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Background: The search for an ideal bone substitute in reconstructive surgery has led to the exploration of various materials, with hydroxyapatite (HaP) emerging as a promising candidate due to its biocompatibility, osteoconductive properties, and structural similarity to human bone. Despite its potential, there is a paucity of data on the long-term safety and efficacy of HaP in facial skeletal reconstruction and augmentation., Methods: We conducted a systematic review following PRISMA 2020 guidelines, searching PubMed/MEDLINE, Google Scholar, CENTRAL, and Web of Science databases for studies on hydroxyapatite facial implants in reconstruction and augmentation., Results: Our search yielded 12 studies that met our inclusion criteria, encompassing 74 patients treated with HaP implants for various indications including facial fractures/defects, aesthetic facial balancing, and after tumor resection. The studies reported on outcomes such as implant integration, complications, aesthetic results, and patient satisfaction, with a general trend indicating positive outcomes for the use of HaP in facial reconstruction., Conclusion: Hydroxyapatite appears to be a viable and effective material for facial skeletal reconstruction and augmentation, offering benefits in terms of biocompatibility, osteoconductivity, and patient outcomes. However, limitations such as low mechanical strength and the need for further research on long-term safety and efficacy were identified. This review underscores the potential of HaP in craniofacial surgery while highlighting areas for future investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Kauke-Navarro, Knoedler, Knoedler and Safi.)

The proper closure of the access cavity between appointments during endodontic treatment is paramount and relies on temporary fillings. This systematic review evaluates the effectiveness of zinc oxide-based materials and glass-ionomer cement (GIC) as temporary coronal sealers after root canal treatment in extracted human teeth. Three databases were searched to identify randomized clinical trials that examined the sealing properties of various temporary sealing materials using dyes or stains as indicators. A total of seven in vitro studies that fulfilled the eligibility criteria were critically analyzed. These indicated significant variations in the relative sealing ability of the coronal breach of endodontically treated teeth, either by zinc oxide or GIC-based materials. While GIC-based material (e.g., Fuji IX and Fuji II) exhibited superior sealing of single-rooted teeth, zinc oxide-based material (e.g., Cavit, Coltosol, Caviton) also showed promising attributes. Resin-modified GIC formulations displayed enhanced physical properties, yet challenges related to adhesive failure and shrinkage during polymerization were observed. Zinc oxide-based materials have demonstrated superior coronal sealing effectiveness over certain GIC in controlled settings. Their premixed nature ensures consistent application and hygroscopic properties improve cavity sealing. However, the focus on dye penetration tests for microleakage in vitro may not fully represent the risk of bacterial infiltration. Thus, in vivo studies are crucial for validating these findings in clinical contexts., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Background: Aesthetic facial bone surgery and facial implantology expand the boundaries of conventional facial surgery that focus on facial soft tissue. This study aimed to reveal novel aesthetic facial measurements to provide tailored treatment concepts and advance patient care., Methods: A total of n=101 study participants (46 females and 55 males) were presented with 120 patient portraits (frontal images in natural head posture; 60 females and 60 males) and asked to assess the facial attractiveness (scale 0-10; "How attractive do you find the person in the image?") and the model capability score (MCS; scale 0-10; "How likely do you think the person in the image could pursue a modelling career?"). For each frontal photograph, defined facial measurements and ratios were taken to analyse their relationship with the perception of facial attractiveness and MCS., Results: The overall attractiveness rating was 4.3 ± 1.1, while the mean MCS was 3.4 ± 1.1. In young males, there was a significant correlation between attractiveness and the zygoma-mandible angle (ZMA)2 (r= - 0.553; p= 0.011). In young and middle-aged females, MCS was significantly correlated with facial width (FW)1-FW2 ratio (r= 0.475; p= 0.034). For all male individuals, a ZMA1 value of 171.79 degrees (Y= 0.313; p= 0.024) was the most robust cut-off to determine facial attractiveness. The majority of human evaluators (n=62; 51.7%) considered facial implants a potential treatment to improve the patient's facial attractiveness., Conclusion: This study introduced novel metrics of facial attractiveness, focusing on the facial skeleton. Our findings emphasized the significance of zygomatic measurements and mandibular projections for facial aesthetics, with FI representing a promising surgical approach to optimize facial aesthetics., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Headache disorders (HD) remain a nationwide challenge for the US healthcare system affecting nearly 60% of the US population. Surgical deactivation of the peripheral trigger site, also referred to as headache surgery, represents an effective treatment for patients with refractory HD pain or non-response to pharmacological regimes. Research stemming from other surgical specialties has underlined the clinical relevance of neural interconnections in refining diagnostic algorithms, adapting surgical techniques, and improving overall patient outcomes. While different HD trigger points have been identified, there is a paucity of studies discussing these mostly sensory neural interconnections between these trigger points in a comprehensive fashion. Herein, we aim to provide an overview of the specific nerves involved in HD and synthesize the current literature on HD nerve interconnections to, ultimately, deduce clinical implications. Overall, this line of research may help refine the perioperative workflow and enhance HD patient care., Competing Interests: Financial Disclosure Statement: We have no conflict of interest to disclose. None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript. Jeffrey Janis receives royalties from Thieme and Springer Publishing., (Copyright © 2024 by the American Society of Plastic Surgeons.)

Malignancies represent a persisting worldwide health burden. Tumor treatment is commonly based on surgical and/or non-surgical therapies. In the recent decade, novel non-surgical treatment strategies involving monoclonal antibodies (mAB) and immune checkpoint inhibitors (ICI) have been successfully incorporated into standard treatment algorithms. Such emerging therapy concepts have demonstrated improved complete remission rates and prolonged progression-free survival compared to conventional chemotherapies. However, the in-toto surgical tumor resection followed by reconstructive surgery oftentimes remains the only curative therapy. Breast cancer (BC), skin cancer (SC), head and neck cancer (HNC), and sarcoma amongst other cancer entities commonly require reconstructive surgery to restore form, aesthetics, and functionality. Understanding the basic principles, strengths, and limitations of mAB and ICI as (neo-) adjuvant therapies and treatment alternatives for resectable or unresectable tumors is paramount for optimized surgical therapy planning. Yet, there is a scarcity of studies that condense the current body of literature on mAB and ICI for BC, SC, HNC, and sarcoma. This knowledge gap may result in suboptimal treatment planning, ultimately impairing patient outcomes. Herein, we aim to summarize the current translational endeavors focusing on mAB and ICI. This line of research may serve as an evidence-based fundament to guide targeted therapy and optimize interdisciplinary anti-cancer strategies., Competing Interests: MP received speaker’s honoraria and travel funds from Amgen, Kite, and Takeda. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2024 Knoedler, Huelsboemer, Hollmann, Alfertshofer, Herfeld, Hosseini, Boroumand, Stoegner, Safi, Perl, Knoedler, Pomahac and Kauke-Navarro.)

Balancing the immune response after solid organ transplantation (SOT) and vascularized composite allotransplantation (VCA) remains an ongoing clinical challenge. While immunosuppressants can effectively reduce acute rejection rates following transplant surgery, some patients still experience recurrent acute rejection episodes, which in turn may progress to chronic rejection. Furthermore, these immunosuppressive regimens are associated with an increased risk of malignancies and metabolic disorders. Despite significant advancements in the field, these IS related side effects persist as clinical hurdles, emphasizing the need for innovative therapeutic strategies to improve transplant survival and longevity. Cellular therapy, a novel therapeutic approach, has emerged as a potential pathway to promote immune tolerance while minimizing systemic side-effects of standard IS regiments. Various cell types, including chimeric antigen receptor T cells (CAR-T), mesenchymal stromal cells (MSCs), regulatory myeloid cells (RMCs) and regulatory T cells (T regs ), offer unique immunomodulatory properties that may help achieve improved outcomes in transplant patients. This review aims to elucidate the role of cellular therapies, particularly MSCs, T cells, T regs , RMCs, macrophages, and dendritic cells in SOT and VCA. We explore the immunological features of each cell type, their capacity for immune regulation, and the prospective advantages and obstacles linked to their application in transplant patients. An in-depth outline of the current state of the technology may help SOT and VCA providers refine their perioperative treatment strategies while laying the foundation for further trials that investigate cellular therapeutics in transplantation surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer GM declared a shared affiliation, though no other collaboration, with one of the authors JI at the time of the review., (Copyright © 2024 Knoedler, Dean, Diatta, Thompson, Knoedler, Rhys, Sherwani, Ettl, Mayer, Falkner, Kilian, Panayi, Iske, Safi, Tullius, Haykal, Pomahac and Kauke-Navarro.)

