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(1) Background: Glycogen storage disease (GSD) represents a group of twenty-three types of metabolic disorders which damage the capacity of body to store glucose classified basing on the enzyme deficiency involved. Affected patients could present some oro-facial alterations: the purpose of this review is to catalog and characterize oral manifestations in these patients. (2) Methods: a systematic review of the literature among different search engines using PICOS criteria has been performed. The studies were included with the following criteria: tissues and anatomical structures of the oral cavity in humans, published in English, and available full text. Review articles and paper published before 1990 were excluded. (3) Results: 757 articles were identified in the initial search. In the end, 45 articles that met the selection criteria has been analyzed. The information extracted from the articles was classified according to the type of GSD (Ia; Ib; II; III; V; XIV). Oral manifestations range from dental caries to severe periodontitis in paediatric patients, from diffuses and recurrent oral ulcers in the cleft lip and palate. (4) Conclusions: Although considered a rare disease, GSD can present a varied number of oral manifestations. Therefore, it is of great importance for the oral medicine specialist to know and classify them.

Background: Oral squamous cell carcinoma (OSCC) accounts for more than 90% of oral epithelial malignancies and often arises from precursor lesions, whose diagnosis is based on biopsy and histopathology. In vivo reflectance confocal microscopy (RCM) images the vital tissues at microscopic resolution, well correlating with conventional histopathology, but it is poorly investigated in oral oncology. The present work aims to describe RCM cytoarchitectural findings in oral mucosae affected by OSCC and its precursors. Materials and Methods: A series of clinically suspected oral lesions underwent RCM imaging before conventional biopsy and histopathological assessment in order to identify features suggestive of tumoral changes. Sensitivity (SE), specificity (SP), positive and negative predictive values (PPV and NPV) of RCM compared to histopathology were calculated. Results: Totally, 30 sites in 20 patients were considered and clinically classified into 16 “leukoplakia”/“ traumatism”, nine erosive-ulcerative lesions, three verrucous lesions, and two healthy mucosae, as control. The histopathological “positivity,” due to the presence of various degrees of dysplasia and/or neoplasia, was found in 11 lesions; the RCM “positivity” was referred to nine lesions reporting the RCM detection of polymorphism, multinucleated cells, irregular cellular maturation, altered nuclear/cytoplasm ratio, and abnormal blood vessels. After excluding three verrucous lesions from the RCM analysis, due to the low laser penetration through the hyperkeratotic layers, the results well correlated with histopathology, reporting 1.000 (SE), 0.933 (SP), 0.909 (PPV), and 1.000 (NPV). Conclusion: RCM can reveal dysplastic/neoplastic signs occurring in oral lesions, thus supporting their diagnostic pathway. Background: Oral squamous cell carcinoma (OSCC) accounts for more than 90% of oral epithelial malignancies and often arises from precursor lesions, whose diagnosis is based on biopsy and histopathology. In vivo reflectance confocal microscopy (RCM) images the vital tissues at microscopic resolution, well correlating with conventional histopathology, but it is poorly investigated in oral oncology. The present work aims to describe RCM cytoarchitectural findings in oral mucosae affected by OSCC and its precursors. Materials and Methods: A series of clinically suspected oral lesions underwent RCM imaging before conventional biopsy and histopathological assessment in order to identify features suggestive of tumoral changes. Sensitivity (SE), specificity (SP), positive and negative predictive values (PPV and NPV) of RCM compared to histopathology were calculated. Results: Totally, 30 sites in 20 patients were considered and clinically classified into 16 “leukoplakia”/“ traumatism”, nine erosive-ulcerative lesions, three verrucous lesions, and two healthy mucosae, as control. The histopathological “positivity,” due to the presence of various degrees of dysplasia and/or neoplasia, was found in 11 lesions; the RCM “positivity” was referred to nine lesions reporting the RCM detection of polymorphism, multinucleated cells, irregular cellular maturation, altered nuclear/cytoplasm ratio, and abnormal blood vessels. After excluding three verrucous lesions from the RCM analysis, due to the low laser penetration through the hyperkeratotic layers, the results well correlated with histopathology, reporting 1.000 (SE), 0.933 (SP), 0.909 (PPV), and 1.000 (NPV). Conclusion: RCM can reveal dysplastic/neoplastic signs occurring in oral lesions, thus supporting their diagnostic pathway.

