UW Neurological Surgery Recent PubMed Publications

A complex suite of loci and elements in eukaryotic type II topoisomerases determine selective sensitivity to distinct poisoning agents.

Nucleic Acids Res. 2019 09 05;47(15):8163-8179

Authors: Blower TR, Bandak A, Lee ASY, Austin CA, Nitiss JL, Berger JM

Abstract
Type II topoisomerases catalyze essential DNA transactions and are proven drug targets. Drug discrimination by prokaryotic and eukaryotic topoisomerases is vital to therapeutic utility, but is poorly understood. We developed a next-generation sequencing (NGS) approach to identify drug-resistance mutations in eukaryotic topoisomerases. We show that alterations conferring resistance to poisons of human and yeast topoisomerase II derive from a rich mutational 'landscape' of amino acid substitutions broadly distributed throughout the entire enzyme. Both general and discriminatory drug-resistant behaviors are found to arise from different point mutations found at the same amino acid position and to occur far outside known drug-binding sites. Studies of selected resistant enzymes confirm the NGS data and further show that the anti-cancer quinolone vosaroxin acts solely as an intercalating poison, and that the antibacterial ciprofloxacin can poison yeast topoisomerase II. The innate drug-sensitivity of the DNA binding and cleavage region of human and yeast topoisomerases (particularly hTOP2β) is additionally revealed to be significantly regulated by the enzymes' adenosine triphosphatase regions. Collectively, these studies highlight the utility of using NGS-based methods to rapidly map drug resistance landscapes and reveal that the nucleotide turnover elements of type II topoisomerases impact drug specificity.

PMID: 31287876 [PubMed - indexed for MEDLINE]

The experience of recurrent fallers in the first year after stroke.

Disabil Rehabil. 2019 01;41(2):142-149

Authors: Walsh ME, Galvin R, Williams DJP, Harbison JA, Murphy S, Collins R, McCabe DJH, Crowe M, Horgan NF

Abstract
PURPOSE: Understanding the experiences of fallers after stroke could inform falls-prevention interventions, which have not yet shown effectiveness in this population. The aim of this study was to explore the experience of recurrent fallers post-stroke in relation to recovery and living with falls.
METHODS: Participants who had more than one fall in the first year after stroke were identified from a prospective cohort study. The methods of grounded theory informed data collection and analysis. Semi-structured interviews were conducted, audio-recorded and transcribed. Coding was conducted and categories were developed inductively.
RESULTS: Nine stroke survivors aged 53-85 were interviewed 18-22 months post-discharge. Participants had experienced between 2 and 9 falls and one participant suffered a fracture. Three inter-linked categories were identified: (i) Judging the importance of falls by exploring cause and consequence, (ii) getting back up, and (iii) being careful.
CONCLUSIONS: Stroke survivors' assessment of their own falls-risk and their individual priorities contribute to their decisions around activity participation. "Being careful" could be described as a form of self-managing falls-risk. The inclusion of self-management principles, peer-educators, and education to rise from the floor in falls-management programmes warrants investigation. Not all falls were considered equally important by participants. This could be considered when defining falls-related outcomes. Implications for Rehabilitation Healthcare professionals may be able to offer an increased sense of control to stroke survivors through education about how to avoid particular causes and consequences of falls. Falls-related advice should be specific, relevant to the individual, and respectful of their sense of identity. Being able to rise from the floor appears to be important for coping with falls and falls-risk. Professionals should be cognisant of the potential differences of opinion between stroke survivors and their families around management of falls-risk.

PMID: 28950730 [PubMed - indexed for MEDLINE]

The authors reply.

Pediatr Crit Care Med. 2019 07;20(7):695-696

Authors: Lele AV, Watanitanon A, Lakireddy V, Clark-Bell C, Moore A, Zimmerman JJ, Chesnut RM, Armstead W, Vavilala MS

PMID: 31274807 [PubMed - indexed for MEDLINE]

Alternate Week Gemcitabine and Capecitabine: An Effective Treatment for Patients With Pancreatic Adenocarcinoma.

