[Characterization and risk prediction of cardiovascular surgeries with cardiopulmonary bypass: a cross-sectional study] / Caracterización y predicción del riesgo de cirugías cardiovasculares con uso de bomba de circulación extracorpórea.

Introduction: Cardiovascular surgery risk prediction models are widely applied in medical practice. However, they have been criticized for their low methodological quality and scarce external validation. An additional limitation added in Latin America is that most of these models have been developed in the United States or Europe, which present marked geographical differences. The objective of this study is to characterize the postoperative clinical events of cardiovascular surgeries with the use of cardiopulmonary bypass pump in a local setting and to evaluate the prediction of postoperative mortality using the EuroSCORE II predictive model. Methods: Cross-sectional study in an urban university hospital in Buenos Aires. Patients ≥21 years of age were included, with a clinical indication for on-pump cardiovascular surgery. Patients with incomplete clinical data regarding EuroSCORE II variables or in-hospital survival, ≥95 years of age, or undergoing heart transplantation were excluded. Results: 195 patients were enrolled. Postoperative mortality estimated by EuroSCORE II presented a clear underestimation of risk (3.0% vs 7.7%). Discrimination (AUC = 0.82; 95% CI 0.74-0.92) and goodness of fit of the model were adequate (χ2 = 7.91; p = 0.4418). The most frequent postoperative complications were postoperative heart failure (35.9%), vasoplegic shock (13.3%), and cardiogenic shock (10.26%). Conclusion: The EuroSCORE II is an appropriate tool to discriminate between different risk categories in patients undergoing on-pump cardiovascular surgery, although it underestimates the risk.

Introducción: Los modelos de predicción de riesgo de cirugías cardiovasculares se aplican ampliamente a la práctica médica. Sin embargo, han sido criticados por su baja calidad metodológica y escasa validación externa. En América Latina se agrega la limitación de que la mayoría de estos modelos fueron desarrollados en Estados Unidos o Europa, existiendo diferencias geográficas marcadas. Objetivo: El objetivo de este estudio es caracterizar los eventos clínicos postoperatorios de cirugías cardiovasculares con uso de bomba de circulación extracorpórea en un escenario local y evaluar la predicción de mortalidad postoperatoria del modelo predictivo EuroSCORE II. Métodos: Corte transversal en un hospital universitario urbano de Buenos Aires. Se incluyeron a pacientes ≥21 años de edad, con indicación de cirugía cardiovascular con uso de bomba. Se excluyeron a pacientes con datos clínicos incompletos respecto a las variables del EuroSCORE II o respecto a la sobrevida intrahospitalaria, con ≥95 años de edad o sometidos a trasplante cardíaco. Resultados: Se enrolaron 195 pacientes. La mortalidad postoperatoria estimada por el EuroSCORE II presentó una clara subestimación del riesgo (3,0% vs 7,7%). La discriminación (AUC = 0,82; IC95% 0,74-0,92) y la bondad del ajuste del modelo fueron adecuadas (χ2 = 7,91; p = 0,4418). Las complicaciones postoperatorias más frecuentes fueron insuficiencia cardíaca postoperatoria (35,9%), shock vasopléjico (13,3%) y shock cardiogénico (10,26%). Conclusión: El EuroSCORE II es una herramienta apropiada para discriminar entre diferentes categorías de riesgo en pacientes sometidos a cirugías cardiovasculares con uso de bomba, si bien subestima el riesgo.

Carbon ion radiotherapy eradicates medulloblastomas with chromothripsis in an orthotopic Li-Fraumeni patient-derived mouse model.

BACKGROUND: Medulloblastomas with chromothripsis developing in children with Li-Fraumeni Syndrome (germline TP53 mutations) are highly aggressive brain tumors with dismal prognosis. Conventional photon radiotherapy and DNA-damaging chemotherapy are not successful for these patients and raise the risk of secondary malignancies. We hypothesized that the pronounced homologous recombination deficiency in these tumors might offer vulnerabilities that can be therapeutically utilized in combination with high linear energy transfer carbon ion radiotherapy. METHODS: We tested high-precision particle therapy with carbon ions and protons as well as topotecan with or without PARP inhibitor in orthotopic primary and matched relapsed patient-derived xenograft models. Tumor and normal tissue underwent longitudinal morphological MRI, cellular (markers of neurogenesis and DNA damage-repair), and molecular characterization (whole-genome sequencing). RESULTS: In the primary medulloblastoma model, carbon ions led to complete response in 79% of animals irrespective of PARP inhibitor within a follow-up period of 300 days postirradiation, as detected by MRI and histology. No sign of neurologic symptoms, impairment of neurogenesis or in-field carcinogenesis was detected in repair-deficient host mice. PARP inhibitors further enhanced the effect of proton irradiation. In the postradiotherapy relapsed tumor model, median survival was significantly increased after carbon ions (96 days) versus control (43 days, P < .0001). No major change in the clonal composition was detected in the relapsed model. CONCLUSION: The high efficacy and favorable toxicity profile of carbon ions warrants further investigation in primary medulloblastomas with chromothripsis. Postradiotherapy relapsed medulloblastomas exhibit relative resistance compared to treatment-naïve tumors, calling for exploration of multimodal strategies.