UW Neurological Surgery Recent PubMed Publications

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]

Systems Biology Approaches to Understanding the Human Immune System.

Front Immunol. 2020;11:1683

Authors: Dhillon BK, Smith M, Baghela A, Lee AHY, Hancock REW

Abstract
Systems biology is an approach to interrogate complex biological systems through large-scale quantification of numerous biomolecules. The immune system involves >1,500 genes/proteins in many interconnected pathways and processes, and a systems-level approach is critical in broadening our understanding of the immune response to vaccination. Changes in molecular pathways can be detected using high-throughput omics datasets (e.g., transcriptomics, proteomics, and metabolomics) by using methods such as pathway enrichment, network analysis, machine learning, etc. Importantly, integration of multiple omic datasets is becoming key to revealing novel biological insights. In this perspective article, we highlight the use of protein-protein interaction (PPI) networks as a multi-omics integration approach to unravel information flow and mechanisms during complex biological events, with a focus on the immune system. This involves a combination of tools, including: InnateDB, a database of curated interactions between genes and protein products involved in the innate immunity; NetworkAnalyst, a visualization and analysis platform for InnateDB interactions; and MetaBridge, a tool to integrate metabolite data into PPI networks. The application of these systems techniques is demonstrated for a variety of biological questions, including: the developmental trajectory of neonates during the first week of life, mechanisms in host-pathogen interaction, disease prognosis, biomarker discovery, and drug discovery and repurposing. Overall, systems biology analyses of omics data have been applied to a variety of immunology-related questions, and here we demonstrate the numerous ways in which PPI network analysis can be a powerful tool in contributing to our understanding of the immune system and the study of vaccines.

PMID: 32849587 [PubMed - in process]

Characterization of immune responses and the lung transcriptome in a murine model of IL-33 challenge.

Biochim Biophys Acta Mol Basis Dis. 2020 12 01;1866(12):165950

Authors: Piyadasa H, Lloyd D, Lee AHY, Altieri A, Hemshekhar M, Osawa N, Basu S, Blimkie T, Falsafi R, Halayko AJ, Hancock REW, Mookherjee N

Abstract
IL-33 induces airway inflammation and hyper-responsiveness in respiratory diseases. Although defined as a therapeutic target, there are limited studies that have comprehensively investigated IL-33-mediated responses in the lungs in vivo. In this study, we characterized immunological and physiological responses induced by intranasal IL-33 challenge, in a mouse model. We identified specific cytokines, IL-4, IL-5, IL-6, IL-10, IP-10 and MIP1-α, that are increased in bronchoalveolar lavage and lung tissues by IL-33. Using transcriptomics (RNA-Seq) we demonstrated that 2279 transcripts were up-regulated and 1378 downregulated (≥ 2-fold, p < 0.01) in lung tissues, in response to IL-33. Bioinformatic interrogation of the RNA-Seq data was used to predict biological pathways and upstream regulators involved in IL-33-mediated responses. We showed that the mRNA and protein of STAT4, a predicted upstream regulator of IL-33-induced transcripts, was significantly enhanced in the lungs following IL-33 challenge. Overall, this study provides specific IL-33-induced molecular targets and endpoints that can be used as a resource for in vivo studies, e.g. in preclinical murine models examining novel interventions to target downstream effects of IL-33.

PMID: 32841733 [PubMed - indexed for MEDLINE]

Long-term outcomes of sutureless and rapid-deployment aortic valve replacement: a systematic review and meta-analysis.

