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BACKGROUND Restoration of facial animation and sensation are highly important for the outcome after facial allotransplantation. The identification of healthy nerves for neurotization, through recipient to donor nerve coaptation, is of particular importance for successful nerve regeneration within the allograft. However, due to the severity of the initial injury and resultant scar formation, a lack of healthy nerve stumps in the recipient is a commonly encountered problem. In this study, we evaluate the technical feasibility of performing nerve transfers in facial transplantation for both sensory and motor neurotization. METHODS Fifteen fresh cadaver heads were used in this study. The study was divided in two parts. First, the technical feasibility of nerve transfer from the cervical plexus (CP) to the mental nerve (MN) and the masseter nerve (MaN) to the buccal branches of the facial nerve (BBFN) was assessed. Next, we performed nerve transfers in simulated face transplants to describe the surgical technique focusing on sensory restoration of the midface and upper lip by neurotization of the infraorbital nerve (ION), sensory restoration of the lower lip by neurotization of the MN, and smile reanimation by neurotization of the BBFN. RESULTS In all specimens coaptation of at least one of branches of the CP to the mental nerve was possible as well as between the masseter nerve to the buccal branch of the facial nerve. In simulated face transplant procedures nerve transfers of the supraorbital nerve (SON) to the infraorbital nerve (ION), cervical plexus branches to the mental nerve, and masseter nerve to facial nerve are all technically possible. CONCLUSION Nerve transfers are a technically feasible option that could theoretically be used in face transplantation either as a primary nerve reconstruction when there are no available healthy nerves, or as a secondary procedure for enhancement of functional outcomes. The supraorbital nerve, branches of the cervical plexus an

Background: To investigate possible differences in the effects of soluble factors from oral squamous cell carcinoma (SCC) cells (UT-SCC-87) and normal oral keratinocytes (NOK) on fibroblast expression of genes involved in tumor stroma turnover. Materials and Methods: Transwell co-cultures with fibroblasts in collagen gels, and SCC cells or NOK in inserts were carried out. Fibroblast gene expression was measured with real-time polymerase chain reaction (PCR). Results: The expression of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) was up-regulated in co-cultures with SCC cells but not with NOK. In contrast, both SCC cells and NOK regulated matrix metalloproteinase-1 (MMP1) and -3, and tissue inhibitor of metalloproteinases-2 (TIMP2) and -3 to a similar extent, while MMP2 and TIMP1 were largely unaffected. Interleukin 1 alpha (IL1 alpha) up-regulated both MMP1 and MMP3 and down-regulated PAI-1, TIMP2 and -3. Conclusion: SCC and NOK regulate fibroblast expression of genes involved in tumor stroma turnover differentially in vitro. These observations may contribute to a better understanding of the mechanisms behind extracellular matrix turnover in tumors.

Background: The collected experience from facial allotransplantations has shown that the recovery of sensory function of the face graft is unpredictable. Unavailability of healthy donor nerves, especially in central face defects may contribute to this fact. Herein, the technical feasibility of transferring the supraorbitary nerve (SO) to the infraorbitary nerve (IO) in a model of central facial transplantation was investigated. Methods: Five heads from fresh cadavers were dissected with the aid of 3× loupe magnification. Measurements of the maximum length of dissection of the SO nerve through a supraciliary incision and the IO nerve from the skin of the facial flap to the infraorbital foramen were performed. The distance between supraorbital and infraorbital foramens and the calibers of both nerves were also measured. In all dissections, we simulated a central allotransplantation procedure and assessed the feasibility of directly transferring the SO to the IO nerve. Results: The average maximum length of dissection for the IO and SO nerve was 1.4 ± 0.3 cm and 4.5 ± 1.0 cm, respectively. The average distance between the infraorbital and supraorbital foramina was 4.6 ± 0.3 cm. The average calibers of the nerves were of 1.1 ± 0.2 mm for the SO nerve and 2.9 ± 0.4 mm for the IO nerve. We were able to perform tension-free SO to IO nerve coaptations in all specimens. Conclusion: SO to IO nerve transfer is an anatomically feasible procedure in central facial allotransplantation. This technique could be used to improve the restoration of midfacial sensation by the use of a healthy recipient nerve in case of the recipient IO nerves are not available secondary to high-energy trauma.

