Riesgo de mortalidad en candidemia en niños oncohematológicos: revisión sistemática / Mortality risk in candidemia in children with cancer and blood disorders: a systematic review

Introducción: La tasa de mortalidad de la candidemia es variable, pero puede estar influenciada por la patología de base, en especial aquella que condiciona la presencia de neutropenia. En niños con patología oncohematológica, son pocos los trabajos que han abordado la mortalidad relacionada a candidemias y sus factores asociados. Las preguntas que promueven esta revisión sistemática, son: ¿Cuáles son las características epidemiológicas, clínicas y de evolución de los pacientes pediátricos oncohematológicos con candidemia? ¿Cuál es la mortalidad relacionada con esta entidad? Materiales y métodos: Revisión sistemática de la literatura. Se utilizaron los siguientes términos de búsqueda: candidemia por Candida spp. y los siguientes filtros humanos, niños y adolescentes y patología oncohematológica. Se revisaron los artículos publicados en inglés, español o francés hasta el 21 de septiembre de 2023. Las referencias bibliográficas de los artículos incluidos se revisaron manualmente para identificar estudios relevantes adicionales. Resultados: Se encontraron 66 artículos. Del análisis cualitativo realizado en sus textos completos, quedaron finalmente 4 estudios que se consideró que cumplían con los criterios de inclusión. Todos los artículos seleccionados sumaron 191 pacientes con diversas patologías oncohematológicas. La presencia de accesos vasculares fue frecuente en esta serie y la no extracción del catéter venoso central fue el factor más prevalente entre los que fallecieron. El agente infectante predominante fue Candida no albicans y la mortalidad osciló entre el 11,3 y el 31% con una mediana de 25%. No fue posible establecer si la especie de Candida influía en la letalidad

Introduction: The mortality rate of candidemia is variable, but may be influenced by underlying diseases, especially those causing neutropenia. In children with cancer and blood disorders, few studies have addressed mortality related to candidemia and its associated factors. The questions that motivated this systematic review were: What are the epidemiological, clinical and outcome characteristics of pediatric cancer patients with candidemia? What is the mortality related to this condition? Materials and methods: Systematic review of the literature. The following search terms were used: Candida spp., candidemia, with the following filters: human, children and adolescents, and cancer and blood disorders. Articles published in English, Spanish, or French up to September 21, 2023 were reviewed. References of included articles were manually reviewed to identify additional relevant studies. Results: 66 articles were identified. From the qualitative analysis carried out on their full texts, 4 studies that were considered to meet the inclusion criteria were finally selected. The selected articles included a total of 191 patients with various types of cancer and blood disorders. The presence of vascular access was common in this series and failure to remove the central venous catheter was the most prevalent factor among those who died. The predominant infectious agent was non-albicans Candida and mortality ranged from 11.3% to 31% with a median of 25%. It was not possible to establish whether Candida species influenced mortality.

Riesgo de mortalidad en infecciones invasivas por Mucor SPP. en niños con enfermedades hemato-oncológicas: revisión sistemática / Mortality risk of invasive Mucor spp. infections in children with cancer: A systematic review

Los estudios sobre la infección fúngica invasiva (IFI) por Mucor spp. en pacientes pediátricos con patología hematooncológica, son de baja solidez científica, lo que dificulta conocer en profundidad sus características y evolución. Con el objetivo de analizar la evolución fatal de esos pacientes, se llevó a cabo esta revisión sistemática (RS). Material y métodos: La búsqueda bibliográfica se realizó con fecha 23 de marzo de 2023, en las principales bases de datos (Medline (a través de Pubmed), Embase (a través de Embase-Elsevier), The Cochrane Library (a través de Wiley), Cinahl (a través de Ebsco HOST), SCI-EXPANDED, SciELO (a través de la WOS) y Scopus (a través de Scopus-Elsevier), libre (mediante el motor Google) y revisando las citas de los artículos incluidos. Resultados: Se rescataron 1393 artículos, de los cuales se descartaron 1386 por diversas razones. Mediante el análisis de los textos completos, finalmente se incluyeron 7 estudios. Todos los estudios eran series de casos (nivel 4). La mediana de la frecuencia de muerte observada fue de 36,6% (Q1 20% - Q347%). Conclusiones: Esta RS mostró en niños con patología hemato-oncológica, que la mortalidad por IFI por Mucor spp. alcanzó a casi un tercio de los pacientes (AU)

