UW Neurological Surgery Recent PubMed Publications

Bioprinted Skin Recapitulates Normal Collagen Remodeling in Full-thickness Wounds.

Tissue Eng Part A. 2019 Dec 20;:

Authors: Jorgensen AM, Varkey M, Gorkun A, Clouse C, Xu L, Chou Z, Murphy S, Molnar J, Lee SJ, Yoo JJ, Soker S, Atala A

Abstract
Over 1 million burn injuries are treated annually in the United States, and current tissue engineered skin fails to meet the need for full-thickness replacement. Bioprinting technology has allowed fabrication of full-thickness skin and has demonstrated the ability to close full-thickness wounds. However, analysis of collagen remodeling in wounds treated with bioprinted skin has not been reported. The purpose of this study is to demonstrate the utility of bioprinted skin for epidermal barrier formation and normal collagen remodeling in full-thickness wounds. Human keratinocytes, melanocytes, fibroblasts, dermal microvascular endothelial cells, follicle dermal papilla cells, and adipocytes were suspended in fibrinogen bioink and bioprinted to form a tri-layer skin structure. Bioprinted skin was implanted onto 2.5 x 2.5cm full-thickness excisional wounds on athymic mice, compared with wounds treated with hydrogel only or untreated wounds. Total wound closure, epithelialization, and contraction was quantified, and skin samples were harvested at 21 days for histology. Picrosirius red staining was used to quantify collagen fiber orientation, length, and width. Immunohistochemical (IHC) staining was performed to confirm epidermal barrier formation, dermal maturation, vascularity, and human cell integration. All bioprinted skin treated wounds closed by day 21, compared with open control wounds. Wound closure in bioprinted skin treated wounds was primarily due to epithelialization. In contrast, control hydrogel and untreated groups had sparse wound coverage and incomplete closure driven primarily by contraction. Picrosirius red staining confirmed a normal basket weave collagen organization in bioprinted skin-treated wounds compared with parallel collagen fibers in hydrogel only and untreated wounds. IHC staining at day 21 demonstrated the presence of human cells in the regenerated dermis, the formation of a stratified epidermis, dermal maturation, and blood vessel formation in bioprinted skin, none of which were present in control hydrogel treated wounds. Bioprinted skin accelerated full-thickness wound closure by promoting epidermal barrier formation, without increasing contraction. This healing process is associated with human cells from the bioprinted skin laying down a healthy, basket-weave collagen network. The remodeled skin is phenotypically similar to human skin and composed of a composite of graft and infiltrating host cells.

PMID: 31861970 [PubMed - as supplied by publisher]

Medical oncology management of advanced hepatocellular carcinoma 2019: a reality check.

Front Med. 2019 Dec 21;:

Authors: Lee A, Lee FC

Abstract
In terms of global cancer-related deaths, hepatocellular carcinoma (HCC) has the fourth highest mortality rate. Up until 2017, treatment of advanced HCC was largely limited to sorafenib, an oral tyrosine kinase inhibitor, with little to no success in the development of alternative treatment options. However, in the past two years, there has been an unprecedented increase in both the number and type of treatment options available for HCC. As of 2019, the US FDA has approved four oral tyrosine kinase inhibitors, two immune checkpoint inhibitors, and one anti-angiogenesis antibody for the treatment of HCC. Even with this new variety, systemic treatment of advanced HCC remains largely unsatisfactory, and the median survival rate stands at approximately one year. The expected breakthrough of using immune checkpoint inhibitors in advanced HCC did not materialize in 2019. The use of immune checkpoint inhibitors in conjunction with oral tyrosine kinase inhibitors or anti-angiogenesis medications is the current clinical research trend, the results of which are eagerly anticipated. Despite limited progress in survival, HCC research is currently experiencing a period of growth and innovation, and there is hope for significant advances in the treatment of advanced HCC as the field continues to develop.

PMID: 31863306 [PubMed - as supplied by publisher]

Recurrent Giant Middle Cerebral Artery Aneurysm: Reclipping With a Second Radial Artery Bypass: 2-Dimensional Operative Video.

Oper Neurosurg (Hagerstown). 2018 11 01;15(5):602

Authors: Shetty R, Sekhar LN

PMID: 31860717 [PubMed - indexed for MEDLINE]

A mixed-methods needs assessment of traumatic brain injury care in a low- and middle-income country setting: building neurocritical care capacity at two major hospitals in Cambodia.

