This doctoral thesis describes unusual skin and soft-tissue tumors, which were the basis of the postgraduate study of Ladislav Hadravský, MD at Medical faculty in Pilsen of Charles University in Prague during 2013 - 2016. It contains documented cases of skin and soft-tissue tumors related to hereditary syndromes, unusual morphology, rare biological behavior, minor causal association with the respective disease, or different phenotypes. These cases were published in journals with the impact factor and in peer-reviewed journals. Regarding skin tumors, the study focused on sebaceous tumors of the skin, which may occur within Muir-Torre syndrome. In the retrospective study of sebaceous skin tumors, two unusual cases were found: the case of aggressive extraocular sebaceous carcinoma on the scalp in a patient with Muir-Torre syndrome and the case of multiple sebaceous skin tumors in a patient with MUTYH-associated polyposis of the colon mimicking Muir-Torre syndrome. As far as soft-tissue tumors are concerned, the study aimed at the morphological comparison of cases of myxoinflammatory fibroblastic sarcoma and pleomorhic hyalinizing angiectatic tumor.

The thesis reports on 6 studies (2 of which were part of a multi-centre trial) examining hydration and fluid balance. The first study described in this thesis investigated the impact of hydration status on Dual energy x-ray absorptiometry (DXA) and other methods that are popular tools to determine body composition in athletes. We observed that it is important to ensure a euhydration when assessing body composition, particularly when considering changes associated with nutritional or exercise interventions. The second and third studies reported identified beverages that promote longer term fluid retention and maintenance of fluid balance in adults. We investigated the effects of 13 different commonly consumed drinks on urine output and fluid balance when ingested in a euhydrated state, with a view to establishing a beverage hydration index (BHI), i.e., the volume of urine produced after drinking expressed relative to a standard treatment (still water) for each beverage. The beverages with the highest BHI were oral rehydration solution, full fat milk and skimmed milk. BHI may be a useful measure to identify the short term hydration potential of different beverages when ingested in a euhydrated state. The fourth study aimed to systematically examine the influence of carbohydrate, sodium and caffeine content of beverages on the BHI. The BHI was greater in beverages with higher carbohydrate or higher sodium content, but not influenced by caffeine. The carbohydrate content of beverages has no effect on BHI at concentration up to 10% carbohydrate. Sodium content of beverages in concentrations of 27mmol/L and higher can improve the hydration potential of beverages. Caffeine doses in beverages up to 400mg/L do not have an impact upon diuresis when ingested in a euhydrated state. The fifth study compared net fluid balance (NFB) responses to the ingestion of commonly consumed drinks in young and older men. We observed that in young adults milk helps to maintain positive net fluid balance for longer than other drinks. In older adults this effect of milk is not observed despite similar net electrolyte balance responses. Future work should more fully explore these potential differences in fluid balance responses to drink ingestion between young and older adults. The final study investigated the hydration habits of Scottish young and older adults (+50 years old), identifying their fluid choices, volume, and preferences in relation to time of day. The results showed that 26.1% of the young females, 30.3% of the young males, 25.8% of the older females and 50.4% of the older males did not meet the European (EU) Food Safety Authority (EFSA) fluid intake recommendations. We also observed that the difference between those who met and those who did not meet the EFSA adequate intake could be attributed to differences in water ingestion, mainly during the mid-morning (after breakfast until 11 am) and during the early-afternoon (after lunch time up to 5 pm). It was concluded that these moments might be key when implementing interventions to improve hydration status especially in the older population.

