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Objectives COVIDTrach is a UK multicentre prospective cohort study project that aims to evaluate the outcomes of tracheostomy in patients with COVID-19 receiving mechanical ventilation and record the incidence of SARS-CoV-2 infection among healthcare workers involved in the procedure.Design Data on patient demographic, clinical history and outcomes were entered prospectively and updated over time via an online database (REDCap). Clinical variables were compared with outcomes, with logistic regression used to develop a model for mortality. Participants recorded whether any operators tested positive for SARS-CoV-2 within 2 weeks of the procedure.Setting UK National Health Service departments involved in treating patients with COVID-19 receiving mechanical ventilation.Participants The cohort comprised 1605 tracheostomy cases from 126 UK hospitals collected between 6 April and 26 August 2020.Main outcome measures Mortality following tracheostomy, successful wean from mechanical ventilation and length of time from tracheostomy to wean, discharge from hospital, complications from tracheostomy, reported SARS-CoV-2 infection among operators.Results The median time from intubation to tracheostomy was 15 days (IQR 11, 21). 285 (18%) patients died following the procedure. 1229 (93%) of the survivors had been successfully weaned from mechanical ventilation at censoring and 1049 (81%) had been discharged from hospital. Age, inspired oxygen concentration, positive end-expiratory pressure setting, fever, number of days of ventilation before tracheostomy, C reactive protein and the use of anticoagulation and inotropic support independently predicted mortality. Six reports were received of operators testing positive for SARS-CoV-2 within 2 weeks of the procedure.Conclusions Tracheostomy appears to be safe in mechanically ventilated patients with COVID-19 and to operators performing the procedure and we identified clinical parameters that are predictive of mortality.Trial registration number The study is registered with ClinicalTrials.Gov (NCT04572438).

