UW Neurological Surgery Recent PubMed Publications

Microvascular Decompression of Facial Nerve and Pexy of the Left Vertebral Artery for Left Hemifacial Spasm: 3-Dimensional Operative Video.

Oper Neurosurg (Hagerstown). 2018 Mar 29;:

Authors: Cheng CY, Shetty R, Martinez V, Sekhar LN

Abstract
A 73-yr-old man presented with intractable left hemifacial spasm of 4 yr duration. Brain magnetic resonance imaging showed significant compression of left facial nerve by the left vertebral artery (VA) and anterior inferior cerebellar artery (AICA).The patient underwent a left retrosigmoid craniotomy and a microvascular decompression of the cranial nerve (CN) VII. Intraoperatively, we found that the distal AICA had a protracted subarcuate extradural course.1 This was relieved by intra/extradural dissection. The left VA and the AICA loop were compressing the root exit zone of CN VII. The VA was mobilized, and pexy into the petrosal dura was done with 8-0 nylon sutures (Ethilon Nylon Suture, Ethicon Inc, a subsidiary of Johnson & Johnson, Somerville, New Jersey). Once this was done, the lateral spread disappeared.2 The AICA loop was decompressed with 2 pieces of Teflon felt (Bard PTFE felt, Bard peripheral Vascular Inc, a subsidiary of CR Bard Inc, Temp, Arizona). After this, wave V of the brainstem auditory evoked potential (BAEP) disappeared completely, with no recovery despite the application of the nicardipine on the internal auditory artery (IAA). The IAA appeared to be stretched by the microvascular decompression. Arachnoidal dissection was done to release the CN VIII and an additional felt piece was placed to elevate the AICA loop; the BAEP recovered completely. The patient had a complete disappearance of the hemifacial spasm postoperatively, and hearing was unchanged.This 3-D video shows the technical nuances of performing a vertebropexy, release of the AICA from its extradural subarcuate course, and the surgical maneuvers in the event of an unexpected change in neuromonitoring response. The suture technique of vertebropexy is preferred to a loop technique, to avoid kinking of the VA.3Informed 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: 29617905 [PubMed - as supplied by publisher]

Fewer thromboembolic events after implementation of a venous thromboembolism risk stratification tool.

J Surg Res. 2018 05;225:148-156

Authors: Turrentine FE, Sohn MW, Wilson SL, Stanley C, Novicoff W, Sawyer RG, Williams MD

Abstract
BACKGROUND: Deep venous thrombosis and pulmonary embolus are leading preventable causes of death after surgery. Venous thromboembolism (VTE) prophylaxis management guidelines, with evidenced-based recommendations, are available in the literature. However, over 40% of "at-risk" surgical patients fail to receive appropriate VTE prophylaxis. Decision support-based interventions to reduce venous thromboembolic events were explored.
METHODS: A venous thromboembolic risk stratification tool embedded in the electronic medical record, Epic, linking risk category to venous thromboembolic prophylaxis order sets was created, implemented, and analyzed for general surgery patients. Logistic regression analysis was used to compare rates of venous thromboembolic events before and after the intervention, controlling for age, gender, race, body mass index, inpatient status, transfer status, elective/emergent case status, American Society of Anesthesiologists classification, and wound classification.
RESULTS: Venous thromboembolic events in the preintervention and postintervention periods were 55 (1.25%) and 12 (0.64%), respectively (P = 0.033). All-cause mortality events decreased after intervention from 49 (1.12%) to 14 (0.75%; P = 0.187). Multivariable analyses show that the risk of a venous thromboembolic event after intervention was half (odds ratio = 0.532; 95% confidence interval, 0.284-0.997; P = 0.049) as likely compared to that in the preintervention period. From 2012 to 2015, our institution moved from the ninth decile (poor) to the first decile (best) for the incidence of venous thromboembolic events among 760 National Surgical Quality Improvement Program hospitals across the nation.
CONCLUSIONS: Postoperative thromboembolic events decreased after implementation of a VTE risk stratification tool, linking risk category to venous thromboembolic prophylaxis order sets, embedded in the electronic medical record, Epic.

