UW Neurological Surgery Recent PubMed Publications

Health and economic outcomes of treatment with extended-release naltrexone among pre-release prisoners with opioid use disorder (HOPPER): protocol for an evaluation of two randomized effectiveness trials.

Addict Sci Clin Pract. 2020 Apr 22;15(1):15

Authors: Murphy SM, Jeng PJ, Poole SA, Jalali A, Vocci FJ, Gordon MS, Woody GE, Polsky D

Abstract
BACKGROUND: Persons with an opioid use disorder (OUD) who were incarcerated face many challenges to remaining abstinent; concomitantly, opioid-overdose is the leading cause of death among this population, with the initial weeks following release proving especially fatal. Extended-release naltrexone (XR-NTX) is the most widely-accepted, evidence-based OUD pharmacotherapy in criminal justice settings, and ensures approximately 30 days of protection from opioid overdose. The high cost of XR-NTX serves as a barrier to uptake by many prison/jail systems; however, the cost of the medication should not be viewed in isolation. Prison/jail healthcare budgets are ultimately determined by policymakers, and the benefits/cost-offsets associated with effective OUD treatment will directly and indirectly affect their overall budgets, and society as a whole.
METHODS: This protocol describes a study funded by the National Institute of Drug Abuse (NIDA) to: evaluate changes in healthcare utilization, health-related quality-of-life, and other resources associated with different strategies of XR-NTX delivery to persons with OUD being released from incarceration; and estimate the relative "value" of each strategy. Data from two ongoing, publicly-funded, randomized-controlled trials will be used to evaluate these questions. In Study A, (XR-NTX Before vs. After Reentry), participants are randomized to receive their first XR-NTX dose before release, or at a nearby program post-release. In Study B, (enhanced XR-NTX vs. XR-NTX), both arms receive XR-NTX prior to release; the enhanced arm receives mobile medical (place of residence) XR-NTX treatment post-release, and the XR-NTX arm receives referral to a community treatment program post-release. The economic data collection instruments required to evaluate outcomes of interest were incorporated into both studies from baseline. Moreover, because the same instruments are being used in both trials on comparable populations, we have the opportunity to not only assess differences in outcomes between study arms within each trial, but also to merge the data sets and test for differences across trials.
DISCUSSION: Initiating XR-NTX for OUD prior to release from incarceration may improve patient health and well-being, while also producing downstream cost-offsets. This study offers the unique opportunity to assess the effectiveness and cost-effectiveness of multiple strategies, according to different stakeholder perspectives.

PMID: 32321570 [PubMed - in process]

Changes to management of a non-pandemic illness during the COVID-19 pandemic: case study of invasive management of acute coronary syndrome.

N Z Med J. 2020 04 24;133(1513):101-106

Authors: Coffey S, Moynagh A, Green B, Edmond J, Wilkins GT, Pemberton J, Wilkins B, Williams MJ, Arnold B

Abstract
The coronavirus 2019 (COVID-19) pandemic requires significant changes to standard operating procedures for non-COVID-19 related illnesses. Balancing the benefit from standard evidence-based treatments with the risks posed by COVID-19 to patients, healthcare workers and to the population at large is difficult due to incomplete and rapidly changing information. In this article, we use management of acute coronary syndromes as a case study to show how these competing risks and benefits can be resolved, albeit incompletely. While the risks due to COVID-19 in patients with acute coronary syndromes is unclear, the benefits of standard management are well established in this condition. As an aid to decision making, we recommend systematic estimation of the risks and benefits for management of any condition where there is likely to be an increase in non-COVID-19 related mortality and morbidity due to changes in routine care.

PMID: 32325474 [PubMed - indexed for MEDLINE]

Daratumumab, Lenalidomide, Bortezomib, & Dexamethasone for Transplant-eligible Newly Diagnosed Multiple Myeloma: GRIFFIN.

