From benchtop to clinic: a translational analysis of the immune response to submicron topography and its relevance to bone healing.

Proper regulation of the innate immune response to bone biomaterials after implantation is pivotal for successful bone healing. Pro-inflammatory M1 and anti-inflammatory M2 macrophages are known to have an important role in regulating the healing response to biomaterials. Materials with defined structural and topographical features have recently been found to favourably modulate the innate immune response, leading to improved healing outcomes. Calcium phosphate bone grafts with submicron-sized needle-shaped surface features have been shown to trigger a pro-healing response through upregulation of M2 polarised macrophages, leading to accelerated and enhanced bone regeneration. The present review describes the recent research on these and other materials, all the way from benchtop to the clinic, including in vitro and in vivo fundamental studies, evaluation in clinically relevant spinal fusion models and clinical validation in a case series of 77 patients with posterolateral and/or interbody fusion in the lumbar and cervical spine. This research demonstrates the feasibility of enhancing biomaterial-directed bone formation by modulating the innate immune response through topographic surface features.

Systematic review of benefits or harms of routine anaesthetist-inserted throat packs in adults: practice recommendations for inserting and counting throat packs: An evidence-based consensus statement by the Difficult Airway Society (DAS), the British Association of Oral and Maxillofacial Surgery (BAOMS) and the British Association of Otorhinolaryngology, Head and Neck Surgery (ENT-UK).

Throat packs are commonly inserted by anaesthetists after induction of anaesthesia for dental, maxillofacial, nasal or upper airway surgery. However, the evidence supporting this practice as routine is unclear, especially in the light of accidentally retained throat packs which constitute 'Never Events' as defined by NHS England. On behalf of three relevant national organisations, we therefore conducted a systematic review and literature search to assess the evidence base for benefit, and also the extent and severity of complications associated with throat pack use. Other than descriptions of how to insert throat packs in many standard texts, we could find no study that sought to assess the benefit of their insertion by anaesthetists. Instead, there were many reports of minor and major complications (the latter including serious postoperative airway obstruction and at least one death), and many descriptions of how to avoid complications. As a result of these findings, the three national organisations no longer recommend the routine insertion of throat packs by anaesthetists but advise caution and careful consideration. Two protocols for pack insertion are presented, should their use be judged necessary.

Micro-CT scouting for transmission electron microscopy of human tissue specimens.

Transmission electron microscopy (TEM) provides sub-nanometre-scale details in volumetric samples. Samples such as pathology tissue specimens are often stained with a metal element to enhance contrast, which makes them opaque to optical microscopes. As a result, it can be a lengthy procedure to find the region of interest inside a sample through sectioning. We describe micro-CT scouting for TEM that allows noninvasive identification of regions of interest within a block sample to guide the sectioning step. In a tissue pathology study, a bench-top micro-CT scanner with 10 µm resolution was used to determine the location of patches of the mucous membrane in osmium-stained human nasal scraping samples. Once the regions of interest were located, the sample block was sectioned to expose that location, followed by ultra-thin sectioning and TEM to inspect the internal structure of the cilia of the membrane epithelial cells with nanometre resolution. This method substantially reduced the time and labour of the search process from typically 20 sections for light microscopy to three sections with no added sample preparation.

Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE): a physiological method of increasing apnoea time in patients with difficult airways.

