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.

Zur Diagnostik von Rupturen der Rotatorenmanschette wird häufig die im Vergleich zur Sonografie deutlich kostenintensivere Magnetresonanztomografie durchgeführt. Ein Grund hierfür ist, dass es zum Teil schwierig ist, standardisierte statische Sonografie-Bilder zu gewinnen, was die reproduzierbare, untersucherunabhängige diagnostische Information verringert. Ziel des ersten Teils der Arbeit war es einerseits, zu analysieren, ob mit der 3D-Sonografie diese Probleme verringert werden könnten und andererseits die Sensitivität mit dem 2D-Ultraschall zur Diagnostik von Komplett- und Partialrupturen zu vergleichen. Bei der Untersuchung von 114 Patienten konnten mit dem 3D-Ultraschall Rupturen der Rotatorenmanschette gut dargestellt werden. Der Vergleich zwischen 2D- und 3D-Ultraschall ergab keinen statistisch signifikanten Unterschied zwischen beiden Verfahren für die Diagnostik von Komplett- und Partialrupturen. Ein Vorteil war die Möglichkeit der untersucherunabhängigen simultanen Auswertung von drei standardisierten Schnittebenen zu einem späteren Zeitpunkt. Bei der Verwendung biodegradierbarer Anker zur Fixierung von Weichteilen können ossäre Reaktionen auftreten. Ziel war es, die frühen Reaktionen des umgebenden Gewebes auf einen Poly-(L-co-D/L-Lactid) 70/30 Anker im Vergleich zu einem Titananker im Schafsknochen zu analysieren. Innerhalb von 20 Wochen nach Implantation zeigte sich keinerlei Verlust von Knochensubstanz im Bereich des distalen Schafsfemur bei Ankern aus Titan oder aus Polylactid. Vielmehr zeigte sich eine ausgeprägte Neuformation von spongiösem Knochen in die Implantathohlräume vor allem für das biodegradierbare Material. Daher sollten neben materialbedingten Ursachen auch biomechanische Ursachen wie zyklische Belastungen für mögliche Osteolysen in Betracht gezogen werden. Die arthroskopische subacromiale Dekompression (ASD) ist ein häufig durchgeführtes Verfahren zur Therapie von Subachromialsyndromen. Es sollten die eigenen Ergebnisse seit 1993 unter Berücksichtigung von Nebendiagnosen sowie die Möglichkeit, verschiedene Scores und VAS auch telefonisch erheben zu können, analysiert werden. Die Untersuchung von 422 Schultern zwischen 1,5 und 9,5 Jahren (durchschnittlich 4,8 Jahre) nach der Operation zeigte, dass die ASD mit überwiegend guten und sehr guten subjektiven und objektiven Resultaten (ca. 75%) ein zuverlässiges operatives Verfahren ist. Im Gegensatz zu einem laufenden Rentenverfahren hatten Rupturen der Rotatorenmanschette zum Zeitpunkt der Operation keinen negativen Einfluss auf das Operationsergebnis. Bei Nichtbeachtung der Pathologie des superioren Labrums und bei Rezidivoperation kam es zu einem erhöhten Anteil an Therapieversagern. Die telefonische Erhebung verschiedener Schulter-Scores (ausgenommen Constant-Score) und der VAS lieferte valide Resultate, die eine klinische Untersuchung entbehrlich machen und insbesondere bei Langzeitstudien eine wesentlich höhere Nachuntersuchungsrate ermöglichen. Das Konzept der winkelstabilen Osteosynthese ermöglicht eine weichteilschonende, minimal-invasive Frakturstabilisierung. Um eine sichere Verankerung von winkelstabilen Schrauben zu erreichen, ist eine korrekte Positionierung der Schraube in der Platte erforderlich. In biomechanischen Testungen konnte gezeigt werden, dass bei einer geringen Abweichung des Insertionswinkels winkelstabiler Schrauben von bis zu 5° vom optimalen Winkel immer noch eine hohe Stabilität der Schrauben-/Plattenverbindung gewährleistet war. Ab einem Winkel von über 5° kam es zu einer signifikanten Abnahme der Festigkeit dieser Verbindung. Um eine optimale Festigkeit der Verbindung Schraube/Platte zu erreichen und das Risiko der Schraubenlockerung zu minimieren, ist die konsequente Benutzung eines Zielgerätes zu empfehlen. Die klinische Nachuntersuchung von 53 Patienten mit winkelstabiler Osteosynthese bei proximaler Humerusfraktur zeigte eine mit der Literatur vergleichbare Komplikationsrate bei verringertem sekundären Dislokationsrisiko. Es zeigte sich aber auch die Problematik dieser Fakturen mit langer Nachbehandlungsdauer und dem Risiko einer Humeruskopfnekrose im Verlauf. Winkelstabile Implantate ermöglichten eine sichere Stabilisierung von proximalen Humerusfrakturen, konnten jedoch eine insuffiziente Anwendung - wie eine fehlerhafte Verankerung der Kopfverriegelungsschrauben - nicht kompensieren. Erhöht war das Risiko einer Schraubenperforation durch die Sinterung des Kopfes auf das