Studies on invasive fungal infection (IFI) by Mucor spp. in pediatric patients with cancer have a low level of evidence, which makes it difficult to elucidate its characteristics and progression. To analyze the fatal outcome of these patients, this systematic review (SR) was conducted. Material and methods: A literature search was carried out on March 23, 2023, in the following main databases (Medline (via Pubmed), Embase (via Embase-Elsevier), The Cochrane Library (via Wiley), Cinahl (via Ebsco HOST), SCI-EXPANDED, SciELO (via the WOS) and Scopus (via Scopus-Elsevier). Additionally, a complementary search was carried out using free search engines (such as Google) and by reviewing the references of the included articles. Results: A total of 1393 articles were retrieved, of which 1386 were excluded for various reasons. After a thorough analysis of the full-text articles, 7 studies were ultimately included in the review. All studies were case series (level 4). The median observed death rate was 36.6% (IQR, 20% - 47%). Conclusions: This SR showed that in children with hematological-oncological disease, mortality due to IFI by Mucor spp. affected almost one third of the patients (AU)

Factores estresantes en progenitores de neonatos ingresados en una Unidad de Cuidados Intensivos / Stress factors in parents of newborns admitted to an Intensive Care Unit

Introducción y objetivo. El estrés ocasionado por el ingreso de un recién nacido altera la dinámica y estructura de la unidad familiar. El objetivo de este estudio es analizar los factores estresantes percibidos por los padres/ madres de recién nacidos ingresados en una Unidad de Cuidados Intensivos Neonatales. Método. Estudio descriptivo transversal realizado en la Unidad de Neonatología del Hospital Universitario Río Hortega de Valladolid durante un periodo de un año. Se incluyeron a los padres/madres de recién nacidos ingresados en Unidad de Cuidados Intensivos durante más de 48 horas, obteniendo un total de 60 pacientes. Se recogieron variables sociodemográficas y clínicas de los progenitores y del recién nacido, y se aplicó la traducción y adaptación propia de la Escala de estrés parental. La participación en el estudio fue de manera voluntaria. Resultados. El nivel de estrés general obtenido para madres y padres fue entre moderado y extremadamente estresante (78,1%), siendo las madres las que mostraron niveles de estrés más elevados en los rangos superiores, con un 50% entre muy estresante y extremadamente estresante, mientras que los padres se mantuvieron en niveles moderados con un 42,4%. La subescala más afectada tras la evaluación de la Escala de estrés parental fue rol parental, concretamente el factor separación madre/padrerecién nacido (65,6% entre muy y extremadamente estresante). Encontramos significancia estadística (p< 0,021) al relacionar el nivel de estrés general con la distancia en kilómetros desde el hospital al domicilio. Conclusión. La hospitalización de un recién nacido genera estrés y ansiedad en los padres/madres alterando el vínculo afectivo (AU)

Introduction and objective. The stress caused by the admission of a newborn alters the dynamics and structure of the family unit. The objective of this study is to analyze to analyze the stressors perceived by parents of newborns admitted to a Neonatal Intensive Care Unit. Methods. Descriptive cross-sectional study carried out in the Neonatol Unit of Río Hortega University Hospital in Valladolid, during a one-year period. It included parents of newborns admitted to the Neonatal Intensive Care Unit for more than 48 hours, obtaining a total of 60 patients. Sociodemographic and clinical variables of the parents and newborns were collected and the translation and adaptation of the Parental Stressor Scale was applied. Participation in the study was voluntary. Results. The general stress level obtained for mothers and fathers was moderate to extremely stressful (78.1%), it is the mothers that show the highest stress levels in the upper ranges, with 50% of them between very stressful and extremely stressful; while fathers remained at moderate levels with 42.4%. The most affected subscale after the evaluation of the Parental Stressor Scale was the parental role, specifically the mother/father-newborn separation factor (65.6% between very and extremely stressful). The was a statistically significant association (p< 0.021) between general stress and distance from residency to hospital (AU)

Mortalidad en niños con bacteriemia por Stenotrophomonas maltophilia: revisión sistemática / Mortality in children with Stenotrophomonas maltophilia-related bacteremia: A systematic review

