scholarly journals Single Evaluation of Use of a Mixed Reality Headset for Intra-Procedural Image-Guidance during a Mock Laparoscopic Myomectomy on an Ex-Vivo Fibroid Model

2022 ◽  
Vol 12 (2) ◽  
pp. 563
Author(s):  
Matin Torabinia ◽  
Alexandre Caprio ◽  
Tamatha B. Fenster ◽  
Bobak Mosadegh
Keyword(s):  
African American Women ◽  
Image Guidance ◽  
Mixed Reality ◽  
Ex Vivo ◽  
Uterine Fibroids ◽  
Standard Of Care ◽  
Patient Specific ◽  
Benign Tumors ◽  
Mri Scan ◽  
Custom Made

Uterine fibroids represent the highest prevalence of benign tumors in women, with reports ranging from 4.5% to 68.6%, with a significant bias towards African American women. For uterine fibroids, a significant decision is determining whether fibroids can be successfully removed using minimally invasive (MI) techniques or their removal requires open surgery. Currently, the standard-of-care for intra-procedural visualization for myomectomies is ultrasound, which has low image quality and requires a specially trained assistant. Currently, the state-of-the-art is to obtain a pre-procedural MRI scan of the patient, which can be used for diagnosis and pre-procedural planning. Although proven incredibly useful pre-procedurally, MRI scans are not often used intra-procedurally due to the inconvenient visualization as 2D slices, which are seen on 2D monitors that do not intuitively convey the depth or orientation of the fibroids, as needed to effectively perform myomectomies. To address this limitation, herein, we present the use of a mixed reality headset (i.e., Microsoft HoloLens 2), as a tool for intra-procedural image-guidance during a mock myomectomy of an ex vivo animal uterus. In this work, we created a patient-specific holographic rendering by performing image segmentation of an MRI scan of a custom-made uterine fibroid animal model. A physician qualitatively assessed the usefulness of the renderings for fibroid localization, as compared to the same visualization on a 2D monitor. In conclusion, the use of mixed reality as an intra-procedural image guidance tool for myomectomies was perceived as a better visualization technique that could lead to improvements in MI approaches and make them accessible to patients from lower socioeconomic populations.

scholarly journals Robot-assisted Ultrasound-guided Tracking of Anatomical Structures for the Application of Focused Ultrasound

2020 ◽  
Vol 6 (3) ◽  
pp. 123-126
Author(s):  
Michael Unger ◽  
Johann Berger ◽  
Bjoern Gerold ◽  
Andreas Melzer
Keyword(s):  
Focused Ultrasound ◽  
Varicose Veins ◽  
Tracking System ◽  
Tracking Error ◽  
Uterine Fibroids ◽  
High Intensity Focused Ultrasound ◽  
Robot Assisted ◽  
Anatomical Structures ◽  
Surgical Tool ◽  
Custom Made

AbstractHigh intensity focused ultrasound is used as a surgical tool to treat completely non-invasively several diseases. Examples of clinical applications are uterine fibroids, prostate cancer, thyroid nodules, and varicose veins. Precise targeting is key for improving the treatment outcome. A method for an automated, robot-assisted tracking system was developed and evaluated. A wireless ultrasound scanner was used to acquire images of the target, in this case, a blood vessel. The active contour approach by Chan and Vese was used to segment and track while moving the scanner along the target structure with a collaborative robotic arm. The performance was assessed using a custom made Agar phantom. The mean tracking error, which is defined as the remaining distance of the lesion to the images’ centre line, was 0.27 mm ± 0.18 mm.

scholarly journals Augmented Reality, Mixed Reality, and Hybrid Approach in Healthcare Simulation: A Systematic Review

2021 ◽  
Vol 11 (5) ◽  
pp. 2338
Author(s):  
Rosanna Maria Viglialoro ◽  
Sara Condino ◽  
Giuseppe Turini ◽  
Marina Carbone ◽  
Vincenzo Ferrari ◽  
...  
Keyword(s):  
Augmented Reality ◽  
Mixed Reality ◽  
Ethical Issues ◽  
Medical Training ◽  
Hybrid Approach ◽  
Dental Surgery ◽  
Feasibility Assessment ◽  
Hybrid Approaches ◽  
Custom Made ◽  
Improved Performance