rigide Implantat. / Goal of the study was evaluation of advantages and limitations of shoulder diagnosis and different techniques of minimal invasive shoulder surgery. MRI has become the standard for diagnosis of rotator cuff lesions, since it can be difficult to obtain standardized ultrasound images. Goal of the study was analysis of sensitivity of 3D- in comparison to 2D-ultrasound. Examination of 114 patients showed excellent visualization of rotor cuff defects with 3D-ultrasound. Comparison to 2D-ultrasound showed no statistical significant difference between both methods for diagnosis of full- and partial thickness defects of the rotator cuff. Advantage of 3D-ultrasound was the possibility of simultaneous visualization of three standardized planes. For the reattachment of ligaments and tendons biodegradable implants are increasingly used today. However, with the use of biodegradable implants early and late osteolysis has been reported. Goal of this study was to analyze the early osseous integration of a newly designed suture anchor in comparison to a titanium implant. The implants made of Poly-(L-co-D/L-lactide) 70/30 or titanium were inserted into the cancellous bone of the distal femoral condyle in four sheep. The animals were followed radiographically over a period of 20 weeks in which no final implant degradation was anticipated. After sacrifice new bone formation was quantitatively and local tissue response qualitatively analyzed from microradiographs and histological sections were examined. New bone formation was seen around both implant materials within 20 weeks. Inside the recess of the polylactide suture anchor there was significantly higher bony ingrowth (p = 0.026) as compared to the titanium implant. Histologically non of the materials did show any inflammatory reaction. These data indicate that early osteolysis around Poly-(L-co-D/L-lactide) 70/30 suture anchors in cancellous bone may not be attributable to the material properties but rather to other reasons such as the mechanical situation at the implant-bone interface. Arthroscopic subacromial decompression (ASD) has become a well established procedure to treat chronic subacromial impingement syndrome. Goal of the study was to retrospectively evaluate the outcome and to evaluate the validity of data collection by telephone interview. The examination of 422 patients average 4.8 years after peration showed in 75% goog and excellent results. The average Constant score (raw score) improved from 46 to 80 Pts. Patients who had a second ASD had good results in only 25%. Patients with running workers compensation application showed no satisfying outcome. Lesions of the rotator cuff were shown to have no significant influence on the outcome in comparison to patients with intact rotator cuff. Additionally, it was shown that the assessment of various shoulder scores (except Constant Score) by telephone interview is possible. Internal fixators with angular stability have been developed in order to provide high stability without compression of the plate on to the bone. The insertion angle of the screw must correspond precisely to the axis of the screw hole. The objective of this study was to examine the relationship between the stability of the locked screw-plate on the insertion angle of the screw. Locking screws were inserted in a isolated or combined locking hole with the use of an aiming device. The screws were inserted with an axis deviation of 0°(optimal condition), 5° and 10°. The samples were tested under shear or axial (push out) loading conditions until failure occurred. Locking screws inserted in the isolated locking hole (PC-Fix) showed a significant decrease of failure load if inserted at 5° and 10° angle. Screws inserted in the combined locking hole (LCP) also showed a significant decrease of push-out force of 77% with 10° axis deviation. A locking head screw exhibits a high stability with a moderate axis deviation in the angle of insertion of up to 5°. However there is a significant decrease in stability with increasing axis deviation (>5°). A aiming device is recommended to provide an optimal fixation with angular stability. Clinical Examination of 53 patients with angular stable osteosynthesis of proximal humeral fractures showed a rate of complications, which can be compared with literature with lower risk of secondary dislocation. Implants with angular stability allow stable fixation of proximal humeral fractures however the risk of screw perforation is higher.

