UW Neurological Surgery Recent PubMed Publications

Economic evaluation of telephone-based concussion management for combat-related mild traumatic brain injury.

J Telemed Telecare. 2018 May;24(4):282-289

Authors: Richardson JS, Guzauskas GF, Fann JR, Temkin NR, Bush NE, Bell KR, Gahm GA, Smolenski DJ, Brockway JA, Hansen RN

Abstract
Introduction Mild traumatic brain injury (mTBI) is an unfortunately common repercussion of military service in a combat zone. The CONTACT study tested an individualized telephone support intervention employing problem solving therapy (PST) for mTBI in soldiers recently returned from deployment. We sought to determine the cost effectiveness of this intervention from a military healthcare system perspective. Methods We conducted an intent-to-treat post-hoc analysis by building a decision analytic model that evaluated the choice between using PST or education only (EO). The model included cost-minimization and cost-effectiveness analyses. The incremental cost-effectiveness ratios (ICERs) were calculated as the differences in costs of PST versus EO relative to the differences in the outcomes of participants. Results The PST intervention resulted in an annual per-enrolee cost of $1027 (95% CI: $836 to $1248), while EO costs were $32 (95% CI: $25 to $39), resulting in a net incremental cost of $996 per enrolee (95% CI: $806 to $1,217). The ICERs were $68,658/QALY based on EQ-5D (95% CI: -$463,535 to $596,661) and $49,284/QALY based on SF-6D (95% CI: $26,971 to $159,309). Estimates of treatment costs in a real-world setting were accompanied by substantially lower ICERs that are within accepted thresholds for willingness-to-pay. Discussion Although the intervention had short-term benefits sufficient to yield acceptable ICERs, there was no long-term effect of PST over EO observed in the study. Consequently, we suggest that future studies examine the use of low-cost approaches, such as booster relapse-prevention calls, that may lead to a sustained treatment benefit for this population.

PMID: 28372513 [PubMed - indexed for MEDLINE]

Intra- and Peri-operative Complications Associated with Endoscopic Spine Surgery: A multi-institutional study.

World Neurosurg. 2018 Sep 10;:

Authors: Sen RD, White-Dzuro G, Ruzevick J, Kim CW, Witt JP, Telfeian AE, Wang MY, Hofstetter CP

Abstract
OBJECT: The purpose of this study is to report on intra- and peri-operative complications associated with working channel endoscopic spine surgery.
METHODS: This study is a retrospective chart review of a multi-institutional patient cohort operated on by surgeons within the Endoscopic Spine Study Group (ESSG) between May, 2010 and June, 2017.
RESULTS: Our study cohort consisted of a total of 553 consecutive cases with an average age of 57 years. The most common procedure was an endoscopic discectomy (n = 377, 68%) followed by foraminotomy (n = 156, 28.2%), laminectomy (n = 55, 9.9%), and medial facetectomy (n = 29, 5.2%). Overall, the rate of intra- and perioperative complications was 2.7%. There were 3 durotomies (0.54%), 2 epidural hematomas (0.36%), 2 patients developed a complex pain disorder (0.36%), 4 recurrent disc herniations within 3 months (1.1%), 4 systemic complications (1.1%) and no wound infections. No risk factors were identified with regards to age, gender, approach or number of segments.
CONCLUSIONS: Endoscopic spine surgery is associated with favorable rates of intra- and peri-operative complications compared to literature reports of comparable MIS and open surgeries. Our report proposes safe and effective strategies for management of these complications.

PMID: 30213674 [PubMed - as supplied by publisher]

Methimazole-Induced Pauci-Immune Glomerulonephritis and Anti-Phospholipid Syndrome: An Important Association to Be Aware of.

J Clin Med Res. 2018 Oct;10(10):786-790

Authors: Qaisar H, Hossain MA, Akula M, Cheng J, Patel M, Min Z, Kuzyshyn H, Levitt M, Coley SM, Asif A

Abstract
While methimazole (MMI) is the first line treatment for hyperthyroidism, this medication is not devoid of adverse effects. In this article, we present a 70-year-old male who admitted the hospital with right lower extremity pain and rash. The patient was recently treated with MMI for hyperthyroidism. Imaging studies revealed bilateral renal and splenic infarcts along with thrombosis of popliteal artery. Laboratory data revealed hematuria and proteinuria with positive (MPO), anti-proteinase-3 (PR3) and anti-cardiolipin IgG antibodies. Renal biopsy revealed pauci-immune glomerulonephritis and features with anti-phospholipid antibody syndrome (APS). MMI was discontinued and the patient was treated successfully with steroid therapy and anti-coagulation with resolution of proteinuria, hematuria and normalization of laboratory parameters. While MMI-induced pauci-immune glomerulonephritis has been previously reported, its association with APS has never been described before. Our case demonstrates that this rare diagnosis can be treated by early withdrawal of MMI and initiation of steroids along with anticoagulation.

