Live Animal Models Research Articles

WITHDRAWN

TYPE: Abstract TOPIC: Biotechnology PURPOSE: Development of diaphragmatic paralysis/paresis may lead to dyspnea, respiratory distress, and even respiratory failure.In prolonged cases, the diaphragm atrophies, which renders surgical palliation or pacemaker ineffective.To address this pervasive issue, we have designed and pilot-tested an artificial diaphragm. METHODS: We embedded nano-electromagnetic coils in an elastic polymeric non-immunogenic resin plate.Two plates were superimposed: the top plate is superiorly convex and mobile; the lower plate is flat, and the edges are sutured to adjacent tissues.The device is inserted into the deficiency left by the paralyzed diaphragm.Passing current through the coils, activates the magnetic fields of the plates: if they are charged opposingly, the top mobile plate moves towards the inferior fix plate, pulling the convex portion down, increasing the lung volume(i.e., inspiration).When the currents are reversed (similar magnetic fields), the plates repel each other: the convex plate moves upward, compressing the lung(i.e., expiration).This two-plate package is connected to and controlled by a rechargeable microchip and synchronized with stimulations of the phrenic nerve, to adjust with the respiration rate. RESULTS: We built and surgically affixed the artificial diaphragm double-set to the resected diaphragm of a sheep cadaver model.The sheep was intubated and attached to a mechanical ventilator, set on spontaneous (CPAP) mode with zero pressure support or PEEP.The diaphragm-model generated volumes of up to 850 ML/breath, with MIP=18cmH2O and MEP=14cmH2O. CONCLUSIONS: This device was pilot tested to mimic the inspiratory/expiratory motions of the diaphragm when tested on a cadaveric animal model.It must now be tested on a live animal model. CLINICAL IMPLICATIONS: Assist ventilation, improving patients' QOL. DISCLOSURE: Nothing to declare. KEYWORD: diaphragmatic assist device

The effectiveness of a live animal model in a laparoscopic partial nephrectomy for renal cancer training – a survey study

Introduction. A laparoscopic partial nephrectomy for kidney cancer is a technically demanding procedure. Among many training approaches a live animal model is considered to be one of the most promising. Material and methods. During nine editions of a two day live animal laparoscopy course, nine urologists took part in exercises aimed at mastering a partial nephrectomy for kidney cancer. After finishing the courses, an online survey was sent to all participants in order to evaluate the practical implications of the training on a live animal model. Results. Seven participants responded to the survey. Two attended one course, two attended two courses and three attended more than twice. The number of partial nephrectomies performed during the course ranged from 0 to 20. All participants declared good understanding of the knot formation and stated that they use their obtained knowledge on a regular basis. Six of seven participants would like to repeat the course. All participants would recommend this course to colleagues with no partial nephrectomy experience. Discussion. A live animal laparoscopy course for experienced urologists can yield positive results in terms of techni­cal abilities and the implementation of minimally invasive techniques into clinical practice. It seems that this type of advanced simulation is better for clinicians than residents. The high level of satisfaction and willingness to repeat the course seem to back up this hypothesis. Conclusions. The live animal model seems to be an interesting tool in advanced training in minimally invasive partial nephrectomy for kidney cancer.

Efficient capture of circulating tumor cells with low molecular weight folate receptor-specific ligands

Retrieval of circulating tumor cells (CTC) has proven valuable for assessing a patient's cancer burden, evaluating response to therapy, and analyzing which drug might treat a cancer best. Although most isolation methods retrieve CTCs based on size, shape, or capture by tumor-specific antibodies, we explore here the use of small molecule tumor-specific ligands linked to magnetic beads for CTC capture. We have designed folic acid-biotin conjugates with different linkers for the capture of folate receptor (FR) + tumor cells spiked into whole blood, and application of the same technology to isolate FR + CTCs from the peripheral blood of both tumor-bearing mice and non-small cell lung patients. We demonstrate that folic acid linked via a rigid linker to a flexible PEG spacer that is in turn tethered to a magnetic bead enables optimal CTC retrieval, reaching nearly 100% capture when 100 cancer cells are spiked into 1 mL of aqueous buffer and ~ 90% capture when the same quantity of cells is diluted into whole blood. In a live animal model, the same methodology is shown to efficiently retrieve CTCs from tumor-bearing mice, yielding cancer cell counts that are proportional to total tumor burden. More importantly, the same method is shown to collect ~ 29 CTCs/8 mL peripheral blood from patients with non-small cell lung cancer. Since the ligand-presentation strategy optimized here should also prove useful in targeting other nanoparticles to other cells, the methods described below should have general applicability in the design of nanoparticles for cell-specific targeting.