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

[ES] La cirugía laparoscopia está considerada uno de los principales avances quirúrgicos en las últimas décadas. Esta técnica ha demostrado numerosas ventajas comparadas con la cirugía convencional abierta y ha sido extensamente usada para procesos quirúrgicos en el área abdominal. Para el paciente, la cirugía laparoscópica supone diversas ventajas, como por ejemplo menor dolor post operativo, tiempos de recuperación menores, menor riesgo de infección, o reducción del trauma. Para el cirujano en cambio, la situación es completamente diferente, esta práctica requiere mayor esfuerzo, concentración y estrés mental que la práctica convencional abierta. Además fuerza al cirujano a adoptar posiciones no-neutras en falanges, manos, muñecas, y brazos. Estas posturas no-neutras son la principal causa de fatiga muscular y aumentan el riesgo de problemas musculo-esqueléticos. Estos problemas han sido ampliamente estudiados por diferentes equipos de investigación, los cuales están tratando de mejorar la experiencia del cirujano en el quirófano. El enfoque utilizado en este estudio es diferente del utilizado anteriormente por la mayoría de estos equipos, los cuales suelen propones soluciones basadas en cambios ergonómicos con la intención de mejorar la geometría del mango de pistola convencional, ya que se considera ergonómicamente deficiente. El problema con este enfoque, es que las deficiencias no se encuentran únicamente en el mango, sino en la utilización de un punto de entrada fijo que fuerza a los cirujanos a mantener posiciones desfavorables. En este trabajo, se introduce el concepto "Libertad Postural" en el ámbito de la cirugía, este se basa en la hipótesis de que, si las herramientas no forzaran la posición de los cirujanos, estos mantendrían posiciones más favorables y cercanas al rango de posiciones neutras durante los procesos laparoscópicos. Los beneficios de este concepto han sido demostrados por medio de análisis de movimiento y de electromiografía de superficie, los cuales indican que la "Libertad Postural" es causante de un claro aumento de las posiciones neutras y de la reducción de la fatiga muscular, y han sido testeados por cirujanos en entornos simulados, los cuales encuentran beneficioso utilizar la "Libertad Postural" como característica base de este nuevo diseño de herramienta laparoscópica. En la sección final de este trabajo se propone un diseño que implementa el concepto de libertad postura con el cual se reduciría la fatiga muscular y los problemas musculo esqueléticos asociados a la práctica laparoscópica. Este diseño tiene la característica de actuar como una nueva sección del brazo, siendo una articulación que soporta los giros y grandes desplazamientos que normalmente tienen que desarrollar los brazos del cirujano. Además, esta solución es económica y fácil de fabricar, lo cual permitiría su uso por cirujanos de todo el mundo. / [CAT] La cirurgia laparoscòpia està considerada un dels principals avanços quirúrgics en les últimes dècades. Aquesta tècnica ha demostrat nombrosos avantatges comparats amb la cirurgia convencional oberta i ha sigut extensament usada per a processos quirúrgics en l'àrea abdominal. Per al pacient, la cirurgia laparoscòpica suposa diversos avantatges, com per exemple menor dolor post operatiu, temps de recuperació menors, menor risc d'infecció, o reducció del trauma. Per al cirurgià en canvi, la situació és completament diferent, aquesta pràctica requereix major esforç, concentració i estrés mental que la pràctica convencional oberta. A més força al cirurgià a adoptar posicions no-neutres en falanges, mans, nines, i braços. Aquestes postures no-neutres són la principal causa de fatiga muscular i augmenten el risc de problemes musculo-esquelètics. Aquests problemes han sigut àmpliament estudiats per diferents equips d'investigació, els quals estan tractant de millorar l'experiència del cirurgià en el quiròfan. L'enfocament utilitzat en aquest estudi és diferent de l'utilitzat anteriorment per la majoria d'aquests equips, els quals solen proposes solucions basades en canvis ergonòmics amb la intenció de millorar la geometria del mànec de pistola convencional, ja que es considera ergonòmicament deficient. El problema amb aquest enfocament, és que les deficiències no es troben únicament