Background: The endometrial cancer molecular classification has been integrated into the 2020 World Health Organization (WHO) diagnostic classification and European treatment guidelines, and... Show moreBackground: The endometrial cancer molecular classification has been integrated into the 2020 World Health Organization (WHO) diagnostic classification and European treatment guidelines, and provides direction towards more effective and less toxic adjuvant treatment strategies for women with endometrial cancer. Primary objective(s): The RAINBO program of clinical trials will investigate four molecular class-directed adjuvant treatment strategies following surgical resection to either increase cure rates through the addition of novel targeted therapies or safely reduce toxicity and improve quality of life through treatment de-escalation. Study hypothesis: Molecular-directed adjuvant treatment strategies will improve clinical outcomes and reduce toxicity of unwarranted therapies in women with endometrial cancer. The overarching and translational research RAINBO program will advance knowledge of predictive and prognostic (bio)markers that will improve prognostication and treatment allocation. Trial design: The RAINBO program is a platform of four international clinical trials and an overarching research program. The randomized phase III p53abn-RED trial for women with invasive stage I-III p53abn endometrial cancer compares adjuvant chemoradiation followed by olaparib for 2 years with adjuvant chemoradiation alone. The randomized phase III MMRd-GREEN trial for women with stage II (with lymphovascular space invasion (LVSI)) or stage III mismatch repair-deficient (MMRd) endometrial cancer compares adjuvant radiotherapy with concurrent and adjuvant durvalumab for 1 year to radiotherapy alone. The randomized phase III NSMP-ORANGE trial is a treatment de-escalation trial for women with estrogen receptor positive stage II (with LVSI) or stage III no specific molecular profile (NSMP) endometrial cancer comparing radiotherapy followed by progestin for 2 years to adjuvant chemoradiation. The POLEmut-BLUE trial is a phase II trial in which the safety of de-escalation of adjuvant therapy is investigated for women with stage I-III POLEmut endometrial cancer: no adjuvant therapy for lower-risk disease and no adjuvant therapy or radiotherapy alone for higher-risk disease. The overarching RAINBO program will combine data and tumor material of all participants to perform translational research and evaluate molecular class-based adjuvant therapy in terms of efficacy, toxicity, quality of life, and cost-utility. Major inclusion/exclusion criteria: Inclusion criteria include a histologically confirmed diagnosis of endometrial cancer treated by hysterectomy and bilateral salpingo-oophorectomy with or without lymphadenectomy or sentinel lymph node biopsy, with no macroscopic residual disease after surgery and no distant metastases, and molecular classification according to the WHO 2020 algorithm. Primary endpoint(s): Recurrence-free survival at 3 years in the p53abn-RED, MMRd-GREEN, and NSMP-ORANGE trials and pelvic recurrence at 3 years in the POLEmut-BLUE trial. Sample size: The p53abn-RED trial will include 554 patients, the MMRd-GREEN trial 316, the NSMP-ORANGE trial 600, and the POLEmut-BLUE trial 145 (120 for lower-risk disease and approximately 25 for higher-risk disease). The overarching research program will pool the four sub-trials resulting in a total sample size of around 1600. Estimated dates for completing accrual and presenting results: The four clinical trials will have different completion dates; main results are expected from 2028. Show less
OBJECTIVE Direct injury to the corpus callosum (CC) due to neurosurgical interventions in infants with posthemorrhagic ventricular dilatation (PHVD) has not been reported in the literature. The... Show moreOBJECTIVE Direct injury to the corpus callosum (CC) due to neurosurgical interventions in infants with posthemorrhagic ventricular dilatation (PHVD) has not been reported in the literature. The authors observed a subset of infants who had suffered penetrating CC injury after neurosurgical interventions for PHVD and hypothesized that this pattern of injury may result in suboptimal CC maturation and neurodevelopmental impairment.METHODS In this multicenter, retrospective, observational study, 100 preterm and 17 full-term infants with PHVD were included and compared with 23 preterm controls. Both neonatal and postneonatal brain MRI scans were assessed for injury, and measurements were performed on postneonatal MRI scans at 2 years' corrected age. Neurodevelopmental outcome was assessed at 2 years' corrected age.RESULTS A total of 269 brain MRI scans of 140 infants were included. Of infants with PHVD, 48 (41%) had penetrating CC injury following