PMID: 29605025 [PubMed - indexed for MEDLINE]

Plasmodium falciparum Liver Stage Infection and Transition to Stable Blood Stage Infection in Liver-Humanized and Blood-Humanized FRGN KO Mice Enables Testing of Blood Stage Inhibitory Antibodies (Reticulocyte-Binding Protein Homolog 5) In Vivo.

Front Immunol. 2018;9:524

Authors: Foquet L, Schafer C, Minkah NK, Alanine DGW, Flannery EL, Steel RWJ, Sack BK, Camargo N, Fishbaugher M, Betz W, Nguyen T, Billman ZP, Wilson EM, Bial J, Murphy SC, Draper SJ, Mikolajczak SA, Kappe SHI

Abstract
The invention of liver-humanized mouse models has made it possible to directly study the preerythrocytic stages of Plasmodium falciparum. In contrast, the current models to directly study blood stage infection in vivo are extremely limited. Humanization of the mouse blood stream is achievable by frequent injections of human red blood cells (hRBCs) and is currently the only system with which to study human malaria blood stage infections in a small animal model. Infections have been primarily achieved by direct injection of P. falciparum-infected RBCs but as such, this modality of infection does not model the natural route of infection by mosquito bite and lacks the transition of parasites from liver stage infection to blood stage infection. Including these life cycle transition points in a small animal model is of relevance for testing therapeutic interventions. To this end, we used FRGN KO mice that were engrafted with human hepatocytes and performed a blood exchange under immune modulation to engraft the animals with more than 50% hRBCs. These mice were infected by mosquito bite with sporozoite stages of a luciferase-expressing P. falciparum parasite, resulting in noninvasively measurable liver stage burden by in vivo bioluminescent imaging (IVIS) at days 5-7 postinfection. Transition to blood stage infection was observed by IVIS from day 8 onward and then blood stage parasitemia increased with a kinetic similar to that observed in controlled human malaria infection. To assess the utility of this model, we tested whether a monoclonal antibody targeting the erythrocyte invasion ligand reticulocyte-binding protein homolog 5 (with known growth inhibitory activity in vitro) was capable of blocking blood stage infection in vivo when parasites emerge from the liver and found it highly effective. Together, these results show that a combined liver-humanized and blood-humanized FRGN mouse model infected with luciferase-expressing P. falciparum will be a useful tool to study P. falciparum preerythrocytic and erythrocytic stages and enables the testing of interventions that target either one or both stages of parasite infection.

PMID: 29593746 [PubMed]

Alcohol-Related Nurse Care Management in Primary Care: A Randomized Clinical Trial.

JAMA Intern Med. 2018 05 01;178(5):613-621

Authors: Bradley KA, Bobb JF, Ludman EJ, Chavez LJ, Saxon AJ, Merrill JO, Williams EC, Hawkins EJ, Caldeiro RM, Achtmeyer CE, Greenberg DM, Lapham GT, Richards JE, Lee AK, Kivlahan DR