Simulation-based medical training is considered an effective tool to acquire/refine technical skills, mitigating the ethical issues of Halsted’s model. This review aims at evaluating the literature on medical simulation techniques based on augmented reality (AR), mixed reality (MR), and hybrid approaches. The research identified 23 articles that meet the inclusion criteria: 43% combine two approaches (MR and hybrid), 22% combine all three, 26% employ only the hybrid approach, and 9% apply only the MR approach. Among the studies reviewed, 22% use commercial simulators, whereas 78% describe custom-made simulators. Each simulator is classified according to its target clinical application: training of surgical tasks (e.g., specific tasks for training in neurosurgery, abdominal surgery, orthopedic surgery, dental surgery, otorhinolaryngological surgery, or also generic tasks such as palpation) and education in medicine (e.g., anatomy learning). Additionally, the review assesses the complexity, reusability, and realism of the physical replicas, as well as the portability of the simulators. Finally, we describe whether and how the simulators have been validated. The review highlights that most of the studies do not have a significant sample size and that they include only a feasibility assessment and preliminary validation; thus, further research is needed to validate existing simulators and to verify whether improvements in performance on a simulated scenario translate into improved performance on real patients.

scholarly journals Novel strain-level resolution of Crohn’s disease mucosa-associated microbiota via an ex vivo combination of microbe culture and metagenomic sequencing

2021 ◽  
Author(s):  
J. J. Teh ◽  
E. M. Berendsen ◽  
E. C. Hoedt ◽  
S. Kang ◽  
J. Zhang ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Ex Vivo ◽  
Taxonomic Composition ◽  
Strain Level ◽  
Patient Specific ◽  
Rrna Gene ◽  
Metagenomic Sequencing ◽  
Functional Characterisation ◽  
Bacterial Lineages

AbstractThe mucosa-associated microbiota is widely recognized as a potential trigger for Crohn’s disease pathophysiology but remains largely uncharacterised beyond its taxonomic composition. Unlike stool microbiota, the functional characterisation of these communities using current DNA/RNA sequencing approaches remains constrained by the relatively small microbial density on tissue, and the overwhelming amount of human DNA recovered during sample preparation. Here, we have used a novel ex vivo approach that combines microbe culture from anaerobically preserved tissue with metagenome sequencing (MC-MGS) to reveal patient-specific and strain-level differences among these communities in post-operative Crohn’s disease patients. The 16 S rRNA gene amplicon profiles showed these cultures provide a representative and holistic representation of the mucosa-associated microbiota, and MC-MGS produced both high quality metagenome-assembled genomes of recovered novel bacterial lineages. The MC-MGS approach also produced a strain-level resolution of key Enterobacteriacea and their associated virulence factors and revealed that urease activity underpins a key and diverse metabolic guild in these communities, which was confirmed by culture-based studies with axenic cultures. Collectively, these findings using MC-MGS show that the Crohn’s disease mucosa-associated microbiota possesses taxonomic and functional attributes that are highly individualistic, borne at least in part by novel bacterial lineages not readily isolated or characterised from stool samples using current sequencing approaches.

scholarly journals An Innovative and Cost-Advantage CAD Solution for Cubitus Varus Surgical Planning in Children

2021 ◽  
Vol 11 (9) ◽  
pp. 4057
Author(s):  
Leonardo Frizziero ◽  
Gian Maria Santi ◽  
Christian Leon-Cardenas ◽  
Giampiero Donnici ◽  
Alfredo Liverani ◽  
...  
Keyword(s):  
Computer Aided Design ◽  
Low Cost ◽  
Cost Effective ◽  
Varus Deformity ◽  
Patient Specific ◽  
Cubitus Varus ◽  
Surgical Guide ◽  
Traditional Procedure ◽  
Custom Made ◽  
Patient Specific Instruments

