Dokument-ID Dokumenttyp Verfasser/Autoren Herausgeber Haupttitel Abstract Auflage Verlagsort Verlag Erscheinungsjahr Seitenzahl Schriftenreihe Titel Schriftenreihe Bandzahl ISBN Quelle der Hochschulschrift Konferenzname Quelle:Titel Quelle:Jahrgang Quelle:Heftnummer Quelle:Erste Seite Quelle:Letzte Seite URN DOI Abteilungen OPUS4-31102 Wissenschaftlicher Artikel Kämmerer, Peer W.; Tribius, Silke; Cohrs, Lena; Engler, Gabriel; Ettl, Tobias; Freier, Kolja; Frerich, Bernhard; Ghanaati, Shahram; Gosau, Martin; Haim, Dominik; Hartmann, Stefan; Heiland, Max; Herbst, Manuel; Hoefert, Sebastian; Hoffmann, Jürgen; Hölzle, Frank; Howaldt, Hans-Peter; Kreutzer, Kilian; Leonhardt, Henry; Lutz, Rainer; Moergel, Maximilian; Modabber, Ali; Neff, Andreas; Pietzka, Sebastian; Rau, Andrea; Reichert, Torsten E.; Smeets, Ralf; Sproll, Christoph; Steller, Daniel; Wiltfang, Jörg; Wolff, Klaus-Dietrich; Kronfeld, Kai; Al-Nawas, Bilal Adjuvant radiotherapy in patients with squamous cell carcinoma of the oral cavity or oropharynx and solitary ipsilateral lymph node metastasis (pN1) — a prospective multicentric cohort study (1) Background: Evaluation of impact of adjuvant radiation therapy (RT) in patients with oral squamous cell carcinoma of the oral cavity/oropharynx (OSCC) of up to 4 cm (pT1/pT2) and solitary ipsilateral lymph node metastasis (pN1). A non-irradiated group with clinical follow-up was chosen for control, and survival and quality of life (QL) were compared; (2) Methods: This prospective multicentric comprehensive cohort study included patients with resected OSCC (pT1/pT2, pN1, and cM0) who were allocated into adjuvant radiation therapy (RT) or observation. The primary endpoint was overall survival. Secondary endpoints were progression-free survival and QL after surgery; (3) Results: Out of 27 centers, 209 patients were enrolled with a median follow-up of 3.4 years. An amount of 137 patients were in the observation arm, and 72 received adjuvant irradiation. Overall survival did not differ between groups (hazard ratio (HR) 0.98 [0.55-1.73], p = 0.94). There were fewer neck metastases (HR 0.34 [0.15-0.77]; p = 0.01), as well as fewer local recurrences (HR 0.41 [0.19-0.89]; p = 0.02) under adjuvant RT. For QL, irradiated patients showed higher values for the symptom scale pain after 0.5, two, and three years (all p < 0.05). After six months and three years, irradiated patients reported higher symptom burdens (impaired swallowing, speech, as well as teeth-related problems (all p < 0.05)). Patients in the RT group had significantly more problems with mouth opening after six months, one, and two years (p < 0.05); (4) Conclusions: Adjuvant RT in patients with early SCC of the oral cavity and oropharynx does not seem to influence overall survival, but it positively affects progression-free survival. However, irradiated patients report a significantly decreased QL up to three years after therapy compared to the observation group. 2023 Cancers 15 6 urn:nbn:de:bvb:20-opus-311024 10.3390/cancers15061833 Klinik und Poliklinik für Mund-, Kiefer- und Plastische Gesichtschirurgie OPUS4-11036 Wissenschaftlicher Artikel Hartmann, Stefan; Lessner, Grit; Mentzel, Thomas; Kübler, Alexander C.; Müller-Richter, Urs An adult spindle cell rhabdomyosarcoma in the head and neck region with long-term survival: a case report Introduction Spindle cell rhabdomyosarcoma of the head and neck is a very rare tumor in adults. We report on one case with long-term survival. Case presentation A 41-year-old nonsmoking Caucasian man presented in June 2007 with a painless swelling under his tongue. A diagnosis of a soft tissue sarcoma, and a myofibrosarcoma in particular, was made via biopsy. After multimodal treatment, including local and systemic therapy, our patient remained disease-free until September 2010. The local recurrence was treated unsuccessfully with various chemotherapy regimens. In September 2011, our patient underwent surgical resection again, and a spindle cell rhabdomyosarcoma was diagnosed. To analyze the mismatch between the original diagnosis of a myofibrosarcoma and the second diagnosis, the two specimens were reassessed, and a final diagnosis of a spindle cell rhabdomyosarcoma was made. In 2012 and 2013, our patient suffered further recurrences that were surgically treated, and he is still alive with disease six years and 10 months after the initial diagnosis in June 2007. Conclusions In adults, the spindle cell rhabdomyosarcoma tumor is very rare in the head and neck region. In contrast to childhood tumors, spindle cell rhabdomyosarcoma in adulthood is often associated with a poor prognosis. In the present case, the radical surgical treatment might have helped to prolong the patient's overall survival, which has lasted more than six years. To our knowledge, this is the longest overall survival reported so far for this tumor entity in the head and neck region. 