Blood. 2020 Apr 23;:

Authors: Voorhees PM, Kaufman JL, Laubach JP, Sborov DW, Reeves B, Rodriguez C, Chari A, Silbermann R, Costa LJ, Anderson LD, Nathwani N, Shah N, Efebera YA, Holstein SA, Costello C, Jakubowiak A, Wildes T, Orlowski RZ, Shain KH, Cowan AJ, Murphy SP, Lutska Y, Pei H, Ukropec J, Vermeulen J, de Boer C, Hoehn D, Lin T, Richardson PG

Abstract
Lenalidomide, bortezomib, and dexamethasone (RVd) followed by autologous stem cell transplantation (ASCT) is standard frontline therapy for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). This study evaluated addition of daratumumab (D) to RVd in ASCT-eligible NDMM patients. Patients (N=207) were randomized 1:1 to receive RVd ±D induction (4 cycles), ASCT, RVd ±D consolidation (2 cycles), and lenalidomide ±D maintenance (26 cycles). At the primary endpoint analysis, the stringent complete response (sCR) rate by the end of post-ASCT consolidation favored D-RVd over RVd (42.4% vs 32.0%; odds ratio, 1.57; 95% confidence interval [CI], 0.87-2.82; 1-sided P=0.068) and met the prespecified 1-sided alpha of 0.10. With longer follow-up (median, 22.1 months), responses continued to deepen; rates of sCR improved for D-RVd versus RVd (62.6% vs 45.4%; P=0.0177), as did rates of minimal residual disease negativity (10-5 threshold) in the intent-to-treat population (51.0% vs 20.4%; P<0.0001). Four (3.8%) and 7 (6.8%) patients in the D-RVd and RVd groups progressed, respectively, and 24-month progression-free survival rates were 95.8% (D-RVd) and 89.8% (RVd). Grade 3/4 hematologic adverse events were more common with D-RVd. More infections occurred with D-RVd, but rates of grade 3/4 infections were similar. Median CD34+ cell yield was 8.2´106/kg for D-RVd and 9.4´106/kg for RVd, although plerixafor use was more common in the D-RVd arm. There was no difference in median times to neutrophil or platelet engraftment. In summary, daratumumab with RVd induction and consolidation improved depth of response in patients with transplant-eligible NDMM, with no new safety concerns. Clinicaltrials.gov NCT02874742.

PMID: 32325490 [PubMed - as supplied by publisher]

The importance of reporting house dust mite endotoxin abundance: impact on the lung transcriptome.

Am J Physiol Lung Cell Mol Physiol. 2020 06 01;318(6):L1229-L1236

Authors: Pascoe CD, Jha A, Basu S, Mahood T, Lee A, Hinshaw S, Falsafi R, Hancock REW, Mookherjee N, Halayko AJ

Abstract
The abundance of lipopolysaccharide (LPS) in house dust mite (HDM) preparations is broad and mirrors the variability seen in the homes of people with asthma. LPS in commercially available stocks ranges from 31 to 5,2000 endotoxin units. The influence of vastly different LPS loads on the mechanisms that define the immune and inflammatory phenotype of HDM-challenged mice has not been defined. This aim of the study was to understand the lung phenotype of mice challenged with HDM extract containing high or low levels of LPS. Female BALB/c mice were sensitized for 2 wk with commercial HDM extract containing either high (36,000 endotoxin units; HHDM) or low (615 endotoxin units; LHDM) levels of LPS. Lung phenotype was characterized by measuring lung function, total and differential cell counts, cytokine abundance, and the lung transcriptome by RNA-sequencing. LPS levels in HDM stocks used for preclinical asthma research in mice remain poorly reported. In 2019, only 14% of papers specified LPS concentration in HDM lots. Specific differences existed in airway responsiveness between mice challenged with HHDM or LHDM. HHDM- and LHDM-induced cytokine profiles of bronchial lavage were significantly different and the lung transcriptome was differentially enriched for genes involved in DNA damage repair or cilium movement, following HHDM or LHDM challenge, respectively. The abundance of LPS in commercially available HDM influences the phenotype of allergic airways inflammation in mice. Failure to report the level of LPS in HDM extracts used in animal models of airway disease will lead to inconsistency in reproducibility and reliability of published data.

PMID: 32320279 [PubMed - indexed for MEDLINE]

Identification of reference markers for characterizing honey bee (Apis mellifera) hemocyte classes.