Orthognathic surgery aims to correct dentoskeletal and facial discrepancies. The expected benefits are functional, cosmetic, and psychological. In a previous publication, this group assessed the determinants of patient satisfaction to formulate the Northwick Park Orthognathic Questionnaire (NOQ). The aim of the present study was to validate this questionnaire. A total of 118 postoperative patients prospectively completed the NOQ, 30 of whom completed the questionnaire a second time. The mean completion rate was 87.6 ± 10%. Response reproducibility was high: 92% of patients gave identical responses (range 81-100%). The intra-class correlation coefficient (ICC) was 0.96 (0.96 ± 0.072). Average test-retest scores for each domain were as follows (range in parenthesis): reasons for treatment 93% (60-100%), preoperative experience 96% (81-100%), preparation for surgery 95% (81-100%), inpatient experience 89% (55-100%), post-discharge experience 83% (55-100%), benefits of treatment 92% (71-100%), overall patient education 91% (62-100%). Internal validity using Cronbach's alpha was 0.72 (standard deviation 0.23, range 0.5-1). The results confirm the consistency of responses and the reliability of the information collected with the NOQ. The NOQ is a novel questionnaire and a valid metric to quantify a patient's perception of their experience. Its adoption may aid in making targeted improvements to patient care., (Copyright © 2021 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Oxidized alginate hydrogels are appealing alternatives to natural alginate due to their favourable biodegradability profiles and capacity to self-crosslink with amine containing molecules facilitating functionalization with extracellular matrix cues, which enable modulation of stem cell fate, achieve highly viable 3-D cultures, and promote cell growth. Stem cell metabolism is at the core of cellular fate (proliferation, differentiation, death) and metabolomics provides global metabolic signatures representative of cellular status, being able to accurately identify the quality of stem cell differentiation. Herein, umbilical cord blood mesenchymal stem cells (UCB MSCs) were encapsulated in novel oxidized alginate hydrogels functionalized with the glycine-histidine-lysine (GHK) peptide and differentiated towards the osteoblastic lineage. The ADA-GHK hydrogels significantly improved osteogenic differentiation compared to gelatin-containing control hydrogels, as demonstrated by gene expression, alkaline phosphatase activity and bone extracellular matrix deposition. Metabolomics revealed the high degree of metabolic heterogeneity in the gelatin-containing control hydrogels, captured the enhanced osteogenic differentiation in the ADA-GHK hydrogels, confirmed the similar metabolism between differentiated cells and primary osteoblasts, and elucidated the metabolic mechanism responsible for the function of GHK. Our results suggest a novel paradigm for metabolomics-guided biomaterial design and robust stem cell bioprocessing. STATEMENT OF SIGNIFICANCE: Producing high quality engineered bone grafts is important for the treatment of critical sized bone defects. Robust and sensitive techniques are required for quality assessment of tissue-engineered constructs, which result to the selection of optimal biomaterials for bone graft development. Herein, we present a new use of metabolomics signatures in guiding the development of novel oxidised alginate-based hydrogels with umbilical cord blood mesenchymal stem cells and the glycine-histidine-lysine peptide, demonstrating that GHK induces stem cell osteogenic differentiation. Metabolomics signatures captured the enhanced osteogenesis in GHK hydrogels, confirmed the metabolic similarity between differentiated cells and primary osteoblasts, and elucidated the metabolic mechanism responsible for the function of GHK. In conclusion, our results suggest a new paradigm of metabolomics-driven design of biomaterials., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Orthognathic surgery aims to correct dentoskeletal and facial discrepancies. Treatment usually requires a minimum of 18 months, necessitating that patients are adequately satisfied with the treatment provided. This study aimed to assess the determinants of patient satisfaction following treatment. One hundred and eighteen patients who had undergone orthognathic surgery were included prospectively. All participants completed a questionnaire regarding their reasons for undergoing treatment, treatment logistics, treatment outcomes, and satisfaction throughout their journey. Most patients were 'very satisfied' (71.2%) or 'satisfied' (19.5%) with the overall treatment. The majority wished to improve their smile (78.0%); post-treatment, 89.0% of patients reported an improved smile. Almost half of the patients (46.6%) stayed in hospital for only one night, and 41.5% took over 4 weeks off work or school post-surgery. People with postoperative breathing difficulties spent more days in hospital (P=0.021), but importantly, the duration of hospital stay did not differ between maxillary advancement, bilateral sagittal split osteotomy, and bimaxillary surgery (P=0.78). In conclusion, patient satisfaction was high following orthognathic treatment. The results highlight areas for improvement, such as information delivery to the patient throughout the treatment journey, and show that the presence of ongoing problems is an important predictor of patient satisfaction., (Copyright © 2018. Published by Elsevier Ltd.)

We report the use of unilateral condylectomy to treat the recurrent dislocation of the temporomandibular joint (TMJ) in a 21-year-old woman with Ehlers-Danlos syndrome. Eighteen months after operation the patient had no further dislocation on full mouth opening, and no surgical complications., (Copyright © 2018 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

The reconstruction of mandibular defects using particulate grafts is a proven technique that restores the osseous anatomy effectively. Secondary osseous reconstruction can be accomplished with endoscopic assistance and reduced-access incisions if an intermediate spacer is placed during resection. Two patients required reconstruction after resection of mandibular ameloblastomas. We used a modified protocol that involved the implantation of a graft of particulate corticocancellous bone after removal of the spacer, and prepared the recipient site under endoscopic guidance with small extraoral incisions. The grafts healed uneventfully and matured into ossicles suitable for the placement of osseointegrated implants., (Copyright © 2018 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Conditioned medium from human hepatocarcinoma cells (HepG2-CM) has been shown to stimulate the osteogenic/chondrogenic differentiation of murine embryonic stem cells (mESCs). HepG2-CM is considered to contain visceral endoderm (VE)-like signals and attempts have recently been made to characterize it, using proteomic profiling, with fibronectin being identified as one promising candidate. Herein, we investigated whether fibronectin is able to mimic the activities of HepG2-CM during the osteogenic differentiation of mESCs. Specifically, the addition of RGD peptides and heparin in HepG2-CM significantly reduced the growth- and adhesion-promoting effects of HepG2-CM, in addition to suppressing its osteogenic-inductive activity. Furthermore, direct addition of fibronectin to basal medium was able to reproduce, at least partially, the function of HepG2-CM. In particular, fibronectin induced the early onset of osteogenic differentiation in mESCs, as confirmed by gene expression of osteogenic markers, and resulted in the three-fold higher calcium deposition at day 11 of osteogenic culture compared to the control group. These data clearly suggest that fibronectin contributes to the biological activities of HepG2-CM and plays a stimulatory role during the process of osteogenesis in mESCs. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