PMID: 30214651 [PubMed]

Dabigatran-Induced Acute Interstitial Nephritis: An Important Complication of Newer Oral Anticoagulation Agents.

J Clin Med Res. 2018 Oct;10(10):791-794

Authors: Patel S, Hossain MA, Ajam F, Patel M, Nakrani M, Patel J, Alhillan A, Hammoda M, Alrefaee A, Levitt M, Asif A

Abstract
Acute kidney injury (AKI) due to an acute interstitial nephritis (AIN) is common and can lead to increased morbidity and mortality. Medications such as antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPI) and rifampin are common offending agents. Anticoagulant-associated AIN is more frequently reported with the use of warfarin; however, only few case reports have reported an association with the use of novel oral anticoagulants (NOACs). Herein, we report the case of a 59-year-old male who developed AKI after initiating dabigatran for the treatment of atrial fibrillation. Laboratory data demonstrated elevated blood urea nitrogen (BUN) of 115 mg/dL (baseline = 35 mg/dL) and serum creatinine (Cr) of 5.06 mg/dL (baseline = 1.3 mg/dL). Urinalysis revealed eosinophiluria. Renal biopsy disclosed diffuse tubulointerstitial nephritis and eosinophils and confirmed the diagnosis of AIN. At 1 week, renal function improved (BUN/Cr = 53/2.73 mg/dL) with steroid therapy and discontinuation of dabigatran. With an increasing use of NOACs, it is important to monitor renal function to diagnose AIN in a timely fashion. Early diagnosis and prompt treatment can mitigate serious renal damage induced by dabigatran.

PMID: 30214652 [PubMed]

Development of best practices to minimize wound complications after complex tethered spinal cord surgery: a modified Delphi study.

J Neurosurg Pediatr. 2018 Dec 01;22(6):701-709

Authors: Alexiades NG, Ahn ES, Blount JP, Brockmeyer DL, Browd SR, Grant GA, Heuer GG, Hankinson TC, Iskandar BJ, Jea A, Krieger MD, Leonard JR, Limbrick DD, Maher CO, Proctor MR, Sandberg DI, Wellons JC, Shao B, Feldstein NA, Anderson RCE

Abstract
OBJECTIVEComplications after complex tethered spinal cord (cTSC) surgery include infections and cerebrospinal fluid (CSF) leaks. With little empirical evidence to guide management, there is variability in the interventions undertaken to limit complications. Expert-based best practices may improve the care of patients undergoing cTSC surgery. Here, authors conducted a study to identify consensus-driven best practices.METHODSThe Delphi method was employed to identify consensual best practices. A literature review regarding cTSC surgery together with a survey of current practices was distributed to 17 board-certified pediatric neurosurgeons. Thirty statements were then formulated and distributed to the group. Results of the second survey were discussed during an in-person meeting leading to further consensus, which was defined as ≥ 80% agreement on a 4-point Likert scale (strongly agree, agree, disagree, strongly disagree).RESULTSSeventeen consensus-driven best practices were identified, with all participants willing to incorporate them into their practice. There were four preoperative interventions: (1, 2) asymptomatic AND symptomatic patients should be referred to urology preoperatively, (3, 4) routine preoperative urine cultures are not necessary for asymptomatic AND symptomatic patients. There were nine intraoperative interventions: (5) patients should receive perioperative cefazolin or an equivalent alternative in the event of allergy, (6) chlorhexidine-based skin preparation is the preferred regimen, (7) saline irrigation should be used intermittently throughout the case, (8) antibiotic-containing irrigation should be used following dural closure, (9) a nonlocking running suture technique should be used for dural closure, (10) dural graft overlay should be used when unable to obtain primary dural closure, (11) an expansile dural graft should be incorporated in cases of lipomyelomeningocele in which primary dural closure does not permit free flow of CSF, (12) paraxial muscles should be closed as a layer separate from the fascia, (13) routine placement of postoperative drains is not necessary. There were three postoperative interventions: (14) postoperative antibiotics are an option and, if given, should be discontinued within 24 hours; (15) patients should remain flat for at least 24 hours postoperatively; (16) routine use of abdominal binders or other compressive devices postoperatively is not necessary. One intervention was prioritized for additional study: (17) further study of additional gram-negative perioperative coverage is needed.CONCLUSIONSA modified Delphi technique was used to develop consensus-driven best practices for decreasing wound complications after cTSC surgery. Further study is required to determine if implementation of these practices will lead to reduced complications. Discussion through the course of this study resulted in the initiation of a multicenter study of gram-negative surgical site infections in cTSC surgery.

