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Yiwen Dong,1– 3 Litao Yao,2– 4,* Lei Cai,1 Mi Jin,1 Tymour Forouzanfar,2,3 Lianjun Wu,1 Jinsong Liu,1,* Gang Wu2,3 1School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Science, Amsterdam, Amsterdam, the Netherlands; 3Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam (UvA) and Vrije Universiteit Amsterdam (VU), Amsterdam, the Netherlands; 4Department of Dentistry, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Litao Yao, Department of Dentistry, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China, Zhejiang, Email yaolt@srrsh.com Jinsong Liu, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China, Email jinsong0719@wmu.edu.cnIntroduction: An antibacterial and pro-osteogenic coaxially electrospun nanofiber guided bone regeneration (GBR) membrane was fabricated to satisfy the complicated and phased requirements of GBR process.Methods: In this study, we synthesize dual-functional coaxially electrospun nanofiber GBR membranes by encapsulating parathyroid hormone (PTH) in the core layer and magnesium oxide nanoparticles (MgONPs) in the shell layer (MgONPs-PCL/PTH-PCL). Herein, the physicochemical characterization of MgONPs-PCL/PTH-PCL, the release rates of MgONPs and PTH, and antibacterial efficiency of the new membrane were evaluated. Furthermore, the pro-osteogenicity of the membranes was assessed both in-vitro and in-vivo.Results: We successfully fabricated a coaxially electrospun nanofiber MgONPs-PCL/PTH-PCL membrane with the majority of nanofibers (> 65%) ranged from 0.40~0.60μm in diameter. MgONPs-PCL/PTH-PCL showed outstanding antibacterial potential against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) through the release of MgONPs. We also discovered that the incorporation of MgONPs significantly prolonged the release of PTH. Furthermore, both the in-vivo and in-vitro studies demonstrated that high dosage of PTH promoted pro-osteogenicity of the membrane to improve bone regeneration efficacy with the presence of MgONPs.Conclusion: The new composite membrane is a promising approach to enhance bone regeneration in periodontitis or peri-implantitis patients with large-volume bone defects.Keywords: antibacterial property, pro-osteogenicity, coaxially electrospun, barrier membrane, guided bone regeneration

Background: Skeletal muscle mass (SMM) and chronic inflammation are associated with postoperative complications and survival. Methods: Patients with head and neck cancer (HNC) undergoing microvascular free flap reconstruction were included. SMM and neutrophil-to-lymphocyte ratio (NLR) were measured and their association with treatment outcomes analyzed. Results: Five hundred and fifty-four patients were included. Predictors for complications were elevated NLR in all flaps (OR 1.5), low SMM in radial forearm flap (OR 2.0), and elevated NLR combined with low SMM in fibula flap surgery (OR 4.3). Patients with solely elevated NLR were at risk for flap-related complications (OR 3.0), severe complications (OR 2.2), and when combined with low SMM for increased length of hospital stays (LOS) (+3.9 days). In early-stage HNC, low SMM (HR 2.3), and combined elevated NLR with low SMM (HR 2.6) were prognostics for decreased overall survival. Conclusions: SMM and NLR are predictive for poor outcomes in patients with HNC undergoing microvascular reconstruction.

Incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing globally and the human papillomavirus (HPV) has been linked to this increase. This study aimed to present a comprehensive overview of OPSCC trends in incidence rates by age group and investigate differences in risk factors profile. Netherlands Cancer Registry data from 1989-2018 were analyzed to calculate the annual percentage change (APC) over European standardized incidence rates by gender and age group using joinpoint regression software. Smoking, alcohol drinking and HPV-status were available for 2015-2018. During 1989-2018, 13 048 cases of OPSCC were reported with a male-to-female ratio of 2.1:1. The overall incidence rate increased by 5.4% (APC) annually from 1989 to 1996 but slowed thereafter by 1.2%. Significant declines were found in patients of 35-44 years (APCs -3.7%). Adults aged 45-59 years displayed significant increases from 1989 to 2001, followed by a significant decline. In patients >= 60 years, the incidence rates increased overall, with APC for women being consistently higher than men. The data on HPV status was available for 69% of the patients, of whom 47% were HPV+. Smoking and alcohol consumption were more prevalent, that is 75 and 76 % respectively. The declining trends of OPSCC for Dutch people aged 35-44 years from 1989 to 2018 and for those aged 45-59 years from 2002 onwards are inconsistent to trends reported elsewhere in the developed countries. The prevalence of smoking and drinking alcohol was quite high in all age groups, whereas the proportion of HPV-positivity was relatively low.