Mesenchymal stem cells (MSCs) of fetal origin, such as umbilical cord blood MSCs (UCB MSCs), have emerged as a promising cell source for musculoskeletal tissue regeneration because of their higher proliferation potential, lack of donor site morbidity, and their off-the-shelf potential. MSCs differentiated toward the osteogenic lineage exhibit a specific metabolic phenotype characterized by reliance to oxidative phosphorylation for energy production and reduced glycolytic rates. Currently, limited information exists on the metabolic transitions at different stages of the osteogenic process after osteoinduction with different agents. Herein, the osteoinduction efficiency of BMP-2 and dexamethasone on UCB MSCs was assessed using gas chromatography-mass spectrometry (GC-MS) metabolomics analysis, revealing metabolic discrepancies at 7, 14, and 21 days of induction. Whereas both agents when administered individually were able to induce collagen I, osteocalcin, and osteonectin expression, BMP-2 was less effective than dexamethasone in promoting alkaline phosphatase expression. The metabolomics analysis revealed that each agent induced distinct metabolic alterations, including changes in amino acid pools, glutaminolysis, one-carbon metabolism, glycolysis, and tricarboxylic acid cycle. Importantly, we showed that in vitro-differentiated UCB MSCs acquire a metabolic physiology similar to primary osteoblasts when induced with dexamethasone but not with BMP-2, highlighting the fact that metabolomics analysis is sensitive enough to reveal potential differences in the osteogenic efficiency and can be used as a quality control assay for evaluating the osteogenic process.

Introduction: The need for fracture healing enhancement for the management of fracture complications such as non-union and for the achievement of early function in fracture patients is constantly increasing. Therefore, the development and evaluation of novel pharmaceutical agents is mandatory in order to accelerate the process and increase bone union rates., Areas Covered: This review summarizes the most recent knowledge on the pharmacological enhancement of fracture repair. It provides a synopsis of the most important preclinical and clinical studies published over the past five years on long bone fracture healing., Expert Opinion: To date, limited drugs seem to have the potential for clinical use in fracture healing enhancement and the field is progressing very slowly. Among anti-osteoporotic drugs, only PTH and anti-sclerostin antibodies have such a potential but further research is needed before clinical use. The same applies also to BMPs, the use of which still carries major drawbacks that should be overcome before their widespread clinical utilization. Other drugs and growth factors, such as statins, VEGF, FGF, EPO, could be future key players in fracture healing but evidence is still lacking. Further in depth understanding of the healing process is essential in order to identify novel effective pharmacological agents.

We describe a case of extensive osteonecrosis of the mandible after a dental extraction in a 71-year-old woman who was taking alendronic acid (Fosamax(®), Merck) for osteoporosis. Bone damaged by bisphosphonate-related osteonecrosis of the jaw (BRONJ), also now known as medication-related osteonecrosis of the jaw (MRONJ), can be regenerated and filled with endosseous implants using non-vascularised autologous grafts., (Copyright © 2015. Published by Elsevier Ltd.)

Introduction: The production of functional alternatives to bone autografts and the development new treatment strategies for cartilage defects are great challenges that could be addressed by the field of tissue engineering. Umbilical cord mesenchymal stem cells (MSCs) can be used to produce cost-effective, atraumatic and possibly autologous bone and cartilage grafts., Areas Covered: MSCs can be isolated from umbilical cord Wharton's jelly, perivascular tissue and blood using various techniques. Those cells have been characterized and phenotypic similarities with bone marrow-derived MSCs (BM-MSCs) and embryonic stem cells have been found. Findings on their differentiation into the osteogenic and chondrogenic lineage differ between studies and are not as consistent as for BM-MSCs., Expert Opinion: MSCs from umbilical cords have to be more extensively studied and the mechanisms underlying their differentiation have to be clarified. To date, they seem to be an attractive alternative to BM-MSCs. However, further research with suitable scaffolds and growth factors as well as with novel scaffold fabrication and culture technology should be conducted before they are introduced to clinical practice and replace BM-MSCs.

