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BACKGROUNDProstate cancer is multifocal with distinct molecular subtypes. The utility of genomic subtyping has been challenged due to inter- and intrafocal heterogeneity. We sought to characterize the subtype-defining molecular alterations of primary prostate cancer across all tumor foci within radical prostatectomy (RP) specimens and determine the prevalence of collision tumors.METHODSFrom the Early Detection Research Network cohort, we identified 333 prospectively collected RPs from 2010 to 2014 and assessed ETS-related gene (ERG), serine peptidase inhibitor Kazal type 1 (SPINK1), phosphatase and tensin homolog (PTEN), and speckle type BTB/POZ protein (SPOP) molecular status. We utilized dual ERG/SPINK1 immunohistochemistry and fluorescence in situ hybridization to confirm ERG rearrangements and characterize PTEN deletion, as well as high-resolution melting curve analysis and Sanger sequencing to determine SPOP mutation status.RESULTSBased on index focus alone, ERG, SPINK1, PTEN, and SPOP alterations were identified in 47.5%, 10.8%, 14.3%, and 5.1% of RP specimens, respectively. In 233 multifocal RPs with ERG/SPINK1 status in all foci, 139 (59.7%) had discordant molecular alterations between foci. Collision tumors, as defined by discrepant ERG/SPINK1 status within a single focus, were identified in 29 (9.4%) RP specimens.CONCLUSIONInterfocal molecular heterogeneity was identified in about 60% of multifocal RP specimens, and collision tumors were present in about 10%. We present this phenomenon as a model for the intrafocal heterogeneity observed in previous studies and propose that future genomic studies screen for collision tumors to better characterize molecular heterogeneity.FUNDINGEarly Detection Research Network US National Cancer Institute (NCI) 5U01 CA111275-09, Center for Translational Pathology at Weill Cornell Medicine (WCM) Department of Pathology and Laboratory Medicine, US NCI (WCM SPORE in Prostate Cancer, P50CA211024-01), R37CA215040, Damon Runyon Cancer Research Foundation, US MetLife Foundation Family Clinical Investigator Award, Norwegian Cancer Society (grant 208197), and South-Eastern Norway Regional Health Authority (grant 2019016 and 2020063).

PURPOSE: Biobanking tissue of high quality and fidelity is imperative for cancer genomics research. Since it is a challenging process, we sought to develop a protocol that improves the fidelity and quantity of biobanked primary prostate cancer (PCa) tissue. MATERIALS AND METHODS: We conducted a pilot study evaluating pathologic concordance of biobanked tissue and the radical prostatectomy specimen using either standard protocol (SP) vs next-generation protocol (NGP). RESULTS: There were no significant differences in clinical and pathologic characteristics (age, BMI, pre-operative PSA, prostate weight, race, final prostatectomy Gleason score, or pathologic tumor and nodal stages) between the two protocol arms. Utilization of the NGP compared to the SP resulted in a significantly higher rate of pathologic concordance between the biobanked and RP specimens (61.8% vs 37.9%, p=0.0231) as well as a nearly two-fold increase in the amount of biobanked tumor tissue (330 mm(3) vs 174 mm(3), p

INTRODUCTION AND OBJECTIVES:The risk of prostate needle biopsy (PNBx) infections and sepsis is increasing, with recent estimates of 7% and 3%, respectively. Each post-PNBx infection costs an estima...

Stroke is one of the leading causes of morbidity and mortality in developed countries and an immense amount of medical care resources are devoted to combat the poststroke debilitating consequences. The key to develop effective and clinically applicable treatment methodologies is a better understanding of the pathophysiology of the disease, including the root causes and targets for pharmacology. Developing these foundations requires the use of standard animal models that mimic the physicochemical process of the diseases that can reliably replicate results in order to test and fine-tune therapeutic modalities. Middle cerebral artery occlusion (MCAO), endothelin-1-induced ischemic stroke, photothrombosis, devascularization, embolization, and spontaneous infarction using hemorrhage are some examples of different animal models. Reliability of MCAO has been proved and due to the ability to induce reperfusion similar to tissue plasminogen activator (tPA) therapy, this model is widely used in preclinical studies. Here, we describe a detailed methodology on how to develop MCAO stroke in rodents using intra-arterial insertion of filament to occlude the middle cerebral artery. This approach allows for the study of a wide array of basic pathophysiology mechanisms, regenerative medicine and rehabilitation therapy.

Atrial fibrillation (AF) is the most common cardiac arrhythmia associated with substantial increases in death, heart failure, and stroke. It is important for healthcare providers in all fields to also gain an understanding of the novel techniques used in surgical treatment of AF. Clinicians must now decide between many different options. There are modified Maze procedures, catheter-based or minimally invasive surgical approaches to isolate the triggers and foci in the left atrium responsible for AF. A recently proposed radial approach can also be employed in substitution of the traditional geographical maze surgery. Finally, different energy sources, such as cryoablation, radiofrequency, microwave, and laser, can be used to create lesions in the atrium. Especially in the fields of neurology, psychiatry, and psychology, an understanding of these treatments is important for the management of AF patients with neurological pathology.

Vagus nerve stimulation (VNS) is currently FDA-approved for treatment of both medically refractory partial-onset seizures and severe, recurrent refractory depression which have failed to respond to medical interventions. Because of its ability to regulate mechanisms well-studied in neuroscience, such as norepinephrine and serotonin release, the vagus nerve may play an important role in regulating cerebral blood flow, edema, inflammation, glutamate excitotoxicity, and neurotrophic processes. There is strong evidence that these same processes are important in stroke pathophysiology. We reviewed the literature for the role of VNS in improving ischemic stroke outcomes by performing a systematic search for publications in Medline (1966-2014) with keywords “vagus nerve stimulation AND stroke” in subject headings and key words with no language restrictions. Of the 73 publications retrieved, we identified 7 studies from 3 different research groups that met our final inclusion criteria of research studies addressing the role of vagus nerve stimulation in ischemic stroke. Results from these studies suggest that VNS has promising efficacy in reducing stroke volume and attenuating neurological deficits in ischemic stroke models. Given the lack of success in Phase III trials for stroke neuroprotection, it is important to develop new therapies targeting different neuroprotective pathways. Further studies of the possible role of VNS, through normally physiologically active mechanisms, in ischemic stroke therapeutics should be conducted in both animal models and clinical studies. In addition, recent advent of a non-invasive, transcutaneous VNS could provide the potential for easier clinical translation.

Background: Spontaneous intracranial hypotension (SIH) is one of the relatively misdiagnosed pathophysiological entities by virtue of its presentation. SIH is a condition involving reduced intracranial pressure usually secondary to dural tear. There is recent increase in reporting of its varied presentation in literature. Critical care physicians and neurosurgeons are recognizing it in higher numbers than before. SIH is characterized by sudden onset of orthostatic headache and may be associated with neck stiffness, nausea, vomiting, tinnitus, deafness, and cognitive abnormalities. Since its imaging characteristics resemble classic subdural hematoma from other causes wrong diagnosis and intervention might have devastating outcome. Case Description: Here we discuss a case presented to us with severe headache of sudden onset without any associated problems. Patient was initially being treated as sinusitis and later diagnosed as bilateral subdural hematoma and surgical intervention was being considered. Thorough history taking and physical examination lead to strong suspicion of intracranial hypotension (IH) and patient showed dramatic improvement with epidural blood patch. Conclusion: SIH is a commonly misdiagnosed entity. A high index of suspicion is required for timely diagnosis, in order to minimize unwanted therapeutic interventions that can worsen the patient’s condition and to help initiate early and simple interventions.