Truth Lies in the Depths: Novel Insights into Facial Aesthetic Measurements from a U.S. Survey Panel.

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 .

From standard therapies to monoclonal antibodies and immune checkpoint inhibitors - an update for reconstructive surgeons on common oncological cases.

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.

Immune modulation in transplant medicine: a comprehensive review of cell therapy applications and future directions.

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 (Tregs), 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, Tregs, 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.

Neural Interconnections of Extracranial Nerves in Headache Surgery: Anatomical Landmarks and Clinical Implications - A Review of Literature.

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.

Surface modification of PEEK implants for craniofacial reconstruction and aesthetic augmentation-fiction or reality?

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.

Early outcomes and risk factors for complications after facial alloplastic implant surgery: An ACS-NSQIP study.

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.

Balancing beauty and science: a review of facial implant materials in craniofacial surgery.

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.

Application possibilities of artificial intelligence in facial vascularized composite allotransplantation-a narrative review.

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.

Face the Future-Artificial Intelligence in Oral and Maxillofacial Surgery.

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.

From bench to bedside - current clinical and translational challenges in fibula free flap reconstruction.

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.

Nodal tumor volume as a prognostic factor for oral squamous cell carcinoma-a systematic review.

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.

Cytomegalovirus-related Complications and Management in Facial Vascularized Composite Allotransplantation: An International Multicenter Retrospective Cohort Study.

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.

A systematic review of immunomodulatory strategies used in skin-containing preclinical vascularized composite allotransplant models.

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.

Donor and Recipient Matching in Facial Vascularized Composite Allotransplantation: A Closer Look at the Donor Pool.

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.

Three-Dimensional Osteosynthesis Plates for the Surgical Treatment of Mandibular Fractures.

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.

Full facial retransplantation in a female patient-Technical, immunologic, and clinical considerations.

There is limited experience with facial retransplantation (fRT). We report on the management of facial retransplantation in a facial vascularized composite allotransplant recipient following irreversible allograft loss 88 months after the first transplant. Chronic antibody-mediated rejection and recurrent cellular rejection resulted in a deteriorated first allograft and the patient underwent retransplantation. We summarize the events between the two transplantations, focusing on the final rejection episode. We describe the surgical technique of facial retransplantation, the immunological and psychosocial management, and the 6-month postoperative outcomes. Removal of the old allograft and inset of the new transplant were done in one operation. The donor and recipient were a good immunological match. The procedure was technically complex, requiring more proximal arterial anastomoses and an interposition vein graft. During the first and second transplantation, the facial nerve was coapted at the level of the branches. There was no hyperacute rejection in the immediate postoperative phase. Outcomes 6 months postoperatively are promising. We provide proof-of-concept that facial retransplantation is a viable option for patients who suffer irreversible facial vascularized composite allograft loss.

Dynamic Maxillary Sinus Changes of Facial Vascularized Composite Allotransplants.

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.

The impact of the size of bone substitute granules on macrophage and osteoblast behaviors in vitro.

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 (CO3Ap). 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 CO3Ap_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.

Pathologies of oral and sinonasal mucosa following facial vascularized composite allotransplantation.

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.

Long-term Outcomes After Facial Allotransplantation: Systematic Review of the Literature.

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.