Three-dimensional evaluation of mandibular lingula: Comparisons of skeletal angle classifications and growth patterns.

OBJECTIVES: This study aimed to evaluate the position of the mandibular lingula (ML) in adult patients (aged between 18 and 35 years old) with different skeletal and growth patterns using cone-beam computed tomography (CBCT). DESIGN: Cross-sectional. SETTING: Dentistry department of University. SUBJECTS: Subjects comprised CBCT images of 150 adult patients, including 300 rami. METHODS AND MATERIALS: In total, 150 CBCT aged between 18 and 35 were selected and divided into three main groups of 50 samples based on their skeletal relationships (classes I, II and III). Patients were subdivided based on their growth pattern (vertical vs. horizontal), resulting in 25 samples per subgroup. Distances between the mandibular lingula and occlusal plane (ML-OP), sigmoid notch (ML-SN), external oblique ridge (ML-EOR), internal oblique ridge (ML-IOR), posterior border of the ramus (ML-PBR), inferior border of the ramus (ML-IBR), and horizontal and vertical distances to the mandibular foramen (ML-hMF and ML-vMF). One-way ANOVA variance analysis was employed to compare different angle classifications, and Bonferroni analysis was used for multiple comparisons. The Student's t-test was also used to compare growth patterns within each main group and genders within the subgroup. RESULTS: The study revealed statistically significant differences in the position of the mandibular lingula between different angle classifications, growth patterns, and genders. Class II samples showed a more anterior position of the ML, whereas Class III samples displayed a more posterior position of the ML. Patients with horizontal growth patterns and Angle Class III had a more posteriorly positioned ML. Gender differences were observed, particularly in Class I and Class III classifications, suggesting that gender may influence the variability of ML position in these specific classifications. CONCLUSION: The position of the mandibular lingula showed high variability among individuals with different angle classifications, growth patterns and genders.

Intact social cognitive processes in outpatients with anorexia nervosa: a pilot study.

OBJECTIVE: The aim of the study was to assess social cognition in community patients suffering from anorexia nervosa (AN) compared to healthy controls. METHODS: 25 women diagnosed with AN and 25 women matched for education level and age were involved in the study. Both subject groups were assessed using a set of validated experimental tasks, such as the facial expression recognition test, short recognition memory test for faces, 'Reading the mind in the eyes' test. Patients were assessed for symptoms of: eating disorder (the eating attitudes test-EAT-26), OCD (the Yale-Brown obsessive compulsive scale-Y-BOCS) and depression (Beck depression inventory-BDI). The research hypothesis indicated that patients suffering from anorexia represent no significant difference in social cognitive functioning in comparison to the healthy controls. These assessment scales were used to identify whether there are any problems according to social cognitive functioning especially emotion recognition and theory of mind (ToM). The primary outcome assessment was to identify social cognitive deficits in anorexic outpatients and secondary outcome was to verify whether these problems in emotional functioning found in women in acute phase of AN are state or trait effects. RESULTS: Anorexic patients showed significantly higher scores on EAT-26, BDI and Y-BOCS. No significant differences were found in performance of social cognitive tests and facial perception test. DISCUSSION: No marked alterations were found in social cognitive functioning in community patients with average body mass index (BMI) of 17.6. This may indicate that social cognition is a very complex construct to be reliably measured in anorexia nervosa considering relatively limited psychometric data for many social cognitive tasks. Further longitudinal studies are needed to untangle ongoing controversy whether social cognitive deficits in AN could be state or trait related.

The Effects of Ageing on Differentiation and Characterisation of Human Mesenchymal Stem Cells.

BACKGROUND: Mesenchymal stem cells (MSC) are unique in their ability to self-renew and differentiate into one of many lineage possibilities. It is therefore integral to preserve these qualities to prevent the far reaching effects of a defective stem cell. Human mesenchymal stem cells (hMSC) are precursors for and can differentiate into osteoblasts, adipocytes and chondrocytes. They were originally found in the bone marrow, but have also been located in the umbilical cord, adipose tissue and muscle. Few studies have been conducted into the in vivo effects of age on these cells. This contribution reviews current knowledge surrounding the effects of age on the characteriation and differentiation of human mesenchymal stem cells. METHOD: 471 articles were found using a combination of Online published articles from January 1983 to January 2016 were searched using the Cochrane Library, PubMed, Medline, Scopus, Web of Science and Science Direct databases. There were no existing systematic reviews on this research topic. RESULTS: Nine studies were identified that met the predefined selection criteria. Three studies were used to assess the effects of ageing on characterisation of hMSC with no conclusive results. The cumulative results of these studies show that the effect of ageing on characterisation of hMSC remains inconclusive. Seven studies were used to assess the differentiation potentials of hMSC showing that age either decreased or altered lineage preference in hMSC differentiation. CONCLUSION: There is indication that ageing affects hMSC characterisation and differentiation, however it is not conclusive. There are not enough high quality controlled clinical trials to make reliable conclusions.

