International Hackathon as a Tool to Augment Education, Collaboration, and Innovation in Global Neurosurgery.

BACKGROUND AND OBJECTIVES: Health care providers' exposure to global surgical disparities is limited in current nursing and/or medical school curricula. For instance, global health is often associated with infectious diseases or maternal health without acknowledging the growing need for surgical care in low- and middle-income countries (LMICs). We propose an international virtual hackathon based on neurosurgical patient cases in under-resourced settings as an educational tool to bring awareness to global surgical disparities and develop relationships among trainees in different countries. METHODS: Participants were recruited through email listservs, a social media campaign, and prize offerings. A 3-day virtual hackathon event was administered, which included workshops, mentorship, keynote panels, and pitch presentations to judges. Participants were presented with real patient cases and directed to solve a barrier to their care. Surveys assessed participants' backgrounds and event experience. The hackathon was executed through Zoom at Harvard Innovation Lab in Boston, MA, on March 25 to 27, 2022. Participants included medical students, with additional participants from business, engineering, or current health care workers. RESULTS: Three hundred seven applications were submitted for 100 spots. Participants included medical students, physicians, nurses, engineers, entrepreneurs, and undergraduates representing 25 countries and 82 cities. Fifty-one participants previously met a neurosurgeon, while 39 previously met a global health expert, with no difference between LMIC and high-income countries' respondents. Teams spent an average of 2.75 hours working with mentors, and 88% of postevent respondents said the event was "very" or "extremely conducive" to networking. Projects fell into 4 categories: access, language barriers, education and training, and resources. The winning team, which was interdisciplinary and international, developed an application that analyzes patient anatomy while performing physical therapy to facilitate remote care and clinical decision-making. CONCLUSION: An international virtual hackathon can be an educational tool to increase innovative ideas to address surgical disparities in LMICs and establish early collaborative relationships with medical trainees from different countries.

Brain AVM surgery without endovascular embolization in a low to middle income country.

We treated a 20-year-old woman in Paraguay with a ruptured intraventricular Spetzler-Martin Grade 3 AVM, and illustrate microsurgical resection without embolization in this video.

Middle meningeal artery embolization for refractory chronic subdural hematoma in a pediatric victim of nonaccidental trauma: illustrative case.

BACKGROUND: Chronic subdural hematoma (cSDH) in children is associated with several etiologies, one of which is nonaccidental trauma (NAT). Performed alone or as an adjunct to surgical intervention, middle meningeal artery (MMA) embolization may be effective in resolving and preventing the recurrence of cSDH in adult patients. However, MMA embolization for pediatric cSDH has not been adequately evaluated, and there exists no consensus on the appropriate selection of pediatric patients for this minimally invasive procedure. Appreciating the variable underlying pathophysiology of pediatric cSDH will enable the development of guidelines for patient selection. OBSERVATIONS: A 14-month-old female patient presented with depressed consciousness, seizure-like activity, and apneic episodes. She was diagnosed with bilateral subacute on chronic SDH associated with NAT, and imaging revealed diffuse brain atrophy. Despite undergoing burr hole drainage, she developed refractory cSDH and was treated with bilateral MMA embolization. At her 10-month follow-up, magnetic resonance imaging revealed a decrease in the size of the subdural collections, and she was tolerating feeds, at her neurological baseline, and seizure-free. LESSONS: Infants and young children with symptomatic cSDH secondary to NAT, whose tissue dynamics are reminiscent of cSDH in elderly patients with diffuse brain atrophy, may derive the most benefit from MMA embolization.

Functional Outcomes of Primary Arthrodesis (PA) Versus Open Reduction and Internal Fixation (ORIF) in the Treatment of Lisfranc Injuries.

