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Background: Cell-free heme-containing proteins mediate endothelial injury in a variety of disease states including subarachnoid hemorrhage and sepsis by increasing endothelial permeability. Inflammatory cells are also attracted to sites of vascular injury by monocyte chemotactic protein 1 (MCP-1) and other chemokines. We have identified a novel peptide hormone, adropin, that protects against hemoglobin-induced endothelial permeability and MCP-1-induced macrophage migration., Methods: Human microvascular endothelial cells were exposed to cell-free hemoglobin (CFH) with and without adropin treatment before measuring monolayer permeability using a FITC-dextran tracer assay. mRNA and culture media were collected for molecular studies. We also assessed the effect of adropin on macrophage movement across the endothelial monolayer using an MCP-1-induced migration assay., Results: CFH exposure decreases adropin expression and increases paracellular permeability of human endothelial cells. Treating cells with synthetic adropin protects against the increased permeability observed during the natural injury progression. Cell viability was similar in all groups and Hmox1 expression was not affected by adropin treatment. MCP-1 potently induced macrophage migration across the endothelial monolayer and adropin treatment effectively reduced this phenomenon., Conclusions: Endothelial injury is a hallmark of many disease states. Our results suggest that adropin treatment could be a valuable strategy in preventing heme-mediated endothelial injury and macrophage infiltration. Further investigation of adropin therapy in animal models and human tissue specimens is needed., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Brian L. Hoh reports financial support was provided by National Institutes of Health. William S. Dodd & Brian L. Hoh reports financial support was provided by The Brain Aneurysm Foundation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Postoperative urinary retention (POUR) is a common complication after spine surgery and is associated with prolongation of hospital stay, increased hospital cost, increased rate of urinary tract infection, bladder overdistention, and autonomic dysregulation. POUR incidence following spine surgery ranges between 5.6% and 38%; no reliable prediction tool to identify those at higher risk is available, and that constitutes an important gap in the literature. The objective of this study was to develop and validate a preoperative risk model to predict the occurrence of POUR following routine elective spine surgery., Methods: The authors conducted a retrospective chart review of consecutive adults who underwent lumbar spine surgery between June 1, 2017, and June 1, 2019. Patient characteristics, preexisting ICD-10 codes, preoperative pain and opioid use, preoperative alpha-1 blocker use, details of surgical planning, development of POUR, and management strategies were abstracted from electronic medical records. A binomial logistic model and a multilayer perceptron (MLP) were optimized using training and validation sets. The models' performance was then evaluated on model-naïve patients (not a part of either cohort). The models were then stacked to take advantage of each model's strengths and to avoid their weaknesses. Four additional models were developed from previously published models adjusted to include only relevant factors (i.e., factors known preoperatively and applied to the lumbar spine)., Results: Overall, 891 patients were included in the cohort, with a mean of 59.6 ± 15.5 years of age, 52.7% male, BMI 30.4 ± 6.4, American Society of Anesthesiologists class 2.8 ± 0.6, and a mean of 5.6 ± 5.7 comorbidities. The rate of POUR was found to be 25.9%. The two models were comparable, with an area under the curve (AUC) of 0.737 for the regression model and 0.735 for the neural network. By combining the two models, an AUC of 0.753 was achieved. With a regression model probability cutoff of 0.24 and a neural network cutoff of 0.23, maximal sensitivity and specificity were achieved, with specificity 68.2%, sensitivity 72.9%, negative predictive value 88.2%, and positive predictive value 43.4%. Both models individually outperformed previously published models (AUC 0.516-0.645) when applied to the current data set., Conclusions: This predictive model can be a powerful preoperative tool in predicting patients who will be likely to develop POUR. By using a combination of regression and neural network modeling, good sensitivity, specificity, and NPV are achieved.

Carotid artery injuries are serious complications of endoscopic endonasal surgery. As these occur rarely, simulation training offers an avenue for technique and algorithm development in resident learners. This study develops a realistic cadaveric model for the training of crisis resource management in the setting of cavernous carotid artery injury. An expanded endonasal approach and right cavernous carotid injury is performed on a cadaveric head. The cadaver's right common carotid artery is cannulated and connected to a perfusion pump delivering pressurized simulated blood. A simulation mannequin is incorporated into the model to allow for vital sign feedback. Surgical and anesthesia resident learners are tasked with obtaining vascular control with a muscle patch technique and medical management over the course of 3 clinical scenarios with increasing complexity. Crisis management instructions for an endoscopic endonasal approach to the cavernous carotid artery and blood pressure control were provided to the learners prior to beginning the simulation. An independent reviewer evaluated the learners on communication skills, crisis management algorithms, and implementation of appropriate skill sets. After each scenario, residents were debriefed on how to improve technique based on evaluation scores in areas of situational awareness, decision-making, communications and teamwork, and leadership. After the simulation, learners provided feedback on the simulation and this data was used to improve future simulations. The benefit of this cadaveric model is ease of set-up, cost-effectiveness, and reproducibility.

Posterior circulation aneurysms are difficult to treat with the current methods of coiling and clipping. To address limitations in training, we developed a cadaveric model to train learners on endoscopic clipping of posterior circulation aneurysms. An endoscopic transclival approach (ETA) and a transorbital precaruncular approach (TOPA) to successfully access and clip aneurysms of the posterior circulation are described. The model has flexibility in that a colored silicone compound can be injected into the cadaveric vessels for the purpose of training learners on vascular anatomy. The other option is that the model could be connected to a vascular perfusion pump allowing real-time appreciation of a pulsatile or ruptured aneurysm. This cadaveric model is the first of its kind for training of endoscopic clipping of posterior circulation aneurysms. Learners will develop proficiency in endoscopic skills, appropriate dissection, and appreciation for relative anatomy while developing an algorithm that can be employed in a real operative arena. Going forward, various clinical scenarios can be developed to enhance the realism, allow learners from different specialties to work together, and emphasize the importance of teamwork and effective communication.