Dev Comp Immunol. 2020 Apr 19;:103701

Authors: Gábor E, Cinege G, Csordás G, Rusvai M, Honti V, Kolics B, Török T, Williams MJ, Kurucz É, Andó I

Abstract
Cell mediated immunity of the honey bee (Apis mellifera) involves the activity of several hemocyte populations, currently defined by morphological features and lectin binding characteristics. The objective of the present study was to identify molecular markers capable of characterizing subsets of honey bee hemocytes. We developed and employed monoclonal antibodies with restricted reactions to functionally distinct hemocyte subpopulations. Melanizing cells, known as oenocytoids, were defined by an antibody to prophenoloxidase, aggregating cells were identified by the expression of Hemolectin, and phagocytic cells were identified by a marker expressed on granulocytes. We anticipate that this combination of antibodies not only allows for the detection of functionally distinct hemocyte subtypes, but will help to further the exploration of hematopoietic compartments, as well as reveal details of the honey bee cellular immune defense against parasites and microbes.

PMID: 32320738 [PubMed - as supplied by publisher]

Evaluating angioarchitectural characteristics of glial and metastatic brain tumors with conventional magnetic resonance imaging.

J Clin Neurosci. 2020 Jun;76:46-52

Authors: Abecassis IJ, Cordy B, Durfy S, Andre JB, Levitt MR, Ellenbogen RG, Silbergeld DL, Ko AL

Abstract
Primary and metastatic brain tumors can overlap in traditional imaging features detected on preoperative conventional magnetic resonance imaging (MRI). The research objective was to determine whether morphological vascular characteristics present in routine preoperative imaging using traditional MRI sequences are predictive of primary versus metastatic brain tumors; secondarily to determine association of conventional and vascular-related imaging parameters with intraoperative blood loss, pathological invasion, and World Health Organization (WHO) tumor grade. A retrospective review analyzed 100 consecutive intracranial tumor surgeries, 50 WHO grade II-IV gliomas and 50 intracranial metastases. Two blinded expert readers independently evaluated preoperative MRIs, obtained via standard morphological imaging sequences, for adjacent or intra-tumoral arterial aneurysm, peritumoral venous ectasia, prominence, or engorgement ("aberrant peritumoral vessels"), and prominent intra-tumoral flow voids. Multivariate analysis was performed to develop models predictive of glioma and glioblastoma (GBM). Aberrant peritumoral vessels and prominent intra-tumoral flow voids were statistically significant predictors of glioma in univariate analyses (p = 0.048, p = 0.001, respectively) and when combined in multivariate analysis (OR = 5.23, p = 0.001), particularly for GBM (OR = 9.08, p < 0.001). Multivariate modeling identified prominent intra-tumoral flow voids and FLAIR invasion as the strongest combined predictors of gliomas and GBM. Aberrant peritumoral vessels and larger tumor volume predicted higher intraoperative blood loss in all analyses. No vascular-related parameters predicted pathological invasion on multivariate analysis. Aberrant peritumoral vessels and prominent intra-tumoral flow voids were predictive of gliomas, specifically GBM. These vascular characteristics, evaluated on routine clinical preoperative MRI imaging, may aid in distinguishinggliomafrom brainmetastases andmay predict intraoperative blood loss.

PMID: 32312627 [PubMed - indexed for MEDLINE]

Neurointervention for emergent large vessel occlusion during the covid-19 pandemic.

J Neurointerv Surg. 2020 Apr 20;:

Authors: Fiorella D, Fargen KM, Leslie-Mazwi TM, Levitt M, Probst S, Bergese S, Hirsch JA, Albuquerque FC

PMID: 32312799 [PubMed - as supplied by publisher]

Stochastic growth pattern of untreated human glioblastomas predicts the survival time for patients.

