A Prospective Phase I/II Clinical Trial of High-Dose Proton Therapy for Chordomas and Chondrosarcomas.

Purpose: The purpose of this study was to evaluate the feasibility and safety of dose-escalated proton beam therapy for treating chordomas and chondrosarcomas of the skull base and spine. Methods: A prospective cohort of 54 patients (42 with chordomas and 12 with chondrosarcomas) was enrolled between 2010 and 2018. The primary endpoints were feasibility and <20% rate of acute grade ≥3 toxicity, and secondary endpoints included cancer-specific outcomes and toxicities. Patients were followed with magnetic resonance imaging or computed tomography at 3-month intervals. Proton beam therapy was delivered with doses up to 79.2 Gy using protons only, combination protons/intensity modulated radiation therapy (IMRT), or IMRT only. Results: Feasibility endpoints were met, with only 2 out of 54 patient radiation therapy plans failing to meet dosimetric constraints with protons, and 4 out of 54 experiencing a delay or treatment break >5 days, none for toxicities related to treatment. There were no grade 4 acute toxicities and 1 grade 3 acute toxicity (sensory neuropathy). The only 2 grade 3 late toxicities recorded, osteoradionecrosis and intranasal carotid blowout (mild and not emergently treated), occurred in a single patient. We report overall survival as 83% at 5 years, with local failure-free survival and progression-free survival rates of 72% and 68%, respectively. Five patients developed distant disease, and among the 9/54 patients who died, 4 deaths were not attributed to treatment or recurrence. Conclusions: Our findings suggest that high-dose proton therapy alone or in combination with IMRT is a safe and effective treatment option for chordomas and chondrosarcomas of the skull base and spine.

Transient Elevation of Plasma Glucocorticoids Supports Psilocybin-Induced Anxiolysis in Mice.

While correlations between drug-induced cortisol elevation, self-reported anxiety, and treatment outcomes have been reported for human studies during psilocybin-assisted psychotherapy, the mechanistic relationship between psychedelic-associated alterations in plasma glucocorticoid responses and the time course of anxious responsiveness remains unclear. Using rodents, both time-bound manipulation of glucocorticoid concentrations and assessment of anxiety-like behaviors can be achieved. Here, 3 mg/kg IP psilocybin was found to have anxiolytic-like effects in C57BL/6 male mice at 4 h after treatment. These effects were not altered by pretreatment with a 5-HT2A antagonist but were blunted by pretreatment with a glucocorticoid receptor antagonist or suppression of psilocybin-induced corticosterone elevations. Anxiolytic-like effects were also observed at 4 h following treatment with the nonpsychedelic 5-HT2A agonist lisuride at a dose causing a similar increase in plasma glucocorticoids as that seen with psilocybin, as well as following stress-induced (via repeated injection) glucocorticoid release alone. Psilocybin's anxiolytic-like effects persisted at 7 days following administration. The long-term anxiolytic effects of psilocybin were lost when psilocybin was administered to animals with ongoing chronic elevations in plasma corticosterone concentrations. Overall, these experiments indicate that acute, resolvable psilocybin-induced glucocorticoid release drives the postacute anxiolytic-like effects of psilocybin in mice and that its long-term anxiolytic-like effects can be abolished in the presence of chronically elevated plasma glucocorticoid elevations.

The Adjustable Cranial Plate: A Novel Implant Designed to Eliminate the Need for Cranioplasty Surgery Following a Hemicraniectomy Operation.