Penetrating traumatic brain injury (pTBI) often occurs with systemic insults such as hemorrhagic shock (HS) and hypoxemic (HX). This study examines rat models of penetrating ballistic-like brain injury (PBBI) and HX+HS to assess whether the blood levels of brain and systemic response biomarkers phosphorylated neurofilament-heavy protein (pNF-H), neurofilament-light protein (NF-L), αII-spectrin, heat shock protein (HSP70), and high mobility group box 1 protein (HMGB1) can distinguish pTBI from systemic insults and guide in pTBI diagnosis, prognosis, and monitoring. Thirty rats were randomly assigned to sham, PBBI, HS+HX, and PBBI+HS+HX groups. PBBI and sham groups underwent craniotomy with and without probe insertion and balloon expansion, respectively. HX and HS was then simulated by blood withdrawal and fraction of inspired oxygen (FIO 2 ) reduction. Biomarker serum concentrations were determined at one (D1) and two (D2) days post-injury with enzyme-linked immunosorbent assay (ELISA) methods. Axonal injury-linked biomarkers pNF-H and NF-L serum levels in PBBI groups were higher than those in sham and HX+HS groups at D1 and D2 post-injury. The same was true for PBBI+HX+HS compared with sham (D2 only for pNF-H) and HX+HS groups. However, pNF-H and NF-L levels in PBBI+HX+HS groups were not different than their PBBI counterparts. At D1, αII-spectrin levels in the HX+HS and PBBI+HS+HX groups were higher than the sham groups. αII-spectrin levels in the HX+HS group were higher than the PBBI group. This suggests HX+HS as the common insult driving αII-spectrin elevations. In conclusion, pNF-H and NF-L may serve as specific serum biomarkers of pTBI in the presence or absence of systemic insults. αII-spectrin may be a sensitive acute biomarker in detecting systemic insults occurring alone or with pTBI., Competing Interests: This article was prepared while Angela Boutte, Deborah Shear, and Lai Yee Leung were employed at the Geneva Foundation/Walter Reed Army Institute of Research. The opinions expressed in this article are the author's own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the U.S. government., (© Xue Li et al., 2021; Published by Mary Ann Liebert, Inc.)

Chronic traumatic encephalopathy is a disease afflicting individuals exposed to repetitive neurotrauma. Unfortunately, diagnosis is made by postmortem pathologic analysis, and treatment options are primarily symptomatic. In this clinical update, we review clinical and pathologic diagnostic criteria and recommended symptomatic treatments. We also review animal models and recent discoveries from pre-clinical studies. Furthermore, we highlight the recent advances in diagnosis using diffusor tensor imaging, functional magnetic resonance imaging, positron emission tomography, and the fluid biomarkers t-tau, sTREM2, CCL11, NFL, and GFAP. We also provide an update on emerging pharmaceutical treatments, including immunotherapies and those that target tau acetylation, tau phosphorylation, and inflammation. Lastly, we highlight the current literature gaps and guide future directions to further improve clinical diagnosis and management of patients suffering from this condition.

Background: Cholesterol granulomas of the petrous apex are benign cysts affecting 0.6 patients per 1 million. The pathophysiology involves cholesterol crystals and lipids that are surrounded by giant cells. The cholesterol deposits induce an inflammatory response likely from acute hemorrhage leading to the formation of a fibrous capsule. The capsule expands over time compressing nearby cranial nerves (VI-VIII), which can cause worsening symptoms. Surgical resection has been shown to provide excellent improvement in symptoms. Historically, open approaches such as the infracochlear, infralabyrinthine, and middle fossa have been used. Herein we present a case showing the feasibility and clinical utility of using an endoscopic endonasal transclival approach for treatment of these tumors., Case: A 44-year-old female presented with history of intermittent double vision, dizziness, nausea, and headaches for 3 years. She developed a partial left CN6 palsy with significant diplopia and episodes of left facial weakness. The worsening symptoms prompted presentation to the ED where MRI and CT scan revealed a left petrous apex lesion (1.8 × 1.7 cm) with hyperintensity on T1 and T2 imaging, suggestive of cholesterol granuloma. She underwent an endoscopic transclival resection of the lesion: drainage of left petrous apex cholesterol granuloma and stent placement from left petrous apex into sphenoid sinus (novel technique). This was done to allow continued communication and drainage of the tumor bed from the petrous apex into the sphenoid sinus with the intent to minimize the risk of recurrence. At the postop visit both 6th nerve palsy and diplopia had resolved. Imaging is stable 2 years after the surgery., Discussion: The placement of the stent in this case was done to prevent symptom recurrence. 11% of patients that do not receive a stent will have symptom recurrence within one year. From the historical literature, only 4% of patients who had stent placement developed cyst recurrence or expansion on follow-up imaging. Stent placement has been shown to prevent cyst enlargement within the first few months after surgery. We demonstrate that the endoscopic endonasal transclival approach provided good visualization of the tumor, allowed for an adequate working window for resection, and provided a sufficient approach for stent placement.

The correlation of neuroinflammation with the development of cerebral vasospasm following subarachnoid hemorrhage has been well documented in the literature; both clinical and preclinical. The exact mechanisms by which this process occurs, however, are poorly elucidated. Recent evidence indicates that interleukin-6 is not only an important prognostic biomarker for subarachnoid hemorrhage and subsequent vasospasm development but also an integral component in the progression of injury following initial insult. In this review, we briefly highlight other pathways under investigation and focus heavily on what has been discovered regarding the role of interleukin 6 and cerebral vasospasm following subarachnoid hemorrhage. A proposed mechanistic pathway is highlighted in written and graphical format. A discussion regarding the human correlative findings and initial pre-clinical mechanistic studies is addressed. Finally, in the future investigation section, innovative developments and a clear description of areas warranting further scientific inquiry are emphasized. This review will catalyze continued discovery in this area of emerging significance and aid in the quest for effective vasospasm treatment where limited clinical therapeutics currently exist., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To determine the impact of telemedicine visits, compared to in-person visits, on patient satisfaction in an established community hospital-based multidisciplinary central nervous system (CNS) clinic., Methods: Telemedicine options - virtual visits and teleconferencing - were introduced in July 2020. Both radiation oncologist and neurosurgeon were simultaneously present for the telemedicine visit. Descriptive patient demographics, survey responses, and travel time and distance calculations were analyzed. Satisfaction score was compared to previously published data., Results: A total of twenty-five telemedicine visits (n=22 video; n=3 phone) were completed since July 2020. Patient demographics are as follows: mean age was 59 years (range=22-81), women (9) and men (16), repeat telemedicine visits n=10, malignant CNS disease (17) and benign disease (5). Mean one-way distance traveled was 165.07 miles (median=114; range=0.8-358). Mean roundtrip travel time was estimated at 5h 5min. Mean telemedicine visit duration was 15.3 mins (range=4-46). Mean patient satisfaction score for telemedicine visits was 4.84., Conclusion: Patients who opted for the telemedicine visits found them just as effective as in-person visits, saving time and travel costs as well as ensuring patient safety during the current COVID-19 pandemic. The telemedicine visit platform facilitates the multidisciplinary clinic model and should be considered for more widespread utilization (Tab. 3, Fig. 1, Ref. 18).

