Nodal staging in head and neck squamous cell carcinoma by combining different imaging techniques

Head and neck cancer accounts for around 4% of all malignancies. The presence of cervical lymph node metastases will reduce expected survival with approximately 50%. Therapy should thus be as effective as possible with a minimum of therapeutic side effects and depends next to tumour size on the presence or absence of nodal metastases. Physical examination and imaging with magnetic resonance imaging (MRI), positron emission tomography – computed tomography (PET-CT), ultrasound (US), ultrasound guided fine needle aspiration (USgFNAC) are commonly used to examine cervical lymph node metastases, but in 30% of the cases, they are still overlooked. New imaging techniques such as real time image fusion of ultrasound and PET-CT and micro flow imaging (MFI) are thus developed. The aim of this thesis was to improve the detection rate of lymph node metastases by improving the selection criteria of nodes for ultrasound guided fine needle aspiration to prove cytological malignancy.<br/

Plant-based oral care product exhibits antibacterial effects on different stages of oral multispecies biofilm development in vitro

Background: Excessive biofilm formation on surfaces in the oral cavity is amongst the main reasons for severe infection development like periodontitis and peri-implantitis. Mechanical biofilm removal as well as the use of adjuvant antiseptics supports the prevention of pathogenic biofilm formation. Recently, the antibacterial effect of the oral care product REPHA-OS®, based on medicinal plant extracts and essential oils, has been demonstrated on oral pathogens grown on agar plates. In the present study, the effectiveness of the product on medical relevant oral biofilm development should be demonstrated for the first time. Methods: An established in vitro oral multispecies biofilm, composed of Streptococcus oralis, Actinomyces naeslundii, Veillonella dispar and Porphyromonas gingivalis, was used to analyze the antibacterial effect of different REPHA-OS® concentrations on planktonic bacteria, biofilm formation and mature biofilms. It was quantified using metabolic activity assays and live/dead fluorescence staining combined with three-dimensional confocal laser-scanning microscopy. Additionally, effects on species distribution inside the biofilm were assessed by means of quantitative real-time PCR. Results: REPHA-OS® showed statistically significant antimicrobial effects on all stages of biofilm development: a minimal inhibitory concentration of 5% could be detected for both, for planktonic bacteria and for biofilm formation. Interestingly, only a slightly higher concentration of 10% was necessary to completely kill all bacteria in mature biofilms also. In contrast, an influence on the biofilm matrix or the species distribution could not be observed. The effect could be attributed to the herbal ingredients, not to the contained ethanol. Conclusion: The strong antibacterial effect of REPHA-OS® on different stages of oral biofilm development strengthens its application as an alternative adjuvant in oral care therapies

Influence of the Available Surface Area and Cell Elasticity on Bacterial Adhesion Forces on Highly Ordered Silicon Nanopillars

[Image: see text] Initial bacterial adhesion to solid surfaces is influenced by a multitude of different factors, e.g., roughness and stiffness, topography on the micro- and nanolevel, as well as chemical composition and wettability. Understanding the specific influences and possible interactive effects of all of these factors individually could lead to guidance on bacterial adhesion and prevention of unfavorable consequences like medically relevant biofilm formation. On this way, the aim of the present study was to identify the specific influence of the available surface area on the adhesion of clinically relevant bacterial strains with different membrane properties: Gram-positive Staphylococcus aureus and Gram-negative Aggregatibacter actinomycetemcomitans. As model surfaces, silicon nanopillar specimens with different spacings were fabricated using electron beam lithography and cryo-based reactive ion etching techniques. Characterization by scanning electron microscopy and contact angle measurement revealed almost defect-free highly ordered nanotopographies only varying in the available surface area. Bacterial adhesion forces to these specimens were quantified by means of single-cell force spectroscopy exploiting an atomic force microscope connected to a microfluidic setup (FluidFM). The nanotopographical features reduced bacterial adhesion strength by reducing the available surface area. In addition, the strain-specific interaction in detail depended on the bacterial cell’s elasticity and deformability as well. Analyzed by confocal laser scanning microscopy, the obtained results on bacterial adhesion forces could be linked to the subsequent biofilm formation on the different topographies. By combining two cutting-edge technologies, it could be demonstrated that the overall bacterial adhesion strength is influenced by both the simple physical interaction with the underlying nanotopography and its available surface area as well as the deformability of the cell

