Emergent Management of Severe Hypothermia, Acidemia, and Coagulopathy in Operative Penetrating Ballistic Cranial Trauma.

Hypothermia in a trauma patient has been associated with increased morbidity and mortality and is more frequently seen in those sustaining traumatic brain injuries (TBIs). Acidosis is an important consequence of hypothermia that leads to derangements across the spectrum of the coagulation cascade. Here, we present a case of a 31-year-old male presented after suffering a right parietal penetrating ballistic injury with an associated subdural hematoma and 7 mm midline shift requiring decompressive craniectomy and external ventricular drain (EVD) placement in the setting of severe hypothermia (28°C) and acidosis (pH 7.12). With aggressive rewarming intraoperatively, the use of full-body forced-air warming, warmed IV fluids, and increasing the ambient room temperature, the patient's acidosis and hypothermia improved to pH 7.20 and 34°C. Despite these aggressive attempts to rewarm the patient, he developed coagulopathy in the setting of concurrent hypothermia and acidosis. This case highlights the importance of prompt reversal of hypothermia due to its potentially fatal effects, particularly in the setting of severe TBIs. We discuss the critical aspects of surgical management of the injury and anesthetic management of hypothermia, acidosis, and coagulopathy perioperatively.

Recurrent Gastrointestinal Stromal Tumor With Chondroid Differentiation After Imatinib Therapy: An Unusual Case and Literature Review.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the gastrointestinal tract and is most commonly seen in the stomach. The standard treatment for patients with advanced GISTs include both surgical resection and imatinib therapy. There have been cases that document the alterations of patients' GIST histomorphology both with primary GIST prior to imatinib therapy and with recurrent GIST after imatinib therapy. However, there has been no documented case of a patient who has recurrent GIST with chondroid differentiation at the primary site after imatinib therapy. In this article, we report an incidental finding of a 58-year-old patient who had two treatments of imatinib therapy prior to surgical resection of her recurrent GIST in her stomach. We also explore through a mini-literature review the various cases of GIST with chondroid differentiation that have been reported to compare the histomorphology, immunophenotype, and patient demographic of these cases. This article is significant for reporting a rare finding of GIST after imatinib therapy and highlights the various presentations that GIST could acquire after imatinib therapy that exclude another malignant process, such as chondrosarcoma.

Resection of a Recurrent Lumbar Chordoma With Intradural Extension and Complex Dural Repair: 2-Dimensional Operative Video.

Chordomas are derived from embryonic notochord remnants and comprise 1%-4% of all bone tumors.1 Nearly all chordomas arise in the axial skeleton, with 50% in the sacrococcygeal region, 35% in the skull base and 15% within mobile spine vertebrae.1,2 Regional recurrence after en bloc surgery is common and 30%-40% of patients develop metastatic disease.3-6 In this operative video, we present a 41-year old man who previously underwent en bloc lateral L1 corpectomy and received high-dose hybrid photon and proton radiation therapy for treatment of his L1 chordoma. On surveillance imaging, 2 years post op MRI revealed recurrence of the chordoma, now extending to the L2-3 epidural space. Further radiation alone was considered but was not performed due to lack of separation between the tumor and neural elements, thus increasing the risk of radiation-induced neurological injury. Combination revision surgical resection with subsequent boost radiation therapy was pursued instead. The technical nuances to achieve complex ventral and dorsal dural repair after removal of a transdural lumbar chordoma are shown in detail. Postoperatively, the patient had no new neurological deficits. At 13 months postoperatively, he reports no new pain, can ambulate without assistance, and completed 33 treatments of radiation therapy with proton beam. The patient consented to the procedure and to the publication of his image.

Genome-wide association study reveals GmFulb as candidate gene for maturity time and reproductive length in soybeans (Glycine max).