Pseudolesions are defined as physiological or paraphysiological changes of the oral normal anatomy that can easily be misdiagnosed for pathological conditions such as potentially malignant lesions, infective and immune diseases, or neoplasms. Pseudolesions do not require treatment and a surgical or pharmacological approach can constitute an overtreatment indeed. This review aims to describe the most common pseudolesions of oral soft tissues, their possible differential diagnosis and eventual related systemic diseases or syndromes. The pseudolesions frequently observed in clinical practice and reported in literature include Fordyce granules, leukoedema, geographic tongue, fissured tongue, sublingual varices, lingual fimbriae, vallate papillae, white and black hairy tongue, Steno's duct hypertrophy, lingual tonsil, white sponge nevus, racial gingival pigmentation, lingual thyroid, and eruptive cyst. They could be misdiagnosed as oral potential malignant disorders, candidiasis, Human Papilloma Virus (HPV)-related affections, oral autoimmune diseases, or benign and malignant tumors. In some cases, pseudolesions feature in a syndromic panel, for example, fissured tongue in Melkersson-Rosenthal syndrome. It is strictly fundamental for dentists to know and to distinguish oral pseudolesions from pathological conditions, in order to avoid overtreatment. Pseudolesions are defined as physiological or paraphysiological changes of the oral normal anatomy that can easily be misdiagnosed for pathological conditions such as potentially malignant lesions, infective and immune diseases, or neoplasms. Pseudolesions do not require treatment and a surgical or pharmacological approach can constitute an overtreatment indeed. This review aims to describe the most common pseudolesions of oral soft tissues, their possible differential diagnosis and eventual related systemic diseases or syndromes. The pseudolesions frequently observed in clinical practice and reported in literature include Fordyce granules, leukoedema, geographic tongue, fissured tongue, sublingual varices, lingual fimbriae, vallate papillae, white and black hairy tongue, Steno's duct hypertrophy, lingual tonsil, white sponge nevus, racial gingival pigmentation, lingual thyroid, and eruptive cyst. They could be misdiagnosed as oral potential malignant disorders, candidiasis, Human Papilloma Virus (HPV)-related affections, oral autoimmune diseases, or benign and malignant tumors. In some cases, pseudolesions feature in a syndromic panel, for example, fissured tongue in Melkersson-Rosenthal syndrome. It is strictly fundamental for dentists to know and to distinguish oral pseudolesions from pathological conditions, in order to avoid overtreatment.

Technological development has interested most of the dentistry's branches leading to the use of other medical technologies non previously involved in dental practice. This study aims to evaluate the potential role of non-invasive imaging techniques in oral pathology workflow. Optical coherence tomography has been described by several authors as a promising aid for differential diagnosis of autoimmune diseases and to detect epithelial subversion of the oral mucosa before the clinical manifestation of oral mucositis. High-frequency ultrasound offers the chance to assess lesional dimensions both in benign and malignant lesions with a high dimensional reliability compared with histopathology. Reflectance confocal microscopy seems to be helpful in the early detection of cytological changes due to its high resolution, suggesting a more interesting role in the analysis of malignant lesions. The study presented highlighted the potential role of noninvasive in vivo imaging although further studies are needed for the further validation of these techniques.

Objective: The aim of this study was to test the efficacy of autoantibodies to desmoglein 1 and desmoglein 3 detected by ELISA and indirect immunofluorescence in the diagnosis of oral pemphigus and to correlate the antibody titres with the severity of the disease. Materials and Methods: We report a retrospective cohort study of 22 patients with oral pemphigus and 64 controls from a single tertiary centre. Data about histopathological examination, direct immunofluorescence, indirect immunofluorescence and ELISA were analysed. Global validation of ELISA and IIF both alone and combined was established by calculating sensitivity, specificity, accuracy and both positive predictive value and negative predictive value. The relationship between Oral Disease Severity Score values and ELISA titres was analysed using Pearson's coefficient. Results: The best diagnostic performance was observed for anti-desmoglein 3 ELISA. The sensitivity was 75% and specificity 100% and positive predictive value and negative predictive value were 92.5% and accuracy 93.9%. The level of agreement with histopathology+direct immunofluorescence was substantial (k=.758). Anti-desmoglein 3 titres showed a significant correlation with Oral Disease Severity Score (p&nbsp

Objective The purpose of this study was to describe an unusual case of intraoral juvenile xanthogranuloma (JXG) and to perform a systematic review to investigate the available literature regarding oral JXGs. Study design We present a new case of oral JXG arising in a 36-year-old Italian woman and conducted a systematic literature review in PubMed, Web of Science and Scopus, according to the PRISMA guidelines. Results Our review of the English-language literature yielded 34 cases of oral JXG, which are included in our case report. Conclusions JXG is a non-Langerhans cell histiocytosis. Oral JXG has been reported, but it is a rare manifestation. Because of the rarity of oral lesions and possible variations in the clinical and histological presentation, the correct diagnosis can be challenging, requiring a careful clinical and histopathological evaluation with adjuvant immunohistochemical studies.

Down syndrome (DS) is a genetic disorder associated with early-onset periodontitis and other periodontal diseases (PDs). The present work aimed to systematically review the scientific literature reporting studies in vivo on oral microbiota features in subjects with DS and related periodontal health and to highlight any correlation and difference with subjects not affected by DS, with and without PDs. PubMed, Web of Science, Scopus and Cochrane were searched for relevant studies in May 2021. The participants were subjects affected by Down syndrome (DS) with and without periodontal diseases; the study compared subjects with periodontal diseases but not affected by DS, and DS without periodontal diseases; the outcomes were the differences in oral microbiota/periodontopathogen bacterial composition among subjects considered; the study design was a systematic review. Study quality was assessed with risk of bias in non-randomized studies of interventions (ROBINS-I). Of the 954 references retrieved, 26 studies were considered. The conclusions from the qualitative assessment of the papers revealed an increasing knowledge over the last years of the microbiota associated with DS and their periodontal diseases, in comparison with healthy subjects and subjects with other kinds of mental disabilities. Few data have emerged on the mycobiome and virobiome of DS, hence, further investigations are still necessary.

