Evaluation of liver tissue by ultrasound elastography and clinical parameters in children with multiple blood cell transfusions.

BACKGROUND: Children receiving multiple blood cell transfusions are prone to iron overload and successive tissue damage in liver parenchyma, making noninvasive screening options desirable. Ultrasound (US) elastography using acoustic radiation force impulse (ARFI) imaging enables evaluation of liver parenchyma stiffness, and MRI allows for quantification of liver iron concentration. OBJECTIVE: The objective was to correlate US elastography with MRI in children who had undergone bone marrow transplantation and to evaluate the modification of liver tissue with US in combination with clinical parameters at follow-up. MATERIALS AND METHODS: ARFI, T2*-weighted MRI and a clinical score (HepScore, based on parameters of liver function) were performed in 45 patients (24 male; mean age 9.7 years) before and 100 days and 365 days after transplantation. All received multiple blood transfusions (mean number 22.2 up until 1 year after transplantation). We correlated US findings and HepScore with MRI findings. RESULTS: We observed signs of iron accumulation in 29/45 (64.4%) patients on MRI (T2*<10 ms) and 15/45 (33.3%) showed increased tissue stiffness (ARFI>5.5 kPa). Correlation of elastography and MRI was not significant (P=0.57; n=51 matched measurements). Comparing US elastography with HepScore in receiver operating characteristic (ROC) curve analysis indicated a cut-off for affected parenchyma if HepScore was >5 points (sensitivity 67%, specificity 68%). Simultaneous increases of both indicated tissue alteration. CONCLUSION: Combining US and HepScore enabled detection of liver tissue alteration through iron overload, but we found no direct significant effect of estimated iron from MRI on ARFI imaging.

Firth's logistic regression with rare events: accurate effect estimates and predictions?

Firth's logistic regression has become a standard approach for the analysis of binary outcomes with small samples. Whereas it reduces the bias in maximum likelihood estimates of coefficients, bias towards one-half is introduced in the predicted probabilities. The stronger the imbalance of the outcome, the more severe is the bias in the predicted probabilities. We propose two simple modifications of Firth's logistic regression resulting in unbiased predicted probabilities. The first corrects the predicted probabilities by a post hoc adjustment of the intercept. The other is based on an alternative formulation of Firth's penalization as an iterative data augmentation procedure. Our suggested modification consists in introducing an indicator variable that distinguishes between original and pseudo-observations in the augmented data. In a comprehensive simulation study, these approaches are compared with other attempts to improve predictions based on Firth's penalization and to other published penalization strategies intended for routine use. For instance, we consider a recently suggested compromise between maximum likelihood and Firth's logistic regression. Simulation results are scrutinized with regard to prediction and effect estimation. We find that both our suggested methods do not only give unbiased predicted probabilities but also improve the accuracy conditional on explanatory variables compared with Firth's penalization. While one method results in effect estimates identical to those of Firth's penalization, the other introduces some bias, but this is compensated by a decrease in the mean squared error. Finally, all methods considered are illustrated and compared for a study on arterial closure devices in minimally invasive cardiac surgery. Copyright © 2017 John Wiley & Sons, Ltd.

Leave-one-out cross-validation, penalization, and differential bias of some prediction model performance measures-a simulation study.

BACKGROUND: The performance of models for binary outcomes can be described by measures such as the concordance statistic (c-statistic, area under the curve), the discrimination slope, or the Brier score. At internal validation, data resampling techniques, e.g., cross-validation, are frequently employed to correct for optimism in these model performance criteria. Especially with small samples or rare events, leave-one-out cross-validation is a popular choice. METHODS: Using simulations and a real data example, we compared the effect of different resampling techniques on the estimation of c-statistics, discrimination slopes, and Brier scores for three estimators of logistic regression models, including the maximum likelihood and two maximum penalized likelihood estimators. RESULTS: Our simulation study confirms earlier studies reporting that leave-one-out cross-validated c-statistics can be strongly biased towards zero. In addition, our study reveals that this bias is even more pronounced for model estimators shrinking estimated probabilities towards the observed event fraction, such as ridge regression. Leave-one-out cross-validation also provided pessimistic estimates of the discrimination slope but nearly unbiased estimates of the Brier score. CONCLUSIONS: We recommend to use leave-pair-out cross-validation, fivefold cross-validation with repetitions, the enhanced or the .632+ bootstrap to estimate c-statistics, and leave-pair-out or fivefold cross-validation to estimate discrimination slopes.

Percutaneous cannulation for cardiopulmonary bypass in minimally invasive surgery is associated with reduced groin complications.

OBJECTIVES: Femoral cutdown is standard in most centres if groin cannulation is used for cardiopulmonary bypass in minimally invasive cardiac surgery (MICS). Arterial closure devices (ACDs) allow placement of larger cannulas percutaneously, but its benefit in MICS is unclear. We assessed our results with percutaneous groin cannulation using ACDs in comparison with conventional surgical access in patients undergoing MICS. METHODS: We reviewed 445 consecutive patients having undergone MICS between October 2010 and March 2015. Of those, 92 (21%) were performed with conventional surgical access to the groin vessels and 353 (79%) with the use of ACDs. RESULTS: Operative risk was higher in the ACD group [logistic EuroSCORE 7.9% (SD: 8.1) vs 10.6% (SD: 12.3); P = 0.010]. The use of ACDs significantly reduced operation time [193 min (SD: 43.8) vs 173 min (SD: 47.1); P < 0.001] and hospital stay [Cutdown: median 9 days (8, 14); ACD: median 9 days (7, 12), P = 0.040] without affecting the time to full mobilization. The incidence of any complication was significantly lower in the ACD group (2.3% vs 8.7%; P = 0.007). Complications with conventional cannulation consisted of lymphatic fistulae (n = 4), wound infections (n = 2), stenosis (n = 1) and haematoma (n = 1). In the ACD group, there were local dissections (n = 2) and stenoses (n = 3). There was 1 haematoma in both groups. There were 2 vascular injuries in the ACD group (n = 2), leading to conversion to surgical access. CONCLUSIONS: Percutaneous groin cannulation using ACDs for establishing cardiopulmonary bypass in minimally invasive valve surgery significantly reduces groin complications, operation time and hospital stay. However, the remaining complications are mainly of vascular nature versus wound infection and lymph fistulae with cutdown.