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Vertigo is defined as the illusion of internal or external motion. The evaluation of a patient with vertigo in the primary care setting should not necessarily focus on providing a specific diagnosis. Rather, the physician should aim to localize the lesion. This practice streamlines the workup of patients. This article provides detailed information regarding appropriate organ system-based clinical history and the clinical workup of vertigo. Additional signs and symptoms that can facilitate appropriate referral and treatment are highlighted. Although disorder-specific treatments exist the mainstay of therapy for vertigo-induced pathology is physical therapy.

A focused history, otoscopic and tuning fork examination and formal hearing testing are the diagnostic pillars for the workup of hearing loss and tinnitus. The causes of hearing loss and tinnitus are varied and range from relatively common age-related hearing loss to rare tumors of the brain and skull base. In this chapter, the authors explain the diagnostic workup of hearing loss and tinnitus, review the pathophysiology of the most common causes, and describe the treatments available.

Clinical use of various forms of immunotherapeutic drugs in glioblastoma (GBM), has highlighted severe T cell dysfunction such as exhaustion in GBM patients. However, reversing T cell exhaustion using immune checkpoint inhibitors in GBM clinical trials has not shown significant overall survival benefit. Phenotypically, CD8+ T cells with downregulated CD28 coreceptors, low CD27 expression, increased CD57 expression, and telomere shortening are classified as senescent T cells. These senescent T cells are normally seen as part of aging and also in many forms of solid cancers. Absence of CD28 on T cells leads to several functional irregularities including reduced TCR diversity, incomplete activation of T cells, and defects in Ag-induced proliferation. In the context of GBM, presence and/or function of these CD8+CD28– T cells is unknown. In this clinical correlative study, we investigated the effect of aging as well as tumor microenvironment on CD8+ T cell phenotype as an indicator of its function in GBM patients. We systematically analyzed and describe a large population of CD8+CD28– T cells in both the blood and tumor-infiltrating lymphocytes of GBM patients. We found that phenotypically these CD8+CD28– T cells represent a distinct population compared with exhausted T cells. Comparative transcriptomic and pathway analysis of CD8+CD28– T cell populations in GBM patients revealed that tumor microenvironment might be influencing several immune related pathways and thus further exaggerating the age associated immune dysfunction in this patient population.

Objective Treatment of ruptured cerebral aneurysms by endovascular coiling is associated with a better neurologic outcome when compared with neurosurgical clipping but has a higher risk for target aneurysm rebleeding after treatment. We hypothesize that aggressive retreatment of coiled aneurysms will lead to fewer recurrent hemorrhages as compared with historical values of 2.3%–3.0%. Methods All first-time Guglielmi detachable coil–embolized cerebral aneurysms were retrospectively reviewed at a single institution from 2004 to 2015. Aneurysm retreatment after first-time embolization was recorded as well as time to retreatment. Retreatment at our institution is routinely performed for incomplete coiling with etiologies including incomplete initial coiling, coil compaction, and aneurysmal dilatation. Aneurysm rerupture was treated with additional coiling. Kaplan-Meier survival analysis was performed to evaluate embolization durability. Results There were 214 aneurysms that met inclusion criteria. Mean (standard deviation) follow-up was 2.74 (2.24) years. Aneurysms that were patent or recanalized were retreated. Mean (standard deviation) time to retreatment was 9 (9) months. Overall, 46 (21.5%) aneurysms required retreatment. Retreatment was performed for coil compaction/remnant growth, recanalization, persistent remnant, and rebleed. Two (0.9%) patients had recurrent aneurysm hemorrhage and both were treated with additional coil embolization. There were no new long-term neurologic deficits caused by aneurysm retreatment. Conclusions Aggressive retreatment of previously ruptured, coiled cerebral aneurysms for persistent aneurysm patency reduces the recurrent hemorrhage risk to that historically seen in neurosurgically clipped aneurysms with minimal additional morbidity. This study validates a large body of literature demonstrating the significance of post-treatment aneurysm remnants and their association with recurrent hemorrhage.