PMID: 30215584 [PubMed - indexed for MEDLINE]

Variation in the management of isolated craniosynostosis: a survey of the Synostosis Research Group.

J Neurosurg Pediatr. 2018 Dec 01;22(6):627-631

Authors: Kestle JRW, Lee A, Anderson RCE, Gociman B, Patel KB, Smyth MD, Birgfeld C, Pollack IF, Goldstein JA, Tamber M, Imahiyerobo T, Siddiqi FA, Synostosis Research Group

Abstract
OBJECTIVEThe authors created a collaborative network, the Synostosis Research Group (SynRG), to facilitate multicenter clinical research on craniosynostosis. To identify common and differing practice patterns within the network, they assessed the SynRG surgeons' management preferences for sagittal synostosis. These results will be incorporated into planning cooperative studies.METHODSThe SynRG consists of 12 surgeons at 5 clinical sites. An email survey was distributed to SynRG surgeons in late 2016, and responses were collected through early 2017. Responses were collated and analyzed descriptively.RESULTSAll of the surgeons-7 plastic/craniofacial surgeons and 5 neurosurgeons-completed the survey. They varied in both experience (1-24 years) and sagittal synostosis case volume in the preceding year (5-45 cases). Three sites routinely perform preoperative CT scans. The preferred surgical technique for children younger than 3 months is strip craniectomy (10/12 surgeons), whereas children older than 6 months are all treated with open cranial vault surgery. Pre-incision cefazolin, preoperative complete blood count panels, and an arterial line were used by most surgeons, but tranexamic acid was used routinely at 3 sites and never at the other 2 sites. Among surgeons performing endoscopic strip craniectomy surgery (SCS), most create a 5-cm-wide craniectomy, whereas 2 surgeons create a 2-cm strip. Four surgeons routinely send endoscopic SCS patients to the intensive care unit after surgery. Two of the 5 sites routinely obtain a CT scan within the 1st year after surgery.CONCLUSIONSThe SynRG surgeons vary substantially in the use of imaging, the choice of surgical procedure and technique, and follow-up. A collaborative network will provide the opportunity to study different practice patterns, reduce variation, and contribute multicenter data on the management of children with craniosynostosis.

PMID: 30215587 [PubMed - indexed for MEDLINE]

Comparison of Tumor Regression Grading of Residual Pancreatic Ductal Adenocarcinoma Following Neoadjuvant Chemotherapy Without Radiation: Would Fewer Tier-Stratification Be Favorable Toward Standardization?

Am J Surg Pathol. 2019 03;43(3):334-340

Authors: Kim SS, Ko AH, Nakakura EK, Wang ZJ, Corvera CU, Harris HW, Kirkwood KS, Hirose R, Tempero MA, Kim GE

Abstract
To assess whether the College of American Pathologists (CAP) and the Evans grading systems for neoadjuvant chemotherapy without radiation-treated pancreatectomy specimens are prognostic, and if a 3-tier stratification scheme preserves data granularity. Conducted retrospective review of 32 patients with ordinary pancreatic ductal adenocarcinoma treated with neoadjuvant therapy without radiation followed by surgical resection. Final pathologic tumor category (AJCC eighth edition) was 46.9% ypT1, 34.4% ypT2, and 18.7% ypT3. Median follow-up time was 29.8 months, median disease-free survival (DFS) was 19.6 months, and median overall survival (OS) was 34.2 months. CAP score 1, 2, 3 were present in 5 (15.6%), 18 (56.3%), and 9 (28.1%) patients, respectively. Evans grade III, IIb, IIa, and I were present in 10 (31.2%), 8 (25.0%), 7 (21.9%), and 7 (21.9%) patients, respectively. OS (CAP: P=0.005; Evans: P=0.001) and DFS (CAP: P=0.003; Evans: P=0.04) were statistically significant for both CAP and Evans. Stratified CAP scores 1 and 2 versus CAP score 3 was statistically significant for both OS (P=0.002) and DFS (P=0.002). Stratified Evans grades I, IIa, and IIb versus Evans grade III was statistically significant for both OS (P=0.04) and DFS (P=0.02). CAP, Evans, and 3-tier stratification are prognostic of OS and DFS.

PMID: 30211728 [PubMed - indexed for MEDLINE]

Screening for Pfhrp2/3-Deleted Plasmodium falciparum, Non-falciparum, and Low-Density Malaria Infections by a Multiplex Antigen Assay.

