UW Neurological Surgery Recent PubMed Publications

Microsurgical Resection of Recurrent Cavernous Sinus Hemangioma by Superior and Lateral Approach: 2-Dimensional Operative Video.

Oper Neurosurg (Hagerstown). 2019 Nov 05;:

Authors: Zeeshan Q, Hernandez JPC, Moore MK, Sekhar LN

Abstract
This video shows the technical nuances of microsurgical resection of recurrent cavernous sinus (CS) hemangioma by superior and lateral approach.  A 77-yr-old woman presented with headache and difficulty in vision in right eye for 6 mo. She had previously undergone attempted resection of a right CS tumor in another hospital with partial removal, and the tumor had grown significantly. Neurological examination revealed proptosis, cranial nerve 3 palsy, and loss of vision in right eye (20/200). Left side visual acuity was 20/20.  Brain magnetic resonance imaging (MRI) demonstrated a large CS mass with homogeneous enhancement, measuring 3.3 × 3.3 × 2.6 cm, extending into the suprasellar cistern with mass effect on the right optic nerve. It extended anteriorly to the region of the right orbital apex and abuted the basilar artery posteriorly.  She underwent right frontotemporal craniotomy, posterolateral orbitotomy and anterior clinoidectomy as well as optic nerve decompression, and the CS tumor was removed by superior and lateral approach. An incision was made into the superior wall of the CS medial to the third nerve. On lateral aspect the tumor had extended outside the CS through the Parkinson's triangle. Posteriorly it extended through the clival dura. Anteriorly tumor encased the carotid artery and it was gradually dissected away. At the end of the operation, all of the cranial nerves were intact.  Postoperative MRI showed near complete tumor resection with preservation of the internal carotid artery. At 6 mo follow-up her modified Rankin Scale was 1 and vision in left eye was normal.  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: 31687770 [PubMed - as supplied by publisher]

Opportunities and challenges of translational 3D bioprinting.

Nat Biomed Eng. 2020 04;4(4):370-380

Authors: Murphy SV, De Coppi P, Atala A

Abstract
3D-printed orthopaedic devices and surgical tools, printed maxillofacial implants and other printed acellular devices have been used in patients. By contrast, bioprinted living cellular constructs face considerable translational challenges. In this Perspective, we first summarize the most recent developments in 3D bioprinting for clinical applications, with a focus on how 3D-printed cartilage, bone and skin can be designed for individual patients and fabricated using the patient's own cells. We then discuss key translational considerations, such as the need to ensure close integration of the living device with the patient's vascular network, the development of biocompatible bioinks and the challenges in deriving a physiologically relevant number of cells. Lastly, we outline untested regulatory pathways, as well as logistical challenges in material sourcing, manufacturing, standardization and transportation.

PMID: 31695178 [PubMed - indexed for MEDLINE]

Acute peripheral inflammation and post-traumatic sleep differ between sexes after experimental diffuse brain injury.

Eur J Neurosci. 2019 Nov 02;:

Authors: Saber M, Giordano KR, Hur Y, Ortiz JB, Morrison H, Godbout JP, Murphy SM, Lifshitz J, Rowe RK

Abstract
Identifying differential responses between sexes following traumatic brain injury (TBI) can elucidate the mechanisms behind disease pathology. Peripheral and central inflammation in the pathophysiology of TBI can increase sleep in male rodents, but this remains untested in females. We hypothesized that diffuse TBI would increase inflammation and sleep in males more so than in females. Diffuse TBI was induced in C57BL/6J mice and serial blood samples were collected (baseline, 1, 5, 7 days post-injury [DPI]) to quantify peripheral immune cell populations and sleep regulatory cytokines. Brains and spleens were harvested at 7DPI to quantify central and peripheral immune cells, respectively. Mixed effects regression models were used for data analysis. Female TBI mice had 77-124% higher IL-6 levels than male TBI mice at 1 and 5DPI, whereas IL-1β and TNF-α levels were similar between sexes at all timepoints. Despite baseline sex differences in blood-measured Ly6Chigh monocytes (females had 40% more than males), TBI reduced monocytes by 67% in TBI mice at 1DPI. Male TBI mice had 31-33% more blood-measured and 31% more spleen-measured Ly6G+ neutrophils than female TBI mice at 1 and 5DPI, and 7DPI, respectively. Compared with sham, TBI increased sleep in both sexes during the first light and dark cycles. Male TBI mice slept 11-17% more than female TBI mice, depending on the cycle. Thus, sex and TBI interactions may alter the peripheral inflammation profile and sleep patterns, which might explain discrepancies in disease progression based on sex.