Introducción: En los niños, la bacteriemia por Stenotrophomonas maltophilia es considerada una complicación severa y asociada a una elevada mortalidad. Con el objetivo de conocer la mortalidad asociada a esa condición, se realizó una revisión sistemática de la literatura. Material y métodos: Se aplicó una estrategia de búsqueda bibliográfica con las palabras clave: bacteriemia por Stenotrophomonas maltophilia, niños y adolescentes como únicos filtros. Se informan la mediana y los valores intercuartílicos de la frecuencia de la mortalidad reportada por los estudios incluidos. Resultados: Se identificaron 165 estudios potencialmente útiles. De ellos, se seleccionaron finalmente, 9 estudios para ser incluidos. La incidencia de mortalidad a consecuencia de una bacteriemia por S.maltophilia fue del 25%; Q25: 11­Q75: 36; rango: 6,06 a 40,6. Consideraciones finales: La bacteriemia por Sm tuvo un alto porcentaje de mortalidad en especial en pacientes con patología subyacente y uso de procedimientos invasivos y el uso inadecuado de antibióticos empíricos (AU)

Introduction: In children, Stenotrophomonas maltophilia-related bacteremia is considered a severe complication associated with high mortality. With the aim to determine the mortality associated with this condition, a systematic review of the literature was conducted. Material and methods: A literature search strategy was applied using the keywords: bacteremia due to Stenotrophomonas maltophilia, children, and adolescents as the only filters. The median and interquartile ranges of the mortality rates described in the studies included are reported. Results: A total of 165 potentially useful studies were identified, of which nine were finally selected to be included in the analysis. The incidence of S.maltophilia bacteremia-related mortality was 25%; Q25: 11­Q75: 36; range: 6.06 to 40.6. Final considerations: S.maltophilia-related bacteremia was associated with a high mortality rate especially in patients with an underlying disease, when invasive procedures were performed, and when emperical antibiotics were inadequately used (AU)

¿Es la fibromialgia causa de fracaso de una descompresión subacromial artroscópica? / Is fibromyalgia a cause of arthroscopic subacromial decompression failure?

La descompresión subacromial artroscópica aislada (DSA) es un procedimiento quirúrgico ampliamente utilizado que presenta un elevado porcentaje de éxito. Sin embargo, hasta un 25% de los pacientes puede presentar dolor residual tras la intervención. No está claro si el procesamiento aberrante del dolor, como ocurre en la fibromialgia (FM), podría ejercer un efecto deletéreo en los resultados obtenidos. Para testar esta hipótesis hemos realizado un estudio casos-controles retrospectivo de los pacientes en los que se ha realizado una descompresión subacromial artroscópica como procedimiento quirúrgico único. Material y métodos: Se seleccionaron 26 pacientes con diagnóstico preoperatorio de fibromialgia de una serie de 293 pacientes intervenidos mediante DSA entre 2008-2015. Seis pacientes se perdieron durante el seguimiento. Cada paciente con diagnóstico de fibromialgia fue emparejado con un control (n=20). Los resultados fueron evaluados mediante la escala DASH, Constant, Constant relativo a la edad y sexo (rCS) y la escala visual analógica (EVA). La satisfacción del paciente fue evaluada con una pregunta dicotómica. Se consideró fracaso del procedimiento la presencia de una puntuación superior a 3 en la EVA en el último seguimiento. Resultados: La media de edad de los grupos FM/control fue de 51/48 años, con un seguimiento medio de 36/42 meses respectivamente. Ambos grupos experimentaron una mejoría postoperatoria significativa en las escalas de EVA, DASH y rCS (p<0,001) en comparación con los valores preoperatorios. Los valores medios postoperatorios FM/control fueron Constant 63,5/74 (p=0,07), rCS 82/88 (p=0,18), DASH 38,9/20,7 (p=0,009), EVA 3,8/2,8 (p=0,2). El 85% de los pacientes del grupo control manifestaron estar satisfechos con los resultados de la cirugía frente al 55% del grupo FM (p=0,03). La tasa de fracasos en el grupo FM fue del 60% frente al 30% en el grupo control (p=0,056). Conclusiones: La fibromialgia puede ser considerada como factor pronóstico que condiciona un peor resultado postoperatorio tras DSA. Sin embargo, debido a la mejoría clínica que experimentan estos pacientes frente a su estado preoperatorio, recomendamos realizar este tratamiento quirúrgico cuando exista indicación