Fornicotomy has been used to treat intractable temporal lobe epilepsy with mixed success historically; however, modern advances in stereotactic, neurosurgical, and imaging techniques offer new opportunities to target the fornix with greater precision and safety. In this review, we discuss the historical uses and quantify the outcomes of fornicotomy for the treatment of temporal lobe epilepsy, highlight the potential mechanisms of benefit, and address what is known about the side effects of the procedure. We find that fornicotomy, with or without anterior commissurotomy, resulted in 61% (83/136) of patients having some seizure control benefit. We discuss the potential operative approaches for targeting the fornix, including laser ablation and the use of focused ultrasound ablation. More work is needed to address the true efficacy of fornicotomy in the modern surgical setting. This review is intended to serve as a framework for developing this approach., (Copyright © 2019 by the Congress of Neurological Surgeons.)

The frontal lobe urinary control center is an important regulator of urinary function. Neurologic injury often causes damage or temporary dysfunction of this center and other related urinary control pathways. Little has been reported about this topic in the literature although a majority of neurologic injury patients suffer from some type of urinary dysfunction. In this review, we highlight what is known about urinary dysfunction based on injury type (traumatic brain injury, hemorrhagic stroke, ischemic stroke, subarachnoid hemorrhage, subdural hematoma, and epilepsy). We discuss both clinical and pre-clinical data and pinpoint areas warranting further investigation. In the final section, we provide proposed practice suggestions for managing these patients clinically with the intended goal for refinement in these approaches following further clinical trials., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Several groups have instituted helmet initiatives with varying success across the world. Helmet use has been well documented to prevent traumatic brain injury. Despite the known benefits, many people, including university students, refuse to utilize helmets when riding bikes, mopeds, or motorcycles. We recognized a need within our community regarding the lack of helmet use at University of Florida and developed a program to institute change., Methodology: We identified community champions and hosted weekly round table discussion initiatives. Through these round table discussions we identified events already going on within the community and developed new opportunities to promote helmet use. We had stories from survivors and parents, utilized school administration support, and partnered with local bike shops., Results: The pilot initiative was successful in increasing awareness across the city and got stakeholders excited in the process. It also spearheaded more data driven initiatives that will look at reduction of traumatic brain injuries in the clinical setting., Conclusion: This project highlights the University of Florida Helmet Initiative that has already generated renewed interest in safety and traumatic brain injury prevention. The school of nursing has implemented safety protocols and further support is being garnered by the administration across campus. Most importantly we have identified community champions that will carry the work forward.

Despite advances in chemotherapy and radiation, stage IV breast cancer presents a serious challenge to clinicians in light of the continued poor outcomes for patients. Stage IV breast cancer frequently metastasizes to the brain often necessitating neurosurgical intervention. The goals of the neurosurgeon are to adequately address metastatic disease to the central nervous system, limit morbidity for the patients, while preserving as much neurologic function as possible, and to help guide next steps regarding need for radiation and immunotherapy. In this review, we provide a background overview of the role of neurosurgery in managing stage IV metastatic breast cancer involving the brain, discuss what is known about brain metastasis, and highlight avenues for future study and investigation.

Primary angiitis of the central nervous system (PACNS) is a rare form of vasculitis. It is a diagnosis of exclusion and often diagnosed post mortem on pathologic evaluation. Cerebral angiography can be suggestive, but biopsy is required. Symptoms can vary from headache to focal cranial nerve deficits. On the more severe spectrum, patients can present with ischemic and vary rarely hemorrhagic stroke. We present in this case report key clinical pearls regarding suspected diagnosis. Younger patients with cortical hemorrhages may have PACNS instead of the more common cerebral amyloid angiopathy. Early suspicion may aid in initiating effective treatment as we highlight in the discussion.

Desmoplastic fibromas are rare benign bone tumors occurring primarily in long bones and mandible. In this case report, we present a desmoplastic fibroma originating from the left frontal bone. This is an exceptionally rare presentation of this pathology and the associated imaging and pathologic slides are highly educational. We discuss the relevance to the literature and how to manage these patients clinically.