Pancreas. 2019 08;48(7):927-930

Authors: Johns C, Diaz CL, Hwang J, Kerridge WD, Ko AH, Tempero MA

Abstract
OBJECTIVE: Determine whether a regimen of fixed dose rate gemcitabine plus capecitabine is effective and tolerable for advanced pancreatic adenocarcinoma.
METHODS: We performed a retrospective analysis of 62 patients with locally advanced or metastatic pancreatic adenocarcinoma treated at the University of California San Francisco between 2008 and 2016. Treatment was an alternate week schedule of fixed dose rate 1000 mg/m gemcitabine and capecitabine 1000 mg/m (58 patients), 1200 mg/m (12 patients), or 650 mg/m (1 patient) for intended 12 cycles. We evaluated overall survival (OS), progression-free survival (PFS), radiologic response, and adverse events necessitating treatment modification.
RESULTS: For metastatic patients, median OS was 10.3 months (95% confidence interval [CI], 6.7-12.1 months), and PFS was 5.6 months (95% CI, 2.6-7.7 months). In locally advanced patients, OS was 12.0 months (95% CI, 4.9-17.1 months), and PFS was 5.4 months (95% CI, 2.5-9.4 months). Radiologic response for metastatic disease (42 patients) was 19% objective response, 45% stable disease, and 36% progressive disease. Treatment required modification for 22 patients due to adverse events, most frequently hand-foot syndrome (18 patients).
CONCLUSIONS: Alternate week schedule of fixed dose rate gemcitabine and capecitabine was active and tolerable for advanced pancreatic adenocarcinoma. Overall survival and PFS were comparable to first-line treatments. Importantly, adverse effects appear less severe than first-line treatments.

PMID: 31268983 [PubMed - indexed for MEDLINE]

Perturbations of the ZED1 pseudokinase activate plant immunity.

PLoS Pathog. 2019 07;15(7):e1007900

Authors: Bastedo DP, Khan M, Martel A, Seto D, Kireeva I, Zhang J, Masud W, Millar D, Lee JY, Lee AH, Gong Y, Santos-Severino A, Guttman DS, Desveaux D

Abstract
The Pseudomonas syringae acetyltransferase HopZ1a is delivered into host cells by the type III secretion system to promote bacterial growth. However, in the model plant host Arabidopsis thaliana, HopZ1a activity results in an effector-triggered immune response (ETI) that limits bacterial proliferation. HopZ1a-triggered immunity requires the nucleotide-binding, leucine-rich repeat domain (NLR) protein, ZAR1, and the pseudokinase, ZED1. Here we demonstrate that HopZ1a can acetylate members of a family of 'receptor-like cytoplasmic kinases' (RLCK family VII; also known as PBS1-like kinases, or PBLs) and promote their interaction with ZED1 and ZAR1 to form a ZAR1-ZED1-PBL ternary complex. Interactions between ZED1 and PBL kinases are determined by the pseudokinase features of ZED1, and mutants designed to restore ZED1 kinase motifs can (1) bind to PBLs, (2) recruit ZAR1, and (3) trigger ZAR1-dependent immunity in planta, all independently of HopZ1a. A ZED1 mutant that mimics acetylation by HopZ1a also triggers immunity in planta, providing evidence that effector-induced perturbations of ZED1 also activate ZAR1. Overall, our results suggest that interactions between these two RLCK families are promoted by perturbations of structural features that distinguish active from inactive kinase domain conformations. We propose that effector-induced interactions between ZED1/ZRK pseudokinases (RLCK family XII) and PBL kinases (RLCK family VII) provide a sensitive mechanism for detecting perturbations of either kinase family to activate ZAR1-mediated ETI.

PMID: 31269090 [PubMed - indexed for MEDLINE]

Potential Adverse Consequences of Early Discharge for Newborns Who Meet American Academy of Pediatrics Criteria.

Clin Pediatr (Phila). 2018 03;57(3):352-354

Authors: Gorman S, Lee A, Amin R, Burns JJ

PMID: 28357921 [PubMed - indexed for MEDLINE]

Synchronous identification of a dysembryoplastic neuroepithelial tumor (DNET) and an oligodendroglioma in a patient: A case report.