J Neurosurg. 2019 Dec 20;:1-7

Authors: Barkley AS, Spece LJ, Barros LM, Bonow RH, Ravanpay A, Ellenbogen R, Huoy P, Thy T, Sothea S, Pak S, LoGerfo J, Lele AV

Abstract
OBJECTIVE: The high global burden of traumatic brain injury (TBI) disproportionately affects low- and middle-income countries (LMICs). These settings also have the greatest disparity in the availability of surgical care in general and neurosurgical care in particular. Recent focus has been placed on alleviating this surgical disparity. However, most capacity assessments are purely quantitative, and few focus on concomitantly assessing the complex healthcare system needs required to care for these patients. The objective of the present study was to use both quantitative and qualitative assessment data to establish a comprehensive approach to inform capacity-development initiatives for TBI care at two hospitals in an LMIC, Cambodia.
METHODS: This mixed-methods study used 3 quantitative assessment tools: the World Health Organization Personnel, Infrastructure, Procedures, Equipment, Supplies (WHO PIPES) checklist, the neurosurgery-specific PIPES (NeuroPIPES) checklist, and the Neurocritical Care (NCC) checklist at two hospitals in Phnom Penh, Cambodia. Descriptive statistics were obtained for quantitative results. Qualitative semistructured interviews of physicians, nurses, and healthcare administrators were conducted by a single interviewer. Responses were analyzed using a thematic content analysis approach and coded to allow categorization under the PIPES framework.
RESULTS: Of 35 healthcare providers approached, 29 (82.9%) participated in the surveys, including 19 physicians (65.5%) and 10 nurses (34.5%). The majority had fewer than 5 years of experience (51.7%), were male (n = 26, 89.7%), and were younger than 40 years of age (n = 25, 86.2%). For both hospitals, WHO PIPES scores were lowest in the equipment category. However, using the NCC checklist, both hospitals scored higher in equipment (81.2% and 62.7%) and infrastructure (78.6% and 69.6%; hospital 1 and 2, respectively) categories and lowest in the training/continuing education category (41.7% and 33.3%, hospital 1 and 2, respectively). Using the PIPES framework, analysis of the qualitative data obtained from interviews revealed a need for continuing educational initiatives for staff, increased surgical and critical care supplies and equipment, and infrastructure development. The analysis further elucidated barriers to care, such as challenges with time availability for experienced providers to educate incoming healthcare professionals, issues surrounding prehospital care, maintenance of donated supplies, and patient poverty.
CONCLUSIONS: This mixed-methods study identified areas in supplies, equipment, and educational/training initiatives as areas for capacity development for TBI care in an LMIC such as Cambodia. This first application of the NCC checklist in an LMIC setting demonstrated limitations in its use in this setting. Concomitant qualitative assessments provided insight into barriers otherwise undetected in quantitative assessments.

PMID: 31860819 [PubMed - as supplied by publisher]

Health literacy, sociodemographic factors, and cognitive training in the active study of older adults.

Int J Geriatr Psychiatry. 2019 04;34(4):563-570

Authors: Verney SP, Gibbons LE, Dmitrieva NO, Kueider AM, Williams MW, Meyer OL, Manly JJ, Sisco SM, Marsiske M

Abstract
OBJECTIVE: Health literacy is critical for understanding information from health-care providers and correct use of medications and includes the capacity to filter other information in navigating health care systems. Older adults with low health literacy exhibit more chronic health conditions, worse physical functioning, and poorer mental health. This study examined the relationship between sociodemographic variables and health literacy, and the impact of cognitive training on change in health literacy over 10 years in older adults.
METHODS: Participants (N = 2,802) aged 65 years and older completed assessments, including reading and numeracy health literacy items, as part of the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study. We evaluated baseline sociodemographic variables and change in health literacy over a 10-year period in individuals exposed to cognitive training in reasoning, processing speed, memory, or a no-contact control condition.
RESULTS: Age, sex, race, education level, and general cognitive functioning at baseline were all associated with baseline health literacy in older adults. Predictors of change in health literacy over the 10-year follow-up were age, race, education level, general cognitive functioning, and neighborhood income; disparities in health literacy because of race attenuated over time, while the effect of age increased over time. Health literacy was generally stable across the ACTIVE intervention groups over 10 years.
CONCLUSIONS: The present study showed important disparities in health literacy level and change over 10 years. Cognitive training did not significantly impact health literacy, suggesting that alternative approaches are needed to reduce the disparities.