300 cases of non-melanoma cutaneous lesion procedures carried out by the Oral and Maxillofacial Surgery and Dermatology departments in a North West London hospital over a 6 month period between September 2011 and February 2012 were included in a retrospective case control study. The results from each speciality were compared. The mean age of the OMFS group was 75.8 years compared to 69.9 years in the dermatology group. There was no statistically significant difference in gender between the 2 groups. The OMFS group treated a higher proportion of atypical (17%) and malignant (64.9%) cases compared to the dermatology group (11.3% and 50.5% respectively). This could also account for the fact that the OMFS group carried out a higher number of full excisions compared to dermatology. Both groups had a similar number of false positives (a benign lesion initially diagnosed as malignant) and a similar proportion of false negatives (a malignant lesion initially diagnosed as benign). Overall, the results show that both specialities had similar outcomes when managing non-melanoma cutaneous lesions. Both groups adhere to the guidelines set out by the British Association of Dermatologists and the National Institute of Clinical Excellence when managing such lesions., (Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.)

Introduction: Mesenchymal stem cells (MSCs) are multipotent stromal cells characterized by their ability to differentiate into adipocytes, chondrocytes, osteocytes and a number of other lineages. Investigation into their use has increased in recent years as characterization of their immunomodulatory properties has developed, and their role in the pathophysiology of joint disease has been suggested., Areas Covered: MSCs demonstrate immunosuppressive functionality by suppressing T- and B-cell responses following activation by cytokines such as IL-6 and IL-1α. They also can be induced to exert pro-inflammatory effects in the presence of acute inflammatory environment due to the actions of TNF-α and IFN-γ. In inflammatory joint diseases such as rheumatoid arthritis, MSCs in bone marrow migrate to joints by a TNF-α-dependent mechanism and may be in part responsible for the disease process. MSCs have also been demonstrated in increased numbers in periarticular tissues in osteoarthritis, which may reflect an attempt at joint regeneration., Expert Opinion: Clinical applications for MSCs have shown promise in a number of inflammatory and autoimmune disorders. Future work is likely to further reveal the immunosuppressive characteristics of MSCs, their role in the pathophysiology of joint diseases and provide the basis for new avenues for treatment.

Ludwig's angina was first detailed by the German surgeon Wilhelm Friedrich von Ludwig in 1836. We present a case which needed awake fibreoptic intubation due to severe trismus and a prolonged period intubated in the Intensive Care Unit after incision and drainage of neck spaces and removal of his lower wisdom teeth. He was finally discharged a week after admission and followed up in the outpatient clinic. The case is presented with clinical photographs and a video of the fibreoptic intubation to illustrate the airway.

We review the current status of robotic surgery in the head and neck region and its role in oral and maxillofacial surgery., (Copyright © 2011 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Prostaglandin E(2) is known to be a potent metabolite in bone biology. Its effects are mediated via four receptor subtypes with different properties, effects and mechanisms of action. The EP2 and EP4 receptors have been extensively investigated as bone anabolic therapy targets in the literature. The aim of this review was to analyse the available evidence supporting the use of selective agonists for those receptors for anabolic bone application purposes. Although several studies report on the presence of the EP2 receptor in several cell types, efforts to directly confirm the presence of this receptor in human bone cells have not been successful. The EP4 receptor however has been identified in human bone cells and its significant role in bone biology has been demonstrated with the use of selective agonists, antagonists and transgenic small animals. The use of selective EP4 agonists reversed established osteoporotic changes, enhanced the boneimplant interface strength and was shown to have a synergistic effect when used with other bone cell targeting pharmacological agents such as BMP-2 and bisphosphonates. Further elucidation of the side-effect profile of prostanoid and non-prostanoid agonists is required for these agents to proceed towards clinical applications.