BACKGROUND: Decompressive hemicraniectomy (DHC) is performed to relieve life-threatening intracranial pressure elevations. After swelling abates, a cranioplasty is performed for mechanical integrity and cosmesis. Cranioplasty is costly with high complication rates. Prior attempts to obviate second-stage cranioplasty have been unsuccessful. The Adjustable Cranial Plate (ACP) is designed for implantation during DHC to afford maximal volumetric expansion with later repositioning without requiring a second major operation. METHODS: The ACP has a mobile section held by a tripod fixation mechanism. Centrally located gears adjust the implant between the up and down positions. Cadaveric ACP implantation was performed. Virtual DHC and ACP placement were done using imaging data from 94 patients who had previously undergone DHC to corroborate our cadaveric results. Imaging analysis methods were used to calculate volumes of cranial expansion. RESULTS: The ACP implantation and adjustment procedures are feasible in cadaveric testing without wound closure difficulties. Results of the cadaveric study showed total volumetric expansion achieved was 222 cm3. Results of the virtual DHC procedure showed the volume of cranial expansion achieved by removing a standardized bone flap was 132 cm3 (range, 89-171 cm3). Applied to virtual craniectomy patients, the total volume of expansion achieved with the ACP implantation operation was 222 cm3 (range, 181-263 cm3). CONCLUSIONS: ACP implantation during DHC is technically feasible. It achieves a volume of cranial expansion that will accommodate that observed following survivable hemicraniectomy operations. Moving the implant from the up to the down position can easily be performed as a simple outpatient or inpatient bedside procedure, thus potentially eliminating second-stage cranioplasty procedures.

Long-term cost of breast cancer treatment to the United States Medicare Program by stage at diagnosis.

INTRODUCTION: Breast cancer treatment includes increasingly complex and expensive treatments. Accordingly, the current estimates of the cost of breast cancer treatment are out of date. METHODS: The SEER-Medicare Data Link provided 142,837,978 paid Medicare claims from 398,148 female beneficiaries between the ages of 22 and 110 diagnosed with breast cancer between 2007 and 2016. These claims were compared with 153,071,044 claims from 443,952 Medicare beneficiaries without a cancer diagnosis. The total, fully adjudicated, amounts for each claim were summed to determine total treatment cost for each beneficiary. These costs were then aggregated by year after diagnosis and stage at diagnosis. The actuarial survival of beneficiaries with cancer was calculated using the Kaplan-Meier method. RESULTS: Mean costs for the control group were $8,019 per year. The 10-year cost of cancer treatment in Medicare beneficiaries was directly related to stage at diagnosis and ranged from $103,573 for stage 0 cancers to $376,573 for stage 4 cancers. The highest cost occurred during the first 2 years after diagnosis, the time of the beneficiary's initial treatment. Following the first 2 years, healthcare costs remained elevated for at least 10 years after diagnosis. CONCLUSIONS: The 10-year treatment cost of female Medicare beneficiaries with breast cancer increases with increasing stage at diagnosis. Any effective screening technology that reduces stage at diagnosis will result in significant treatment cost savings to the Medicare program.

Electrophysiological signatures of acute systemic lipopolysaccharide-induced inflammation: potential implications for delirium science.

BACKGROUND: Novel preventive therapies are needed for postoperative delirium, which especially affects older patients. A mouse model is presented that captures inflammation-associated cortical slow wave activity (SWA) observed in patients, allowing exploration of the mechanistic role of prostaglandin-adenosine signalling. METHODS: EEG and cortical cytokine measurements (interleukin 6, monocyte chemoattractant protein-1) were obtained from adult and aged mice. Behaviour, SWA, and functional connectivity were assayed before and after systemic administration of lipopolysaccharide (LPS)+piroxicam (cyclooxygenase inhibitor) or LPS+caffeine (adenosine receptor antagonist). To avoid the confounder of inflammation-driven changes in movement which alter SWA and connectivity, electrophysiological recordings were classified as occurring during quiescence or movement, and propensity score matching was used to match distributions of movement magnitude between baseline and post-LPS administration. RESULTS: LPS produces increases in cortical cytokines and behavioural quiescence. In movement-matched data, LPS produces increases in SWA (likelihood-ratio test: χ2(4)=21.51, P<0.001), but not connectivity (χ2(4)=6.39, P=0.17). Increases in SWA associate with interleukin 6 (P<0.001) and monocyte chemoattractant protein-1 (P=0.001) and are suppressed by piroxicam (P<0.001) and caffeine (P=0.046). Aged animals compared with adult animals show similar LPS-induced SWA during movement, but exaggerated cytokine response and increased SWA during quiescence. CONCLUSIONS: Cytokine-SWA correlations during wakefulness are consistent with observations in patients with delirium. Absence of connectivity effects after accounting for movement changes suggests decreased connectivity in patients is a biomarker of hypoactivity. Exaggerated effects in quiescent aged animals are consistent with increased hypoactive delirium in older patients. Prostaglandin-adenosine signalling may link inflammation to neural changes and hence delirium.