Background: Facial implantology (FI) is a growing field in facial surgery that focuses on harmonizing and balancing facial features. Despite its increasing popularity, larger-scale studies on FI outcomes and risks are scarce., Methods: The ACS-NSQIP (2008-2021) was queried to identify patients who underwent combined/isolated alloplastic FI surgery of the malar/mandibular region. Based on CPT codes (21125; 21270), procedures were subdivided into combined or isolated FI surgery of the malar or the mandibular region., Results: The study population included 84 patients, of which n = 19 (23%), n = 10 (12%), n = 33 (39%), and n = 22 (26%) underwent combined malar, isolated malar, combined mandibular, and isolated mandibular FI surgery, respectively. Isolated malar (total n = 10) and mandibular FI surgery (total n = 22) patients had relatively high comorbidity rates with up to n = 6 (60%) active smokers and n = 9 (41%) with hypertension, respectively. Combined malar (n = 19) and mandibular FI surgeries (n = 33) had the highest complication rates with n = 3 (16%) and n = 5 (15%) patients experiencing any complications. For both isolated malar and mandibular FI procedures, n = 1 (10% and 4.5%) patient reported any complications., Conclusion: In this study, we accessed the ACS-NSQIP database and found alloplastic augmentation for zygoma and mandible to be safe. Patients who underwent combined procedures and mandibular augmentation were more likely to show complications or require inpatient stay. Most alloplastic augmentations of mandible or zygoma were combined with other procedures (62%) which suggests that alloplastic facial implants (in the academic setting) are often used as an adjunct in the treatment of complex craniofacial disorders., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Facial implantology, a crucial facet of plastic and reconstructive surgery, focuses on optimizing implant materials for facial augmentation and reconstruction. This manuscript explores the use of Polyetheretherketone (PEEK) implants in craniofacial surgery, highlighting the challenges and advancements in this field. While PEEK offers mechanical resilience, durability, and compatibility with imaging modalities, its biologically inert nature hinders integration with the host tissue, which may lead to complications. In this systematic review, our aim was to assess the current state of knowledge regarding the clinical evaluation of Polyetheretherketone (PEEK) implants in facial implantology, with a focus on craniofacial augmentation and reconstruction in human studies. Additionally, we explore and discuss surface and structural modifications that may enhance bioreactivity and reduce complications in PEEK implants. A systematic review identified 32 articles detailing the use of PEEK Patient-Specific Implants (PSIs) in 194 patients for both reconstructive and aesthetic purposes. Complications, including infections and implant failures, were reported in 18% of cases, suggesting the need for improved implant materials. The discussion delves into the limitations of PEEK, prompting the exploration of surface and structural modifications to enhance its bioreactivity. Strategies, such as hydroxyapatite coating, titanium coating, and porous structures show promise in improving osseointegration and reducing complications. However, the literature review did not reveal reports of coated or modified PEEK in facial reconstructive or aesthetic surgery. In conclusion, although PEEK implants have been successfully used in craniofacial reconstruction, their biological inertness poses challenges. Surface modifications, particularly hydroxyapatite coatings, provide opportunities to promote osseointegration. Future research should focus on prospective long-term studies, especially in craniofacial surgery, to investigate the stability of uncoated PEEK implants and the potential benefits of surface modifications in clinical applications. Patient-specific PEEK implants hold promise for achieving durable craniofacial reconstruction and augmentation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Kauke-Navarro, Knoedler, Knoedler, Deniz and Safi.)

Facial reconstruction and augmentation, integral in facial plastic surgery, address defects related to trauma, tumors infections, and congenital skeletal deficiencies. Aesthetic considerations, including age-related facial changes, involve volume loss and diminished projection, often associated with predictable changes in the facial skeleton. Autologous, allogeneic, and alloplastic implants are used to address these concerns. Autologous materials such as bone, cartilage, and fat, while longstanding options, have limitations, including unpredictability and resorption rates. Alloplastic materials, including metals, polymers, and ceramics, offer alternatives. Metals like titanium are biocompatible and used primarily in fracture fixation. Polymers, such as silicone and polyethylene, are widely used, with silicone presenting migration, bony resorption, and visibility issues. Polyethylene, particularly porous polyethylene (MedPor), was reported to have one of the lowest infection rates while it becomes incorporated into the host. Polyether-ether-ketone (PEEK) exhibits mechanical strength and compatibility with imaging modalities, with custom PEEK implants providing stable results. Acrylic materials, like poly-methylmethacrylate (PMMA), offer strength and is thus mostly used in the case of cranioplasty. Bioceramics, notably hydroxyapatite (HaP), offer osteoconductive and inductive properties, and HaP granules demonstrate stable volume retention in facial aesthetic augmentation. Combining HaP with other materials, such as PLA, may enhance mechanical stability. 3D bioprinting with HaP-based bioinks presents a promising avenue for customizable and biocompatible implants. In conclusion, various materials have been used for craniofacial augmentation, but none have definitively demonstrated superiority. Larger randomized controlled trials are essential to evaluate short- and long-term complications comprehensively, potentially revolutionizing facial balancing surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Kauke-Navarro, Knoedler, Knoedler, Deniz, Stucki and Safi.)

Facial vascularized composite allotransplantation (FVCA) is an emerging field of reconstructive surgery that represents a dogmatic shift in the surgical treatment of patients with severe facial disfigurements. While conventional reconstructive strategies were previously considered the goldstandard for patients with devastating facial trauma, FVCA has demonstrated promising short- and long-term outcomes. Yet, there remain several obstacles that complicate the integration of FVCA procedures into the standard workflow for facial trauma patients. Artificial intelligence (AI) has been shown to provide targeted and resource-effective solutions for persisting clinical challenges in various specialties. However, there is a paucity of studies elucidating the combination of FVCA and AI to overcome such hurdles. Here, we delineate the application possibilities of AI in the field of FVCA and discuss the use of AI technology for FVCA outcome simulation, diagnosis and prediction of rejection episodes, and malignancy screening. This line of research may serve as a fundament for future studies linking these two revolutionary biotechnologies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Knoedler, Knoedler, Allam, Remy, Miragall, Safi, Alfertshofer, Pomahac and Kauke-Navarro.)

Artificial intelligence (AI) has emerged as a versatile health-technology tool revolutionizing medical services through the implementation of predictive, preventative, individualized, and participatory approaches. AI encompasses different computational concepts such as machine learning, deep learning techniques, and neural networks. AI also presents a broad platform for improving preoperative planning, intraoperative workflow, and postoperative patient outcomes in the field of oral and maxillofacial surgery (OMFS). The purpose of this review is to present a comprehensive summary of the existing scientific knowledge. The authors thoroughly reviewed English-language PubMed/MEDLINE and Embase papers from their establishment to 1 December 2022. The search terms were (1) "OMFS" OR "oral and maxillofacial" OR "oral and maxillofacial surgery" OR "oral surgery" AND (2) "AI" OR "artificial intelligence". The search format was tailored to each database's syntax. To find pertinent material, each retrieved article and systematic review's reference list was thoroughly examined. According to the literature, AI is already being used in certain areas of OMFS, such as radiographic image quality improvement, diagnosis of cysts and tumors, and localization of cephalometric landmarks. Through additional research, it may be possible to provide practitioners in numerous disciplines with additional assistance to enhance preoperative planning, intraoperative screening, and postoperative monitoring. Overall, AI carries promising potential to advance the field of OMFS and generate novel solution possibilities for persisting clinical challenges. Herein, this review provides a comprehensive summary of AI in OMFS and sheds light on future research efforts. Further, the advanced analysis of complex medical imaging data can support surgeons in preoperative assessments, virtual surgical simulations, and individualized treatment strategies. AI also assists surgeons during intraoperative decision-making by offering immediate feedback and guidance to enhance surgical accuracy and reduce complication rates, for instance by predicting the risk of bleeding.

