Introduction: As the number of minimally invasive technologies increases in the field of thoracic surgery, so have the number of learning curve analyses performed for these innovations. Variation in learning curve methodology makes between-study comparisons and evidence syntheses difficult. Furthermore, poorly described and reported learning curve analyses make the results difficult to apply to different clinical settings. The objective of this systematic review is to characterize the variability in the methods used to construct and describe learning curves, with the goal of identifying shortcomings and potential areas for improvement in this line of research. Methods: A search of Ovid Medline, Ovid Embase, EBSCO CINAHL, and Web of Science was performed. Studies of learning curves of anatomical lung resection operations in adult patients published in the English language were eligible for inclusion. Two reviewers independently assessed studies for eligibility, and extracted relevant data. Results: The search yielded 56 articles eligible for inclusion in the present review. A variety of methods were used to construct the learning curve, with chronological grouping of cases being the most commonly used technique in 22 (39.29%) studies, followed by the cumulative sum method, employed in 21 (37.50%) studies. A total of 15 unique metrics were used for learning curve analyses; operative time was the most common metric, used in 39 (69.64%) studies. A large proportion of studies failed to provide details on learning curve parameters such as competency thresholds, surgeon’s prior experience, case complexity, and learning curve definition. Considerable heterogeneity was found in the methods and reporting standards of learning curve evaluations in minimally invasive thoracic surgery. Conflicts of Interest: None. Funding Source: Boris Family Centre for Robotic Surgery. / Thesis / Master of Science (MSc)

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Yes / Recovering high-quality 3D point clouds from monocular endoscopic images is a challenging task. This paper proposes a novel deep learning-based computational framework for 3D point cloud reconstruction from single monocular endoscopic images. An unsupervised mono-depth learning network is used to generate depth information from monocular images. Given a single mono endoscopic image, the network is capable of depicting a depth map. The depth map is then used to recover a dense 3D point cloud. A generative Endo-AE network based on an auto-encoder is trained to repair defects of the dense point cloud by generating the best representation from the incomplete data. The performance of the proposed framework is evaluated against state-of-the-art learning-based methods. The results are also compared with non-learning based stereo 3D reconstruction algorithms. Our proposed methods outperform both the state-of-the-art learning-based and non-learning based methods for 3D point cloud reconstruction. The Endo-AE model for point cloud completion can generate high-quality, dense 3D endoscopic point clouds from incomplete point clouds with holes. Our framework is able to recover complete 3D point clouds with the missing rate of information up to 60%. Five large medical in-vivo databases of 3D point clouds of real endoscopic scenes have been generated and two synthetic 3D medical datasets are created. We have made these datasets publicly available for researchers free of charge. The proposed computational framework can produce high-quality and dense 3D point clouds from single mono-endoscopy images for augmented reality, virtual reality and other computer-mediated medical applications.

Irreversible electroporation (IRE) is a non-thermal tissue ablation modality in which electrical pulses are used to generate targeted disruption of cellular membranes. Clinically, IRE is administered by inserting one or more needles within or around a region of interest, then applying a series of short, high amplitude pulsed electric fields (PEFs). The treatment effect is dictated by the local field magnitude, which is quite high near the electrodes but dissipates exponentially. When cells are exposed to fields of sufficient strength, nanoscale "pores" form in the membrane, allowing ions and macromolecules to rapidly travel into and out of the cell. If enough pores are generated for a substantial amount of time, cell homeostasis is disrupted beyond recovery and cells eventually die. Due to this unique non-thermal mechanism, IRE generates targeted cell death without injury to extracellular proteins, preserving tissue integrity. Thus, IRE can be used to treat tumors precariously positioned near major vessels, ducts, and nerves. Since its introduction in the late 2000s, IRE has been used successfully to treat thousands of patients with focal, unresectable malignancies of the pancreas, prostate, liver, and kidney. It has also been used to decellularize tissue and is gaining attention as a cardiac ablation technique. Though IRE opened the door to treating previously inoperable tumors, it is not without limitation. One drawback of IRE is that pulse delivery results in intense muscle contractions, which can be painful for patients and causes electrodes to move during treatment. To prevent contractions in the clinic, patients must undergo general anesthesia and temporary pharmacological paralysis. To alleviate