Aim: Aim of this case report is to describe oro-facial abnormalities in a patient affected by Helsmoortel-Van der Aa syndrome, a rare autism syndrome, with not well described dental and cranial malformations. Case Report: Helsmoortel-Van der Aa Syndrome is a rare autosomal genetic syndrome causing mental impairment and autism, craniofacial dysmorphism, chest deformity and multiple organs dysfunction. Oro-facial involvement in Helsmoortel-Van der Aa syndrome has not been thoroughly described yet. The present article reports a case of a 9 years old male patient affected by Helsmoortel-Van der Aa Syndrome, presenting with oral breathing typical facies, high arched palate, II class and dental crowding. The patient teething was adequate to his age. The enamel of incisors and molars showed demineralization areas and dark spots, a clinical picture consistent with molar incisor hypomineralization syndrome. These hypo-mineralized areas are more susceptible to cavities, in fact the patient’s 4.6 tooth was decayed. The child was brought to our attention due to a mucocele on the lower lip, confirmed by histopathologic examination. Available data on oro-dental manifestation of this syndrome are rather poor and inconsistent, also due to the rarity of the disease. The finding of enamel abnormalities in the presented case could suggest a potential genetic etiopathogenesis linked to the same genes causing Helsmoortel-Van der Aa syndrome.

Background: Reactive oxygen species (ROS) and free radicals are physiologically produced during cellular metabolism. When their balance is disrupted in favor of ROS, a condition called oxidative stress occurs. Oxidative stress represents a widespread phenomenon involved in several pathological conditions. The aim of the present review was to report current knowledge on oxidative stress related to oral mucosal diseases. Materials and Methods: Articles from 2000 to 2018 were selected for relevance, validity and quality, from results obtained in PubMed, MEDLINE and Google Scholar using the following search terms: oxidative stress and oral lichen, oral pemphigus, aphthous stomatitis, oral leukoplakia, oral cancer, oral squamous cell carcinoma and oral carcinoma. All articles were independently screened for eligibility by the authors. Results: This narrative review integrates extensive information from all relevant published studies focusing on oxidative stress in oral mucosal diseases. We outline the pathogenetic function of oxidative stress in the most frequent inflammatory, potentially malignant and malignant diseases of the oral mucosa and provide detailed findings from human research. Conclusion: Although variability in findings between individual studies exists, it justifies the conclusion that oxidative stress is a significant process in the oral mucosal diseases pathogenesis. Background: Reactive oxygen species (ROS) and free radicals are physiologically produced during cellular metabolism. When their balance is disrupted in favor of ROS, a condition called oxidative stress occurs. Oxidative stress represents a widespread phenomenon involved in several pathological conditions. The aim of the present review was to report current knowledge on oxidative stress related to oral mucosal diseases. Materials and Methods: Articles from 2000 to 2018 were selected for relevance, validity and quality, from results obtained in PubMed, MEDLINE and Google Scholar using the following search terms: oxidative stress and oral lichen, oral pemphigus, aphthous stomatitis, oral leukoplakia, oral cancer, oral squamous cell carcinoma and oral carcinoma. All articles were independently screened for eligibility by the authors. Results: This narrative review integrates extensive information from all relevant published studies focusing on oxidative stress in oral mucosal diseases. We outline the pathogenetic function of oxidative stress in the most frequent inflammatory, potentially malignant and malignant diseases of the oral mucosa and provide detailed findings from human research. Conclusion: Although variability in findings between individual studies exists, it justifies the conclusion that oxidative stress is a significant process in the oral mucosal diseases pathogenesis.

Down syndrome (DS) is an autosomal disorder associated with mental and physical involvement. The typical craniofacial phenotype and the dental anomalies in DS subjects have been widely described, but a systematic report on the manifestations affecting the oral mucosae in children with DS is still lacking. This systematic review aimed to establish the prevalence of oral mucosal manifestations in children/young adults with DS. Pubmed, Web of Science, and Scopus were investigated in September 2020. Documents in English on DS children/young adults (up to 25 years) reporting oral mucosal findings were considered. Study quality was assessed with ROBIN-I. Of the 150 references retrieved, 14 studies were considered eligible. The risk of bias ranged from low to unclear. Fissured tongue appeared to increase with age and was more prevalent in DS children than in the general population. Lip fissures and cheilitis were heterogeneously reported. Candida spp. carriage with and without active candidiasis was more frequent in DS children/young adults than in controls. C. albicans was the most prevalent species. Few other oral mucosal conditions have been reported sporadically. The heterogeneity of the works revealed the need for more appropriate oral examination to intercept the oral manifestations of oral mucosa and prevent recurrent candidiasis.