There has been an increasing trend in oral squamous cell carcinoma (OSCC) in patients under 45 years of age. The aim of this study was to evaluate the burden of OSCC in the Netherlands between 1989 and 2018 among young adults (age 20 34 years) when compared to adults (age 35-44 years), and to describe the burden in older groups as well, utilizing cancer registry data to characterize incidence patterns by age, sex, and risk factors. A total of 18,963 cases of OSCC were reported. The overall incidence rate, as measured by annual percentage change (APC), increased significantly from 1989 to 2010 by 1.3% per year (95% confidence interval (CI) 0.9-1.7%) but decreased thereafter by -0.9% (95% CI -2.5% to 0.7%). Annual incidence increased significantly by 2.4% (95% CI 1.1-3.8%) for patients aged 20-34 years, while it decreased for those aged 35-44 years by -0.9% (95% CI -1.7% to 0.0%). In patients older than 60 years, incidence rates increased overall (60-74 years: APC 1.8%, 95% CI 1.5-2.1%; >= 75 years: APC 1.5%, 95% CI 1.2-1.9%). Overall, 66.5% of patients were smokers and 65.3% were alcohol consumers. The marked differences in incidence within the young age subgroups warrants further investigation to elucidate any likely disparity in biological process and clinical outcomes in these populations.

Background: Oral functioning and rehabilitation in patients after condylar trauma can be measured by objective functional outcomes and patient-reported outcomes. The similarities or differences between these outcomes may contribute to the decision if open treatment (OT) or closed treatment (CT) will obtain the most advantageous results. Objectives: The aim of this study was to compare OT versus CT for unilateral condylar mandibular neck or base fractures in a two-centre controlled clinical trial by objective functional outcomes and patient-reported outcomes measured at 6 weeks and 6 months follow-up. Additionally, these outcomes were compared within each group. Methods: Patients were enrolled between January 2017 and November 2019. In one centre, patients received OT by extra-oral open reduction and internal fixation. In another centre, patients received CT by maxillomandibular fixation. Objective measurements included the mixing ability test (MAT) and mandibular active range of motion (ROM). Patient-reported outcomes included the mandibular function impairment questionnaire (MFIQ) and visual analogue scale (VAS) for pain. Independent t-tests and Mann–Whitney U-tests were used to determine differences between the treatment groups at 6 weeks and 6 months follow-up. Paired t-tests and Wilcoxon signed rank tests were used to determine differences within each group. Results: Thirty-three patients were enrolled. No differences were found between the groups treated with OT or CT for MAT, ROM, MFIQ and VAS. Both groups showed functional improvement. Conclusion: Good objective functional outcomes and patient-reported outcomes were achieved with both OT and CT in patients with unilateral condylar mandibular neck or base fractures.

This study aimed to analyze the efficacy of stem cell-based tissue engineering for the treatment of alveolar cleft (AC) and cleft palate (CP) defects in animal models. Systematic review and meta-analysis. Preclinical studies on alveolar cleft repair in maxillofacial practice. Electronic search was performed using PubMed, Embase, and Cochrane databases. Pre-clinical studies, where stem cell-based tissue engineering was used in the reconstruction of AC and CP in animal models were included. Quality of the selected articles was evaluated using SYRCLE (SYstematic Review Centre for Laboratory animal Experimentation). Review of alveolar cleft bone augmentation interventions in preclinical models. Outcome parameters registered were new bone formation (NBF) and/or bone mineral density (BMD). Thirteen large and twelve small animal studies on AC (21) and CP (4) reconstructions were included. Studies had an unclear-to-high risk of bias. Bone marrow mesenchymal stem cells were the most widely used cell source. Meta-analyses for AC indicated non-significant benefits in favor of: (1) scaffold + cells over scaffold-only (NBF P = .13); and (2) scaffold + cells over empty control (NBF P = .66; BMD P = .31). Interestingly, dog studies using regenerative grafts showed similar to superior bone formation compared to autografts. Meta analysis for the CP group was not possible. AC and CP reconstructions are enhanced by addition of osteogenic cells to biomaterials. Directions and estimates of treatment effect are useful to predict therapeutic efficacy and guide future clinical trials of bone tissue engineering.

Objectives Although bowel symptoms are often predominant, inflammatory bowel disease (IBD) patients can have several oral manifestations. The aim of this study was to investigate the prevalence of dental caries and periodontal disease in patients with Crohn’s disease (CD) and ulcerative colitis (UC) compared to an age and gender-matched control group of patients without IBD. Material and methods The DMFT (Decayed, Missing, Filled Teeth) scores and the DPSI (Dutch Periodontal Screening Index) of 229 IBD patients were retrieved from the electronic health record patient database axiUm at the Academic Centre for Dentistry Amsterdam (ACTA) and were compared to the DMFT scores and DPSI from age and gender-matched non-IBD patients from the same database. Results The total DMFT index was significantly higher in the IBD group compared to the control group. When CD and UC were analyzed separately, a statistically significant increased DMFT index was observed in CD patients but not in UC patients. The DPSI did not differ significantly between the IBD and non-IBD groups for each of the sextants. However, in every sextant, IBD patients were more frequently edentulous compared to the control patients. Conclusion CD patients have significantly more dental health problems compared to a control group. Periodontal disease did not differ significantly between IBD and non-IBD groups as determined by the DPSI. Clinical relevance It is important that IBD patients and physicians are instructed about the correlation between their disease and oral health problems. Strict oral hygiene and preventive dental care such as more frequent checkups should be emphasized by dental clinicians.