these concerns, high-frequency irreversible electroporation (H-FIRE) was introduced. H-FIRE improves upon IRE by substituting the long (~100 µs) monopolar pulses with bursts of short (~1 µs) bipolar pulses. These pulse waveforms substantially reduce the extent of muscle excitation and electrochemical effects. Within a burst, each pulse is separated from its neighboring pulses by a short delay, generally between 1 and 5 µs. Since its introduction, H-FIRE burst waveforms have generally been constructed simply by choosing the duration of constitutive pulses within the burst, with little attention given to this delay. This is quite reasonable, as it has been well documented that pulse duration plays a critical role in determining ablation size. In this dissertation, we explore the role of these latent periods within burst waveforms as well as their interaction with other pulse parameters. Our central hypothesis is that tuning the latent periods will allow for improved ablation size with reduced muscle contractions over traditional waveforms. After gaining a simple understanding of how pulse width and delay interact in vitro, we demonstrate theoretically that careful tuning of the delay within (interphase) and between (interpulse) bipolar pulses in a burst can substantially reduce nerve excitation. We then analyze how pulse duration, polarity, and delays affect the lethality of burst waveforms toward determining the most optimal parameters from a clinical perspective. Knowing that even the most ideal waveform will require slightly increased voltages over what is currently used clinically, we compare the clinical efficacy of two engineered thermal mitigation strategies to determine what probe design modifications will be needed to successfully translate H-FIRE to the clinic while maintaining large, non-thermal ablation volumes. Finally, we translate these findings in two studies. First, we demonstrate that burst waveforms with an improved delay structure allow for enhanced safety and larger ablation volumes in vivo. And finally, we examine the efficacy of H-FIRE in spontaneous canine liver tumors while also comparing the ablative effect of H-FIRE in tumor and non-neoplastic tissue in a veterinary clinical setting. / Doctor of Philosophy / Cancer is soon to become the most common cause of death in the United States. In 2023, approximately 2 million new cases of cancer will be diagnosed, leading to roughly 650 thousand lost lives. Interestingly, about half of newly diagnosed cancers are caught in the early stages before the disease has spread throughout the body. With effective local intervention, these patients could potentially be cured of their malignancy. Surgical removal of the tumor is the gold standard, but it is often not possible due to tumor location, patient comorbidities, or organ health status. In some instances, focal thermal ablation with radiofrequency or microwave energy can be performed when resection is not possible. These treatments entail the delivery of thermal energy through a needle electrode, which causes local tissue damage through coagulation (cooking) of the tissue. However, thermal ablation destroys tissue indiscriminately, meaning that any nearby blood vessels or neural components will also be damaged, which precludes thousands of patients from treatment each year. Irreversible electroporation (IRE) was introduced to overcome these challenges and provide a treatment option for patients diagnosed with otherwise untreatable tumors. IRE uses pulsed electric fields to generate nanoscale pores in cell membranes, which lead to a homeostatic imbalance and cell death. Because IRE is a membrane-based effect, it does not rely on thermal effects to generate cellular injury, which allows it to be administered to tumors that are adjacent to critical tissue structures such as major nerves and vasculature. Though IRE opened the door to treating otherwise inoperable tumors, procedures are technically challenging and require specialized anesthesia protocols. High-frequency irreversible electroporation (H-FIRE) was introduced by our group roughly a decade ago to simplify the procedure through the use of an alternate pulsing strategy. These higher frequency pulses offer several advantages such as limiting muscle contractions and reducing the risk of cardiac interference, both of which were concerns with IRE. However, H-FIRE ablations have been limited in size, and there is limited knowledge regarding the optimal pulsing strategy needed in order to maximize the ratio of therapeutic benefits to undesirable side effects like muscle stimulation and Joule heating. In this dissertation, we sought to understand how different pulse parameters affect these outcomes. Using a combination of computational, benchtop, and in vivo experiments, we comprehensively characterized the behavior of user-tunable pulse parameters and identified optimal methods for constructing H-FIRE protocols. We then translated our findings in a proof-of-principle study to demonstrate the ability of newly introduced waveform designs to increase ablation size with H-FIRE. Overall, this dissertation improves our understanding of how H-FIRE waveform selection affects clinical outcomes, introduces a new strategy for maximizing therapeutic outcomes with minimal side effects, and provides a framework for selecting parameters for specific applications.

