UW Neurological Surgery Recent PubMed Publications

Isoalantolactone induces apoptosis through ROS-mediated ER stress and inhibition of STAT3 in prostate cancer cells.

J Exp Clin Cancer Res. 2018 Dec 12;37(1):309

Authors: Chen W, Li P, Liu Y, Yang Y, Ye X, Zhang F, Huang H

Abstract
BACKGROUND: Prostate cancer is one of the most commonly diagnosed cancers in men worldwide. Currently available therapies for metastatic prostate cancer are only marginally effective. Therefore, new therapeutic agents are urgently needed to improve patient outcome. Isoalantolactone (IATL), an active sesquiterpene naturally present in many vegetables and medicinal plants, is known to induce cell death and apoptosis in various cancer cell lines. Nevertheless, antitumor mechanisms initiated by IATL in cancer cells have not been fully defined.
METHODS: Cell apoptosis and cellular ROS levels were analyzed by flow cytometry. Western blot and qRT-PCR were used to analyze the protein and mRNA levels of indicated molecules, respectively. Nude mice xenograft model was used to test the effects of IATL on prostate cancer cell growth in vivo.
RESULTS: In this study, we found that IATL dose-dependently inhibited cancer cell growth and induced apoptosis in PC-3 and DU145 cells. Mechanistically, our data found that IATL induced reactive oxygen species (ROS) production, resulting in the activation of endoplasmic reticulum stress pathway and eventually cell apoptosis in prostate cancer cells. IATL also decreased the protein expression levels of p-STAT3 and STAT3, and the effects of IATL were reversed by pretreatment with N-acetyl-L-cysteine (NAC). In vivo, we found that IATL inhibited the growth of prostate cancer xenografts without exhibiting toxicity. Treatment of mice bearing human prostate cancer xenografts with IATL was also associated with induction of ER stress and inhibtion of STAT3.
CONCLUSION: In summary, our results unveil a previously unrecognized mechanism underlying the biological activity of IATL, and provide a novel anti-cancer candidate for the treatment of prostate cancer.

PMID: 30541589 [PubMed - indexed for MEDLINE]

Discussion: Craniometric Analysis of Endoscopic Suturectomy for Bilateral Coronal Craniosynostosis.

Plast Reconstr Surg. 2019 01;143(1):199-201

Authors: Hopper RA, Lee A

PMID: 30589794 [PubMed - indexed for MEDLINE]

Misclassification of Myocardial Injury as Myocardial Infarction: Implications for Assessing Outcomes in Value-Based Programs.

JAMA Cardiol. 2019 05 01;4(5):460-464

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

Abstract
Importance: Similar to other patients with acute myocardial infarction, patients with type 2 myocardial infarction (T2MI) are included in several value-based programs, including the Hospital Readmissions Reduction Program and the Hospital Value-Based Purchasing Program. To our knowledge, whether nonischemic myocardial injury is being misclassified as T2MI is unknown and may have implications for these programs.
Objective: To determine whether patients with nonischemic myocardial injury are being miscoded as having T2MI and if this has implications for 30-day readmission and mortality rates.
Design, Settings, and Participants: Using the new International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code, we identified patients who were coded as having T2MI between October 2017 and May 2018 at Massachusetts General Hospital. Strict adjudication using the fourth universal definition of MI was then applied.
Main outcome and Measures: Clinical adjudication of T2MI and 30-day readmission and mortality rates as a function of T2MI or nonischemic myocardial injury.
Results: Of 633 patients, 369 (58.3%) were men and 514 (81.2%) were white. After strict adjudication, 359 (56.7%) had T2MI, 265 (41.9%) had myocardial injury, 6 (0.9%) had type 1 MI, and 3 (0.5%) had unstable angina. Patients with T2MI had a higher prevalence of cardiovascular comorbidities than those with myocardial injury. Patients with T2MI and myocardial injury had high in-hospital mortality rates (10.6% and 8.7%, respectively; P = .50). Of those discharged alive (563 [88.9%]), 30-day readmission rates (22.7% vs 21.1%; P = .68) and mortality rates (4.4% vs 7.4%; P = .14) were comparable among patients with T2MI and myocardial injury.
Conclusions and Relevance: A substantial percentage of patients coded as having T2MI actually have myocardial injury. Both conditions have high 30-day readmission and mortality rates. Including patients with high-risk myocardial injury may have substantial implications for value-based programs.