2014 urn:nbn:de:bvb:20-opus-110362 10.1186/1752-1947-8-208 Pathologisches Institut OPUS4-27881 Wissenschaftlicher Artikel Vollmer, Andreas; Saravi, Babak; Vollmer, Michael; Lang, Gernot Michael; Straub, Anton; Brands, Roman C.; Kübler, Alexander; Gubik, Sebastian; Hartmann, Stefan Artificial intelligence-based prediction of oroantral communication after tooth extraction utilizing preoperative panoramic radiography Oroantral communication (OAC) is a common complication after tooth extraction of upper molars. Profound preoperative panoramic radiography analysis might potentially help predict OAC following tooth extraction. In this exploratory study, we evaluated n = 300 consecutive cases (100 OAC and 200 controls) and trained five machine learning algorithms (VGG16, InceptionV3, MobileNetV2, EfficientNet, and ResNet50) to predict OAC versus non-OAC (binary classification task) from the input images. Further, four oral and maxillofacial experts evaluated the respective panoramic radiography and determined performance metrics (accuracy, area under the curve (AUC), precision, recall, F1-score, and receiver operating characteristics curve) of all diagnostic approaches. Cohen's kappa was used to evaluate the agreement between expert evaluations. The deep learning algorithms reached high specificity (highest specificity 100% for InceptionV3) but low sensitivity (highest sensitivity 42.86% for MobileNetV2). The AUCs from VGG16, InceptionV3, MobileNetV2, EfficientNet, and ResNet50 were 0.53, 0.60, 0.67, 0.51, and 0.56, respectively. Expert 1-4 reached an AUC of 0.550, 0.629, 0.500, and 0.579, respectively. The specificity of the expert evaluations ranged from 51.74% to 95.02%, whereas sensitivity ranged from 14.14% to 59.60%. Cohen's kappa revealed a poor agreement for the oral and maxillofacial expert evaluations (Cohen's kappa: 0.1285). Overall, present data indicate that OAC cannot be sufficiently predicted from preoperative panoramic radiography. The false-negative rate, i.e., the rate of positive cases (OAC) missed by the deep learning algorithms, ranged from 57.14% to 95.24%. Surgeons should not solely rely on panoramic radiography when evaluating the probability of OAC occurrence. Clinical testing of OAC is warranted after each upper-molar tooth extraction. 2022 Diagnostics 12 6 urn:nbn:de:bvb:20-opus-278814 10.3390/diagnostics12061406 Klinik und Poliklinik für Mund-, Kiefer- und Plastische Gesichtschirurgie OPUS4-31271 Wissenschaftlicher Artikel Vollmer, Andreas; Vollmer, Michael; Lang, Gernot; Straub, Anton; Shavlokhova, Veronika; Kübler, Alexander; Gubik, Sebastian; Brands, Roman; Hartmann, Stefan; Saravi, Babak Associations between periodontitis and COPD: An artificial intelligence-based analysis of NHANES III A number of cross-sectional epidemiological studies suggest that poor oral health is associated with respiratory diseases. However, the number of cases within the studies was limited, and the studies had different measurement conditions. By analyzing data from the National Health and Nutrition Examination Survey III (NHANES III), this study aimed to investigate possible associations between chronic obstructive pulmonary disease (COPD) and periodontitis in the general population. COPD was diagnosed in cases where FEV (1)/FVC ratio was below 70% (non-COPD versus COPD; binary classification task). We used unsupervised learning utilizing k-means clustering to identify clusters in the data. COPD classes were predicted with logistic regression, a random forest classifier, a stochastic gradient descent (SGD) classifier, k-nearest neighbors, a decision tree classifier, Gaussian naive Bayes (GaussianNB), support vector machines (SVM), a custom-made convolutional neural network (CNN), a multilayer perceptron artificial neural network (MLP), and a radial basis function neural network (RBNN) in Python. We calculated the accuracy of the prediction and the area under the curve (AUC). The most important predictors were determined