Isolated arthroscopic subacromial decompression (IASD) is a widely used surgical procedure with high success rates. However, up to 25% of patients experience residual pain. It is unclear whether aberrant central nervous system processing of pain as described in fibromyalgia (FM) could have a detrimental effect on outcomes. To test this hypothesis, the authors conducted a retrospective case- control study of patients undergoing IASD. Material and methods: Between 2008 and 2015, 26 patients with preoperative diagnosis of fibromyalgia and an IASD procedure were identified. Six patients were lost to follow-up. Each fibromyalgia patient was matched with one control patient (n=20) recruited from the remainder with IASD. Outcomes were assessed by DASH score (Disability Arm Shoulder and Hand), Constant (CS), relative Constant score (rCS) and Visual Analogue Scale (VAS). Patient satisfaction was determined with a single 2-level question. Failure of the IASD was defined as persistent pain (VAS>3) at last follow-up. Results: The average age of the sample was FM/Control group 51/48, with a mean follow-up of 36/42 months respectively. Both groups exhibited significant clinical improvement in the pain VAS, DASH and rCS at final follow-up (P<.001) compared with the preoperative scores. Mean postoperative scores FM/Control group were: Constant 63.5/74 (P=.07), rCS 82/88 (P=.18), DASH 38.9/20.7 (P=.009), VAS 3.8/2.8 (P=.2). Eighty-five percent of patients in the control group were satisfied with the surgery compared with 55% in the FM group (P=.03). Failure of the procedure was 60% in the FM group, and 30% in the control group (P=.056). Conclusions: Fibromyalgia can be considered a prognostic factor of a poor postoperative outcome after an IASD. However the clinical improvement experienced by these patients over their preoperative situation leads us to recommend their surgical treatment when indicated

Is fibromyalgia a cause of arthroscopic subacromial decompression failure? / ¿Es la fibromialgia causa de fracaso de una descompresión subacromial artroscópica?

Isolated arthroscopic subacromial decompression (IASD) is a widely used surgical procedure with high success rates. However, up to 25% of patients experience residual pain. It is unclear whether aberrant central nervous system processing of pain as described in fibromyalgia (FM) could have a detrimental effect on outcomes. To test this hypothesis, the authors conducted a retrospective case- control study of patients undergoing IASD. MATERIAL AND METHODS: Between 2008 and 2015, 26 patients with preoperative diagnosis of fibromyalgia and an IASD procedure were identified. Six patients were lost to follow-up. Each fibromyalgia patient was matched with one control patient (n=20) recruited from the remainder with IASD. Outcomes were assessed by DASH score (Disability Arm Shoulder and Hand), Constant (CS), relative Constant score (rCS) and Visual Analogue Scale (VAS). Patient satisfaction was determined with a single 2-level question. Failure of the IASD was defined as persistent pain (VAS>3) at last follow-up. RESULTS: The average age of the sample was FM/Control group 51/48, with a mean follow-up of 36/42 months respectively. Both groups exhibited significant clinical improvement in the pain VAS, DASH and rCS at final follow-up (P<.001) compared with the preoperative scores. Mean postoperative scores FM/Control group were: Constant 63.5/74 (P=.07), rCS 82/88 (P=.18), DASH 38.9/20.7 (P=.009), VAS 3.8/2.8 (P=.2). Eighty-five percent of patients in the control group were satisfied with the surgery compared with 55% in the FM group (P=.03). Failure of the procedure was 60% in the FM group, and 30% in the control group (P=.056). CONCLUSIONS: Fibromyalgia can be considered a prognostic factor of a poor postoperative outcome after an IASD. However the clinical improvement experienced by these patients over their preoperative situation leads us to recommend their surgical treatment when indicated.

Comparison of corneal biomechanical properties of patients with dry eye secondary to Sjögren's syndrome and healthy subjects.