A Systematic Review of Mesenchymal Stem Cells in Spinal Cord Injury, Intervertebral Disc Repair and Spinal Fusion.

Spinal surgery presents a challenge for both neurosurgery and orthopaedic surgery. Due to the heterogeneous differentiation potential of mesenchymal stem cells, there is much interest in the treatment of spine surgery. Animal and human trials focussing on the efficacy of mesenchymal stem cells in spinal cord injury, spine fusion and disc degeneration were included in this systematic review. Published articles up to January 2016 from MEDLINE, PubMed and Ovid were used by searching for specific terms. Of the 2595 articles found, 53 met the selection criteria and were included for analysis (16 on spinal cord injury, 28 on intervertebral disc repair and 9 on spinal fusion). Numerous studies reported better results when the mesenchymal stem cells were used in co-culture with other cells or used in scaffolds. Mesenchymal stem cells were also found to have an immune-modulatory role, which can improve surgical outcome. This systematic review suggests that mesenchymal stem cells can be used safely and effectively for these spinal surgery treatments. Whilst, in certain studies, mesenchymal stem cells did not necessarily show improved results from existing treatments, they provide an alternative option. This can reduce morbidity that arises from current surgical treatment.

Tissue Engineering in Achilles Tendon Reconstruction: A Systematic Review of Preclincal Studies.

BACKGROUND: Tissue engineering is now being used in Achilles tendon (AT) repair in animal models. There are many preclinical studies that have used different types of stem cells for AT repair. However, there are no systematic reviews that evaluate all these studies to see which type of stem cell provides the most improvement for AT repair in animal models. Sahni V et al.,(1) divided the multiple stem cell types into three broad categories; Tendon derived stem cells (TDSCs), mesenchymal stem cells (MSCs) and embryonic stem cells (ESCs). These three categories have been used in this systematic review to group the different stem cell types together and to also see which category of stem cells provide superior enhancement of AT repair. METHOD: All studies that have focused on using different types of stem cells in animal models for AT repair and have also included an outcome measure to identify any improvement made with stem cells have been included in this systematic review. Online published articles from 1946 to January 2016 were searched using Ovid MEDLINE (R) and PubMed databases. RESULTS: Of the 181 articles found and assessed for eligibility, 15 articles met predefined selection criteria and were included in this systematic review. Stem cells can either augment current methods of surgical repair or can provide an alternative route for tendon regeneration because of their unique ability of improving histological characteristics and biomechanical properties. CONCLUSION: This systematic review shows that stem cells can provide an improvement in AT repair in animal models. Histological analysis of the tendon tissue as well as biomechanical tests such as ultimate failure load have been used to show this improvement in AT repair. Nevertheless, we do not know which type of stem cell, from the three broad categories, provides a superior enhancement of AT regeneration in animal models. Our results underscore a need for a head-to-head comparison of the different types of stem cells used in AT repair with or without current methods of surgical repair.

A Systematic Review And Meta-Analysis of Clinical Trials of Mesenchymal Stem Cell Therapy for Cartilage Repair.

BACKGROUND: Osteoarthritis (OA) is a major global burden creating significant morbidity worldwide. Current curative therapies are expensive, challenging to access and have significant risks, making them infeasible and difficult in many cases. Mesenchymal stem cells (MSCs) can be applied to joints and may regenerate the cartilage damaged in OA, this therapy may be advantageous to existing treatments. OBJECTIVE: We systematically reviewed clinical trials of MSCs for cartilage repair and provide an overview of the literature in this area here. MEDLINE, Embase, CENTRAL, clinicaltrials.gov and Open- Grey were searched for controlled trials and case series with >5 patents involving MSC therapy for cartilage repair. The controlled trials were meta-analysed and the primary outcome measure was improvement in pain over the control group. A narrative synthesis was composed for the case series. RESULTS: A significant reduction in pain was found with the use of MSCs over controls: Standardised mean difference=-1.27 (95% Confidence intervals -1.95 to -0.58). However, the data was extremely heterogeneous with I2=95%, this may be attributed to differing therapies, clinical indication for treatment and joints treated amongst others. Case series showed improvements in treated patients with a variety of differing treatments and by many outcomes. There were no severe adverse outcomes found across all studies that could be attributed to MSCs, implying their safety. CONCLUSION: We conclude that MSCs have significant potential for the treatment of OA, however, larger, more consistent trials are needed for conclusive analysis.