Sci Rep. 2020 04 20;10(1):6642

Authors: Ma Z, Niu B, Phan TA, Stensjøen AL, Ene C, Woodiwiss T, Wang T, Maini PK, Holland EC, Tian JP

Abstract
Glioblastomas are highly malignant brain tumors. Knowledge of growth rates and growth patterns is useful for understanding tumor biology and planning treatment logistics. Based on untreated human glioblastoma data collected in Trondheim, Norway, we first fit the average growth to a Gompertz curve, then find a best fitted white noise term for the growth rate variance. Combining these two fits, we obtain a new type of Gompertz diffusion dynamics, which is a stochastic differential equation (SDE). Newly collected untreated human glioblastoma data in Seattle, US, re-verify our model. Instead of growth curves predicted by deterministic models, our SDE model predicts a band with a center curve as the tumor size average and its width as the tumor size variance over time. Given the glioblastoma size in a patient, our model can predict the patient survival time with a prescribed probability. The survival time is approximately a normal random variable with simple formulas for its mean and variance in terms of tumor sizes. Our model can be applied to studies of tumor treatments. As a demonstration, we numerically investigate different protocols of surgical resection using our model and provide possible theoretical strategies.

PMID: 32313150 [PubMed - indexed for MEDLINE]

Applications of Benchtop NMR in the Organic Chemistry Instructional Laboratory.

Magn Reson Chem. 2020 Apr 19;:

Authors: Morrison RW, Zhang M

Abstract
The instructional organic chemistry laboratory has been substantially improved through the implementation of benchtop NMR analysis. When used in conjunction with unknown reaction components in multi-outcome experiments, NMR analysis transforms the laboratory exercise into an investigative inquiry wherein students elucidate structures for their products and thereby deduce their unknown reaction components. This analytical approach closely models the research laboratory and is a valuable preparatory tool for undergraduate researchers. Three newly developed multi-outcome experiments based upon the Diels-Alder cycloaddition, the synthesis of carboxylic amides, and the Friedel-Crafts alkylation are herein described to illustrate the utility of benchtop NMR analysis in the instructional laboratory.

PMID: 32307736 [PubMed - as supplied by publisher]

Basic science review of birth tissue uses in ophthalmology.

Taiwan J Ophthalmol. 2020 Jan-Mar;10(1):3-12

Authors: Tighe S, Mead OG, Lee A, Tseng SCG

Abstract
The birth tissue is predominantly comprised of amniotic membrane (AM) and umbilical cord (UC), which share the same cell origin as the fetus. These versatile biological tissues have been used to treat a wide range of conjunctival and corneal conditions since 1940. The therapeutic benefits of the birth tissue stem from its anti-inflammatory and anti-scarring properties that orchestrate regenerative healing. Although the birth tissue also contains many cytokines, growth factors, and proteins, the heavy chain 1-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) matrix has been identified to be a major active tissue component responsible for AM/UC's multifactorial therapeutic actions. HC-HA/PTX3 complex is abundantly present in fresh and cryopreserved AM/UC, but not in dehydrated tissue. In this review, we discuss the tissue anatomy, the molecular mechanism of action based on HC-HA/ PTX3 to explain their therapeutic potentials, and the various forms available in ophthalmology.

PMID: 32309118 [PubMed]

Factors associated with age of death in sudden unexpected infant death.

Acta Paediatr. 2020 Apr 18;:

Authors: Allen K, Anderson TM, Chajewska U, Ramirez JM, Mitchell EA

Abstract
AIM: This study aimed to systematically analyze the pregnancy, birth, and demographic-related factors associated with age of death in sudden unexpected infant death (SUID).
METHODS: Data were analyzed from the Centers for Disease Control and Prevention';s Cohort Linked Birth/Infant Death dataset (2011-2013; 11,737,930 live births). SUID was defined as deaths from sudden infant death syndrome, ill-defined causes, or accidental suffocation and strangulation in bed. There were 9,668 SUID deaths (7-364 days; gestation >28 weeks; 0.82/1000 live births). The odds of death at different ages were compared to determine which variables significantly affect the SUID age of death.
RESULTS: 43 features indicated a significant change in age of death with two main patterns: 1) younger chronologic age at death was associated with maternal smoking and factors associated with lower socioeconomic status, and 2) older age associated with low birthweight, prematurity and admission to the neonatal intensive care unit. However, when age was corrected for gestation, these factors were associated with younger age.
CONCLUSION: Factors that varied with age of death are well-documented risk factors for SUID. The majority of these risk factors were associated with younger age at death after allowing for gestational age at birth.