Abstract
Importance: Experts recommend that alcohol use disorders (AUDs) be managed in primary care, but effective approaches are unclear.
Objective: To test whether 12 months of alcohol care management, compared with usual care, improved drinking outcomes among patients with or at high risk for AUDs.
Design, Setting, and Participants: This randomized clinical trial was conducted at 3 Veterans Affairs (VA) primary care clinics. Between October 11, 2011, and September 30, 2014, the study enrolled 304 outpatients who reported heavy drinking (≥4 drinks per day for women and ≥5 drinks per day for men).
Interventions: Nurse care managers offered outreach and engagement, repeated brief counseling using motivational interviewing and shared decision making about treatment options, and nurse practitioner-prescribed AUD medications (if desired), supported by an interdisciplinary team (CHOICE intervention). The comparison was usual primary care.
Main Outcomes and Measures: Primary outcomes, assessed by blinded telephone interviewers at 12 months, were percentage of heavy drinking days in the prior 28 days measured by timeline follow-back interviews and a binary good drinking outcome, defined as abstinence or drinking below recommended limits in the prior 28 days (according to timeline follow-back interviews) and no alcohol-related symptoms in the past 3 months as measured by the Short Inventory of Problems.
Results: Of 304 participants, 275 (90%) were male, 206 (68%) were white, and the mean (SD) age was 51.4 (13.8) years. At baseline, both the CHOICE intervention (n = 150) and usual care (n = 154) groups reported heavy drinking on 61% of days (95% CI, 56%-66%). During the 12-month intervention, 137 of 150 patients in the intervention group (91%) had at least 1 nurse visit, and 77 of 150 (51%) had at least 6 nurse visits. A greater proportion of patients in the intervention group than in the usual care group received alcohol-related care: 42% (95% CI, 35%-49%; 63 of 150 patients) vs 26% (95% CI, 19%-35%; 40 of 154 patients). Alcohol-related care included more AUD medication use: 32% (95% CI, 26%-39%; 48 of 150 patients in the intervention group) vs 8% (95% CI, 5%-13%; 13 of 154 patients in the usual care group). No significant differences in primary outcomes were observed at 12 months between patients in both groups. The percentages of heavy drinking days were 39% (95% CI, 32%-47%) and 35% (95% CI, 28%-42%), and the percentages of patients with a good drinking outcome were 15% (95% CI, 9%-22%; 18 of 124 patients) and 20% (95 % CI, 14%-28%; 27 of 134 patients), in the intervention and usual care groups, respectively (P = .32-.44). Findings at 3 months were similar.
Conclusions and Relevance: The CHOICE intervention did not decrease heavy drinking or related problems despite increased engagement in alcohol-related care.
Trial Registration: clinicaltrials.gov Identifier: NCT01400581.

PMID: 29582088 [PubMed - indexed for MEDLINE]

In Reply: Cranial Chordoma: A New Preoperative Grading System.

Neurosurgery. 2018 06 01;82(6):E180

Authors: Brito da Silva H, Sekhar L

PMID: 29566169 [PubMed - indexed for MEDLINE]

Implementation of a nationwide health economic consultation service to assist substance use researchers: Lessons learned.

Subst Abus. 2018;39(2):185-189

Authors: Murphy SM, Leff JA, Linas BP, Morgan JR, McCollister K, Schackman BR

Abstract
BACKGROUND: Health economic evaluation findings assist stakeholders in improving the quality, availability, scalability, and sustainability of evidence-based services, and in maximizing the efficiency of service delivery. The Center for Health Economics of Treatment Interventions for Substance Use Disorders, HCV, and HIV (CHERISH) is a NIDA-funded multi-institutional center of excellence whose mission is to develop and disseminate health-economic research on healthcare utilization, health outcomes, and health-related behaviors that informs substance use disorder treatment policy, and HCV and HIV care of people who use substances.
METHODS: We designed a consultation service that is free to researchers whose work aligns with CHERISH's mission. The service includes up to six hours of consulting time. After prospective consultees submit their request online, they receive a screening call from the consultation service director, who connects them with a consultant with relevant expertise. Consultees and consultants complete web-based evaluations following the consultation; consultees also complete a six-month follow-up. We report on the status of the service from its inception in July 2015 through June 2017.
RESULTS: We have received 28 consultation requests (54% Early Stage Investigators, 57% MD or equivalent, 28% PhD, 61% women) on projects typically related to planning a study or grant application (93%); 71% were HIV/AIDS-related. Leading topics included cost-effectiveness (43%), statistical-analysis/econometrics (36%), cost (32%), cost-benefit (21%), and quality-of-life (18%). All consultees were satisfied with their overall experience, and felt that consultation expectations and objectives were clearly defined and the consultant's expertise was matched appropriately with their needs. Results were similar for consultants, who spent a median of 3 hours on consultations.
CONCLUSIONS: There is a need for health-economic methodological guidance among substance use, HCV, and HIV researchers. Lessons learned pertain to the feasibility of service provision, the need to implement systems to measure and improve service value, and strategies for service promotion.

PMID: 29558284 [PubMed - indexed for MEDLINE]

Preclinical Profile of AB-423, an Inhibitor of Hepatitis B Virus Pregenomic RNA Encapsidation.

