UW Neurological Surgery Recent PubMed Publications

Stereotactic Brain Biopsy Hemorrhage Risk Factors and Implications for Post-Operative Care at a Single Institution: An Argument For Post Operative Imaging.

World Neurosurg. 2020 Sep 18;:

Authors: Barkley AS, Sullivan LT, Gibson AW, Camacho D, Barber JK, Ko AL, Silbergeld DL, Ravanpay AC

Abstract
OBJECTIVE: To determine pre-operative factors contributing to post-operative hemorrhage after stereotactic biopsy (STB), clinical implications of post-operative hemorrhage, and the role of post-operative imaging in clinical management.
METHODS: Retrospective review of STB (2005-2018) across 2 institutions including patients >18 years undergoing first STB. Patients with prior craniotomy, open biopsy or prior STB were excluded. Pre-operative variables included age, gender, neurosurgeon seniority, STB method. Post-operative variables included pathology, post-operative hemorrhage on CT, immediate and 30-day post-operative seizure, infection, post-operative hospital stay duration, 30-day return to OR. Analysis used Fisher's exact tests for categorical variables.
RESULTS: Overall, 410 patients were included. Average age was 56.5 (±16.5) years; 60% (n=248) were male. The majority of biopsies were performed by senior neurosurgeons (66%, n=270); frontal lobe (42%, n=182) and glioblastoma (45%, n=186) were the most common location and pathology. Post-operative hemorrhage occurred in 28% (114) of patients with 20% <0.05 cm3 and 8% >0.05 cm3. Post-operative hemorrhage of any size was associated with increased rate of post-operative deficit within both 24 hours and 30 days, post-operative seizure, and length of hospital stay when controlling for pathology. Hemorrhages >0.05cm3 had a 16% higher rate of return to the OR for evacuation, due to clinical deterioration as opposed to radiographic progression.
CONCLUSION: Post biopsy hemorrhage was associated with higher risk of immediate and delayed post-operative deficit and seizure. Post-operative CT should be used to determine whether STB patients can be discharged same day or admitted for observation; clinical evaluation should determine return to OR for evacuation.

PMID: 32956884 [PubMed - as supplied by publisher]

Seawater transmission and infection dynamics of pilchard orthomyxovirus (POMV) in Atlantic salmon (Salmo salar).

J Fish Dis. 2020 Sep 17;:

Authors: Samsing F, Rigby M, Tengesdal HK, Taylor RS, Farias D, Morrison RN, Godwin S, Giles C, Carson J, English CJ, Chong R, Wynne JW

Abstract
The Tasmanian salmon industry had remained relatively free of major viral diseases until the emergence of pilchard orthomyxovirus (POMV). Originally isolated from wild pilchards, POMV is of concern to the industry as it can cause high mortality in farmed salmon (Salmo salar). Field observations suggest the virus can spread from pen to pen and between farms, but evidence of passive transmission in sea water was unclear. Our aim was to establish whether direct contact between infected and naïve fish was required for transmission, and to examine viral infection dynamics. Atlantic salmon post-smolts were challenged with POMV by either direct exposure via cohabitation or indirect exposure via virus-contaminated sea water. POMV was transmissible in sea water and direct contact between fish was not required for infection. Head kidney and heart presented the highest viral loads in early stages of infection. POMV survivors presented low viral loads in most tissues, but these remained relatively high in gills. A consistent feature was the infiltration of viral-infected melanomacrophages in different tissues, suggesting an important role of these in the immune response to POMV. Understanding POMV transmission and host-pathogen interactions is key for the development of improved surveillance tools, transmission models and ultimately for disease prevention.

PMID: 32944982 [PubMed - as supplied by publisher]

Oncolytic HSV Vectors and Anti-Tumor Immunity.

Curr Issues Mol Biol. 2020 Sep 17;41:381-468

Authors: Glorioso JC, Cohen JB, Goins WF, Hall B, Jackson JW, Kohanbash G, Amankulor N, Kaur B, Caligiuri MA, Chiocca EA, Holland EC, Quéva C

Abstract
The therapeutic promise of oncolytic viruses (OVs) rests on their ability to both selectively kill tumor cells and induce anti-tumor immunity. The potential of tumors to be recognized and eliminated by an effective anti-tumor immune response has been spurred on by the discovery that immune checkpoint inhibition can overcome tumor-specific cytotoxic T cell (CTL) exhaustion and provide durable responses in multiple tumor indications. OV-mediated tumor destruction is now recognized as a powerful means to assist in the development of anti-tumor immunity for two important reasons: (i) OVs, through the elicitation of an anti-viral response and the production of type I interferon, are potent stimulators of inflammation and can be armed with transgenes to further enhance anti-tumor immune responses; and (ii) lytic activity can promote the release of tumor-associated antigens (TAAs) and tumor neoantigens that function as in situ tumor-specific vaccines to elicit adaptive immunity. Oncolytic herpes simplex viruses (oHSVs) are among the most widely studied OVs for the treatment of solid malignancies, and Amgen's oHSV Imlygic® for the treatment of melanoma is the only OV approved in major markets. Here we describe important biological features of HSV that make it an attractive OV, clinical experience with HSV-based vectors, and strategies to increase applicability to cancer treatment.

