The effect of preoperative embolization on giant cell tumors of the bone localized in the iliosacral region of the pelvis.

INTRODUCTION: Giant cell tumors of the bone (GCTB) are aggressive neoplasms, with rare occurrences in the posterior pelvis and sacral area. Surgical challenges in this region include the inability to apply a tourniquet and limited cementation post-curettage due to proximity to neurovascular structures, leading to potential complications. This case-control study explores the impact of preoperative embolization on GCTB located in the iliosacral region. METHODS: Five surgeries (January-December 2021) for pelvic GCTB (3 sacrum, 2 posterior ilium) were performed on four patients. Diagnosis was confirmed through preoperative CT-guided biopsies. One surgery involved curettage with PMMA cement filling, while four surgeries had curettage without cavity filling. Preoperative embolization of the tumor feeding vessel occurred approximately 16 h before surgery in two cases. Denosumab treatment was not administered. RESULTS: Tumor volume, assessed by preoperative MRI, was comparable between patients with and without preoperative embolization (p = .14). Surgeries without embolization had a mean intraoperative blood loss of 3250 ml, erythrocyte transfusion volume of 1125 ml, and a mean surgical time of 114.5 min for two surgeries. Surgeries with preoperative embolization showed a mean intraoperative blood loss of 1850 ml, no erythrocyte transfusion requirement, and a mean surgical time of 68 min. CONCLUSION: Curettage of GCTB in the posterior pelvis and sacrum presents challenges, with significant intraoperative blood loss impacting surgical time and transfusion needs. Preoperative embolization may be beneficial in reducing blood loss during surgery in these cases.

A modified motor-clutch model reveals that neuronal growth cones respond faster to soft substrates.

Neuronal growth cones sense a variety of cues including chemical and mechanical ones to establish functional connections during nervous system development. Substrate-cytoskeletal coupling is an established model for adhesion-mediated growth cone advance; however, the detailed molecular and biophysical mechanisms underlying the mechanosensing and mechanotransduction process remain unclear. Here, we adapted a motor-clutch model to better understand the changes in clutch and cytoskeletal dynamics, traction forces, and substrate deformation when a growth cone interacts with adhesive substrates of different stiffnesses. Model parameters were optimized using experimental data from Aplysia growth cones probed with force-calibrated glass microneedles. We included a reinforcement mechanism at both motor and clutch level. Furthermore, we added a threshold for retrograde F-actin flow that indicates when the growth cone is strongly coupled to the substrate. Our modeling results are in strong agreement with experimental data with respect to the substrate deformation and the latency time after which substrate-cytoskeletal coupling is strong enough for the growth cone to advance. Our simulations show that it takes the shortest time to achieve strong coupling when substrate stiffness was low at 4 pN/nm. Taken together, these results suggest that Aplysia growth cones respond faster and more efficiently to soft than stiff substrates.

Automatic registration with continuous pose updates for marker-less surgical navigation in spine surgery.

Established surgical navigation systems for pedicle screw placement have been proven to be accurate, but still reveal limitations in registration or surgical guidance. Registration of preoperative data to the intraoperative anatomy remains a time-consuming, error-prone task that includes exposure to harmful radiation. Surgical guidance through conventional displays has well-known drawbacks, as information cannot be presented in-situ and from the surgeon's perspective. Consequently, radiation-free and more automatic registration methods with subsequent surgeon-centric navigation feedback are desirable. In this work, we present a marker-less approach that automatically solves the registration problem for lumbar spinal fusion surgery in a radiation-free manner. A deep neural network was trained to segment the lumbar spine and simultaneously predict its orientation, yielding an initial pose for preoperative models, which then is refined for each vertebra individually and updated in real-time with GPU acceleration while handling surgeon occlusions. An intuitive surgical guidance is provided thanks to the integration into an augmented reality based navigation system. The registration method was verified on a public dataset with a median of 100% successful registrations, a median target registration error of 2.7 mm, a median screw trajectory error of 1.6°and a median screw entry point error of 2.3 mm. Additionally, the whole pipeline was validated in an ex-vivo surgery, yielding a 100% screw accuracy and a median target registration error of 1.0 mm. Our results meet clinical demands and emphasize the potential of RGB-D data for fully automatic registration approaches in combination with augmented reality guidance.