Simple Summary Oral squamous cell carcinoma (OSCC) accounts for 90–95% of malignant tumors of the lip and oral cavity and is associated with high mortality in the advanced stages. Early diagnosis is a challenge for oral pathologists and dentists, due to the ambiguous appearance of early OSCC, which is often misdiagnosed, mistreated, and associated with diagnostic delay. The gold standards for OSCC diagnosis are biopsy and histopathological assessment, but these procedures are invasive and time-consuming. Adjunctive noninvasive techniques allow the definition of the malignant features of a suspicious lesion in real time and noninvasively, thus improving the diagnostic procedure. The present review aimed to focus on some of the main promising noninvasive imaging techniques, to highlight their perspective adoption in a three-step diagnosis, which is idealistically faster and better, as well as enables the patient’s compliance. Abstract Oral squamous cell carcinoma (OSCC) is the most prevalent form of cancer of lips and oral cavity, and its diagnostic delay, caused by misdiagnosis at the early stages, is responsible for high mortality ratios. Biopsy and histopathological assessment are the gold standards for OSCC diagnosis, but they are time-consuming, invasive, and do not always enable the patient’s compliance, mainly in cases of follow-up with the need for more biopsies. The use of adjunctive noninvasive imaging techniques improves the diagnostic approach, making it faster and better accepted by patients. The present review aims to focus on the most consolidated diagnostic techniques, such as vital staining and tissue autofluorescence, and to report the potential role of some of the most promising innovative techniques, such as narrow-band imaging, high-frequency ultrasounds, optical coherence tomography, and in vivo confocal microscopy. According to their contribution to OSCC diagnosis, an ideal three-step diagnostic procedure is proposed, to make the diagnostic path faster, better, and more accurate.

The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a high-risk viral agent involved in the recent pandemic stated worldwide by the World Health Organization. The infection is correlated to a severe systemic and respiratory disease in many cases, which is clinically treated with a multi-drug pharmacological approach. The purpose of this investigation was to evaluate through a literature overview the effect of adjuvant therapies and supplements for the SARS-CoV-2 infection. The research has analyzed the advantage of the EK1C4, by also assessing the studies on the resveratrol, vitamin D, and melatonin as adjuvant supplements for long hauler patients’ prognosis. The evaluated substances reported important benefits for the improvement of the immune system and as a potential inhibitor molecules against SARS-CoV-2, highlighting the use of sartans as therapy. The adjuvant supplements seem to create an advantage for the healing of the long hauler patients affected by chronic symptoms of constant chest and heart pain, intestinal disorders, headache, difficulty concentrating, memory loss, and tachycardia.

Potential topics included, but were not limited to, translational research, bioengineering types, clinical engineering, system modeling, biosignal processing, stem cells, bioscaffolds, biomedical devices, health informatics, bioinformatics, biotechnology, biomechanics, computational mechanobiology, microbiota, and the role of oral health and disease in contributing to general health and systemic conditions. Because glycogen storage disease (GSD) represents a group of twenty-three types of metabolic disorders which damage the capacity of the body to store glucose classified based on the enzyme deficiency involved and affected patients could present some oro-facial alterations, Romano et al. conducted a systematic review of the literature among different search engines using PICOS criteria, to catalog and characterize oral manifestations in these patients [18]. [...]the steroid-refractory relapsed MS on FTY, however serious, can be treated with DFPP;second, given the good clinical improvement due to the DFPP-induced neuroinflammatory components removal, this clinical condition can be associated with a Lucchinetti pattern II of demyelination [20]. Since early 2020, COVID-19, a consequence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly affected millions of people worldwide. Currently, little published research exists evaluating the stability of commercial vitamin A products during storage. [...]in a further study, Yang et al. aimed to determine the storage stability of five commercial sources of vitamin A in premix, and provide a guideline for product formulation and application [23].

Various bi-directional associations exist between oral health and gastro-intestinal diseases. The oral microbiome plays a role in the gastro-intestinal carcinogenesis and fusobacteria are the most investigated bacteria involved. This paper aims to review the current knowledge and report the preliminary data on salivary levels of Fusobacterium nucleatum, Porphyromonas gingivalis and Candida albicans in subjects with different gastro-intestinal conditions or pathologies, in order to determine any differences. The null hypothesis was “subjects with different gastro-intestinal diseases do not show significant differences in the composition of the oral microbiota”. Twenty-one subjects undergoing esophagastroduodenoscopy or colonscopy were recruited. For each subject, a salivary sample was collected before the endoscopy procedure, immediately stored at −20 °C and subsequently used for genomic bacterial DNA extraction by real-time PCR. Low levels of F. nucleatum and P. gingivalis were peculiar in the oral microbiota in subjects affected by Helicobater pylori-negative chronic gastritis without cancerization and future studies will elucidate this association. The level of C. albicans did not statistically differ among groups. This preliminary study could be used in the future, following further investigation, as a non-invasive method for the search of gastrointestinal diseases and associated markers.