PMID: 30548889 [PubMed - indexed for MEDLINE]

Prospective Validation of an mRNA-based Urine Test for Surveillance of Patients with Bladder Cancer.

Eur Urol. 2019 05;75(5):853-860

Authors: Valenberg FJPV, Hiar AM, Wallace E, Bridge JA, Mayne DJ, Beqaj S, Sexton WJ, Lotan Y, Weizer AZ, Jansz GK, Stenzl A, Danella JF, Shepard B, Cline KJ, Williams MB, Montgomery S, David RD, Harris R, Klein EW, Bradford TJ, Wolk FN, Westenfelder KR, Trainer AF, Richardson TA, Egerdie RB, Goldfarb B, Zadra JA, Ge S, Zhao S, Simon IM, Campbell SA, Rhees B, Bates MP, Higuchi RG, Witjes JA

Abstract
BACKGROUND: A fast, noninvasive test with high sensitivity (SN) and a negative predictive value (NPV), which is able to detect recurrences in bladder cancer (BC) patients, is needed. A newly developed urine assay, Xpert Bladder Cancer Monitor (Xpert), measures five mRNA targets (ABL1, CRH, IGF2, UPK1B, and ANXA10) that are frequently overexpressed in BC.
OBJECTIVE: To validate Xpert characteristics in patients previously diagnosed with non-muscle-invasive BC.
DESIGN, SETTING, AND PARTICIPANTS: Voided precystoscopy urine samples were prospectively collected at 22 sites. Xpert, cytology, and UroVysion were performed. If cystoscopy was suspicious for BC, a histologic examination was performed. Additionally, technical validation was performed and specificity was determined in patients without a history or clinical evidence of BC.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Test characteristics were calculated based on cystoscopy and histology results, and compared between Xpert, cytology, and UroVysion.
RESULTS AND LIMITATIONS: Of the eligible patients, 239 with a history of BC had results for all assays. The mean age was 71 yr; 190 patients were male, 53 never smoked, and 64% had previous intravesical immunotherapy (35%) or chemotherapy (29%). Forty-three cases of recurrences occurred. Xpert had overall SN of 74% (95% confidence interval [CI]: 60-85) and 83% (95% CI: 64-93) for high-grade (HG) tumors. The NPV was 93% (95% CI: 89-96) overall and 98% (95% CI: 94-99) for HG tumors. Specificity was 80% (95% CI: 73-85). Xpert SN and NPV were superior to those of cytology and UroVysion. Specificity in non-BC individuals (n=508) was 95% (95% CI: 93-97).
CONCLUSIONS: Xpert has an improved NPV compared with UroVysion and cytology in patients under follow-up for BC. It represents a promising tool for excluding BC in these patients, reducing the need for cystoscopy.
PATIENT SUMMARY: Xpert is an easy-to-perform urine test with good performance compared with standard urine tests. It should help optimize the follow-up of recurrent bladder cancer patients.

PMID: 30553612 [PubMed - indexed for MEDLINE]

Intermittent Hypoxia Disrupts Adult Neurogenesis and Synaptic Plasticity in the Dentate Gyrus.

J Neurosci. 2019 02 13;39(7):1320-1331

Authors: Khuu MA, Pagan CM, Nallamothu T, Hevner RF, Hodge RD, Ramirez JM, Garcia AJ