The ability of soybean [Glycine max (L.) Merr.] to adapt to different latitudes is attributed to genetic variation in major E genes and quantitative trait loci (QTLs) determining flowering time (R1), maturity (R8), and reproductive length (RL). Fully revealing the genetic basis of R1, R8, and RL in soybeans is necessary to enhance genetic gains in soybean yield improvement. Here, we performed a genome-wide association analysis (GWA) with 31,689 single nucleotide polymorphisms (SNPs) to detect novel loci for R1, R8, and RL using a soybean panel of 329 accessions with the same genotype for three major E genes (e1-as/E2/E3). The studied accessions were grown in nine environments and observed for R1, R8 and RL in all environments. This study identified two stable peaks on Chr 4, simultaneously controlling R8 and RL. In addition, we identified a third peak on Chr 10 controlling R1. Association peaks overlap with previously reported QTLs for R1, R8, and RL. Considering the alternative alleles, significant SNPs caused RL to be two days shorter, R1 two days later and R8 two days earlier, respectively. We identified association peaks acting independently over R1 and R8, suggesting that trait-specific minor effect loci are also involved in controlling R1 and R8. From the 111 genes highly associated with the three peaks detected in this study, we selected six candidate genes as the most likely cause of R1, R8, and RL variation. High correspondence was observed between a modifying variant SNP at position 04:39294836 in GmFulb and an association peak on Chr 4. Further studies using map-based cloning and fine mapping are necessary to elucidate the role of the candidates we identified for soybean maturity and adaptation to different latitudes and to be effectively used in the marker-assisted breeding of cultivars with optimal yield-related traits.

Cannabis Use Disorder Trends and Health Care Utilization After Cervical and Lumbar Spine Fusions.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To identify differences in complication rates after cervical and lumbar fusion over the first postoperative year between those with and without cannabis use disorder (CUD) and to assess how CUD affects opioid prescription patterns. SUMMARY OF BACKGROUND DATA: Cannabis is legal for medical purposes in 36 states and for recreational use in 18 states. Cannabis has multisystem effects and may contribute to transient vasoconstrictive, prothrombotic, and inflammatory effects. METHODS: The IBM MarketScan Database (2009-2019) was used to identify patients who underwent cervical or lumbar fusions, with or without CUD. Exact match hospitalization and postdischarge outcomes were analyzed at index, six, and 12 months. RESULTS: Of 72,024 cervical fusion (2.0% with CUD) and 105,612 lumbar fusion patients (1.5% with CUD), individuals with CUD were more likely to be young males with higher Elixhauser index. The cervical CUD group had increased neurological complications (3% vs. 2%) and sepsis (1% vs. 0%) during the index hospitalization and neurological (7% vs. 5%) and wound complications (5% vs. 3%) at 12 months. The lumbar CUD group had increased wound (8% vs. 5%) and myocardial infarction (MI) (2% vs. 1%) complications at six months and at 12 months. For those with cervical myelopathy, increased risk of pulmonary complications was observed with CUD at index hospitalization and 12-month follow-up. For those with lumbar stenosis, cardiac complications and MI were associated with CUD at index hospitalization and 12 months. CUD was associated with opiate use disorder, decreasing postoperatively. CONCLUSIONS: No differences in reoperation rates were observed for CUD groups undergoing cervical or lumbar fusion. CUD was associated with an increased risk of stroke for the cervical fusion cohort and cardiac (including MI) and pulmonary complications for lumbar fusion at index hospitalization and six and 12 months postoperatively. Opiate use disorder and decreased opiate dependence after surgery also correlated with CUD.

Genomic Variations Explorer (GenVarX): a toolset for annotating promoter and CNV regions using genotypic and phenotypic differences.

The rapid growth of sequencing technology and its increasing popularity in biology-related research over the years has made whole genome re-sequencing (WGRS) data become widely available. A large amount of WGRS data can unlock the knowledge gap between genomics and phenomics through gaining an understanding of the genomic variations that can lead to phenotype changes. These genomic variations are usually comprised of allele and structural changes in DNA, and these changes can affect the regulatory mechanisms causing changes in gene expression and altering the phenotypes of organisms. In this research work, we created the GenVarX toolset, that is backed by transcription factor binding sequence data in promoter regions, the copy number variations data, SNPs and Indels data, and phenotypes data which can potentially provide insights about phenotypic differences and solve compelling questions in plant research. Analytics-wise, we have developed strategies to better utilize the WGRS data and mine the data using efficient data processing scripts, libraries, tools, and frameworks to create the interactive and visualization-enhanced GenVarX toolset that encompasses both promoter regions and copy number variation analysis components. The main capabilities of the GenVarX toolset are to provide easy-to-use interfaces for users to perform queries, visualize data, and interact with the data. Based on different input windows on the user interface, users can provide inputs corresponding to each field and submit the information as a query. The data returned on the results page is usually displayed in a tabular fashion. In addition, interactive figures are also included in the toolset to facilitate the visualization of statistical results or tool outputs. Currently, the GenVarX toolset supports soybean, rice, and Arabidopsis. The researchers can access the soybean GenVarX toolset from SoyKB via https://soykb.org/SoybeanGenVarX/, rice GenVarX toolset, and Arabidopsis GenVarX toolset from KBCommons web portal with links https://kbcommons.org/system/tools/GenVarX/Osativa and https://kbcommons.org/system/tools/GenVarX/Athaliana, respectively.