Blowout fractures in the medial orbital wall may lead to enophthalmos, ocular dysmotility, and diplopia. Ten consecutive patients with unilateral, isolated fractures of the medial orbital wall were retrospectively studied. The radiologic accuracy of the medial orbital wall reconstructions and the long-term clinical outcomes were assessed. All cases were treated through a bicoronal approach and by use of porous polyethylene-titanium implants. The total fracture area and the orbital volume increase from the blowout were measured on computed tomographic scans. Next, we evaluated the reconstruction in the posterior part of the medial wall. This was done by calculating the ratio between the defect area and the implant area located behind the anterior ethmoidal canal. The patients were examined at least 1 year after the operation, and the rates of enophthalmos and diplopia were evaluated. The mean fracture defect area was 2.45 cm(2) (range, 0.41-4.16 cm(2)), and the mean volume increase from the blowout fractures was 1.82 cm(3) (range, 0.53-2.76 cm(3)). The orbital volume was accurately restored in all patients. However, the ratio of implant to defect area behind the anterior ethmoidal canal ranged from 0% to 100% (mean, 47.3%). None of the patients had enophthalmos or diplopia at the long-term follow-up. The results confirm that restoration of orbital volume is important to prevent postoperative enophthalmos in isolated medial orbital blowout fractures. Complete reconstruction of the most posterior part of the medial orbital wall seems to be of lesser importance.

This article presents a treatment strategy for early release of interalveolar synechiae, aiming to facilitate early oral feeding and prevent temporomandibular joint ankylosis. The treatment results of 2 patients with van der Woude syndrome were retrospectively studied. Both patients underwent early surgical release of interalveolar synechiae under general anesthesia through fiberscopic nasal intubation. The 2 patients were treated at the ages of 6 and 14 days, respectively. The interincisival distances increased from 5 and 6 mm preoperatively to 11 and 10 mm immediately after surgery. This was increased further to 25 and 20 mm at long-term follow-up (6 and 24 months). In conclusion, synechiae between the upper and lower jaws can be safely treated at a very early age under general anesthesia with fiberscopic nasotracheal intubation. The purpose of early intervention in these cases is to facilitate oral feeding and prevent temporomandibular joint ankylosis.

Virtual surgical planning and computer-aided surgery were used to treat a mono-ostotic fibrous dysplasia of the right zygoma. Mirroring of the contralateral zygoma sets the target for the contouring of the affected zygomatic bone. An optical system for computer-guided surgery was used. Instruments were calibrated and visualized in real time on screen. Achievement of the virtually set target for the orbitozygomatic anatomy was assessed during surgery. Postoperative computed tomography and clinical follow-up confirmed an excellent result with regard to facial symmetry and eye bulb position. The volume of the orbit was increased from 24.2 to 26.0 mL compared with a contralateral orbital volume of 25.7 mL. Computer-guided surgery may be a useful tool in the surgical reduction of craniofacial fibrous dysplasia.

To investigate the mechanisms behind the antifibrotic effect associated with epidermal regeneration, the expression of 12 fibroblast genes important for the modulation of the extracellular matrix (ECM), as well as alpha-smooth muscle actin, was studied in a keratinocyte-fibroblast organotypic skin culture model. The study was performed over time during epidermal generation and in the presence or absence of the profibrotic factor transforming growth factor-beta. the Presence of epidermal differentiation markers in the model was essentially coherent with that of native skin. Fibroblast gene expression was analyzed with real-time polymerase chain reaction after removal of the epidermal layer. After 2 days of air-exposed culture, 11 out of the 13 genes studied were significantly regulated by keratinocytes in the absence or presence of transforming growth factor-beta. The regulation of connective tissue growth factor, collagen I and III, fibronectin, plasmin system regulators, matrix metalloproteinases and their inhibitors as well as alpha-smooth muscle actin was consistent with a suppression of ECM formation or contraction. Overall, the results support a view that keratinocytes regulate fibroblasts to act catabolically on the ECM in epithelialization processes. This provides possible mechanisms for the clinical observations that reepithelialization and epidermal wound coverage counteract excessive scar formation.