J Infect Dis. 2019 01 09;219(3):437-447

Authors: Plucinski MM, Herman C, Jones S, Dimbu R, Fortes F, Ljolje D, Lucchi N, Murphy SC, Smith NT, Cruz KR, Seilie AM, Halsey ES, Udhayakumar V, Aidoo M, Rogier E

Abstract
Background: Detection of Plasmodium antigens provides evidence of malaria infection status and is the basis for most malaria diagnosis.
Methods: We developed a sensitive bead-based multiplex assay for laboratory use, which simultaneously detects pan-Plasmodium aldolase (pAldo), pan-Plasmodium lactate dehydrogenase (pLDH), and P. falciparum histidine-rich protein 2 (PfHRP2) antigens. The assay was validated against purified recombinant antigens, monospecies malaria infections, and noninfected blood samples. To test against samples collected in an endemic setting, Angolan outpatient samples (n = 1267) were assayed.
Results: Of 466 Angolan samples positive for at least 1 antigen, the most common antigen profiles were PfHRP2+/pAldo+/pLDH+ (167, 36%), PfHRP2+/pAldo-/pLDH- (163, 35%), and PfHRP2+/pAldo+/pLDH- (129, 28%). Antigen profile was predictive of polymerase chain reaction (PCR) positivity and parasite density. Eight Angolan samples (1.7%) had no or very low PfHRP2 but were positive for 1 or both of the other antigens. PCR analysis confirmed 3 (0.6%) were P. ovale infections and 2 (0.4%) represented P. falciparum parasites lacking Pfhrp2 and/or Pfhrp3.
Conclusions: These are the first reports of Pfhrp2/3 deletion mutants in Angola. High-throughput multiplex antigen detection can inexpensively screen for low-density P. falciparum, non-falciparum, and Pfhrp2/3-deleted parasites to provide population-level antigen estimates and identify specimens requiring further molecular characterization.

PMID: 30202972 [PubMed - indexed for MEDLINE]

Suboptimal lipid management before and after ischaemic stroke and TIA-the North Dublin Population Stroke Study.

Ir J Med Sci. 2018 Aug;187(3):739-746

Authors: Ní Chróinín D, Ní Chróinín C, Akijian L, Callaly EL, Hannon N, Kelly L, Marnane M, Merwick Á, Sheehan Ó, Horgan G, Duggan J, Kyne L, Dolan E, Murphy S, Williams D, Kelly PJ

Abstract
BACKGROUND: Few population-based studies have assessed lipid adherence to international guidelines for primary and secondary prevention in stroke/transient ischaemic attack (TIA) patients.
AIMS: This study aims to evaluate adherence to lipid-lowering therapy (LLT) guidelines amongst patients with ischaemic stroke/TIA.
METHODS: Using hot and cold pursuit methods from multiple hospital/community sources, all stroke and TIA cases in North Dublin City were prospectively ascertained over a 1-year period. Adherence to National Cholesterol Education Programme (NCEP) III guidelines, before and after index ischaemic stroke/TIA, was assessed.
RESULTS: Amongst 616 patients (428 ischaemic stroke, 188 TIA), total cholesterol was measured following the qualifying event in 76.5% (471/616) and low-density lipoprotein (LDL) in 60.1% (370/616). At initial stroke/TIA presentation, 54.1% (200/370) met NCEP III LDL goals. Compliance was associated with prior stroke (odds ratio [OR] 2.19, p = 0.02), diabetes (OR 1.91, p = 0.04), hypertension (OR 1.57, p = 0.03), atrial fibrillation (OR 1.78, p = 0.01), pre-event LLT (OR 2.85, p < 0.001) and higher individual LDL goal (p = 0.001). At stroke/TIA onset, 32.7% (195/596) was on LLT. Nonetheless, LDL exceeded individual NCEP goal in 29.2% (56/192); 21.6% (53/245) warranting LLT was not on treatment prior to stroke/TIA onset. After index stroke/TIA, 75.9% (422/556) was on LLT; 15.3% (30/196) meeting NCEP III criteria was not prescribed a statin as recommended. By 2 years, actuarial survival was 72.8% and 11.9% (59/497) experienced stroke recurrence. No association was observed between initial post-event target adherence and 2-year outcomes.
CONCLUSIONS: In this population-based study, LLT recommended by international guidelines was under-used, before and after index stroke/TIA. Strategies to improve adherence are needed.

PMID: 29368282 [PubMed - indexed for MEDLINE]

Centers for Disease Control and Prevention Guideline on the Diagnosis and Management of Mild Traumatic Brain Injury Among Children.

