BACKGROUND: Recurrent aphthous stomatitis (RAS) is a common chronic inflammatory oral disease that negatively impacts the quality of life. Current therapies aim to reduce pain and healing process yet challenges such as rapid loss due to salivary flushing in topical drugs and adverse effects due to prolonged use of systemic medications require further notice. Low-level laser therapy is reported with immediate pain relief and faster healing thus preserving the potential for optimal treatment modalities. This review critically analyses and summarizes the effectiveness of LLLT in reducing pain scores and healing time of RAS.
METHODS: A systematic search was conducted in ScienceDirect, PubMed, and Scopus using keywords of low-level laser therapy, photo-biomodulation therapy, and recurrent aphthous stomatitis. RCTs between 1967 to June 2022, presenting characteristics of the laser and reporting pain score and/or healing time of RAS after irradiation were included. Animal studies and recurrent aphthous ulcers with a history of systemic conditions were excluded. Studies were critically appraised using the RoB 2 tool. A meta-analysis was performed using inverse variance random effects.
RESULTS: Fourteen trials with a total of 664 patients were included. Reduced pain was reported in 13 studies, while shortened healing time was presented in 4. The pooling of two studies after CO2 irradiation demonstrated faster healing time compared to placebo (MD - 3.72; 95% CI - 4.18, - 3.25).
CONCLUSIONS: Pain score and healing time of RAS were reduced after irradiation with LLLT. RoB resulted in \"some concerns\" urging well-designed RCTs with larger samples to further assess each laser application for comparison.
BACKGROUND: PROSPERO CRD42022355737.

Background Recurrent aphthous stomatitis (RAS) is a chronic oral ulcerative condition with an elusive etiology that is associated with excruciating pain. Psychological factors have been suspected as a possible risk factor in its onset and development. Depression, anxiety, and stress play pivotal roles in how people experience pain. Hence, we aimed to explore the relationship between depression, anxiety, stress, and the severity of pain perceived due to recurrent ulcers in RAS patients. Materials and methods A cross-sectional comparative study was conducted on 248 patients, comprising 124 diagnosed with RAS and 124 healthy subjects without this oral condition. Patients from both of these groups were matched with regard to age and sex and recruited over a period of one year from a dental hospital in Bengaluru, India. Patients with any other oral lesions, painful oral conditions, or systemic and psychological illnesses were excluded. Depression, anxiety, and stress were assessed in these patients using the Depression Anxiety Stress Scale 21 (DASS-21). Utilizing a Visual Analog Scale, ulcer-related pain was assessed in patients with RAS. The data were analyzed using the chi-square test and Pearson\'s correlation test in IBM SPSS Statistics for Windows, Version 26.0 (released 2019, IBM Corp., Armonk, NY). Results The chi-square analysis showed that participants with RAS showed a statistically significant higher prevalence of extreme stress (n = 39, 31.5%), extreme anxiety (n = 82, 66.1%), and depression (n = 38, 30.6%) as opposed to those without this oral condition. A moderately positive correlation was observed in the Pearson\'s test between the severity of pain experienced and stress and anxiety (r = 0.65 and 0.60, respectively, p < 0.05), while a mild positive correlation was observed between the severity of pain and depression (r = 0.35, p < 0.05). Conclusion Depression, anxiety, and stress influenced the severity of pain in these lesions, dictating the need for a holistic approach that integrates psychological interventions in the management of such chronic oral conditions with psychological links.

UNASSIGNED: Recurrent aphthous stomatitis (RAS) is a common oral mucosal disease. Despite a variety of scientific articles have been available till date, merely a few scientometric analyses have been systematically carried out in this field. The objective of this study was to recognize the hotspots and research trends related to RAS via bibliometric approach.
UNASSIGNED: The Elsevier\'s Scopus database was searched to retrieve qualified literature through an advanced search strategy on 9 Feb 2023. The basic information was collected as following: article type, publication year, journals, impact factor, the count of citations, citation density, keywords, authors, contributing institutions and country.
UNASSIGNED: A list of 986 publications were identified from 1933 to 2022, and the number of citations for each paper varied from 0 to 283. A steady increasing trend in the number of documents could be observed each decade with the summit in 2010s. Controlled study (n = 334) and major clinical study (n = 192) were the most common types of study design. Scully C (n = 26) was identified as the most productive author. United States (n = 166) and Turkey (n = 101) top the list of dedicating countries.
UNASSIGNED: This report would offer profound insight into the current status of RAS research and serve as a reference source for anyone planning to enhance the quality of future work.

