TY - JOUR A1 - Kämmerer, Peer W. A1 - Tribius, Silke A1 - Cohrs, Lena A1 - Engler, Gabriel A1 - Ettl, Tobias A1 - Freier, Kolja A1 - Frerich, Bernhard A1 - Ghanaati, Shahram A1 - Gosau, Martin A1 - Haim, Dominik A1 - Hartmann, Stefan A1 - Heiland, Max A1 - Herbst, Manuel A1 - Hoefert, Sebastian A1 - Hoffmann, Jürgen A1 - Hölzle, Frank A1 - Howaldt, Hans-Peter A1 - Kreutzer, Kilian A1 - Leonhardt, Henry A1 - Lutz, Rainer A1 - Moergel, Maximilian A1 - Modabber, Ali A1 - Neff, Andreas A1 - Pietzka, Sebastian A1 - Rau, Andrea A1 - Reichert, Torsten E. A1 - Smeets, Ralf A1 - Sproll, Christoph A1 - Steller, Daniel A1 - Wiltfang, Jörg A1 - Wolff, Klaus-Dietrich A1 - Kronfeld, Kai A1 - Al-Nawas, Bilal T1 - 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 JF - Cancers N2 - (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. KW - oral squamous cell carcinoma KW - oropharyngeal carcinoma KW - surgery KW - resection KW - radiotherapy KW - survival KW - progression-free survival KW - quality of life KW - prospective KW - multicentric KW - lymph node KW - pN1 Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311024 SN - 2072-6694 VL - 15 IS - 6 ER - TY - JOUR A1 - Hartmann, Stefan A1 - Lessner, Grit A1 - Mentzel, Thomas A1 - Kübler, Alexander C. A1 - Müller-Richter, Urs T1 - An adult spindle cell rhabdomyosarcoma in the head and neck region with long-term survival: a case report N2 - 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. KW - Rhabdomyosarcoma KW - Spindle cell KW - Adult KW - Surgery KW - Head Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-110362 ER - TY - JOUR A1 - Vollmer, Andreas A1 - Saravi, Babak A1 - Vollmer, Michael A1 - Lang, Gernot Michael A1 - Straub, Anton A1 - Brands, Roman C. A1 - Kübler, Alexander A1 - Gubik, Sebastian A1 - Hartmann, Stefan T1 - Artificial intelligence-based prediction of oroantral communication after tooth extraction utilizing preoperative panoramic radiography JF - Diagnostics N2 - 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. KW - artificial intelligence KW - deep learning KW - X-ray KW - tooth extraction KW - oroantral fistula KW - operative planning Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-278814 SN - 2075-4418 VL - 12 IS - 6 ER - TY - JOUR A1 - Vollmer, Andreas A1 - Vollmer, Michael A1 - Lang, Gernot A1 - Straub, Anton A1 - Shavlokhova, Veronika A1 - Kübler, Alexander A1 - Gubik, Sebastian A1 - Brands, Roman A1 - Hartmann, Stefan A1 - Saravi, Babak T1 - Associations between periodontitis and COPD: An artificial intelligence-based analysis of NHANES III JF - Journal of Clinical Medicine N2 - 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. KW - COPD KW - periodontitis KW - bone loss KW - machine learning KW - prediction KW - artificial intelligence KW - model KW - gingivitis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312713 SN - 2077-0383 VL - 11 IS - 23 ER - TY - JOUR A1 - Vollmer, Andreas A1 - Vollmer, Michael A1 - Lang, Gernot A1 - Straub, Anton A1 - Kübler, Alexander A1 - Gubik, Sebastian A1 - Brands, Roman C. A1 - Hartmann, Stefan A1 - Saravi, Babak T1 - Automated assessment of radiographic bone loss in the posterior maxilla utilizing a multi-object detection artificial intelligence algorithm JF - Applied Sciences N2 - 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. KW - radiographic bone loss KW - alveolar bone loss KW - maxillofacial surgery KW - deep learning KW - classification KW - artificial intelligence KW - object detection Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-305050 SN - 2076-3417 VL - 13 IS - 3 ER - TY - JOUR A1 - Straub, Anton A1 - Stapf, Maximilian A1 - Fischer, Markus A1 - Vollmer, Andreas A1 - Linz, Christian A1 - Lâm, Thiên-Trí A1 - Kübler, Alexander A1 - Brands, Roman C. A1 - Scherf-Clavel, Oliver A1 - Hartmann, Stefan T1 - Bone concentration of ampicillin/sulbactam: a pilot study in patients with osteonecrosis of the jaw JF - International Journal of Environmental Research and Public Health N2 - 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. KW - osteonecrosis of the jaw KW - ARONJ KW - MRONJ KW - ONJ KW - osteoradionecrosis KW - antibiotic bone concentration KW - jaw bone KW - beta-lactam KW - ampicillin Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297413 