PURPOSE: The goal of this study is to determine whether any difference in corneal biomechanical properties exists between Sjögren's syndrome dry eye patients and healthy subjects. METHODS: Thirty-one patients diagnosed with Sjögren's syndrome and associated dry eye manifestations and 44 healthy individuals were included in the study. Ultrasonic pachymetry (UP) was used to measure central corneal thickness (CCT). Corneal biomechanical parameters were obtained using ocular response analyzer (ORA). The main parameters assessed were corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann correlated intraocular pressure (IOPg) and corneal compensated IOP (IOPcc). A Student's t-test for independent groups was performed to compare the mean of these variables between both groups. RESULTS: Mean CH values in Sjögren's syndrome and healthy subject eyes were 10.1mmHg and 11.18mmHg respectively, representing a statistically significant difference (P=0.003). No other variable measured differed between cases and controls (P>0.05). Mean CRF values were 9.51mmHg and 10.37mmHg respectively, and mean CCT measured by UP in cases and controls was 527.41µm and 552.51µm respectively. CONCLUSIONS: Sjögren's syndrome can influence corneal biomechanical properties, specifically CH. ORA measurements should be considered of interest in the evaluation of Sjögren syndrome subjects.

Rab1 in cell signaling, cancer and other diseases.

The endoplasmic reticulum (ER) and Golgi membrane system have major roles in cell signaling and regulation of the biosynthesis/transport of proteins and lipids in response to environmental cues such as amino acid and cholesterol levels. Rab1 is the founding member of the Rab small GTPase family, which is known to mediate dynamic membrane trafficking between ER and Golgi. Growing evidence indicate that Rab1 proteins have important functions beyond their classical vesicular transport functions, including nutrient sensing and signaling, cell migration and presentation of cell-surface receptors. Moreover, deregulation of RAB1 expression has been linked to a myriad of human diseases such as cancer, cardiomyopathy and Parkinson's disease. Further investigating these new physiological and pathological functions of Rab1 should provide new opportunities for better understanding of the disease processes and may lead to more effective therapeutic interventions.

JC virus reactivation in patients with autoimmune rheumatic diseases treated with rituximab.

OBJECTIVES: To evaluate the presence of John Cunningham virus (JCV) DNA in patients with autoimmune rheumatic diseases (ARDs) treated with rituximab (RTX). METHOD: We assessed the JCV DNA levels in peripheral blood mononuclear cell (PBMC), serum, and urine samples by quantitative real-time polymerase chain reaction (qPCR) in a cohort of 42 ARD patients (20 of whom were being treated with RTX) and 42 healthy donors. Approximately 1 year later, we collected further samples from 32 of these 42 ARD patients, all of whom were being treated with RTX. We studied the association between these viral DNA prevalences and various clinical and demographic variables. RESULTS: The viral prevalence in PBMC, serum, and urine samples was 2.4% (1/42), 0%, and 50% (21/42), respectively, in the healthy donors, and 26% (8/31), 16% (5/31), and 86% (25/29), respectively, in the patients treated with RTX. The viral prevalences were not associated with any of the demographic or clinical variables included in the study. CONCLUSIONS: We detected a viral reactivation in PBMCs and serum during the RTX treatment that did not seem to be influenced by either use of immunosuppressive drugs or the length of treatment with the monoclonal antibody. Although this reactivation was asymptomatic, the viral presence in blood could increase the probability of the appearance of a neurotrophic variant of JCV.

Long-term drug survival of biological agents in patients with rheumatoid arthritis in clinical practice.

OBJECTIVES: To assess and compare the long-term drug survival (time to drug discontinuation) of biological agents (BA) in patients with rheumatoid arthritis (RA) in clinical practice. Factors associated with discontinuation of BAs were also investigated. METHOD: We conducted an observational longitudinal study of RA patients taking BAs from 1999 to 2013. The primary endpoint was BA discontinuation due to: adverse drug reactions (ADRs), inefficacy, and other causes. Incidence rates of discontinuation (IRs) per 100 patient-years were estimated using survival techniques. Comparisons between BA discontinuation rates and other associated factors were made using Cox regression models. RESULTS: We included 851 courses of BA therapy (1869 patient-years). Adalimumab (33%) was the BA most frequently used, followed by etanercept (24.4%), infliximab, and rituximab. Treatment was suspended in 558 cases [IR 29.8, 95% confidence interval (CI) 27-32]. In the first year of therapy 68% continued on BAs, and after 10 years the retention rate did not exceed 10%. The IR due to inefficacy was 12.1 (95% CI 10.6-13.8) and the IR of ADRs was 13.6 (95% CI 12-15). The unadjusted IR was higher for rituximab than for tumour necrosis factor (TNF) antagonists. In multivariate analysis, infliximab was the BA with the highest risk of discontinuation, compared to adalimumab. Calendar period, taking subsequent courses of BAs, concomitant therapy, and specific comorbidities were also independent factors associated with discontinuation. CONCLUSIONS: After several years of BA treatment in clinical practice, the survival rate was low, mainly as a result of ADRs and inefficacy. We also found differences between the discontinuation rates of BAs and other clinical factors that modify their survival.