OBJECTIVES: To determine whether primary arthrodesis (PA) or open reduction and internal fixation (ORIF) results in better functional outcomes through patient-reported outcome measures (PROMs). Reoperation rates and surgical characteristics among the 2 groups are evaluated as well. DESIGN: A retrospective cohort study. SETTING: Level 1 trauma center. PATIENTS: Eighty-one patients treated using PA or ORIF for Lisfranc injuries between January 2010 and January 2019. MAIN OUTCOME MEASUREMENTS: PROMs were collected using the validated Foot and Ankle Ability Measure questionnaire. Follow-up ranged from 1 to 10 years posttreatment. RESULTS: Two hundred patients underwent ORIF, and 72 patients underwent PA. Eighty-one of 272 patients responded to the questionnaire. The Foot and Ankle Ability Measure revealed activities of daily living subscores for PA and ORIF of 69.78 ± 18.61 and 73.53 ± 25.60, respectively ( P = 0.48). The Sports subscores for PA (45.81 ± 24.65) and ORIF (56.54 ± 31.13) were not significantly different ( P = 0.11). Perceived levels of activities of daily living ( P = 0.32) and Sports ( P = 0.81) function, compared with preinjury levels, were also not significantly different between the 2 groups. Rates of reoperation were nearly identical for PA (28.1%) and ORIF (30.6%) ( P = 1.00). CONCLUSION: Our results suggest that neither PA nor ORIF is superior regarding functional outcomes or rates of reoperation in the surgical treatment of Lisfranc injuries when appropriately triaged by the treating surgeon. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

A novel ground truth dataset enables robust 3D nuclear instance segmentation in early mouse embryos.

For investigations into fate specification and cell rearrangements in live images of preimplantation embryos, automated and accurate 3D instance segmentation of nuclei is invaluable; however, the performance of segmentation methods is limited by the images' low signal-to-noise ratio and high voxel anisotropy and the nuclei's dense packing and variable shapes. Supervised machine learning approaches have the potential to radically improve segmentation accuracy but are hampered by a lack of fully annotated 3D data. In this work, we first establish a novel mouse line expressing near-infrared nuclear reporter H2B-miRFP720. H2B-miRFP720 is the longest wavelength nuclear reporter in mice and can be imaged simultaneously with other reporters with minimal overlap. We then generate a dataset, which we call BlastoSPIM, of 3D microscopy images of H2B-miRFP720-expressing embryos with ground truth for nuclear instance segmentation. Using BlastoSPIM, we benchmark the performance of five convolutional neural networks and identify Stardist-3D as the most accurate instance segmentation method across preimplantation development. Stardist-3D, trained on BlastoSPIM, performs robustly up to the end of preimplantation development (> 100 nuclei) and enables studies of fate patterning in the late blastocyst. We, then, demonstrate BlastoSPIM's usefulness as pre-train data for related problems. BlastoSPIM and its corresponding Stardist-3D models are available at: blastospim.flatironinstitute.org.

Association between implementation of a coordinated care pathway in idiopathic scoliosis patients and a reduction in perioperative outcome disparities.

BACKGROUND: There are well-documented racial and ethnic disparities in treatment and perioperative outcomes for patients with adolescent idiopathic scoliosis. AIMS: We hypothesize that the implementation of a coordinated care pathway for pediatric patients undergoing posterior spinal fusion for adolescent idiopathic scoliosis may be associated with a reduction in racial and ethnic disparities in perioperative outcomes. METHODS: This is a retrospective pre- and post-test cohort study of patients who underwent posterior spinal fusion for adolescent idiopathic scoliosis at our institution between July 1, 2013 and August 5, 2019. We implemented a coordinated care pathway in March 2015. Patient demographics included age, race, ethnicity, weight, gender, insurance status, ASA class, time between the date surgery was ordered and the date surgery occurred, degree of scoliosis, and the number of spinal levels fused. The primary outcome was length of stay. The secondary outcomes included transfusion rates, pain scores, and postoperative complications. Multivariable regression models compared outcome medians across race/ethnicity. Disparities were defined as the difference in adjusted outcomes by race/ethnicity. RESULTS: Four hundred twenty-four patients underwent posterior spinal fusion for adolescent idiopathic scoliosis at our institution (116 prepathway and 308 postpathway). The median length of stay of Black patients was 1.0 day (95% CI: 0.4, 1.5; p = .006) longer than White patients prepathway. Prepathway patients who self-identified as Other had a 1.2 (95% CI: 0.5, 1.9; p = .004) higher median average pain score on postoperative day 1 compared with White patients. On postoperative day 2, patients who identified as Other had 2.0 (95% CI: 0.8, 3.2; p = .005) higher pain score compared with White patients prepathway. Postpathway, there were no significant differences in outcomes by race/ethnicity. CONCLUSIONS: Our study supports the hypothesis that use of a coordinated care pathway is associated with a reduction in racial and ethnic disparities in length of stay and pain scores in pediatric patients undergoing posterior spinal fusion.

