UW Neurological Surgery Recent PubMed Publications

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]

Commentary: Local Control and Toxicity of Multilevel Spine Stereotactic Body Radiotherapy.

Neurosurgery. 2020 02 01;86(2):E173-E174

Authors: Dunne EM, Liu M, Hofstetter C, Saigal R, Lo SS

PMID: 31628748 [PubMed - indexed for MEDLINE]

Direct Pulp Capping: Which is the Most Effective Biomaterial? A Retrospective Clinical Study.

Materials (Basel). 2019 Oct 16;12(20):

Authors: Paula A, Carrilho E, Laranjo M, Abrantes AM, Casalta-Lopes J, Botelho MF, Marto CM, Ferreira MM

Abstract
(1) Background: Recently, tricalcium silicate cements, such as Biodentine™, have emerged. This biomaterial has a calcium hydroxide base and characteristics like mineral aggregate trioxide cements, but has tightening times that are substantially more suitable for their application and other clinical advantages. (2) Methods: A retrospective clinical study was conducted with 20 patients, which included a clinical evaluation of the presence or absence of pulp inflammation compatible symptoms, radiographic evaluation of the periapical tissues, and structural alterations of the coronary restoration that supports pulp capping therapies with Biodentine™ and WhiteProRoot®MTA. (3) Results: This clinical study revealed similar success rates between mineral trioxide cement and tricalcium silicates cements at 6 months, with 100% and 95% success rates, respectively. There were no statistically significant differences between both biomaterials and between these and the various clinical circumstances, namely the absolute isolation of the operating field, exposure size, the aetiology of exposure, and even the type of restorative material used. (4) Conclusions: Biodentine™ demonstrated a therapeutic effect on the formation of a dentin bridge accompanied by slight inflammatory signs, with a high clinical success rate, indicating the possibility of its effective and safe use in dental pulp direct capping in humans, similar to the gold standard material.

PMID: 31623190 [PubMed]

Cytotoxic effects of a chlorhexidine mouthwash and of an enzymatic mouthwash on human gingival fibroblasts.

Odontology. 2020 Apr;108(2):260-270

Authors: Coelho AS, Laranjo M, Gonçalves AC, Paula A, Paulo S, Abrantes AM, Caramelo F, Ferreira MM, Silva MJ, Carrilho E, Botelho MF

Abstract
The aim of this study was to evaluate the cytotoxic effects of an enzymatic mouthwash and of a chlorhexidine mouthwash on human gingival fibroblasts. The metabolic activity of the fibroblasts exposed to each mouthwash was assessed by the MTT assay and the protein content was assessed by the SRB assay. The flow cytometry was used to evaluate the cell cycle and the types of cell death. The oxidative status was evaluated through the DCF and the DHE probes and the intracellular GSH concentration and the mitochondrial membrane potential through JC-1. The cytotoxicity of both mouthwashes was found to be dependent on the exposure time and on the concentration. However, the cytotoxicity of the enzymatic mouthwash was found to be lower than that of the chlorhexidine mouthwash. A trend towards increased oxidative stress was observed for both mouthwashes. After exposing the fibroblasts to the mouthwashes, a G2/M phase block was observed and cell death occurred predominantly by necrosis. The effects of chlorhexidine on fibroblasts were identified at lower concentrations than those used in clinical practice. Therefore, the use of chlorhexidine as an antiseptic in surgical and postoperative situations should be limited. In order to clarify the clinical significance of the enzymatic mouthwash cytotoxicity new clinical studies will be necessary.

PMID: 31624978 [PubMed - indexed for MEDLINE]

Chemoprophylaxis vaccination: Phase 1 study to explore stage-specific immunity to Plasmodium falciparum in U.S. adults.

Clin Infect Dis. 2019 Oct 17;:

Authors: Healy SA, Murphy SC, Hume JCC, Shelton L, Kuntz S, Van Voorhis WC, Moodie Z, Metch B, Wang R, Silver-Brace T, Fishbaugher M, Kennedy M, Finney OC, Chaturvedi R, Hobbs CV, Warner-Lubin M, Talley AK, Wong-Madden S, Stuart K, Wald A, Kappe SH, Kublin JG, Duffy PE

