Análisis farmacogenético retrospectivo de una paciente pediátrica en tratamiento anticoagulante: caso clínico

We present the clinical case of a 10-year-old patient diagnosed with dilated cardiomyopathy who registered INR values above 10 upon receiving standard doses of acenocoumarol, as well as other values reported as uncoagulable, forcing the discontinuation and restart of treatment more than once. Expected and stable INR levels were achieved after more than 30 days of treatment, surprisingly with half the recommended dose for a patient of her age and weight. We decided to conduct a retrospective pharmacogenomic analysis including nucleotide genetic polymorphisms (SNPs) with different degrees of association with the dose/response to antivitamin K (AVK) drugs: rs2108622 (gene CYP4F2), rs9923231, rs7294 (gene VKORC1), rs1799853, and rs1057910 (CYP2C9 gene) using TaqMan^® RT-PCR. The patient was homozygous for rs9923231 (VKORC1) and heterozygous for rs2108622 (CYP4F2), a genetic profile strongly associated with a requirement of lower AVK doses as shown by national and international evidence.In conclusion, the pharmacogenetic analysis confirmed that this patient''s genetic conditions, involving low expression of the VKA therapeutic target, required a lower dose than that established in clinical protocols as recommended by the Food and Drug Administration (FDA) and the PharmGKB^® for coumarin drugs. A previous genotypic analysis of the patient would have allowed reaching the therapeutic range sooner, thus avoiding potential bleeding risks. This shows the importance of pharmacogenetic analyses for highly variable treatments with a narrow therapeutic range.     

Sarcopenia y albúmina sanguínea: revisión sistemática con metaanálisis

Sarcopenia is characterized by loss of muscle mass during aging, which can have consequences for the individuals'' health. There are many ways to detect it, among them, with the use of blood biomarkers such as albumin, although the association between the two has not been confirmed yet.This review synthesizes the knowledge on the association between sarcopenia and serum albumin among elderly individuals through a systematic review and meta-analysis focused on the etiology and risk factors. We used the Joanna Briggs Institute software for the review and conducted a search in MEDLINE, Embase, CINAHL, and LILACS databases while two reviewers conducted an independent manual search. EpiDat, version 3.1 was used for the meta-analysis; mean differences with the albumin scores disaggregated by sarcopenia were analyzed by the random-effects model. The degree of heterogeneity was assessed with the DerSimonian and Laird Q test.We analyzed 630 articles and finally included 14 in the review. Higher blood albumin levels were found in the meta-analysis, which was statistically significant among the elderly adults who did not present sarcopenia compared to those who did. Although there are studies exploring the association between albumin and sarcopenia, there is a need to continue evaluating its association with biological markers and comparing them to verify which can be used to detect sarcopenia among the elderly.     

Grupos de riesgo citogenético de leucemia mieloide aguda pediátrica a partir del análisis de supervivencia en un hospital de referencia para cáncer en Perú

Introduction:

Acute myeloid leukemia is a heterogeneous disorder characterized by immature myeloid cell proliferation. Cytogenetic analysis has revealed the presence of chromosomal aberrations important to patient prognosis.

Objective:

To determine cytogenetic risk groups of pediatric patients with acute myeloid leukemia according to overall survival.

Materials and methods:

In this cross-sectional observational study, the clinical records of pediatric patients diagnosed with de novo acute myeloid leukemia admitted to the Instituto Nacional de Enfermedades Neoplásicas between 2001 and 2011 with cytogenetic analysis of bone marrow were included. Cytogenetic risk groups were established according to the criteria of the Medical Research Council. Overall survival curves were generated with the Kaplan-Meier method and compared using the Mantel-Cox test and Cox regression with the software R, version 3.3.2.

Results:

A total of 130 patients were included, 68 males (52.3%) and 62 females (47.7%), most of them with subtype M2 (33%). The average age was 7.7 years (range: 0-15 years).Chromosomal aberrations were observed in 60.8% of the patients, the most frequent of which was the translocation t(8;21). According to the overall survival analysis, two cytogenetic risk groups were established: favorable and unfavorable.

Conclusion:

Two groups of cytogenetic risk were determined: high (or unfavorable) and standard (favorable).