Antimicrob Agents Chemother. 2018 06;62(6):

Authors: Mani N, Cole AG, Phelps JR, Ardzinski A, Cobarrubias KD, Cuconati A, Dorsey BD, Evangelista E, Fan K, Guo F, Guo H, Guo JT, Harasym TO, Kadhim S, Kultgen SG, Lee ACH, Li AHL, Long Q, Majeski SA, Mao R, McClintock KD, Reid SP, Rijnbrand R, Snead NM, Micolochick Steuer HM, Stever K, Tang S, Wang X, Zhao Q, Sofia MJ

Abstract
AB-423 is a member of the sulfamoylbenzamide (SBA) class of hepatitis B virus (HBV) capsid inhibitors in phase 1 clinical trials. In cell culture models, AB-423 showed potent inhibition of HBV replication (50% effective concentration [EC50] = 0.08 to 0.27 μM; EC90 = 0.33 to 1.32 μM) with no significant cytotoxicity (50% cytotoxic concentration > 10 μM). Addition of 40% human serum resulted in a 5-fold increase in the EC50s. AB-423 inhibited HBV genotypes A through D and nucleos(t)ide-resistant variants in vitro Treatment of HepDES19 cells with AB-423 resulted in capsid particles devoid of encapsidated pregenomic RNA and relaxed circular DNA (rcDNA), indicating that it is a class II capsid inhibitor. In a de novo infection model, AB-423 prevented the conversion of encapsidated rcDNA to covalently closed circular DNA, presumably by interfering with the capsid uncoating process. Molecular docking of AB-423 into crystal structures of heteroaryldihydropyrimidines and an SBA and biochemical studies suggest that AB-423 likely also binds to the dimer-dimer interface of core protein. In vitro dual combination studies with AB-423 and anti-HBV agents, such as nucleos(t)ide analogs, RNA interference agents, or interferon alpha, resulted in additive to synergistic antiviral activity. Pharmacokinetic studies with AB-423 in CD-1 mice showed significant systemic exposures and higher levels of accumulation in the liver. A 7-day twice-daily administration of AB-423 in a hydrodynamic injection mouse model of HBV infection resulted in a dose-dependent reduction in serum HBV DNA levels, and combination with entecavir or ARB-1467 resulted in a trend toward antiviral activity greater than that of either agent alone, consistent with the results of the in vitro combination studies. The overall preclinical profile of AB-423 supports its further evaluation for safety, pharmacokinetics, and antiviral activity in patients with chronic hepatitis B.

PMID: 29555628 [PubMed - indexed for MEDLINE]

A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite.

Nat Med. 2018 05;24(4):408-416

Authors: Kisalu NK, Idris AH, Weidle C, Flores-Garcia Y, Flynn BJ, Sack BK, Murphy S, Schön A, Freire E, Francica JR, Miller AB, Gregory J, March S, Liao HX, Haynes BF, Wiehe K, Trama AM, Saunders KO, Gladden MA, Monroe A, Bonsignori M, Kanekiyo M, Wheatley AK, McDermott AB, Farney SK, Chuang GY, Zhang B, Kc N, Chakravarty S, Kwong PD, Sinnis P, Bhatia SN, Kappe SHI, Sim BKL, Hoffman SL, Zavala F, Pancera M, Seder RA

Abstract
Development of a highly effective vaccine or antibodies for the prevention and ultimately elimination of malaria is urgently needed. Here we report the isolation of a number of human monoclonal antibodies directed against the Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) from several subjects immunized with an attenuated Pf whole-sporozoite (SPZ) vaccine (Sanaria PfSPZ Vaccine). Passive transfer of one of these antibodies, monoclonal antibody CIS43, conferred high-level, sterile protection in two different mouse models of malaria infection. The affinity and stoichiometry of CIS43 binding to PfCSP indicate that there are two sequential multivalent binding events encompassing the repeat domain. The first binding event is to a unique 'junctional' epitope positioned between the N terminus and the central repeat domain of PfCSP. Moreover, CIS43 prevented proteolytic cleavage of PfCSP on PfSPZ. Analysis of crystal structures of the CIS43 antigen-binding fragment in complex with the junctional epitope determined the molecular interactions of binding, revealed the epitope's conformational flexibility and defined Asn-Pro-Asn (NPN) as the structural repeat motif. The demonstration that CIS43 is highly effective for passive prevention of malaria has potential application for use in travelers, military personnel and elimination campaigns and identifies a new and conserved site of vulnerability on PfCSP for next-generation rational vaccine design.