Introduction: Bone grafting is used to repair large bone defects and autograft is recognised as producing the best clinical outcome, which is partly due to its cellular component. When autograft is unavailable, allograft and bone graft substitutes can be used; however, they rely on the host bed to provide cellular osteogenic activity., Areas Covered: Bone graft substitutes have the potential to benefit from the addition of stem cells aimed at enhancing the rate and quality of defect repair. Mesenchymal stem cells (MSCs) can be isolated from bone marrow or periosteum and culture expanded. Other sources of primary cells include muscle, adipose tissue, human umbilical cord and the pluripotent embryonic stem cells (ESCs)., Expert Opinion: MSCs isolated from bone marrow have been the best characterised approach for osteogenic differentiation. Their use with synthetic scaffolds such as hydroxyapatite and tricalcium phosphate has produced promising clinical results. MSCs derived from adipose tissue, muscle or human umbilical cord cells combined with various scaffolds are an attractive option. Further in vivo and clinical investigation of their potential is required. Pluripotent ESCs have a theoretical advantage over MSCs; however, purification, cell-specific differentiation, effective delivery vehicles-scaffolds and teratogenesis control are still under in vitro and in vivo evaluation.

Introduction: Recent evidence suggests that antibiotics exert direct effects on bone at a cellular level, disrupting mitochondrial function and cell activity. This comprehensive literature review aims to evaluate evidence for the effects of antibiotics and antimicrobials on bone and discuss the clinical implications., Areas Covered: A literature search was conducted on electronic databases covering a period from 1969 to 2010. Studies were included if they reported in vivo and in vitro experimental findings regarding the use of antibiotics and synthetic antibacterials in both animals and humans, focusing on bone cell function and especially fracture repair., Expert Opinion: Current research suggests that these negative results could be due to direct effects of antibiotics on mitochondrial physiology within mammalian cells. Treatment doses of antibiotics, especially those released from topical delivery systems such as bone cements, result in antibiotic concentrations thousands of times higher than those required to inhibit bacterial growth. Our findings suggest a need to develop current antibiotic delivery systems to elute sufficient doses to inhibit bacterial growth without negative effects on bone physiology and fracture repair processes.

This final review in a series of three focuses on how the advances made in the realm of molecular and cellular bone biology have been translated into experimental animal and human surgery., (Copyright © 2010. Published by Elsevier Ltd.)

Introduction: In patients suffering from schizophrenia and bipolar disorder, antipsychotics are the mainstay of treatment worldwide. By blocking D(2) brain mesolimbic receptors, antipsychotics are believed to reduce and control psychotic experiences, but recent evidence has suggested that they may also have adverse effects on bone mineral architecture and fracture incidence., Areas Covered: This study reviews current literature surrounding the use of antipsychotics and their effects on bone homeostasis. The primary medical search engines used for the study are Ovid MEDLINE (1950 - April 2010), EMBASE (1988 - April 2010) and PsychINFO (1987 - April 2010) databases., Expert Opinion: Typical antipsychotics, in addition to the atypical antipsychotics risperidone and amisulpride, have been shown to increase serum prolactin levels in in vivo human studies. Results from animal and human in vitro and in vivo studies have demonstrated that high concentrations of prolactin have been shown to adversely affect bone cell metabolism and accelerate the rate bone mineral density loss, thereby increasing fracture risk. Increasing awareness of the side effect profile of antipsychotic medications on bone metabolism may prompt clinicians to screen patients at high risk of antipsychotic-induced osteoporosis and provide treatment, which may reduce the incidence of potentially avoidable fractures.