OBJECTIVE: The purpose of this study was to determine the therapeutic effect of the Punica granatum (PG) flower on recurrent aphthous stomatitis in comparison with corticosteroid therapy.
METHODS: This cross-over randomized clinical trial was conducted on the patients who had been referred to Shiraz Dental School for their RAS in 2021. All the participants used both P. granatum flower tablets and Triadent a month apart for wash-out time and all compared themselves. In the experimental group, 30 patients received pomegranate flower tablets, three tablets daily, for 6 days. In the control group, oral paste Triadent has been prescribed three times a day for 6 days. The visual analog scale (VAS) and the size of RAS were evaluated on Days 0-6. Data were analyzed by SPSS version 21. The Wilcoxon test was used.
RESULTS: The mean age of participants was 27.8 ± 14.77 years old. In this study, 15 patients (50%) were men and 15 patients (50%) were women. The mean value of VAS after using prescribed treatment in both evaluated groups on all days was significantly different such that the VAS values were lower for PG flower tablets than Triadent (p value < 0.05). The size of oral lesions in participants who used PG flower tablets was significantly less than those who used Triadent on all evaluation days (p value < 0.05) except on Day 1 (p value = 0.29). The descending slope of VAS from Days 1 to 6 for both Triadent and PG flower tablet users was significant and noticeable. (p value < 0.05).
CONCLUSIONS: According to the result of this study, both P. granatum flower tablet and Triadent are useful in reducing the size, period of healing, and VAS of patients with RAS, but the PG flower tablet is more effective.

Recurrent aphthous stomatitis (RAS) refers to a sore and frequently recurring inflammation of the oral tissues, distinguished by the presence of small ulcers that cause significant discomfort and cannot be attributed to any underlying disease. Different treatments have been used for RAS. This review aims to provide a comprehensive overview of the treatment options over the past decade for recurrent aphthous stomatitis (RAS), encompassing both natural and synthetic treatments. It will utilize clinical efficacy studies conducted in vivo and in vitro, along with a focus on the pharmaceutical approach through advancements in drug delivery development. We conducted a thorough literature search from 2013 to 2023 in prominent databases such as PubMed, Scopus, and Cochrane, utilizing appropriate keywords of recurrent aphthous stomatitis, and treatment. A total of 53 clinical trials with 3022 patients were included, with 35 using natural materials in their research and a total of 16 articles discussing RAS treatment using synthetic materials. All the clinical trials showed that natural and synthetic medicines seemed to benefit RAS patients by reducing pain score, ulcer size, and number of ulcers and shortening the healing duration.

