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Objectives: Bisphosphonates (BPs) are powerful inhibitors of osteoclastogenesis and are used to prevent osteoporotic bone loss and reduce the risk of osteoporotic fracture in patients suffering from postmenopausal osteoporosis. Patients with breast cancer or gynecological malignancies being treated with BPs or those receiving bone-targeted therapy for metastatic prostate cancer are at increased risk of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Although BPs markedly ameliorate osteoporosis, their adverse effects largely limit the clinical application of these drugs. This study focused on providing a deeper understanding of one of the most popular BPs, the alendronate (ALN)-induced perturbation of the bone proteome and microenvironmental pathophysiology. Methods: To understand the molecular mechanisms underlying ALN-induced side-effects, an unbiased and global proteomics approach combined with big data bioinformatics was applied. This was followed by biochemical and functional analyses to determine the clinicopathological mechanisms affected by ALN. Results: The findings from this proteomics study suggest that the RIPK3/Wnt/GSK3/β-catenin signaling pathway is significantly perturbed upon ALN treatment, resulting in abnormal angiogenesis, inflammation, anabolism, remodeling, and mineralization in bone cells in an in vitro cell culture system. Conclusion: Our investigation into potential key signaling mechanisms in response to ALN provides a rational basis for suppressing BP-induced adverse effect and presents various therapeutic strategies.

Erdheim-Chester Disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by histiocytic infiltration of multiple organ systems, including the bony skeleton, central nervous system, cardiovascular system, lungs, and kidneys. Manifestations of the disease are highly variable, ranging from focal disease to multisystem involvement. Oral manifestations are exceedingly rare, with only 10 known reports of ECD involving the jaws. The objective of this case report is to highlight the radiographic, clinical, and histological features of ECD involving the maxillofacial complex. A 35-year-old male admitted for sepsis secondary to pyelonephritis and suspected diabetes insipidus received an extensive workup for ECD versus IgG4 disease versus lymphoma. The oral-maxillofacial surgery service was consulted for biopsy of maxillary lesions noted to have increased activity on positron emission tomography. Intraoral biopsy yielded the characteristic histopathological features of ECD, confirming the diagnosis. We compare the clinical, radiographic, and microscopic features of ECD with past findings, contributing to the profile of this rare disease.

Implants can be a treatment option when there is sufficient quantity and quality of bone to provide support for long-term success. In the reconstruction of defects, autogenous bone remains the gold standard for its osteogenic and compatibility properties. However, the disadvantage of secondary surgery and the associated donor site morbidity prompts researchers to develop the ideal bone substitute for optimum bone reconstruction. Parathyroid hormone (PTH1-34) has provided a new option for improvement in bone regeneration. This study used a pig model to evaluate the effectiveness of parathyroid hormone when added to a xenograft, Bio-Oss, in reconstructing mandible defects. Six domestic pigs were used to create 3 posterior mandibular defects measuring 2 × 1-cm bilaterally with a total of 36 defects to simulate tooth extraction sites in humans. The defects were grafted in random order and divided into 3 groups as follows: control (no graft), Bio-Oss without PTH, and Bio-Oss with PTH. Defects were assessed with cone beam computerized tomography (CBCT), micro computerized tomography (microCT), nanoindentation, and histology. Results showed that adding PTH1-34 significantly enhanced the graft construct. CBCT showed a significant increase in the degree of bone mineralization. Nanoindentation showed increased hardness of regenerated bone and accelerated bone mineralization with PTH. MicroCT analysis revealed a trend toward higher bone regeneration and mineralization. The histological analysis showed a positive trend of the increase in cortical bone thickness and mineral apposition rate. In conclusion, the local addition of PTH1-34 to a xenograft has shown promising results to enhance bone regeneration in the reconstruction of mandibular defects.

Historically, patients who developed malignant hyperthermia had an extremely high rate of mortality. Today, if treated appropriately, patients who experience an episode of malignant hyperthermia will most likely survive. This dramatic decrease in mortality associated with malignant hyperthermia is due to several factors, including an increased understanding of the disease, improved diagnostic and monitoring equipment, and the development of lifesaving pharmacologic agents. This article presents the very likely case of acute malignant hyperthermia in a 24-year-old man with special needs, who presented for restorative dentistry under general anesthesia in the outpatient clinic of The Ohio State University's College of Dentistry.

