Publications by authors named "Guillaume Kugener"

Minimally invasive spine surgery (MISS) is increasingly performed using endoscopic and microscopic visualization, and the captured video can be used for surgical education and development of predictive artificial intelligence (AI) models. Video datasets depicting adverse event management are also valuable, as predictive models not exposed to adverse events may exhibit poor performance when these occur. Given that no dedicated spine surgery video datasets for AI model development are publicly available, we introduce Simulated Outcomes for Durotomy Repair in Minimally Invasive Spine Surgery (SOSpine).

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Background And Objectives: Assessment and feedback are critical to surgical education, but direct observational feedback by experts is rarely provided because of time constraints and is typically only qualitative. Automated, video-based, quantitative feedback on surgical performance could address this gap, improving surgical training. The authors aim to demonstrate the ability of Shannon entropy (ShEn), an information theory metric that quantifies series diversity, to predict surgical performance using instrument detections generated through deep learning.

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Unlabelled: Diffuse midline gliomas are uniformly fatal pediatric central nervous system cancers that are refractory to standard-of-care therapeutic modalities. The primary genetic drivers are a set of recurrent amino acid substitutions in genes encoding histone H3 (H3K27M), which are currently undruggable. These H3K27M oncohistones perturb normal chromatin architecture, resulting in an aberrant epigenetic landscape.

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Background: Intraoperative tool movement data have been demonstrated to be clinically useful in quantifying surgical performance. However, collecting this information from intraoperative video requires laborious hand annotation. The ability to automatically annotate tools in surgical video would advance surgical data science by eliminating a time-intensive step in research.

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Unlabelled: Relapse of acute myeloid leukemia (AML) after allogeneic bone marrow transplantation has been linked to immune evasion due to reduced expression of major histocompatibility complex class II (MHCII) genes through unknown mechanisms. In this work, we developed CORENODE, a computational algorithm for genome-wide transcription network decomposition that identified a transcription factor (TF) tetrad consisting of IRF8, MYB, MEF2C, and MEIS1, regulating MHCII expression in AML cells. We show that reduced MHCII expression at relapse is transcriptionally driven by combinatorial changes in the expression of these TFs, where MYB and IRF8 play major opposing roles, acting independently of the IFNγ/CIITA pathway.

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Major vascular injury resulting in uncontrolled bleeding is a catastrophic and often fatal complication of minimally invasive surgery. At the outset of these events, surgeons do not know how much blood will be lost or whether they will successfully control the hemorrhage (achieve hemostasis). We evaluate the ability of a deep learning neural network (DNN) to predict hemostasis control ability using the first minute of surgical video and compare model performance with human experts viewing the same video.

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Objective: While the utilization of machine learning (ML) for data analysis typically requires significant technical expertise, novel platforms can deploy ML methods without requiring the user to have any coding experience (termed AutoML). The potential for these methods to be applied to neurosurgical video and surgical data science is unknown.

Methods: AutoML, a code-free ML (CFML) system, was used to identify surgical instruments contained within each frame of endoscopic, endonasal intraoperative video obtained from a previously validated internal carotid injury training exercise performed on a high-fidelity cadaver model.

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Background: Deep neural networks (DNNs) have not been proven to detect blood loss (BL) or predict surgeon performance from video.

Objective: To train a DNN using video from cadaveric training exercises of surgeons controlling simulated internal carotid hemorrhage to predict clinically relevant outcomes.

Methods: Video was input as a series of images; deep learning networks were developed, which predicted BL and task success from images alone (automated model) and images plus human-labeled instrument annotations (semiautomated model).

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Importance: Surgical data scientists lack video data sets that depict adverse events, which may affect model generalizability and introduce bias. Hemorrhage may be particularly challenging for computer vision-based models because blood obscures the scene.

Objective: To assess the utility of the Simulated Outcomes Following Carotid Artery Laceration (SOCAL)-a publicly available surgical video data set of hemorrhage complication management with instrument annotations and task outcomes-to provide benchmarks for surgical data science techniques, including computer vision instrument detection, instrument use metrics and outcome associations, and validation of a SOCAL-trained neural network using real operative video.

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Acute myeloid leukemia with KMT2A (MLL) rearrangements is characterized by specific patterns of gene expression and enhancer architecture, implying unique core transcriptional regulatory circuitry. Here, we identified the transcription factors MEF2D and IRF8 as selective transcriptional dependencies of KMT2A-rearranged AML, where MEF2D displays partially redundant functions with its paralog, MEF2C. Rapid transcription factor degradation followed by measurements of genome-wide transcription rates and superresolution microscopy revealed that MEF2D and IRF8 form a distinct core regulatory module with a narrow direct transcriptional program that includes activation of the key oncogenes MYC, HOXA9, and BCL2.