Lors de l'analyse 3D du mouvement humain basée sur des marqueurs cutanés, la position des os ne peut être qu'indirectement estimée. Au cours d'une tâche, les déformations des tissus mous génèrent des déplacements des marqueurs par rapport à l'os : les artefacts de tissus mous (STA), entraînant des effets dévastateurs sur l'estimation de la position. La compensation des STA demeure une question ouverte. L'objectif de cette thèse est de contribuer à la solution de cette question cruciale. La modélisation des STA en utilisant des variables spécifiques mesurables est une condition préalable à son élimination. Un modèle corrigeant les trajectoires individuelles de marqueurs de la cuisse, calibré par des mesures directes des STA, est d'abord présenté. Les STA sont modélisés comme une combinaison linéaire des angles articulaires impliqués. Trois représentations des STA par une série de modes sont proposées : déplacements de marqueurs individuels, transformations géométriques de clusters de marqueurs (MCGT), et variations de forme de l'enveloppe de peau. Le MCGT permet de dissocier les composantes rigides et non rigides. Il a été démontré que seule la composante rigide affecte la cinématique articulaire. Un modèle de cette composante est alors défini pour les clusters cuisse et jambe. Un compromis acceptable entre la correction des STA et le nombre de paramètres a ainsi été obtenu. Les principales applications sont de générer une simulation réaliste des STA ; et surtout, en se concentrant sur la composante rigide, le modèle permet une reconstruction satisfaisante des STA avec moins de paramètres, ce qui facilite son incorporation dans un algorithme d'estimation de la position osseuse / In 3D human movement analysis performed using stereophotogrammetry and skin markers, bone pose can be only indirectly estimated. During a task, soft tissue deformations make the markers move with respect to the underlying bone generating soft tissue artefacts (STA), causing devastating effects on pose estimation and its compensation remains an open issue. The thesis’ aim was to contribute to the solution of this crucial issue. Modelling STA using measurable trial-specific variables is a prerequisite for its removal from marker trajectories. Two STA model architectures are proposed. A thigh marker-level model is first presented. STA was modeled as a linear combination of joint angles involved in the task. The model was calibrated with direct STA measures. The considerable number of model parameters led to defining STA approximations. Three definitions were proposed to represent STA as series of modes : individual marker displacements, marker-cluster geometrical transformations (MCGT), and skin envelope shape variations. Modes were selected using two criteria : modal energy and selecting them a priori. The MCGT allows to select either rigid or non-rigid components. It was also demonstrated that only the rigid component affects joint kinematics. A model of thigh and shank rigid component at cluster-level was then defined. An acceptable trade-off between STA compensation and number of parameters was obtained. These results lead to two main potential applications : generate realistic STAs for simulation

Background: Hibernomas are rare benign soft-tissue tumours arising from brown fat tissue. Although imaging characteristics are not specific certain imaging features, common locations and patient demographics may suggest hibernoma as a differential diagnosis. Case presentation: We report on two 48-year-old male patients with hibernoma. The tumour presented with local swelling of the inguinal region in the first patient and was an incidental imaging finding in the second patient. Imaging included magnetic resonance imaging in both patients and computed tomography as well as 18 F-fluorodeoxyglucose positron emission tomography-computed tomography in the second patient. In both cases histological diagnosis was initially based on excisional and needle core biopsy, respectively. Complete surgical resection confirmed the diagnosis of hibernoma thereafter. Conclusion: In soft tissue tumours with fatty components hibernoma may be included into the differential diagnosis. Because of the risk of sampling errors in hibernoma-like tissue components of myxoid and well-differentiated liposarcoma, complete resection is mandatory. This article also reviews the current imaging literature of hibernomas.

Objective: Epithelioid sarcoma (ES) presents unique clinical features in comparison to other sarcoma subtypes. Data regarding the benefits of chemotherapy are very limited. Combination regimens using gemcitabine and docetaxel (Gem/Doce) have proven to be effective, especially in uterine and nonuterine leiomyosarcoma. Yet, there is no available data on the efficacy of Gem/Doce in ES. Methods: A retrospective analysis of the three participating institutions was performed. Twenty-eight patients with an ES diagnosis presented at one of the participating institutions between 1989 and 2012. Of this group, 17 patients received chemotherapy. Results: Patients’ median overall survival (OS) after the beginning of palliative chemotherapy was 21 months, and the 1-year OS was 87%. Twelve patients received Gem/Doce with a clinical benefit rate of 83%. The median progression-free survival (PFS) was 8 months for all patients receiving Gem/Doce. The best response was complete remission in 1 patient and partial remission in 6 patients. All 6 patients receiving Gem/Doce as a first-line treatment showed measurable responses with a median PFS of 9 months. Conclusions: In this retrospective study, Gem/Doce was an effective chemotherapeutic regimen for ES. Prospective studies are needed to better assess the effects of this combination drug therapy.

