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.

Assessment of sleep disturbance in oral lichen planus and validation of PSQI: A case-control multicenter study from the SIPMO (Italian Society of Oral Pathology and Medicine).

BACKGROUND: The wellbeing of oral lichen planus patients (OLPs) may be strongly influenced by a poor quality of sleep (QoS) and psychological impairment. The aims were to analyze the prevalence of sleep disturbance, anxiety, and depression in OLPs and to validate the Pittsburgh Sleep Quality Index (PSQI) in OLPs. METHODS: Three hundred keratotic OLPs (K-OLPs), 300 with predominant non-keratotic OLP (nK-OLPs), and 300 controls were recruited in 15 Italian universities. The PSQI, Epworth Sleepiness Scale (ESS), Hamilton Rating Scales for Depression and Anxiety (HAM-D and HAM-A), Numeric Rating Scale (NRS), and Total Pain Rating Index (T-PRI) were administered. RESULTS: Oral lichen planus patients had statistically higher scores than the controls in the majority of the PSQI sub-items (p-values < 0.001**). Moreover, OLPs had higher scores in the HAM-D, HAM-A, NRS, and T-PRI (p-values < 0.001**). No differences in the PSQI sub-items' scores were found between the K-OLPs and nK-OLPs, although nK-OLPs suffered from higher levels of anxiety, depression, and pain (p-values: HAM-A, 0.007**, HAM-D, 0.009**, NRS, <0.001**, T-PRI, <0.001**). The female gender, anxiety, depression (p-value: 0.007**, 0.001**, 0.020*) and the intensity of pain, anxiety, and depression (p-value: 0.006**, <0.001**, 0.014*) were independent predictors of poor sleep (PSQI > 5) in K-OLPs and nK-OLPs, respectively. The PSQI's validation demonstrated good internal consistency and reliability of both the total and subscale of the PSQI. CONCLUSIONS: The OLPs reported an overall impaired QoS, which seemed to be an independent parameter according to the regression analysis. Hence, clinicians should assess QoS in OLPs and treat sleep disturbances in order to improve OLPs management.

Evaluating the Suitability and Potential Efficiency of Cannabis sativa Oil for Patients with Primary Burning Mouth Syndrome: A Prospective, Open-Label, Single-Arm Pilot Study.

OBJECTIVE: To evaluate the use of a Cannabis sativa oil in the management of patients diagnosed with primary burning mouth syndrome (BMS). DESIGN: Prospective, open-label, single-arm pilot study. SETTING: University hospital. SUBJECTS: Seventeen patients with diagnosed BMS were included. METHODS: Subjects were treated for 4 weeks with a full cannabis plant extract, which was prepared from standardized plant material (cannabis flos) in specialized pharmacies by means of Romano-Hazekamp extraction and was diluted in oil (1 g of cannabis in 10 g of olive oil). The primary outcome was the change in pain intensity (assessed by the visual analog scale, Present Pain Intensity scale, McGill Pain Questionnaire, and Oral Health Impact Profiles) at the end of the protocol and during the succeeding 24 weeks; the neuropathic pain was also investigated with a specific interview questionnaire (DN4-interview [Douleur Neuropathique en 4 Questions]). Levels of anxiety and depression were considered as secondary outcomes, together with reported adverse events due to the specified treatment. RESULTS: Subjects showed a statistically significant improvement over time in terms of a clinical remission of the oral symptoms. Levels of anxiety and depression also changed statistically, displaying a favorable improvement. No serious reactions were detailed. None of the patients had to stop the treatment due to adverse events. CONCLUSIONS: In this pilot evaluation, the C. sativa oil provided was effective and well tolerated in patients with primary BMS. Further bigger and properly defined randomized controlled trials, with different therapeutic approaches or placebo control, are needed, however.

Value of colchicine as treatment for recurrent oral ulcers: A systematic review.