PMID: 32304589 [PubMed - as supplied by publisher]

Cardiac-cerebral-renal associations in pediatric traumatic brain injury: Preliminary findings.

J Clin Neurosci. 2020 Jun;76:126-133

Authors: Lele AV, Alunpipatthanachai B, Clark-Bell C, Watanitanon A, Min Xu M, Anne Moore RVT, Zimmerman JJ, Portman MA, Chesnut RM, Vavilala MS

Abstract
OBJECTIVE: The clinical epidemiology of organ outcomes in pediatric traumatic brain injury (TBI) has not been examined. We describe associated markers of cerebral, cardiac and renal injury after pediatric TBI.
DESIGN: Prospective observational study.
PATIENTS: Children 0-18 years who were hospitalized with TBI.
MEASUREMENTS: Measures of myocardial (at least one elevated plasma troponin [cTnI] ≥ 0.4 ng/ml) and multiorgan (hemodynamic variables, cerebral perfusion, and renal) function were examined within the first ten days of hospital admission and within 24 h of each other.
MAIN RESULTS: Data from 28 children who were 11[IQR 10.3] years, male (64.3%), with isolated TBI (67.9%), injury severity score (ISS) 25[10], and admission Glasgow coma score (GCS) 11[9] were examined. Overall, 50% (14 children) had elevated cTnI, including those with isolated TBI (57.9%; 11/19), polytrauma (33.3%; 3/9), mild TBI (57.1% 8/14), and severe TBI (42.9%; 6/11). Elevated cTnI occurred within the first six days of admission and across all age groups, in both sexes, and regardless of TBI lesion type, GCS, and ISS. Age-adjusted admission tachycardia was associated with cTnI elevation (AUC 0.82; p < 0.001). Reduced urine output occurred more commonly in patients with isolated TBI (27.3% elevated cTnI vs. 0% normal cTnI).
CONCLUSIONS: Myocardial injury commonly occurs during the first six days after pediatric TBI irrespective of injury severity, age, sex, TBI lesion type, or polytrauma. Age-adjusted tachycardia may be a clinical indicator of myocardial injury, and elevated troponin may be associated with cardio-cerebro-renal dysfunction.

PMID: 32299773 [PubMed - indexed for MEDLINE]

Society of NeuroInterventional Surgery recommendations for the care of emergent neurointerventional patients in the setting of COVID-19.

J Neurointerv Surg. 2020 06;12(6):539-541

Authors: Fraser JF, Arthur AS, Chen M, Levitt M, Mocco J, Albuquerque FC, Ansari SA, Dabus G, Jayaraman MV, Mack WJ, Milburn J, Mokin M, Narayanan S, Puri AS, Siddiqui AH, Tsai JP, Klucznik RP

PMID: 32295835 [PubMed - indexed for MEDLINE]

Early repatriation post-thrombectomy: a model of care which maximises the capacity of a stroke network to treat patients with large vessel ischaemic stroke.

J Neurointerv Surg. 2020 Dec;12(12):1166-1171

Authors: Griffin E, Murphy S, Sheehan M, Power S, Brennan P, O'Hare A, Looby S, McWilliams S, Moynihan B, Williams D, Boyle K, O'Neill D, Collins R, Dolan E, Cassidy T, Harbison J, O'Connor M, Alderson J, Thornton J

