Guidelines for blood test monitoring of methotrexate toxicity in juvenile idiopathic arthritis
JOURNAL OF RHEUMATOLOGY
Authors: Ortiz-Alvarez, O; Morishita, K; Avery, G; Green, J; Petty, RE; Tucker, LB; Malleson, PN; Cabral, DA
Abstract
Objective. To assess the utility of the American College of Rheumatology guidelines for monitoring methotrexate (MTX)-related toxicity in a cohort of children with juvenile idiopathic arthritis (JIA). Methods. Eighty-nine patients with JIA treated with MTX were monitored prospectively: aspartate aminotransferase (AST), alanine aminotransferase (ALT), complete blood count (CBC), and differential blood count were measured prior to starting MTX, and then monthly. Significantly abnormal blood tests (SABT) were prospectively defined as (1) significantly elevated liver enzymes (SELE) greater than twice the upper limit of normal; (2) granulocyte count < 1.5 x 10(9)/l; (3) lymphocyte count < 0.9 x 10(9)/l; or (4) hemoglobin decreased by > 2 g/l from previous level. Clinical interventions, current and cumulative MTX dose, duration of treatment, comorbidity, and concurrent medications at the time of the first SABT identification were recorded. Independent t tests and chi-squared tests were used for comparisons, and the probability of developing a SABT was calculated by Kaplan-Meier survival analysis. Results. Forty percent of patients had a SABT: 26% had hematological abnormalities and 14% bad SELE. Ninety-five percent of patients with SABT had symptoms consistent with a viral infection when the SABT was drawn and MTX dose was withheld until results had normalized on repeat testing. SABT persisting beyond one month occurred in only, 2 patients, and their abnormalities resolved by 6 months with no specific identified cause; they resumed MTX at a later time without recurrence of SABT. There were no differences between patients with and without SABT with respect to current or cumulative MTX dose, duration of treatment, and concurrent medications at the time of the SABT. The probability of developing a SABT was estimated to be 11% at 3 months, compared to 10% probability of having an abnormal blood test by chance alone. Conclusion. Routine blood tests every 4 to 8 weeks in children with JIA are unnecessarily frequent.
Reduction in Inflammatory Gene Expression in Skeletal Muscle from Roux-en-Y Gastric Bypass Patients Randomized to Omentectomy
PLOS ONE
Authors: Tamboli, Robyn A.; Hajri, Tahar; Jiang, Aixiang; Marks-Shulman, Pamela A.; Williams, D. Brandon; Clements, Ronald H.; Melvin, Willie; Bowen, Benjamin P.; Shyr, Yu; Abumrad, Naji N.; Flynn, Charles Robb
Abstract
Objectives: To examine the effects of Roux-en-Y gastric bypass (RYGB) surgery with and without laparoscopic removal of omental fat (omentectomy) on the temporal gene expression profiles of skeletal muscle. Design: Previously reported were the whole-body metabolic effects of a randomized, single-blinded study in patients receiving RYGB surgery stratified to receive or not receive omentectomy. In this follow up study we report on changes in skeletal muscle gene expression in a subset of 21 patients, for whom biopsies were collected preoperatively and at either 6 months or 12 months postoperatively. Methodology/Principal Findings: RNA isolated from skeletal muscle biopsies of 21 subjects (8 without omentectomy and 13 with omentectomy) taken before RYGB or at 6 and 12 months postoperatively were subjected to gene expression profiling via Exon 1.0 S/T Array and Taqman Low Density Array. Robust Multichip Analysis and gene enrichment data analysis revealed 84 genes with at least a 4-fold expression difference after surgery. At 6 and 12 months the RYGB with omentectomy group displayed a greater reduction in the expression of genes associated with skeletal muscle inflammation (ANKRD1, CDR1, CH25H, CXCL2, CX3CR1, IL8, LBP, NFIL3, SELE, SOCS3, TNFAIP3, and ZFP36) relative to the RYGB non-omentectomy group. Expressions of IL6 and CCL2 were decreased at all postoperative time points. There was differential expression of genes driving protein turnover (IGFN1, FBXW10) in both groups over time and increased expression of PAAF1 in the non-omentectomy group at 12 months. Evidence for the activation of skeletal muscle satellite cells was inferred from the up-regulation of HOXC10. The elevated post-operative expression of 22 small nucleolar RNAs and the decreased expression of the transcription factors JUNB, FOS, FOSB, ATF3 MYC, EGR1 as well as the orphan nuclear receptors NR4A1, NR4A2, NR4A3 suggest dramatic reorganizations at both the cellular and genetic levels. Conclusions/Significance: These data indicate that RYGB reduces skeletal muscle inflammation, and removal of omental fat further amplifies this response.