INTRODUÇÃO: Tem-se afirmado que a via de acesso minimamente invasiva na artroplastia total de joelho (ATJ) por não agredir o músculo quadríceps femoral permite reabilitação mais precoce. A fim de verificar a influência da preservação do aparelho extensor no ato cirúrgico, avaliou-se a força da musculatura extensora e flexora do joelho em pacientes submetidos à ATJ por duas vias de acesso diferentes. MÉTODOS: Este estudo comparou, no período de janeiro de 2005 a julho de 2006, os valores de torque máximo e de trabalho total obtidos por dinamometria isocinética aos seis meses de pós-operatório. Foram avaliados 12 indivíduos submetidos à ATJ por via de acesso minimamente invasiva e 8 indivíduos submetidos à ATJ por via de acesso transquadricipital. RESULTADOS: A análise estatística dos valores de torque máximo e de trabalho total absolutos e corrigidos pelo peso corporal não demonstrou diferença entre os dois grupos. CONCLUSÃO: Não há diferença de força da musculatura extensora e flexora do joelho aos seis meses de cirurgia. / INTRODUCTION: It has been stated that for total knee arthroplasty (TKA), the minimally invasive approach permits earlier rehabilitation because it is not prejudicial for the femoral quadriceps muscle. To verify the influence of preserving the extensor apparatus during surgery, strength of the knee extension and flexion muscles was evaluated in patients submitted to TKA with different approaches. METHODS: The values of maximum torque and total work obtained by isokinetic dynamometry six months after surgery were compared for the MIS group of 12 individuals submitted to TKA by the minimally invasive surgical approach and the Control group of eight others submitted to TKA by the transquadricipital approach, between January 2005 and July 2006. RESULTS: Statistical analysis of the absolute values of maximum torque and total work corrected by body weights did not show a difference between the two groups. CONCLUSION: There was no difference in the extension and flexion strength of the knee muscles six months after surgery.

INTRODUÇÃO: Tem-se afirmado que a via de acesso minimamente invasiva na artroplastia total de joelho (ATJ) por não agredir o músculo quadríceps femoral permite reabilitação mais precoce. A fim de verificar a influência da preservação do aparelho extensor no ato cirúrgico, avaliou-se a força da musculatura extensora e flexora do joelho em pacientes submetidos à ATJ por duas vias de acesso diferentes. MÉTODOS: Este estudo comparou, no período de janeiro de 2005 a julho de 2006, os valores de torque máximo e de trabalho total obtidos por dinamometria isocinética aos seis meses de pós-operatório. Foram avaliados 12 indivíduos submetidos à ATJ por via de acesso minimamente invasiva e 8 indivíduos submetidos à ATJ por via de acesso transquadricipital. RESULTADOS: A análise estatística dos valores de torque máximo e de trabalho total absolutos e corrigidos pelo peso corporal não demonstrou diferença entre os dois grupos. CONCLUSÃO: Não há diferença de força da musculatura extensora e flexora do joelho aos seis meses de cirurgia. / INTRODUCTION: It has been stated that for total knee arthroplasty (TKA), the minimally invasive approach permits earlier rehabilitation because it is not prejudicial for the femoral quadriceps muscle. To verify the influence of preserving the extensor apparatus during surgery, strength of the knee extension and flexion muscles was evaluated in patients submitted to TKA with different approaches. METHODS: The values of maximum torque and total work obtained by isokinetic dynamometry six months after surgery were compared for the MIS group of 12 individuals submitted to TKA by the minimally invasive surgical approach and the Control group of eight others submitted to TKA by the transquadricipital approach, between January 2005 and July 2006. RESULTS: Statistical analysis of the absolute values of maximum torque and total work corrected by body weights did not show a difference between the two groups. CONCLUSION: There was no difference in the extension and flexion strength of the knee muscles six months after surgery.