Ludwig's angina (LA) is a gangrenous cellulitis of the neck that spreads via continuity of the fascial planes. Treatment of LA includes aggressive antibiotic therapy as well as surgical drainage in many cases. The most common cause of infection is odontogenic and can be due to both aerobic and anaerobic bacteria. Signs and symptoms of LA include bilateral cervical swelling, dysphagia, drooling, neck tenderness, elevation and posterior distension of the tongue, restricted neck movement, trismus, dyspnea, and stridor, which can result in difficult airway management. Proper preoperative assessment of patients with LA should include identifying features that may cause difficulties with mask ventilation, direct laryngoscopy, and intubation. Alternative methods of ventilation should be considered and immediately accessible, including a plan on how and when they would be used in the event that a patient cannot be mask ventilated or intubated. Marking external anatomical airway landmarks prior to manipulating the airway can save vital time if an emergent airway becomes necessary.

Cell specific and cytokine targeted therapeutics have underperformed in systemic lupus erythematosus (SLE). Mesenchymal stem cells (MSCs) have emerged as a novel therapy to address the dysregulation in autoimmune diseases but also have limitations. Human gingiva derived MSCs (GMSCs) are superior in regulating immune responses. Here, we demonstrate that the adoptive transfer of GMSCs homes to and maintains in the kidney and has a robust therapeutic effect in a spontaneous lupus nephritis model. Specifically, GMSCs limits the development of autoantibodies as well as proteinuria, decreases the frequency of plasma cells and lupus nephritis histopathological scores by directly suppressing B cells activation, proliferation and differentiation. The blockage of CD39

Objectives With advances in healthcare leading to longer life expectancy, the edentulous geriatric population is increasing. Expectantly, head and neck trauma surgeons will encounter atrophic (edentulous) mandible fractures in their practice. The objectives of this paper are to review the prevalence, etiology, and diagnosis of atrophic mandible fractures with a descriptive discussion on the different methods of treatment. Materials and Methods The review included a search using PubMed (National Library of Medicine, NCBI) and Medline from 1950–2016 with keywords such as “atrophic mandible” with the addition of the words fracture and computerised guided technology and Virtual Surgical Planning (VSP). Results This search produced 499 articles. Of those 499 articles, 18 were included in this critical review. Management discussion identified papers to provide the most powerful evidence in the decreasing order of strength by cohort studies, case-control studies, surveys, and case-series. The update provides new information on virtual surgical planning that will assist in time under general anaesthesia for complex case management. Conclusions A comprehensive update reviewed all forms of treatment from soft diet to open reduction with computerised technology to provide head and neck trauma surgeons a better basis for clinical management of these fractures.

The calcifying odontogenic cyst is a rare developmental odontogenic lesion with a distinguishing cystic lining containing "ghost" epithelial cells. The variation in clinical, radiographic, and histologic findings makes the treatment decision difficult for these lesions. There are very few reports on treatment, with enucleation and curettage being the standard surgical method of choice for the cystic type and excision of the tumor for the solid type. A 2-stage surgical approach consisting of initial decompression with tube placement followed by a secondary procedure of enucleation and curettage is common for other large odontogenic cysts, such as dentigerous and odontogenic keratocysts. To the authors' knowledge, this is the first case managed with an intended 2-stage approach in the form of decompression followed by enucleation and curettage.

Bone marrow aspirate concentrate (BMAC) is a potentially useful biological product for bone regeneration. This study investigated whether BMAC can be enriched by local minor corticotomies. Five 4-month-old domestic pigs were used with each pig undergoing two minor corticotomies at one randomly-selected tibia. Two weeks after the operation, bone marrow was aspirated from both tibiae and processed into BMAC samples. The amount of mesenchymal stem cells (MSCs) and the concentration of several regenerative growth factors contained in BMAC, as well as the proliferative and osteogenic differentiation capacity of MSCs, were compared between the corticotomy and the control sides. Another four weeks later, healing of the corticotomies was evaluated by radiographic and histological methods. The results demonstrated that BMAC from the corticotomy side contained significantly more MSCs than the control side. MSCs from the corticotomy side also proliferated significantly faster and tended to have stronger osteogenic differentiation than those from the control side. In contrast, the protein concentration of TGF-β, BMP-2 and PDGF contained in BMAC was only minimally changed by the corticotomies. The corticotomies in all pigs healed uneventfully, showing complete obliteration of the corticotomy gaps on CT images. Comparison between the two sides showed that the corticotomy side had thicker and denser cortical bone and more abundant osteogenic cell differentiation than the control side. These findings suggest that the quantity and proliferative/osteogenic differentiation capacity of MSCs contained in local BMAC can be enhanced by minor corticotomies, and spontaneous healing of the corticotomy can be completed within 6 weeks of the operation.