In forensic science one frequently has to deal with unidentified skeletonised remains. When conventional methods of identification have proven unsuccessful, forensic facial reconstruction (FFR) may be used, often as a last resort, to assist the process. FFR relies on the relationships between the facial features, subcutaneous soft tissues and underlying bony structure of the skull. The aim of this study was to develop soft tissue thickness (STT) values for South African black females for application to FFR, to compare these values to existing literature or databases, and to test the accuracy and recognisability of reconstructions using these values. It also established whether population-specific STT values are necessary for FRR. Computerised tomography scanning was used to determine average populationspecific STT values at 28 facial landmarks of 154 black females. The Manchester method of facial reconstruction was employed to build faces, for which antemortem photographs were available, on two skulls that were provided by the South African Police Service’s (SAPS) Forensic Science Laboratory. Different data sets of STT values, namely values from this study, two sets of data from American blacks and a South African mixed ancestry group, were used to build four faces for each of the skulls. Two identification sessions were then held. In the first session, 30 observers were asked to select matches from a random group of 20 photographs of black females which included the two actual images. The identification rates calculated for each photograph revealed that the highest rates of a positive match were for the reconstructions based on South African values. In the second session another group of 30 volunteers were asked to match to each photograph the most similar of the four reconstructions made of that particular individual. The reconstructions with STT values from the current (South African) study were selected more often than the other data sets. Although shortcomings do exist, the identification sessions indicated that FFR can be of value. Furthermore, population-specific STT values are important, since skulls reconstructed using these values were selected or identified statistically significantly more often than the others. AFRIKAANS : In forensiese wetenskap het mens dikwels te doen met ongeïdentifiseerde skeletmateriaal. Wanneer die konvensionele metodes van identifikasie onsuksesvol is, mag forensiese gesigsrekonstruksie (FGR) gebruik word, dikwels as `n laaste uitweg, om die proses te help. FGR is afhanklik van die verhouding tussen die gelaatstrekke, subkutane sagte weefsels en onderliggende benige struktuur van die skedel. Die doel van hierdie studie was om sagte weefsel dikte (SWD) waardes vir Suid-Afrikaanse swart vroue te ontwikkel vir gebruik met FGR, om hierdie waardes te vergelyk met bestaande literatuur of databasisse, en die akkuraatheid en herkenbaarheid van rekonstruksies waar hierdie waardes gebruik was te toets. Dit is gedoen ten einde vas te stel of bevolking-spesifieke SWD waardes nodig is vir FGR. Gerekenariseerde tomografie skandering is gebruik om die gemiddelde bevolkingspesifieke SWD waardes op 28 gesigslandmerke van 154 swart vroue te bepaal. Die Manchester metode van gesigsrekonstruksie is gebruik om twee skedels, waarvan antemortem foto’s beskikbaar was en wat voorsien is deur die Suid Afrikaanse Polisie Diens (SAPD) se Forensiese Wetenskap Laboratorium, op te bou. Verskeie data stelle vir SWD waardes, naamlik waardes verkry in hierdie studie, twee stelle Amerikaanse waardes vir swart vroue en `n Suid Afrikaanse groep van gemengde afkoms, is vir hierdie studie gebruik om vier gesigte van elk van die skedels te bou. Twee identifikasie sessies is gehou. In die eerste sessie is 30 deelnemers gevra om passende foto’s uit `n algemene versameling van 20 foto’s van swart vroue te kies. Dit het die twee ware gesigte ingesluit. Die identifikasie waardes wat bereken is vir elke foto het getoon dat die hoogste waardes vir die werklike foto’s verkry is op rekonstruksies gebasseer op Suid-Afrikaanse waardes. In die tweede sessie was `n ander groep van 30 vrywillgers gevra om die mees soortgelyke van die vier rekonstruksies by die foto van die betrokke individu te pas. Die rekonstruksies met SWD waardes van die huidige (Suid Afrikaanse) studie was meer dikwels gekies as die van ander data stelle. Hoewel verskeie tekortkominge bestaan, het die identifikasie sessies getoon dat FGR van waarde kan wees. Verder is bevolking-spesifieke SWD waardes belangrik, aangesien skedels wat opgebou is met hierdie waardes statisties beduidend meer dikwels gekies of geïdentifiseer is as die ander. / Dissertation (MSc)--University of Pretoria, 2010. / Anatomy / unrestricted