Abstract
Individuals with sleep apnea often exhibit changes in cognitive behaviors consistent with alterations in the hippocampus. It is hypothesized that adult neurogenesis in the dentate gyrus is an ongoing process that maintains normal hippocampal function in many mammalian species, including humans. However, the impact of chronic intermittent hypoxia (IH), a principal consequence of sleep apnea, on hippocampal adult neurogenesis remains unclear. Using a murine model, we examined the impact of 30 d of IH (IH30) on adult neurogenesis and synaptic plasticity in the dentate gyrus. Although IH30 did not affect paired-pulse facilitation, IH30 suppressed long-term potentiation (LTP). Immunohistochemical experiments also indicate that IH perturbs multiple aspects of adult neurogenesis. IH30 increased the number of proliferating Sox2+ neural progenitor cells in the subgranular zone yet reduced the number of doublecortin-positive neurons. Consistent with these findings, cell lineage tracing revealed that IH30 increased the proportion of radial glial cells in the subgranular zone, yet decreased the proportion of adult-born neurons in the dentate gyrus. While administration of a superoxide anion scavenger during IH did not prevent neural progenitor cell proliferation, it mitigated the IH-dependent suppression of LTP and prevented adult-born neuron loss. These data demonstrate that IH causes both reactive oxygen species-dependent and reactive oxygen species-independent effects on adult neurogenesis and synaptic plasticity in the dentate gyrus. Our findings identify cellular and neurophysiological changes in the hippocampus that may contribute to cognitive and behavioral deficits occurring in sleep apnea.SIGNIFICANCE STATEMENT Individuals with sleep apnea experience periods of intermittent hypoxia (IH) that can negatively impact many aspects of brain function. Neurons are continually generated throughout adulthood to support hippocampal physiology and behavior. This study demonstrates that IH exposure attenuates hippocampal long-term potentiation and reduces adult neurogenesis. Antioxidant treatment mitigates these effects indicating that oxidative signaling caused by IH is a significant factor that impairs synaptic plasticity and reduces adult neurogenesis in the hippocampus.

PMID: 30587544 [PubMed - indexed for MEDLINE]

Age and sex-mediated differences in six-month outcomes after mild traumatic brain injury in young adults: a TRACK-TBI study.

Neurol Res. 2019 Jul;41(7):609-623

Authors: Yue JK, Levin HS, Suen CG, Morrissey MR, Runyon SJ, Winkler EA, Puffer RC, Deng H, Robinson CK, Rick JW, Phelps RRL, Sharma S, Taylor SR, Vassar MJ, Cnossen MC, Lingsma HF, Gardner RC, Temkin NR, Barber J, Dikmen SS, Yuh EL, Mukherjee P, Stein MB, Cage TA, Valadka AB, Okonkwo DO, Manley GT, TRACK-TBI Investigators

Abstract
Introduction: Risk factors for young adults with mTBI are not well understood. Improved understanding of age and sex as risk factors for impaired six-month outcomes in young adults is needed. Methods: Young adult mTBI subjects aged 18-39 years (18-29y; 30-39y) with six-month outcomes were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study. Multivariable regressions were performed for outcomes with age, sex, and the interaction factor age-group*sex as variables of interest, controlling for demographic and injury variables. Mean-differences (B) and 95% CIs are reported. Results: One hundred mTBI subjects (18-29y, 70%; 30-39y, 30%; male, 71%; female, 29%) met inclusion criteria. On multivariable analysis, age-group*sex was associated with six-month post-traumatic stress disorder (PTSD; PTSD Checklist-Civilian version); compared with female 30-39y, female 18-29y (B= -19.55 [-26.54, -4.45]), male 18-29y (B= -19.70 [-30.07, -9.33]), and male 30-39y (B= -15.49 [-26.54, -4.45]) were associated with decreased PTSD symptomatology. Female sex was associated with decreased six-month functional outcome (Glasgow Outcome Scale-Extended (GOSE): B= -0.6 [1.0, -0.1]). Comparatively, 30-39y scored higher on six-month nonverbal processing speed (Wechsler Adult Intelligence Scale-Processing Speed Index (WAIS-PSI); B= 11.88, 95% CI [1.66, 22.09]). Conclusions: Following mTBI, young adults aged 18-29y and 30-39y may have different risks for impairment. Sex may interact with age for PTSD symptomatology, with females 30-39y at highest risk. These results may be attributable to cortical maturation, biological response, social modifiers, and/or differential self-report. Confirmation in larger samples is needed; however, prevention and rehabilitation/counseling strategies after mTBI should likely be tailored for age and sex.

PMID: 31007155 [PubMed - indexed for MEDLINE]

Effects of Electronic Cigarettes on Oral Cavity: A Systematic Review.