Abstract
BACKGROUND: Chemoprophylaxis vaccination with sporozoites (CVac) with chloroquine induces protection against homologous P. falciparum sporozoite (PfSPZ) challenge, but whether blood-stage parasite exposure is required for protection remains unclear. Chloroquine suppresses and clears blood-stage parasitemia, while other antimalarial drugs such as primaquine act against liver-stage parasites. Here, we evaluate CVac regimens using chloroquine or primaquine as the partner drug to discern whether blood stage parasite exposure impacts protection against homologous controlled human malaria infection.
METHODS: In a phase 1, randomized, partial double-blind, placebo-controlled study of 36 malaria-naïve adults, all CVac subjects received chloroquine prophylaxis and bites from 12-15 P. falciparum-infected mosquitoes (CVac-chloroquine arm) at 3 monthly iterations, and some received post-exposure primaquine (CVac-primaquine/chloroquine arm). Drug control subjects received primaquine, chloroquine, and uninfected mosquito bites. After chloroquine washout, subjects, including treatment-naïve infectivity controls, underwent homologous PfSPZ controlled human malaria infection and were monitored for parasitemia for 21 days.
RESULTS: No serious adverse events occurred. During CVac, all but one subject in the study remained blood smear-negative while only one subject (primaquine/chloroquine arm) remained PCR-negative. Upon challenge, compared to infectivity controls, 3/3 chloroquine arm subjects displayed delayed patent parasitemia (p=0.01) but not sterile protection, while 3/11 primaquine/chloroquine subjects remained blood smear negative.
CONCLUSIONS: CVac-primaquine/chloroquine is safe and induces sterile immunity to P. falciparum in some recipients, but a single 45 mg dose of primaquine post-exposure does not completely prevent blood-stage parasitemia. Unlike previous studies, CVac-chloroquine did not produce sterile immunity.
CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT01500980.

PMID: 31621832 [PubMed - as supplied by publisher]

Do patient characteristics moderate the effect of extended-release naltrexone (XR-NTX) for opioid use disorder?

J Subst Abuse Treat. 2018 02;85:61-65

Authors: Friedmann PD, Wilson D, Nunes EV, Hoskinson R, Lee JD, Gordon M, Murphy SM, Bonnie RJ, Chen DT, Boney TY, O'Brien CP

Abstract
BACKGROUND: Extended release naltrexone (XR-NTX) injected intramuscularly monthly has been shown to reduce relapse in persons with opioid use disorder. Baseline factors, including patients' demographics, comorbidities and lifestyle, may help identify patients who will benefit most or least from XR-NTX treatment.
METHODS: Potential moderators of XR-NTX's effect were examined in the largest North American randomized open-label effectiveness trial of XR-NTX. Relapse status (Yes/No) at 6-month follow-up was regressed on treatment group (XR-NTX, N=153; or Treatment-as-Usual [TAU], N=155), baseline covariates, and their two-way interaction to identify moderator effects. Baseline covariates included age, gender, summary scores for depression, suicidal thoughts, drug abuse risk, substance use, medical, psychiatric and employment status, socialization, legal and family/social issues, history of abuse and quality of life measures.
RESULTS: Alcohol use to intoxication in the 30days before randomization was a significant moderator: during the treatment phase, those who reported being recently intoxicated before randomization to XR-NTX relapsed to opioids at a rate (56%) similar to TAU (58%), while those without alcohol intoxication in the prior 30days had a lower rate of opioid relapse (41% vs. 65%, respectively, P<0.04).
CONCLUSIONS: XR-NTX appeared to work equally well across subgroups with diverse demographic, addiction, mental health and environmental characteristics, with the possible exception of working better among those without recent alcohol intoxication. These findings should be reassuring to practitioners increasingly using XR-NTX as medical addiction therapy in diverse and often vulnerable populations.

PMID: 28236511 [PubMed - indexed for MEDLINE]

Quantitative Volumetric Imaging and Clinical Outcome Characterization of Symptomatic Concussion in 10- to 14-Year-Old Adolescent Athletes.

J Head Trauma Rehabil. 2018 Nov/Dec;33(6):E1-E10

Authors: Mac Donald CL, Barber J, Wright J, Coppel D, De Lacy N, Ottinger S, Peck S, Panks C, Zalewski K, Sun S, Temkin N

Abstract
OBJECTIVE: Prior work suggests that younger athletes may be more vulnerable to postconcussive syndrome. We investigated measures of clinical outcome and quantitative volumetric imaging in 10- to 14-year-old adolescent athletes to better understand the impact of concussion on this younger population.
SETTING: Outpatient clinics.
PARTICIPANTS: Ten- to 14-year-old symptomatic pediatric sports concussion patients and typically developing active controls.
DESIGN: Prospective, observational multiclinic study.
MAIN MEASURES: Demographics, magnetic resonance imaging, clinical assessments (neurocognitive function, postconcussive symptoms, mental health symptoms, quality of life).
RESULTS: Neuropsychological performance was comparable between groups while symptoms of mental health were discriminating and comprised the top regression model describing factors related to overall health behavior impairment. Concussion patients had smaller total brain volume as well as total intracranial volume in comparison with controls even though there was no difference on measures of natural development (age, height, weight, education, gender, and handedness).
CONCLUSIONS: Findings indicate that 10- to 14-year-old concussion patients symptomatic at 1 month more likely exhibit mental health symptoms impairing health behavior than cognitive dysfunction. There may be a vulnerability for those with smaller brain volumes at the time of the exposure. The study provides new data to support further investigation into risk factors for prolonged symptoms in this younger athlete population.

PMID: 29385018 [PubMed - indexed for MEDLINE]