A review of multiomics platforms in pituitary adenoma pathogenesis

Pituitary adenomas (PA), or pituitary neuroendocrine tumors (PitNETs), represent 15% of all central nervous system tumors. Classic description of PitNETs solely by hormonal classification has given way to key transcription factors that play a role in the pathology of PitNETs including steroidogenic factor-1 (SF-1), t-box pituitary transcription factor (TPIT), and pituitary transcription factor 1 (PIT-1). Germline mutations in various familial PitNETs are discussed including those in familial isolated pituitary adenoma (FIPA), multiple endocrine neoplasia (MEN), neurofibromatosis 1 (NF1), and Carney complex. Recent advances in next generation sequencing have improved insight into the pathogenesis of PitNETs. A review of key studies in evaluating the genomic analysis of PitNETs was performed. Chromosomal mutations, whole exome sequencing, microRNA genomics, methylomics and transcriptomics were analyzed. Moreover, the multiomic analysis of various genomic panels has helped to better understand PA classification

Genetics of the Hippocampal Transcriptome in Mouse: A Systematic Survey and Online Neurogenomics Resource

Differences in gene expression in the CNS influence behavior and disease susceptibility. To systematically explore the role of normal variation in expression on hippocampal structure and function, we generated an online microarray database for a diverse panel of strains of mice, including most common inbred strains and numerous recombinant inbred lines (www.genenetwork.org). Using this resource, coexpression networks for families of genes can be generated rapidly to test causal models related to function. The data set is optimized for quantitative trait locus (QTL) mapping and was used to identify over 5500 QTLs that modulate mRNA levels. We describe a wide variety of analyses and novel synthetic approaches that take advantage of this resource, and demonstrate how both the data and associated tools can be applied to the study of gene regulation in the hippocampus and relations to structure and function

Arrhythmia and death following percutaneous revascularization in ischemic left ventricular dysfunction: Prespecified analyses from the REVIVED-BCIS2 trial

BACKGROUND: Ventricular arrhythmia is an important cause of mortality in patients with ischemic left ventricular dysfunction. Revascularization with coronary artery bypass graft or percutaneous coronary intervention is often recommended for these patients before implantation of a cardiac defibrillator because it is assumed that this may reduce the incidence of fatal and potentially fatal ventricular arrhythmias, although this premise has not been evaluated in a randomized trial to date. METHODS: Patients with severe left ventricular dysfunction, extensive coronary disease, and viable myocardium were randomly assigned to receive either percutaneous coronary intervention (PCI) plus optimal medical and device therapy (OMT) or OMT alone. The composite primary outcome was all-cause death or aborted sudden death (defined as an appropriate implantable cardioverter defibrillator therapy or a resuscitated cardiac arrest) at a minimum of 24 months, analyzed as time to first event on an intention-to-treat basis. Secondary outcomes included cardiovascular death or aborted sudden death, appropriate implantable cardioverter defibrillator (ICD) therapy or sustained ventricular arrhythmia, and number of appropriate ICD therapies. RESULTS: Between August 28, 2013, and March 19, 2020, 700 patients were enrolled across 40 centers in the United Kingdom. A total of 347 patients were assigned to the PCI+OMT group and 353 to the OMT alone group. The mean age of participants was 69 years; 88% were male; 56% had hypertension; 41% had diabetes; and 53% had a clinical history of myocardial infarction. The median left ventricular ejection fraction was 28%; 53.1% had an implantable defibrillator inserted before randomization or during follow-up. All-cause death or aborted sudden death occurred in 144 patients (41.6%) in the PCI group and 142 patients (40.2%) in the OMT group (hazard ratio, 1.03 [95% CI, 0.82–1.30]; P =0.80). There was no between-group difference in the occurrence of any of the secondary outcomes. CONCLUSIONS: PCI was not associated with a reduction in all-cause mortality or aborted sudden death. In patients with ischemic cardiomyopathy, PCI is not beneficial solely for the purpose of reducing potentially fatal ventricular arrhythmias. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01920048

Radiation of meningioma dural tail may not improve tumor control rates.

Introduction: Dural tails are thickened contrast-enhancing portions of dura associated with some meningiomas. Prior studies have demonstrated the presence of tumor cells within the dural tail, however their inclusion in radiation treatment fields remains controversial. We evaluated the role of including the dural tail when treating a meningioma with stereotactic radiation and the impact on tumor recurrence. Methods: This is a retrospective, single-institution, cohort study of patients with intracranial World Health Organization (WHO) grade 1 meningioma and identified dural tail who were treated with stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) from January 2012 to December 2018. SRS and FSRT subgroups were categorized based on coverage or non-coverage of the dural tail by the radiation fields, as determined independently by a radiation oncologist and a neurosurgeon. Demographics, tumor characteristics, radiation plans, and outcomes were evaluated. High grade tumors were analyzed separately. Results: A total of 187 WHO grade 1 tumors from 177 patients were included in the study (median age: 62 years, median follow-up: 40 months, 78.1% female) with 104 receiving SRS and 83 receiving FSRT. The dural tail was covered in 141 (75.4%) of treatment plans. There was no difference in recurrence rates (RR) or time to recurrence (TTR) between non-coverage or coverage of dural tails (RR: 2.2% vs 3.5%, Conclusion: Inclusion of the dural tail in the SRS or FSRT volumes for meningioma treatment does not seem to reduce recurrence rate. Improved understanding of dural tail pathophysiology, tumor grade, tumor spread, and radiation response is needed to better predict the response of meningiomas to radiotherapy

Does Pre-Operative Opiate Choice Increase Risk of Post-Operative Infection and Subsequent Surgery?

BACKGROUND: Opioids are commonly prescribed for chronic pain prior to spinal surgery and research has shown an increased rate of post-operative adverse events in these patients. OBJECTIVE: This study compared the incidence of two-year subsequent surgical procedures and post-operative adverse events in patients undergoing lumbar fusion with or without 90-day pre-operative opioid use. We hypothesized that patients using preoperative opioids to have a higher incidence of subsequent surgery and adverse outcomes. METHODS: A retrospective cohort study was performed using Optum Pan-Therapeutic Electronic Health Records database including adult patients who had their first lumbar fusion between 2015 and 2018. The daily average preoperative opioid dosage 90 days prior to fusion was determined as morphine equivalent dose (MED) and further categorized into high-dose (MED\u3e100mg/day) and low-dose (1-100mg/day). Clinical outcomes were compared after adjusting for confounders. RESULTS: A total of 23,275 patients were included, with 2,112 (10%) patients using opioids preoperatively. There was a significantly higher incidence of infection compared to non-users (12.3% versus 10.1%; P=0.01). There was no association between subsequent fusion surgery (7.9% versus 7.5%, P=0.52) and subsequent decompression surgery (4.1% versus 3.6%; P=0.3) between opioid users and non-users. Regarding post-operative infection risk, low-dose users showed significantly higher incidence (12.7% versus 10.1%; P CONCLUSION: Consistent with prior publications, opioid use was significantly associated with a higher incidence of two-year post-operative infection compared to non-use. Low-dose opioid users had higher post-operative infection rates than non-users