The study of CAD (computer aided design) modeling, design and manufacturing techniques has undergone a rapid growth over the past decades. In medicine, this development mainly concerned the dental and maxillofacial sectors. Significant progress has also been made in orthopedics with pre-operative CAD simulations, printing of bone models and production of patient-specific instruments. However, the traditional procedure that formulates the surgical plan based exclusively on two-dimensional images and interventions performed without the aid of specific instruments for the patient and is currently the most used surgical technique. The production of custom-made tools for the patient, in fact, is often expensive and its use is limited to a few hospitals. The purpose of this study is to show an innovative and cost-effective procedure aimed at prototyping a custom-made surgical guide for address the cubitus varus deformity on a pediatric patient. The cutting guides were obtained through an additive manufacturing process that starts from the 3D digital model of the patient’s bone and allows to design specific models using Creo Parametric. The result is a tool that adheres perfectly to the patient’s bone and guides the surgeon during the osteotomy procedure. The low cost of the methodology described makes it worth noticing by any health institution.

scholarly journals Generation of vascular chimerism within donor organs

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shahar Cohen ◽  
Shirly Partouche ◽  
Michael Gurevich ◽  
Vladimir Tennak ◽  
Vadym Mezhybovsky ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Patient Specific ◽  
Machine Perfusion ◽  
Organ Perfusion ◽  
Perfusion Process ◽  
Hind Limbs ◽  
Porcine Organs ◽  
Immunological Barrier

AbstractWhole organ perfusion decellularization has been proposed as a promising method to generate non-immunogenic organs from allogeneic and xenogeneic donors. However, the ability to recellularize organ scaffolds with multiple patient-specific cells in a spatially controlled manner remains challenging. Here, we propose that replacing donor endothelial cells alone, while keeping the rest of the organ viable and functional, is more technically feasible, and may offer a significant shortcut in the efforts to engineer transplantable organs. Vascular decellularization was achieved ex vivo, under controlled machine perfusion conditions, in various rat and porcine organs, including the kidneys, liver, lungs, heart, aorta, hind limbs, and pancreas. In addition, vascular decellularization of selected organs was performed in situ, within the donor body, achieving better control over the perfusion process. Human placenta-derived endothelial progenitor cells (EPCs) were used as immunologically-acceptable human cells to repopulate the luminal surface of de-endothelialized aorta (in vitro), kidneys, lungs and hind limbs (ex vivo). This study provides evidence that artificially generating vascular chimerism is feasible and could potentially pave the way for crossing the immunological barrier to xenotransplantation, as well as reducing the immunological burden of allogeneic grafts.

scholarly journals Extra-gastric expression of the proton pump H+/K+-ATPase in the gills and kidney of the teleost Oreochromis niloticus

2020 ◽  
Vol 223 (16) ◽  
pp. jeb214890
Author(s):  
Ebtesam Ali Barnawi ◽  
Justine E. Doherty ◽  
Patrícia Gomes Ferreira ◽  
Jonathan M. Wilson
Keyword(s):  
Oreochromis Niloticus ◽  
Cellular Localization ◽  
Ex Vivo ◽  
Uptake Inhibition ◽  
Custom Made ◽  
Potassium Regulation ◽  
Immunohistochemical Techniques ◽  
Collecting Tubules ◽  
First Time

ABSTRACTPotassium regulation is essential for the proper functioning of excitable tissues in vertebrates. The H+/K+-ATPase (HKA), which is composed of the HKα1 (gene: atp4a) and HKβ (gene: atp4b) subunits, has an established role in potassium and acid–base regulation in mammals and is well known for its role in gastric acidification. However, the role of HKA in extra-gastric organs such as the gill and kidney is less clear, especially in fishes. In the present study in Nile tilapia, Oreochromis niloticus, uptake of the K+ surrogate flux marker rubidium (Rb+) was demonstrated in vivo; however, this uptake was not inhibited with omeprazole, a potent inhibitor of the gastric HKA. This contrasts with gill and kidney ex vivo preparations, where tissue Rb+ uptake was significantly inhibited by omeprazole and SCH28080, another gastric HKA inhibitor. The cellular localization of this pump in both the gill and kidney was demonstrated using immunohistochemical techniques with custom-made antibodies specific for Atp4a and Atp4b. Antibodies against the two subunits showed the same apical ionocyte distribution pattern in the gill and collecting tubules/ducts in the kidney. Atp4a antibody specificity was confirmed by western blotting. RT-PCT was used to confirm the expression of both subunits in the gill and kidney. Taken together, these results indicate for the first time K+ (Rb+) uptake in O. niloticus and that HKA is implicated, as shown through the ex vivo uptake inhibition by omeprazole and SCH28080, verifying a role for HKA in K+ absorption in the gill's ionocytes and collecting tubule/duct segments of the kidney.

