UW Neurological Surgery Recent PubMed Publications

Chronic psychosocial stress during pregnancy affects maternal behavior and neuroendocrine function and modulates hypothalamic CRH and nuclear steroid receptor expression.

Transl Psychiatry. 2020 Jan 16;10(1):6

Authors: Zoubovsky SP, Hoseus S, Tumukuntala S, Schulkin JO, Williams MT, Vorhees CV, Muglia LJ

Abstract
Postpartum depression (PPD) affects up to 20% of mothers and has negative consequences for both mother and child. Although exposure to psychosocial stress during pregnancy and abnormalities in the hypothalamic pituitary adrenal (HPA) axis have been linked to PPD, molecular changes in the brain that contribute to this disease remain unknown. This study utilized a novel chronic psychosocial stress paradigm during pregnancy (CGS) to investigate the effects of psychosocial stress on maternal behavior, neuroendocrine function, and gene expression changes in molecular regulators of the HPA axis in the early postpartum period. Postpartum female mice exposed to CGS display abnormalities in maternal behavior, including fragmented and erratic maternal care patterns, and the emergence of depression and anxiety-like phenotypes. Dysregulation in postpartum HPA axis function, evidenced by blunted circadian peak and elevation of stress-induced corticosterone levels, was accompanied by increased CRH mRNA expression and a reduction in CRH receptor 1 in the paraventricular nucleus of the hypothalamus (PVN). We further observed decreased PVN expression of nuclear steroid hormone receptors associated with CRH transcription, suggesting these molecular changes could underlie abnormalities in postpartum HPA axis and behavior observed. Overall, our study demonstrates that psychosocial stress during pregnancy induces changes in neuroendocrine function and maternal behavior in the early postpartum period and introduces our CGS paradigm as a viable model that can be used to further dissect the molecular defects that lead to PPD.

PMID: 32066677 [PubMed - in process]

Variability in estimated gene expression among commonly used RNA-seq pipelines.

Sci Rep. 2020 02 17;10(1):2734

Authors: Arora S, Pattwell SS, Holland EC, Bolouri H

Abstract
RNA-sequencing data is widely used to identify disease biomarkers and therapeutic targets using numerical methods such as clustering, classification, regression, and differential expression analysis. Such approaches rely on the assumption that mRNA abundance estimates from RNA-seq are reliable estimates of true expression levels. Here, using data from five RNA-seq processing pipelines applied to 6,690 human tumor and normal tissues, we show that nearly 88% of protein-coding genes have similar gene expression profiles across all pipelines. However, for >12% of protein-coding genes, current best-in-class RNA-seq processing pipelines differ in their abundance estimates by more than four-fold when applied to exactly the same samples and the same set of RNA-seq reads. Expression fold changes are similarly affected. Many of the impacted genes are widely studied disease-associated genes. We show that impacted genes exhibit diverse patterns of discordance among pipelines, suggesting that many inter-pipeline differences contribute to overall uncertainty in mRNA abundance estimates. A concerted, community-wide effort will be needed to develop gold-standards for estimating the mRNA abundance of the discordant genes reported here. In the meantime, our list of discordantly evaluated genes provides an important resource for robust marker discovery and target selection.

PMID: 32066774 [PubMed - indexed for MEDLINE]

Probing prodrug metabolism and reciprocal toxicity with an integrated and humanized multi-tissue organ-on-a-chip platform.

Acta Biomater. 2020 Feb 14;:

Authors: Rajan SAP, Aleman J, Wan M, Zarandi NP, Nzou G, Murphy S, Bishop CE, Sadri-Ardekani H, Shupe T, Atala A, Hall AR, Skardal A

Abstract
Current drug development techniques are expensive and inefficient, partially due to the use of preclinical models that do not accurately recapitulate in vivo drug efficacy and cytotoxicity. To address this challenge, we report on an integrated, in vitro multi-organoid system that enables parallel assessment of drug efficiency and toxicity on multiple 3D tissue organoids. Built in a low-cost, adhesive film-based microfluidic device, these miniaturized structures require less than 200 µL fluid volume and are amenable to both matrix-based 3D cell culture and spheroid aggregate integration, each supported with an in situ photocrosslinkable hyaluronic acid hydrogel. Here, we demonstrate this technology first with a three-organoid device consisting of liver, cardiac, and lung constructs. We show that these multiple tissue types can be kept in common circulation with high viability for 21 days and validate the platform by investigating liver metabolism of the prodrug capecitabine into 5-fluorouracil (5-FU) and observing downstream toxicity in lung and cardiac organoids. Then we expand the integrated system to accommodate six humanized constructs, including liver, cardiac, lung, endothelium, brain, and testes organoids. Following a 14-day incubation in common media, we demonstrate multi-tissue interactions by metabolizing the alkylating prodrug ifosfamide in the liver organoid to produce chloroacetaldehyde and induce downstream neurotoxicity. Our results establish an expandable, multi-organoid body-on-a-chip system that can be fabricated easily and used for the accurate characterization of drug interactions in vitro.