PMID: 31677290 [PubMed - as supplied by publisher]

Electrophysiology of Sensory and Motor Nerve Root Fibers in Selective Dorsal Rhizotomies.

Pediatr Neurosurg. 2020;55(1):17-25

Authors: Martinez V, Browd S, Osorio M, Hooper E, Slimp J, Bo X, Kinney GA

Abstract
AIMS: Spasticity remains a major impediment in the treatment of cerebral palsy (CP). The single-level selective dorsal rhizotomy (SDR) is a minimally invasive intervention that reduces spasticity in select patients. We provide a descriptive set of normative data that practitioners can utilize to help guide the single-level SDR procedure, including (1) physiological threshold values used to dissociate ventral from dorsal roots; (2) response characteristics of muscles; (3) descriptions of abnormal physiological responses; and (4) percentage of rootlets transected during surgery.
METHODS: We examined data from 38 patients with CP who underwent SDR. Dorsal and ventral roots were classified based on the amplitude of electromyographic (EMG) responses, number of muscles activated, and abnormal response characteristics.
RESULTS: Ventral roots activated more muscles at significantly lower stimulus thresholds and demonstrated larger EMG responses than did dorsal roots. Of the transections made, 64.72 ± 1.69% of each rootlet was transected. Ventral and dorsal roots can be readily separated based on a few key physiological characteristics including response thresholds and the spread of muscle activation. It was observed that a threshold of approximately 0.4 mA could be used to dissociate ventral and dorsal roots during surgery.
CONCLUSIONS: These data illustrate the range of physiological variance observed while performing SDR in patients with spastic CP. Notably, we encountered outlier patients whose roots demonstrated aberrant response characteristics and displayed uncharacteristically low dorsal root thresholds or abnormally high ventral root thresholds. Practitioners should be prepared to individualize their threshold criteria and customize treatment on a patient-by-patient basis.

PMID: 31678975 [PubMed - indexed for MEDLINE]

Growth Rate of Plasmodium falciparum: Analysis of Parasite Growth Data From Malaria Volunteer Infection Studies.

J Infect Dis. 2020 03 02;221(6):963-972

Authors: Wockner LF, Hoffmann I, Webb L, Mordmüller B, Murphy SC, Kublin JG, O'Rourke P, McCarthy JS, Marquart L

Abstract
BACKGROUND: Growth rate of malaria parasites in the blood of infected subjects is an important measure of efficacy of drugs and vaccines.
METHODS: We used log-linear and sine-wave models to estimate the parasite growth rate of the 3D7 strain of Plasmodium falciparum using data from 177 subjects from 14 induced blood stage malaria (IBSM) studies conducted at QIMR Berghofer. We estimated parasite multiplication rate per 48 hours (PMR48), PMR per life-cycle (PMRLC), and parasite life-cycle duration. We compared these parameters to those from studies conducted elsewhere with infections induced by IBSM (n = 66), sporozoites via mosquito bite (n = 336), or injection (n = 51).
RESULTS: The parasite growth rate of 3D7 in QIMR Berghofer studies was 0.75/day (95% confidence interval [CI], .73-.77/day), PMR48 was 31.9 (95% CI, 28.7-35.4), PMRLC was 16.4 (95% CI, 15.1-17.8), and parasite life-cycle was 38.8 hours (95% CI, 38.3-39.2 hours). These parameters were similar to estimates from IBSM studies elsewhere (0.71/day, 95% CI, .67-.75/day; PMR48 26.6, 95% CI, 22.2-31.8) but significantly higher (P < .001) than in sporozoite studies (0.47/day, 95% CI, .43-.50/day; PMR48 8.6, 95% CI, 7.3-10.1).
CONCLUSIONS: Parasite growth rates were similar across different IBSM studies and higher than infections induced by sporozoite.

PMID: 31679015 [PubMed - indexed for MEDLINE]

Personal trauma among healthcare providers: implications for screening practices.