Clin Neuropathol. 2019 Nov/Dec;38(6):269-275

Authors: Ravanpay AC, Gabikian P, Marshall D, Williams JR, Huber B, Silbergeld DL

Abstract
Synchronous gliomas of different histopathology are quite rare in non-syndromic, non-irradiated patients. Although "mixed" gliomas are not infrequent, and malignant gliomas often contain areas of disparate differentiation (e.g., glioblastoma with ependymal differentiation), it is unusual to find gliomas of different lineage presenting concurrently. We present a case of synchronous gliomas, one dysembryoplastic neuroepithelial tumor (DNET) and the other oligodendroglioma.

PMID: 31262396 [PubMed - indexed for MEDLINE]

Strategies to Mitigate Toxicities From Stereotactic Body Radiation Therapy for Spine Metastases.

Neurosurgery. 2019 12 01;85(6):729-740

Authors: Schaub SK, Tseng YD, Chang EL, Sahgal A, Saigal R, Hofstetter CP, Foote M, Ko AL, Yuh WTC, Mossa-Basha M, Mayr NA, Lo SS

Abstract
Improvements in systemic therapy are translating into more patients living longer with metastatic disease. Bone is the most common site of metastasis, where spinal lesions can result in significant pain impacting quality of life and possible neurological dysfunction resulting in a decline in performance status. Stereotactic body radiation therapy (SBRT) of the spine has emerged as a promising technique to provide durable local control, palliation of symptoms, control of oligoprogressive sites of disease, and possibly augment the immune response. SBRT achieves this by delivering highly conformal radiation therapy to allow for dose escalation due to a steep dose gradient from the planning target volume to nearby critical organs at risk. In our review, we provide an in-depth review and expert commentary regarding seminal literature that defined clinically meaningful toxicity endpoints with actionable dosimetric limits and/or clinical management strategies to mitigate toxicity potentially attributable to SBRT of the spine. We placed a spotlight on radiation myelopathy (de novo, reirradiation after conventional external beam radiation therapy or salvage after an initial course of spinal SBRT), plexopathy, vertebral compression fracture, pain flare, esophageal toxicity, myositis, and safety regarding combination with concurrent targeted or immune therapies.

PMID: 31264703 [PubMed - indexed for MEDLINE]

A more efficient conditional mouse model of Dravet syndrome: Implications for epigenetic selection and sex-dependent behaviors.

J Neurosci Methods. 2019 09 01;325:108315

Authors: Williams AD, Kalume F, Westenbroek RE, Catterall WA

Abstract
BACKGROUND: Dravet Syndrome (DS) is an epileptic disorder characterized by spontaneous and thermally-induced seizures, hyperactivity, cognitive deficits, autistic-like behaviors, and Sudden Unexpected Death in Epilepsy (SUDEP). DS is caused by de novo loss-of-function mutations in the SCN1A gene. Selective loss of GABAergic interneuron excitability is the primary cause of the disease. Up to 60% of Scn1a+/- mice die from SUDEP before sexual maturity.
NEW METHOD: We used Cre-Lox technology to conditionally delete Scn1a in all epiblast-derived somatic cells by crossing a floxed Scn1a mouse with a mouse expressing Cre under the Meox2 promoter.
RESULTS: Parental Scn1a flox (F) mice, parental Meox2 Cre+ mice, and their F/+:Meox2-Cre- offspring were phenotypically normal and did not prematurely die. In contrast, F/+:Meox2-Cre+ offspring recapitulated DS seizure and behavioral phenotypes. Unexpectedly, male F/+:Meox2-Cre+ mice demonstrated impaired social interaction, while females did not.
COMPARISON WITH EXISTING METHOD: In the previous models, colony maintenance required breeding SUDEP survivors, which greatly increased colony size required to sustain experimental animal production, and raised the concern that surviving breeders have epigenetic traits that impart new phenotypes to their offspring. Our method greatly facilitates breeding, recapitulates DS phenotypes, eliminates concerns about parents that are survivors, and provides initial evidence for unexpected sex-dependent social interaction impairment.
CONCLUSIONS: We introduce a more efficient mouse model of human DS that demonstrates an efficient breeding strategy free from potential inherited epigenetic changes and reveals an unexpected sex-specific impairment of social interaction in DS. This new model should have great value to investigators of DS.