Optogenetic Activation of Afferent Pathways in Brain Slices and Modulation of Responses by Volatile Anesthetics.

Anesthetics influence consciousness in part via their actions on thalamocortical circuits. However, the extent to which volatile anesthetics affect distinct cellular and network components of these circuits remains unclear. Ex vivo brain slices provide a means by which investigators may probe discrete components of complex networks and disentangle potential mechanisms underlying the effects of volatile anesthetics on evoked responses. To isolate potential cell type- and pathway-specific drug effects in brain slices, investigators must be able to independently activate afferent fiber pathways, identify non-overlapping populations of cells, and apply volatile anesthetics to the tissue in aqueous solution. In this protocol, methods to measure optogenetically-evoked responses to two independent afferent pathways to neocortex in ex vivo brain slices are described. Extracellular responses are recorded to assay network activity and targeted whole-cell patch clamp recordings are conducted in somatostatin- and parvalbumin-positive interneurons. Delivery of physiologically relevant concentrations of isoflurane via artificial cerebral spinal fluid to modulate cellular and network responses is described.

Reduced Clostridioides difficile infection in a pragmatic stepped-wedge initiative using admission surveillance to detect colonization.

BACKGROUND: Clostridioides difficile Infection (CDI) is a persistent healthcare issue. In the US, CDI is the most common infectious cause of hospital-onset (HO) diarrhea. OBJECTIVE: Assess the impact of admission testing for toxigenic C. difficile colonization on the incidence of HO-CDI. DESIGN: Pragmatic stepped-wedge Infection Control initiative. SETTING: NorthShore University HealthSystem is a four-hospital system near Chicago, IL. PATIENTS: All patients admitted to the four hospitals during the initiative. INTERVENTIONS: From September 2017 through August 2018 we conducted a quality improvement program where admitted patients had a peri-rectal swab tested for toxigenic C. difficile. All colonized patients were placed into contact precautions. MEASUREMENTS: We tested admissions who: i) had been hospitalized within two months, ii) had a past C. difficile positive test, and/or iii) were in a long-term care facility within six months. We measured compliance with all other practices to reduce the incidence of HO-CDI. RESULTS: 30% of admissions were tested and 8.3% were positive. In the year prior to the initiative (Period 1) there were 63,057 admitted patients when HO-CDI incidence was 5.96 cases/10,000 patient days. During the 12-month initiative (Period 2) there were 62,760 admissions and the HO-CDI incidence was 4.23 cases/10,000 patient days (p = 0.02). There were no other practice or antibiotic use changes. Continuing admission surveillance provided a HO-CDI incidence of 2.9 cases/10,000 patient days during the final 9 months of 2018 (p<0.0001 compared to Period 1), equaling <1 case/1,000 admissions. LIMITATIONS: This was not a randomized controlled trial, and multiple prevention practices were in place at the time of the admission surveillance initiative. CONCLUSION: Admission C. difficile surveillance testing is an important tool for preventing hospital-onset C. difficile infection. REGISTRATION: This quality improvement initiative is registered at ClinicalTrials.gov. The unique registration identifier number is NCT04014608.

Pigmented Villonodular Synovitis Presenting as Unilateral Hearing Loss: Review of the Literature and Case Report.