Fibula free flaps (FFF) represent a working horse for different reconstructive scenarios in facial surgery. While FFF were initially established for mandible reconstruction, advancements in planning for microsurgical techniques have paved the way toward a broader spectrum of indications, including maxillary defects. Essential factors to improve patient outcomes following FFF include minimal donor site morbidity, adequate bone length, and dual blood supply. Yet, persisting clinical and translational challenges hamper the effectiveness of FFF. In the preoperative phase, virtual surgical planning and artificial intelligence tools carry untapped potential, while the intraoperative role of individualized surgical templates and bioprinted prostheses remains to be summarized. Further, the integration of novel flap monitoring technologies into postoperative patient management has been subject to translational and clinical research efforts. Overall, there is a paucity of studies condensing the body of knowledge on emerging technologies and techniques in FFF surgery. Herein, we aim to review current challenges and solution possibilities in FFF. This line of research may serve as a pocket guide on cutting-edge developments and facilitate future targeted research in FFF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Baecher, Hoch, Knoedler, Maheta, Kauke-Navarro, Safi, Alfertshofer and Knoedler.)

Oral squamous cell carcinoma (OSCC) is a complex disease with a high potential for lymph node metastasis and poor survival rates. Accurate nodal staging is crucial for prognostic assessment and treatment planning in OSCC. Recent research has suggested that nodal tumor volume (NTV) may be a more accurate indicator of nodal disease burden than traditional staging methods. However, the prognostic significance of NTV in OSCC remains unclear. This systematic review aims to evaluate the existing evidence on the relationship between NTV and prognosis in OSCC. A comprehensive search of electronic databases was conducted, and studies meeting inclusion criteria were critically appraised and synthesized. Our review identified 23 studies that investigated the prognostic significance of NTV in OSCC. The majority of studies reported that larger NTV was associated with poorer survival outcomes, although the strength of the association varied. The review also identified several areas for future research, including the standardization of NTV measurement and the integration of NTV into the broader landscape of OSCC management. In conclusion, our review suggests that NTV holds promise as a novel prognostic factor in OSCC, but more research is needed to fully elucidate its potential and inform clinical decision-making., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Bernasconi, Bilic, Kauke-Navarro and Safi.)

Background: There is a paucity of data on the impact of cytomegalovirus (CMV) serostatus and CMV infection on outcomes in facial vascularized composite allotransplantation., Methods: This international, multicenter, retrospective cohort study presents data on CMV and basic transplant-related demographics, including pretransplant viral D/R serostatus, and duration of antiviral prophylaxis. CMV-related complications (viremia, disease), allograft-related complications (rejection episodes, loss), and mortality were analyzed., Results: We included 19 patients, 4 of whom received CMV high-risk transplants (D+/R-). CMV viremia was noted in 6 patients (all 4 D+/R- patients and 2 D-/R+), mostly within the first-year posttransplant, shortly after discontinuation of antiviral prophylaxis (median 2 mo). CMV disease occurred in 2 D+/R- patients. The high-risk group experienced relatively more rejection episodes per month follow-up. None of D+/R- patients suffered allograft loss due to rejection (longest follow-up: 121 mo)., Conclusions: D+/R- patients were at increased risk of CMV-related complications. Although a higher number of rejections was noted in this group, none of the D+/R- patients lost their allograft or died because of CMV or rejection. Thus, CMV D+/R- face transplantation can likely be safely performed with prophylaxis, active surveillance, and prompt treatment., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Acute rejection remains a vexing problem in vascularized composite allotransplantation (VCA). Available immunosuppressive regimens are successful at minimizing alloimmune response and allowing VCA in humans. However, repeated rejection episodes are common, and systemic side effects of the current standard regimen (Tacrolimus, MMF, Prednisone) are dose limiting. Novel immunomodulatory approaches to improve allograft acceptance and minimize systemic toxicity are continuously explored in preclinical models. We aimed to systematically summarize past and current approaches to help guide future research in this complex field., Methods: We conducted a systematic review of manuscripts listed in the MEDLINE and PubMed databases. For inclusion, articles had to primarily investigate the effect of a therapeutic approach on prolonging the survival of a skin-containing preclinical VCA model. Non-VCA studies, human trials, anatomical and feasibility studies, and articles written in a language other than English were excluded. We followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines., Results: The search retrieved 980 articles of which 112 articles were ultimately included. The majority of investigations used a rat model. An orthotopic hind limb VCA model was used in 53% of the studies. Cell and drug-based approaches were investigated 58 and 52 times, respectively. We provide a comprehensive review of immunomodulatory strategies used in VCA preclinical research over a timeframe of 44 years., Conclusion: We identify a transition from anatomically non-specific to anatomical models mimicking clinical needs. As limb transplants have been most frequently performed, preclinical research focused on using the hind limb model. We also identify a transition from drug-based suppression therapies to cell-based immunomodulation strategies., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objectives: Mandible fractures can be treated with different plate systems, that is, miniplates or three-dimensional (3D) plates. This systematic review describes the effectiveness and clinical outcomes of 3D plates used in fractures of the mandible and aims to critically evaluate its risks and benefits., Materials and Methods: A comprehensive electronic search was conducted without date but with restriction to articles written in English. Studies in humans, including randomized or quasi-randomized controlled trials and retrospective studies, were included. The outcome parameters measured were number of patients, fracture classification, results, follow-up period, postoperative complications, and mean age of patients. Major complications were defined as those needing additional surgical intervention, for example, malocclusion, infection or plate fracture. Accordingly, complications not needing additional surgical intervention were defined as minor (ie, dehiscence, trismus)., Results: Guided by the PRISMA statement and the Cochrane Handbook for Systematic Reviews of Interventions, the authors identified 44 publications with a total of 1790 patients. Among the articles selected for the final review, there were 32 reported prospective studies, 12 reported retrospective studies. Regarding the evaluation of quality, 8 studies showed a low value of the risk of bias, 17 a moderate risk, and 19 a high risk. There were statistically significant advantages for 3D plates in mandibular fractures in terms of postoperative complications, for example, wound dehiscences or plate fracture., Conclusions: The 3D plate is an effective treatment modality for mandibular fractures, with low incidence of major complications, decreased length of operation time, and increased stability of osteosynthesis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by Mutaz B. Habal, MD.)

Objective: Bone substitute (BS) size might influence the clinical outcomes of guided bone regeneration (GBR) procedures. The aim of the present study was to investigate the influence of BS size on macrophage (Mφ) and osteoblast behaviors in vitro., Materials and Methods: Two different granule sizes (S and M/L) were assessed for four different commercial BSs: deproteinized bovine bone mineral (DBBM), biphasic calcium phosphate type 1 (BCP1), BCP type 2 (BCP2), and carbonate apatite (CO 3 Ap). The BSs were compared for their impacts on the cell viability and differentiation potential of THP-1-derived Mφs and human osteoblast-like Saos-2 cells., Results: The smaller granules showed higher material volumes and surface areas than the larger granules. Significantly higher viability of Mφs and Saos-2 cells was observed with the DBBM_L-size granules than with the DBBM_S-size granules. Gene expression experiments in Mφs revealed few differences between the two sizes of each BS, although higher CD206 mRNA levels were observed in the BCP1_L group and the CO 3 Ap_M group than in the respective S-size groups on day 1. Only DBBM showed significantly higher mRNA levels of osteogenic markers, including Runx2 and osteocalcin, in Saos-2 cells in the S-size group than in the L-size group., Conclusions: The S-size and L-size DBBM granules exhibited clear differences in cell outcomes: cells cultured on the S-size granules exhibited lower cell viability, higher osteopromotive ability, and no noticeable Mφ polarization changes., Clinical Relevance: A smaller granule size might be advantageous due to greater bone regeneration potential in the use of DBBM granules to treat defects., (© 2021. The Author(s).)