JAMA Pediatr. 2018 11 01;172(11):e182853

Authors: Lumba-Brown A, Yeates KO, Sarmiento K, Breiding MJ, Haegerich TM, Gioia GA, Turner M, Benzel EC, Suskauer SJ, Giza CC, Joseph M, Broomand C, Weissman B, Gordon W, Wright DW, Moser RS, McAvoy K, Ewing-Cobbs L, Duhaime AC, Putukian M, Holshouser B, Paulk D, Wade SL, Herring SA, Halstead M, Keenan HT, Choe M, Christian CW, Guskiewicz K, Raksin PB, Gregory A, Mucha A, Taylor HG, Callahan JM, DeWitt J, Collins MW, Kirkwood MW, Ragheb J, Ellenbogen RG, Spinks TJ, Ganiats TG, Sabelhaus LJ, Altenhofen K, Hoffman R, Getchius T, Gronseth G, Donnell Z, O'Connor RE, Timmons SD

Abstract
Importance: Mild traumatic brain injury (mTBI), or concussion, in children is a rapidly growing public health concern because epidemiologic data indicate a marked increase in the number of emergency department visits for mTBI over the past decade. However, no evidence-based clinical guidelines have been developed to date for diagnosing and managing pediatric mTBI in the United States.
Objective: To provide a guideline based on a previous systematic review of the literature to obtain and assess evidence toward developing clinical recommendations for health care professionals related to the diagnosis, prognosis, and management/treatment of pediatric mTBI.
Evidence Review: The Centers for Disease Control and Prevention (CDC) National Center for Injury Prevention and Control Board of Scientific Counselors, a federal advisory committee, established the Pediatric Mild Traumatic Brain Injury Guideline Workgroup. The workgroup drafted recommendations based on the evidence that was obtained and assessed within the systematic review, as well as related evidence, scientific principles, and expert inference. This information includes selected studies published since the evidence review was conducted that were deemed by the workgroup to be relevant to the recommendations. The dates of the initial literature search were January 1, 1990, to November 30, 2012, and the dates of the updated literature search were December 1, 2012, to July 31, 2015.
Findings: The CDC guideline includes 19 sets of recommendations on the diagnosis, prognosis, and management/treatment of pediatric mTBI that were assigned a level of obligation (ie, must, should, or may) based on confidence in the evidence. Recommendations address imaging, symptom scales, cognitive testing, and standardized assessment for diagnosis; history and risk factor assessment, monitoring, and counseling for prognosis; and patient/family education, rest, support, return to school, and symptom management for treatment.
Conclusions and Relevance: This guideline identifies the best practices for mTBI based on the current evidence; updates should be made as the body of evidence grows. In addition to the development of the guideline, CDC has created user-friendly guideline implementation materials that are concise and actionable. Evaluation of the guideline and implementation materials is crucial in understanding the influence of the recommendations.

PMID: 30193284 [PubMed - indexed for MEDLINE]

Diagnosis and Management of Mild Traumatic Brain Injury in Children: A Systematic Review.

JAMA Pediatr. 2018 11 01;172(11):e182847

Authors: Lumba-Brown A, Yeates KO, Sarmiento K, Breiding MJ, Haegerich TM, Gioia GA, Turner M, Benzel EC, Suskauer SJ, Giza CC, Joseph M, Broomand C, Weissman B, Gordon W, Wright DW, Moser RS, McAvoy K, Ewing-Cobbs L, Duhaime AC, Putukian M, Holshouser B, Paulk D, Wade SL, Herring SA, Halstead M, Keenan HT, Choe M, Christian CW, Guskiewicz K, Raksin PB, Gregory A, Mucha A, Taylor HG, Callahan JM, DeWitt J, Collins MW, Kirkwood MW, Ragheb J, Ellenbogen RG, Spinks TJ, Ganiats TG, Sabelhaus LJ, Altenhofen K, Hoffman R, Getchius T, Gronseth G, Donnell Z, O'Connor RE, Timmons SD