Background Traditional paradigms of care recommend close audiology follow-up and regular speech perception outcomes assessment indefinitely for cochlear implant (CI) recipients after device activation. However, there is scant published data on actual compliance with this paradigm in clinical practice. Methods A multi-center cochlear implant database was queried to identify follow-up rates after cochlear implantation. Follow-up rates where speech perception outcomes assessment occurred at 1-, 3-, 6-, 12-, 18-, and 24-months post-activation were determined by tabulating observed follow-up divided by expected follow-up (O/E ratio) expressed as a percentage. To determine all-cause audiology follow-up rates (with or without testing speech perception outcomes assessment), the database patients from two participating centers (one private practice and one academic center) were similarly analyzed using electronic health record (EHR) data to calculate O/E rates where audiology follow-up occurred for any reason. Results O/E follow-up rates where speech perception outcomes assessment occurred was 42, 40, 31, 29, 5, and 22% for 1-, 3-, 6-, 12-, 18-, and 24-months post-activation, respectively (n = 2,554). All-cause audiology follow-up rates (with or without speech perception outcomes assessment) using EHR-confirmed data from two individual centers were 97, 94, 81, 66, 41, and 35% at 1-, 3-, 6-, 12-, 18-, and 24-months post-activation visits, respectively (n = 118). Conclusions Compliance with audiology follow-up and speech perception outcomes assessment is generally low and decreases significantly as time post-activation increases. Future paradigms of care for CI should be designed recognizing the significant attrition that occurs with CI follow-up.

OBJECTIVE Report the details of an unusual case of initially unilateral intradural spontaneous otogenic pneumocephalus in which the patient developed contralateral pneumocephalus after surgical repair of temporal bone and dural defects on the initial side. Discuss the lessons learned concerning management and pathophysiology of this rare case. PATIENT A 73-year-old male presenting with bilateral retro-orbital pain and headache was found to have unilateral intradural pneumocephalus in the temporal lobe with an adjacent defect in the temporal bone. INTERVENTION Surgical repair of the initial defect in the temporal bone and dura via a middle cranial fossa approach with obliteration of the mastoid cavity. RESULTS The patient's symptoms and degree of pneumocephalus on first affected side decreased initially after surgery. Two weeks after surgery he developed worsening pneumocephalus on the contralateral side in the temporal and frontal lobes with weakness and mild somnolence. This side was repaired via a similar technique without mastoid obliteration. Two weeks after surgery the patient recovered to normal level of consciousness with mild residual weakness. CONCLUSIONS Spontaneous otogenic intradural pneumocephalus is an extremely rare but serious condition related to defects in the temporal bone and dura. The precise mechanism by which this occurs is poorly understood. This unusual case where there were bilateral defects presenting with spontaneous otogenic pneumocephalus in sequence illustrates that it represents a rare sequelae of processes which thin the skull base. These processes should be addressed in addition to acute management of the defect and intracranial air.

OBJECTIVE Compare outcomes for patients who were seen via telemedicine visits after otology/neurotology surgical procedures with those who were seen in traditional office visits. STUDY DESIGN Retrospective case review. SETTING Tertiary care academic medical center. PATIENTS Inclusion criteria were patients who underwent otologic/neurotologic surgery and were seen in at least one telemedicine visit for postoperative care. INTERVENTION (S) Telemedicine visit for postoperative care. MAIN OUTCOME MEASURE (S) Comparison of the number of patient calls, unplanned visits, and delayed complications between telemedicine patients and controls matched for age, procedure, and American Society of Anesthesiologists (ASA) status. RESULTS Eighteen patients were seen in telemedicine visits postoperatively after the following otologic/neurotologic surgical procedures: cochlear implant surgery (10), vestibular schwannoma resection (4), combined middle fossa and transmastoid cerebrospinal fluid (CSF) leak repair (2), middle fossa repair of superior canal dehiscence (1), and stapedectomy (1). All telehealth visits were for the second postoperative visit. The mean number of patient calls after surgery was 2.3 for the telemedicine group and 1.9 for matched controls which was not a statistically significant difference (p = 0.466). Both groups each had two patients who went to the emergency room, with one in each group being admitted. There was one delayed complication in the control group. CONCLUSION Our preliminary experience suggests telemedicine may be used safely in caring for patients after otologic/neurotologic surgery, though it may be associated with more patient phone calls. Further study and experience, including assessing patient satisfaction, will clarify the future role of telemedicine in otology and neurotology.

Knowledge of the isocitrate dehydrogenase (IDH) mutation status of glioma patients could provide insights for decision-making during brain surgery. However, pathology is not able to provide such information intraoperatively. Here we describe the first application of a miniature mass spectrometer (MS) to the determination of IDH mutation status in gliomas intraoperatively. The instrumentation was modified to be compatible with use in the operating room. Tandem MS was performed on the oncometabolite, 2-hydroxyglutarate, and a reference metabolite, glutamate, which is not involved in the IDH mutation. Ratios of fragment ion intensities were measured to calculate an IDH mutation score, which was used to differentiate IDH mutant and wild-type tissues. The results of analyzing 25 biopsies from 13 patients indicate that reliable determination of IDH mutation status was achieved (p = 0.0001, using the Kruskal-Wallis non-parametric test). With its small footprint and low power consumption and noise level, this application of miniature mass spectrometers represents a simple and cost-effective platform for an important intraoperative measurement. Graphical abstract.