Numerous studies have demonstrated the potential efficacy of percutaneous image-guided interventions over open surgical interventions. The conventional image-guided procedures are limited by the freehand technique, requiring mental 3D registration and hand-eye coordination for needle placement. The outcomes of these procedures are associated with longer duration and increased patient discomfort with high radiation exposure. Previously, a static image overlay system was proposed for aiding needle interventions. Certain drawbacks associated with the static system limited the clinical translation. To overcome the ergonomic issues and longer calibration duration associated with static system, an adjustable image overlay system was proposed. The system consisted of monitor and semi-transparent mirror, attached together to an articulated mobile arm. The 90-degree mirror-monitor configuration was proposed to improve the physician access around the patient. MicronTracker was integrated for dynamic tracking of the patient and device. A novel method for auto-direct calibration of the virtual image overlay plane was proposed. Due to large mechanical structure, the precise movement was limited and consumed useful space in the procedure room. A mobile image overlay system with reduced system weight and smaller dimensions was proposed to eliminate the need for mechanical structure. A tablet computer and beamsplitter were used as the display device and mirror respectively. An image overlay visualization module of the 3D Slicer was developed to project the correct image slice upon the tablet device. The system weight was reduced to 1 kg and the image overlay plane tracking precision (0.11mm STD=0.05) was similar to the printed physical markers. The auto-calibration of the image overlay plane can be done in two simple steps, away from the patient table and without additional phantom. Based on the successful pre-clinical testing of the previous static system, the mobile image overlay system with reduced weight, increased tracking precision and easier maneuverability, can be possibly hand-held by the physician to explore the image volume over the patient and be used for a wide range of procedures. The mobile image overlay system shall be classified as Class II device as per FDA regulations, do not require extensive verification and validation efforts and further improves the commercialization opportunities. / Thesis (Master, Mechanical and Materials Engineering) -- Queen's University, 2014-06-26 18:51:03.958

Die pyogene Spondylodiszitis als bakterielle Osteomyelitis der Wirbelsäule ist eine seltene Entität der bakteriell-entzündlichen Pathologien des Stütz- und Bewegungsapparates. Trotz adäquater Behandlungsstrategien, wird auch heute noch eine Mortalitätsrate von 5% bis 20% beschrieben. Vor allem die in dem vorwiegend älteren Patientenkollektiv deutlich erhöhte Prävalenz an metabolischen oder kardiopulmonalen Komorbiditäten fordert moderne Therapiekonzepte, die eine risikoarme, jedoch effektive Eradifizierung des bakteriell-entzündlichen Fokus mit schneller Wiederherstellung der prämorbiden Mobilität ermöglichen. Ausgehend von zwei grundlagenwissenschaftlichen Studien, wurden in der vorliegenden Habilitationsschrift zunächst die komplexen Zusammenhänge von lokaler Gewebsveränderungen und systemischer Entzündung erörtert. Hierbei zeigten die Analysen humaner degenerativer und traumatischer Bandscheibenzellen, dass die Apoptose, insbesondere die Herabregulation anti-apoptotischer Schlüsselkomponenten wie das Bcl-2, als mögliche Schnittstelle im katabolen Stoffwechsel der extrazellulären Bandscheibenmatrix diskutiert werden kann. In der generalisierten bakteriellen Entzündung (Sepsis), ließ sich durch die gentherapeutisch gewebsständige Überexpression von antiapoptotischen und antiinflammatorischen Interleukin-10 (IL-10), auch im IL-10-defzienten Organismus, eine deutliche Reduktion der systemischen proinflammatorischen Immunantwort mit verbesserter Überlebensrate septischer Tiere erzielen. Jedoch birgt der substantielle Gewebeschaden bei pyogener Spondylodiszitis nicht selten die Gefahr der konsekutiven Instabilität mit neurologischen Komplikationen und stellt damit eine besondere chirurgische Herausforderung dar. Daher wurden in drei weiteren klinischen Studien unsere, in den letzten 10 Jahren etablierten, lösungsorientierten Strategien erläutert. Zur Überbrückung größerer knöcherner Defekte gelang mit der Implantation expandierbarer Titancages eine sichere knöcherne Durchbauung mit vollständiger Ausheilung des Infektes. Im Beobachtungszeitraum von mehr als 3 Jahren war bei keinem der Patienten ein Infektrezidiv zu verzeichnen. In komplexen Fällen von monosegmentaler Spondylodiszitis der LWS mit multisegmentaler epiduraler Abszedierung, führte die epidurale Katheterspülung über den dorsalen Zugang für die Spondylodese zu einer folgenlosen Ausheilung. Damit konnte ein zusätzliches, iatrogenes Trauma mit multisegmentalen Lamintomien über die Distanz des epiduralen Abszesses vermieden werden. In einer weiteren Studie mit einem Beobachtungszeitraum von bis zu 5 Jahren, erzielte die Implantation von Poly-Ether-Ether-Keton (PEEK) Cages zur dorsalen intersomatischen Fusion bei pyogener