Background: Based on recent findings, we speculated the existence of the lung, heart, and kidney axis as the main pathway for the COVID-19 disease progression. Methods: This paper reports on an observational study conducted by a team of researchers and doctors of the 118-Pre-Hospital and Emergency Department of SG Moscati of Taranto City in Italy. The study was conducted on a totality of 185 participants that were divided into three groups. The study group included COVID-19 affected patients (PP n = 80), the first control group included patients with different pathologies (non-COVID-19 NNp n = 62) of the SG Moscati Hospital, and the second control group included healthy individuals (NNh n = 43). The core of the current trial was focused on assessing the level of the vitamin D (serum 25(OH) D concentration), IL-6, and the renal glomerular filtrate (eGFR) in COVID-19 disease and non-COVID-19 patients in both groups. Results: It was observed that the majority of COVID-19-infected patients showed a progressive multi-organ involvement, especially in regard to the lung, kidney, and heart. The majority of the COVID-19 patients exhibited preexisting comorbidities which include cardiovascular, respiratory, and renal disorders accompanied by a severely low level of vitamin D, extremely high level of IL-6, and low glomerular filtration rate (eGFR). The significant overall damages exerted by the immune-mediated responses under the hyper-expression of proinflammatory cytokines and interleukins, such as IL-6, may be facilitated by either a decreased level of vitamin D or the ageing process. The reduced presence of vitamin D was often found together with a reduced functionality of renal activity, as revealed by the low eGFR, and both were seen to be concomitant with an increased mortality risk in patients with lung disorders and heart failure (HF), whether it is showed at baseline or it develops during manifestation of COVID-19. Therefore, the documentation of the modifiable risk factors related to SARS-CoV-2 and lung impairment in older patients with kidney and heart disease may help the clinician to better manage the situation. Conclusions: This paper addresses how a low level of vitamin D and older age may be indicative of systemic worsening in patients with COVID-19, with a goal of providing a broader context in which to view a better therapeutic approach.

Nowadays, there is a considerable interest to study the biological and microbiological changes that accompany orthodontic treatment. Growing knowledge on oral microbiota allows, day after day, to identify and characterize the microbial arrangements specifically associated with oral and extra-oral conditions. The aim of the present work is to highlight any further correlations between orthodontic appliances and the qualitative and quantitative modifications of the oral microbiota, such as predisposing factors for the onset of caries, periodontal diseases, and other infections, which can impact the oral and systemic health of the orthodontic patients. When compared with subjects without orthodontic appliances, orthodontic patients reported significant qualitative and quantitative differences in supra- and subgingival plaque during the entire treatment period. Certain components of fixed appliances (mainly bonded molar brackets, ceramic brackets, and elastomeric ligatures) showed high risks of periodontal disease and tooth decay for patients. An unclear prevalence of Candida spp. and the paucity of studies on viruses and protozoas in the oral microbiota of orthodontic patients need to be further investigated. The evidence emerging from this study could guide clinicians in modulating the timing of controls and enhance patient motivation to prevent the formation of mature plaque, thus reducing the risks of oral-plaque-related diseases.

Oral cancer is the most common malignancy of the head and neck region, characterized by a poor prognosis. Novel prognostic markers are needed to better stratify these patients. Lymphovascular invasion (LVI) has been included in the eighth edition of the AJCC Cancer Staging Manual as an additional prognostic factor, but its influence on the recurrence risk and lymph node metastasis is relatively understudied. This is a comprehensive review of the literature on the clinical and prognostic role of LVI in oral cancer. A relevant search of the PubMed, Scopus, and Web of Science databases yielded 29 articles that satisfied the inclusion criteria. Findings indicated that LVI is an independent negative prognostic factor in oral cancer patients and appears to be associated with cervical lymph node metastasis and loco-regional recurrence. Notably, in oral tongue cancer, survival outcomes progressively worsen when LVI is associated with other adverse pathological features, especially in the early stages. Therefore, these patients could benefit from elective neck dissection and/or adjuvant therapy. The high variability of LVI prevalence hinders the comparison of literature results. Several methodological limitations were found to be present in the collected articles, including the lack of a rigorous definition for LVI, the difficult detection in routine histological section, the presence of potential confounders, the retrospective nature, and an inadequate sample size in most studies. Therefore, it is necessary to conduct prognostic studies using standardized methods to define and quantify LVI.

Objective. The aim of this study was to obtain data from a review of cases of brown tumors (BT), which are benign lesions of bone characterized by giant cells that arise during hyperparathyroidism (HPTH). BTs may affect the maxillofacial area and manifest as a brownish, slow-growing swelling causing difficulty in the differential diagnosis. Study Design. We present data from 4 new cases of oral BTs based on a systematic literature review conducted by searching EMBASE, Medline, and CENTRAL databases, according to the PRISMA guidelines. Only articles in English were considered. Individual patient data were analyzed to identify risk factors for multiple or extraoral maxillofacial BTs. Results. In total, 167 cases (163 from 136 articles and 4 new cases; mean age 36.6 years; male-to-female ratio 1:2) were retrieved. The onset of extraoral maxillofacial BTs (odds ratio [OR] 176.3; 95% confidence interval [CI] 18.7

Background Bisphosphonates (BPs) contrast the bone fragility and improve bone density in some metastatic cancers and bone diseases, such as Osteogenesis Imperfecta (OI). BPs use has been associated with osteonecrosis of the jaws (BRONJs) in adults needing for invasive dental procedures. Aim To conduct a systematic review on BRONJ occurrence after dental surgery in paediatric population under BPs therapy for OI, so as to identify the pre-surgical protocols adopted. Design According to PRISMA guidelines, Pubmed, Web of Science (WoS) and Cochrane were investigated on September 2018, and re-checked on July 2019. Inclusion criteria were English-language papers on children/young adults (until 24 years old) reporting dental/oral surgery procedures. Results Totally, 60 articles were found. After title/abstract reviews and duplicates exclusion, 22 eligible titles underwent full-text evaluation. Finally, 10 studies were included. Conclusions The lack of BRONJ occurrence in paediatric population suffering OI and treated with BPs, was confirmed, but the reasons are still debated, being the BPs therapies and the surgical strategies various and not standardized. Longitudinal studies should evaluate what happens to those former children once adult, to evaluate the delayed BRONJs onset associated with the occurrence of comorbidities during the adulthood.