PMID: 32068138 [PubMed - as supplied by publisher]

Geographic Variation in Sudden Unexpected Infant Death in the United States.

J Pediatr. 2020 05;220:49-55.e2

Authors: Mitchell EA, Yan X, Ren SY, Anderson TM, Ramirez JM, Lavista Ferres JM, Johnston R

Abstract
OBJECTIVES: To assess the geographic variation of sudden unexpected infant death (SUID) and test if variation in geographic factors, such as state, latitude, and longitude, play a role in SUID risk across the US.
STUDY DESIGN: We analyzed the Centers for Disease Control and Prevention's Cohort Linked Birth/Infant Death dataset (2005-2010; 22 882 SUID cases, 25 305 837 live births, rate 0.90/1000). SUID was defined as infant deaths (ages 7-364 days) that included sudden infant death syndrome, ill-defined and unknown cause of mortality, and accidental suffocation and strangulation in bed. SUID geographic variation was analyzed using 2 statistical models, logistic regression and generalized additive model (GAM).
RESULTS: Both models produced similar results. Without adjustment, there was marked geographic variation in SUID rates, but the variation decreased after adjusting for covariates including known risk factors for SUID. After adjustment, nine states demonstrated significantly higher or lower SUID mortality than the national average. Geographic contribution to SUID risk in terms of latitude and longitude were also attenuated after adjustment for covariates.
CONCLUSION: Understanding why some states have lower SUID rates may enhance SUID prevention strategies.

PMID: 32061407 [PubMed - indexed for MEDLINE]

Pulmonary sarcomatoid carcinoma presenting as subcutaneous nodules.

Proc (Bayl Univ Med Cent). 2020 Jan;33(1):67-68

Authors: Tambe A, Ramadas P, Williams M, Gambhir HS, Naous R

Abstract
Subcutaneous nodules secondary to metastasis can be a presenting symptom of lung cancer. Underlying cancer must be ruled out in patients presenting with multiple subcutaneous nodules with suspicious history, physical, and radiological findings. Prognosis is extremely poor with limited treatment options.

PMID: 32063775 [PubMed]

Nowhere to Go: The Challenge of Health Care Transition for Youth with Hydrocephalus.

World Neurosurg. 2020 Feb;134:647-649

Authors: Williams MA, van der Willigen T, Gray DD, Hamilton MG

PMID: 32059266 [PubMed - indexed for MEDLINE]

Translating basic science discoveries into improved outcomes for glioblastoma.

Clin Cancer Res. 2020 Feb 14;:

Authors: Dirks PB, Gilbert MR, Holland EC, Maher EA, Weiss WA

Abstract
Members of the scientific and clinical neuro-oncology community met in April 2019 to discuss the current challenges and opportunities associated with translating basic science discoveries in glioblastoma to improved survival for patients. A summary of key points of these discussions is presented in this report.

PMID: 32060102 [PubMed - as supplied by publisher]

Health care transition in pediatric neurosurgery: a consensus statement from the American Society of Pediatric Neurosurgeons.

J Neurosurg Pediatr. 2020 Feb 14;:1-9

Authors: Rocque BG, Weprin BE, Blount JP, Hopson BD, Drake JM, Hamilton MG, Williams MA, White PH, Orrico KO, Martin JE