Background: Cerebrospinal fluid rhinorrhea from a lateral skull base defect refractory to spontaneous healing and/or conservative management is most commonly managed via open surgery. Approach for repair is dictated by location of the defect, which may require surgical exploration. The final common pathway is the eustachian tube (ET). Endoscopic ET obliteration via endonasal and lateral approaches is under development. Whereas ET anatomy has been studied, surgical landmarks have not been previously described or quantified. We aimed to define surgical parameters of specific utility to endoscopic ET obliteration., Methods: A literature review was performed of known ET anatomic parameters. Next, using a combination of endoscopic and open techniques in cadavers, we cannulated the intact ET and dissected its posterior component to define the major curvature position of the ET, defined as the genu, and quantified the relative distances through the ET lumen. The genu was targeted as a major obstacle encountered when cannulating the ET from the nasopharynx., Results: Among 10 ETs, we found an average distance of 23 ± 5 mm from the nasopharynx to the ET genu, distance of 24 ± 3 mm from the genu to the anterior aspect of the tympanic membrane and total ET length of 47 ± 4 mm., Conclusions: Although membranous and petrous components of the ET are important to its function, the genu may be a more useful surgical landmark. Basic surgical parameters for endoscopic ET obliteration are defined., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Mild traumatic brain injury accounts for the majority of head injuries and has been correlated with neurodegeneration and dementia. While repetitive mild traumatic brain injury is highly correlated to neurodegeneration, the correlation of a single mild traumatic brain injury with neurodegeneration is still unclear. Because tau aggregates are the main form of mild traumatic brain injury induced pathology, toxic forms of tau protein most likely play a role in the development of post-mild traumatic brain injury neurodegeneration. Therefore, it becomes crucial to characterize the properties of soluble tau aggregates in single versus repetitive mild traumatic brain injury. Herein, we isolated tau oligomers from wild-type mice exposed to single or repetitive mild traumatic brain injury and characterized the tau aggregates at functional, biochemical and biophysical levels. We demonstrated that single versus repetitive mild traumatic brain injuries frequencies lead to the formation of different tau oligomeric polymorphisms. These polymorphisms express different long-term potentiation impairment potencies, toxicity potentials, morphologies and strain indicating properties. To our knowledge, this is the first evidence that soluble tau oligomers derived from single versus repetitive mild traumatic brain injuries form distinct polymorphisms that possibly correlate with the risk of neurodegeneration after mild traumatic brain injury., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Glioblastoma is a fatal brain cancer with low median and yearly survival rates. Standard of care for treating glioblastoma is gross total resection (GTR) coupled with the Stupp protocol, but various factors influence the interventions undertaken and survival achieved. As health disparities exist in rural areas, survival in these areas needs to be assessed to understand which factors detract from the successes of these standard medical interventions., Methods: We retrospectively determined impact of age at diagnosis, number of lesions, the molecular marker O 6 -methylguanine methyltransferase (MGMT), extent of surgery, and completion of the Stupp protocol on survival in patients treated at West Virginia University Hospitals. We also compared our findings with a pre-Stupp protocol study done in West Virginia in 1996., Results: Age <60 years at diagnosis, having the MGMT gene methylated, having a unifocal tumor, receiving GTR, adhering to the Stupp protocol, and undergoing a treatment course of GTR followed by the Stupp protocol significantly increased survival. Comparison with the 1996 study showed that although overall median survival has not increased, all interventions involving GTR have resulted in a significantly higher survival., Conclusions: We can serve our patient population by offering GTR to all adult patients with glioblastoma when no contraindications exist and ensuring that patients follow the Stupp protocol. After discharge, the Stupp protocol may not be followed or completed for a variety of reasons. In the future, we aim to assess these reasons and analyze other significant interventional and socioeconomic factors that influence survival., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Extradural hematomas (EDH) are considered life threatening in that the risk for brain herniation is significant. The current accepted understanding within the literature is to treat EDH via surgical evacuation of the hematoma., Cases: In this case-series we report 62 cases of EDH managed conservatively without surgical intervention. Inclusion criteria were: Glasgow comma scale score 13-15, extradural hematoma confirmed by CT being less than 40 mm, less than 6 mm of midline shift, and no other surgical lesions present. Patients were initially observed in a surgical intensive care unit prior to discharge and had closely scheduled follow-up., Results: Of the 62 cases none required emergent intervention and the majority had interval resolution of the epidural hematoma over time. Resolution was apparent by 21 days and definitive by 3 to 6 months., Conclusion: Patients with EDH who have a high Glasgow comma scale score 13-15, volume <40 mm, and less than 6 mm of midline shift should be considered for conservative management. Our study indicates that these patients will have interval resolution of hematoma over time without worsening of symptoms.

Concussion in athletes can contribute to early neuropsychological changes that may be indicative of future neurodegenerative disease. One of the hallmark findings of chronic traumatic encephalopathy is anxiety and impulsive behavior that often develops early in the course of the disease. The behavioral dysfunction can be grouped into a broader category referred to as cognitive disruption. The current gold standard for diagnosing chronic neurodegeneration is post-mortem evaluation of tauopathy to identify neurofibrillary tau tangles in neurons. Few studies, however, have looked at clinical correlations between acute injury and chronic neurodegeneration in terms of behavior. This lack of focus towards translational study has limited advancements towards treatment. In this pilot investigation, the acute cognitive and emotional (anger, impulsivity, and anxiety) affects of concussion in a cohort of collegiate athletes (n = 30) are examined and compared to findings in the post-mortem pathologic features of chronic traumatic encephalopathy. Specifically, the role of the seroternergic system with alpha synuclein and tauopathy staining and the potential for early clinically relevant behavioral and pharmaceutical interventions was investigated. The purpose was to determine if athletes began demonstrating cognitive disruption present in post-mortem evaluation during the acute phase of injury. The acute data was collected via questionnaires within ten days of the athletes' concussion diagnosis. Results demonstrated that 11 of 30 athletes (36%) scored in a diagnosable range of anxiety post-concussion, and athletes scored above the norm in state-anger ( M = 22.9, SD = 9.99), indicating severe emotional disturbance. A limitation is that due to the long time frame from acute injury to the development of neurodegeneration individual athletes cannot be tracked in longevity thus limiting the findings to the realm of correlation. The findings from this pilot study warrant further investigation into the neuropsychological aspects for how to manage concussion and prevent degenerative disease.

Cerebrospinal fluid (CSF) leaks occur in approximately 10% of patients undergoing a translabyrinthine, retrosigmoid, or middle fossa approach for vestibular schwannoma resection. Cerebrospinal fluid rhinorrhea also results from trauma, neoplasms, and congenital defects. A high degree of difficulty in repair sometimes requires repetitive microsurgical revisions-a rate of 10% of cases is often cited. This can not only lead to morbidity but is also costly and burdensome to the health care system. In this case-based theoretical analysis, the authors summarize the literature regarding endoscopic endonasal techniques to obliterate the eustachian tube (ET) as well as compare endoscopic endonasal versus open approaches for repair. Given the results of their analysis, they recommend endoscopic endonasal ET obliteration (EEETO) as a first- or second-line technique for the repair of CSF rhinorrhea from a lateral skull base source refractory to spontaneous healing and CSF diversion. They present a case in which EEETO resolved refractory CSF rhinorrhea over a 10-month follow-up after CSF diversions, wound reexploration, revised packing of the ET via a lateral microscopic translabyrinthine approach, and the use of a vascularized flap had failed. They further summarize the literature regarding studies that describe various iterations of EEETO. By its minimally invasive nature, EEETO imposes less morbidity as well as less risk to the patient. It can be readily implemented into algorithms once CSF diversion (for example, lumbar drain) has failed, prior to considering open surgery for repair. Additional studies are warranted to further demonstrate the outcome and cost-saving benefits of EEETO as the data until now have been largely empirical yet very hopeful. The summaries and technical notes described in this paper may serve as a resource for those skull base teams faced with similar challenging and otherwise refractory CSF leaks from a lateral skull base source.