Automatic breach detection during spine pedicle drilling based on vibroacoustic sensing.

Pedicle drilling is a complex and critical spinal surgery task. Detecting breach or penetration of the surgical tool to the cortical wall during pilot-hole drilling is essential to avoid damage to vital anatomical structures adjacent to the pedicle, such as the spinal cord, blood vessels, and nerves. Currently, the guidance of pedicle drilling is done using image-guided methods that are radiation intensive and limited to the preoperative information. This work proposes a new radiation-free breach detection algorithm leveraging a non-visual sensor setup in combination with deep learning approach. Multiple vibroacoustic sensors, such as a contact microphone, a free-field microphone, a tri-axial accelerometer, a uni-axial accelerometer, and an optical tracking system were integrated into the setup. Data were collected on four cadaveric human spines, ranging from L5 to T10. An experienced spine surgeon drilled the pedicles relying on optical navigation. A new automatic labeling method based on the tracking data was introduced. Labeled data was subsequently fed to the network in mel-spectrograms, classifying the data into breach and non-breach. Different sensor types, sensor positioning, and their combinations were evaluated. The best results in breach recall for individual sensors could be achieved using contact microphones attached to the dorsal skin (85.8%) and uni-axial accelerometers clamped to the spinous process of the drilled vertebra (81.0%). The best-performing data fusion model combined the latter two sensors with a breach recall of 98%. The proposed method shows the great potential of non-visual sensor fusion for avoiding screw misplacement and accidental bone breaches during pedicle drilling and could be extended to further surgical applications.

Neuronal NADPH oxidase is required for neurite regeneration of Aplysia bag cell neurons.

NADPH oxidase (Nox), a major source of reactive oxygen species (ROS), is involved in neurodegeneration after injury and disease. Nox is expressed in both neuronal and non-neuronal cells and contributes to an elevated ROS level after injury. Contrary to the well-known damaging effect of Nox-derived ROS in neurodegeneration, recently a physiological role of Nox in nervous system development including neurogenesis, neuronal polarity, and axonal growth has been revealed. Here, we tested a role for neuronal Nox in neurite regeneration following mechanical transection in cultured Aplysia bag cell neurons. Using a novel hydrogen peroxide (H2 O2 )-sensing dye, 5'-(p-borophenyl)-2'-pyridylthiazole pinacol ester (BPPT), we found that H2 O2 levels are elevated in regenerating growth cones following injury. Redistribution of Nox2 and p40phox in the growth cone central domain suggests Nox2 activation after injury. Inhibiting Nox with the pan-Nox inhibitor celastrol reduced neurite regeneration rate. Pharmacological inhibition of Nox is correlated with reduced activation of Src2 tyrosine kinase and F-actin content in the growth cone. Taken together, these findings suggest that Nox-derived ROS regulate neurite regeneration following injury through Src2-mediated regulation of actin organization in Aplysia growth cones.

Atypical peripheral actin band formation via overactivation of RhoA and nonmuscle myosin II in mitofusin 2-deficient cells.

Cell spreading and migration play central roles in many physiological and pathophysiological processes. We have previously shown that MFN2 regulates the migration of human neutrophil-like cells via suppressing Rac activation. Here, we show that in mouse embryonic fibroblasts, MFN2 suppresses RhoA activation and supports cell polarization. After initial spreading, the wild-type cells polarize and migrate, whereas the Mfn2-/- cells maintain a circular shape. Increased cytosolic Ca2+ resulting from the loss of Mfn2 is directly responsible for this phenotype, which can be rescued by expressing an artificial tether to bring mitochondria and endoplasmic reticulum to close vicinity. Elevated cytosolic Ca2+ activates Ca2+/calmodulin-dependent protein kinase II, RhoA, and myosin light-chain kinase, causing an overactivation of nonmuscle myosin II, leading to a formation of a prominent F-actin ring at the cell periphery and increased cell contractility. The peripheral actin band alters cell physics and is dependent on substrate rigidity. Our results provide a novel molecular basis to understand how MFN2 regulates distinct signaling pathways in different cells and tissue environments, which is instrumental in understanding and treating MFN2-related diseases.

