UW Neurological Surgery Recent PubMed Publications

Anal squamous cell carcinoma: are we improving outcomes?

ANZ J Surg. 2018 10;88(10):1013-1016

Authors: Mackowski A, Levitt M, Makin G, Salama P, Tan P, Penter C, Platell C

Abstract
BACKGROUND: Anal squamous cell carcinoma (SCC) is a rare malignancy. The purpose of this study was to review a single institution's experience.
METHODS: All patients with anal SCC from St John of God Subiaco Hospital database were identified over a 10-year period (2006-2016). Patients with stage 1 anal verge tumours underwent wide local excision, all remaining patients were offered chemoradiation (CRT) as an initial treatment modality (a fluorouracil-based regimen in conjunction with mitomycin). Outcomes included recurrence, overall survival and survival following salvage surgery.
RESULTS: Forty-seven patients were identified. Median age was 60 years and median follow-up was 2.73 years. Five-year rates of recurrence and overall survival were 35.8% (95% confidence interval (CI) 23.2-52.4%) and 65.4% (95% CI 47.0-78.7%), respectively. Locoregional failure occurred most commonly at the primary site. Eight patients underwent salvage abdominoperineal resection for persistent or recurrent disease, and four of these patients died within 5 years.
CONCLUSION: CRT is a proven and reasonable effective approach in managing anal cancer. Observed recurrence and overall survival rates in this study resemble the published data. Despite newer methods of treatment being investigated, the treatment for anal SCC has not significantly changed in the past four decades and novel approaches are needed to further improve outcomes.

PMID: 30159994 [PubMed - indexed for MEDLINE]

Periodontitis and multiple markers of cardiometabolic risk in the fourth decade: A cohort study.

Community Dent Oral Epidemiol. 2018 12;46(6):615-623

Authors: Shearer DM, Thomson WM, Cameron CM, Ramrakha S, Wilson G, Wong TY, Williams MJA, McLean R, Theodore R, Poulton R

Abstract
OBJECTIVES: To examine associations between periodontitis at ages 32 and 38 and a range of early cardiometabolic risk biomarkers at age 38.
METHODS: Periodontal probing depth and bleeding on probing data collected during the age-32 and age-38 assessments in the Dunedin Multidisciplinary Health and Development Study were used to quantify periodontal inflammatory load. Retinal microvascular abnormalities, endothelial dysfunction, and metabolic syndrome data were collected during the age-38 assessment. Regression models were used to examine associations between these cardiometabolic risk markers and (1) the inflammatory load at age 38 and (2) the change in inflammatory load between ages 32 and 38.
RESULTS: Periodontal inflammatory load was recorded for 890 Study members at age 32, 891 at age 38, and 856 at both ages. Retinal vessel data were available for 922, endothelial dysfunction data for 909 and metabolic syndrome data for 905 at age 38. Neither the inflammatory load of periodontitis at 38 nor the changes in inflammatory load 32-38 were found to be associated with any of the three cardiometabolic risk markers.
CONCLUSIONS: Periodontitis was not associated with markers of cardiometabolic risk at this relatively early stage in the life course. It is possible that any influence of periodontitis on cardiometabolic health develops later in life, or periodontitis is not involved in the putative causal chain comprising systemic inflammation, cardiometabolic risk markers, and subsequent cardiovascular risk.

PMID: 30160305 [PubMed - indexed for MEDLINE]

MAP1B mutations cause intellectual disability and extensive white matter deficit.

Nat Commun. 2018 Aug 27;9(1):3456

Authors: Walters GB, Gustafsson O, Sveinbjornsson G, Eiriksdottir VK, Agustsdottir AB, Jonsdottir GA, Steinberg S, Gunnarsson AF, Magnusson MI, Unnsteinsdottir U, Lee AL, Jonasdottir A, Sigurdsson A, Jonasdottir A, Skuladottir A, Jonsson L, Nawaz MS, Sulem P, Frigge M, Ingason A, Love A, Norddhal GL, Zervas M, Gudbjartsson DF, Ulfarsson MO, Saemundsen E, Stefansson H, Stefansson K