Cannula cricothyroidotomy in the impalpable neck: An observational study of simulated 'can't intubate, can't oxygenate' scenarios by teams following a cannula-first algorithm in live anaesthetised pigs.

Live animal models can be used to train anaesthetists to perform emergency front-of-neck-access. Cannula cricothyroidotomy success reported in previous wet lab studies contradicts human clinical data. This prospective, observational study reports success of a cannula-first 'can't intubate, can't oxygenate' algorithm for impalpable anatomy during high fidelity team simulations using live, anaesthetised pigs.Forty-two trained anaesthesia teams were instructed to follow the Royal Perth Hospital can't intubate, can't oxygenate algorithm to re-oxygenate a desaturating pig with impalpable neck anatomy (mean (standard deviation, SD) 16.2 (3.5) kg); mean (SD) tracheal internal diameter 11 (1.4) mm. Teams were informed that failure would prompt veterinary-led euthanasia.All teams performed percutaneous cannula cricothyroidotomy as the initial technique, with a median (interquartile range, IQR (range)) start time of 42 (35-50 (24-93)) s. First-pass percutaneous cannula success was 29% to both insufflate tracheal oxygen and re-oxygenate. Insufflation success improved with repeated percutaneous attempts (up to three), but prolonged hypoxia time increasingly necessitated euthanasia (insufflation 57%; re-oxygenation 48%). First, second and third percutaneous attempts achieved insufflation at median (IQR (range)) 74 (64-91 (46-110)) s, 111 (95-136 (79-150)) s and 141 (127-159 (122-179)) s, respectively. Eighteen teams failed with percutaneous cannulae and performed scalpel techniques, predominantly dissection cannulation (n = 17) which achieved insufflation in all cases (insufflation 100%; re-oxygenation 47%). Scalpel attempts were started at median (IQR (range)) 142 (133-218 (97-293)) s and achieved insufflation at 232 (205-303 (152-344)) s.While percutaneous cannula cricothyroidotomy could rapidly re-oxygenate, the success rate was low and teams repeated attempts beyond the recommended 60 s time frame, delaying transition to the more successful dissection cannula technique. We recommend this 'cannula-first' can't intubate, can't oxygenate algorithm adopts a 'single best effort' strategy for percutaneous cannula, with failure prompting a scalpel technique.

Development and future promise of salivary gland organoids and salivary gland tumor organoids

Salivary glands are important organs in the oral and maxillofacial region. Environment and genetic factors may cause salivary gland tumors or non-neoplastic diseases, but the mechanisms of those diseases are still unclear. One of the important reasons is the short of researching media and model. As a new technique and research model, organoids have been widely used in the research of various diseases. Organoid culture plays a bridging role between two-dimensional cell culture and living animal models, and it is also the most promising translational research model that could connect the clinical research to basic research. This review will discuss the recent development of organoid techniques in the culture of normal salivary glands and salivary gland tumors, also their applications and challenges in tissue engineering, etiological research, and tumor therapy.

Molecular Spatiomics by Proximity Labeling.