Loss-of-function of an α-SNAP gene confers resistance to soybean cyst nematode.

Plant-parasitic nematodes are one of the most economically impactful pests in agriculture resulting in billions of dollars in realized annual losses worldwide. Soybean cyst nematode (SCN) is the number one biotic constraint on soybean production making it a priority for the discovery, validation and functional characterization of native plant resistance genes and genetic modes of action that can be deployed to improve soybean yield across the globe. Here, we present the discovery and functional characterization of a soybean resistance gene, GmSNAP02. We use unique bi-parental populations to fine-map the precise genomic location, and a combination of whole genome resequencing and gene fragment PCR amplifications to identify and confirm causal haplotypes. Lastly, we validate our candidate gene using CRISPR-Cas9 genome editing and observe a gain of resistance in edited plants. This demonstrates that the GmSNAP02 gene confers a unique mode of resistance to SCN through loss-of-function mutations that implicate GmSNAP02 as a nematode virulence target. We highlight the immediate impact of utilizing GmSNAP02 as a genome-editing-amenable target to diversify nematode resistance in commercially available cultivars.

The modified occipital condyle screw: A quantitative anatomic study investigating the feasibility of a novel instrumented fixation technique for craniocervical fusion.

Study Design: Prospective human anatomical study. Objective: Occipitocervical fusion with occipital plate or condyle screws has shown higher failure rates in those with skeletal dysplasia. The modified occipital condyle screw connects the occipital condyle to the pars basilaris of the occipital bone that may achieve fortified bony purchase and serve as a more rigid fixation point. We evaluate anatomical feasibility of a novel cranial fixation technique designed to decrease risk of pseudarthrosis. Materials and Methods: Occipital condyles were analyzed morphologically using multiplanar three-dimensional reconstructed, ultra-thin section computed tomography. The following parameters were obtained: occipital condyle length, maximal cross section, location of hypoglossal canal, axial and sagittal orientation of the long axis, occipital condyle pedicle (OCP) diameter, maximal length of OCP screw, and entry point. Results: Forty patients with total of 80 occipital condyles were analyzed and the following measurements were obtained: occipital condyle length 24.1 mm (20.5-27.7, standard deviation [SD]: 2.2); condyle maximum axial cross-section 12.6 mm (9-15.8, SD: 1.9); length of OCP screw 38.9 mm (29.3-44, SD: 5.7); diameter of OCP 3.4 mm (3.2-3.6, SD: 0.2); clearance below hypoglossal canal 4.5 mm (3.4-7, SD: 1.1); and distance of screw entry point from condylar foramen 2 mm (range 0-4, SD 1.6). Conclusion: The modified occipital condyle screw connects the condyle with the clivus through the pars basilaris and represents a safe and technically feasible approach to achieve craniocervical fusion in skeletally mature individuals. This cephalad anchor point serves as an alternate fixation point of the occipitocervical junction with increased strength of construct and decreased risk of hardware failure or pseudarthrosis given cortical bone purchase and longer screw instrumentation.

Immune-Mediated Necrotizing Myopathy With Concurrent Statin Use After Routine COVID-19 Inoculation: A Case Report.