Obesity and survival among women with ovarian cancer: results from the Ovarian Cancer Association Consortium.

BACKGROUND: Observational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer. METHODS: We used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype. RESULTS: Overall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage was observed for women who were obese (BMI: 30-34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99-1.23); BMI: ⩾35, pHR: 1.12 (95% CI: 1.01-1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m(-2)) and endometrioid subtypes (pHR: 1.08 per 5 kg m(-2)), and more modest for the high-grade serous (pHR: 1.04 per 5 kg m(-2)) subtype, but only the association with high-grade serous cancers was significant. CONCLUSIONS: Higher BMI is associated with adverse survival among the majority of women with ovarian cancer.

Association of valine and leucine at HLA-DRB1 position 11 with radiographic progression in rheumatoid arthritis, independent of the shared epitope alleles but not independent of anti-citrullinated protein antibodies.

OBJECTIVE: For decades it has been known that the HLA-DRB1 shared epitope (SE) alleles are associated with an increased risk of development and progression of rheumatoid arthritis (RA). Recently, the following variations in the peptide-binding grooves of HLA molecules that predispose to RA development have been identified: Val and Leu at HLA-DRB1 position 11, Asp at HLA-B position 9, and Phe at HLA-DPB1 position 9. This study was undertaken to investigate whether these variants are also associated with radiographic progression in RA, independent of SE and anti-citrullinated protein antibody (ACPA) status. METHODS: A total of 4,911 radiograph sets from 1,878 RA patients included in the Leiden Early Arthritis Clinic (The Netherlands), Umeå (Sweden), Hospital Clinico San Carlos-Rheumatoid Arthritis (Spain), and National Data Bank for Rheumatic Diseases (US) cohorts were studied. HLA was imputed using single-nucleotide polymorphism data from an Immunochip, and the amino acids listed above were tested in relation to radiographic progression per cohort using an additive model. Results from the 4 cohorts were combined in inverse-variance weighted meta-analyses using a fixed-effects model. Analyses were conditioned on SE and ACPA status. RESULTS: Val and Leu at HLA-DRB1 position 11 were associated with more radiographic progression (meta-analysis P = 5.11 × 10(-7)); this effect was independent of SE status (meta-analysis P = 0.022) but not independent of ACPA status. Phe at HLA-DPB1 position 9 was associated with more severe radiographic progression (meta-analysis P = 0.024), though not independent of SE status. Asp at HLA-B position 9 was not associated with radiographic progression. CONCLUSION: Val and Leu at HLA-DRB1 position 11 conferred a risk of a higher rate of radiographic progression independent of SE status but not independent of ACPA status. These findings support the relevance of these amino acids at position 11.

The 11q23.3 genomic region-rs964184-is associated with cardiovascular disease in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is an inflammatory disease associated with high risk of cardiovascular (CV) events. Recently, the rs964184 polymorphism has been associated with coronary artery disease in nonrheumatic Caucasian individuals. 2160 Spanish RA patients were genotyped for the rs964184 polymorphism. Sex, age at diagnosis and traditional CV risk factors (diabetes mellitus, dyslipidemia and smoking habit) were associated with increased risk of CV events. Interestingly, RA patients carrying the rs964184 GG genotype had significantly higher risk of CV events than those with CC genotype [hazard ratio (HR) = 2.91, 95% confidence interval (CI): 1.36-6.26, P = 0.006] after adjusting the results for sex, age at diagnosis and traditional CV risk factors. Our results indicate that rs964184 polymorphism is associated with CV disease in RA.