Abstract
Discovery of coding variants in genes that confer risk of neurodevelopmental disorders is an important step towards understanding the pathophysiology of these disorders. Whole-genome sequencing of 31,463 Icelanders uncovers a frameshift variant (E712KfsTer10) in microtubule-associated protein 1B (MAP1B) that associates with ID/low IQ in a large pedigree (genome-wide corrected P = 0.022). Additional stop-gain variants in MAP1B (E1032Ter and R1664Ter) validate the association with ID and IQ. Carriers have 24% less white matter (WM) volume (β = -2.1SD, P = 5.1 × 10-8), 47% less corpus callosum (CC) volume (β = -2.4SD, P = 5.5 × 10-10) and lower brain-wide fractional anisotropy (P = 6.7 × 10-4). In summary, we show that loss of MAP1B function affects general cognitive ability through a profound, brain-wide WM deficit with likely disordered or compromised axons.

PMID: 30150678 [PubMed - in process]

Cerebrospinal Fluid Shunting Complications in Children.

Pediatr Neurosurg. 2017;52(6):381-400

Authors: Hanak BW, Bonow RH, Harris CA, Browd SR

Abstract
Although cerebrospinal fluid (CSF) shunt placement is the most common procedure performed by pediatric neurosurgeons, shunts remain among the most failure-prone life-sustaining medical devices implanted in modern medical practice. This article provides an overview of the mechanisms of CSF shunt failure for the 3 most commonly employed definitive CSF shunts in the practice of pediatric neurosurgery: ventriculoperitoneal, ventriculopleural, and ventriculoatrial. The text has been partitioned into the broad modes of shunt failure: obstruction, infection, mechanical shunt failure, overdrainage, and distal catheter site-specific failures. Clinical management strategies for the various modes of shunt failure are discussed as are research efforts directed towards reducing shunt complication rates. As it is unlikely that CSF shunting will become an obsolete procedure in the foreseeable future, it is incumbent on the pediatric neurosurgery community to maintain focused efforts to improve our understanding of and management strategies for shunt failure and shunt-related morbidity.

PMID: 28249297 [PubMed - indexed for MEDLINE]

Predictors of tobacco and alcohol co-use from ages 15 to 32: The Amsterdam Growth and Health Longitudinal Study.

Exp Clin Psychopharmacol. 2018 Dec;26(6):549-559

Authors: McPherson SM, Burduli E, Smith CL, Brooks O, Orr MF, Barbosa-Leiker C, Hoekstra T, McDonell MG, Murphy SM, Layton M, Roll JM

Abstract
Tobacco and alcohol are often used in tandem over time, but specific predictors of course and patterns of course over time need explication. We examined differences in alcohol and tobacco course among an adolescent population as they transitioned into young adulthood across a 17-year period. Data came from participants (n = 303 for ages 15-21, n = 196 for ages 21 to 32; 52% female and 54% female, respectively) enrolled in the Amsterdam Growth and Health Longitudinal Study, an epidemiologic investigation examining disease across the life span. We utilized parallel latent growth modeling to assess the impact of sex, personality traits, cholesterol, blood pressure, and body mass index (BMI), on initial status and linear change over time in course of tobacco and alcohol. Females reported less alcohol use at adolescent baseline (β = -21.79), less increase during adolescence (β = -7.92, p < .05), slower decrease during young adulthood (β = 4.67, p < .05), and more rapid decline in tobacco use during young adulthood (β = -70.85, p < .05), relative to males. Alcohol and tobacco use baseline status' and change over time were all significantly associated with one another during both adolescence and young adulthood (p < .05; aside from alcohol baseline and slope during young adulthood). Effects of BMI, cholesterol, blood pressure, and personality traits were also observed on tobacco and alcohol course. In light of the strong, but sex dependent relationship between alcohol and tobacco course, particularly from ages 15 to 21, prevention efforts to curb heavy alcohol and tobacco use should consider targeting course taking into account biological sex and other notable covariates. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID: 30148405 [PubMed - indexed for MEDLINE]

CT cervico-cerebral angiography in acute stroke. Can we justify aortic arch imaging?