PMID: 32938804 [PubMed - as supplied by publisher]

Daily Generation of a Footward Fluid Shift Attenuates Ocular Changes Associated with Head-Down Tilt Bedrest.

J Appl Physiol (1985). 2020 Sep 17;:

Authors: Lawley JS, Babu G, Janssen SLJE, Petersen LG, Hearon CM, Dias KA, Sarma S, Williams MA, Whitworth LA, Levine BD

Abstract
Astronauts have presented with a constellation of visual changes referred to as spaceflight-associated neuro-ocular syndrome (SANS). However, early markers of microgravity-induced optic remodeling have not been fully identified nor have countermeasures been developed. In order to identify early markers of SANS, we studied 10 subjects with optical coherence tomography and ultrasound when upright and supine, and again after 24 hours of 6-degree head down tilt (HDT) bedrest. Upon acute transition from upright to supine, choroid area (2.24±0.53 to 2.28±0.52 mm2, p=0.001) and volume (9.51±2.08 to 9.73±2.08 mm3, p=0.002) increased. After 24 hours of HDT bedrest, subfoveal choroidal thickness (372±93 to 381±95 µm, p=0.02) , choroid area (2.25±0.52 to 2.33±0.54 mm2, p=0.08) and volume (9.64±2.03 to 9.82±2.08 mm3, p=0.08) increased relative to the supine position. Subsequently, 7 subjects spent 3 days in -6 deg HDT bedrest to assess whether low-level lower body negative pressure (LBNP) could prevent the observed choroidal engorgement during bedrest. Maintaining the -6 deg HDT position for 3 days caused choroid area (Δ0.11 mm2, p=0.05) and volume (Δ0.45 mm3, p=0.003) to increase. When participants also spent 8 hours daily under -20mmHg LBNP, choroid volume still increased, but substantially (40%) less than in the control trial (Δ0.27 mm3, p=0.05). Moreover, the increase in choroid area was diminished (Δ0.03 mm2, p=0.13), indicating that low-level LBNP attenuates the choroid expansion associated with 3 days of -6 deg HDT bedrest. These data suggest that low-level LBNP may be an effective countermeasure for SANS.

PMID: 32940563 [PubMed - as supplied by publisher]

A dual role for Cav1.4 Ca2+ channels in the molecular and structural organization of the rod photoreceptor synapse.

Elife. 2020 09 17;9:

Authors: Maddox JW, Randall KL, Yadav RP, Williams B, Hagen J, Derr PJ, Kerov V, Della Santina L, Baker SA, Artemyev N, Hoon M, Lee A

Abstract
Synapses are fundamental information processing units that rely on voltage-gated Ca2+ (Cav) channels to trigger Ca2+-dependent neurotransmitter release. Cav channels also play Ca2+-independent roles in other biological contexts, but whether they do so in axon terminals is unknown. Here, we addressed this unknown with respect to the requirement for Cav1.4 L-type channels for the formation of rod photoreceptor synapses in the retina. Using a mouse strain expressing a non-conducting mutant form of Cav1.4, we report that the Cav1.4 protein, but not its Ca2+ conductance, is required for the molecular assembly of rod synapses; however, Cav1.4 Ca2+ signals are needed for the appropriate recruitment of postsynaptic partners. Our results support a model in which presynaptic Cav channels serve both as organizers of synaptic building blocks and as sources of Ca2+ ions in building the first synapse of the visual pathway and perhaps more broadly in the nervous system.

PMID: 32940604 [PubMed - indexed for MEDLINE]

Investigating effects of soil chemicals on density of small mammal bioindicators using spatial capture-recapture models.

PLoS One. 2020;15(9):e0238870

Authors: Gaukler SM, Murphy SM, Berryhill JT, Thompson BE, Sutter BJ, Hathcock CD