Abstract
OBJECTIVE: The number of children with complex medical conditions surviving to adulthood is increasing. A planned transition to adult care systems is essential to the health maintenance of these patients. Guidance has been established for the general health care transition (HCT) from adolescence to adulthood. No formal assessment of the performance of pediatric neurosurgeons in HCT has been previously performed. No "best practice" for this process in pediatric neurosurgery currently exists. The authors pursued two goals in this paper: 1) define the current state of HCT in pediatric neurosurgery through a survey of the membership of the American Society of Pediatric Neurosurgeons (ASPN) on current methods of HCT, and 2) develop leadership-endorsed best-practice guidelines for HCT from pediatric to adult neurosurgical health care.
METHODS: Completion of the Current Assessment of Health Care Transition Activities survey was requested of 178 North American pediatric neurosurgeons by using a web-based questionnaire to capture HCT practices of the ASPN membership. The authors concurrently conducted a PubMed/MEDLINE-based literature review of HCT for young adults with special health care needs, surgical conditions, and/or neurological conditions for the period from 1990 to 2018. Selected articles were assembled and reviewed by subject matter experts and members of the ASPN Quality, Safety, and Advocacy Committee. Best-practice recommendations were developed and subjected to peer review by external expert groups.
RESULTS: Seventy-six responses to the survey (43%) were received, and 62 respondents (82%) answered all 12 questions. Scores of 1 (lowest possible score) were recorded by nearly 60% of respondents on transition policy, by almost 70% on transition tracking, by 85% on transition readiness, by at least 40% on transition planning as well as transfer of care, and by 53% on transition completion. Average responses on all core elements were < 2 on the established 4-point scale. Seven best-practice recommendations were developed and endorsed by the ASPN leadership.
CONCLUSIONS: The majority of pediatric neurosurgeons have transition practices that are poor, do not meet the needs of patients and families, and should be improved. A structured approach to transition, local engagement with adult neurosurgical providers, and national partnerships between pediatric and adult neurosurgery organizations are suggested to address current gaps in HCT for patients served by pediatric neurosurgeons.

PMID: 32059192 [PubMed - as supplied by publisher]

Prolonged methamphetamine exposure during a critical period in neonatal Sprague-Dawley rats does not exacerbate egocentric and allocentric learning deficits but increases reference memory impairments.

Int J Dev Neurosci. 2020 Feb 11;:

Authors: Williams MT, Amos-Kroohs RM, Vorhees CV

Abstract
Children exposed to methamphetamine (MA) in utero have cognitive deficits. MA administration in rats for 5-10 days between postnatal day (P)6-20 produces cognitive deficits. The purpose of this study was to determine if extending MA administration by 5 days within P6-20 would exacerbate allocentric (Morris water maze) and egocentric (Cincinnati water maze) learning deficits. Sprague-Dawley female and male offspring (split-litter design) were administered saline (SAL) or MA (10 mg/kg) four times daily from P6-20 to create four groups: (1) SAL from P6-20, (2) MA from P6-20 (MA6-20), (3) MA from P6-15 (MA6-15), or (4) MA from P11-20 (MA11-20); the latter groups received saline on days they did not receive MA. Egocentric, allocentric, and conditioned freezing tests began on P60. The MA6-15 and MA6-20 groups showed egocentric deficits, all MA groups had allocentric deficits but no differences in conditioned freezing compared with SAL controls. The MA6-15 and MA6-20 groups had similar deficits in learning and memory that were larger than in the MA11-20 group. Learning in both mazes was sex dependent, but no interactions with MA were found. The data demonstrate that extending the exposure period of MA beyond the sensitive periods (P6-15 and P11-20) did not exacerbate the cognitive deficits.

PMID: 32043612 [PubMed - as supplied by publisher]

The Functional Status Examination in Mild Traumatic Brain Injury: A TRACK-TBI Sub-Study.

Arch Clin Neuropsychol. 2019 Oct 24;34(7):1165-1174

Authors: Zahniser E, Temkin NR, Machamer J, Barber J, Manley GT, Markowitz AJ, Dikmen SS, TRACK-TBI Investigators

Abstract
OBJECTIVE: The Functional Status Examination (FSE) is a comprehensive measure of functional status post-traumatic brain injury (TBI) that has primarily been used in studies of moderate-to-severe TBI. The present observational study examines functional status using the FSE among patients who sustained mild TBIs (mTBIs; defined as Glasgow Coma Scale [GCS] = 13-15 at admission) seen in a Level 1 trauma center. Study aims included examining the course of functional status following mTBI, as well as exploring relationships of the FSE and other relevant constructs among those with GCS = 13-15.
METHOD: Participants were assessed at 2 weeks (n = 112), 3 months (n = 113), 6 months (n = 106), and 12 months (n = 88) post-injury for changes in functional status resulting both (a) from all injuries and (b) from TBI only.
RESULTS: Among seven domains of day-to-day functioning, participants generally experienced the greatest disruption in their primary activity (work or school) and in leisure and recreation. Subjects' overall functional status tended to improve over time, with sharpest increases in functionality occurring in the first 3 months post-injury. However, some subjects continued to report functional limitations even at 12 months post-injury. Functional status was largely unrelated to neurocognitive functioning, but related strongly to post-traumatic symptoms, life satisfaction, and emotional well-being, particularly at 3 months post-injury and beyond.
CONCLUSION: Findings indicate that functional impairments related to mTBI may be more likely to persist than widely believed, with those who experience lingering functional deficits at particular risk for emotional health difficulties.