Background/Objectives: Recurrent aphthous stomatitis (RAS) is one of the most common oral mucosal lesions and a very debilitating lesion, especially in paediatric and adolescent patients. The current pharmacotherapy offers a pain relief but not without side effects, and therefore photobiomodulation (PBM) can be an alternative therapy. To the authors\' best knowledge, no published study has explored the efficacy of λ 980 nm laser PBM in the management of all RAS subtypes in paediatric and adolescent patients, and therefore, this prospective observational clinical study was conducted to bridge this gap by evaluating λ 980 nm laser PBM efficacy in symptomatic RAS management in paediatric and adolescent patients. The objectives were to evaluate (1) pain intensity alleviation; (2) wound healing rate; (3) wound size closure; (4) a complete resolution; (5) evidence of recurrence; and (6) patients\' treatment satisfaction. Methods: The study\'s variables were assessed at the following timepoints: T0: pre-treatment; T1: immediately after first PBM session; T2: 5 hours (h) post first PBM session (via telephone call); T3: immediately after second PBM session (three days post first PBM session); T4: three-day follow-up (after complete PBM treatments); T5: two-week follow-up; and T6: three-month follow-up. The following PBM dosimetry and treatment protocols were employed: λ 980 nm; 300 mW; 60 s; 18 J; CW; flattop beam profile of 1 cm2 spot size; 18 J/cm2; and twice-a-week irradiation (72 h interval). Results: At T1, significant immediate pain intensity relief was reported. 33.33% recorded \"4\" and 66.67% reported \"5\" on the quantitative numeric pain intensity scale (NPIS), and this continued to improve significantly (83.33%) at T2. All the subjects reported \"0\" on the NPIS at T3, T4, T5 and T6. There was a significant reduction in the lesion surface area (>50% complete healing) at T3 compared to T0. Complete healing (100%) with no evidence of scarring and lesion recurrence observed at T4, T5 and T6. Very good patients\' satisfaction was reported at all timepoints. Conclusions: This is the first report demonstrating λ980 nm efficacy in all RAS subtype management in paediatric and adolescent patients with a 3-month follow-up, whereby its PBM dosimetry and treatment protocols were effective from scientific and practical standpoints, and hence multicentre RCTs with large data are warranted to validate its reproducibility and to enrich the knowledge of PBM application in all RAS subtypes.

Background: Cod liver oil has anti-inflammatory properties and could help regulate recurrent aphthous stomatitis (RAS). An orthogonal experiment was used to evaluate and improve the dosage form of compound cod liver oil, which has replaced the previously used liniment preparation based on film method. Methods: An orthogonal experiment was adopted, and the appearance and film-forming time of the film coating agents were used as indicators. The optimal ratio in the preparation process for the compound cod liver oil film agent was then optimized. A method for determination of compound cod liver oil film was established using High-Performance Liquid Chromatography (HPLC). Results: The results indicate that the blank films prepared using 55 mg polyvinyl alcohol (PVA) (PVA low), 45 mg of PVA (PVA medium), and 10 mg glycerol had the optimal performance, which was defined as PVAa. The drug-carrying film prepared from 3 mL PVAa (i.e., film-forming material with the optimal proportion), 30 mg dexamethasone acetate, and 30 mg metronidazole had the optimal performance. The verified sample has a complete and smooth appearance, uniform thickness and color, and no evident bubbles, which meets the requirements for a film agent defined in the Chinese Pharmacopoeia, 2020 edition. HPLC was used to determine the major components: dexamethasone acetate, metronidazole, and dyclonine hydrochloride, and the optimal separation effect was obtained. The method has advantages of good specificity, good linear results, high recovery rate, and good repeatability. Conclusion: This study proposes an optimized compound cod liver oil film former agent and preparation method. The results indicate that the compound cod liver oil film former agent had good performance, reflecting the high feasibility of this research method. The detection method of compound cod liver oil film was established by HPLC. The method was feasible, and the validity and stability of the formulation and preparation technology were guaranteed. The role of the newly developed agent in patients with RAS should be investigated further.