Emergency and difficult tracheal intubations are hazardous undertakings where successive laryngoscopy-hypoxaemia-re-oxygenation cycles can escalate to airway loss and the 'can't intubate, can't ventilate' scenario. Between 2013 and 2014, we extended the apnoea times of 25 patients with difficult airways who were undergoing general anaesthesia for hypopharyngeal or laryngotracheal surgery. This was achieved through continuous delivery of transnasal high-flow humidified oxygen, initially to provide pre-oxygenation, and continuing as post-oxygenation during intravenous induction of anaesthesia and neuromuscular blockade until a definitive airway was secured. Apnoea time commenced at administration of neuromuscular blockade and ended with commencement of jet ventilation, positive-pressure ventilation or recommencement of spontaneous ventilation. During this time, upper airway patency was maintained with jaw-thrust. Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) was used in 15 males and 10 females. Mean (SD [range]) age at treatment was 49 (15 [25-81]) years. The median (IQR [range]) Mallampati grade was 3 (2-3 [2-4]) and direct laryngoscopy grade was 3 (3-3 [2-4]). There were 12 obese patients and nine patients were stridulous. The median (IQR [range]) apnoea time was 14 (9-19 [5-65]) min. No patient experienced arterial desaturation < 90%. Mean (SD [range]) post-apnoea end-tidal (and in four patients, arterial) carbon dioxide level was 7.8 (2.4 [4.9-15.3]) kPa. The rate of increase in end-tidal carbon dioxide was 0.15 kPa.min(-1) . We conclude that THRIVE combines the benefits of 'classical' apnoeic oxygenation with continuous positive airway pressure and gaseous exchange through flow-dependent deadspace flushing. It has the potential to transform the practice of anaesthesia by changing the nature of securing a definitive airway in emergency and difficult intubations from a pressured stop-start process to a smooth and unhurried undertaking.

Johnson square procedure for lentigo maligna and lentigo maligna melanoma.

BACKGROUND: Lentigo maligna (LM) and lentigo maligna melanoma (LMM) can be difficult to manage surgically. Predetermined margins can be inadequate because of subclinical spread, or can affect function when margins are adjacent to the eye or mouth. AIM: To describe our 5-year experience in Nottingham of using the staged square procedure (Johnson square) in excising difficult facial LM and LMM. METHODS: The square procedure is a staged technique useful for ill-defined lesions and for lesions that have a high recurrence rate due to subclinical spread. It uses paraffin wax-embedded peripheral vertical sections for margin control, ensuring complete clearance as the surgical margins are usually examined at distances of 2-5 mm from the periphery of the lesion. RESULTS: We treated 21 patients with LM or LMM with the staged square procedure over a 5-year period. Of the 21 patients, 10 needed only one stage of surgery, 6 needed two stages, 3 needed three stages and 2 needed four stages. To date, there has been only one recurrence, which was of an extensive lesion that crossed the medial canthus, making margin control impossible because of the anatomical limitations. CONCLUSIONS: The staged square procedure is an effective treatment for LM and LMM. It attempts to conserve tissue while ensuring a higher clearance rate. This offers favourable cosmetic outcomes and better prognosis, especially for facial LM and LMM.

Novel Ameloblastin Variants, Contrasting Amelogenesis Imperfecta Phenotypes.

Amelogenesis imperfecta (AI) comprises a group of rare, inherited disorders with abnormal enamel formation. Ameloblastin (AMBN), the second most abundant enamel matrix protein (EMP), plays a critical role in amelogenesis. Pathogenic biallelic loss-of-function AMBN variants are known to cause recessive hypoplastic AI. A report of a family with dominant hypoplastic AI attributed to AMBN missense change p.Pro357Ser, together with data from animal models, suggests that the consequences of AMBN variants in human AI remain incompletely characterized. Here we describe 5 new pathogenic AMBN variants in 11 individuals with AI. These fall within 3 groups by phenotype. Group 1, consisting of 6 families biallelic for combinations of 4 different variants, have yellow hypoplastic AI with poor-quality enamel, consistent with previous reports. Group 2, with 2 families, appears monoallelic for a variant shared with group 1 and has hypomaturation AI of near-normal enamel volume with pitting. Group 3 includes 3 families, all monoallelic for a fifth variant, which are affected by white hypoplastic AI with a thin intact enamel layer. Three variants, c.209C>G; p.(Ser70*) (groups 1 and 2), c.295T>C; p.(Tyr99His) (group 1), and c.76G>A; p.(Ala26Thr) (group 3) were identified in multiple families. Long-read AMBN locus sequencing revealed these variants are on the same conserved haplotype, implying they originate from a common ancestor. Data presented therefore provide further support for possible dominant as well as recessive inheritance for AMBN-related AI and for multiple contrasting phenotypes. In conclusion, our findings suggest pathogenic AMBN variants have a more complex impact on human AI than previously reported.

Evaluation of ozonated olive oil with or without adjunctive application of calcium sodium phosphosilicate on post-surgical root dentin hypersensitivity: a randomized, double-blinded, controlled, clinical trial.