PMID: 29554083 [PubMed - indexed for MEDLINE]

National Football League Head, Neck and Spine Committee's Concussion Diagnosis and Management Protocol: 2017-18 season.

Br J Sports Med. 2018 Jul;52(14):894-902

Authors: Ellenbogen RG, Batjer H, Cardenas J, Berger M, Bailes J, Pieroth E, Heyer R, Theodore N, Hsu W, Nabel E, Maroon J, Cantu R, Barnes R, Collins J, Putukian M, Lonser R, Solomon G, Sills A

Abstract
One of the National Football League's (NFL) Head, Neck and Spine Committee's principal goals is to create a 'best practice' protocol for concussion diagnosis and management for its players. The science related to concussion diagnosis and management continues to evolve, thus the protocol has evolved contemporaneously. The Fifth International Conference on Concussion in Sport was held in Berlin in 2016, and guidelines for sports concussion diagnosis and management were revised and refined. The NFL Head, Neck and Spine Committee has synthesised the most recent empirical evidence for sports concussion diagnosis and management including the Berlin consensus statement and tailored it to the game played in the NFL. One of the goals of the Committee is to provide a standardised, reliable, efficient and evidence-based protocol for concussion diagnosis and management that can be applied in this professional sport during practice and game day. In this article, the end-of-season version of the 2017-18 NFL Concussion Diagnosis and Management Protocol is described along with its clinical rationale. Immediate actions for concussion programme enhancement and research are reviewed. It is the Committee's expectation that the protocol will undergo refinement and revision over time as the science and clinical practice related to concussion in sports crystallise.

PMID: 29549147 [PubMed - indexed for MEDLINE]

CaBP1 regulates Cav1 L-type Ca2+ channels and their coupling to neurite growth and gene transcription in mouse spiral ganglion neurons.

Mol Cell Neurosci. 2018 04;88:342-352

Authors: Yang T, Choi JE, Soh D, Tobin K, Joiner ML, Hansen M, Lee A

Abstract
CaBP1 is a Ca2+ binding protein that is widely expressed in neurons in the brain, retina, and cochlea. In heterologous expression systems, CaBP1 interacts with and regulates voltage-gated Cav Ca2+ channels but whether this is the case in neurons is unknown. Here, we investigated the cellular functions of CaBP1 in cochlear spiral ganglion neurons (SGNs), which express high levels of CaBP1. Consistent with the role of CaBP1 as a suppressor of Ca2+-dependent inactivation (CDI) of Cav1 (L-type) channels, Cav1 currents underwent greater CDI in SGNs from mice lacking CaBP1 (C-KO) than in wild-type (WT) SGNs. The coupling of Cav1 channels to downstream signaling pathways was also disrupted in C-KO SGNs. Activity-dependent repression of neurite growth was significantly blunted and unresponsive to Cav1 antagonists in C-KO SGNs in contrast to WT SGNs. Moreover, Cav1-mediated Ca2+ signals and phosphorylation of cAMP-response element binding protein were reduced in C-KO SGNs compared to WT SGNs. Our findings establish a role for CaBP1 as an essential regulator of Cav1 channels in SGNs and their coupling to downstream pathways controlling activity-dependent transcription and neurite growth.

PMID: 29548764 [PubMed - indexed for MEDLINE]

Current approach to meningiomas of the medial sphenoid wing and the cavernous sinus.

Neurol India. 2018 Mar-Apr;66(2):335-341

Authors: Sekhar LN, Qazi Z

PMID: 29547151 [PubMed - indexed for MEDLINE]

A better approach to in vivo developmental neurotoxicity assessment: Alignment of rodent testing with effects seen in children after neurotoxic exposures.