Biofilmvolumen und Azidifizierung in den ersten in situ auf bukkal und palatinal exponiertem Bracketmaterial gebildeten Biofilmen

Purpose: Acidification by bacterial biofilms at the bracket/tooth interface is one of the most common problems in fixed orthodontic treatments, which can lead to white spot lesions (WSL) and caries. As lingual brackets were shown to exhibit reduced WSL formation clinically, the aim of this in situ study was to compare initial intraoral biofilm formation and acidification on bracket-like specimens placed buccally and palatally in the upper jaw as a possible cause for this observation. Methods: Intraoral biofilm was collected from splints equipped with buccally and palatally exposed test specimens, which were worn by 12 volunteers for a total of 48 h. The test specimens consisted of standard bracket material cylinders on top of a hydroxyapatite disc to represent the bracket/tooth interface. They were analyzed for three-dimensional biofilm volume and live/dead distribution by fluorescence staining and confocal laser scanning microscopy as well as for acidification by fluorescence-based pH ratiometry. Results: Similar general biofilm morphology with regard to volume and viability could be detected for buccally and palatally exposed specimens. For pH values, biofilms from both positions showed increased acidification at the bottom layer. Interestingly, the pH value at the top layers of the biofilms was slightly lower on palatally than on buccally exposed specimens, which may likely be due to anatomic conditions. Conclusion: Based on the results of this study, initial intraoral biofilm formation and acidification is almost similar on the bracket material/biomimetic tooth interface when placed buccally or palatally in the upper jaw. As lingual brackets were shown to exhibit reduced WSL formation clinically, future studies should investigate further factors like bracket geometry.Zielsetzung: Die durch bakterielle Biofilme verursachte Ansäuerung an der Bracket/Zahn-Grenzfläche ist eines der häufigsten Probleme während der festsitzenden kieferorthopädischen Behandlung, das zu White-Spot-Läsionen (WSL) und Karies führen kann. Da linguale Multibracketapparaturen klinisch eine verminderte WSL-Bildung aufweisen, war das Ziel dieser In-situ-Studie, die initiale intraorale Biofilmbildung und Ansäuerung an bukkal und palatinal im Oberkiefer platzierten Bracket-ähnlichen Probekörpern als mögliche Ursache zu analysieren. Methoden: Mit Probekörpern bestückte Miniplastschienen dienten der intraoralen Biofilmgewinnung in 12 Probanden für insgesamt 48 h. Die Probekörper wurden bukkal und palatinal platziert und bestanden aus Standard-Bracketmaterialzylindern, welche auf Hydroxylapatitscheiben befestigt wurden, sodass die Bracket/Zahn-Grenzfläche imitiert werden konnte. Die Analyse des dreidimensionalen Biofilmvolumens und der Lebend/tot-Verteilung erfolgte durch Fluoreszenzfärbung und konfokale Laserscanningmikroskopie. Die Auswertung der Ansäuerung erfolgte durch fluoreszenzbasierte pH-Ratiometrie. Ergebnisse: In Bezug auf das Volumen und die Viabilität konnte für bukkal und palatinal exponierte Probekörper eine allgemein ähnliche Biofilmmorphologie nachgewiesen werden. An beiden Positionen war eine erhöhte Ansäuerung in den unteren Schichten des Biofilms zu detektieren. Interessanterweise war der pH-Wert in den obersten Schichten der Biofilme bei palatinal positionierten Probekörpern etwas niedriger als bei bukkal positionierten Probekörpern, was vermutlich durch anatomische Gegebenheiten bedingt ist. Schlussfolgerung: Basierend auf den Ergebnissen dieser Studie ist die initiale intraorale Biofilmbildung und Ansäuerung an der Grenzfläche zwischen Bracketmaterial und biomimetischem Zahn bei bukkaler bzw. palatinaler Platzierung im Oberkieferbereich ähnlich. Da linguale Multibracketapparaturen klinisch eine reduzierte WSL-Bildung aufweisen, sollten zukünftige Studien weitere Faktoren wie die Bracketgeometrie untersuchen