PMID: 30608522 [PubMed - indexed for MEDLINE]

Traditional Intravenous Fluid Versus Oral Fluid Administration in Primary Total Knee Arthroplasty: A Randomized Trial.

J Arthroplasty. 2020 Jan 22;:

Authors: Jennings JM, Mejia M, Williams MA, Johnson RM, Yang CC, Dennis DA

Abstract
BACKGROUND: Optimal perioperative fluid management has not been established in patients undergoing orthopedic surgical procedures. Our purpose was to investigate the effects of perioperative fluid management (ie, preoperative, intraoperative, and postoperative) on patients undergoing total knee arthroplasty (TKA).
METHODS: One hundred thirty patients who met inclusion criteria undergoing primary unilateral TKA were prospectively randomized into traditional (TFG) vs oral (OFG) perioperative fluid management groups. The primary outcome was change in body weight (BW). Secondary outcome measures included knee motion, leg girth, bioelectrical impendence, quadriceps activation, functional outcomes testing, Knee injury and Osteoarthritis Outcome Score JR, VR-12, laboratory values, vital signs, patient satisfaction, pain scores, and adverse events.
RESULTS: The TFG had increased BW the evening of surgery (7.0 ± 4.3 vs 3.0 ± 3.9, P < .0001), postoperative day (POD) #1 (9.1 ± 4.3 vs 4.7 ± 3.9, P < .0001), and POD #2 (6.2 ± 5.0 vs 4.4 ± 4.0, P = .032). Bioelectrical impedance showed less limb edema in the OFG (4.2 ± 29.7 vs 17.8 ± 30.3, P < .0001) on POD #1. Urine specific gravity differences were seen preoperatively between groups (OFG, more hydrated, P = .002). Systolic blood pressure decrease from the baseline was greater in the OFG on arrival to the floor (19.4 ± 13.5 vs 10.6 ± 12.8, P < .0001) and 8 (23.4 ± 13.3 vs 17.0 ± 12.9, P = .006) and 16 (25.8 ± 13.8 vs 25.8 ± 13.8, P = .046) hours after floor arrival. The TFG had more urine output on POD #1 (3369 mL ± 1343 mL vs 2435 mL ± 1151 mL, P < .0001). The OFG were more likely to go home on POD #1 than the TFG (63 vs 56, P = .02).
CONCLUSION: Oral fluid intake with IVF restriction in the perioperative period after TKA may offer short-term benefits with swelling and BW fluctuations. The authors continue to limit perioperative IVFs and encourage patient initiated fluid intake.

PMID: 32037213 [PubMed - as supplied by publisher]

Transforaminal Endoscopic Lumbar Discectomy and Foraminotomy with Modified Radiofrequency Nerve Stimulator and Continuous Electromyography Under General Anesthesia.