using feature importance analysis. Results: Overall, 15,868 participants and 19 feature variables were included. Based on k-means clustering, the data were separated into two clusters that identified two risk characteristic groups of patients. The algorithms reached AUCs between 0.608 (DTC) and 0.953% (CNN) for the classification of COPD classes. Feature importance analysis of deep learning algorithms indicated that age and mean attachment loss were the most important features in predicting COPD. Conclusions: Data analysis of a large population showed that machine learning and deep learning algorithms could predict COPD cases based on demographics and oral health feature variables. This study indicates that periodontitis might be an important predictor of COPD. Further prospective studies examining the association between periodontitis and COPD are warranted to validate the present results. 2022 Journal of Clinical Medicine 11 23 urn:nbn:de:bvb:20-opus-312713 10.3390/jcm11237210 Klinik und Poliklinik für Mund-, Kiefer- und Plastische Gesichtschirurgie OPUS4-30505 Wissenschaftlicher Artikel Vollmer, Andreas; Vollmer, Michael; Lang, Gernot; Straub, Anton; Kübler, Alexander; Gubik, Sebastian; Brands, Roman C.; Hartmann, Stefan; Saravi, Babak Automated assessment of radiographic bone loss in the posterior maxilla utilizing a multi-object detection artificial intelligence algorithm Periodontitis is one of the most prevalent diseases worldwide. The degree of radiographic bone loss can be used to assess the course of therapy or the severity of the disease. Since automated bone loss detection has many benefits, our goal was to develop a multi-object detection algorithm based on artificial intelligence that would be able to detect and quantify radiographic bone loss using standard two-dimensional radiographic images in the maxillary posterior region. This study was conducted by combining three recent online databases and validating the results using an external validation dataset from our organization. There were 1414 images for training and testing and 341 for external validation in the final dataset. We applied a Keypoint RCNN with a ResNet-50-FPN backbone network for both boundary box and keypoint detection. The intersection over union (IoU) and the object keypoint similarity (OKS) were used for model evaluation. The evaluation of the boundary box metrics showed a moderate overlapping with the ground truth, revealing an average precision of up to 0.758. The average precision and recall over all five folds were 0.694 and 0.611, respectively. Mean average precision and recall for the keypoint detection were 0.632 and 0.579, respectively. Despite only using a small and heterogeneous set of images for training, our results indicate that the algorithm is able to learn the objects of interest, although without sufficient accuracy due to the limited number of images and a large amount of information available in panoramic radiographs. Considering the widespread availability of panoramic radiographs as well as the increasing use of online databases, the presented model can be further improved in the future to facilitate its implementation in clinics. 2023 Applied Sciences 13 3 urn:nbn:de:bvb:20-opus-305050 10.3390/app13031858 Klinik und Poliklinik für Mund-, Kiefer- und Plastische Gesichtschirurgie OPUS4-29741 Wissenschaftlicher Artikel Straub, Anton; Stapf, Maximilian; Fischer, Markus; Vollmer, Andreas; Linz, Christian; Lâm, Thiên-Trí; Kübler, Alexander; Brands, Roman C.; Scherf-Clavel, Oliver; Hartmann, Stefan Bone concentration of ampicillin/sulbactam: a pilot study in patients with osteonecrosis of the jaw Osteonecrosis of the jaw (ONJ) occurs typically after irradiation of the head and neck area or after the intake of antiresorptive agents. Both interventions can lead to compromised bone perfusion and can ultimately result in infection and necrosis. Treatment usually consists of surgical necrosectomy and prolonged antibiotic therapy, usually through beta-lactams such as ampicillin/sulbactam. The poor blood supply in particular raises the question as to whether this form of antibiosis can achieve sufficient concentrations in the bone. Therefore, we investigated the antibiotic concentration in plasma and bone samples in a prospective study. Bone samples were collected from the necrosis core and in the vital surrounding bone. The measured concentrations in plasma for ampicillin and sulbactam