<p>The subcutaneous injection has emerged as a common approach for self-administration of biotherapeutics due to the patient comfort and cost-effectiveness. However, the available knowledge about transport and absorption of these agents after subcutaneous injection is limited. Here we aim to find drug distribution in the tissue and lymphatic uptake after subcutaneous (SC) injection. In the first part of the study, a mathematical framework to study the subcutaneous drug delivery from injection to lymphatic uptake is presented. A three-dimensional poroelastic model is exploited to find the biomechanical response of the tissue by taking into account tissue deformation during the injection. The results show that including tissue deformability noticeably changes tissue poromechanical response due to the significant dependence of interstitial pressure on tissue deformation. Moreover, the importance of the amount of lymph fluid at the injection site and injection rate on the drug uptake to lymphatic capillaries is highlighted. Finally, the variability of lymphatic uptake due to uncertainty in parameters, including tissue poromechanical and lymphatic absorption parameters, is evaluated. It is found that interstitial pressure due to injection is the major contributing factor in short-term lymphatic absorption, while the amount of lymph fluid at the site of injection determines the long-term absorption of the drug. Finally, it is shown that the lymphatic uptake results are consistent with experimental data available in the literature.</p><p>In the second part, drug transport and distribution in different tissue layers are studied. A single-layer model of the tissue as a base study was first explored. During injection, the difference between the permeability of the solvent and solute results in a higher drug concentration proportional to the inverse of the permeability ratio. Then the effects of layered tissue properties with primary layers, including epidermis, dermis, subcutaneous, and muscle layers, on tissue biomechanical response to injection and drug transport are studied. The drug distributes mainly in the SQ layer due to its lower elastic moduli. Finally, the effect of secondary tissue elements like the deep fascia layer and the network of septa fibers inside the SQ tissue is investigated. The Voronoi algorithm is exploited to create random geometry of the septa network. It is shown how drug molecules accumulate around these tissue components as observed in experimental SC injection. Next, the effect of injection rate on drug concentration is studied. Higher injection rates slightly increase the drug concentration around septa fibers. Finally, it is demonstrated that the concentration-dependent viscosity increases the concentration of biotherapeutics in the direction of septa fibers.</p><p>In the third part of this thesis, a poro-hyperelastic model of the tissue is exploited to find the biomechanical response of the tissue together with a transport model based on an advection-diffusion equation in large-deformation poro-hyperelastic Media. The process of mAbs transport to the lymphatic system is explored. This process has two major parts. First, the initial phase, where mAbs are dispersed in the tissue as a result of momentum exerted by injection. This stage last for only a few minutes after the injection. Then there is the second stage, which can take tens of hours, and as a result, monoclonal antibodies (mAbs) molecules are transported from the subcutaneous layer towards initial lymphatics in the dermis to enter the lymphatic system. In third chapter, both stages are studied. The process of plume formation, interstitial pressure, and velocity development is explored. Then the effect of the injection device, injection site, and sensitivity of long-term lymphatic uptake due to variability in permeability, diffusivity, viscosity, and binding of mAbs are investigated. Then the results are used to find an equivalent lymphatic uptake coefficient that is widely used in pharmacokinetic (PK) models to study the absorption of mAbs. We show that the injection rate is the least, and the injection site is the most important parameter in the uptake of mAbs. Injection depth and mAbs dose also significantly alter lymphatic absorption. Finally, the computational model is validated against experimental studies available in the literature.</p>

This doctoral thesis describes unusual skin and soft-tissue tumors, which were the basis of the postgraduate study of Ladislav Hadravský, MD at Medical faculty in Pilsen of Charles University in Prague during 2013 - 2016. It contains documented cases of skin and soft-tissue tumors related to hereditary syndromes, unusual morphology, rare biological behavior, minor causal association with the respective disease, or different phenotypes. These cases were published in journals with the impact factor and in peer-reviewed journals. Regarding skin tumors, the study focused on sebaceous tumors of the skin, which may occur within Muir-Torre syndrome. In the retrospective study of sebaceous skin tumors, two unusual cases were found: the case of aggressive extraocular sebaceous carcinoma on the scalp in a patient with Muir-Torre syndrome and the case of multiple sebaceous skin tumors in a patient with MUTYH-associated polyposis of the colon mimicking Muir-Torre syndrome. As far as soft-tissue tumors are concerned, the study aimed at the morphological comparison of cases of myxoinflammatory fibroblastic sarcoma and pleomorhic hyalinizing angiectatic tumor.