Abdominal Aortic Aneurysm: From Clinical Imaging to Realistic Replicas

2013 ◽  
Vol 136 (1) ◽  
Author(s):  
Sergio Ruiz de Galarreta ◽  
Aitor Cazón ◽  
Raúl Antón ◽  
Ender A. Finol
Keyword(s):  
Wall Thickness ◽  
Physiological Stress ◽  
Ex Vivo ◽  
Casting Process ◽  
Aortic Aneurysms ◽  
Optical Methods ◽  
Patient Specific ◽  
Uniaxial Tensile ◽  
Element Analysis ◽  
Abdominal Aortic

The goal of this work is to develop a framework for manufacturing nonuniform wall thickness replicas of abdominal aortic aneurysms (AAAs). The methodology was based on the use of computed tomography (CT) images for virtual modeling, additive manufacturing for the initial physical replica, and a vacuum casting process and range of polyurethane resins for the final rubberlike phantom. The average wall thickness of the resulting AAA phantom was compared with the average thickness of the corresponding patient-specific virtual model, obtaining an average dimensional mismatch of 180 μm (11.14%). The material characterization of the artery was determined from uniaxial tensile tests as various combinations of polyurethane resins were chosen due to their similarity with ex vivo AAA mechanical behavior in the physiological stress configuration. The proposed methodology yields AAA phantoms with nonuniform wall thickness using a fast and low-cost process. These replicas may be used in benchtop experiments to validate deformations obtained with numerical simulations using finite element analysis, or to validate optical methods developed to image ex vivo arterial deformations during pressure-inflation testing.

scholarly journals 543 Sensitive quantification and tracking of the active components of a Clonal Neoantigen T cell (cNeT) therapy: From manufacture to peripheral circulation

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A572-A572
Author(s):  
Samra Turajlic ◽  
Mariam Jamal-Hanjani ◽  
Andrew Furness ◽  
Ruth Plummer ◽  
Judith Cave ◽  
...  
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
Active Sites ◽  
Active Component ◽  
Ex Vivo ◽  
Immune Monitoring ◽  
Patient Specific ◽  
Active Components ◽  
Link Type ◽  
The Uk