Lymphoma presenting as a scalp mass is a rare but serious medical condition mandating aggressive treatment and neurosurgical intervention. We report a case of 53-year-old male who presented with a large right sided frontal scalp mass and a smaller mass located on the left frontal scalp. After discussion with the patient, it was decided to resect the larger mass for definitive diagnosis. After subtotal resection of the mass, biopsy revealed WHO grade 1 follicular lymphoma (FL), diffuse pattern stage IV. The patient was subsequently treated with 4 grays (Gy) of palliative radiotherapy over 2 fractions to the right frontal scalp and systemic chemo-immunotherapy (6 cycles) followed by rituximab maintenance. Lumbar puncture to obtain cerebrospinal fluid was done a month after therapy began and the results were negative for spread of malignant cells. Approximately 3 months after initiation of therapy, PET/CT showed no evidence of active malignancy and MRI revealed a complete internal resolution of the enlarged right frontal scalp mass. We use this case to provide a detailed discussion regarding disease pathophysiology, early diagnosis, and management.

Background and Importance: High flow orbital apex or middle fossa cerebrospinal fluid (CSF) leaks can be life threatening and complex to repair. These leaks associated with large dural defects are most commonly repaired with an open temporalis muscle patch or free flaps, but these flaps do not always stop the leak., Clinical Presentation: A 65-year-old patient presented two years after orbital exenteration and radiation for squamous cell carcinoma. He developed multi-organism meningitis and pneumocephalus secondary to a large high-flow orbital apex/middle fossa CSF leak. To repair the leak, a combined endoscopic transorbital/endonasal approach with pedicled nasospetal flap and dermis fat graft was used. We describe the unique endoscopic technique that was used to treat the life threatening high flow orbital apex/middle fossa CSF leak. The technique allowed the use of the transposed pedicled flap, which is an alternative to the free flap in controlling CSF leak. Cisternogram post-operatively and clinical exam confirmed resolution of CSF leak. Although a critically ill patient at admission with a modified Rankin scale (MRS) of 5, he was discharged home on continued IV antibiotic therapy with a MRS of 3. Endoscopic evaluation at three months after treatment showed the effectiveness of the flap and he continued to improve clinically., Conclusion: This is the first case to describe a combined endoscopic transorbital and endonasal repair of high flow orbital apex/middle fossa CSF leak with a pedicled nasoseptal flap. These techniques can be utilized during initial reconstruction after orbital exenteration or as a salvage flap.

The brain is an integrated network of multiple variables that when compromised create a diseased state. The neuropathology of temporal lobe epilepsy (TLE), stroke, and traumatic brain injury (TBI) demonstrate both similarity and complexity that reflects this integrated variability; TLE with its live human tissue resection provides opportunity for translational science to demonstrate scale equivalent experimentation between the macroscopic world of clinical disease and the microscopic world of basic science. The extended value of this research is that the neuroinflammatory abnormalities that occur throughout astrocytes with hippocampal sclerosis and damaged or even reversed signaling pathways (inhibition to excitation such as with gaba-aminobutyric acid) are similar to those seen in post-stroke and TBI models. In evaluation of the epilepsy population this interconnectedness of pathology warrants further evaluation with collaborative efforts. This review summarizes patterns that could shift experimentation closer to the macro level of humanity, but still represent the micro world of genetics, epigenetics, and neuro-injury across etiologies of physiologic dysfunction such as TLE, stroke, and TBI with evaluation of cell function using electrophysiology. In conclusion we demonstrate the plausibility of electrophysiologic voltage and current measurement of brain tissue by patch clamp analysis to specify actual electrophysiologic function for comparison to electroencephalography in order to aid neurologic evaluation. Finally, we discuss the opportunity with multiscale modeling to display integration of the hyperpolarization cyclic-nucleotide gated channel, the depolarized calcium channels, and sodium-potassium-chloride-one/potassium-chloride-two co-transporter channels as potential mechanisms utilized as tri-coordinate biomarkers with these three forms of neurologic disease at a molecular scale of electrophysiologic pathology., Competing Interests: Competing Interests The authors have declared that no competing interests exist.

Posttraumatic Stress Disorder (PTSD) is a devastating condition that can develop after blast Traumatic Brain Injury (TBI). Ongoing work has been performed to understand how PTSD develops after injury. In this review, we highlight how PTSD affects individuals, discuss what is known about the physiologic changes to the hypothalamic pituitary axis and neurotransmitter pathways, and present an overview of genetic components that may predispose individuals to developing PTSD. We then provide an overview of current treatment strategies to treat PTSD in veterans and present new strategies that may be useful going forward. The need for further clinical and pre-clinical studies is imperative to improve diagnosis, treatment, and management for patients that develop PTSD following blast TBI.

Growing skull fracture remains a rare but clinically significant complication of traumatic skull fractures in children less than 3 years of age. Dog attacks on children commonly cause head and neck injuries. We report the first case of growing skull fracture caused by a Rottweiler bite in a 21 days old neonate. Early diagnosis and surgical repair resulted in excellent outcome.

Simulation training is emerging as a cost-effective way to train residents on the skill sets necessary to excel as fully functioning physicians. Until recently, the simulated resident training environments have primarily focused on handling a medical crisis with learners from the same specialty. A dual otolaryngology and anesthesiology simulation was established to improve teamwork and communication skills between specialties. One otolaryngology resident was paired with one anesthesia resident per trial in our study. The multispecialty team addressed three clinical simulation scenarios to manage a cavernous carotid artery-bleeding crisis with an endoscopic endonasal approach. An independent reviewer evaluated each individual based on situation awareness, decision-making, communications and teamwork, as well as leadership. Residents improved on blood loss, pre and post anatomical exam scores, and communication measures through the course of the scenarios. Residents from both specialties rated the simulation highly and wanted further simulation training in the future. Multidisciplinary simulation training is a novel approach for improving communication skills between specialties prior to entering the wards, clinic, or operative arena. The lessons learned from this multidisciplinary simulation transcend the individual experience by allowing trainees to develop algorithms for crisis management and to improve on aspects of teamwork, leadership, and communication skills that can be applied throughout their careers.