Multilayered Adsorption of Commensal Microflora on Implant Surfaces: an Unconventional and Innovative Method to Prevent Bacterial Infections Associated with Biomaterials

Biomaterials may be colonized with infectious biofilms and this frequently leads to progressive loss of tissue. Bacteria encased within biofilms resist antibiotics and the host immune system. With life-threatening complications and the antibiotic resistance crisis, novel therapeutic approaches are essentially required to treat biofilm infections. Commensal microflora—particularly streptococci—modulate the immune system's ability to protect from pathogens. In imitation of this natural phenomenon, the present study describes a novel method of applying the commensal, Streptococcus oralis, as a coating on implants to prevent infectious biofilms. Implants are coated with a simple thermal process to circumvent sepsis persuaded by live microflora and for a stable multilayered coating. Titanium discs coated with S. oralis antagonize the biofilm-making capabilities of single, dual, or multispecies periodontal pathogens: Porphyromonas gingivalis, Treponema denticola, Veillonella dispar, and Actinomyces naeslundii—under both static and flow conditions. The bacterial adhesion force measured with atomic force microscopy (AFM) reduces on coated titanium suggesting that electrostatic interactions are mainly responsible for the decrease in maximum adhesion peak. Importantly, S. oralis coated implants are compatible with human gingival fibroblasts. S. oralis coating may provide a potent novel approach to prevent potentially fatal biofilm infections on biomaterials

Antibacterial properties and abrasion-stability: Development of a novel silver-compound material for orthodontic bracket application

Purpose: Bacteria-induced white spot lesions are a common side effect of modern orthodontic treatment. Therefore, there is a need for novel orthodontic bracket materials with antibacterial properties that also resist long-term abrasion. The aim of this study was to investigate the abrasion-stable antibacterial properties of a newly developed, thoroughly silver-infiltrated material for orthodontic bracket application in an in situ experiment. Methods: To generate the novel material, silver was vacuum-infiltrated into a sintered porous tungsten matrix. A tooth brushing simulation machine was used to perform abrasion equal to 2 years of tooth brushing. The material was characterized by energy dispersive X‑ray (EDX) analysis and roughness measurement. To test for antibacterial properties in situ, individual occlusal splints equipped with specimens were worn intraorally by 12 periodontal healthy patients for 48 h. After fluorescence staining, the quantitative biofilm volume and live/dead distribution of the initial biofilm formation were analyzed by confocal laser scanning microscopy (CLSM). Results: Silver was infiltrated homogeneously throughout the tungsten matrix. Toothbrush abrasion only slightly reduced the material’s thickness similar to conventional stainless steel bracket material and did not alter surface roughness. The new silver-modified material showed significantly reduced biofilm accumulation in situ. The effect was maintained even after abrasion. Conclusion: A promising, novel silver-infiltrated abrasion-stable material for use as orthodontic brackets, which also exhibit strong antibacterial properties on in situ grown oral biofilms, was developed. The strong antibacterial properties were maintained even after surface abrasion simulated with long-term toothbrushing

Evaluation of Streptococcus oralis adhesion and biofilm formation on laser-processed titanium

To prevent implant-associated infections, surface modifications need to be developed that prevent bacterial colonisation and biofilm formation. In the present study, titanium surfaces were processed by nanosecond-pulsed laser ablation to generate a variety of different structures (anatase, rutile, Osteon, as well as Osteon additionally coated with silver and clove nanoparticles). Analysis of adhesion and biofilm formation of the oral pioneer bacterium Streptococcus oralis could demonstrate antibacterial properties of anatase surfaces. For clinical translation, the effect should be enhanced by further adaption and combined with the osseointegrative Osteon structur

PH-responsive release of chlorhexidine from modified nanoporous silica nanoparticles for dental applications