PMID: 31265868 [PubMed - indexed for MEDLINE]

Reduced cell attachment to poly(2-hydroxyethyl methacrylate)-coated ventricular catheters in vitro.

J Biomed Mater Res B Appl Biomater. 2018 04;106(3):1268-1279

Authors: Hanak BW, Hsieh CY, Donaldson W, Browd SR, Lau KKS, Shain W

Abstract
The majority of patients with hydrocephalus are dependent on ventriculoperitoneal shunts for diversion of excess cerebrospinal fluid. Unfortunately, these shunts are failure-prone and over half of all life-threatening pediatric failures are caused by obstruction of the ventricular catheter by the brain's resident immune cells, reactive microglia and astrocytes. Poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogels are widely used for biomedical implants. The extreme hydrophilicity of PHEMA confers resistance to protein fouling, making it a strong candidate coating for ventricular catheters. With the advent of initiated chemical vapor deposition (iCVD), a solvent-free coating technology that creates a polymer in thin film form on a substrate surface by introducing gaseous reactant species into a vacuum reactor, it is now possible to apply uniform polymer coatings on complex three-dimensional substrate surfaces. iCVD was utilized to coat commercially available ventricular catheters with PHEMA. The chemical structure was confirmed on catheter surfaces using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. PHEMA coating morphology was characterized by scanning electron microscopy. Testing PHEMA-coated catheters against uncoated clinical-grade catheters in an in vitro hydrocephalus catheter bioreactor containing co-cultured astrocytes and microglia revealed significant reductions in cell attachment to PHEMA-coated catheters at both 17-day and 6-week time points. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1268-1279, 2018.

PMID: 28631360 [PubMed - indexed for MEDLINE]

First confirmed case of chronic traumatic encephalopathy in a professional bull rider.

Acta Neuropathol. 2018 02;135(2):303-305

Authors: Keene CD, Latimer CS, Steele LM, Mac Donald CL

PMID: 29285625 [PubMed - indexed for MEDLINE]

Obstructive sleep apnea and orthodontics: An American Association of Orthodontists White Paper.

Am J Orthod Dentofacial Orthop. 2019 Jul;156(1):13-28.e1

Authors: Behrents RG, Shelgikar AV, Conley RS, Flores-Mir C, Hans M, Levine M, McNamara JA, Palomo JM, Pliska B, Stockstill JW, Wise J, Murphy S, Nagel NJ, Hittner J

Abstract
The Board of Trustees of the American Association of Orthodontists asked a panel of medical and dental experts in sleep medicine and dental sleep medicine to create a document designed to offer guidance to practicing orthodontists on the suggested role of the specialty of orthodontics in the management of obstructive sleep apnea. This White Paper presents a summary of the Task Force's findings and recommendations.

PMID: 31256826 [PubMed - indexed for MEDLINE]

Solubilized Amnion Membrane Hyaluronic Acid Hydrogel Accelerates Full-Thickness Wound Healing.

Stem Cells Transl Med. 2017 11;6(11):2020-2032

Authors: Murphy SV, Skardal A, Song L, Sutton K, Haug R, Mack DL, Jackson J, Soker S, Atala A