TDP-43 proteinopathy in aging: Associations with risk-associated gene variants and with brain parenchymal thyroid hormone levels.

TDP-43 proteinopathy is very prevalent among the elderly (affecting at least 25% of individuals over 85 years of age) and is associated with substantial cognitive impairment. Risk factors implicated in age-related TDP-43 proteinopathy include commonly inherited gene variants, comorbid Alzheimer's disease pathology, and thyroid hormone dysfunction. To test parameters that are associated with aging-related TDP-43 pathology, we performed exploratory analyses of pathologic, genetic, and biochemical data derived from research volunteers in the University of Kentucky Alzheimer's Disease Center autopsy cohort (n = 136 subjects). Digital pathologic methods were used to discriminate and quantify both neuritic and intracytoplasmic TDP-43 pathology in the hippocampal formation. Overall, 46.4% of the cases were positive for TDP-43 intracellular inclusions, which is consistent with results in other prior community-based cohorts. The pathologies were correlated with hippocampal sclerosis of aging (HS-Aging) linked genotypes. We also assayed brain parenchymal thyroid hormone (triiodothyronine [T3] and thyroxine [T4]) levels. In cases with SLCO1A2/IAPP or ABCC9 risk associated genotypes, the T3/T4 ratio tended to be reduced (p = .051 using 2-tailed statistical test), and in cases with low T3/T4 ratios (bottom quintile), there was a higher likelihood of HS-Aging pathology (p = .025 using 2-tailed statistical test). This is intriguing because the SLCO1A2/IAPP and ABCC9 risk associated genotypes have been associated with altered expression of the astrocytic thyroid hormone receptor (protein product of the nearby gene SLCO1C1). These data indicate that dysregulation of thyroid hormone signaling may play a role in age-related TDP-43 proteinopathy.

The Amygdala as a Locus of Pathologic Misfolding in Neurodegenerative Diseases.

Over the course of most common neurodegenerative diseases the amygdala accumulates pathologically misfolded proteins. Misfolding of 1 protein in aged brains often is accompanied by the misfolding of other proteins, suggesting synergistic mechanisms. The multiplicity of pathogenic processes in human amygdalae has potentially important implications for the pathogenesis of Alzheimer disease, Lewy body diseases, chronic traumatic encephalopathy, primary age-related tauopathy, and hippocampal sclerosis, and for the biomarkers used to diagnose those diseases. Converging data indicate that the amygdala may represent a preferential locus for a pivotal transition from a relatively benign clinical condition to a more aggressive disease wherein multiple protein species are misfolded. Thus, understanding of amygdalar pathobiology may yield insights relevant to diagnoses and therapies; it is, however, a complex and imperfectly defined brain region. Here, we review aspects of amygdalar anatomy, connectivity, vasculature, and pathologic involvement in neurodegenerative diseases with supporting data from the University of Kentucky Alzheimer's Disease Center autopsy cohort. Immunohistochemical staining of amygdalae for Aß, Tau, α-synuclein, and TDP-43 highlight the often-coexisting pathologies. We suggest that the amygdala may represent an "incubator" for misfolded proteins and that it is possible that misfolded amygdalar protein species are yet to be discovered.