Methotrexate Triglutamate as a Determinant of Clinical Response in Mexican Patients With Rheumatoid Arthritis: Pharmacokinetics and Dose Recommendation.

Methotrexate is the gold standard treatment in rheumatoid arthritis. Once absorbed, it is internalized in cells, where glutamate residues are added to produce polyglutamated forms, which are responsible for the effect of methotrexate. The aim of the current study is to determine the relationship between methotrexate triglutamate concentrations and the clinical evolution in rheumatoid arthritis patients, as well as to characterize the variability in both features to propose strategies for low-dose methotrexate optimization. The quantification of methotrexate triglutamate concentration in red blood cells was performed through ultra-performance liquid chromatography coupled with mass spectrometry. Polymorphisms of genes involved in the formation of polyglutamates were determined by real-time polymerase chain reaction. A multivariate regression was performed to determine the covariates involved in the variability of methotrexate triglutamate concentrations and a population pharmacokinetics model was developed through nonlinear mixed-effects modeling. Disease activity score changed according to methotrexate triglutamate concentrations; patients with good response to treatment had higher concentrations than moderate or nonresponding patients. The methotrexate triglutamate concentrations were related to time under treatment, dose, red blood cells, and body mass index. A 1-compartment open model was selected to estimate the pharmacokinetic parameters; the typical total clearance (L/day) was determined as 1.45 * (body mass index/28 kg/m2 ) * (red blood cells/4.6 × 106 cells/µL) and the volume of distribution was 52.4 L, with an absorption rate of 0.0346/day and a fraction metabolized of 1.03%. Through the application of the model, the initial dose of methotrexate is proposed on the basis of stochastic simulations and considering methotrexate triglutamate concentrations found in responders patients.

Surgical procedure versus medical treatment for infective endocarditis associated to mortality in Mexican population.

BACKGROUND: Early surgical procedures on patients with infective endocarditis (IE) have shown a clearly benefit to reduce embolization at the central nervous system. We conducted a retrospective cohort in Mexican population to evaluate mortality and clinical outcomes in patients with IE with or without surgical intervention. OBJECTIVES: Our aim was to evaluate factors associated with mortality in patients with IE and compare both groups with and without a surgical intervention. METHODS: We evaluated a retrospective cohort of patients who had been diagnosed with IE according to the Duke's criteria at our Institution in SLP, Mexico, from January 2001 to September 2016. We compared the risk factors associated to mortality of patients with or without surgery. Our primary outcome was mortality within 6 months of follow-up after the diagnosis. RESULTS: We included 105 patients, 51 (48.6%) were men, median age 46 [Q1 30, Q3 59] years, 36 patients (34.3%) received surgical treatment (STG), and 69 (65.7%) only medical treatment (MTG) group; 41 patients (39%) died during the study period; in the surgery group eight patients died (22%); and 33 in the MT group (47%) p = 0.049. Adjusted for APACHE II, surgery, creatinine levels and the size of vegetation, the surgery group had lower mortality than patients on MTG (HR 0.36, p = 0.047). CONCLUSION: As previously described in the literature, patients who underwent surgery had lower mortality than the patients who only received medical treatment; however, the Mexican population is different to other populations group, due to higher risk of diabetes mellitus (28%) versus (10%) in global risk of DM in the world and its complications and other chronic diseases as arterial systemic hypertension. Thus, surgical treatment must be elected as goal standard treatment in patient's whit IE and presence of vegetation.