Introduction: Stenotic nares are one of the most important characteristics of brachycephalic obstructive airway syndrome (BOAS), which was first described in 1949. However, although they have been mentioned in most texts about brachycephalic malformations, few studies have attempted to characterize the nasal entrance of dogs morphologically or functionally, and none of them have described it objectively with landmarks. Recently, as the popularity of brachycephalic dogs has exploded worldwide, innumumberable dogs are suffering from BOAS due to structural malformations. In the point of view of animal welfare, stenotic nares should be objectively evaluated to provide evidence of torture breeding. Objectives: The aim of this study was to objectively measure and thus characterize the nasal entrance stenosis of brachycephalic dogs in comparison to non-brachycephalic dogs. To this end, the following objectives were defined: 1. Our aim is to use three-dimensional (3D) soft-tissue morphometry to objectively measure the externally visible part of the nasal entrance of healthy and brachycephalic dogs. 2. Our aim is to define specific soft-tissue landmarks and parameters to objectively characterize the nasal entrance of dogs. 3. Compare 3D high-resolution scanning with computed tomography (CT) using the newly defined parameters. 4. Reexamine the nasal entrance with 3D scan six months after surgical correction of nasal entrance stenosis (Ala-vestibuloplasty). Animals, Material and Methods: Forty-five brachycephalic and 45 non-brachycephalic dogs were included in this study between 2018 and 2020. All the animals were referred to the Ear, Nose, and Throat Unit of the Small Animal Department at the University of Leipzig, either for surgical correction of BOAS or for endoscopic examination. Animals were excluded if their nasal entrance was potentially affected due to disease or previous surgery. All dogs were scanned with a 3D scanner under general anesthesia using a standardized anesthetic protocol before endoscopic intervention. The 3D scans and CT images were later imported into two advanced software (Amira, Thermo Fisher and Facial Analysis Tool) for objective measurement of the nasal entrance. Intra-observer error and ala-vestibuloplasty (AVP) efficacy of the CT images and 3D scans were tested and compared. All the data were normalized using Shapiro–Wilk normality test. All statistical analyses were later performed using Pearson or Spearman test for correlation, paired t-test, or t-test. Paired t-test was used to test whether the mean difference between pairs of measurements was zero. If it was not the same group of animals, t-test was used instead. Results: We defined new specific soft-tissue landmarks to calculate the nasal opening area (NOA) and stenotic angle (SA) to objectively describe the canine nasal entrance. The NOA and SA were significantly smaller in brachycephalic dogs than in non-brachycephalic dogs, and the NOA was significantly correlated with body weight, whereas SA was not. After nasal entrance correction via AVP, the nasal entrances were 295%left and 233%right larger than before surgery in brachycephalic dogs. Intra-observer reliability was tested with excellent significance through NOA measurements. Comparison between the 3D scanner and CT was measured with the NOA, and it did not show a significant difference between the methods. Conclusion: Obtaining the NOA and SA using 3D surface scans seems to be a reliable and reproducible tool for precise objective evaluation of the visible canine nasal entrance. With the measurement of derived NOA and SA, all the brachycephalic dogs in the study