AIM: This study was conducted to evaluate the efficacy of ozonated olive oil with or without adjunctive application of mineral wash containing calcium sodium phosphosilicate on the reversal of post-surgical root dentin hypersensitivity. METHODS: A double-blinded, randomized controlled clinical trial was conducted on 51 participants with root dentin hypersensitivity (RDH). Participants were randomLy assigned to 4 groups: Group A, ozonated olive oil (OZO): Group B, ozonated olive oil and mineral wash: Group C, placebo olive oil (PPO) and mineral wash: Group D, placebo olive oil only. Active treatment was carried out in-clinic and followed by at-home care with a remineralising paste. The response to various pain stimuli was periodically assessed with a visual analogue scale. Additionally, scanning electron microscopic study assessed the dentinal tubule occlusion and change in tubular surface area after treatment. RESULTS: The group B participants showed a significant decrease in tooth level and global sensitivity over the period (P<0.001). Moreover, the intergroup comparison also revealed a significant result (P<0.001). Similarly, participants of group C also showed a significant reduction in sensitivity over the period (P<0.001). Whereas, no significant (P>0.05) difference was detected between group A and group D for tooth level and global sensitivity analysis. The SEM study result showed a significantly (P<0.001) enhanced tubule occlusion and decreased tubular surface area in group B specimens compared to other group specimens. CONCLUSION: OZO, as a mono-therapy is not efficient in reducing post-surgical RDH. However, the adjunctive application of mineral wash containing calcium sodium phosphosilicate has positive impact on the reversal of post-surgical root dentin hypersensitivity.

An unusual presentation of juvenile systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multisystem disorder with a diverse spectrum of clinical abnormality. Despite advances in our understanding of the disease, the aetiology and outcome remains unknown. We describe a 13-year-old boy who presented with paronychia, mouth ulcers and associated neutropenia. Appropriate investigations including a bone-marrow biopsy revealed a shift to the left, and in the absence of any other immunological abnormalities, a diagnosis of idiopathic neutropenia was made. The patient was successfully treated with granulocyte colony-stimulating factor but subsequently re-presented during the winter months with a purpuric facial eruption affecting his cheeks and ears. On histological examination of a biopsy taken from the ear, a microvascular thrombosis was seen. Laboratory investigations were positive for anticardiolipin antibodies, neutropenia and antinuclear antibodies (ANA), suggesting a diagnosis of juvenile (J)JSLE with antiphospholipid syndrome. This is an unusual presentation of SLE in a prepubertal white boy, with a malar and helical vasculopathy as a novel cutaneous presentation of JSLE.

Effect of subgingival application of topical ozonated olive oil in the treatment of chronic periodontitis: a randomized, controlled, double blind, clinical and microbiological study.

AIM: The aim of this paper was to evaluate the efficacy of ozonated olive oil as a monotherapy and an adjunct to scaling and root planing in the treatment of chronic periodontitis METHODS: A split mouth, double-blinded, randomized controlled clinical trial was conducted on 20 subjects diagnosed with chronic periodontitis. Quadrants of each subject were randomly assigned to four groups and treated accordingly: Group A, scaling and root planing (SRP): Group B, topical ozonated olive oil (OZO) as an adjunct to scaling and root planing: Group C, topical ozonated olive oil as a monotherapy and: Group D, topical chlorhexidine gel as a monotherapy. The quadrants were analyzed clinically by plaque index, gingival index, sulcus bleeding index, probing pocket depth, and clinical attachment level at baseline, 2, 4, 6 and 8 weeks of time intervals. The subjects were also analyzed for perceived pain, discomfort or tooth hypersensitivity (quadrant wise) on a Visual Analogue Scale (VAS). Additionally, subgingival plaque samples were collected from the two predetermined sites of each quadrant at baseline, 4 and 8 weeks for the analysis of total bacterial counts (TBCs) and the detection of frequency of eight putative periodontopathogens by polymerase chain reaction (PCR) method. RESULTS: The adjunctive use of the OZO with SRP resulted in a significant improvement (P<0.001) of clinical parameters as well as microbiological parameters over the time and in comparison to the control groups. The OZO as monotherapy also showed a significant improvement (P<0.001) in clinical parameters as well as microbiological parameters over the time without any documented side effects. However, there was a significant increase (P<0.05) in dentinal hypersensitivity following OZO as an adjunct to scaling and root planing therapy. CONCLUSION: The OZO, as an adjunctive therapy as well as a mono-therapy is efficient in improving periodontal conditions.

