% in the control population and 77% in SSc (p<0.0001). We did not find differences between the prevalence of low BMD in the south (79%) and in the north of Spain (76.3%); but patients from the north had lower levels of vitamin D (27.4±16.2 ng/dL vs. 20.7±11.0 ng/dl; p<0.031). Low levels of vitamin D (<30ng/ml) were found in 69 patients out of 90, ten of them with insufficiency (<10ng/ml). Eighty-four point six percent of the patients with low levels of vitamin D (<30ng/ml) had LBMD compared whith 66.7% of those with normal levels (p=0.073). CONCLUSIONS: The prevalence of osteoporosis/osteopenia in Spanish patient with SSc is very high. Although there are a high prevelence of vitamin D deficiency, we could not demonstrate a relationship of vitamin D deficiency with low mineral density.

Síndrome de Sjögren primario y edema en las manos / Primary Sjogren syndrome and hands edema

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Uveítis recidivante y enfermedad celíaca / Relapsing uveitis and celiac disease

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