Toxicol Appl Pharmacol. 2018 09 01;354:176-190

Authors: Vorhees CV, Sprowles JN, Regan SL, Williams MT

Abstract
High throughput screens for developmental neurotoxicity (DN) will facilitate evaluation of chemicals and can be used to prioritize those designated for follow-up. DN is evaluated under different guidelines. Those for drugs generally include peri- and postnatal studies and juvenile toxicity studies. For pesticides and commercial chemicals, when triggered, include developmental neurotoxicity studies (DNT) and extended one-generation reproductive toxicity studies. Raffaele et al. (2010) reviewed 69 pesticide DNT studies and found two of the four behavioral tests underperformed. There are now many epidemiological studies on children showing adverse neurocognitive effects, yet guideline DN studies fail to assess most of the functions affected in children; nor do DN guidelines reflect the advances in brain structure-function relationships from neuroscience. By reducing the number of test ages, removing underperforming tests and replacing them with tests that assess cognitive abilities relevant to children, the value of DN protocols can be improved. Testing for the brain networks that mediate higher cognitive functions need to include assessments of working memory, attention, long-term memory (explicit, implicit, and emotional), and executive functions such as cognitive flexibility. The current DNT focus on what can be measured should be replaced with what should be measured. With the wealth of data available from human studies and neuroscience, the recommendation is made for changes to make DN studies better focused on human-relevant functions using tests of proven validity that assess comparable functions to tests used in children. Such changes will provide regulatory authorities with more relevant data.

PMID: 29544898 [PubMed - indexed for MEDLINE]

Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial.

JAMA Oncol. 2018 05 10;4(5):e180013

Authors: Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, Sun W, Jalal SI, Shah MA, Metges JP, Garrido M, Golan T, Mandala M, Wainberg ZA, Catenacci DV, Ohtsu A, Shitara K, Geva R, Bleeker J, Ko AH, Ku G, Philip P, Enzinger PC, Bang YJ, Levitan D, Wang J, Rosales M, Dalal RP, Yoon HH

Abstract
Importance: Therapeutic options are needed for patients with advanced gastric cancer whose disease has progressed after 2 or more lines of therapy.
Objective: To evaluate the safety and efficacy of pembrolizumab in a cohort of patients with previously treated gastric or gastroesophageal junction cancer.
Design, Setting, and Participants: In the phase 2, global, open-label, single-arm, multicohort KEYNOTE-059 study, 259 patients in 16 countries were enrolled in a cohort between March 2, 2015, and May 26, 2016. Median (range) follow-up was 5.8 (0.5-21.6) months.
Intervention: Patients received pembrolizumab, 200 mg, intravenously every 3 weeks until disease progression, investigator or patient decision to withdraw, or unacceptable toxic effects.
Main Outcomes and Measures: Primary end points were objective response rate and safety. Objective response rate was assessed by central radiologic review per Response Evaluation Criteria in Solid Tumors, version 1.1, in all patients and those with programmed cell death 1 ligand 1 (PD-L1)-positive tumors. Expression of PD-L1 was assessed by immunohistochemistry. Secondary end points included response duration.
Results: Of 259 patients enrolled, most were male (198 [76.4%]) and white (200 [77.2%]); median (range) age was 62 (24-89) years. Objective response rate was 11.6% (95% CI, 8.0%-16.1%; 30 of 259 patients), with complete response in 2.3% (95% CI, 0.9%-5.0%; 6 of 259 patients). Median (range) response duration was 8.4 (1.6+ to 17.3+) months (+ indicates that patients had no progressive disease at their last assessment). Objective response rate and median (range) response duration were 15.5% (95% CI, 10.1%-22.4%; 23 of 148 patients) and 16.3 (1.6+ to 17.3+) months and 6.4% (95% CI, 2.6%-12.8%; 7 of 109 patients) and 6.9 (2.4 to 7.0+) months in patients with PD-L1-positive and PD-L1-negative tumors, respectively. Forty-six patients (17.8%) experienced 1 or more grade 3 to 5 treatment-related adverse events. Two patients (0.8%) discontinued because of treatment-related adverse events, and 2 deaths were considered related to treatment.
Conclusions and Relevance: Pembrolizumab monotherapy demonstrated promising activity and manageable safety in patients with advanced gastric or gastroesophageal junction cancer who had previously received at least 2 lines of treatment. Durable responses were observed in patients with PD-L1-positive and PD-L1-negative tumors. Further study of pembrolizumab for this group of patients is warranted.
Trial Registration: clinicaltrials.gov Identifier: NCT02335411.