Native pulmonary valve endocarditis requiring pulmonary valve replacement in adulthood: a case series.

Native pulmonary valve endocarditis is a rare phenomenon as native valve endocarditis tends to typically affect the left sided heart valves. However, the right-sided heart valves can be affected in patients with a history of intravenous drug use, whereby the tricuspid valve is most commonly affected. We present two cases who were diagnosed with native pulmonary valve endocarditis in the absence of congenital heart disease. In the first case, the native pulmonary valve endocarditis was probably a derivative of compounding factors of an enlarged underlying pulmonary artery and staphylococcal bacteraemia. In the second case, a common causal organism of native valve endocarditis following dental treatment and the resultant echocardiography findings was of significant interest. In summary, native pulmonary valve endocarditis is relatively rare complication in the adult population, especially in the absence of congenital heart disease.

A prospective, up-down sequential allocation study investigating the effectiveness of vital capacity breaths using high-flow nasal oxygenation versus a tight-fitting face mask to pre-oxygenate term pregnant women.

BACKGROUND: The role of high flow nasal oxygenation (HFNO) for pre-oxygenation before obstetric general anaesthesia remains unclear. This study aimed to determine the number of vital capacity breaths using HFNO required to pre-oxygenate 90% of parturients to an end-tidal oxygen concentration fraction (FETO2) of ≥0.90 (termed EN90). METHODS: Using up-down, sequential allocation trial design, volunteer term parturients undergoing caesarean delivery were investigated with HFNO with their mouth closed, followed by mouth open, and if FETO2 ≥0.90 was not achieved after a maximum of 20 vital capacity breaths, pre-oxygenation was attempted with a face mask. The primary outcome was the number of vital capacity breaths required using HFNO (mouth open and closed) to achieve EN90. Secondary outcomes included assessment of EN90 using mouth open versus mouth closed and face mask pre-oxygenation, maternal satisfaction and evaluation of fetal cardiotocography. RESULTS: Twenty women at term were recruited. Successful pre-oxygenation occurred in 4 (20%), 3 (15%) and 14 (70%) women with HFNO mouth closed, HFNO mouth open, and via face mask respectively. At up to 20 vital capacity breaths, face mask pre-oxygenation was more successful at achieving EN90 compared with both HFNO with a closed (P=0.006) or open (P=0.001) mouth. Closed mouth HFNO did not outperform open mouth pre-oxygenation. CONCLUSION: Face mask pre-oxygenation is more effective at achieving EN90 compared with to HFNO within a clinically acceptable number of vital capacity breaths. Further studies are needed to determine the role of HFNO in optimising the time before desaturation and for apnoeic oxygenation in term parturients.

Oral disease and subsequent cardiovascular disease in people with type 2 diabetes: a prospective cohort study based on the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) trial.

AIMS/HYPOTHESIS: While there are plausible biological mechanisms linking oral health with cardiovascular disease (CVD) and mortality rates, no study, to our knowledge, has examined this association in a representative population of people with type 2 diabetes. METHODS: We used the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) study, a large, detailed, randomised controlled trial among a general population of individuals with type 2 diabetes. For the purposes of the present analyses, data from the trial are used within a prospective cohort study design. A total of 10,958 men and women, aged 55 to 88 years and with type 2 diabetes, participated in a baseline medical examination, during which they counted their number of natural teeth and reported the number of days that their gums had bled over the preceding year. Study members were followed up for mortality and morbidity over 5 years. RESULTS: After controlling for a range of potential confounding factors, the group with no teeth had a markedly increased risk of death due to all causes (HR 1.48, 95% CI 1.24-1.78), CVD (1.35, 1.05-1.74) and non-CVD (1.64, 1.26-2.13), relative to the group with the most teeth (≥22 teeth). Frequency of bleeding gums was not associated with any of the outcomes of interest. There was no suggestion that treatment group or sex modified these relationships. CONCLUSIONS/INTERPRETATION: In people with type 2 diabetes, oral disease, as indexed by fewer teeth, was related to an increased risk of death from all causes and of death due to CVD and non-CVD.

