Surgical treatment compared with "wait and see" in patients affected by oral leukoplakia to prevent oral cancer: Preliminary data from a multicenter randomized controlled trial.

OBJECTIVE: Oral leukoplakia (OL) is one of the most common and investigated oral potentially malignant disorders (OPMD). Preventing OSCC occurrence should be the primary outcome in the clinical management of OL. Surgical removal of OL is performed by most clinicians, although its effectiveness in reducing OSCC onset has still not been established by randomized controlled trials (RCT). Wait and see approach is characterized by frequent clinical examinations and periodical biopsies of OL, avoiding unnecessary surgical procedures. This is the first multicenter RCT in literature aiming at comparing the effectiveness of surgical removal and the "wait and see" approach in preventing OSCC onset in patients affected by dysplastic and non-dysplastic OL. METHODS: Two Italian referral care centres for oral diseases were involved in this multicenter two-arm RCT comparing the surgical removal of OL (group A) and the "wait and see" approach (group B), with the aim of reducing oral cancer onset. RESULTS: This report shows preliminary data on the first 161 patients, with a mean follow-up of 19.14 ± 11.25 months. Eight cases of OSCC occurred (6 out 8 involving the tongue): one case in group A and seven cases in group B. Moreover, OL recurred in 13 (20%) cases after surgical excision. CONCLUSIONS: Within the limitations of this preliminary report, these initial data underline the increased risk of OSCC onset in the case of OL of the tongue in the presence of epithelial dysplasia in group B ("wait and see") compared to group A (surgery). This RCT is currently ongoing at the same clinical departments, with the aim of enrolling 310 patients and collecting data at 5-year follow-up, in order to achieve conclusive results, in an evidence-based medicine approach.

Assessment of the current knowledge about infective endocarditis prevention among dental hygienists in Italy: A national survey.

OBJECTIVES: To date, there is a lack of data regarding the acceptance of the guidelines for infective endocarditis (IE) prevention among dentists in Italy, and similarly, there are no data on the understanding and compliance of those among dental hygienists (DH). Thus, we tried to assess the ability of DH to recognize and manage categories of patients at high risk of EI, to identify which dental procedures are at increased risk and to assess the level of knowledge of doses and how antibiotic prophylaxis should be administered in specific cases. METHODS: An anonymous questionnaire was prepared and made accessible online by sharing a Google Forms® link; general personal data and educational background information were collected to obtain a profile of the participants. RESULTS: A total of 362 DH answered to our web-based survey, showing a prevalent female percentage (86.7%) and the most represented age group of 30-39 years old (43.1%). Regarding the gender differences, there were not overall statistically significant differences; similarly, we did not find any differences regarding the overall number of wrong questions if considering the different ages of the participant and the year of graduation. Graduates in Northern Italy have mistaken fewer questions than graduates in other geographical areas. CONCLUSION: To the best of our knowledge, this is the largest survey about the knowledge of IE for DH ever performed. Because the overprescription of antibiotics contributes to the development of drug resistance, antibiotic stewardship should be at the forefront of patient care. Our data reflect the need for placing a greater emphasis on IE prophylaxis education in training and during continuing professional development events for DH.

Herpes simplex virus type 1 in periapical pathoses: Systematic review and meta-analysis.

OBJECTIVES: The objective of this systematic review and meta-analysis of observational studies was to assess whether herpes simplex virus type 1 (HSV-1) can infect endodontic periapical lesions. MATERIALS AND METHODS: Studies with cross-sectional design investigating HSV-1 in periapical tissues of patients with symptomatic and asymptomatic acute and chronic apical periodontitis were searched through MEDLINE, Scopus, Embase, Web of Science, and Google Scholar. Pooled HSV-1 prevalence proportion with 95% confidence interval (95CI) in periapical lesions was assessed with both fixed-effect and random-effects models, with/without adjustment for study quality and publication bias. Result robustness was investigated through sensitivity and subgroup analyses. RESULTS: Literature search, performed twice, provided 84 items, and eight remained for the meta-analysis; globally, there were 194 patients mostly adults. The pooled HSV-1 prevalence proportions, assessed with various methods, were 6.9% (95CI, 3.8-11.3%, fixed-effect); 6.8% (95CI, 3.6-11.0%, random-effects); 8.1% (95CI, 4.4-14.5%, quality-adjusted); and 4.8% (95CI, 2.0-11.4%; adjusted for small-study effect). CONCLUSIONS: The results indicated that HSV-1 can colonize the periapical tissues of 3%-11% patients with periapical diseases. Such data do not imply a causative role of HSV-1 in disease development and advancement. Well-designed and large-sized prospective cohort studies should be added in the literature panorama.