Women Health. 2020 May-Jun;60(5):570-584

Authors: Cooper C, Coleman J, Irvin N, Lee A, Antoine D

Abstract
Screening rates for trauma are low in health care settings. We examined the association between health care providers' (HCPs) experience of physical or sexual trauma and their screening of female patients for trauma. HCPs at an urban academic medical institution were surveyed from September through November 2016. The Brief Trauma (BTQ) and Sexual and Physical Abuse History Questionnaires (SPAHQ) assessed their own experiences of trauma. The Screening Practices Questionnaire (SPQ) assessed HCPs trauma screening. Multiple regression analyses were performed. Among 212 respondents aged 22-67 years, most were female (78.3%) and white (76.1%). Nurses (41.0%) were the largest occupational group. Overall, 85.8% reported having experienced trauma. No significant difference was observed in median SPQ scores between HCPs who had experienced trauma (3.88 [Interquartile Range (IQR) 3.44-4.31]) and those who had not (4.00 [IQR 3.47-4.33], p = .645). In an adjusted model, screening policy awareness and having an obstetrics & gynecology or psychiatry specialty were associated with higher SPQ scores (p < .001). The prevalence of trauma experience in this sample was high, but not associated with screening. Screening policy awareness and practice specialty were associated with screening. HCP factors associated with greater trauma screening should be explored.

PMID: 31665985 [PubMed - indexed for MEDLINE]

Bioprinted trachea constructs with patient-matched design, mechanical and biological properties.

Biofabrication. 2019 12 31;12(1):015022

Authors: Ke D, Yi H, Est-Witte S, George S, Kengla C, Lee SJ, Atala A, Murphy SV

Abstract
Tracheal stenosis is a rare but life-threatening disease. Primary clinical procedures for treating this disease are limited if the region requiring repair is long or complex. This study is the first of its kind to fabricate bioprinted tracheal constructs with separate cartilage and smooth muscle regions using polycaprolactone (PCL) and human mesenchymal stem cell (hMSC)-laden hydrogels. Our final bioprinted trachea showed comparable elastic modulus and yield stress compared to native tracheal tissue. In addition, both cartilage and smooth muscle formation were observed in the desired regions of our bioprinted trachea through immunohistochemistry and western blot after two weeks of in vitro culture. This study demonstrates a novel approach to manufacture tissue engineered trachea with mechanical and biological properties similar to native trachea, which represents a step closer to overcoming the clinical challenges of treating tracheal stenosis.

PMID: 31671417 [PubMed - indexed for MEDLINE]

Immune and Cytokine Dysfunction in Cystic Fibrosis.

Am J Respir Cell Mol Biol. 2019 11;61(5):656-658

Authors: Leung ST, Khoury O, Barrios C, Ortega VE, Atala A, Murphy SV

PMID: 31674827 [PubMed - indexed for MEDLINE]

Endovascular Coil Retrieval Using Dual Synchronous Solitaire Revascularization Devices.

Oper Neurosurg (Hagerstown). 2018 09 01;15(3):E19-E22

Authors: Nerva JD, Morton RP, Kelly CM, Hallam DK, Levitt MR

Abstract
BACKGROUND AND IMPORTANCE: Coil migration is a potential complication of endovascular aneurysm treatment. Dislodged coils into the parent artery require retrieval to prevent thromboembolic complications. A variety of techniques for coil retrieval have been described, including the use of single stentrievers and aspiration catheters.
CLINICAL PRESENTATION: The use of 2 stentrievers, as opposed to a single device, was thought to be advantageous in coil removal by the additional point of friction due to the extensive length of coil stretching and earlier failure of a single device.
CONCLUSION: In this report, 2 synchronous Solitaire FR Revascularization Devices (Covidien/Medtronic, Dublin, Ireland) were deployed, 1 distal and 1 proximal, to retrieve an inadvertently deployed coil.

PMID: 29106636 [PubMed - indexed for MEDLINE]

Functional Status Examination (FSE) Yields Higher Measurement Precision of Functional Limitations After Traumatic Injury Than the GOSE: A Preliminary Study.