Genomic duplication resulting in increased copy number of genes encoding the sister chromatid cohesion complex conveys clinical consequences distinct from Cornelia de Lange.

BACKGROUND: Cornelia de Lange syndrome (CdLS) is a multisystem congenital anomaly disorder. Heterozygous point mutations in three genes (NIPBL, SMC3 and SMC1A), encoding components of the sister chromatid cohesion apparatus, are responsible for approximately 50-60% of CdLS cases. Recent studies have revealed a high degree of genomic rearrangements (for example, deletions and duplications) in the human genome, which result in gene copy number variations (CNVs). CNVs have been associated with a wide range of both Mendelian and complex traits including disease phenotypes such as Charcot-Marie-Tooth type 1A, Pelizaeus-Merzbacher, Parkinson, Alzheimer, autism and schizophrenia. Increased versus decreased copy number of the same gene can potentially cause either similar or different clinical features. METHODS AND RESULTS: This study identified duplications on chromosomes 5 or X using genome wide array comparative genomic hybridisation (aCGH). The duplicated regions contain either the NIPBL or the SMC1A genes. Junction sequences analyses revealed the involvement of three genomic rearrangement mechanisms. The patients share some common features including mental retardation, developmental delay, sleep abnormalities, and craniofacial and limb defects. The systems affected are the same as in CdLS, but clinical manifestations are distinct from CdLS; particularly the absence of the CdLS facial gestalt. CONCLUSIONS: The results confirm the notion that duplication CNV of genes can be a common mechanism for human genetic diseases. Defining the clinical consequences for a specific gene dosage alteration represents a new "reverse genomics" trend in medical genetics that is reciprocal to the traditional approach of delineation of the common clinical phenotype preceding the discovery of the genetic aetiology.

Comparative evaluation of a single 2.0-mm AO locking reconstruction plate with conventional miniplate osteosynthesis for treatment of linear non-comminuted fractures of symphysis and parasymphsis region of the mandible.

The objective of the study was to evaluate and compare the relative efficacy of treating linear non-comminuted mandibular fracture of symphysis and parasymphysis region using single 2.0-mm AO locking reconstruction plate or using two conventional miniplates. In this study, 80 patients of symphysis or parasymphysis fracture were divided randomly in two equal groups and treated with open reduction and internal fixation using two 2.5-mm miniplates or with a single 2.0-mm AO locking reconstruction plate. Operating time in case of open reduction and fixation using a single 2.0-mm locking reconstruction plate was significantly less when compared to open reduction and fixation using two conventional miniplates. Both groups showed satisfactory fracture reduction and healing. No postoperative malocclusion was noted, and both groups showed comparable improvement in masticatory efficiency. In conclusion, fracture fixation using a single 2.0-mm AO locking reconstruction plate without use of a second plate at the superior border for treatment of linear non comminuted mandibular fracture in symphysis and parasymphysis region gives comparable results as with treatment by conventional miniplate system and provides significant savings in operating time, ease of use and decrease in amount of hardware incorporated in the body.

Phenotype and Variant Spectrum in the LAMB3 Form of Amelogenesis Imperfecta.

Amelogenesis imperfecta (AI) is a heterogeneous group of inherited disorders characterized by abnormal formation of dental enamel, either in isolation or as part of a syndrome. Heterozygous variants in laminin subunit beta 3 ( LAMB3) cause AI with dominant inheritance in the absence of other cosegregating clinical features. In contrast, biallelic loss-of-function variants in LAMB3 cause recessive junctional epidermolysis bullosa, characterized by life-threatening skin fragility. We identified 2 families segregating autosomal dominant AI with variable degrees of a distinctive hypoplastic phenotype due to pathogenic variants in LAMB3. Whole exome sequencing revealed a nonsense variant (c.3340G>T, p.E1114*) within the final exon in family 1, while Sanger sequencing in family 2 revealed a variant (c.3383-1G>A) in the canonical splice acceptor site of the final exon. Analysis of cDNA from family 2 revealed retention of the final intron leading to a premature termination codon. Two unerupted third molar teeth from individual IV:5 in family 2 were subject to computerized tomography and scanning electron microscopy. LAMB3 molar teeth have a multitude of cusps versus matched controls. LAMB3 enamel was well mineralized but pitted. The architecture of the initially secreted enamel was abnormal, with cervical enamel appearing much less severely affected than coronal enamel. This study further defines the variations in phenotype-genotype correlation for AI due to variants in LAMB3, underlines the clustering of nonsense and frameshift variants causing AI in the absence of junctional epidermolysis bullosa, and highlights the shared AI phenotype arising from variants in genes coding for hemidesmosome proteins.