Abstract
Monitoring the ecological impacts of environmental pollution and the effectiveness of remediation efforts requires identifying relationships between contaminants and the disruption of biological processes in populations, communities, or ecosystems. Wildlife are useful bioindicators, but traditional comparative experimental approaches rely on a staunch and typically unverifiable assumption that, in the absence of contaminants, reference and contaminated sites would support the same densities of bioindicators, thereby inferring direct causation from indirect data. We demonstrate the utility of spatial capture-recapture (SCR) models for overcoming these issues, testing if community density of common small mammal bioindicators was directly influenced by soil chemical concentrations. By modeling density as an inhomogeneous Poisson point process, we found evidence for an inverse spatial relationship between Peromyscus density and soil mercury concentrations, but not other chemicals, such as polychlorinated biphenyls, at a site formerly occupied by a nuclear reactor. Although the coefficient point estimate supported Peromyscus density being lower where mercury concentrations were higher (β = -0.44), the 95% confidence interval overlapped zero, suggesting no effect was also compatible with our data. Estimated density from the most parsimonious model (2.88 mice/ha; 95% CI = 1.63-5.08), which did not support a density-chemical relationship, was within the range of reported densities for Peromyscus that did not inhabit contaminated sites elsewhere. Environmental pollution remains a global threat to biodiversity and ecosystem and human health, and our study provides an illustrative example of the utility of SCR models for investigating the effects that chemicals may have on wildlife bioindicator populations and communities.

PMID: 32941472 [PubMed - indexed for MEDLINE]

Interactions between genetics and environment shape Camelina seed oil composition.

BMC Plant Biol. 2020 Sep 14;20(1):423

Authors: Brock JR, Scott T, Lee AY, Mosyakin SL, Olsen KM

Abstract
BACKGROUND: Camelina sativa (gold-of-pleasure) is a traditional European oilseed crop and emerging biofuel source with high levels of desirable fatty acids. A twentieth century germplasm bottleneck depleted genetic diversity in the crop, leading to recent interest in using wild relatives for crop improvement. However, little is known about seed oil content and genetic diversity in wild Camelina species.
RESULTS: We used gas chromatography, environmental niche assessment, and genotyping-by-sequencing to assess seed fatty acid composition, environmental distributions, and population structure in C. sativa and four congeners, with a primary focus on the crop's wild progenitor, C. microcarpa. Fatty acid composition differed significantly between Camelina species, which occur in largely non-overlapping environments. The crop progenitor comprises three genetic subpopulations with discrete fatty acid compositions. Environment, subpopulation, and population-by-environment interactions were all important predictors for seed oil in these wild populations. A complementary growth chamber experiment using C. sativa confirmed that growing conditions can dramatically affect both oil quantity and fatty acid composition in Camelina.
CONCLUSIONS: Genetics, environmental conditions, and genotype-by-environment interactions all contribute to fatty acid variation in Camelina species. These insights suggest careful breeding may overcome the unfavorable FA compositions in oilseed crops that are predicted with warming climates.

PMID: 32928104 [PubMed - in process]

UQCRH downregulation promotes Warburg effect in renal cell carcinoma cells.

Sci Rep. 2020 09 14;10(1):15021

Authors: Luo Y, Medina Bengtsson L, Wang X, Huang T, Liu G, Murphy S, Wang C, Koren J, Schafer Z, Lu X

Abstract
Ubiquinol-cytochrome c reductase hinge protein (UQCRH) is the hinge protein for the multi-subunit complex III of the mitochondrial electron transport chain and is involved in the electron transfer reaction between cytochrome c1 and c. Recent genome-wide transcriptomic and epigenomic profiling of clear cell renal cell carcinoma (ccRCC) by The Cancer Genome Atlas (TCGA) identified UQCRH as the top-ranked gene showing inverse correlation between DNA hypermethylation and mRNA downregulation. The function and underlying mechanism of UQCRH in the Warburg effect metabolism of ccRCC have not been characterized. Here, we verified the clinical association of low UQCRH expression and shorter survival of ccRCC patients through in silico analysis and identified KMRC2 as a highly relevant ccRCC cell line that displays hypermethylation-induced UQCRH extinction. Ectopic overexpression of UQCRH in KMRC2 restored mitochondrial membrane potential, increased oxygen consumption, and attenuated the Warburg effect at the cellular level. UQCRH overexpression in KMRC2 induced higher apoptosis and slowed down in vitro and in vivo tumor growth. UQCRH knockout by CRISPR/Cas9 had little impact on the metabolism and proliferation of 786O ccRCC cell line, suggesting the dispensable role of UQCRH in cells that have entered a Warburg-like state through other mechanisms. Together, our study suggests that loss of UQCRH expression by hypermethylation may promote kidney carcinogenesis through exacerbating the functional decline of mitochondria thus reinforcing the Warburg effect.

PMID: 32929120 [PubMed - indexed for MEDLINE]

A Retrospective Evaluation of Airway Anatomy in Young Children and Implications for One-Lung Ventilation.