Background: Facial vascularized composite allotransplantation (fVCA) represents a reconstructive approach that enables superior improvements in functional and esthetic restoration compared with conventional craniomaxillofacial reconstruction. Outcome reports of fVCA are usually limited to short-term follow-up or single-center experiences. We merge scientific literature on reported long-term outcome data to better define the risks and benefits of fVCA., Methods: We conducted a systematic review of PubMed/MEDLINE databases in accordance with PRISMA guidelines. English full-text articles providing data on at least 1 unique fVCA patient, with ≥3 years follow-up, were included., Results: The search yielded 1812 articles, of which 28 were ultimately included. We retrieved data on 23 fVCA patients with mean follow-up of 5.3 years. More than half of the patients showed improved quality of life, eating, speech, and motor and sensory function following fVCA. On average, the patients had 1 acute cell-mediated rejection and infectious episode per year. The incidence rates of acute rejection and infectious complications were high within first-year posttransplant but declined thereafter. Sixty-five percent of the patients developed at least 1 neoplastic or metabolic complication after transplantation. Chronic vascular rejection was confirmed in 2 patients, leading to allograft loss after 8 and 9 years. Two patient deaths occurred 3.5 and 10.5 years after transplant due to suicide and lung cancer, respectively., Conclusions: Allograft functionality and improvements in quality of life suggest a positive risk-benefit ratio for fVCA. Recurrent acute rejection episodes, chronic rejection, immunosuppression-related complications, and heterogeneity in outcome reporting present ongoing challenges in this field., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Identifying a donor for facial vascularized composite allotransplant recipients can be a lengthy, emotionally challenging process. Little is known about the relative distribution of key donor characteristics among potential donors. Data on actual wait times of patients are limited, making it difficult to estimate wait times for future recipients., Methods: The authors retrospectively reviewed charts of nine facial vascularized composite allotransplant patients and provide data on transplant wait times and patient characteristics. In addition, they analyzed the United Network for Organ Sharing database of dead organ donors. After excluding donors with high-risk characteristics (e.g., active cancer or risk factors for blood-borne disease transmission), the authors calculated the distribution of relevant donor-recipient matching criteria (i.e., ethnicity, body mass index, age, ABO blood group, cytomegalovirus, Epstein-Barr virus, hepatitis C virus) among 65,201 potential donors., Results: The median wait time for a transplant was 4 months (range, 1 day to 17 months). The large majority of United Network for Organ Sharing-recorded deaths from disease were white (63 percent) and male (58 percent). Female donors of black, Hispanic, or Asian descent are underrepresented, with 7, 5, and 1 percent of all recorded deaths from disease, respectively. Potential donors show cytomegalovirus and Epstein-Barr virus seropositivity of 65 and 95 percent, respectively. The number of annual hepatitis C-positive donors increased over time., Conclusions: Actual facial vascularized composite allotransplant wait times vary considerably. Although most patients experience acceptable wait times, some with underrepresented characteristics exceed acceptable levels. Cytomegalovirus-seropositive donors present a large portion of the donor pool, and exclusion for seronegative patients may increase wait time. Hepatitis C-seropositive donors may constitute a donor pool for underrepresented patient groups in the future., (Copyright © 2021 by the American Society of Plastic Surgeons.)

Background: Cutaneous changes of facial vascularized composite allotransplants (fVCAs) are extensively described in the literature. Parts of the nose, nasal, and oral cavities are included in most fVCAs. Distinctively, the nose and mouth are lined by mucosa. Little is known about the histopathology and complications of the mucosa involved in fVCA patients., Methods: The study constitutes a retrospective cohort study of nine fVCA patients. Medical records were reviewed for information about changes of oral and nasal mucous membranes. Types of mucosal lesions were recorded and analyzed. Uni- and multivariate generalized estimating equation (GEE) models were used to assess the odds of developing mucosal inflammation in the presence of clinico-pathologic variables., Results: A total of 186 clinical encounters with examination of oral and nasal mucous membranes were included. Membranes were devoid of clinical pathology in 101 instances (53% of all clinical assessments). Ulcerations/erosions (27%), edema (18%), and erythema (14%) were the most common lesions. Oral lesions affected the lips (58%), buccal mucosa (38%), and palate (5%). Sinonasal processes predominantly affected nasal vestibules and septae. In univariate analysis, sirolimus, skin rejection, and skin Banff grade were associated with the presence of an acute inflammatory mucosal lesion (p<0.05). In multivariate analysis, skin Banff grade and sirolimus were independent predictors of mucosal inflammation., Conclusion: Pathologies of fVCA mucous membranes are more common than previously reported. Mucosal assessment plays an important role in the pleomorphic allograft rejection process evaluation rather than diagnosis and treatment based on cutaneous pathology.  A closer look at the pathophysiology of fVCA mucosal rejection and inflammation is warranted., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Summary: Skin is one of the target tissues of rejection in face transplants and, because of its easy accessibility, has become the gold standard in the diagnosis of rejection. The allograft contains deeper tissues where rejection can occur, but samples cannot be obtained because of difficult access. Deep tissue changes were monitored on computed tomographic scans of the midface in six face transplant recipients with the help of image segmentation. The maxillary sinus was identified as a dynamic anatomical compartment. Observed changes in volume of the aeration relative to the opacification (aeration coefficient) of the maxillary sinus were quantified with the help of image segmentation. Changes in the aeration coefficient as a surrogate of mucosal swelling were quantified and related to time, treatment, and skin rejection grade. Lower aeration coefficients were found only in patients with transplanted maxillary sinus mucosa. Pathologic changes were not observed in face transplant recipients with a native maxillary sinus. The data show that the aeration coefficient was significantly lower at the time of biopsy-proven allograft rejection. Neither mechanical, nor infectious, nor medication side effects sufficiently explain the findings presented herein. The authors' findings are important to consider for clinical management of face transplant patients who receive parts of the sinonasal tract. The authors identify a potential radiologic biomarker of deep tissue allograft rejection. In the future, the proposed methodology might prove useful in monitoring deeper dynamic tissue changes in vascularized composite allografts and might help in designing patient-specific, individualized treatment strategies., Competing Interests: Disclosure:No author states any conflicts of interest., (Copyright © 2021 by the American Society of Plastic Surgeons.)

Background: Local immunosuppression in vascularized composite allotransplantation (VCA) aims to minimize immunosuppressant-related toxic and malignant side effects. Promising allograft survival data have been published by multiple workgroups. In this systematic review, we examine preclinical animal studies that investigated local immunosuppression in VCA., Material and Methods: We conducted a systematic review of manuscripts listed in the MEDLINE and PubMed database concerning preclinical VCA models. Papers included had to be available as full-text and written in English. Non-VCA studies, human trials, and studies using cell-based therapy strategies were excluded. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines., Results: Literature research retrieved 980 articles. Ten studies published between 2010 and 2019 met the inclusion and exclusion criteria. Seven out of ten articles demonstrated a significant prolongation of allograft survival by using local immunosuppression. Five articles employed tacrolimus (TAC) as the main immunosuppressive agent. Seven studies performed hind-limb VCA in a rat model., Conclusion: The easily accessible location of skin containing VCAs makes it an ideal candidate for local immunosuppression. Published preclinical data are very promising in terms of improved allograft survival and reduced systemic toxicity., Competing Interests: Declaration of Competing Interest None., (Published by Elsevier Ltd.)

Background: Facial vascularized composite allotransplantation (fVCA) presents an established approach to restore form and function of patients with catastrophic facial defects. Skin is one of the target tissues of the rejection process, and due to its easy accessibility has become the gold standard in the diagnosis of rejection. Mucosal rejection frequently occurs; however, the added value of mucosal rejection assessment for patient management is unknown., Methods: We conducted a systematic review of manuscripts listed in the MEDLINE/PubMed and GoogleScholar databases to identify articles that provide data on mucosal rejection following fVCA. For inclusion, papers had to be available as full-text and written in English. Non-VCA studies and animal studies were excluded. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines., Results: We included 17 articles that described changes in allotransplanted mucosa of fVCAs. These articles yielded data on 168 BANFF graded biopsies of corresponding skin and mucosa biopsies. Rejection grades were consistently higher in mucosal biopsies. Concordance between allograft skin and mucosa biopsy grades increased with an increasing skin-BANFF grade. Mucosa rejection grades were on average lower in the early stages of the posttransplant period (postoperative mo 12)., Conclusions: The mucosa of facial allotransplants is one of the primary targets of rejection. The data indicates that higher-grade skin rejection does not occur in absence of mucosal rejection. Further investigations are needed to elucidate the exact role of mucosal biopsies for fVCA patient management.