Abstract
BACKGROUND AND PURPOSE: Healthcare systems are challenged to provide access to thrombectomy in acute stroke patients. Either the "drip and ship" or "mothership" models result in increased numbers of patients in the endovascular stroke centre (ESC). We describe our approach for a "drip, ship, retrieve and leave" model repatriating patients immediately or within 24 hours of thrombectomy.
METHODS: We included consecutive patients who underwent thrombectomy from January 2016 to June 2018. Patients from local region primary stroke centres (PSC) are immediately repatriated and those from remote region PSCs are admitted for 24 hours before repatriation. Key parameters recorded included clinical, radiological and timeline data as well as 90-day modified Rankin Scale (mRS). Patients who stayed beyond the intended time period in the ESC were analysed.
RESULTS: From January 2016 to June 2018, 435 patients were transferred, with 352 patients in the local region group and 83 in the remote region group. The median NIHSS was 16 with a median ASPECTS of 9. Good functional outcome was seen in 47% of patients with a mortality rate of 19%. The local region group that were repatriated at the intended time period had a 90-day mRS 0-2 of 47% compared with 20% of those admitted to the ESC (P=0.006). Mortality rates were 20% and 27% respectively (P=0.377). The remote region group, repatriated at 24 hours' post-emergency endovascular thrombectomy had 90-day mRS 0-2 of 65% compared with 41% in the group admitted (P=0.042). Mortality rates were 4% and 22% respectively (P=0.007).
CONCLUSION: This model enables the treatment of large numbers of patients with large vessel occlusion acute ischaemic stroke with thrombectomy within a national stroke service and system of care which would not otherwise be facilitated.

PMID: 32295836 [PubMed - indexed for MEDLINE]

Neuroticism may not reflect emotional variability.

Proc Natl Acad Sci U S A. 2020 04 28;117(17):9270-9276

Authors: Kalokerinos EK, Murphy SC, Koval P, Bailen NH, Crombez G, Hollenstein T, Gleeson J, Thompson RJ, Van Ryckeghem DML, Kuppens P, Bastian B

Abstract
Neuroticism is one of the major traits describing human personality, and a predictor of mental and physical disorders with profound public health significance. Individual differences in emotional variability are thought to reflect the core of neuroticism. However, the empirical relation between emotional variability and neuroticism may be partially the result of a measurement artifact reflecting neuroticism's relation with higher mean levels-rather than greater variability-of negative emotion. When emotional intensity is measured using bounded scales, there is a dependency between variability and mean levels: at low (or high) intensity, it is impossible to demonstrate high variability. As neuroticism is positively associated with mean levels of negative emotion, this may account for the relation between neuroticism and emotional variability. In a metaanalysis of 11 studies (N = 1,205 participants; 83,411 observations), we tested whether the association between neuroticism and negative emotional variability was clouded by a dependency between variability and the mean. We found a medium-sized positive association between neuroticism and negative emotional variability, but, when using a relative variability index to correct for mean negative emotion, this association disappeared. This indicated that neuroticism was associated with experiencing more intense, but not more variable, negative emotions. Our findings call into question theory, measurement scales, and data suggesting that emotional variability is central to neuroticism. In doing so, they provide a revisionary perspective for understanding how this individual difference may predispose to mental and physical disorders.

PMID: 32295883 [PubMed - indexed for MEDLINE]

Anterior Column Realignment: Analysis of Neurological Risk and Radiographic Outcomes.

Neurosurgery. 2020 09 01;87(3):E347-E354

Authors: Saigal R, Akbarnia BA, Eastlack RK, Bagheri A, Tran S, Brown D, Bagheri R, Mundis GM

Abstract
BACKGROUND: Anterior column realignment (ACR) is a less invasive alternative to 3-column osteotomy for the correction of sagittal imbalance. We hypothesized that ACR would correct sagittal imbalance with an acceptable neurological risk.
OBJECTIVE: To assess long-term neurological and radiographic outcomes after ACR.
METHODS: Patients ≥18 yr who underwent ACR from 2005 to 2013 were eligible. Standing scoliosis radiographs were studied at preoperation, postoperation (≤6 wk), and at minimum 2 yr of follow-up. Clinical/radiographic data were collected through a retrospective chart review, with thoracic 1 spino-pelvic inclination (T1SPi) used as the angular surrogate for sagittal vertical axis.
RESULTS: A total of 26 patients had complete data, with a mean follow-up of 2.8 yr (1.8-7.4). Preoperative, sagittal parameters were lumbar lordosis (LL) of -16.1°, pelvic incidence (PI)-LL of 41.7°, T1SPi of 3.6°, and pelvis tilt (PT) of 32.4°. LL improved by 30.6° (P < .001) postoperation. Mean changes in PT (-8.3), sacral slope (8.9), T1SPi (-4.9), and PI-LL (-33.5) were all significant. The motion segment angle improved by 26.6°, from 5.2° to -21.4° (P < .001). Neurological complications occurred in 32% patients postoperation (n = 8; 1 patient with both sensory and motor). New thigh numbness/paresthesia developed in 3 (13%) patients postoperation; only 1 (4%) persisted at latest follow-up. A total of 6 (24%) patients developed a new lower extremity motor deficit postoperation, with 4 (8%) having persistent new weakness at last follow-up. Out of 8 patients with preoperative motor deficit, half saw improvement postoperation and 75% improved by last follow-up.
CONCLUSION: There was net motor improvement, with 24% of patients improving and 16% having persistent new weakness at latest follow-up; 60% were unchanged. Radiographic results demonstrate that ACR is a useful tool to treat severe sagittal plane deformity.