A Systematic Review of Clinical Studies Investigating Mesenchymal Stem Cells for Fracture Non-Union and Bone Defects.

BACKGROUND: Fracture non-union is a significant problem with a wide range demographic and massive socioeconomic elements, as well as the clinical difficulties it presents. Conventional treatments with autograft and allograft bone grafting pose serious difficulties, thus, it is necessary to develop novel techniques with our ever increasing knowledge of bioengineering using natural materials. OBJECTIVE: To search for current evidence regarding the treatment of fracture non-union or bone defects using mesenchymal stem cells (MSCs). RESULTS: The results presented in this review show that the use of mesenchymal stem cells for the treatment of non-union and bone defects is optimistic. Several papers had positive outcomes to report. There is a need for higher level evidence. CONCLUSION: A strong need of clinical results is required to further progress in cell therapy. Launched trials will hopefully provide this information in the near future. If clinical trials are positive, further development of complex tissue engineering techniques may be developed to treat large bone defects.

Preclinical Studies on Biomaterial Scaffold use in Knee Ligament Regeneration: A Systematic Review.

BACKGROUND: Knee joint trauma may result in damage of the intra-articular ligaments, with rupture of the anterior cruciate ligament (ACL) a common and troublesome injury due to poor capabilities for spontaneous regeneration. Autograft and allograft surgical reconstructions are the mainstay of treatment, but have associated risks of failure, therefore tissue-engineering techniques aiming to regenerate the native ACL are being researched as a potential alternative treatment. OBJECTIVES: This article aims to review the current evidence produced by ex vivo and in vivo studies investigating biomaterial scaffolding and mesenchymal stem cell (MSC) techniques in orthopaedic tissue engineering of ACL injuries. METHODS: Databases searched were Ovid MEDLINE, Cochrane Library, Embase, Elsevier Scopus, Web of Science and NCBI PubMed, with search terms 'ligament', 'scaffold', 'mesenchymal stem cell' and 'tissue engineering'. RESULTS: 1132 articles were identified, with 19 articles suitable for review inclusion. Of the eligible studies, 10 used biologic scaffold material, 6 used synthetic constructs, and hybrid scaffolds were employed in the remaining 3 studies. CONCLUSIONS: A large amount of preclinical evidence for viability of MSC seeded biomaterial scaffolds in ACL regeneration exists. Studies show that with stimulation, MSCs adhere and proliferate well on various scaffold materials ranging from silk to engineered polymers. Hybrid scaffolds are particularly promising, and with further research, the best features from strong natural substances such as silk, and biologically inert synthetic materials could be combined. Currently, there are few plans to begin human clinical trials, but preclinical studies are moving into larger animal models.

Knee Ligament Injury and the Clinical Application of Tissue Engineering Techniques: A Systematic Review.

BACKGROUND: The incidence of knee ligament injury is increasing and represents a significant cost to healthcare providers. Current interventions include tissue grafts, suture repair and non-surgical management. These techniques have demonstrated good patient outcomes but have been associated graft rejection, infection, long term immobilization and reduced joint function. The limitations of traditional management strategies have prompted research into tissue engineering of knee ligaments. OBJECTIVE: This paper aims to evaluate whether tissue engineering of knee ligaments offers a viable alternative in the clinical management of knee ligament injuries. A search of existing literature was performed using OVID Medline, Embase, AMED, PubMed and Google Scholar, and a manual review of citations identified within these papers. RESULTS: Silk, polymer and extracellular matrix based scaffolds can all improve graft healing and collagen production. Fibroblasts and stem cells demonstrate compatibility with scaffolds, and have been shown to increase organized collagen production. These effects can be augmented using growth factors and extracellular matrix derivatives. Animal studies have shown tissue engineered ligaments can provide the biomechanical characteristics required for effective treatment of knee ligament injuries. CONCLUSION: There is a growing clinical demand for a tissue engineered alternative to traditional management strategies. Currently, there is limited consensus regarding material selection for use in tissue engineered ligaments. Further research is required to optimize tissue engineered ligament production before clinical application. Controlled clinical trials comparing the use of tissue engineered ligaments and traditional management in patients with knee ligament injury could determine whether they can provide a cost-effective alternative.