ConspectusProximity labeling can be defined as an enzymatic “in-cell” chemical reaction that catalyzes the proximity-dependent modification of biomolecules in live cells. Since the modified proteins can be isolated and identified via mass spectrometry, this method has been successfully utilized for the characterization of local proteomes such as the sub-mitochondrial proteome and the proteome at membrane contact sites, or spatiotemporal interactome information in live cells, which are not “accessible” via conventional methods. Currently, proximity labeling techniques can be applied not only for local proteome mapping but also for profiling local RNA and DNA, in addition to showing great potential for elucidating spatial cell–cell interaction networks in live animal models. We believe that proximity labeling has emerged as an essential tool in “spatiomics,” that is, for the extraction of spatially distributed biological information in a cell or organism.Proximity labeling is a multidisciplinary chemical technique. For a decade, we and other groups have engineered it for multiple applications based on the modulation of enzyme chemistry, chemical probe design, and mass analysis techniques that enable superior mapping results. The technique has been adopted in biology and chemistry. This “in-cell” reaction has been widely adopted by biologists who modified it into an in vivo reaction in animal models. In our laboratory, we conducted in vivo proximity labeling reactions in mouse models and could successfully obtain the liver-specific secretome and muscle-specific mitochondrial matrix proteome. We expect that proximity reaction can further contribute to revealing tissue-specific localized molecular information in live animal models.Simultaneously, chemists have also adopted the concept and employed chemical “photocatalysts” as artificial enzymes to develop new proximity labeling reactions. Under light activation, photocatalysts can convert the precursor molecules to the reactive species via electron transfer or energy transfer and the reactive molecules can react with proximal biomolecules within a definite lifetime in an aqueous solution. To identify the modified biomolecules by proximity labeling, the modified biomolecules should be enriched after lysis and sequenced using sequencing tools. In this analysis step, the direct detection of modified residue(s) on the modified proteins or nucleic acids can be the proof of their labeling event by proximal enzymes or catalysts in the cell. In this Account, we introduce the basic concept of proximity labeling and the multidirectional advances in the development of this method. We believe that this Account may facilitate further utilization and modification of the method in both biological and chemical research communities, thereby revealing unknown spatially distributed molecular or cellular information or spatiome.

Effect of Breathing on UWB Propagation Characteristics for Ingestible and Implantable Devices

Wireless in-body devices are those in which a medical sensor is introduced&#x2013;implanted or ingested&#x2013; inside the human body and communicates with a remote node. Some in-body applications demand high data rates, so ultrawideband (UWB) spectrum has been proposed as a good candidate because of its large bandwidth available. Besides, breathing can lead to internal movement of the torso and consequently, of devices installed in this area. Thus, the radio channel performance can be affected by such movement leading to a malfunction of the radio interface of the medical device. This work aims at analyzing the effect of breathing on the propagation channel by means of <i>in vivo</i> measurements in living animal models. Continuous wave (CW) measurements have been carried out for five different frequencies in the lower part of the UWB band, and the effects of breathing on the relative received power (module and phase) are analyzed and discussed.

SPECT imaging properties of the CdTe-Timepix3 detector used in a new prototype FullSPECT 3D multimodal preclinical imaging system: Comparison with scintillation gamma camera

Small animal SPECT imaging represents a fast-evolving method for a noninvasive molecular imaging of metabolism, diseases, or malfunctions in live animal models. Preclinical imaging is important for translational research related to development and testing of new tracers, diagnostic and therapeutic methods for clinical application, and helps also in basic biological research. The small animal imaging requires better spatial resolution compared to human imaging. The improvement on the detector side should be implemented because the currently used scintillation gamma cameras are now touching their limits. The main goal of this work aims on introduction of a new concept of our prototype system (FullSPECT 3D) and comparison of the performance of its hybrid semiconductor Timepix3 based detector, and standard scintillation gamma camera in a commercially available device (Albira Preclinical Imaging System) for SPECT imaging on phantom and animal model. We compared both detector types on widely used 99mTc-HDP (for bone scan), and 125I labeled antibody biodistribution assays. The images taken with a single Timepix3 based detector were comparable and in some parameters exceeded standard detectors under similar geometry in 2D projections. The differences in 3D reconstructed images were not calculated because of the huge difference in the reconstruction algorithms, nevertheless the 3D images are shown as well. The future SPECT systems could benefit from the speed, energy resolution and size of Timepix3 based detectors and open the way to construction of very fast multimodal imagers requiring less ionizing radiation delivered to the patient.

Ventricular Infusion and Nanoprobes Identify Cerebrospinal Fluid and Glymphatic Circulation in Human Nerves.