Background: Chronic rhinosinusitis (CRS) is a multifaceted disease with a significant genetic component. The importance of taste receptor signaling has recently been highlighted in CRS; single nucleotide polymorphisms (SNPs) of bitter tastant-responsive G-protein-coupled receptors have been linked with CRS and with altered innate immune responses to multiple bacterially derived signals. Objective: To determine in CRS the frequency of six SNPs in genes with known bitter tastant signaling function. Methods: Genomic DNA was isolated from 74 CRS volunteers in West Virginia, and allele frequency was determined and compared with demographically matched data from the 1,000 Genomes database. Results: For two SNPs in a gene recently associated with bitterant signaling regulation, RGS21, there were no associations with CRS (although the frequency of the minor allele of RGS21, rs7528947, was seen to increase with increasing Lund-Mackay CT staging score). Two TAS2R bitter taste receptor gene variants (TAS2R19 rs10772420 and TAS2R38 rs713598), identified in prior CRS genetics studies, were found to have similar associations in this study. Conclusion: Unique to our study is the establishment of an association between CRS in this patient population and GNB3 SNP rs5443, a variation in an established G protein component downstream of bitterant receptor signal transduction.

Objective: Examine the effects of a multi-disciplinary skull base conference (MDSBC) on the management of patients seen for skull base pathology in a neurotology clinic. Methods: Retrospective case review of patients who were seen in a neurotology clinic at a tertiary academic medical center for pathology of the lateral skull base and were discussed at an MDSBC between July 2019 and February 2020. Patient characteristics, nature of the skull base pathology, and pre- and post-MDSBC plan of care was categorized. Results: A total of 82 patients with pathology of the lateral skull base were discussed at a MDSBC during an 8-month study period. About 54 (65.9%) had a mass in the internal auditory canal and/or cerebellopontine angle while 28 (34.1%) had other pathology of the lateral skull base. Forty-nine (59.8%) were new patients and 33 (40.2%) were established. The management plan changed in 11 (13.4%, 7.4-22.6 95% CI) patients as a result of the skull base conference discussion. The planned management changed from some form of treatment to observation in 4 patients, and changed from observation to some form of treatment in 4 patients. For 3 patients who underwent surgery, the planned approach was altered. Conclusions: For a significant proportion of patients with pathology of the lateral skull base, the management plan changed as a result of discussion at an MDSBC. Although participants of a MDSBC would agree of its importance, it is unclear how an MDSBC affects patient outcomes.

Objective: The aim of this study was to determine the incidence of cochlear fibrosis after vestibular schwannoma (VS) resection via middle cranial fossa (MCF) approach. Design: A retrospective case review was conducted. Setting: The review was conducted in a tertiary care academic medical center. Participants: Patients who (1) underwent resection of VS via MCF approach between 2013 and 2018, (2) had complete pre- and post-audiometric testing, and (3) had clinical follow-up with magnetic resonance imaging (MRI) for at least 1 year after surgery were included. Main Outcome Measure(s): The main outcome of this study was cochlear fibrosis as assessed by MRI 1 year after surgery. Results: Fifty-one patients underwent VS resection via MCF technique during the study period. Of 31 patients with AAO-HNS class A or B preoperative hearing ability, 18 (58.0%) maintained class A, B, or C hearing postoperatively. Of 16 patients who lost hearing and had MRI 1 year after surgery, 11 (61.1%) had MRI evidence of fibrosis in at least some portion of the labyrinth and 4 (22.2%) showed evidence of cochlear fibrosis. Of 16 patients with preserved hearing and MRI 1 year after surgery, 4 (25%) had fibrosis in some portion of the labyrinth, with no fibrosis in the cochlea. Conclusions: In patients who lose hearing during VS resection with the MCF approach, there is usually MRI evidence of fibrosis in the labyrinth 1 year after surgery. However, there is also, but less commonly, fibrosis involving the cochlea. It is unclear if this will affect the ability to insert a cochlear implant electrode array.