Ann Cardiothorac Surg. 2020 Jul;9(4):265-279

Authors: Williams ML, Flynn CD, Mamo AA, Tian DH, Kappert U, Wilbring M, Folliguet T, Fiore A, Miceli A, D'Onofrio A, Cibin G, Gerosa G, Glauber M, Fischlein T, Pollari F

Abstract
Background: Sutureless and rapid-deployment aortic valve replacement (SURD-AVR) has become a prominent area of research as the medical community evaluate its place amongst other aortic valve interventions. The main advantages of SURD-AVR established to date are the reduced cross-clamp and cardiopulmonary bypass (CPB) times, as well as facilitating minimally invasive surgery in high-risk surgical patients. This current systematic review and meta-analysis, to our knowledge, is the first focusing on long-term outcomes regarding safety, efficacy and durability of SURD-AVR from available current literature.
Methods: A literature search via six electronic databases was performed from their inception to November 2019. Inclusion criteria for this systematic review included survival and postoperative echocardiographic outcomes greater than five years in patients who underwent SURD-AVR with either Perceval or Intuity valves. Studies were identified and data extracted by two independent reviewers. Long-term survival outcomes were aggregated using digitized Kaplan-Meier curves where available.
Results: After applying predefined inclusion and exclusion criteria, four studies were identified for review. All four studies were observational and in total reported data for 1,998 patients. Almost half (42.4%) of patients underwent SURD-AVR via full sternotomy, with almost one third (30.1%) also undergoing concomitant cardiac procedures. Aggregate overall survival rates at 1-, 2-, 3-, and 5-year follow-up were 94.9%, 91.2%, 89.0%, and 84.2%, respectively. Incidence of strokes (4.8%), severe paravalvular leaks (PVLs) (1.5%) and permanent pacemaker (PPM) insertion (8.2%) at up to 5-year follow-up were acceptable. At 5-year follow-up hemodynamic outcomes were also acceptable for mean pressure gradient (MPG) (range, 8.8-13.6 mmHg), peak pressure gradient (PPG) (range, 18.9-21.1 mmHg) and effective orifice area (EOA) (range, 1.5-1.8 cm2).
Conclusions: Evaluation of the evidence reporting long-term outcomes of SURD-AVR suggests that it is a safe procedure for AVR with low rates of complications. Long-term outcomes presented in this review show that not only does SURD-AVR have acceptable survival rates, but also good hemodynamic performance at 5-year follow-up.

PMID: 32832408 [PubMed - as supplied by publisher]

Early clinical and sociodemographic experience with patients hospitalized with COVID-19 at a large American healthcare system.

EClinicalMedicine. 2020 Aug 19;:100504

Authors: McCarthy CP, Murphy S, Jones-O'Connor M, Olshan DS, Khambhati JR, Rehman S, Cadigan JB, Cui J, Meyerowitz EA, Philippides G, Friedman LS, Kadar AY, Hibbert K, Natarajan P, Massaro AF, Bohula EA, Morrow DA, Woolley AE, Januzzi JL, Wasfy JH

Abstract
Background: Despite over 4 million cases of novel coronavirus disease 2019 (COVID-19) in the United States, limited data exist including socioeconomic background and post-discharge outcomes for patients hospitalized with this disease.
Methods: In this case series, we identified patients with COVID-19 admitted to 3 Partners Healthcare hospitals in Boston, Massachusetts between March 7th, 2020, and March 30th, 2020. Patient characteristics, treatment strategies, and outcomes were determined.
Findings: A total of 247 patients hospitalized with COVID-19 were identified; the median age was 61 (interquartile range [IQR]: 50-76 years), 58% were men, 30% of Hispanic ethnicity, 21% enrolled in Medicaid, and 12% dual-enrolled Medicare/Medicaid. The median estimated household income was $66,701 [IQR: $50,336-$86,601]. Most patients were treated with hydroxychloroquine (72%), and statins (76%; newly initiated in 34%). During their admission, 103 patients (42%) required intensive care. At the end of the data collection period (June 24, 2020), 213 patients (86.2%) were discharged alive, 2 patients (0.8%) remain admitted, and 32 patients (13%) have died. Among those discharged alive (n = 213), 70 (32.9%) were discharged to a post-acute facility, 31 (14.6%) newly required supplemental oxygen, 19 (8.9%) newly required tube feeding, and 34 (16%) required new prescriptions for antipsychotics, benzodiazepines, methadone, or opioids. Over a median post-discharge follow-up of 80 days (IQR, 68-84), 22 patients (10.3%) were readmitted.
Interpretation: Patients hospitalized with COVID-19 are frequently of vulnerable socioeconomic status and often require intensive care. Patients who survive COVID-19 hospitalization have substantial need for post-acute services.