Cell specific and cytokine targeted therapeutics have underperformed in systemic lupus erythematosus (SLE). Mesenchymal stem cells (MSCs) have emerged as a novel therapy to address the dysregulation in autoimmune diseases but also have limitations. Human gingiva derived MSCs (GMSCs) are superior in regulating immune responses. Here, we demonstrate that the adoptive transfer of GMSCs homes to and maintains in the kidney and has a robust therapeutic effect in a spontaneous lupus nephritis model. Specifically, GMSCs limits the development of autoantibodies as well as proteinuria, decreases the frequency of plasma cells and lupus nephritis histopathological scores by directly suppressing B cells activation, proliferation and differentiation. The blockage of CD39-CD73 pathway dramatically abrogates the suppressive capacities of GMSCs in vitro and in vivo and highlights the significance of this signaling pathway in SLE. Collectively, manipulation of GMSCs provides a promising strategy for the treatment of patients with SLE and other autoimmune diseases.

BACKGROUND AND OBJECTIVES Impaired bone formation of the buccal alveolar plate after tooth extraction during adolescence increases the difficulty of future implant restoration. This study was undertaken to assess the feasibility and efficacy of transplanting autogenous scaffold-free culture-expanded mesenchymal stem cell (MSC) sheets to the buccal alveolar bone surface to stimulate local bone growth. MATERIAL AND METHODS Mandibular bone marrow was aspirated from 3-month-old pigs (n = 5), from which MSCs were isolated and culture expanded. Triple-layer MSC sheets were then fabricated using temperature-responsive tissue culture plates. One month after bone marrow aspirations, the same pigs underwent bilateral extraction of mandibular primary molars, immediately followed by transplantation of 3 autogenous triple-layer MSC sheets on to the subperiosteal buccal alveolar surface of 1 randomly chosen side. The contralateral side (control) underwent the same periosteal reflection surgery without receiving MSC sheet transplantation. Six weeks later, the animals were killed and specimens from both sides were immediately harvested for radiographic and histological analysis. Buccal alveolar bone thickness, tissue mineral density (TMD), mineral apposition and bone volume fraction (BV/TV) were quantified and compared between the MSC sheet and control sides using paired t-tests. RESULTS Triple-layer MSC sheets were reliably fabricated and the majority of cells remained vital before transplantation. The thickness of buccal bone tended to increase with MSC sheet transplantation (P = .18), with 4 of 5 animals showing an average of 1.82 ± 0.73 mm thicker bone on the MSC sheet side than the control side. After being normalized by the TMD of intracortical bone, the TMD of surface cortical bone was 0.5-fold higher on the MSC sheet side than the control side (P

Minimizing risk to the integrity of the facial nerve is a critical measure of surgical success in temporomandibular joint (TMJ) surgeries. The surgeon must have a keen understanding of the regional anatomy combined with a planned dissection to protect the facial nerve in their approach to the joint [1]. Facial nerve injury may have devastating effects on the patient esthetically and functionally due to impairment of the frontalis and/or orbicularis oculi muscles. According to Liu et al., the most current review of the literature reveals that the incidence of facial nerve injury in conjunction with open TMJ surgery ranges from 12.5 to 32% [2]. The chapter will provide a review on the anatomy of the facial nerve, procedures leading to potential injury, recognition of injury, and multiple methods of management.

Although anatomy often seems static, the continual innovation of new surgical techniques and approaches, in reality, make it a dynamic field. The first essential principal of any surgery is the comprehensive knowledge of the anatomic area and its physiology. This assertion is especially true in functional and or cosmetic nasal surgery.