Abstract
Importance: In recent years, there has been an exponential increase in the research guiding pediatric mild traumatic brain injury (mTBI) clinical management, in large part because of heightened concerns about the consequences of mTBI, also known as concussion, in children. The CDC National Center for Injury Prevention and Control's (NCIPC) Board of Scientific Counselors (BSC), a federal advisory committee, established the Pediatric Mild TBI Guideline workgroup to complete this systematic review summarizing the first 25 years of literature in this field of study.
Objective: To conduct a systematic review of the pediatric mTBI literature to serve as the foundation for an evidence-based guideline with clinical recommendations associated with the diagnosis and management of pediatric mTBI.
Evidence Review: Using a modified Delphi process, the authors selected 6 clinical questions on diagnosis, prognosis, and management or treatment of pediatric mTBI. Two consecutive searches were conducted on PubMed, Embase, ERIC, CINAHL, and SportDiscus. The first included the dates January 1, 1990, to November 30, 2012, and an updated search included December 1, 2012, to July 31, 2015. The initial search was completed from December 2012 to January 2013; the updated search, from July 2015 to August 2015. Two authors worked in pairs to abstract study characteristics independently for each article selected for inclusion. A third author adjudicated disagreements. The risk of bias in each study was determined using the American Academy of Neurology Classification of Evidence Scheme. Conclusion statements were developed regarding the evidence within each clinical question, and a level of confidence in the evidence was assigned to each conclusion using a modified GRADE methodology. Data analysis was completed from October 2014 to May 2015 for the initial search and from November 2015 to April 2016 for the updated search.
Findings: Validated tools are available to assist clinicians in the diagnosis and management of pediatric mTBI. A significant body of research exists to identify features that are associated with more serious TBI-associated intracranial injury, delayed recovery from mTBI, and long-term sequelae. However, high-quality studies of treatments meant to improve mTBI outcomes are currently lacking.
Conclusions and Relevance: This systematic review was used to develop an evidence-based clinical guideline for the diagnosis and management of pediatric mTBI. While an increasing amount of research provides clinically useful information, this systematic review identified key gaps in diagnosis, prognosis, and management.

PMID: 30193325 [PubMed - indexed for MEDLINE]

Risk factors, clinical findings, and outcomes in pregnancies with coronary artery dissection: A case series.

Eur J Prev Cardiol. 2019 03;26(5):544-548

Authors: Lee AC, Haddad A, Fries MH, Al-Kouatly HB

PMID: 30180768 [PubMed - indexed for MEDLINE]

Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq.

Nat Commun. 2018 Sep 04;9(1):3588

Authors: Karaayvaz M, Cristea S, Gillespie SM, Patel AP, Mylvaganam R, Luo CC, Specht MC, Bernstein BE, Michor F, Ellisen LW

Abstract
Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by extensive intratumoral heterogeneity. To investigate the underlying biology, we conducted single-cell RNA-sequencing (scRNA-seq) of >1500 cells from six primary TNBC. Here, we show that intercellular heterogeneity of gene expression programs within each tumor is variable and largely correlates with clonality of inferred genomic copy number changes, suggesting that genotype drives the gene expression phenotype of individual subpopulations. Clustering of gene expression profiles identified distinct subgroups of malignant cells shared by multiple tumors, including a single subpopulation associated with multiple signatures of treatment resistance and metastasis, and characterized functionally by activation of glycosphingolipid metabolism and associated innate immunity pathways. A novel signature defining this subpopulation predicts long-term outcomes for TNBC patients in a large cohort. Collectively, this analysis reveals the functional heterogeneity and its association with genomic evolution in TNBC, and uncovers unanticipated biological principles dictating poor outcomes in this disease.

PMID: 30181541 [PubMed - in process]

The relationship between defense mechanisms and religious coping using a new two-factor solution for the Defense Style Questionnaire-40.

Bull Menninger Clin. 2018;82(3):224-252

Authors: Prout TA, Gottdiener WH, Camargo A, Murphy S

Abstract
This study examined the factor structure of the Defense Style Questionnaire (DSQ-40) and explored the relationships between defense mechanisms and religious coping in a diverse sample of 380 college students. In contrast with the three-factor model of defenses proposed by the developers of the DSQ-40, principal axis factoring yielded two internally consistent components: adaptive and maladaptive defense styles. Endorsement of adaptive defenses was positively correlated with the use of positive religious coping strategies and negatively correlated with negative religious coping. Maladaptive defenses were associated with the endorsement of negative religious coping strategies. Clinical implications of these findings are discussed and recommendations are made for future use of the DSQ-40.

PMID: 30179043 [PubMed - indexed for MEDLINE]

Does the future of laparoscopic sleeve gastrectomy lie in the outpatient surgery center? A retrospective study of the safety of 3162 outpatient sleeve gastrectomies.

Surg Obes Relat Dis. 2018 Oct;14(10):1442-1447

Authors: Surve A, Cottam D, Zaveri H, Cottam A, Belnap L, Richards C, Medlin W, Duncan T, Tuggle K, Zorak A, Umbach T, Apel M, Billing P, Billing J, Landerholm R, Stewart K, Kaufman J, Harris E, Williams M, Hart C, Johnson W, Lee C, Lee C, DeBarros J, Orris M, Schniederjan B, Neichoy B, Dhorepatil A, Cottam S, Horsley B