Population-based cohort study to assess the gingival lesions in 1319 patients with lichen planus.

AIMS: Oral lichen planus (OLP) is a chronic immune disease. In this paper, we evaluated the overall characters, clinical presentation, and outcome of gingival lesions in OLP Italian patients. METHODS AND RESULTS: A retrospective cohort study was accomplished: a total of 1319 charts were investigated, of whom 922 were female (69.9%): 617 patients (46.8%) manifested white lesions and 702 red ones (53.2%). While most patients had several oral sites of involvement, the gingiva was the unique location in 103 cases. Symptoms were reported in 480 patients (36.4%): 286 patients with erosive OLP, 103 with atrophic form, and 91 with a white form. Long-lasting surveillance showed that only 40 patients (3.03%) had a total clinical signs remission. Regarding OLP medical treatment provided, patients attending less frequently a dental office underwent more often a specific therapy. CONCLUSIONS: To the best of our knowledge, this is the biggest collections of patients with gingival OLP ever described; exclusive gingival lesions are, however, rare and unlikely to undergo a malignant transformation. Moreover, gum lesions seemed to anticipate the appearance of oral lesions and a higher rate of OLP therapy was observed in patients with less frequent dental check-ups and oral hygiene instructions.

Potential use of optical coherence tomography in oral potentially malignant disorders: in-vivo case series study.

BACKGROUND: Evidence confirms that the use of Optical Coherence Tomography (OCT) in oral medicine can be a reliable aid for the diagnosis and management of Oral Potentially Malignant Disorders (OPMDs). Several authors described the ability of this system to detect the structural changes of the epithelia involved by the OPMDs. The purpose of this case series is to provide a suggestion for interpretation of OCT images from different OPMDs, compared to OCT images of healthy tissues. METHODS: A sample of 11 OPMDs patients was recruited and analyzed with OCT. The images obtained were then compared with an OCT repertoire image. In this work the reflectance degree was considered, together with the analysis of the increased/decreased thicknesses of the various layers. Keratin Layer (KL), Epithelial Layer (EP), Lamina Propria (LP), Basal Membrane (BM) assessment, for each lesion, was performed. RESULTS: OCT measurements of KL, EP and LP layers, together with BM assessing, should aid the physicians to recognize and describe different oral lesions, relating them to the corresponding oral pathology. CONCLUSION: More studies like this, on larger samples, are needed to validate the results and provide, in the future, a kind of manual that could guide clinicians to correctly interpret the OCT images in relation to the causing pathologies. TRIAL REGISTRATION: The present trial has been registered with ISRCTN (#17,893,224).

Herpes simplex virus type 1 in subgingival plaque and periodontal diseases. Meta-analysis of observational studies.

BACKGROUND AND OBJECTIVES: This meta-analysis of observational studies (PROSPERO registration number CRD42021236054) sought to investigate strength and generalizability of the association of herpes simplex virus type 1 (HSV-1) in subjects with plaque-induced gingivitis and periodontitis, since the data from literature are contrasting. MATERIAL AND METHODS: Case-control and cross-sectional studies, investigating HSV-1 in subgingival plaque/crevicular fluid and periodontal status, were searched through MEDLINE via PubMed, Scopus, Web of Science and Google Scholar. From each study the crude odds ratio (OR) with 95% confidence interval (95CI) was extracted, and the pooled OR was assessed for periodontitis, chronic and aggressive, and gingivitis. The meta-analytic method was chosen based on the level of heterogeneity. The generalizability of results, determined by the meta-analysis bias, was investigated through secondary analyses including sensitivity analyses for study quality, publication bias, and study inclusion, and subgroup analyses for quality of scientific journals that published the primary studies, world Region, subgingival plaque sampling method and study design. RESULTS: Twelve studies were included (738 cases, 551 controls). The pooled ORs were 4.4 (95CI, 1.9-10.2) for any periodontitis; specifically, 2.8 (95CI, 1.0-8.3) for chronic periodontitis, 11.8 (95CI, 5.4-25.8) for aggressive periodontitis and 4.8 (95CI, 2.1-11.0) for gingivitis. These estimates were statistically significant, excluding for chronic periodontitis, resulting marginally significant (p = .05). Secondary analyses on any and aggressive periodontitis, and, partly, chronic periodontitis corroborated the results, while the material was insufficient for secondary analyses on gingivitis. CONCLUSIONS: The results obtained indicated that HSV-1 is associated with periodontitis, while data about gingivitis are inconclusive. HSV-1 investigation in subgingival plaque could help assess periodontitis risk and severity and, if causal association were confirmed, could contribute to its control.