SARS-CoV-2 has been associated with multiple disease processes and chronic sequela. Much less understood are the neurological effects, ranging from headaches, pro-thrombotic state, encephalitis, and myopathic processes. Many case reports have documented post-SARS-CoV-2 virus effects; however, this case highlights the possibility of a less commonly described neurological manifestation possibly related to the BNT162b2 mRNA Pfizer vaccine. There is scant literature on immune-mediated necrotizing myopathy (IMNM) triggered after COVID-19 vaccination. The BNT162b2 mRNA COVID-19 vaccine (Pfizer, BioNTech) has proven to be safe and effective in reducing transmission of COVID-19, but post-vaccination neurological events, including venous sinus thrombosis, transverse myelitis, and immune-mediated diseases, such as Guillain-Barré syndrome, have been reported. We report a case of IMNM with HMG-CoA reductase antibody positivity in the setting of BNT162b2 vaccination. The patient presented with progressive muscle weakness with rhabdomyolysis and necrotizing autoimmune myopathy proven on muscle biopsy after the second dose of the BNT162b2 vaccine. Ultimately, this case report highlights the importance of clinical suspicion for early diagnosis and initiation of treatment after symptoms concerning necrotizing myopathy.

Spinal cord epidural stimulation for motor and autonomic function recovery after chronic spinal cord injury: A case series and technical note.

Background: Traumatic spinal cord injury (tSCI) is a debilitating condition, leading to chronic morbidity and mortality. In recent peer-reviewed studies, spinal cord epidural stimulation (scES) enabled voluntary movement and return of over-ground walking in a small number of patients with motor complete SCI. Using the most extensive case series (n = 25) for chronic SCI, the present report describes our motor and cardiovascular and functional outcomes, surgical and training complication rates, quality of life (QOL) improvements, and patient satisfaction results after scES. Methods: This prospective study occurred at the University of Louisville from 2009 to 2020. scES interventions began 2-3 weeks after surgical implantation of the scES device. Perioperative complications were recorded as well as long-term complications during training and device related events. QOL outcomes and patient satisfaction were evaluated using the impairment domains model and a global patient satisfaction scale, respectively. Results: Twenty-five patients (80% male, mean age of 30.9 ± 9.4 years) with chronic motor complete tSCI underwent scES using an epidural paddle electrode and internal pulse generator. The interval from SCI to scES implantation was 5.9 ± 3.4 years. Two participants (8%) developed infections, and three additional patients required washouts (12%). All participants achieved voluntary movement after implantation. A total of 17 research participants (85%) reported that the procedure either met (n = 9) or exceeded (n = 8) their expectations, and 100% would undergo the operation again. Conclusion: scES in this series was safe and achieved numerous benefits on motor and cardiovascular regulation and improved patient-reported QOL in multiple domains, with a high degree of patient satisfaction. The multiple previously unreported benefits beyond improvements in motor function render scES a promising option for improving QOL after motor complete SCI. Further studies may quantify these other benefits and clarify scES's role in SCI patients.

The Allele Catalog Tool: a web-based interactive tool for allele discovery and analysis.

BACKGROUND: The advancement of sequencing technologies today has made a plethora of whole-genome re-sequenced (WGRS) data publicly available. However, research utilizing the WGRS data without further configuration is nearly impossible. To solve this problem, our research group has developed an interactive Allele Catalog Tool to enable researchers to explore the coding region allelic variation present in over 1,000 re-sequenced accessions each for soybean, Arabidopsis, and maize. RESULTS: The Allele Catalog Tool was designed originally with soybean genomic data and resources. The Allele Catalog datasets were generated using our variant calling pipeline (SnakyVC) and the Allele Catalog pipeline (AlleleCatalog). The variant calling pipeline is developed to parallelly process raw sequencing reads to generate the Variant Call Format (VCF) files, and the Allele Catalog pipeline takes VCF files to perform imputations, functional effect predictions, and assemble alleles for each gene to generate curated Allele Catalog datasets. Both pipelines were utilized to generate the data panels (VCF files and Allele Catalog files) in which the accessions of the WGRS datasets were collected from various sources, currently representing over 1,000 diverse accessions for soybean, Arabidopsis, and maize individually. The main features of the Allele Catalog Tool include data query, visualization of results, categorical filtering, and download functions. Queries are performed from user input, and results are a tabular format of summary results by categorical description and genotype results of the alleles for each gene. The categorical information is specific to each species; additionally, available detailed meta-information is provided in modal popups. The genotypic information contains the variant positions, reference or alternate genotypes, the functional effect classes, and the amino-acid changes of each accession. Besides that, the results can also be downloaded for other research purposes. CONCLUSIONS: The Allele Catalog Tool is a web-based tool that currently supports three species: soybean, Arabidopsis, and maize. The Soybean Allele Catalog Tool is hosted on the SoyKB website ( https://soykb.org/SoybeanAlleleCatalogTool/ ), while the Allele Catalog Tool for Arabidopsis and maize is hosted on the KBCommons website ( https://kbcommons.org/system/tools/AlleleCatalogTool/Zmays and https://kbcommons.org/system/tools/AlleleCatalogTool/Athaliana ). Researchers can use this tool to connect variant alleles of genes with meta-information of species.