BackgroundEx-vivo expanded tumour infiltrating lymphocytes (TIL) show promise in delivering durable responses among several solid tumour indications. However, characterising, quantifying and tracking the active component of TIL therapy remains challenging as the expansion process does not distinguish between tumour reactive and bystander T-cells. Achilles Therapeutics has developed ATL001, a patient-specific TIL-based product, manufactured using the VELOS™ process that specifically targets clonal neoantigens present in all tumour cells within a patient. Two Phase I/IIa clinical trials of ATL001 are ongoing in patients with advanced Non-Small Cell Lung Cancer, CHIRON (NCT04032847), and metastatic or recurrent melanoma, THETIS (NCT03997474). Extensive product characterisation and immune-monitoring are performed through Achilles’ manufacturing and translational science programme. This enables precise quantification and characterisation of the active component of this therapy – Clonal Neoantigen T cells (cNeT) – during manufacture and following patient administration, offering unique insight into the mechanism of action of ATL001 and aiding the development of next generation processes.MethodsATL001 was manufactured using procured tumour and matched whole blood from 8 patients enrolled in the THETIS (n=5) and CHIRON (n=3) clinical trials. Following administration of ATL001, peripheral blood samples were collected up to week 6. The active component of the product was detected via re-stimulation with clonal neoantigen peptide pools and evaluation of IFN-γ and/or TNF-α production. Deconvolution of individual reactivities was achieved via ELISPOT assays. Immune reconstitution was evaluated by flow cytometry. cNeT expansion was evaluated by restimulation of isolated PBMCs with peptide pools and individual peptide reactivities (ELISPOT).ResultsThe median age was 57 (range 30 – 71) and 6/8 patients were male. The median number of previous lines of systemic anti-cancer treatment at the time of ATL001 dosing was 2.5 (range 1 – 5). Proportion of cNeT in manufactured products ranged from 0.20% - 77.43% (mean 26.78%) and unique single peptide reactivities were observed in 7 of 8 products (range 0 – 28, mean 8.6). Post-dosing, cNeTs were detected in 5/8 patients and cNeT expansion was observed in 3/5 patients.ConclusionsThese data underscore our ability to sensitively detect, quantify and track the patient-specific cNeT component of ATL001 – during manufacture and post dosing. As the dataset matures, these metrics of detection and expansion will be correlated with product, clinical and genomic characteristics to determine variables associated with peripheral cNeT dynamics and clinical response.ReferencesNCT04032847, NCT03997474Ethics ApprovalThe first 8 patients described have all been located within the UK and both trials (CHIRON and THETIS) have been approved by the UK MHRA (among other international bodies, e.g FDA). Additionally, these trials have been approved by local ethics boards at active sites within the UK. Patient‘s are fully informed by provided materials and investigators prior to consenting to enrol into either ATL001 trial.

scholarly journals 248 Empiric profiling of peripheral T cell recall responses to tumor mutanomes versus in silico predictions in NSCLC patients undergoing pembrolizumab treatment ± chemotherapy

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A268-A268
Author(s):  
Madison Milaszewski ◽  
James Loizeaux ◽  
Emily Tjon ◽  
Crystal Cabral ◽  
Tulin Dadali ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Combination Therapy ◽  
In Silico ◽  
Ex Vivo ◽  
T Cell Responses ◽  
Patient Specific ◽  
In Silico Prediction ◽  
Cell Responses ◽  
In Silico Predictions