en el mànec, sinó en la utilització d'un punt d'entrada fix que força als cirurgians a mantindre posicions desfavorables. En aquest treball, s'introdueix el concepte "Llibertat Postural" en l'àmbit de la cirurgia, aquest es basa en la hipòtesi que, si les eines no forçaren la posició dels cirurgians, aquests mantindrien posicions més favorables i pròximes al rang de posicions neutres durant els processos laparoscòpics. Els beneficis d'aquest concepte han sigut demostrats per mitjà d'anàlisi de moviment i de electromiografía de superfície, els quals indiquen que la "Llibertat Postural" és causant d'un clar augment de les posicions neutres i de la reducció de la fatiga muscular, i han sigut testats per cirurgians en entorns simulats, els quals troben beneficiós utilitzar la "Llibertat Postural" com a característica base d'aquest nou disseny d'eina laparoscòpica. En la secció final d'aquest treball es proposa un disseny que implementa el concepte de llibertat postura amb el qual es reduiria la fatiga muscular i els problemes *musculo esquelètics associats a la pràctica laparoscòpica. Aquest disseny té la característica d'actuar com una nova secció del braç, sent una articulació que suporta els girs i grans desplaçaments que normalment han de desenvolupar els braços del cirurgià. A més, aquesta solució és econòmica i fàcil de fabricar, la qual cosa permetria el seu ús per cirurgians de tot el món. / [EN] Laparoscopic surgery is considered one of the main surgical advances in the last decades, this technique has demonstrated numerous advantages compared to open conventional surgery and it is widely used in abdominal procedures around the world. For the patient, laparoscopic surgery suppose less post-operative pain, shorter recovery time, lower risk of infection, and reduction of the trauma among other benefits. For the surgeon, the situation is completely different, this practice requires more effort, concentration and mental stress than conventional open procedures. It forces the surgeon to adopt non-neutral postures with phalanges, hands, wrists, and arms being this non-neutral postures the main cause of muscular fatigue and high risk of musculoskeletal disorders. The poor ergonomic postures accelerate muscle fatigue and pain because, outside the neutral range, muscles require more energy to generate the same contractile force than in neutral position. This increase of muscular fatigue is associated with the potential to commit errors that may harm the patient during the surgery. Because this problem is widely studied and different research centers are already trying to improve their surgeons experience in the operation room, the approach used during this work is different than most of the ones presented in previous works. Generally, the solutions proposed are based on ergonomic changes in the handle shape of the instrument, because the conventional pistol-grip handle is considered ergonomically poor. But the problem is not only in the shape of the handle but also in the fixed point of entrance that force the positions for the surgeon despite the handle¿s shape. In this work, the concept of postural freedom in laparoscopic surgery is introduced and evaluated. The postural freedom concept is based on the hypothesis that the surgeon involuntarily would maintain neutral postures if the instrument does not force him or her to reach extreme position with the upper limbs. The benefits of this concept has been demonstrated, by means of electromyography and motion capture. It reduces the localized muscular fatigue and increases the number of neutral postures during laparoscopic simulations. In the final section it is proposed a design that implements the postural freedom concept with, according on the results, the potential to reduce the localized muscular fatigue and the musculoskeletal problems associated to the practice. The design proposed here acts as a new section on the arm, being an articulation that support the turns and big displacements that currently suffer the surgeon¿s body. The solution is affordable and easy to manufacture and could be used by surgeons worldwide. / Pace Bedetti, HM. (2019). The effect of "Postural Freedom" in laparoscopic surgery [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/122312 / TESIS

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.