J Neurotrauma. 2019 Oct 30;:

Authors: Nelson LD, Brett BL, Magnus BE, Balsis S, McCrea M, Manley GT, Temkin N, Dikmen S

Abstract
The Glasgow Outcome Scale-Extended (GOSE) is one of the most widely used measures of functional limitations after traumatic brain injury (TBI) and is the primary outcome measure used in clinical trials of acute TBI treatment. However, the GOSE appears insensitive to the full spectrum of TBI-related functional limitations, which may limit its potential to capture treatment effects or correlate with other variables that impact outcome. The Functional Status Examination (FSE) was designed to improve upon the assessment of injury-related functional limitations using a standardized assessment and wider possible score range. The aim of this pilot study was to employ item response theory (IRT) to test the hypothesis that the FSE yields more precise estimation of functional outcome than the GOSE. Traumatically-injured patients (N = 100, 77 TBI, 23 orthopedic injuries) were interviewed at 3 months post-injury using both the GOSE and FSE structured interviews. IRT was used to quantify and compare the tests' information functions, which reflect the degree to which each instrument precisely measures functional limitations across the severity spectrum. Findings were consistent with predictions: The FSE yielded stronger measurement of functional limitations (i.e., higher test information) across a wider range of severity than the GOSE, whether scoring the GOSE from all interview items or using the traditional GOSE overall score. While the FSE appears to be a promising alternative measure to the GOSE, further research is needed to cross-validate these findings in a larger sample and understand how to best deploy it in clinical and translational research.

PMID: 31663425 [PubMed - as supplied by publisher]

A management algorithm for patients with intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC).

Intensive Care Med. 2019 12;45(12):1783-1794

Authors: Hawryluk GWJ, Aguilera S, Buki A, Bulger E, Citerio G, Cooper DJ, Arrastia RD, Diringer M, Figaji A, Gao G, Geocadin R, Ghajar J, Harris O, Hoffer A, Hutchinson P, Joseph M, Kitagawa R, Manley G, Mayer S, Menon DK, Meyfroidt G, Michael DB, Oddo M, Okonkwo D, Patel M, Robertson C, Rosenfeld JV, Rubiano AM, Sahuquillo J, Servadei F, Shutter L, Stein D, Stocchetti N, Taccone FS, Timmons S, Tsai E, Ullman JS, Vespa P, Videtta W, Wright DW, Zammit C, Chesnut RM

Abstract
BACKGROUND: Management algorithms for adult severe traumatic brain injury (sTBI) were omitted in later editions of the Brain Trauma Foundation's sTBI Management Guidelines, as they were not evidence-based.
METHODS: We used a Delphi-method-based consensus approach to address management of sTBI patients undergoing intracranial pressure (ICP) monitoring. Forty-two experienced, clinically active sTBI specialists from six continents comprised the panel. Eight surveys iterated queries and comments. An in-person meeting included whole- and small-group discussions and blinded voting. Consensus required 80% agreement. We developed heatmaps based on a traffic-light model where panelists' decision tendencies were the focus of recommendations.
RESULTS: We provide comprehensive algorithms for ICP-monitor-based adult sTBI management. Consensus established 18 interventions as fundamental and ten treatments not to be used. We provide a three-tier algorithm for treating elevated ICP. Treatments within a tier are considered empirically equivalent. Higher tiers involve higher risk therapies. Tiers 1, 2, and 3 include 10, 4, and 3 interventions, respectively. We include inter-tier considerations, and recommendations for critical neuroworsening to assist the recognition and treatment of declining patients. Novel elements include guidance for autoregulation-based ICP treatment based on MAP Challenge results, and two heatmaps to guide (1) ICP-monitor removal and (2) consideration of sedation holidays for neurological examination.
CONCLUSIONS: Our modern and comprehensive sTBI-management protocol is designed to assist clinicians managing sTBI patients monitored with ICP-monitors alone. Consensus-based (class III evidence), it provides management recommendations based on combined expert opinion. It reflects neither a standard-of-care nor a substitute for thoughtful individualized management.

PMID: 31659383 [PubMed - indexed for MEDLINE]

Brain Stem Cavernous Malformations: Operative Nuances of a Less-Invasive Resection Technique.