© International & American Associations for Dental Research 2021.Accurate segmentation of the jaw (i.e., mandible and maxilla) and the teeth in cone beam computed tomography (CBCT) scans is essential for orthodontic diagnosis and treatment planning. Although various (semi)automated methods have been proposed to segment the jaw or the teeth, there is still a lack of fully automated segmentation methods that can simultaneously segment both anatomic structures in CBCT scans (i.e., multiclass segmentation). In this study, we aimed to train and validate a mixed-scale dense (MS-D) convolutional neural network for multiclass segmentation of the jaw, the teeth, and the background in CBCT scans. Thirty CBCT scans were obtained from patients who had undergone orthodontic treatment. Gold standard segmentation labels were manually created by 4 dentists. As a benchmark, we also evaluated MS-D networks that segmented the jaw or the teeth (i.e., binary segmentation). All segmented CBCT scans were converted to virtual 3-dimensional (3D) models. The segmentation performance of all trained MS-D networks was assessed by the Dice similarity coefficient and surface deviation. The CBCT scans segmented by the MS-D network demonstrated a large overlap with the gold standard segmentations (Dice similarity coefficient: 0.934 ± 0.019, jaw; 0.945 ± 0.021, teeth). The MS-D network–based 3D models of the jaw and the teeth showed minor surface deviations when compared with the corresponding gold standard 3D models (0.390 ± 0.093 mm, jaw; 0.204 ± 0.061 mm, teeth). The MS-D network took approximately 25 s to segment 1 CBCT scan, whereas manual segmentation took about 5 h. This study showed that multiclass segmentation of jaw and teeth was accurate and its performance was comparable to binary segmentation. The MS-D network trained for multiclass segmentation would therefore make patient-specific orthodontic treatment more feasible by strongly reducing the time required to segment multiple anatomic structures in CBCT scans.

Objectives c-Met, a receptor tyrosine kinase, is involved in the growth, invasion and metastasis of a variety of cancers. In a set of cell lines from several solid tumors, a five-fold increase in c-Met expression after irradiation has been reported. This study aimed to assess if c-Met is likewise abundantly expressed in oral tongue squamous cell carcinoma (OTSCC) upon exposure to irradiation, followed by a Met-induced biological response. Materials and methods Six OTSCC cell lines were exposed to gamma radiation doses of 2, 4, and 6 Gray. The changes in c-Met protein levels were assessed by western blot and flow cytometry. c-Met gene expression, cell migration, proliferation and cell cycle assays were performed as phenotypic readouts. Results Irradiation resulted in upregulation of c.Met in all cell lines with different time kinetics. On average the cells displayed minimal c-Met expression on their surface ranging from 5 to 30% of total protein. Abrupt downregulation of c-Met surface expression occurred one hour after radiation but recovered 48 h post-radiation. Intracellularly, the highest level of expression was found on day 5 after radiation exposure. Irradiation induced aggressive invasive potential of the cells as determined in cell migration assays, particularly in cell lines with the highest c-Met expression. Conclusions These results provide novel insights into both intracellular and extracellular dynamics of c-Met expression profiles upon irradiation of OTSCC cells in vitro. It might also suggest that radiation enhances cell migration, indicative of invasiveness, through c-Met up-regulation, at least for certain types of OTSCC cells.

Computer-assisted surgery (CAS) allows clinicians to personalize treatments and surgical interventions and has therefore become an increasingly popular treatment modality in maxil-lofacial surgery. The current maxillofacial CAS consists of three main steps: (1) CT image reconstruction, (2) bone segmentation, and (3) surgical planning. However, each of these three steps can introduce errors that can heavily affect the treatment outcome. As a consequence, tedious and time-consuming manual post-processing is often necessary to ensure that each step is performed adequately. One way to overcome this issue is by developing and implementing neural networks (NNs) within the maxillofacial CAS workflow. These learning algorithms can be trained to perform specific tasks without the need for explicitly defined rules. In recent years, an extremely large number of novel NN approaches have been proposed for a wide variety of applications, which makes it a difficult task to keep up with all relevant developments. This study therefore aimed to summarize and review all relevant NN approaches applied for CT image reconstruction, bone segmentation, and surgical planning. After full text screening, 76 publications were identified: 32 focusing on CT image reconstruction, 33 focusing on bone segmentation and 11 focusing on surgical planning. Generally, convolutional NNs were most widely used in the identified studies, although the multilayer perceptron was most commonly applied in surgical planning tasks. Moreover, the drawbacks of current approaches and prom-ising research avenues are discussed.Dentomaxillofacial Radiology (2022) 51, 20210437. doi: 10.1259/dmfr.20210437