J Cardiothorac Vasc Anesth. 2020 Aug 12;:

Authors: Downard MG, Lee AJ, Heald CJ, Anthony EY, Singh J, Templeton TW

Abstract
OBJECTIVE: One-lung ventilation (OLV) in children remains a niche practice with few studies to guide best practices. The objective of this study was to describe lower airway anatomy relevant to establishment of OLV in young children.
DESIGN: Retrospective, observational study using pre-existing studies in the electronic health record.
SETTING: Single institution, academic medical center, tertiary-care hospital.
PARTICIPANTS: Pediatric patients <8 years old.
INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: Chest computed tomographic scans of 111 children 4 days to 8 years of age were reviewed. Measurements were taken from the thyroid isthmus to the carina, carina to first lobar branch on the left and right, diameter of the trachea at the carina, and diameter of the left and right mainstem bronchi. Dimensions were correlated with the outer diameter of endotracheal tubes and bronchial blockers. The left mainstem bronchus is consistently smaller than the right. Lung isolation using a mainstem technique on the left should use an endotracheal tube a half size smaller than would be used for tracheal intubation. The length from the carina to the first lobar branch on the left is consistently 3 times longer than on the right. Further, age-delineated bronchial diameters suggest that the clinician should transition from a 5F to a 7F Arndt bronchial blocker at 3-to-4 years of age.
CONCLUSION: A more detailed and accurate understanding of pediatric lower airway anatomy may assist the clinician in successfully performing OLV in young children.

PMID: 32921610 [PubMed - as supplied by publisher]

Cannabis use, other drug use, and risk of subsequent acute care in primary care patients.

Drug Alcohol Depend. 2020 Aug 08;216:108227

Authors: Matson TE, Lapham GT, Bobb JF, Johnson E, Richards JE, Lee AK, Bradley KA, Glass JE

Abstract
BACKGROUND: Cannabis and other drug use is associated with adverse health events, but little is known about the association of routine clinical screening for cannabis or other drug use and acute care utilization. This study evaluated whether self-reported frequency of cannabis or other drug use was associated with subsequent acute care.
METHOD: This retrospective cohort study used EHR and claims data from 8 sites in Washington State that implemented annual substance use screening. Eligible adult primary care patients (N = 47,447) completed screens for cannabis (N = 45,647) and/or other drug use, including illegal drug use and prescription medication misuse, (N = 45,255) from 3/3/15-10/1/2016. Separate single-item screens assessed frequency of past-year cannabis and other drug use: never, less than monthly, monthly, weekly, daily/almost daily. An indicator of acute care utilization measured any urgent care, emergency department visits, or hospitalizations ≤19 months after screening. Adjusted Cox proportional hazards models estimated risk of acute care.
RESULTS: Patients were predominantly non-Hispanic White. Those reporting cannabis use less than monthly (Hazard Ratio [HR] = 1.12, 95 % CI = 1.03-1.21) or daily (HR = 1.24; 1.10-1.39) had greater risk of acute care during follow-up than those reporting no use. Patients reporting other drug use less than monthly (HR = 1.34; 1.13-1.59), weekly (HR = 2.21; 1.46-3.35), or daily (HR = 2.53; 1.86-3.45) had greater risk of acute care than those reporting no other drug use.
CONCLUSION: Population-based screening for cannabis and other drug use in primary care may have utility for understanding risk of subsequent acute care. It is unclear whether findings will generalize to U.S. states with broader racial/ethnic diversity.

PMID: 32911133 [PubMed - as supplied by publisher]

Concurrent Deep Brain Stimulation Reduces the Direct Cortical Stimulation Necessary for Motor Output.

Mov Disord. 2020 Sep 11;:

Authors: Weaver KE, Caldwell DJ, Cronin JA, Kuo CH, Kogan M, Houston B, Sanchez V, Martinez V, Ojemann JG, Rane S, Ko AL

Abstract
BACKGROUND: Converging literatures suggest that deep brain stimulation (DBS) in Parkinson's disease affects multiple circuit mechanisms. One proposed mechanism is the normalization of primary motor cortex (M1) pathophysiology via effects on the hyperdirect pathway.
OBJECTIVES: We hypothesized that DBS would reduce the current intensity necessary to modulate motor-evoked potentials from focally applied direct cortical stimulation (DCS).
METHODS: Intraoperative subthalamic DBS, DCS, and preoperative diffusion tensor imaging data were acquired in 8 patients with Parkinson's disease.
RESULTS: In 7 of 8 patients, DBS significantly reduced the M1 DCS current intensity required to elicit motor-evoked potentials. This neuromodulation was specific to select DBS bipolar configurations. In addition, the volume of activated tissue models of these configurations were significantly associated with overlap of the hyperdirect pathway.
CONCLUSIONS: DBS reduces the current necessary to elicit a motor-evoked potential using DCS. This supports a circuit mechanism of DBS effectiveness, potentially involving the hyperdirect pathway that speculatively may underlie reductions in hypokinetic abnormalities in Parkinson's disease. © 2020 International Parkinson and Movement Disorder Society.