Oper Neurosurg (Hagerstown). 2018 08 01;15(2):153-173

Authors: Singh H, Elarjani T, da Silva HB, Shetty R, Kim L, Sekhar LN

Abstract
BACKGROUND: Different operative techniques are reported for the resection of brainstem cavernous malformations (BSCMs). The senior author has previously reported on a less-invasive technique of entering the brain stem with piecemeal removal of BSCMs, especially the deep-seated ones.
OBJECTIVE: To present a larger series of these lesions, emphasizing the approach to the brain stem via case selection. We discuss the nuances of the less-invasive operative technique through case illustrations and intraoperative videos.
METHODS: A retrospective review of 46 consecutive cases of BSCMs, with their clinical and radiographic data, was performed. Nine cases were selected to illustrate 7 different operative approaches, and discuss surgical nuances of the less-invasive technique unique to each.
RESULTS: Postoperative morbidity, defined as an increase in modified Rankin Scale, was observed in 5 patients (10.9%). A residual BSCM was present in 2 patients (4.3%); both underwent reoperation to remove the remainder. At follow-up of 31.1 ± 27.8 mo, 3 patients experienced recurrence (6.5%). Overall, 65% of our patients improved, 20% stayed the same, and 11% worsened postsurgery. Two patients died, yielding a mortality of 4.3%.
CONCLUSION: Using the less-invasive resection technique for piecemeal BSCM removal, in appropriately selected patients, has yielded comparable to improved patient outcomes over existing large series. In our experience, lateral, anterolateral, and posterolateral approaches are favorable over direct midline (dorsal or ventral) approaches. A thorough understanding of brain-stem safe-entry zones, in conjunction with appropriate approach selection, is key to a good outcome in challenging cases.

PMID: 29228395 [PubMed - indexed for MEDLINE]

Left transradial access for cerebral angiography.

J Neurointerv Surg. 2020 Apr;12(4):427-430

Authors: Barros G, Bass DI, Osbun JW, Chen SH, Brunet MC, Peterson EC, Walker M, Kelly CM, Levitt MR

Abstract
INTRODUCTION: Transradial access is increasingly used among neurointerventionalists as an alternative to the transfemoral route. Currently available data, building on the interventional cardiology experience, primarily focus on right radial access. However, there are clinical scenarios when left-sided access may be indicated. The purpose of this study was to evaluate the technical feasibility of left transradial access to cerebral angiography across three institutions.
METHODS: A retrospective chart review was performed for patients who underwent cerebral angiography accessed via the left radial artery at three institutions between January 2018 and July 2019. The outcome variables studied were successful catheterization, vascular complications, and fluoroscopic time.
RESULTS: Nineteen patients underwent a total of 25 cerebral angiograms via left transradial access for cerebral aneurysms (n=15), basilar occlusion (n=1), carotid stenosis (n=1), arteriovenous malformation (n=1), and cervical neurofibroma (n=1). There were 12 diagnostic angiograms and 13 interventional angiograms. The left transradial approach was chosen due to left vertebrobasilar pathology (n=22), right subclavian stenosis (n=2), and previous right arm amputation (n=1). There was one instance of radial artery spasm, which resolved after catheter removal, and one conversion to transfemoral access in an interventional case due to lack of distal catheter support. There were no procedural complications.
CONCLUSIONS: Left transradial access in diagnostic and interventional cerebral angiography is a technically feasible, safe, and an effective alternative when indicated, and may be preferable for situations in which pathology locations or anatomic limitations preclude right-sided radial access.

PMID: 31649205 [PubMed - indexed for MEDLINE]

Human Mesenchymal glioblastomas are characterized by an increased immune cell presence compared to Proneural and Classical tumors.

Oncoimmunology. 2019;8(11):e1655360

Authors: Kaffes I, Szulzewsky F, Chen Z, Herting CJ, Gabanic B, Velázquez Vega JE, Shelton J, Switchenko JM, Ross JL, McSwain LF, Huse JT, Westermark B, Nelander S, Forsberg-Nilsson K, Uhrbom L, Maturi NP, Cimino PJ, Holland EC, Kettenmann H, Brennan CW, Brat DJ, Hambardzumyan D

Abstract
Glioblastoma (GBM) is the most aggressive malignant primary brain tumor in adults, with a median survival of 14.6 months. Recent efforts have focused on identifying clinically relevant subgroups to improve our understanding of pathogenetic mechanisms and patient stratification. Concurrently, the role of immune cells in the tumor microenvironment has received increasing attention, especially T cells and tumor-associated macrophages (TAM). The latter are a mixed population of activated brain-resident microglia and infiltrating monocytes/monocyte-derived macrophages, both of which express ionized calcium-binding adapter molecule 1 (IBA1). This study investigated differences in immune cell subpopulations among distinct transcriptional subtypes of GBM. Human GBM samples were molecularly characterized and assigned to Proneural, Mesenchymal or Classical subtypes as defined by NanoString nCounter Technology. Subsequently, we performed and analyzed automated immunohistochemical stainings for TAM as well as specific T cell populations. The Mesenchymal subtype of GBM showed the highest presence of TAM, CD8+, CD3+ and FOXP3+ T cells, as compared to Proneural and Classical subtypes. High expression levels of the TAM-related gene AIF1, which encodes the TAM-specific protein IBA1, correlated with a worse prognosis in Proneural GBM, but conferred a survival benefit in Mesenchymal tumors. We used our data to construct a mathematical model that could reliably identify Mesenchymal GBM with high sensitivity using a combination of the aforementioned cell-specific IHC markers. In conclusion, we demonstrated that molecularly distinct GBM subtypes are characterized by profound differences in the composition of their immune microenvironment, which could potentially help to identify tumors amenable to immunotherapy.