Objective Transconjunctival approach to the lower one-third of the orbit is commonly used to avoid transcutaneous incisions when surgical access is needed. A lateral canthotomy is used in conjunction with this approach if increased lateral exposure is required. A major disadvantage to lateral canthotomy is difficulty in resuspension of the lateral canthal tendon, which can lead to unaesthetic outcomes. The present report describes two cases of lateral tarsal incision or, as we decided to call it, the “lateral tarsotomy” technique. This simple approach is used to increase lateral access to the orbit without the need for lateral canthotomy. Study Design Two patients presented with internal orbital wall trauma that required repair; access was achieved with a transconjunctival approach in conjunction with lateral tarsotomy. The patients were followed up at 1 week, 1 month, and 3 months to document the development of possible unaesthetic and poor functional outcomes. Results Excellent cosmetic results were observed, with no noticeable deformity at the tarsotomy site. There was no evidence of ectropion, entropion, scleral show, and visible scars. Conclusions The above results suggest that the lateral tarsotomy approach is a practical alternative to lateral canthotomy when increased lateral exposure is required.

A variety of techniques and materials has been used to provide the structural base of bone and soft tissue support for dental implants. Alveolar bone augmentation techniques include different surgical approaches such as guided bone regeneration, onlay grafting, interpositional grafting, distraction osteogenesis, ridge splitting, and socket preservation. In the case presented, a technique was used to augment the alveolar bone three-dimensionally with autologous “bone rings” and immediate implant placement in a 1-stage procedure following teeth extraction. Bone rings (circular osteotomies) were outlined at the symphysis area using trephine burs, and a central osteotomy for implant placement was done before its removal. The rings were then removed and sculptured to fit the extraction socket; this was followed by screwing the implant through the ring, gaining its primary stability from the prepared basal bone.

Tracheostomy is an important life-saving procedure performed by many surgical specialties. The indications for tracheostomy are vast, most commonly for the relief of upper airway obstruction, uncontrolled tracheobroncheal secretions, obstructive sleep apnea and prolonged intubation due to respiratory insufficiency. Placement of a tracheostomy tube allows long term airway access and allows for removal of translaryngeal endotracheal tube (ETT tube). A brief discussion of anatomy and physiology, tracheostomy types, complications and post operative nursing care will be described.

The standard of care regarding tooth loss replacement is evolving towards the use of dental implants. The practice of fixed bridges and partial prosthesis can be and are iatrogenic to the existing teeth and bone. Prosthetics in the restoration of partial and complete edentulous conditions with implants has become the most important determinant. Because of this principle the emphasis has focused on optimization of the alveolus to receive a root form implant. Dental implants are a viable treatment option when there is sufficient quantity and quality of bone to achieve the desired functional and esthetic results. The reduction in bone volume has many etiologies. The most common are a result of: Periodontal disease, pneuma‐ tization of the maxillary sinus, long term ill-fitting dentures, and the general progression of osteoporosis with aging. Initially, malposition or short implants were used in areas of deficient bone volume. This often resulted in compromised prosthetic design and poor long term treatment outcomes. Today’s treatment plans first consider the prosthesis options. This necessitates reconstruction and modifications of the pre-existing anatomy provide the ideal environment needed for optimal implant placement. The deformity is often a composite loss of both bone and soft tissue. The alveolar bone loss frequently occurs in a three dimension‐ al pattern. Multiple options and techniques have been advocated for correction and recon‐ struction of the atrophied alveolar bones. They include the following: Guided bone regeneration (GBR), onlay bone grafting (OBG), interpositional bone grafting (IBG), distrac‐ tion osteogenesis (DO), ridgesplit (RS), and sinus augmentation techniques (SA). [1-3] The complexity of the defect dictates the selection of the appropriate technique. The reconstruc‐ tion must also take into account the three dimensional spatial relation of one arch to the opposing arch.