Mechanical Stimulation Protocols of Human Derived Cells in Articular Cartilage Tissue Engineering - A Systematic Review.

Mechanical stimulation is a key factor in articular cartilage generation and maintenance. Bioreactor systems have been designed and built in order to deliver specific types of mechanical stimulation. The focus has been twofold, applying a type of preconditioning in order to stimulate cell differentiation, and to simulate in vivo conditions in order to gain further insight into how cells respond to different stimulatory patterns. Due to the complex forces at work within joints, it is difficult to simulate mechanical conditions using a bioreactor. The aim of this review is to gain a deeper understanding of the complexities of mechanical stimulation protocols by comparing those employed in bioreactors in the context of tissue engineering for articular cartilage, and to consider their effects on cultured cells. Allied and Complementary Medicine 1985 to 2016, Ovid MEDLINE[R] 1946 to 2016, and Embase 1974 to 2016 were searched using key terms. Results were subject to inclusion and exclusion criteria, key findings summarised into a table and subsequently discussed. Based on this review it is overwhelmingly clear that mechanical stimulation leads to increased chondrogenic properties in the context of bioreactor articular cartilage tissue engineering using human cells. However, given the variability and lack of controlled factors between research articles, results are difficult to compare, and a standardised method of evaluating stimulation protocols proved challenging. With improved standardisation in mechanical stimulation protocol reporting, bioreactor design and building processes, along with a better understanding of joint behaviours, we hope to perform a meta-analysis on stimulation protocols and methods.

A Systemic Review of Adult Mesenchymal Stem Cell Sources and their Multilineage Differentiation Potential Relevant to Musculoskeletal Tissue Repair and Regeneration.

BACKGROUND: Adult mesenchymal stem cells (MSCs) were first isolated from bone marrow by Friedenstein in 1976. These cells were clonogenic, non-haematopoietic, and able to replicate extensively in vitro. The fields of regenerative medicine and tissue engineering have grown dramatically since their inception. In the decades since, MSCs have been identified from mesoderm-, endoderm- and ectoderm-derived tissues. In light of our ageing population, the need for effective cell-based therapies for tissue repair and regeneration is ever-expanding. OBJECTIVES: The purpose of this systematic review was to summarise evidence from the most recent studies outlining different sources of adult MSCs and their suitability in musculoskeletal applications. METHODS: Online published articles were searched for using the PubMed/MEDLINE and Ovid databases, and relevant articles fulfilling the pre-defined eligibility criteria were analysed. RESULTS: To date, MSCs have been isolated from a number of adult tissues, including trabecular bone, adipose tissue, bone marrow, synovium, dermis, periodontal ligament, dental pulp, bursa and the umbilical cord. Bone marrow MSCs are currently considered the gold standard, with which newly discovered sources are compared on the basis of their renewal capabilities and multipotency. Furthermore, MSCs have been successful in the regeneration of osteonecrosis, osteoarthritis, bony defects, fracture remodeling and so on. CONCLUSION: Unfortunately, significant hurdles remain and will need to be overcome before tissue engineering using MSCs becomes routine in clinical practice. Thus, further research and understanding are required into the safe and effective sourcing and application of mesenchymal stem cells in musculoskeletal applications.

The Use of Growth Factors and Mesenchymal Stem Cells in Orthopaedics: In particular, their use in Fractures and Non-Unions: A Systematic Review.