OBJECTIVE Traditionally, auditory brainstem implants (ABIs) have been placed via the translabyrinthine or retrosigmoid approaches. In select patients, a modified extended middle cranial fossa (xMCF) approach with tentorial ligation may be advantageous for vestibular schwannoma (VS) resection and auditory rehabilitation. This manuscript describes the application of this modification of the MCF approach for simultaneous VS resection and ABI placement. PATIENTS Patients with neurofibromatosis type 2, profound bilateral sensorineural hearing loss, single functioning sigmoid/jugular venous system, and giant (>4 cm) VS. INTERVENTIONS Simultaneous VS resection and ABI placement via a modified xMCF approach with tentorial ligation. MAIN OUTCOME MEASURES Extent of tumor removal and brainstem decompression, access to lateral recess of the fourth ventricle, functional hearing improvement, surgical complications. RESULTS Two patients met indications and underwent surgery. There were no immediate or delayed surgical complications. Both had subtotal tumor removal with significant decompression of the brainstem and ABI placement. One patient achieved voice and environmental sound awareness at 35 to 55 dbHL across frequencies. The second patient presented with failure to thrive and multiple lower cranial neuropathies in addition to the above-listed indications. She was hospitalized multiple times after surgery due to failure to thrive and recurrent aspiration pneumonia. Her device was never activated, and she expired 1 year after surgery. CONCLUSIONS The xMCF with tentorial ligation is an additional approach for tumor resection and ABI placement in selected patients with neurofibromatosis type 2. Future studies will further define when this approach is most applicable as well as the challenges and pitfalls.

OBJECTIVE Determine if changes in middle ear absorbance measured with wide-band tympanometry (WBT) occur following hearing-preservation cochlear implantation (CI). Such measures may provide insight into the mechanisms of acoustic hearing loss postimplantation. STUDY DESIGN Clinical capsule report. SETTING Tertiary academic referral center. DESIGN WBT absorbance was measured bilaterally during pre- and postoperative clinical office visits in five unilaterally-implanted cochlear implant recipients. Pre- and postoperative WBT measures were compared within each subject in the implanted and contralateral, unimplanted ears. RESULTS In general, WBT absorbance measurements show a broad spectral pattern including two or three distinct peaks measured over a frequency range of 226 to 8000 Hz. Grand average and linear mixed model comparisons between the pre- and postoperative WBT patterns show significantly reduced (p

Objective 1) Determine tumor control, symptomatic control, and complication rates of primary radiosurgery (PRS) for treatment of glomus jugulare tumors (GJTs) via systematic review and meta-analysis. 2) Identify risk factors for these outcomes. Data sources 1) Search of English articles in PubMed, Web of Science, Cochrane, and EBSCOhost databases from January 1950 to August 2017. Study selection Inclusion criteria: 1) treated GJT patients who had no previous treatment with radiosurgery, 2) follow-up with magnetic resonance imaging for at least 12 months, 3) reported pre and posttreatment symptoms, tumor control, or complications for individual PRS patients or for PRS patients as a cohort. Data extraction The following were extracted: number of patients, level of evidence, mean age, mean pretreatment tumor volume, tumor control rate, criteria for change in tumor size, symptom control rate, and complications. At the individual patient level the following were extracted: age, number of treatment fractions, total radiation dose to tumor margin, pretreatment tumor volume, Fisch or Glasscock-Jackson stage, pre- and posttreatment symptoms, tumor control, symptom control/improvement, length of follow-up, and complications. Data synthesis Fifteen studies encompassing 91 patients met criteria. Tumor control was achieved in 92% of patients, symptom control in 93%, and complications occurred in 8%. There was one major complication. Smaller tumor volume predicted improvement in symptoms with PRS. Conclusions In the short term, PRS is safe and effective at controlling growth and clinical symptoms for patients with GJTs, though there exists significant selection bias, inconsistent reporting, and clinical heterogeneity among existing studies.

Objective Compare the incidence of skin and surgical site complications for children undergoing percutaneous and transcutaneous bone conduction implant (pBCI and tBCI) surgery via systematic review and meta-analysis of the available data. Data sources 1) Search of PubMed, Web of Science, and EBSCOhost databases from January 2012 to April 2017. 2) References of studies meeting initial criteria. Study selection Inclusion criteria were studies that involved patients less than 18 years old undergoing tBCI or pBCI surgery with a BI300 implant and reported skin complications, implant loss, and need for revision surgery. Exclusion criterion was use of a previous generation implant. Data extraction Implants used, number of patients, age, surgical technique, Holgers score, incidence of skin complication, implant loss, and reoperation. Bias assessment performed with the Newcastle-Ottawa Scale. Data synthesis Twenty-two studies (14 tBCI, 8 pBCI) met criteria. Meta-analysis was performed using a random effects model. Cochran's Q score and I inconsistency were used to assess for heterogeneity. Overall estimated skin complication rate for tBCIs was 6.3% versus 30% for pBCIs (p = 4 × 10). Implant loss was 0% for tBCIs and 5.3% for pBCIs (p = 0.004). Reoperation rate was 3.0% and 6.2% for tBCIs and pBCIs respectively (p = 0.00002). Conclusion There is strong evidence to suggest that in pediatric patients, the incidence of skin complications, implant loss, and rate of reoperation are higher for pBCIs compared with tBCIs. This information should be part of any discussion about BCI surgery on a pediatric patient.