PMID: 31646100 [PubMed]

Cost-Effectiveness of Buprenorphine-Naloxone Versus Extended-Release Naltrexone to Prevent Opioid Relapse.

Ann Intern Med. 2019 01 15;170(2):90-98

Authors: Murphy SM, McCollister KE, Leff JA, Yang X, Jeng PJ, Lee JD, Nunes EV, Novo P, Rotrosen J, Schackman BR

Abstract
Background: Not enough evidence exists to compare buprenorphine-naloxone with extended-release naltrexone for treating opioid use disorder.
Objective: To evaluate the cost-effectiveness of buprenorphine-naloxone versus extended-release naltrexone.
Design: Cost-effectiveness analysis alongside a previously reported randomized clinical trial of 570 adults in 8 U.S. inpatient or residential treatment programs.
Data Sources: Study instruments.
Target Population: Adults with opioid use disorder.
Time Horizon: 24-week intervention with an additional 12 weeks of observation.
Perspective: Health care sector and societal.
Interventions: Buprenorphine-naloxone and extended-release naltrexone.
Outcome Measures: Incremental costs combined with incremental quality-adjusted life-years (QALYs) and incremental time abstinent from opioids.
Results of Base-Case Analysis: Use of the health care sector perspective and a willingness-to-pay threshold of $100 000 per QALY showed buprenorphine-naloxone to be preferable to extended-release naltrexone in 97% of bootstrap replications at 24 weeks and in 85% at 36 weeks. Similar results were obtained with incremental time abstinent from opioids as an outcome and with use of the societal perspective.
Results of Sensitivity Analysis: The base-case results were sensitive to the cost of the 2 treatments and the success of randomized treatment initiation.
Limitation: Relatively short follow-up for a chronic condition, substantial missing data, no information on patient out-of-pocket and social service costs.
Conclusion: Buprenorphine-naloxone is preferred to extended-release naltrexone as first-line treatment when both options are clinically appropriate and patients require detoxification before initiating extended-release naltrexone.
Primary Funding Source: National Institute on Drug Abuse, National Institutes of Health.

PMID: 30557443 [PubMed - indexed for MEDLINE]

Worldwide research productivity in the field of full-endoscopic spine surgery: a bibliometric study.

Eur Spine J. 2020 01;29(1):153-160

Authors: Lin GX, Kotheeranurak V, Mahatthanatrakul A, Ruetten S, Yeung A, Lee SH, Ahn Y, Kim HS, Hofstetter C, Lee JH, Choi KC, Lewandrowski KU, Kim JS

Abstract
PURPOSE: To investigate the quantity and quality of articles in the field of full-endoscopic spine surgery (FESS) from different countries and assess characteristics of worldwide research productivity.
METHODS: Articles published from 1997 to July 23, 2018, were screened using the Web of Science database. All studies were assessed for the following parameters: the number of total publications, h-index, contribution of countries, authors, journals, and institutions.
RESULTS: A total of 408 articles were identified between 1997 and 2018. Between 1997 and 2017, the number of published articles tended to increase by 41 times. The largest number of articles was from China (30.15%), followed by South Korea (28.68%), the USA (13.97%), Germany (9.31%), and Japan (4.90%). The highest h-index was found for articles from South Korea (23), followed by the USA (18), Germany (16), China (11), and Japan (7). The highest number of articles was published in World Neurosurgery (12.50%), followed by Pain Physician (10.29%), Spine (6.62%), European Spine Journal (4.66%), and Journal of Neurosurgery: Spine (4.17%). Wooridul Spine Hospital published the largest number of articles (10.29%), followed by Tongji University (5.88%), University of Witten/Herdecke (5.39%), Brown University (5.15%), and Third Military Medical University (3.43%).
CONCLUSIONS: The number of articles published in the field of FESS has increased rapidly in the past 20 years. In terms of quantity, China is the most contributive country based on the number of publications. High-quality papers as measured by h-index and the large quantity is from South Korea (second only to China). These slides can be retrieved under Electronic Supplementary Material.