World Neurosurg. 2020 05;137:102-110

Authors: Hussain I, Rapoport BI, Krause K, Kinney G, Hofstetter CP, Elowitz E

Abstract
BACKGROUND: Transforaminal endoscopic lumbar approaches involve working in Kambin's triangle. These procedures are performed on awake patients or under general anesthesia with continuous electromyography. Potential morbidity of this approach includes injury to exiting and traversing nerve roots, as substantial dissection or cauterization of overlying tissues is required for visualization.
METHODS: We developed a novel connection system that accepts input from a bipolar radiofrequency probe to allow direct nerve stimulation in conjunction with electromyography. This study included 30 consecutive patients undergoing transforaminal endoscopic lumbar approaches for discectomies (73.3%), foraminal stenosis (23.3%), or lateral recess stenosis (3.3%). Demographic, operative, and outcomes data were collected.
RESULTS: Average age of patients was 61.4 years, and the L4-5 segment was most commonly treated (65.6%). Electrophysiologic mapping of the exiting nerve root was attempted in 28 patients with an average stimulation threshold of 8.6 ± 0.9 mA. Mapping of the traversing nerve root was attempted in 12 patients with an average stimulation threshold of 6.0 ± 0.8 mA. There were no instances of new postoperative sensorimotor deficits or dysesthesia. These findings persisted through mean and median follow-up of 294 days and 165 days, respectively. No patient required subsequent lumbar surgery.
CONCLUSIONS: Our modified instrumentation and technique allow for accurate identification of the exiting and traversing nerve roots with minimal changes to the workflow of transforaminal endoscopic lumbar approaches. Modification of a bipolar radiofrequency device connection arrangement is simple, inexpensive, and reusable. In this study, no patients developed injury or pain related to nerve root dysfunction.

PMID: 32036064 [PubMed - indexed for MEDLINE]

Maintenance of Certification and the Platinum Rule: An Existential Crisis.

Mayo Clin Proc. 2020 02;95(2):228-230

Authors: Ellenbogen RG, Connolly ES, Meyer FB

PMID: 32029083 [PubMed - indexed for MEDLINE]

Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis.

J Am Coll Cardiol. 2020 02 11;75(5):467-478

Authors: Awadalla M, Mahmood SS, Groarke JD, Hassan MZO, Nohria A, Rokicki A, Murphy SP, Mercaldo ND, Zhang L, Zlotoff DA, Reynolds KL, Alvi RM, Banerji D, Liu S, Heinzerling LM, Jones-O'Connor M, Bakar RB, Cohen JV, Kirchberger MC, Sullivan RJ, Gupta D, Mulligan CP, Shah SP, Ganatra S, Rizvi MA, Sahni G, Tocchetti CG, Lawrence DP, Mahmoudi M, Devereux RB, Forrestal BJ, Mandawat A, Lyon AR, Chen CL, Barac A, Hung J, Thavendiranathan P, Picard MH, Thuny F, Ederhy S, Fradley MG, Neilan TG

Abstract
BACKGROUND: There is a need for improved methods for detection and risk stratification of myocarditis associated with immune checkpoint inhibitors (ICIs). Global longitudinal strain (GLS) is a sensitive marker of cardiac toxicity among patients receiving standard chemotherapy. There are no data on the use of GLS in ICI myocarditis.
OBJECTIVES: This study sought to evaluate the role of GLS and assess its association with cardiac events among patients with ICI myocarditis.
METHODS: This study retrospectively compared echocardiographic GLS by speckle tracking at presentation with ICI myocarditis (cases, n = 101) to that from patients receiving an ICI who did not develop myocarditis (control subjects, n = 92). Where available, GLS was also measured pre-ICI in both groups. Major adverse cardiac events (MACE) were defined as a composite of cardiogenic shock, arrest, complete heart block, and cardiac death.
RESULTS: Cases and control subjects were similar in age, sex, and cancer type. At presentation with myocarditis, 61 cases (60%) had a normal ejection fraction (EF). Pre-ICI, GLS was similar between cases and control subjects (20.3 ± 2.6% vs. 20.6 ± 2.0%; p = 0.60). There was no change in GLS among control subjects on an ICI without myocarditis (pre-ICI vs. on ICI, 20.6 ± 2.0% vs. 20.5 ± 1.9%; p = 0.41); in contrast, among cases, GLS decreased to 14.1 ± 2.8% (p < 0.001). The GLS at presentation with myocarditis was lower among cases presenting with either a reduced (12.3 ± 2.7%) or preserved EF (15.3 ± 2.0%; p < 0.001). Over a median follow-up of 162 days, 51 (51%) experienced MACE. The risk of MACE was higher with a lower GLS among patients with either a reduced or preserved EF. After adjustment for EF, each percent reduction in GLS was associated with a 1.5-fold increase in MACE among patients with a reduced EF (hazard ratio: 1.5; 95% confidence interval: 1.2 to 1.8) and a 4.4-fold increase with a preserved EF (hazard ratio: 4.4; 95% confidence interval: 2.4 to 7.8).
CONCLUSIONS: GLS decreases with ICI myocarditis and, compared with control subjects, was lower among cases presenting with either a preserved or reduced EF. Lower GLS was strongly associated with MACE in ICI myocarditis presenting with either a preserved or reduced EF.