were 126.3 ± 77.6 and 60.2 ± 35.0 µg/mL, respectively. In vital bone and necrotic bone samples, the ampicillin/sulbactam concentrations were 6.3 ± 7.8/1.8 ± 2.0 µg/g and 4.9 ± 7.0/1.7 ± 1.7 µg/g, respectively. These concentrations are substantially lower than described in the literature. However, the concentration seems sufficient to kill most bacteria, such as Streptococci and Staphylococci, which are mostly present in the biofilm of ONJ. We, therefore, conclude that intravenous administration of ampicillin/sulbactam remains a valuable treatment in the therapy of ONJ. Nevertheless, increasing resistance of Escherichia coli towards beta-lactam antibiotics have been reported and should be considered. 2022 International Journal of Environmental Research and Public Health 19 22 urn:nbn:de:bvb:20-opus-297413 10.3390/ijerph192214917 Institut für Hygiene und Mikrobiologie OPUS4-32451 Wissenschaftlicher Artikel Straub, Anton; Vollmer, Andreas; Lâm, Thiên-Trí; Brands, Roman C.; Stapf, Maximilian; Scherf-Clavel, Oliver; Bittrich, Max; Fuchs, Andreas; Kübler, Alexander C.; Hartmann, Stefan Evaluation of advanced platelet-rich fibrin (PRF) as a bio-carrier for ampicillin/sulbactam Objectives Mechanisms of wound healing are often impaired in patients with osteonecrosis of the jaw (ONJ). According to the guidelines for the treatment of this disease, early surgical intervention is indicated. However, surgery often faces complications such as wound healing disorders. The application of platelet-rich fibrin (PRF) after necrosectomy between bone and mucosa may constitute a promising approach to improve surgical results. An aspect that was not investigated until now is that PRF acts as a "bio-carrier" for antibiotics previously applied intravenously. Materials and methods We investigated the antimicrobial properties of PRF in 24 patients presenting ONJ undergoing systemic antibiosis with ampicillin/sulbactam. We measured the concentration of ampicillin/sulbactam in plasma and PRF and performed agar diffusion tests. Ampicillin/sulbactam was applied intravenously to the patient 10 minutes for blood sampling for PRF. No further incorporation of patients' blood or PRF product with antibiotic drugs was obtained. Four healthy patients served as controls. Results Our results revealed that PRF is highly enriched with ampicillin/sulbactam that is released to the environment. The antibiotic concentration in PRF was comparable to the plasma concentration of ampicillin/sulbactam. The inhibition zone (IZ) of PRF was comparable to the standard ampicillin/sulbactam discs used in sensitivity testing. Conclusions The results of our study demonstrated that PRF is a reliable bio-carrier for systemic applied antibiotics and exhibits a large antimicrobial effect. Clinical relevance We describe a clinically useful feature of PRF as a bio-carrier for antibiotics. Especially when applied to poorly perfused tissues and bone such as in ONJ, the local release of antibiotics can reduce wound healing disorders like infections. 2022 7033-7044 Clinical Oral Investigations 26 12 urn:nbn:de:bvb:20-opus-324515 10.1007/s00784-022-04663-y Institut für Hygiene und Mikrobiologie OPUS4-27885 Wissenschaftlicher Artikel Straub, Anton; Brands, Roman; Borgmann, Anna; Vollmer, Andreas; Hohm, Julian; Linz, Christian; Müller-Richter, Urs; Kübler, Alexander C.; Hartmann, Stefan Free skin grafting to reconstruct donor sites after radial forearm flap harvesting: a prospective study with platelet-rich fibrin (PRF) Reconstruction of the donor site after radial forearm flap harvesting is a common procedure in maxillofacial plastic surgery. It is normally carried out with split-thickness or full-thickness free skin grafts. Unfortunately, free skin graft transplantation faces wound healing impairments such as necrosis, (partial) graft loss, or tendon exposure. Several studies have investigated methods to reduce these impairments and demonstrated improvements if the wound bed is optimised, for example, through negative-pressure wound therapy or vacuum-assisted closure. However, these methods are device-dependent, expansive, and time-consuming. Therefore, the application of platelet-rich fibrin (PRF) to the wound bed could be a simple, cost-effective, and device-independent method to optimise wound-bed conditions instead. In this study, PRF membranes were applied between the wound bed and skin graft. Results of this study indicate improvements in the PRF versus non-PRF group (93.44% versus 86.96% graft survival, p = 0.0292). PRF applied to the wound bed increases graft survival and reduces impairments. A possible explanation for this is the release of growth factors, which stimulate angiogenesis and fibroblast migration. Furthermore, the solid PRF membranes act as a mechanical barrier ("lubrication" layer) to protect the skin graft from tendon motion. The results of this study support the application of PRF in donor-site reconstruction with free skin grafts. 