Background:Growing evidence suggests that cerebrospinal fluid circulates in human nerves. Several conditions encountered by the plastic surgeon may be related to dysregulation of this system, including nerve transection, stretch injuries, and peripheral neuropathy. The purpose of this study was to show how ventricular infusion and nanoprobes identify CSF and glymphatic circulation in neural sheaths of human nerves.Methods:The technique of ventricular infusion using buffered saline was developed in 2017. The technique was used in a series of eight fresh cadavers before dissection of the median nerve, and combined with fluorescent imaging and nanoprobe injections in selected specimens.Results:Eight cadaver specimens underwent ventricular infusion. There were six female and two male specimens, ages 46–97 (mean 76.6). Ventricular cannulation was performed successfully using coordinates 2 cm anterior to coronal suture and 2.5 cm lateral to sagittal suture. Depth of cannulation ranged from 44 to 56 mm (mean 49.7). Ventricular saline infusion complemented by nanoprobe injection suggests CSF flows in neural sheaths, including pia meninges, epineurial channels, perineurium, and myelin sheaths (neurolemma).Conclusions:Ventricular infusion and nanoprobes identify CSF flow in neural sheaths of human nerves. CSF flow in nerves is an open circulatory system that occurs via channels, intracellular flow, and cell-to-cell transport associated with glial cells. Neural sheaths, including neurolemma, may participate in glucose and solute transport to axons. These techniques may be used in anatomic dissection and live animal models, and have been extended to the central nervous system to identify direct ventricle-to-pia meninges CSF pathways.

Surgical Training for Transanal Total Mesorectal Excision in a Live Animal Model: A Preliminary Experience.

Background: In this preliminary experience, the feasibility and effectiveness of surgical training with an animal model for transanal total mesorectal excision (TaTME) were evaluated. Methods: The training was conducted in two experimental animal laboratories in Italy authorized by the Italian Ministry of Health, using female Danish Landrace pigs under the supervision of surgeons with extensive experience in TaTME, animal laboratory training and cadaver laboratory training. The procedure was divided into separate steps, and all the participants were guided step-by-step throughout the entirety of the procedure. Results: During all the editions of the animal laboratory, all the procedures were completed with no major damage to the anatomical structures or intraoperative death of the animals. Live animal tissue is very similar to human tissue, helping trainees improve their tactile feedback. The bleeding effect improved the value of the training and taught the participants how to address this complication. The lack of mesorectal tissue in pigs compared with humans was the main difference. Animal laboratories should not be considered alternatives to cadaver laboratories but as complementary training activities due to their effectiveness and lower costs. Conclusions: Surgical training in animal models for TaTME seems to be effective and could be an opportunity to improve training alongside the use of a cadaver laboratory and proctoring.

Transfer of virtual reality endoscopy training to live animal colonoscopy: a randomized control trial of proficiency vs. repetition-based training.

BackgroundLow first-time pass rates of the Fundamentals of Endoscopic Surgery (FES) exam stimulated development of virtual reality (VR) simulation curricula for test preparation. This study evaluates the transfer of VR endoscopy training to live porcine endoscopy performance and compares the relative effectiveness of a proficiency-based vs repetition-based VR training curriculum.MethodsNovice endoscopists completed pretesting including the FES manual skills examination and Global Assessment of GI Endoscopic Skills (GAGES) assessment of porcine upper and lower endoscopy. Participants were randomly assigned one of two curricula: proficiency-based or repetition-based. Following curriculum completion, participants post-tested via repeat FES examination and GAGES porcine endoscopy assessments. The two cohorts pre-to-post-test differences were compared using ANCOVA.ResultsTwenty-two residents completed the curricula. There were no differences in demographics or clinical endoscopy experience between the groups. The repetition group spent significantly more time on the simulator (repetition: 242.2 min, SD 48.6) compared to the proficiency group (proficiency: 170.0 min, SD 66.3; p = 0.013). There was a significant improvement in porcine endoscopy (pre: 10.6, SD 2.8, post: 16.6, SD 3.4; p < 0.001) and colonoscopy (pre: 10.4, SD 2.7, post: 16.4, SD 4.2; p < 0.001) GAGES scores as well as FES manual skills performance (pre: 270.9, SD 105.5, post: 477.4, SD 68.9; p < 0.001) for the total cohort. There was no difference in post-test GAGES performance or FES manual skills exam performance between the two groups. Both the proficiency and repetition group had a 100% pass rate on the FES skills exam following VR curriculum completion.ConclusionA VR endoscopy curriculum translates to improved performance in upper and lower endoscopy in a live animal model. VR curricula type did not affect FES manual skills examination or live colonoscopy outcomes; however, a proficiency curriculum is less time-consuming and can provide a structured approach to prepare for both the FES exam and clinical endoscopy.

Evaluation of the Versius Robotic Surgical System for Procedures in Small Cavities.