AccuCalc: A Python Package for Accuracy Calculation in GWAS.

The genome-wide association study (GWAS) is a popular genomic approach that identifies genomic regions associated with a phenotype and, thus, aims to discover causative mutations (CM) in the genes underlying the phenotype. However, GWAS discoveries are limited by many factors and typically identify associated genomic regions without the further ability to compare the viability of candidate genes and actual CMs. Therefore, the current methodology is limited to CM identification. In our recent work, we presented a novel approach to an empowered "GWAS to Genes" strategy that we named Synthetic phenotype to causative mutation (SP2CM). We established this strategy to identify CMs in soybean genes and developed a web-based tool for accuracy calculation (AccuTool) for a reference panel of soybean accessions. Here, we describe our further development of the tool that extends its utilization for other species and named it AccuCalc. We enhanced the tool for the analysis of datasets with a low-frequency distribution of a rare phenotype by automated formatting of a synthetic phenotype and added another accuracy-based GWAS evaluation criterion to the accuracy calculation. We designed AccuCalc as a Python package for GWAS data analysis for any user-defined species-independent variant calling format (vcf) or HapMap format (hmp) as input data. AccuCalc saves analysis outputs in user-friendly tab-delimited formats and also offers visualization of the GWAS results as Manhattan plots accentuated by accuracy. Under the hood of Python, AccuCalc is publicly available and, thus, can be used conveniently for the SP2CM strategy utilization for every species.

Health Care Utilization and Associated Economic Burden of Postoperative Surgical Site Infection after Spinal Surgery with Follow-Up of 24 Months.

BACKGROUND: Surgical site infection (SSI) may lead to vertebral osteomyelitis, diskitis, paraspinal musculoskeletal infection, and abscess, and remains a significant concern in postoperative management of spinal surgery. SSI is associated with greater postoperative morbidity and increased health care payments. METHODS: We conducted a retrospective analysis using MarketScan to identify health care utilization payments and risk factors associated with SSI that occurs postoperatively. Known patient- or procedure-related risk factors were searched across those receiving spine surgery who developed postoperative infection. RESULTS: A total of 33,061 patients who developed infection after spinal surgery were identified in Marketscan. Overall payments at 6 months, including index hospitalization for those with infection, were $53,573 and $46,985 for the cohort with no infection. At 24 months, the infection group had overall payments of $83,280 and $66,221 for no infection. Risk factors with largest effect size most likely to contribute to infection versus no infection were depression (4.6%), diabetes (3.7), anemia (3.3%), two or more levels (2.8%), tobacco use (2.2%), trauma (2.1%), neoplasm (1.8%), congestive heart failure (1.3%), instrumentation (1.1%), renal failure (0.9%), intravenous drug use (0.8%), and malnutrition (0.5%). CONCLUSIONS: SSIs were associated with significant health care utilization payments at 24 months of follow-up. The following clinical and procedural risk factors appear to be predictive of postoperative SSI: depression, diabetes, anemia, two or more levels, tobacco use, trauma, neoplasm, congestive heart failure, instrumentation, renal failure, intravenous drug use, and malnutrition. Interpretation of modifiable and nonmodifiable risk factors for infection informs surgeons of expected postoperative course and preoperative risk for this most common and deleterious postoperative complication to spinal surgery.

Intrathecal and Oral Baclofen Use in Adults With Spinal Cord Injury: A Systematic Review of Efficacy in Spasticity Reduction, Functional Changes, Dosing, and Adverse Events.