Zielsetzung: In dieser Studie wurde an 15 gesunden Rindern die Methode der Thorakoskopie erprobt mit dem Ziel, eine Grundlage für den weiteren Einsatz dieses Verfahrens am bovinen Thorax zu schaffen. Im Mittelpunkt standen die Entwicklung einer geeigneten Untersuchungstechnik und die Beschreibung der endoskopisch dargestellten, im Pleuraspalt gelegenen Organe sowie möglicher pathologischer Befunde. Weiterhin galt es Komplikationen zu ermitteln und anhand der Erfahrungen aus diesem Versuch Indikationen für den Einsatz dieses minimal-invasiven Verfahrens beim Rind zu formulieren. Methodik: Alle Tiere wurden einer links- und rechtsseitigen Thorakoskopie jeweils mit und ohne intrapleurale Insufflation von Kohlenstoffdioxid über einen interkostalen Zugang unterzogen. Im Rahmen des Versuches fanden folglich vier Thorakoskopien je Rind und insgesamt 60 Thorakoskopien mit einer Wartezeit von 24 Stunden zwischen den einzelnen Untersuchungen statt. Die Untersuchungen erfolgten am im Zwangsstand fixierten, lokal anästhesierten Tier. Der endoskopische Zugang lag stets auf Höhe des Tuber coxae und variierte vom 8. bis zum 10. Interkostalraum. Nach interkostaler Schnittinzision wurde eine Zitzenkanüle bis in den Pleuraspalt vorgeschoben. Der spontane Einstrom von Raumluft in das Cavum pleurae führte zum Teilkollaps des ipsilateralen Lungenflügels. Die Kanüle wurde durch eine Trokar-Hülsen-Einheit ersetzt und die Hülse stellte nach Entfernung des Trokars den Zugang für die Optik. Je Hemithorax wurde die Untersuchungszeit auf 20 Minuten festgelegt. Sie begann im kranialen Pleuraspalt, wurde über (dorso)-kranial, (dorso)-medial, (dorso)-kaudal, ventrokaudal und ventral fortgeführt und endete mit ventrokranial ausgerichteter Optik. Ergebnisse: Die meisten im Cavum pleurae gelegenen Organe konnten ohne die Insufflation von CO2 ausreichend adspiziert werden. Während der links- und rechtsseitigen Thorakoskopien gelang die Adspektion großer Bereiche der Pleura costalis mit den Mm. intercostales interni sowie den Aa. et Vv. intercostales dorsales, Anteile der Lungenflügel und des Ligamentum pulmonale, der Aorta thoracica, des thorakalen Ösophagus, des M. longus colli, von Lymphknoten des Lc. thoracicum dorsale sowie der Lnn. mediastinales caudales, der Pars thoracica des Truncus sympathicus und des Truncus vagalis dorsalis des N. vagus. Des Weiteren konnten der M. psoas major, Anteile des Diaphragmas und der V. phrenica cranialis, der Hiatus aorticus, der Arcus lumbocostalis sowie unregelmäßig die A. et V. bronchoesophagea adspiziert werden. Die Untersuchung des rechten kranialen Pleuraspaltes war mit Einschränkungen behaftet und spiegelte sich in einer reduzierten Darstellung der sympathische Nervenfasern aus dem Ggl. cervicothoracicum, des Truncus costocervicalis dextra sowie der V. costocervicalis dextra wider. Linksseitig war die Betrachtung dieser Organe bzw. der korrespondierenden linksseitig angelegten Organe regelmäßig möglich. Weiterhin gelang während der linksseitigen Untersuchung die Adspektion des Ln. tracheobronchalis sinister, des Truncus brachiocephalicus sowie der V. azygos sinistra. Rechtsseitig konnte die V. azygos dextra stets adspiziert werden. Die Darstellung des Ductus thoracicus erfolgte nur bei einem der untersuchten Rinder infolge einer pathologischen Kompression. Während der Untersuchungen unter passivem Lungenkollaps war das Perikard nur bei einer rechtsseitigen Thorakoskopie zu sehen. Die Zweituntersuchungen des ipsilateralen Pleuraspaltes fanden während der Insufflation von CO2 bis zu einem Überdruck von 5 mm Hg statt. Dies sollte einen stärkeren Lungenkollaps bewirken und damit die Sicht auf intrapleural gelegene Organe verbessern. Während der Insufflation waren beidseits größere Anteile der Rippen und des Zwerchfells sowie das Perikard linksseitig bei drei Rindern und rechtsseitig bei einem Rind darstellbar. Postoperative Röntgenaufnahmen dienten dem Ausschluss des Vorhandenseins eines ipsi- oder kontralateralen Pneumothorax. Schlussfolgerung: Die Studie zeigt, dass Thorakoskopien an stehenden, gesunden Rindern sicher und komplikationsarm durchzuführen sind. Die beschriebene, minimal-invasive Technik stellt eine wertvolle, zusätzliche Methode zur tierschonenden Abklärung intrathorakaler Erkrankungen beim Rind dar. Der