Background: The Versius® is a recently approved robotic surgical system for general surgery procedures in adults. Before any application in children, data of its feasibility and safety in small cavities has to be compiled, beginning with inanimate models. Therefore, the aim of this preclinical study was to assess the Versius® system for its performance in small boxes simulating small body cavities. Methods: In total, 8 cardboard boxes of decreasing volumes (15.75 L to 106 mL) were used. The procedures, two single stitches with two square knots each, were performed in every box, starting in the largest and consecutively exchanging the box to the next smaller one. The evaluation included procedure time, port placement and pivot point setup, arrangement of the robotic arms and instrumentation, amount of internal and external instrument–instrument collisions and instrument–box collisions. Results: All procedures could be successfully performed in all boxes. The procedure time decreased due to the learning curve in the first four boxes (15.75 to 1.87 L) and consecutively increased from boxes of 1.22 L up to the smallest box with the dimensions of 4.4 × 4.9 × 4.9 cm3. This may be based on the progress of complexity of the procedures in small cavities, which is also depicted by the synchronous increase of the internal instrument–instrument and instrument–box collisions. Conclusion: With the use of the Versius® robotic surgical system, we were able to perform robotic reconstructive procedures, such as intracorporal suturing and knot tying, in cavities as small as 106 mL. Whether this system is comparable or even superior to conventional laparoscopic surgery in small cavities, such as in children, has to be evaluated. Furthermore, before any application in newborns or infants, ongoing evaluation of this system should be performed in a live animal model.

Design and validation of a therapeutic EUS training program using a live animal model: Taking training to the next level

Background and Objectives: EUS has evolved into a therapeutic modality for gastrointestinal disorders. Simulators, ex vivo models, and phantoms are the current teaching methods for therapeutic EUS (TEUS). We create and evaluate a high-fidelity simulated live animal model (HiFi SAM) for teaching endoscopists TEUS. Materials and Methods: Designing a curriculum that uses HiFi SAM and enables trainees to perform realistic procedures with expert mentors. Results: Twenty-seven trainees participated in a 3-day program with 6 h of theoretical and 14 h of hands using life HiFi SAM. Eighteen experts participated. Twenty-two (20–25) TEUS were defined for each HiFi SAM, and 616 were performed in all. Of 616/264 (43%) were evaluated with a mean of 88 per course (ranging between 80 and 95). Ninety-one percent (240/264) of the procedures were completed successfully. In 24, success was not achieved due to technical and/or model problems. Student rating of HiFi SAM was: 71% excellent rating (scale 8–10) and 95% excellent/good. The HiFi SAM procedure evaluation was (scale 1–5): fine-needle biopsy: 4.79, radiofrequency: 4.76, common bile duct and gallbladder drainage: 4.75, cystic drainages: 4.72, neurolysis: 4.55, microbiopsy: 4.50, and hepatogastric drainage: 4.04, with an overall satisfaction rate of 4.56 (91%). A short survey showed: 83% would recommend absolutely (17% most likely), 33% think that ITEC training was sufficient for their practice, and 66% would like additional training, especially more practice in specific techniques rather than more clinical case discussion. Regarding impact on their practice, 66% of the trainees started a new procedure and/or noted improvement in previous ones. Conclusion: HiFi SAM is a complex model; however, experts and trainees are satisfied with the training this new curriculum provided.

An Exploratory Study of the Ability to Measure Cervical Medial Branch Sensory Nerve Action Potentials in a Live Animal Model

An Exploratory Study of the Ability to Measure Cervical Medial Branch Sensory Nerve Action Potentials in a Live Animal Model

Design and validation of a therapeutic EUS training program using a live animal model: Taking training to the next level.