The prompt use of rituximab could decrease adverse effects in patient with pemphigus vulgaris: A preliminary evaluation.

BACKGROUND: The systemic use of corticosteroid is the treatment of choice for patients with pemphigus vulgaris (PV), but adverse effects are frequent. To date, the use of rituximab (RTX) for PV patients is usually indicated when they failed first-line immunosuppressive therapies. The early use of RTX could theoretically lessen adverse effects. METHODS: We performed a single-center study on patients with predominantly oral PV, treated with systemic corticosteroid and the prompt use of 1000 mg of intravenous RTX two weeks apart. We evaluated the clinical response and the reported adverse effect during a period of 24 months, comparing those with a previously published series. RESULTS: The study group comprised 11 patients, while the control group comprised 98 patients. The average time to achieve complete clinical remission was 3.2 ± 2.72 months. Study group took steroids for a mean time of 11.09 ± 2.02 months, and they are all actually disease-free with no medication. Only three patients (27.3%) developed plain side effects. The effect of the length of the corticosteroid therapy on the side effects (also adjusted by sex, age, and clinical oral involvement) was statistically different in the two groups: the prompt use of RTX reduced of 94% the chance to have adverse effects (P = .001). CONCLUSIONS: This is the first report of the use of RTX as first line of therapy for PV patients with predominantly oral involvement. With the proposed regimen, the adverse effects have been minimized compared with classic systemic corticosteroid-centered therapy. Multi-center randomized controlled trail is however necessary.

Treatment of angular cheilitis: A narrative review and authors' clinical experience.

Angular cheilitis (AC) is a clinical entity first described in the XIX century, characterized by erythema, rhagades, ulcerations, and crusting of one or both lip commissures and perilabial skin, responsible of an unpleasant and painful discomfort. Aim of this manuscript was to examine and evaluate the therapeutic options actually available for AC. Despite antifungals being the first-line treatment for most of clinicians, very limited scientific evidence supports their reliability, with just two RCTs published between the 70's and the 80's. Furthermore, alternative topical treatments, various techniques of occlusal vertical dimension restoration, B-vitamin supplementation, anti-drooling prosthetic device, and photodynamic therapy have been experimented and proposed, mostly in the form of case reports or case series on a small number of individuals. Our group found in 1% isoconazole nitrate (ISN) and 0.1% diflucortolone valerate (DFV) ointment the most consistent AC treatment, due to the broad spectrum of ISN against many species of dermatohpytes and bacteria, and the anti-inflammatory properties displayed by DFV. However, further and well-designed trials on larger samples of patients are needed to assess the differential profile of consistency of the treatments outlined in literature and claimed by the authors of this paper.

Long-term evaluation of pemphigus vulgaris: A retrospective consideration of 98 patients treated in an oral medicine unit in north-west Italy.

BACKGROUND: Despite the frequency of oral involvement, there are unexpectedly few studies of either on the oral manifestations of pemphigus or their long-term management, and diagnostic delay in Dentistry is frequent. METHODS: We have examined outcome of patients presenting with predominantly oral pemphigus vulgaris (PV). Ninety-eight subjects were followed up for 85.12 months and treated with systemic steroids: 48 of them received adjunctive therapy with azathioprine, 16 with rituximab, 13 with mycophenolate mofetil, three with immunoglobulin and one with dapsone. RESULTS: Clinical remission was achieved in 80 patients (84.21%); 39 of them were off therapy and 41 on therapy. Fifteen patients were not in remission, having been under systemic therapy for 72.16 months. Sixty-nine patients developed detectable adverse effects. Two fatal outcomes were recorded. Each additional year of steroid therapy ensured 47% chance of developing 1 or 2 side effects, and 64% chance of developing more than 3 (ORs 1.47, CI 1.162-1.903; ORs 1.64, CI 1.107-2.130, respectively). CONCLUSION: In one of the largest available cohort with the longest follow-up ever reported, we observed that the management remains need-based and patient-specific, still relying on systemic corticosteroids.

Effect of a structured plaque control on MMP-1 and MMP-9 crevicular levels in patients with desquamative gingivitis associated with oral lichen planus.