PMID: 29543932 [PubMed - indexed for MEDLINE]

THE SUCCESS OF INTRAVITREAL INJECTIONS.

Ulster Med J. 2017 May;86(2):149-150

Authors: O'Donnell M, Williams M

PMID: 29535495 [PubMed - in process]

Association of Early Myocardial Workload and Mortality Following Severe Traumatic Brain Injury.

Crit Care Med. 2018 06;46(6):965-971

Authors: Krishnamoorthy V, Vavilala MS, Chaikittisilpa N, Rivara FP, Temkin NR, Lele AV, Gibbons EF, Rowhani-Rahbar A

Abstract
OBJECTIVES: To examine the impact of early myocardial workload on in-hospital mortality following isolated severe traumatic brain injury.
DESIGN: Retrospective cohort study.
SETTING: Data from the National Trauma Databank, a multicenter trauma registry operated by the American College of Surgeons, from 2007 to 2014.
PATIENTS: Adult patients with isolated severe traumatic brain injury (defined as admission Glasgow Coma Scale < 8 and head Abbreviated Injury Score ≥ 4).
INTERVENTIONS: Admission rate-pressure product, categorized into five levels based on published low, normal, and submaximal human thresholds: less than 5,000; 5,000-9,999; 10,000-14,999; 15,000-19,999; and greater than 20,000.
MEASUREMENTS AND MAIN RESULTS: Data from 26,412 patients were analyzed. Most patients had a normal rate-pressure product (43%), 35% had elevated rate-pressure product, and 22% had depressed rate-pressure product at hospital admission. Compared with the normal rate-pressure product group, in-hospital mortality was 22 percentage points higher in the lowest rate-pressure product group (cumulative mortality, 50.2%; 95% CI, 43.6-56.9%) and 11 percentage points higher in the highest rate-pressure product group (cumulative mortality, 39.2%; 95% CI, 37.4-40.9%). The lowest rate-pressure product group was associated with a 50% increased risk of mortality, compared with the normal rate-pressure product group (adjusted relative risk, 1.50; 95% CI, 1.31-1.76%; p < 0.0001), and the highest rate-pressure product group was associated with a 25% increased risk of mortality, compared with the normal rate-pressure product group (adjusted relative risk, 1.25; 95% CI, 1.18-1.92%; p < 0.0001). This relationship was blunted with increasing age. Among patients with normotension, those with depressed and elevated rate-pressure products experienced increased mortality.
CONCLUSIONS: Adults with severe traumatic brain injury experience heterogeneous myocardial workload profiles that have a "U-shaped" relationship with mortality, even in the presence of a normal blood pressure. Our findings are novel and suggest that cardiac performance is important following severe traumatic brain injury.

PMID: 29509569 [PubMed - indexed for MEDLINE]

Coagulopathy induced by traumatic brain injury: systemic manifestation of a localized injury.

Blood. 2018 05 03;131(18):2001-2006

Authors: Zhang J, Zhang F, Dong JF

Abstract
Traumatic brain injury (TBI)-induced coagulopathy is a common and well-recognized risk for poor clinical outcomes, but its pathogenesis remains poorly understood, and treatment options are limited and ineffective. We discuss the recent progress and knowledge gaps in understanding this lethal complication of TBI. We focus on (1) the disruption of the brain-blood barrier to disseminate brain injury systemically by releasing brain-derived molecules into the circulation and (2) TBI-induced hypercoagulable and hyperfibrinolytic states that result in persistent and delayed intracranial hemorrhage and systemic bleeding.

PMID: 29507078 [PubMed - indexed for MEDLINE]

Implementation of the 2017 Berlin Concussion in Sport Group Consensus Statement in contact and collision sports: a joint position statement from 11 national and international sports organisations.

