Citations

Abstract Aims To investigate valve sizing and the haemodynamic relevance of the predicted left ventricular outflow tract (LVOT) in patients with mitral annular calcification (MAC) undergoing transatrial transcatheter valve implantation (THV). Methods and results In total, 21 patients undergoing transatrial THV, multiplanar reconstruction (MPR), maximum intensity projection (MIP), and cubic spline interpolation (CSI) were compared for MA sizing during diastole. In addition, predicted neo-LVOT areas were measured in 18 patients and correlated with the post-procedural haemodynamic dimensions. The procedure was successful in all patients (100%). Concomitant aortic valve replacement was performed in eight patients (43%) (AVR group). Sizing using MPR and MIP yielded comparable results in terms of area, perimeter, and diameter, whereas the dimensions obtained with CSI were systematically smaller. The simulated mean systolic neo-LVOT area was 133.4 ± 64.2 mm2 with an anticipated relative LVOT area reduction (neo-LVOT area/LVOT area × 100) of 59.3 ± 14.7%. The systolic relative LVOT area reduction, but not the absolute neo-LVOT area, was found to predict the peak (r = 0.69; P = 0.002) and mean (r = 0.65; P = 0.004) post-operative aortic gradient in the overall population as well as separately in the AVR (peak: r = 0.91; P = 0.002/mean: r = 0.85; P = 0.002) and no-AVR (peak: r = 0.89; P = 0.003/mean: r = 0.72; P = 0.008) groups. Conclusion In patients with severe MAC undergoing transatrial transcatheter valve implantation, MPR, and MIP yielded comparable annular dimensions, while values obtained with CSI tended to be systematically smaller. Mitral annular area and the average annular diameter appear to be reliable parameters for valve selection. Simulated relative LVOT reduction was found to predict the post-procedural aortic gradients.

Background. This systematic review was commissioned to identify new variables associated with transplant outcomes that are not currently collected by the Organ Procurement and Transplantation Network (OPTN). Methods. We identified 81 unique studies including 1 193 410 patients with median follow-up of 36 months posttransplant, reporting 108 unique risk factors. Results. Most risk factors (104) were recipient related; few (4) were donor related. Most risk factors were judged to be practical and feasible to routinely collect. Relative association measures were small to moderate for most risk factors (ranging between 1.0 and 2.0). The strongest relative association measure for a heart transplant outcome with a risk factor was 8.6 (recipient with the previous Fontan operation), for a kidney transplant 2.8 (sickle cell nephropathy as primary cause of end-stage renal disease), for a liver transplant 14.3 (recipient serum ferritin >500 µg/L), and for a lung transplant 6.3 (Burkholderia cepacia complex infection for 1 y or less). OPTN may consider some of these 108 variables for future collection to enhance transplant research and clinical care. Conclusions. Evidence-based approaches can be used to determine variables collected in databases and registries. Several candidate variables have been identified for OPTN.

Background . Hypertriglyceridemia and hyperglycemia coexist in 30-60% of patients with diabetes. The impact of hypertriglyceridemia regarding HbA1c assay reliability remains uncertain. Therefore, we conducted a prospective in vivo controlled study with the aim of defining the association between triglyceride levels and HbA1c. Methods . A total of 44 patients with an index-hospital admission diagnosis of diabetic ketoacidosis or hypertriglyceridemia-induced pancreatitis, as a model for acute elevation of triglycerides, were recruited. Blood samples were drawn for the measurement of HbA1c, triglycerides, glucose, and hemoglobin at baseline and subsequently 24 and 48 hours after admission. HbA1c analysis was performed with high-performance liquid chromatography Bio-Rad D10 (NGSP approved). Results . All patients completed the study protocol. A difference between mean triglycerides from day 0 (baseline) to day 2 of 1567.2 mg/dL was observed. We found a difference between mean serum HbA1c from days 0 to 2 of 0.09% [1 mmol/mol] ( p = 0.004 ). Moreover, a weak correlation between the mean difference of HbA1c and triglycerides from baseline to day 2 was found to be statistically significant ( r = 0.256 , p = 0.015 ). None of these findings, however, are clinically significant. Conclusion . Triglycerides do not impair the interpretation of HbA1c assay. Patients and clinicians can now be confident that hypertriglyceridemia is not an important factor when interpreting HbA1c results.