Factors affecting augmented reality head-mounted device performance in real OR.

PURPOSE: Over the last years, interest and efforts to implement augmented reality (AR) in orthopedic surgery through head-mounted devices (HMD) have increased. However, the majority of experiments were preclinical and within a controlled laboratory environment. The operating room (OR) is a more challenging environment with various confounding factors potentially affecting the performance of an AR-HMD. The aim of this study was to assess the performance of an AR-HMD in a real-life OR setting. METHODS: An established AR application using the HoloLens 2 HMD was tested in an OR and in a laboratory by two users. The accuracy of the hologram overlay, the time to complete the trial, the number of rejected registration attempts, the delay in live overlay of the hologram, and the number of completely failed runs were recorded. Further, different OR setting parameters (light condition, setting up partitions, movement of personnel, and anchor placement) were modified and compared. RESULTS: Time for full registration was higher with 48 s (IQR 24 s) in the OR versus 33 s (IQR 10 s) in the laboratory setting (p < 0.001). The other investigated parameters didn't differ significantly if an optimal OR setting was used. Within the OR, the strongest influence on performance of the AR-HMD was different light conditions with direct light illumination on the situs being the least favorable. CONCLUSION: AR-HMDs are affected by different OR setups. Standardization measures for better AR-HMD performance include avoiding direct light illumination on the situs, setting up partitions, and minimizing the movement of personnel.

Sonification as a reliable alternative to conventional visual surgical navigation.

Despite the undeniable advantages of image-guided surgical assistance systems in terms of accuracy, such systems have not yet fully met surgeons' needs or expectations regarding usability, time efficiency, and their integration into the surgical workflow. On the other hand, perceptual studies have shown that presenting independent but causally correlated information via multimodal feedback involving different sensory modalities can improve task performance. This article investigates an alternative method for computer-assisted surgical navigation, introduces a novel four-DOF sonification methodology for navigated pedicle screw placement, and discusses advanced solutions based on multisensory feedback. The proposed method comprises a novel four-DOF sonification solution for alignment tasks in four degrees of freedom based on frequency modulation synthesis. We compared the resulting accuracy and execution time of the proposed sonification method with visual navigation, which is currently considered the state of the art. We conducted a phantom study in which 17 surgeons executed the pedicle screw placement task in the lumbar spine, guided by either the proposed sonification-based or the traditional visual navigation method. The results demonstrated that the proposed method is as accurate as the state of the art while decreasing the surgeon's need to focus on visual navigation displays instead of the natural focus on surgical tools and targeted anatomy during task execution.

Introducing a brain-computer interface to facilitate intraoperative medical imaging control - a feasibility study.

BACKGROUND: Safe and accurate execution of surgeries to date mainly rely on preoperative plans generated based on preoperative imaging. Frequent intraoperative interaction with such patient images during the intervention is needed, which is currently a cumbersome process given that such images are generally displayed on peripheral two-dimensional (2D) monitors and controlled through interface devices that are outside the sterile filed. This study proposes a new medical image control concept based on a Brain Computer Interface (BCI) that allows for hands-free and direct image manipulation without relying on gesture recognition methods or voice commands. METHOD: A software environment was designed for displaying three-dimensional (3D) patient images onto external monitors, with the functionality of hands-free image manipulation based on the user's brain signals detected by the BCI device (i.e., visually evoked signals). In a user study, ten orthopedic surgeons completed a series of standardized image manipulation tasks to navigate and locate predefined 3D points in a Computer Tomography (CT) image using the developed interface. Accuracy was assessed as the mean error between the predefined locations (ground truth) and the navigated locations by the surgeons. All surgeons rated the performance and potential intraoperative usability in a standardized survey using a five-point Likert scale (1 = strongly disagree to 5 = strongly agree). RESULTS: When using the developed interface, the mean image control error was 15.51 mm (SD: 9.57). The user's acceptance was rated with a Likert score of 4.07 (SD: 0.96) while the overall impressions of the interface was rated as 3.77 (SD: 1.02) by the users. We observed a significant correlation between the users' overall impression and the calibration score they achieved. CONCLUSIONS: The use of the developed BCI, that allowed for a purely brain-guided medical image control, yielded promising results, and showed its potential for future intraoperative applications. The major limitation to overcome was noted as the interaction delay.

