Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

SummaryWe report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine

Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma

SummaryWe describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers

Risk of Ischemic Stroke after Intracranial Hemorrhage in Patients with Atrial Fibrillation

We aimed to estimate the risk of ischemic stroke after intracranial hemorrhage in patients with atrial fibrillation.Using discharge data from all nonfederal acute care hospitals and emergency departments in California, Florida, and New York from 2005 to 2012, we identified patients at the time of a first-recorded encounter with a diagnosis of atrial fibrillation. Ischemic stroke and intracranial hemorrhage were identified using validated diagnosis codes. Kaplan-Meier survival statistics and Cox proportional hazard analyses were used to evaluate cumulative rates of ischemic stroke and the relationship between incident intracranial hemorrhage and subsequent stroke.Among 2,084,735 patients with atrial fibrillation, 50,468 (2.4%) developed intracranial hemorrhage and 89,594 (4.3%) developed ischemic stroke during a mean follow-up period of 3.2 years. The 1-year cumulative rate of stroke was 8.1% (95% CI, 7.5-8.7%) after intracerebral hemorrhage, 3.9% (95% CI, 3.5-4.3%) after subdural hemorrhage, and 2.0% (95% CI, 2.0-2.1%) in those without intracranial hemorrhage. After adjustment for the CHA2DS2-VASc score, stroke risk was elevated after both intracerebral hemorrhage (hazard ratio [HR], 2.8; 95% CI, 2.6-2.9) and subdural hemorrhage (HR, 1.6; 95% CI, 1.5-1.7). Cumulative 1-year rates of stroke ranged from 0.9% in those with subdural hemorrhage and a CHA2DS2-VASc score of 0, to 33.3% in those with intracerebral hemorrhage and a CHA2DS2-VASc score of 9.In a large, heterogeneous cohort, patients with atrial fibrillation faced a substantially heightened risk of ischemic stroke after intracranial hemorrhage. The risk was most marked in those with intracerebral hemorrhage and high CHA2DS2-VASc scores

Scientific studies for the restauration of two wooden arm reliquaries from the Cathedral of Palermo

Dedicated to Saint Generosi and Saint Rosana, the reliquary arms, recalling the shape of a body part, are today located in the Relics Chapel in Palermo Cathedral. They are probably dated to the second half of the 18th century and are attributed to an unknown artist. The aims of this study were to investigate the decorative techniques, verify the state of conservation of the constitutive materials, measure the microclimate condition in the Relics Chapel, in order to set up a correct preventive conservation strategy. In this regard, an integrated scientific investigation was performed focusing on environmental monitoring (thermo-hygrometric parameters) by HOBO system, characterization of materials constituting the artefacts through optical and scanning electron microscopy (SEM-EDS), and X-ray fluorescence spectroscopy (XRF). The results lead to defining the appropriate restoration project for the two gilded wooden reliquaries

Cumulative ischemic stroke rates in atrial fibrillation patients, stratified by intracranial hemorrhage status.

<p>Differences between groups were significant (<i>P</i> < 0.001 for test of trend).</p