Abstract Purpose: The role of surgery for first relapse locally recurrent retroperitoneal sarcoma (RPS-LR1) is uncertain. We report outcomes of the largest RPS-LR1 series and propose a new prognostic nomogram. Experimental Design: Patients with consecutive RPS-LR1 without distant metastases who underwent resection at 22 centers (2002–2011) were included. Endpoints were disease-free and overall survival (DFS, OS) and crude-cumulative-incidence (CCI) of local/distant recurrence from second surgery. Nomograms predicting DFS and OS from second surgery were developed and validated (calibration plots); discrimination was assessed (Harrell C index). Results: Of 684 patients identified, full prognostic variable data were available for 602. Initial surgery for primary RPS was performed at our institutions in 188 patients (31%) and elsewhere in 414 (69%). At a median follow-up of 119 months [Interquartile range (IQR), 80–169] from initial surgery and 75 months (IQR 50–105) from second surgery, 6-year DFS and OS were 19.2% [95% confidence interval (CI), 16.0–23.0%] and 54.1% (95% CI, 49.8–58.8%), respectively. Recurrence patterns and survival probability were histology-specific, with liposarcoma subtypes having the highest 6-year CCI of second local recurrence (LR, 60.2%–70.9%) and leiomyosarcoma (LMS) having higher 6-year CCI of distant metastasis (DM, 36.3%). Nomograms included age at second surgery, multifocality, grade, completeness of second surgery, histology, chemotherapy/radiotherapy at first surgery, and number of organs resected at first surgery. OS and DFS nomograms showed good calibration and discriminative ability (C index 0.70 and 0.67, respectively). Conclusions: We developed nomograms to predict DFS and OS for patients undergoing RPS-LR1 resection. Nomograms provide individualized, disease-relevant estimations of survival for RPS-LR1 patients and assist in clinical decisions.

Male and female glioblastomas are biologically distinct, and improving outcomes may require sex-specific approaches to treatment.

Abstract DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N = 1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of P < 7.94 × 10−7. Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely MAPT, HOXB3, ABHD8, ARHGAP27, and SKAP1. We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression. Significance: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.

Purpose Although the life expectancy of patients with follicular lymphoma (FL) has increased, little is known of their causes of death (CODs) in the rituximab era. Patients and Methods We pooled two cohorts of newly diagnosed patients with FL grade 1-3A. Patients were enrolled between 2001 and 2013 in two French referral institutions (N = 734; median follow-up 89 months) and 2002 and 2012 in the University of Iowa and Mayo Clinic Specialized Program of Research Excellence (SPORE; N = 920; median follow-up 84 months). COD was classified as being a result of lymphoma, other malignancy, treatment related, or all other causes. Results Ten-year overall survival was comparable in the French (80%) and US (77%) cohorts. We were able to classify COD in 248 (88%) of 283 decedents. In the overall cohort, lymphoma was the most common COD, with a cumulative incidence of 10.3% at 10 years, followed by treatment-related mortality (3.0%), other malignancy (2.9%), other causes (2.2%), and unknown (3.0%). The 10-year cumulative incidence of death as a result of lymphoma or treatment was higher than death as a result of all other causes for each age group (including patients ≥ 70 years of age at diagnosis [25.4% v 16.6%]) Follicular Lymphoma International Prognostic Index score 3 to 5 (27.4% v 5.2%), but not Follicular Lymphoma International Prognostic Index score 0 to 1 (4.0% v 3.7%); for patients who failed to achieve event-free survival within 24 months from diagnosis (36.1% v 7.0%), but not for patients who achieved event-free survival within 24 months of diagnosis (6.7% v 5.7%); and for patients with a history of transformed FL (45.9% v 4.7%), but not among patients without (8.1% v 6.2%). Overall, 77 of 140 deaths as a result of lymphoma occurred in patients whose FL transformed after diagnosis. Conclusion Despite the improvement in overall survival in patients with FL in the rituximab era, their leading COD remains lymphoma, especially after disease transformation. Treatment-related mortality also represents a concern, which supports the need for less-toxic therapies.