Template guided cervical pedicle screw instrumentation.

Background: Pedicle screw instrumentation of the cervical spine, although technically challenging due to the potential risk of serious neurovascular injuries, is biomechanically favorable for stabilization purposes. Patient-specific templates are increasingly used in the thoracolumbar spine with excellent accuracy. The aim of this study was to evaluate the accuracy of cervical pedicle screw placement with patient-specific templates in a clinical setting and to report the European experience so far. Methods: Multicentric, retrospectively obtained data of twelve patients who underwent dorsal instrumentation of the cervical spine with 3D-printed patient-specific templates were analyzed. Postoperative computed tomography (CT) scans were used to evaluate pedicle perforation and screw deviations between the planned and actual screw position. Furthermore, surgical time, radiation exposure, blood loss and immediate postoperative complications were analyzed. Results: A total of 86 screws were inserted, of which 82 (95.3%) were fully contained inside the pedicle. All perforations (four screws, 4.7%) were within the safe zone of 2 mm and did not result in any neurovascular complications. Overall, median deviation from planned entry point (Euclidean distance) was 1.2 mm (0.1 - 11 mm), median deviation from the planned trajectory (Euler angle) was 4.4° (0.2-71.5°), median axial and sagittal trajectory deviation from the planned trajectory were 2.5° (0 - 57.5°) and 3.3° (0 - 54.9°), respectively. Median operative time was 168 minutes (111 - 564 minutes), median blood loss was 300 ml (150 - 1300 ml) and median intraoperative fluoroscopic dose was 321.2 mGycm2 (102.4 - 825.0 mGycm2). Overall complications were one adjacent segment kyphosis, one transient C5 palsy and one wound healing disorder. Conclusion: Patient-specific 3D-printed templates provide a highly accurate option for placing cervical pedicle screws for dorsal instrumentation of the cervical spine.

Spinal decompression with patient-specific guides.

BACKGROUND CONTEXT: Patient-specific instruments (PSI) have been well established in spine surgery for pedicle screw placement. However, its utility in spinal decompression surgery is yet to be investigated. PURPOSE: The purpose of this study was to investigate the feasibility and utility of PSI in spinal decompression surgery compared with conventional freehand (FH) technique for both expert and novice surgeons. STUDY DESIGN: Human cadaver study. METHODS: Thirty-two midline decompressions were performed on 4 fresh-frozen human cadavers. An expert spine surgeon and an orthopedic resident (novice) each performed 8 FH and 8 PSI-guided decompressions. Surgical time for each decompression method was measured. Postoperative decompression area, cranial decompression extent in relation to the intervertebral disc, and lateral recess bony overhang were measured on postoperative CT-scans. In the PSI-group, the decompression area and osteotomy accuracy were evaluated. RESULTS: The surgical time was similar in both techniques, with 07:25 min (PSI) versus 06:53 min (FH) for the expert surgeon and 12:36 min (PSI) vs. 11:54 (FH) for the novice surgeon. The postoperative cranial decompression extent and the lateral recess bony overhang did not differ between both techniques and surgeons. Further, the postoperative decompression area was significantly larger with the PSI than with the FH for the novice surgeon (477 vs. 305 mm2; p=.01), but no significant difference was found between both techniques for the expert surgeon. The execution of the decompression differed from the preoperative plan in the decompression area by 5%, and the osteotomy planes had an accuracy of 1-3 mm. CONCLUSION: PSI-guided decompression is feasible and accurate with similar procedure time to the standard FH technique in a cadaver model, which warrants further investigation in vivo. In comparison to the FH technique, a more extensive decompression was achieved with PSI in the novice surgeon's hands in this study. CLINICAL SIGNIFICANCE: The PSI-guided spinal decompression technique may be a useful alternative to FH decompression in certain situations. A special potential of the PSI technique could lie in the technical aid for novice surgeons and in situations with unconventional anatomy or pathologies such as deformity or tumor. This study serves as a starting point toward PSI-guided spinal decompression, but further in vivo investigations are necessary.