Purpose To evaluate the effect of implant-based dental rehabilitation (IDR) on health-related quality of life (HRQoL) in head and neck cancer (HNC) patients after reconstruction with a free vascularized fibula flap (FFF). Methods Eligible patients were identified by retrospectively reviewing the medical records of patients treated in Amsterdam UMC-VUmc. HRQoL data were used from OncoQuest, a hospital-based system to collect patient-reported outcome measures in routine care. Data were used of the EORTC QLQ-C30 and QLQ-H&N 35 before FFF reconstruction (T0) and after completing IDR (T1). Data were statistically analysed with the chi-square test, independent samples t test and linear mixed models. Results Out of 96 patients with maxillofacial FFF reconstruction between January 2006 and October 2017, 57 patients (19 with and 38 without IDR) had HRQoL data at T0 and T1. In the cross-sectional analysis, patients with IDR scored significantly better at T0 and T1 on several EORTC domains compared to the patients without IDR. Weight loss was significantly different in the within-subject analysis between T0 and T1 for patients with IDR (p = 0.011). However, there were no significant differences in the mean changes of all the EORTC QLQ-C30 and EORTC QLQ-H&N35 scores between the defined timepoints for patients with IDR compared to those without. Conclusions In this study, no differences were found in the course of HRQoL in HNC patients who had undergone IDR after maxillofacial FFF reconstruction, compared to those who had not. Patients should be preoperatively informed to have realistic expectations regarding the outcome of IDR.

The repair of large-volume bone defects (LVBDs) remains a great challenge in the fields of orthopedics and maxillofacial surgery. Most clinically available bone-defect-filling materials lack proper degradability and efficient osteoinductivity. In this study, we synthesized a novel biomimetically-precipitated nanocrystalline calcium phosphate (BpNcCaP) with internally incorporated bone morphogenetic protein-2 (BpNcCaP + BMP-2) with an aim to develop properly degradable and highly osteoinductive granules to repair LVBDs. We first characterized the physicochemical properties of the granules with different incorporation amounts of BMP-2 using scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. We evaluated the cytotoxicity and cytocompatibility of BpNcCaP by assessing the viability and adhesion of MC3T3-E1 pre-osteoblasts using PrestoBlue assay, Rhodamine-Phalloidin and DAPI staining, respectively. We further assessed the

Custom‐made polymethyl methacrylate (PMMA) bone cement is used to treat cranial bone defects but whether it is cytotoxic is still unsure. Possible PMMA‐induced adverse effects in vivo affect mesenchymal stem cells and osteoblasts at the implant site. We aimed to investigate whether PMMA affects osteogenic and osteoclast activation potential of human mesenchymal stem cells and/or osteoblasts. Immediately after polymerization, PMMA was added to cultured human adipose stem cells (hASCs) or human osteoblasts (hOBs). Medium lactate dehydrogenase was measured (day 1), metabolic activity, proliferation, osteogenic and osteoclast‐activation marker expression (day 1 and 7), and mineralization (day 14). PMMA did not affect lactate dehydrogenase, KI67 gene expression, or metabolic activity in hASCs and hOBs. PMMA transiently decreased DNA content in hOBs only. PMMA increased COL1 gene expression in hASCs, but decreased RUNX2 in hOBs. PMMA did not affect osteocalcin or alkaline phosphatase (ALP) expression, ALP activity, or mineralization. Only in hOBs, PMMA decreased RANKL/OPG ratio. In conclusion, PMMA is not cytotoxic and does not adversely affect the osteogenic potential of hASCs or hOBs. Moreover, PMMA does not enhance production of osteoclast factors by hASCs and hOBs in vitro. Therefore, PMMA bone cement seems highly suitable to treat patients with cranial bone defects.

Objectives: In this cadaveric study, the accuracy of CAS guided mandibular and maxillary reconstruction including immediate dental implant placement in different Brown defect classes is assessed. Materials and methods: The virtual planning and surgical procedure was conducted according to a newly proposed Amsterdam UMC reconstruction protocol. Postoperative evaluation was performed according to a previously proposed evaluation guideline. Results: Fourteen mandibular and 6 maxillary reconstructions were performed. Average mandibular angle deviations were 1.52°±1.32, 1.85°±1.58, 1.37°±1.09, 1.78°±1.37, 2.43°±1.52 and 2.83°±2.37, respectively for the left and right axial angles, left and right coronal angles and left and right sagittal angles. A total of 62 dental implants were placed in neomandibles with an average dXYZ values of 3.68 ± 2.21 mm and 16 in neomaxillas with an average dXYZ values of 3.24 ± 1.7 mm. Conclusion: Promising levels of accuracy were achieved for all mandibular angles. Dental implant positions approached the preoperative preferred positions well, within the margin to manufacture prosthetic devices.