J Evid Based Dent Pract. 2019 12;19(4):101318

Authors: Ralho A, Coelho A, Ribeiro M, Paula A, Amaro I, Sousa J, Marto C, Ferreira M, Carrilho E

Abstract
INTRODUCTION: The increase in the use of electronic cigarettes (e-cigs) in young people and the lack of knowledge of the health effects of smoking in the short and long term are worrying. Although the oral cavity is the first to interact directly with the e-cig aerosol, studies on potential oral cavity lesions are still limited and there is some controversy about safety.
OBJECTIVE: To perform a systematic review to evaluate the adverse effects of e-cigs on oral health.
MATERIALS AND METHODS: The research was conducted using Cochrane Library, Embase, PubMed, and Web of Science. The research was limited to articles in English, Portuguese, and Spanish, published between January 2003 and November 2018. The research question was formulated according to the population, intervention, comparison, outcome (PICO) strategy. The quality of the methodology of each study was evaluated following the guidelines described in the Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) tool.
RESULTS: The initial search resulted in 432 articles, of which only eight were included for analysis. Periodontal and peri-implant clinical and radiographic parameters (plaque index, clinical attachment loss, probing depth, peri-implant bone loss, and radiographic bone level) are worse, and proinflammatory cytokine levels are higher among electronic and conventional cigarette smokers than among nonsmokers. Bleeding on probing was higher in nonsmokers than in conventional cigarette smokers and e-cig users. Nine different lesions of the oral mucosa were detected, with nicotinic stomatitis, hairy tongue, and angular cheilitis being more prevalent in e-cig consumers.
CONCLUSION: The results suggest that e-cigs are less harmful than conventional cigarettes. However, there is also a greater susceptibility of e-cig consumers to developing alterations in oral biological tissues than ex-smokers or nonsmokers. There is still a clear need for the development of new studies.

PMID: 31843181 [PubMed - indexed for MEDLINE]

The role of prefrontal cortex in the control of feature attention in area V4.

Nat Commun. 2019 12 16;10(1):5727

Authors: Bichot NP, Xu R, Ghadooshahy A, Williams ML, Desimone R

Abstract
When searching for an object in a cluttered scene, we can use our memory of the target object features to guide our search, and the responses of neurons in multiple cortical visual areas are enhanced when their receptive field contains a stimulus sharing target object features. Here we tested the role of the ventral prearcuate region (VPA) of prefrontal cortex in the control of feature attention in cortical visual area V4. VPA was unilaterally inactivated in monkeys performing a free-viewing visual search for a target stimulus in an array of stimuli, impairing monkeys' ability to find the target in the array in the affected hemifield, but leaving intact their ability to make saccades to targets presented alone. Simultaneous recordings in V4 revealed that the effects of feature attention on V4 responses were eliminated or greatly reduced while leaving the effects of spatial attention on responses intact. Altogether, the results suggest that feedback from VPA modulates processing in visual cortex during attention to object features.

PMID: 31844117 [PubMed - indexed for MEDLINE]

Magnetic resonance vessel wall imaging in cerebrovascular diseases

Neurosurg Focus. 2019 12 13;47(6):E4

Authors: Young CC, Bonow RH, Barros G, Mossa-Basha M, Kim LJ, Levitt MR

Abstract
Cerebrovascular diseases manifest as abnormalities of and disruption to the intracranial vasculature and its capacity to carry blood to the brain. However, the pathogenesis of many cerebrovascular diseases begins in the vessel wall. Traditional luminal and perfusion imaging techniques do not provide adequate information regarding the differentiation, onset, or progression of disease. Intracranial high-resolution MR vessel wall imaging (VWI) has emerged as an invaluable technique for understanding and evaluating cerebrovascular diseases. The location and pattern of contrast enhancement in intracranial VWI provides new insight into the inflammatory etiology of cerebrovascular diseases and has potential to permit earlier diagnosis and treatment. In this report, technical considerations of VWI are discussed and current applications of VWI in vascular malformations, blunt cerebrovascular injury/dissection, and steno-occlusive cerebrovascular vasculopathies are reviewed.

PMID: 31846249 [PubMed - indexed for MEDLINE]

Quantifying neurologic disease using biosensor measurements in-clinic and in free-living settings in multiple sclerosis.

