Faculty Bibliography

INTRODUCTION/BACKGROUND:Current management of ischemic priapism revolves around 3 principles: resolving the acute event, preserving erectile function, and reducing the risk of future recurrences. Although more conservative management options, such as aspiration, irrigation, and surgical shunts, are effective in many patients, those who are refractory to these interventions or have prolonged priapism may benefit from placement of a penile prosthesis (PP). AIM/OBJECTIVE:To provide a comprehensive overview of priapism management, highlight the current literature on the utility of penile implants for refractory priapism, and provide insight from a high-volume center on surgical decision making and technique. METHODS:A complete review of the current guidelines and associated literature was performed. Associated algorithms were evaluated, and our experience was overlaid on the data present in the literature. MAIN OUTCOME MEASURES/METHODS:The current management algorithm for priapism was evaluated. Subsequently, the data on acute and delayed PP placement were assessed. Rates of postoperative infection, erectile dysfunction, and patient satisfaction were also examined. RESULTS:Overall, both delayed and early PP implants are associated with higher rates of failure than routine PP implants. In patients with refractory or prolonged priapism, early implantation may be technically easier, with decreased loss of penile length and associated complications. CONCLUSION/CONCLUSIONS:Patients should be evaluated on an individual basis and counseled on the risks and benefits of PP implantation in early and delayed time frames. Although there is no definitive evidence at this time regarding the ideal device or timing of implantation, there are well-established pros and cons of malleable vs inflatable prostheses and of acute vs delayed implantation. Mishra K, Loeb A, Bukavina L, et al. Management of Priapism: A Contemporary Review. Sex Med Rev 2020;8:131-139.

Andexanet-alpha is a specific reversal agent for direct factor Xa inhibitors (dFXaI). We aimed to project utilization rates and cost of andexanet for reversal of dFXaI-related major hemorrhage compared to 4-factor prothrombin complex concentrates (4F-PCC). A retrospective, multicenter review was conducted between 1/1/2014 and 7/15/2018 of patients who received 4F-PCC for reversal of dFXaI-related life-threatening hemorrhages. Total hospital reimbursements/patient were calculated based on national average MS-DRG payments adjusting for Medicare discounts. The projected cost for andexanet (based on dose and insurance) and % reimbursement/patient was compared to the actual cost of 4F-PCC. Hemostasis at 24 h (excellent/good vs. poor) and 30-day thrombotic complications were assessed. Of 126 patients who received 4F-PCC to reverse dFXaI, 46 (~ 10 per-year) met inclusion criteria. The median projected cost of andexanet was $22,120/patient, compared to $5670/patient for 4F-PCC (P < 0.001). The median hospital reimbursement was $11,492/hospitalization. The projected cost of andexanet alone would exceed the entire hospital reimbursement in 74% of patients by a median of $7604, while 4F-PCC cost exceeded the total hospital payments in 7% of patients in the same cohort (P < 0.001). Hemostasis was excellent/good in 72% of patients post-4F-PCC, compared to 82% in andexanet trials. Thromboembolic events occurred in 4% of patients following 4F-PCC versus 10% in andexanet trials. The projected cost of andexanet would exceed the national average hospital reimbursement/patient in nearly 75% of patients by over $7500/hospitalization. 4F-PCC was significantly less expensive, had lower rates of thrombosis, but also lower rates of good/excellent hemostasis compared to published data for andexanet.

AIMS:Exposure to recurrent hypoglycemia (RH) is common in diabetic patients receiving glucose-lowering therapies and is implicated in causing cognitive impairments. Despite the significant effect of RH on hippocampal function, the underlying mechanisms are currently unknown. Our goal was to determine the effect of RH exposure on hippocampal metabolism in treated streptozotocin-diabetic rats. METHODS:Hyperglycemia was corrected by insulin pellet implantation. Insulin-treated diabetic (ITD) rats were exposed to mild/moderate RH once a day for 5 consecutive days. RESULTS:The effect of RH on hippocampal metabolism revealed 65 significantly altered metabolites in the RH group compared with controls. Several significant differences in metabolite levels belonging to major pathways (eg, Krebs cycle, gluconeogenesis, and amino acid metabolism) were discovered in RH-exposed ITD rats when compared to a control group. Key glycolytic enzymes including hexokinase, phosphofructokinase, and pyruvate kinase were affected by RH exposure. CONCLUSION:Our results demonstrate that the exposure to RH leads to metabolomics alterations in the hippocampus of insulin-treated streptozotocin-diabetic rats. Understanding how RH affects hippocampal metabolism may help attenuate the adverse effects of RH on hippocampal functions.

De novo mutations arising on the paternal chromosome make the largest known contribution to autism risk, and correlate with paternal age at the time of conception. The recurrence risk for autism spectrum disorders is substantial, leading many families to decline future pregnancies, but the potential impact of assessing parental gonadal mosaicism has not been considered. We measured sperm mosaicism using deep-whole-genome sequencing, for variants both present in an offspring and evident only in father's sperm, and identified single-nucleotide, structural and short tandem-repeat variants. We found that mosaicism quantification can stratify autism spectrum disorders recurrence risk due to de novo mutations into a vast majority with near 0% recurrence and a small fraction with a substantially higher and quantifiable risk, and we identify novel mosaic variants at risk for transmission to a future offspring. This suggests, therefore, that genetic counseling would benefit from the addition of sperm mosaicism assessment.