PMID: 32029128 [PubMed - indexed for MEDLINE]

Clinicopathologic Characteristics and Impact of Oophorectomy for Ovarian Metastases from Colorectal Cancer.

Oncologist. 2020 Feb 07;:

Authors: Ursem C, Zhou M, Paciorek A, Atreya CE, Ko AH, Venook A, Zhang L, Van Loon K

Abstract
BACKGROUND: As survival with metastatic colorectal cancer (CRC) and imaging modalities improve, detection of ovarian metastases may be increasing. The ovary may serve as a sanctuary site for malignant cells; however, there is a paucity of data regarding the role for oophorectomy.
METHODS: This is a single-institution retrospective study of patients with CRC with ovarian metastases from 2009 to 2017. We evaluated patient, disease, and treatment related factors associated with overall survival (OS) from initial diagnosis of metastatic CRC.
RESULTS: Of 108 patients assessed, the median age was 50, 19% had localized disease at initial presentation, 64% had ovarian metastases at initial CRC diagnosis, and 77% underwent oophorectomy. Median OS was 29.6 months across all patients, and it was 36.7 months in patients who underwent oophorectomy versus 25.0 months in patients who did not (hazard ratio [HR] 0.54). In multivariate analysis, the effect of oophorectomy on OS suggested protection but was not statistically significant (HR 0.57). Resection of primary tumor was performed in 71% of patients, which was independently associated with improved OS (HR 0.21). Twelve patients (11%) remained alive at 5 years after diagnosis of metastatic disease.
CONCLUSION: Although it has been previously reported that patients with CRC with ovarian metastases have poor prognosis, the median OS for this cohort was comparable to existing OS data for patients with metastatic CRC. In patients treated with chemotherapy, we did not find the ovarian metastasis to frequently serve as a sanctuary site of disease. However, we found that in carefully selected patients, oophorectomy may confer a survival benefit.
IMPLICATIONS FOR PRACTICE: In colorectal cancer (CRC) ovarian metastasis is not necessarily associated with worse prognosis than metastasis to other sites. In carefully selected patients with ovarian metastases from CRC, oophorectomy may confer a survival benefit. Specifically, development of ovarian metastasis early in the disease course, resection of the primary tumor, and limited extraovarian metastatic disease are clinical features that are potentially associated with benefit from oophorectomy. A subset of patients with ovarian metastasis from CRC have potential to become long-term survivors (>5 years).

PMID: 32031306 [PubMed - as supplied by publisher]

Paraburkholderia madseniana sp. nov., a phenolic acid-degrading bacterium isolated from acidic forest soil.

Int J Syst Evol Microbiol. 2020 Mar;70(3):2137-2146

Authors: Wilhelm RC, Murphy SJL, Feriancek NM, Karasz DC, DeRito CM, Newman JD, Buckley DH

Abstract
RP11T was isolated from forest soil following enrichment with 4-hydroxybenzoic acid. Cells of RP11T are aerobic, non-sporulating, exhibit swimming motility, and are rods (0.8 µm by 1.4 µm) that often occur as diplobacillus or in short chains (3-4 cells). Optimal growth on minimal media containing 4-hydroxybenzoic acid (µ=0.216 hr-1) occurred at 30 °C, pH 6.5 or 7.0 and 0% salinity. Comparative chemotaxonomic, genomic and phylogenetic analyses revealed the isolate was distinct from its closest relative type strains identified as Paraburkholderia aspalathi LMG 27731T, Paraburkholderia fungorum LMG 16225T and Paraburkholderia caffeinilytica CF1T. Strain RP11T is genetically distinct from P. aspalathi, its closest relative, in terms of 16S rRNA gene sequence similarity (98.7%), genomic average nucleotide identity (94%) and in silico DNA-DNA hybridization (56.7 %±2.8). The composition of fatty acids and substrate utilization pattern differentiated strain RP11T from its closest relatives, including growth on phthalic acid. Strain RP11T encoded the greatest number of aromatic degradation genes of all eleven closely related type strains and uniquely encoded a phthalic acid dioxygenase and paralog of the 3-hydroxybenzoate 4-monooxygenase. The only ubiquinone detected in strain RP11T was Q-8, and the major cellular fatty acids were C16 : 0, 3OH-C16 : 0, C17 : 0 cyclo, C19 : 0 cyclo ω8c, and summed feature 8 (C18 : 1 ω7c/ω6c). On the basis of this polyphasic approach, it was determined that strain RP11T represents a novel species from the genus Paraburkholderia for which the name Paraburkholderia madseniana sp. nov. is proposed. The type strain is RP11T (=DSM 110123T=LMG 31517T).