PMID: 30879022 [PubMed - indexed for MEDLINE]

Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform.

Sci Rep. 2017 08 18;7(1):8837

Authors: Skardal A, Murphy SV, Devarasetty M, Mead I, Kang HW, Seol YJ, Shrike Zhang Y, Shin SR, Zhao L, Aleman J, Hall AR, Shupe TD, Kleensang A, Dokmeci MR, Jin Lee S, Jackson JD, Yoo JJ, Hartung T, Khademhosseini A, Soker S, Bishop CE, Atala A

Abstract
Many drugs have progressed through preclinical and clinical trials and have been available - for years in some cases - before being recalled by the FDA for unanticipated toxicity in humans. One reason for such poor translation from drug candidate to successful use is a lack of model systems that accurately recapitulate normal tissue function of human organs and their response to drug compounds. Moreover, tissues in the body do not exist in isolation, but reside in a highly integrated and dynamically interactive environment, in which actions in one tissue can affect other downstream tissues. Few engineered model systems, including the growing variety of organoid and organ-on-a-chip platforms, have so far reflected the interactive nature of the human body. To address this challenge, we have developed an assortment of bioengineered tissue organoids and tissue constructs that are integrated in a closed circulatory perfusion system, facilitating inter-organ responses. We describe a three-tissue organ-on-a-chip system, comprised of liver, heart, and lung, and highlight examples of inter-organ responses to drug administration. We observe drug responses that depend on inter-tissue interaction, illustrating the value of multiple tissue integration for in vitro study of both the efficacy of and side effects associated with candidate drugs.

PMID: 28821762 [PubMed - indexed for MEDLINE]

Aspirin for the Primary Prevention of Cardiovascular Disease: Weighing Up the Evidence.

Am J Med. 2019 09;132(9):1007-1008

Authors: Murphy S, McCarthy CP, McEvoy JW

PMID: 30871925 [PubMed - indexed for MEDLINE]

Improving estimation of puma (Puma concolor) population density: clustered camera-trapping, telemetry data, and generalized spatial mark-resight models.

Sci Rep. 2019 03 14;9(1):4590

Authors: Murphy SM, Wilckens DT, Augustine BC, Peyton MA, Harper GC

Abstract
Obtaining reliable population density estimates for pumas (Puma concolor) and other cryptic, wide-ranging large carnivores is challenging. Recent advancements in spatially explicit capture-recapture models have facilitated development of novel survey approaches, such as clustered sampling designs, which can provide reliable density estimation for expansive areas with reduced effort. We applied clustered sampling to camera-traps to detect marked (collared) and unmarked pumas, and used generalized spatial mark-resight (SMR) models to estimate puma population density across 15,314 km2 in the southwestern USA. Generalized SMR models outperformed conventional SMR models. Integrating telemetry data from collars on marked pumas with detection data from camera-traps substantially improved density estimates by informing cryptic activity (home range) center transiency and improving estimation of the SMR home range parameter. Modeling sex of unmarked pumas as a partially identifying categorical covariate further improved estimates. Our density estimates (0.84-1.65 puma/100 km2) were generally more precise (CV = 0.24-0.31) than spatially explicit estimates produced from other puma sampling methods, including biopsy darting, scat detection dogs, and regular camera-trapping. This study provides an illustrative example of the effectiveness and flexibility of our combined sampling and analytical approach for reliably estimating density of pumas and other wildlife across geographically expansive areas.

PMID: 30872785 [PubMed - indexed for MEDLINE]

Climate-Altered Wetlands Challenge Waterbird Use and Migratory Connectivity in Arid Landscapes.

