Complete screening of exons 2, 3, and 4 of kras and nras genes reveals a higher number of clinically relevant mutations than food and drug administration quantitative polymerase chain reaction-based commercial kits

Abstract Background: The presence of clinically relevant mutations in KRAS and NRAS genes determines the response of anti-epidermal growth factor receptor antibody therapy for metastatic colorectal cancer (mCRC). The only quantitative polymerase chain reaction (qPCR)-based diagnostic tests approved by the Food and Drug Administration (FDA) screen merely for mutations in codons 12 and 13 of KRAS. Objective: The objective of the study was to study the frequency of clinically relevant mutations in KRAS and NRAS genes that are not included in FDA-approved qPCR tests. Methods: Formalin-fixed paraffin-embedded tumor specimens from 1113 mCRC Mexican patients from different health institutions across the country were analyzed by Sanger sequencing for KRAS mutations in exons 2, 3, and 4. Furthermore, 83 were analyzed in exons 2, 3, and 4 of NRAS. Results: From the specimens tested for KRAS, 33.69% harbored a mutation. From these, 71.77% were in codon 12 and 27.69% in codon 13 (both located in exon 2). Codons 59 (exon 3) and 146 (exon 4) accounted for the remaining 0.54%. From the 83 specimens, in which NRAS was analyzed, three mutations were found in codon 12 (3.61%). Approximately 6% of RAS mutated specimens would have been falsely reported as RAS wild type if an FDA-approved qPCR diagnostic test had been used. Conclusions: While these kits based on qPCR can be very practical and highly sensitive, their mutation coverage ignores mutations from poorly genetically characterized populations.

Depresión en artritis reumatóide / Depression in Rheumatoid Arthritis

Resumen Introducción: La depresión es una importante comorbilidad en pacientes con artritis reumatoide; diversos factores como la actividad de la enfermedad, el dolor y la discapacidad contribuyen a su desarrollo. Materiales y métodos: Se realizó un estudio transversal en pacientes con artritis reumatoide para determinar la prevalencia de depresión, utilizando el cuestionario Patient health questionnaire (PHQ-9) y su relación con la actividad de la enfermedad mediante DAS-28 y la discapacidad funcional mediante HAQ-DI. Resultados: El 42,9% de los pacientes presentaron depresión. Se encontró una asociación entre depresión con DAS-28 y HAQ-DI, ya que el 70% de los pacientes con alta actividad de la enfermedad y el 38% de los pacientes con discapacidad funcional presentaron depresión de moderada a grave. El número de articulaciones dolorosas y tumefactas fue mayor en los pacientes con depresión grave que en aquellos con depresión leve. Los pacientes con mayor depresión referían un dolor más intenso según la escala visual del dolor.

Abstract Introduction: Depression is significant comorbidity in patients with rheumatoid arthritis (RA), with many factors, such as disease activity, pain, and disability determining its development. Materials and method: A cross-sectional study including patients with rheumatoid arthritis was conducted to determine prevalence of depression using the Patient Health Questionnaire (PHQ-9), and its relationship with disease activity using DAS-28. The HAQ-DI was used to determine functional disability and the number of painful and swollen joints. Results: Depression was observed in 42.9% of the patients. An association was found between depression, DAS-28 and HAQ-DI. It was also found that 70% of the patients with high activity disease and 38% of the patients with functional disability had moderate-severe depression. The number of painful and swollen joints was greater in patients with severe depression than in patients with mild depression. Patients with greater depression referred to more intense pain according to the visual analogue pain scale.