The ability of recombinant human bone morphogenetic protein 2 on absorbable collagen sponge (rhBMP2/ACS) to regenerate bone in segmental defect has been well characterized. However, clinical results of rhBMP2/ACS constructs in secondary reconstruction of large mandibular and craniofacial defects have not been consistent. We hypothesized that rhBMP2 delivery triggers an endogenous response in the soft tissues surrounding the defect, in the form of expression of BMP2 and vascular endothelial growth factor (VEGF). Such osteogenic response will occur only after immediate, as opposed to delayed, rhBMP2 delivery, suggesting a new explanation to the difference in bone regeneration between the two settings. A 35-mm segmental bone and periosteum defect was created on one side of the mandible in 16 dogs divided in three groups. Group 1 (Gp1, n=6) ACS was loaded with 8 mL of rhBMP2 (0.2 mg/mL). In Gp2 (n=5) the same dose of rhBMP2/ACS was delivered into the defect 4 weeks after surgery. In Gp3 (control; n=5) the defect was reconstructed using ACS loaded with 8 mL of buffer only (devoid of rhBMP2). Tissues were collected after 12 weeks of reconstruction in all groups. Direct measurement of physical dimensions of regenerates and bone morphometry was performed to evaluate bone regeneration. The mRNA expression of both BMP2 and VEGF in the soft tissue surrounding the defect was evaluated using real-time quantitative PCR. Both BMP2 and VEGF proteins were quantified in immunostained sections. Immunoflurescence colocalization of BMP2 and acetylated low density lipoprotein (AcLDL) was done to detect the source of BMP2. Immediate delivery yielded better bone regeneration. Both BMP2 and VEGF mRNA expression was upregulated only in Gp1 (+7.3, p=0.001; +1.53, p=0.001, respectively). BMP2 protein was significantly higher in the immediate reconstruction group; however, VEGF protein was undetected in the examined sections. Immediate delivery of rhBMP2 seemed to induce endogenous release of BMP2 from the surrounding soft tissues, an effect that was lacking in delayed delivery and may explain the variability of clinical results associated with BMP2 use. Colocalization of BMP2 and endothelial cells (ECs) suggested that ECs could be the source of endogenous BMP2.

Purpose To evaluate the efficacy of using a single lag screw combined with an arch bar in the management of anterior mandibular fractures and to compare this method with the traditional application of 2 lag screws. Materials and Methods We designed and implemented a randomized clinical trial and enrolled a sample of patients with anterior mandibular fractures. Twenty adult male patients were randomly divided into 2 equal groups according to the number of lag screws used for fracture fixation after securing the occlusion with intermaxillary fixation. In group A, the fractures were treated using 2 lag screws. In group B, the fractures were treated using a single lag screw and an arch bar on the teeth, spanning the fracture line. Clinical and radiographic evaluations were used to evaluate the efficacy of each fixation method immediately and at 2 and 4 months postoperatively. Results The clinical examination showed stable fixation with no mobility or infection in all cases. One patient in group A showed a slight occlusal discrepancy that was managed with occlusal adjustment. The pretraumatic occlusal relationship of all other patients was re-established. Postoperative radiographs showed properly reduced fracture segments with gradual bone healing. No significant difference was noted ( P > .05) between the 2 groups in the development of postoperative complications. Conclusions The use of 1 lag screw in conjunction with an arch bar across the fracture line is rigid and stable enough to manage anterior mandibular fractures without the need for supplemental intermaxillary fixation. The use of a single lag screw offers several advantages compared with the traditional use of 2 lag screws. These advantages include decreased cost, use of materials, healing time, and risk of associated morbidity.

This study compared cellular responses of maxillary sinuses after augmentation with anorganic bovine-derived hydroxyapatite matrix linked to the cell binding polypeptide P-15 (ABM/P-15) or PepGen P-15 and allogenic freeze-dried cranial bone slabs. Five adult Macaque fascicularis monkeys were used. On one side, the floor of the sinus was augmented with ABM/P-15, while the other side was augmented with 2 cranial bone slabs. Trephine bone biopsies were obtained 6, 12, and 24 weeks postgrafting. Animals were sacrificed 8 months after grafting. Soft X-ray microradiography was used to determine bone density. The volume fraction (Vv) of regenerated bone, the number of mesenchymal cells, and the numbers of proliferating cell nuclear antigen (PCNA)- and alkaline phosphatase–positive cells at different augmentation sites were measured and compared. Basal bone heights were calculated at surgery and compared with total heights of the augmented sinus floors 8 months postgrafting. Bone formation, number of mesenchymal cells, PCNA index, and alkaline phosphatase index were significantly higher for the ABM/P-15 side than for the allogenic bone–augmented side. Both sides ended with a significant increase in bone height. The PCNA index decreased significantly over time (P < .05), while the alkaline phosphatase index increased significantly (P < .05) over time on both sides. Both graft materials have led to significant augmentation of the floor of the maxillary sinus with new bone; however, new bone formation and maturation were faster on the ABM/P-15 sites.

and tissue harvesting, microCT scans were performed on each of the specimens in order to provide objective measurements in evaluating the quality of the newly regenerated bone. Following imaging, specimens were fixed for 48 hours in a 10% neutral-buffered solution, sequentially dehydrated in 70%, 95%, and 100% ethanol, and then infiltrated and embedded in methylmethacrylate. Embedded specimens were sectioned to 25-um thickness and examined under ultraviolet light to evaluate new bone formation as marked by tetracycline labeling.