3D nanomechanical mapping of subcellular and sub-nuclear structures of living cells by multi-harmonic AFM with long-tip microcantilevers.

Recent developments such as multi-harmonic Atomic Force Microscopy (AFM) techniques have enabled fast, quantitative mapping of nanomechanical properties of living cells. Due to their high spatiotemporal resolution, these methods provide new insights into changes of mechanical properties of subcellular structures due to disease or drug response. Here, we propose three new improvements to significantly improve the resolution, identification, and mechanical property quantification of sub-cellular and sub-nuclear structures using multi-harmonic AFM on living cells. First, microcantilever tips are streamlined using long-carbon tips to minimize long-range hydrodynamic interactions with the cell surface, to enhance the spatial resolution of nanomechanical maps and minimize hydrodynamic artifacts. Second, simultaneous Spinning Disk Confocal Microscopy (SDC) with live-cell fluorescent markers enables the unambiguous correlation between observed heterogeneities in nanomechanical maps with subcellular structures. Third, computational approaches are then used to estimate the mechanical properties of sub-nuclear structures. Results are demonstrated on living NIH 3T3 fibroblasts and breast cancer MDA-MB-231 cells, where properties of nucleoli, a deep intracellular structure, were assessed. The integrated approach opens the door to study the mechanobiology of sub-cellular structures during disease or drug response.

A Co-purification Method for Efficient Production and Src Kinase-mediated Phosphorylation of Aplysia Cortactin.

Cortactin is an actin-binding protein that regulates processes like cell migration, endocytosis, and tumor cell metastasis. Although cortactin is associated with actin-cytoskeletal dynamics in non-neuronal cells and cell-free systems, the exact mechanisms underlying its fundamental roles in neuronal growth cones are not fully explored. Recent reports show that Aplysia Src2 tyrosine kinase induces phosphorylation of cortactin as a mechanism to control lamellipodia protrusion and filopodia formation in cultured Aplysia bag cell neurons ( He et al., 2015 ; Ren et al., 2019 ). In order to provide in vitro evidence for Src2-mediated phosphorylation of cortactin, we developed a robust and cost-effective method for the efficient expression and purification of Aplysia cortactin and Src2 kinase that can be used for biochemical studies including phosphorylation assays. By co-purifying cortactin and Src kinase with a phosphatase (YopH) from Yersinia enterocolitica, we eliminated the problem of non-specific phosphorylation of induced proteins by bacterial kinases and also reduced costs by bypassing the need for commercial enzymatic treatments. This protocol is reproducible and can be modified to produce homogenous non-phosphorylated proteins during recombinant protein expression in Escherichia coli.

SpineDepth: A Multi-Modal Data Collection Approach for Automatic Labelling and Intraoperative Spinal Shape Reconstruction Based on RGB-D Data.

Computer aided orthopedic surgery suffers from low clinical adoption, despite increased accuracy and patient safety. This can partly be attributed to cumbersome and often radiation intensive registration methods. Emerging RGB-D sensors combined with artificial intelligence data-driven methods have the potential to streamline these procedures. However, developing such methods requires vast amount of data. To this end, a multi-modal approach that enables acquisition of large clinical data, tailored to pedicle screw placement, using RGB-D sensors and a co-calibrated high-end optical tracking system was developed. The resulting dataset comprises RGB-D recordings of pedicle screw placement along with individually tracked ground truth poses and shapes of spine levels L1-L5 from ten cadaveric specimens. Besides a detailed description of our setup, quantitative and qualitative outcome measures are provided. We found a mean target registration error of 1.5 mm. The median deviation between measured and ground truth bone surface was 2.4 mm. In addition, a surgeon rated the overall alignment based on 10% random samples as 5.8 on a scale from 1 to 6. Generation of labeled RGB-D data for orthopedic interventions with satisfactory accuracy is feasible, and its publication shall promote future development of data-driven artificial intelligence methods for fast and reliable intraoperative registration.

ROS Live Cell Imaging During Neuronal Development.