Ir J Med Sci. 2019 May;188(2):661-666

Authors: Sugrue G, O'Reilly MK, Byrne D, Crockett MT, Murphy S, Kavanagh EC

Abstract
OBJECTIVES: Computed tomography cervico-cerebral angiography (CTCCA) plays a pivotal role in the evaluation of acute stroke. Currently no evidence justifies the inclusion of the upper chest in the CTCCA field of view. The aim of this study was to assess the prevalence and clinical significance of vascular findings identified on CTCCA in the head, neck, and upper chest regions in patients presenting with acute stroke symptoms.
METHODS: A retrospective review of radiology images and reports of 900 consecutive patients (425 men, 475 women; mean age 63.2 years, age range 19-99 years) with a suspected acute stroke who underwent CTCCA in the emergency department between January 2011 and July 2016. Clinically significant vascular CTCCA findings were recorded for each patient within the head, neck, and upper chest regions, respectively.
RESULTS: Of the 900 patients, clinically significant vascular CTCCA findings were identified in 404/900 (44.8%) patients. 218/900 (24.2%) were located within the head region; 174/900 (19.3%) within the neck; and 12/900 (2.4%) in the upper chest. Of the 12 vascular findings located within the upper chest, 3/900 (0.33%) were related to a clinically significant posterior circulation infarct.
CONCLUSIONS: Routine inclusion of the upper chest on CTCCA is currently difficult to justify in the evaluation of a suspected acute anterior circulation stroke, contributing significantly to total radiation dose without demonstrating significant extra-cranial vascular findings. Prospective studies adopting narrower fields of view excluding the upper chest are necessary.

PMID: 30143966 [PubMed - indexed for MEDLINE]

Inside out: Repurposing endobronchial intubation to facilitate extraluminal placement of a 5 Fr Arndt bronchial blocker in young infants.

Paediatr Anaesth. 2018 07;28(7):668-669

Authors: Templeton TW, Lawrence AE, Lee AJ, Templeton LB

PMID: 30133914 [PubMed - indexed for MEDLINE]

A Preregistered Study of Competing Predictions Suggests That Men Do Overestimate Women's Sexual Intent.

Psychol Sci. 2017 02;28(2):253-255

Authors: Murray DR, Murphy SC, von Hippel W, Trivers R, Haselton MG

PMID: 28056212 [PubMed - indexed for MEDLINE]

Factors Affecting Stereotactic Accuracy in Image-Guided Deep Brain Stimulator Electrode Placement.

Stereotact Funct Neurosurg. 2017;95(5):315-324

Authors: Ko AL, Ibrahim A, Magown P, Macallum R, Burchiel KJ

Abstract
BACKGROUND/AIMS: Intraoperative imaging allows near-real-time assessment of stereotactic accuracy during implantation of deep brain stimulation (DBS) electrodes. Such technology can be used to examine factors impacting stereotactic error.
METHODS: Intraoperative CT imaging was reviewed in patients undergoing DBS placement at Oregon Health and Sciences University. Coordinates of the target electrode were compared to the operative plan to characterize the magnitude and direction of stereotactic error with respect to side of implantation, target, and electrode approach angles.
RESULTS: One hundred sixty-nine leads in 94 patients were examined. Targets were GPi (n = 86), STN (n = 31), and Vim (n = 52). The average Euclidean error was 1.63 mm (SD 0.87). The error magnitude was higher for Vim (1.95 mm) than for GPi (1.44 mm), while STN (1.65 mm) did not differ from either Vim or GPi (ANOVA: F = 6.15, p = 0.003). Electrodes targeting Vim and STN were significantly more likely to deviate medially compared to those targeting GPi (ANOVA: F = 9.13, p < 0.001). The coronal approach angle affected the error when targeting Vim (ρ = 0.338, p = 0.01). These findings were confirmed during multivariate analyses.
CONCLUSIONS: This study shows a significant effect of target on the accuracy of electrode placement for DBS. Targeting Vim results in a greater Euclidean error and a greater medial deviation off target. These systematic deviations should be taken into account during electrode implantation.

PMID: 28889124 [PubMed - indexed for MEDLINE]

Tracking large Anterior Mitral Leaflet displacements by incorporating optical flow in an active contours framework.