Background: This study aimed to investigate the prognostic implications of comorbidity/risk factors in a cohort of patients with OSCC., Methods: The prospective study included patients with biopsy-proven primary OSCC. The impact of potential predictors on (post)operative complications, days spent in the ICU, and length of hospitalization was analyzed using both univariate and multivariate analysis., Results: Using a microvascular free flap (p = 0.009) and tobacco abuse (p = 0.005) had statistically significant impacts on postoperative complications in univariate, but not in multivariate, analysis. The duration of anesthesia (p < 0.001), type of neck dissection (p = 0.014), reconstruction type (p < 0.001), and red blood cell transfusion during operation (p = 0.007) had statistically significant impacts on spending ≥ 3 days in ICU in univariate analysis, with reconstruction type (p = 0.022) and red blood cell transfusion during operation (p = 0.034) having similar impacts in multivariate analysis. The duration of anesthesia (p < 0.001), pT (p = 0.009), type of neck dissection (p = 0.046), reconstruction type (p < 0.001), and microvascular free flap (p < 0.001) had a statistically significant impacts on length of hospitalization in univariate analysis, with reconstruction type (p < 0.001) also having a significant impact in multivariate analysis., Conclusion: None of the investigated variables showed a significant effect on the prediction of (post)operative complications according to the Clavien-Dindo classification. The type of reconstruction proved to be a valid predictor for the time spent in ICU as well as for the overall length of hospitalization. Red blood cell transfusion during operation further predicted the time spent in ICU after operation. Both variables should be taken into account when performing a comprehensive planning of the patients' hospitalization., Competing Interests: Declaration of Competing Interest All authors have declared that there are no potential conflicts of interest., (Copyright © 2020 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Machine perfusion (MP) has evolved as a promising approach for the ex situ preservation in organ transplantation. However, the literature on the use of MP in human vascularized composite allografts is scarce. The aim of this study was to evaluate the effects of hypothermic MP with an acellular perfusate in human upper extremities and compare with the current gold standard of static cold storage (SCS)., Methods: Six upper extremities were assigned to either MP (n = 3) or SCS (n = 3) conditions for 24 h. MP-extremities were perfused with oxygenated Steen solution at a constant pressure of 30 mm Hg and 10°C., Results: Median total ischemia time was 213 min (range, 127-222 min). Myoglobin, creatine-kinase (CK) showed increased levels at the start of MP (medians: myoglobin: 4377 ng/mL, CK: 1442 U/L), peaking 6 h after perfusate exchange (medians: myoglobin: 9206 ng/mL, CK: 3995 U/L) at timepoint 24. Lactate levels decreased from a median of 6.9-2.8 mmol/L over time. Expression of hypoxia-inducible factor 1-alpha peaked in the SCS-group after 8 h, followed by a decrease. Increased hypoxia-inducible factor 1-alpha expression in the MP group was delayed until 20 h. Perfusion pressure, temperature, and circuit flow were maintained at median of 30.88 mm Hg, 9.77°C, and 31.13 mL/min, respectively. Weight increased 1.4% in the SCS group and 4.3% in the MP group over 24 h., Conclusions: Hypothermic ex situ perfusion with an oxygenated acellular Steen solution may extend the allowable extracorporeal preservation time by a factor of 4-6 compared to SCS and holds promise to be beneficial for vascularized composite allograft recipients and victims of traumatic major limb amputation.

Supplemental Digital Content is available in the text., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

The aim of this study was to provide volumetric data of the pterygopalatine fossa by semiautomatic segmentation based upon cone beam computed tomography.Cone beam computed tomography (CBCT) images of 100 patients were analyzed. By using the open source software "ITK-Snap," the volumetric measurements of 200 pterygopalatine fossae were performed. For statistical investigations paired t test, and independent Student t test were performed. Also, the Pearsons chi-square test was applied. P values P < 0.05 were considered significant.The mean volume was 578.376 mm for the right and 560.979 mm for the left side. The results indicated statistically significant differences according to the right and the left pterygopalatine fossa, regardless of gender (P < 0.05). The analysis of differences between males and females did not show any significant results (P > 0.05), although males present a slightly larger volume than females. According to the median age (59 years), younger patients presented smaller volumes, whereas older patients presented larger volumes. Nevertheless, no statistically significant differences according to age (χ = 3.520; P > 0.05) could be found.Clinical intervention with the application of local anesthetics into the complex and vulnerable anatomy of the pterygopalatine fossa makes a thorough knowledge about the volumetric capacity indispensable. Therefore, the semiautomatic segmentation of CBCT images provides a useful, available and validated tool. Our results show that a final injected anesthetic volume larger than 1 ml exceeds the pterygopalatine fossa capacity considerably and could cause complications. To prevent this, volumetric analysis of this region can provide further information and enables an individualized patients' treatment.

Background: Long-term outcomes after face transplantation are rarely reported in the scientific literature. Here we present outcome data of a partial face allograft recipient 10 years after transplantation., Methods: Medical records were reviewed for functional and psychosocial outcomes as well as complications. Histopathologic analyses of autopsy tissues and characterization of skin immune cells were performed., Results: The patient retained long-term motor and sensory function, though with a noticeable drop in sensory function after year 5. Social reintegration of the patient was marked by reconnection with his family and participation in public social activities. Immunosuppressive therapy consisted of tacrolimus (target levels 6-8 ng/mL after the first year), mycophenolate, and prednisone, while steroids were completely weaned between years 1 and 7. One acute cellular rejection episode of grade II or higher occurred on average per year and led to chronic skin changes (papillary dermal sclerosis with superficial hyalinization, epidermal thinning with loss of rete ridges, perieccrine fibrosis), but the allograft vessels, muscles, adipose tissue, and bone were spared. Allograft skin was characterized by increased number of CD4+ TNF-α/IL17A producing T-cells as compared with native skin. Long-term kidney function was maintained at 60 mL/min estimated glomerular filtration rate. Unfortunately, the preexisting hepatitis C virus infection with liver cirrhosis was resistant to 3 treatments with new direct-acting antivirals and eventually hepatocellular carcinoma developed, causing the patient's death 10 years after transplantation., Conclusion: This report suggests that face transplants can maintain their function for at least 10 years. Chronic skin changes can occur independently of allograft vasculopathy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The pterygopalatine fossa (PPF) is a complex and paired anatomical structure located at the skull base. A clinically and surgically relevant structure located in the pterygopalatine fossa is the sphenopalatine ganglion. Electrical stimulation of the sphenopalatine ganglion is one possible method of treating cluster headache. The pterygomaxillary fissure (PMF) defines the pterygopalatine fossa laterally and determines the surgical approach. As part of preoperative surgical planning, each patient undergoes a preoperative head computed tomography or a cone beam computed tomography. In our study cone beam computed tomography images of 90 male and 110 female PMF were analyzed. Generally, males have a wider fissure than females. Moreover, a significant inter-subject difference could be shown between males and females. The analysis of the right and left PMF according to gender and age does not show any significant intra-subject differences. Following an established protocol for high-resolution CT images the measurements were classified into four fissure types and also analyzed according to gender and age. Fissure type I is significantly more often present in males, whereas the smaller fissure types (II, III, and IV) are significantly more often found in females. Older patients presented statistically significant more often with type I, whereas the younger patients showed more often the narrower types II and IV. Due to the fact that narrow fissures smaller than 2 mm could limit the insertion of neurostimulator implants in the PPF, special attention should be paid to females and younger patients during preoperative planning.