Reactive oxygen species (ROS) are well-established signaling molecules, which are important in normal development, homeostasis, and physiology. Among the different ROS, hydrogen peroxide (H2O2) is best characterized with respect to roles in cellular signaling. H2O2 has been implicated during the development in several species. For example, a transient increase in H2O2 has been detected in zebrafish embryos during the first days following fertilization. Furthermore, depleting an important cellular H2O2 source, NADPH oxidase (NOX), impairs nervous system development such as the differentiation, axonal growth, and guidance of retinal ganglion cells (RGCs) both in vivo and in vitro. Here, we describe a method for imaging intracellular H2O2 levels in cultured zebrafish neurons and whole larvae during development using the genetically encoded H2O2-specific biosensor, roGFP2-Orp1. This probe can be transiently or stably expressed in zebrafish larvae. Furthermore, the ratiometric readout diminishes the probability of detecting artifacts due to differential gene expression or volume effects. First, we demonstrate how to isolate and culture RGCs derived from zebrafish embryos that transiently express roGFP2-Orp1. Then, we use whole larvae to monitor H2O2 levels at the tissue level. The sensor has been validated by the addition of H2O2. Additionally, this methodology could be used to measure H2O2 levels in specific cell types and tissues by generating transgenic animals with tissue-specific biosensor expression. As zebrafish facilitate genetic and developmental manipulations, the approach demonstrated here could serve as a pipeline to test the role of H2O2 during neuronal and general embryonic development in vertebrates.

Pedicle subtraction osteotomy with patient-specific instruments.

BACKGROUND: Although the utility of patient-specific instruments (PSI) has been well established for complex osteotomies in orthopedic surgery, it is yet to be comparatively analyzed for complex spinal deformity correction, such as pedicle subtraction osteotomy (PSO). METHODS: Six thoracolumbar human cadavers were used to perform nine PSOs using the free-hand (FH) technique and nine with PSI (in total 18 PSOs). Osteotomy planes were planned on the basis of preoperative computed tomography (CT). A closing-wedge angle of 30° was targeted for each PSO. Postoperative CT scans were obtained to measure segmental lordosis correction and the deviation from the planned 30° correction as well as the osseous gap of posterior elements. RESULTS: The time required to perform a PSO was 18:22 (range 10:22-26:38) min and 14:14 (range 10:13-22:16) min in the PSI and FH groups, respectively (p = 0.489). The PSI group had a significantly higher lordosis gain (29°, range 23-31° vs. 21°, range 13-34°; p = 0.015). The lordosis gain was significantly more accurate with PSI (deviation angle: 1°; range 0-7°) than with the FH technique (9°; range 4-17°; p = 0.003). PSI achieved a significantly smaller residual osseous gap of the posterior elements (5 mm; range 0-9 mm) than the FH group (11 mm; range 3-27 mm; p = 0.043).With PSI, an angular difference of 3° (range 1-12°), a translational offset of 1 (range 0-6) mm at the level of the lamina, and a vertebral body entry point deviation of 1 (range 0-4) mm was achieved in the osteotomies. CONCLUSIONS: PSI-guided PSO can be a more feasible and accurate approach in achieving a planned lordosis angle than the traditional FH technique in a cadaver model. This approach further reduced osseous gaps, potentially promoting higher fusion rates in vivo.

Operator independent reliability of direct augmented reality navigated pedicle screw placement and rod bending.

BACKGROUND: AR based navigation of spine surgeries may not only provide accurate surgical execution but also operator independency by compensating for potential skill deficits. "Direct" AR-navigation, namely superposing trajectories on anatomy directly, have not been investigated regarding their accuracy and operator's dependence.Purpose of this study was to prove operator independent reliability and accuracy of both AR assisted pedicle screw navigation and AR assisted rod bending in a cadaver setting. METHODS: Two experienced spine surgeons and two biomedical engineers (laymen) performed independently from each other pedicle screw instrumentations from L1-L5 in a total of eight lumbar cadaver specimens (20 screws/operator) using a fluoroscopy-free AR based navigation method. Screw fitting rods from L1 to S2-Ala-Ileum were bent bilaterally using an AR based rod bending navigation method (4 rods/operator). Outcome measures were pedicle perforations, accuracy compared to preoperative plan, registration time, navigation time, total rod bending time and operator's satisfaction for these procedures. RESULTS: 97.5% of all screws were safely placed (<2 mm perforation), overall mean deviation from planned trajectory was 6.8±3.9°, deviation from planned entry point was 4±2.7 mm, registration time per vertebra was 2:25 min (00:56 to 10:00 min), navigation time per screw was 1:07 min (00:15 to 12:43 min) rod bending time per rod was 4:22 min (02:07 to 10:39 min), operator's satisfaction with AR based screw and rod navigation was 5.38±0.67 (1 to 6, 6 being the best rate). Comparison of surgeons and laymen revealed significant difference in navigation time (1:01 min; 00:15 to 3:00 min vs. 01:37 min; 00:23 to 12:43 min; p = 0.004, respectively) but not in pedicle perforation rate. CONCLUSIONS: Direct AR based screw and rod navigation using a surface digitization registration technique is reliable and independent of surgical experience. The accuracy of pedicle screw insertion in the lumbar spine is comparable with the current standard techniques.