Connective tissue growth factor (CTGF/CCN2) is a matricellular protein induced by transforming growth factor (TGF)-beta and intimately involved with tissue repair and overexpressed in various fibrotic conditions We previously showed that keratmocytes in vitro downregulate TGF-beta-induced expression of CTGF in fibroblasts by an interleukin (IL)-1 alpha-dependent mechanism. Here, we investigated further the mechanisms of this downregulation by both IL-1 alpha and beta Human dermal fibroblasts and NIH 3T3 cells were treated with IL-1 alpha or beta in presence or absence of TGF-beta 1. IL-1 suppressed basal and TGF-beta-induced CTGF mRNA and protein expression. IL-1 alpha and beta inhibited TGF-beta-stimulated CTGF promoter activity, and the activity of a synthetic minimal promoter containing Smad 3-binding CAGA elements Furthermore. IL-1 alpha and beta inhibited TGF-beta-stimulated Smad 3 phosphorylation, possibly linked to an observed increase in Smad 7 mRNA expression. In addition. RNA interference suggested that TGF-beta activated kinase1 (TAK1) is necessary for IL-1 inhibition of TGF-beta-stimulated CTGF expression. These results add to the understanding of how the expression of CTGF in human dermal fibroblasts is regulated, which in turn may have implications for the pathogenesis of fibrotic conditions involving the skin.

Reconstruction of the fractured orbit serves to prevent functional and aesthetic posttraumatic sequels. In 2004, the surgical protocol at our unit was modified with respect to techniques for surgical access, types, and materials for reconstruction. The modifications were as follows: (a) introduction of medial orbital wall reconstructions through a bicoronal approach, (b) transconjunctival approach instead of the subciliary approach, and (c) porous polyethylene or porous polyethylene-titanium instead of autologous bone grafts. To evaluate the different surgical techniques and materials used, orbital reconstructions performed at our unit from 2000 to 2007 were retrospectively studied. In total, 177 primary or first-time secondary reconstructions were performed in 176 patients. The overall rate of early complications requiring medical or surgical intervention was 6.4%, and the reoperation rate was 3.4%. There were no statistically significant differences in the frequency of cicatricial eyelid complications between the subciliary and the transconjunctival approaches. There was a reduction in operative time with the use of implants compared with the use of bone. The overall rate of infections was 2%; however, there were no infections in the group treated with implants. Seven patients had secondary surgery for persistent enophthalmos, 4 of them due to defects in the medial orbital wall that had not been corrected at the time of primary reconstruction of the orbital floor. In conclusion, porous polyethylene/porous polyethylene-titanium is a safe material for orbital reconstructions. Reconstruction of the medial orbital wall is important to prevent posttraumatic enophthalmos, particularly in combined medial wall-orbital floor fractures.

The treatment of orbital fractures aims at the restoration of orbital anatomy and prevention of posttraumatic sequels. The treatment of facial fractures in patients with traumatic brain injury may necessitate a postponement of fracture surgery to allow for brain recovery. However, such delay of reconstruction in complex orbital fractures may lead to inferior results. Fourteen pediatric patients with complex orbital fractures were retrospectively reviewed. Eleven patients (79%) had brain injury, with a mean Glasgow Coma Scale score of 8.6 at initial evaluation. Fracture patterns were highly complex with many bilateral and multiple orbital wall fractures. Six patients (43%) had injuries to the medial canthal tendon, as part of a naso-orbito-ethmoid fracture. Mean follow-up time was 4.7 years (range, 1.2-13.1 years). Eleven patients (79%) had reconstructive surgery early (within 3 weeks), and 3 (29%) patients had the surgery postponed. Four patients had secondary surgeries for enophthalmos and medial canthal dislocation. Eighty-two percent of patients with brain injury had a good overall neurologic outcome (Glasgow Outcome Scale score of 1 or 2). Sixty-seven percent of patients had a good aesthetic outcome without any need for revisional surgery. Medial canthal injury and late surgery both correlated with an inferior aesthetic result. In conclusion, good results with respect to mental outcome and aesthetics can be achieved in highly complex orbital fractures combined with brain injury. Delayed surgery and medial canthal tendon injury predispose for posttraumatic sequels and secondary surgery.