PMID: 32914888 [PubMed - as supplied by publisher]

Tau Is Elevated in Pediatric Patients on Extracorporeal Membrane Oxygenation.

ASAIO J. 2020 01;66(1):91-96

Authors: Lee AE, Pandiyan P, Liu MM, Williams MA, Everett AD, Mueller GP, Morriss MC, Raman L, Carlson D, Gatson JW

Abstract
Neurologic injury is a known and feared complication of extracorporeal membrane oxygenation (ECMO). Neurologic biomarkers may have a role in assisting in early identification of such. Axonal biomarker tau has not been investigated in the pediatric ECMO population. The objective of this study is to evaluate plasma levels of tau in pediatric patients supported with ECMO. Eighteen patients requiring ECMO support in a quaternary pediatric intensive care unit at a university-affiliated children's hospital from October 2015 to February 2017 were enrolled. Patients undergoing extracorporeal cardiopulmonary resuscitation or recent history of bypass were excluded. Plasma tau was measured using enzyme-linked immunosorbent assay. Neuroimaging was reviewed for acute neurologic injury, and tau levels were analyzed to assess for correlation. Tau was significantly higher in ECMO patients than in control subjects. Sixty-one percent of subjects had evidence of acute brain injury on neuroimaging, but tau level did not correlate with injury. Subjects with multifocal injury all experienced infarction and had significantly higher tau levels on ECMO day 3 than patients with isolated injury. In addition, peak tau levels of neuro-injured subjects were compared with controls and noninjured ECMO subjects using receiver operating curve analysis. This study demonstrates preliminary evidence of axonal injury in pediatric ECMO patients.

PMID: 30507848 [PubMed - indexed for MEDLINE]

Endoscopic Spine Surgery in Athletes: Cases series and review of literature.

World Neurosurg. 2020 Sep 03;:

Authors: Sivakanthan S, Williams JR, Feroze AH, Eaton J, Pan ZJ, Boop S, McGrath LB, Harmon K, Hofstetter CP

Abstract
OBJECTIVE: Degenerative spine disease is common in athletes and can progress to requiring surgical intervention. Traditional open surgical techniques necessitate prolonged recovery time and time away from play. Newly developed endoscopic surgical techniques may promote faster healing, recovery and increased return to play. The goal of this article is to summarize the current evidence in return to play after spine surgery and to present our series of three athletes undergoing endoscopic spine surgery.
METHODS: A complete search of all Pubmed Indexed articles pertaining to spine surgery in athletes was conducted. This was supplemented by a three patient case series of our own endoscopic spine experience in athletes.
RESULTS: There are no current widely accepted guidelines for return to play after spinal surgery. The best evidence available cites a return to play of 81% at 5.2 to 8.7 months after traditional open and minimally invasive surgery while endoscopic surgery produces an average 88% return to play rate at 3 months.
CONCLUSION: While return to play can vary widely, case based evidence as well as biomechanical principles support endoscopic spine surgery as a viable surgical modality for the treatment of spinal pathologies in athletes.

PMID: 32891833 [PubMed - as supplied by publisher]

Letter: An International Investigation Into the COVID-19 Pandemic and Workforce Depletion in Highly Specialized Neurointerventional Units - Insights From Stroke Thrombectomy and Aneurysm Registry and Endovascular Neurosurgery Research Group.

Neurosurgery. 2020 Sep 07;:

Authors: Alawieh A, Al Kasab S, Almallouhi E, Levitt MR, Jabbour PM, Sweid A, Starke RM, Saini V, Fargen KM, Wolfe SQ, Arthur AS, Goyal N, Fragata I, Maier I, Matouk C, Howard BM, Grossberg JA, Cawley M, Kan P, Hafeez M, Singer J, Crowley RW, Joshi KC, Brinjikji W, Savastano LE, Ogilvy CS, Gomez-Paz S, Levy E, Waqas M, Mokin M, Veznedaroglu E, Binning M, Mascitelli J, Yoo AJ, Soomro J, Williamson RW, Chalhoub RM, Grande A, Crosa R, Webb S, Psychogios M, Ducruet AF, Albuquerque FC, Majmundar N, Turner R, Casagrande W, Al-Mufti F, De Leacy R, Mocco J, Fessler RD, Osanai T, Chowdhry SA, Park M, Schirmer CM, Ringer A, Spiotta AM, STAR and ENRG collaborators

PMID: 32893855 [PubMed - as supplied by publisher]

Monitoring of ammonia in marine waters using a passive sampler with biofouling resistance and neural network-based calibration.