were found to have stenotic nares, and all they required AVP to relieve breathing difficulty. The brachycephalic nasal entrances were increased significantly after AVP, the modified nare correction surgery. We consider the results of our study strong evidence that the breeding of brachycephalic dogs is torture breeding. The restriction of nasal breathing due to the extreme reduction of the nasal entrance to a fraction of the size of that of non-brachycephalic dogs is obvious evidence of this.:1 INTRODUCTION - 1 - 1.1 General Introduction - 1 - 1.2 Objectives - 2 - 2 OVERVIEW OF THE LITERATURE - 3 - 2.1 Brachycephalic Obstructive Airway Syndrome (BOAS) - 3 - 2.1.1 General Introduction of BOAS - 3 - 2.1.2 How to Define Brachycephalic Dogs - 3 - 2.1.3 Commonly Affected Breeds - 4 - 2.2 The Canine Nasal Entrance - 4 - 2.2.1 Anatomy of the Canine Nasal Entrance and Stenosis - 4 - 2.2.2 Pathophysiology of Stenotic Nares in Brachycephalic Dogs - 5 - 2.3 Diagnosis of Stenotic Nares - 9 - 2.3.1 Visual Assessment - 9 - 2.3.2 Nostril Ratio - 11 - 2.3.3 Air Volume of the Nasal Entrance - 11 - 2.4 Development of Morphometry in Brachycephalic Dogs - 11 - 2.5 3D Scanners for 3D Model Reconstruction - 12 - 2.6 Landmarks - 14 - 2.6.1 Introduction of Landmarks - 14 - 2.6.2 Development of Landmarks in Human Medicine - 15 - 2.6.3 Development of Landmarks in Veterinary Medicine - 16 - 2.6.4 Cephalometric Analysis Software - 17 - 3 ANIMALS AND METHODS - 19 - 3.1 Animals - 19 - 3.2 Methods - 19 - 3.2.1 3D Scanning Process and Set-ups of Canine Nasal Entrance - 19 - 3.2.2 Cephalomorphometric Software - 20 - 3.2.3 Cephalometric Landmarks - 20 - 3.2.4 Advanced Morphometric Parameters for Nares - 22 - 3.2.5 Efficacy of Ala-Vestibuloplasty (AVP) - 24 - 3.2.6 Comparison between CT and the 3D Scanning Tool - 24 - 3.2.7 Intra-observer Reliability - 25 - 3.2.8 Statistics - 25 - 4 RESULTS - 26 - 4.1 Brachycephalic Dogs and Non-brachycephalic Dogs - 26 - 4.2 The Nasal Opening Area (NOA) - 28 - 4.3 Efficacy of Ala-Vestibulopasty - 30 - 4.4 Stenotic Angle (SA) - 31 - 4.5 Comparison between CT and the 3D Scanning Tool - 32 - 4.6 Intra-observer Reliability - 34 - 5 DISCUSSION - 36 - 5.1 The Nasal Entrance - 36 - 5.2 Method: the 3D Scanner - 37 - 5.3 Method: Comparison between CT and the 3D Scanner - 38 - 5.4 Method: Landmarks and Reproducibility, Intra-observer Reliability - 39 - 5.5 Nasal Opening Area (NOA) and Efficacy of Ala-Vestibuloplasty (AVP) - 42 - 5.6 Stenotic Angle (SA) - 44 - 5.7 Animal Welfare - 45 - 6 SUMMARY - 47 - 7 ZUSAMMENFASSUNG - 49 - 8 REFERENCES - 51 - / Einleitung: Die Naseneingangstenose ist eine der wichtigsten Merkmale des brachyzephalen Syndroms (BOAS), das erstmals 1949 beschrieben wurde. Obwohl diese komplexe Stenose in den meisten Texten über brachyzephale Fehlbildungen erwähnt wird, haben nur wenige Studien versucht, den Naseneingang von Hunden morphologisch oder funktionell zu charakterisieren. Eine objektive Beschreibung mit Landmarken ist bisher nicht bekannt. In den letzten Jahren ist die Popularität brachyzephaler Hunde weltweit explodiert. Unzählige Hunde leiden aufgrund struktureller Fehlbildungen an BOAS. Unter dem Gesichtspunkt des Tierschutzes sollte die einzige, mit bloßem Auge sichtbare Stenose der oberen Atemwege brachyzephaler Hunde, die Stenose des Naseneingangs objektiv bewertet werden können, um Hinweise auf eine Qualzucht zu belegen. Zielsetzung: Ziel dieser Studie war es, den Naseneingang von brachyzephalen Hunden im Vergleich zu nicht-brachyzephalen Hunden objektiv zu messen und damit die Stenose des Naseneingangs zu charakterisieren und eine chirurgische Therapie, die Ala-Vestibuloplastie (AVP), zu evaluieren. Zu diesem Zweck wurden die folgenden Ziele definiert: 1. Anwendung der dreidimensionalen (3D) Weichteilmorphometrie zur objektiven Messung des äußerlich sichtbaren Teils des Naseneingangs von gesunden und brachyzephalen Hunden. 