BACKGROUND: In oral medicine, colchicine is a therapeutic alternative for idiopathic recurrent aphthous stomatitis (RAS), Behçet disease (BD), periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome, and mouth and genitals ulcers with inflamed cartilage (MAGIC) syndrome. The present review aims to evaluate reliability of colchicine against recurrent oral ulcers. METHODS: A systematic review was conducted, with the following PICO (Patient, Intervention, Control, Outcome) question: "In populations with idiopathic or secondary recurrent oral ulcers, is colchicine more effective in improving pain and accelerating healing, compared to other intervention or placebo?" RESULTS: Seven RCTs and 3 OCTs were considered eligible. Four RCTs focused on BD, two RCTs and three OCTs on RAS, and one RCT on PFAPA syndrome. Heterogeneity between RCTs prevented from meta-analysis. Regarding BD, no significant difference between colchicine and placebo was found in two of three placebo-controlled RCTs, whereas the third RCT showed benefit. A comparative RCT found ciclosporin more effective than colchicine for oral lesions of BD. One open-label RCT showed promising but partial results on colchicine in reducing PFAPA attacks, when compared to corticosteroids. Concerning RAS, colchicine appeared less effective than clofazimine, thalidomide and dapsone, and with outcomes similar to low-dosage corticosteroids but higher gastric discomfort than prednisolone. One OCT reported positive results compared with no treatment but a RCT found no difference with placebo. CONCLUSION: Role of colchicine as treatment for idiopathic or secondary recurrent oral ulcers is still controversial. Further standardized RCTs and crossover trials are needed.

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.

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.

Lack of evidence in reducing risk of MRONJ after teeth extractions with systemic antibiotics.

A systematic review was carried out to identify if periprocedural administration of systemic antibiotics could decrease risk of medication-related osteonecrosis of the jaws (MRONJ) in patients under antiresorptive and/or biologic agents for teeth extraction. PubMed/MEDLINE and Scopus were systematically searched for case-series with more than 10 patients, retrospective/prospective studies, and trials concerning this issue. Manual searching of references from previous reviews was also carried out. Of 1,512 results, 17 studies were included, focusing on antibiotics for extraction in patients under intravenous bisphosphonates (8 studies), oral bisphosphonates (2 studies), oral and intravenous bisphosphonates (6 studies), and denosumab (1 study), of which 12 performed dental extraction with surgical flap. With no trials found, "quality in prognosis studies" (QUIPS) tool was used to evaluate risk of bias. First-line treatment was 2-3 grams of oral amoxicillin in 76.4% of studies; 300-600 mg of clindamycin was the alternative treatment in 23.5% of studies. Treatment ranged from 3 to 20 days, consisting of 6-7 days in 47% of studies. No microbiologic insight was provided. A significantly higher risk of MRONJ for patients unexposed to antibiotics was provided in one retrospective study. QUIPS tool revealed moderate-high risk of bias. With empirical data from bias-carrying, heterogeneous observational studies, the validity of antibiotics is yet to be established.

Effectiveness of Nonpharmacologic Treatments of Burning Mouth Syndrome: A Systematic Review.

AIMS: To assess the efficacy of nonpharmacologic treatments for burning mouth syndrome (BMS). METHODS: PubMed, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials were systematically searched. Reference lists from the latest systematic reviews (2015 to 2020) on BMS treatment in the PubMed, Scopus, Web of Science, and Cochrane Library databases were also scrutinized. Randomized controlled trials (RCTs) or clinical controlled trials (CCTs) in English were considered eligible. Trials on photobiomodulation were excluded to avoid redundancy with recent publications. Risk of bias was established through the Cochrane Risk of Bias tool for RCTs and the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool for CCTs. RESULTS: This review included 27 RCTs and 6 open clinical trials (OCTs) describing 14 different nonpharmacologic interventions. Eleven trials experimented with 600 to 800 mg/day of alpha-lipoic acid for 30 to 120 days, with 7 placebo-controlled studies showing significant pain relief. Four trials tested topical and systemic capsaicin for 7 to 30 days, with 2 placebo-controlled studies revealing significant efficacy. Four of the 5 trials testing acupuncture offered favorable evidence of pain relief. Two trials reported significant pain relief after a 2- to 3-month regimen with tongue protectors and showed no difference after aloe vera addition. Short-term pain relief was reported in anecdotal placebo-controlled trials deploying tocopherol, catuama, ultramicronized palmitoylethanolamide, group psychotherapy, cognitive therapy, and repetitive transcranial magnetic stimulation of the prefrontal cortex. Most therapies were safe. CONCLUSION: Evidence was collected from highly biased, short-term, heterogenous studies mainly focused on BMS-related pain, with scarce data on quality of life, psychologic status, dysgeusia, and xerostomia. Long-term effectiveness of nonpharmacologic treatments should be further investigated, with a more rigorous, bias-proof study design.

Effect of two different alcohol-free chlorhexidine formulations in mouthrinses on the immediate postoperative period for oral mucosal biopsies.