Environ Pollut. 2020 Dec;267:115457

Authors: O'Connor Šraj L, Almeida MIGS, Sharp SM, McKelvie ID, Morrison R, Kolev SD

Abstract
A biofouling resistant passive sampler for ammonia, where the semi-permeable barrier is a microporous hydrophobic gas-diffusion membrane, has been developed for the first time and successfully applied to determine the time-weighted average concentration of ammonia in estuarine and coastal waters for 7 days. Strategies to control biofouling of the membrane were investigated by covering it with either a copper mesh or a silver nanoparticle functionalised cotton mesh, with the former approach showing better performance. The effects of temperature, pH and salinity on the accumulation of ammonia in the newly developed passive sampler were studied and the first two parameters were found to influence it significantly. A universal calibration model for the passive sampler was developed using the Group Method Data Handling algorithm based on seawater samples spiked with known concentrations of total ammonia under conditions ranging from 10 to 30 °C, pH 7.8 to 8.2 and salinity 20 to 35. The newly developed passive sampler is affordable, user-friendly, reusable, sensitive, and can be used to detect concentrations lower than the recently proposed guideline value of 160 μg total NH3-N L-1, for a 99% species protection level, with the lowest concentration measured at 17 nM molecular NH3 (i.e., 8 μg total NH3-N L-1 at pH 8.0 and 20 °C). It was deployed at four field sites in the coastal waters of Nerm (Port Phillip Bay), Victoria, Australia. Good agreement was found between molecular ammonia concentrations obtained with passive and discrete grab sampling methods (relative difference, - 12% to - 19%).

PMID: 32889515 [PubMed - indexed for MEDLINE]

Developing microsurgical milestones for psychomotor skills in neurological surgery residents as an adjunct to operative training: the home microsurgery laboratory.

J Neurosurg. 2020 Sep 04;:1-11

Authors: Abecassis IJ, Sen RD, Ellenbogen RG, Sekhar LN

Abstract
OBJECTIVE: A variety of factors contribute to an increasingly challenging environment for neurological surgery residents to develop psychomotor skills in microsurgical technique solely from operative training. While adjunct training modalities such as cadaver dissection and surgical simulation are embraced and practiced at our institution, there are no formal educational milestones defined to help residents develop, measure, and advance their microsurgical psychomotor skills in a stepwise fashion when outside the hospital environment. The objective of this report is to describe an efficient and convenient "home microsurgery lab" (HML) assembled and tested by the authors with the goal of supporting a personalized stepwise advancement of microsurgical psychomotor skills.
METHODS: The authors reviewed the literature on previously published simulation practice models and designed adjunct learning modules utilizing the HML. Five milestones were developed for achieving proficiency with each graduated exercise, referencing the Accreditation Council for Graduate Medical Education (ACGME) guidelines. The HML setup was then piloted with 2 neurosurgical trainees.
RESULTS: The total cost for assembling the HML was approximately $850. Techniques for which training was provided included microinstrument handling, tissue dissection, suturing, and microanastomoses. Five designated competency levels were developed, and training exercises were proposed for each competency level.
CONCLUSIONS: The HML offers a unique, entirely home-based, affordable adjunct to the operative neurosurgical education mandated by the ACGME operative case logs, while respecting resident hospital-based education hours. The HML provides surgical simulation with specific milestones, which may improve confidence and the microsurgical psychomotor skills required to perform microsurgery, regardless of case type.

PMID: 32886917 [PubMed - as supplied by publisher]

Acceptability of a Mobile Phone-Based Augmented Reality Game for Rehabilitation of Patients With Upper Limb Deficits from Stroke: Case Study.

JMIR Rehabil Assist Technol. 2020 Sep 02;7(2):e17822

Authors: LaPiana N, Duong A, Lee A, Alschitz L, Silva RML, Early J, Bunnell A, Mourad P