2. Definition spezifischer Weichteil-Landmarken und Parameter zur objektiven Charakterisierung des Naseneingangs von Hunden. 3. Methoden-Vergleich zwischen den hochauflösenden 3D-Scans und der Computertomographie (CT) unter Verwendung der neu definierten Parameter. 4. Kontrolluntersuchung mit 3D-Scan sechs Monate nach der chirurgischen Korrektur der Naseneingangsstenose (Ala-Vestibuloplastik). Tiere und Methoden: 45 brachyzephale und 45 nicht-brachyzephale Hunde wurden zwischen 2018 und 2020 in diese Studie aufgenommen und wurden an die Hals-Nasen-Ohren-Abteilung der Kleintierklinik der Universität Leipzig überwiesen, zur endoskopischen Untersuchung der oberen Atemwege und gegebenenfalls zur chirurgischen Korrektur der BOAS-assozierten Stenosen. Ausgeschlossen wurden Tiere, deren Naseneingang aufgrund von Krankheiten oder einer früheren Operation verändert war. Alle Hunde wurden nach einem standardisierten Anästhesieprotokoll anästhesiert, ein Computertomogramm des Kopfes erstellt und vor dem endoskopischen Eingriff wurde der Kopf mit einem 3D-Scanner gescannt. Die 3D-Scans und CT-Bilder wurden in zwei Softwareprogramme (Amira, Thermo Fisher und Facial Analysis Tool) zur objektiven Messung des Naseneingangs importiert. Zur genauen Charakterisierung wurden neue Landmarken am Naseneingang definiert und zur Berechnung von zwei neuen, abgeleiteten Parametern, der Nasenöffnungsfläche (NOA) und dem stenotischen Winkel (SA) verwendet. Der Intraobserver-Fehler und die Wirksamkeit der Ala-Vestibuloplastie wurden anhand der CT-Bilder und 3D-Scans mit demselben Verfahren geprüft und verglichen. Alle statistischen Analysen wurden später mit dem Pearson-Test oder dem Spearman-Test für die Korrelation, dem gepaarten t-Test oder dem t-Test durchgeführt. Der gepaarte t-Test wurde verwendet, um zu prüfen, ob der Mittelwertunterschied zwischen Paaren von Messungen gleich Null war. Handelte es sich nicht um dieselbe Gruppe von Tieren, wurde stattdessen der t-Test verwendet. Ergebnisse: Mit den neu definierten spezifischen Weichteil-Landmarken und den abgeleiteten Parametern NOA und SA konnte der Naseneingang aller brachyzephalen und nicht-brachyzephalen Hunde objektiv beschrieben werden. NOA und SA waren bei brachyzephalen Hunden signifikant kleiner als bei nicht-brachyzephalen Hunden. NOA korrelierte in beiden Gruppen signifikant mit dem Körpergewicht. Dagegen zeigte SA keine Korrelation mit dem Körpergewicht. Nach der chirurgischen AVP waren die Naseneingänge bei allen brachyzephalen Hunden größer als vor der Operation, mit einer Zunahme der NOA links um 295 % und rechts um 233 %. Die Intraobserver-Zuverlässigkeit wurde durch NOA-Messungen getestet und war hoch signifikant. Zum Methoden-Vergleich zwischen 3D-Scanner und CT wurde die Nasenöffnungsfläche jeweils am gemessen und zeigte keinen signifikanten Unterschied zwischen den Methoden. Schlussfolgerungen: Morphometrische Messungen mit 3D-Oberflächenscans scheinen ein zuverlässiges und reproduzierbares Instrument zur präzisen, objektiven Bewertung des Naseneingangs des Hundes zu sein. Bei der Messung der abgeleiteten Flächen (NOA) und Winkel (SA) wurde bei allen brachyzephalen Hunden dieser Studie eine Naseneingangsstenose festgestellt. Nach der chirurgischen Korrektur der brachyzephalen Naseneingangsstenose, der AVP, waren die Nasenöffnungen deutlich vergrößert. Die Einschränkung der Nasenatmung durch die extreme