OBJECTIVES: No data are available in the literature on the extent to which the immune host-response and bacterial-elicited inflammation separately contributes to the increase in gingival crevicular fluid (GCF) levels of inflammatory biomarkers in patients affected by desquamative gingivitis (DG) secondary to oral lichen planus (OLP). The aim of this study was to investigate the effect of a structured plaque control intervention on GCF levels of MMP-1 and MMP-9 in OLP patients with DG and to compare them with those of non-OLP patients. MATERIALS AND METHODS: The study population consisted of 18 unrelated Caucasian patients with DG, while 18 periodontally healthy subjects were recruited for the control group. Periodontal parameters and GCF biomarker amounts were evaluated at baseline and 2 months after a structured plaque control intervention, comprising professional oral hygiene sessions, manual toothbrushing, and interdental cleaning advice, only for DG patients. Determination of MMP-1 and MMP-9 levels was carried out by means of an enzyme-linked immunosorbent assay. RESULTS: Plaque control program led to improvement in all examined clinical parameters and resulted in significant decrease in GCF total amount and concentration of MMP-1 and MMP-9 in comparison to baseline (p < 0.001). However, MMP-1 and MMP-9 levels in DG patients were still significantly higher than those in the healthy control group (p < 0.01). CONCLUSIONS: These findings would seem to support an intrinsic upregulated expression of MMPs in DG patients that is exacerbated by bacterial plaque. CLINICAL RELEVANCE: The present outcomes provide further scientific grounds for the importance of strict professional oral hygiene sessions in DG patients.

Salivary extracellular vesicle-associated miRNAs as potential biomarkers in oral squamous cell carcinoma.

BACKGROUND: Several studies in the past have investigated the expression of micro RNAs (miRNAs) in saliva as potential biomarkers. Since miRNAs associated with extracellular vesicles (EVs) are known to be protected from enzymatic degradation, we evaluated whether salivary EVs from patients with oral squamous cell carcinoma (OSCC) were enriched with specific subsets of miRNAs. METHODS: OSCC patients and controls were matched with regards to age, gender and risk factors. Total RNA was extracted from salivary EVs and the differential expression of miRNAs was evaluated by qRT-PCR array and qRT-PCR. The discrimination power of up-regulated miRNAs as biomarkers in OSCC patients versus controls was evaluated by the Receiver Operating Characteristic (ROC) curves. RESULTS: A preliminary qRT-PCR array was performed on samples from 5 OSCC patients and 5 healthy controls whereby a subset of miRNAs were identified that were differentially expressed. On the basis of these results, a cohort of additional 16 patients and 6 controls were analyzed to further confirm the miRNAs that were up-regulated or selectively expressed in the previous pilot study. The following miRNAs: miR-302b-3p and miR-517b-3p were expressed only in EVs from OSCC patients and miR-512-3p and miR-412-3p were up-regulated in salivary EVs from OSCC patients compared to controls with the ROC curve showing a good discrimination power for OSCC diagnosis. The Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analysis suggested the possible involvement of the miRNAs identified in pathways activated in OSCC. CONCLUSIONS: In this work, we suggest that salivary EVs isolated by a simple charge-based precipitation technique can be exploited as a non-invasive source of miRNAs for OSCC diagnosis. Moreover, we have identified a subset of miRNAs selectively enriched in EVs of OSCC patients that could be potential biomarkers.

Paget's disease of jaw bones as primary manifestation: A case report of a proper diagnosis made by general dentist.

OBJECTIVE: To present a case of early diagnosis mandibular Paget's disease of bone (PDB), recognised by a general dentist. BACKGROUND: PDB is responsible of rapid bone resorption and disorganised bone formation. MATERIALS AND METHODS: The patient was a 72-year-old female patient complaining of dental malposition and blatant prognathism. CONCLUSION: Clinicians should consider PDB in differential diagnosis for an elderly patient undergoing unexplained alteration in face profile and occlusion.

Impact of a sodium carbonate spray combined with professional oral hygiene procedures in patients with Sjögren's syndrome: an explorative study.

OBJECTIVES: The aim of this study was to make an initial estimation on the effects of a sodium bicarbonate and xylitol spray (Cariex® ), associated with non-surgical periodontal therapy, in participants with primary Sjögren's syndrome. BACKGROUND: Sjögren's syndrome (SS) is a multisystem autoimmune disease that predominantly involves salivary and lachrymal glands, with the clinical effect of dry eyes and mouth. MATERIALS AND METHODS: A prospective cohort of 22 women and two men has been evaluated. They were randomized into three groups (eight patients each): Group A) those treated once with non-surgical periodontal therapy, education and motivation to oral hygiene, associated with the use of Cariex® ; Group B) treated only with Cariex® ; Group C) treated only with non-surgical periodontal therapy, education and motivation to oral hygiene. Clinical variables described after treatment were unstimulated whole salivary flow, stimulated whole salivary flow, salivary pH, reported pain (using Visual Analogue Scale) and the Periodontal Screening and Recording index. RESULTS: Salivary flow rate improved in all groups, but the difference was statistically significant only in those treated with Cariex® , alone or in combination with periodontal therapy. Gingival status improved in participants who underwent periodontal non-surgical therapy while remained unchanged in those only treated with Cariex® . Reported pain decreased in all groups, showing the best result in participants treated with periodontal therapy together with Cariex® . CONCLUSIONS: We propose a practical approach for improving gingival conditions and alleviating oral symptoms in patients with SS. Future randomized and controlled trials are however required to confirm these results as well as larger population, and also assessing other parameters due to oral dryness, possible oral infections and more comprehensive periodontal indices.