Abstract
The early and effective treatment of wounds is vital to ensure proper wound closure and healing with appropriate functional and cosmetic outcomes. The use of human amnion membranes for wound care has been shown to be safe and effective. However, the difficulty in handling and placing thin sheets of membrane, and the high costs associated with the use of living cellularized tissue has limited the clinical application of amniotic membrane wound healing products. Here, we describe a novel amnion membrane-derived product, processed to result in a cell-free solution, while maintaining high concentrations of cell-derived cytokines and growth factors. The solubilized amnion membrane (SAM) combined with the carrier hyaluronic acid (HA) hydrogel (HA-SAM) is easy to produce, store, and apply to wounds. We demonstrated the efficacy of HA-SAM as a wound treatment using a full-thickness murine wound model. HA-SAM significantly accelerated wound closure through re-epithelialization and prevented wound contraction. HA-SAM-treated wounds had thicker regenerated skin, increased total number of blood vessels, and greater numbers of proliferating keratinocytes within the epidermis. Overall, this study confirms the efficacy of the amnion membrane as a wound treatment/dressing, and overcomes many of the limitations associated with using fresh, cryopreserved, or dehydrated tissue by providing a hydrogel delivery system for SAM. Stem Cells Translational Medicine 2017;6:2020-2032.

PMID: 28941321 [PubMed - indexed for MEDLINE]

Characterization of Motor and Non-Motor Behavioral Alterations in the Dj-1 (PARK7) Knockout Rat.

J Mol Neurosci. 2019 Oct;69(2):298-311

Authors: Kyser TL, Dourson AJ, McGuire JL, Hemmerle AM, Williams MT, Seroogy KB

Abstract
Parkinson's disease is a neurodegenerative disorder that encompasses a constellation of motor and non-motor symptoms. The etiology of the disease is still poorly understood because of complex interactions between environmental and genetic risk factors. Using animal models to assess these risk factors may lead to a better understanding of disease manifestation. In this study, we assessed the Dj-1 knockout (KO) genetic rat model in a battery of motor and non-motor behaviors. We tested the Dj-1 KO rat, as well as age-matched wild-type (WT) control rats, in several sensorimotor tests at 2, 4, 7, and 13 months of age. The Dj-1-deficient rats were found to rear and groom less, and to have a shorter stride length than their WT counterparts, but to take more forelimb and hindlimb steps. In non-motor behavioral tasks, performed at several different ages, we evaluated the following: olfactory function, anxiety-like behavior, short-term memory, anhedonia, and stress coping behavior. Non-motor testing was conducted as early as 4.5 months and as late as 17 months of age. We found that Dj-1 KO animals displayed deficits in short-term spatial memory as early as 4.5 months of age during place preference testing, as well as impaired coping strategies in the forced swim test, which are consistent with a parkinsonian-like phenotype. In some instances, effects of chronic stress were evaluated in the Dj-1-deficient rats, as an initial test of an environmental challenge combined with a genetic disposition for PD. Although some of the results were mixed with differential effects across several of the behaviors, the combination of the changes we observed indicates that the Dj-1 KO rat may be a promising model for the assessment of the prodromal stage of Parkinson's disease, but further evaluation is necessary.

PMID: 31250274 [PubMed - indexed for MEDLINE]

Advocacy in pediatric neurosurgery: results from a 2017 survey of the American Society of Pediatric Neurosurgeons.

J Neurosurg Pediatr. 2019 Jun 28;:1-5

Authors: LoPresti M, Lam S, Orrico K, Browd SR, Ellenbogen RG, Martin J

Abstract
OBJECTIVE: Pediatric neurosurgeons are unswerving advocates for public health-related issues in children, with most providers participating in local, regional, national, or international efforts. Collective advocacy efforts by organized pediatric neurosurgeons have not been undertaken to date.
METHODS: A 10-item survey was administered to members of the American Society of Pediatric Neurosurgeons (ASPN) in order to evaluate attitudes and opinions regarding the development of a formal advocacy effort by the organization.
RESULTS: Seventy-nine of 178 registered members of the ASPN (44.38%) participated in the survey. Participants were 82.61% male, with age, stage of career, and practice type varied. Although there was unequivocal support for participation in organized advocacy, respondents were divided on methods and topics for advocacy. In this survey, the ASPN membership prioritized public health and clinical issues over economic issues that affected children.
CONCLUSIONS: Most respondents favored the drafting of position statements on key issues and partnerships with larger organizations to pursue an advocacy agenda. The survey provides data regarding pediatric neurosurgeons' attitudes that may assist with the design of a successful advocacy program.