Objective To predict the cost-effectiveness of implementing routine gene expression classifier testing for thyroid nodules with indeterminate fine-needle aspiration cytology, by utilizing a real cohort of patients as a comparator. Study Design Cost-effectiveness analysis of a retrospective cohort compared with a simulated cohort. Setting Tertiary academic medical center. Subjects and Methods We reviewed the records of all patients who underwent ultrasound-guided fine-needle aspiration from 2010 to 2014 at a tertiary academic medical center. All patients with Bethesda class III or IV cytopathology had the details of their management catalogued over the subsequent 2 years of care. These patients were assigned to the standard-of-care arm of the study. We compared the third-party payer costs of care and the proportion of patients who underwent surgery with a simulated cohort who underwent gene expression classifier testing after an initial indeterminate fine-needle aspiration (molecular test arm). Results The cost of managing 1 nodule over 2 years was $2399 higher (range, $397-$4399) for the molecular test group than the standard of care group. The molecular test group had a 13.1% decrease (base parameters; range, 0.73%-45.09%) in the number of patients undergoing surgery. Conclusion When applied to a real cohort of patients, routine gene expression classifier is predicted to reduce the number of patients undergoing surgery but will increase cost of care. Cost-effectiveness is heavily dependent on prevalence of malignancy and gene expression classifier specificity.

Objective The natural history and long-term durability of Guglielmi detachable coil (GDC) embolization is still unknown. We hypothesize a stepwise decrease in durability of embolized cerebral aneurysms as stratified by the Modified Raymond-Roy Classification (MRRC). Methods First-time GDC-embolized cerebral aneurysms were retrospectively reviewed from 2004 to 2015. Loss of durability (LOD) was defined by change in aneurysm size or patency seen on serial radiographic follow-up. Kaplan-Meier survival analysis was performed to evaluate embolization durability. Multivariate Cox regression modeling was used to assess baseline aneurysm and patient characteristics for their effect on LOD. Results A total of 427 patients with 443 aneurysms met the inclusion criteria. Overall, 89 (21%) aneurysms met LOD criteria. Grade 1 aneurysms had statistically significantly greater durability than did all other MRRC grades. Grade 3b aneurysms had significantly worse durability than did all other aneurysm grades. There was no difference in durability between grade 2 and 3a aneurysms. Of aneurysms with LOD, 26 (29%) experienced worsening of MRRC grade. Thirty-five (24%) initial MRRC grade 2, 72 (45%) initial MRRC grade 3a, and 6 (22%) initial MRRC grade 3b aneurysms progressed to MRRC grade 1 without retreatment. In our multivariate analysis, only initial MRRC grade was statistically significantly associated with treatment durability (P Conclusions MRRC grade is independently associated with first-time GDC-embolized cerebral aneurysm durability. Achieving MRRC grade 1 occlusion outcome is significantly associated with greater long-term GDC durability. Although few aneurysms experience further growth and/or recanalization, most incompletely obliterated aneurysms tend to remain stable over time or even progress to occlusion. Grading scales such as the MRRC are useful for characterizing aneurysm occlusion but may lack sensitivity and specificity for characterizing changes in aneurysm morphology over time.

Patients diagnosed with neurofibromatosis type 2 (NF2) are extremely likely to develop meningiomas, in addition to vestibular schwannomas. Meningiomas are a common primary brain tumor; many NF2 patients suffer from multiple meningiomas. In NF2, patients have mutations in the NF2 gene, specifically with loss of function in a tumor-suppressor protein that has a number of synonymous names, including: Merlin, Neurofibromin 2, and schwannomin. Merlin is a 70 kDa protein that has 10 different isoforms. The Hippo Tumor Suppressor pathway is regulated upstream by Merlin. This pathway is critical in regulating cell proliferation and apoptosis, characteristics that are important for tumor progression. Mutations of the NF2 gene are strongly associated with NF2 diagnosis, leading to benign proliferative conditions such as vestibular schwannomas and meningiomas. Unfortunately, even though these tumors are benign, they are associated with significant morbidity and the potential for early mortality. In this review, we aim to encompass meningiomas and vestibular schwannomas as they pertain to NF2 by assessing molecular genetics, common tumor types, and tumor pathogenesis.