Felaktig behandling av orbitafrakturer kan ge svåra resttillstånd med påverkan på ögats funktion och utseende. Korrekt anatomisk rekonstruktion av orbitans väggar kräver ofta stor vana vid orbitakirurgi. Nya anatomiska standardimplantat ger förutsättningar för rekonstruktioner med hög precision, men placering av dessa implantat kräver extensiv friläggning av ögonhålan.

In the healing of cutaneous wounds, paracrine communication between keratinocytes and fibroblasts regulates cell differentiation, proliferation and synthesis of extracellular matrix. Deficient epidermal coverage, as seen in burn-wounds, frequently results in hypertrophic scars. Previous studies suggest that keratinocytes downregulate the production of collagen and profibrotic factors in fibroblasts. We hypothesized that keratinocytes downregulate the expression of the profibrotic factor connective tissue growth factor (CTGF) in fibroblasts, and regulate fibroblast expression of genes important to wound healing. In keratinocyte-fibroblast cocultures, keratinocytes downregulated CTGF mRNA and protein in fibroblasts, through the secretion of interleukin-1 (IL-1) α. Using Affymetrix DNA microarrays, it was demonstrated that factors from keratinocytes regulate the expression of 69 genes important to wound healing. The regulation of 16 of these genes was confirmed by Northern blotting, and IL-1α from keratinocytes regulated all the 16 genes examined. IL-1-mediated CTGF gene regulation was further investigated. Both IL-1 isoforms, α and β, suppressed CTGF expression through an inhibition of CTGF promoter activity. Interestingly, transforming growth factor-β-stimulated Smad phosphorylation was not affected by IL-1. Finally, we hypothesized that CTGF is downregulated in burn wound by split-thickness skin grafting and that the expression of CTGF is suppressed during reepithelialization. The expression of CTGF protein was decreased in successfully skin-grafted wound areas, and increased in open, granulating burn wounds. Moreover, CTGF protein expression was absent beneath the migrating edge of reepithelialization ex vivo. In conclusion, we demonstrate that, in in vitro models, keratinocyte-derived IL-1α regulates the expression of CTGF and other genes with importance to wound healing. Furthermore, it is shown that CTGF expression is suppressed by epidermal wound coverage i bur

Objective: To investigate if academic achievement among children with nonsyndromic orofacial clefts (OFC) differs compared to nonaffected children. Methods: A register-based cohort of all children born with Cleft lip (CL), Cleft Lip and Palate (CLP) and Cleft Palate only (CPO) in Sweden between 1973 and 2004, with records in the Swedish school grade register (SGR) (n=6286), was compared to a matched community cohort (n=61352). Outcome measures were academic achievements in mathematics and Swedish in school years 3, 5, 6, 9 and upper secondary school, all subjects’ grades in schoolyear 9, and university degree. Binomial-, ordinal logistic-, linear-, and binary logistic regression were used, and a number of covariates were adjusted for. Results: In the third school year, children with CLP and CPO demonstrated lower odds of passing the mathematics’ national standard tests (NSTs) (CLP; aOR 0.72, 95% CI 0.54-0.95 and CPO; aOR 0.54, 95% CI 0.418-0.697). CPO was associated with lower odds of passing Swedish NST (OR 0.54, 95% CI 0.40-0.72). In the ninth school year, students with CLP and CPO had lower grades in mathematics (CLP; aOR 0.87, 95% CI 0.78-0.97 and CPO; aOR 0.81, 95% CI 0.73-0.91), lower average percentile grade (CLP; coefficient -2.71, 95% CI (- 4.07)-(-1.36) and CPO; -3.23, 95% CI (-4.715)-(-1.736)) and CLP also presented lower Swedish grades (aOR 0.89, 95 % CI 0.80-0.99). At upper secondary school, students with CLP and CPO had lower grades in mathematics (CLP; aOR 0.85, 95% CI 0.75-0.98 and CPO; aOR 0.87, 95% CI 0.76-0.999). Only individuals with CPO had reduced odds of graduating from university (aOR 0.81, 95% CI 0.665-0.983). Conclusions: Our findings of worse academic achievements in children with OFC throughout the educational system emphasize the need to screen children with clefts for learning difficulties to provide additional support in school.