PMID: 32297951 [PubMed - indexed for MEDLINE]

Phase I clinical trial of temsirolimus and perifosine for recurrent glioblastoma.

Ann Clin Transl Neurol. 2020 Apr 15;:

Authors: Kaley TJ, Panageas KS, Pentsova EI, Mellinghoff IK, Nolan C, Gavrilovic I, DeAngelis LM, Abrey LE, Holland EC, Omuro A, Lacouture ME, Ludwig E, Lassman AB

Abstract
PURPOSE: Malignant glioma (MG) is the most deadly primary brain cancer. Signaling though the PI3K/AKT/mTOR axis is activated in most MGs and therefore a potential therapeutic target. The mTOR inhibitor temsirolimus and the AKT inhibitor perifosine are each well-tolerated as single agents but with limited activity reclinical data demonstrate synergistic anti-tumor effects from combined treatment. Therefore, we initiated a phase I trial of combined therapy in recurrent MGs to determine safety and a recommended phase II dose.
METHODS: Adults with recurrent MG, Karnofsky Performance Status ≥ 60 were enrolled, with no limit on the number of prior therapies. Temsirolimus dose was escalated using standard 3 + 3 design from 15 mg to 170 mg administered once weekly. Perifosine was fixed as a 600 mg load on day 1 followed by 100 mg nightly (single agent MTD) until dose level 7 when the load increased to 900 mg.
RESULTS: We treated 35 patients with with glioblastoma (17) or other MGs (18; including nine anaplastic astrocytoma, nine anaplastic oligodendroglioma, one anaplastic oligoastrocytoma, and two low grade astrocytomas with radiographic transformation to MG). We observed five dose-limiting toxicities (DLTs): one at dose level 3 (50mg temsirolimus), then two at dose level 7 expansion (170 mg temsirolimus), and then two more at dose level 6 expansion (170 mg temsirolimus). DLTs included thrombocytopenia (n = 3), intracerebral hemorrhage (n = 1) and lung infection (n = 1).
CONCLUSION: Combining the mTOR inhibitor temsirolimus dosed at 115 mg weekly and the AKT inhibitor perifosine dosed at 100 mg daily (following 600 mg load) is tolerable in heavily pretreated adults with recurrent MGs.

PMID: 32293798 [PubMed - as supplied by publisher]

Investigating the Suitability of Semicarbazide as an Indicator of Preharvest Nitrofurazone Use in Raw Chicken.

J Food Prot. 2020 Aug 01;83(8):1368-1373

Authors: Johnston J, Duverna R, Williams M, Kishore R, Yee C, Jarosh J

Abstract
ABSTRACT: Semicarbazide (SEM) is the U.S. Food and Drug Administration's official marker for nitrofurazone use in food animals. The U.S. Department of Agriculture Food Safety and Inspection Service conducted a study to evaluate the source of SEM that was identified by a U.S. trading partner in a subset of chicken samples presented for inspection, even though nitrofurazone has been banned from use in U.S. food-producing animals since 2002. The study design included analyses to detect and quantify total and bound SEM in chicken collected from the eight U.S. establishments that were associated with the reported detection of SEM. Samples were collected immediately following evisceration, chilling, and cutting carcass into parts (cut-up). Although antimicrobial interventions (processes to reduce pathogen concentrations) are typically used at all three of these processing steps, the product contact time during chilling is significantly longer (hours versus seconds) than during evisceration and cut-up. In addition, parts were analyzed after 0, 10, 20, and 30 days of frozen storage. No postevisceration samples tested positive for SEM; however, most samples collected postchilling and after cut-up tested positive. The absence of SEM in postevisceration samples and detection in the subsequent postchilling samples and after the cut-up samples suggest that the detection of SEM in the sampled products is not indicative of preharvest nitrofurazone use and may be a result of postharvest processing in these establishments.
HIGHLIGHTS:

PMID: 32294171 [PubMed - indexed for MEDLINE]

The Endoscopic Trans-Superior Articular Process Approach: A Novel Minimally Invasive Surgical Corridor to the Lateral Recess.

Oper Neurosurg (Hagerstown). 2020 Apr 13;:

Authors: Hasan S, White-Dzuro B, Barber JK, Wagner R, Hofstetter CP

Abstract
BACKGROUND: Transforaminal approaches to the lumbar spine are typically performed utilizing Kambin's triangle as approach corridor; however, degenerative changes can distort anatomy and expose the exiting nerve root to inadvertent injury.
OBJECTIVE: To describe the surgical technique of a novel full-endoscopic approach to access the lateral recess and report clinical outcomes.
METHODS: The trans-superior articular process (SAP) approach involves partial resection of the SAP, allowing access to the lateral recess both ventral and dorsal to the traversing nerve root. A retrospective review of 40 patients who had undergone a trans-SAP approach for decompression of lateral recess pathology was conducted. Outcomes were measured using visual analog scores (VAS) and Oswestry Disability Index (ODI) at 2 wk, 3 mo, and at last follow-up.
RESULTS: At a mean follow-up of 24 mo, patients experienced statistically significant improvement of the VAS for ipsilateral leg pain, VAS for back pain, and ODI when comparing preoperative values to all postoperative time points. The percentage of patients reaching a minimally clinically important difference for VAS leg pain and ODI was approximately 90% and 88%, respectively. The complication profile was favorable with no dural tears and no postoperative motor or sensory deficits. One patient required revision, with a total reoperation rate of 3%.
CONCLUSION: The trans-SAP approach is a novel approach that utilizes a safe surgical corridor via the SAP to access lateral recess pathology. Our initial clinical experience suggests that the trans-SAP approach allows for treatment of lateral recess and foraminal pathology with low complication rates.

PMID: 32281629 [PubMed - as supplied by publisher]

Timing of Ossification of the Anterior Skull Base in Syndromic Synostosis.

J Craniofac Surg. 2020 Jul-Aug;31(5):1256-1260

Authors: Nassar AH, Mercan E, Massenburg BB, Lee A, Brown J, Skladman R, Guo Y, Hopper RA

Abstract
The anterior skull base undergoes a progressive ossification after birth. This has implications on the epidural dissection of early trans-craniofacial osteotomy procedures such as monobloc advancements. Our purpose was to determine the rate of ossification in syndromic synostosis patients relative to a normal cohort to establish when maturation of the anterior skull base is complete. The authors analyzed CT scans from 35 patients with Crouzon, Apert or Pfeiffer syndrome, and 84 patients without any craniofacial anomaly between the ages of 0 and 6 years. The non-ossified anterior skull base area was measured using 3D Slicer. The authors compared the sizes of the defects at different ages between the three syndromes and with the control group using Mann-Whitney test. Significance was set at P < 0.05. All patients less than 12 months of age had a measurable defect anterior to the cribriform whereas patients greater than five years of age had full ossification of the anterior skull base with no evidence of defect. The relationship of defect size and age at scan was non-linear, with most defects closing rapidly in the first six months. The temporal closure pattern of the defect was similar between the three syndromes and the control group with no significant difference. Our findings indicate that syndromic children undergo skull base maturation at the same rate as non-syndromic cases, with the majority ossified by three years of age. Anterior skull base surgeries performed before three years should optimize visualization of this area during dissection.

PMID: 32282683 [PubMed - indexed for MEDLINE]