Stereotactic radiosurgery (SRS) has emerged as a common adjuvant modality used with surgery for resectable brain metastases (BMs). However, the optimal sequence of the multi-modality therapy has not been established. The goal of the study is to evaluate 6-month local control utilizing pre-operative SRS followed by surgical resection for patients with 1–4 brain metastases. This prospective, single arm, phase II trial will recruit patients with up to 4 brain metastases and at least one resectable lesion. All lesions will be treated with SRS and symptomatic lesions will be resected within 1–4 days after SRS. Patients will be monitored for 6-month local control, in-brain progression free survival, distant in-brain failure, rate of leptomeningeal spread, radiation necrosis and overall survival. Additionally, we will also perform correlative radiobiological molecular studies to assess the effect of radiation dosing on the tumor tissue and clinical outcomes. We expect that pre-operative SRS to the gross tumor prior to surgical resection will improve local control and decrease leptomeningeal failure. Our study is the second prospective trial to investigate the efficacy of pre-operative SRS in the treatment of multiple BMs. In addition, the correlative molecular studies will be the first to investigate early response of BMs at a cellular and genetic level in response to radiation doses and potentially provide molecular prognostic markers for local control and overall survival. Clinicaltrials.gov identifier: NCT03398694 (registration date: January 12, 2018).

Objective: Determine the effect of complete malleus removal during canal wall up tympanomastoidectomy for cholesteatoma on ossiculoplasty success and rate of residual cholesteatoma. Methods: We reviewed the operative, audiogram, and clinical reports of patients who underwent canal wall up tympanomastoidectomy for cholesteatoma between 2009 and 2016 at a tertiary academic medical center with at least 8 months of follow-up after surgery. To control for extent of disease, we independently catalogued the subsites of the middle ear and mastoid that cholesteatoma involved from each operation. We performed multivariate logistic regression to determine the independent effect of complete removal of the malleus on the rate of residual disease and success of ossiculoplasty. Results: One hundred eighty surgeries were included in the analysis. For ossiculoplasty success, the adjusted odds ratio of complete malleus removal was 1.7 (95% CI, 0.43-7.0, P = .43), which was not statistically significant. For residual disease, the adjusted odds ratio of complete malleus removal versus not was 0.29 (95% CI, 0.074-1.1, P = .076), which approached but did not meet statistical significance. Conclusion: Though complete malleus removal does not independently decrease the rate of residual cholesteatoma, it may be a safe technique as it did not compromise ossiculoplasty success.

INTRODUCTION We sought to determine whether intrabronchial oxygenation would provide adequate gas exchange during both anesthesia induced apneic and cardiopulmonary arrest and cardiac massage (CPR). METHODS Ten pigs underwent general anesthesia with mechanical ventilation. Blood gases were measured in each animal at 4 min intervals for up to 28 min. An intrabronchial catheter (4 L/min O2) was inserted through an endotracheal tube after respirator cessation. Group A animals (6) were resuscitated with the catheter but without CPR. Group B animals (4) were rendered apneic and cardioplegic and resuscitated by CPR for 28 min using the intrabronchial device. RESULTS All group A animals were resuscitated and survived after 24 min of apnea. Mean pO2 decreased from 378 mmHg (95% confidence interval [CI], 288-468) to 292 mmHg (95% CI, 246-339), P = 0.009; pCO2 increased from 52 mmHg (95% CI, 43-61) to 137 mmHg (95% CI, 116-158), P

The last year has seen major changes at Legal Theory. Two of the journals’ editors—David Brink (Professor of Philosophy, University of California, San Diego) and Matthew Adler (Professor of Law, Duke Law School)—stepped down after years of outstanding editorial work. We gratefully acknowledge their invaluable contributions in sustaining and improving the journal. As each editor stepped down, a new editor stepped in. Connie Rosati (Professor of Philosophy, University of Arizona) began work as an editor in the fall of 2016. In the spring of 2017, Mitchell Berman (Professor of Law, University of Pennsylvania Law School) joined the journal.

Frontal sinus cranialization is commonly indicated for posterior table fractures with significant comminution, displacement, or cerebrospinal fluid leaks. This study assessed the clinical outcomes of conservative management.A 10-year retrospective review of all frontal sinus fractures treated at a level 1 trauma center was performed using medical records and radiographic images.A total of 875 patients with frontal sinus fractures were identified, and 68 had posterior table involvement. Nine died within the first 48 hours from other injuries. The remaining 59 patients constituted the study population. Average follow-up approached 1 year (342 days). The more common mechanisms of injury were blunt interpersonal violence (29 percent) and motor vehicle accidents (27 percent). Concurrent central nervous system injury was common (73 percent), and the average Glasgow Coma Scale score was 12.7. Posterior wall fracture pattern was nondisplaced and noncomminuted in 33 patients (54 percent) and comminuted and/or displaced in 27 (46 percent). Cerebrospinal fluid leak was recorded in 11 patients (19 percent). Conservative management was the more common strategy (78 percent), followed by open reduction and internal fixation with sinus preservation (12 percent), obliteration (8 percent), and cranialization (2 percent). Of the 27 patients with comminuted and/or displaced fractures, 16 (59 percent) underwent conservative management, and 11 (41 percent) underwent surgical management, but only one patient (2 percent) underwent cranialization. There was no incidence of intracranial infection, except for one patient who died from encephalitis secondary to a gunshot wound to the head.The vast majority of frontal sinus fractures involving the posterior table, including those with comminution, displacement, or cerebrospinal fluid leaks, can be safely managed without cranialization.Therapeutic, IV.