Abstract
BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a safe and effective procedure that can be performed as an outpatient procedure.
OBJECTIVES: The aim of the study was to determine whether same-day discharge LSG is safe when performed in an outpatient surgery center.
SETTING: Outpatient surgery centers.
METHODS: The medical records of 3162 patients who underwent primary LSG procedure by 21 surgeons at 9 outpatient surgery centers from January 2010 through February 2018 were retrospectively reviewed.
RESULTS: Three thousand one hundred sixty-two patients were managed with enhanced recovery after surgery protocol and were included in this analysis. The mean age and preoperative body mass index were 43.1 ± 10.8 years and 42.1 ± 7.1 kg/m2, respectively. Sleep apnea, type 2 diabetes, gastroesophageal reflux disease, hypertension, and hyperlipidemia were seen in 14.4%, 13.5%, 24.7%, 30.4%, and 17.6% patients, respectively. The mean total operative time was 56.4 ± 16.9 minutes (skin to skin). One intraoperative complication (.03%) occurred. The hospital transfer rate was .2%. The 30-day follow-up rate was 85%. The postoperative outcomes were analyzed based on the available data. The 30-day readmission, reoperation, reintervention, and emergency room visit rates were .6%, .6%, .2%, and .1%, respectively. The 30-day mortality rate was 0%. The total short-term complication rate was 2.5%.
CONCLUSIONS: Same-day discharge seems to be safe when performed in an outpatient surgery center in selected patients. It would appear that outpatient surgery centers are a viable option for patients with minimal surgical risks.

PMID: 30170954 [PubMed - indexed for MEDLINE]

Method and Apparatus for the Automated Delivery of Continuous Neural Stem Cell Trails Into the Spinal Cord of Small and Large Animals.

Neurosurgery. 2019 10 01;85(4):560-573

Authors: Kutikov AB, Moore SW, Layer RT, Podell PE, Sridhar N, Santamaria AJ, Aimetti AA, Hofstetter CP, Ulich TR, Guest JD

Abstract
BACKGROUND: Immature neurons can extend processes after transplantation in adult animals. Neuronal relays can form between injected neural stem cells (NSCs) and surviving neurons, possibly improving recovery after spinal cord injury (SCI). Cell delivery methods of single or multiple bolus injections of concentrated cell suspensions thus far tested in preclinical and clinical experiments are suboptimal for new tract formation. Nonuniform injectate dispersal is often seen due to gravitational cell settling and clumping. Multiple injections have additive risks of hemorrhage, parenchymal damage, and cellular reflux and require additional surgical exposure. The deposition of multiply delivered cells boluses may be uneven and discontinuous.
OBJECTIVE: To develop an injection apparatus and methodology to deliver continuous cellular trails bridging spinal cord lesions.
METHODS: We improved the uniformity of cellular trails by formulating NSCs in hyaluronic acid. The TrailmakerTM stereotaxic injection device was automatized to extend a shape memory needle from a single-entry point in the spinal cord longitudinal axis to "pioneer" a new trail space and then retract while depositing an hyaluronic acid-NSC suspension. We conducted testing in a collagen spinal models, and animal testing using human NSCs (hNSCs) in rats and minipigs.
RESULTS: Continuous surviving trails of hNSCs within rat and minipig naive spinal cords were 12 and 40 mm in length. hNSC trails were delivered across semi-acute contusion injuries in rats. Transplanted hNSCs survived and were able to differentiate into neural lineage cells and astrocytes.
CONCLUSION: The TrailmakerTM creates longitudinal cellular trails spanning multiple levels from a single-entry point. This may enhance the ability of therapeutics to promote functional relays after SCI.

PMID: 30169668 [PubMed - indexed for MEDLINE]

Microsurgical Excision of T12-L1 Pial Arteriovenous Malformation: 3-Dimensional Operative Video.

Oper Neurosurg (Hagerstown). 2018 Aug 30;:

Authors: Zeeshan Q, Cheng CY, Ghodke BV, Sekhar LN

Abstract
This 29-yr-old man presented with progressive paraparesis, sensory loss, allodynia, bowel, and bladder dysfunction for 9 mo, acutely exacerbated in the preceding 24 h. Magnetic resonance imaging scan showed multiple dilated vessels involving the thoracic cord. Spinal angiogram revealed a T12-L1 pial arteriovenous malformation (AVM)/arteriovenous fistula on the left side. It was fed by an L1 radicular artery that filled the anterior spinal artery, which in turn had multiple feeders to a pial AVM. Because of the supply from the anterior spinal artery with multiple feeders to the AVM, and the danger of infarction of the conus, embolization was not performed.He underwent T11-L1 laminectomy laterally to the pedicles and excision of AVM. There was one large arterialized vein in the midline that had a fistulous connection with an artery coursing up from inferiorly. Despite occlusion of this fistula, the vein was still arterialized. On further exploration, there was a large artery coming in to the subarachnoid space at the T11 level and coursing inferiorly, and entering the intradural pial AVM with a glomus of vessels located at the T12 level in the left anterolateral subpial aspect of the cord. This major artery as well as multiple smaller vessels going into it were cauterized and divided, and the AVM was totally excised.Postoperative angiogram showed complete excision of the nidus. At 1 mo follow-up, he had complete recovery of motor and bladder functions but bowel dysfunction persisted. He was independent for his daily activities.Informed consent was obtained from the patient prior to the surgery that included videotaping of the procedure and its distribution for educational purposes. All relevant patient identifiers have also been removed from the video and accompanying radiology slides.