Spondylodiszitis eine sehr gute, stabile knöcherne Durchbauung des infizierten Segmentes, ebenfalls ohne Infektrezidiv. Diese Abweichung vom herkömmlichen Standard mit Titanimplantaten erwies sich somit als sichere Alternative mit den für PEEK charakteristischen, verbesserten Eigenschaften. Im Vergleich zu herkömmlichen Operationsverfahren, verspricht die Integration dieser Ergebnisse in die Weiterentwicklung minimal-invasiver Techniken, insbesondere im multimorbiden Patientenklientel, mindestens gleichwertig gute Ergebnisse bei deutlich reduziertem Operationstrauma.:1. EINFÜHRUNG IN DIE THEMATIK 1 1.1 Die pyogene Spondylodiszitis 1 1.1.1 Epidemiologie, Ätiologie und Pathophysiologie 2 1.1.2 Diagnostik und Therapie 6 1.1.2.1 Konservative Therapie 11 1.1.2.2 Operative Therapie 12 1.2 Biomechanische Aspekte 14 1.3 Wissenschaftliche Fragestellung 15 2. ORIGINALARBEITEN 20 2.1 Apoptosis of human intervertebral discs after trauma compares to degenerated discs involving both receptor-mediated and mitochondrial-dependent pathways 20 2.2 Endogenous IL-10 regulates sepsis-induced thymic apoptosis and improves survival in septic IL-10 null mice 30 2.3 Reconstruction of large defects in vertebral osteomyelitis with expandable titanium cages 39 2.4 Single-stage epidural catheter lavage with posterior spondylodesis in lumbar pyogenic spondylodiscitis with multilevel abscess formation 45 2.5 Single-stage debridement and spinal fusion using PEEK-cages through a posterior approach for eradication of lumbar pyogenic spondylodiscitis: A safe treatment strategy for a detrimental condition 52 3. ZUSAMMENFASSUNG UND AUSBLICK 62 4. LITERATURVERZEICHNIS 78 5. APPENDIX 98 5.1 Tabellen und Abbildungen 98 Tabelle 1 & 2 98 Tabelle 3 & 4 99 Abbildung 1 100 Abbildung 2 101 Abbildung 3 102 Abbildung 4 103 Abbildung 5 104 5.2 Selbständigkeitserklärung 105 5.3 Danksagung 106 5.4 Curriculum Vitae 108

Les affections sinusales sont la première cause de jetage nasal unilatéral chez les chevaux. Cependant, la complexité anatomique de la région rend le diagnostic difficile avec la radiologie et l’endoscopie, et l’utilisation des techniques diagnostiques plus avancées comme la tomodensitométrie est souvent limitée par le manque de disponibilité et les coûts. Par conséquent, la sinusoscopie est souvent la technique disponible avec le meilleur taux diagnostic (70%) mais demeure invasive (trépanation de 10 à 15 mm) et peu pratique dans certains cas. Notre hypothèse est que le développement d’une technique de sinusoscopie peu invasive (TSPI), réalisée par une mini-trépanation avec une aiguille 14G (2 mm de diamètre), combinée à l’utilisation d’un nouvel endoscope flexible de 2 mm de diamètre, peut permettre d’obtenir une évaluation exhaustive des différents sinus paranasaux. Durant les deux premières phases du projet, réalisées sur des cadavres, les repères anatomiques pour réaliser une mini-trépanation des différents sinus ont été déterminés puis la visualisation des différents compartiments sinusaux a été évaluée en attribuant un score pour chaque structure sinusale. Dans une troisième phase, la TSPI a été appliquée sur des chevaux debout sous sédation afin de déterminer la faisabilité et les éventuelles complications chez des chevaux vivants. Les repères déterminés durant la phase 1 ont permis une exploration exhaustive et satisfaisante des sinus durant les deux phases suivantes. L’ensemble des chevaux a bien toléré la procédure et aucune complication sérieuse n’a été rapportée. La technique développée est facile à réaliser et peu faciliter le diagnostic des affections sinusales par tous les vétérinaires spécialistes ou non. / Paranasal sinus disease is the most common cause of unilateral nasal discharge in horses. However, achieving a definitive diagnosis using radiology and endoscopy is difficult due to the complex anatomy of the sinuses, and the use of computed tomography (gold standard) is often limited due to its cost and low availability. Consequently, sinoscopy is often the available diagnostic technique with the highest diagnostic rate (70%) but it remains invasive (10 to 15 mm trepanation) and unpractical in some cases. Our hypothesis is that the development of a minimally invasive sinoscopic technique (MIST), performed through a mini-trepanation with a 14G needle (2 mm trephination) and combined with the use of a novel flexible 2mm diameter endoscope, can allow an exhaustive evaluation of the paranasal sinuses. During the first two cadaveric phases of the project, we determined the exact anatomic landmarks to perform the mini-trepanation in the different sinuses, and the visualization of the different sinus compartments was assessed by attributing a score to each sinusal structure. In the last phase of the study, the MIST was performed on standing sedated horses to determine the feasibility and possible complications associated to the technique. The landmarks determined in the first phase allowed a thorough evaluation of the sinuses in the following phases. The horses tolerated well the procedure and no serious complications were reported. The technique developed during this study is easy to perform and could facilitate the diagnosis of paranasal sinus diseases for all veterinarians specialized or not.