OBJECTIVE: Oral tongue squamous cell carcinoma (OTSCC) frequently harbors non-functional p53 and depends on G2/M checkpoint mediated by WEE1. WEE1 suppression has been identified as a promising anti-tumor strategy. This study investigated the capacity of WEE1 kinase inhibitor (MK-1775) and its underlying mechanisms in enhancing radiation responses of OTSCC cells in vitro.MATERIALS AND METHODS: WEE1 kinase expression and its downstream target (CDK1) were investigated in OTSCC versus normal oral tissue. A synergistic combination of MK-1775 with radiation on OTSCC cell lines with different p53 statuses was assessed by viability assay. The radio-sensitizing effects of MK-1775 on apoptosis, cell cycle, DNA damage, and mitotic entry were also determined.RESULTS: Irradiation enhanced CDK1 expression in all tested cell lines, though the effect was far more pronounced in p53 mutated cell lines. MK-1775 exhibited inhibitory effects against the survival of all cell lines and enhanced their response to the radiation. These effects were strongly elicited by induction of apoptosis and lethal mitosis, but less likely by abrogation of radiation-induced G2 arrest.CONCLUSION: These results demonstrate the efficacy of MK-1775 in enhancing the radiation effect on OTSCC in vitro associated with a significant apoptotic death rate, identifying WEE1 inhibitor as a potent radiosensitizer in OTSCC irrespective of p53 mutational status.

Objectives. Ameloblastoma is a slow-growing epithelial odontogenic neoplasm of the jaws with a high recurrence rate. The main treatment strategies for this lesion are radical or conservative surgical approaches. The aim of the present study was to analyze clinical presentations, histological types, and treatment strategies of recurrent ameloblastoma and to define its disease-free survival (DFS) rate. Materials and Methods. Twenty-four cases of recurrent ameloblastomas, treated between January 2009 and July 2021, were enrolled in this study. Medical files from each patient, including gender, age, size of the lesion, localization, patient complaints, clinical manifestation, radiographic appearance, histological type, surgical management, and treatment results were reviewed and analyzed retrospectively. Result. Out of 69 operated primary ameloblastomas, the rate of recurrence was 35%. Out of 24 recurrent cases, 21 developed after conservative treatment and 3 after radical treatment. In most cases, recurrences were found in the mandible (n = 20). A unilocular pattern was predominant in radiographic examination (44%). Estimated 3-year DFS was 84.5 ± 4.8%, and the 5-year and 10-year DFS were 73.0 ± 6.3% and 43.9 ± 8.343.9 ± 8.3%, respectively. Conclusion. Results obtained in the present retrospective study proved the necessity of long-term follow-up after both conservative and radical treatment approaches. The DFS median in our study was 8 years (95% CI 6 years–10 years). For recurrent cases, radical resection with histologically free margins after exact MRI determination of the ameloblastoma border within the soft tissues should be considered as the method of choice to avoid secondary recurrence.

Background Gastrointestinal diseases can have oral manifestations. The aim of this study was to investigate the knowledge of gastroenterologists and dentists about gastrointestinal diseases with oral manifestations and to assess the frequency, extent and content of communication between gastroenterologists and oral healthcare professionals. Methods Separate questionnaires were developed and sent to all 523 gastroenterologists and a random selection of 500 dentists in the Netherlands. Both questionnaires contained questions about demographic characteristics of the participants, 10 statements about gastrointestinal diseases with possible oral manifestations and questions about the communication between gastroenterologists and oral healthcare professionals. Additionally, the questionnaire for gastroenterologists contained 9 statements about general dentistry and the questionnaire for dentist had 9 questions about gastrointestinal diseases. Results Gastroenterologists answered 47.6% ± 31.9% of the questions correct about gastrointestinal diseases with possible oral manifestations and 57.5% ± 27.9% of the questions correct about general dentistry. Dentists answered 26.6% ± 20.5% of the questions correct about possible oral manifestations of gastrointestinal diseases and 50.3% ± 18.7% of the questions correct about gastrointestinal diseases. Gastroenterologists and dentists valued interdisciplinary consultation as very useful with scores of 4.07 ± 0.70 and 4.67 ± 0.49 on a 5-point Likert scale, respectively, but the frequency of consultation was considered insufficiently with a mean score of 2.88 ± 1.01 and 2.24 ± 1.05 on a 5-point Likert scale, respectively. Conclusions This study suggests that the knowledge of gastroenterologists and dentists about gastrointestinal diseases with oral manifestations could be improved. Interdisciplinary consultation was considered valuable for the optimal treatment of their patients but was assessed as insufficient.

