Development of a Polygenic Risk Score to Predict Diverticulitis.

BACKGROUND: Despite its prevalence and associated morbidity, we remain limited in our ability to predict the course of a patient with diverticular disease. Although several clinical and genetic risk factors have been identified, we do not know how these factors relate to one another. OBJECTIVE: Our aim was to determine whether a polygenic risk score could improve risk prediction for diverticulitis and recurrent diverticulitis compared with a model using only clinical factors. DESIGN: This is an observational study. SETTING: The study examines the predictive ability of a polygenic risk score for diverticulitis developed using prior genome-wide association studies and validated using the MyCode biobank. PATIENTS: This study included patients of European ancestry in the Geisinger Health System who were enrolled in the MyCode Community Health biobanking program. MAIN OUTCOME MEASURES: The ability of a polygenic risk score to predict diverticulosis, diverticulitis, and recurrent diverticulitis was the main outcome measure of this study. RESULTS: A total of 60,861 patients were included, of whom 9912 (16.3%) had diverticulosis or diverticulitis (5015 with diverticulosis and 4897 with diverticulitis). When divided into deciles, our polygenic risk score stratified patients by risk of both diverticulosis and diverticulitis with a 2-fold difference in disease risk between the highest and lowest deciles for diverticulitis and a 4.8-fold difference for recurrent complicated diverticulitis. When compared with clinical factors alone, our polygenic risk score was able to improve risk prediction of recurrent diverticulitis. LIMITATIONS: Our population is largely located in a single geographic region and were classified by disease status, using international classification of diseases codes. CONCLUSIONS: This predictive model stratifies patients based on genetic risk for diverticular disease. The increased frequency of recurrent disease in our high-risk patients suggests that a polygenic risk score, in addition to other factors, may help guide the discussion regarding surgical intervention. See Video Abstract . DESARROLLO DE UNA PUNTUACIN DE RIESGO POLIGNICO PARA PREDECIR LA DIVERTICULITIS: ANTECEDENTES:A pesar de su prevalencia y morbilidad asociada, nuestra capacidad para predecir el curso en un paciente con enfermedad diverticular sigue siendo limitada. Si bien se han identificado varios factores de riesgo clínicos y genéticos, no sabemos cómo se relacionan estos factores entre sí.OBJETIVO:Determinar si una puntuación de riesgo poligénico podría mejorar la predicción del riesgo de diverticulitis y diverticulitis recurrente en comparación con un modelo que utiliza solo factores clínicos.DISEÑO:Un estudio observacional que examina la capacidad predictiva de una puntuación de riesgo poligénico para la diverticulitis desarrollada usando estudios previos de asociación amplia del genoma y validada usando el biobanco MyCode.ÁMBITOS Y PACIENTES:Pacientes de ascendencia europea en el Sistema de Salud Geisinger que estaban inscritos en el programa de biobancos MyCode Community Health.PRINCIPALES MEDIDAS DE VALORACIÓN:La capacidad de una puntuación de riesgo poligénico para predecir diverticulosis, diverticulitis y diverticulitis recurrente.RESULTADOS:Se incluyeron un total de 60.861 pacientes, de los cuales 9.912 (16,3%) presentaban diverticulosis o diverticulitis (5.015 con diverticulosis y 4.897 con diverticulitis). Cuando se dividió en deciles, nuestra puntuación de riesgo poligénico estratificó a los pacientes según el riesgo de diverticulosis y diverticulitis con una diferencia de 2 veces en el riesgo de enfermedad entre los deciles más alto y más bajo para diverticulitis y una diferencia de 4,8 veces para diverticulitis complicada recurrente. En comparación con los factores clínicos solos, nuestra puntuación de riesgo poligénico pudo mejorar la predicción del riesgo de diverticulitis recurrente.LIMITACIONES:Nuestra población se encuentra en gran parte en una sola región geográfica y se clasificó por estado de enfermedad utilizando códigos de clasificación internacional de enfermedades.CONCLUSIONES:Este modelo predictivo estratifica a los pacientes en función del riesgo genético de enfermedad diverticular. La mayor frecuencia de enfermedad recurrente en nuestros pacientes de alto riesgo sugiere que un puntaje de riesgo poligénico, además de otros factores, puede ayudar a guiar la discusión sobre la intervención quirúrgica. (Traducción- Dr. Ingrid Melo ).

Screening, Surveillance, and Treatment of Anal Intraepithelial Neoplasia.

The prevalence of anal intraepithelial neoplasia has been increasing, especially in high-risk patients, including men who have sex with men, human immunodeficiency virus positive patients, and those who are immunosuppressed. Several studies with long-term follow-up have suggested that rate of progression from high-grade squamous intraepithelial lesions to invasive anal cancer is ∼ 5%. This number is considerably higher for those at high risk. Anal cytology has been used to attempt to screen high-risk patients for disease; however, it has been shown to have very little correlation to actual histology. Patients with lesions should undergo history and physical exam including digital rectal exam and standard anoscopy. High-resolution anoscopy can be considered as well, although it is of questionable time and cost-effectiveness. Nonoperative treatments include expectant surveillance and topical imiquimod or 5-fluorouracil. Operative therapies include wide local excision and targeted ablation with electrocautery, infrared coagulation, or cryotherapy. Recurrence rates remain high regardless of treatment delivered and surveillance is paramount, although optimal surveillance regimens have yet to be established.