PMID: 32838244 [PubMed - as supplied by publisher]

Reliability and Validity of a 6-Minute Yo-Yo Intermittent Endurance Test Level 2 in Subelite Part Time Male Soccer Players.

J Strength Cond Res. 2020 Aug 18;:

Authors: Gibson N, Easton C, Williams M, McCunn R, Gibson NV

Abstract
Gibson, N, Easton, C, Williams, M, McCunn, R, Gibson, NV. Reliability and validity of a 6-minute Yo-Yo Intermittent Endurance Test Level 2 in subelite part time male soccer players. J Strength Cond Res XX(X): 000-000, 2020-The aim of this study was to assess the reliability and relationship to maximal intermittent running performance of the 6-minute Yo-Yo Intermittent Endurance Test Level 2 (YYIET2), among subelite part time soccer players. Twenty male soccer players (15-22 years) completed three 6-minute YYIET2 trials with heart rate (HR), PlayerLoad, and rating of perceived exertion assessed during the protocol and HR and blood lactate assessed during 5 minutes of recovery. Subjects also completed a maximal version of the YYIET2 and the maximal Yo-Yo Intermittent Recovery Test Level 1 (YYIRT1) and 2 (YYIRT2). Heart rate at 4 and 6 minutes, PlayerLoad at 4 minutes, and HR recovery at 2, 3, 4, and 5 minutes during recovery from the 6-minute YYIET2 demonstrated little variance between tests. Correlations between variables measured during and after the 6-minute YYIET2 and distance covered in maximal tests ranged from r = 0.02 to -0.72. The 6-minute YYIET2 provides practitioners with a method of reliably assessing HR responses within subelite part time soccer players, although large correlations with maximal assessments suggest it can be used as a proxy measure for maximal intermittent running performance. Given its ease of administration and low time cost, the 6-minute YYIET2 offers practitioners a useful means of tracking training status and movement efficiency in players longitudinally.

PMID: 32826831 [PubMed - as supplied by publisher]

The potassium channel Kv4.2 regulates dendritic spine morphology, electroencephalographic characteristics and seizure susceptibility in mice.

Exp Neurol. 2020 Aug 18;:113437

Authors: Tiwari D, Schaefer TL, Schroeder-Carter LM, Krzeski JC, Bunk AT, Parkins EV, Snider A, Danzer R, Williams MT, Vorhees CV, Danzer SC, Gross C

Abstract
The voltage-gated potassium channel Kv4.2 is a critical regulator of dendritic excitability in the hippocampus and is crucial for dendritic signal integration. Kv4.2 mRNA and protein expression as well as function are reduced in several genetic and pharmacologically induced rodent models of epilepsy and autism. It is not known, however, whether reduced Kv4.2 is just an epiphenomenon or a disease-contributing cause of neuronal hyperexcitability and behavioral impairments in these neurological disorders. To address this question, we used male and female mice heterozygous for a Kv.2 deletion and adult-onset manipulation of hippocampal Kv4.2 expression in male mice to assess the role of Kv4.2 in regulating neuronal network excitability, morphology and anxiety-related behaviors. We observed a reduction in dendritic spine density and reduced proportions of thin and stubby spines but no changes in anxiety, overall activity, or retention of conditioned freezing memory in Kv4.2 heterozygous mice compared with wildtype littermates. Using EEG analyses, we showed elevated theta power and increased spike frequency in Kv4.2 heterozygous mice under basal conditions. In addition, the latency to onset of kainic acid-induced seizures was significantly shortened in Kv4.2 heterozygous mice compared with wildtype littermates, which was accompanied by a significant increase in theta power. By contrast, overexpressing Kv4.2 in wildtype mice through intrahippocampal injection of Kv4.2-expressing lentivirus delayed seizure onset and reduced EEG power. These results suggest that Kv4.2 is an important regulator of neuronal network excitability and dendritic spine morphology, but not anxiety-related behaviors. In the future, manipulation of Kv4.2 expression could be used to alter seizure susceptibility in epilepsy.