Sci Rep. 2019 Mar 15;9(1):4666

Authors: Haig SM, Murphy SP, Matthews JH, Arismendi I, Safeeq M

Abstract
Wetlands in arid landscapes provide critical habitat for millions of migratory waterbirds across the world and throughout their annual cycle. The scope and scale of understanding avian use of these wetlands in conjunction with changes in climate are daunting yet critical to address lest we lose continent-wide migratory pathways. Here, we assess changes in waterbird use of North America's Pacific Flyway in the Great Basin by examining water availability and climate trends over the past 100 years. We found recent (1980-2015) climate warming has significantly reduced the amount and shifted seasonality of water flowing into wetlands. Further, we found remarkable changes in waterbird species composition over time. We propose that a reduced hydroperiod and lower water quality from reduction in water level and flow limits sites used by waterbirds. These factors reduce chick survivorship as they cannot metabolize saline water, which makes suitable freshwater conditions a limiting resource. Collectively, climate-induced changes in Great Basin wetlands suggest a major shift in freshwater ecosystems, resulting in degradation of a continental migratory route. This work illustrates the importance of examining multi-scale changes in critical regional resources to understand their impact across a hemispheric flyway and provides a model to examine other flyways.

PMID: 30874622 [PubMed - in process]

Clot Analysis in Acute Ischemic Stroke.

Stroke. 2019 04;50(4):e106-e109

Authors: Walker M, Levitt MR, Gibbons EF, Horne DJ, Corcorran MA

PMID: 30869564 [PubMed - indexed for MEDLINE]

Dynamic molecular changes during the first week of human life follow a robust developmental trajectory.

Nat Commun. 2019 03 12;10(1):1092

Authors: Lee AH, Shannon CP, Amenyogbe N, Bennike TB, Diray-Arce J, Idoko OT, Gill EE, Ben-Othman R, Pomat WS, van Haren SD, Cao KL, Cox M, Darboe A, Falsafi R, Ferrari D, Harbeson DJ, He D, Bing C, Hinshaw SJ, Ndure J, Njie-Jobe J, Pettengill MA, Richmond PC, Ford R, Saleu G, Masiria G, Matlam JP, Kirarock W, Roberts E, Malek M, Sanchez-Schmitz G, Singh A, Angelidou A, Smolen KK, EPIC Consortium, Brinkman RR, Ozonoff A, Hancock REW, van den Biggelaar AHJ, Steen H, Tebbutt SJ, Kampmann B, Levy O, Kollmann TR

Abstract
Systems biology can unravel complex biology but has not been extensively applied to human newborns, a group highly vulnerable to a wide range of diseases. We optimized methods to extract transcriptomic, proteomic, metabolomic, cytokine/chemokine, and single cell immune phenotyping data from <1 ml of blood, a volume readily obtained from newborns. Indexing to baseline and applying innovative integrative computational methods reveals dramatic changes along a remarkably stable developmental trajectory over the first week of life. This is most evident in changes of interferon and complement pathways, as well as neutrophil-associated signaling. Validated across two independent cohorts of newborns from West Africa and Australasia, a robust and common trajectory emerges, suggesting a purposeful rather than random developmental path. Systems biology and innovative data integration can provide fresh insights into the molecular ontogeny of the first week of life, a dynamic developmental phase that is key for health and disease.

PMID: 30862783 [PubMed - indexed for MEDLINE]

Endoscopic Spine Surgery Past, Present, and Future.

Bull Hosp Jt Dis (2013). 2019 Mar;77(1):75-84

Authors: Hasan S, Hofstetter CP

Abstract

PMID: 30865869 [PubMed - indexed for MEDLINE]

Pancreatic Adenocarcinoma, Version 1.2019.