PMID: 32027304 [PubMed - indexed for MEDLINE]

Statistical guidelines for handing missing data in traumatic brain injury clinical research.

J Neurotrauma. 2020 Feb 01;:

Authors: Nielson JL, Cooper SR, Seabury S, Luciani D, Fabio A, Temkin N, Ferguson AR

Abstract
Missing data is a persistent and unavoidable problem in even the most carefully designed traumatic brain injury (TBI) clinical research. Missing data patterns may result from participant drop out, non-compliance, technical issues, or even death. This review describes the types of missing data that are common in TBI research, and assesses the strengths and weaknesses of the statistical approaches used to draw conclusions and make clinical decisions from these data. We review recent innovations in missing values analysis (MVA), a relatively new branch of statistics, as applied to clinical TBI data. Our discussion focuses on studies from the International Traumatic Brain Injury Research (InTBIR) initiative project: TRACK-TBI, CREACTIVE, and ADAPT. In addition, using data from the TRACK-TBI pilot study (N=586) and the completed clinical trial assessing valproate (VPA) for the treatment of post-traumatic epilepsy (N=379) we present real-world examples of typical missing data patterns and the application of statistical techniques to mitigate the impact of missing data in order to draw sound conclusions from ongoing clinical studies.

PMID: 32008424 [PubMed - as supplied by publisher]

A Consensus-Based Management Protocol For The Treatment Of Severe Traumatic Brain Injury Based On Imaging And Clinical Examination For Use When Intracranial Pressure Monitoring Is Not Employed.

J Neurotrauma. 2020 Feb 04;:

Authors: Chesnut R, Temkin N, Videtta W, Petroni G, Lujan S, Pridgeon J, Dikmen S, Chaddock K, Barber J, Machamer J, Guadagnoli N, Hendrickson P, Aguilera S, Alanis V, Bello Quezada ME, Bautista Coronel E, Bustamante LA, Cacciatroi A, Carricondo CJ, Carvajal F, Davila R, Dominguez M, Figueroa JA, Fillipi MM, Godoy D, Gomez DC, Lacerda Gallardo AJ, Guerra Garcia JA, Zerain GF, Lavendez Cuientas LA, Lequipe C, Grajales Yuca GV, Jibaja Vega M, Kessler ME, Lopez Delgado HJ, Sandi Lora F, Mazzola AM, Maldonado RM, Mezquia de Pedro N, Martinez Zubieta JR, Mijangos Mendez JC, Mora J, Ochoa Parra JM, Pahnke PB, Paranhos J, Pinero G, Rivadeneira Pilacuán FA, Mendez Rivera MN, Romero Figueroa RL, Rubiano A, Saraguro Orozco AM, Silesky Jiménez JI, Silva Naranjo LV, Soler Morejon C, Urbina Z

Abstract
Globally, intracranial pressure (ICP) monitoring use in severe traumatic brain injury (sTBI) is inconsistent and susceptible to resource limitations and clinical philosophies. For situations without monitoring, there is no published comprehensive management algorithm specific to identifying and treating suspected intracranial hypertension (SICH) outside of the one ad hoc protocol in the BEST TRIP trial. As part of an ongoing NIH-supported project, a consensus conference involving 43 experienced Latin American Intensivists and Neurosurgeons who routinely care for sTBI patients without ICP monitoring, refined, revised, and augmented the original BEST TRIP algorithm. Based on BEST TRIP trial data and pre-meeting polling, 11 issues were target for development. We used Delphi-based methodology to codify individual statements and the final algorithm, using a group agreement threshold of 80%. The resulting algorithm defines SICH and addresses both general management and specific treatment. SICH treatment modalities are organized into tiers to guide treatment escalation and tapering. Treatment schedules were developed to facilitate targeted management of disease severity. A decision-support model, based on the group's combined practices, is provided to guide this process. This algorithm provides the first comprehensive management algorithm for treating sTBI patients when ICP monitoring is not available. It is intended to provide a framework to guide clinical care and direct future research toward sTBI management. Due to the dearth of relevant literature, it is explicitly consensus based, and is provided solely as a resource (a "consensus-based curbside consult") to assist in treating sTBI in general intensive care units in resource-limited environments.