Background/UNASSIGNED:F]PARPi, as a diagnostic tool to differentiate between brain cancers and treatment-related changes. Methods/UNASSIGNED:F]PARPi acquisition on a dedicated positron emission tomography/magnetic resonance (PET/MR) scanner. Lesion diagnosis was established by pathology when available or by Response Assessment in Neuro-Oncology (RANO) or RANO-BM response criteria. Resected tissue also underwent PARPi-FL staining and PARP1 immunohistochemistry. Results/UNASSIGNED:F]PARPi uptake on PET/MR in active brain cancers and low uptake in treatment-related changes independent of blood-brain barrier disruption. Immunohistochemistry results confirmed higher PARP1 expression in cancerous than in noncancerous tissue. Specificity was also corroborated by blocking fluorescent tracer uptake with an excess unlabeled PARP inhibitor in patient cancer biospecimen. Conclusions/UNASSIGNED:F]PARPi as a diagnostic tool to evaluate patients with brain cancers and possible treatment-related changes.

Background/UNASSIGNED:Pediatric intracranial aneurysms tend to differ in etiology, size, and location from their adult counterparts, and they are often less amenable to microsurgical clip reconstruction techniques. Endovascular treatment with detachable coils is an accepted treatment technique for pediatric patients, though high recurrence rates have been reported with coil embolization of large and giant aneurysms in this population. While the Pipeline Embolization Device (PED) is FDA-approved for adult intracranial aneurysms, the use of PEDs in pediatric patients is considered off-label. Case Descriptions/UNASSIGNED:We present 3 cases of pediatric intracranial aneurysms in a 5-year-old male, a 12-year-old male, and a 12-year-old female who presented with symptoms including seizure, headache, and blurred vision. The 2 male patients were found to have intradural vertebral artery saccular aneurysms, while the female patient had a paraophthalmic right internal carotid complex aneurysm. After endovascular reconstruction of the aneurysms with PEDs, follow-up angiography showed complete occlusion of the previous aneurysms with no residual aneurysm filling in all 3 cases. Conclusion/UNASSIGNED:While further investigation is needed, the evidence presented here supports the conclusion that the PED can be an effective and viable treatment strategy in the pediatric population.

OBJECTIVE:To assay EEG signal quality recorded with tripolar concentric ring electrodes (TCREs) compared to regular EEG electrodes. METHODS:EEG segments were recorded simultaneously by TCREs and regular electrodes, low-pass filtered at 35 Hz (REG35) and 70 Hz (REG70). Clips were rated blindly by nine electroencephalographers for presence or absence of key EEG features, relative to the "gold-standard" of the clinical report. RESULTS:TCRE showed less EMG artifact (F = 15.4, p < 0.0001). Overall quality rankings were not significantly different. Focal slowing was better detected by TCRE and spikes were better detected by regular electrodes. Seizures (n = 85) were detected by TCRE in 64 cases (75.3%), by REG70 in 75 (88.2%) and REG35 in 69 (81.2%) electrodes. TCRE detected 9 (10.6%) seizures not detected by one of the other 2 methods. In contrast, 14 seizures (16.5%) were not detected by TCRE, but were by REG35 electrodes. Each electrode detected interictal spikes when the other did not. CONCLUSIONS:TCRE produced similar overall quality and confidence ratings versus regular electrodes, but less muscle artifact. TCRE recordings detected seizures in 7% of instances where regular electrodes did not. SIGNIFICANCE/CONCLUSIONS:The combination of the two types increased detection of epileptiform events compared to either alone.

PURPOSE/OBJECTIVE:). To test whether knowledge of these additional parameters can improve the clinical utility of brain MRS, we compare the conventional and multiparametric approaches in terms of expected classification accuracy in differentiating controls from patients with neurological disorders. THEORY AND METHODS/UNASSIGNED:(conventional MRS); using metabolite concentrations corrected using per-subject values (multiparametric MRS); and using an optimal linear multiparametric estimator comprised of the metabolites' concentrations and relaxation constants (multiparametric MRS). Additional simulations were conducted to find the minimal intra-subject precision needed for each parameter. RESULTS:Compared with conventional MRS, multiparametric approaches yielded area under the curve improvements for almost all neuropathologies and regions of interest. The median area under the curve increased by 0.14 over the entire dataset, and by 0.24 over the 10 instances with the largest individual increases. CONCLUSIONS:Multiparametric MRS can substantially improve the clinical utility of MRS in diagnosing and assessing brain pathology, motivating the design and use of novel multiparametric sequences.

Studies of sensorimotor integration often use sensory stimuli that require a simple motor response, such as a reach or a grasp. Recent advances in neural recording techniques, motion capture technologies, and time-synchronization methods enable studying sensorimotor integration using more complex sensory stimuli and performed actions. Here, we demonstrate that prehensile actions that require using complex sensory instructions for manipulating different objects can be characterized using high-density electroencephalography and motion capture systems. In 20 participants, we presented stimuli in different sensory modalities (visual, auditory) containing different contextual information about the object with which to interact. Neural signals recorded near motor cortex and posterior parietal cortex discharged based on both the instruction delivered and object manipulated. Additionally, kinematics of the wrist movements could be discriminated between participants. These findings demonstrate a proof-of-concept behavioral paradigm for studying sensorimotor integration of multidimensional sensory stimuli to perform complex movements. Such a framework will prove vital for studying neural control of movements in clinical populations in which sensorimotor integration is impaired due to information no longer being communicated correctly between brain regions (e.g. stroke). Such a framework is the first step towards developing a neural rehabilitative system for restoring function more effectively.