Guía de práctica clínica para el manejo de cáncer de cuello uterino estadios tempranos / Clinical practice guideline for the management of early-stage cervical cancer

Introducción: Este artículo resume la guía de práctica clínica (GPC) para el manejo de cáncer de cuello uterino estadios tempranos (IA1, IA2, IB1, IB2 o IIA1) en el Seguro Social del Perú (EsSalud). Objetivo: Proveer recomendaciones clínicas basadas en evidencia para el manejo de cáncer de cuello uterino estadios tempranos en EsSalud. Material y métodos: Se conformó un grupo elaborador de la guía (GEG) que incluyó médicos especialistas y metodólogos. El GEG formuló 8 preguntas clínicas a ser respondidas por la presente GPC. Se realizó búsquedas sistemáticas de revisiones sistemáticas y ­cuando fue considerado pertinente­ estudios primarios en Pubmed, Embase y CENTRAL durante el 2017 - 2018. Se seleccionó la evidencia para responder cada una de las preguntas clínicas planteadas. La certeza de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones de trabajo periódicas, el GEG usó la metodología GRADE para revisar la evidencia y formular las recomendaciones, los puntos de buenas prácticas clínicas y los flujogramas de manejo. Finalmente, la GPC fue aprobada con Resolución N° 27-IETSI-ESSALUD-2020. Resultados: La presente GPC abordó 8 preguntas clínicas abordando el manejo del cáncer de cuello uterino en estadios tempranos. En base a dichas preguntas se formularon 10 recomendaciones (2 recomendaciones fuertes y 8 recomendaciones condicionales), 7 puntos de buena práctica clínica, y 4 flujogramas. Conclusión: El presente artículo resume la metodología y las conclusiones basadas en evidencias de la GPC para el manejo del cáncer de cuello uterino en estadios tempranos en EsSalud.

Introduction: This article summarizes the clinical practice guideline (CPG) for the management of early stage cervical cancer (IA1, IA2, IB1, IB2 or IIA1) in the Social Security of Peru (EsSalud). Objective: To provide evidence-based clinical recommendations for the management of early stage cervical cancer in EsSalud. Material and methods: A guideline development group (GEG) was formed that included medical specialists and methodologists. The GEG formulated 8 clinical questions to be answered by this CPG. Systematic searches of systematic reviews and -when considered relevant- primary studies were performed in Pubmed, Embase and CENTRAL during 2017 - 2018. Evidence was selected to answer each of the clinical questions posed. The certainty of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic working meetings, the GEG used the GRADE methodology to review the evidence and formulate recommendations, good clinical practice points, and management flowcharts. Finally, the CPG was approved by Resolution No. 27-IETSI-ESSALUD-2020. Results: This CPG addressed 8 clinical questions on the management of early stage cervical cancer. Based on these questions, 10 recommendations were formulated (2 strong recommendations and 8 conditional recommendations), 7 points of good clinical practice, and 4 flowcharts. Conclusion: This article summarizes the methodology and evidence-based conclusions of the CPG for the management of early stage cervical cancer in EsSalud.

A prospective study of brachytelephalangic chondrodysplasia punctata: identification of arylsulfatase E mutations, functional analysis of novel missense alleles, and determination of potential phenocopies.

PURPOSE: The only known genetic cause of brachytelephalangic chondrodysplasia punctata is X-linked chondrodysplasia punctata 1 (CDPX1), which results from a deficiency of arylsulfatase E (ARSE). Historically, ARSE mutations have been identified in only 50% of male patients, and it was proposed that the remainder might represent phenocopies due to maternal-fetal vitamin K deficiency and maternal autoimmune diseases. METHODS: To further evaluate causes of brachytelephalangic chondrodysplasia punctata, we established a Collaboration Education and Test Translation program for CDPX1 from 2008 to 2010. Of the 29 male probands identified, 17 had ARSE mutations that included 10 novel missense alleles and one single-codon deletion. To determine pathogenicity of these and additional missense alleles, we transiently expressed them in COS cells and measured arylsulfatase E activity using the artificial substrate, 4-methylumbelliferyl sulfate. In addition, clinical data were collected to investigate maternal effects and genotype-phenotype correlations. RESULTS: In this study, 58% of males had ARSE mutations. All mutant alleles had negligible arylsulfatase E activity. There were no obvious genotype-phenotype correlations. Maternal etiologies were not reported in most patients. CONCLUSION: CDPX1 is caused by loss of arylsulfatase E activity. Around 40% of male patients with brachytelephalangic chondrodysplasia punctata do not have detectable ARSE mutations or known maternal etiological factors. Improved understanding of arylsulfatase E function is predicted to illuminate other etiologies for brachytelephalangic chondrodysplasia punctata.

Clinical and molecular analysis of arylsulfatase E in patients with brachytelephalangic chondrodysplasia punctata.

X-linked Recessive Chondrodysplasia Punctata (CDPX1) is due to a defect in arylsulfatase E (ARSE), located on Xp22.3. Neither the substrate nor function of the encoded warfarin-sensitive arylsulfatase has been identified and molecular analysis remains the only confirmatory diagnostic test. Nevertheless, the majority of patients evaluated have not had identifiable mutations in ARSE, and thus far 23 patients have been reported. The major clinical features in these patients are also present in a group now recognized as phenocopies, due to vitamin K deficiency in early gestation or maternal autoimmune disease. We evaluated the ARSE gene in 11 patients who met clinical criteria for CDPX1. We amplified all exons and intronic flanking sequence from each patient, and investigated suspected deletions or rearrangements by southern analysis. We identified mutations in seven individuals. Of the remainder, three had maternal conditions that further expand the phenocopy group. Thus, this group might represent a proportion of the mutation-negative patients in previous studies. We extracted clinical information from all prior reports over the past decade and show that there are few distinguishing features on examination between these two groups of patients. This study supports heterogeneity for CDPX1-like phenotypes and sorting these out will help to define the biological pathway and genetic contributors.