OBJECTIVE: Recurrent Aphthous Stomatitis (RAS) known as recurrent aphthous ulcer is a common and painful ulcerations in oral cavity. It has been suggested that hematological parameters seems to be considered as an etiologic factor. So, this meta-analysis and systematic review was aimed to examine the relationship between RAS and hematological parameters.
METHODS: Relevant studies were found using online international databases including Scopus, Science direct, Web of science (ISI), PubMed, and Google Scholar search engine between 2000 and October 2023. The quality of all papers was determined by NOS checklist. Heterogeneity between the results of primary studies was evaluated with I-square index and publication bias was performed by Egger\'s test and funnel plots. Also, sensitivity analysis was done to check the effect of each of the primary studies on the overall estimate. Also, the statistical analyses were done using Stata software Ver. 11.
RESULTS: By combining the results of primary studies, the standardized mean difference (SMD) of vitamin B12, ferritin, folic acid, hemoglobin, iron and zinc indices with a 95% confidence interval (CI) between the case (patients with RAS) and control (Healthy) groups were estimated -0.52(-0.89, -0.14), -0.20(-0.51, 0.11), -0.42(-0.95, 0.11), -0.58(-0.90, -0.27), 0.01(-0.12, 0.15), -0.33(-0.81, 0.14) respectively. The patients with vitamin B12, ferritin, folic acid, and iron deficiencies and reduced hemoglobin (Hb) level reported 2.93(2.28, 3.78), 2.50(1.48, 4.22), 1.51(0.53, 4.29), 1.46(0.70, 3.03), and 2.14(1.38, 3.32), times more susceptible to develop RAS than healthy individuals.
CONCLUSIONS: The results of the meta-analysis indicated that the SMD of vitamin B12 serum and Hb levels in the case group was 52%. Our result have also showed that the odds ratio of vitamin B12, ferritin deficiencies, and decreased Hb level in case group was 2.93, 2.50, and 2.14 times more than healthy group.

UNASSIGNED: Recurrent oral ulcers and severe periodontal diseases in patients with quantitative or qualitative neutrophil defects highlight the important role of neutrophils in maintaining oral mucosal barrier homeostasis. Recurrent aphthous stomatitis (RAS) is a common oral mucosal disease affecting up to 25% of the population, yet its etiopathogenesis remains unclear, and management is unsatisfactory. This review aims to gain insight into the pathogenesis of RAS.
UNASSIGNED: This narrative review examines the characteristics of oral and blood neutrophils, the associations between neutrophil defects and the occurrence of oral ulcers, and the evidence for the involvement of neutrophils in RAS. To conduct the review, relevant literature was searched in PubMed and Google Scholar, which was then thoroughly reviewed and critically appraised.
UNASSIGNED: Neutropenia, specifically a decrease in the number of oral neutrophils, impaired extravasation, and defective ROS production appear to be associated with oral ulcers, while defects in granule enzymes or NETosis are unlikely to have a link to oral ulcers. The review of the histopathology of RAS shows that neutrophils are concentrated in the denuded area but are latecomers to the scene and early leavers. However, the evidence for the involvement of neutrophils in the pathogenesis of RAS is inconsistent, leading to the proposal of two different scenarios involving either impaired or hyperactive neutrophils in the pathogenesis of RAS.

Background: Recurrent Aphthous Stomatitis (RAS) is a common ulcerative disease of the oral mucosa which is characterized by pain, and recurrent lesions in the oral cavity. This condition is quite painful, causing difficulty in eating, speaking and swallowing. Topical medications have been used for this condition, but the obstacle in using topical medications is the difficulty of achieving drug effects due to saliva wash out. This problem can be overcome by film hydrogel formulation which can protect the ulcer and reduce the pain to some extent. α-mangostin is a xanthone isolated from the rind of the mangosteen fruit. One of the activities of α-mangostin is anti-inflammatory effects, which operate through the characteristic mechanism of inhibiting the inflammatory response. This protocol study aims to investigate the efficacy of an α-mangostin hydrogel film with a chitosan alginate base for recurrent aphthous stomatitis (RAS) in comparison with a placebo over a period of 7 days. Study design: This is a two-arm, double blinding, randomized controlled trial enrolling patients with RAS. The efficacy test of α-mangostin Hydrogel Film will be tested against the placebo. Patients with RAS will be allocated randomly into the two arms and the hydrogel film will be administered for 7 days. The diameter of ulcer and visual analog scale (VAS) score will be used as the primary efficacy endpoint. The outcome measure will be compared between the two arms at the baseline, day 3, day 5, and at the end of 7 days. Discussion: The purpose of this clinical research is to provide scientific evidence on the efficacy of α-mangostin hydrogel film with a chitosan alginate basis in treating recurrent aphthous stomatitis. The trial is expected to improve our capacity to scientifically confirm the anti-inflammatory effectiveness of α-mangostin compounds in a final formulation that is ready to use. Trial registration: NCT06039774 (14 September 2023).