AIM: The aim was to look at current evidence for treating non-unions or delayed fracture healing in regard to novel methods applying mesenchymal stem cells (MSCs) and growth factors (GF). METHODS: Pre-clinical and clinical trials focusing on the use of Mesenchymal Stem Cells and Growth Factors for fracture healing were included in this review. Published articles were identified using specific search terms in Medline, Cochrane Library, PubMed, Scopus and Web of Science. RESULTS: Of the 580 articles found, 82 met my selection criteria and were included, with 39 papers involving trials on the effects of GFs and MSCs on non-unions or bone repair. These included 11 articles on MSCs, 10 on Bone Morphogenetic Proteins, 2 on Vascular-Endothelial GF, 5 on Insulin like-GF, 4 on Transforming-GF-ß, 4 on Platelet-Rich Plasma, 1 on Platelet Derived-GF and 2 on Fibroblast-GF, with the other articles included qualitatively. Overall results were positive with the addition of MSCs, Bone Morphogenetic Proteins, VEGF, IGF and TGF-ß in aiding fracture healing compared to controls, with mixed results for other factors. CONCLUSION: Overall this review shows promising results regarding the use of MSCs and various Growth factors in the treatment of fractures and non-unions, as well as synergistic effects observed when combined together. However more research is indicated as these methods are still in the early stages of development.

The Urgent Need for Evidence in Arthroscopic Meniscal Surgery.

BACKGROUND: Arthroscopic surgery of the knee is one of the most frequently performed orthopaedic procedures. One-third of these procedures are performed for meniscal injuries. It is essential that this commonly performed surgery be supported by robust evidence. PURPOSE: To compare the effectiveness of arthroscopic surgery for meniscal injuries in all populations. STUDY DESIGN: Systematic review. METHODS: An online search was conducted for randomized controlled trials (RCTs) and systematic reviews (SRs) that compared treatment options for meniscal injury. The following databases (inception to April 2015) were included in the search: CENTRAL; MEDLINE; EMBASE; NHS Evidence; National Guideline Clearing House, Database of Abstracts of Reviews of Effects, Health Technology Assessment; ISRCTN; Clinicaltrials.gov ; WHO trials platform. Only studies whose participants were selected on the basis of meniscal injury were included; no restrictions were placed on patient demographics. Two independent reviewers applied AMSTAR (A Measurement Tool to Assess Systematic Reviews) criteria for SRs and the Cochrane Collaboration risk-of-bias tool for RCTs. RESULTS: Nine RCTs and 8 SRs were included in the review. No difference was found between arthroscopic meniscal debridement compared with nonoperative management as a first-line treatment strategy for patients with knee pain and a degenerative meniscal tear (mean difference: Knee injury and Osteoarthritis Outcome Score, 1.6 [95% CI, -2.2 to 5.2], pain visual analog scale, -0.06 [95% CI, -0.28 to 0.15]). Some evidence was found to indicate that patients with resistant mechanical symptoms who initially fail nonoperative management may benefit from meniscal debridement No studies compared meniscal repair with meniscectomy or nonoperative management. Initial evidence suggested that meniscal transplant might be favorable in certain patient groups. CONCLUSION: Further evidence is required to determine which patient groups have good outcomes from each intervention. Given the current widespread use of arthroscopic meniscal surgeries, more research is urgently needed to support evidence-based practice in meniscal surgery in order to reduce the numbers of ineffective interventions and support potentially beneficial surgery.

Pilon fracture: a case report of a 45-year-old dental technician.

Pilon fractures are complex and difficult-to-treat fractures of the lower extremity that account for about 1% of all lower extremity fractures and up to 10% of tibial fractures. The injury is caused by high energy axial load either from motor vehicle accidents or a fall from height. The treatment of these fractures has caused controversy among surgeons due to mixed outcomes. Here we report a case of pilon fracture in a 45 year old male patient who has sustained the injury as a result of a fall from a height of approximately 12 feet. We describe why it is absolutely crucial that the patient is treated with external fixation initially and evaluate its merits and drawbacks as well as ways to minimize the complications associated with external fixation of open intra-articular distal tibial fractures.

Orthopaedic approaches to proximal humeral fractures following trauma.

Proximal humeral fractures have been a topic of discussion in medical literature dating back as far as 3rd century BC. Today, these fractures are the most common type of humeral fractures and account for about 5-6% of all fractures in adults with the incidence rising rapidly with age. In broad terms the management of proximal humeral fractures can be divided into two categories: conservative versus surgical intervention. The aim of treatment is to stabilize the fracture, aid better union and reduce pain during the healing process. Failure to achieve this can result in impairment of function, and significantly weaken the muscles inserting onto the proximal humerus. With the rising incidence of proximal humeral fractures, especially among the elderly, the short and long term burden for patients as well as the wider society is increasing. Furthermore, there is a lack of consistency in the definitive treatment and management of displaced fractures. This systematic review of literature compares the surgical treatment of proximal humeral fractures with their conservative management, by evaluating the available randomised controlled trials on this topic.