Osteoporosis (OP) is a bone disease consisting of a progressive loss of bone mineral density (BMD) and therefore resulting in greater susceptibility to fractures. OP shares a number of risk factors and demographic characteristics with periodontitis (PD), a bacteria-induced chronic inflammation of periodontal structures that leads to loss of alveolar bone and teeth. In the last decade, with the advent of gut and oral microbiome studies and profiling, a growing diagnostic and prognostic significance has been attributed to dysbiosis associated with various systemic and organ-specific pathologies. This evidence has inspired research on modulating the microbiota to restore health by the use of prebiotics and probiotics. The aim of this work is to overview the bidirectional interrelationships between OP and PD, reporting the most recent evidence on triggering factors and, mainly, the role of gut and oral dysbiosis in the onset and progression of both OP and PD, with the perspective in their therapy.

Osteoradionecrosis (ORN) of the jaw is considered the most severe long-term adverse effect that can occur in radiation therapy patients. Teeth extractions and dental diseases are the main risk factors for ORN in irradiated patients. The aim of this case series was to evaluate the outcome of primary root canal treatments performed on patients who underwent head and neck radiotherapy and to evaluate any ORN related to the endodontic treatment. In this case series, primary root canal therapies (absence of radiolucency) were performed on 10 teeth of 8 patients who underwent radiotherapy for head and neck cancers. Radiation doses to the periapical area were calculated using the radiotherapy planning computed tomographic scan. After a 277-day mean follow-up, all patients were asymptomatic, no teeth showed periapical radiolucency, and no ORN was observed. Even if a limitation of buccal opening occurred after radiotherapy and complicated the endodontic procedures, root canal therapy seemed to be safe and a valid alternative to tooth extraction.

Oral cancers have been proven to arise from precursors lesions and to be related to risk behaviour such as alcohol consumption and smoke. However, the present paper focuses on the role of chronic inflammation, related to chronical oral infections and/or altered immune responses occurring during dysimmune and autoimmune diseases, in the oral cancerogenesis. Particularly, oral candidiasis and periodontal diseases introduce a vicious circle of nonhealing and perpetuation of the inflammatory processes, thus leading toward cancer occurrence via local and systemic inflammatory modulators and via genetic and epigenetic factors.

The accumulation of adipose tissue in the body occurs because the energy introduced with food and drink exceeds that expense, but to understand why this imbalance is established and why it is maintained over time, it is important to consider the main causes and risk factors of excess weight. In this review, we will refer to the main factors linked to obesity, starting from oxidative stress to hormonal factors including the role of obesity in breast cancer. Among the many hypotheses formulated on the etiopathology of obesity, a key role can be attributed to the relationship between stress oxidative and intestinal microbiota. Multiple evidences tend to show that genetic, epigenetic, and lifestyle factors contribute to determine in the obese an imbalance of the redox balance correlated with the alteration of the intestinal microbial flora. Obesity acts negatively on the wound healing, in fact several studies indicate morbid obesity significantly increased the risk of a post-operative wound complication and infection. Currently, in the treatment of obesity, medical interventions are aimed not only at modifying caloric intake, but also to modulate and improve the composition of diet with the aim of rebalancing the microbiota-redox state axis. The accumulation of adipose tissue in the body occurs because the energy introduced with food and drink exceeds that expense, but to understand why this imbalance is established and why it is maintained over time, it is important to consider the main causes and risk factors of excess weight. In this review, we will refer to the main factors linked to obesity, starting from oxidative stress to hormonal factors including the role of obesity in breast cancer. Among the many hypotheses formulated on the etiopathology of obesity, a key role can be attributed to the relationship between stress oxidative and intestinal microbiota. Multiple evidences tend to show that genetic, epigenetic, and lifestyle factors contribute to determine in the obese an imbalance of the redox balance correlated with the alteration of the intestinal microbial flora. Obesity acts negatively on the wound healing, in fact several studies indicate morbid obesity significantly increased the risk of a post-operative wound complication and infection. Currently, in the treatment of obesity, medical interventions are aimed not only at modifying caloric intake, but also to modulate and improve the composition of diet with the aim of rebalancing the microbiota-redox state axis.

Background: West Syndrome is a rare epileptic encephalopathy involving infantile spasms, altered electroencephalographic pattern with hypsarrhythmia, and psychomotor development delay. It arises in paediatric patients, generally within the first year of life, in symptomatic or idiopathic form depending on the presence of hereditary features or not. Case report: In this report it is described the case of a West syndrome patient affected by multiple caries, gingival enlargement, dental eruption abnormalities, high-arched palate and MIH, treated at the dental clinic of University of Bari “Aldo Moro”. Discussion: West patients present with multiple oral abnormalities, including altered eruption timing, teeth agenesis, teeth shape and position abnormalities, plaque and calculus accumulation, malocclusions and bad oral habits (mouth breathing, nails biting). Conclusion:: West Syndrome patients’ oral hygiene is generally bad due to their motor difficulty and to their low compliance towards dentists, which entails general anaesthesia to perform dental treatment. West Syndrome pharmacological treatment is usually based on antiepileptic drugs and/or ACTH. These medications are well known for their ability to induce gingival enlargement, increasing the possibility of plaque accumulation and gingivitis development.