PMID: 32013721 [PubMed - as supplied by publisher]

Adoption of coronary artery disease - Reporting and Data System (CAD-RADS™) and observed impact on medical therapy and systolic blood pressure control.

J Cardiovasc Comput Tomogr. 2020 Sep - Oct;14(5):421-427

Authors: Hull RA, Berger JM, Boster JM, Williams MU, Sharp AJ, Fentanes E, Maroules CD, Cury RC, Thomas DM

Abstract
BACKGROUND: CAD-RADS was developed to standardize communication of per-patient maximal stenosis on coronary CT angiography (CCTA) and provide treatment recommendations and may impact primary prevention care and resource utilization. The authors sought to evaluate CAD-RADS adoption on preventive medical therapy and risk factor control amongst a mixed provider population.
METHODS: Statins, aspirin (ASA), systolic blood pressure and, when available, lipid panel changes were abstracted for 1796 total patients undergoing CCTA in the 12 months before (non-standard reporting, NSR, cohort) and after adoption of the CAD-RADS reporting template. Only initiation of a medication in a treatment naïve patient, escalation from baseline dose, or transition to a higher potency was considered an escalation/initiation in lipid therapy.
RESULTS: The CAD-RADS reporting template was utilized in 83.7% (751/897) of CCTAs after the CAD-RADS adoption period. After adjusting for any coronary artery disease (CAD) on CCTA, statin initiation/escalation was more commonly observed in the CAD-RADS cohort (aOR 1.46; 95%CI 1.12-1.90, p = 0.005), driven by higher rates of new statin initiation (aOR 1.79; 95%CI 1.23-2.58, p = 0.002). This resulted in a higher observed rates of total cholesterol improvement in the CAD-RADS cohort (58% vs 49%, p = 0.016). New ASA initiation was similar between reporting templates after adjustment for CAD on CCTA (aOR 1.40; 95%CI 0.97-2.02, p = 0.069). The ordering provider's specialty (cardiology vs non-cardiology) did not significantly impact the observed differences in initiation/escalation of statins and ASA (pinteraction = NS).
CONCLUSIONS: Adoption of CAD-RADS reporting was associated with increased utilization of preventive medications, regardless of ordering provider specialty.

PMID: 32005447 [PubMed - indexed for MEDLINE]

Clinical Perspectives on Headache after Traumatic Brain Injury.

PM R. 2020 Jan 31;:

Authors: Hoffman JM, Lucas S, Dikmen S, Temkin N

Abstract
INTRODUCTION: Headache after traumatic brain injury (TBI) is frequent and persistent over the first year after injury. Providers may need to focus on different symptoms presentations depending on their patient's TBI severity.
OBJECTIVE: We evaluated headache symptoms in those with moderate-to-severe TBI compared to those with mild TBI and examined our data from two perspectives: 1) from providers who treat individuals after TBI and manage multiple post-injury symptoms including headache, and 2) from headache specialists who see individuals after TBI to manage headache.
DESIGN: Prospective enrollment of individuals after TBI with telephone follow up at one-year post-injury.
SETTING: Enrollment from hospital then community follow up.
PARTICIPANTS: 346 individuals with moderate-to-severe TBI were enrolled during acute inpatient rehabilitation across seven TBI Model System Centers. 189 individuals with mild TBI were enrolled within one week of injury at a single center.
INTERVENTION: None.
MAIN OUTCOME MEASURE: Headache frequency, headache type, pain intensity, headache impact test-6 item (HIT-6), and depressive symptoms measured one year after injury.
RESULTS: Headache prevalence is high in both TBI groups. TBI Providers are more likely to evaluate and treat headache from individuals sustaining a mild TBI vs moderate-to-severe TBI. Those with mild TBI are most likely to report tension-type headache followed by migraine-type headache. The migraine-type headache has higher impact (HIT-6) and greater pain intensity. Headache specialists may encounter those with moderate-to-severe TBI who report more frequent headache and higher average pain scores compared to those with mild TBI. The severity of TBI was unrelated to depressive symptoms one year after injury, but those with headache were significantly more likely to have higher scores.
CONCLUSIONS: TBI Providers vs headache specialists should be aware of differences in patient symptom presentation to their respective clinics. Ongoing assessment of headache and depression over time is important following TBI of any severity. This article is protected by copyright. All rights reserved.

PMID: 32003524 [PubMed - as supplied by publisher]