PMID: 31642995 [PubMed - indexed for MEDLINE]

Assessing drug efficacy against Plasmodium falciparum liver stages in vivo.

JCI Insight. 2018 01 11;3(1):

Authors: Flannery EL, Foquet L, Chuenchob V, Fishbaugher M, Billman Z, Navarro MJ, Betz W, Olsen TM, Lee J, Camargo N, Nguyen T, Schafer C, Sack BK, Wilson EM, Saunders J, Bial J, Campo B, Charman SA, Murphy SC, Phillips MA, Kappe SH, Mikolajczak SA

Abstract
Malaria eradication necessitates new tools to fight the evolving and complex Plasmodium pathogens. These tools include prophylactic drugs that eliminate Plasmodium liver stages and consequently prevent clinical disease, decrease transmission, and reduce the propensity for resistance development. Currently, the identification of these drugs relies on in vitro P. falciparum liver stage assays or in vivo causal prophylaxis assays using rodent malaria parasites; there is no method to directly test in vivo liver stage activity of candidate antimalarials against the human malaria-causing parasite P. falciparum. Here, we use a liver-chimeric humanized mouse (FRG huHep) to demonstrate in vivo P. falciparum liver stage development and describe the efficacy of clinically used and candidate antimalarials with prophylactic activity. We show that daily administration of atovaquone-proguanil (ATQ-PG; ATQ, 30 mg/kg, and PG, 10 mg/kg) protects 5 of 5 mice from liver stage infection, consistent with the use in humans as a causal prophylactic drug. Single-dose primaquine (60 mg/kg) has similar activity to that observed in humans, demonstrating the activity of this drug (and its active metabolites) in FRG huHep mice. We also show that DSM265, a selective Plasmodial dihydroorotate dehydrogenase inhibitor with causal prophylactic activity in humans, reduces liver stage burden in FRG huHep mice. Finally, we measured liver stage-to-blood stage transition of the parasite, the ultimate readout of prophylactic activity and measurement of infective capacity of parasites in the liver, to show that ATQ-PG reduces blood stage patency to below the limit of quantitation by quantitative PCR (qPCR). The FRG huHep model, thus, provides a platform for preclinical evaluation of drug candidates for liver stage causal prophylactic activity, pharmacokinetic/pharmacodynamics studies, and biological studies to investigate the mechanism of action of liver stage active antimalarials.

PMID: 29321371 [PubMed - indexed for MEDLINE]

Stromal cells from perinatal and adult sources modulate the inflammatory immune response in vitro by decreasing Th1 cell proliferation and cytokine secretion.

Stem Cells Transl Med. 2020 01;9(1):61-73

Authors: Khoury O, Atala A, Murphy SV

Abstract
Many immune-mediated conditions are associated with a dysregulated imbalance toward a Th1 response leading to disease onset, severity, and damage. Many of the therapies such as immunomodulators or anti-TNF-α antibodies often fall short in preventing disease progression and ameliorating disease conditions. Thus, new therapies that can target inflammatory environments would have a major impact in preventing the progression of inflammatory diseases. We investigated the role of human stromal cells derived from the amniotic fluid (AFSCs), the placenta (PLSCs), and bone marrow-derived mesenchymal stromal cells (BM-MSCs) in modulating the inflammatory response of in vitro-stimulated circulating blood-derived immune cells. Immune cells were isolated from the blood of healthy individuals and stimulated in vitro with antigens to activate inflammatory responses to stimuli. AFSC, BM-MSCs, and PLSCs were cocultured with stimulated leukocytes, neutrophils, or lymphocytes. Inflammatory cytokine production, neutrophil migration, enzymatic degranulation, T cell proliferation, and subsets were evaluated. Coculture of all three stromal cell types decreased the gene expression of inflammatory cytokines and enzymes such as IL-1β, IFN-γ, TNF-α, neutrophil elastase, and the transcription factor NF-κB in lipopolysaccharide-stimulated leukocytes. With isolated phytohemagglutinin-stimulated peripheral blood mononuclear cells, cells coculture leads to a decrease in lymphocyte proliferation. This effect correlated with decreased numbers of Th1 lymphocytes and decreased secreted levels of IFN-γ.