Antecedentes: Los procedimientos quirúrgicos tempranos en pacientes con endocarditis infecciosa (EI) han mostrado un beneficio claro para reducir la embolización en el sistema nervioso central. Realizamos una cohorte retrospectiva en ­población mexicana para evaluar la mortalidad y los resultados clínicos en pacientes con EI con o sin intervención quirúrgica. Objetivos: Nuestro objetivo fue evaluar los factores asociados a la mortalidad en pacientes con endocarditis infecciosa y comparar ambos grupos con y sin intervención quirúrgica. Métodos: Evaluamos una cohorte retrospectiva de pacientes que habían sido diagnosticados de EI según los criterios de Duke en nuestra Institución en SLP, México, desde enero de 2001 a septiembre de 2016. Comparamos los factores de riesgo asociados a la mortalidad de pacientes con o sin cirugía. Nuestro resultado primario fue la mortalidad dentro de los 6 meses de seguimiento después del diagnóstico. Resultados: Se incluyeron 105 pacientes, 51 (48.6%) eran hombres, mediana de edad46 [Q1 30, Q3 59] años, 36 pacientes (34.3%) recibieron tratamiento quirúrgico (STG) y 69 (65.7%) solo grupo de tratamiento médico (MTG); 41 pacientes (39%) murieron durante el período de estudio; en el grupo de cirugía fallecieron 8 pacientes (22%) y en el grupo de MT (47%) 33 p = 0.049. Ajustado por APACHE II, cirugía, niveles de creatinina y tamaño de la vegetación, el grupo de cirugía tuvo menor mortalidad que los pacientes en MTG (HR 0.36, p = 0.047). Conclusión: Como se ha descrito anteriormente en la literatura, los pacientes que se sometieron a cirugía tuvieron menor mortalidad que los pacientes que solo recibieron tratamiento médico, sin embargo, la población mexicana es diferente a otros grupos poblacionales, debido a un mayor riesgo de diabetes mellitus (28%) vs (10%) en otros países y sus complicaciones y otras enfermedades crónicas como hipertensión arterial sistémica. Por tanto, el tratamiento quirúrgico debe ser elegido como principal método de tratamiento en pacientes con endocarditis infecciosa y presencia de vegetaciones.

IgG4 deposits in pure and combined membranous lupus nephritis.

The aim of this study is to determine the frequency and prognosis of IgG4 deposits in renal biopsy of patients with membranous lupus nephritis (MLN). This is a retrospective cohort study in which we included patients with class V alone or combined (III/V or IV/V) of lupus nephritis according to the 2004 ISN/RPS. All the patients included must have availability of renal tissue for immunohistochemistry analyses. We excluded other classes of lupus nephritis. The renal tissue was examined by a nephro-pathologist. We included 65 patients with MLN; of these, 24 (37 %) were class V, and the other had proliferative concomitant with membranous patterns. Seven renal specimens had IgG4 deposits (10 %). Patients with IgG4 deposits had higher levels of eosinophils in serum. All of the patients with IgG4 had renal involvement as first manifestations of systemic lupus erythematosus. The rate of renal failure was 42 and 43 % in IgG4 positive and negative, respectively, 28 % of IgG4 required renal replacement therapy. From a histological view, 42 % of IgG4 had evidence of arteriolar vasculitis in renal biopsies. Lupus patients with IgG4 deposits were more likely to have renal involvement as a first manifestation of systemic lupus erythematosus, and they course with a worse prognosis since they required more dialysis. Also, they have more probability of vascular inflammation on the renal biopsy.

Laboratory biomarkers for guiding therapy with methotrexate in rheumatoid arthritis.

Methotrexate (MTX) is a first-line drug for the treatment of several rheumatic diseases. However, it is difficult to predict the response to this drug based on clinical manifestations. Although different mechanisms of action have been proposed for the antiinflammatory and immunosuppressive effects of MTX, the best characterized are blockade of the de novo synthesis of purines and pyrimidines, which inhibits DNA synthesis, and induction of adenosine release, which downregulates the effector functions of different immune cells. Thus, variants of the enzymes and other molecules involved in these metabolic pathways are expected to play a relevant role in the therapeutic effect or toxicity of MTX in patients with rheumatoid arthritis (RA). Accordingly, polymorphisms of the genes encoding these proteins have been widely associated with the response to or discontinuation of MTX. In addition, variants of the genes involved in the transportation of MTX inside and outside cells and in its metabolism have also been associated with the efficacy or toxicity of this drug in patients with RA. However, published results are contradictory, and no consensus regarding the best laboratory markers of MTX efficacy has been reached. Therefore, additional prospective studies with a large number of patients are necessary to identify the combination of genetic and nongenetic factors that can predict, with a reasonable level of confidence, the efficacy and toxicity of MTX in patients with RA.