© 2021 The Author(s)The study aimed at evaluating, comprehensively, implant-based dental rehabilitation in head and neck cancer patients after maxillofacial reconstruction with a vascularized free fibula flap (FFF). Data were obtained by retrospectively reviewing the medical records of patients treated in Amsterdam UMC-VU Medical Center. Dental implant survival and implant success according to the Albrektsson criteria were analyzed. Additionally, prosthetic-related outcomes were studied, with a focus on functional dental rehabilitation. In total, 161 implants were placed in FFFs, with a mean follow-up of 4.9 years (range 0.2–23.4). Implant survival was 55.3% in irradiated FFFs and 96% in non-irradiated FFFs. Significant predictors for implant failure were tobacco use and irradiation of the FFF. Implant success was 40.4% in irradiated FFFs and 61.4% in non-irradiated FFFs, mainly due to implant failure and non-functional implants. Implant-based dental rehabilitation was started 45 times in 42 patients, out of 161 FFF reconstructions (27.9%). Thirty-seven patients completed the dental rehabilitation, 29 of whom achieved functional rehabilitation. Irradiation of the FFF negatively influenced attainment of functional rehabilitation. For patients with functional rehabilitation, the body mass index varied at different timepoints: FFF reconstruction, 24.6; dental implantation 23.5; and after placing dental prosthesis, 23.9. Functional implant-based dental rehabilitation, if started, can be achieved in the majority of head and neck cancer patients after FFF reconstruction. Actively smoking patients with an irradiated FFF should be clearly informed about the increased risk for implant and prosthetic treatment failure.

Background and objective: Over the past decade, convolutional neural networks (CNNs) have revolutionized the field of medical image segmentation. Prompted by the developments in computational resources and the availability of large datasets, a wide variety of different two-dimensional (2D) and threedimensional (3D) CNN training strategies have been proposed. However, a systematic comparison of the impact of these strategies on the image segmentation performance is still lacking. Therefore, this study aimed to compare eight different CNN training strategies, namely 2D (axial, sagittal and coronal slices), 2.5D (3 and 5 adjacent slices), majority voting, randomly oriented 2D cross-sections and 3D patches. Methods: These eight strategies were used to train a U-Net and an MS-D network for the segmentation of simulated cone-beam computed tomography (CBCT) images comprising randomly-placed non-overlapping cylinders and experimental CBCT images of anthropomorphic phantom heads. The resulting segmentation performances were quantitatively compared by calculating Dice similarity coefficients. In addition, all segmented and gold standard experimental CBCT images were converted into virtual 3D models and compared using orientation-based surface comparisons. Results: The CNN training strategy that generally resulted in the best performances on both simulated and experimental CBCT images was majority voting. When employing 2D training strategies, the segmentation performance can be optimized by training on image slices that are perpendicular to the predominant orientation of the anatomical structure of interest. Such spatial features should be taken into account when choosing or developing novel CNN training strategies for medical image segmentation. Conclusions: The results of this study will help clinicians and engineers to choose the most-suited CNN training strategy for CBCT image segmentation. (c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

Objectives Histatin 1(Hst 1) has been proved to promote wound healing. However, there was no specific study on the regulation made by Hst 1 of fibroblasts in the process of wound healing. This research comprehensively studied the regulation of Hst 1 on the function of fibroblasts in the process of wound healing and preliminary mechanism about it. Materials and methods The full‐thickness skin wound model was made on the back of C57/BL6 mice. The wound healing, collagen deposition and fibroblast distribution were detected on days 3, 5 and 7 after injury. Fibroblast was cultured in vitro and stimulated with Hst 1, and then, their biological characteristics and functions were detected. Results Histatin 1 can effectively promote wound healing, improve collagen deposition during and after healing and increase the number and function of fibroblasts. After healing, the mechanical properties of the skin also improved. In vitro, the migration ability of fibroblasts stimulated by Hst 1 was significantly improved, and the fibroblasts transformed more into myofibroblasts, which improved the function of contraction and collagen secretion. In fibroblasts, mTOR signalling pathway can be activated by Hst 1. Conclusions Histatin 1 can accelerate wound healing and improve the mechanical properties of healed skin by promoting the function of fibroblasts. The intermolecular mechanisms need to be further studied, and this study provides a direction about mTOR signalling pathway., Histatin 1 may be activated by G protein coupled receptors on the surface of cell membrane. Subsequently, PI3K / Akt / mTOR signaling pathway was activated to promote the migration of fibroblasts and the transformation of fibroblasts into myofibroblasts. By regulating the function of fibroblasts, it can improve the healing speed of acute wound and the mechanical properties of skin after healing.