NPJ Digit Med. 2019;2:123

Authors: Chitnis T, Glanz BI, Gonzalez C, Healy BC, Saraceno TJ, Sattarnezhad N, Diaz-Cruz C, Polgar-Turcsanyi M, Tummala S, Bakshi R, Bajaj VS, Ben-Shimol D, Bikhchandani N, Blocker AW, Burkart J, Cendrillon R, Cusack MP, Demiralp E, Jooste SK, Kharbouch A, Lee AA, Lehár J, Liu M, Mahadevan S, Murphy M, Norton LC, Parlikar TA, Pathak A, Shoeb A, Soderberg E, Stephens P, Stoertz AH, Thng F, Tumkur K, Wang H, Rhodes J, Rudick RA, Ransohoff RM, Phillips GA, Bruzik E, Marks WJ, Weiner HL, Snyder TM

Abstract
Technological advances in passive digital phenotyping present the opportunity to quantify neurological diseases using new approaches that may complement clinical assessments. Here, we studied multiple sclerosis (MS) as a model neurological disease for investigating physiometric and environmental signals. The objective of this study was to assess the feasibility and correlation of wearable biosensors with traditional clinical measures of disability both in clinic and in free-living in MS patients. This is a single site observational cohort study conducted at an academic neurological center specializing in MS. A cohort of 25 MS patients with varying disability scores were recruited. Patients were monitored in clinic while wearing biosensors at nine body locations at three separate visits. Biosensor-derived features including aspects of gait (stance time, turn angle, mean turn velocity) and balance were collected, along with standardized disability scores assessed by a neurologist. Participants also wore up to three sensors on the wrist, ankle, and sternum for 8 weeks as they went about their daily lives. The primary outcomes were feasibility, adherence, as well as correlation of biosensor-derived metrics with traditional neurologist-assessed clinical measures of disability. We used machine-learning algorithms to extract multiple features of motion and dexterity and correlated these measures with more traditional measures of neurological disability, including the expanded disability status scale (EDSS) and the MS functional composite-4 (MSFC-4). In free-living, sleep measures were additionally collected. Twenty-three subjects completed the first two of three in-clinic study visits and the 8-week free-living biosensor period. Several biosensor-derived features significantly correlated with EDSS and MSFC-4 scores derived at visit two, including mobility stance time with MSFC-4 z-score (Spearman correlation -0.546; p = 0.0070), several aspects of turning including turn angle (0.437; p = 0.0372), and maximum angular velocity (0.653; p = 0.0007). Similar correlations were observed at subsequent clinic visits, and in the free-living setting. We also found other passively collected signals, including measures of sleep, that correlated with disease severity. These findings demonstrate the feasibility of applying passive biosensor measurement techniques to monitor disability in MS patients both in clinic and in the free-living setting.

PMID: 31840094 [PubMed]

Chemotherapy in Esthesioneuroblastoma/Olfactory Neuroblastoma: An Analysis of the Surveillance Epidemiology and End Results (SEER) 1973-2015 Database.

Am J Clin Oncol. 2020 03;43(3):203-209

Authors: Cranmer LD, Chau B, Rockhill JK, Ferreira M, Liao JJ

Abstract
OBJECTIVE: Chemotherapy has been proposed as an adjunct to primary local therapy in esthesioneuroblastoma (ENB)/olfactory neuroblastoma (ON), but its role has not been precisely defined. Here, we evaluated its role in ENB treatment.
MATERIALS AND METHODS: The Surveillance Epidemiology and End Results (SEER) database was queried for ENB/ON (International Classification of Diseases-3 9522). Cases met criteria for inclusion if they were unique, had a primary location in the nasal cavity, and had adequate information for Kadish staging derivation. Univariable and multivariable Cox analyses assessed chemotherapy treatment effect on disease-specific survival (DSS) and overall survival (OS). Multiple imputation addressed missing data. A P<0.05 was designated for statistical significance.
RESULTS: In adjusted multivariable analyses, chemotherapy treatment was associated with inferior DSS (hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.21-2.51; P=0.003) and OS (HR, 1.71; 95% CI, 1.26-2.32; P=0.001). Among the subset with local or regional disease treated with surgery and/or radiation therapy, chemotherapy remained associated with inferior outcomes DSS (HR, 2.78; 95% CI, 1.63-4.74; P<0.001) and OS (HR, 2.18; 95% CI, 1.45-3.27; P<0.001). Chemotherapy treatment misclassification did not explain these findings.
CONCLUSIONS: This analysis does not support chemotherapy to improve either DSS or OS in primary ENB/ON treatment, after controlling for known ENB prognostic factors available from SEER. Other prognostic and treatment selection factors could exist which were not controlled in these analyses. Chemotherapy could beneficially affect outcomes other than DSS or OS. Although the concerns have been expressed regarding chemotherapy treatment misclassification in SEER, their analyses did not identify such misclassification as an explanation for our findings.