Triple therapy with non-biologic DMARDs for rheumatoid arthritis or biologic therapy. Is it the same? / Triple terapia con FARME no biológico o tratamiento biológico para artritis reumatoide. ¿Son lo mismo?

No disponible

CKD-EPI is the most reliable equation to estimate renal function in patients with systemic lupus erythematosus.

BACKGROUND: No study has determined the best equation for estimating renal function in patients with systemic lupus erythematosus (SLE), starting from a gold standard test. OBJECTIVE: To evaluate the performance of cistatin/creatinine based equations for estimating renal function in patients with SLE. METHODS: We conducted two phases: the first phase included 14 patients in which iothalamate clearance was used to determine the glomerular filtration rate (GFR) and compared with different equations based on cystatin C and/or creatinine. In the second phase, we used the best equation (a cystatin and creatinine-based equation) as "reference standard" to compare 5 creatinine-based equations in 55 patients with SLE. RESULTS: In the first phase the equation developed by Stevens and colleagues (based on creatinine and cystatin C), was the best equation. In phase 2, the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation was the best equation with bias of -2. 1 ml/min/1.73, accuracy (P30) of 94.5% and precision (interquartile range of differences) of -2.1 ml/min/1.73. CONCLUSIONS: Our data suggest that CKD-EPI is the best creatinine-based equation to estimate GFR in patients with SLE.

CKD-EPI is the most reliable equation to estimate renal function in patients with systemic lupus erythematosus

Background: No study has determined the best equation for estimating renal function in patients with systemic lupus erythematosus (SLE), starting from a gold standard test. Objective: To evaluate the performance of cistatin/creatinine based equations for estimating renal function in patients with SLE. Methods: We conducted two phases: the first phase included 14 patients in which iothalamate clearance was used to determine the glomerular filtration rate (GFR) and compared with different equations based on cystatin C and/or creatinine. In the second phase, we used the best equation (a cystatin and creatinine-based equation) as "reference standard" to compare 5 creatinine-based equations in 55 patients with SLE. Results: In the first phase the equation developed by Stevens and colleagues (based on creatinine and cystatin C), was the best equation. In phase 2, the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation was the best equation with bias of -2.1ml/min/1.73, accuracy (P30) of 94.5% and precision (interquartile range of differences) of -2.1 ml/min/1.73. Conclusions: Our data suggest that CKD-EPI is the best creatinine-based equation to estimate GFR in patients with SLE (AU)

Antecedentes: Ningún estudio ha podido determinar cuál es la mejor ecuación para calcular la función renal en pacientes con lupus eritematoso sistémico (LES) partiendo del análisis de una evaluación de referencia. Objetivo: Evaluar el rendimiento de las ecuaciones basadas en cistatina/creatinina en la estimación de la función renal en pacientes con LES. Métodos: Realizamos el estudio en dos fases: la primera incluía 14 pacientes en los que el aclaramiento de yotalamato se utilizó para determinar la tasa de filtración glomerular (FG) y se comparó con diferentes ecuaciones basadas en cistatina C y/o creatinina En la segunda fase, utilizamos la mejor ecuación (basada en cistatina y creatinina) como «estándar de referencia» para comparar 5 ecuaciones basadas en creatinina en 55 pacientes con LES. Resultados: En la primera fase, la ecuación desarrollada por Stevens et al. (basada en creatinina y cistatina C) fue considerada la mejor. En la fase dos, la ecuación CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) fue considerada la mejor con una desviación de 2,1 ml/min/1,73, exactitud (P30 %) del 94,5 % y precisión (rango intercuartílico de las diferencias) de 2,1 ml/min/1,73. Conclusiones: Nuestros datos sugieren que la ecuación CKD-EPI es la mejor ecuación basada en creatinina para estimar la FG en pacientes con LES (AU)

Impacto económico de estimar la función renal en pacientes con lupus eritematoso sistémico / Economic impact of estimating renal function in patients with systemic lupus erythematosus

No disponible