Fracture repair is characterized by cytokine production and hypoxia. To better predict cytokine modulation of mesenchymal stem cell (MSC)‐aided bone healing, we investigated whether interleukin 4 (IL‐4), IL‐6, and their combination, affect osteogenic differentiation, vascular endothelial growth factor (VEGF) production, and/or mammalian target of rapamycin complex 1 (mTORC1) activation by MSCs under normoxia or hypoxia. Human adipose stem cells (hASCs) were cultured with IL‐4, IL‐6, or their combination for 3 days under normoxia (20% O 2) or hypoxia (1% O 2), followed by 11 days without cytokines under normoxia or hypoxia. Hypoxia did not alter IL‐4 or IL‐6‐modulated gene or protein expression by hASCs. IL‐4 alone decreased runt‐related transcription factor 2 (RUNX2) and collagen type 1 (COL1) gene expression, alkaline phosphatase (ALP) activity, and VEGF protein production by hASCs under normoxia and hypoxia, and decreased mineralization of hASCs under hypoxia. In contrast, IL‐6 increased mineralization of hASCs under normoxia, and enhanced RUNX2 gene expression under normoxia and hypoxia. Neither IL‐4 nor IL‐6 affected phosphorylation of the mTORC1 effector protein P70S6K. IL‐4 combined with IL‐6 diminished the inhibitory effect of IL‐4 on ALP activity, bone nodule formation, and VEGF production, and decreased RUNX2 and COL1 expression, similar to IL‐4 alone, under normoxia and hypoxia. In conclusion, IL‐4 alone, but not in combination with IL‐6, inhibits osteogenic differentiation and angiogenic stimulation potential of hASCs under normoxia and hypoxia, likely through pathways other than mTORC1. These results indicate that cytokines may differentially affect bone healing and regeneration when applied in isolation or in combination.

Purpose: Mild traumatic brain injury (TBI) is common but accurate diagnosis and its clinical consequences have been a problem. Maxillofacial trauma does have an association with TBI. Neuron-specific enolase (NSE) has been developed to evaluate neuronal damage. The objective of this study was to investigate the accuracy of NSE serum levels to detect mild brain injury of patients with sustained maxillofacial fractures during motor vehicle accidents. Methods: Blood samples were drawn from 40 healthy people (control group) and 48 trauma patients who had sustained isolated maxillofacial fractures and mild brain injury in motor vehicle accidents. Brain injuries were graded by Glasgow Coma Scale. In the trauma group, correlations between the NSE serum value and different facial fracture sites were also assessed. Results: The NSE serum level (mean ± SD, ng/ml) in the 48 patients with maxillofacial fractures and mild TBI was 13.12 ± 9.68, significantly higher than that measured in the healthy control group (7.72 ± 1.82, p

BackgroundOsteoradionecrosis (ORN) of the mandible is a severe complication of radiation therapy in head and neck cancer patients. Treatment of advanced stage mandibular osteoradionecrosis may consist of segmental resection and osseous reconstruction, often sacrificing the inferior alveolar nerve (IAN). New computer-assisted surgery (CAS) techniques can be used for guided IAN preservation and 3D radiotherapy isodose curve visualization for patient specific mandibular resection margins. This study introduces a novel treatment concept combining these CAS techniques for treatment of advanced stage ORN.MethodsOur advanced stage ORN treatment concept includes consecutively: 1) determination of the mandibular resection margins using a 3D 50 Gy isodose curve visualization, 2) segmental mandibular resection with preservation of the IAN with a two-step cutting guide, and 3) 3D planned mandibular reconstruction using a hand-bent patient specific reconstruction plate. Postoperative accuracy of the mandibular reconstruction was evaluated using a guideline. Objective and subjective IAN sensory function was tested for a period of 12 months postoperatively.ResultsFive patients with advanced stage ORN were treated with our ORN treatment concept using the fibula free flap. A total of seven IANs were salvaged in two men and three women. No complications occurred and all reconstructions healed properly. Neither non-union nor recurrence of ORN was observed. Sensory function of all IANs recovered after resection up to 100 percent, including the patients with a pathologic fracture due to ORN. The accuracy evaluation showed angle deviations limited to 3.78 degrees. Two deviations of 6.42° and 7.47° were found. After an average of 11,6 months all patients received dental implants to complete oral rehabilitation.ConclusionsOur novel ORN treatment concept shows promising results for implementation of 3D radiotherapy isodose curve visualization and IAN preservation. Sensory function of all IANs recovered after segmental mandibular resection.

Background Acute skin wounds may compromise the skin barrier, posing a risk of infection. Small intestinal submucosa (SIS) is widely used to treat acute and chronic wounds. However, the efficacy of SIS to accelerate wound healing still needs to be improved to meet clinical demands. To tackle this problem, platelet-rich plasma (PRP) is used due to its potency to promote proliferation, migration and adhesion of target cells. In this study, we applied PRP and SIS to skin wounds to explore their effects on wound healing by evaluating re-epithelialization, collagen production, angiogenesis and the inflammatory response. Methods A 1 × 1-cm full-thickness skin defect was established in mice. Sixty mice were divided into four treatment groups: PRP + SIS, PRP, SIS and control. On days 3, 5, 7, 10 and 14 post-surgery, tissue specimens were harvested. Haematoxylin and eosin, Masson’s trichrome, immunohistochemical and immunofluorescence double staining were used to visualize epidermal thickness, collagen and vascular regeneration and inflammation. Results Wound contraction in the PRP and PRP + SIS groups was significantly greater, compared with the other groups, on days 3 and 5 post-surgery. A histological analysis showed higher collagen expression in the PRP and PRP + SIS groups on day 7, which was associated with a thicker epidermal layer on day 14. In addition, immunohistochemical staining showed that CD31-positive blood vessels and vascular endothelial growth factor expression in the PRP + SIS and PRP groups were significantly higher, compared with the control group. Furthermore, immunofluorescence double staining showed that the number of M1 and M2 macrophages in the PRP + SIS and PRP groups was higher, compared with the control and SIS groups alone, on day 3. However, on day 7, the number of M1 macrophages dramatically decreased in the PRP + SIS and PRP groups. The ratio of M2 to M1 macrophages in the PRP + SIS and PRP groups was 3.97 and 2.93 times that of the control group and 4.56 and 3.37 times that of the SIS group, respectively. Conclusion Co-administration of SIS and PRP has a better effect on promoting angiogenesis, re-epithelialization and collagen regeneration in managing acute wound healing than either agent alone.