The body constitution of patients and intubation scales as predictors of difficult intubation considered in relation to the experience of the intubator.

The aims of the study were to identify factors that may result in difficulties in intubation, and to compare the results obtained when an experienced and when a less experienced anaesthesiologist was involved. The 96 patients included in the study were evaluated for difficult intubation according to the following scales: Mallampati, upper lip bite test (ULBT) and Patil. The mobility of the cervical segments of the vertebral column, the distance between the jugular notch of the sternum and the chin and the anatomical constitution of the body were other factors that were taken into consideration. Statistical analysis was performed in order to identify factors that may result in difficulties in intubation for an experienced and for a less experienced anaesthesiologist.

Flapless dental implant surgery and use of cone beam computer tomography guided surgery.

Flapless implant surgery is increasing in popularity, particularly due to advances and increased usage of cone beam computed tomography (CBCT) and dental implant treatment planning software allowing three-dimensional assessment of the implant site. It is the aim of the article to provide an overview of flapless implant surgery and CBCT guided flapless implant surgery and summarise the literature with regard to the effectiveness of this surgical technique.

Tooth wear risk assessment and care-planning in general dental practice.

Objective To assess charting, risk assessment and treatment-planning of tooth wear between recently qualified and experienced dentists in general dental practice.Design Service evaluation.Setting Multi-setting evaluation of three mixed NHS/Private general dental practices in North-East London.Methods The clinical notes of new patient examinations on dentate adults presenting from the 1 October 2016 to 31 December 2016 were audited collecting data on tooth wear charting, risk assessment and treatment planning. Data were analysed using descriptives, chi square and logistic regressions in SPSS. Significance was inferred at p <0.05.Results Foundation dentists and experienced dentists performed 85 and 200 new patient examinations, respectively, during the evaluation period. Tooth wear was charted for 48% of those attending foundation dentists and 5% of those attending experienced dentists. Diet was assessed in 50.6% of patients examined by foundation dentists and 1.0% of patients examined by experienced dentists. Foundation dentists were more likely to chart tooth wear, risk assess and preventively manage tooth wear compared to experienced dentists (p <0.001).Conclusion This service evaluation highlights that improvements are required in recording, risk assessing and preventive treatment planning of erosive tooth wear. Experienced dentists were less likely to risk assess tooth wear and less likely to provide preventive treatment. Experienced GDPs may benefit from re-training in this area.

A randomised comparison of the single use LMA Flexible with the reusable LMA Flexible in paediatric dental day-case patients.

In this study we compared the performance of the single use flexible laryngeal mask airway (LMA Flexible) with the original reusable LMA Flexible in paediatric dento-alveolar day-case surgery. The aim of the study was to determine whether these two supraglottic airway devices were clinically equivalent when used for simple dental extractions in children under general anaesthesia. This randomised comparative trial in 100 healthy children used first attempt airway insertion success as its primary outcome measure. Secondary outcomes included the adequacy of ventilation, incidence of airway obstruction and the requirement for device manipulation and the incidence of adverse airway outcomes during recovery from anaesthesia. No difference was found between the devices in first attempt insertion success rate (94% with reusable LMA Flexible and 90% with single use LMA Flexible, p = 0.358), and ease of insertion was also similar (p = 0.5). Both devices performed equally well during surgery, with no significant differences in episodes of intra-operative airway compromise (p = 0.387), and both the single use and reusable LMA Flexible displayed excellent recovery characteristics, with no occurrences of emergence airway obstruction. No blood was discovered within the inner LMA tube shaft in either device, implying that both protected against tracheobronchial soiling. We conclude therefore that the single use LMA Flexible is an acceptable alternative to the reusable LMA Flexible.