BACKGROUND/AIMS: To review the existing literature on pigmented villonodular synovitis (PVNS) of the temporomandibular joint (TMJ) and report a rare case of PVNS of the TMJ presenting with unilateral hearing loss. METHODS: Review of the existing literature and a description of personal experience with PVNS of the TMJ presenting with unilateral hearing loss. RESULTS: Review of the existing literature revealed 76 reported cases of PVNS of the TMJ. The most common presenting symptom was of a slowly enlarging mass or swelling of the preauricular area, with dysfunctional TMJ also frequently reported. All patients underwent surgical excision with some pursuing radiation as adjuvant therapy. Presented Patient: A 46-year-old man presented with several months of unilateral subjective hearing loss and aural fullness. Imaging revealed a mass centered along the superior TMJ with expansion through the squamous temporal bone and extra-axial intracranial extension into the middle cranial fossa. Imaging characteristics and fine-needle aspiration biopsy were consistent with PVNS. INTERVENTION: The patient underwent near-total excision of the mass via frontotemporal craniectomy and lateral temporal bone resection. FOLLOW-UP: At the 16-month follow-up there was no evidence of disease recurrence. CONCLUSION: PVNS of the TMJ represents a rare entity that can present with a variety of symptoms including unilateral hearing loss.

The Wishbone: A Cranial Midline Localizing Device.

OBJECTIVE: The Wishbone device is designed to enable surgeons to quickly and accurately localize the cranial midline. It is intended to be of particular use when localizing the burr hole site during posterior ventriculoperitoneal shunt (VPS) surgery. METHODS: The Wishbone is a simple mechanical device with 2 adjustable caliper arms that reversibly attach to a patient's left and right external auditory canals. The Wishbone's laser localizer illuminates the midline scalp. The Wishbone was used to localize the posterior midline in a pilot series of patients undergoing VPS surgery. Midline localization and ventricular catheter placement accuracy were determined using findings from postoperative computed tomography scans. RESULTS: The Wishbone is a mechanically robust device and proved easy for surgeons to use. Forty patients underwent VPS surgery using the Wishbone to localize the posterior midline. The localization procedure took less than 3 minutes. The average distance separating the Wishbone-localized midline scalp location and the computed tomography-defined anatomical midline was 2.9 mm (95% confidence interval 1.6-4.1 mm). In all cases, the ventricular catheter entered the ipsilateral lateral ventricle. The catheter tips were placed in the ipsilateral (n = 34) or contralateral (n = 5) frontal horn in all but 1 patient. In 1 patient, the catheter tip entered the parenchyma due to a burr hole localization error in the rostrocaudal dimension, unrelated to the Wishbone. CONCLUSIONS: We describe a simple, efficient, and cost-effective system for accurately localizing the posterior cranial midline. A larger patient series is required to definitively compare its clinical utility relative to frameless stereotaxis-based midline localization methods.

A prospective clinical trial of proton therapy for chordoma and chondrosarcoma: Feasibility assessment.

BACKGROUND/OBJECTIVES: Proton therapy (PRT) has emerged as a treatment option for chordomas/chondrosarcomas to escalate radiation dose more safely. We report results of a phase I/II trial of PRT in patients with chordoma/chondrosarcoma. METHODS: Twenty adult patients with pathologically confirmed, nonmetastatic chordoma or chondrosarcoma were enrolled in a single-institution prospective trial of PRT from 2010 to 2014. Seventeen patients received adjuvant PRT and three received definitive PRT. Median dose was 73.8 Gy(RBE; range 68.4-79.2 Gy) using PRT-only (n = 6) or combination PRT/intensity-modulated radiotherapy (IMRT) (n = 14). Quality-of-life (QOL) and fatigue were assessed weekly and every 3 months posttreatment with the Functional Assessment of Cancer Therapy - Brain (FACTBr) and Brief Fatigue Inventory. Primary endpoint was feasibility (90% completing treatment with < 10 day treatment delay and ≤ 20% unexpected acute grade ≥ 3 toxicity). RESULTS: Tumors included chordomas of the skull base (n = 10), sacrum (n = 5), and cervical spine (n = 3), and skull base chondrosarcomas (n = 2). Median age was 57. The 80% had positive margins/gross disease. Median follow-up was 37 months. Feasibility endpoints were met. The 3-year local control and progression-free survival was 86% and 81%. There were no deaths. Two patients had acute grade 3 toxicity (both fatigue). One had late grade 3 toxicity (epistaxis and osteoradionecrosis). There were no significant differences in patient reported fatigue or QOL from baseline to the end-of-treatment. CONCLUSIONS: We report favorable local control, survival, and toxicity following PRT.