Conf Proc IEEE Eng Med Biol Soc. 2017 07;2017:3244-3247

Authors: Saad Sultan M, Martins N, Costa E, Veiga D, Ferreira MJ, Mattos S, Tavares Coimbra M

Abstract
Echocardiography is an important tool to detect early evidence of mitral valve degradation associated with rheumatic heart disease. The segmentation and tracking of the Anterior Mitral Leaflet helps to quantify the morphologic valve anomalies, such as the leaflet thickening, shape and the mobility changes. The tracking of this leaflet throughout the cardiac cycle is still an open challenge in the research community. The widely used active contours segmentation framework fails when faced with large leaflet displacement. In this work, we propose the integration of optical flow in an open-ended active contour framework to address this difficulty. This additional information promotes solutions with contours next to high leaflet displacements, resulting in superior performance. The algorithm was tested on 9 fully annotated real clinical videos, acquired from the parasternal long axis view. The algorithm is compared with our previous work. Results show a clear improvement in situations where the leaflet exhibits large displacement or irregular shapes, with an average error of 4.5 pixels and a standard deviation of 2 pixels.

PMID: 29060589 [PubMed - indexed for MEDLINE]

Bridging the HIV-syphilis testing gap: dual testing among men who have sex with men living in China.

Sex Transm Infect. 2019 06;95(4):251-253

Authors: Ong JJ, Liao M, Lee A, Fu H, Pan SW, Tang W, Wei C, Dan W, Yang B, Yang L, Wang C, Tucker JD

Abstract
OBJECTIVES: The WHO recommends dual testing for HIV and syphilis among key populations, including men who have sex with men (MSM). We assessed the proportion of men who had dual tested and reasons for not dual testing.
METHODS: In 2017, an online survey of MSM was conducted in eight cities from two provinces in China. Data on sociodemographics and sexual behaviours were collected. Descriptive analysis was used to examine the experience of dual testing. Multivariable logistic regression identified characteristics associated with men who had dual tested.
RESULTS: Among 802 men who had ever tested for HIV, 297 dual tested (37%, 95% CI 34 to 40). Men dual tested in a variety of settings: public hospital (35%), voluntary counselling and testing sites (28%), self-testing at home (18%), community-based organisation (8%), community health centre (7%), other (3%) or private hospital (1%). Greater odds for dual testing was found in men who had disclosed their sexuality to a healthcare provider (adjusted OR (AOR) 1.81, 95% CI 1.27 to 2.59, p=0.001), and who had substantial (AOR 2.71, 95% CI 1.67 to 4.41, p<0.001) or moderate community engagement in sexual health (AOR 2.30, 95% CI 1.49 to 3.57, p<0.001), compared with those with no community engagement. The most common reasons for not dual testing were no knowledge that they could be dual tested (34%), did not ask the doctor to be dual tested (25%) and did not believe they were at risk for syphilis (19%).
CONCLUSIONS: Chinese MSM are dual testing through a variety of test sites, including home self-testing. However, the overall dual testing rate remains low despite recent efforts to integrate HIV and syphilis testing.

PMID: 30126948 [PubMed - indexed for MEDLINE]

On the importance of accounting for nuclear quantum effects in ab initio calibrated force fields in biological simulations.

Proc Natl Acad Sci U S A. 2018 09 04;115(36):8878-8882

Authors: Pereyaslavets L, Kurnikov I, Kamath G, Butin O, Illarionov A, Leontyev I, Olevanov M, Levitt M, Kornberg RD, Fain B

Abstract
In many important processes in chemistry, physics, and biology the nuclear degrees of freedom cannot be described using the laws of classical mechanics. At the same time, the vast majority of molecular simulations that employ wide-coverage force fields treat atomic motion classically. In light of the increasing desire for and accelerated development of quantum mechanics (QM)-parameterized interaction models, we reexamine whether the classical treatment is sufficient for a simple but crucial chemical species: alkanes. We show that when using an interaction model or force field in excellent agreement with the "gold standard" QM data, even very basic simulated properties of liquid alkanes, such as densities and heats of vaporization, deviate significantly from experimental values. Inclusion of nuclear quantum effects via techniques that treat nuclear degrees of freedom using the laws of classical mechanics brings the simulated properties much closer to reality.

PMID: 30127031 [PubMed - indexed for MEDLINE]

Prime-and-Trap Malaria Vaccination To Generate Protective CD8+ Liver-Resident Memory T Cells.