A pH-sensitive stimulus-response system for controlled drug release was prepared by modifying nanoporous silica nanoparticles (NPSNPs) with poly(4-vinylpyridine) using a bismaleimide as linker. At physiological pH values, the polymer serves as gate keeper blocking the pore openings to prevent the release of cargo molecules. At acidic pH values as they can occur during a bacterial infection, the polymer strains become protonated and straighten up due to electrostatic repulsion. The pores are opened and the cargo is released. The drug chlorhexidine was loaded into the pores because of its excellent antibacterial properties and low tendency to form resistances. The release was performed in PBS and diluted hydrochloric acid, respectively. The results showed a considerably higher release in acidic media compared to neutral solvents. Reversibility of this pH-dependent release was established. In vitro tests proved good cytocompatibility of the prepared nanoparticles. Antibacterial activity tests with Streptococcus mutans and Staphylococcus aureus revealed promising perspectives of the release system for biofilm prevention. The developed polymer-modified silica nanoparticles can serve as an efficient controlled drug release system for long-term delivery in biomedical applications, such as in treatment of biofilm-associated infections, and could, for example, be used as medical implant coating or as components in dental composite materials

Adhesion Forces of Oral Bacteria to Titanium and the Correlation with Biophysical Cellular Characteristics

Bacterial adhesion to dental implants is the onset for the development of pathological biofilms. Reliable characterization of this initial process is the basis towards the development of anti-biofilm strategies. In the present study, single-cell force spectroscopy (SCFS), by means of an atomic force microscope connected to a microfluidic pressure control system (FluidFM), was used to comparably measure adhesion forces of different oral bacteria within a similar experimental setup to the common implant material titanium. The bacteria selected belong to different ecological niches in oral biofilms: the commensal pioneers Streptococcus oralis and Actinomyces naeslundii; secondary colonizer Veillonella dispar; and the late colonizing pathogens Porphyromonas gingivalis as well as fimbriated and non-fimbriated Aggregatibacter actinomycetemcomitans. The results showed highest values for early colonizing pioneer species, strengthening the link between adhesion forces and bacteria’s role in oral biofilm development. Additionally, the correlation between biophysical cellular characteristics and SCFS results across species was analyzed. Here, distinct correlations between electrostatically driven maximum adhesion force, bacterial surface elasticity and surface charge as well as single-molecule attachment points, stretching capability and metabolic activity, could be identified. Therefore, this study provides a step towards the detailed understanding of oral bacteria initial adhesion and could support the development of infection-resistant implant materials in future

Injury patterns and emergency department mortality after unsuccessful suicide : a descriptive study of a consecutive case series

We hypothesized that trauma bay management and 24-hour emergency department (ED) mortality of patients that survived unsuccessful suicide attempts differ from other patients. Severely injured patients after an unsuccessful suicide attempt can be admitted to resuscitation rooms of any ED. To our knowledge, 24-hour mortality has not been investigated yet. We studied such patients admitted to the resuscitation room of a large ED. This consecutive case series included 64 patients who were evaluated in the resuscitation room because of an unsuccessful suicide attempt. Patient variables were recorded including method of suicide attempt, injuries, hemodynamic status, and treatment. Most patients were male [57 patients (89%)], and the most frequent methods were ingestion of harmful devices or substances [15 patients (23%)]; hanging [9 patients (14%)]; and strangulation [9 patients (14%)]. There were 2 patients who died in the ED: 1 from a self-inflicted gunshot to the head and the other from self-inflicted herbal poisoning. The frequency of emergency airway intervention was greater in patients after unsuccessful attempted suicide [18 patients, 28% (95% confidence interval [CI], 17.2%, 39%; endotracheal intubation, 17 patients; emergency tracheotomy, 1 patient] than all ED patients [1458 patients (16%); (95% CI, 14.9%, 16.4%; P = 0.005)]. Following attempted survived suicide, 24-hour ED mortality was 3% and 4% within the control group; the difference is insignificant (P = 0.9596). However, ED mortality showed a trend toward earlier death within the suicidal group. Resuscitation room mortality of patients that survived unsuccessful suicide does not differ from the general population of an ED resuscitation room