United States Medical Licensing Exam Step I Score as a Predictor of Neurosurgical Career Beyond Residency.

BACKGROUND: United States Medical Licensing Exam (USMLE) Step I score is cited as one of the most important factors when for applying to neurosurgery residencies. No studies have documented a correlation between USMLE Step I score and metrics of neurosurgical career trajectory beyond residency. OBJECTIVE: To determine whether USMLE Step I exam scores are predictive of neurosurgical career beyond residency, as defined by American Board of Neurological Surgery (ABNS) certification status, practice type, academic rank, and research productivity. METHODS: A database of neurosurgery residency applicants who matched into neurosurgery from 1997 to 2007 was utilized that included USMLE Step I score. Online databases were used to determine h-index, National Institutes of Health (NIH) grant funding, academic rank, practice type, and ABNS certification status of each applicant. Linear regression and nonparametric testing determined associations between USMLE Step I scores and these variables. RESULTS: USMLE Step I scores were higher for neurosurgeons in academic positions (237) when compared to community practice (234) and non-neurosurgeons (233, P < .01). USMLE Step I score was not different between neurosurgeons of different academic rank (P = .21) or ABNS certification status (P = .78). USMLE Step I score was not correlated with h-index for academic neurosurgeons (R2 = 0.002, P = .36). CONCLUSION: USMLE Step I score has little utility in predicting the future careers of neurosurgery resident applicants. A career in academic neurosurgery is associated with a slightly higher USMLE Step I score. However, USMLE Step I score does not predict academic rank or productivity (h-index or NIH funding) nor does USMLE Step I score predict ABNS certification status.

Dural Arteriovenous Fistula Associated With a Vestibular Tumor: An Unusual Case and Review of the Literature.

Intracranial dural arteriovenous fistulae (DAVF) are rare vascular malformations. They are generally considered to be acquired lesions, often attributed to dural sinus thrombosis and intracranial venous hypertension. The authors encountered a case of DAVF associated with an octreotide-positive vestibular schwannoma. A 46-year-old female had symptoms of right ear congestion accompanied by pulsatile tinnitus and mild hearing loss. Magnetic resonance imaging (MRI) identified a lobulated mass centered at the cerebellopontine angle. Preoperatively, on cerebral angiography, there was an incidental discovery of a DAVF in the right posterior fossa. The decision was made to proceed with resection of the tumor in a staged fashion. Her latest follow-up MRI showed no evidence of recurrent tumor. This is the second reported case of DAVF associated with an intracranial schwannoma. Findings are discussed along with a thorough review of the literature. This case, combined with the data from the literature review, led us to believe that tumor-related angiogenesis might contribute to DAVF formation.

Ultrasound-Guided Core-Needle Versus Vacuum-Assisted Breast Biopsy: A Cost Analysis Based on the American Society of Breast Surgeons' Mastery of Breast Surgery Registry.