Background: There is unmet need for non-invasive immunomonitoring to improve diagnosis and treatment of acute rejection in vascularized composite allotransplantation (VCA). Circulating matrix metalloproteinase 3 (MMP3) was described as a candidate non-invasive biomarker to predict treatment response to acute rejection in clinical VCA. However, larger validation studies are yet to be reported to allow for more definitive conclusions. Methods: We retrospectively measured MMP3 levels using ELISA in a total of 140 longitudinal serum samples from six internal and three external face transplant recipients, as well as three internal and seven external upper extremity transplant recipients. The control groups comprised serum samples from 36 kidney transplant recipients, 14 healthy controls, and 38 patients with autoimmune skin disease. A linear mixed model was used to study the effect of rejection state (pre-transplant, no-rejection, non-severe rejection (NSR), and severe rejection) on MMP3 levels. Results: In VCA, MMP3 levels increased significantly ( p < 0.001) between pre- and post-transplant no-rejection states. A further increase occurred during severe rejection ( p < 0.001), while there was no difference in MMP3 levels between non-severe and no-rejection episodes. A threshold of 5-fold increase from pre-transplant levels could discriminate severe from NSR with 76% sensitivity and 81% specificity (AUC = 0.79, 95% CI = 0.65-0.92, p < 0.001). In kidney transplantation, the MMP3 levels were significantly ( p < 0.001) elevated during antibody-mediated rejection but not during T-cell mediated rejection (TCMR) ( p = 0.547). MMP3 levels in healthy controls and autoimmune skin disease patients were comparable with either pre-transplant or no-rejection/NSR episodes of VCA patients. Conclusion: The results of this study suggest that serum MMP3 protein is a promising marker for stratifying patients according to severity of rejection, complementary to biopsy findings., (Copyright © 2019 Kollar, Uffing, Borges, Shubin, Aoyama, Dagot, Haug, Kauke, Safi, Talbot, Morelon, Dakpe, Pomahac and Riella.)

Objectives: The aim of the study was to investigate the association between meningioma volume and the occurrence of clinic-radiologic signs of tumor aggressiveness. For volumetric approximation, the authors evaluated the method of semiautomatic image segmentation at hand of high-resolution MRI-image sequences., Methods: ITK-SNAP was utilized for semiautomatic image segmentation of 58 gadolinium-contrast enhanced T1-weighted thin-slice MRI datasets for volumetric analysis. Furthermore, multimodal imaging datasets (including T2, FLAIR, T1) were evaluated for radiological biomarkers of aggressiveness and growth potential. Thereby generated data was checked for association with retrospectively collected data points., Results: Location (P = 0.001), clinical disease manifestation (P = 0.033), peritumoral edema (P = 0.038), tumor intrinsic cystic degeneration (P = 0.007), three-dimensional complexity (P = 0.022), and the presence of meningioma mass effect (P = 0.001) were statistically associated with higher tumor volumes. There was no association between higher tumor volumes and histopathological tumor grade., Conclusion: The size of a meningioma does not seem to reliably predict tumor grade. Growth potential seems to be influenced by tumor location. Higher tumor volumes were significantly associated with the occurrence of clinical symptoms.

For horizontal bone deficiency alveolar ridge osteotomy is considered an option for augmentation. Major advantages are the option for a one-stage approach and the absence of donor site morbidity. However, the conventional technique is associated with complications such as perforations and fractures of the cortical bone. A case using a 3D based modified, full-guided alveolar ridge expansion is described to explain the technique step by step. Main features of modified technique: successive application of surgical guides for ridge osteotomy and expansion - implementation of virtually determined splitting vector, which allows guided bone splitting along a guide surface of template in an ideal direction - osteotomy as deep as implant length. The example shows that the 3D based modified alveolar ridge osteotomy is a suitable alternative to the conventional technique as it has several advantages such as fewer fractures and perforations of the cortical vestibular bone. The individualized preoperative planning helps to minimize complications. However, long-term outcomes and a study, conducted on a study group, is needed to evaluate the benefits of our presented treatment protocol., (Copyright © 2019 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objectives: The aim of this in vitro study was to evaluate osteotomy speed, heat development, and bone structure influence from osteotomies performed by various piezoelectric devices and insert tips. These devices and tips were compared among each other with regard to conventional rotatory and oscillating systems with special focus on the insert tip design and thickness., Material and Methods: The osteotomies were conducted on porcine ribs utilizing 12 different insert tips (straight and angulated) and three conventional systems. After time and temperature measurements, histological analysis was carried out. Light microscopy was used to evaluate the roughness of the osteotomic surface and to search for indications of thermal bone necrosis. A special software analyzing tool was employed to determine cutting width (mm) and debris (%)., Results: All piezoelectric tips created smooth cuts. Cutting widths in general were wider than the actual insert tip size with a tendency for narrow straight insert tips producing relatively wide osteotomies, whereas narrow angulated inserts produced relatively small osteotomies. None of the samples demonstrated distinct indication of necrosis. Overall, there was only a small amount of debris in all osteotomy gaps. Conventional rotatory saws were faster and created less heat compared to all tested piezoelectric systems. Straight tips proved faster osteotomy speed than angulated tips. Thin insert tips indicated to have a positive correlation to osteotomy time and performed faster than conventional microsaw. The average temperature rise was lower when using conventional systems, but critical exceeding temperatures were only observed in short-time exceptional cases. In general, temperature rise was less when using angulated inserts., Conclusion: All tested tips are appropriate for bone surgery. Only small differences were found among the piezoelectric insert tips. Although conventional rotatory systems in general performed faster osteotomies, special designed and thin piezoelectric insert tips seem to have a positive influence on osteotomy speed. Ultimately, none of the tested devices or inserts combined all best features of speed, heat development, bone structure influence, and safety., Clinical Relevance: Narrow and straight piezoelectric insert tips demonstrated reduced osteotomy times. Nevertheless, a combination of conventional and piezoelectric systems in clinical practice might be the best way to work time-efficient, patient-oriented, and safe. The choice of instrument should be based on clinical experience of the user and should be evaluated individually depending on the case.

Objectives: Tumor invasion into blood and/or lymphatic vessels, perineural invasion, and histopathological grading are evaluated to assess the biological aggressiveness of oral squamous cell carcinoma (OSCC). We aim to assess the prognostic impact of a novel scoring system, based upon the aforementioned histological parameters., Materials and Methods: Retrospective chart review of 334 patients with treatment-naive squamous cell carcinoma of the oral cavity. Statistical analysis was performed using univariate and multivariate analysis. Histological grade G1 or G2 were assigned 0 points and G3 or G4 1 point. Invasion of the lymphatic vessels, blood vessels, or perineural space was given 1 point. Zero points were given, when invasion was not detectable. The final score was conducted through addition of each parameter. Therefore, our scoring system ranged between 0 and 4 points., Results: T-classification (p < 0.001), N-classification (p < 0.001), UICC stage (p < 0.001), extracapsular spread (p < 0.001), locoregional recurrence (p < 0.001), and overall survival (p < 0.001) were significantly associated with the OSCC-Histoscore. In multivariate analysis, T-classification (p = 0.001), N-classification (p = 0.039), resection margins (p = 0.038), and OSCC-Histoscore (p < 0.001) were independent prognostic markers for overall survival rate., Conclusion: Our presented OSCC-Histoscore serves as a strong independent prognostic parameter for 5-year overall survival (OS) and predicts OS better than T-classification, N-classification, and resection margins., Clinical Relevance: Our presented histoscore improves prediction of the overall survival of patients with OSCC.

Introduction: Published data on procalcitonin (PCT) levels after microsurgical interventions are very scarce, although infection within these patients is not only associated with severe morbidity but also significantly higher mortality rates., Material and Methods: Retrospective study on 20 patients, who were operated on by a single experienced plastic and reconstructive surgeon within one year (June 2017-June 2018). The authors included all patients, who received microvascular transplants for reconstruction of soft tissue defects. Furthermore, age above 18 years and appropriate documentation allowing sufficient data collection were defined as inclusion criteria. The authors excluded all patients with perioperative systemic inflammation and transplant loss, as our aim was to solely determine and evaluate potential alterations of serological PCT levels after microsurgical interventions., Results: The PCT cutoff level to differentiate physiological and pathological levels was defined as 0.1 μg/L. There was no detectable increase in procalcitonin in all of our 20 patients, for whom the authors performed microvascular transplantation to reconstruct soft tissue defects., Conclusion: Serological PCT levels remain stable after the considered surgical interventions and therefore PCT levels might be utilized to identify systemic inflammation, thus helping to reduce severe complications by early individualized antiinfective treatment strategies.