diagnostische, palliative oder therapeutische Nutzen muss in weiterführenden Untersuchungen ermittelt werden. / Objective: A study on 15 healthy cows was conducted to prove the thoracoscopic technique with the aim to establish a basis for further application of this procedure on cattle. Focus was on developing an adequate examination technique, displaying and describing of physical as well as pathological findings on intrathoracic organs examined endoscopically. Furthermore perioperative complications and indications of this minimally invasive method on cattle should be presented. Methods: The animals underwent a left and right side thoracoscopy under passive lung collapse and under insufflation of CO2. Therefore four thoracoscopies at each cow and a total of 60 thoracoscopies were performed with a waiting time of 24 hours between each examination. The cows were restrained in a stock and locally anesthetized. The endoscopic portal was lined up horizontally with the level of the ventral margin of the coxal tuber, at the point where the local anaesthetic had been injected and varied between the eighth and the tenth intercostal space. After a vertical stab incision through the skin and subcutaneous tissues a blunt stainless teat cannula was introduced into the pleural space. At this point air streamed spontaneously into the pleural space following by an ipsilateral lung collapse. The teat cannula was then removed and replaced by a sharp guarded trocar. After that the trocar was removed and the endoscope was passed through the remaining cannula. The time assessment for examination of each thorax was 20 minutes, started in the cranial pleural space, was continued in the (dorso)-cranial, (dorso)-medial, (dorso)-caudal, ventrocaudal und ventral direction and ended with ventrocranially aligned optic. Results: Most of the intrathoracic organs were seen without additional CO2 insufflation. During left and right side thoracoscopies large parts of the costal pleura, the internal intercostal muscles, the dorsal intercostal veins and arteries, parts of the lungs and the pulmonary ligament, the thoracic aorta, the thoracic part of the esophagus and the longus colli muscle, caudal mediastinal lymph nodes and lymph nodes associated with the dorsal thoracic lymph center, the thoracic part of the sympathic trunk and the dorsal vagus nerve were seen. Furthermore the psoas major muscle, parts of the diaphragm and the cranial phrenic vein, the aortic hiatus, the lumbocostal arch and intermittently the broncho-esophageal artery and vein could be identified. There were some constraints during right side thoracoscopy of the cranial pleural space which caused a limited view at the sympathic nerve fibres associated with the cervicothoracic ganglion, the right costocervical trunk and the right costocervical vein. At the left side these organs, the corresponding left side organs respectively, were constantly seen. Moreover during the exam at the left pleural space the left tracheobronchial lymph node, the brachiocephalic trunk and the left azygos could be well identified. During right side thoracoscopy the right azygos vein was always visible. In one case the presentation of the thoracic duct succeeded as a result of its pathological compression. During examination under passive lung collapse the pericard was visualized in one cow during right side thoracoscopy. The second thoracoscopies of the ipsilateral pleural space were conducted during insufflation of CO2 with a pressure of 5 mm Hg. A stronger lung collapse should result during insufflation with an enhanced view of the organs located intrapleurally. During insufflation at both sides larger parts of the ribs and diaphragm as well as the pericard on the left side at three cattle and on the right side at one cattle could be seen. Postoperative radiographies ensured the absence of an ipsi- or contralateral pneumothorax. Conclusion: This study shows that thoracoscopies on standing healthy cattle could be safely performed without major perioperative complications or side effects. The described minimally invasive procedure is a valuable, gentle and additional method to diagnose intrathoracic diseases in cattle. The use of thoracoscopy as diagnostic tool, for curative and palliative therapy should be identified in further studies.