Background Nonsyndromic orofacial clefts (OFC) are associated with neurodevelopmental disorders. The aim of this study was to compare children with bilateral clefts with unilateral clefts regarding psychiatric disorders. Methods We utilized data on all children born in Sweden between 1973 and 2012 with unilateral cleft lip (UCL), bilateral cleft lip (BCL), unilateral cleft lip and palate (UCLP) and bilateral cleft lip and palate (BCLP). We performed Cox regression analyses with direct comparisons between bilateral and unilateral clefts compared to matched community cohorts and adjusted for confounders. Results Children with BCL showed risk increases for any psychiatric disorder (aHR 2.13, 95% CI 1.04-4.36), including intellectual disability (aHR 5.31, 95% CI 1.29-21.78) compared to UCL. Children with BCLP demonstrated risk increases for any psychiatric disorder (aHR 1.55, 95% CI 1.20-2.01), including speech and language disorders (aHR 1.99, 95% CI 1.00-3.97), neurodevelopmental disorders (aHR 1.66, 95% CI 1.11-2.47) and other psychiatric disorders (aHR 1.54, 95% CI 1.11-2.15), such as personality disorders (aHR 5.76, 95% CI 2.13- 15.55) compared to UCLP. Conclusions This large nationwide register study shows for the first time that individuals with bilateral clefts demonstrate elevated risks of psychiatric disorders compared to unilateral clefts.

The bone density analysis system is a new method to analyze the amount of bone healed in cranial vault defects. Craniotomy creates such defects to treat pediatric patients with craniosynostosis. This method uses the variations in the resonance of a microwave sensor attached to the area under test in the patient. Data were collected from infants treated for craniosynostosis through craniotomy surgery in clinical trials. The data, which consist of resonance parameters (frequency, amplitude, and Q-factor) is collected using a microwave-based biomedical sensor. This sensor could detect changes in the resonance as changes in the permittivity of the various tissues at the ISM band. By observing differences between a reference and target defect points, bone healing over time could be accessed. In this paper, we analyze the validity of a proposed Computational Simulation Technology (CST) based numerical model for the sensor and extend the clinical data analysis from previous works with our bone density analysis system. The validity of the model is analyzed by comparing its outcomes to available measurements from numerical simulations, phantoms mimicking living tissues and clinical trial. In the data analysis, a hypothesis is formulated and tested regarding the healing over time. By deriving a set of parameters for each collected dataset in the clinical trials, a distinct pattern was found which shows visible changes such as edema and tissue thickening over the course of the healing process with this technique. Moreover, we manage to distinguish significant differences between the reference and defect points after the craniosynostosis surgery.

Background Image-based analysis of intracranial volume and craniofacial bones is highly valuable in studying outcome of surgery for craniosynostosis. Conventional segmentation of intracranial volume and calvarial bones is time consuming and subjective. Here, a deep learning approach is applied to perform fully automated image segmentation of the intracranial volume and calvarial bones in patients with non-syndromic sagittal craniosynostosis. We apply the established UNet architecture with its subsequent improvements as it has been used in numerous works for biomedical image segmentation since its inception. Methods Pre- and postoperative CT scans were collected from 50 + 52 patients with non-syndromic sagittal craniosynostosis. All participants underwent surgery between the ages of three and six months using the H-craniectomy technique. Manual reference annotations of the intracranial volume and calvarial bones (frontal-, parietal- and occipital bones) were produced using in-house developed software and further refined in 3DSlicer. Modified UNets with a ResNet encoder were trained to automate the segmentation tasks. Networks were trained locally on a single NVIDIA RTX 2080 graphics card and evaluated using 10-fold cross validation. Results The average dice score for the intracranial volume networks was 0.983, and the extracted volume measurements deviated with a mean absolute error of 8.0 ± 5.4 ml from references. An average dice score of 0.798 was achieved for the calvarial bones network, subsequent descriptive statistics were extracted from the reference and generated segmentations to assess Hounsfield units as a proxy for bone density. Conclusion We present a fully automated deep learning approach to assess intracranial volume and attributes of calvarial bones from pre- and postoperative CT images in patients with non-syndromic sagittal craniosynostosis. This framework can be applied to multi-center research with large study populations in a time efficient ma