ABSTRACTBackground and Objectives:EUS has evolved into a therapeutic modality for gastrointestinal disorders. Simulators, ex vivo models, and phantoms are the current teaching methods for therapeutic EUS (TEUS). We create and evaluate a high-fidelity simulated live animal model (HiFi SAM) for teaching endoscopists TEUS.Materials and Methods:Designing a curriculum that uses HiFi SAM and enables trainees to perform realistic procedures with expert mentors.Results:Twenty-seven trainees participated in a 3-day program with 6 h of theoretical and 14 h of hands using life HiFi SAM. Eighteen experts participated. Twenty-two (20–25) TEUS were defined for each HiFi SAM, and 616 were performed in all. Of 616/264 (43%) were evaluated with a mean of 88 per course (ranging between 80 and 95). Ninety-one percent (240/264) of the procedures were completed successfully. In 24, success was not achieved due to technical and/or model problems. Student rating of HiFi SAM was: 71% excellent rating (scale 8–10) and 95% excellent/good. The HiFi SAM procedure evaluation was (scale 1–5): fine-needle biopsy: 4.79, radiofrequency: 4.76, common bile duct and gallbladder drainage: 4.75, cystic drainages: 4.72, neurolysis: 4.55, microbiopsy: 4.50, and hepatogastric drainage: 4.04, with an overall satisfaction rate of 4.56 (91%). A short survey showed: 83% would recommend absolutely (17% most likely), 33% think that ITEC training was sufficient for their practice, and 66% would like additional training, especially more practice in specific techniques rather than more clinical case discussion. Regarding impact on their practice, 66% of the trainees started a new procedure and/or noted improvement in previous ones.Conclusion:HiFi SAM is a complex model; however, experts and trainees are satisfied with the training this new curriculum provided.

Sequential detection of hypochlorous acid and sulfur dioxide derivatives by a red-emitting fluorescent probe and bioimaging applications in vitro and in vivo.

Hypochlorous acid (HOCl) and sulfur dioxide derivatives (SO32−/HSO3−) play critical roles in complex signal transduction and oxidation pathways. Therefore, it is meaningful and valuable to detect both HOCl and SO2 derivatives in biosystems by a fluorescence imaging assay. In this work, we developed a red-emitting fluorescent probe (DP) by the condensation of malononitrile and phenothiazine derivatives through a C Created by potrace 1.16, written by Peter Selinger 2001-2019 ]]> C double bond. DP was designed with a donor–π–acceptor (D–π–A) structure, which enables absorption and emission in the long wavelength region. In the presence of HOCl, specific oxidation of the thioether of phenothiazine in DP to a sulfoxide derivative (DPO) occurs, resulting in a hypochromic shift (572 nm to 482 nm) of the absorption spectra and “OFF–ON” response of the maximum emission at 608 nm. After the activation of the CC double bond by oxidation, DPO reacts specifically with SO32−/HSO3−via a 1,4-nucleophilic addition reaction leading to a decrease in the intensity of the absorption and emission spectra, which enabled the realization of sequential detection of HOCl and SO32−/HSO3− by a single fluorescent probe. The detection limits of DP for HOCl and SO32−/HSO3− were calculated to be 81.3 nM and 70.8 nM/65.1 nm, respectively. The results of fluorescence microscopic imaging indicated that DP shows potential for the detection of intracellular HOCl and SO32−/HSO3−. Using adult zebrafish and nude mice as live animal models, DP was successfully used for the fluorescence imaging of HOCl and SO32−/HSO3−in vivo.

Use of 3D-printed animal models as a standard method to test avian behavioral responses toward nest intruders in the studies of avian brood parasitism

Living and/or non-living animal models are often used as stimuli to observe the behavioral responses of the target animals. In the past, parasites, predators, and harmless controls have been used to test host anti-parasitism defense behavior, and their taxidermy specimens have been widely used as a set of standard methods for the study of avian brood parasitism. In recent years, with the rapid development of 3D-printing technology, 3D-printed bird models are expected to be applied as a standard method in the study of avian brood parasitism. To evaluate the use of 3D-printed models, this study tests the reaction of Oriental Reed Warbler (Acrocephalus orientalis) towards predators, parasites, or controls, and compares the reaction among different nest intruders and between taxidermy specimens and 3D-printed animal models. It was found that the Oriental Reed Warbler responded most aggressively to the parasite, followed by predator, and finally the control; the results were consistent between the reaction to taxidermy specimens and 3D-printed animal models, indicating that 3D-printed models could serve as a substitute for taxidermy specimens. We propose a series of advantages of using 3D-printed models and suggest them to be a standard method for widespread use in future studies of avian brood parasitism.

Post-Traumatic Osteoarthritis Assessment in Emerging and Advanced Pre-Clinical Meniscus Repair Strategies: A Review.