Leflunomide discontinuation in rheumatoid arthritis and influence of associated disease-modifying anti-rheumatic drugs: a survival analysis.

OBJECTIVES: The aims of this study were to describe the rate of leflunomide discontinuation in rheumatoid arthritis (RA) patients, in standard clinical practice, and to analyse which factors could influence this rate, paying particular attention to the concomitant treatment with other disease-modifying anti-rheumatic drugs (DMARDs). METHOD: We selected RA patients, diagnosed according to the 1987 American College of Rheumatology (ACR) criteria, attending the rheumatology outpatient clinic of the San Carlos Clinical Hospital (Madrid, Spain), who had started treatment with leflunomide between 1 January 2006 and 1 January 2011. Clinical records were examined until withdrawal of the drug, loss of follow-up, or 1 October 2011. Kaplan-Meier curves were set to account for leflunomide withdrawal. Cox bivariate and multivariate regression models were conducted to examine risk factors for leflunomide discontinuation. RESULTS: The incident rate (IR) for leflunomide discontinuation, regardless of the cause, was 27 per 100 patient-years [95% confidence interval (CI) 22-31]. We observed, in both the bivariate and multivariate regression analysis, that those aged > 75 years at the start of the leflunomide treatment and undergoing concurrent treatment with methotrexate (MTX) and/or hydroxychloroquine (HC) had a significantly higher risk of leflunomide discontinuation. CONCLUSIONS: An older age at the start of the treatment with leflunomide, or concomitant treatment with MTX and/or HC, could be associated with a higher risk of leflunomide discontinuation, regardless of the cause. Therefore, when taking MTX or HC, patients receiving leflunomide should be closely monitored early to detect the occurrence of adverse reactions, and hence prevent their aggravation.

Expression of human endogenous retrovirus HERV-K18 is associated with clinical severity in osteoarthritis patients.

OBJECTIVES: The aim of this study was to evaluate the involvement of human endogenous retrovirus K18 (HERV-K18) in osteoarthritis (OA), by genotyping the HERV-K18 env locus in OA patients and controls, and analysing HERV-K18 RNA expression and its association with OA risk and clinical variables. METHOD: We recruited 558 patients with symptomatic OA and 600 controls. We performed the genotyping by TaqMan assays and the analysis of expression by quantitative real-time polymerase chain reaction (qRT-PCR). Scores on the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC), the Lequesne index, and the Stanford Health Assessment Questionnaire (HAQ) were analysed with regard to the expression levels of HERV-K18. RESULTS: The 18.3 haplotype tended towards an association with OA risk and concordantly this haplotype was associated with a higher HERV-K18 expression (p = 0.05). We found statistically significant differences when we compared the scores on the WOMAC, the Lequesne index for knee and hip, and the HAQ between OA patients with higher expression [normalization ratio (NR) > 10] and OA patients without HERV-K18 expression (p = 0.0003, 0.0005, 0.002, and 0.05, respectively), and also when the comparison was made between OA patients with higher expression (NR > 10) and OA patients with low expression of HERV-K18 (NR = 1) for the WOMAC and the Lequesne index for knee and hip (p = 0.002, 0.013, and 0.006, respectively). CONCLUSIONS: We found an association between health status measurement systems and severity index for OA and the levels of expression of HERV-K18. These results suggest the possible involvement of HERV-K18 in the aetiopathogenesis of the disease.

Single-nucleotide polymorphisms at the 9p21.3 genomic region not associated with the risk of cardiovascular disease in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic polygenic inflammatory disease associated with accelerated atherosclerosis and high risk of cardiovascular disease (CVD). In this study, we evaluated the potential association of 9p21.3 single-nucleotide polymorphisms (SNPs) - previously linked to coronary artery disease - and CVD risk in 2001 Spanish RA patients genotyped for 9p21.3 SNPs using TaqMan™ assays. Carotid intima media thickness (cIMT) and presence of carotid plaques were also analyzed. Cox regression model did not disclose significant differences between patients who experienced CVD and those who did not. Neither association was found between cIMT or carotid plaques and SNPs allele distribution. In conclusion, results do not support a role of rs10116277 or rs1537375 SNPs in CVD risk in Spanish RA patients.