PURPOSE: To evaluate the cost-efficacy of vacuum-assisted ultrasound-guided breast biopsy instruments compared to ultrasound-guided 14-gauge spring-loaded core-needle biopsy. METHODS: The American Society of Breast Surgeons' Mastery of Breast Surgery Registry was reviewed. Biopsy findings, any rebiopsy, and the instrument used were abstracted for 31,451 ultrasound-guided biopsy procedures performed between 2001 and July 2014. Rates of cancer diagnosis and rebiopsy were calculated for each instrument. A linear mathematical model was developed to calculate total cost per cancer diagnosis, including procedural costs and the costs of any additional surgical rebiopsy procedures. Mean cost per cancer diagnosis with confidence limits was then determined for 14-gauge spring-loaded core-needle biopsy and 14 different vacuum-assisted instruments. For 14-gauge spring-loaded core-needle biopsy, mean cost per cancer diagnosis was $4346 (4327-$4366). For the vacuum-assisted instruments, mean cost per cancer diagnosis ranged from a low of $3742 ($3732-$3752) to a high of $4779 ($4750-$4809). RESULTS: Vacuum-assisted instruments overall were more cost-effective than core with a mean cost per cancer diagnosis of $4052 ($4038-$4067) (p < 0.05). Tethered vacuum-assisted instruments performed best with a mean cost per cancer diagnosis of $3978 ($3964-$3991) (p < 0.05). Nontethered devices had a mean cost per cancer diagnosis of $4369 ($4350-$4388), a result no better than core (p < 0.05). CONCLUSIONS: Ultrasound-guided vacuum-assisted breast biopsy had a lower mean cost per cancer diagnosis than 14-gauge spring-loaded core-needle biopsy. This advantage was only seen in tethered vacuum-assisted instruments. Within device families, larger instruments tended to outperform smaller instruments.

Propensity score analysis of endoscopic and open approaches to malignant paranasal and anterior skull base tumor outcomes.

OBJECTIVES/HYPOTHESIS: Malignant sinonasal and skull base tumors are now being resected using an endoscopic technique, but there has been controversy regarding the oncologic safety of this approach. Various studies have compared the outcomes from endoscopic surgery to those from open techniques; however, all have been limited by substantial differences in the patient populations receiving each approach. In this study we compare outcomes of open and endoscopic techniques and use propensity score matching to control for these differences in the patient populations. STUDY DESIGN: Retrospective cohort study including all patients > 18 years old receiving primary surgery for malignant sinonasal or skull base tumors at our institution from 2002 to 2013. RESULTS: One hundred twenty-four patients met criteria; 82 received endoscopic-only surgery, and 42 had an open component to their approach. There was an 86% 3-year overall survival and a 74% disease-free survival. Without controlling for differences in the groups, the endoscopic patients fared significantly better in survival, recurrence rates, wound infections, and length of hospital stay. When using propensity score matching to account for patient comorbidities and tumor size, there were no significant differences in any outcomes except length of the hospital stay. A multivariate regression analysis yielded the same results. CONCLUSION: In this study, endoscopic surgery was shown to be a safe alternative to the open technique, even when controlling for the favorable patient and tumor characteristics in endoscopic patients. This is the first study to account for these differences with a rigorous statistical methodology. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1724-1729, 2016.

Automated tumor volumetry using computer-aided image segmentation.

RATIONALE AND OBJECTIVES: Accurate segmentation of brain tumors, and quantification of tumor volume, is important for diagnosis, monitoring, and planning therapeutic intervention. Manual segmentation is not widely used because of time constraints. Previous efforts have mainly produced methods that are tailored to a particular type of tumor or acquisition protocol and have mostly failed to produce a method that functions on different tumor types and is robust to changes in scanning parameters, resolution, and image quality, thereby limiting their clinical value. Herein, we present a semiautomatic method for tumor segmentation that is fast, accurate, and robust to a wide variation in image quality and resolution. MATERIALS AND METHODS: A semiautomatic segmentation method based on the geodesic distance transform was developed and validated by using it to segment 54 brain tumors. Glioblastomas, meningiomas, and brain metastases were segmented. Qualitative validation was based on physician ratings provided by three clinical experts. Quantitative validation was based on comparing semiautomatic and manual segmentations. RESULTS: Tumor segmentations obtained using manual and automatic methods were compared quantitatively using the Dice measure of overlap. Subjective evaluation was performed by having human experts rate the computerized segmentations on a 0-5 rating scale where 5 indicated perfect segmentation. CONCLUSIONS: The proposed method addresses a significant, unmet need in the field of neuro-oncology. Specifically, this method enables clinicians to obtain accurate and reproducible tumor volumes without the need for manual segmentation.

Preferential effect of isoflurane on top-down vs. bottom-up pathways in sensory cortex.