PMID: 31638323 [PubMed - indexed for MEDLINE]

Impact of an educational intervention on eye gaze behaviour in retinal image interpretation by consultant and trainee ophthalmologists.

Health Informatics J. 2019 Oct 19;:1460458219881337

Authors: Shirley K, Williams M, McLaughlin L, Parker N, Bond R

Abstract
This study uses eye-tracking technology to assess the differences in gaze behaviours between ophthalmologists of different experience levels while interpreting retinal images of diabetic retinopathy. The differences in gaze behaviours before and after a teaching intervention which introduced a suggested search strategy is also investigated. A total of 9 trainees and 10 consultant ophthalmologists interpreted six retinal images. They were then shown a 5-min tutorial that demonstrated a search strategy. This was followed by six further retinal image interpretations. Participants completed questionnaires indicating clinical signs seen, appropriate retinopathy grade, and confidence. Eye movements were tracked during each interpretation.Overall, trainees compared to consultants demonstrated more uncertain and unstructured gaze behaviours. Trainee eye gaze metrics included: longer interpretation time, 36.5 s (SD = 6.2 vs. 31.4 s) (SD = 4.2) (p = 0.024), higher visit count, 17.38 visits (SD = 5.13) versus 12.18 visits(SD = 2.64) (p = 0.01), higher proportion of fixation, 57.0 per cent (SD = 5) versus 50.5 per cent (SD = 5) (p = 0.05) and shorter time to first fixation, 0.232 s (SD = 0.10) versus 0.821 s (SD = 0.77) (p = 0.001), respectively. The teaching intervention resulted in more focused gaze patterns in both groups. Pre-intervention and post-intervention mean proportion fixation on areas of interest were 38.6 per cent (SD = 6.8) and 51.8 per cent (SD = 13.9) for the trainee group, respectively, and 39.9 per cent (SD = 4.1) and 50.9 per cent (SD = 9.3) for the consultant group (p = 0.01).Consultants used more systematic and efficient approaches than trainees during interpretation. After the introduction of a suggested search strategy, trainees showed trends towards consultant eye gaze behaviours. Eye tracking gives an interesting insight into the thought processes of physicians carrying out complex tasks. The implication is that eye tracking may have future use in teaching and assessment. Its use in objectively assessing different teaching strategies could be a valuable tool for medical education.

PMID: 31630618 [PubMed - as supplied by publisher]

CA 19-9 Response: A Surrogate to Predict Survival in Patients With Metastatic Pancreatic Adenocarcinoma.

Am J Clin Oncol. 2019 12;42(12):898-902

Authors: Diaz CL, Cinar P, Hwang J, Ko AH, Tempero MA

Abstract
OBJECTIVE: The objective of this study was to determine the features of carbohydrate antigen (CA) 19-9 decline that correlates best with survival benefit in patients with metastatic pancreatic cancer.
METHODS: This is a retrospective study of 225 patients with metastatic pancreatic cancer receiving first-line therapy. Analysis was performed by the Kaplan-Meier method and Cox-proportional hazards ratios. CA 19-9 decline was grouped into quartiles within different CA 19-9 baseline groups. Time to nadir and CA 19-9 decline at month-2 (M2) of therapy were evaluated for patients with a baseline level ≥1000 U/mL.
RESULTS: No significant trend in survival was observed across baseline CA 19-9 levels. The greatest survival benefit was seen with a ≥75% decline to nadir. Among those with a ≥75% decline and baseline ≥1000 U/mL, 43 of 57 patients had a >50% decline at M2 of therapy and additional survival benefit was observed with a slower decline to nadir. Small sample sizes limited analysis of other baseline groups. CA 19-9 decline at M2 was not predictive.
CONCLUSIONS: In patients with a CA 19-9 ≥1000 U/mL, serial CA 19-9 levels may be considered as a surrogate for serial imaging to evaluate treatment response, with a ≥75% decline indicating the greatest survival benefit. Survival was improved further in the setting of a slower decline to nadir with the highest benefit seen in patients with a nadir occurring at 4 months or longer.

PMID: 31634155 [PubMed - indexed for MEDLINE]