SN - 1660-4601 VL - 19 IS - 22 ER - TY - JOUR A1 - Fuchs, Andreas A1 - Kreczy, Dorothea A1 - Brückner, Theresa A1 - Gbureck, Uwe A1 - Stahlhut, Philipp A1 - Bengel, Melanie A1 - Hoess, Andreas A1 - Nies, Berthold A1 - Bator, Julia A1 - Klammert, Uwe A1 - Linz, Christian A1 - Ewald, Andrea T1 - Bone regeneration capacity of newly developed spherical magnesium phosphate cement granules JF - Clinical Oral Investigations N2 - Objectives Magnesium phosphate-based cements begin to catch more attention as bone substitute materials and especially as alternatives for the more commonly used calcium phosphates. In bone substitutes for augmentation purposes, atraumatic materials with good biocompatibility and resorbability are favorable. In the current study, we describe the in vivo testing of novel bone augmentation materials in form of spherical granules based on a calcium-doped magnesium phosphate (CaMgP) cement. Materials and Methods Granules with diameters between 500 and 710 μm were fabricated via the emulsification of CaMgP cement pastes in a lipophilic liquid. As basic material, two different CaMgP formulations were used. The obtained granules were implanted into drill hole defects at the distal femoral condyle of 27 New Zealand white rabbits for 6 and 12 weeks. After explantation, the femora were examined via X-ray diffraction analysis, histological staining, radiological examination, and EDX measurement. Results Both granule types display excellent biocompatibility without any signs of inflammation and allow for proper bone healing without the interposition of connective tissue. CaMgP granules show a fast and continuous degradation and enable fully adequate bone regeneration. Conclusions Due to their biocompatibility, their degradation behavior, and their completely spherical morphology, these CaMgP granules present a promising bone substitute material for bone augmentation procedures, especially in sensitive areas. Clinical Relevance The mostly insufficient local bone supply after tooth extractions complicates prosthetic dental restoration or makes it even impossible. Therefore, bone augmentation procedures are oftentimes inevitable. Spherical CaMgP granules may represent a valuable bone replacement material in many situations. KW - implantation KW - calcium-magnesium phosphate cement KW - cement pastes KW - prefabricated granules KW - bone replacement material Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-268872 SN - 1436-3771 VL - 26 IS - 3 ER - TY - JOUR A1 - Winter, Anna A1 - Schulz, Stefan M. A1 - Schmitter, Marc A1 - Müller-Richter, Urs A1 - Kübler, Alexander A1 - Kasper, Sylvia A1 - Hartmann, Stefan T1 - Comprehensive geriatric assessment and quality of life aspects in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) JF - Journal of Clinical Medicine N2 - To define frailty in older cancer patients, the aim of this study was to assess the geriatric status and quality of life (QoL) aspects in patients suffering from recurrent/metastatic head and neck squamous cell carcinoma (r/m HNSCC) under palliative treatment. A comprehensive geriatric assessment (CGA) was performed on 21 r/m HNSCC patients at two defined assessments, and the QoL aspects and the impact of descriptive data were evaluated. The Kolmogorov–Smirnov test, Spearman’s rho correlation, and two-way mixed ANOVA were used for statistical analysis. All patients were found to be “frail”. Pain, fatigue, and the burden of illness were the highest-rated symptoms. Oral function and orofacial appearance were highly impaired. A significant impact of descriptive data on the CGA and QoL results was found (all p ≤ 0.05). Thus, the CGA results revealed high frailty, severe comorbidities, and high impairments in QoL aspects. The CGA and QoL results were negatively affected by the primary HNSCC treatment approach, the need for prosthetic treatment, and worse oral functional capacity. Therefore, frailty in r/m HNSCC patients seems to be multidimensional. The evaluation of the CGA and QoL aspects in r/m HNSCC patients can be recommended to detect special needs, organize aftercare, and improve the support for frail and vulnerable cancer patients to create a multidisciplinary treatment approach. KW - frailty KW - geriatric cancer patient KW - recurrent/metastatic head and neck squamous cell carcinoma KW - oral health-related quality of life KW - prosthetic rehabilitation KW - oral functional capacity Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-363096 SN - 2077-0383 VL - 12 IS - 17 ER - TY - JOUR A1 - Schmitz, Werner A1 - Ries, Elena A1 - Koderer, Corinna A1 - Völter, Maximilian Friedrich A1 - Wünsch, Anna Chiara A1 - El-Mesery, Mohamed A1 - Frackmann, Kyra A1 - Kübler, Alexander Christian A1 - Linz, Christian A1 - Seher, Axel T1 - Cysteine restriction in murine L929 fibroblasts as an alternative strategy to methionine restriction in cancer therapy JF - International Journal of Molecular Sciences N2 - Methionine restriction (MetR) is an efficient method of amino acid restriction (AR) in cells and organisms that induces low energy metabolism (LEM) similar to caloric restriction (CR). The implementation of MetR as a therapy for cancer or other diseases is not simple since the elimination of a single amino acid in the diet is difficult. However, the in vivo turnover rate of cysteine is usually higher than the rate of intake through food. For this reason, every cell can enzymatically synthesize cysteine from methionine, which enables the use of specific enzymatic inhibitors. In this work, we analysed the potential of cysteine restriction (CysR) in the murine cell line L929. This study determined metabolic fingerprints using mass spectrometry (LC/MS). The profiles were compared with profiles created in an earlier work under MetR. The study was supplemented by proliferation studies using D-amino acid analogues and inhibitors of intracellular cysteine synthesis. CysR showed a proliferation inhibition potential comparable to that of MetR. However, the metabolic footprints differed significantly and showed that CysR does not induce classic LEM at the metabolic level. Nevertheless, CysR offers great potential as an alternative for decisive interventions in general and tumour metabolism at the metabolic level. KW - methionine restriction KW - cysteine restriction KW - mass spectrometry KW - LC/MS KW - cancer therapy KW - caloric restriction KW - homocysteine KW - amino acid analogues KW - cysteine synthase inhibitor Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265486 SN - 1422-0067 VL - 22 IS - 21 ER - TY - JOUR A1 - Ewald, Andrea A1 - Fuchs, Andreas A1 - Boegelein, Lasse A1 - Grunz, Jan-Peter A1 - Kneist, Karl A1 - Gbureck, Uwe A1 - Hoelscher-Doht, Stefanie T1 - Degradation and bone-contact biocompatibility of two drillable magnesium phosphate bone cements in an in vivo rabbit bone defect model JF - Materials N2 - The use of bone-cement-enforced osteosynthesis is a growing topic in trauma surgery. In this context, drillability is a desirable feature for cements that can improve fracture stability, which most of the available cement systems lack. Therefore, in this study, we evaluated a resorbable and drillable magnesium-phosphate (MgP)-based cement paste considering degradation behavior and biocompatibility in vivo. Two different magnesium-phosphate-based cement (MPC) pastes with different amounts of phytic acid (IP 6) as setting retarder (MPC 22.5 and MPC 25) were implanted in an orthotopic defect model of the lateral femoral condyle of New Zealand white rabbits for 6 weeks. After explantation, their resorption behavior and material characteristics were evaluated by means of X-ray diffraction (XRD), porosimetry measurement, histological staining, peripheral quantitative computed tomography (pQCT), cone-beam computed tomography (CBCT) and biomechanical load-to-failure tests. Both cement pastes displayed comparable results in mechanical strength and resorption kinetics. Bone-contact biocompatibility was excellent without any signs of inflammation. Initial resorption and bone remodeling could be observed. MPC pastes with IP 6 as setting retardant have the potential to be a valuable alternative in distinct fracture patterns. Drillability, promising resorption potential and high mechanical strength confirm their suitability for use in clinical routine. KW - magnesium phosphate cement KW - phytic acid KW - drillability KW - bone replacement material Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-362824 SN - 1996-1944 VL - 16 IS - 13 ER -