PMID: 31252384 [PubMed - as supplied by publisher]

Acellular Dermal Matrix as a Definitive Reconstructive Option for Management of a Large Myelomeningocele Defect in the Setting of Severe Lumbar Kyphosis.

World Neurosurg. 2019 Sep;129:363-366

Authors: Susarla SM, Hauptman J, Ettinger R, Sittler B, Ellenbogen RG

Abstract
BACKGROUND: Severe kyphosis is infrequently seen in neonates with myelomeningoceles. Spinal skeletal dysmorphology complicates repair, as local tissue may be insufficient to cover the dural repair. Although neonatal kyphectomy has been proposed as a potential solution to this problem, it carries significant potential risks that may not be acceptable to families.
CASE DESCRIPTION: A neonate presented with a large myelomeningocele defect with associated severe lumbar kyphosis. Kyphectomy was both declined by the family owing to the potential surgical risks and deemed not appropriate by the surgeons based on the challenging anatomic considerations. Soft tissue closure was not possible with local tissue rearrangement. Acellular dermal matrix was used as a definitive soft tissue coverage option, with complete epithelialization noted at 8 weeks postoperatively.
CONCLUSIONS: Acellular dermal matrix is a potentially useful adjunct for definitive reconstruction of complex neonatal soft tissue defects where local tissue is not available.

PMID: 31247357 [PubMed - indexed for MEDLINE]

Clinical outcomes and cost-effectiveness analysis for the treatment of basilar tip aneurysms.

J Neurointerv Surg. 2019 Dec;11(12):1210-1215

Authors: Abecassis IJ, Sen R, Kelly CM, Levy S, Barber J, Ghodke B, Levitt M, Kim LJ, Sekhar LN

Abstract
BACKGROUND: Endovascular treatment of basilar tip aneurysms is less invasive than microsurgical clipping, but requires closer follow-up.
OBJECTIVE: To characterize the additional costs associated with endovascular treatment of basilar tip aneurysms rather than microsurgical clipping.
MATERIALS AND METHODS: We obtained clinical records and billing information for 141 basilar tip aneurysms treated with clip ligation (n=48) or endovascular embolization (n=93). Costs included direct and indirect costs associated with index hospitalization, as well as re-treatments, follow-up visits, imaging studies, rehabilitation, and disability. Effectiveness of treatment was quantified by converting functional outcomes (modified Rankin Scale (mRS) score) into quality-adjusted life-years (QALYs). Cost-effectiveness was performed using cost/QALY ratios.
RESULTS: Average index hospitalization costs were significantly higher for patients with unruptured aneurysms treated with clip ligation ($71 400 ± $47 100) compared with coil embolization ($33 500 ± $22 600), balloon-assisted coiling ($26 200 ± $11 600), and stent-assisted coiling ($38 500 ± $20 900). Multivariate predictors for higher index hospitalization cost included vasospasm requiring endovascular intervention, placement of a ventriculoperitoneal shunt, longer length of stay, larger aneurysm neck and width, higher Hunt-Hess grade, and treatment-associated complications. At 1 year, endovascular treatment was associated with lower cost/QALY than clip ligation in unruptured aneurysms ($52 000/QALY vs $137 000/QALY, respectively, p=0.006), but comparable rates in ruptured aneurysms ($193 000/QALY vs $233 000/QALY, p=0.277). Multivariate predictors for higher cost/QALY included worse mRS score at discharge, procedural complications, and larger aneurysm width.
CONCLUSIONS: Coil embolization of basilar tip aneurysms is associated with a lower cost/QALY. This effect is sustained during follow-up. Clinical condition at discharge is the most significant predictor of overall cost/QALY at 1 year.

PMID: 31239332 [PubMed - indexed for MEDLINE]

Sex Differences in Patient Characteristics, Treatment Strategies, and Outcomes for Type 2 Myocardial Infarction.