PMID: 31842117 [PubMed - indexed for MEDLINE]

Modulating neuroinflammation and oxidative stress to prevent epilepsy and improve outcomes after traumatic brain injury.

Neuropharmacology. 2019 Dec 06;:107907

Authors: Eastman CL, D'Ambrosio R, Ganesh T

Abstract
Traumatic brain injury (TBI) is a leading cause of death and disability in young adults worldwide. TBI survival is associated with persistent neuropsychiatric and neurological impairments, including posttraumatic epilepsy (PTE). To date, no pharmaceutical treatment has been found to prevent PTE or ameliorate neurological/neuropsychiatric deficits after TBI. Brain trauma results in immediate mechanical damage to brain cells and blood vessels that may never be fully restored given the limited regenerative capacity of brain tissue. This primary insult unleashes cascades of events, prominently including neuroinflammation and massive oxidative stress that evolve over time, expanding the brain injury, but also clearing cellular debris and establishing homeostasis in the region of damage. Accumulating evidence suggests that oxidative stress and neuroinflammatory sequelae of TBI contribute to posttraumatic epileptogenesis. This review will focus on possible roles of reactive oxygen species (ROS), their interactions with neuroinflammation in posttraumatic epileptogenesis, and emerging therapeutic strategies after TBI. We propose that inhibitors of the professional ROS-generating enzymes, the NADPH oxygenases and myeloperoxidase alone, or combined with selective inhibition of cyclooxygenase mediated signaling may have promise for the treatment or prevention of PTE and other sequelae of TBI.

PMID: 31837825 [PubMed - as supplied by publisher]

A Multi-Criteria Decision-Making Model for Evaluating Senior Daycare Center Locations.

Int J Environ Res Public Health. 2019 12 10;16(24):

Authors: Lee AHI, Kang HY

Abstract
Many developed and developing countries are facing an imminent population aging and rapid demographics changing problem. The need of various kinds of eldercare is increasing tremendously. A senior daycare center, very similar to a daycare center for toddlers and preschoolers, can provide the elderly a place to go during daytime and have a more diversified social life. In this research, a senior daycare center location evaluation problem is studied, and a model for facilitating the decision-making of the senior daycare center location is constructed by considering the benefits, opportunities, costs, and risks (BOCR) of the locations. Senior daycare center location evaluation factors are listed first through literature review and interview with experts. These factors are used to construct a network, which is applied to prepare a questionnaire to ask about the influences of a criterion to other criteria. The interrelationships among the criteria are calculated by adopting fuzzy interpretative structural modeling (FISM). Based on the results from the FISM, a fuzzy analytic network process (FANP) questionnaire is given out, and the results are used to determine the priorities of the criteria. In addition, the final ranking of the senior daycare center locations can be obtained. The research results can provide references for prospective senior daycare center providers for making relevant decisions.

PMID: 31835613 [PubMed - indexed for MEDLINE]

Endovascular management of iatrogenic dissection into the petrous segment of the internal carotid artery during mechanical thrombectomy for acute stroke.

J Clin Neurosci. 2020 Jan;71:273-274

Authors: Bass DI, Walker M, Kim LJ, Levitt MR

Abstract
Iatrogenic dissection of the internal carotid artery is a well-known complication that can occur during mechanical thrombectomy for acute stroke. The vast majority of these injuries are limited to the cervical segment, and only in exceptional circumstances do they require surgical intervention. In the present case, extension of the lesion into the petrous segment of the carotid artery resulted in an acute neurologic decline necessitating emergent endovascular repair. We discuss the nuances of managing an exceptionally rare presentation of this complication.

PMID: 31836382 [PubMed - indexed for MEDLINE]

Editorial.

Curr Opin Pharmacol. 2019 Dec 10;:

Authors: Williams M, Trist D

PMID: 31836467 [PubMed - as supplied by publisher]

Litter effects: Comments on Golub and Sobin's "Statistical modeling of litter as a random effect in mixed models to manage "intralitter likeness"".