Statins are potent inhibitors of cholesterol synthesis. Several statins are available with different molecular and pharmacokinetic properties. Simvastatin is more lipophilic than pravastatin and has a higher affinity to phospholipid membranes than atorvastatin, allowing its passive diffusion through the cell membrane. In vitro studies on bone marrow stromal cells, osteoblast-like cells, and embryonic stem cells have shown statins to have cholesterol-independent anabolic effects on bone metabolism; alas, statins were supplemented in osteogenic medium, which does not facilitate elucidation of their potential osteoinductive properties. Embryonic stem cells (ESCs), derived from the inner cell mass of the blastocyst, are unique in that they enjoy perpetual self-proliferation, are pluripotent, and are able to differentiate toward all the cellular lineages composing the body, including the osteogenic lineage. Consequently, ESCs represent a potentially potent cell source for future clinical cellular therapies of various bone diseases, even though there are several hurdles that still need to be overcome. Herein we demonstrate, for the first time to our knowledge, that simvastatin induces murine ESC (mESC) differentiation toward the osteogenic lineage in the absence of osteoinductive supplements. Specifically, we found that a simvastatin concentration in the micromolar range and higher was toxic to the cells and that an effective concentration for osteoinduction is 0.1 nM, as shown by increased alizarin red staining as well as increased osteocalcin and osetrix gene expression. These results suggest that in the future, lipophilic simvastatin may provide a novel pharmacologic agent for bone tissue engineering applications., (© 2010 American Society for Bone and Mineral Research.)

Importance of the Field: Bone is one of the most transplanted tissues worldwide. Autograft is the ideal bone graft but is not widely used because of donor site morbidity and restricted availability. Allograft is easily accessible but can transmit infections and elicit an immune response., Areas Covered in This Review: This review identifies all in vitro and in vivo evidence of immune responses following bone transplantation and highlights methods of improving host tolerance to bone allotransplantation., What the Reader Will Gain: In humans, the presence of anti-HLA specific antibodies against freeze-dried and fresh-frozen bone allografts has been demonstrated. Fresh-frozen bone allograft can still generate immune reactions whilst freeze-dried bone allografts present with less immunogenicity but have less structural integrity. This immune response can have an adverse effect on the graft's incorporation and increase the incidence of rejection. Decreasing the immune reaction against the allograft by lowering the immunogenic load of the graft or lowering the host immune response, would result in improved bone incorporation., Take Home Message: It is essential that the complex biological processes related to bone immunogenicity are understood, since this may allow the development of safer and more successful ways of controlling the outcome of bone allografting.

Aims: This study surveyed members of the Oral Surgery (OS) register and requested a self assessment of their surgical competencies with regard to both core and extended procedures, as defined by the OS curriculum. Details of education, training backgrounds and working patterns were also requested., Methods: Members of the OS register were identified on the General Dental Council website and mailed a questionnaire. Replies were anonymous., Results: Three hundred and seventy-three valid replies were received. Seventy-five percent of respondents were on the OS specialist list only (single registrants) and 25% of respondents were on both the OS and oral and maxillofacial surgery (OMFS) specialist lists (dual-registrants). Sixty-two percent of single registrants did not feel comfortable performing all core procedures compared to 13% of dual-registrants. Fifty-one percent of OS single registrants felt comfortable performing some extended procedures, as did 99% of dual-registrants. Fifty percent of single registrants and 100% of dual-registrants had a higher qualification. Thirty-seven percent of single registrants had undergone some formally-approved registrar-level training; 98% of dual-registrants had done likewise. Twenty-one percent of single registrants practised exclusively in the private sector compared to 8% of dual-registrants., Conclusion: Extended competencies are being practised by members of the OS register with wide-ranging educational and training backgrounds.

Background: Platelet-derived growth factor (PDGF) has been shown in vivo to increase bone formation and supplement fracture healing, and may have a role as a therapeutic agent in the treatment of bone loss and fracture healing in humans., Objective: A comprehensive review of the recent literature on the effect of PDGF on bone mineral density and fracture healing., Methods: In vitro and in vivo evidence was systematically collected using medical search engines MEDLINE/OVID (1950 to March 2008) and EMBASE (1980 to March 2008) databases., Results/conclusion: Evidence to date suggests that PDGF-BB, and to a lesser extent PDGF-AA, may have potential therapeutic use in the treatment of osteoporosis and bone healing in humans. Additionally, by targeting alpha-receptors on osteoblasts, a potential anabolic effect on bone metabolism in humans can be anticipated; however, more research needs to be done to assess the role of beta-receptors in human bone.