Abstract
BACKGROUND: Upper limb functional deficits are common after stroke and result from motor weakness, ataxia, spasticity, spatial neglect, and poor stamina. Past studies employing a range of commercial gaming systems to deliver rehabilitation to stroke patients provided short-term efficacy but have not yet demonstrated whether or not those games are acceptable, that is, motivational, comfortable, and engaging, which are all necessary for potential adoption and use by patients.
OBJECTIVE: The goal of the study was to assess the acceptability of a smartphone-based augmented reality game as a means of delivering stroke rehabilitation for patients with upper limb motor function loss.
METHODS: Patients aged 50 to 70 years, all of whom experienced motor deficits after acute ischemic stroke, participated in 3 optional therapy sessions using augmented reality therapeutic gaming over the course of 1 week, targeting deficits in upper extremity strength and range of motion. After completion of the game, we administered a 16-item questionnaire to the patients to assess the game's acceptability; 8 questions were answered by rating on a scale from 1 (very negative experience) to 5 (very positive experience); 8 questions were qualitative.
RESULTS: Patients (n=5) completed a total of 23 out of 45 scheduled augmented reality game sessions, with patient fatigue as the primary factor for uncompleted sessions. Each patient consented to 9 potential game sessions and completed a mean of 4.6 (SE 1.3) games. Of the 5 patients, 4 (80%) completed the questionnaire at the end of their final gaming session. Of note, patients were motivated to continue to the end of a given gaming session (mean 4.25, 95% CI 3.31-5.19), to try other game-based therapies (mean 3.75, 95% CI 2.81-4.69), to do another session (mean 3.50, 95% CI 2.93-4.07), and to perform other daily rehabilitation exercises (mean 3.25, 95% CI 2.76-3.74). In addition, participants gave mean scores of 4.00 (95% CI 2.87-5.13) for overall experience; 4.25 (95% CI 3.31-5.19) for comfort; 3.25 (95% CI 2.31-4.19) for finding the study fun, enjoyable, and engaging; and 3.50 (95% CI 2.52-4.48) for believing the technology could help them reach their rehabilitation goals. For each of the 4 patients, their reported scores were statistically significantly higher than those generated by a random sampling of values (patient 1: P=.04; patient 2: P=.04; patient 4: P=.004; patient 5: P=.04).
CONCLUSIONS: Based on the questionnaire scores, the patients with upper limb motor deficits following stroke who participated in our case study found our augmented reality game motivating, comfortable, engaging, and tolerable. Improvements in augmented reality technology motivated by this case study may one day allow patients to work with improved versions of this therapy independently in their own home. We therefore anticipate that smartphone-based augmented reality gaming systems may eventually provide useful postdischarge self-treatment as a supplement to professional therapy for patients with upper limb deficiencies from stroke.

PMID: 32876580 [PubMed]

Quantification of Plasmodium knowlesi versus Plasmodium falciparum in the rhesus liver: implications for malaria vaccine studies in rhesus models.

Malar J. 2020 Aug 31;19(1):313

Authors: Shears MJ, Seilie AM, Kim Lee Sim B, Hoffman SL, Murphy SC

Abstract
BACKGROUND: Rhesus macaques are valuable pre-clinical models for malaria vaccine development. The Plasmodium knowlesi/rhesus and Plasmodium falciparum/rhesus models are two established platforms for malaria vaccine testing, and both have previously been used to assess live-attenuated sporozoite vaccines. However, there is evidence that the susceptibility of the rhesus liver to P. knowlesi versus P. falciparum sporozoites likely differs, potentially complicating comparisons between these two platforms.
METHODS: To quantify the differing susceptibility of rhesus to P. knowlesi and P. falciparum sporozoites, animals were infected by direct venous inoculation of purified, cryopreserved wild-type P. knowlesi sporozoites (PkSPZ) or P. falciparum sporozoites (PfSPZ). The entire liver was collected 5 days post-infection, and parasite burden in each liver lobe was quantified using an ultrasensitive Plasmodium 18S rRNA RT-PCR biomarker assay. The potential of using 18S rRNA copy number in the rhesus liver to directly measure the efficacy of vaccines targeting P. falciparum sporozoites and liver stages was also theoretically evaluated.
RESULTS: Infection of rhesus with a high dose of PkSPZ led to consistently high burden liver stage infections (range 9.5-10.1 log10 copies 18S rRNA/g of liver), with similar amounts of parasite 18S rRNA detected in every liver lobe. Inoculation of rhesus with high doses of PfSPZ led to more variable, lower liver burdens (range 4.9-6.6 log10 copies 18S rRNA/g of liver in infected lobes), with parasite 18S rRNA below the limit of detection in some liver lobes. The low signal and heterogeneity of liver burden in the PfSPZ-infected animals indicates that even this extremely sensitive molecular assay cannot be used to assess reliably vaccine efficacy in the P. falciparum/rhesus platform.
CONCLUSIONS: Detection of 18S rRNA in the liver following high dose intravenous PfSPZ confirmed that rhesus are modestly susceptible to wild-type P. falciparum sporozoites. However, comparison of 18S rRNA RT-PCR biomarker signal indicates that the P. falciparum liver burden was 3-5 logs lower than in PkSPZ-infected animals. Quantification of this difference in liver stage burden will help guide and interpret data from pre-clinical studies of live-attenuated sporozoite vaccines in rhesus models.

PMID: 32867784 [PubMed - in process]

Assessment of Intracranial Atherosclerotic Plaques Using 3D Black-Blood MRI: Comparison With 3D Time-of-Flight MRA and DSA.