Salivary glands (SG) arise from ectodermal tissue between 6 and 12th weeks of intrauterine life through finely regulated epithelial-mesenchymal interactions. For this reason, different types of structural congenital anomalies, ranging from asymptomatic anatomical variants to alterations associated with syndromic conditions, have been described. Notable glandular parenchyma anomalies are the SG aplasia and the ectopic SG tissue. Major SG aplasia is a developmental anomaly, leading to variable degrees of xerostomia, and oral dryness. Ectopic SG tissue can occur as accessory gland tissue, salivary tissue associated with branchial cleft anomalies, or true heterotopic SG tissue. Among salivary ducts anomalies, congenital atresia is a rare developmental anomaly due to duct canalization failure in oral cavity, lead to salivary retention posterior to the imperforate orifice. Accessory ducts originate from the invagination of the developing duct in two places or from the premature ventral branching of the main duct. Heterotopic ducts may arise from glandular bud positioned in an anomalous site lateral to the stomodeum or from the failure of the intraoral groove development, hindering their proximal canalization. These anomalies require multidisciplinary approach to diagnosis and treatment. While ectopic or accessory SG tissue/ducts often do not require any treatment, patients with SG aplasia could benefit from strategies for restoring SG function. This article attempts to review the literature on SG parenchyma and ducts anomalies in head and neck region providing clinicians with a comprehensive range of clinical phenotypes and possible future applications of bioengineered therapies for next-generation of regenerative medicine.

Background: In vivo reflectance confocal microscopy (RCM) is an imaging technique that can virtually biopsy vital tissues, noninvasively and in real time. It results in horizontal virtual slices at a microscopic resolution that correlates well with conventional histopathology. Despite the widespread use of RCM in dermatology, it is still rarely applied to the study of oral pathologies. The aim of the present work is to describe RCM cellular and architectural findings in oral mucosae affected by oral lichen planus (OLP). Materials and Methods: A series of conventionally diagnosed OLP lesions underwent RCM imaging with a portable reflectance confocal microscope that could scan from the surface to the submucosa. The confocal findings were collected, described, and compared with the literature. Results: A total of 31 oral sites affected by OLP in 12 patients were considered. According to their clinical appearance, 22 lesions showed a reticular-plaque pattern, six lesions were mainly atrophic-erosive, and the remaining three presented a mixed pattern. RCM examination showed hypergranulosis, epithelial disarray, spongiosis, necrotic keratinocytes, epithelial and subepithelial inflammatory cell infiltration, and dilated vessels; all findings were in lichen planus, with differences noted between the “white” and “red” manifestations of this pathology. Conclusions: The use of RCM in routine clinical oral pathology tests is recommended to avoid recurrence of OLP and changes in its responsiveness to therapy, thus limiting the need for biopsy of lesions suspected of tumoral changes. Background: In vivo reflectance confocal microscopy (RCM) is an imaging technique that can virtually biopsy vital tissues, noninvasively and in real time. It results in horizontal virtual slices at a microscopic resolution that correlates well with conventional histopathology. Despite the widespread use of RCM in dermatology, it is still rarely applied to the study of oral pathologies. The aim of the present work is to describe RCM cellular and architectural findings in oral mucosae affected by oral lichen planus (OLP). Materials and Methods: A series of conventionally diagnosed OLP lesions underwent RCM imaging with a portable reflectance confocal microscope that could scan from the surface to the submucosa. The confocal findings were collected, described, and compared with the literature. Results: A total of 31 oral sites affected by OLP in 12 patients were considered. According to their clinical appearance, 22 lesions showed a reticular-plaque pattern, six lesions were mainly atrophic-erosive, and the remaining three presented a mixed pattern. RCM examination showed hypergranulosis, epithelial disarray, spongiosis, necrotic keratinocytes, epithelial and subepithelial inflammatory cell infiltration, and dilated vessels; all findings were in lichen planus, with differences noted between the “white” and “red” manifestations of this pathology. Conclusions: The use of RCM in routine clinical oral pathology tests is recommended to avoid recurrence of OLP and changes in its responsiveness to therapy, thus limiting the need for biopsy of lesions suspected of tumoral changes.

Candida albicans is a dimorphic yeast strongly gram positive able to live as normal commensal organism in the oral cavity of healthy people. It is the yeast more frequently isolated in the oral cavity. Under local and systemic factors related to the host conditions, it becomes virulent and responsible of oral diseases known as oral candidiasis. It has been shown that the presence of denture is a predisposing factor to the onset of pathologies related to C. albicans. Clinical studies have shown that C. albicans is not only able to adhere to the mucous surfaces, but also to stick to the acrylic resins of the dental prostheses. Both the plaque accumulated on the denture and the poor oral hygiene contribute to the virulence of Candida, offering the clinical picture of Candida-associated denture stomatitis. The therapeutic strategies currently adopted in the clinical practice to overcome these fungal infections provide for the use of topical and/or systemic antifungal and topical antiseptics and disinfectants, the irradiation with microwaves and the accurate mechanical removal of the bacterial plaque from the denture surfaces and from the underlying mucosa. A correct oral hygiene is important for the control of the bacterial biofilm present on the denture and on the oral mucosa and it is the fundamental base for the prophylaxis and the therapy of the Candidaassociated denture stomatitis.