BackgroundEffective immune checkpoint blockade (ICB) treatment is dependent on T-cell recognition of patient-specific mutations (neoantigens). Empirical identification of neoantigens ex vivo has revealed shortcomings of in silico predictions.1 To better understand the impact of ICB treatment on T cell responses and differences between in silico and in vitro methods, neoantigen-specific T cell responses were evaluated in patients with non-small cell lung cancer undergoing first-line therapy with pembrolizumab ± chemotherapy.MethodsTumor and whole blood samples were collected from 14 patients prior to and after immunotherapy; seven each in monotherapy and combination therapy cohorts. The ex vivo ATLAS™ platform was used to profile neoantigen-specific T-cell responses. Patient-specific tumor mutations identified by next-generation sequencing (NGS) were expressed individually as ATLAS clones, processed patient-specific autologous antigen presenting cells, and presented to their T cells in vitro. ATLAS-verified antigens were compared with epitope predictions made using algorithms.ResultsOn average, 150 (range 37–339) non-synonymous mutations were identified. Pre-treatment, ATLAS identified T cell responses to a median of 15% (9–25%) of mutations, with nearly equal proportions of neoantigens (8%, 5–15%) and Inhibigens™, targets of suppressive T cell responses (8%, 3–13%). The combination therapy cohort had more confirmed neoantigens (46, 20–103) than the monotherapy cohort (7, 6–79). After treatment, the median ratio of CD4:CD8 T cells doubled in the monotherapy but not combination cohort (1.2 to 2.4 v. 1.6 to 1.3). Upon non-specific stimulation, T cells from patients on combination therapy expanded poorly relative to monotherapy (24 v. 65-fold, p = 0.014); no significant differences were observed pre-treatment (22 v. 18-fold, p = 0.1578). Post-treatment, the median number of CD8 neoantigens increased in the combination therapy cohort (11 to 15) but in monotherapy were mostly unchanged (6 to 7). Across timepoints, 36% of ATLAS-identified responses overlapped. In silico analysis resulted in 1,895 predicted epitopes among 961 total mutations; among those, 30% were confirmed with ATLAS, although nearly half were Inhibigens, which could not be predicted. Moreover, 50% of confirmed neoantigens were missed by in silico prediction.ConclusionsMonotherapy and combination therapy had differential effects on CD4:CD8 T cell ratios and their non-specific expansion. A greater proportion of neoantigens was identified than previously reported in studies employing in silico predictions prior to empirical verification.2 Overlap between confirmed antigens and in silico prediction was observed, but in silico prediction continued to have a large false negative rate and could not characterize Inhibigens.AcknowledgementsWe would like to acknowledge and thank the patients and their families for participating in this study.ReferencesLam H, McNeil LK, Starobinets H, DeVault VL, Cohen RB, Twardowski P, Johnson ML, Gillison ML, Stein MN, Vaishampayan UN, DeCillis AP, Foti JJ, Vemulapalli V, Tjon E, Ferber K, DeOliveira DB, Broom W, Agnihotri P, Jaffee EM, Wong KK, Drake CG, Carroll PM, Davis TA, Flechtner JB. An empirical antigen selection method identifies neoantigens that either elicit broad antitumor T-cell responses or drive tumor growth. Cancer Discov 2021;11(3):696–713. doi: 10.1158/2159- 8290.CD-20-0377. Epub 2021 January 27. PMID: 33504579. Rosenberg SA. Immersion in the search for effective cancer immunotherapies. Mol Med 27,63(2021). https://doi.org/10.1186/s10020-021-00321-3

scholarly journals Early Outcomes of Patient-Specific Modular Cones for Substitution of Methaphysial and Diaphysial Bone Defects in Revision Knee Arthroplasty

2019 ◽  
Vol 25 (2) ◽  
pp. 9-18 ◽  
Author(s):  
A. A. Cherny ◽  
A. N. Kovalenko ◽  
S. S. Bilyk ◽  
A. O. Denisov ◽  
A. V. Kazemirskiy ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Scoring Systems ◽  
Bone Defects ◽  
Patient Specific ◽  
Implant Fixation ◽  
Diaphyseal Bone ◽  
Custom Made ◽  
The Stability ◽  
Valid Solution

The aim of this study was the assessment of early outcomes of patient-specific three-dimensional titanium cones with specified porosity parameters to compensate for extensive metaphysical-diaphyseal bone defects in RTKA.Materials and Methods. Since 2017 till 2019 30 patient-specific titanium cones (12 femoral and 18 tibial) implanted during 26 RTKAS. Clinical outcomes evaluated using KSS, WOMAC and fjS-12 scoring systems on average 10 (2–18) months after surgery. At the same time the stability of implant fixation analyzed using frontal, lateral and axial knee roentgenograms.Results. During all procedures there were no technical difficulties in positioning and implantation of custom-made titanium cones. At the time of preparation of the publication, none of the patients had indications for further surgical intervention, as well as intra- and postoperative complications. Six months after surgery all scores improved significantly: KSS from 23 (2–42, SD 19.96) to 66.5 (62–78, SD 7.68), WOMAC from 59 (56–96, SD 28.31) to 32.25 (19–46, SD 11.76), the index FJS-12 was 29.16 points (0–68.75, SD 30.19). The average scores continued to improve up to 18 months: KSS — 97.5 (88–108, SD 9.14), WOMAC — 16.5 (9–24, SD 6.45), FJS-12 — 45.85 (25–75, SD 22.03). No radiolucent lines were noticed during this period of observation.Conclusion. The original additive technology of designing and producing patient-specific titanium cones for compensation of extensive metaphyseal-diaphyseal bone defects in RTKA is a valid solution at least in the short term. A longer follow-up period is required to assess its medium-and long-term reliability compared to existing alternative surgical solutions.

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