Neurotoxicol Teratol. 2020 Jan - Feb;77:106852

Authors: Vorhees CV, Williams MT

Abstract
The importance of litter effects (clustering of variance among offspring in rodents) has been known for decades. The standard approach was to treat the entire litter as a unit or to select one male and one female from each litter to prevent oversampling. These methods work but are imperfect. Treating the litter as a whole fails to use valuable interindividual differences among offspring, and selecting representative pups fails to use all the data available. Golub and Sobin [https://doi.org/10.1016/j.ntt.2019.106841] address this using a better method. They show that using litter as a random factor in mixed linear models resolves this conundrum. As they demonstrate, such models control for litter clustering by partitioning litter variance from error variance. This reduces error variance and increases the power of F-tests of the independent variable(s). In our experience, this is the optimal solution. But as good as mixed linear models are when used with litter as a random factor, if other aspects of the experimental design are not appropriate, this cannot compensate for threats to validity from small sample sizes, dams not strictly randomly assigned to groups, repeated measure covariance structures not appropriately modeled, interactions not properly sliced, or a posteriori group comparisons not controlled for multiple comparisons. Appropriate handling of litter is only one consideration of experimental design and statistical analysis that when used in combination lead to valid, reproducible data.

PMID: 31837394 [PubMed - indexed for MEDLINE]

Relationship between epicardial adipose tissue thickness and epicardial adipocyte size with increasing body mass index.

Adipocyte. 2019 12;8(1):412-420

Authors: Aitken-Buck HM, Moharram M, Babakr AA, Reijers R, Van Hout I, Fomison-Nurse IC, Sugunesegran R, Bhagwat K, Davis PJ, Bunton RW, Williams MJA, Stiles MK, Jones PP, Coffey S, Lamberts RR

Abstract
Macroscopic deposition of epicardial adipose tissue (EAT) has been strongly associated with numerous indices of obesity and cardiovascular disease risk. In contrast, the morphology of EAT adipocytes has rarely been investigated. We aimed to determine whether obesity-driven adipocyte hypertrophy, which is characteristic of other visceral fat depots, is found within EAT adipocytes. EAT samples were collected from cardiac surgery patients (n = 49), stained with haematoxylin & eosin, and analysed for mean adipocyte size and non-adipocyte area. EAT thickness was measured using echocardiography. A significant positive relationship was found between EAT thickness and body mass index (BMI). When stratified into standardized BMI categories, EAT thickness was 58.7% greater (p = 0.003) in patients from the obese (7.3 ± 1.8 mm) compared to normal (4.6 ± 0.9 mm) category. BMI as a continuous variable significantly correlated with EAT thickness (r = 0.56, p < 0.0001). Conversely, no correlation was observed between adipocyte size and either BMI or EAT thickness. No difference in the non-adipocyte area was found between BMI groups. Our results suggest that the increased macroscopic EAT deposition associated with obesity is not caused by adipocyte hypertrophy. Rather, alternative remodelling via adipocyte proliferation might be responsible for the observed EAT expansion.

PMID: 31829077 [PubMed - indexed for MEDLINE]

Presynaptic Mechanisms and KCNQ Potassium Channels Modulate Opioid Depression of Respiratory Drive.

Front Physiol. 2019;10:1407

Authors: Wei AD, Ramirez JM

Abstract
Opioid-induced respiratory depression (OIRD) is the major cause of death associated with opioid analgesics and drugs of abuse, but the underlying cellular and molecular mechanisms remain poorly understood. We investigated opioid action in vivo in unanesthetized mice and in in vitro medullary slices containing the preBötzinger Complex (preBötC), a locus critical for breathing and inspiratory rhythm generation. Although hypothesized as a primary mechanism, we found that mu-opioid receptor (MOR1)-mediated GIRK activation contributed only modestly to OIRD. Instead, mEPSC recordings from genetically identified Dbx1-derived interneurons, essential for rhythmogenesis, revealed a prevalent presynaptic mode of action for OIRD. Consistent with MOR1-mediated suppression of presynaptic release as a major component of OIRD, Cacna1a KO slices lacking P/Q-type Ca2+ channels enhanced OIRD. Furthermore, OIRD was mimicked and reversed by KCNQ potassium channel activators and blockers, respectively. In vivo whole-body plethysmography combined with systemic delivery of GIRK- and KCNQ-specific potassium channel drugs largely recapitulated these in vitro results, and revealed state-dependent modulation of OIRD. We propose that respiratory failure from OIRD results from a general reduction of synaptic efficacy, leading to a state-dependent collapse of rhythmic network activity.

PMID: 31824331 [PubMed]