Traumatic brain injury (TBI) is characterized by acute neurological dysfunction and associated with the development of chronic traumatic encephalopathy (CTE) and Alzheimer's disease. We previously showed that cis phosphorylated tau (cis P-tau), but not the trans form, contributes to tau pathology and functional impairment in an animal model of severe TBI. Here we found that in human samples obtained post TBI due to a variety of causes, cis P-tau is induced in cortical axons and cerebrospinal fluid and positively correlates with axonal injury and clinical outcome. Using mouse models of severe or repetitive TBI, we showed that cis P-tau elimination with a specific neutralizing antibody administered immediately or at delayed time points after injury, attenuates the development of neuropathology and brain dysfunction during acute and chronic phases including CTE-like pathology and dysfunction after repetitive TBI. Thus, cis P-tau contributes to short-term and long-term sequelae after TBI, but is effectively neutralized by cis antibody treatment.Induction of the cis form of phosphorylated tau (cis P-tau) has previously been shown to occur in animal models of traumatic brain injury (TBI), and blocking this form of tau using antibody was beneficial in a rodent model of severe TBI. Here the authors show that cis P-tau induction is a feature of several different forms of TBI in humans, and that administration of cis P-tau targeting antibody to rodents reduces or delays pathological features of TBI.

Background: Sarcoidosis is a chronic, multisystem disease characterised by non-necrotising granulomatous inflammation of unknown aetiology. Most commonly, the lungs, lymph nodes, skin and eyes are affected in sarcoidosis; however, nervous system involvement occurs in approximately 5%-15% of cases. Any part of the nervous system can be affected by sarcoidosis., Cases: Herein we describe three unusual patient presentations of neurosarcoidosis, one with optic neuritis, a second with hydrocephalus and a third with cervical myelopathy., Conclusions: We include pertinent details about their presentations, imaging findings, pathology, management and clinical course., Competing Interests: Competing interests: None., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Aim: To examine the differences in metabolic risk factors (RFs) by gender in the Asian Indian (AI) population in the United States., Methods: Using cross-sectional data from 1038 randomly selected Asian Indians, we investigated the relationship between metabolic syndrome (MetS) RFs, cardiovascular disease, and diabetes., Results: A greater percent of women in this group had increased waist circumference and low high density lipoprotein (HDL) levels than men, but AI males had increased blood glucose, increased blood pressure, and increased triglycerides compared to females. Those individuals who met the MetS criteria had increased cardiovascular disease. One of the biggest single RFs for cardiovascular disease and diabetes reported in the literature for AIs is low HDL., Conclusion: Our results show that lack of knowledge about diabetes, low physical activity, increased body mass index, and age were the factors most significantly correlated with low HDL in this population. Future studies and prospective trials are needed to further elucidate causes of the MetS and diabetes in AIs., Competing Interests: Conflict-of-interest statement: The authors declare they have no conflict of interest.

Purpose  Simulation training offers a useful opportunity to appreciate vascular anatomy and develop the technical expertise required to clip intracranial aneurysms of the posterior circulation. Materials and Methods  In cadavers, a comparison was made between the endoscopic transclival approach (ETA) alone and a combined multiportal approach using the ETA and a transorbital precaruncular approach (TOPA) to evaluate degrees of freedom, angles of visualization, and ergonomics of aneurysm clip application to the posterior circulation depending on basilar apex position relative to the posterior clinoids. Results  ETA alone provided improved access to the posterior circulation when the basilar apex was high riding compared with the posterior clinoids. ETA + TOPA provided a significantly improved functional working area for instruments and visualization of the posterior circulation for a midlevel basilar apex. A single-shaft clip applier provided improved visualization and space for instruments. Proximal and distal vascular control and feasibility of aneurysmal clipping were demonstrated. Conclusions  TOPA is a medial orbital approach to the central skull base; a transorbital neuroendoscopic surgery approach. This anatomical simulation provides surgical teams an alternative to the ETA approach alone to address posterior circulation aneurysms, and a means to preoperatively prepare for intraoperative anatomical and surgical instrumentation challenges.

Background: Several cadaveric studies demonstrate reliable localization of the transverse sinus and the transverse sigmoid junction (TSJ). These studies use the line drawn from the inion to the posterior root of the zygoma (IZ) and the asterion, respectively. We investigated how the size difference between the right and left transverse sinuses (TS) and sigmoid sinuses (SS) affected the accuracy of their respective superficial landmarks, particularly with regards to where this relationship may result in unsafe and/or complicated surgical access., Methods: We utilized Vitrea software to render three-dimensional images based on computed tomographic angiography (CTA). We measured the relationship between the TS and SS to their respective superficial landmarks., Results: We analyzed 50 patients in this study. The distal TS was found caudal to the inion-to-zygoma (IZ) line on average by 5.0 ± 4.3 mm on the right and 6.4 ± 9.3 mm on the left. The mid TS was found cranial on average 3.5 ± 5.7 mm on the right and 3.2 ± 6.0 mm cranial on the left to the superior nuchal line (SNL). The distance from the asterion to the SS was 11.5 ± 2.4 mm medial on the right and 12.1 ± 4.4 mm medial on the left. The average distance was greater on the left than the right when using the IZ landmark. This was directly proportional to the size difference of the sinuses ( r 2 = 0.15, P = 0.03)., Conclusions: Statistically significant differences between the right and left TS and SS were seen in terms of size. This appeared to correlate nicely to the differences observed between the locations of the TSs' and their respective superficial landmarks., Competing Interests: There are no conflicts of interest.

