Echocardiographic assessment of tricuspid regurgitation and pericardial effusion after cardiac device implantation

Background: The frequency of cardiac implantable electronic device (CIED) implantations is constantly increasing. Pericardial effusion (PE) and tricuspid regurgitation (TR) may occur after CIED implantation. The aim of the present study is to evaluate the prevalence and risk factors for new occurrences or progression of TR and PE early after CIED implantation. Methods: This is an on-going, single-center, observational study of patients after their first CIED implantation, with an echocardiographic evaluation within 60 days before and 7 days after the procedure. Data are presented for first 110 consecutive patients who underwent CIED implantation from August 2015 to July 2016. Results: Median age was 75 years, and 44% were women. In total, 87 (79%) pacemakers, 21 (19%) implantable cardioverter-defibrillators and 2 cardiac resynchronization therapy devices were implanted. After CIED implantation, there was TR progression in 17 (16%) patients: 5 patients developed moderate TR, none developed severe TR. An increase in TR was more often observed after implantations performed by operators in training than by certified operators (35% vs. 12%, p = 0.02). New PE after the procedure was observed in 8 (7%) patients and was trivial ( < 5 mm) in all cases. Patients with new PE after implantation had lower baseline hemoglobin levels and tended to be women. Conclusions: New PE and an increase in TR severity are rare complications early after CIED implantation. Operator experience might be related to TR progression. Increasing the number of patients in the current on-going study will allow a more reliable assessment of the prevalence and risk factors of these complications

Targeted sequencing of cancer-related genes reveals a recurrent TOP2A variant which affects DNA binding and coincides with global transcriptional changes in glioblastoma

High-grade gliomas are aggressive, deadly primary brain tumors. Median survival of patients with glioblastoma (GBM, WHO grade 4) is 14 months and \u3c10% of patients survive 2 years. Despite improved surgical strategies and forceful radiotherapy and chemotherapy, the prognosis of GBM patients is poor and did not improve over decades. We performed targeted next-generation sequencing with a custom panel of 664 cancer- and epigenetics-related genes, and searched for somatic and germline variants in 180 gliomas of different WHO grades. Herein, we focus on 135 GBM IDH-wild type samples. In parallel, mRNA sequencing was accomplished to detect transcriptomic abnormalities. We present the genomic alterations in high-grade gliomas and the associated transcriptomic patterns. Computational analyses and biochemical assays showed the influence of TOP2A variants on enzyme activities. In 4/135 IDH-wild type GBMs we found a novel, recurrent mutation in the TOP2A gene encoding topoisomerase 2A (allele frequency [AF] = 0.03, 4/135 samples). Biochemical assays with recombinant, wild type (WT) and variant proteins demonstrated stronger DNA binding and relaxation activity of the variant protein. GBM patients carrying the altered TOP2A had shorter overall survival (median OS 150 vs 500 days, P = .0018). In the GBMs with the TOP2A variant we found transcriptomic alterations consistent with splicing dysregulation. luA novel, recurrent TOP2A mutation, which was found exclusively in four GBMs, results in the TOP2A E948Q variant with altered DNA binding and relaxation activities. The deleterious TOP2A mutation resulting in transcription deregulation in GBMs may contribute to disease pathology