Background The ameloblastoma management is still challenging to the high recurrence rates and significant morbidity associated with radical treatment. The purpose of this 10-year retrospective study was to analyze the influence of ameloblastoma type and treatment strategy on the long-term outcomes and recurrence rates. Material and Methods The retrospective analyses of 64 histologically-confirmed ameloblastoma cases was performed. The possible risk factors for recurrence and the development of complications were estimated statistically. Results The treatment strategy applied for this group of patients was the following: thirty-four patients (53.1%) were treated conservatively with enucleation or extended bone curettage. Radical treatment (bone resection) was applied in 30 (46.9%) cases. The follow-up period ranged from 2 to 10 years (mean value 4.28 ± 3,26). General recurrence rate consisted 32.8%. This study did not find significant correlations between clinical or histopathological features of the ameloblastoma and the recurrence rate. The only factor that significantly influence recurrence rate was the treatment strategy (41% in conservative treatment vs 15% in radical treatment, p

OBJECTIVES: Patients with inflammatory bowel disease have an increased risk of developing oral health problems. The aim of this study was to investigate whether oral diseases in these patients are related to inflammation of the intestine and if there is a correlation between inflammatory bowel disease-specific health-related quality of life (IBD-HR-QOL) and oral health problems.STUDY DESIGN: The study was a cross-sectional survey and analysis of self-reported oral health of individuals with a stoma for Crohn's disease (CD), ulcerative colitis (UC), and treated colon cancer (CC). Validated international questionnaires were sent to members of the Stoma Federation of The Netherlands. Because there was an unequal distribution of male and female patients with CD and CC, data of 169 age-matched female patients with CD, UC, and CC with a stoma were analyzed.RESULTS: Patients with CD had significantly more oral health problems compared with those with UC or CC. Patients with CD and UC both had significantly more gingival-related problems compared with patients with CC. There was a significant negative correlation between IBD-HR-QOL and oral health problems.CONCLUSIONS: In the 3 distinguishable groups of patients with a stoma, patients with CD had an increased risk for oral health problems, independently from surgical removal of (a part of) the inflamed intestine, suggesting a general increased susceptibility of patients with CD for oral health problems.

In the field of rare bone diseases in particular, a broad care team of specialists embedded in multidisciplinary clinical and research environment is essential to generate new therapeutic solutions and approaches to care. Collaboration among clinical and research departments within a University Medical Center is often difficult to establish, and may be hindered by competition and non-equivalent cooperation inherent in a hierarchical structure. Here we describe the “collaborative organizational model” of the Amsterdam Bone Center (ABC), which emerged from and benefited the rare bone disease team. This team is often confronted with pathologically complex and under-investigated diseases. We describe the benefits of this model that still guarantees the autonomy of each team member, but combines and focuses our collective expertise on a clear shared goal, enabling us to capture synergistic and innovative opportunities for the patient, while avoiding self-interest and possible harmful competition.

Background/Aims Management of maxillofacial trauma in the geriatric population poses a great challenge due to anatomical variations and medical comorbidities. The aim of this study was to analyze the management variables, timing, and outcomes of facial fractures in elderly patients (aged 70 years or more) at several European departments of oral and maxillofacial surgery. Materials and Methods This study was based on a systematic computer-assisted database that allowed the recording of data from all geriatric patients with facial fractures from the involved maxillofacial surgical units across Europe between 2013 and 2017. Results A total of 1334 patients were included in the study: 665 patients underwent closed or open surgical treatment. A significant association (P lt .005) was found between the presence of concomitant injuries and a prolonged time between hospital admission and treatment. The absence of indications to treatment was associated with comorbidities and an older age (P lt .000005). Conclusions Elderly patients require specific attention and multidisciplinary collaboration in the diagnosis and sequencing of trauma treatment. A prudent attitude may be kept in selected cases, especially when severe comorbidities are associated and function is not impaired., Peer-reviewed manuscript: [http://smile.stomf.bg.ac.rs/handle/123456789/2528]