Resistance prediction in AML: analysis of 4601 patients from MRC/NCRI, HOVON/SAKK, SWOG and MD Anderson Cancer Center

Therapeutic resistance remains the principal problem in acute myeloid leukemia (AML). We used area under receiver-operating characteristic curves (AUCs) to quantify our ability to predict therapeutic resistance in individual patients, where AUC=1.0 denotes perfect prediction and AUC=0.5 denotes a coin flip, using data from 4601 patients with newly diagnosed AML given induction therapy with 3+7 or more intense standard regimens in UK Medical Research Council/National Cancer Research Institute, Dutch–Belgian Cooperative Trial Group for Hematology/Oncology/Swiss Group for Clinical Cancer Research, US cooperative group SWOG and MD Anderson Cancer Center studies. Age, performance status, white blood cell count, secondary disease, cytogenetic risk and FLT3-ITD/NPM1 mutation status were each independently associated with failure to achieve complete remission despite no early death (‘primary refractoriness’). However, the AUC of a bootstrap-corrected multivariable model predicting this outcome was only 0.78, indicating only fair predictive ability. Removal of FLT3-ITD and NPM1 information only slightly decreased the AUC (0.76). Prediction of resistance, defined as primary refractoriness or short relapse-free survival, was even more difficult. Our limited ability to forecast resistance based on routinely available pretreatment covariates provides a rationale for continued randomization between standard and new therapies and supports further examination of genetic and posttreatment data to optimize resistance prediction in AML.

The Freedom SOLO bovine pericardial stentless valve: Single-center experience, outcome and long-term durability

Abstract Objectives We report our institutional experience and long-term results with the Sorin Freedom SOLO bovine pericardial stentless bioprosthesis. Methods Between January 2005 and November 2009, 149 patients (mean age 73.6±8.7 years, 68 [45.6%] female) underwent isolated (n=75) or combined (n=74) aortic valve replacement (AVR) using the SOLO in our institution. Follow-up was 100% complete with an average follow-up time of 5.9±2.6 years (maximum 9.6 years) and a total of 885.3 patient years. Results Operative (30-day) mortality was 2.7% (1.3% for isolated AVR [n=1] and 4.0% for combined procedures [n=3]). All causes of death were not valve-related. Preoperative peak (mean) gradients of 74.2±23.0 mmHg (48.6 ± 16.3 mmHg) decreased to 15.6±5.4 (8.8±3.0) after AVR, and remained low for up to 9 years. The postoperative effective orifice area (EOA) was 1.6 ±0.57 cm2, 1.90±0.45 cm2, 2.12±0.48 cm2 and 2.20±0.66 cm2 for the valve sizes 21, 23, 25 and 27, respectively; with absence of severe prosthesis-patient-mismatch (PPM) and 0.7% (n=1) moderate PPM. During follow-up, Twenty-six patients experienced structural valve deterioration (SVD) and 14 patients underwent explantation. Kaplan-Meier estimates for freedom from death, explantation and SVD at 9 years averaged 0.57 [0.47‒0.66], 0.82 [0.69‒0.90] and 0.70 [0.57‒0.79], respectively. Conclusions The Freedom SOLO stentless aortic valve is safe to implant and shows excellent early and mid-term hemodynamic performance. However, SVD was observed in a substantial number of patients after only 5 ̶ 6 years and the need for explantation increased markedly, suggesting low durability.

Novel emboli protection system during cardiac surgery: a multi-center, randomized, clinical trial.

BACKGROUND Stroke is a major cause of morbidity and mortality during open-heart surgery. Up to 60% of intraoperative cerebral events are emboli induced. This randomized, controlled, multicenter trial is the first human study evaluating the safety and efficacy of a novel aortic cannula producing simultaneous forward flow and backward suction for extracting solid and gaseous emboli from the ascending aorta and aortic arch upon their intraoperative release. METHODS Sixty-six patients (25 females; 68±10 years) undergoing elective aortic valve replacement surgery, with or without coronary artery bypass graft surgery, were randomized to the use of the CardioGard (CardioGard Medical, Or-Yehuda, Israel) Emboli Protection cannula ("treatment") or a standard ("control") aortic cannula. The primary endpoint was the volume of new brain lesions measured by diffusion-weighted magnetic resonance imaging (DW-MRI), performed preoperatively and postoperatively. Device safety was investigated by comparisons of complications rate, namely neurologic events, stroke, renal insufficiency and death. RESULTS Of 66 patients (34 in the treatment group), 51 completed the presurgery and postsurgery MRI (27 in the treatment group). The volume of new brain lesion for the treatment group was (mean±standard error of the mean) 44.00±64.00 versus 126.56±28.74 mm3 in the control group (p=0.004). Of the treatment group, 41% demonstrated new postoperative lesions versus 66% in the control group (p=0.03). The complication rate was comparable in both groups. CONCLUSIONS The CardioGard cannula is safe and efficient in use during open-heart surgery. Efficacy was demonstrated by the removal of a substantial amount of emboli, a significant reduction in the volume of new brain lesions, and the percentage of patients experiencing new brain lesions.

Association between Head Injury and Helmet Use in Alpine Skiers: Cohort Study from a Swiss Level I Trauma Center.

The association between helmet use during alpine skiing and incidence and severity of head injuries was analyzed. All patients admitted to a level 1 trauma center for traumatic brain injuries (TBIs) sustained from skiing accidents during the seasons 2000-2001 and 2010-2011 were eligible. Primary outcome was the association between helmet use and severity of TBI measured by Glasgow Coma Scale (GCS), computed tomography (CT) results, and necessity of neurosurgical intervention. Of 1362 patients injured during alpine skiing, 245 (18%) sustained TBI and were included. TBI was fatal in 3%. Head injury was in 76% minor (Glasgow Coma Scale, 13-15), 6% moderate, and 14% severe. Number and percentage of TBI patients showed no significant trend over the investigated seasons. Forty-five percent of the 245 patients had pathological CT findings and 26% of these required neurosurgical intervention. Helmet use increased from 0% in 2000-2001 to 71% in 2010-2011 (p<0.001). The main analysis, comparing TBI in patients with or without a helmet, showed an adjusted odds ratio (OR) of 1.44 (p=0.430) for suffering moderate-to-severe head injury in helmet users. Analyses comparing off-piste to on-slope skiers revealed a significantly increased OR among off-piste skiers of 7.62 (p=0.004) for sustaining a TBI requiring surgical intervention. Despite increases in helmet use, we found no decrease in severe TBI among alpine skiers. Logistic regression analysis showed no significant difference in TBI with regard to helmet use, but increased risk for off-piste skiers. The limited protection of helmets and dangers of skiing off-piste should be targeted by prevention programs.