J Immunol. 2018 10 01;201(7):1984-1993

Authors: Olsen TM, Stone BC, Chuenchob V, Murphy SC

Abstract
Tissue-resident memory CD8+ T (Trm) cells in the liver are critical for long-term protection against pre-erythrocytic Plasmodium infection. Such protection can usually be induced with three to five doses of i.v. administered radiation-attenuated sporozoites (RAS). To simplify and accelerate vaccination, we tested a DNA vaccine designed to induce potent T cell responses against the SYVPSAEQI epitope of Plasmodium yoelii circumsporozoite protein. In a heterologous "prime-and-trap" regimen, priming using gene gun-administered DNA and boosting with one dose of RAS attracted expanding Ag-specific CD8+ T cell populations to the liver, where they became Trm cells. Vaccinated in this manner, BALB/c mice were completely protected against challenge, an outcome not reliably achieved following one dose of RAS or following DNA-only vaccination. This study demonstrates that the combination of CD8+ T cell priming by DNA and boosting with liver-homing RAS enhances formation of a completely protective liver Trm cell response and suggests novel approaches for enhancing T cell-based pre-erythrocytic malaria vaccines.

PMID: 30127085 [PubMed - indexed for MEDLINE]

Current Challenges of Bioprinted Tissues Toward Clinical Translation.

Tissue Eng Part B Rev. 2019 02;25(1):1-13

Authors: Ke D, Murphy SV

Abstract
IMPACT STATEMENT: This review has a broad overview of the current challenges of bioprinted tissues towards clinical translations and future directions to overcome those challenges. The development of this field has a huge impact on the situation of an insufficient number of organ donors for life-saving organ transplantations.

PMID: 30129878 [PubMed - indexed for MEDLINE]

Nonpathogenic Colonization with Chlamydia in the Gastrointestinal Tract as Oral Vaccination for Inducing Transmucosal Protection.

Infect Immun. 2018 02;86(2):

Authors: Wang L, Zhu C, Zhang T, Tian Q, Zhang N, Morrison S, Morrison R, Xue M, Zhong G

Abstract
Chlamydia has been detected in the gastrointestinal tracts of humans and animals. We now report that gastrointestinal Chlamydia muridarum is able to induce robust transmucosal protection in mice. C. muridarum colonization in the gastrointestinal tract correlated with both a shortened course of C. muridarum genital tract infection and stronger protection against subsequent genital tract challenge infection. Mice preinoculated intragastrically with C. muridarum became highly resistant to subsequent C. muridarum infection in the genital tract, resulting in prevention of pathology in the upper genital tract. The transmucosal protection in the genital tract was rapidly induced, durable, and dependent on major histocompatibility complex (MHC) class II antigen presentation but not MHC class I antigen presentation. Although a deficiency in CD4+ T cells only partially reduced the transmucosal protection, depletion of CD4+ T cells from B cell-deficient mice completely abolished the protection, suggesting a synergistic role of both CD4+ T and B cells in the gastrointestinal C. muridarum-induced transmucosal immunity. However, the same protective immunity did not significantly affect C. muridarum colonization in the gastrointestinal tract. The long-lasting colonization with C. muridarum was restricted to the gastrointestinal tract and was nonpathogenic to either gastrointestinal or extragastrointestinal tissues. Furthermore, gastrointestinal C. muridarum did not alter the gut microbiota or the development of gut mucosal resident memory T cell responses to a nonchlamydial infection. Thus, Chlamydia may be developed into a safe and orally deliverable replicating vaccine for inducing transmucosal protection.

PMID: 29133348 [PubMed - indexed for MEDLINE]

A Holistic Approach to Cybersecurity Starts at the Top.

Front Health Serv Manage. 2018;35(1):30-36

Authors: Murphy SP

PMID: 30124512 [PubMed - indexed for MEDLINE]

Author Correction: Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis.