OBJECTIVE: To examine the efficacy, dosing, and safety profiles of intrathecal and oral baclofen in treating spasticity after spinal cord injury (SCI). DATA SOURCES: PubMed and Cochrane Databases were searched from 1970-2018 with keywords baclofen, spinal cord injury, and efficacy. STUDY SELECTION: The database search yielded 588 sources and 10 additional relevant publications. After removal of duplicates, 398 publications were screened. DATA EXTRACTION: Data were extracted using the following population, intervention, comparator, outcomes, and study designs criteria: studies including adult patients with SCI with spasticity; the intervention could be oral or intrathecal administration of baclofen; selection was inclusive for control groups, surgical management, rehabilitation, and alternative pharmaceutical agents; outcomes were efficacy, dosing, and adverse events. Randomized controlled trials, observational studies, and case reports were included. Meta-analyses and systematic reviews were excluded. DATA SYNTHESIS: A total of 98 studies were included with 1943 patients. Only 4 randomized, double-blinded, and placebo-controlled trials were reported. Thirty-nine studies examined changes in the Modified Ashworth Scale (MAS; 34 studies) and Penn Spasm scores (Penn Spasm Frequency; 19 studies), with average reductions of 1.7±1.3 and 1.6±1.4 in individuals with SCI, respectively. Of these data, a total of 6 of the 34 studies (MAS) and 2 of the 19 studies (Penn Spasm Frequency) analyzed oral baclofen. Forty-three studies addressed adverse events with muscle weakness and fatigue frequently reported. CONCLUSIONS: Baclofen is the most commonly-prescribed antispasmodic after SCI. Surprisingly, there remains a significant lack of large, placebo-controlled, double-blinded clinical trials, with most efficacy data arising from small studies examining treatment across different etiologies. In the studies reviewed, baclofen effectively improved spasticity outcome measures, with increased efficacy through intrathecal administration. Few studies assessed how reduced neural excitability affected residual motor function and activities of daily living. A host of adverse events were reported that may negatively affect quality of life. Comparative randomized controlled trials of baclofen and alternative treatments are warranted because these have demonstrated promise in relieving spasticity with reduced adverse events and without negatively affecting residual motor function.

Trends and Outcomes in Patients with Dementia Undergoing Spine Fusions: A Matched Nationwide Inpatient Sample Analysis.

BACKGROUND: The aim of our study was to define the trends and outcomes in patients with a preexisting diagnosis of dementia who underwent spine fusions using a large national database. METHODS: The Nationwide Inpatient Sample database was queried using the International Classification of Diseases, Ninth Revision and Tenth Revision, from 1998 to 2018. We included patients who underwent spine fusions with or without the diagnosis of dementia. Outcomes were trends, complications, length of stay (LOS), discharge disposition, and mortality. RESULTS: A cohort of 4495 patients (N = 1,390,657; 0.32%) with dementia who underwent spine fusions was identified. There was an increasing trend of spine fusions in patients with the diagnosis of dementia. Most patients with dementia were white (77% vs. 69%), with ≥3 comorbidities (70% vs. 23%), had Medicare insurance (83% vs. 34%) compared with patients without dementia (P < 0.0001). Overall, 38% of patients had complications after spine fusions compared with 21% of patients without dementia during the study period. Median LOS was significantly longer in patients with dementia compared with patients without dementia (6 vs. 4 days). Patients with dementia were less likely to be discharged home (19% vs. 40%) and incurred higher in-hospitalization charges ($139,101 vs. $101,629) compared with patients without dementia. No differences in terms of in-hospital mortality were noted across the cohorts (1.4% vs. 1.6%). CONCLUSIONS: Patients with dementia had 1.5 times longer LOS and 1.4 times higher index hospitalization charges and were 2.5 times more likely to have complications and 71% less likely to be discharged home, with no difference in mortality compared with patients without dementia after spine fusions.

A novel Synthetic phenotype association study approach reveals the landscape of association for genomic variants and phenotypes.