PMID: 30169720 [PubMed - as supplied by publisher]

Sternocleidomastoid Encephalomyosynangiosis for Treatment-Resistant Moyamoya Disease.

Oper Neurosurg (Hagerstown). 2019 07 01;17(1):E23-E28

Authors: Chiarelli PA, Patel AP, Lee A, Chandra SR, Sekhar LN

Abstract
BACKGROUND AND IMPORTANCE: Refractory ischemic symptoms in moyamoya disease are a challenging problem, particularly in situations in which multiple direct and indirect revascularization techniques have already been employed. In addition, revascularization of the parietal lobes is difficult, as this area is a watershed between the middle cerebral artery and posterior cerebral artery distributions.
CLINICAL PRESENTATION: This is the case of a 50-yr-old woman with hemibody sensorimotor deficits, who had previously undergone bilateral arterial bypass and temporalis myosynangiosis. A method for indirect surgical cerebral revascularization is described, utilizing a rotated and tunneled sternocleidomastoid flap. The perfused muscle is approximated to the cortical surface, with adjacent sulci dissected to expose the underlying vasculature. After sternocleidomastoid encephalomyosynangiosis, the patient experienced symptomatic improvement, along with the appearance of new pial collateral vasculature on diagnostic cerebral angiography. Pre- and postoperative dynamic perfusion computed tomography with acetazolamide challenge demonstrate an increase in cerebral blood flow and decrease in mean transit time, as well as improved cerebrovascular reserve.
CONCLUSION: Sternocleidomastoid encephalomyosynangiosis using a tunneled muscle flap is a useful method for revascularization of the parietal and occipital lobes, particularly for refractory moyamoya in cases where a variety of other options have been exhausted.

PMID: 30169838 [PubMed - indexed for MEDLINE]

Characterization of the immune microenvironment of diffuse intrinsic pontine glioma: implications for development of immunotherapy.

Neuro Oncol. 2019 01 01;21(1):83-94

Authors: Lieberman NAP, DeGolier K, Kovar HM, Davis A, Hoglund V, Stevens J, Winter C, Deutsch G, Furlan SN, Vitanza NA, Leary SES, Crane CA

Abstract
Background: Diffuse intrinsic pontine glioma (DIPG) is a uniformly fatal CNS tumor diagnosed in 300 American children per year. Radiation is the only effective treatment and extends overall survival to a median of 11 months. Due to its location in the brainstem, DIPG cannot be surgically resected. Immunotherapy has the ability to target tumor cells specifically; however, little is known about the tumor microenvironment in DIPGs. We sought to characterize infiltrating immune cells and immunosuppressive factor expression in pediatric low- and high-grade gliomas and DIPG.
Methods: Tumor microarrays were stained for infiltrating immune cells. RNA was isolated from snap-frozen tumor tissue and Nanostring analysis performed. DIPG and glioblastoma cells were co-cultured with healthy donor macrophages, T cells, or natural killer (NK) cells, and flow cytometry and cytotoxicity assays performed to characterize the phenotype and function, respectively, of the immune cells.
Results: DIPG tumors do not have increased macrophage or T-cell infiltration relative to nontumor control, nor do they overexpress immunosuppressive factors such as programmed death ligand 1 and/or transforming growth factor β1. H3.3-K27M DIPG cells do not repolarize macrophages, but are not effectively targeted by activated allogeneic T cells. NK cells lysed all DIPG cultures.
Conclusions: DIPG tumors have neither a highly immunosuppressive nor inflammatory microenvironment. Therefore, major considerations for the development of immunotherapy will be the recruitment, activation, and retention of tumor-specific effector immune cells.

PMID: 30169876 [PubMed - indexed for MEDLINE]

Analysis and visualization of linked molecular and clinical cancer data by using Oncoscape.

Nat Genet. 2018 09;50(9):1203-1204

Authors: McFerrin LG, Zager M, Zhang J, Krenn G, McDermott R, Horse-Grant D, Silgard E, Colevas K, Shannon P, Bolouri H, Holland EC

PMID: 30158685 [PubMed - indexed for MEDLINE]