J Am Coll Cardiol. 2019 06 25;73(24):3230-3232

Authors: McCarthy CP, Murphy S, Cohen JA, Rehman S, Jones-O'Connor M, Olshan DS, Singh A, Vaduganathan M, Januzzi JL, Wasfy JH

PMID: 31221266 [PubMed - indexed for MEDLINE]

Effects of interleukin-6 receptor blockade on allergen-induced airway responses in mild asthmatics.

Clin Transl Immunology. 2019;8(6):e1044

Authors: Revez JA, Bain LM, Watson RM, Towers M, Collins T, Killian KJ, O'Byrne PM, Gauvreau GM, Upham JW, Ferreira MA

Abstract
Background: Interleukin (IL)-6 signalling has been implicated in allergic asthma by animal, genetic association and clinical studies. In this study, we tested the hypothesis that tocilizumab (TCZ), a human monoclonal antibody that blocks IL-6 signalling, can prevent the development of allergen-induced bronchoconstriction in humans.
Methods: We performed a randomised, double-blind, placebo-controlled study, with eligible participants completing two allergen inhalation challenge tests, conducted before and after treatment with a single dose of TCZ or placebo. The primary efficacy endpoint was the magnitude of the late asthmatic response recorded between 3 and 7 after allergen challenge. The secondary efficacy endpoint was the early asthmatic response, measured 20 min to 2 h after allergen challenge.
Results: A total of 66 patients enrolled between September 2014 and August 2017, when the trial was stopped for futility based on results from an interim analysis. Eleven patients fulfilled all eligibility criteria assessed at baseline and were subsequently randomised to the TCZ (n = 6) or placebo (n = 5) groups. Both the primary and secondary efficacy endpoints were not significantly different between the two groups. Five patients reported adverse events (AEs), three in the TCZ group (11 AEs) and two in the placebo group (four AEs). Only one AE was TCZ-related (mild neutropenia), and there were no serious AEs. Significant treatment effects were observed for serum levels of C-reactive protein, IL-6 and soluble IL-6R levels.
Conclusion: In a small proof-of-concept clinical trial, we found no evidence that a single dose of tocilizumab was able to prevent allergen-induced bronchoconstriction. (Trial registered in the Australian New Zealand Clinical Trials Registry, number ACTRN12614000123640).

PMID: 31223480 [PubMed]

Bow Hunter's Syndrome: Complete Microsurgical Decompression of Vertebral Artery by Far Lateral Retrocondylar Approach: 3-Dimensional Operative Video.

Oper Neurosurg (Hagerstown). 2019 Jun 21;:

Authors: Zeeshan Q, Hernandez JPC, Sekhar LN

Abstract
This 50-yr-old man had a 15-yr history of presyncopal episodes that were precipitated by turning his head to the right, and had worsened recently. Cerebral angiogram demonstrated complete cessation of anterograde flow in left vertebral artery (VA) at the level of the C1 sulcus arteriosus while turning head to right, indicating dynamic compression at the C1 level.  Patient underwent left extreme lateral retrocondylar approach, partial C1 laminectomy and opening of the C1 foramen with complete microsurgical decompression of the VA. After skin incision, meticulous muscle dissection was performed and superior and inferior oblique muscles were disconnected from the tubercle of C1. The VA was exposed, and three areas of constriction were visible, first at the atlanto-occipital membrane laterally; second, located more medially as the artery curved around the occipital condyle to enter the posterior fossa; and third, located anterior to C2 nerve root. The artery was dissected from all the surrounding tissues, preserving the C2 nerve root, and the Cl foramen was opened completely. The Cl lamina was also partially resected and grooved to allow free placement of the VA. The VA was also decompressed near the C2 foramen. Postoperative computed tomography angiogram of the head and neck showed complete decompression of VA. The patient had no episodes of presyncope or dizziness while turning head to right and his mRs was 0 at 8 mo follow up.  This 3D video shows the technical nuances of decompression of V3 segment of VA in bow hunters's syndrome.  Informed consent was obtained from the patient prior to the surgery that included videotaping of the procedure and its distribution for educational purposes. All relevant patient identifiers have also been removed from the video and accompanying radiology slides.

PMID: 31225628 [PubMed - as supplied by publisher]