neurosurgical interventions. The median (IQR) CC midsagittal surface area was smaller in infants with CC injury when compared with infants with PHVD who had intact CC and controls (190 mm(2) [149-262 mm(2)] vs 268 mm(2) [206-318 mm(2)] vs 289 mm(2) [246-320 mm(2)], respectively; p < 0.001). In the univariate analysis, the area of the CC was associated with cognitive Z score (coefficient 0.009 [95% CI 0.005-0.012], p < 0.001) and motor Z score (coefficient 0.009 [95% CI 0.006-0.012], p < 0.001). In the multivariable model, CC injury was not independently associated with cognitive and motor Z score after adjusting for gestational age and presence of periventricular hemorrhagic infarction (coefficient 0.04 [95% CI -0.36 to 0.46] and -0.37 [95% CI -0.83 to 0.09], p = 0.7 and 0.1, respectively).CONCLUSIONS CC injury was not uncommon following neurosurgical interventions for PHVD in both preterm and full-term infants. At the age of 2 years, the CC midsagittal surface area was smaller in infants with injury, but CC injury was not independently associated with cognitive and motor outcomes at 2 years' corrected age. Show less
BackgroundAcute alcohol intoxication is very common in patients with severe traumatic brain injury (TBI). Whether there is an independent association between alcohol intoxication and mortality is... Show moreBackgroundAcute alcohol intoxication is very common in patients with severe traumatic brain injury (TBI). Whether there is an independent association between alcohol intoxication and mortality is debated. This study hypothesized that alcohol intoxication is independently associated with less mortality after severe TBI (sTBI).MethodsThis retrospective observational cohort study included all patients with sTBI [head-Abbreviated Injury Score (AIS) >= 3, corresponding to serious head injury or worse] admitted from 1 January 2011 to 31 December 2016 in an academic level I trauma center. Patients were classified as with alcohol intoxication or without intoxication based on blood alcohol concentration or description of alcohol intoxication on admission. The primary endpoint was in-hospital mortality. Multivariable logistic regression analysis, including patient and injury characteristics, was used to assess independent association with alcohol intoxication.ResultsOf the 2865 TBI patients, 715 (25%) suffered from alcohol intoxication. They were younger (mean age 46 vs. 68 years), more often male (80 vs. 57%) and had a lower median Glasgow Coma Scale upon arrival (14 vs. 15) compared to the no-intoxication group. There was no difference in injury severity by head AIS or Rotterdam CT. Alcohol intoxication had an unadjusted association with in-hospital mortality [unadjusted odds ratio (OR) 0.51; 95% confidence interval (CI), 0.38-0.68]; however, there was no independent association after adjusting for potentially confounding patient and injury characteristics (adjusted OR 0.72; 95% CI, 0.48-1.09).ConclusionIn this retrospective study, there was no independent association between alcohol intoxication and higher in-hospital mortality in emergency patients with sTBI. Show less
Cardiovascular computed tomography (CCT) has undergone rapid maturation over the last decade and is now of proven clinical utility in the diagnosis and management of coronary artery disease, in... Show moreCardiovascular computed tomography (CCT) has undergone rapid maturation over the last decade and is now of proven clinical utility in the diagnosis and management of coronary artery disease, in guiding structural heart disease intervention, and in the diagnosis and treatment of congenital heart disease. The next decade will undoubtedly witness further advances in hardware and advanced analytics that will potentially see an increasingly core role for CCT at the center of clinical cardiovascular practice. In coronary artery disease assessment this may be via improved hemodynamic adjudication, and shear stress analysis using computational flow dynamics, more accurate and robust plaque characterization with spectral or photon- counting CT, or advanced quantification of CT data via artificial intelligence, machine learning, and radiomics. In structural heart disease, CCT is already pivotal to procedural planning with adjudication of gradients before and following intervention, whereas in congenital heart disease CCT is already used to support clinical decision making from neonates to adults, often with minimal radiation dose. In both these areas the role of computational flow dynamics, advanced tissue printing, and image modelling has the potential to revolutionize the way these complex conditions are managed, and CCT is likely to become an increasingly critical enabler across the whole advancing field of cardiovascular medicine. (c) 2019 by the American College of Cardiology Foundation. Show less