Br J Sports Med. 2018 May;52(10):635-641

Authors: Patricios JS, Ardern CL, Hislop MD, Aubry M, Bloomfield P, Broderick C, Clifton P, Echemendia RJ, Ellenbogen RG, Falvey ÉC, Fuller GW, Grand J, Hack D, Harcourt PR, Hughes D, McGuirk N, Meeuwisse W, Miller J, Parsons JT, Richiger S, Sills A, Moran KB, Shute J, Raftery M

Abstract
The 2017 Berlin Concussion in Sport Group Consensus Statement provides a global summary of best practice in concussion prevention, diagnosis and management, underpinned by systematic reviews and expert consensus. Due to their different settings and rules, individual sports need to adapt concussion guidelines according to their specific regulatory environment. At the same time, consistent application of the Berlin Consensus Statement's themes across sporting codes is likely to facilitate superior and uniform diagnosis and management, improve concussion education and highlight collaborative research opportunities. This document summarises the approaches discussed by medical representatives from the governing bodies of 10 different contact and collision sports in Dublin, Ireland in July 2017. Those sports are: American football, Australian football, basketball, cricket, equestrian sports, football/soccer, ice hockey, rugby league, rugby union and skiing. This document had been endorsed by 11 sport governing bodies/national federations at the time of being published.

PMID: 29500252 [PubMed - indexed for MEDLINE]

The interdependence of excitation and inhibition for the control of dynamic breathing rhythms.

Nat Commun. 2018 02 26;9(1):843

Authors: Baertsch NA, Baertsch HC, Ramirez JM

Abstract
The preBötzinger Complex (preBötC), a medullary network critical for breathing, relies on excitatory interneurons to generate the inspiratory rhythm. Yet, half of preBötC neurons are inhibitory, and the role of inhibition in rhythmogenesis remains controversial. Using optogenetics and electrophysiology in vitro and in vivo, we demonstrate that the intrinsic excitability of excitatory neurons is reduced following large depolarizing inspiratory bursts. This refractory period limits the preBötC to very slow breathing frequencies. Inhibition integrated within the network is required to prevent overexcitation of preBötC neurons, thereby regulating the refractory period and allowing rapid breathing. In vivo, sensory feedback inhibition also regulates the refractory period, and in slowly breathing mice with sensory feedback removed, activity of inhibitory, but not excitatory, neurons restores breathing to physiological frequencies. We conclude that excitation and inhibition are interdependent for the breathing rhythm, because inhibition permits physiological preBötC bursting by controlling refractory properties of excitatory neurons.

PMID: 29483589 [PubMed - indexed for MEDLINE]

Lawful physician-hastened death: AAN position statement.

Neurology. 2018 02 27;90(9):420-422

Authors: Russell JA, Epstein LG, Bonnie RJ, Conwit R, Graf WD, Kirschen M, Kurek JA, Larriviere DG, Pascuzzi RM, Rizzo M, Sattin JA, Simmons Z, Taylor L, Tsou A, Williams MA, Ethics, Law, and Humanities Committee (a joint committee of the AAN, ANA, and CNS), Ethics, Law and Humanities Committee, a joint committee of the AAN, ANA and CNS

PMID: 29483313 [PubMed - indexed for MEDLINE]

Endovascular stent-coiling of a giant basilar artery aneurysm through a previous radial artery bypass.

J Clin Neurosci. 2018 May;51:100-102

Authors: Ozdemir B, Kelly CM, Levitt MR, Kim LJ

Abstract
Giant, partially-thrombosed basilar artery (BA) aneurysms are extraordinarily difficult to treat. Due to the high risk of rupture exclusion of these aneurysms from the circulation is imperative. In certain instances, direct clipping is unsuitable, and high-flow bypass and proximal parent vessel clip occlusion is required. We report a case of a recurrent partially-thrombosed giant BA apex aneurysm treated with endovascular stent-coiling through a previous radial artery bypass graft. Following the initial bypass and aneurysm trapping six years prior, the patient was neurologically stable until three months prior to admission when he developed new diplopia and left third nerve palsy. Imaging studies demonstrated interval enlargement of the thrombosed portion of the aneurysm and increased size in the filling portion of the aneurysm. In the present case, the existing radial artery bypass graft between left VA and left PCA permitted successful stent-assisted embolization of the recurrent BA aneurysm. To our knowledge, this is the first published case of endovascular stent-coiling of a BA aneurysm through a radial artery bypass graft. This novel technique can be a useful alternative for endovascular aneurysm treatment in these challenging lesions.

PMID: 29483014 [PubMed - indexed for MEDLINE]