2022 Journal of Clinical Medicine 11 12 urn:nbn:de:bvb:20-opus-278854 10.3390/jcm11123506 Klinik und Poliklinik für Mund-, Kiefer- und Plastische Gesichtschirurgie OPUS4-23622 Wissenschaftlicher Artikel Boschert, Verena; Teusch, Jonas; Aljasem, Anwar; Schmucker, Philipp; Klenk, Nicola; Straub, Anton; Bittrich, Max; Seher, Axel; Linz, Christian; Müller-Richter, Urs D. A.; Hartmann, Stefan HGF-induced PD-L1 expression in head and neck cancer: preclinical and clinical findings Head and neck squamous cell carcinoma (HNSCC) is a widespread disease with a low survival rate and a high risk of recurrence. Nowadays, immune checkpoint inhibitor (ICI) treatment is approved for HNSCC as a first-line treatment in recurrent and metastatic disease. ICI treatment yields a clear survival benefit, but overall response rates are still unsatisfactory. As shown in different cancer models, hepatocyte growth factor/mesenchymal-epithelial transition (HGF/Met) signaling contributes to an immunosuppressive microenvironment. Therefore, we investigated the relationship between HGF and programmed cell death protein 1 (PD-L1) expression in HNSCC cell lines. The preclinical data show a robust PD-L1 induction upon HGF stimulation. Further analysis revealed that the HGF-mediated upregulation of PD-L1 is MAP kinase-dependent. We then hypothesized that serum levels of HGF and soluble programmed cell death protein 1 (sPD-L1) could be potential markers of ICI treatment failure. Thus, we determined serum levels of these proteins in 20 HNSCC patients before ICI treatment and correlated them with treatment outcomes. Importantly, the clinical data showed a positive correlation of both serum proteins (HGF and sPD-L1) in HNSCC patient's sera. Moreover, the serum concentration of sPD-L1 was significantly higher in ICI non-responsive patients. Our findings indicate a potential role for sPD-L1 as a prognostic marker for ICI treatment in HNSCC. 2020 International Journal of Molecular Sciences 21 20 urn:nbn:de:bvb:20-opus-236220 10.3390/ijms21228770 Klinik und Poliklinik für Mund-, Kiefer- und Plastische Gesichtschirurgie OPUS4-26232 Wissenschaftlicher Artikel Koderer, Corinna; Schmitz, Werner; Wünsch, Anna Chiara; Balint, Julia; El-Mesery, Mohamed; Volland, Julian Manuel; Hartmann, Stefan; Linz, Christian; Kübler, Alexander Christian; Seher, Axel Low energy status under methionine restriction is essentially independent of proliferation or cell contact inhibition Nonlimited proliferation is one of the most striking features of neoplastic cells. The basis of cell division is the sufficient presence of mass (amino acids) and energy (ATP and NADH). A sophisticated intracellular network permanently measures the mass and energy levels. Thus, in vivo restrictions in the form of amino acid, protein, or caloric restrictions strongly affect absolute lifespan and age-associated diseases such as cancer. The induction of permanent low energy metabolism (LEM) is essential in this process. The murine cell line L929 responds to methionine restriction (MetR) for a short time period with LEM at the metabolic level defined by a characteristic fingerprint consisting of the molecules acetoacetate, creatine, spermidine, GSSG, UDP-glucose, pantothenate, and ATP. Here, we used mass spectrometry (LC/MS) to investigate the influence of proliferation and contact inhibition on the energy status of cells. Interestingly, the energy status was essentially independent of proliferation or contact inhibition. LC/MS analyses showed that in full medium, the cells maintain active and energetic metabolism for optional proliferation. In contrast, MetR induced LEM independently of proliferation or contact inhibition. These results are important for cell behaviour under MetR and for the optional application of restrictions in cancer therapy. 2022 Cells 11 3 urn:nbn:de:bvb:20-opus-262329 10.3390/cells11030551 Theodor-Boveri-Institut für Biowissenschaften