The mechanism of loss of consciousness (LOC) under anesthesia is unknown. Because consciousness depends on activity in the cortico-thalamic network, anesthetic actions on this network are likely critical for LOC. Competing theories stress the importance of anesthetic actions on bottom-up "core" thalamo-cortical (TC) vs. top-down cortico-cortical (CC) and matrix TC connections. We tested these models using laminar recordings in rat auditory cortex in vivo and murine brain slices. We selectively activated bottom-up vs. top-down afferent pathways using sensory stimuli in vivo and electrical stimulation in brain slices, and compared effects of isoflurane on responses evoked via the two pathways. Auditory stimuli in vivo and core TC afferent stimulation in brain slices evoked short latency current sinks in middle layers, consistent with activation of core TC afferents. By contrast, visual stimuli in vivo and stimulation of CC and matrix TC afferents in brain slices evoked responses mainly in superficial and deep layers, consistent with projection patterns of top-down afferents that carry visual information to auditory cortex. Responses to auditory stimuli in vivo and core TC afferents in brain slices were significantly less affected by isoflurane compared to responses triggered by visual stimuli in vivo and CC/matrix TC afferents in slices. At a just-hypnotic dose in vivo, auditory responses were enhanced by isoflurane, whereas visual responses were dramatically reduced. At a comparable concentration in slices, isoflurane suppressed both core TC and CC/matrix TC responses, but the effect on the latter responses was far greater than on core TC responses, indicating that at least part of the differential effects observed in vivo were due to local actions of isoflurane in auditory cortex. These data support a model in which disruption of top-down connectivity contributes to anesthesia-induced LOC, and have implications for understanding the neural basis of consciousness.

Implementation of a departmental picture archiving and communication system: a productivity and cost analysis.

BACKGROUND: Digital radiology enhances productivity and results in long-term cost savings. However, the viewing, storage, and sharing of outside imaging studies on compact discs at ambulatory offices and hospitals pose a number of unique challenges to a surgeon's efficiency and clinical workflow. OBJECTIVE: To improve the efficiency and clinical workflow of an academic neurosurgical practice when evaluating patients with outside radiological studies. METHODS: Open-source software and commercial hardware were used to design and implement a departmental picture archiving and communications system (PACS). RESULTS: The implementation of a departmental PACS system significantly improved productivity and enhanced collaboration in a variety of clinical settings. Using published data on the rate of information technology problems associated with outside studies on compact discs, this system produced a cost savings ranging from $6250 to $33600 and from $43200 to $72000 for 2 cohorts, urgent transfer and spine clinic patients, respectively, therefore justifying the costs of the system in less than a year. CONCLUSION: The implementation of a departmental PACS system using open-source software is straightforward and cost-effective and results in significant gains in surgeon productivity when evaluating patients with outside imaging studies.

GABA and glutamate are not colocalized in mossy fiber terminals of developing rodent hippocampus.

It has been hypothesized that, in the developing rodent hippocampus, mossy fiber terminals release GABA together with glutamate. Here, we used transgenic glutamic acid decarboxylase-67 (GAD67)-GFP expressing mice and multi-label immunohistochemistry to address whether glutamatergic and GABAergic markers are colocalized. We demonstrate that in the dentate gyrus, interneurons positive for GABA/GAD are sparsely distributed along the edge of the hilus, in a different pattern from that of the densely packed granule cells. Co-staining for synaptophysin and vesicular glutamate transporter1 (VGLUT1) in postnatal day 14 brain sections from both mice and rats showed mossy fiber terminals as a group of large (2-5 µm in diameter) VGLUT1-positive excitatory presynaptic terminals in the stratum lucidum of area CA3a/b. Furthermore, co-staining for synaptophysin and vesicular GABA transporter (VGAT) revealed a group of small-sized (∼0.5 µm in diameter) inhibitory presynaptic terminals in the same area where identified mossy fiber terminals were present. The two types of terminals appeared to be mutually exclusive, and showed no colocalization. Thus, our results do not support the hypothesis that GABA is released as a neurotransmitter from mossy fiber terminals during development.

Clinical trials in head injury.

Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate significant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research.