Oral Lichen Planus (OLP) is a common disease of unknown aetiology affecting oral mucosae by T-cell mediated chronic inflammation. OLP diagnosis is made by evaluating both clinical and histological criteria. Pharmacological treatment is useful in symptomatic cases. Life-long clinical follow-up is essential, due to low-risk of malignant transformation. In vivo Reflectance Confocal Microscopy (RCM) offers a real-time virtual biopsy of the being tissues and does not require surgical excision nor histopathological processing. RCM was used to capture OLP lesions in order to clinically differentiate them from other clinical entities.

Lymph node metastases are responsible for shorter survival in oral squamous cell carcinoma (OSCC). The aim of the present study was to assess the node metastasis frequency and survival according to the node metastasis features in 121 neck dissections (NDs) performed for OSCC, identifying evidence-based correlations and contrasts with previous literature. The retrospective study involved 121 patients affected by OSCC who had undergone modified radical ND (MRND) for therapeutic, elective reasons or after intraoperative positivity to metastasis of sentinel lymph nodes (SLN+). Node metastasis frequency and behaviour (typical vs. atypical) and their number and distribution according to pre-surgical cTNM cancer staging were considered and overall survival Kaplan-Meier curves were calculated for each group in order to compare mortality according to ND type (elective, therapeutic, after SLN+), lymph node metastatic pattern (typical or atypical), size (micrometastasis vs. macrometastasis) and number. Results showed statistically significant different overall survival according to pre-surgical staging, number of lymph nodes harvested and intent to surgery. Sentinel lymph node resulted in the sole positive node affected by metastasis in small cT1- cT2/cN0 OSCC and an ND subsequent to its positivity during intraoperative assessment may be considered an overtreatment.

Malignant tumours of the nasal cavities and paranasal sinuses are uncommon. They constitute less than one per cent of all tumours and less than three per cent of head and neck tumours. Carcinoma of the maxillary sinus is the most common of the sinonasal malignancies. In this anatomical site a case of adenocarcinoma, not otherwise specified, was documented, mainly from a histological perspective and discussed considering all types of differential diagnoses.

Oncogenic HPVs are necessarily involved in cervical cancer but their role in oral carcinogenesis is debated. To detect HPV in oral cancer, 38 cases of formalin fixed-paraffin embedded OSCC were studied by both DNA genotyping (MY09/11 L1 consensus primers in combination with GP5-GP6 primer pair followed by sequencing) and immunohistochemistry (monoclonal Abs against capsid protein and HPV-E7 protein, K1H8 DAKO and clone 8C9 INVITROGEN, respectively). HPV-16 tonsil cancer was used as positive control. The overall prevalence of HPV infection in OSCCs was 10.5%. Amplification of DNA samples showed single HPV DNA infection in 3 cases (HPV16; HPV53; HPV70) and double infection in one case of cheek cancer (HPV31/HPV44). The overall HR-HPV prevalence was 7.5%. E-7 antigen was immunohistochemically detected in all HPV-positive cases. HPV+ OSCC cases showed an overall better outcome than HPV negative oral cancers, as evaluated by Kaplan-Meier curves. HPVs exert their oncogenic role after DNA integration, gene expression of E5, E6 and E7 loci and p53/pRb host proteins suppression. This study showed that HPV-E7 protein inactivating pRb is expressed in oral cancer cells infected by oncogenic HPV other than classical HR-HPV-16/18. Interestingly HPV-70, considered a low risk virus with no definite collocation in oncogenic type category, gives rise to the expression of HPV-E7 protein and inactivate pRb in oral cancer. HPV-70, as proved in current literature, is able to inactivates also p53 protein, promoting cell immortalization. HPV-53, classified as a possible high risk virus, expresses E7 protein in OSCC, contributing to oral carcinogenesis. We have identified among OSCCs, a subgroup characterized by HPV infection (10.5%). Finally, we have proved the oncogenic potential of some HPV virus types, not well known in literature.

Verrucous carcinoma (also known as Ackerman tumor) is an uncommon exophytic low-grade well-differentiated variant of squamous cell carcinoma. This neoplasm typically involves the oral cavity, larynx, genitalia, skin, and esophagus. It is well known for its locally aggressiveness and for its clinically slow-growing behaviour with minimal metastatic potential. Verrucous carcinoma of oral cavity is so closely aligned with the use of snuff and chewing tobacco that it has been called the “snuff dipper's cancer”. Recent studies have proved the role of HPV. The typical clinical presentation of oral verrucous carcinoma has long been known, as its remarkably innocuous appearance and biological behaviour. In this work, we report a review of the scientific literature and describe a troublesome case of oral verrucous cancer.