Nat Genet. 2018 Aug 16;:

Authors: Waage J, Standl M, Curtin JA, Jessen LE, Thorsen J, Tian C, Schoettler N, 23andMe Research Team, AAGC collaborators, Flores C, Abdellaoui A, Ahluwalia TS, Alves AC, Amaral AFS, Antó JM, Arnold A, Barreto-Luis A, Baurecht H, van Beijsterveldt CEM, Bleecker ER, Bonàs-Guarch S, Boomsma DI, Brix S, Bunyavanich S, Burchard EG, Chen Z, Curjuric I, Custovic A, den Dekker HT, Dharmage SC, Dmitrieva J, Duijts L, Ege MJ, Gauderman WJ, Georges M, Gieger C, Gilliland F, Granell R, Gui H, Hansen T, Heinrich J, Henderson J, Hernandez-Pacheco N, Holt P, Imboden M, Jaddoe VWV, Jarvelin MR, Jarvis DL, Jensen KK, Jónsdóttir I, Kabesch M, Kaprio J, Kumar A, Lee YA, Levin AM, Li X, Lorenzo-Diaz F, Melén E, Mercader JM, Meyers DA, Myers R, Nicolae DL, Nohr EA, Palviainen T, Paternoster L, Pennell CE, Pershagen G, Pino-Yanes M, Probst-Hensch NM, Rüschendorf F, Simpson A, Stefansson K, Sunyer J, Sveinbjornsson G, Thiering E, Thompson PJ, Torrent M, Torrents D, Tung JY, Wang CA, Weidinger S, Weiss S, Willemsen G, Williams LK, Ober C, Hinds DA, Ferreira MA, Bisgaard H, Strachan DP, Bønnelykke K

Abstract
In the version of this article initially published, in Fig. 3, the y-axis numbering did not match the log scale indicated in the axis label. The error has been corrected in the HTML and PDF version of the article.

PMID: 30116036 [PubMed - as supplied by publisher]

Defining the Rhythmogenic Elements of Mammalian Breathing.

Physiology (Bethesda). 2018 09 01;33(5):302-316

Authors: Ramirez JM, Baertsch N

Abstract
Breathing's remarkable ability to adapt to changes in metabolic, environmental, and behavioral demands stems from a complex integration of its rhythm-generating network within the wider nervous system. Yet, this integration complicates identification of its specific rhythmogenic elements. Based on principles learned from smaller rhythmic networks of invertebrates, we define criteria that identify rhythmogenic elements of the mammalian breathing network and discuss how they interact to produce robust, dynamic breathing.

PMID: 30109823 [PubMed - indexed for MEDLINE]

Proteomic analysis of monolayer-integrated proteins on lipid droplets identifies amphipathic interfacial α-helical membrane anchors.

Proc Natl Acad Sci U S A. 2018 08 28;115(35):E8172-E8180

Authors: Pataki CI, Rodrigues J, Zhang L, Qian J, Efron B, Hastie T, Elias JE, Levitt M, Kopito RR

Abstract
Despite not spanning phospholipid bilayers, monotopic integral proteins (MIPs) play critical roles in organizing biochemical reactions on membrane surfaces. Defining the structural basis by which these proteins are anchored to membranes has been hampered by the paucity of unambiguously identified MIPs and a lack of computational tools that accurately distinguish monolayer-integrating motifs from bilayer-spanning transmembrane domains (TMDs). We used quantitative proteomics and statistical modeling to identify 87 high-confidence candidate MIPs in lipid droplets, including 21 proteins with predicted TMDs that cannot be accommodated in these monolayer-enveloped organelles. Systematic cysteine-scanning mutagenesis showed the predicted TMD of one candidate MIP, DHRS3, to be a partially buried amphipathic α-helix in both lipid droplet monolayers and the cytoplasmic leaflet of endoplasmic reticulum membrane bilayers. Coarse-grained molecular dynamics simulations support these observations, suggesting that this helix is most stable at the solvent-membrane interface. The simulations also predicted similar interfacial amphipathic helices when applied to seven additional MIPs from our dataset. Our findings suggest that interfacial helices may be a common motif by which MIPs are integrated into membranes, and provide high-throughput methods to identify and study MIPs.

PMID: 30104359 [PubMed - indexed for MEDLINE]

Striving to Move Beyond Chemotherapy in Advanced Pancreatic Cancer.

J Oncol Pract. 2016 09;12(9):808-10

Authors: Ko AH

PMID: 27621334 [PubMed - indexed for MEDLINE]