With the exception of oligoastrocytoma, mixed gliomas are rarely encountered, and the astrocytic component of mixed oligoastrocytoma is almost always fibrillary and diffusely infiltrative. Pleomorphic xanthoastrocytoma (PXA) has occasionally been described in conjunction with ganglioglioma, as well as in 1 case of oligodendroglioma. In this latter case, described by Perry et al., 1p/19q codeletions were not detected. The authors report on a 25-year-old woman with a combined PXA/oligodendroglioma in which concurrent 1p/19q codeletions were detected in the oligodendroglial component only. The patient presented with a 1-month history of headaches. Neuroimaging revealed a heterogeneous left temporal mass with focal enhancement, cystic changes, hemorrhage, and left-to-right midline shift. The patient underwent a craniotomy and gross-total resection. Pathological examination revealed a glial tumor composed of 2 apparently distinct components. The largest component exhibited a prominent fascicular, reticulin-rich, spindle cell arrangement admixed with areas of highly pleomorphic cells, with bizarre cytological features reminiscent of PXA. A smaller component was composed of cellular sheets and lobules of oligodendroglial cells. Both components were characterized by anaplastic features. Dual-color fluorescence in situ hybridization for 1p/19q codeletions was performed. Only the oligodendroglial component showed the combined 1p/19q deletions. This case represents the first instance in which PXA has been reported in conjunction with an oligodendroglioma exhibiting the “molecular signature” characteristic of oligodendroglial neoplasms. The different genetic alterations seen in the 2 components of this neoplasm argue in favor of a “collision tumor” rather than a mixed glioma of the same genotype.

Object Organ transplantation for renal, liver, cardiac, and pulmonary failure has become more common in recent years, and patients are living longer as a result of improved organ preservation methods, immunosuppressive regimens, and general posttransplant care. Some of these patients undergo spine fusion surgery following organ transplantation, and there is little available information concerning outcomes. The authors report on their experience with and the outcomes of spine fusion in this rare and unique immunosuppressed patient group. Methods Using the Current Procedural Terminology and ICD-9 codes for solid organ transplants, bone marrow transplantations (BMTs), and spine fusion surgeries, the authors searched their patient database between 1997 and 2008. Data points of interest included primary diagnosis, type of organ transplant, immunosuppressant drug therapy, complications from spine surgery, and radiographic analysis of spine fusion. Spine fusion was assessed with CT or radiography at the latest follow-up. Results The database search results revealed 5999 patients who underwent heart, lung, liver, kidney, pancreas, intestine, or bone marrow transplant between 1997 and 2008. Eighteen of the 5999 patients underwent a spine fusion surgery while receiving immunosuppressive therapy. Organ transplants included kidney, liver, heart, pancreas, and allogenic BMT. There were 3 deaths unrelated to spine fusion within 1 year of the surgery and 1 death immediately after spine surgery. Graft-versus-host disease developed in 1 patient when prednisone was stopped prior to the spine surgery. Thirteen patients underwent follow-up radiographic imaging at an average of 25 months after spine surgery; 12 demonstrated radiographic fusion. Conclusions The results suggest that spine fusion rates are adequate despite immunosuppressive therapy in patients undergoing spinal fusion after transplant procedures. The data also illustrate the high morbidity and mortality rates found in the organ transplant patient population.

Object Endoscopic surgery has been reported to be more cost-effective and safer than open craniotomy for resection of colloid cysts, despite a 5–10% conversion rate to craniotomy, a 5% recurrence rate, a 5–10% ventricular shunting rate, a 5–10% epilepsy rate, and a 3–4 day hospital stay. In 1985, the authors developed a interhemispheric, transcallosal, subchoroidal, fornix-sparing approach that allowed safe total resection of the colloid cyst and that appeared to be superior to the endoscopic approach. The long-term results are analyzed and compared with findings in the literature. Methods Fifty-seven consecutive colloid cysts were totally removed via a 3 ×3–in paramedian craniotomy flap and a microscopic interhemispheric, transcallosal, subchoroidal approach sparing the ipsilateral fornix. The length of the callosotomy was 1.5–2 cm in all patients. The mean follow-up duration was 12 years (range 2–22 years). A retrospective analysis comparing the authors' results with those reported in the endoscopic literature was performed. Results All patients had 1-year postoperative imaging studies (CT or MR imaging) documenting gross-total resection with no deaths, infection, hemiparesis, seizures, or disconnection syndrome. One surgery was complicated by bilateral subdural hematomas, which were successfully treated. There has been a zero recurrence rate. Three patients required a permanent ventriculoperitoneal shunt (including 2 who required emergency ventriculostomy before surgery). The mean hospital stay was 4.8 days (range 2–24 days). There was 1 patient with permanent short-term memory loss who presented with a herniation syndrome requiring emergency ventriculostomy. Conclusions The interhemispheric, transcallosal, subchoroidal, fornix-sparing approach to gross-total resection of colloid cysts is safe and led to a zero recurrence rate with no permanent neurological sequelae including epilepsy, and these results are superior to any reported results with endoscopy.