Verkleinerung des Naseneingangs auf einen Bruchteil der Größe von nicht-brachyzephalen Hunden, betrachten wir als eindeutigen Beweis dafür, dass die Zucht von brachyzephalen Hunden eine Qualzucht ist.:1 INTRODUCTION - 1 - 1.1 General Introduction - 1 - 1.2 Objectives - 2 - 2 OVERVIEW OF THE LITERATURE - 3 - 2.1 Brachycephalic Obstructive Airway Syndrome (BOAS) - 3 - 2.1.1 General Introduction of BOAS - 3 - 2.1.2 How to Define Brachycephalic Dogs - 3 - 2.1.3 Commonly Affected Breeds - 4 - 2.2 The Canine Nasal Entrance - 4 - 2.2.1 Anatomy of the Canine Nasal Entrance and Stenosis - 4 - 2.2.2 Pathophysiology of Stenotic Nares in Brachycephalic Dogs - 5 - 2.3 Diagnosis of Stenotic Nares - 9 - 2.3.1 Visual Assessment - 9 - 2.3.2 Nostril Ratio - 11 - 2.3.3 Air Volume of the Nasal Entrance - 11 - 2.4 Development of Morphometry in Brachycephalic Dogs - 11 - 2.5 3D Scanners for 3D Model Reconstruction - 12 - 2.6 Landmarks - 14 - 2.6.1 Introduction of Landmarks - 14 - 2.6.2 Development of Landmarks in Human Medicine - 15 - 2.6.3 Development of Landmarks in Veterinary Medicine - 16 - 2.6.4 Cephalometric Analysis Software - 17 - 3 ANIMALS AND METHODS - 19 - 3.1 Animals - 19 - 3.2 Methods - 19 - 3.2.1 3D Scanning Process and Set-ups of Canine Nasal Entrance - 19 - 3.2.2 Cephalomorphometric Software - 20 - 3.2.3 Cephalometric Landmarks - 20 - 3.2.4 Advanced Morphometric Parameters for Nares - 22 - 3.2.5 Efficacy of Ala-Vestibuloplasty (AVP) - 24 - 3.2.6 Comparison between CT and the 3D Scanning Tool - 24 - 3.2.7 Intra-observer Reliability - 25 - 3.2.8 Statistics - 25 - 4 RESULTS - 26 - 4.1 Brachycephalic Dogs and Non-brachycephalic Dogs - 26 - 4.2 The Nasal Opening Area (NOA) - 28 - 4.3 Efficacy of Ala-Vestibulopasty - 30 - 4.4 Stenotic Angle (SA) - 31 - 4.5 Comparison between CT and the 3D Scanning Tool - 32 - 4.6 Intra-observer Reliability - 34 - 5 DISCUSSION - 36 - 5.1 The Nasal Entrance - 36 - 5.2 Method: the 3D Scanner - 37 - 5.3 Method: Comparison between CT and the 3D Scanner - 38 - 5.4 Method: Landmarks and Reproducibility, Intra-observer Reliability - 39 - 5.5 Nasal Opening Area (NOA) and Efficacy of Ala-Vestibuloplasty (AVP) - 42 - 5.6 Stenotic Angle (SA) - 44 - 5.7 Animal Welfare - 45 - 6 SUMMARY - 47 - 7 ZUSAMMENFASSUNG - 49 - 8 REFERENCES - 51 -

Background: The shoulder joint is one of the most freely movable joints in the human body and has therefore high importance for upper limb functionality. Several techniques have been developed to replace the glenohumeral joint including humeral hemiarthroplasty, anatomical total shoulder arthroplasty, and reverse total shoulder arthroplasty, depending on the underlying pathology. For the soft tissue reconstruction, the innervated latissimus dorsi musculocutaneous flap is a reliable solution flap in shoulder and arm reconstruction. - Case presentation: We present the case of a 16-year-old male patient with a complete destruction of the shoulder joint and soft tissues after ballistic trauma. We performed the reconstruction of the shoulder joint using a humeral hemiarthroplasty with a mesh fixation to the remaining glenoid. The soft tissue coverage and the restoration of the deltoid muscle function were insured with a pedicled innervated latissimus dorsi musculocutaneous flap. One year postoperatively, the patient showed a good function of the shoulder joint with an excellent aesthetical result and no pain. - Conclusion: The pedicled latissimus dorsi musculocutaneous flap can safely restore the shoulder function, while the humeral hemiarthroplasty with mesh fixation can be a reliable solution for the reconstruction of a completely destructed shoulder joint.