J Natl Compr Canc Netw. 2019 03 01;17(3):202-210

Authors: Tempero MA, Malafa MP, Chiorean EG, Czito B, Scaife C, Narang AK, Fountzilas C, Wolpin BM, Al-Hawary M, Asbun H, Behrman SW, Benson AB, Binder E, Cardin DB, Cha C, Chung V, Dillhoff M, Dotan E, Ferrone CR, Fisher G, Hardacre J, Hawkins WG, Ko AH, LoConte N, Lowy AM, Moravek C, Nakakura EK, O'Reilly EM, Obando J, Reddy S, Thayer S, Wolff RA, Burns JL, Zuccarino-Catania G

Abstract
The NCCN Guidelines for Pancreatic Adenocarcinoma discuss the diagnosis and management of adenocarcinomas of the exocrine pancreas and are intended to assist with clinical decision-making. These NCCN Guidelines Insights discuss important updates to the 2019 version of the guidelines, focusing on postoperative adjuvant treatment of patients with pancreatic cancers.

PMID: 30865919 [PubMed - indexed for MEDLINE]

Personal Control Over Decisions to Participate in Research by Persons With Histories of Both Substance Use Disorders and Criminal Justice Supervision.

J Empir Res Hum Res Ethics. 2018 04;13(2):160-172

Authors: Chen DT, Ko TM, Allen AA, Bonnie RJ, Suratt CE, Appelbaum PS, Nunes EV, Friedmann PD, Lee JD, Gordon MS, McDonald R, Wilson D, Boney TY, Murphy SM, O'Brien CP

Abstract
Individuals must feel free to exert personal control over decisions regarding research participation. We present an examination of participants' perceived personal control over, as well as reported pressures and threats from others, influencing their decision to join a study assessing the effectiveness of extended-release naltrexone in preventing opioid dependence relapse. Most participants endorsed a strong sense of control over the decision; few reported pressures or threats. Although few in number, participants' brief narrative descriptions of the pressures and threats are illuminating and provide context for their perceptions of personal control. Based on this work, we propose a useful set of tools to help ascertain participants' sense of personal control in joining research.

PMID: 29460668 [PubMed - indexed for MEDLINE]

Maternal Smoking Before and During Pregnancy and the Risk of Sudden Unexpected Infant Death.

Pediatrics. 2019 04;143(4):

Authors: Anderson TM, Lavista Ferres JM, Ren SY, Moon RY, Goldstein RD, Ramirez JM, Mitchell EA

Abstract
OBJECTIVES: Maternal smoking during pregnancy is an established risk factor for sudden unexpected infant death (SUID). Here, we aim to investigate the effects of maternal prepregnancy smoking, reduction during pregnancy, and smoking during pregnancy on SUID rates.
METHODS: We analyzed the Centers for Disease Control and Prevention Birth Cohort Linked Birth/Infant Death Data Set (2007-2011: 20 685 463 births and 19 127 SUIDs). SUID was defined as deaths at <1 year of age with International Classification of Diseases, 10th Revision codes R95 (sudden infant death syndrome), R99 (ill-defined or unknown cause), or W75 (accidental suffocation or strangulation in bed).
RESULTS: SUID risk more than doubled (adjusted odds ratio [aOR] = 2.44; 95% confidence interval [CI] 2.31-2.57) with any maternal smoking during pregnancy and increased twofold between no smoking and smoking 1 cigarette daily throughout pregnancy. For 1 to 20 cigarettes per day, the probability of SUID increased linearly, with each additional cigarette smoked per day increasing the odds by 0.07 from 1 to 20 cigarettes; beyond 20 cigarettes, the relationship plateaued. Mothers who quit or reduced their smoking decreased their odds compared with those who continued smoking (reduced: aOR = 0.88, 95% CI 0.79-0.98; quit: aOR = 0.77, 95% CI 0.67-0.87). If we assume causality, 22% of SUIDs in the United States can be directly attributed to maternal smoking during pregnancy.
CONCLUSIONS: These data support the need for smoking cessation before pregnancy. If no women smoked in pregnancy, SUID rates in the United States could be reduced substantially.

PMID: 30858347 [PubMed - indexed for MEDLINE]

Emergency department utilization among individuals with idiopathic intracranial hypertension.