We have studied the application of voltage gradients to injured spinal cord which enhanced regeneration of axons and reduced their retrograde degeneration after injury. This led to an implanted electronic device producing electrical fields sufficient to induce regeneration in both ascending and descending tracts of white matter (called oscillating field stimulation [OFS]), which has been associated with behavioral recovery in animal models of spinal cord injury (SCI). OFS has also proven to benefit neurologically complete spinal cord injured dogs and humans in clinical trials. These studies, however, have failed to confirm benefit if applied after the sub-acute period of SCI. Here we report on combining OFS with the application of a non-toxic neurotrophic factor, inosine, using a behavioral model for "chronic" SCI, the cutaneous trunci muscle (CTM) reflex in adult guinea pigs. Inosine was delivered subcutaneously in guinea pigs for 28 days using implantable "osmotic pumps"--alone or in combination with OFS. In all animals, experimental and control treatments were withheld for three months after a right lateral hemisection of the thoracic spinal cord. Both inosine and the combination therapy produced a statistically significant recovery of CTM receptive fields silenced permanently by spinal cord hemisection in controls--though the combination therapy enhanced the time of the appearance of recovered regions of skin. Retransection of the cord in three recovered animals eliminated the CTM recovery confirming changes in neural connections were restricted to the cord and not due to changes in cutaneous peripheral innervation. Morphometry of anterogradely labeled white matter revealed a statistically enhanced regeneration of ascending and descending projections in animals treated with the combination "therapy" compared to inosine alone. These data suggest that combining neurotrophic factors of differing modes of action likely enhance the outcome from "chronic" SCI.

Cyclin A2 (Ccna2), normally silenced after birth in the mammalian heart, can induce cardiac repair in small-animal models of myocardial infarction. We report that delivery of the Ccna2 gene to infarcted porcine hearts invokes a regenerative response. We used a catheter-based approach to occlude the left anterior descending artery in swine, which resulted in substantial myocardial infarction. A week later, we performed left lateral thoracotomy and injected adenovirus carrying complementary DNA encoding CCNA2 or null adenovirus into peri-infarct myocardium. Six weeks after treatment, we assessed cardiac contractile function using multimodality imaging including magnetic resonance imaging, which demonstrated ~18% increase in ejection fraction of Ccna2-treated pigs and ~4% decrease in control pigs. Histologic studies demonstrate in vivo evidence of increased cardiomyocyte mitoses, increased cardiomyocyte number, and decreased fibrosis in the experimental pigs. Using time-lapse microscopic imaging of cultured adult porcine cardiomyocytes, we also show that Ccna2 elicits cytokinesis of adult porcine cardiomyocytes with preservation of sarcomeric structure. These data provide a compelling framework for the design and development of cardiac regenerative therapies based on cardiomyocyte cell cycle regulation.

An analysis of 44 cauda equina syndrome cases.To determine the neurologic outcome of cauda equina syndrome cases, in light of the significant medical implications of this disorder.Cauda equina syndrome from lumbar disc herniation accounts for up to 1% of all disc herniations. Most of the literature supports surgery within 24 hours as a means of improving the outcome.A retrospective chi 2 analysis was performed of 44 patients surgically treated for lumbar disc herniation who initially sought treatment for cauda equina syndrome.In 20 patients, diagnosis was made and surgery performed within 48 hours of the cauda equina syndrome onset, including 18 patients (90%) who underwent surgery within 24 hours. In 24 patients, surgery was performed more than 48 hours after the onset of cauda equina syndrome, with a mean delay of 9 days, including 17 patients (71%) with a mean delay of 3.7 days. Causes for delay were patient-related in 4 cases (17%) and physician-related in 20 cases (83%). According to chi 2 analysis, a greater chance of persistent bladder/sphincter problem (P = 0.008), persistent severe motor deficit (P = 0.006), persistent pain (P = 0.025), and sexual dysfunction (P = 0.006) existed with delayed surgery.The data strongly support the management of cauda equina syndrome from lumbar disc herniation as a diagnostic and surgical emergency.