A randomized pilot study to assess the safety and the value of low-level laser therapy versus clonazepam in patients with burning mouth syndrome.

Comparison between low-level laser therapy (LLLT) and clonazepam for treating burning mouth syndrome (BMS) patients has never been documented; the aim of this study was to assess the effects of LLLT photobiomodulation versus medical therapy with clonazepam on BMS. Thirty-three patients (25 female, 8 male, mean age = 67.12) were randomly allocated to two different groups: the first one (group A, 18 patients) underwent two laser irradiation sessions weekly for 5 weeks, whereas the second one (group B, 15 patients) received topical clonazepam therapy [half a tablet (2 mg) in the mouth without swallowing for 3 min, three times a day for 21 days]. LLLT was delivered with a continuous wave 980-nm aluminum gallium arsenide (AlGaAs) diode laser and the output of 300 mW, delivering a Fluence of 10 J/cm(2), using a "spot technique," with an average power density of about 1 W/cm(2). The laser probe was held perpendicularly at a distance of about 2 mm from the mucosa. Visual analogue scale (VAS), McGill Pain Questionnaire, present pain intensity (PPI), and Oral Health Impact Profile (OHIP-49) assessed sensation of pain. Hospital Anxiety and Depression Scale and Geriatric Depression Scale assessed levels of anxiety and depression. Twelve weeks after the end of treatment, patients treated with LLLT experienced a decrease in pain sensation reported for all the parameters analyzed: VAS (P = 0.004), McGill Pain Questionnaire (P = 0.002), PPI (P = 0.002), and OHIP-49 (P = 0.010). The group treated with clonazepam had less favorable results for VAS (P = 0.33), McGill Pain Questionnaire (P = 0.005), PPI (P = 0.013), and OHIP-49 (P = 0.25). Levels of anxiety and depression did not change statistically in any groups (P > 0.05). Comparing the two groups, LLLT appeared to be superior in improving pain perception, but statistically only at 8 weeks after the end of the protocol proposed (P = 0.026). Based on this preliminary trial, LLLT is capable of reducing the symptoms of patients with BMS with a constant and long-lasting effect, experienced since the end of the first applications.

Effects of bisphosphonate treatment on DNA methylation in osteonecrosis of the jaw.

Bisphosphonates are used in the treatment of hypocalcaemia, mainly in cancer and osteoporosis. Some patients experience adverse events, such as BP-related osteonecrosis of the jaw (BRONJ). DNA methylation plays a key role in gene regulation in many tissues, but its involvement in bone homeostasis is not well characterized, and no information is available regarding altered methylation in BRONJ. Using the Illumina Infinium HumanMethylation27 BeadChip assay, we performed an epigenome-wide association study in peripheral blood samples from 68 patients treated with nitrogenous BP, including 35 with BRONJ. Analysis of the estimated cumulative BP exposure distribution indicated that the exposure of the case group to BP was slightly higher than that of the control group; more severely affected cases (i.e., with BRONJ in both mandible and maxilla) were significantly more exposed to BP than were those with BRONJ only in the mandible or maxilla (one-sided Wilcoxon rank sum test, p=0.002). Logistic regression analysis confirmed the positive association between cumulative bisphosphonates exposure and risk of BRONJ (OR 1.015 per mg of cumulative exposure, 95% CI 1.004-1.032, p=0.036). Although no statistically significant differences were observed between case and control groups, methylation levels of probes mapping on three genes, ERCC8, LEPREL1 and SDC2, were strongly associated with cumulative BP exposure levels (p<1.31E-007). Enrichment analysis, combining differentially methylated genes with genes involved in the mevalonate pathway, showed that BP treatment can affect the methylation pattern of genes involved in extracellular matrix organization and inflammatory responses, leading to more frequent adverse effects such as BRONJ. Differences in DNA methylation induced by BP treatment could be involved in the pathogenesis of the bone lesion.