INTRODUCTION: Genome-Wide Association Studies (GWAS) identify tagging variants in the genome that are statistically associated with the phenotype because of their linkage disequilibrium (LD) relationship with the causative mutation (CM). When both low-density genotyped accession panels with phenotypes and resequenced data accession panels are available, tagging variants can assist with post-GWAS challenges in CM discovery. OBJECTIVES: Our objective was to identify additional GWAS evaluation criteria to assess correspondence between genomic variants and phenotypes, as well as enable deeper analysis of the localized landscape of association. METHODS: We used genomic variant positions as Synthetic phenotypes in GWAS that we named "Synthetic phenotype association study" (SPAS). The extreme case of SPAS is what we call an "Inverse GWAS" where we used CM positions of cloned soybean genes. We developed and validated the Accuracy concept as a measure of the correspondence between variant positions and phenotypes. RESULTS: The SPAS approach demonstrated that the genotype status of an associated variant used as a Synthetic phenotype enabled us to explore the relationships between tagging variants and CMs, and further, that utilizing CMs as Synthetic phenotypes in Inverse GWAS illuminated the landscape of association. We implemented the Accuracy calculation for a curated accession panel to an online Accuracy calculation tool (AccuTool) as a resource for gene identification in soybean. We demonstrated our concepts on three examples of soybean cloned genes. As a result of our findings, we devised an enhanced "GWAS to Genes" analysis (Synthetic phenotype to CM strategy, SP2CM). Using SP2CM, we identified a CM for a novel gene. CONCLUSION: The SP2CM strategy utilizing Synthetic phenotypes and the Accuracy calculation of correspondence provides crucial information to assist researchers in CM discovery. The impact of this work is a more effective evaluation of landscapes of GWAS associations.

Machine learning in clinical diagnosis, prognostication, and management of acute traumatic spinal cord injury (SCI): A systematic review.

Background: Machine learning has been applied to improve diagnosis and prognostication of acute traumatic spinal cord injury. We investigate potential for clinical integration of machine learning in this patient population to navigate variability in injury and recovery. Materials and methods: We performed a systematic review using PRISMA guidelines through PubMed database to identify studies that use machine learning algorithms for clinical application toward improvements in diagnosis, management, and predictive modeling. Results: Of the 132 records identified, a total of 13 articles met inclusion criteria and were included in final analysis. Of the 13 articles, 5 focused on diagnostic accuracy and 8 were related to prognostication or management of traumatic spinal cord injury. Across studies, 1983 patients with spinal cord injury were evaluated with most classifying as ASIA C or D. Retrospective designs were used in 10 of 13 studies and 3 were prospective. Studies focused on MRI evaluation and segmentation for diagnostic accuracy and prognostication, investigation of mean arterial pressure in acute care and intraoperative settings, prediction of ambulatory and functional ability, chronic complication prevention, and psychological quality of life assessments. Decision tree, random forests (RF), support vector machines (SVM), hierarchical cluster tree analysis (HCTA), artificial neural networks (ANN), convolutional neural networks (CNN) machine learning subtypes were used. Conclusions: Machine learning represents a platform technology with clinical application in traumatic spinal cord injury diagnosis, prognostication, management, rehabilitation, and risk prevention of chronic complications and mental illness. SVM models showed improved accuracy when compared to other ML subtypes surveyed. Inherent variability across patients with SCI offers unique opportunity for ML and personalized medicine to drive desired outcomes and assess risks in this patient population.

Effects of deep brain stimulation target on the activation and suppression of action impulses.

OBJECTIVE: Deep brain stimulation (DBS) is an effective treatment to improve motor symptoms in Parkinson's disease (PD). The Globus Pallidus (GPi) and the Subthalamic Nucleus (STN) are the most targeted brain regions for stimulation and produce similar improvements in PD motor symptoms. However, our understanding of stimulation effects across targets on inhibitory action control processes is limited. We compared the effects of STN (n = 20) and GPi (n = 13) DBS on inhibitory control in PD patients. METHODS: We recruited PD patients undergoing DBS at the Vanderbilt Movement Disorders Clinic and measured their performance on an inhibitory action control task (Simon task) before surgery (optimally treated medication state) and after surgery in their optimally treated state (medication plus their DBS device turned on). RESULTS: DBS to both STN and GPi targets induced an increase in fast impulsive errors while simultaneously producing more proficient reactive suppression of interference from action impulses. CONCLUSIONS: Stimulation in GPi produced similar effects as STN DBS, indicating that stimulation to either target increases the initial susceptibility to act on strong action impulses while concomitantly improving the ability to suppress ongoing interference from activated impulses. SIGNIFICANCE: Action impulse control processes are similarly impacted by stimulating dissociable nodes in frontal-basal ganglia circuitry.

