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 ).

Neurofibromatosis-associated Gastrointestinal Stromal Tumor Causing Small Bowel Obstruction.

Multiple gastrointestinal stromal tumors (GISTs) of the small intestine is an uncommon finding but can be a marker for underlying neurofibromatosis type 1 (NF1). We present the case of the 38-year-old male without prior NF1 diagnosis who presented with a small bowel obstruction. His physical exam was notable for cutaneous nodules and café-au-lait spots. He progressed to peritonitis and underwent an exploratory laparotomy, which revealed a 6-cm hemorrhagic mass along the antimesenteric border of the jejunum, causing obstruction and perforation. Pathology was consistent with GISTs. NF1-associated GISTs differ from wild-type GISTs in that they are unlikely to have C-KIT and PDGFRA mutations and therefore do not respond to imatinib. Treatment is largely limited to surgical resection; however, there is evidence that MEK inhibitors may prove an additional treatment strategy.

Acute Kidney Injury After Large Ventral Hernia Repair Requiring Transversus Abdominis Release.

BACKGROUND: Acute kidney injury (AKI) is a known postoperative complication of open ventral hernia repair contributing to increased costs, hospital length of stay, and mortality. The aim of this study was to identify whether the muscle injury that occurs in a posterior separation of components via transversus abdominis release (TAR) contributes to a higher incidence of postoperative AKI. METHODS: A retrospective cohort study of patients who underwent open retrorectus ventral hernia repair with and without TAR at a single institution between 2012 and 2019 was performed. Patients who underwent a separation of components via either unilateral or bilateral transversus abdominis release were compared to those who did not undergo TAR as part of their hernia repair (non-TAR). The outcome of interest was the development of postoperative AKI. Acute kidney injury was defined as an increase in creatinine of greater than 50% of the preoperative baseline. Univariate and multivariate analyses were performed to determine the influence of TAR on the development of AKI. RESULTS: There were 523 patients who met inclusion criteria, of which 159 (30.4%) had a TAR as part of their retrorectus hernia repair. No differences were found in preoperative characteristics between the TAR and non-TAR group including age, gender, history of kidney disease, or history of diabetes. By contrast, the TAR group had significantly greater median estimated blood loss (100 mL vs 75 mL, P < .01), mean positive intraoperative fluid balance (2255 mL vs 1887 mL, P < .01), and operative duration (321 min vs 269 min, P < .001). The rate of AKI in the TAR group was 11% (n = 18) vs 6% (n = 23, P = .0503) in the non-TAR group. On multivariate analysis controlling for patient characteristics and intraoperative factors, TAR was the only factor with a significantly increased odds of AKI (OR 1.97, 95% CI 0.994-3.905, P = .0521). CONCLUSIONS: In patients with large ventral hernias requiring retrorectus repair, performing a TAR is associated with a nearly 2-fold increase in the development of postoperative AKI. These findings suggest that these patients should be optimized perioperatively with emphasis on fluid resuscitation, limiting nephrotoxic medications and monitoring urine output.