Surgical management of syndromic versus non-syndromic craniofacial fibrous dysplasia: a systematic review and meta-analysis.

The main purpose of this study was to identify an algorithm for the surgical management of fibrous dysplasia in syndromic (McCune-Albright syndrome) and non-syndromic patients (monostotic and polyostotic subtypes). The secondary objectives were to assess the prevalence of affected craniofacial bones and the main clinical presentation. The authors performed a systematic review and meta-analysis by conducting a comprehensive electronic search from 1 January 2000 to 31 December 2019. A total of 1260 patients were included. The maxilla was the most affected facial bone (41%) (p<0.001, CI 38.3 to 43.8) and facial asymmetry was the chief complaint (p<0.001, CI 31.7 to 37.1). Conservative surgery registered higher recurrence rates than radical resection in both syndromic (84%) (p<0.001, CI 70.9 to 92.8) and non-syndromic patients (26%) (p<0.001, CI 21.8 to 30.6). Compared with prophylactic decompression, therapeutic optic nerve decompression (OND) showed better postoperative outcomes in both syndromic (p=0.9, CI 18.6 to 55.9) and non-syndromic patients (p=0.09, CI 9.3 to 28.4). Watchful waiting showed excellent results in both subgroups when asymptomatic (p<0.001). Syndromic and non-syndromic patients share the same treatment strategies. Radical resection is the preferred surgical technique to eradicate the disease, but it is often difficult to perform due to the extent and location of the disease. Furthermore, the authors advise early therapeutic over prophylactic OND to prevent optic nerve atrophy. Asymptomatic patients should be managed expectantly. Finally, medical management helps reduce the symptoms of bone pain (p=0.02 in non-syndromic and p<0.001 in syndromic patients).

Maxillofacial trauma in ethnic minorities: has Brexit promoted an increase in violence and discrimination?

The main objective of this study was to evaluate whether the 2016 Brexit referendum has contributed to an increase in maxillofacial injuries specifically targeted against ethnic minority groups in the district of North London. The secondary objectives were to identify the most common types of injuries following the assaults and the number of patients admitted to hospital. A total of 1,391 people was assaulted between 1 January 2014 and 31 December 2018. They were classified into the following categories: White (62.4%), Asian (13.6%), Black/African-Caribbean (11.9%), Other (Arab) (9%) and Mixed Ethnic Group (3.2%). A shift in the proportion of ethnicities affected, rather than an increase in the overall number of injuries, was observed during the five-year period. A significant increase in assaults against individuals of Asian ethnicity (p<0.01) and against Croatians (p<0.01) was recorded between 2014 and 2018. Peaks in assaults against white non-British individuals and Romanians were also identified in 2017 (p=0.04 and p<0.01, respectively). Furthermore, the White British (p=0.02), Asian (p<0.01) ethnic groups and the Spanish, Romanian, Italian, Russian, Lithuanian, Albanian and Croatian (p<0.01) nationalities experienced a significantly disproportionate number of attacks compared to their population share in North London during this five-year period. The most common injuries were contusion, and fractures of the nasal bones and mandible at 24.2%, 17.1%, and 16.5%, respectively. A total of 415 patients (29.8%) required hospital admission for treatment and 47.6% received conservative treatment. The authors have concluded that the Brexit vote may have played an important role in increasing violence and hate crime against specific ethnic minorities.

Injury to the inferior alveolar and lingual nerves in successful and failed coronectomies: systematic review.

The aim of this systematic review was to evaluate the incidence of damage to the inferior alveolar (IAN) and dental nerves in successful coronectomies, and to compare the results with coronectomies that failed. To the best of our knowledge no such analyses have been reported. Between January 1990 and October 2016 we surveyed published papers to find those that examined clinical outcomes after coronectomy. Fourteen met the criteria for final inclusion. Of 2087 coronectomies, 152 failed (7%). Successful procedures were associated with a low overall incidence of injury to the IAN (0.5%) and lingual nerve (0.05%). The incidence of injury to the IAN in failed coronectomies was 2.6%. The incidence of permanent paraesthesia was 0.05% in successful coronectomies and 1.3% in those that failed. No permanent injury to the lingual nerve was reported. Mobility (36%, 55/152) and migration or exposure (33%, 50/152) of roots were the most common underlying causes of failure. Coronectomy seems to be safe, but it depends on the patient and the technique used. To ensure adequate assessment of postoperative complications, we strongly recommend systematic evaluation of the reduction in sensitivity of the lower lip, chin, or tongue, and a standard follow up.

A saturated N-acylethanolamine other than N-palmitoyl ethanolamine with anti-inflammatory properties: a neglected story...