Objective: Endoscopic surgical treatment of pituitary tumors, lateral invading tumors, or aneurysms requires surgeons to operate adjacent to the cavernous sinus. During these endoscopic endonasal procedures, the carotid artery is vulnerable to surgical injury at its genu. The objective of this simulation model was to evaluate trainees regarding management of a potentially life-threatening vascular injury., Methods: Cadaveric heads were prepared in accordance with the Oregon Health & Science University body donation program. An endoscopic endonasal approach was used, and a perfusion pump with a catheter was placed in the ipsilateral common carotid artery at its origin in the neck. Learners used a muscle graft to establish vascular control and were evaluated over 3 training sessions. Simulation assessment, blood loss during sessions, and performance metric data were collected for learners., Results: Vascular control was obtained at a mean arterial pressure of 65 mm Hg using a muscle graft correctly positioned at the arteriotomy site. Learners improved over the course of training, with senior residents (n = 4) performing better across all simulation categories (situation awareness, decision making, communications and teamwork, and leadership); the largest mean difference was in communication and teamwork. Additionally, learner performance concerning blood loss improved between sessions (t = 3.667, P < 0.01)., Conclusions: In this pilot endoscopic endonasal simulation study, we successfully demonstrate a vascular complication perfusion model. Learners were able to gain direct applicable expertise in endoscopic endonasal techniques, instrumentation use, and teamwork required to optimize the technique. Learners gained skills of vascular complication management that transcend this model., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Isolated splenic metasisis is a rare finding in colorectal carcinoma. We report a case of metastatic cecal adenocarcinoma to the spleen. In spring 2011, a 53-yearold woman underwent en bloc right hemicolectomy with partial omentectomy. The tumor was Stage III pT3 pN2a M0. She received four months of modified FOLFOX6 chemotherapy and one month of capecitabine. In spring 2012, a PET/CT revealed a low attenuation focus in the spleen consistent with metastatic adenocarcinoma, so she underwent splenectomy. Additional imaging has revealed no disease recurrence. There are only a small number of case reports for isolated splenic metastasis; thus, no standardized treatment course has been developed.

The role of dietary tracking on weight loss remains unexplored despite being part of multiple diabetes and weight management programs. Hence, participants of the Diabetes Prevention and Management (DPM) program (12 months, 22 sessions) tracked their food intake for the duration of the study. A scatterplot of days tracked versus total weight loss revealed a nonlinear relationship. Hence, the number of possible tracking days was divided to create the 3 groups of participants: rare trackers (<33% total days tracked), inconsistent trackers (33-66% total days tracked), and consistent trackers (>66% total days tracked). After controlling for initial body mass index, hemoglobin A 1c , and gender, only consistent trackers had significant weight loss (-9.99 pounds), following a linear relationship with consistent loss throughout the year. In addition, the weight loss trend for the rare and inconsistent trackers followed a nonlinear path, with the holidays slowing weight loss and the onset of summer increasing weight loss. These results show the importance of frequent dietary tracking for consistent long-term weight loss success.

Latex allergy confounded by IV infiltration presents a serious problem for pediatric patients. If unrecognized, it can lead to serious neurologic deficits, loss of limb mobility, compartment syndrome, and ultimately lasting disability. Appropriate early recognition can prevent progression to these devastating outcomes. In this case report, we present an infant with IV infiltration and latex allergy. The case is used to highlight important clinical diagnostic criteria, treatment approaches, and how to prevent detrimental outcomes. We provide a detailed review of the literature and highlight the key teaching points in a reader-friendly reference table.

Introduction: Adenocarcinoma of the colon can metastasize to multiple organs but very rarely metastasizes to the axilla., Case: We present a case of a 56-year-old male with metastatic colon adenocarcinoma that metastasized to the rectum and then the axilla. Three years after initial diagnosis and treatment of right colon mucinous adenocarcinoma a metastatic mass was found in the rectum. The mass was successfully resected, but within a year of finding the rectal mass, metastatic disease to the axilla was discovered., Conclusion: This case provides valuable teaching points about routes of metastasis and the importance of continued clinical follow-up in patients diagnosed with adenocarcinoma of the colon., Competing Interests: Conflicts of Interest: No conflicts to disclose.

Progressive neurodegenerative diseases plague millions of individuals both in the United States and across the world. The current pathology of progressive neurodegenerative tauopathies, such as Alzheimer's disease (AD), Pick's disease, frontotemporal dementia (FTD), and progressive supranuclear palsy, primarily revolves around phosphorylation and hyperphosphorylation of the tau protein. However, more recent evidence suggests acetylation of tau protein at lysine 280 may be a critical step in molecular pathology of these neurodegenerative diseases prior to the tau hyperphosphorylation. Secondary injury cascades such as oxidative stress, endoplasmic reticulum stress, and neuroinflammation contribute to lasting damage within the brain and can be induced by a number of different risk factors. These injury cascades funnel into a common pathway of early tau acetylation, which may serve as the catalyst for progressive degeneration. The post translational modification of tau can result in production of toxic oligomers, contributing to reduced solubility as well as aggregation and formation of neurofibrillary tangles, the hallmark of AD pathology. Chronic Traumatic Encephalopathy (CTE), caused by repetitive brain trauma is also associated with a hyperphosphorylation of tau. We postulated acetylation of tau at lysine 280 in CTE disease could be present prior to the hyperphosphorylation and tested this hypothesis in CTE pathologic specimens. We also tested for ac-tau 280 in early stage Alzheimer's disease (Braak stage 1). Histopathological examination using the ac tau 280 antibody was performed in three Alzheimer's cases and three CTE patients. Presence of ac-tau 280 was confirmed in all cases at early sites of disease manifestation. These findings suggest that tau acetylation may precede tau phosphorylation and could be the first "triggering" event leading to neuronal loss. To the best of our knowledge, this is the first study to identify acetylation of the tau protein in CTE. Prevention of tau acetylation could possibly serve as a novel target for stopping neurodegeneration before it fully begins. In this study, we highlight what is known about tau acetylation and neurodegeneration., Competing Interests: Conflict of Interest The authors declared that they have no conflict of interest.

Background  Endoscopic skull base approaches are being used to address complicated neurovascular pathology. These approaches are safest when proximal vascular control of the cavernous carotid artery (CavCA) can be obtained. Methods  We present a cadaver-based anatomic simulation study showing the feasibility of clip placement for the CavCA as it courses through the cavernous sinus. The arterial vessels were injected with red microfil (Flow Tech, Carver, Massachusetts) to enhance visibility. The endoscope was directed through a precaruncular transorbital approach and instrumentation was managed through an endonasal transsphenoidal approach. Results  The dual approach minimized the "coning down" and instrument "sword fighting" that occurs as the rod lens endoscope and instruments are used laterally and posterior toward the clivus and brainstem. The precaruncular transorbital approach improved visualization of the clip application and improved the functional working area. The transorbital port allowed better appreciation of the distal clip tines, and the laterally positioned cranial nerves. Conclusions  The advantages may be most realized in the setting of endoscopic endonasal resection of highly vascular lesions and/or bleeding from a ruptured aneurysm being clipped. Simulated training provides an excellent opportunity to enhance skill sets and increase familiarity with anatomical visualization before entering the operative arena.