PMID: 32822706 [PubMed - as supplied by publisher]

Insulin-like growth factor 1-receptor signaling stimulates GRP78 expression through the PI3K/AKT/mTOR/ATF4 axis.

Cell Signal. 2020 Aug 14;:109736

Authors: Ha DP, Lee AS

Abstract
GRP78, a major molecular chaperone, is critical for the folding and maturation of membrane and secretory proteins and serves as the master regulator of the unfolded protein response. Thus, GRP78 is frequently upregulated in highly proliferative cells to cope with elevated protein synthesis and metabolic stress. IGF-1 is a potent regulator of cell growth, metabolism and survival. Previously we discovered that GRP78 is a novel downstream target of IGF-1 signaling by utilizing mouse embryonic fibroblast model systems where the IGF-1 receptor (IGF-1R) was either overexpressed (R+) or knockout (R-). Here we investigated the mechanisms whereby GRP78 is upregulated in the R+ cells. Our studies revealed that suppression of PI3K/AKT/mTOR downstream of IGF-1R signaling resulted in concurrent decrease in GRP78 and the transcription factor ATF4. Through knock-down and overexpression studies, we established ATF4 as the essential downstream nodal of the PI3K/AKT/mTOR signaling pathway critical for GRP78 transcriptional upregulation mediated by IGF-1R.

PMID: 32805346 [PubMed - as supplied by publisher]

Anatomic Gradients in the Microbiology of Spinal Fusion Surgical Site Infection and Resistance to Surgical Antimicrobial Prophylaxis.

Spine (Phila Pa 1976). 2020 Aug 12;:

Authors: Long DR, Bryson-Cahn C, Pergamit R, Tavolaro C, Saigal R, Chan JD, Lynch JB

Abstract
STUDY DESIGN: Retrospective hospital-registry study.
OBJECTIVE: To characterize the microbial epidemiology of surgical site infection (SSI) in spinal fusion surgery and the burden of resistance to standard surgical antibiotic prophylaxis.
SUMMARY OF BACKGROUND DATA: SSI persists as a leading complication of spinal fusion surgery despite the growth of enhanced recovery programs and improvements in other measures of surgical quality. Improved understandings of SSI microbiology and common mechanisms of failure for current prevention strategies are required to inform the development of novel approaches to prevention relevant to modern surgical practice.
METHODS: Spinal fusion cases performed at a single referral center between January 2011 and June 2019 were reviewed and SSI cases meeting National Healthcare Safety Network criteria were identified. Using microbiologic and procedural data from each case, we analyzed the anatomic distribution of pathogens, their differential time to presentation, and correlation with methicillin-resistant Staphylococcus aureus screening results. Susceptibility of isolates cultured from each infection were compared with the spectrum of surgical antibiotic prophylaxis administered during the index procedure on a per-case basis. Susceptibility to alternate prophylactic agents was also modeled.
RESULTS: Among 6727 cases, 351 infections occurred within 90 days. An anatomic gradient in the microbiology of SSI was observed across the length of the back, transitioning from cutaneous (gram-positive) flora in the cervical spine to enteric (gram-negative/anaerobic) flora in the lumbosacral region (correlation coefficient 0.94, p < 0.001). The majority (57.5%) of infections were resistant to the prophylaxis administered during the procedure. Cephalosporin-resistant gram-negative infection was common at lumbosacral levels and undetected methicillin-resistance was common at cervical levels.
CONCLUSIONS: Individualized infection prevention strategies tailored to operative level are needed in spine surgery. Endogenous wound contamination with enteric flora may be a common mechanism of infection in lumbosacral fusion. Novel approaches to prophylaxis and prevention should be prioritized in this population.
LEVEL OF EVIDENCE: 3.

PMID: 32796459 [PubMed - as supplied by publisher]