Oral biopsy is a common surgical practice. To date, few authors have described the healing of mucosal wounds following oral biopsy. The aim of the present single-center, prospective, randomized, controlled study is to evaluate the differences between two chlorhexidine (CHX) mouthrinses and a treatment-free approach in the immediate postoperative period following oral mucosal biopsy. 354 patients were included in this study and were randomly allocated to three groups: A) CHX 0.12% mouthrinse (twice daily, 10 mL rinse for 30 s), B) CHX 0.20% mouthrinse (twice daily, 10 mL rinse for 30 s), and C) no topical treatment. 118 patients were treated in group A and 115 in group B; 121 received no therapy in group C, reporting the greatest improvement in related symptoms. Outcome variables included the age, gender, site and size of lesions, visual analog score (VAS), Oral Health Impact Profile questionnaire (OHIP-14), and number of painkillers taken during the first week post-surgery. Use of a CHX 0.12% mouthrinse exhibited the poorest outcome. On the other hand, best clinical healing was found for patients treated with CHX 0.20%. These findings suggest that regardless of its concentration, CHX was found to be ineffective in reducing related symptoms, whereas CHX 0.20% can be recommended to facilitate enhanced healing.

Case Report: Sporadic Burkitt lymphoma misdiagnosed as dental abscess in a 15-year-old girl.

Background: Burkitt lymphoma (BL) is a non-Hodgkin's B-cell tumor that can be classified into three variants, based on clinical characteristics and epidemiology: endemic, human immunodeficiency-related and sporadic. Oral sporadic BL is quite an unusual entity, with the gastrointestinal trait being often the first site of appearance. Clinical finding: A 15-year-old patient that presented a symptomatic swelling of the right maxilla, unsuccessfully treated as a primary endodontic disease, displaying solid tissue on CT scan, "starry sky" pattern on oral biopsy, multifocal bone and lymph node uptake on PET. Diagnoses, interventions, and outcomes: A diagnosis of stage IV BL was formulated; Rituximab was then administered for three months according to Inter-B-NHL ritux 2010 protocol and CYM (cytarabine and methotrexate) chemotherapy. The patient was followed-up for three years, with no recurrence. Conclusion: It is important for general dental practitioners to suspect a malignancy in the differential diagnosis of unresponsive odontogenic infections in young healthy patients.

Subgingival Microbiota in White Patients With Desquamative Gingivitis: A Cross-Sectional Study.

BACKGROUND: Presence of epithelial desquamation, erythema, and erosions on gingival tissue is usually described in the literature as desquamative gingivitis (DG). A wide range of autoimmune/dermatologic disorders can manifest as DG, although the two more common are oral lichen planus and mucous membrane pemphigoid. The aim of this study is to investigate prevalence of 11 periodontopathogenic microorganisms in patients with DG and to compare it with the microbiologic status of individuals affected by plaque-induced gingivitis (pGI). METHODS: Cross-sectional clinical and microbiologic data were obtained from 66 patients (33 in each group). Subgingival plaque samples were analyzed using semiquantitative polymerase chain reaction analysis. RESULTS: Statistically significant difference, but with little clinical significance, was observed in gingival conditions between the two groups, probably due to the worse home control hygiene of patients with DG. Prevalence and levels of Aggregatibacter actinomycetemcomitans, Eikenella corrodens, and Fusobacterium nucleatum/periodonticum were statistically higher in samples from patients with DG than in those with pGI. In multivariate regression models, subgingival colonization of A. actinomycetemcomitans and F. nucleatum/periodonticum was not statistically associated with DG, whereas, high levels of E. corrodens were associated with 13-fold increased odds for DG. CONCLUSIONS: Microbiologic differences were found in subgingival plaque for patients with DG and pGI. This may suggest possible association between periodontal pathogens and DG.

Delayed Diagnosis of Osteonecrosis of the Jaw (ONJ) Associated with Bevacizumab Therapy in Colorectal Cancer Patients: Report of Two Cases.

Medication-induced Osteonecrosis of the Jaw (MRONJ) has been reported not only after use of antiresorptive agents (bisphosphonates and denosumab), but also in cancer patients receiving antiangiogenic agents, alone or combined with antiresorptive drugs. We report two cases of MRONJ observed in colorectal cancer patients after bevacizumab therapy only. MRONJ was diagnosed, respectively, two and seven months after a tooth extraction; both the patients had received two courses of bevacizumab infusions (for a total of 29 and 10 administrations, respectively). We discuss if tooth extraction during or after antiangiogenic therapy could be a potential trigger of MRONJ, but also if an underlying bone disease not evident before oral surgery might be a possible cause. A careful drug history has to be registered by dental specialists in cancer patients before oral surgery and adequate imaging might be obtained to avoid a delayed diagnosis.