J Magn Reson Imaging. 2020 Aug 31;:

Authors: Tian X, Tian B, Shi Z, Wu X, Peng W, Zhang X, Malhotra A, Mossa-Basha M, Sekhar L, Liu Q, Lu J, Hu C, Zhu C

Abstract
BACKGROUND: Noninvasive assessment of intracranial stenosis is important to manage ischemic stroke patients. However, few previous studies have compared 3D black-blood MRI with 3D time-of-flight (TOF), magnetic resonance angiography (MRA), and digital subtraction angiography (DSA) for intracranial artery plaque assessment.
PURPOSE: To compare 3D black-blood MRI and 3D TOF-MRA, using DSA as the reference standard for intracranial stenosis and atherosclerotic plaque assessment in patients with posterior circulation stroke or transient ischemic attacks (TIAs).
STUDY TYPE: Prospective, cohort study.
POPULATION: One hundred and one patients with posterior circulation stroke and/or TIA (age 63 ± 10 years, 84 male) who underwent DSA and MRI within 4 weeks of each other.
FIELD STRENGTH/SEQUENCE: 3D fast-spin-echo MRI for intracranial vessel wall imaging (IVWI) and 3D TOF at 3T.
ASSESSMENT: Two radiologists independently measured the degree of stenosis on 3D IVWI and TOF, using DSA as a reference. Plaque enhancement was recorded when the plaque was stenosis-free on DSA.
STATISTICAL TESTS: Shapiro-Wilk's test, Student's t-test, Mann-Whitney U-test, Spearman correlation, Bland-Altman analysis, and interclass correlation coefficient (ICC).
RESULTS: A total of 238 intracranial plaques (203 posterior, 35 anterior) were included. 3D IVWI showed better agreement with DSA in measuring stenosis than TOF (ICC = 0.89 vs. 0.64). 3D IVWI had higher sensitivity and specificity for detecting stenosis >50% and stenosis >75% than TOF, using DSA as the standard. TOF significantly overestimated the degree of stenosis compared to DSA (65 ± 19% vs. 51 ± 15%, P < 0.001). DSA did not observe 62 nonstenotic plaques (26.1%) that were shown only on 3D IVWI, in which 36 plaques (58.1%) showed contrast enhancement. The interreader agreement for measuring stenosis were excellent, with ICCs >0.90 for all three modalities.
DATA CONCLUSION: 3D black-blood MRI is accurate and reproducible for quantifying intracranial artery stenosis compared with DSA, and performs better than 3D TOF. As compared to DSA, it detects more nonstenotic plaques.
LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

PMID: 32864816 [PubMed - as supplied by publisher]

International experience of mechanical thrombectomy during the COVID-19 pandemic: insights from STAR and ENRG.

J Neurointerv Surg. 2020 Nov;12(11):1039-1044

Authors: Al Kasab S, Almallouhi E, Alawieh A, Levitt MR, Jabbour P, Sweid A, Starke RM, Saini V, Wolfe SQ, Fargen KM, Arthur AS, Goyal N, Pandhi A, Fragata I, Maier I, Matouk C, Grossberg JA, Howard BM, Kan P, Hafeez M, Schirmer CM, Crowley RW, Joshi KC, Tjoumakaris SI, Chowdry S, Ares W, Ogilvy C, Gomez-Paz S, Rai AT, Mokin M, Guerrero W, Park MS, Mascitelli JR, Yoo A, Williamson R, Grande AW, Crosa RJ, Webb S, Psychogios MN, Ducruet AF, Holmstedt CA, Ringer AJ, Spiotta AM, STAR collaborators

Abstract
BACKGROUND: In response to the COVID-19 pandemic, many centers altered stroke triage protocols for the protection of their providers. However, the effect of workflow changes on stroke patients receiving mechanical thrombectomy (MT) has not been systematically studied.
METHODS: A prospective international study was launched at the initiation of the COVID-19 pandemic. All included centers participated in the Stroke Thrombectomy and Aneurysm Registry (STAR) and Endovascular Neurosurgery Research Group (ENRG). Data was collected during the peak months of the COVID-19 surge at each site. Collected data included patient and disease characteristics. A generalized linear model with logit link function was used to estimate the effect of general anesthesia (GA) on in-hospital mortality and discharge outcome controlling for confounders.
RESULTS: 458 patients and 28 centers were included from North America, South America, and Europe. Five centers were in high-COVID burden counties (HCC) in which 9/104 (8.7%) of patients were positive for COVID-19 compared with 4/354 (1.1%) in low-COVID burden counties (LCC) (P<0.001). 241 patients underwent pre-procedure GA. Compared with patients treated awake, GA patients had longer door to reperfusion time (138 vs 100 min, P=<0.001). On multivariate analysis, GA was associated with higher probability of in-hospital mortality (RR 1.871, P=0.029) and lower probability of functional independence at discharge (RR 0.53, P=0.015).
CONCLUSION: We observed a low rate of COVID-19 infection among stroke patients undergoing MT in LCC. Overall, more than half of the patients underwent intubation prior to MT, leading to prolonged door to reperfusion time, higher in-hospital mortality, and lower likelihood of functional independence at discharge.

PMID: 32843359 [PubMed - indexed for MEDLINE]