Int J Health Care Qual Assur. 2019 Feb 11;32(1):152-163

Authors: Murphy S, Friesner DL, Rosenman R, Waslo CS, Au J, Tanne E

Abstract
PURPOSE: Idiopathic intracranial hypertension (IIH) can be a debilitating disorder that is difficult to identify and treat. Failure to adequately manage IIH symptoms may force patients to present at emergency departments (EDs) seeking symptom relief. The purpose of this paper is to empirically characterize ED use by previously diagnosed IIH patients.
DESIGN/METHODOLOGY/APPROACH: Patients diagnosed with IIH, and who registered with the Intracranial Hypertension Registry by 2014, were solicited for study inclusion. A survey was designed to elicit ED use during the period 2010-2012. Information on demographic and socioeconomic characteristics, IIH signs and symptoms, time since diagnosis, perspectives of ED use and quality of life was collected. Quality of life was assessed using an adaptation of the Migraine-Specific Quality of Life Questionnaire. Data were analyzed using descriptive statistics and nonparametric hypothesis tests.
FINDINGS: In total, 39 percent of IIH patients used emergency services over the study period; those that did used the services intensely. These patients were more likely to be non-white, live in households making less than $25,000 annually, have public insurance and have received a diversional shunt procedure. Patients who used the ED were less likely to live in households making $100,000, or more, annually and have private insurance. Participants who used the ED had significantly lower quality-of-life scores, were younger and had been diagnosed with IIH for less time.
ORIGINALITY/VALUE: ED staff and outside physicians can utilize the information contained in this study to more effectively recognize the unique circumstances of IIH patients who present at EDs.

PMID: 30859875 [PubMed - indexed for MEDLINE]

Far lateral approach to anterior foramen magnum meningiomas - When should condyle be drilled?

Neurol India. 2019 Jan-Feb;67(1):59-60

Authors: Sekhar L, Zeeshan Q

Abstract

PMID: 30860093 [PubMed - indexed for MEDLINE]

Deltamethrin Exposure Daily From Postnatal Day 3-20 in Sprague-Dawley Rats Causes Long-term Cognitive and Behavioral Deficits.

Toxicol Sci. 2019 06 01;169(2):511-523

Authors: Pitzer EM, Sugimoto C, Gudelsky GA, Huff Adams CL, Williams MT, Vorhees CV

Abstract
Pyrethroids are synthetic insecticides that act acutely on voltage gated sodium channels to prolong channel opening and depolarization. Epidemiological studies find that exposure to pyrethroids are associated with neurological and developmental abnormalities in children. The long-term effects of type II pyrethroids, such as deltamethrin (DLM), on development have received little attention. We exposed Sprague-Dawley rats to DLM by gavage at doses of 0, 0.25, 0.5, and 1.0 mg/kg/day from postnatal day (P) 3-20 in a split-litter design. Following behavioral testing as adults, monoamine levels, release, and mRNA were assessed via high performance liquid chromatography, microdialysis, and qPCR, respectively. Long-term potentiation (LTP) was assessed at P25-35. Developmental DLM exposure resulted in deficits in allocentric and egocentric learning and memory, increased startle reactivity, reduced conditioned contextual freezing, and attenuated MK-801 induced hyperactivity compared with controls. Startle and egocentric learning were preferentially affected in males. Deltamethrin-treated rats exhibited increased CA1 hippocampal LTP, decreased extracellular dopamine release by microdialysis, reduced dopamine D1 receptor mRNA expression in neostriatum, and decreased norepinephrine levels in the hippocampus. The data indicate that neonatal DLM exposure has adverse long-term effects on learning, memory, startle, glutamatergic function, LTP, and norepinephrine.

PMID: 30850843 [PubMed - indexed for MEDLINE]

Left Ventricular Thrombus: Contemporary Etiologies, Treatment Strategies, and Outcomes.