Lipomatous meningiomas are a very rare form of brain meningiomas consisting of fat accumulation within the tumor. Magnetic resonance imaging (MRI) or computerized tomographic (CT) imaging can be utilized to visualize the fat accumulations, but histopathologic staining is necessary in order to make a definitive diagnosis. The key histopathologic feature is the identification of adipocyte-like cells within the tumor, but other markers have also been identified. In this case report and review of the literature, we discuss how to recognize the symptoms associated with lipomatous meningiomas and the definitive treatment approach for these rare tumors., Competing Interests: The authors declare they have no conflicts of interest.

Careful fluid management is a cornerstone of neonatology because the cardiovascular, respiratory, and gastrointestinal systems in the newborn are sensitive to overhydration. Fluid management in gastroschisis is complicated by insensible fluid loss and postoperative third-space fluid shifts. Study of perioperative fluid management in gastroschisis is limited and has not undergone careful scrutiny. We reviewed perioperative fluid administration and urine output in all infants with gastroschisis over a 5-year period. Data included whether the patient underwent primary closure or staged repair, weight, and events during hospitalization (length of hospitalization and duration of gastric decompression, parenteral nutrition, and ventilator support). Paired t test gave statistical comparisons with significance at P < 0.05. From 2010 to 2014, 24 patients underwent abdominal closure, 17 had primary and 7 had staged closures. Fluid administration exceeded 100 mL/kg/d after primary closure, and was significantly higher (>150 mL/kg/d; P < 0.05) after staged closure on postoperative days 0 to 5. Postoperative urinary output exceeded 75 mL/kg/d for all patients, with higher volumes reaching 100 mL/kg/d after staged closure on postoperative days 4 to 6 (P < 0.05). Two patients died of sepsis. All survivors were discharged with intestinal continuity and gaining weight on oral feeding. Patients with gastroschisis received large volumes of fluid after operation despite similarly high urine output and positive daily fluid balances. The amounts of fluid administered after both primary and staged closure may be excessive and potentially deleterious.

Suprapubic catheter placement has associated complications such as bowel injury, bladder injury, or bleeding. This case describes the management of an elderly patient who had suprapubic catheter placement complicated by small bowel obstruction. The catheter had continued production of urine. Further patient treatment required abdominal exploration and bowel resection.

Patients with spinal vascular lesions present with unique symptoms and have important anatomical and physiologic changes that must be considered prior to treatment. In this mini-review, we provide an overview of normal spinal vascular anatomy and discuss several key spinal vascular lesions. We provide an overview of cavernous malformations, intradural arteriovenous malformations, perimedullary arteriovenous fistulas, and dural arteriovenous fistulas. Important considerations are addressed in terms of pathologic characterization, specific imaging findings, and treatment approaches.

The epidemic of obesity and diabetes in the United States poses major challenge to the prevention and management of chronic diseases. Furthermore, when this is viewed in other components of the metabolic syndrome (i.e., the burden of high cholesterol and hypertension), the prevalence of the metabolic syndrome continues to rise in the USA continued challenge is how to deal with this epidemic from a medical and public health standpoint. Community Based Participatory Research (CBPR) is a unique approach and offers a novel perspective for answering this challenge. A critical set of goals for CBPR is to address health disparities and social inequalities while getting community members engaged in all aspects of the research process. Utilizing the West Virginia Diabetes Prevention and Management Program and trained Health Coaches as a model, we discuss topics of consideration related to CBPR, involving trained health coaches, optimizing early adoption of healthy lifestyle behaviors, and enhancing participation. Through careful project planning and design, questions regarding disparities increasing susceptibility and preventive efforts within the community can be addressed successfully. These topics are part of a broader integration of theories such as participatory research, community engagement, and outcomes measurement. The understanding of the pathophysiology and epidemiology of the metabolic syndrome can help frame an appropriate strategy for establishing long-term community-wide changes that promote health. In order to continue to improve investigations for preventing the metabolic syndrome, it will be necessary to have aggressive efforts at the individual and population level for developing culturally sensitive programs that start early and are sustainable in practical environments such as the workplace. In this comprehensive review, we will discuss practical considerations related to project design, implementation, and how to measure effectiveness in regards to reducing the burden of the metabolic syndrome.

Background: The USMLE Step 1 score helps differentiate applicants for competitive residency programs. Students frequently ask medical educators how to prepare for this high-stakes exam. Multiple resources exist such as books, training programs, and question banks. The purpose of this study is to provide medical educators with data on which resources correlate with higher exam scores., Methods: 164 medical students at West Virginia University School of Medicine were given a survey following the completion of Step 1. The survey contained questions about resources used and exam date. De-identified data was paired with class quartile rankings and Step 1 scores. Average Step 1 scores were calculated for each resource and a student's t-test was used to compare between groups. Test dates were also broken into quintiles and average Step 1 scores were compared between groups., Results: Students who used the USMLE World question bank had higher Step 1 scores (M=229, SE=1.4) compared to students who did not use this resource (M=215, SE=4.2). Commercial preparation courses were not associated with improved scores. The timing of when the exam was taken was also not associated with significant differences between scores., Conclusions: Interactive study options offer the best choice to improve USMLE Step 1 scores.

This case report details the osteonecrosis of the interphalangeal (IP) joint of the thumb two months after a rattlesnake bite. It describes the clinical presentation, imaging studies, histological review, pathology review, and review of literature. Our patient was a fifty-one year-old male who obtained a poisonous snakebite to the thumb. While in the hospital for acute treatment, a blood blister was debrided. He was seen two weeks after discharge for further debridement of epidermolysis. Patient presented one month later with a hand x-ray demonstrating bony erosions, and a bone scan showing active changes in the IP joint of his right thumb. He was taken to the OR for further debridement and definitive diagnosis. Pathology results confirmed osteonecrosis with negative bone cultures. The clinical presentation, diagnosis, and operative management of osteonecrosis offer a unique challenge, especially in a patient presenting with osteonecrosis from a poisonous snakebite.