Surgical Process Modeling for Open Spinal Surgeries.

Modern operating rooms are becoming increasingly advanced thanks to the emerging medical technologies and cutting-edge surgical techniques. Current surgeries are transitioning into complex processes that involve information and actions from multiple resources. When designing context-aware medical technologies for a given intervention, it is of utmost importance to have a deep understanding of the underlying surgical process. This is essential to develop technologies that can correctly address the clinical needs and can adapt to the existing workflow. Surgical Process Modeling (SPM) is a relatively recent discipline that focuses on achieving a profound understanding of the surgical workflow and providing a model that explains the elements of a given surgery as well as their sequence and hierarchy, both in quantitative and qualitative manner. To date, a significant body of work has been dedicated to the development of comprehensive SPMs for minimally invasive baroscopic and endoscopic surgeries, while such models are missing for open spinal surgeries. In this paper, we provide SPMs common open spinal interventions in orthopedics. Direct video observations of surgeries conducted in our institution were used to derive temporal and transitional information about the surgical activities. This information was later used to develop detailed SPMs that modeled different primary surgical steps and highlighted the frequency of transitions between the surgical activities made within each step. Given the recent emersion of advanced techniques that are tailored to open spinal surgeries (e.g., artificial intelligence methods for intraoperative guidance and navigation), we believe that the SPMs provided in this study can serve as the basis for further advancement of next-generation algorithms dedicated to open spinal interventions that require a profound understanding of the surgical workflow (e.g., automatic surgical activity recognition and surgical skill evaluation). Furthermore, the models provided in this study can potentially benefit the clinical community through standardization of the surgery, which is essential for surgical training.

Neuronal NADPH oxidase 2 regulates growth cone guidance downstream of slit2/robo2.

NADPH oxidases (Nox) are membrane-bound multi-subunit protein complexes producing reactive oxygen species (ROS) that regulate many cellular processes. Emerging evidence suggests that Nox-derived ROS also control neuronal development and axonal outgrowth. However, whether Nox act downstream of receptors for axonal growth and guidance cues is presently unknown. To answer this question, we cultured retinal ganglion cells (RGCs) derived from zebrafish embryos and exposed these neurons to netrin-1, slit2, and brain-derived neurotrophic factor (BDNF). To test the role of Nox in cue-mediated growth and guidance, we either pharmacologically inhibited Nox or investigated neurons from mutant fish that are deficient in Nox2. We found that slit2-mediated growth cone collapse, and axonal retraction were eliminated by Nox inhibition. Though we did not see an effect of either BDNF or netrin-1 on growth rates, growth in the presence of netrin-1 was reduced by Nox inhibition. Furthermore, attractive and repulsive growth cone turning in response to gradients of BDNF, netrin-1, and slit2, respectively, were eliminated when Nox was inhibited in vitro. ROS biosensor imaging showed that slit2 treatment increased growth cone hydrogen peroxide levels via mechanisms involving Nox2 activation. We also investigated the possible relationship between Nox2 and slit2/Robo2 signaling in vivo. astray/nox2 double heterozygote larvae exhibited decreased area of tectal innervation as compared to individual heterozygotes, suggesting both Nox2 and Robo2 are required for establishment of retinotectal connections. Our results provide evidence that Nox2 acts downstream of slit2/Robo2 by mediating growth and guidance of developing zebrafish RGC neurons.