Introduction: Microsurgical interposition of vein grafts is an extraordinarily filigree surgical technique, which requires both sound theoretical knowledge and solid manual skills. Although there are a large number of training models, the majority of these are either relatively expensive, technically complex, or employ synthetic materials with poor resemblance to human tissue. The authors' model allows training of ex vivo vein graft interposition on gradually thawed cryopreserved vessels and it, therefore, is cost-efficient and readily available when needed. Furthermore, it respects the 3R-principle (Reduce-Refine-Replace), as it is based on rat cadaveric vessels., Methods: Three trainees with basic microsurgical experience, but without prior performance of vein graft interpositioning, were chosen to perform 20 femoral vein graft (5 mm) interpositions into femoral artery defects. The patency and leakage rate served as qualitative variable and operation time as a quantitative variable for efficiency control., Results: For the first half of trials, the trainees had a patency failure rate of 50% and for the second half a rate of 13.3%. The leakage rate noticeably decreased from 44.4% in the first half of trials to 10% in the second half. Although the trainees needed 60 minutes on average for their first 10 trials, they improved to 51 minutes for their last 10 anastomoses., Conclusion: The authors' microsurgical model offers a simple, low-cost simulation training, specifically designed for learning of vein graft interposition into arterial defects. The model is associated with a high learning curve, based on an objective control of the anastomoses by assessment of the patency, leakage, and operation time.

Introduction: The subject of the present study was a systematic comparative analysis of the rheumatoid arthritis (RA)-induced pathomechanisms in the temporomandibular joint with those of the limb joints using the serum-induced arthritis K/BxN model., Methods: In 18 BALB/c mice the induction of RA was performed according to the Kouskoff method. Another healthy cohort served as controls (n = 12). Joint swelling of the paws was measured using a micrometer. Functional data were obtained analyzing locomotion. Three-dimensional examination of the temporomandibular joint was performed with micro-computed tomography imaging, followed by histological evaluation of the extremity joints and the temporomandibular joint. Additionally, immunohistochemical investigations were carried out to evaluate inflammatory and immunological changes., Results: Measurement of joint swelling showed a significant increase in the diameter of the paws, as well as a decrease in locomotor activity compared to control animals and the time before arthritis induction. Histological and immunohistochemical investigations showed clear signs of inflammation in the extremity joints. In contrast, no histological or immunohistochemical indications of an inflammatory process were detectable in the temporomandibular joint. In addition, the three-dimensional analysis by micro-computed tomography of the temporomandibular joints did not show any obvious morphological changes., Conclusion: For the first time, using the K/BxN model we could demonstrate that, due to its anatomical and mechanical conditions, the temporomandibular joint seems to be less susceptible to the initiation of RA compared to limb joints. Therefore, additional investigations are needed on other arthritis models as well, in order to further improve our understanding of the pathogenesis and defense mechanisms of the disease., (© 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Purpose: The aim of this prospective work was to examine oral leukoplakia for their podoplanin expression to determine whether podoplanin expression is associated with the degree of dysplasia., Materials and Methods: We took biopsy samples from 50 patients with oral leukoplakia in 2013. The preparations studied by immunohistochemistry were analyzed in correlation with the degree of dysplasia and other clinicopathological variables., Results: The Chi-square test showed a significant correlation between podoplanin expression and the degree of dysplasia according to the squamous intraepithelial neoplasia (SIN) classification (p = 0.033). Also, a significant association between age grouping and podoplanin expression was found. We were able to show that the distribution is the same for both age groups in relation to the score of podoplanin expression (p = 0.003)., Conclusion: In a comparable retrospective work of our working group, it could be shown that podoplanin is a reliable predictive marker for the assessment of the risk of malignant transformation. The present work was able to substantiate the assumption that podoplanin not only plays an important role in the context of malignant degeneration but also exerts a major influence in advance., (Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: Size characterization of osteolytic jaw lesions (OJL), in particular of neoplastic nature, is heterogeneously performed and lacks standardization in the medical literature and clinical practice. An OJL's volume holds promise as a surrogate for treatment response and prognosis. We comparatively evaluate various methods for size characterization of odontogenic OJLs., Methods: We retrospectively performed semiautomatic image segmentation of CBCT data sets for volume approximation of neoplastic (51) and non-neoplastic odontogenic OJLs (100). We assessed the three greatest orthogonal diameters and calculated the volume using the cuboid- and ellipsoid-formula. Image segmentation was carried out using ITK-SNAP. Image segmentation-based volume approximation served as reference. Intra- and inter-rater variability were evaluated at hand of Bland-Altman-Analysis and dice similarity coefficient (DSC)., Results: Concerning the intrarater variability, we found the DSC to be highest for image segmentation-based volume approximation, simultaneously showing the tightest limits of agreement and greatest reliability. The cuboid formula showed consistent overestimation of the lesion's volume with a percent mean difference of -52 % (upper and lower limits of agreement +8.57 %  and -112.63%, respectively). In mean, the ellipsoid formula underestimated the lesion's volume by 10.1% (upper and lower limits of agreement +76.8%  and -56.6%, respectively). Inter rater variability was higher for formula-based volume approximation. Volume and multilocularity ( p = 0.001) correlate with aggressiveness and growth potential., Conclusions: Segmentation-based volume approximation holds great promise for patient individualized treatment planning and clinical management. The data suggest that maximum tumour diameter-based size characterization, especially the cuboid-formula and the maximum diameter alone, should not be recommended.

The authors present a novel biological nonliving epineurial nerve coaptation training model, which allows cost-efficient practicing on organic mammal nerves and offers an objective performance control on the basis of successful suturing and respecting the 3R model.Anatomic dissection of 40 rat cadavers was performed. Four residents without prior microneurosurgical experience were included. Each trainee performed 20 epineurial nerve coaptations. The number of successful sutures served as qualitative variable and operation time as a quantitative variable for efficiency control.The rate for successful sutures was 51.9% in the first half of trials and improved to 94.4% in the second half. Whereas, the trainees needed a mean time of 34 minutes for the first 10 coaptations, the last 10 coaptations were performed within 24.5 minutes.The authors' presented model is an easily accessible, low-cost microneurosurgical simulation model, allowing a realistic and instructive performance of epineurial nerve coaptation. Because cadaveric nerves are used, an approval of the local ethics committee is not needed. Furthermore, anatomic knowledge about the topography related to the harvest of the sciatic nerve of rats is provided in this study.

Background: This study aims at investigating the prognostic significance of lymph node ratio (LNR) in a cohort of patients with oral squamous cell carcinomas (OSCC), treated with neoadjuvant radiochemotherapy followed by radical surgery., Methods: The study included 171 treatment-naive patients with biopsy-proven primary OSCC, being reviewed retrospectively. All patients received a concomitant neoadjuvant radiochemotherapy (RCT) followed by radical surgery of the primary tumor and neck dissection based on the pretreatment staging results. The Kaplan-Meier survival analysis method was used to estimate the events of interest for overall survival (OS). Prognostic factors were identified through univariate and multivariate analysis., Results: The 5-year overall survival rate for all patients was 48 %. In univariate analysis, patient's age and data compiled from the histopathological examination as margin status, extracapsular spread, ypT, ypN, ypUICC, number of positive lymph nodes and lymph node ratio (LNR) had a statistically significant impact on overall survival. Multivariate analysis revealed an independent significant impact of patient age, ypT, margin status and LNR on OS. ypN showed no statistical significant impact on OS., Conclusion: Our results show that LNR is an important predictor for OS in patients with OSCC that were treated with neoadjuvant radiochemotherapy and radical surgery., (Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

The present investigation constitutes a retrospective evaluation of the outcome in children who received surgical correction of a scaphocephalic phenotype by median total vertex craniectomy. Between September 2009 and September 2015, a total of 35 infants with non-syndromic scaphocephaly were treated according to the same standardized operative technique of total vertex craniectomy by a single surgeon approach. At the time of surgery, the patients were between 3 and 12 months of age, with a median of 5 months. The mean duration of the procedure was 94 min. The duration of postoperative follow-up was a mean of 24 months (range 6-49 months). A total of 34 (97%) patients were successfully treated by total vertex craniectomy and were thus classified as category I according to the Whitaker score. Only one individual was assigned to category IV, necessitating secondary major craniofacial corrective surgery. Aesthetic outcomes were excellent in 34 cases and poor in one case. No major complication occurred. The reoperation rate was 3%. The surgical method we present herein is a wide median craniectomy which can be applied in young individuals with non-syndromic single-suture scaphocephaly., (Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: For successful reshaping of the cranial vault in terms of corrective fronto-orbital advancement (FOA) efficient and reliable internal fixation systems for stabilization of bone fragments are indispensable. The rate of complications and feasibility of corrective FOA with the usage of titanium-based rigid fixation systems is rarely analyzed and discussed., Methods: The authors retrospectively reviewed the medical records of 42 patients who received corrective FOA with the implementation of titanium internal rigid fixation and consecutive secondary surgery for removal. The reliability of the fixation system was judged by the outcome of the FOA as evaluated by the Whitaker score, esthetic outcome as well as by the complication rate of the secondary intervention, necessary for removal of the fixation system., Results: All patients were categorized as Whitaker I (no further treatment desirable). Esthetic outcome was excellent in all patients as judged by surgeon and parents. Mean age at the time of FOA was 9.3 months. Time to removal, duration of the second hospital stay for removal of the fixation system, and duration of surgical drains were on average 5 months, 2 days, and 1.7 days, respectively. Mean duration of the secondary surgery was 63 min. No complications occurred., Conclusion: Our investigation supports the usage of titanium internal rigid fixation systems in pediatric craniofacial surgery, thereby providing a reliable alternative to avoid the well-documented problems of bio-absorbable plate fixation systems.