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Article Synopsis
  • The authors conducted a systematic review to evaluate the use of robotic systems in neurosurgery, particularly focusing on procedures involving the skull base and sellar regions.
  • They searched for literature published between 1990 and 2021, identifying relevant studies including both cadaveric and human clinical research, while excluding those exclusively related to ENT applications.
  • The review revealed that the da Vinci Surgical System was the most commonly reported robotic system for skull base surgeries, offering benefits such as enhanced visualization and dexterity, although limitations persisted due to the robot's physical constraints and a lack of drilling capabilities.
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Objective: Experts can assess surgeon skill using surgical video, but a limited number of expert surgeons are available. Automated performance metrics (APMs) are a promising alternative but have not been created from operative videos in neurosurgery to date. The authors aimed to evaluate whether video-based APMs can predict task success and blood loss during endonasal endoscopic surgery in a validated cadaveric simulator of vascular injury of the internal carotid artery.

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CRISPR-Cas9-based genetic screens have successfully identified cell type-dependent liabilities in cancer, including acute myeloid leukemia (AML), a devastating hematologic malignancy with poor overall survival. Because most of these screens have been performed using established cell lines, evaluating the physiologic relevance of these targets is critical. We have established a CRISPR screening approach using orthotopic xenograft models to validate and prioritize AML-enriched dependencies , including in CRISPR-competent AML patient-derived xenograft (PDX) models tractable for genome editing.

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Objective: Virtual reality (VR) and augmented reality (AR) systems are increasingly available to neurosurgeons. These systems may provide opportunities for technical rehearsal and assessments of surgeon performance. The assessment of neurosurgeon skill in VR and AR environments and the validity of VR and AR feedback has not been systematically reviewed.

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Background: Renal medullary carcinomas (RMCs) are rare kidney cancers that occur in adolescents and young adults of African ancestry. Although RMC is associated with the sickle cell trait and somatic loss of the tumor suppressor, SMARCB1, the ancestral origins of RMC remain unknown. Further, characterization of structural variants (SVs) involving SMARCB1 in RMC remains limited.

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Article Synopsis
  • * The study identifies NXT1 as a selective and rapidly lethal target in neuroblastoma, showing that it forms a crucial component of mRNA export alongside NXF1.
  • * A novel mechanism of synthetic lethality is proposed between NXT1 and NXT2, suggesting a therapeutic strategy to selectively eliminate NXF1 in tumor cells while minimizing toxicity to normal cells.
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Article Synopsis
  • New therapeutic targets are being identified from CRISPR-based screens in adult cancers, raising questions about their applicability to pediatric cancers, which have fewer mutations.
  • Researchers created a pioneering pediatric cancer dependency map that included 13 types of pediatric solid and brain tumors, analyzing 82 cell lines with CRISPR-Cas9 to uncover essential genes for survival.
  • The study revealed that despite having fewer mutations, pediatric cancer cells exhibit similar complexity in genetic dependencies as adult cancer cells, suggesting that targeted treatments for childhood cancers will need to be developed separately from existing adult oncology drugs.
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Objective: Internal carotid artery injury (ICAI) is a rare, life-threatening complication of endoscopic endonasal approaches that will be encountered by most skull base neurosurgeons and otolaryngologists. Rates of surgical proficiency for managing ICAI are not known, and the role of simulation to improve performance has not been studied on a nationwide scale.

Methods: Attending and resident neurosurgery and otorhinolaryngology surgeons (n = 177) were recruited from multicenter regional and national training courses to assess training outcomes and validity at scale of a prospective educational intervention to improve surgeon technical skills using a previously validated, perfused human cadaveric simulator.

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Objective: Computer vision (CV) is a subset of artificial intelligence that performs computations on image or video data, permitting the quantitative analysis of visual information. Common CV tasks that may be relevant to surgeons include image classification, object detection and tracking, and extraction of higher order features. Despite the potential applications of CV to intraoperative video, however, few surgeons describe the use of CV.

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Purpose: Functional pituitary adenomas (FPAs) cause severe neuro-endocrinopathies including Cushing's disease (CD) and acromegaly. While many are effectively cured following FPA resection, some encounter disease recurrence/progression or hormonal non-remission requiring adjuvant treatment. Identification of risk factors for suboptimal postoperative outcomes may guide initiation of adjuvant multimodal therapies.

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Background: Attending assessment is a critical part of endoscopic education for gastroenterology fellows. The aim of this study was to develop and validate a concise, web-based assessment tool to evaluate real-time fellow performance in upper endoscopy.

Methods: We developed the Skill Assessment in Fellow Endoscopy Training (SAFE-T) upper endoscopy tool to capture both summative and formative feedback in a concise, five-part questionnaire.

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Few therapies target the loss of tumor suppressor genes in cancer. We examine CRISPR-SpCas9 and RNA-interference loss-of-function screens to identify new therapeutic targets associated with genomic loss of tumor suppressor genes. The endosomal sorting complexes required for transport (ESCRT) ATPases VPS4A and VPS4B score as strong synthetic lethal dependencies.

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