N-acylethanolamines, which include the endocannabinoid anandamide and the cannabinoid receptor-inactive saturated compounds N-palmitoyl ethanolamine and N-stearoyl ethanolamine, are ethanolamines of long-chain fatty acids degraded by fatty acid amide hydrolase (FAAH) known to accumulate in degenerating tissues and cells. Whilst much evidence supports a protective anti-inflammatory role of both anandamide and N-palmitoyl ethanolamine, very little information is available with regard to the bioactivity of N-stearoyl ethanolamine. Employing a murine model of passive IgE-induced cutaneous anaphylaxis, we have found that N-stearoyl ethanolamine is endowed with marked anti-inflammatory properties in vivo, supporting the hypothesis that endogenous N-stearoyl ethanolamine is, in analogy to N-palmitoyl ethanolamine, a bioactive signalling lipid capable of downregulating allergic inflammation in the skin. This effect, although mimicked by synthetic, non-selective, CB(1)/CB(2) receptor agonists, such as WIN55, 212-2, was not sensitive to CB(1) or CB(2) receptor antagonists, but rather was fully reversed by capsazepine, a competitive antagonist of the TRPV1 receptor. Moreover, CB(1) receptor antagonists, although effective in antagonising the WIN55,212-2-induced hypothermia, did not reduce the anti-inflammatory effect of WIN55,212-2, whilst CB(2) receptor antagonists, per se inactive, potentiated the WIN55,212-2 effect, suggesting an involvement of non-CB(1)/CB(2) receptors in the anti-inflammatory action of WIN55,212-2. All this, together with demonstration of FAAH as a major regulator of the in vivo concentrations of saturated N-stearoyl ethanolamine, in addition to N-palmitoyl ethanolamine, raise the speculation that pharmacological treatments with saturated N-acylethanolamines such as N-stearoyl ethanolamine, or alternatively FAAH inhibitors able to increase their local concentration, rather than selective CB receptor agonists, might be of promising therapeutic benefit in reducing allergic inflammation in the skin.

Quercetin protects cutaneous tissue-associated cell types including sensory neurons from oxidative stress induced by glutathione depletion: cooperative effects of ascorbic acid.

Oxidation reactions are essential biological reactions necessary for the formation of high-energy compounds used to fuel metabolic processes, but can be injurious to cells when produced in excess. Cutaneous tissue is especially susceptible to damage mediated by reactive oxygen species and low-density lipoprotein oxidation, triggered by dysmetabolic diseases, inflammation, environmental factors, or aging. Here we have examined the ability of the flavonoid quercetin to protect cutaneous tissue-associated cell types from injury induced by oxidative stress, and possible cooperative effects of ascorbic acid. Human skin fibroblasts, keratinocytes, and endothelial cells were cultured in the presence of buthionine sulfoximine (BSO), an irreversible inhibitor of glutathione (GSH) synthesis. Depletion of intracellular levels of GSH leads to an accumulation of cellular peroxides and eventual cell death. Quercetin concentration-dependently (EC50: 30-40 microM) reduced oxidative injury of BSO to all cell types, and was also effective when first added after BSO washout. BSO caused marked decreases in the intracellular level of GSH, which remained depressed in quercetin-protected cells. Ascorbic acid, while by itself not cytoprotective synergized with quercetin, lowered the quercetin EC50 and prolonged the window for cytoprotection. The related flavonoids rutin and dihydroquercetin also decreased BSO-induced injury to dermal fibroblasts, albeit less efficaciously so than quercetin. The cytoprotective effect of rutin, but not that of dihydroquercetin, was enhanced in the presence of ascorbic acid. Further, quercetin rescued sensory ganglion neurons from death provoked by GSH depletion. Direct oxidative injury to this last cell type has not been previously demonstrated. The results show that flavonoids are broadly protective for cutaneous tissue-type cell populations subjected to a chronic intracellular form of oxidative stress. Quercetin in particular, paired with ascorbic acid, may be of therapeutic benefit in protecting neurovasculature structures in skin from oxidative damage.

Skin photosensitizing agents and the role of reactive oxygen species in photoaging.

In this paper, the role of reactive oxygen species in photoaging is presented. Many photosensitizing agents are known to generate reactive oxygen species (singlet oxygen (1O2), superoxide anion (O2.-) and .OH radicals). Although photoaging (dermatoheliosis) of human skin is caused by UVB and UVA radiation, the hypothesis tested here in the pathogenesis of photoaging of human skin is the free radical theory involving the generation of reactive oxygen species by UVA (320-400 nm) radiation and their damaging oxidative effects on cutaneous collagen and other model proteins. The UVA-generated reactive oxygen species cause cross-linking of proteins (e.g. collagen), oxidation of sulfydryl groups causing disulfide cross-links, oxidative inactivation of certain enzymes causing functional impairment of cells (fibroblasts, keratinocytes, melanocytes, Langerhans cells) and liberation of proteases, collagenase and elastase. The skin-damaging effects of UVA appear to result from type II, oxygen-mediated photodynamic reactions in which UVA or near-UV radiation in the presence of certain photosensitizing chromophores (e.g., riboflavin, porphyrins, nicotinamide adenine dinucleotide phosphate (NADPH), etc.) leads to the formation of reactive oxygen species (1O2, O2.-, .OH). Four specific observations are presented to illustrate the concept: (1) the production of 1O2 and O2.- by UVB, UVA and UVA plus photosensitizing agents (such as riboflavin, porphyrin and 3-carbethoxypsoralens) as a function of UV exposure dose, the sensitizer concentration and the pH of the irradiated solution; (2) the formation of protein cross-links in collagen, catalase and superoxide dismutase by 1O2 and O2.- (.OH) and the resulting denaturation of proteins and enzyme activities as a function of UVA exposure dose; (3) the protective role of selective quenchers of 1O2 and O2.- (e.g. alpha-tocopherol acetate, beta-carotene, sodium azide, ascorbic acid, etc.) against the photoinactivation of enzymes and the prevention of the protein cross-linking reaction; (4) the possible usefulness of certain antioxidants or quenchers that interact with the UVA-induced generation of reactive oxygen species in the amelioration of the process of photoaging.