Surgical repair of meniscus injury is intended to help alleviate pain, prevent further exacerbation of the injury, restore normal knee function, and inhibit the accelerated development of post-traumatic osteoarthritis (PTOA). Meniscus injuries that are treated poorly or left untreated are reported to significantly increase the risk of PTOA in patients. Current surgical approaches for the treatment of meniscus injuries do not eliminate the risk of accelerated PTOA development. Through recent efforts by scientists to develop innovative and more effective meniscus repair strategies, the use of biologics, allografts, and scaffolds have come into the forefront in pre-clinical investigations. However, gauging the extent to which these (and other) approaches inhibit the development of PTOA in the knee joint is often overlooked, yet an important consideration for determining the overall efficacy of potential treatments. In this review, we catalog recent advancements in pre-clinical therapies for meniscus injuries and discuss the assessment methodologies that are used for gauging the success of these treatments based on their effect on PTOA severity. Methodologies include histopathological evaluation of cartilage, radiographic evaluation of the knee, analysis of knee function, and quantification of OA predictive biomarkers. Lastly, we analyze the prevalence of these methodologies using a systemic PubMed® search for original scientific journal articles published in the last 3-years. We indexed 37 meniscus repair/replacement studies conducted in live animal models. Overall, our findings show that approximately 75% of these studies have performed at least one assessment for PTOA following meniscus injury repair. Out of this, 84% studies have reported an improvement in PTOA resulting from treatment.

A Steep Early Learning Curve for Endoscopic Submucosal Dissection in the Live Porcine Model

Background: Endoscopic submucosal dissection (ESD) is a demanding procedure requiring high level of expertise. ESD training programs incorporate procedures with live animal models. This study aimed to assess the early learning curve for performing ESD on live porcine models by endoscopists without any or with limited previous ESD experience. Methods: In a live porcine model ESD workshop, number of resections, completeness of the resections, en bloc resections, adverse events, tutor intervention, type of knife, ESD time and size of resected specimens were recorded. ESD speed was calculated. Results: A total of 70 procedures were carried out by 17 trainees. The percentage of complete resections, en bloc resections and ESD speed increased from the first to the latest procedures (88.2%–100%, 76.5%–100%, 8.6–31.4 mm²/min, respectively). The number of procedures in which a trainee needed tutor intervention and the number of adverse events also decreased throughout the procedures (4 to 0 and 6 to 0, respectively). During the workshop, when participants changed to a different type of knife, ESD speed slightly decreased (18.5 mm²/min to 17.0 mm²/min) and adverse events increased again (0–2). Conclusions: Through successive procedures, complete resections, en bloc resections, and ESD speed improve whereas adverse events decrease, supporting the role of the live porcine model in the preclinical learning phase. Changing ESD knives has a momentarily negative impact on the learning curve.

Endoscopic Submucosal Dissection Skills Transfer to Clinical Practice after Hands-On Workshops: An International Survey

Background: Endoscopic submucosal dissection (ESD) is a complex procedure, requiring enhanced technical skills. Translation into clinical practice of ESD training programs has not been documented. Our aim was to assess ESD training pathways of endoscopists participating in dedicated workshops and its clinical impact on ESD outcomes. Methods: Participants of live porcine models ESD workshops, from 2013 to 2019, were included. They were invited to complete a survey focusing on human ESD performance after training, prior skills/competencies, complete learning pathway, and clinical outcomes. Results: From 118 invited participants, 40 (34%) completed the questionnaire. Nineteen (47%) endoscopists performed human ESD after the workshop, predominantly male (89%). At the beginning of human ESD, endoscopists had a mean of 7.7 (standard deviation (SD) 4.1) years of endoscopic experience and were all performing endoscopic mucosal resection (and emergency endoscopy. Before ESD practice, 100% of the participants were trained with live animal models and 68% with ex vivo models. The majority started clinical ESD in the lower third of the stomach or rectum (90%), with lesions ≤30 mm (89%). Each endoscopist performed a median of 19 (interquartile range 8–32) cumulative ESDs, over a mean of 3.9 (SD 2.0) years. Total en bloc resection rate was 92%, R0 resection rate 88%, and curative resection rate 86%, whereas adverse events remained <10%. Endoscopists with >10 human ESD procedures achieve clinical competence thresholds. Conclusions: Participants of ESD workshops are adequately skilled prior to clinical ESD, complying with recommendations for training and properly implementing the technique. Transfer to clinical practice, of prior ESD skills obtained in hands-on training courses, was documented. Structured training programs achieve clinical outcomes exceeding established standards, namely in the very initial clinical phase.