J Am Coll Cardiol. 2019 04 23;73(15):2007-2009

Authors: McCarthy CP, Murphy S, Venkateswaran RV, Singh A, Chang LL, Joice MG, Rivero JM, Vaduganathan M, Januzzi JL, Bhatt DL

PMID: 30846340 [PubMed - indexed for MEDLINE]

Underutilization of Cardiac Rehabilitation for Type 2 Myocardial Infarction.

J Am Coll Cardiol. 2019 04 23;73(15):2005-2007

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

PMID: 30846342 [PubMed - indexed for MEDLINE]

Immunotherapy for brain tumors: understanding early successes and limitations.

Expert Rev Neurother. 2018 03;18(3):251-259

Authors: Lieberman NAP, Vitanza NA, Crane CA

Abstract
INTRODUCTION: Adverse effects and toxicities related to standard treatments for brain tumors significantly reduce patients' quality of life. Although most immunotherapy approaches for solid tumors have not been successful, several early-phase clinical trials are beginning to reveal a potential role for immunotherapy in the treatment of brain tumors. In particular, methods that activate the innate immune system and induce a polyclonal anti-cancer response have demonstrated that brain tumors are susceptible to immune-mediated tumor destruction. Compared with conventional therapies, modulation of the immune system may improve both survivorship and quality of life during and following treatment. Areas covered: An overview of mechanisms of immunotherapy in the context of current treatments for adult and pediatric brain tumors is provided. Results from recent clinical trials will be discussed, focusing on the favorable safety and efficacy profiles of immunotherapeutics. Expert commentary: Although it is too early to judge the long-term safety of immunotherapy for the treatment of patients with brain tumors, early results suggest that these drugs are well-tolerated and may improve survival and quality of life. Importantly, approaches that activate an anti-tumor immune response lay the framework for iterative development of immunotherapies that can reliably treat patients with brain tumors.

PMID: 29322843 [PubMed - indexed for MEDLINE]

Endovascular thrombectomy in pediatric patients with large vessel occlusion.

J Neurointerv Surg. 2019 Jul;11(7):729-732

Authors: Shoirah H, Shallwani H, Siddiqui AH, Levy EI, Kenmuir CL, Jovin TG, Levitt MR, Kim LJ, Griauzde J, Pandey AS, Gemmete JJ, Abruzzo T, Arthur AS, Elijovich L, Hoit D, Cheema A, Aghaebrahim A, Sauvageau E, Hanel R, Ringer AJ, Nascimento FA, Kan P, Mocco J

Abstract
BACKGROUND: Pediatric acute ischemic stroke with underlying large vessel occlusion is a rare disease with significant morbidity and mortality. There is a paucity of data about the safety and outcomes of endovascular thrombectomy in these cases, especially with modern devices.
METHODS: We conducted a retrospective review of all pediatric stroke patients who underwent endovascular thrombectomy in nine US tertiary centers between 2008 and 2017.
RESULTS: Nineteen patients (63.2% male) with a mean (SD) age of 10.9(6) years and weight 44.6 (30.8) kg were included. Mean (SD) NIH Stroke Scale (NIHSS) score at presentation was 13.9 (5.7). CT-based assessment was obtained in 88.2% of the patients and 58.8% of the patients had perfusion-based assessment. All procedures were performed via the transfemoral approach. The first-pass device was stentriever in 52.6% of cases and aspiration in 36.8%. Successful revascularization was achieved in 89.5% of the patients after a mean (SD) of 2.2 (1.5) passes, with a mean (SD) groin puncture to recanalization time of 48.7 (37.3) min (median 41.5). The mean (SD) reduction in NIHSS from admission to discharge was 10.2 (6.2). A good neurological outcome was achieved in 89.5% of the patients. One patient had post-revascularization seizure, but no other procedural complications or mortality occurred.
CONCLUSIONS: Endovascular thrombectomy is safe and feasible in selected pediatric patients. Technical and neurological outcomes were comparable to adult literature with no safety concerns with the use of standard adult devices in patients as young as 18 months. This large series adds to the growing literature but further studies are warranted.

PMID: 30842301 [PubMed - indexed for MEDLINE]