Customized implants have simplified surgical procedures and have improved patient outcome in craniomaxillofacial surgery. Traditionally, patient-specific data is gathered by conventional computed tomography (CT). However, cone-beam CT (CBCT) can generate a 3D reconstruction of the area of interest with a lower dose of radiation at reduced cost. In this study, we investigated the feasibility of using CBCT data to design and generate customized implants for patients requiring craniomaxillofacial reconstruction. We used CBCT to generate 62 implants for 51 consecutive patients admitted to our department between January 2015 and December 2017. The indications for reconstruction and types of reconstruction were very variable. In all cases, the implants were well fitted and no implant-related complications were detected. Pre-surgical planning was faster and more efficient as we did not have to consult a radiologist. Although CBCT data is more difficult to process than conventional CT data for the implant provider, the clinical advantages are pronounced and we now use CBCT as standard in our department. In conclusion, we have shown that using CBCT to design and manufacture customized implants for reconstruction of the craniomaxillofacial area is feasible and recommend this approach to other departments., (Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Purpose: Fractures of the orbital floor and orbital rim are frequently treated in maxillofacial departments. Various approaches to the orbital floor are described in the literature. We present an investigation of a modified subciliary approach (laterocaudal approach) with respect to its feasibility and clinical outcome., Materials and Methods: Our retrospective study investigated 130 well-documented cases of patients with orbital floor fractures who received surgical reconstruction using a laterocaudal approach, and compared the results with the current literature, with a focus on subciliary and transconjunctival approaches., Results: 111 patients (85.4%) presented a Vancouver scar scale (VSS) of 0.14 patients (10.8%) had a VSS score of 1. No patients had a VSS of 2. Just five patients (3.8%) had a slight ectropium and therefore a VSS score of 3., Conclusion: The laterocaudal approach can be safely performed and presents advantages over comparable techniques such as the subciliary and transconjunctival approaches if performed correctly., (Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

In consideration of the 3-R-rule (Refine-Replace-Reduce) as a guideline for promoting ethical use of animals for surgical training, we present a novel training model for microvessel anastomosis. In a rat cadaveric study, we evaluated the surgical anatomy of the common carotid artery (CCA), external jugular vein (EJV) and femoral vessels (FV) which were then used as templates for the present investigation. Anatomical dissection of 30 rat cadavers was performed. Two residents without prior microsurgical experience were included in the study and performed 5 CCA, 5 femoral artery, 5 EJV and 5 femoral vein anastomoses. Patency and leakage served as qualitative variables and operation time as a quantitative variable for efficiency control. The average time improved for arterial and venous anastomoses (45 min-22 and 60 to 32 min, respectively) for both surgeons. While both surgeons experienced patency failure or leakage within the first half of performed arterial and venous anastomoses, they could improve to a 100% patency rate without the occurrence of leakage for the last half of trials. The rat head & neck anatomy presents various characteristics related to the harvest of the vessels of interest. We provide anatomical knowledge about the topography related to the harvest of the CCA, EJV, and FV. Our model is an easily accessible, low-cost microsurgical simulation model, allowing a realistic and instructive performance of anastomoses. Since cadaveric vessels are used, an approval of the local ethics committee is not needed., (Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Introduction: Recent studies highlighted the prognostic superiority of lymph node volume towards the conventional N Classification. However, data on the importance of neck lymph node volume, obtained by semiautomatic segmentation of CT images, do not exist for locoregional recurrence in patients with oral squamous cell carcinoma (OSCC)., Methods: Retrospective chart review of 100 patients, who were diagnosed and treated between 2006-2014. Inclusion criteria were patients with treatment-naive oral squamous cell carcinoma and primarily curative intended surgery with negative resection margins, for whom a preoperative computed tomography (CT) of the head and neck region was performed. Furthermore, comprehensive neck dissection (level I-V) due to ipsilateral lymph node metastasis was chosen as inclusion criterion. Exclusion criteria were neoadjuvant chemoradiotherapy, T4b classification, perioperative death, unresectable disease, synchronous malignancy, follow-up < 3 months and inadequate information to correctly determine clinicopathological characteristics., Results: Pathological N Classification (p = 0.001), central necrosis (p = 0.008) and lymph node volume (p < 0.001) significantly affected locoregional recurrence (p < 0.001). Multivariate analysis indicated N Classification (p = 0.06) and volume (p < 0.001) as indepedent risk factors for locoregional recurrence., Conclusion: Volumetric measurement serves as a better risk stratification tool than the conventional N Classification for OSCC. A lymph node volume of more than 6.86 cm 3 goes along with a 20-fold higher risk for locoregional failure., (Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Sinonasal sarcomas are rare and heterogeneous in nature. Continuously collecting data influencing the prognosis is fundamental for optimizing therapeutic assessment of this highly destructive neoplasm., Methods: We conducted a single-institution retrospective cohort study considering 27 patients with sinonasal sarcoma., Results: The overall survival (OS) rates for 1 year and 5 years were calculated as 74% and 36%, respectively. Extent of the primary tumor (P = .010), nodal spread (P = .009), and age (P = .004) significantly reduced the OS. Disease-free survival (DFS) was significantly reduced by age (P = .003), extent of the primary (P = .006), nodal (P = .004), and hematogenous (P = .048) spread. Multimodal therapy including surgery improved the OS and DFS rates (P < .05)., Conclusion: Prognosis is poor due to late disease recognition. However, multimodal therapeutic regimens, including surgery, may improve the outcome., (© 2018 Wiley Periodicals, Inc.)

Purpose: Lymph node ratio (LNR) essentially improves assessment of prognosis and therapeutic decision making for patients with oral squamous cell carcinoma, as it considers both the number of positive lymph nodes and the number of dissected lymph nodes. Mandibular infiltration by oral squamous cell carcinoma is a vital clinicopathological feature, significantly worsens prognosis. However, to the best of our knowledge, data on the influence of LNR on prognosis for patients with OSCC and mandibular infiltration are not available., Materials and Methods: A retrospective chart review of 89 patients with treatment-naive oral squamous cell carcinoma and histopathologically proven mandibular infiltration (pT4a) was performed. Exclusion criteria were primarily curative intended surgery (radical tumor resection, neck dissection and segmental mandibulectomy) with negative resection margins. Exclusion criteria were neoadjuvant chemoradiotherapy, erosive infiltration of the mandible, T4b classification, perioperative death, unresectable disease, synchronous malignancy, follow-up <3 months, and inadequate information to correctly determine clinicopathological characteristics., Results: We observed a significant correlation on univariate analysis between locoregional recurrence and pathologic N classification (p = 0.004), perineural invasion (p = 0.005) and lymph node ratio (p < 0.001). On multivariate analysis, lymph node ratio (p = 0.028) was shown to be an independent indicator for locoregional recurrence., Conclusion: LNR predicted locoregional recurrence better than the conventional nodal staging system and therefore might serve as a more precise risk stratification tool. LNR >7% led to a 11.419-fold higher risk for locoregional recurrence of patients with mandibular infiltration due to OSCC., (Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)