90-Day Bundled Payment Simulation, Health Care Utilization, and Complications following Craniopharyngioma Resection in Adult Patients.

Context Bundled payment and health care utilization models inform cost optimization and surgical outcomes. Economic analysis of payment plans for craniopharyngioma resection is unknown. Objective This study aimed to identify impact of endocrine and nonendocrine complications (EC and NEC, respectively) on health care utilization and bundled payments following craniopharyngioma resection. Design This study is presented as a retrospective cohort analysis (2000-2016) with 2 years of follow-up. Setting The study included national inpatient hospitalization and outpatient visits. Patients Patients undergoing craniopharyngioma resection were divided into the following four groups: group 1, no complications (NC); group 2, only EC; group 3, NEC; and group 4, both endocrine and nonendocrine complications (ENEC). Interventions This study investigated transphenoidal or subfrontal approach for tumor resection. Main Outcome Hospital readmission, health care utilization up to 24 months following discharge, and 90-day bundled payment performances are primary outcomes of this study. Results Median index hospitalization payments were significantly lower for patients in NC cohort ($28,672) compared with those in EC ($32,847), NEC ($36,259), and ENEC ($32,596; p < 0.0001). Patients in ENEC incurred higher outpatient services and overall median payments at 6 months (NC: 38,268; EC: 49,844; NEC: 68,237; and ENEC: 81,053), 1 year (NC: 46,878; EC: 58,210; NEC: 81,043; and ENEC: 94,768), and 2 years (NC: 58,391; EC: 70,418; NEC: 98,838; and ENEC: 1,11,841; p < 0.0001). The 90-day median bundled payment was significantly different among the cohorts with the highest in ENEC ($60,728) and lowest in the NC ($33,089; p < 0.0001). Conclusion ENEC following surgery incurred almost two times the overall median payments at 90 days, 6 months, 1 year. and 2 years compared with those without complications. Bundled payment model may not be a feasible option in this patient population. Type of complications and readmission rates should be considered to optimize payment model prediction following craniopharyngioma resection.

Restoring Segmental Spinal Alignment in Mini-Open Lateral Spinal Deformity Surgery-Determiners of Radiographic Outcome.

OBJECTIVE: Both under- and overcorrection are risk factors for junctional failure after deformity correction. This study investigates which factors determine the segmental radiographic outcome in mini-open lateral deformity surgery. METHODS: A single-center operative database was searched for patients undergoing multilevel mini-open lateral corrective surgery of degenerative spinal deformities. Preoperative and postoperative whole spine x-rays and computed tomography scans were compared for change in global and segmental alignment parameters. Linear regression analyses were performed to study the impact of surgical level, preoperative segmental sagittal Cobb angle, presence of bridging osteophytes, disc height, ankylosis of facet joints, and implantation site of the interbody device on postoperative increase in segmental lordosis, foraminal height, and foraminal width. RESULTS: A total of 49 patients were identified with a mean age of 68.7 years. At a mean, 4.2 segments were fused using a lateral approach, while the posterior stage comprised either minimally invasive surgery or open instrumentation. Upper instrumented vertebra was L2 (range T4-L3), and lower instrumented vertebra was L5 (range L4-pelvis) in most cases. Mean radiographic values pre- and postoperatively were as follows: C7 sagittal vertical axis +79.6 mm, +60 mm; lumbar lordosis 32.9°, 41.6°; pelvic tilt 21.1°, 21.8°; global coronal Cobb 16.3°, 10.8°; increase in segmental sagittal Cobb angle was significantly and inversely correlated with preoperative sagittal Cobb and positively correlated with preoperative coronal Cobb angle. No other variable showed significant correlations. Preoperative foraminal width and height showed significant and inverse correlation with change in postoperative foraminal width and height. CONCLUSION: Segmental sagittal correction is significantly influenced by preoperative loss of lordosis and coronal Cobb angle. Neither presence of osteophytes nor ankylosed facet joints, disc height, or implantation site of the interbody device had an influence on sagittal alignment goals. Only preoperative foraminal dimensions impact inversely the degree of foraminal decompression; no other factor investigated showed significant impact. CLINICAL RELEVANCE: Only preoperative lordosis and coronal Cobb angle influence sagittal correction.